Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

There is a large gap between production and demand of plant oil in China, which leads to the heavy reliance on imports. Diacylglycerol acyltransferase (DGAT) and phospholipid: diacylglycerol acyltransferase (PDAT) are two key enzymes responsible for the synthesis of triacylglycerol, thereby affecting the yield and quality of plant oil. This paper comprehensively reviews the research progress in DGAT and PDAT in terms of their biological functions in plant oil synthesis, the molecular mechanisms of regulating plant lipid metabolism, growth, and development under stress, and their roles in driving oil synthesis under the background of synthetic biology. Furthermore, future research and application of DGAT and PDAT are prospected. This review aims to provide a basis for deeply understanding the molecular mechanism of plant oil synthesis and improving the quality and productivity of oil crops by the utilization of DGAT and PDAT genes.
Diacylglycerol O-Acyltransferase/physiology* ; Plant Oils/metabolism* ; Acyltransferases/metabolism* ; Lipid Metabolism/genetics* ; Gene Expression Regulation, Plant ; Triglycerides/biosynthesis*

Objective To understand the status quo of job embeddedness and turnover intention of hospital nurses,and to explore their correlation.Methods Using convenient sampling method,we selected 538 nursing workers from 8 tertiary hospi-tals in Guangzhou,and conducted an electronic questionnaire survey with job embeddedness Scale and Turnover Intention Scale.Results The total average score of job embeddedness was(3.41±1.26),and the total average score of turnover intention was(2.66±0.94).There was a negative correlation between job embeddedness and turnover intention(r =-0.060,P＞0.05).Conclusion The scores of job embeddedness and turnover intention of hospital nurses are at the middle level,and job embed-dedness is negatively correlated with the total average score of turnover intention.It is suggested that the management mode of hospital nurses should be standardized,the legitimate rights and interests of nurses should be guaranteed,the construction of pro-fessional certification system should be promoted,the nurses'positive job embeddedness should be promoted,the hospital nurs-ing staff should be stabilized,and the satisfaction of nursing service should be improved.

Previous research on traditional Chinese medicine tongue inspection has mainly focused on its development,clinical application,and objectification,ignoring the fundamental question of "why tongue inspection is important in traditional Chinese medicine diagnosis" and neglecting the dominant role of traditional Chinese medicine brain thinking activities during diagnosis. Therefore,applying modern cognitive neuroscience technology to explore the impact of tongue inspection information on traditional Chinese medicine diagnostic thinking from an empirical research perspective may open up a new path for future tongue inspection research. This article proposes the combined application of eye tracking and event-related potential technology,drawing on the experimental paradigm of text reading inference correction in cognitive psychology,to collect eye movement and electroencephalogram data of participants induced by changes in tongue information during the reading process of traditional Chinese medicine medical records. This method can achieve synchronous observation of the focus areas and electroencephalogram signals of the subjects during the reading process,and provide cognitive scientific evidence for "why tongue inspection is important in traditional Chinese medicine diagnosis" through statistical data analysis. This research approach integrates the theories,techniques,and methods of traditional Chinese medicine and cognitive science,and is of great significance for developing cognitive thinking research in traditional Chinese medicine.

Objective To investigate the characteristics of Clostridioides difficile infection(CDI)in patients hospitalized for diarrhea and analyze the risk factors for CDI.Methods Stool samples were collected from 306 patients with diarrhea hospitalized in 3 university hospitals in a mid-south city of China from October to December,2020.C.difficile was isolated by anaerobic culture,and qRT-PCR was used to detect the expressions of toxin A(tcdA)and B(tcdB)genes and the binary toxin genes(cdtA and cdtB).Multilocus sequence typing(MLST)was performed for the isolated strains without contaminating strains as confirmed by 16S rDNA sequencing.Etest strips were used to determine the drug resistance profiles of the isolated strains,and the risk factors of CDI in the patients were analyzed.Results CDI was detected in 25(8.17%)out of the 306 patients.All the patients tested positive for tcdA and tcdB but negative for the binary toxin genes.Seven noncontaminated C.difficile strains with 5 ST types were isolated,including 3 ST54 strains and one strain of ST129,ST98,ST53,and ST631 types each,all belonging to clade 1 and sensitive to metronidazole and vancomycin.Hospitalization within the past 6 months(OR=3.675;95%CI:1.405-9.612),use of PPIs(OR=7.107;95%CI:2.575-19.613),antibiotics for≥1 week(OR=7.306;95%CI:2.274-23.472),non-steroidal anti-inflammatory drugs(OR=4.754;95%CI:1.504-15.031)in the past month,and gastrointestinal disorders(OR=5.050;95%CI:1.826-13.968)were all risk factors for CDI in the patients hospitalized for diarrhea.Conclusion The CDI rate remains low in the hospitalized patients with diarrhea in the investigated hospitals,but early precaution measures are recommended when exposure to the risk factors is reported to reduce the risk of CDI in the hospitalized patients.

Purpose/Significance A prediction model is constructed based on real-world data to achieve prediction and early screening of type 2 diabetic microvascular complications.Method/Process Based on the real world data of Nanjing Drum Tower Hospital in the past 10 years,a particle swarm optimization based deep belief network(PSO-DBN)prediction model for microvascular complica-tions in type 2 diabetes mellitus is constructed by taking test results and medical record documents into consideration.Result/Conclusion The PSO-DBN model can predict diabetic microvascular complications,and the performance is better than that of random forest and sup-port vector machine(SVM)benchmark models,it provides references for the research of disease prediction model of real-world data.

