Long-term exposure to advanced lipid peroxidation end products impairs cognitive function through microbiota-gut-brain axis.

The frequent intake of ultra-processed, heat-processed, and fat-enriched foods rich in dietary advanced lipoxidation end-products (ALEs) has been correlated with cognitive decline; however, the underlying mechanisms of action remain unexplored. This study investigated the impact of a 12-month dietary exposure to ALEs on learning, memory, and Aß1-42 accumulation in mice, with a focus on the AMPK/SIRT1 signaling pathway and ADAM10 expression. The gut microbiota and metabolomic profiles revealed ALEs-induced gut dysbiosis and cognitive impairment, highlighting modulation through the microbiota-gut-brain axis. Key findings include increased pathogenic bacteria and decreased beneficial bacteria, linked to metabolite profile changes that affect neurotoxic Aß1-42 peptide accumulation. This long-term comprehensive study underscores the need for dietary guidelines to reduce ALE intake and mitigate neurodegenerative disease risk, highlighting the intricate interplay between diet, gut microbiota, and cognitive health.

Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy.

AIMS: The purpose of this study was to investigate the role of DGUOK in the pro-gression of colorectal cancer (CRC) and its impact on the sensitivity of CRC cells to 5-FU treatment. METHODS: We conducted bioinformatics analysis and qRT-PCR to evaluate DGUOK expression in CRC tissues/cells. Cell viability of CRC cells treated with 5-FU was assessed using CCK-8 and colony formation assays. Autophagy levels were determined through immunofluorescence assays and Western blot analysis. Additionally, the influence of p-p38 on autophagy was inves-tigated via Western blotting. A rescue assay was performed to confirm whether DGUOK/p38 affects 5-FU sensitivity in CRC cells through autophagy. RESULTS: Our findings indicate that DGUOK is upregulated in CRC tissues compared to normal tissues, correlating with increased cell proliferation and migration. Functionally, inhibition of DGUOK enhances autophagy, thereby decreasing the sensitivity of CRC cells to 5-FU. This ef-fect is partly mediated by DGUOK's impact on the mitogen-activated protein kinase (MAPK) pathway, specifically promoting the phosphorylation of p38 MAPK, a crucial regulator in au-tophagy pathways. CONCLUSION: These results suggest that DGUOK could serve as a novel marker for predicting the efficacy of 5-FU in CRC treatment.

Identification of three novel P450 enzymes involved in the oxidative modification of a newly discovered fusicoccane diterpene.

Fusicoccane (FC)-type diterpenoids are a class of diterpenoids characterized by a unique 5-8-5 ring system and exhibit diverse biological activities. Recently, we identified a novel FC-type diterpene synthase MgMS, which produces a myrothec-15(17)-en-7-ol (1) hydrocarbon skeleton, however, its tailoring congeners have not been elucidated. Here, we discovered two additional gene clusters Bn and Np, each encoding a highly homologous terpene synthase to MgMS but distinct tailoring enzymes. Heterologous expression of the terpene synthases BnMS and NpMS yielded the same product as MgMS. Subsequent introduction of three P450 enzymes MgP450, BnP450 and NpP450 from individual gene clusters resulted in four new FC-type diterpenoids 2-5. Notably, MgP450 serves as the first enzyme responsible for hydroxylation of the C19 methyl group, whereas NpP450 functions as a multifunctional P450 enzyme involved in the oxidations at C5, C6, and C19 positions of the 5-8-5 tricyclic skeleton. C5 oxidation of the hydrocarbon skeleton 1 led to broadening of the NMR signals and incomplete spectra, which was resolved by high-temperature NMR spectral analysis.

