China Science & Technology Forum

[JSCh]

Paralyzed mice with spinal cord injury made to walk again
Small-molecule drug reactivates dormant nerve pathways; could complement regenerative strategies
Date: July 19, 2018
Source: Boston Children's Hospital

A cross section of a mouse spinal cord, stained two different ways, showing increased expression of KCC2 in inhibitory neurons. This increased expression correlated with improved motor function, including ankle movement and stepping.
Credit: Zhigang He Lab, Boston Children's Hospital

Most people with spinal cord injury are paralyzed from the injury site down, even when the cord isn't completely severed. Why don't the spared portions of the spinal cord keep working? Researchers at Boston Children's Hospital now provide insight into why these nerve pathways remain quiet. They also show that a small-molecule compound, given systemically, can revive these circuits in paralyzed mice, restoring their ability to walk.

The study, led by Zhigang He, PhD, in Boston Children's F.M. Kirby Neurobiology Center, was published online July 19 by the journal Cell.

"For this fairly severe type of spinal cord injury, this is most significant functional recovery we know of," says He. "We saw 80 percent of mice treated with this compound recover their stepping ability."

Waking up dormant spinal circuits

Many animal studies looking to repair spinal cord damage have focused on getting nerve fibers, or axons, to regenerate, or to getting new axons to sprout from healthy ones. While impressive axon regeneration and sprouting have been achieved, by He's lab and others, their impacts on the animals' motor function after a severe injury are less clear. Some studies have tried using neuromodulators such as serotonergic drugs to simulate the spinal circuits, but have gotten only transient, uncontrolled limb movement.

He and colleagues took another approach, inspired by the success of epidural electrical stimulation-based strategies, the only treatment known to be effective in patients with spinal cord injury. This treatment applies a current to the lower portion of the spinal cord; combined with rehabilitation training, it has enabled some patients to regain movement.

"Epidural stimulation seems to affect the excitability of neurons," says He. "However, in these studies, when you turn off the stimulation, the effect is gone. We tried to come up with a pharmacologic approach to mimic the stimulation and better understand how it works."

He, first author Bo Chen and colleagues selected a handful of compounds that are already known to alter the excitability of neurons, and are able to cross the blood-brain barrier. They gave each compound to paralyzed mice in groups of 10 via intraperitoneal injection. All mice had severe spinal cord injury, but with some nerves intact. Each group (plus a control group given placebo) was treated for eight to ten weeks.

Inhibiting inhibition by re-activating KCC2

One compound, called CLP290, had the most potent effect, enabling paralyzed mice to regain stepping ability after four to five weeks of treatment. Electromyography recordings showed that the two relevant groups of hindlimb muscles were active. The animals' walking scores remained higher than the controls' up to two weeks after stopping treatment. Side effects were minimal.

CLP290 is known to activate a protein called KCC2, found in cell membranes, that transports chloride out of neurons. The new research shows that inhibitory neurons in the injured spinal cord are crucial to recovery of motor function. After spinal cord injury, these neurons produce dramatically less KCC2. As a result, He and colleagues found, they can't properly respond to signals from the brain. Unable to process inhibitory signals, they respond only to excitatory signals that tell them to keep firing. And since these neurons' signals are inhibitory, the result is too much inhibitory signaling in the overall spinal circuit. In effect, the brain's commands telling the limbs to move aren't relayed.

By restoring KCC2, with either CLP290 or genetic techniques, the inhibitory neurons can again receive inhibitory signals from the brain, so they fire less. This shifts the overall circuit back toward excitation, the researchers found, making it more responsive to input from the brain. This had the effect of reanimating spinal circuits disabled by the injury.

"Restoring inhibition will allow the whole system to be excited more easily," He explains.

"Too much excitation not good, and too much inhibition is not good either. You really need to get a balance. This hasn't been demonstrated in a rigorous way in spinal cord injury before."

Combination treatment?

He and colleagues are now investigating other compounds that act as KCC2 agonists. They believe such drugs, or perhaps gene therapy to restore KCC2, could be combined with epidural stimulation to maximize a patient's function after spinal cord injury.

"We are very excited by this direction," says He. "We want to test this kind of treatment in a more clinically relevant model of spinal cord injury and better understand how KCC2 agonists work."

Bo Chen, Yi Li (Boston Children's Hospital) and Bin Yu (Nantong University, China) were co-first authors on the paper. Xiosong Gu (Nantong University) and Zhigang He are co-senior authors. Coauthors were Zicong Zhang, Benedikt Brommer, Philip Raymond Williams, Yuanyuan Liu, Shane Vincent Hegarty, Junjie Zhu and Yiming Zhang (Boston Children's Hospital); Songlin Zhou (Nantong University); Hong Guo and Yi Lu (Brigham and Women's Hospital, Boston).

