Exploring cellular diversity in lung adenocarcinoma epithelium: Advancing prognostic methods and immunotherapeutic strategies.

Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single-cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learning algorithms to establish a prognostic and immunotherapeutic signature (PIS) for LUAD. In multiple cohorts, PIS outperformed 144 previously published signatures in predicting LUAD prognosis. Importantly, PIS reliably predicted genomic alterations, chemotherapy sensitivity and immunotherapy responses. Immunohistochemistry validated lower expression of immune markers in the low-PIS group, while in vitro experiments underscored the role of the key gene PSMB7 in LUAD progression. In conclusion, PIS represents a novel biomarker facilitating the selection of suitable LUAD patients for immunotherapy, ultimately improving prognosis and guiding clinical decisions.

GbPP2C80 Interacts with GbWAKL14 to Negatively Co-Regulate Resistance to Fusarium and Verticillium wilt via MPK3 and ROS Signaling in Sea Island Cotton.

Fusarium wilt (FW) is widespread in global cotton production, but the mechanism underlying FW resistance in superior-fiber-quality Sea Island cotton is unclear. This study reveals that FW resistance has been the target of genetic improvement of Sea Island cotton in China since the 2010s. The key nonsynonymous single nucleotide polymorphism (SNP, T/C) of gene Gbar_D03G001670 encoding protein phosphatase 2C 80 (PP2C80) results in an amino acid shift (L/S), which is significantly associated with FW resistance of Sea Island cotton. Silencing GbPP2C80 increases FW resistance in Sea Island cotton, whereas overexpressing GbPP2C80 reduces FW resistance in Arabidopsis. GbPP2C80 and GbWAKL14 exist synergistically in Sea Island cotton accessions with haplotype forms "susceptible-susceptible" (TA) and "resistant-resistant" (CC), and interact with each other. CRISPR/Cas9-mediated knockout of GbWAKL14 enhances FW and Verticillium wilt (VW) resistance in upland cotton and overexpression of GbWAKL14 and GbPP2C80 weakens FW and VW resistance in Arabidopsis. GbPP2C80 and GbWAKL14 respond to FW and VW by modulating reactive oxygen species (ROS) content via affecting MPK3 expression. In summary, two tandem genes on chromosome D03, GbPP2C80, and GbWAKL14, functions as cooperative negative regulators in cotton wilt disease defense, providing novel genetic resources and molecular markers for the development of resistant cotton cultivars.

Analysis of clinical characteristics, prognosis and influencing factors in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome: A prospective study for more than five years.

Background: Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that investigates the clinical characteristics and prognosis of bronchiectasis-COPD overlap syndrome (BCOS). Further, we aimed to explore factors associated with acute exacerbation and death in BCOS, which may be of value in its early diagnosis and intervention. Methods: We recruited inpatients with COPD from the second Xiangya Hospital of Central South University in China in August 2016, with follow-up until March 2022. Patients in the BCOS group had to meet the criteria for diagnosing bronchiectasis. We used self-completion questionnaires, clinical records, and self-reported data as primary data collection methods. We used Kaplan-Meier survival analyses and Cox proportional hazard models to assess the risk of severe acute exacerbation and death for BCOS during the follow-up period. Results: A total of 875 patients were included and followed up. Patients in the BCOS group had more females, fewer smokers, lower discharge COPD assessment test (CAT) scores, lower forced vital capacity (FVC), a higher likelihood of co-occurring active tuberculosis, higher levels of eosinophils and inflammatory markers, and a higher rate of positive sputum cultures for Pseudomonas aeruginosa than patients in the COPD-only group. Patients in the acute exacerbation group (AE+) were found to have lower body mass index (BMI), more frequent acute exacerbations, higher modified Medical Research Council (mMRC) dyspnoea grade on admission, higher inflammatory markers, lower FVC, higher rates of using inhaled bronchodilators, and higher rates of both positive and Pseudomonas aeruginosa positive sputum cultures. Patients in the 'death' group were older, had a lower BMI, had spent longer time in the hospital, had higher mMRC dyspnoea grade and CAT scores upon admission and discharge, had higher levels of inflammatory markers, lower rates of using inhaled bronchodilators, were more likely to have a combination of pulmonary heart disease and obsolete pulmonary tuberculosis, as well as a higher rate of fungus-positive sputum cultures. Both erythrocyte sedimentation rate at baseline and Pseudomonas aeruginosa culture positivity were confirmed as independent predictors of severe acute exacerbation in multivariate analysis during the years of follow-up. Fungus culture positivity baseline blood urea nitrogen, baseline lymphocyte count, comorbidities with obsolete pulmonary tuberculosis and comorbidities with pulmonary heart disease were verified as independent predictors of death in multivariate analysis during the years of follow-up. Kaplan-Meier curves under survival analysis demonstrated no statistically significant difference in mortality between the COPD and the BCOS groups at the full one, two, and three years of follow-up. Conclusions: Patients with BCOS present with reduced lung function, increased susceptibility to different complications, elevated blood eosinophils and inflammatory markers, and elevated rates of positive Pseudomonas aeruginosa cultures. These distinctive markers are linked to a greater risk of severe acute exacerbations and mortality.

Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer.

This study aimed to explore the clinical significance of genomics features including tumor mutation burden (TMB) and copy number alteration (CNA) for advanced EGFR mutant lung cancer. We retrospectively identified 1378 patients with advanced EGFR mutant lung cancer and next-generation sequencing tests from three cohorts. Multiple co-occurring genomics alternations occurred in a large proportion (97%) of patients with advanced EGFR mutant lung cancers. Both TMB and CNA were predictive biomarkers for these patients. A joint analysis of TMB and CNA found that patients with high TMB and high CNA showed worse responses to EGFR-TKIs and predicted worse outcomes. TMBhighCNAhigh, as a high-risk genomic feature, showed predictive ability in most of the subgroups based on clinical characteristics. These patients had larger numbers of metastatic sites, and higher rates of EGFR copy number amplification, TP53 mutations, and cell-cycle gene alterations, which showed more potential survival gain from combination treatment. Furthermore, a nomogram based on genomic features and clinical features was developed to distinguish prognosis. Genomic features could stratify prognosis and guide clinical treatment for patients with advanced EGFR mutant lung cancer.

Co-Cu nanoparticles uniformly embedded in the intra-crystalline mesoporous Silicalite-1 for catalytic ammonia borane hydrolysis.

Zeolite-encaged metal nanoparticles (NPs) catalysts are emerging as a new frontier owing to their superior ability to stabilize the structure and catalytic performance in the thermal and environmental catalytic reaction. However, the pore size below 2 nm of the conventional zeolites usually limits the accessibility of metal active sites. Herein, Co-Cu NPs of about 2.5-3.5 nm were uniformly encapsulated in the intracrystalline mesoporous Silicalite-1 (S-1) through alkali-treatment ligand-assisted strategy. The obtained sample (termed CoxCu1-x@HS-1) exhibited efficient activity and stability in the ammonia borane hydrolysis with the highest TOF value of 21.46 molH2·molMe-1·min-1. UV-vis DRS spectra indicated that intracrystalline mesopores have greatly improved the openness and accessibility of the active sites, thus improving their catalytic performance. The introduction of Cu regulates the electronic properties of Co, further increasing hydrogen production activity. This research creates new prospects to design other high-performance hierarchical porous zeolite-confined metal/metal oxide catalysts.

Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy.

PURPOSE: Although immunotherapy improves outcomes in extensive-stage small-cell lung cancer (ES-SCLC), the search for biomarkers predicting treatment success is crucial. Natural killer (NK) cells are potential indicators in various cancers, however, their precise role in ES-SCLC prognosis remains unclear. METHODS: In this retrospective study, 33 patients with ES-SCLC treated with first-line immuno-chemotherapy were enrolled. The peripheral NK cell percentage and its longitudinal dynamics were analyzed using flow cytometry. Progression-free survival (PFS) and overall survival (OS) were calculated as hazard ratio (HR) and compared statistically. RESULTS: The median PFS was better in the group with normal baseline NK cell levels than the low group (7.0 vs. 4.6 months; HR = 0.17; 95% CI 0.07-0.41; P < 0.0001), but there was no association with OS (14.9 vs. 10.3 months; HR = 0.55; 95% CI 0.23-1.31; P = 0.171). Furthermore, the NK cell% for 95.0% of patients increased after immunochemotherapy in the clinical response group (P = 0.0047), which led to a better median PFS (6.3 vs. 2.1 months; HR = 0.23; 95% CI 0.05-0.98; P < 0.0001) and OS (14.9 vs. 5.9 months; HR = 0.20; 95% CI 0.04-1.02; P < 0.0001). Similar trends were observed with NK cell% changes up to disease progression, improving PFS (6.5 vs. 4.3; HR = 0.41; 95% CI 0.12-0.92; P = 0.0049) and OS (17.4 vs. 9.7; HR = 0.42; 95% CI 0.17-1.02; P < 0.0001). CONCLUSION: In patients with ES-SCLC, the percentage and changes in peripheral NK cells can predict the response to combined immunotherapy and chemotherapy.