Efficacy and safety analysis of PD-1 combined with regorafenib in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: To investigate the therapeutic efficacy and safety of programmed death-1 (PD-1) inhibitors combined with regorafenib in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was performed on 82 patients diagnosed with advanced HCC at Lanzhou Petrochemical General Hospital and the Second People's Hospital of Lanzhou City from October 2021 to October 2022. Patients were divided into two groups: the observation group (42 patients) received combined therapy with regorafenib and a PD-1 inhibitor, while the control group (40 patients) received only regorafenib monotherapy. Treatment efficacy, changes in serum tumor markers pre- and post-treatment, incidence of adverse reactions, progression-free survival (PFS), 1-year survival rate, and independent prognostic factors were evaluated for both groups. RESULTS: The treatment efficacy in the observation group was significantly better than that in the control group (P<0.05). Post-treatment levels of VEGF, sIL-2R, and CEA were significantly lower in the observation group compared to the control group (all P<0.05). The incidence of adverse reactions was similar between the two groups (P>0.05). However, the observation group demonstrated a significantly higher median PFS and 1-year survival rate than the control group (both P<0.05). Vascular invasion, degree of differentiation, and treatment regimen were identified as independent prognostic factors affecting outcomes (all P<0.05). CONCLUSION: For patients with advanced HCC, integrating PD-1 inhibitors with regorafenib treatment not only enhances clinical efficacy but also maintains safety. This combination therapy significantly improves progression-free survival and 1-year survival rates, supporting its further clinical application.

Sleep Disturbance Mediates the Associations Between HIV Stigma and Mental and Physical Health Among Black Adults with HIV.

OBJECTIVES: Black Americans have been disproportionally affected by the HIV epidemic, and experience significant disparities in sleep health, mental health, and physical health domains. Using longitudinal data from a sample of Black adults with HIV, the current study examined the associations between stigma and mental and physical health outcomes and how sleep disturbance may play a mediating role. METHODS: Data were drawn from a recent randomized controlled trial. Questionnaires were used to examine internalized and anticipated HIV stigma, perceived discrimination (enacted stigma) based on multiple social identities (i.e., HIV-serostatus, race, sexual orientation), sleep disturbance, mental health problems (depressive and posttraumatic stress disorder [PTSD] symptoms), and mental and physical health-related quality of life (HRQOL) at baseline, 7-month follow-up, and 13-month follow-up assessments. Linear mixed modeling was used to examine main effects of stigma on health outcomes; causal mediation analysis was used to estimate indirect paths through sleep disturbance. RESULTS: Internalized and anticipated HIV stigma and multiple discrimination were associated with more sleep disturbance, more depressive and PTSD symptoms, and poorer mental and physical HRQOL. Results also indicated significant indirect paths (i.e., mediation) through greater sleep disturbance between HIV-related stigma and discrimination and mental health and health-related quality of life. CONCLUSIONS: Results support that sleep disturbance is a mediating pathway through which different forms of stigmas impact health outcomes. Sleep may be an intervention target to help improve mental and physical well-being and reduce health disparities among racial and ethnic minority people with HIV.

Genome-wide analysis of soybean hypoxia inducible gene domain containing genes: a functional investigation of GmHIGD3.

The response of Hypoxia Inducible Gene Domain (HIGD) proteins to hypoxia plays a crucial role in plant development. However, the research on this gene family in soybean has been lacking. In this study, we aimed to identify and comprehensively analyze soybean HIGD genes using the Glycine max genome database. As a result, six GmHIGD genes were successfully identified, and their phylogeny, gene structures, and putative conserved motifs were analyzed in comparison to Arabidopsis and rice. Collinearity analysis indicated that the HIGD gene family in soybean has expanded to some extent when compared to Arabidopsis. Additionally, the cis-elements in the promoter regions of GmHIGD and the transcription factors potentially binding to these regions were identified. All GmHIGD genes showed specific responsiveness to submergence and hypoxic stresses. Expression profiling through quantitative real-time PCR revealed that these genes were significantly induced by PEG treatment in root tissue. Co-expressed genes of GmHIGD were primarily associated with oxidoreductase and dioxygenase activities, as well as peroxisome function. Notably, one of GmHIGD genes, GmHIGD3 was found to be predominantly localized in mitochondria, and its overexpression in Arabidopsis led to a significantly reduction in catalase activity compared to wild-type plants. These results bring new insights into the functional role of GmHIGD in terms of subcellular localization and the regulation of oxidoreductase activity.

Spatial distribution of PAHs and microbial communities in intertidal sediments of the Pearl River Estuary, South China.

