Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior.

Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.

Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn's disease.

Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.

Arginine methyltransferases PRMT2 and PRMT3 are essential for biosynthesis of plant-polysaccharide-degrading enzymes in Penicillium oxalicum.

Many filamentous fungi produce plant-polysaccharide-degrading enzymes (PPDE); however, the regulatory mechanism of this process is poorly understood. A Gal4-like transcription factor, CxrA, is essential for mycelial growth and PPDE production in Penicillium oxalicum. Its N-terminal region, CxrAΔ207-733 is required for the regulatory functions of whole CxrA, and contains a DNA-binding domain (CxrAΔ1-16&Δ59-733) and a methylated arginine (R) 94. Methylation of R94 is mediated by an arginine N-methyltransferase, PRMT2 and appears to induce dimerization of CxrAΔ1-60. Overexpression of prmt2 in P. oxalicum increases PPDE production by 41.4-95.1% during growth on Avicel, compared with the background strain Δku70;hphR+. Another arginine N-methyltransferase, PRMT3, appears to assist entry of CxrA into the nucleus, and interacts with CxrAΔ1-60 in vitro under Avicel induction. Deletion of prmt3 resulted in 67.0-149.7% enhanced PPDE production by P. oxalicum. These findings provide novel insights into the regulatory mechanism of fungal PPDE production.

XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7.

Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.

Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.

Hsp90aa1/JUN/Ccl2 regulatory axis mediates migration and differentiation of NSPCs, promoting the onset and progression of early post-ischemic stroke epilepsy.

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

Europium Ion-Based Magnetic-Trapping and Fluorescence-Sensing Method for Detection of Pathogenic Bacteria.

Europium ions (Eu3+) have been utilized as a fluorescence-sensing probe for a variety of analytes, including tetracycline (TC). When Eu3+ is chelated with TC, its fluorescence can be greatly enhanced. Moreover, Eu3+ possesses 6 unpaired electrons in its f orbital, which makes it paramagnetic. Being a hard acid, Eu3+ can chelate with hard bases, such as oxygen-containing functional groups (e.g., phosphates and carboxylates), present on the cell surface of pathogenic bacteria. Due to these properties, in this study, Eu3+ was explored as a magnetic-trapping and sensing probe against pathogenic bacteria present in complex samples. Eu3+ was used as a magnetic probe to trap bacteria such as Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Bacillus cereus, and Pseudomonas aeruginosa. The addition of TC facilitated the easy detection of magnetic Eu3+-bacterium conjugates through fluorescence spectroscopy, with a detection limit of approximately ∼104 CFU mL-1. Additionally, matrix-assisted laser desorption/ionization mass spectrometry was employed to differentiate bacteria tapped by our magnetic probes.

Phage display-derived alpaca nanobodies as potential therapeutics for Naja atra snake envenomation.

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.

The outcomes of aortic arch repair between open surgical repair and debranching endovascular hybrid surgical repair: A systematic review and meta-analysis.

