First shipment of Australian coal to China at dock in two years

(Bloomberg) – Australia’s first coal shipment to China in more than two years is about to dock, providing clear evidence of a clear thaw in trade relations between the two countries after months of diplomatic talks.

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The bulk carrier Magic Eclipse dropped anchor off the southern port city of Zhanjiang on Thursday morning, according to Bloomberg maritime data. It transports metallurgical coal mined in Australia to the Chinese market. Zhanjiang is a center of steel production in China.

The Australian government welcomes “any action taken to remove barriers to trade,” Trade Secretary Don Farrell said in a statement on Thursday.

China imposed informal restrictions on the use of Australian coal in 2020 after then-Prime Minister Scott Morrison called for an international inquiry into the origins of Covid-19 in Wuhan earlier this year.

Trade sanctions ordered by Beijing also extended to lucrative agricultural exports such as wine, barley and lobster. China is Australia’s largest trading partner.

However, diplomatic relations between Canberra and Beijing have steadily improved following the election of a centre-left Labor government in May. Commerce Minister Wang Wentao met with his counterpart Farrell on Monday for the first bilateral trade talks in more than two years.

The two ministers agreed to “intensify the dialogue” to ensure “the rapid and full resumption of trade”.

A second shipment of coal from Australia is expected to dock in China later this month, cementing renewed trade ties.

(Updates with Commerce Secretary’s statement in third paragraph.)

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Plant found only in the Australian rainforest yields breakthrough cancer drug

[Feb. 4, 2023: Taylor Kubota, Stanford University]

The compound is found naturally in the seeds of the pink fruit of the blushwood tree, Fontainea picrosperma. (PHOTO CREDIT: Creative Commons)

Stanford University researchers have discovered a fast and sustainable way to synthesize a promising cancer-fighting compound in the lab. The compound’s availability was limited because its only currently known natural source is a single plant species that grows exclusively in a small region of rainforest in northeastern Australia.

Dubbed EBC-46 and technically called tigilanol tiglate, the compound works by promoting a localized immune response against tumors. The reaction ruptures the tumor’s blood vessels, eventually killing its cancer cells. EBC-46 recently entered human clinical trials after showing an extremely high success rate in treating a type of cancer in dogs.

However, due to its complex structure, EBC-46 did not appear to be synthetically accessible, meaning that no plausible route to practical laboratory manufacture appeared to exist. However, through an ingenious process, Stanford researchers have demonstrated for the first time how to chemically convert abundant plant source material into EBC-46.

As a bonus, this process can produce “analogues” of EBC-46 – compounds that are chemically similar but may prove even more effective and could potentially treat a surprisingly wide range of other serious diseases. These diseases, which include AIDS, multiple sclerosis and Alzheimer’s disease, all share biological pathways that are influenced by the target of EBC-46, a key enzyme called protein kinase C, or PKC.

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“We are very pleased to announce the first scalable synthesis of EBC-46,” said Paul Wender, Francis W. Bergstrom Professor in the School of Human Sciences, Professor of Chemistry and courtesy of Chemical and Systems Biology at Stanford, and corresponding author. of a study describing the findings in the journal Nature Chemistry. “The ability to produce EBC-46 in the lab really opens up tremendous research and clinical opportunities.”

The study’s co-authors are Zachary Gentry, David Fanelli, Owen McAteer and Edward Njoo, all graduate students in Wender’s lab, as well as former member Quang Luu-Nguyen.

Wender conveyed the research team’s immense satisfaction with the breakthrough in the synthesis of EBC-46. “If you had visited the lab in the first weeks after their success,” Wender said, “you would have seen my exceptional colleagues smiling from ear to ear. They managed to do what many people thought was impossible.

Doctoral students Edward Njoo, David Fanelli, Zach Gentry and Owen McAteer. These researchers succeeded in synthesizing the anti-cancer compound EBC-46. (Image credit: Paul Wender)

From a distant region

Tigilanol tiglate originally appeared in an automated drug candidate screening process by Australian company QBiotics. The compound is found naturally in the seeds of the pink fruit of the blushwood tree, Fontainea picrosperma. Marsupials like musk-kangaroos that eat blushwood fruits avoid the seeds rich in tigilanol tiglate, which ingesting them causes vomiting and diarrhea.

Injection of much lower doses of EBC-46 directly into some solid tumors alters cell signaling by PKC. Specifically, EBC-46 is thought to activate certain forms of PKC, which in turn affect the activity of various proteins in cancer cells and trigger an immune response from the host body.