The exploration of sediment pollution caused by PAHs and its impact on microbial communities can provide valuable insights for the remediation of sediments. The spatial distribution of PAHs and their impact on the microbial community within the Pearl River Estuary were investigated in this study. The findings revealed that the total concentration ranges of 16 PAHs were between 24.26 and 3075.93 ng/g, with naphthalene, fluorene, and phenanthrene potentially exerting adverse biological effects. More PAHs were found to accumulate in subsurface sediments, and their average accumulation rates gradually decreased as the number of rings in PAHs increased, ranging from 180 % for 2-ring to 36 % for 6-ring. The phyla Proteobacteria, Bacteroidetes, Actinobacteria, and Chloroflexi were found to dominate both surface and subsurface sediments The correlation between microbial genera and PAHs contents was weak in sediments with low levels of PAHs contamination, while a more significant positive relationship was observed in sediments with high levels of PAHs contamination. The physicochemical properties of sediments, such as pH, soil structure and Cu significantly influence bacterial community composition in highly contaminated sediments. Additionally, the network analysis revealed that certain bacterial genera, including Novosphingobium, Robiginitalea and Synechococcus_CC9902, played a pivotal role in the degradation of PAHs. These findings are significant in comprehending the correlation between bacterial communities and environmental factors in intertidal ecosystems, and establish a scientific foundation for bioremediation of intertidal zones.

Sleep Problems and Health Outcomes Among Urban American Indian and Alaska Native Adolescents.

Importance: Adolescent sleep problems are prevalent, particularly among racial and ethnic minority groups, and can increase morbidity. Despite the numerous strengths of their racial and ethnic group, urban American Indian and Alaska Native adolescents face significant health disparities but are rarely included in health research. Understanding how sleep problems are associated with health outcomes among American Indian and Alaska Native adolescents may elucidate novel targets for interventions to promote health equity. Objective: To assess whether baseline sleep problems are associated with changes in behavioral and cardiometabolic health outcomes among urban American Indian and Alaska Native adolescents 2 years later. Design, Setting, and Participants: American Indian and Alaska Native adolescents were recruited via flyers and community events for an observational cohort study in California. Baseline assessments were conducted among 142 adolescents from March 1, 2018, to March 31, 2020, and follow-ups were conducted among 114 adolescents from December 1, 2020, to June 30, 2022. Exposures: Baseline actigraphy-assessed sleep duration and efficiency and self-reported sleep disturbances and social jet lag (absolute value of the difference in sleep midpoint on weekends vs weekdays; indicator of circadian misalignment). Main Outcomes and Measures: Main outcome measures included self-reported depression (measured using the Patient Health Questionnaire), anxiety (measured using the Generalized Anxiety Disorder 7-item scale), past year alcohol and cannabis use, body mass index, systolic blood pressure (SBP) and diastolic blood pressure (DBP), waist circumference, and glycosylated hemoglobin (HbA1c). Analyses examined whether baseline sleep was associated with health outcomes at follow-up, controlling for age, sex, and baseline outcome measures. Results: The baseline sample included 142 urban American Indian and Alaska Native adolescents (mean [SD] age, 14.0 [1.4] years; 84 girls [59%]), 80% of whom (n = 114; mean [SD] age, 14.1 [1.3] years; 71 girls [62%]) completed follow-ups. Linear or logistic regressions showed significant negative associations between shorter sleep duration and depression (ß = -1.21 [95% CI, -2.19 to -0.24]), anxiety (ß = -0.89 [95% CI, -1.76 to -0.03]), DBP (ß = -2.03 [95% CI, -3.79 to -0.28]), and HbA1c level (ß = -0.15 [95% CI, -0.26 to -0.04]) and likelihood of alcohol (odds ratio [OR], 0.57 [95% CI, 0.36-0.91]) and cannabis use (full week: OR, 0.59 [95% CI, 0.35-0.99]) at follow-up. Greater social jet lag was associated with significantly higher SBP (ß = 0.06 [95% CI, 0.01-0.11]) at follow-up. Conclusions and Relevance: This cohort study found significant associations between poor sleep and adverse changes in health outcomes. Findings highlight the importance of developing culturally responsive interventions that target sleep as a key modifiable risk factor to improve the health of American Indian and Alaska Native adolescents.

Enhancing sleep health in urban American Indian/Alaska Native adolescents: Implications for culturally tailored interventions.

