Exogenous Melatonin Modulates Photosynthesis and Antioxidant Systems for Improving Drought Tolerance of Sorghum Seedling.

Sorghum faces significant production challenges due to drought stress. Melatonin has been demonstrated to play a crucial role in coping with stresses in plants. This study investigated the effect of exogenous melatonin on the sorghum seedling growth, photosynthetic capacity, and antioxidant system under drought stress. The results indicated that drought stress inhibited the growth of sorghum seedlings by a marked reduction in leaf relative water content, along with a significant increase in both malondialdehyde and hydrogen peroxide content. The drought stress also led to a significant diminution in chlorophyll contents, thereby curtailing the capacity for light energy capture. Furthermore, the efficiency of the photosynthetic electron transport chain was adversely impacted. However, the application of exogenous melatonin notably mitigated the adverse effects on sorghum seedlings under the drought stress. Additionally, it stimulated an elevation in the photosynthetic rate and a decrease in non-photochemical quenching. The exogenous melatonin also facilitated the preservation of the chloroplast ultra-structure and boosted the activity of antioxidant enzymes and the content of non-enzymatic antioxidants. Cluster heat maps and principal component analysis further revealed significant correlations among various parameters under different treatment conditions. These results highlight melatonin's role in improving sorghum's drought tolerance, which is beneficial for agricultural management.

Detection of the Fatty Acid Metabolism-Linked Genes in Lung Adenocarcinoma as Biomarkers for Clinical Prognosis and Immunotherapeutic Targets.

BACKGROUND: Lung cancer, on a global scale, leads to the most common cases of cancer mortalities. Novel therapeutic approaches are urgently needed to disrupt this lethal disease. The rapid development of tumor immunology combining breakthroughs involving fatty acid metabolism brings possibilities. Directing fatty acid metabolism is supposed to help discover potential prognostic biomarkers and treatment targets for lung cancer. METHODS: Through searching the GSE140797 dataset, we identified genes related to fatty acid metabolism as well as fatty acid metabolism-related differentially expressed genes (DEGs). We applied various methods to ascertain the independent prognostic value of the DEGs. The methods we utilized entail prognostic analysis, differential expression analysis, as well as univariate and multivariate Cox regression analyses. The lasso Cox regression model was utilized in examining how DEGs correlate with the immune score, immune checkpoint, ferroptosis, methylation, and OCLR score. The expression levels of ACAT1 and ACSL3 in tissues derived from normal lung and lung adenocarcinoma (LUAD) tissues were compared by qRT-PCR. RESULTS: In this study, ACSL3 and ACAT1 were identified as fatty acid metabolism-related genes utilizing independent prognostic value and as a result, the risk prognostic model was built using these factors. qRT-PCR results implied that ACSL3 and ACAT1 expressions were upregulated and downregulated, correspondingly in tumor tissues. Additional evaluations suggested that ACSL3 and ACAT1 were affirmed to be remarkably correlated with the immune score, methylation, immune checkpoint, OCLR score, and ferroptosis. CONCLUSIONS: ACSL3 and ACAT1 were effective prognostic biomarkers and potential immunotherapeutic targets in LUAD.

PANoptosis: a new insight for oral diseases.

PANoptosis, a burgeoning area of research, is a unique type of programmed cell death typified by pyroptosis, apoptosis, and necroptosis, yet it defies singular classification by any one mode of death. The assembly and activation of PANoptosomes are pivotal processes in PANoptosis, with several PANoptosomes already identified. Linkages between PANoptosis and the pathophysiology of various systemic illnesses are established, with increasing recognition of its association with oral ailments. This paper aims to deepen understanding by conducting a comprehensive analysis of the molecular pathways driving PANoptosis and exploring its potential implications in oral diseases.

Implantable Microneedle-Mediated Eradication of Postoperative Tumor Foci Mitigates Glioblastoma Relapse.

Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2-3 cm) of the initial resected lesion due to the unreachable residual cancerous cells. Here, a completely biodegradable microneedle for surgical cavity delivery glioblastoma-associated macrophages (GAMs)-activating immune nano-stimulator that mitigates glioblastoma relapse is reported. The residual tumor lesion-directed biocompatible microneedle releases the nano-stimulator and toll-like receptor 9 agonist in a controlled manner until the microneedles completely degrade over 1 week, efferently induce in situ phonotypic shifting of GAMs from anti- to pro-inflammatory and the tumor recurrence is obviously inhibited. The implantable microneedles offer a significant improvement over conventional transdermal ones, as they are 100% degradable, ensuring safe application within surgical cavities. It is also revealed that the T cells are recruited to the tumor niche as the GAMs initiate anti-tumor response and eradicate residual GBM cells. Taken together, this work provides a potential strategy for immunomodulating the postoperative tumor niche to mitigate tumor relapse in GBM patients, which may have broad applications in other malignancies with surgical intervention.

