Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: The optimal screening interval for diabetic retinopathy (DR) remains controversial. This study aimed to develop a risk algorithm to predict the individual risk of referable sight-threatening diabetic retinopathy (STDR) in a mainly Chinese population and to provide evidence for risk-based screening intervals. Methods: The retrospective cohort data from 117,418 subjects who received systematic DR screening in Hong Kong between 2010 and 2016 were included to develop and validate the risk algorithm using a parametric survival model. The risk algorithm can be used to predict the individual risk of STDR within a specific time interval, or the time to reach a specific risk margin and thus to allocate a screening interval. The calibration performance was assessed by comparing the cumulative STDR events versus predicted risk over 2 years, and discrimination by using receiver operative characteristics (ROC) curve. Results: Duration of diabetes, glycosylated hemoglobin, systolic blood pressure, presence of chronic kidney disease, diabetes medication, and age were included in the risk algorithm. The validation of prediction performance showed that there was no significant difference between predicted and observed STDR risks in males (5.6% vs. 5.1%, P=0.724) or females (4.8% vs. 4.6%, P=0.099). The area under the receiver operating characteristic curve was 0.80 (95% confidence interval [CI], 0.78 to 0.81) for males and 0.81 (95% CI, 0.79 to 0.83) for females. Conclusion The risk algorithm has good prediction performance for referable STDR. Using a risk-based screening interval allows us to allocate screening visits disproportionally more to those at higher risk, while reducing the frequency of screening of lower risk people.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Background: The global rise in visual impairment, driven by population aging, the increasing prevalence of lifestyle-related chronic diseases, and environmental factors, has made it a critical public health concern, highlighting the urgent need for effective preventive strategies and eye health maintenance. Cuscutae Semen (CS), a traditional Chinese herbal medicine long regarded for its vision-enhancing properties, has been widely used to support ocular health. However, its underlying molecular mechanisms and bioactive constituents remain poorly understood, limiting its modernization and broader clinical application. Objective: This study aims to investigate the restorative effects of CS on visual impairment, elucidate its underlying mechanisms, and identify potential active components. Methods: A zebrafish model of visual impairment was established using mepanipyrim to simulate retinal structural damage and visual dysfunction. The therapeutic effects of CS were systematically evaluated through behavioral analyses and histomorphological observations. To elucidate the underlying mechanisms, an integrated approach was employed, combining transcriptome sequencing (RNA-seq), reverse transcription quantitative polymerase chain reaction validation, and immunofluorescence staining to identify critical genes and pathways involved. Furthermore, macroporous resin column chromatography was employed for the fractionation and screening of potential active components. Results: CS treatment significantly alleviated mepanipyrim-induced ocular abnormalities in zebrafish, restoring approximately 82% of the observed morphological defects. Behavioral assessments revealed that CS-treated zebrafish exhibited markedly increased swimming speed and distance, indicating enhanced visual light sensitivity. Histopathological analysis demonstrated that CS effectively repaired the structure of retinal cell layers. RNA-seq revealed that CS broadly reversed mepanipyrim-induced gene expression disturbances, suggesting a restorative effect on transcriptomic homeostasis. Gene Ontology enrichment analysis identified the phototransduction pathway as a key mediator of CS’s therapeutic effects. This was further supported by reverse transcription quantitative polymerase chain reaction validation of critical genes and immunofluorescence staining, which confirmed the restored expression of Pde6a and Gnat2, key proteins involved in photic signal transmission. Active component screening indicated that high-polar constituents, including chlorogenic acid, may constitute one of the major bioactive fractions responsible for the observed therapeutic effects. Conclusion: This study provides evidence of the vision-protective effects of CS in a zebrafish model, demonstrating that its therapeutic mechanism involves modulation of the phototransduction pathway. Chlorogenic acid was identified as one of the key bioactive constituents contributing to this effect. These findings not only provide scientific validation for the traditional use of CS in ocular protection but also present promising therapeutic prospects for the prevention and treatment of visual impairment.