BACKGROUND: Urban American Indian/Alaska Native (AI/AN) adolescents are vulnerable to sleep and other health-related disparities due to numerous social drivers, including historical trauma and relocation to urban areas. This study aims to identify strategies to increase protective factors and culturally tailor sleep health interventions for this population. METHODS: Using community-based participatory research, the NAYSHAW study conducted in-depth interviews with urban AI/AN adolescents aged 12-19 years to understand critical components needed for developing a culturally sensitive sleep health intervention. Data from two qualitative subsamples (N = 46) and parent surveys (N = 110) were analyzed, focusing on factors that affect sleep health behaviors, including parental involvement, technology, and traditional practices. RESULTS: Key findings include the detrimental impact of electronics use at night and protective effects of traditional practices on sleep. Parental involvement in sleep routines varied by adolescent's age. Adolescents desired sleep health education in interactive formats, whereas parents preferred workshops and digital applications for sleep health strategies. Findings suggest that interventions need to address electronics use and should also be culturally tailored to address the unique experiences of urban AI/AN adolescents. CONCLUSIONS: Results underscore the importance of utilizing community-based strategies to develop culturally tailored sleep interventions for underserved populations, specifically urban AI/AN adolescents. Integrating traditional practices with evidence-based sleep health strategies can provide a holistic approach to improving sleep and overall well-being. Parental education and involvement will be critical to the success of such interventions.

Transdiagnostic Sleep and Circadian Intervention in Youth: Long-term Follow-up of a Randomized Controlled Trial.

OBJECTIVE: This preregistered study compared the effects of the Transdiagnostic Sleep and Circadian Intervention (TranS-C) with psychoeducation (PE) about sleep, health, yoga, meditation, and outdoor appreciation activities on sleep and circadian functioning, health risk, and sleep health behaviors at long-term follow-up (LTFU), an average of 8 years following treatment. We also examined if more sleep health behaviors at LTFU were associated with better sleep and circadian functioning at LTFU and if better sleep and circadian functioning were associated with lower health risk at LTFU. METHOD: At baseline, we randomly assigned adolescents with an eveningness chronotype to TranS-C (n = 89) or PE (n = 87). Of this sample, we assessed 106 young adults (mean age at follow-up = 22.5 years; n = 55 from TranS-C; n = 51 from PE) an average of 8 years following treatment. RESULTS: Despite TranS-C (vs PE) sustaining improvement in circadian functioning through 12-month follow-up, at LTFU, there were no significant differences between the conditions on any outcome, including sleep and circadian functioning, risks in 5 health domains indexed by self-report and ecological momentary assessment, sleep health behaviors, and physical measurements. Across both conditions, measures indicating poorer sleep and circadian functioning were associated with higher health risk across multiple domains, and more sleep health behaviors were associated with lower levels of eveningness at LTFU. CONCLUSION: These results provide an important window into the influence of development on long-term outcomes for youth and raise the possibility that interventions for youth could be enhanced with a focus on habit formation. CLINICAL TRIAL REGISTRATION INFORMATION: Maintaining Behavior Change: A 6-Year Follow-up of Adolescent 'Night-owls'; https://www. CLINICALTRIALS: gov/; NCT05098782. STUDY PREREGISTRATION INFORMATION: Long-term Follow-up of Young Adults Who Received TranS-C to Modify Eveningness Chronotype in Adolescence; https://osf.io/; d5a4g. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in science.

Testing an Intervention to Improve Health Care Worker Well-Being During the COVID-19 Pandemic: A Cluster Randomized Clinical Trial.