The role of serum magnesium in the prediction of acute kidney injury after total aortic arch replacement: A prospective observational study.

Background: Considerable morbidity and death are associated with acute kidney damage (AKI) following total aortic arch replacement (TAAR). The relationship between AKI following TAAR and serum magnesium levels remains unknown. The intention of this research was to access the predictive value of serum magnesium levels on admission to the Cardiovascular Surgical Intensive Care Unit (CSICU) for AKI in patients receiving TAAR. Methods: From May 2018 to January 2020, a prospective, observational study was performed in the Guangdong Provincial People's Hospital CSICU. Patients accepting TAAR admitted to the CSICU were studied. The Kidney Disease: Improving Global Outcomes (KDIGO) definition of serum creatinine was used to define AKI, and KDIGO stages two or three were used to characterize severe AKI. Multivariable logistic regression and area under the curve receiver-operator characteristic curve (AUC-ROC) analysis were conducted to assess the predictive capability of the serum magnesium for AKI detection. Finally, the prediction model for AKI was established and internally validated. Results: Of the 396 enrolled patients, AKI occurred in 315 (79.5%) patients, including 154 (38.8%) patients with severe AKI. Serum magnesium levels were independently related to the postoperative AKI and severe AKI (both, P < 0.001), and AUC-ROCs for predicting AKI and severe AKI were 0.707 and 0.695, respectively. Across increasing quartiles of serum magnesium, the multivariable-adjusted odds ratios (95% confidence intervals) of postoperative AKI were 1.00 (reference), 1.04 (0.50-2.82), 1.20 (0.56-2.56), and 6.19 (2.02-23.91) (P for Trend < 0.001). When serum magnesium was included to a baseline model with established risk factors, AUC-ROC (0.833 vs 0.808, P = 0.050), reclassification (P < 0.001), and discrimination (P = 0.002) were further improved. Conclusions: Serum magnesium levels on admission are an independent predictor of AKI. In TAAR patients, elevated serum magnesium levels were linked to an increased risk of AKI. In addition, the established risk factor model for AKI can be considerably improved by the addition of serum magnesium in TAAR patients hospitalized in the CSICU.

Association Between Length of Buprenorphine or Methadone Use and Nonprescribed Opioid Use Among Individuals with Opioid Use Disorder: A Cohort Study.

BACKGROUND: Opioid use disorder (OUD) affects millions of individuals each year in the United States. Patient retention in medications for opioid use disorder (MOUD) treatment is suboptimal. This study examines and quantifies the associations between each additional month of buprenorphine or methadone use and nonprescribed opioid use. METHODS: Data were obtained from an 18-month longitudinal, observational cohort study of patients (age ≥ 18 years) treated for OUD. Patients completed a baseline self-reported questionnaire between March 2018 and December 2019 and were asked to complete follow-up questionnaires at approximately 3-, 6-, 12-, and 18-months post-baseline until May 2021. Patients treated with buprenorphine or methadone, without taking other MOUD at least 12 months prior to baseline, were included. Outcomes included past 30-day use of prescription opioids nonmedically, heroin, or illegally made fentanyl. A multivariable, multilevel regression model with a binomial distribution and a logit link was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: This study included 353 patients taking buprenorphine (mean [standard deviation, SD] age 39 [11] years; 226 [64%] female), and 785 patients taking methadone (mean [SD] age 42 [12] years; 392 [50%] female). Each additional month of MOUD treatment was associated with a 25% decrease in the odds of past 30-day nonprescribed opioid use for patients taking buprenorphine (aOR [95% CI] = 0.75 [0.68-0.83]), and a 17% decrease for patients taking methadone (aOR = 0.83 [0.79-0.87]). The COVID-19 pandemic (aOR = 9.29 [2.96-29.17]; aOR = 3.19 [1.74-5.86]) and MOUD adverse reaction experiences (aOR = 3.07 [1.11-8.48]; aOR = 2.51 [1.01-6.22]) were significantly associated with higher odds of nonprescribed opioid use among buprenorphine and methadone groups. CONCLUSION: Among patients treated with buprenorphine or methadone, with each additional treatment month since baseline, those who continued with treatment appeared to be more likely to report 17% to 25% decreased odds of past 30-day nonprescribed opioid use. Our findings can be used by clinicians in the shared decision-making process with patients, emphasizing the value of sustained retention in MOUD.

