(+)-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.

Objective To investigate the impact of various health education intervention strategies on the proper use of personal respiratory protective equipment (RPE) among workers exposed to dust. Methods Dust-exposed workers were recruited from 60 selected enterprises in Guangdong Province using cluster random sampling method. They were randomly allocated to the control, low-intensity intervention, and high-intensity intervention groups, with 358, 346, and 371 workers in each group, respectively. Workers in the control group received no designed intervention. Workers in the low-intensity intervention group received traditional plus mobile health education on the proper use of RPE. Workers in the high-intensity intervention group received all components of the low-intensity intervention, supplemented with peer education. The intervention lasted for six months. RPE usage was compared among the three groups of workers before and after the intervention. Results Workers in the control, low-intensity intervention, and high-intensity intervention groups showed higher rates of both RPE wearing and correct RPE wearing after the intervention than before it within their respective groups (RPE wearing rate: 94.1% vs 99.2%, 95.7% vs 100.0%, 94.6% vs 100.0%, all P<0.01; correct RPE wearing rate: 66.8% vs 91.1%, 67.3% vs 95.7%, 66.6% vs 96.5%, all P<0.01). Post-intervention correct RPE wearing rates were highest in the high-intensity intervention group, followed by the low-intensity intervention group, and the control group, with the percentage of 96.50%, 95.66% and 91.06%, respectively (P<0.01). Binary logistic regression analysis result showed that different intervention strategies affected the correct use of personal RPE among dust-exposed workers after adjusting for gender, age, and other confounding factors (P<0.05). Compared with the control group, the rates of correct RPE use increased in the low-intensity intervention group and the high-intensity intervention group (odd ratio was 2.14 and 3.01; 95% confidence interval was 1.12 - 4.10 and 1.53 - 5.91, respectively). Conclusion The implementation of traditional plus mobile health education interventions on the proper use of RPE can promote correct RPE utilization among dust-exposed workers, and integrating peer education further enhances the intervention effectiveness.

Cytidine/uridine monophosphate kinase 2(CMPK2)is an interferon-stimulated gene that plays an important role against viral infections.CMPK2 is also a rate-limiting enzyme in mitochon-dria that maintains intracellular levels of UTP/CTP and can affect inflammation triggered by path-ogenic infections and other causes of alterations in mitochondria.In this article,we review the structure and distribution of CMPK2,its role in responding to pathogenic infections and the regu-lation of inflammation,and the associated signaling pathways.

Objective:To compare the relative proportion of direct action (ray particles directly destroy biological molecules such as DNA and indirect action (radical-mediated oxidative damage) in the damage caused by X-ray and proton irradiation of lung cancer cells.Methods:Unirradiated human lung adenocarcinoma A549 cells and human large cell lung cancer NCI-H460 cells were cultured in media containing 0, 0.125, 0.25, 0.5, 0.75 mol/L dimethyl sulfoxide (DMSO) for 1 h to obtain plating efficiency (PE) values, thereby determining whether DMSO affected cell survival. Following pretreatment with each DMSO concentration, cells were exposed to X-ray irradiation at physical doses of 2, 4, 6, 8 Gy and proton irradiation at equivalent doses of 2, 4, 6, 8 GyE, respectively. Survival fractions (SF) and maximum protection (MP) values were calculated to evaluate the effects of varying DMSO concentrations on post-irradiation cell survival and to quantify the contribution of indirect radiation damage mechanisms (higher MP indicates greater indirect effect contribution). PE, SF, and MP values were determined using clonogenic assays. Comparisons among multiple groups were performed using one-way ANOVA followed by Tukey's multiple comparison, and comparisons between irradiation groups were analyzed using independent samples t-tests. Results:The PE of unirradiated cells treated with varying DMSO concentrations showed no statistically significant differences. Following pretreatment at different DMSO concentrations and subsequent irradiation with X-rays or protons, the protective effect of DMSO reached saturation at 0.5 mol/L. At this concentration, comparison of the average MP values across 4 radiation doses revealed: In A549 cells, the MP value was 54.21%±1.73% for X-ray irradiation group and 39.69%±0.72% for proton irradiation group ( t=16.82, P<0.001); in NCI-H460 cells, the MP value was 52.04%±1.00% for X-ray irradiation group and 41.31%±0.70% for proton irradiation group ( t=10.19, P<0.001). Conclusions:Under biologically equivalent doses, proton irradiation demonstrates greater reliance on direct effects in lung cancer cells killing compared with X-ray irradiation.