Importance: Stress First Aid is an evidence-informed peer-to-peer support intervention to mitigate the effect of the COVID-19 pandemic on the well-being of health care workers (HCWs). Objective: To evaluate the effectiveness of a tailored peer-to-peer support intervention compared with usual care to support HCWs' well-being at hospitals and federally qualified health centers (FQHCs) during the COVID-19 pandemic. Design, Setting, and Participants: This cluster randomized clinical trial comprised 3 cohorts of HCWs who were enrolled from March 2021 through July 2022 at 28 hospitals and FQHCs in the US. Participating sites were matched as pairs by type, size, and COVID-19 burden and then randomized to the intervention arm or usual care arm (any programs already in place to support HCW well-being). The HCWs were surveyed before and after peer-to-peer support intervention implementation. Intention-to-treat (ITT) analysis was used to evaluate the intervention's effect on outcomes, including general psychological distress and posttraumatic stress disorder (PTSD). Intervention: The peer-to-peer support intervention was delivered to HCWs by site champions who received training and subsequently trained the HCWs at their site. Recipients of the intervention were taught to respond to their own and their peers' stress reactions. Main Outcomes and Measures: Primary outcomes were general psychological distress and PTSD. General psychological distress was measured with the Kessler 6 instrument, and PTSD was measured with the PTSD Checklist. Results: A total of 28 hospitals and FQHCs with 2077 HCWs participated. Both preintervention and postintervention surveys were completed by 2077 HCWs, for an overall response rate of 28% (41% at FQHCs and 26% at hospitals). A total of 862 individuals (696 females [80.7%]) were from sites that were randomly assigned to the intervention arm; the baseline mean (SD) psychological distress score was 5.86 (5.70) and the baseline mean (SD) PTSD score was 16.11 (16.07). A total of 1215 individuals (947 females [78.2%]) were from sites assigned to the usual care arm; the baseline mean (SD) psychological distress score was 5.98 (5.62) and the baseline mean (SD) PTSD score was 16.40 (16.43). Adherence to the intervention was 70% for FQHCs and 32% for hospitals. The ITT analyses revealed no overall treatment effect for psychological distress score (0.238 [95% CI, -0.310 to 0.785] points) or PTSD symptom score (0.189 [95% CI, -1.068 to 1.446] points). Post hoc analyses examined the heterogeneity of treatment effect by age group with consistent age effects observed across primary outcomes (psychological distress and PTSD). Among HCWs in FQHCs, there were significant and clinically meaningful treatment effects for HCWs 30 years or younger: a more than 4-point reduction for psychological distress (-4.552 [95% CI, -8.067 to -1.037]) and a nearly 7-point reduction for PTSD symptom scores (-6.771 [95% CI, -13.224 to -0.318]). Conclusions and Relevance: This trial found that this peer-to-peer support intervention did not improve well-being outcomes for HCWs overall but had a protective effect against general psychological distress and PTSD in HCWs aged 30 years or younger in FQHCs, which had higher intervention adherence. Incorporating this peer-to-peer support intervention into medical training, with ongoing support over time, may yield beneficial results in both standard care and during public health crises. Trial Registration: ClinicalTrials.gov Identifier: NCT04723576.

Absolute Configuration of Oxabornyl Polyenes Prugosenes A1-A3 and Structural Revision of Prugosene A2.

Oxabornyl polyenes represent a unique group of polyketides characterized by a central polyene core flanked by a conserved oxabornyl moiety and a structurally diverse oxygen heterocyclic ring. They are widely distributed in fungi and possess a variety of biological activities. Due to the significant spatial separation between the two stereogenic ring systems, it is difficult to establish their overall relative configurations. Here, we isolated three oxabornyl polyenes, prugosenes A1-A3 (1-3), from Talaromyces sp. JNU18266-01. Although these compounds were first reported from Penicillium rugulosum, their overall relative and absolute configurations remained unassigned. By employing ozonolysis in combination with ECD calculations, we were able to establish their absolute configurations, and additionally obtained seven new chemical derivatives (4-10). Notably, through NMR data analysis and quantum chemical calculations, we achieved the structural revision of prugosene A2. Furthermore, prugosenes A1-A3 exhibited potent antiviral activity against the respiratory syncytial virus, with compound 1 displaying an IC50 value of 6.3 µM. Our study thus provides a valuable reference for absolute configuration assignment of oxabornyl polyene compounds.

Application of machine learning in prediction of Pb2+ adsorption of biochar prepared by tube furnace and fluidized bed.

