Genomic and Metagenomic Insights into the Distribution of Nicotine-degrading Enzymes in Human Microbiota.

Introduction: Nicotine degradation is a new strategy to block nicotine-induced pathology. The potential of human microbiota to degrade nicotine has not been explored. Aims: This study aimed to uncover the genomic potentials of human microbiota to degrade nicotine. Methods: To address this issue, we performed a systematic annotation of Nicotine-Degrading Enzymes (NDEs) from genomes and metagenomes of human microbiota. A total of 26,295 genomes and 1,596 metagenomes for human microbiota were downloaded from public databases and five types of NDEs were annotated with a custom pipeline. We found 959 NdhB, 785 NdhL, 987 NicX, three NicA1, and three NicA2 homologs. Results: Genomic classification revealed that six phylum-level taxa, including Proteobacteria, Firmicutes, Firmicutes_A, Bacteroidota, Actinobacteriota, and Chloroflexota, can produce NDEs, with Proteobacteria encoding all five types of NDEs studied. Analysis of NicX prevalence revealed differences among body sites. NicX homologs were found in gut and oral samples with a high prevalence but not found in lung samples. NicX was found in samples from both smokers and non-smokers, though the prevalence might be different. Conclusion: This study represents the first systematic investigation of NDEs from the human microbiota, providing new insights into the physiology and ecological functions of human microbiota and shedding new light on the development of nicotine-degrading probiotics for the treatment of smoking-related diseases.

The role and mechanisms of cordycepin in inhibiting cancer cells.

With the escalating incidence and mortality rates of cancer, there is an ever-growing emphasis on the research of anticancer drugs. Cordycepin, the primary nucleoside antibiotic isolated from Cordyceps militaris, has emerged as a remarkable agent for cancer prevention and treatment. Functioning as a natural targeted antitumor drug, cordycepin assumes an increasingly pivotal role in cancer therapy. This review elucidates the mechanisms of cordycepin in inhibiting tumor cell proliferation, inducing apoptosis, as well as its capabilities in suppressing angiogenesis and metastasis. Moreover, the immunomodulatory effects of cordycepin in cancer treatment are explored. Additionally, the current status, challenges, and future prospects of cordycepin application in clinical trials are briefly discussed. The objective is to provide a valuable reference for the utilization of cordycepin in cancer treatment.

Characterizing Growth-Retarded Japanese Eels (Anguilla japonica): Insights into Metabolic and Appetite Regulation.

During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone (gh) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes (npy and ghrelin) were dramatically downregulated, whereas anorexigenic genes (crh and pyy) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica. The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica, providing novel ideas for enhancing fish growth.

Factors influencing the survival status of the hip joint in post-collapse femoral head necrosis.

BACKGROUND: Despite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed "survival with collapse". This study aims to identify the characteristics of patients suitable for "survival with collapse" in cases of ONFH. METHODS: This cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3-23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors' diagnostic efficacy. RESULTS: The favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p < 0.05). Multivariate logistic regression identified collapse < 3 mm(OR:14.49, 95%CI: 3.52-59.68, p < 0.001), JIC types B (OR: 11.08, 95% CI: 1.07-115.12, p < 0.05) and C1(OR: 5.18, 95% CI: 1.47-18.20, p < 0.05) as independent protective factors for hip function, while BMI (OR: 0.76, 95% CI: 0.59-0.97, p = 0.029) was an independent risk factor. ROC curve analysis demonstrated that both collapse degree (AUC = 0.798, sensitivity = 91.3%, specificity = 68.3%, p < 0.0001) and JIC classification (AUC = 0.787, sensitivity = 80.4%, specificity = 73.2%, p < 0.0001) had satisfactory diagnostic value for hip function. Combining JIC classification and collapse degree (AUC = 0.868, sensitivity = 76.1%, specificity = 85.4%, p < 0.0001) significantly enhanced diagnostic efficacy compared to using either alone (p < 0.05). CONCLUSION: In ONFH, femoral head collapse does not necessarily determine a poor prognosis. Patients with mild collapse (< 3 mm) and preserved anterolateral wall are more likely to retain satisfactory hip function, making them candidates for "survival with collapse."