The study was supported by the National Major Project of Research and Development of China (2017YFA0104701), the National Institute of Neurological Disorders and Stroke (NS096294), the Craig Neilsen Foundation, the Paralyzed Veterans of America Research Foundation and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

Journal Reference:
Bo Chen, Yi Li, Bin Yu, Zicong Zhang, Benedikt Brommer, Philip Raymond Williams, Yuanyuan Liu, Shane Vincent Hegarty, Songlin Zhou, Junjie Zhu, Hong Guo, Yi Lu, Yiming Zhang, Xiaosong Gu, Zhigang He. Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations. Cell, 2018; DOI: 10.1016/j.cell.2018.06.005​

Paralyzed mice with spinal cord injury made to walk again: Small-molecule drug reactivates dormant nerve pathways; could complement regenerative strategies -- ScienceDaily

 

[JSCh]

Polymers can produce micrometre-sized spheres with various internal textures. Credit: D. Liu et al./Angew. Chem. Int. Edn

CHEMISTRY | 18 JULY 2018
An interior-design guide for microscopic spaces
Detailed polymer structures generated in water droplets can be turned into carbon spheres.

Chemists have created microscopic carbon spheres with complex interiors — structures that could have a variety of industrial applications.

Miniature carbon spheres hold promise for energy storage and as catalysts for chemical production. But it is difficult to build micrometre-scale spheres that have the intricate internal architecture needed for synthetic processes.

To produce spheres with the desired properties, Hengquan Yang at Shanxi University in Taiyuan, China, and his colleagues mixed bits of polymer into an oily liquid and suspended small amounts of the mixture inside water droplets. The oil molecules, with the help of some extra ingredients, herded some of the polymer fragments into various patterns. Other fragments migrated to the inner boundary of the water drop, forming a sphere.

After the polymer hardened, it was heated to 600 °C. The resulting carbon shells had interiors that were knobbly, smooth, porous or honeycomb-like. Such spheres could be used to catalyse chemical reactions, store energy and purify water.

Angew. Chem. Int. Edn (2018)


An interior-design guide for microscopic spaces : Research Highlights | Nature.com

 

[JSCh]

July 20, 2018
World’s fastest man-made spinning object could help study quantum mechanics

Tongcang Li and Jonghoon Ahn have levitated a nanoparticle in vacuum and driven it to rotate at high speed, which they hope will help them study the properties of vacuum and quantum mechanics. (Purdue University photo/Vincent Walter)

WEST LAFAYETTE, Ind. — Researchers have created the fastest man-made rotor in the world, which they believe will help them study quantum mechanics.

At more than 60 billion revolutions per minute, this machine is more than 100,000 times faster than a high-speed dental drill. The findings were published in the journal Physical Review Letters.

“This study has many applications, including material science,” said Tongcang Li, an assistant professor of physics and astronomy, and electrical and computer engineering, at Purdue University. “We can study the extreme conditions different materials can survive in.”

Li’s team synthesized a tiny dumbbell from silica and levitated it in high vacuum using a laser. The laser can work in a straight line or in a circle – when it’s linear, the dumbbell vibrates, and when it’s circular, the dumbbell spins.

A spinning dumbbell functions as a rotor, and a vibrating dumbbell functions like an instrument for measuring tiny forces and torques, known as a torsion balance. These devices were used to discover things like the gravitational constant and density of Earth, but Li hopes that as they become more advanced, they’ll be able to study things like quantum mechanics and the properties of vacuum. Watch a video to see how it happens here.

A nanodumbbell levitated by an optical tweezer in vacuum can vibrate or spin, depending on the polarization of the incoming laser. (Purdue University photo/Tongcang Li) Download image​

“People say that there is nothing in vacuum, but in physics, we know it’s not really empty,” Li said. “There are a lot of virtual particles which may stay for a short time and then disappear. We want to figure out what’s really going on there, and that’s why we want to make the most sensitive torsion balance.”

By observing this tiny dumbbell spin faster than anything before it, Li’s team may also be able to learn things about vacuum friction and gravity. Understanding these mechanisms is an essential goal for the modern generation of physics, Li said.

Researchers from Purdue, Peking University, Tsinghua University, and the Collaborative Innovation Center of Quantum Matter in Beijing also contributed to this work. The first author of this work is Jonghoon Ahn, a graduate student in Li’s research group. Li’s research was funded by the National Science Foundation and Office of Naval Research.

A YouTube video is available at

and other multimedia can be found in a Google Drive folder at https://goo.gl/euj7BE. The video was prepared by Erin Easterling, digital producer for the Purdue College of Engineering, 765-496-3388, easterling@purdue.edu.

Writer: Kayla Zacharias, 765-494-9318, kzachar@purdue.edu
Source: Tongcang Li, 765-496-0072, tcli@purdue.edu​

World’s fastest man-made spinning object could help study quantum mechanics - Purdue University

 

[JSCh]

Flexible micro-batteries developed for smart wearable electronics
CGTN
2018-07-21 10:44 GMT+8

Chinese scientists have developed flexible micro-batteries with high energy density and steady performance under extraordinarily high temperatures, the Chinese Academy of Sciences (CAS) announced Thursday.

A research group at CAS Dalian Institute of Chemical Physics reported the development of a prototype of all-solid-state planar lithium ion micro-batteries (LIMBs).

The rapid boom in smart wearable and integrated electronic devices has stimulated the demand for advanced intelligent energy storage systems with high performance, micro size, mechanical flexibility, and high-temperature stability.

The micro-batteries have long-term stability without capacity loss after 3,300 charge cycles at room temperature and maintain high flexibility without capacity decay under repeated bending.

They also have remarkable high-temperature performance of up to 1,000 charge cycles at 100 degrees Celsius.