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF）， and to construct a risk scoring table that can accurately predict the prognosis of patients in the early stage. MethodsA retrospective analysis was performed for the clinical data of 502 patients with ACLF who were admitted to Tangdu Hospital， Air Force Medical University， from January 1， 2010 to December 31， 2020 （training set）， and the influencing factors for 28-day mortality rate were identified. The 69 ACLF patients who were admitted to Tangdu Hospital， Air Force Medical University， from January 1 to December 31， 2021 were enrolled as the validation set. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A univariate Cox regression analysis was used to obtain the early warning indicators associated with the 28-day prognosis of ACLF patients， and variance inflation factors were used to assess multicollinearity among predictors； a multivariate Cox regression analysis was used to construct a risk model for ACLF prognosis （mortality）. A risk scoring table for ACLF prognosis （mortality） was developed based on regression coefficients （β） from the model equation and weight assignments in the nomogram. Internal validation and comparison were performed for the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models （Child-Turcotte-Pugh ［CTP］ score， Model for End-Stage Liver Disease ［MELD］ score， MELD combined with serum sodium concentration ［MELD-Na］ score， and integrated MELD ［iMELD］ score） in the training set， while external validation and comprehensive evaluation of the scoring table and the other scoring models were performed in the validation set. The Nagelkerke’s R² test and the Hosmer-Lemeshow test were used to assess the degree of fitting of the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models， and fitting curves were plotted. C-index was used to assess the discriminatory ability of the scoring table for ACLF prognosis （mortality） and the other scoring models， and the Z-test was used for comparison of C-index between different models. The decision curve analysis was used to compare the clinical benefits of the scoring table for ACLF prognosis （mortality） and the other scoring models. ResultsThe multivariate Cox regression analysis showed that age （hazard ratio ［HR］=1.027， 95% confidence interval ［CI］： 1.015 — 1.039， P<0.001）， hepatic encephalopathy grade （grade 1： HR=2.928， 95%CI： 1.463 — 5.858， P=0.002； grade 2： HR=3.811， 95%CI： 2.078 — 6.988， P<0.001； grade 3： HR=3.916， 95%CI： 1.917 — 8.001， P<0.001； grade 4： HR=6.966， 95%CI： 4.559 — 10.644， P<0.001）， an increase in total bilirubin （TBil） by ≥17.1 μmol/L per day （HR=1.771， 95%CI： 1.248 — 2.513， P=0.001）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， neutrophil count （HR=1.092， 95%CI： 1.060 — 1.126， P<0.001）， and international normalized ratio （HR=1.298， 95%CI： 1.187 — 1.418， P<0.001） were independent risk factors associated with the 28-day mortality rate of ACLF patients， and a risk scoring table was constructed for ACLF prognosis （mortality）. The Nagelkerke’s R² test showed that the risk scoring table for ACLF prognosis （mortality） had an R² value of 0.599 in the training set and 0.722 in the validation set， which were higher than the R² values of CTP， MELD， MELD-Na， and iMELD scores. The Hosmer-Lemeshow test showed that the risk scoring table for ACLF prognosis （mortality） had a P value of 0.280 in the training set and 0.788 in the validation set. The C-index analysis showed that the scoring table had a higher C-index than the other scoring models in the validation set （all P<0.001）， as well as a higher C-index than CTP score in the training set （P<0.001）. The decision curve analysis showed that the risk scoring table for ACLF prognosis （mortality） had higher clinical net benefits than the other scoring models. ConclusionCompared with other scoring models currently used in clinical practice， the novel risk scoring table for ACLF prognosis （mortality） constructed based on the six predictive factors of age， hepatic encephalopathy grade， an increase in TBil by ≥17.1 μmol/L per day， creatinine， neutrophil count， and international normalized ratio has a relatively high value in predicting the 28-day prognosis of ACLF patients.