Surgical Innovation: Comparative Efficacy of Navigation-Assisted Modified MIS-TLIF and Traditional MIS-TLIF in Treating Low-Grade Isthmic Spondylolisthesis in the Elderly.

OBJECTIVE: To compare the efficacy of navigation-assisted modified MIS-TLIF (Minimally invasive transforaminal lumbar interbody fusion) and MIS-TILF in the treatment of low-grade isthmic spondylolisthesis in the elderly. METHODS: We retrospectively included elderly patients with low-grade isthmic spondylolisthesis who underwent surgical treatment at our hospital from January 2019 to January 2022. Based on the surgical method chosen according to the patient's personal preference, the patients were divided into the modified MIS-TLIF group and the MIS-TLIF group. The modified MIS-TLIF group underwent navigation-assisted MIS-TLIF, while the MIS-TLIF group underwent conventional MIS-TLIF. A total of 54 patients (34 males and 20 females) were included in this study, with 26 cases in the modified MIS-TLIF group and 28 cases in the MIS-TLIF group. Relevant data for this study were collected by an independent observer. The demographic characteristics, including age, gender, BMI, comorbidities, surgical level, Meyerding grade, and duration of symptoms before admission, were recorded and compared between the two groups. Perioperative parameters, such as operative time, intraoperative blood loss, postoperative drainage volume, bed rest time, and hospital stay, were also recorded and compared. The lumbar pain visual analog scale (BP-VAS), Oswestry Disability Index (ODI), and lumbar JOA scores were recorded preoperatively and at 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively to evaluate functional recovery in both groups. At 12 months postoperatively, patient satisfaction was assessed using the Macnab criteria (with satisfaction defined as the number of excellent and good outcomes divided by the total number in the group × 100%). The rate of vertebral slippage was recorded preoperatively, at 1 week postoperatively, and at 12 months postoperatively. The accuracy of screw placement was evaluated by CT scan at 1 week postoperatively, and interbody fusion was assessed by CT scan at 12 months postoperatively. Surgical complications were recorded, and their incidence was calculated. RESULTS: The intraoperative blood loss, postoperative drainage volume, bed rest time and hospital stay in the modified MIS-TLIF group were less than those in the MIS-TLIF group (P< 0.05). The BP-VAS (Back Pain Visual Analogue Scale), ODI (Oswestry Disability Index), and JOA (Japanese Orthopaedic Association) modified MIS-TLIF groups improved significantly compared with the MIS-TLIF group at 1 week, 1 month, 3 months, and 6 months after surgery, and the differences between groups were statistically significant (P<0.05). The excellent and good rate of modified MIS-TLIF group was higher than that of MIS-TLIF group, and the difference had statistical significance (P<0.05). The accuracy of screw placement in the modified MIS-TLIF group was higher than that in the MIS-TLIF group, and the difference was statistically significant (P<0.05). The fusion rate in the modified MIS-TLIF group was higher than that in the MIS-TLIF group at 12 months after surgery, and the difference was statistically significant (P<0.05). No statistical difference in the incidence rate of complications between the two groups. CONCLUSION: Compared with MIS-TLIF, navigation-assisted modified MIS-TLIF has the advantages of less trauma, rapid recovery, accurate screw placement, high fusion rate, high surgical satisfaction and good safety.

Complete genome sequence of the 4-hydroxybenzoate-degrading bacterium Gymnodinialimonas sp. 57CJ19, a potential novel species from intertidal sediments.

