ObjectiveThe proteome of biological evidence contains rich genetic information, namely single amino acid polymorphisms (SAPs) in protein sequences. However, due to the lack of efficient and convenient analysis tools, the application of SAP in public security still faces many challenges. This paper aims to meet the application requirements of SAP analysis for forensic biological evidence’s proteome data. MethodsThe software is divided into three modules. First, based on a built-in database of common non-synonymous single nucleotide polymorphisms (nsSNPs) and SAPs in East Asian populations, the software integrates and annotates newly identified exonic nsSNPs as SAPs, thereby constructing a customized SAP protein sequence database. It then utilizes a pre-installed search engine—either pFind or MaxQuant—to perform analysis and output SAP typing results, identifying both reference and variant types, along with their corresponding imputed nsSNPs. Finally, SAPTyper compares the proteome-based typing results with the individual’s exome-derived nsSNP profile and outputs the comparison report. ResultsSAPTyper accepts proteomic DDA mass spectrometry raw data (DDA acquisition mode) and exome sequencing results of nsSNPs as input and outputs the report of SAPs result. The pFind and Maxquant search engines were used to test the proteome data of 2 hair shafts of2 individuals, and both obtained SAP results. It was found that the results of the Maxquant search engine were slightly less than those of pFind. This result shows that SAPTyper can achieve SAP fingding function. Moreover, the pFind search engine was used to test the proteome data of 3 hair shafts from 1 European person and 1 African person in the literature. Among the sites fully matched by the literature method, sites detected by SAPTyper are also included; for semi-matching sites, that is, nsSNPs are heterozygous, both literature method and SAPTyper method had the risk of missing detection for one type of the allele. Comparing the analysis results of SAPTyper with the SAP test results reported in the literature, it was found that some imputed nsSNP sites identified by the literature method but not detected by SAPTyper had a MAF of less than 0.1% in East Asian populations, and therefore they were not included in the common nsSNP database of East Asian populations constructed by this software. Since the database construction of this software is based on the genetic variation information of East Asian populations, it is currently unable to effectively identify representative unique common variation sites in European or African populations, but it can still identify SAP sites shared by these populations and East Asian populations. ConclusionAn automated SAP analysis algorithm was developed for East Asian populations, and the software named SAPTyper was developed. This software provides a convenient and efficient analysis tool for the research and application of forensic proteomic SAP and has important application prospects in individual identification and phenotypic inference based on SAP.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Objective To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability,and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.Methods The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L2 to L5,and cleaning the bilateral articular processes of the L2 to L5.Eighteen SD rats were divided into the normal group,the degenerative group,and the carbonyl cyanide 3-chlorophenylhydrazone(CCCP)group,with 6 rats in each group.The rats in the normal group had no special treatment,the rats in the degenerative group constructed a rat spinal instability model,and the rats in the CCCP group were injected with 5 μL of CCCP(10 μmol/L)in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining,and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen(COL-2A),aggrecan(ACAN),PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A,ACAN,PINK1,Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.Results Compared with the normal group,the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased;while the structure of intervertebral discs for rats in the CCCP group was more intact,and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group,the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated(P<0.05),the expression of mitochon-drial autophagy-related genes of PINK1 and Parkin were significantly decreased(P<0.05),and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased(P<0.05).Compared with the degenerative group,the expression of COL-2A,ACAN,PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated(P<0.05),and the protein levels of Tomm20 and Timm23 were significantly down-regulated(P<0.05).Conclusion Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage,thereby inducing endplate cartilage and intervertebral disc degeneration,and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.

Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.

Gastrointestinal dyskinesia is a central factor contributing to the development of functional dyspepsia(FD),which is characterized by the rupture of the gastrointestinal nerve-Cajal interstitial cell-smooth muscle network.Gan Yu Pi Xu are similar to endoplasmic reticulum stress(ERs)-mitochondrial autophagy homeostasis imbalance.Mitochondrial autophagy disorders are the biological basis of Pi Xu,and Gan Yu is the macroscopic manifestation of ERs,and regulation of ERs-mitochondrial autophagy pathway is an important way to prevent and control FD.In this paper,we start from the theory of"liver-spleen correlation",combine the changes of endoplasmic reticulum and mitochondria in the process of gastrointestinal dyskinesia,reveal the correlation between the pathogenesis of Gan Yu Pi Xu and the autophagy of ERs and mitochondria,and elucidate the mechanism of gastrointestinal dyskinesia by the method of Shu Gan Jian Pi,so as to provide a new point of view for the treatment of gastrointestinal dyskinesia in FD.