Purpose To analyse the expression of aldo-keto reductase AKR1C3 in the tumour tissues of oral squa-mous carcinoma(OSCC)and the correlation of clinical prognosis of patients.Methods Immunohistochemical(IHC)staining was performed to analyze the expression characteristics of AKR1C3 in 86 cases of OSCC tumor tissues and paired paratumor normal tissue.The correlation between AKR1C3 expression and clinical prognosis was evaluated.Ka-plan-Meier survival analysis was conducted to assess the survival outcomes of OSCC patients.Univariate and multivari-ate Cox regression analyses were employed to identify prognostic factors.The findings were further validated by compar-ison with the Cancer Genome Atlas(TCGA)database.Results The expression of AKR1C3 was significantly higher in OSCC tumor tissues than in paratumor normal tissue,with higher expression observed at the invasive front relative to the tumor centers.Immunohistochemical analysis revealed high expression in both tumor cells and tumor-associated fibro-blasts,while no expression was detected in tumor-infiltrating immunocytes.The x2 test was used to compare the rela-tionship between different expression levels of AKR1C3 and clinicopathological features in OSCC,the results showed that high expression of AKR1C3 was strongly associated with higher tumour stage(P=0.001),lymph node metastasis(P=0.023),differentiation(P=0.018),worst pattern of invasion(P=0.024)and depth of invasion(P=0.012).Kaplan-Meier survival curve analysis showed high expression of AKR1C3 was associated with overall survival(P=0.004),disease-free survival(P=0.019),and metastasis-free survival(P=0.05)in OSCC patients.Cox re-gression model was performed for prognostic analysis.Univariate analysis showed that high expression of AKR1C3 in tumour cells was a high-risk factor for patients' tumour stage(P＜0.001),lymph node metastasis(P＜0.001),dif-ferentiation(P＜0.001),worst pattern of invasion(P＜0.001),depth of invasion(P＜0.001).Multivariate analy-sis further showed that high expression of AKR1C3 in tumour cells was an independent prognostic factor in OSCC pa-tients(P=0.025).Conclusion The AKR1C3 expression is closely related to the prognosis of OSCC patients,and patients with high AKR1C3 expression have a poor prognosis,suggesting that AKR1C3 plays an important role in the occurrence and development of OSCC.

Purpose To analyse the expression of aldo-keto reductase AKR1C3 in the tumour tissues of oral squa-mous carcinoma(OSCC)and the correlation of clinical prognosis of patients.Methods Immunohistochemical(IHC)staining was performed to analyze the expression characteristics of AKR1C3 in 86 cases of OSCC tumor tissues and paired paratumor normal tissue.The correlation between AKR1C3 expression and clinical prognosis was evaluated.Ka-plan-Meier survival analysis was conducted to assess the survival outcomes of OSCC patients.Univariate and multivari-ate Cox regression analyses were employed to identify prognostic factors.The findings were further validated by compar-ison with the Cancer Genome Atlas(TCGA)database.Results The expression of AKR1C3 was significantly higher in OSCC tumor tissues than in paratumor normal tissue,with higher expression observed at the invasive front relative to the tumor centers.Immunohistochemical analysis revealed high expression in both tumor cells and tumor-associated fibro-blasts,while no expression was detected in tumor-infiltrating immunocytes.The x2 test was used to compare the rela-tionship between different expression levels of AKR1C3 and clinicopathological features in OSCC,the results showed that high expression of AKR1C3 was strongly associated with higher tumour stage(P=0.001),lymph node metastasis(P=0.023),differentiation(P=0.018),worst pattern of invasion(P=0.024)and depth of invasion(P=0.012).Kaplan-Meier survival curve analysis showed high expression of AKR1C3 was associated with overall survival(P=0.004),disease-free survival(P=0.019),and metastasis-free survival(P=0.05)in OSCC patients.Cox re-gression model was performed for prognostic analysis.Univariate analysis showed that high expression of AKR1C3 in tumour cells was a high-risk factor for patients' tumour stage(P＜0.001),lymph node metastasis(P＜0.001),dif-ferentiation(P＜0.001),worst pattern of invasion(P＜0.001),depth of invasion(P＜0.001).Multivariate analy-sis further showed that high expression of AKR1C3 in tumour cells was an independent prognostic factor in OSCC pa-tients(P=0.025).Conclusion The AKR1C3 expression is closely related to the prognosis of OSCC patients,and patients with high AKR1C3 expression have a poor prognosis,suggesting that AKR1C3 plays an important role in the occurrence and development of OSCC.