A bacterium Gymnodinialimonas sp. 57CJ19, was isolated from the intertidal sediments of Aoshan Bay, and further assays showed that it has the ability to degrade the antibacterial preservative 4-hydroxybenzoate. The complete genome sequence was sequenced, and phylogenomic analyses indicated that strain 57CJ19 represents a potential novel species in the genus Gymnodinialimonas (family Rhodobacteraceae). Its genome contains a 3,861,607-bp circular chromosome with 61.25% G + C content. Gene prediction revealed 3716 protein-encoding genes, 41 tRNA genes, 3 rrn operons, and 3 non-coding RNA genes. Functional annotation revealed a complete metabolic pathway for 4-hydroxybenzoate. The genome sequence of strain 57CJ19 provides new insights into the potential and underlying genomic basis of aromatic compound pollutant degradation by marine bacteria.

Progesterone (P4) ameliorates cigarette smoke-induced chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. METHODS AND RESULTS: The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. CONCLUSION: P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.

Hoffmeister Effect Optimized Hydrogel Electrodes with Enhanced Electrical and Mechanical Properties for Nerve Conduction Studies.

Flexible epidermal electrodes hold substantial promise in realizing human electrophysiological information collections. Conventional electrodes exhibit certain limitations, including the requirement of skin pretreatment, reliance on external object-assisted fixation, and a propensity of dehydration, which severely hinder their applications in medical diagnosis. To tackle those issues, we developed a hydrogel electrode with both transcutaneous stimulation and neural signal acquisition functions. The electrode consists of a composite conductive layer (CCL) and adhesive conductive hydrogel (ACH). The CCL is designed as a laminated structure with high conductivity and charge storage capacity (CSC). Based on the optimization of Hoffmeister effect, the ACH demonstrates excellent electrical (resistivity of 3.56 Ω·m), mechanical (tensile limit of 1,650%), and adhesion properties (peeling energy of 0.28 J). The utilization of ACH as electrode/skin interface can reduce skin contact impedance and noise interference and enhance the CSC and charge injection capacity of electrodes. As a proof of concept, peripheral nerve conduction studies were performed on human volunteers to evaluate the as-fabricated hydrogel electrodes. Compared with the commercial electrodes, our hydrogel electrodes achieved better signal continuity and lower distortion, higher signal-to-noise ratio (~35 dB), and lower stimulation voltages (up to 27% lower), which can improve the safety and comfort of nerve conduction studies.

Photo-crosslinking methacrylated-amylopectin/polyacrylamide hydrogels loading curcumin for applications as degradable, injectable, and antibacterial wound dressings.

The preparation of biodegradable and antibacterial hydrogels has important clinical value. In this work, a novel strategy has been developed to prepare degradable hydrogel dressings without chemical crosslinking agent using methacrylate anhydride (MA)-modified amylopectin (APMA) and polyacrylamide (PAM). After introducing CC bonds, APMA/PAM hydrogels can be formed under light irradiation. This strategy improves the gelling ability of AP and degradation properties of the hydrogel by avoiding the addition of crosslinking agent. The degradation rate of APMA/PAM hydrogel is 74.04 ± 0.69 % within 12 weeks, while that of APMA/PAM hydrogel containing crosslinking agent is only 38.5 ± 0.1 %. The APMA/PAM hydrogel loading curcumin (Cur) (APMA/PAM-Cur) exhibits high antibacterial efficiency of 98.29 ± 0.41 % and 97.18 ± 0.81 % against S. aureus and E. coli, respectively, with light irradiation. Animal experiments show that the APMA/PAM-Cur hydrogel reduces the infiltration of inflammatory factors, increases the density of collagen, and makes the newly formed granulation tissue thicker and tighter. This study not only proves the promising potential of the APMA/PAM-Cur hydrogel as degradable and antibacterial wound dressing for clinical treatment, but also provides a new strategy for developing low-cost, degradable, and antibacterial wound dressings and reducing antibiotic abuse and environmental pollution caused by medical waste.