Data mining by machine learning (ML) has recently come into application in heavy metals purification from wastewater, especially in exploring lead removal by biochar that prepared using tube furnace (TF-C) and fluidized bed (FB-C) pyrolysis methods. In this study, six ML models including Random Forest Regression (RFR), Gradient Boosting Regression (GBR), Support Vector Regression (SVR), Kernel Ridge Regression (KRR), Extreme Gradient Boosting (XGB), and Light Gradient Boosting Machine (LGBM) were employed to predict lead adsorption based on a dataset of 1012 adsorption experiments, comprising 422 TF-C groups from our experiments and 590 FB-C groups from literatures. The XGB model showed superior accuracy and predictive performance for adsorption, achieving R2 values for TF-C (0.992) and FB-C (0.981), respectively. Contrasting inferior results were observed in other models, including RF (0.962 and 0.961), GBR (0.987 and 0.975), SVR (0.839 and 0.763), KRR (0.817 and 0.881), and LGBM (0.975 and 0.868). Additionally, a hybrid dataset combining both biochars in Pb adsorption also indicated high accuracy (0.972) as obtained from XGB model. The investigation revealed that the influence of char characteristics and adsorption conditions on Pb adsorption differs between the two biochar. Specific char characteristics, particularly nitrogen content, significantly influence lead adsorption in both biochar. Interestingly, the influence of pyrolysis temperature (PT) on lead adsorption is found to be greater for TF-C than for FB-C. Consequently, careful consideration of PT is crucial when preparing TF-C biochar. These findings offer practical guidance for optimizing biochar preparation conditions during heavy metal removal from wastewater.

RIOK3 sustains colorectal cancer cell survival under glucose deprivation via an HSP90α-dependent pathway.

Glucose oxidation via the pentose phosphate pathway serves as the primary cellular mechanism for generating nicotinamide adenine dinucleotide phosphate (NADPH). The central regions of solid tumors typically experience glucose deficiency, emphasizing the need for sustained NADPH production crucial to tumor cell survival. This study highlights the crucial role of RIOK3 in maintaining NADPH production and colorectal cancer (CRC) cell survival during glucose deficiency. Our findings revealed upregulated RIOK3 expression upon glucose deprivation, with RIOK3 knockout significantly reducing cancer cell survival. Mechanistically, RIOK3 interacts with heat shock protein 90α (HSP90α), a chaperone integral to various cellular processes, thereby facilitating HSP90α binding to isocitrate dehydrogenase 1 (IDH1). This interaction further upregulates IDH1 expression, enhancing NADPH production and preserving redox balance. Furthermore, RIOK3 inhibition had no discernible effect on intracellular NADPH levels and cell death rates in HSP90α-knockdown cells. Collectively, our findings suggest that RIOK3 sustains colon cancer cell survival in low-glucose environments through an HSP90α-dependent pathway. This highlights the significance of the RIOK3-HSP90α-IDH1 cascade, providing insights into potential targeted therapeutic strategies for CRC in metabolic stress conditions.

The Interaction between Human Microbes and Advanced Glycation End Products: The Role of Klebsiella X15 on Advanced Glycation End Products' Degradation.

Previous studies have shown that advanced glycation end products (AGEs) are implicated in the occurrence and progression of numerous diseases, with dietary AGEs being particularly associated with intestinal disorders. In this study, methylglyoxal-beta-lactoglobulin AGEs (MGO-ß-LG AGEs) were utilized as the exclusive nitrogen source to investigate the interaction between protein-bound AGEs and human gut microbiota. The high-resolution mass spectrometry analysis of alterations in peptides containing AGEs within metabolites before and after fermentation elucidated the capacity of intestinal microorganisms to enzymatically hydrolyze long-chain AGEs into short-chain counterparts. The 16S rRNA sequencing revealed Klebsiella, Lactobacillus, Escherichia-Shigella, and other genera as dominant microbiota at different fermentation times. A total of 187 potential strains of AGE-metabolizing bacteria were isolated from the fermentation broth at various time points. Notably, one strain of Klebsiella exhibited the most robust growth capacity when AGEs served as the sole nitrogen source. Subsequently, proteomics was employed to compare the changes in protein levels of Klebsiella X15 following cultivation in unmodified proteins and proteins modified with AGEs. This analysis unveiled a remodeled amino acid and energy metabolism pathway in Klebsiella in response to AGEs, indicating that Klebsiella may possess a metabolic pathway specifically tailored to AGEs. This study found that fermenting AGEs in healthy human intestinal microbiota altered the bacterial microbiota structure, especially by increasing Klebsiella proliferation, which could be a key factor in AGEs' role in causing diseases, particularly intestinal inflammation.

Fate of sulfur and chlorine during co-incineration of municipal solid waste and industrial organic solid waste.