A novel nomogram for predicting prolonged mechanical ventilation after acute type A aortic dissection surgery: a retrospective study investigating the impact of ventilation duration on postoperative outcomes.

OBJECTIVE: Acute type A aortic dissection (ATAAD) is a devastating cardiovascular disease with extraordinary morbidity and mortality. Prolonged mechanical ventilation (PMV) is a common complication following ATAAD surgery, leading to adverse outcomes. This study aimed to investigate the correlation between mechanical ventilation time (MVT) and prognosis and to devise a nomogram for predicting PMV after ATAAD surgery. METHODS: This retrospective study enrolled 1049 ATAAD patients from 2011 to 2019. Subgroups were divided into < 12 h, 12 h to < 24 h, 24 h to < 48 h, 48 h to < 72 h, and ≥ 72 h according to MVT. Clinical characteristics and outcomes were compared among the groups. Using multivariable logistic regression analyses, we investigated the relationship between each stratification of MVT and mortality. A nomogram was constructed based on the refined multivariable logistic regression model for predicting PMV. RESULTS: The total mortality was 11.8% (124/1049). The results showed that the groups with MVT 48 h to < 72 h and ≥ 72 h had significantly higher operative mortality compared to other MVT categories. Multivariate logistic regression analysis showed that MVT ≥72 h was significantly associated with higher short-term mortality. Thus, a nomogram was presented to elucidate the association between PMV (MVT ≥72 h) and risk factors including advanced age, preoperative cerebral ischemia, ascending aorta replacement, concomitant coronary artery bypass grafting (CABG), longer cardiopulmonary bypass (CPB), and large-volume intraoperative fresh frozen plasma (FFP) transfusion. The nomogram exhibited strong predictive performance upon validation. CONCLUSIONS: Safely extubating patients within 72 h after ATAAD surgery is crucial for achieving favorable outcomes. The developed and validated nomogram provides a valuable tool for predicting PMV and optimizing postoperative care to improve patient prognosis. This novel nomogram has the potential to guide clinical decision-making and resource allocation in the management of ATAAD patients.

Prolonged mechanical ventilation (PMV) is a common complication following ATAAD surgery, leading to adverse outcomes.Safely extubating patients within 72 hours after ATAAD surgery is crucial for achieving favourable outcomes.A novel, validated nomogram incorporating risk factors such as age, comorbidities and intraoperative factors predicts PMV after ATAAD surgery, aiding clinical decision-making and optimizing postoperative care.

Blue Perovskite Lasing Derived from Bound Excitons through Defect Engineering.

All-inorganic perovskite films have emerged as promising candidates for laser gain materials owing to their outstanding optoelectronic properties and straightforward solution processing. However, the performance of blue perovskite lasing still lags far behind due to the inevitable high density of defects. Herein, we demonstrate that defects can be utilized instead of passivated/removed to form bound excitons to achieve excellent blue stimulated emission in perovskite films. Such a strategy emphasizes defect engineering by introducing a deep-level defect in mixed-Rb/Cs perovskite films through octylammonium bromide (OABr) additives. Consequently, the OA-Rb/Cs perovskite films exhibit blue amplified spontaneous emission (ASE) from defect-related bound excitons with a low threshold (13.5 µJ/cm2) and a high optical gain (744.7 cm-1), which contribute to a vertical-cavity surface-emitting laser with single-mode blue emission at 482 nm. This work not only presents a facile method for creating blue laser gain materials but also provides valuable insights for further exploration of high-performance blue lasing in perovskite films.

Substance Use Patterns and Characteristics Using Real World Data from Adolescents Assessed for Substance Use and Treatment Planning-United States, 2017-2021.