Objective:To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)on the proliferation and collagen expression levels of L929 cells,and to clarify its related mechanism.Methods:The BMSCs were extracted from the 4-week-old C57BL/6 mice.The phenotypes of BMSCs were identified by immunofluorescence staining.The L929 cells were divided into control group(L929 cells),co-culture group(L929 cells and BMSCs),inhibitor of Janus kinase(JAK)WP1066 group(WP1066-treated L929 cells and BMSCs),and dimethyl sulfoxide(DMSO)group(DMSO-treated L929 cells and BMSCs).Cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the L929 cells in various groups at different time points;Western blotting method was used to detect the expression levels of type Ⅰ collagen(Col Ⅰ)and type Ⅲ collagen(Col Ⅲ)in the L929 cells in various groups;immunofluorescence staining was used to detect the expressions of Col Ⅰ and Col Ⅲ proteins in the L929 cells in various groups.Results:The fluorescence assay results of surface antigen(SA)showed that the surface markers CD29+,CD45-,CD90+and CD105+were found in the BMSCs.The CCK-8 assay results showed that compared with control group,the proliferation activities of the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the proliferation activity of the L929 cells in WP1066 group was significantly decreased(P＜0.01).The Western blotting method results showed that compared with control group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in WP1066 group were significantly decreased(P＜0.01);compared with DMSO group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in WP1066 group were significantly decreased(P＜0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensities of Col Ⅰ and Col Ⅲ proteins in the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the fluorescence intensities of Col Ⅰ and Col Ⅲ in the L929 cells in WP1066 group were significantly decreased(P＜0.01);compared with DMSO group,the fluorescence intensities of Col Ⅰ and Col Ⅲ in the L929 cells in WP1066 group were significantly decreased(P＜0.01).Conclusion:MSCs can promote the proliferation and collagen production of the L929 cells of the mice through the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway.

Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Combined seawater Hf and Nd isotope compositions have been applied as reliable tracers of water mass mixing and weathering input changes.The establishment of standardized synchronous extraction methods for Fe-Mn oxyhydroxide in sediments,which serve as effective carriers for isotopic signals of ancient seawater,is a prerequisite and key for paleoceanography research.The research material of this study was the surface sediments of the Western Arctic Ocean obtained from China's 7th Arctic Scientific Expedition,and a reliable simultaneous Nd-Hf isotope extraction method in Fe-Mn oxyhydroxide fraction was established through systematic optimization of pretreatment procedures and key extraction parameters.This research focused on analyzing the effects of pretreatment(Milli-Q water pre-wash)and key extraction parameters(leaching time,solution/solid ratios,concentration of EDTA-2Na,and concentration of mixed solution of hydroxyamine hydrochloride(HH)and acetic acid(HAc))on element extraction efficiency and isotopic composition.The experimental results indicated that the Milli-Q water pre-wash was not necessary,Fe-Mn oxyhydroxide extraction could be directly performed.Nd extraction amount in Fe-Mn oxyhydroxide fraction was not sensitive to changes in extraction conditions,while the Hf extraction amount was significantly affected by leaching time,solution/solid ratios and concentration of EDTA-2Na.The optimal conditions for synchronously extracting Nd-Hf isotopes were as follows:adding 20 mL of a mixed solution of 0.005 mol/L HH+1.5%HAc+0.03 mol/L EDTA-2Na per gram of sample,and reaction at room temperature for 3 h under shaking.Through systematic verification of 87Sr/86Sr ratio,εNd value,εHf value,Al/Nd ratio and Al/Hf ratio,it was confirmed that this method could effectively avoid interferences from residual components and accurately obtain Nd-Hf isotope signals of ancient seawater preserved in sediments.The standardized method established in this work provided reliable technical support for reconstructing water mass mixing between the Arctic,North Atlantic,and North Pacific Oceans and riverine input histories.It also provided important reference for the extraction methods of Nd and Hf isotopes from marine sources in sediments from other sea areas around the world.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.