ObjectiveThe accuracy of Y-chromosome haplogroup assignment is crucial for tracing paternal lineage in male samples. With the advancement of high-throughput sequencing technologies, high-density Y-SNP genotyping from whole-genome or array-based data has become a standard method for determiningY-chromosome haplogroups. This study systematically evaluated the performance of 4 commonly used high-density SNP genotyping systems—namely, the Global Screening Array (GSA), Chinese Genotyping Array (CGA), Affymetrix array, and the 1240K capture panel—for haplogroup assignment. This work provides a reference for data comparison across different systems. MethodsWe extracted genotype data for the 4 Y-SNP panels from 30× whole-genome sequencing (WGS) data of 1 590 male samples from the 1000 Genomes Project. Additionally, GSA array genotype data from 384 relative pairs (spanning 1st- to 12th-degree relationships) from 109 Chinese Han families were collected. Haplogroup assignment was performed using Y-LineageTracker v1.3.0 software. We assessed the concordance and resolution of haplogroup assignments between the four Y-SNP panels and the WGS data. The consistency and resolution of haplogroup assignments were also evaluated for both the 1000 Genomes Project samples and the 109 family samples collected in this study. Furthermore, the impact of varying numbers of Y-SNPs on haplogroup assignment was examined. ResultsThe GSA and CGA panels demonstrated superior resolution and discrimination of haplogroup subclades compared with the other two panels. The haplogroup assignments from the GSA, CGA, and 1240K panels showed high concordance with WGS data, with consistency rates exceeding 88.70%, whereas the Affymetrix platform exhibited a significantly lower consistency rate of 61.89%. Specifically, the GSA and CGA panels consistently demonstrated superior performance compared with the other two panels in the assignment of haplogroups O-M175 and H-L901, achieving complete concordance (100%) for both haplogroups. In contrast, the Affymetrix panel erroneously assigned all individuals belonging to haplogroup O-M175 to haplogroup K2-M526. Furthermore, its accuracy for haplogroup H-L901 was exceedingly low, at merely 1.41%. This poor performance was characterized by the misassignment of 98.59% of H-L901 samples—specifically, 1.41% to J-M304 and a predominant 97.18% to F-M89. For haplogroup R-M207, all four panels exhibited uniformly high levels of consistency, with concordance values exceeding 94.00%. Notably, for haplogroup E-M96, the 1240K and Affymetrix panels outperformed the GSA and CGA panels in terms of concordance, representing the first instance in which these two panels surpassed the latter. Conversely, for haplogroups J-M304, Q-M242, and I-M170, all 4 panels showed relatively elevated misclassification rates, with the Affymetrix array demonstrating the poorest overall performance. None of the four panels showed any discordant haplogroup assignments among the familial relative pairs analyzed. A positive correlation was observed between the number of Y-SNPs (ranging from 1 000 to 10 000) and classification consistency; however, classification consistency plateaued when the number of Y-SNPs exceeded 10 000. Furthermore, a random sampling analysis conducted on the GSA and CGA panels demonstrated that the haplogroup misclassification rate exhibited negligible fluctuation across the Y-SNP range of 500 to 1 000. Conversely, a marked enhancement in classification consistency was observed as the number of markers increased from 1 000 to 5 000, ultimately reaching a plateau within the interval of 5 000 to 8 000 markers. ConclusionThese findings indicate that the GSA and CGA panels provide high resolution and concordance, delivering reliable Y-haplogroup assignment for forensic investigations.

