Objective:To investigate the causal effects of plasma lipidomics on pancreatitis using Mendelian ran-domization(MR)and evaluate the roles of intra-pancreatic fat deposition(IPFD)and gallstone disease in this relation-ship.Methods:A bidirectional MR analysis was conducted,with 179 plasma lipids as exposures and acute pancreati-tis(AP)and chronic pancreatitis(CP)as outcomes.Data were sourced from genome-wide association studies(GWAS),the UK Biobank,and the FinnGen project.Two-step Mendelian randomization(TSMR)and multivariable Mendelian ran-domization(MVMR)analyses were applied to assess the mediating roles of IPFD and gallstone disease in the associa-tion between plasma lipids and pancreatitis.Results:MR analysis identified two sterols negatively associated with AP(P＜0.05)and seven sterols negatively associated with CP(P＜0.05).One phospholipid showed a positive association with CP(P＜0.05).IPFD was positively associated with both AP and CP.Gallstone disease was confirmed as a risk fac-tor for AP.However,TSMR analysis indicated that neither IPFD nor gallstone disease mediated the relationship be-tween plasma lipids and pancreatitis.Conclusion:The causal relationship exists among plasma lipomics and AP/CP,also between IPFD,cholelithiasis and pancreatitis.These findings highlight novel risk factors and potential biomarkers to support early diagnosis and intervention for pancreatitis.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

BACKGROUND: Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style. METHODS: We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases. RESULTS: The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals. CONCLUSIONS The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans ; Colonoscopy/methods* ; Deep Learning ; Decision Support Systems, Clinical ; Female ; Male

Objective:To investigate the causal effects of plasma lipidomics on pancreatitis using Mendelian ran-domization(MR)and evaluate the roles of intra-pancreatic fat deposition(IPFD)and gallstone disease in this relation-ship.Methods:A bidirectional MR analysis was conducted,with 179 plasma lipids as exposures and acute pancreati-tis(AP)and chronic pancreatitis(CP)as outcomes.Data were sourced from genome-wide association studies(GWAS),the UK Biobank,and the FinnGen project.Two-step Mendelian randomization(TSMR)and multivariable Mendelian ran-domization(MVMR)analyses were applied to assess the mediating roles of IPFD and gallstone disease in the associa-tion between plasma lipids and pancreatitis.Results:MR analysis identified two sterols negatively associated with AP(P＜0.05)and seven sterols negatively associated with CP(P＜0.05).One phospholipid showed a positive association with CP(P＜0.05).IPFD was positively associated with both AP and CP.Gallstone disease was confirmed as a risk fac-tor for AP.However,TSMR analysis indicated that neither IPFD nor gallstone disease mediated the relationship be-tween plasma lipids and pancreatitis.Conclusion:The causal relationship exists among plasma lipomics and AP/CP,also between IPFD,cholelithiasis and pancreatitis.These findings highlight novel risk factors and potential biomarkers to support early diagnosis and intervention for pancreatitis.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

The inheritance, innovation, and development of traditional Chinese medicine(TCM) need to be based on Chinese medicinal materials. The TCM seed industry is the source of TCM production, which is related to the stable supply and quality safety of TCM. This paper summarizes the basic situation of the TCM seed industry and introduces relevant policies and regulations to TCM seeds in the seed industry and the TCM field. At present, the Management Measures of TCM Seeds and Seedlings has not yet promulgated, and TCM seeds are classified as non-major crops in the category of crops for management. This paper also describes the current situation of TCM seed and seedling system construction, which is in the development stage, from six aspects, including the construction of TCM seed industry technical support system; the establishment of TCM seed standard; the construction of germplasm resource preservation system; TCM seed testing, variety registration, and variety protection; production and management of TCM seeds; TCM seed supervision. According to the development status of the TCM seed industry, four problems are put forward, including imperfect systems and standards relevant to TCM seeds, insufficient supervision and law enforcement regarding TCM seeds, insufficient policy measures and capital investment to promote the development of the industry, and the industry's falling into a low-level cycle.Accordingly, four suggestions are provided, including improving laws, regulations, and policies, perfecting standards and norms,strengthening supervision and law enforcement, and promoting support system construction, in order to boost the high-quality development of the TCM seed industry.
Seeds/chemistry* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/standards* ; Plants, Medicinal/chemistry*