Yield-related quantitative trait loci identification and lint percentage hereditary dissection under salt stress in upland cotton.

Salinity is frequently mentioned as a major constraint in worldwide agricultural production. Lint percentage (LP) is a crucial yield-component in cotton lint production. While the genetic factors affect cotton yield in saline soils are still unclear. Here, we employed a recombinant inbred line population in upland cotton (Gossypium hirsutum L.) and investigated the effects of salt stress on five yield and yield component traits, including seed cotton yield per plant, lint yield per plant, boll number per plant, boll weight, and LP. Between three datasets of salt stress (E1), normal growth (E2), and the difference values dataset of salt stress and normal conditions (D-value), 87, 82, and 55 quantitative trait loci (QTL) were detectable, respectively. In total, five QTL (qLY-Chr6-2, qBNP-Chr4-1, qBNP-Chr12-1, qBNP-Chr15-5, qLP-Chr19-2) detected in both in E1 and D-value were salt related QTL, and three stable QTL (qLP-Chr5-3, qLP-Chr13-1, qBW-Chr5-5) were detected both in E1 and E2 across 3 years. Silencing of nine genes within a stable QTL (qLP-Chr5-3) highly expressed in fiber developmental stages increased LP and decreased fiber length (FL), indicating that multiple minor-effect genes clustered on Chromosome 5 regulate LP and FL. Additionally, the difference in LP caused by Gh_A05G3226 is mainly in transcription level rather than in the sequence difference. Moreover, silencing of salt related gene (GhDAAT) within qBNP-Chr4-1 decreased salt tolerance in cotton. Our findings shed light on the regulatory mechanisms underlining cotton salt tolerance and fiber initiation.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

TET2 stabilized by deubiquitinase USP21 ameliorates cigarette smoke-induced apoptosis in airway epithelial cells.

DNA demethylase TET2 was related with lung function. However, the precise role of TET2 in cigarette smoke (CS)-induced apoptosis of airway epithelium cells, and the mechanisms involved, have yet to be elucidated. Here, we showed that CS decreased TET2 protein levels but had no significant effect on its mRNA levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients and CS-induced COPD mice model and even in airway epithelial cell lines. TET2 could inhibit CS-induced apoptosis of airway epithelial cell in vivo and in vitro. Moreover, we identified ubiquitin-specific protease 21 (USP21) as a deubiquitinase of TET2 in airway epithelial cells. USP21 interacted with TET2 and inhibited CSE-induced TET2 degradation. USP21 downregulated decreased TET2 abundance and further reduced the anti-apoptosis effect of TET2. Thus, we draw a conclusion that the USP21/TET2 axis is involved in CS-induced apoptosis of airway epithelial cells.

[Effects of revegetation on soil nitrogen-fixation and carbon-fixation microbial communities in the Horqin Sandy Land, China]. / 科尔沁沙地植被重建对土壤固氮和固碳菌群的影响.

To determine the diversity of nitrogen-fixing and carbon-fixing microbial groups in aeolian sandy soil and the effects of sand-fixation plantation type on the structures of two microbial groups in the Horqin Sandy Land, we selected six representative sand-fixation vegetations with the same age, including Caragana microphylla, Artemisia halodendron, Salix gordejevii, Hedysarum fruticosum, Populus simonii, and Pinus sylvestris var. mongolica as well as their adjacent natural Ulmus pumila open forest as test objects to investigate the diversities and structures of nifH- and cbbL-carrying microbial communities in soil by high-throughput sequencing technique. The results showed that vegetation type significantly affected soil physical and chemical properties, microbiological activities, diversities and the main compositions of nitrogen-fixing and carbon-fixing microbial communities. The diversity of soil nitrogen-fixing microbial communities under S. gordejevii and P. simonii plantations and that of carbon-fixing microbial communities under P. sylvestris var. mongolica and P. simonii plantations were significantly higher than those of other plantations. Skermanella, Bradyrhizobium, Azospirillum, and Azohydromonas were dominant nitrogen-fixation genera, with the average relative abundance of 22.3%, 21.5%, 20.8%, and 17.8%, respectively. Soil carbon-fixation microbial communities were dominated by Pseudonocardia, Bradyrhizobium, Cupriavidus, and Mesorhizobium, with relative abundance of 22.4%, 18.5%, 10.5%, and 6.0%, respectively. Soil nitrogen-fixing microbial community under C. mirophylla plantation and carbon-fixing communities under S. gordejevii and P. simonii plantations were very close to those of natural U. pumila open forest. Soil organic matter, NH4+-N, and total phosphorus were the direct determining factors for nitrogen-fixing microbial community, while pH, soil moisture, and available phosphorus were main factors influencing carbon-fixing microbial community. These observations potentially provide the scienti-fic foundations for evaluating the ecological benefits of revegetation practice in sandy lands.