ObjectiveThe accuracy of Y-chromosome haplogroup assignment is crucial for tracing paternal lineage in male samples. With the advancement of high-throughput sequencing technologies, high-density Y-SNP genotyping from whole-genome or array-based data has become a standard method for determiningY-chromosome haplogroups. This study systematically evaluated the performance of 4 commonly used high-density SNP genotyping systems—namely, the Global Screening Array (GSA), Chinese Genotyping Array (CGA), Affymetrix array, and the 1240K capture panel—for haplogroup assignment. This work provides a reference for data comparison across different systems. MethodsWe extracted genotype data for the 4 Y-SNP panels from 30× whole-genome sequencing (WGS) data of 1 590 male samples from the 1000 Genomes Project. Additionally, GSA array genotype data from 384 relative pairs (spanning 1st- to 12th-degree relationships) from 109 Chinese Han families were collected. Haplogroup assignment was performed using Y-LineageTracker v1.3.0 software. We assessed the concordance and resolution of haplogroup assignments between the four Y-SNP panels and the WGS data. The consistency and resolution of haplogroup assignments were also evaluated for both the 1000 Genomes Project samples and the 109 family samples collected in this study. Furthermore, the impact of varying numbers of Y-SNPs on haplogroup assignment was examined. ResultsThe GSA and CGA panels demonstrated superior resolution and discrimination of haplogroup subclades compared with the other two panels. The haplogroup assignments from the GSA, CGA, and 1240K panels showed high concordance with WGS data, with consistency rates exceeding 88.70%, whereas the Affymetrix platform exhibited a significantly lower consistency rate of 61.89%. Specifically, the GSA and CGA panels consistently demonstrated superior performance compared with the other two panels in the assignment of haplogroups O-M175 and H-L901, achieving complete concordance (100%) for both haplogroups. In contrast, the Affymetrix panel erroneously assigned all individuals belonging to haplogroup O-M175 to haplogroup K2-M526. Furthermore, its accuracy for haplogroup H-L901 was exceedingly low, at merely 1.41%. This poor performance was characterized by the misassignment of 98.59% of H-L901 samples—specifically, 1.41% to J-M304 and a predominant 97.18% to F-M89. For haplogroup R-M207, all four panels exhibited uniformly high levels of consistency, with concordance values exceeding 94.00%. Notably, for haplogroup E-M96, the 1240K and Affymetrix panels outperformed the GSA and CGA panels in terms of concordance, representing the first instance in which these two panels surpassed the latter. Conversely, for haplogroups J-M304, Q-M242, and I-M170, all 4 panels showed relatively elevated misclassification rates, with the Affymetrix array demonstrating the poorest overall performance. None of the four panels showed any discordant haplogroup assignments among the familial relative pairs analyzed. A positive correlation was observed between the number of Y-SNPs (ranging from 1 000 to 10 000) and classification consistency; however, classification consistency plateaued when the number of Y-SNPs exceeded 10 000. Furthermore, a random sampling analysis conducted on the GSA and CGA panels demonstrated that the haplogroup misclassification rate exhibited negligible fluctuation across the Y-SNP range of 500 to 1 000. Conversely, a marked enhancement in classification consistency was observed as the number of markers increased from 1 000 to 5 000, ultimately reaching a plateau within the interval of 5 000 to 8 000 markers. ConclusionThese findings indicate that the GSA and CGA panels provide high resolution and concordance, delivering reliable Y-haplogroup assignment for forensic investigations.

Liver cancer is one of the world's serious diseases today because of its high frequency and fatality rate, genetic differences, and limited effectiveness of late-stage therapy. Although chemotherapy, targeted therapy, immunotherapy, ablation and transarterial chemoembolisation (TACE) have improved the disease control of some patients, recurrence and acquired resistance are still common, especially for tumors that are hypoxic, nutrient-deprived, acidic-stressed, vascularly insufficient and exposed to repeated drug pressure. A bad environment will cause a change in the quality-control system and metabolism of cancer cells, and as a result, lysosomes have started to alter. In addition to the above catabolic functions of lysosomes, they also take part in autophagic flux, substrate recycling, iron and lipid metabolism, nutrient sensing, drug distribution, membrane repair and cell death signalling. Under the stress of therapy in liver cancer cells, increased lysosomal acidification and enhanced terminal degradation lead to prolonged autophagy; TFEB/TFE3 promotes the formation of new lysosomes and lysophagosomes to sequester weakly basic drugs, thereby reducing the concentration of active drugs and mitigating proteotoxicity and oxidative stress to promote cell survival. The above processes produce a lysosome-dependent resistant phenotype that is particularly relevant to sorafenib and doxorubicin and other drugs whose effectiveness can be reduced by protective autophagy or changes in intracellular location. Conversely, the same dependency on lysosomal homeostasis is also a vulnerability. Natural products and monomeric compounds derived from Chinese herbal medicines have various structures, multiple target regulation capabilities, and the potential to act on several lysosome-related nodes simultaneously. Based on the evidence in this review, it is believed that such compounds may sensitise liver cancer cells by inhibiting V-ATPase-mediated acid hydrolysis, obstructing late-stage autophagy-mediated degradation, disrupting lysosomal calcium or membrane homeostasis, causing lysosomal membrane permeabilisation, reducing compensatory lysosomal biogenesis, promoting ferritin degradation and ferroptosis, or enhancing acid-responsive intracellular delivery. Agents that impair lysosomal function and protective autophagy, compounds that convert enlarged or drug-sequestering lysosomes into lethal targets, and nanodelivery systems that exploit the acidic environment of endolysosomes to co-deliver natural products with chemotherapeutic drugs are examples. Lysosome-targeted intervention will have different effects under different circumstances; for example, inhibiting autophagy may result in an increase in cytotoxic stress in some areas, whereas overstimulation of autophagy or iron release from lysosomes may induce autophagic cell death or ferroptosis in other areas. Therefore, the design of therapy should take into account the status of the tumour microenvironment, autophagic flux, lysosomal pH, TFEB/TFE3 activity, drug sequestration capacity, ferroptosis sensitivity, dosing sequence and delivery route. This review systematically examines the lysosomal homeostasis in the microenvironment of liver cancer, the mechanisms through which lysosomal adaptation contributes to chemoresistance, and the rationale for combining natural products with standard agents such as sorafenib and doxorubicin. Based on basic lysosome biology, pharmacodynamic and delivery data have also been collected; as a result, some applications for future studies have been proposed, such as dynamic monitoring of autophagy flux, in vivo spatial measurements of lysosomal functions, rational optimisation of combination therapy timings, and safety assessments in immunocompetent liver cancer models prior to clinical translation. Translation difficulties are also evident, such as insufficient tumour selectivity, pharmacokinetic limitations, compensatory lysosomal regeneration, toxicity to normal liver and immune cells, and a lack of validated predictive biomarkers. A new way will be found to use biomarkers to divide the patient group, optimize nanoparticles for better delivery, design specific schedules for combined treatments based on the problem they cause within the cell, etc., thereby overcoming drug resistance and reducing the harm patients suffer from toxic treatments. This system can help select biomarkers and rational drug pairs for the next round of lysosome-centred precision trials.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