Lithium-ion batteries (LIBs) are currently the most popular type of batteries, but have shortcomings due to their large size, bulky volume, and heavy weight. They also suffer from several inherent limitations such as liquid electrolyte leakage, flammability, and unsatisfactory safety and flexibility.

Due to their lightweight and high energy density, LIMBs are currently regarded as a highly competitive candidate for on-chip energy storage.

(Top image: Illustration of CAS's all-solid-state planar lithium ion micro-battery /Photo courtesy of the Chinese Academy of Sciences)
Source(s): Xinhua News Agency

 

[JSCh]

China Focus: Chinese helmet aimed at boosting brain power
Source: Xinhua| 2018-07-24 11:23:20|Editor: Liangyu


SHENZHEN, July 24 (Xinhua) -- Chinese scientists are developing a helmet to enhance brain function through monitoring and regulating brain waves and combining artificial intelligence technology.

Wei Pengfei, of the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences, said his team is developing a brain function enhancement system with the goal of improving the brain's ability to perform complex tasks and regulate abnormal emotions.

The helmet could be applied in the training of special personnel to speed up an increase in memory and skills and to alleviate anxiety caused by tension.

The technology is also expected to help treat children with attention deficit hyperactivity disorder (ADHD) and people suffering depression, Alzheimer's disease, aphasia and Parkinson's disease, said Wei.

Surgically-implanted deep-brain stimulation technology first emerged in the 1960s. At the beginning of this century, scientists developed electroencephalogram feedback technology and brain-computer interface technology.

In recent years, non-invasive stimulation and regulation technology has been able to intervene in and regulate brain activities more quickly, becoming a new focus in the brain research and neuroscience field.

The helmet is based on non-invasive brain stimulation and regulation technology, said Wei. It uses flexible electrode sensors to identify brain waves when the brain is performing different tasks. Electrodes then release weak current pulses that can reach specific areas of the brain, altering brain waves, and regulating the active state of its neurons.

"Since brain tissue is very complex, we need to build a computer model first, and then determine the target area and parameters for stimulation," said Wei.

An artificial intelligence algorithm reads brain activity in real time and calculates stimulation parameters to achieve precise and personalized regulation.

The research team, based at the Institute of Brain Cognition and Brain Disease of SIAT, has a research platform for rodents, nonhuman primates and humans.

"Through animal experiments, we have analyzed specific brain areas related to attention cognition, emotional regulation, anxiety, drug addiction, stress and epilepsy. We hope we can intervene in these areas effectively," Wei said.

The team has also developed tests for cognitive ability.

For example, trial participants wore the helmet for about 15 minutes, and then were required to quickly memorize a string of numbers, English letters or words. The test found the average accuracy rate of their memories improved within two hours.

But the data is still insufficient, said Wei. Large-scale double-blind experiments among people of different ages and groups are needed to accumulate convincing data.

"We have only tested the short-term memory of those wearing the helmet, and we're planning to test their week-long memory," Wei said.

So far, researchers have developed the prototype of the first-generation helmet, which can implement feedback control on the brain waves of the cerebral cortex. The team is developing the second generation of the helmet, aiming to achieve deep-brain non-invasive stimulation.

They also intend to cooperate with hospitals in clinical tests on patients with autism, schizophrenia and children with ADHD.

The research was recently selected as one of 30 winning projects at a contest of innovative future technologies in Shenzhen, south China's Guangdong Province. The contest encouraged young Chinese scientists to conceive groundbreaking technologies and trigger innovation.

The United States, Europe and other countries and regions have launched programs to unravel the secrets of the human brain. The brain research will also help the development of artificial intelligence.

 

[JSCh]

First 10,000-ton-level casting 3D printing smart factory goes into operation in Yinchuan
By Hu Dongmei and Zhang Xiaomin | chinadaily.com.cn | Updated: 2018-07-24 10:43

With an annual output of 20,000 tons of sand molds or 10,000 tons of castings, the world's first 10,000-ton-level casting 3D printing smart factory went into operation in Yinchuan, Northwest China's Ningxia Hui autonomous region.

"It is the first launch of 3D printing casting industrial application," said Liu Yi, deputy general manager of the Kocel State Intelligent Casting Industry Innovation Center.

Workshop of the world's first 10,000-ton-level casting 3D printing smart factory. [Provided to chinadaily.com.cn]

Invested and constructed by Kocel Group Limited, the factory is equipped with 12 sets of self-developed 3D printing devices, as well as mobile robots, truss robots, microwave drying equipment, and stereo warehouses.

The entire workshop requires only seven people per shift, all working in air-conditioned environment. There is no crane, no heavy physical labor, and zero emissions. But the production efficiency is more than five times that of traditional casting of the same scale.

Kocel Group Limited started casting 3D printing industrialization research in 2012.

According to Liu, the company has produced a total of five categories, hundreds of kinds, more than 6,000 tons of 3D printing castings.

For instance, the production of engine cylinder head castings previously used metal molds to make nearly 20 parts (sand molds), and needed high-skilled precision assembly. A senior technician must be trained for six months to do the work.

However, with the new technology of 3D printing, it can be completely printed in one session, and the error has fallen from 1 mm to 0.3 mm. Production efficiency can be raised by about three to five times and yield can be increased by 20 to 30 percent, said Liu.

