Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

To develop a rapid differential detection method for porcine epidemic diarrhea virus(PEDV)and transmissible gastroenteritis virus(PEDV),M gene sequences of PEDV and TGEV were compared,the inner and outer primer pairs and probes were designed according to the highly conserved region.PEDV-Probe was labeled with FAM at5'end and BHQ1 at 3'end.TGEV-Probe was labeled with CY5.5 at the 5'end and BHQ2 at the 3'end.After optimizing the reaction condi-tions and system,a dual fluorescent RT-LAMP assay for PEDV and TGEV rapid identification was established.The amplification could be completed within 60 min in a 63 ℃ water bath and then stopped at 85 ℃ for 10 min.Then the tubes were placed in a multicolor imaging system,and the re-sults could be observed under 520 nm and 690 nm dual channels.There was no cross-reaction when other common swine viral pathogens were detected by this method.The sensitivity of the assay was evaluated with a 10-fold diluted recombinant plasmid as templates.The lowest detection limit was 102 copies/μL recombinant plasmid,which was 10 times more sensitive than the conventional RT-PCR method.Seventy-two PEDV-positive samples,49 TGEV-positive samples,and 40 PEDV and TGEV co-infected samples were detected from 175 anal swab samples of diarrheic piglets by the established method,which were all higher than the detection rates of the conventional RT-PCR method.The dual fluorescent RT-LAMP method established in this study can be used to amplify the target gene in an ordinary water bath without gel electrophoresis,which provides technical sup-port for rapid and convenient differential diagnosis of PED and TGE and simultaneous detection of PEDV and TGEV co-infection.

Objective"Astragalus-Leech"medicine pair can reduce cerebral ischemia-reperfusion injury(CIRI),but its mechanism of action is not yet clear.Ferroptosis is a new target of CIRI.In this paper,the mechanism of the"Astragalus-Leech"medicine pair on regulating ferroptosis in the treatment of CIRI was investigated using the network pharmacology approach.Methods The active ingredients and targets of Astragalus-Leech were obtained by searching databases,such as PubChem,SwissTargetPrediction,Batman-TCM,UniProt,TCMSP and other databases,respectively;the CIRI-related targets were collected by searching GeneCards database;the Venny online tool was used to obtain the common targets of"Astragalus-Leech"medicine pairs for active ingredients and CIRI.Cytoscape software was used to construct a network of interrelationships between the active ingredients,disease and predicted targets of the"Astragalus-Leech"medicine pair,the protein interaction network was visualized,and CytoHubba plug-in was used to calculate the core targets.The GO analysis and KEGG analysis of the targets of"Astragalus-Leech"in the treatment of CIRI were performed using R language software.Using FerrDb database,the genes related to the regulation of ferroptosis were obtained,and the common genes among the active ingredients,CIRI and ferroptosis in the"Astragalus-Leech"medicine pair were analyzed to investigate their relationship and make predictions.AutoDockTools 1.5.7 and other softwares were used to verify the molecular docking between the active ingredients and key targets.Results Through searching the databases,28 active ingredients of"Astragalus-Leech"medicine pair,680 predicted gene targets of the drug pair,1513 targets related to CIRI,253 common targets of drug pair-disease,259 targets related to ferroptosis were obtained.28 potential targets,including PIK3CA,RELA,MAPK1,MAPK8,PTGS2,STAT3,SRC,NOS2,etc.on the regulation of ferroptosis and intervention in CIRI,and 279 signaling pathways including PI3K-Akt,Ras,TNF,MAPK,and HIF-1 were obtained through related prediction.Molecular docking showed that there was an interaction between the key components of the drug pair and the core targets.The"Astragalus-Leech"medicine pair may intervene in the development of CIRI by regulating ferroptosis and exert its therapeutic effects.Conclusion Using network pharmacology methods,the potential targets and related pathways of"Astragalus-Leech"on the active ingredients by regulating ferroptosis against CIRI were analyzed,suggesting that"Astragalus-Leech"may play its role in anti-CIRI through oxidative stress and anti-inflammatory pathways to regulate ferroptosis pathway,and provide a basis for further cell and animal experiments.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Objective:To explore the correlation between defecation disorders and diet in patients undergoing sphincter-preserving surgery for rectal cancer.Methods:This study was a cross-sectional survey. From 2021 to 2023, convenience sampling was used to select 159 patients with rectal cancer who underwent sphincter-preserving surgery at Peking University Third Hospital as participants. The General Information Questionnaire, Food Frequency Questionnaire, and Defecation Questionnaire were used for the survey.Results:The incidence of defecation disorders in 159 patients with rectal cancer after sphincter-preserving surgery was 74.2% (118/159), and the types of defecation disorders with high to low incidence were "frequent defecation (96/159, 60.4%) " "constipation (37/159, 23.3%) " "diarrhea (33/159, 20.8%) " and "fecal incontinence" (24/159, 15.1%). Diets were clustered into 9 categories (vegetables and fruits, carbohydrate staple foods, red meat foods, gas producing foods, dairy products, white meat foods, dessert foods, high-fat foods, and spicy and stimulating foods). Binomial Logistic regression analysis showed that red meat foods and gas producing foods were the influencing factors of frequent defecation ( P<0.05), red meat foods was the influencing factor of diarrhea ( P<0.05), and carbohydrate staple foods was the influencing factor of fecal incontinence ( P<0.05) . Conclusions:The incidence of defecation disorders in patients with rectal cancer after sphincter-preserving surgery is relatively high, and the intake of red meat foods, gas producing foods, and carbohydrate staple foods should be appropriately controlled. Clinical medical and nursing staff should pay close attention to the diet of elderly patients.