Real-world prevalence of adverse events with first-line systemic therapies among patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The current guidelines for treating metastatic castration-sensitive prostate cancer (mCSPC) recommend treatment intensification of androgen deprivation therapy (ADT) with the addition of an androgen receptor pathway inhibitor (ARPI), with or without docetaxel. However, the adoption of these treatment options has been slow, leading to therapeutic inertia. This real-world study was conducted to investigate the occurrence of adverse events (AEs) among treated patients diagnosed with mCSPC in the United States. METHODS: This retrospective claim review estimated the occurrence of AEs among patients with mCSPC from January 2014 to June 2021 in the PharMetrics® Plus data set. The study focused on 10 common AEs (fatigue/asthenia, gastrointestinal [GI] AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, sexual function AEs, anemia, hypertension, pain, and edema) known to occur in ≥10% of patients and ≥2% more prevalent than those treated with ADT alone as selected from the US Food and Drug Administration prescribing information and published results from clinical trials. Proportions of patients experiencing these AEs at Day 90, 180, and then every 180 days until month 30 during the follow-up period were estimated using cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting (IPTW) across four treatment groups: ADT alone, ADT + nonsteroidal anti-androgen (NSAA) (bicalutamide, nilutamide, or flutamide), ADT + docetaxel, and ADT + ARPIs (abiraterone, apalutamide, or enzalutamide). ADT-alone cohort was the reference group for all comparisons. RESULTS: A total of 4145 patients were included (ADT alone: 2318, ADT + NSAA: 632, ADT + docetaxel: 471, ADT + ARPIs: 724). At baseline, median (interquartile range [IQR]) age was 64.3 (60.1-73.1) years; most common sites of metastasis were bone only (n = 1886, 45.5%) and node only (n = 1237, 29.8%); most used medications were pain medications (n = 2182, 52.6%) and corticosteroids (n = 1213, 29.3%). Median (IQR) duration of follow-up 10.2 (6.1-16.6) months in ADT alone, 6.7 (4.1-11.5) months in ADT + NSAA, 5.1 (4.3-5.9) months in ADT + docetaxel, and 11.0 (6.6-17.0) months in ADT + ARPI cohort. The reported AEs increased over time for all assessed AEs, across all treatment groups. Compared with ADT alone, no statistically significant difference in the proportion of patients with AEs was seen in the ADT + ARPI or ADT + NSAA cohorts at months 3 and 12; a significantly higher proportion of patients in the ADT + docetaxel cohort experienced 6 of the 10 assessed AEs at month 3 (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia). During the follow-up period, on IPTW analysis, compared with ADT alone, a significantly higher proportion of patients experienced AEs with seven AEs in the ADT + docetaxel group (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia, edema; p < 0.001 for all seven), three AEs in the ADT + ARPI group (hot flash, p = 0.05; anemia, p = 0.01; edema, p = 0.019), and one AE in the ADT + NSAA group (anemia, p = 0.029). The proportion of patients with sexual function AE did not significantly differ between the treatment groups and ADT alone. CONCLUSION: Results of this large, real-world study demonstrated that all treatment groups experienced an increase in the rates of AEs over time, including ADT alone. Most AE rates with ADT + ARPIs were comparable with ADT + NSAA and not significantly different from ADT alone. ADT + docetaxel cohort was associated with significantly higher rates for all AEs over time except hypertension, sexual dysfunction, and pain. This study provides real-world evidence on AEs, beyond controlled clinical trials, and may assist healthcare providers to make better-informed decisions about disease management among patients with mCSPC.

Clinical application of ctDNA in early diagnosis, treatment and prognosis of patients with non-small cell lung cancer.