The 2024 National Education Work Conference pointed out that at the current juncture of the critical period for achieving the goals and tasks of the 14th Five-Year Plan,the implementation of the Education Powerhouse Construction Plan Outline should be taken as the main line of work,and building first-class disciplines is an crucial task for a higher education powerhouse.In 2022,forensic medicine was officially listed as a first-level discipline under the medical category,presenting an un-precedented historical opportunity for the development of forensic medicine.The forensic medicine dis-cipline of Southern Medical University comprehensively improves the quality of talent cultivation and facilitates the construction of first-class disciplines as its main direction.It aims to initiate and imple-ment a high-level faculty team building plan featuring"combining recruitment and cultivation,inter-disciplinary integration";make vigorous efforts to establish a first-level doctoral program,refine advan-tageous second-level disciplines and research directions;and establish an innovative research platform from a high starting point with deep integration.The discipline adheres to moral cultivation and the Five Domains of Education simultaneous development,to build a high-quality talent joint training model.Guided by the construction of the national legal system and industry needs,the discipline will enhance social service capabilities.The forensic medicine construction in our university will continue to contribute to the rule of law in China and educational power.

Objective To construct a competency evaluation model for forensic practitioners,providing a reference for their training and assessment.Methods Based on the iceberg and onion models of com-petency,and with reference to Spencer's Competency Dictionary,literature research was conducted and focus group interviews were employed to preliminarily construct core indices and measurement items for evaluating the competency of forensic practitioners.The Delphi method was applied for two rounds of expert consultation to further refine the competency evaluation index system.The analytic hierarchy process(AHP)was used to calculate the weights of the indices.Results A competency evaluation model for forensic practitioners was constructed,consisting of 7 core indices,encompassing forensic skills,identification service capabilities,and the ability to apply relevant legal knowledge and 49 mea-surement items.The weights of the core indices and measurement items were determined.Conclusion The constructed competency evaluation model for forensic practitioners is scientifically sound and inno-vative,and has unique characteristics of forensic medicine compared with other medical models.

Objective To investigate the neuroprotective effect of rhein(RHE)on ischemic mice and its potential mechanism of reducing inflammatory response and neuronal apoptosis by inhibiting Notch/nuclear factor(NF)-κB signaling pathway.Methods The classical middle cerebral artery occlusion(MCAO)method was used to construct ischemic stroke mouse models.The mice were randomly divided into 5 groups including the sham operation group(sham),the model group(MCAO),the MCAO+edaravone group(Eda),the MCAO+RHE-treated group(RHE),and the MCAO+RHE+Notch activitor Jagged 1 group(RHE+J).Each group has 18 mice.The Bederson scoring system,balance beam walking test and accelerated rotating rod test were used to assess the neurological function and locomotor ability of mice in each group.2,3,5-triphenyltetrazolium chloride(TTC)staining,hematoxylin eosin staining,and TUNEL method were used to assess cerebral infarction,hippocampal morphological damage,and neuronal apoptosis.ELISA was used to analysis the levels of interleukin(IL)-6 and tumor necrosis factor α(TNF-α)in hippocampal tissue.Western blotting was used to analysis caspase-3,Notch 1,Hes1,and NF-κB p65 protein expression.Results Compared with the sham group,Bederson score,balance beam score,cerebral infarct volume,IL-6 and TNF-α levels,the proportion of TUNEL-positively stained cells,caspase-3,Notch1,Hes1,and p-NF-κB p65 protein expression were significantly increased in the MCAO group,whereas the latency to fall decreased significantly(P＜0.05).Compared with the MCAO group,Bederson score,balance beam score,cerebral infarct volume,IL-6 and TNF-α levels,proportion of TUNEL-positively stained cells,caspase-3,Notch1,Hes1,and p-NF-κB p65 protein expression were significantly lower in both Eda and RHE groups,whereas the latency to fall increased significantly(P＜0.05).Compared with the RHE group,Bederson score,balance beam score,cerebral infarction volume,IL-6 and TNF-α levels,the proportion of TUNEL-positively stained cells,caspase-3,Notch1,Hes1,and p-NF-κB p65 protein expression increased significantly in the RHE+J group,whereas the latency to fall decreased significantly(P＜0.05).Conclusion Rhein can significantly improve nerve function in ischemic mice by inhibiting Notch/NF-κB signaling pathway activation,suggesting that rhein has potential clinical application value.

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.