Chronic kidney disease (CKD) has become a significant global public health problem. It is defined as chronic renal structural and functional dysfunction caused by various reasons. The prevalence of obesity and diabetes has increased dramatically in developing countries, which substantially affected the patterns of CKD observed in these regions. It’s inevitable that the disease spectrum of CKD is converting to metabolic diseases. CKD is also considered an independent risk factor for renal aging and cardiovascular disease in the elderly, which usually progresses to end-stage renal disease (ESRD). Renal interstitial fibrosis is the pathological basis of ESRD and is a microscopic manifestation of renal aging. Conversely, renal aging is a risk factor for interstitial fibrosis. Although the healthy kidney has a relatively low lipid level, CKD-associated dyslipidemia has been extensively studied. Nevertheless, less is known about the contribution of lipid disorders to the development of renal senescence and interstitial fibrosis. Recent studies have demonstrated that lipid metabolism disorders occur in the progress of renal aging and interstitial fibrosis. Renal lipids accumulate once lipid uptake and synthesis exceed the balance with lipolysis, which is mainly characterized by increased levels of triglyceride (TG) and oxidized low-density lipoprotein, and decreased levels of high-density lipoprotein. Excessive lipid accumulation in the kidney not only induces lipotoxicity and endoplasmic reticulum stress but also increases intracellular and mitochondrial reactive oxygen species, which induce stress injury and senescence in renal tubular epithelial cells. Pro-inflammatory and pro-fibrotic cytokines in a senescence-associated secretory phenotype secreted by senescent renal tubular epithelial cells further accelerate their senescence as well as the occurrence of inflammation and pericyte loss, promoting secretion of extracellular matrix (ECM) and subsequent fibrosis in the tubulointerstitial compartment. In addition, podocyte hypertrophy also leads to glomerulosclerosis. Currently, most of the studies on inhibiting or even reversing renal interstitial fibrosis are still in the experimental stage. What’s more, effective drugs to slow down renal aging have not been reported. Many inflammatory and fibrotic factors are both components of the senescence-associated secretory phenotype (SASP), nevertheless, they are not sufficient to recognize cellular senescence. Given that indicators of senescence may vary from disease to disease and organ to organ, there is a need for more sensitive and specific senescence assays. Crucial enzymes and regulatory proteins of lipid metabolic pathways are expected to be potential targets for ameliorating renal aging and interstitial fibrosis. Lipid-lowering approach might represent another therapeutic in the management of kidney injury associated with metabolic dysfunction. Thus, clarifying the molecular regulatory mechanisms of lipid metabolism in kidney is extremely important for the delay of renal aging and the treatment of interstitial fibrosis. This review outlines the effects of lipid metabolism disorders on renal aging and renal fibrosis, analyses the role of lipid metabolism disorders in the development of renal diseases, and summarizes the potential targets and strategies for the prevention of renal aging and renal fibrosis based on lipid metabolism regulation, which will provide a reference for the discovery of new targets for the treatment of renal fibrosis.

This data article describes the"Typical Regional Activity Patterns"(TRAP)dataset,which is based on the Tackling Key Problems in Air Pollution Control Program.In order to explore the interaction between air pollution and physical activity,we collected activity patterns of 9,221 residents with different occupations and lifestyles for three consecutive days in typical regions(Jinan and Baoding)where air pollutant concentrations were higher than those in neighboring areas.The TRAP dataset consists of two aspects of information:demographic indicators(personal information,occupation,personal habits,and living situation)and physical activity pattern data(activity location and intensity);additionally,the exposure measures of physical activity patterns are included,which data users can match to various endpoints for their specific purpose.This dataset provides evidence for exploring the attributes of activity patterns of residents in northern China and for interdisciplinary researchers to develop strategies and measures for health education and health promotion.

Objective:To explore the value of color Doppler ultrasound (CDUS) combined with shear wave elastography (SWE) in the diagnosis of thyroid micropapillary carcinoma (PTMC).Methods:The clinical data were retrospectively collected including 51 patients with PTMC (study group) and 49 patients with benign thyroid nodules (control group) who treatment in Maanshan 17 Metallurgical Hospital from October 2020 to December 2022. The clinical data, serum tumor markers, CDUS quantitative parameters, and SWE quantitative parameters were compared between the two groups, the correlation between CDUS, SWE quantitative parameters and serum tumor markers were analyzed by Pearson test, and the diagnostic value of CDUS, SWE quantitative parameters were analyzed by receiver operating characteristic(ROC) curve.Results:The levels of serum carcinoembryonic antigen (CEA), thyroglobulin (TG), galactose hemagglutinin-3 (Gal-3), resistance index (RI), peak systolic flow velocity (PSV), elasticity modulus minimum (E min), elasticity modulus mean (E mean), and elasticity modulus maximum (E max) in the study group were higher than those in the control group: (28.76 ± 4.29) μg/L vs. (15.73 ± 2.96) μg/L, (117.53 ± 25.17) μg/L vs. (49.85 ± 9.64) μg/L, (8.31 ± 2.43) μg/L vs. (3.50 ± 0.82) μg/L, 0.85 ± 0.21 vs. 0.54 ± 0.13, (44.18 ± 8.26) cm/s vs. (22.05 ± 6.49) cm/s, (15.80 ± 1.94) kPa vs. (12.97 ± 1.58) kPa, (38.02 ± 10.39) kPa vs. (23.16 ± 7.83) kPa, (60.13 ± 19.41) kPa vs. (34.65 ± 11.87) kPa, there were statistical differences ( P<0.05). In patients with PTMC, the results of Pearson test showed that, RI, PSV, E min, E mean, and E max were positively correlated with serum CEA, TG, and Gal-3 levels ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of the combined diagnosis of PTMC by RI, PSV, E min, E mean, and E max was 0.937. Conclusions:CDUS combined with SWE can provide reliable reference for clinical diagnosis of PTMC.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.