Cytidine/uridine monophosphate kinase 2(CMPK2)is an interferon-stimulated gene that plays an important role against viral infections.CMPK2 is also a rate-limiting enzyme in mitochon-dria that maintains intracellular levels of UTP/CTP and can affect inflammation triggered by path-ogenic infections and other causes of alterations in mitochondria.In this article,we review the structure and distribution of CMPK2,its role in responding to pathogenic infections and the regu-lation of inflammation,and the associated signaling pathways.

Objective:To compare the relative proportion of direct action (ray particles directly destroy biological molecules such as DNA and indirect action (radical-mediated oxidative damage) in the damage caused by X-ray and proton irradiation of lung cancer cells.Methods:Unirradiated human lung adenocarcinoma A549 cells and human large cell lung cancer NCI-H460 cells were cultured in media containing 0, 0.125, 0.25, 0.5, 0.75 mol/L dimethyl sulfoxide (DMSO) for 1 h to obtain plating efficiency (PE) values, thereby determining whether DMSO affected cell survival. Following pretreatment with each DMSO concentration, cells were exposed to X-ray irradiation at physical doses of 2, 4, 6, 8 Gy and proton irradiation at equivalent doses of 2, 4, 6, 8 GyE, respectively. Survival fractions (SF) and maximum protection (MP) values were calculated to evaluate the effects of varying DMSO concentrations on post-irradiation cell survival and to quantify the contribution of indirect radiation damage mechanisms (higher MP indicates greater indirect effect contribution). PE, SF, and MP values were determined using clonogenic assays. Comparisons among multiple groups were performed using one-way ANOVA followed by Tukey's multiple comparison, and comparisons between irradiation groups were analyzed using independent samples t-tests. Results:The PE of unirradiated cells treated with varying DMSO concentrations showed no statistically significant differences. Following pretreatment at different DMSO concentrations and subsequent irradiation with X-rays or protons, the protective effect of DMSO reached saturation at 0.5 mol/L. At this concentration, comparison of the average MP values across 4 radiation doses revealed: In A549 cells, the MP value was 54.21%±1.73% for X-ray irradiation group and 39.69%±0.72% for proton irradiation group ( t=16.82, P<0.001); in NCI-H460 cells, the MP value was 52.04%±1.00% for X-ray irradiation group and 41.31%±0.70% for proton irradiation group ( t=10.19, P<0.001). Conclusions:Under biologically equivalent doses, proton irradiation demonstrates greater reliance on direct effects in lung cancer cells killing compared with X-ray irradiation.

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.

Bipolar disorder （BD） is a serious chronic emotional disorder with a high suicide rate and a common psychiatric disease. Traditional Chinese medicine （TCM） treatment based on syndrome differentiation of BD has unique advantages and good safety， which is expected to become a breakthrough in the treatment. Based on Expert Consensus on TCM Syndrome Differentiation Criteria for Bipolar Disorder by Professor Yin Dongqing and Professor Jia Hongxiao， this study collated the treatment protocols of BD with various syndrome types according to Meta-analysis of the existing literature in the database and evaluated the evidence level according to the evidence evaluation standard issued by the US Agency for Healthcare Research and Quality （AHRQ）. （1） Depression attack. ① Liver depression and spleen deficiency syndrome： Xiaoyaosan pills or Shugan Jieyu capsules， ② Phlegm dampness and spleen stagnation syndrome： Wendantang modified with Tianwang Buxindan， ③ Heart and spleen deficiency syndrome： Jiuwei Zhenxin Granules or DANG's Ganmai Dazhaotang， ④ Fire heat and internal depression syndrome： Danzhi Xiaoyaosan Granules or Chaihu Longgu Mulitang， ⑤ Liver and kidney deficiency syndrome： JIANG's Buganshen Decoction. （2） Mania episode. ① Heart and liver fire hyperactivity syndrome： Zhengan Ningshen Formula， ② Phlegm heat harassing spirit syndrome： Huatan Xiehuo Dingshen decoction， Lianzhi Tongqiao Anshen decoction， Qingshen Dingkuang decoction or Qingshen Xingnao decoction， ③ Liver and gallbladder dampness-heat syndrome： Longdan Xiegantang. （3） Other syndrome types. ① Liver qi stagnation syndrome： modified Tongqiao Huoxue decoction， Shengyang Yiwei Acupuncture， ② Deficiency of kidney yang syndrome： Jingui Shenqitang， ③ Phlegm accumulation and blood stasis syndrome： modified Tongqiao Huoxue decoction， ④ Qi and Yin deficiency， stagnation of blood stasis syndrome： Xinnaoxin pills， ⑤ Syndrome of blood deficiency generating wind and fire heat harassing spirit： Fangji Dihuangtang.