AIM:This study investigates the effect of fibroblast growth factor 21(FGF21)long-acting ana-logue PF-05231023 on promoting the"browning"of white adipose tissue(WAT)by inhibiting mitophagy in WAT and the molecular mechanisms involved.METHODS:Using a high-fat diet(HFD)to replicate an obesity model in mice,18 C57BL/6J mice were divided into three groups:normal control(NC)group,HFD group,and PF-05231023 intervention(PF+HFD)group,each consisting of 6 mice.After 12 weeks of feeding,the mice were anaesthetized,their eyeballs were removed to collect blood samples,and serum was separated to measure levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)、alanine aminotransferase(ALT),and aspartate aminotransferase(AST)in mouse serum.The inguinal WAT(iWAT),epididymal WAT(eWAT)and liver were collected.Part of the tis-sues were used for Western blot experiments to measure the protein levels of"browning"related markers uncoupling pro-tein-1(Ucp-1)and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),as well as mitophagy-related markers PTEN-induced kinase 1(Pink1),parkin,beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).Another part of the tissues was fixed in paraformaldehyde for subsequent HE and immunohistochemical staining.3T3-L1 cells were induced to mature adipocytes using the classic"cocktail"method.The CCK-8 assay was used to assess the impact of different concentrations of PF-05231023 intervention on cell viability.After 48 h of PF-05231023 intervention,the 3T3-L1 cell clumps were collected for Western blot experiments to measure the expression levels of"browning"related markers Ucp-1 and PGC-1α,as well as mitochondrial autophagy-related markers Pink1,parkin,beclin-1,and LC3-Ⅱ proteins.Oil red O staining was performed to detect cell accumulation,and immunofluorescence staining was used to mea-sure Ucp-1 protein content.Subsequently,3T3-L1 cells were divided into the normal group,PF-05231023 intervention group,Pink1 agonist MTK458 intervention group,and MTK458+PF-05231023 intervention group.Cell clumps were col-lected for Western blot experiments to measure the markers as mentioned above.RESULTS:The key findings of our study indicate that the PF-05231023 intervention did not affect energy intake in mice but significantly reduced the weight,liver weight,and fat weight of mice induced by a high-fat diet(P<0.05).The intervention also decreased lipid accumula-tion(TC,TG、LDL-C)and liver damage(ALT,AST)and alleviated hepatocyte vacuolization and adipocyte size(P<0.05).Compared with the HFD group,the PF-05231023 intervention increased the levels of Ucp-1 and PGC-1α protein expression in iWAT and eWAT(P<0.01).Immunohistochemical staining showed higher Ucp-1 protein content in the PF-05231023 intervention group than in the HFD group.The PF-05231023 intervention dose-dependently increased Ucp-1 and PGC-1α protein expression levels in mature 3T3-L1 cells(P<0.01),reduced cellular lipid accumulation,and immu-nofluorescence staining showed increased Ucp-1 protein content in mature 3T3-L1 cells after PF-05231023 intervention.The PF-05231023 intervention inhibited mitochondrial autophagy-related indicators Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels in iWAT,eWAT,and induced mature 3T3-L1 cells(P<0.05).The MTK intervention increased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,increased Ucp-1 protein expression level,compared with the MTK intervention group,after MTK and PF-05231023 co-intervention,partially decreased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,and partially restored Ucp-1 protein expression level(P<0.01).CONCLUSION:(1)Intervention with PF-05231023 can improve obesity and related metabolic disorders induced by a high-fat diet in mice;(2)PF-05231023 intervention can inhibit white adipose tissue(WAT)and induce mature 3T3-L1 cell mitochondria autophagy,promoting"browning"by inhibiting mitochondrial autophagy;(3)Its mechanism may be related to the inhibi-tion of the Pink1-parkin signalling pathway.

Objective To investigate the antibacterial performance and biocompatibility of silver nanoparticles-coated root canal nickel titanium instruments(AgNPs-NiTi).Methods AgNPs-NiTi was prepared using pulse electrochemical deposition.The morphol-ogy of AgNPs-NiTi was observed using field emission scanning electron microscopy(FE-SEM),and the elemental composition and con-tent were analyzed using X-ray diffraction(XRD)and energy dispersive spectroscopy(EDS).The mechanical properties of AgNPs-NiTi were tested.After Co-culturing AgNPs-NiTi with E.faecalis,the antibacterial effect was detected by colony-forming units method.By constructing an in vitro model of E.faecalis biofilm in the root canal of teeth,the antibacterial effect of AgNPs-NiTi was observed using FE-SEM and live/dead bacterial staining.In addition,AgNPs-NiTi was co-cultured with Raw 264.7 cells,and its cytotoxicity was de-tected by CCK-8.Results The pulse electrochemical deposition was used to construct a silver nanoparticle(AgNPs)coating on NiTi instruments with no significant change in the mechanical properties.AgNPs-NiTi significantly inhibited the proliferation of E.faecalis and damaged E.faecalis biofilm in the root canal.AgNPs-NiTi had no significant influence on the proliferation of Raw264.7 cells and had no cytotoxicity.Conclusion The mechanical properties of AgNPs-NiTi are similar to those of nickel titanium instruments.AgNPs-NiTi inhibits E.faecalis proliferation with good biocompatibility.