Lung cancer is one of the most common malignancies worldwide, with non-small cell lung cancer (NSCLC) being the most common type. As understanding of precise treatment options for NSCLC deepens, circulating tumor DNA (ctDNA) has emerged as a potential biomarker that has become a research hotspot and may represent a new approach for the individualized diagnosis and treatment of NSCLC. This article reviews the applications of ctDNA for the early screening of patients with NSCLC, guiding targeted therapy and immunotherapy, evaluating chemotherapy and postoperative efficacy, assessing prognosis and monitoring recurrence. With the in-depth study of the pathogenesis of NSCLC, plasma ctDNA may become an indispensable part of the precise treatment of NSCLC, which has great clinical application prospects.

[Box: see text].

Treatment patterns and outcomes in patients with nonmetastatic castration-resistant prostate cancer in the United States.

Aim: Androgen receptor pathway inhibitors (ARPIs) prolong metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). This study aimed to evaluate real-world treatment patterns, utilization and survival outcomes in patients with nmCRPC. Patients & methods: This retrospective cohort study used Optum database electronic health records of patients with nmCRPC from 1 January 2007 to 31 December 2020 in the US. Results: Of 1955 patients, >80% received androgen-deprivation therapy (ADT) alone or ADT + first-generation nonsteroidal antiandrogen (NSAA) as first-line treatment, while only 8.24% received ADT + ARPI. ADT + ARPI remained underutilized even among those with high-risk nmCRPC. Further, ADT + NSAA had no survival benefit compared with ADT alone. Conclusion: Practice-improvement strategies are needed for treatment intensification with ARPIs for patients with nmCRPC.

Prostate cancer cells often use hormones called androgens to grow and survive. Hormone therapy is a treatment that lowers the amount of these hormones in the body to slow down the cancer's growth. It includes androgen-deprivation therapy (ADT), which can either be used alone or along with nonsteroidal antiandrogens (NSAAs) or with androgen receptor pathway inhibitors (ARPIs). Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as prostate cancer that has not spread to other parts of the body but exhibits rising levels of serum prostate-specific antigen despite surgery or ADT to reduce androgens. Research shows that ARPIs can improve survival in patients with nmCRPC, but more data on its use are needed. This study looked at the electronic health records of patients with nmCRPC to review the treatment they had received and their survival. Between 2008 and 2020, most patients received ADT alone or with NSAA. Even though the number of patients receiving ADT with ARPI increased during this period, it remained underused, even in patients with a high risk of cancer spreading to other body parts. Post-2018, even after 2 years of these drugs being available, only about one in five patients received ADT with ARPI. Also, people who received ADT with NSAA did not have a longer survival than patients treated with ADT alone. The study indicates that ARPIs, which could improve survival of patients with nmCRPC, are not being utilized optimally. Strategies that promote early use of ARPIs are needed to improve survival of patients with nmCRPC.

Assessing the global distribution and risk of harmful microalgae: A focus on three toxic Alexandrium dinoflagellates.

Harmful dinoflagellates and their resulting blooms pose a threat to marine life and human health. However, to date, global maps of marine life often overlook harmful microorganisms. As harmful algal blooms (HABs) increase in frequency, severity, and extent, understanding the distribution of harmful dinoflagellates and their drivers is crucial for their management. We used MaxEnt, random forest, and ensemble models to map the habitats of the representative HABs species in the genus Alexandrium, including A. catenella, A. minutum, and A. pacificum. Since species occurrence records used in previous studies were solely morphology-based, potentially leading to misidentifications, we corrected these species' distribution records using molecular criteria. The results showed that the key environmental drivers included the distance to the coastline, bathymetry, sea surface temperature (SST), and dissolved oxygen. Alexandrium catenella thrives in temperate to cold zones and is driven by low SST and high oxygen levels. Alexandrium pacificum mainly inhabits the Temperate Northern Pacific and prefers warmer SST and lower oxygen levels. Alexandrium minutum thrives universally and adapts widely to SST and oxygen. By analyzing the habitat suitability of locations with recorded HAB occurrences, we found that high habitat suitability could serve as a reference indicator for bloom risk. Therefore, we have proposed a qualitative method to spatially assess the harmful algae risk according to the habitat suitability. On the global risk map, coastal temperate seas, such as the Mediterranean, Northwest Pacific, and Southern Australia, faced higher risks. Although HABs currently have restricted geographic distributions, our study found these harmful algae possess high environmental tolerance and can thrive across diverse habitats. HAB impacts could increase if climate changes or ocean conditions became more favorable. Marine transportation may also spread the harmful algae to new unaffected ecosystems. This study has pioneered the assessment of harmful algal risk based on habitat suitability.