Workshop of the world's first 10,000-ton-level casting 3D printing smart factory. [Provided to chinadaily.com.cn]

https://twitter.com/x/status/1021643642749050882

 

[Grandy]

It's a 'flying motorbike'! Impressive homemade drone takes off with its Chinese inventor on board

A homemade 'flying motorcycle' has taken to the skies, with its inventor on board.
Zhao Deli, 40, was lifted into the air by eight propellers in Tangxia town, Dongguan city, south China's Guangdong province.
Mr Zhao designed and built the drone himself and - dressed in an all-black protective suit - embarked on the extraordinary flight test on Monday.

Dream comes true: Zhao Deli, 40, took off with his homemade drone in China on Monday

Feeling fantastic: After the flight test, the man said it was like riding a motorbike in the sky

Long way to success: The 40-year-old had put his drone under 1,559 unmanned flight tests

The drone's propellers are affixed to a central frame which is designed to be as lightweight as possible.
The aircraft has a motor installed under the seat, which provides the power for the drone while the rider perches at the top.
Before Monday's flight, the amateur inventor had put the unusual aircraft under unmanned tests for 1,559 times in the space of two years.

With the eight propellers stirring the air and the motor roaring, Mr Zhao's flying vehicle successfully carried him into the air.
After a safe landing onto the ground, the excited Mr Zhao told a reporter from Guangzhou Daily: 'It was like riding a motorbike in the sky.
'My dream has come true after this 1560th flight test.'

'Magical Cloud': The flying bike is a single-seater with eight propellers and a motor to power

Costly: The repairing works are expensive - a pair of propellers costs about 3,000 yuan (£337)

A video on Chinese news site Sohu shows the man leaning forward with his hands on a control panel at the front of his contraption.
Seconds later, all eight propellers start to spin and lift Mr Zhao into the air.
The man-carrying quadcopter levitates in the sky and lands safely on the ground.
He has named the drone 'Jin Dou Yun' or 'Magical Cloud' - a flying cloud ridden by China's very own fictional superhero, Monkey King.

Inspired: Mr Zhao wanted to build a flying motorbike after reading about a hovering surfboard

Off we go: With the eight propellers, the drone successfully carried Mr Zhao into the air

Mr Zhao claimed the flying bike could carry a load of between 110 and 220 pounds (50 and 100 kilograms).
Its maximum takeoff weight of 564 pounds (256 kilograms), top speed of 44 mph (70 km/h) and battery life of 30 minutes make it a market leader, said Mr Zhao.
Mr Zhao was born in a village in south China's Hunan Province. Like most boys, he has always dreamt of flying in the sky one day.
He aced in science subjects at school and enjoyed fixing electrical appliances at home.

Market leader: The aircraft has a top speed of 44 mph and a battery life of 30 minutes

Dedication: Mr Zhao spent two years making his 'dream vehicle' and even sold his house for it

In 2008, Mr Zhao set up a company to sell the drones he invented himself. By then he had invented five drone models, including a petrol drone.
Two years ago, Mr Zhao read about a hovering surfboard in Canada, and that was where he got the inspiration for the 'flying motorbike'.
Despite his enthusiasm, Mr Zhao's road to success was by no means smooth.

He experienced countless failures while trying to make the unmanned aircraft airbourne during the 1,559 flight tests; he even had to sell his house and borrow money from friends in order to fund his project, it is reported.
The inventor was ecstatic after Monday's flight.
He said he hoped to fly across China's Yellow River on the aircraft.
He also planned to modify the 'flying motorbike' before launching it as a commercial product on the market.

Bright future: Mr Zhao hopes to put his man-carrying drone on the production line soon

Ambitious: He also hopes to fly across China's Yellow River while riding his 'Magical Cloud'

Read more:

• 卖房搞无人机失败后 他骑着摩托飞上了天_无人机_环球网
• 牛X！东莞男子自制国内首架“载人飞行摩托”，试飞成功！_搜狐新闻_搜 ...

 

[bobsm]

World First: Chinese Physicists Made a Cold Atomic Clock Work in Space
By Rafi Letzter, Live Science Staff Writer | July 25, 2018 10:24am ET

Telling time precisely is important; it gets you up in the morning and coordinates everything from air travel to the GPS system. And if you do it well enough, you can even use it to navigate outer space.

But telling time is also a major technical challenge. Every clock in the world is inaccurate to some degree. Whatever technology your wristwatch uses to mark the future ticking away into the past, those ticks will be imperfectly measured. Every once in a while, a fraction of a second gets lost. Even atomic clocks — which measure time by observing the ultraprecise oscillations of individual atoms and make up the world's official timekeepers — are imperfect, which is why researchers are always striving to build one that's a bit more accurate than any that have been built before. And now, for the first time, a team of Chinese researchers has figured out how to make one of the most precise atomic-clock technologies currently available work in space.

In a paper published today (July 24) in the journal Nature Communications, a team of researchers from the Shanghai Institute of Optics and Fine Mechanics at the Chinese Academy of Sciences officially announced that they had successfully operated a cold atomic clock for more than 15 months in orbit aboard the now-defunct Chinese space station Tiangong-2. (The accomplishment was originally reported in Science magazine in September 2017, when a version of the paper went live in the preprint journal arXiv before it went through peer review and the formal publication process.) [Wacky Physics: The Coolest Little Particles in Nature]

Cold atomic clocks, which work by laser-cooling atoms to near absolute zero before measuring their oscillations, can be more precise, because at very low temperatures, these "ticks" are more consistent. But actually getting atoms to those temperatures is very difficult on Earth, let alone in the confines of a spacecraft.

