(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

Coronary heart disease has a significant age correlation,and cell aging is the basic factor of aging of the body.Aging endothelial cells can interfere with the development of coronary heart disease through oxidative stress,mitochondrial dysfunction and other ways.This article focused on the mechanism of endothelial cell aging promoting coronary heart disease,which is related to"kidney"in TCM.Kidney has physiological characteristics such as participating in the growth and aging,the interaction of essence and blood,water and liquid metabolism,etc.Deficiency of kidney essence can slow down the generation of kidney turbidity,which can also be followed by blood stasis,phlegm and other pathogenic factors eroding arteries,which is consistent with the role of endothelial cell aging in promoting plaque development and accelerating thrombosis.The article also discussed the biological connotation of treating coronary heart disease from kidney from the perspective of endothelial cell aging,and put forward that the basic principle of treating coronary heart disease from kidney should be tonifying kidney and expelling turbidity,and then treat it according to different syndromes such as heart-kidney disharmony,qi stagnation in the heart and chest,phlegm obstruction in collaterals and blood stasis obstruction in collaterals,providing new ideas for the biological research and clinical application of TCM in the treatment of coronary heart disease.

Objective To investigate the characteristics of cognitive inhibition in children with hearing impairment and the impact of different types of materials on their cognitive inhibition.Methods From June,2024 to January,2025,21 children with hearing impairment from Liaocheng Special Education School and 20 typically developing children from Guotun Town Central Primary School in Yanggu County,Liao-cheng were randomly selected.A directed forgetting task was used in a mixed experimental design.The experi-mental procedure was presented using Eprime 3.0,and recall performance was recorded through paper-and-pen-cil tests.Results Three children with hearing impairment and two typically developing children were dropped down.The children with hearing impairment scored significantly lower on recall tasks than the typically developing children(F=13.545,P<0.001).In the typically developing children,recall performance under the memory condition was sig-nificantly lower than under the forgetting condition(P<0.001).In the children with hearing impairment,there was no significant difference in recall performance between the memory condition and the forgetting condition(P>0.05).Regardless of whether the materials were letters or figures,all the children showed significantly high-er recall scores under the forgetting condition compared to the memory condition(P<0.01).Conclusion Children with hearing impairment exhibit weaker cognitive inhibition compared to typically developing chil-dren.The type of materials doesn't impact individuals'cognitive inhibition performance.

OBJECTIVE To establish a extraction process of Changyan Heji Ⅱ(CYHJ-Ⅱ)based on UPLC-Q-TOF-MS/MS technology combined with response surface analysis,and to optimize the extraction process.METHODS The chemical components in CYHJ-Ⅱ were qualitatively analyzed by UPLC-Q-TOF-MS/MS technology,and the chemical components with good linear relation-ship in mass spectrometry response were selected as process investigation indicators;the extraction process parameters(water addition amount,extraction time and soaking time)were investigated by Box-Behnken design;the comprehensive score was obtained by princi-pal component analysis(PCA),and the optimal process was determined by the comprehensive score combined with response surface a-nalysis.RESULTS Through qualitative analysis,110 components were inferred and identified from CYHJ-Ⅱ,including 2 organic acids,82 flavonoids,13 terpenoids,and 13 alkaloids.Based on the results of qualitative analysis,48 index components with good lin-ear relationships were derived by UPLC-Q-TOF-MS/MS combined with Masshunter mass spectrometry data analysis software.PCA was performed and the comprehensive score was calculated.Response surface analysis was performed with the comprehensive score as an indicator.The optimal extraction process obtained by combining the response surface prediction results and actual production was:soaking for 45 min,8 times the amount of solvent,2 extractions,each time for 120 min.CONCLUSION This study provides a new idea for the investigation of the extraction process of traditional Chinese medicine compound prescriptions and expands a new method for the development of traditional Chinese medicine compound prescriptions.

Objective To investigate the characteristics of cognitive inhibition in children with hearing impairment and the impact of different types of materials on their cognitive inhibition.Methods From June,2024 to January,2025,21 children with hearing impairment from Liaocheng Special Education School and 20 typically developing children from Guotun Town Central Primary School in Yanggu County,Liao-cheng were randomly selected.A directed forgetting task was used in a mixed experimental design.The experi-mental procedure was presented using Eprime 3.0,and recall performance was recorded through paper-and-pen-cil tests.Results Three children with hearing impairment and two typically developing children were dropped down.The children with hearing impairment scored significantly lower on recall tasks than the typically developing children(F=13.545,P<0.001).In the typically developing children,recall performance under the memory condition was sig-nificantly lower than under the forgetting condition(P<0.001).In the children with hearing impairment,there was no significant difference in recall performance between the memory condition and the forgetting condition(P>0.05).Regardless of whether the materials were letters or figures,all the children showed significantly high-er recall scores under the forgetting condition compared to the memory condition(P<0.01).Conclusion Children with hearing impairment exhibit weaker cognitive inhibition compared to typically developing chil-dren.The type of materials doesn't impact individuals'cognitive inhibition performance.

OBJECTIVE To establish a extraction process of Changyan Heji Ⅱ(CYHJ-Ⅱ)based on UPLC-Q-TOF-MS/MS technology combined with response surface analysis,and to optimize the extraction process.METHODS The chemical components in CYHJ-Ⅱ were qualitatively analyzed by UPLC-Q-TOF-MS/MS technology,and the chemical components with good linear relation-ship in mass spectrometry response were selected as process investigation indicators;the extraction process parameters(water addition amount,extraction time and soaking time)were investigated by Box-Behnken design;the comprehensive score was obtained by princi-pal component analysis(PCA),and the optimal process was determined by the comprehensive score combined with response surface a-nalysis.RESULTS Through qualitative analysis,110 components were inferred and identified from CYHJ-Ⅱ,including 2 organic acids,82 flavonoids,13 terpenoids,and 13 alkaloids.Based on the results of qualitative analysis,48 index components with good lin-ear relationships were derived by UPLC-Q-TOF-MS/MS combined with Masshunter mass spectrometry data analysis software.PCA was performed and the comprehensive score was calculated.Response surface analysis was performed with the comprehensive score as an indicator.The optimal extraction process obtained by combining the response surface prediction results and actual production was:soaking for 45 min,8 times the amount of solvent,2 extractions,each time for 120 min.CONCLUSION This study provides a new idea for the investigation of the extraction process of traditional Chinese medicine compound prescriptions and expands a new method for the development of traditional Chinese medicine compound prescriptions.

Coronary heart disease has a significant age correlation,and cell aging is the basic factor of aging of the body.Aging endothelial cells can interfere with the development of coronary heart disease through oxidative stress,mitochondrial dysfunction and other ways.This article focused on the mechanism of endothelial cell aging promoting coronary heart disease,which is related to"kidney"in TCM.Kidney has physiological characteristics such as participating in the growth and aging,the interaction of essence and blood,water and liquid metabolism,etc.Deficiency of kidney essence can slow down the generation of kidney turbidity,which can also be followed by blood stasis,phlegm and other pathogenic factors eroding arteries,which is consistent with the role of endothelial cell aging in promoting plaque development and accelerating thrombosis.The article also discussed the biological connotation of treating coronary heart disease from kidney from the perspective of endothelial cell aging,and put forward that the basic principle of treating coronary heart disease from kidney should be tonifying kidney and expelling turbidity,and then treat it according to different syndromes such as heart-kidney disharmony,qi stagnation in the heart and chest,phlegm obstruction in collaterals and blood stasis obstruction in collaterals,providing new ideas for the biological research and clinical application of TCM in the treatment of coronary heart disease.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.