BACKGROUND: At present, open surgical aortic arch repair (OAR) and debranching hybrid surgical aortic arch repair (HAR) serve as significant therapeutic approaches for aortic arch aneurysm or dissection. It remains unclear which technique is preferable. Our study aimed to compare the short-term and long-term outcomes of these two procedures. METHODS: To identify comparison studies of debranching HAR and OAR, a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from January 2002 to April 2022. This study was registered on PROSPERO (CRD42020218080). RESULTS: Sixteen publications (1316 patients), including six propensity score-matching (PSM) analysis papers, were included in this study. Compared with the HAR group, the patients who underwent OAR were younger (OAR vs HAR: 67.53 ± 12.81 vs 71.29 ± 11.0; P < .00001), had less coronary artery disease (OAR vs HAR: 22.45% vs 32.6%; P = .007), less chronic obstructive pulmonary disease (OAR vs HAR: 16.16% vs 23.92%; P = .001), lower rates of previous stroke (OAR vs HAR: 12.46% vs 18.02%; P = .05), and a lower EuroSCORE (European System for Cardiac Operative Risk Evaluation) score (OAR vs HAR: 6.27 ± 1.04 vs 6.9 ± 3.76; P < .00001). HAR was associated with less postoperative blood transfusion (OAR vs HAR: 12.23% vs 7.91%; P = .04), shorter length of intensive care unit stays (OAR vs HAR: 5.92 ± 7.58 days vs 4.02 ± 6.60 days; P < .00001) and hospital stays (OAR vs HAR: 21.59 ± 17.54 days vs 16.49 ± 18.45 days; P < .0001), lower incidence of reoperation for bleeding complications (OAR vs HAR: 8.07% vs 3.96%; P = .01), fewer postoperative pulmonary complication (OAR vs HAR: 14.75% vs 5.02%; P < .0001), and acute renal failure (OAR vs HAR: 7.54% vs 5.17%; P = .03). In the PSM subgroup, the rates of spinal cord ischemic (OAR vs HAR: 5.75% vs 11.49%; P = .02), stroke (OAR vs HAR: 5.1% vs 17.35%; P = .01), and permanent paraplegia (OAR vs HAR: 2.79% vs 6.08%; P = .006) were lower in the OAR group than that in the HAR group. Although there was no statistically significant difference in 1-year survival rates (HAR vs OAR: hazard ratio [HR]: 1.54; P = .10), the 3-year and 5-year survivals were significantly higher in the OAR group than that in the HAR group (HAR vs OAR: HR: 1.69; P = .01; HAR vs OAR: HR: 1.68; P = .01). In the PSM subgroup, the OAR group was also significantly superior to the HAR group in terms of 3-year and 5-year survivals (HAR vs OAR: HR: 1.73; P = .04; HAR vs OAR: HR: 1.67; P = .04). The reintervention rate in the HAR group was significantly higher than that in the OAR group (OAR vs HAR: 8.24% vs 16.01%; P = .01). The most common reintervention was postoperative bleeding (8.07%) in the OAR group and endoleak (9.67%) in the HAR group. CONCLUSIONS: Our meta-analysis revealed that debranching HAR was associated with fewer perioperative complications than the OAR group, except for postoperative permanent paraplegia, reintervention, and stroke events. The OAR group demonstrated better 3-year and 5-year survivals than the debranching HAR group. However, patients in the OAR group had fewer comorbid factors and were younger than those in the HAR group. High-quality studies and well-powered randomized trials are needed to further evaluate this evolving field.

Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males.

Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.

STAT3 mediates ECM stiffness-dependent progression in ovarian cancer.

The treatment of ovarian cancer remains a medical challenge and its malignant progression is connected with obvious changes in both tissue and cell stiffness. However, the accurate mechanical-responsive molecules and mechanism remains unclear in ovarian cancer. Based on our previous results combined with the crucial regulatory role of STAT3 in the malignant progression of various cancer types, we want to investigate the relationship between STAT3 and matrix stiffness in ovarian cancer and further explore the potential mechanisms. Collagen-coated polyacrylamide gels (1, 6, and 60 kPa) were prepared to mimic soft or hard matrix stiffness. Western blotting, qRT-PCR, flow cytometry, IHC, EdU assays, and TEM were used to evaluate the effect of STAT3 in vitro under different matrix stiffnesses. Furthermore, a BALB/c nude mouse model was established to assess the relationship in vivo. Our results confirmed the differential expression of STAT3/p-STAT3 not only in normal and malignant ovarian tissues but also under different matrix stiffnesses. Furthermore, we verified that STAT3 was a mechanically responsive gene both in vitro and in vivo, and the mechanical response was carried out by altering the migration-related molecules (TNFAIP1) and adhesion-related molecules (LPXN, CNN3). The novel findings suggest that STAT3, a potential therapeutic target for clinical diagnosis and treatment, is a mechanically responsive gene that responds to matrix stiffness, particularly regulation in migration and adhesion in the progression of ovarian cancer.

Complete genome sequence of a novel robigovirus infecting Mentha arvensis.

The complete genomic sequence of a novel robigovirus, provisionally named "Mentha arvensis robigovirus 1" (MARV1), was determined by combining next-generation sequencing (NGS), reverse transcription polymerase chain reaction (RT-PCR), and rapid amplification of cDNA ends (RACE) PCR. The complete genomic sequence of this new virus is 7617 nucleotides in length, excluding the 3' poly(A) tail. The MARV1 genome encodes a putative replicase, "triple gene block" proteins, and a coat protein. Phylogenetic analysis demonstrated that MARV1 is a member of the genus Robigovirus, with closest relationships to African oil palm ringspot virus (AOPRV). Furthermore, MARV1-derived small interfering RNAs (siRNAs) showed typical patterns of plant-virus-derived siRNAs produced by the host antiviral RNA interference pathway. This is the first report of a plant virus of the genus Robigovirus in M. arvensis.

Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis.

Osteoporosis results from overactivation of osteoclasts. There are currently few drug options for treatment of this disease. Since the successful development of allosteric inhibitors, phosphatases have become attractive therapeutic targets. Protein phosphatase 1, regulatory subunit 15 A (PPP1R15A), is a stress-responsive protein, which promotes the UPR (unfolded protein response) and restores protein homeostasis. In this study we investigated the role of PPP1R15A in osteoporosis and osteoclastogenesis. Ovariectomy (OVX)-induced osteoporosis mouse model was established, osteoporosis was evaluated in the left femurs using micro-CT. RANKL-stimulated osteoclastogenesis was used as in vitro models. We showed that PPP1R15A expression was markedly increased in BMMs derived from OVX mice and during RANKL-induced osteoclastogenesis in vitro. Knockdown of PPP1R15A or application of Sephin1 (a PPP1R15A allosteric inhibitor in a phase II clinical trial) significantly inhibited osteoclastogenesis in vitro. Sephin1 (0.78, 3.125 and 12.5 µM) dose-dependently mitigated the changes in NF-κB, MAPK, and c-FOS and the subsequent nuclear factor of activated T cells 1 (NFATc1) translocation in RANKL-stimulated BMMs. Both Sephin1 and PPP1R15A knockdown increased the phosphorylated form of eukaryotic initiation factor 2α (eIF2α); knockdown of eIF2α reduced the inhibitory effects of Sephin1 on NFATc1-luc transcription and osteoclast formation. Furthermore, Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice, injection of Sephin1 (4, 8 mg/kg, i.p.) every two days for 6 weeks significantly inhibited bone loss, and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation, and genetic inhibition or allosteric inhibitors of PPP1R15A, such as Sephin1, can be used to treat osteoporosis. This study revealed that PPP1R15A expression was increased in osteoporosis in both human and mice. Inhibition of PPP1R15A by specific knockdown or an allosteric inhibitor Sephin1 mitigated murine osteoclast formation in vitro and attenuated ovariectomy-induced osteoporosis in vivo. PPP1R15A inhibition also suppressed pathogenic osteoclastogenesis in CD14+ monocytes from osteoporosis patients. These results identify PPP1R15A as a novel regulator of osteoclastogenesis and a valuable therapeutic target for osteoporosis.

Momordica charantia L.-derived exosome-like nanovesicles stabilize p62 expression to ameliorate doxorubicin cardiotoxicity.

BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.

The usage and costs of national drug price-negotiated anticancer medicines in a first-tier city in Northeast China: a study based on health insurance data.

BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China. METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region. RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend. CONCLUSION: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.

Health and care workers in long-term care facilities and their role in preventing emerging infectious diseases: A scoping review.

BACKGROUND: The COVID-19 pandemic has had a tremendous impact on healthcare systems worldwide. In particular, long-term care facilities have proved more susceptible to infection as they care for vulnerable populations at high risk of chronic illness. How this impacts the role and core competencies of health and care workers in these facilities remains less understood. AIM: Describe how health and care workers contribute to the prevention of emerging infectious diseases in long-term care facilities. DESIGN: A scoping review. METHODS: A systematic search of literature dating from 2002 to 2022 was conducted in the following databases: EMBASE, Medline (Ovid), Cochrane Library, CINAHL Plus with Full Text (EBSCOhost), Web of Science, and AgeLine. Studies were selected if they focused on health and care workers in long-term care facilities, offered a perspective on the prevention of emerging infectious diseases or infection prevention and control, and were original qualitative or quantitative studies in English. Data were extracted, cross-checked and analyzed by two researchers, and any difference in views regarding the appropriateness of literature would be resolved by consulting a third researcher. An inductive descriptive approach was applied for the analysis of results, and themes were established via consensus meetings. RESULTS: A total of fourteen studies from Asia, Europe, and the Americas were included. Three themes emerged from the review: "The roles of health and care workers evolve with the times", "The core competencies of health and care workers are essential for preventing emerging infectious diseases in long-term care facilities" and "The key to successful prevention of emerging infectious diseases in long-term care facilities is through a systematic, comprehensive effort that mobilize health and care workers at all levels". Health and care workers had to take on increasingly complex roles and rely on their core competencies to cope with epidemic changes, and facility resources, employee quality and management models were found to have significantly improved infection prevention and control outcomes. CONCLUSIONS: The roles of health and care workers are evolving, and effective infection prevention within long-term care facilities depends on their ability to perform core competencies with skill and confidence. Moreover, a systematic, comprehensive framework, for which this paper proposes three guidelines, is urgently needed to ensure consistent policy implementation within the facility as well as support and access to resources for health and care workers. CLINICAL RELEVANCE: Infection prevention efforts within long-term care facilities must take into account the evolving roles of health and care workers, with a focus on guaranteeing access to resources, training and support that will help them gain the core competencies necessary for juggling those roles. In addition, there is an urgent need for research instruments that will help assess those competencies and identify areas of improvement.