In China, the co-incineration of municipal solid waste (MSW) with industrial organic solid waste (IOSW) is increasingly adopted. Compared with MSW, IOSW contains higher levels of sulfur (S) and chlorine (Cl), presenting significant challenges for controlling S/Cl emissions in MSW incineration plants. In this study, the impact of co-incinerating IOSW was investigated in a 500 t/d incinerator grate, focusing on the emissions and transformation behaviors of S/Cl. IOSW, with a consistent sulfur content of about 0.22 wt% and a more variable chlorine content averaging 0.53 wt%, contains over 40 % organic sulfur and >90 % organic chlorine, higher than in MSW. The results of co-incineration experiments showed that the median SO2 concentration in the flue gas was stable at 50 mg/m3, while HCl concentration decreased initially and then increased as the co-incineration ratio of IOSW rose from 20 % to 40 %. Furthermore, the concentrations of SO2 and HCl were not significantly influenced by wind flow but were positively affected by the rising furnace temperatures. Besides, the co-incineration ratio had minimal impact on sulfur in fly ash before deacidification, primarily derived from the gas stream. However, the (Na + K)/Cl ratio in fly ash progressively increased from 1.5 to 1.9, and the Ca content decreased from 0.35 % to 0.15 % as the co-incineration ratio rose to 40 %, indicating more chlorine migration into the fly ash at higher co-incineration rates. This research offers essential guidance for effectively controlling pollutant emissions during the co-incineration of IOSW, specifically the S/Cl pollutants.

Crosstalk of HDAC4, PP1, and GSDMD in controlling pyroptosis.

Gasdermin D (GSDMD) functions as a pivotal executor of pyroptosis, eliciting cytokine secretion following cleavage by inflammatory caspases. However, the role of posttranslational modifications (PTMs) in GSDMD-mediated pyroptosis remains largely unexplored. In this study, we demonstrate that GSDMD can undergo acetylation at the Lysine 248 residue, and this acetylation enhances pyroptosis. We identify histone deacetylase 4 (HDAC4) as the specific deacetylase responsible for mediating GSDMD deacetylation, leading to the inhibition of pyroptosis both in vitro and in vivo. Deacetylation of GSDMD impairs its ubiquitination, resulting in the inhibition of pyroptosis. Intriguingly, phosphorylation of HDAC4 emerges as a critical regulatory mechanism promoting its ability to deacetylate GSDMD and suppress GSDMD-mediated pyroptosis. Additionally, we implicate Protein phosphatase 1 (PP1) catalytic subunits (PP1α and PP1γ) in the dephosphorylation of HDAC4, thereby nullifying its deacetylase activity on GSDMD. This study reveals a complex regulatory network involving HDAC4, PP1, and GSDMD. These findings provide valuable insights into the interplay among acetylation, ubiquitination, and phosphorylation in the regulation of pyroptosis, offering potential targets for further investigation in the field of inflammatory cell death.

Synchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders.

Highly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.

Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism.

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.

The Effect of Nitrogen Functional Groups on Pb0, PbO, and PbCl2 Adsorption over a Carbonaceous Surface.

Lead (Pb) pollution, especially from the incineration of municipal solid waste (MSW), poses a significant threat to the environment. Among all the effective methods, activated carbon (AC) injection serves as an effective approach for lead removal from flue gas, while the modification of ACs emerges as a crucial pathway for enhancing Pb adsorption capacities. Density functional theory (DFT) is employed in this study to investigate the mechanisms underlying the enhanced adsorption of Pb species (Pb0, PbO, and PbCl2) on nitrogen-functionalized carbonaceous surfaces. The results show that nitrogen-containing groups substantially enhance lead adsorption capacity, with adsorption energies ranging from -526.18 to -288.31 kJ/mol on nitrogen-decorated carbonaceous surfaces, much higher than those on unmodified surfaces (-310.35 to -260.96 kJ/mol). Additionally, electrostatic potential and density-of-states analyses evidence that pyridinic nitrogen atoms remarkably expand charge distribution and strengthen orbital hybridization, thereby augmenting lead capture. This research elucidates the role of nitrogen-containing functional groups in lead adsorption, offering valuable insights for the development of highly efficient biomass-derived activated carbon sorbents for lead removal.