[Quality evaluation and grading standard discussion on Cinnamomi Ramulus].

This study explored the relationship between the appearance traits and internal components of Cinnamomi Ramulus pieces, so as to provide a reference for the quality evaluation and the formulation of grade standards. This study determined the appearance traits and index component contents of 41 batches of Cinnamomi Ramulus pieces in the core producing areas of Guangxi and Guangdongand established the HPLC characteristic map method. The weight of the pieces, the narrowest diameter, and the widest diameter of the tr ansverse section were used as the indices of appearance traits. The content of index components(cinnamic acid and cinnamalde hyde)was determined by the established content determination method. The chromatographic characteristics were determinedon a Waters XBridge C_(18)(4. 6 mm×250 mm, 5 µm) column with a mobile phase consisting of 0. 1% phosphoric acidacetonitrile and gradient elution at the flow rate of 1 mL ·min~(-1). The column temperature was 30 ℃, and the detection wavelength was 254 nm. Cluster analysis, principal component analysis, and other stoichiometric methods were used to analyze the correlation between theap pearance traits and the index/characteristic components of Cinnamomi Ramulus pieces and compare the qu ality differences of the piecesfrom different batches and plac es. The results showed that the larger weight, the narrowest diameter, andthe widest diameter of the tra nsverse section indicated lowercontent of main indexes/characteristic components, and there was a synergistic decreasing trend amongd ifferent components. The overall quality of Cinnamomi Ramulus pieces in Guangdong Province and Guangxi Province was similar, but there were still differences between different origins and different batches of the same origin. It is scientific and feasible to evaluatethe quality of Cinnamomi Ramulus pieces and establish grading standards based on the appearance traits and index/character istic components. The research provides a more scientific and comprehensive basis for the quality control evaluation and standardformulation of Cinnamomi Ramulus.

Generational Immigration Status Modifies the Association Between Psychosocial Distress and Substance Use Among Alternative High School Students.

PURPOSE: Alternative high schools (AHS) are designed to provide individualized education, more flexible scheduling, and smaller class sizes for students referred out of traditional high school. AHS students report higher levels of substance use (SU) and face disproportionately higher levels of trauma and toxic stress than their traditional high school peers. We sought to examine whether generational immigration (GenIm) status modifies the association of mental health and SU among AHS students using a longitudinal study of 1,060 Southern California AHS students. METHODS: Subscales from the 21-item Depression Anxiety Stress Scale were administered. Effect modification was examined by GenIm status defined as first generation (born outside of the United States), second generation (born in the United States with a parent born outside the United States), or third generation (born in the United States with US-born parent(s)). Main outcomes included the number of times different substances were used in the past year over a 3-year period. RESULTS: Multilevel, negative binomial, covariate-adjusted latent growth curve models generated incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of the time-varying association between depression, anxiety, or stress and the use of cigarettes, e-cigarettes, cigars, alcohol, or marijuana. Multiple-group models examined effect modification by GenIm status. DISCUSSION: The link between mental health and SU was stronger among first- and second-generation students than third-generation students. For example, a one-unit increase in stress relative to the average stress of students from the same school was associated with an increase in the rate of e-cigarette use among first-generation (IRR = 2.03, 95% CI = 1.07-3.85), second-generation (IRR = 2.25, 95% CI = 1.86-2.72), and third-generation (IRR = 1.68, 95% CI = 1.31-2.16) students. Effective strategies tailored to subgroups of AHS students are needed to counter disparities between traditional and alternative school systems that may contribute to long-term trajectories of SU.