Cold atomic clocks measure the vibrations of atoms while they're in free fall so that they aren't interacting with anything else. On Earth, that requires constantly nudging an atom up so that it can be measured while it's falling through the detector.

Researchers have managed to make atoms ultracold in free fall before, the team wrote in the paper. But that meant more or less tossing the experiment into the air and letting it fall.

"These methods provide a microgravity environment ranging from several seconds (drop tower, parabolic flight) to several minutes (sounding rocket)," they wrote in the study.

It's difficult to make such a device function in orbit, the researchers wrote, because it has to be much smaller than its counterparts on Earth, pass the safety tests necessary to launch into space, work in microgravity, shield itself against cosmic radiation — and do all that without any quantum physicists on hand to make adjustments if anything were to go wrong.

But space-bound cold atomic clocks do have some advantages, the researchers wrote. Most important, they can study the atomic oscillations over much longer periods. In microgravity, the atom can stay in place longer, allowing for a longer period of measurement.

As Science reported in 2017, researchers with the European Space Agency (ESA) said Tiangong-2's cold atomic clock was not as precise as it could have been. But ESA's clock — which, in theory, would be more precise — has faced delays and has never actually gone up into space.

https://www.space.com/41277-chinese-cold-atomic-clock-orbit.html

 

[JSCh]

A process that takes advantage of powder’s tendency to cake creates a plastic that can be moulded and dyed. Credit: M. Xie et al./Adv. Funct. Mater.

MATERIALS SCIENCE | 24 JULY 2018
A transformation of powder to plastic is a piece of cake
Powder’s propensity to form lumps is put to good use.

Powdered materials often form solid lumps when exposed to moisture, a process called caking. Now, a powder’s tendency to cake — usually an annoyance to manufacturers — has been exploited to create a sturdy but mouldable plastic film.

Yun Yan at Peking University in Beijing and her colleagues formulated a powder that includes two particular types of molecule, both of which contain water-binding segments as well as sections that repel water. When the powder was exposed to moisture and pressure, its chemical bonds rearranged in a process similar to caking. This allowed the powder to congeal within seconds into a transparent film that is roughly as strong as conventional plastic, but that can be moulded into a variety of shapes at room temperature.

The team also embedded the material with dyes that change colour when exposed to certain chemicals. These versions of the film can act as sensors to detect gases such as ammonia or hydrazine, an explosive chemical widely used in industry.

Adv. Funct. Mater. (2018)
​

A transformation of powder to plastic is a piece of cake : Research Highlights | Nature

 

[JSCh]

Academicians given priority in border clearance 1
2018-07-26 16:39:15Ecns.cnEditor : Mo Hong'e

(ECNS) - The State Immigration Administration has announced that special border clearance channels reserved for diplomats will also be used in service of the country's top scientists.

Academicians of two leading organizations – the Chinese Academy of Sciences (CAS) and Chinese Academy of Engineering (CAE) – and their entourages can use special gates to pass through land ports without leaving their cars, and enjoy priorities to complete customs clearance procedures. The policy will be used for both incumbent and retired academicians.

The State Immigration Administration established this year under the Ministry of Public Security said CAS and CAE as two top institutions in China have made great contributions to the country’s prosperity and people’s happiness, while many academicians can be called national heroes.

The two institutes have a total of 1,650 academicians, many of them traveling abroad for scientific research, lectures and academic exchanges, said the administration.

It said the move aims to support academicians in concentrating on scientific research and academic exchanges, and also reflects respect for their contributions.

 

[JSCh]

Mitochondria in the Neurons Talk to the Intestine via Wnt Signaling
Jul 27, 2018

The metabolic disorders have been reported in a range of neurodegenerative diseases. Mitochondrial dysfunction, in particular, has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, and Huntington's disease. The mechanism by which the nervous system elicits distal mitochondrial proteotoxic stress remains unknown.

Dr. TIAN Ye's team at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences and Prof. Andrew Dillin's team at UC Berkeley, together found that retromer-dependent Wnt signaling can propagate mitochondrial proteotoxic stress (UPRmt) from the nervous system to the intestine.

The findings have been published online on July 26th in Cell entitled "Mitochondrial unfolded protein response is mediated cell-non-autonomously by retromer- Dependent Wnt signaling".

Studies in C. elegans have established that the expression of the HD-causing polyQ40 protein in neurons initiates the UPRmt in the intestine, a process that induces global alteration of transcription networks to maintain a functional mitochondrial proteome.
Researchers found that loss-of-function mutations of retromer complex components responsible for recycling the Wnt secretion-factor/MIG-14 prevent Wnt secretion and thereby suppress cell-non-autonomous mitochondrial proteotoxic stress. Neuronal expression of the Wnt ligand/EGL-20 is sufficient to induce UPRmt in the intestine and extend lifespan in C. elegans.

The study indicates that Wnt signaling propagates the mitochondrial proteotoxic stress and that Wnt pathway components should thus be viewed as therapeutic targets for age-onset neurodegenerative diseases.

This work was supported by the National Key R&D Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, and the National Natural Foundation of China.