Paul Wender, Professor Francis W. Bergstrom at the Faculty of Humanities, Professor of Chemistry. (Image credit: Paul Wender)

The resulting inflammation leaks the vasculature or blood vessels of the tumor, and this bleeding causes the tumor growth to die. In external cutaneous malignancies, the tumors crust over and fall off, and ways to deliver EBC-46 to internal tumors are being explored.

In 2020, the European Medicines Agency and the United States Food and Drug Administration approved a drug based on EBC-46 sold under the brand name Stelfonta for the treatment of mast cell cancer, the most common skin tumor. common in dogs.

One study showed a 75% cure rate after a single injection and an 88% cure rate after a second dose. Clinical trials have since begun for skin, head and neck, and soft tissue cancers in humans.

Based on these emerging research and clinical needs, coupled with the geographical limitations of parental seeds, scientists considered establishing dedicated plantations of blushwood trees. But this poses a multitude of problems.

For starters, trees need to be pollinated, which means having the right kind of pollinating animals available, as well as planting trees at the correct density and spacing to support pollination. In addition, seasonal and climatic fluctuations as well as pathogens affect the trees. The abandonment of plots for blushwood trees poses other land use problems.

“For sustainable and reliable production of EBC-46 in the quantities we need,” Wender said, “we really need to go the synthetic route.”

Make EBC-46 from scratch

A good starting point for making EBC-46, Wender and his colleagues recognized, is the plant-derived compound phorbol. Over 7,000 plant species worldwide produce phorbol derivatives, and phorbol-rich seeds are commercially inexpensive. The researchers chose Croton tiglium, commonly known as purifying croton, an herb used in traditional Chinese medicine.

The first step in the preparation of EBC-46, explains Wender, is based on daily experience. “You buy a bag of these seeds, and it’s no different from making coffee in the morning,” Wender said. “They grind the seeds and run a hot solvent through them to extract the active ingredient,” in this case a phorbol-rich oil.

After turning the oil into phorbol, the researchers had to find a way to overcome the previously insurmountable challenge of capping a part of the molecule, called the B ring, with carefully placed oxygen atoms. This is necessary for EBC-46 to interact with PKC and alter the activity of the enzyme in cells.

To guide their chemical and biological studies, the researchers relied on instruments from the Stanford Neuroscience Microscopy Service, the Stanford Cancer Institute Proteomics/Mass Spectrometry Shared Resource, and the Stanford Sherlock Cluster for computational modeling.

Using these tips, the team succeeded in adding additional oxygen atoms to the B ring of phorbol, initially via what is called an ene (pronounced “een”) reaction, which is carried out under conditions of flow, the reactants mixing as they pass through the tubes together running. The team then introduced additional cyclic B groups in a gradual and controlled manner to achieve the desired spatial arrangement of the atoms. In all, only four to six steps were required to obtain EBC-46 analogs and a dozen steps to achieve EBC-46 itself.

Tigilanol tiglate is a natural diterpenoid in clinical trials for the treatment of a wide range of cancers. (CREDIT: Stanford University)

Wender hopes that the much wider availability of EBC-46 and its PKC-affecting cousin compounds made possible by this breakthrough approach will accelerate the search for potentially breakthrough new treatments.

“As we learn more about how cells work, we learn more about how we can control that functionality,” Wender said. “This control of functionality is particularly important when dealing with cells that go rogue in diseases ranging from cancer to Alzheimer’s disease.”

Wender is also a Fellow of Stanford Bio-X and the Stanford Cancer Institute and a member of Sarafan ChEM-H.

For more scientific news, visit our New Innovations section on The lighter side of the news.

Note: The documents provided above are from Stanford University. Content may be edited for style and length.

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Shark bites a minor who was fishing in the Australian sea; capture video

Tiktok user Huntermaster captured on video the moment a minor was bitten by a shark while he was fishing in the sea Australia.

Is about an eight year old Australian boy, who shares fishing and diving videos on his account.

In the video you can see how the minor tries to get into a boat while carrying a fish in his hand; subsequently, he is bitten by a shark on his left side.

“Only felt like a small bite that it was felt only a little in the chest”, commented the infant in an interview with CNN.

Tiktok users comment that the shark was not trying to bite the boy, but went after the fish that the boy had in his hand.

The video has more than 16 million views and more than 11,000 comments.