Transcriptomic and Metabolomic Analyses of Soybean Protein Isolate on Monascus Pigments and Monacolin K Production.

Monascus pigments (MPs) and monacolin K (MK) are important secondary metabolites produced by Monascus spp. This study aimed to investigate the effect of soybean protein isolate (SPI) on the biosynthesis of MPs and MK based on the analysis of physiological indicators, transcriptomes, and metabolomes. The results indicated that the growth, yellow MPs, and MK production of Monascus pilosus MS-1 were significantly enhanced by SPI, which were 8.20, 8.01, and 1.91 times higher than that of the control, respectively. The utilization of a nitrogen source, protease activity, the production and utilization of soluble protein, polypeptides, and free amino acids were also promoted by SPI. The transcriptomic analysis revealed that the genes mokA, mokB, mokC, mokD, mokE, mokI, and mokH which are involved in MK biosynthesis were significantly up-regulated by SPI. Moreover, the glycolysis/gluconeogenesis, pyruvate metabolism, fatty acid degradation, tricarboxylic acid (TCA) cycle, and amino acid metabolism were effectively up-regulated by SPI. The metabolomic analysis indicated that metabolisms of amino acid, lipid, pyruvate, TCA cycle, glycolysis/gluconeogenesis, starch and sucrose, and pentose phosphate pathway were significantly disturbed by SPI. Thus, MPs and MK production promoted by SPI were mainly attributed to the increased biomass, up-regulated gene expression level, and more precursors and energies.

Construction of Highly Accurate Machine Learning Potential Energy Surfaces for Excited-State Dynamics Simulations Based on Low-Level Data Sets.

Machine learning is capable of effectively predicting the potential energies of molecules in the presence of high-quality data sets. Its application in the construction of ground- and excited-state potential energy surfaces is attractive to accelerate nonadiabatic molecular dynamics simulations of photochemical reactions. Because of the huge computational cost of excited-state electronic structure calculations, the construction of a high-quality data set becomes a bottleneck. In the present work, we first built two data sets. One was obtained from surface hopping dynamics simulations at the semiempirical OM2/MRCI level. Another was extracted from the dynamics trajectories at the CASSCF level, which was reported previously. The ground- and excited-state potential energy surfaces of ethylene-bridged azobenzene at the CASSCF computational level were constructed based on the former low-level data set. Although non-neural network machine learning methods can achieve good or modest performance during the training process, only neural network models provide reliable predictions on the latter external test data set. The BPNN and SchNet combined with the Δ-ML scheme and the force term in the loss functions are recommended for dynamics simulations. Then, we performed excited-state dynamics simulations of the photoisomerization of ethylene-bridged azobenzene on machine learning potential energy surfaces. Compared with the lifetimes of the first excited state (S1) estimated at different computational levels, our results on the E isomer are in good agreement with the high-level estimation. However, the overestimation of the Z isomer is unimproved. It suggests that smaller errors during the training process do not necessarily translate to more accurate predictions on high-level potential energies or better performance on nonadiabatic dynamics simulations, at least in the present case.

PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR.

Cancer stem cells (CSCs) are responsible for tumor chemoresistance, and the aryl hydrocarbon receptor (AHR) is indispensable for maintaining CSC characteristics. Here, we aimed to investigate how the interaction between progesterone receptor membrane component 1 (PGRMC1) and AHR contributes to the maintenance of CSC phenotypes in non-small cell lung cancer (NSCLC). Clinical data and tissue microarray analyses indicated that patients with elevated PGRMC1 expression had poorer prognoses. Moreover, PGRMC1 overexpression enhanced CSC phenotypes and chemotherapy resistance in vitro and in vivo by modulating AHR ubiquitination. We then determined the specific interaction sites between PGRMC1 and AHR. Mass spectrometry screening identified tripartite motif containing 56 (TRIM56) as the E3 ligase targeting AHR. Notably, PGRMC1 overexpression inhibited the interaction between TRIM56 and AHR. Overall, our study revealed a regulatory mechanism that involves PGRMC1, AHR, and TRIM56, providing insights for developing CSC-targeting strategies in NSCLC treatment.