BACKGROUND: Although substance use rates among adolescents have decreased, drug overdose deaths among adolescents have increased since 2020, driven largely by illegally made fentanyl (IMF). This study explores substance use patterns and characteristics of adolescents who were assessed for substance use disorder (SUD) treatment to inform prevention and response strategies. METHODS: A convenience sample of adolescents aged 10-18 years assessed for SUD treatment from September 2017 to December 2021 was analyzed using the Comprehensive Health Assessment for Teens. The percentage of lifetime and past 30-day substance use was examined. Adolescent characteristics (e.g., demographics, history of overdoses or hospital visits due to drug/alcohol use) were analyzed by lifetime substances used. RESULTS: Among 5,377 assessments, most were male (58.7%), aged 16-18 years (50.5%), non-Hispanic White (43.1%), enrolled in school (87.3%), and living with their parent(s) (72.4%). The most commonly reported lifetime substances used were marijuana (68.0%), alcohol (54.2%), and prescription opioid misuse (13.6%). The most common past 30-day substance use combination was alcohol and marijuana (35.6%). The percentage of assessments indicating past-year overdoses or hospital visits due to drug/alcohol use was greatest among those who reported lifetime use of IMF (24.0%), followed by heroin (21.4%) and cocaine (15.3%). Overall, 2.3% reported lifetime IMF use and 0.6% thought IMF was causing them the most problems. CONCLUSIONS: Findings inform opportunities to address substance use and increased IMF-involved overdose among adolescents. Continued overdose prevention and response strategies such as evidence-based education campaigns, naloxone distribution and harm reduction efforts, and evidence-based SUD treatment expansion are needed.

Reported Xylazine Use Among Adults Aged ≥18 Years Evaluated for Substance Use Treatment - United States, July 2022-September 2023.

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.

Coping with the concurrent heatwaves and ozone extremes in China under a warming climate.

Intensive human activity has brought about unprecedented climate and environmental crises, in which concurrent heatwaves and ozone extremes pose the most serious threats. However, a limited understanding of the comprehensive mechanism hinders our ability to mitigate such compound events, especially in densely populated regions like China. Here, based on field observations and climate-chemistry coupled modelling, we elucidate the linkage between human activities and the climate system in heat-related ozone pollution. In China, we have observed that both the frequency and intensity of heatwaves have almost tripled since the beginning of this century. Moreover, these heatwaves are becoming more common in urban clusters with serious ozone pollution. Persistent heatwaves during the extremely hot and dry summers of 2013 and 2022 accelerated photochemical ozone production by boosting anthropogenic and biogenic emissions, and aggravated ozone accumulation by suppressing dry deposition due to water-stressed vegetation, leading to a more than 30% increase in ozone pollution in China's urban areas. The sensitivity of ozone to heat is demonstrated to be substantially modulated by anthropogenic emissions, and China's clean air policy may have altered the relationship between ozone and temperature. Climate model projections further highlight that the high-emission climate-socioeconomic scenario tends to intensify the concurrent heat and ozone extremes in the next century. Our results underscore that the implementation of a strict emission strategy will significantly reduce the co-occurrence of heatwaves and ozone extremes, achieving climate and environmental co-benefits.

Realveolarization with inhalable mucus-penetrating lipid nanoparticles for the treatment of pulmonary fibrosis in mice.

The stemness loss-associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy of idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 stemness for IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house-made ionizable lipids for high-efficiency pulmonary mucus penetration and codelivery of dual messenger RNAs (mRNAs), encoding cytochrome b5 reductase 3 and bone morphogenetic protein 4, respectively. After being inhaled in a bleomycin model, LNPs reverses the mitochondrial dysfunction through ameliorating nicotinamide adenine dinucleotide biosynthesis, which inhibits the accelerated senescence of AT2 cells. Concurrently, pathological epithelial remodeling and fibroblast activation induced by impaired AT2 cells are terminated, ultimately prompting alveolar regeneration. Our data demonstrated that the mRNA-LNP system exhibited high protein expression in lung epithelial cells, which markedly extricated the alveolar collapse and prolonged the survival of fibrosis mice, providing a clinically viable strategy against IPF.

Advances in precision gene editing for liver fibrosis: From technology to therapeutic applications.

This review presents a comprehensive exploration of gene editing technologies and their potential applications in the treatment of liver fibrosis, a condition often leading to serious complications such as liver cancer. Through an in-depth review of current literature and critical analysis, the study delves into the intricate signaling pathways underlying liver fibrosis development and examines the promising role of gene editing in alleviating this disease burden. Gene editing technologies offer precise, efficient, and reproducible tools for manipulating genetic material, holding significant promise for basic research and clinical practice. The manuscript highlights the challenges and potential risks associated with gene editing technology. By synthesizing existing knowledge and exploring future perspectives, this study aims to provide valuable insights into the potential of precision gene editing to combat liver fibrosis and its associated complications, ultimately contributing to advances in liver fibrosis research and therapy.