The present study delves into the cellular mechanisms underlying the antiviral effects of dehydrodiisoeugenol(DEH) by focusing on the transcription factor EB(TFEB)/autophagy-lysosome pathway. The cell counting kit-8(CCK-8) was utilized to assess the impact of DEH on the viability of human non-small cell lung cancer cells(A549). The inhibitory effect of DEH on the replication of influenza A virus(H1N1) was determined by real-time quantitative polymerase chain reaction(RT-qPCR). Western blot was employed to evaluate the influence of DEH on the expression level of the H1N1 virus nucleoprotein(NP). The effect of DEH on the fluorescence intensity of NP was examined by the immunofluorescence assay. A mouse model of H1N1 virus infection was established via nasal inhalation to evaluate the therapeutic efficacy of 30 mg·kg~(-1) DEH on H1N1 virus infection. RNA sequencing(RNA-seq) was performed for the transcriptional profiling of mouse embryonic fibroblasts(MEFs) in response to DEH. The fluorescent protein-tagged microtubule-associated protein 1 light chain 3(LC3) was used to assess the autophagy induced by DEH. Western blot was employed to determine the effect of DEH on the autophagy flux of LC3Ⅱ/LC3Ⅰ under viral infection conditions. Lastly, the role of TFEB expression in the inhibition of DEH against H1N1 infection was evaluated in immortalized bone marrow-derived macrophage(iBMDM), both wild-type and TFEB knockout. The results revealed that the half-maximal inhibitory concentration(IC_(50)) of DEH for A549 cells was(87.17±0.247)μmol·L~(-1), and DEH inhibited H1N1 virus replication in a dose-dependent manner in vitro. Compared with the H1N1 virus-infected mouse model, the treatment with DEH significantly improved the body weights and survival time of mice. DEH induced LC3 aggregation, and the absence of TFEB expression in iBMDM markedly limited the ability of DEH to counteract H1N1 virus replication. In conclusion, DEH exerts its inhibitory activity against H1N1 infection by activating the TFEB/autophagy-lysosome pathway.
Influenza A Virus, H1N1 Subtype/genetics* ; Animals ; Autophagy/drug effects* ; Humans ; Mice ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Influenza, Human/metabolism* ; Lysosomes/metabolism* ; Orthomyxoviridae Infections/genetics* ; Eugenol/pharmacology* ; Antiviral Agents/pharmacology* ; Virus Replication/drug effects* ; A549 Cells ; Male

An efficient analytical method was developed for simultaneous detection of alkylamines and alkylamides in food packaging plastics using liquid chromatography-high resolution mass spectrometry(LC-HRMS).Based on the physicochemical properties of alkylamines and alkylamides,as well as the complexity of plastic samples,sample pretreatment and chromatographic-mass spectrometric parameters were optimized.The samples were extracted by vortex-ultrasonic extraction with a methanol-acetonitrile mixture for 15 min,followed by nitrogen evaporation to concentrate the extract,reconstitution,and analysis.The chromatographic mobile phase consisted of 0.1%formic acid aqueous solution and acetonitrile,and a gradient elution was used.The electrospray ionization(ESI)source was operated in positive ion mode,and mass spectrometry data were collected in full scan and data-dependent acquisition modes.Quantification was performed using an isotope-labeled internal standard method.The results showed that within the quantification range of 1-1000 ng/mL,the calibration curves exhibited good linearity(R2>0.99).Some compounds interfered with the validation experiments at higher concentrations,so only 10 kinds of target analytes were validated.Using a mixed food packaging plastic matrix,the recoveries at spiking levels of 40,400,and 4000 ng/g were mostly between 66.0%and 117.1%,with relative standard deviations ranging from 0.6%to 10.6%.The method was applied to detect 14 food packaging plastic samples,and the results showed that the concentrations of alkylamines and alkylamides ranged from not detected to 8924 ng/g.This method offered high sensitivity and accuracy,and was suitable for the screening and quantitative determination of alkylamines and alkylamides in plastics.

OBJECTIVE: We aimed to explore the association between obesity and depression and the role of systemic inflammation in older adults. METHODS: Adults ≥ 65 years old ( n = 1,973) were interviewed at baseline in 2018 and 1,459 were followed up in 2021. General and abdominal obesity were assessed, and serum C-reactive protein (CRP) levels were measured at baseline. Depression status was assessed at baseline and at follow-up. Logistic regression was used to analyze the relationship between obesity and the incidence of depression and worsening of depressive symptoms, as well as the relationship between obesity and CRP levels. The associations of CRP levels with the geriatric depression scale, as well as with its three dimensions, were investigated using multiple linear regressions. RESULTS: General obesity was associated with worsening depression symptoms and incident depression, with an odds ratio ( OR) [95% confidence interval ( CI)] of 1.53 (1.13-2.12) and 1.80 (1.23-2.63), especially among old male subjects, with OR (95% CI) of 2.12 (1.25-3.58) and 2.24 (1.22-4.11), respectively; however, no significant relationship was observed between abdominal obesity and depression. In addition, general obesity was associated with high levels of CRP, with OR (95% CI) of 2.58 (1.75-3.81), especially in subjects free of depression at baseline, with OR (95% CI) of 3.15 (1.97-5.04), and CRP levels were positively correlated with a score of specific dimension (life satisfaction) of depression, P < 0.05. CONCLUSION General obesity, rather than abdominal obesity, was associated with worsening depressive symptoms and incident depression, which can be partly explained by the systemic inflammatory response, and the impact of obesity on depression should be taken more seriously in the older male population.
Humans ; Male ; Aged ; Depression/etiology* ; C-Reactive Protein/metabolism* ; Obesity, Abdominal/epidemiology* ; Longitudinal Studies ; Inflammation/epidemiology* ; Obesity/complications*

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*