[Spatio-temporal Evolution of Drought and Its Impact on Key Resources in the Important Ecological Functional Area: A Case Study in the Yellow River Basin].

This study explored the characteristics of spatial and temporal changes in drought in the Yellow River Basin from 2001 to 2020 based on TVPDI, surface runoff, vegetation net primary productivity, and grain yield data. Further, the effects of drought on water resources, grain resources, and vegetation resources were also analyzed using data spatialization methods, slope trend analysis, and Pearson correlation analysis. The results showed that:① The spatial distribution of drought in the Yellow River basin was stepped from southeast to northwest, and 60.6 % of the basin was in drought. The overall trend of drought in the basin was decreasing annually, and 94 % of the basin was gradually changing from drought to wet conditions, and the trend of drought from spring to winter decreased first and then increased. ② From the spatial and temporal changes in important resources in the basin, 53 % of the key surface runoff areas showed an increasing trend and were mainly located in the southwest of the basin; the net primary productivity (NPP) of vegetation and grain yield of food resources also showed an increasing trend. ③ Drought and the three types of resources showed significant spatial correlations, and the higher the degree of drought, the more significant the effects on surface runoff, vegetation productivity, and grain yield. However, the important resources in areas that had become wetter in recent years had not increased significantly, which indicated that the effects of drought on the three types of important resources had a time lag, and their lags had significant differences in spatial distribution and geographical differentiation patterns. This study has important theoretical implications for agricultural production, drought mitigation, and ecological conservation in the Yellow River Basin.

Potential molecular and cellular mechanisms of the effects of cuproptosis-related genes in the cardiomyocytes of patients with diabetic heart failure: a bioinformatics analysis.

Background: Diabetes mellitus is an independent risk factor for heart failure, and diabetes-induced heart failure severely affects patients' health and quality of life. Cuproptosis is a newly defined type of programmed cell death that is thought to be involved in the pathogenesis and progression of cardiovascular disease, but the molecular mechanisms involved are not well understood. Therefore, we aimed to identify biomarkers associated with cuproptosis in diabetes mellitus-associated heart failure and the potential pathological mechanisms in cardiomyocytes. Materials: Cuproptosis-associated genes were identified from the previous publication. The GSE26887 dataset was downloaded from the GEO database. Methods: The consistency clustering was performed according to the cuproptosis gene expression. Differentially expressed genes were identified using the limma package, key genes were identified using the weighted gene co-expression network analysis(WGCNA) method, and these were subjected to immune infiltration analysis, enrichment analysis, and prediction of the key associated transcription factors. Consistency clustering identified three cuproptosis clusters. The differentially expressed genes for each were identified using limma and the most critical MEantiquewhite4 module was obtained using WGCNA. We then evaluated the intersection of the MEantiquewhite4 output with the three clusters, and obtained the key genes. Results: There were four key genes: HSDL2, BCO2, CORIN, and SNORA80E. HSDL2, BCO2, and CORIN were negatively associated with multiple immune factors, while SNORA80E was positively associated, and T-cells accounted for a major proportion of this relationship with the immune system. Four enriched pathways were found to be associated: arachidonic acid metabolism, peroxisomes, fatty acid metabolism, and dorsoventral axis formation, which may be regulated by the transcription factor MECOM, through a change in protein structure. Conclusion: HSDL2, BCO2, CORIN, and SNORA80E may regulate cardiomyocyte cuproptosis in patients with diabetes mellitus-associated heart failure through effects on the immune system. The product of the cuproptosis-associated gene LOXL2 is probably involved in myocardial fibrosis in patients with diabetes, which leads to the development of cardiac insufficiency.