Wnt signaling mediates cell-non-autonomous mitochondrial proteostasis stress (Image by ZHANG Qian)



Mitochondria in the Neurons Talk to the Intestine via Wnt Signaling---Chinese Academy of Sciences

 

[JSCh]

Desert bush spider could help develop new drugs and insecticides
27 July 2018

Professor Glenn King​

A toxin from the desert bush spider is helping researchers understand more about human and insect biology, which could lead to new treatments for health conditions and bee-friendly insecticides.

Scientists from The University of Queensland and Princeton University have used the potent insecticidal toxin—Dc1a—to investigate the molecular structure of sodium channels, which play important roles in the nervous system of humans and insects.

Professor Glenn King from UQ’s Institute for Molecular Bioscience (IMB) said to design better drugs and insecticides, you needed to know how to turn sodium channels on and off at the atomic level.

“Humans have nine sodium channels, each with different functions – for example, one type plays a central role in the perception of pain, another is essential to the function of the skeletal muscles we use for movement, and a third channel is used by the nerves that control our heart rhythm,” he said.

“If you design a drug to target one sodium channel to block pain, you have to ensure it won’t hit the others and cause paralysis or heart failure.

“And when designing insecticides, it’s critical that chemicals that disrupt sodium channels in pest insects don’t affect those found in humans or ecologically important insects such as bees.”

Professor King and PhD student Yan Jiang showed that Dc1a toxin binds to the on-off switch of an insect sodium channel, with the UQ and Princeton University researchers able to solve a high-resolution structure of the channel-toxin complex using cryo-electron microscopy.

“I think the most exciting part of this discovery is how Dc1a binds to the voltage sensor region—the on-off-switch of the sodium channel—as these regions are slightly different in each sodium channel,” Professor King said.

“By targeting the voltage sensor as opposed to the pore of the channel, you can potentially make a drug or insecticide that’s very selective.”

Professor King said the discovery provides a foundation for designing ecofriendly insecticides that will kill pest insects but won’t harm bees, humans or pets.

There is also scope for designing drugs that selectively target certain human sodium channels, which could lead to new treatments for conditions such as chronic pain, epilepsy and heart arrhythmia.

The research was published in Science (DOI: 10.1126/science.aau2596) and funded by organisations included the Australian Research Council and National Health and Medical Research Council.



Desert bush spider could help develop new drugs and insecticides - UQ News - The University of Queensland, Australia

Huaizong Shen, Zhangqiang Li, Yan Jiang, Xiaojing Pan, Jianping Wu, Ben Cristofori-Armstrong, Jennifer J. Smith, Yanni K. Y. Chin, Jianlin Lei, Qiang Zhou, Glenn F. King, Nieng Yan. Structural basis for the modulation of voltage-gated sodium channels by animal toxins. Science (2018). DOI: 10.1126/science.aau2596.​

 

[JSCh]

Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis
27 JULY 2018

The Zuo Group at the School of Physical Science and Technology recently developed a photocatalytic methane conversion methodology which can directly transform methane, ethane and other gaseous alkanes into value-added liquid product. This breakthrough in organic chemistry provides a novel, green and mild catalytic platform for natural gas utilization, and could lead to broad applications in the energy/chemical industry. Their result was published as “Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis” in Science on July 27th. Postdoctoral researchers Anhua Hu and Jingjing Guo are co-first authors, graduate student Hui Pan is the second author, and Zuo Zhiwei is the corresponding author.

Methane and other gaseous alkanes have been traditionally viewed more as clean energy fuels than economical chemical feedstocks by the chemical community. With dwindling oil supplies and the growing importance of reducing worldwide dependence on petroleum-based chemical products, the recent discovery of huge volumes of unconventional reservoirs and soaring production of natural gas has made these gaseous hydrocarbons economically attractive and strategically important basic raw materials. The intrinsic inertness of C–H bond in methane and other gaseous alkanes has, however, brought extreme challenges for catalytic systems. These challenges are not only in the activation step, but also in controlling chemoselectivity to avoid solvent functionalization and overfunctionalization under frequently utilized harsh conditions (high temperature, superacids or strong oxidants). Moreover, the gaseous substrates’ low solubility in most solvents has raised substantial practical difficulties. Elegant catalytic systems utilizing transition metals such as Pd, Ir, Rh, Ru have been reported; however, the “grand challenge” remains the development of efficient catalytic systems with inexpensive catalysts and ambient conditions.

The Zuo group has been focused on the development of sustainable catalyst for highly efficient transformations. The unique electron structure of high valence cerium complexes, as well as their unique photophysical properties, attracted their research attention to explore valuable synthetic methodologies utilizing the ligand-to-metal charge transfer (LMCT) excitation process, a common photoexcitation manifold among coordination complexes of transition metal with an empty valence shell which has been under-investigated in synthetic organic transformations via modern photoredox catalysis. In 2016, they first found that CeCl3 could act as photocatalyst in the C-C bond cleavage and amination of cycloalkanols. Then, in 2017, they demonstrated that the LMCT process could be utilized with 1,5-HAT event for the selective distal C-H functionalization of primary alcohols. On the basis of this work, after 2202 trials and optimizations, they have developed a general and highly efficient platform for the catalytic functionalization of methane and other gaseous alkanes under LED irradiation at ambient temperature with abundant and inexpensive cerium salts as photocatalysts. Critically, the use of LMCT catalysis to generate highly reactive alkoxy radicals enables the challenging HAT event from the strong C–H bonds of the light alkanes employed. This photocatalytic platform has enabled a number of direct transformations of methane and other gaseous hydrocarbons, including amination, alkylation, and arylation, and offers intriguing opportunities for further functionalization of feedstock alkanes.