Starting with screening strains to construct synthetic microbial communities (SynComs) for traditional food fermentation.

With the elucidation of community structures and assembly mechanisms in various fermented foods, core communities that significantly influence or guide fermentation have been pinpointed and used for exogenous restructuring into synthetic microbial communities (SynComs). These SynComs simulate ecological systems or function as adjuncts or substitutes in starters, and their efficacy has been widely verified. However, screening and assembly are still the main limiting factors for implementing theoretic SynComs, as desired strains cannot be effectively obtained and integrated. To expand strain screening methods suitable for SynComs in food fermentation, this review summarizes the recent research trends in using SynComs to study community evolution or interaction and improve the quality of food fermentation, as well as the specific process of constructing synthetic communities. The potential for novel screening modalities based on genes, enzymes and metabolites in food microbial screening is discussed, along with the emphasis on strategies to optimize assembly for facilitating the development of synthetic communities.

Directed-evolution mutations enhance DNA-binding affinity and protein stability of the adenine base editor ABE8e.

Adenine base editors (ABEs), consisting of CRISPR Cas nickase and deaminase, can chemically convert the A:T base pair to G:C. ABE8e, an evolved variant of the base editor ABE7.10, contains eight directed evolution mutations in its deaminase TadA8e that significantly increase its base editing activity. However, the functional implications of these mutations remain unclear. Here, we combined molecular dynamics (MD) simulations and experimental measurements to investigate the role of the directed-evolution mutations in the base editing catalysis. MD simulations showed that the DNA-binding affinity of TadA8e is higher than that of the original deaminase TadA7.10 in ABE7.10 and is mainly driven by electrostatic interactions. The directed-evolution mutations increase the positive charge density in the DNA-binding region, thereby enhancing the electrostatic attraction of TadA8e to DNA. We identified R111, N119 and N167 as the key mutations for the enhanced DNA binding and confirmed them by microscale thermophoresis (MST) and in vivo reversion mutation experiments. Unexpectedly, we also found that the directed mutations improved the thermal stability of TadA8e by ~ 12 °C (Tm, melting temperature) and that of ABE8e by ~ 9 °C, respectively. Our results demonstrate that the directed-evolution mutations improve the substrate-binding ability and protein stability of ABE8e, thus providing a rational basis for further editing optimisation of the system.

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.

Hepatitis B-related hepatocellular carcinoma: classification and prognostic model based on programmed cell death genes.

Instruction: Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Programmed cell death (PCD) is a critical process in suppressing tumor growth, and alterations in PCD-related genes may contribute to the progression of HBV-HCC. This study aims to develop a prognostic model that incorporates genomic and clinical information based on PCD-related genes, providing novel insights into the molecular heterogeneity of HBV-HCC through bioinformatics analysis and experimental validation. Methods: In this study, we analyzed 139 HBV-HCC samples from The Cancer Genome Atlas (TCGA) and validated them with 30 samples from the Gene Expression Omnibus (GEO) database. Various bioinformatics tools, including differential expression analysis, gene set variation analysis, and machine learning algorithms were used for comprehensive analysis of RNA sequencing data from HBV-HCC patients. Furthermore, among the PCD-related genes, we ultimately chose DLAT for further research on tissue chips and patient cohorts. Besides, immunohistochemistry, qRT-PCR and Western blot analysis were conducted. Results: The cluster analysis identified three distinct subgroups of HBV-HCC patients. Among them, Cluster 2 demonstrated significant activation in DNA replication-related pathways and tumor-related processes. Analysis of copy number variations (CNVs) of PCD-related genes also revealed distinct patterns in the three subgroups, which may be associated with differences in pathway activation and survival outcomes. DLAT in tumor tissues of HBV-HCC patients is upregulated. Discussion: Based on the PCD-related genes, we developed a prognostic model that incorporates genomic and clinical information and provided novel insights into the molecular heterogeneity of HBV-HCC. In our study, we emphasized the significance of PCD-related genes, particularly DLAT, which was examined in vitro to explore its potential clinical implications.

Spinosin ameliorates osteoarthritis through enhancing the Nrf2/HO-1 signaling pathway.