Discovery of Sesquiterpene Lactones with Cytotoxicity from the Herb of Youngia japonica.

In the process of searching for anti-breast cancer agents, five sesquiterpene lactones (1-5), including two previously undescribed ones, yjaponica B-C (1-2), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1 cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC50 value of 10.60 µM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl-2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti-breast cancer agent.

Establishment and validation of a nomogram for dropout intention in Chinese early year medical undergraduates.

BACKGROUND: The attrition rate of Chinese medical students is high. This study utilizes a nomogram technique to develop a predictive model for dropout intention among Chinese medical undergraduates based on 19 individual and work-related characteristics. METHOD: A repeated cross-sectional study was conducted, enrolling 3536 medical undergraduates in T1 (August 2020-April 2021) and 969 participants in T2 (October 2022) through snowball sampling. Demographics (age, sex, study phase, income, relationship status, history of mental illness) and mental health factors (including depression, anxiety, stress, burnout, alcohol use disorder, sleepiness, quality of life, fatigue, history of suicidal attempts (SA), and somatic symptoms), as well as work-related variables (career choice regret and reasons, workplace violence experience, and overall satisfaction with the Chinese healthcare environment), were gathered via questionnaires. Data from T1 was split into a training cohort and an internal validation cohort, while T2 data served as an external validation cohort. The nomogram's performance was evaluated for discrimination, calibration, clinical applicability, and generalization using receiver operating characteristic curves (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). RESULT: From 19 individual and work-related factors, five were identified as significant predictors for the construction of the nomogram: history of SA, career choice regret, experience of workplace violence, depressive symptoms, and burnout. The AUC values for the training, internal validation, and external validation cohorts were 0.762, 0.761, and 0.817, respectively. The nomogram demonstrated reliable prediction and discrimination, with adequate calibration and generalization across both the training and validation cohorts. CONCLUSION: This nomogram exhibits reasonable accuracy in foreseeing dropout intentions among Chinese medical undergraduates. It could guide colleges, hospitals, and policymakers in pinpointing students at risk, thus informing targeted interventions. Addressing underlying factors such as depressive symptoms, burnout, career choice regret, and workplace violence may help reduce the attrition of medical undergraduates. TRIAL REGISTRATION: This is an observational study. There is no Clinical Trial Number associated with this manuscript.

Complementary use of visual and olfactory cues to assess capture of Bactrocera dorsalis (Hendel): Implementation and field verification via an IoT-based automatic monitoring system.

This study examined the effect of combining visual and olfactory cues to attract oriental fruit flies (OFFs). Six different colored light-emitting diodes (LEDs) served as a visual attractant and methyl eugenol served as olfactory bait to lure male flies. An internet of things (IoT)-based pest monitoring system, consisting of sensor nodes, a gateway, and automatic counting traps, was deployed in the field to automatically collect environmental data and pest counts. The results of the calibrated experiments indicated that green, yellow, or red LEDs exhibited better performance in attracting flies than white, purple, or blue LEDs or no LEDs. With an accurate combination of visual and olfactory cues, the proposed IoT-based pest monitoring system may be an effective tool in agricultural pest management, given its advantages for efficiently capturing OFFs in a labor and time saving manner, providing accurate information regarding increases in pest populations, and enabling long-term, real-time data collection.

Discovery of sesquiterpene lactones with anti-inflammatory effect from Youngia japonica.

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.