In June 2022, a carbon monoxide poisoning accident with hidden source occurred in a bonded gold/silver wire manufacturing enterprise in Guangzhou, causing 10 people to be poisoned, of which 1 was caused by carbon monoxide poisoning and 9 by carbon monoxide contact reaction. The symptoms were dizziness, fatigue and vomiting. After 5 to 7 h, the saturation of carboxyhemoglobin in finger pulse was 4% to 10%, and the saturation of carboxyhemoglobin in blood gas biochemical analysis was 1.9% to 5.8%. The concentration of carbon monoxide detected in the carbon borne purification plant of the enterprise was 34.46-37.26 mg/m 3. It was judged that the accident was carbon monoxide poisoning caused by carbon monoxide gas being transported to the work post along the gas transmission pipeline due to abnormal operation of the carbon borne purification plant. By investigating the source and cause of poison, this paper provides a warning for the similar process to prevent similar events, and provides a new idea for the identification of chemical poisoning risk. At the same time, it is warned that similar enterprises should fully consider the risk of poisoning under specific circumstances, strengthen equipment maintenance and repair, and prevent the occurrence of similar incidents.

Glioma has high incidence and poor prognosis. Glioma pathogenesis is the research hotspot and difficulty in related fields. N6-methyladenin (m6A) is closely related to glioma development, and m6A related proteins play important roles in glioma, which is a potential therapeutic target for glioma. In this paper, the upstream regulatory mechanism of m6A related proteins is reviewed, and the prospect of m6A related proteins as diagnostic markers and potential therapeutic targets for glioma is discussed.

In June 2022, a carbon monoxide poisoning accident with hidden source occurred in a bonded gold/silver wire manufacturing enterprise in Guangzhou, causing 10 people to be poisoned, of which 1 was caused by carbon monoxide poisoning and 9 by carbon monoxide contact reaction. The symptoms were dizziness, fatigue and vomiting. After 5 to 7 h, the saturation of carboxyhemoglobin in finger pulse was 4% to 10%, and the saturation of carboxyhemoglobin in blood gas biochemical analysis was 1.9% to 5.8%. The concentration of carbon monoxide detected in the carbon borne purification plant of the enterprise was 34.46-37.26 mg/m 3. It was judged that the accident was carbon monoxide poisoning caused by carbon monoxide gas being transported to the work post along the gas transmission pipeline due to abnormal operation of the carbon borne purification plant. By investigating the source and cause of poison, this paper provides a warning for the similar process to prevent similar events, and provides a new idea for the identification of chemical poisoning risk. At the same time, it is warned that similar enterprises should fully consider the risk of poisoning under specific circumstances, strengthen equipment maintenance and repair, and prevent the occurrence of similar incidents.

The aim of this study was to develop a blocking enzyme-linked immunosorbent assay (bELISA) based on a biotinylated nanobody target the S1 protein of porcine epidemic diarrhea virus (PEDV) for detecting the anti-PEDV antibodies and evaluating the immune effect of the vaccine. The gene encoding the single-domain antibody sdAb3 target the PEDV S1 protein was amplified and the Avitag sequence was fused at its 3'-end. The PCR product was cloned into the expression vector pET-21b for expression and purification of the sdAb3-Avitag protein. The purified sdAb3-Avitag fusion protein was biotinylated and its activity was determined. Using the recombinant S1 protein as a coating antigen, a bELISA was established and optimized. Serum samples were tested in parallel by the bELISA and a commercial kit. The recombinant vector pET21b-sdAb3-Avitag was constructed to express the tagged sdAb3. After induction for expression, the biotin-labeled sdAb3 (sdAb3-Biotin) with high purity and good activity was obtained. For the optimized bELISA, the coating concentration of the S1 protein was 200 ng/well, the serum dilution was 1:2 and incubated for 2 h, the dilution ratio of the biotinylated sdAb3 was 1:8 000 and incubated for 30 min, the dilution of the enzyme-labeled antibody was 1:5 000 and incubated for 30 min. The bELISA had no cross reaction with the sera of major porcine viruses including transmissible gastroenteritis virus, porcine reproductive and respiratory syndrome virus and showed good specificity and reproducibility. For a total of 54 porcine serum samples tested, the overall compliance rate of the bELISA with a commercial kit was 92.56%. This study developed a rapid and reliable bELISA method, which can be used for serosurveillance and vaccine evaluation for PEDV.
Animals ; Antibodies, Viral ; Coronavirus Infections/veterinary* ; Enzyme-Linked Immunosorbent Assay ; Porcine epidemic diarrhea virus/genetics* ; Reproducibility of Results ; Sensitivity and Specificity ; Single-Domain Antibodies ; Swine ; Swine Diseases

The treatment of central nervous system diseases has always been a hot topic,owning to its complexity and existence of blood-brain barrier.In recent years,studies on mesenchymal stem cells-derived exosomes (MSCs-EVS) showed that MSCs-EVS are not only potential therapeutic drugs for central nervous system diseases,but also natural carriers of therapeutic drugs due to their good biocompatibility and ability to cross the blood-brain barrier.This paper reviews the application and underling mechanism of MSCs-EVS in treatment of central nervous system diseases,and looks forward to its applications in central nervous system disease.