Osteoarthritis (OA) is a common degenerative joint disease in the elderly, while oxidative stress-induced chondrocyte degeneration plays a key role in the pathologic progression of OA. One possible reason is that the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which acts as the intracellular defense factor against oxidative stress, is significantly inhibited in chondrocytes. Spinosin (SPI) is a potent Nrf2 agonist, but its effect on OA is still unknown. In this study, we found that SPI can alleviate tert-Butyl hydroperoxide (TBHP)-induced extracellular matrix degradation of chondrocytes. Additionally, SPI can effectively activate Nrf2, heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) in chondrocytes under the TBHP environment. When Nrf2 was silenced by siRNA, the cartilage protective effect of SPI was also weakened. Finally, SPI showed good alleviative effects on OA in mice. Thus, SPI can ameliorate oxidative stress-induced chondrocyte dysfunction and exhibit a chondroprotective effect through activating the Nrf2/HO-1 pathway, which may provide a novel and promising option for the treatment of OA.

Public Health Interventions and Overdose-Related Outcomes Among Persons With Opioid Use Disorder.

Importance: Given the high number of opioid overdose deaths in the US and the complex epidemiology of opioid use disorder (OUD), systems models can serve as a tool to identify opportunities for public health interventions. Objective: To estimate the projected 3-year association between public health interventions and opioid overdose-related outcomes among persons with OUD. Design, Setting, and Participants: This decision analytical model used a simulation model of the estimated US population aged 12 years and older with OUD that was developed and analyzed between January 2019 and December 2023. The model was parameterized and calibrated using 2019 to 2020 data and used to estimate the relative change in outcomes associated with simulated public health interventions implemented between 2021 and 2023. Main Outcomes and Measures: Projected OUD and medications for OUD (MOUD) prevalence in 2023 and number of nonfatal and fatal opioid-involved overdoses among persons with OUD between 2021 and 2023. Results: In a baseline scenario assuming parameters calibrated using 2019 to 2020 data remained constant, the model projected more than 16 million persons with OUD not receiving MOUD treatment and nearly 1.7 million persons receiving MOUD treatment in 2023. Additionally, the model projected over 5 million nonfatal and over 145 000 fatal opioid-involved overdoses among persons with OUD between 2021 and 2023. When simulating combinations of interventions that involved reducing overdose rates by 50%, the model projected decreases of up to 35.2% in nonfatal and 36.6% in fatal opioid-involved overdoses among persons with OUD. Interventions specific to persons with OUD not currently receiving MOUD treatment demonstrated the greatest reduction in numbers of nonfatal and fatal overdoses. Combinations of interventions that increased MOUD initiation and decreased OUD recurrence were projected to reduce OUD prevalence by up to 23.4%, increase MOUD prevalence by up to 137.1%, and reduce nonfatal and fatal opioid-involved overdoses among persons with OUD by 6.7% and 3.5%, respectively. Conclusions and Relevance: In this decision analytical model study of persons with OUD, findings suggested that expansion of evidence-based interventions that directly reduce the risk of overdose fatality among persons with OUD, such as through harm reduction efforts, could engender the highest reductions in fatal overdoses in the short-term. Interventions aimed at increasing MOUD initiation and retention of persons in treatment projected considerable improvement in MOUD and OUD prevalence but could require a longer time horizon for substantial reductions in opioid-involved overdoses.

Metabonomics analysis of the flavor characteristics of Wuyi Rock Tea (Rougui) with "rock flavor" and microbial contributions to the flavor.

Wuyi Rock Tea (WRT) has different characteristics of "rock flavor" due to different production areas. In this study, we investigated the flavor characteristics and key components of "rock flavor" and the influence of microorganisms on the substances by combining metabolomics and microbiomics with the Rougui WRTs from the Zhengyan, Banyan, and Waishan production areas. The results showed that Rougui has a strong floral and fruity aroma, which is mainly brought by hotrienol, and the sweet, smooth, and fresh taste is composed of epicatechin gallate, epigallocatechin, epigallocatechin gallate, caffeine, theanine, soluble sugar, and sweet and bitter amino acids. Bacteria Chryseobacterium, Pedobacter, Bosea, Agrobacterium, Stenotrophomonas, and Actinoplanes mainly influence the production of hotrienol, epicatechin gallate, and theanine. Fungi Pestalotiopsis, Fusarium, Elsinoe, Teichospora and Tetracladium mainly influence the production of non-volatile compounds. This study provides a reference for the biological formation mechanism of the characteristic aroma of WRT's "rock falvor".