Professor Kuiling Ding, Chinese Academy of Sciences (CAS) academician and dean of Shanghai Institute of Organic Chemistry at CAS, said, “The direct functionalization of C–H bond in methane is one of the basic chemical transformations in energy and chemical processes. The high stability and low polarity of the C–H bond has brought extreme challenges for methane functionalization, therefore harsh conditions such as high temperature and high pressure are often required. The C–H functionalization of methane under mild conditions is considered a “holy grail” in the chemistry community. Through the exquisite design of the photocatalytic system, this work by the Zuo group showcases a new breakthrough in methane conversion at room temperature, and provides a new pathway for the extensive utilization of methane feedstock.”

Professor David MacMillan, one of the pioneers of modern photoredox catalysis, member of the National Academy of Sciences (USA), distinguished professor at Princeton University said, “The results of this study by the Zuo group are simply astonishing. Over the last decade, there have been many new directions arising from photoredox with significant societal impact. This study introduces a new direction (LMCT) wherein alkanes such as methane and ethane can undergo direct amination. The potential for use in sectors such as pharmaceuticals, agrochemical, and fine chemical, among others, are clearly evident. This is a remarkable paper from a young Chinese chemist that will be widely influential on a global scale. I cannot wait to see what he will do next.”

Experts from Shell, senior principal scientist Alexander van der Made and program lead methane to product Sander Van Bavel both spoke highly of the paper, “This paper on photocatalytic functionalization of alkanes showcases excellent and intriguing chemistry on the very relevant topic of alkane activation. Moreover, the paper presents a key first step towards a green route to activate alkanes under mild conditions. Ultimately, this route could lead to more extensive use of abundantly available natural gas as feedstock by chemical industry.”

“ShanghaiTech University has been striving to construct an independent and innovative academic atmosphere with full academic freedom, allowing our PIs to release their energy and creativity to the greatest extent. The breakthrough of the Zuo Group is a positive demonstration. The research group creatively used the unique rare-earth resources of China to solve the key scientific problem of methane activation, which has great importance for China and the world, in a very short period of time.” said Peidong Yang, Founding Dean of School of Physical Science and Technology, member of the National Academy of Sciences (USA) and professor at University of California, Berkeley.

This work was funded by the National Natural Science Foundation of China (21772121) and the “Thousand Plan” Youth Program.

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Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis | ShanghaiTech University

Anhua Hu, Jing-Jing Guo, Hui Pan, Zhiwei Zuo. Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis. Science (2018). DOI: 10.1126/science.aat9750​

 

[JSCh]

China's first stem cell hospital opens in Boao
By Ma Zhiping and Liu Xiaoli in Boao, Hainan | chinadaily.com.cn | Updated: 2018-07-29 14:51

China Stem Cell Group Co Ltd, a Shanghai-based company, announced the opening of its affiliated stem cell hospital in Boao Lecheng International Medical Tourism Pilot Zone in Hainan on Saturday.

The hospital, the only one in the sector in China and equipped with a hundred 100 pre-clean laminar air flow rooms for patients, will be able to handle 1,000 blood stem cell transplantations annually, said Ruan Changgeng, an academician of the Chinese Academy of Engineering and director of the Blood Research Institute of Jiangsu Province, who has been appointed as the honorary head of the hospital, together with another three academicians as chief scientists.

Ruan said the hospital will help effectively reduce the shortage of transplantation resources in the country.

Lu Wei, vice-president of China Stem Cell Group, said the hospital will focus on blood stem cell transplants while also engaging itself in developing a top-level platform for the country's stem cell industry, which will combine disease prevention, medical treatment, research on clinical applications of stem cell technology, education, and rehabilitation.

"So far the company has helped with 3,500 umbilical cord blood transplants, the largest number in the country. About 58.9 percent of the patients who have received the transplants are still alive after five years, which is at an advanced international level for the time being," Lu added.

Hainan Boao Lecheng International Medical Tourism Pilot Zone, the only one of its kind in China, enjoys nine preferential policies granted by the State Council ever since 2013, such as carrying out stem cell clinical applications without central government permission.

"The policies enable the hospital to conduct pilot applications in the sector," said Lu, adding that Hainan's new talent introduction policy is also attracting more medical professionals to come to the island province.

"A total of 27 medical projects have been completed or are under construction in the pilot zone, and another 38 projects have passed medical technology appraisals, and in total the administration office has talked with developers of 101 high-end medical and healthcare projects," He Pengfei, deputy director of the zone's administration office, said Saturday.

He added that eight of them have opened medical services to the public so far.

All projects in the pilot zone are expected to be completed in about five years. By then, the zone is estimated to receive 5 million tourists a year.

 

[JSCh]

NEWS | 01 AUGUST 2018
Entire yeast genome squeezed into one lone chromosome
In a dramatic restructuring, two teams have created versions of baker’s yeast with vastly reduced chromosome counts.

Ewen Callaway

Brewer’s yeast is a single-celled organism that usually has 16 chromosomes.Credit: Thomas Deerinck, NCMIR/Getty

For millions of years, brewer’s yeast and its close relatives have packed their DNA into 16 distinct chromosomes. Now, two teams have used CRISPR gene-editing to stuff all of yeast’s genetic material — save a few non-essential pieces — into just one or two chromosomes. The feat represents the most dramatic restructuring yet of a complex genome and could help scientists understand why organisms split their DNA over chromosomes. And, to the researchers’ surprise, the changes had little effect on most functions of the yeast (Saccharomyces cerevisiae).

“That was the biggest shocker — that you can just get away with this and yeast seem to shrug its shoulders,” says Jef Boeke, a geneticist at New York University whose team jammed the yeast genome onto a pair of chromosomes1. A China-based group used a different technique to make yeast with one ‘super-chromosome’2. Both teams report their findings in Nature on 1 August.

Genetics 101
Yeast belongs to the eukaryotes, the branch of life that includes humans, plants and animals and whose cells store genetic material in a membrane-bound nucleus. But the number of chromosomes that eukaryotes have varies wildly and seems to have no correlation with the amount of genetic information they possess. In humans, genetic material is spread over 46 chromosomes, whereas male jack jumper ants (Myrmecia pilosula) have just 1. Single-celled brewer’s yeast — whose genome, at 12 million DNA letters long, is hundreds of times shorter than that of humans — boasts 16 chromosomes.

“We don’t know why they have such different numbers,” says Zhongjun Qin, a molecular biologist at the Chinese Academy of Sciences’ Shanghai Institute of Plant Physiology and Ecology, whose team created the lone-chromosome yeast strain. “I thought it was probably random.”

Qin and his colleagues reasoned that if an organism’s chromosome count were down to chance rather than an underlying rule of nature, there should be no reason that a yeast cell shouldn’t be viable with 1 chromosome instead of 16. Researchers in the past had fused two3 — even four4 — yeast chromosomes together, and another team split the 16 chromosomes into 33. All products had viable cells5. But no one had ever performed such extreme genetic surgery as Qin and his colleagues set out to do several years ago.

Their initial attempts ended in failure — until they turned to the genome-editing tool CRISPR–Cas9, which is adept at excising specific DNA sequences. Qin and his colleagues used CRISPR to remove DNA at telomeres, the ends of chromosomes that protect them from degrading. They also snipped out centromeres, sequences in the middle that are important to DNA replication.

These changes paved the way for a fit of tidying that would make home-organization guru Marie Kondo proud. The researchers first fused two chromosomes, then joined this product to another one, and in successive rounds, to another and another — until they were left with a lone-chromosome yeast strain (see ‘Minimal yeast’).

Source: Refs 1, 2

Boeke’s team also used CRISPR to remove superfluous telomeres and centromeres to create strains with progressively fewer chromosomes. They ended up with a yeast strain that had two extra-long chromosomes, but they could not get the pair to fuse into one. (Boeke is also leading a separate, international effort to synthesize an entire yeast genome from scratch.)

One explanation for the difference is that Qin’s team also jettisoned 19 repetitive stretches of DNA. These sequences might have interfered with the mechanism that cells use to stitch two chromosomes into one, suggests Qin. Or, Boeke says, it could be down to chance: there are about 10–19 different ways to arrange yeast’s 16 chromosomes into 1, and the Chinese team might simply have hit a winning combination.

Growing pains
Both strains of ‘minimal’ yeast looked normal under a microscope, and the changes to chromosome number had little impact on their gene activity. But while Boeke’s strain underwent normal asexual reproduction and grew as efficiently as 16-chromosome strains, the lone-chromosome yeast divided more slowly.

The only major defect — in both strains — was in sexual reproduction, in which yeast cells with two genome copies produce ‘spores’ that have only one. The Chinese team’s single-chromosome strain grew even more slowly compared with normal yeast when its genome was doubled through mating, and it produced fewer spores.

Boeke and his colleagues observed defects when they tried to coax yeast strains with differing numbers of chromosomes to produce spores. This genetic incompatability could be used to prevent synthetic yeast, released into the environment from mating with wild strains, Boeke says. He also notes that the two-chromosome yeast might qualify as a distinct species because it can’t breed with normal yeast, despite having near-identical DNA.

Scientists tend to focus on the role of DNA-sequence changes in creating new species, but these studies suggest that natural chromosome fusions could also play a part, says Gianni Liti, a geneticist at the University of Cote d’Azur in Nice, France, who reviewed the papers and wrote an accompanying essay6.

William Noble, a computational biologist at the University of Washington in Seattle, says that studying such strains could help to explain why nearly all eukaryotes apportion their DNA into multiple chromosomes. “Why bother?” he says. “If you only needed one, it would be the ‘Occam’s razor’ solution.



Entire yeast genome squeezed into one lone chromosome | Nature.com

Yangyang Shao, Ning Lu, Zhenfang Wu, Chen Cai, Shanshan Wang, Ling-Li Zhang, Fan Zhou, Shijun Xiao, Lin Liu, Xiaofei Zeng, Huajun Zheng, Chen Yang, Zhihu Zhao, Guoping Zhao, Jin-Qiu Zhou, Xiaoli Xue & Zhongjun Qin. Creating a functional single-chromosome yeast. Nature (2018). DOI: https://doi.org/10.1038/s41586-018-0382-x​