Non-filamentous bulking of activated sludge induced by graphene oxide: Insights from extracellular polymeric substances.

Widespread use of nanomaterials raises concerns. The underlying mechanism by which graphene oxide (GO) nanoparticles causes poor settleability of activated sludge remains unclear. To explore this mechanism, three reactors with different GO concentrations were established. Extended Derjaguin-Landau-Verwey-Overbeek theory indicated that GO destroyed the property of extracellular polymeric substances (EPS), increasing the energy barrier between bacteria. Low levels of uronic acid and hydrogen bonding in exopolysaccharide weakened the EPS gelation increasing aggregation repulsion. Lager amounts of hydrophilic amino acid and looser structure of extracellular proteins for exposing inner hydrophilic groups significantly contributed to the hydrophilicity of EPS. Both changes implied deterioration in EPS structure under GO stress. Metagenome demonstrated a decrease in genes responsible for capsular polysaccharide colonization and genes regulated the translocation of loose proteins were increased, which increased repulsion between bacteria. This study elucidated that changes in EPS secretion under GO exposure are the underlying causes of poor settleability.

Production of bilirubin via whole-cell transformation utilizing recombinant Corynebacterium glutamicum expressing a ß-glucuronidase from Staphylococcus sp. RLH1.

Bilirubin, a key active ingredient of bezoars with extensive clinical applications in China, is produced through a chemical process. However, this method suffers from inefficiency and adverse environmental impacts. To address this challenge, we present a novel and efficient approach for bilirubin production via whole-cell transformation. In this study, we employed Corynebacterium glutamicum ATCC13032 to express a ß-glucuronidase (StGUS), an enzyme from Staphylococcus sp. RLH1 that effectively hydrolyzes conjugated bilirubin to bilirubin. Following the optimization of the biotransformation conditions, a remarkable conversion rate of 79.7% in the generation of bilirubin was obtained at temperate 40 °C, pH 7.0, 1 mM Mg2+ and 6 mM antioxidant NaHSO3 after 12 h. These findings hold significant potential for establishing an industrially viable platform for large-scale bilirubin production.

Highly Optically Selective and Thermally Insulating Porous Calcium Silicate Composite SiO2 Aerogel Coating for Daytime Radiative Cooling.

Daytime radiative cooling technology offers a low-carbon, environmentally friendly, and nonpower-consuming approach to realize building energy conservation. It is important to design materials with high solar reflectivity and high infrared emissivity in atmospheric windows. Herein, a porous calcium silicate composite SiO2 aerogel water-borne coating with strong passive radiative cooling and high thermal insulation properties is proposed, which shows an exceptional solar reflectance of 94%, high sky window emissivity of 96%, and 0.0854 W/m·K thermal conductivity. On the SiO2/CaSiO3 radiative cooling coating (SiO2-CS-coating), a strategy is proposed to enhance the atmospheric window emissivity by lattice resonance, which is attributed to the eight-membered ring structure of porous calcium silicate, thereby increasing the atmospheric window emissivity. In the daytime test (solar irradiance 900W/m2, ambient temperature 43 °C, wind speed 0.53 m/s, humidity 25%), the temperature inside the box can achieve a cooling temperature of 13 °C lower than that of the environment, which is 30 °C, and the theoretical cooling power is 96 W/m2. Compared with the commercial white coating, SiO2-CS-coating can save 70 kW·h of electric energy in 1 month, and the energy consumption is reduced by 36%. The work provides a scalable, widely applicable radiative-cooling coating for building comfort, which can greatly reduce indoor temperatures and is suitable for building surfaces.

PU.1 alleviates the inhibitory effects of cigarette smoke on endothelial progenitor cell function and lung-homing through Wnt/ß-catenin and CXCL12/CXCR4 pathways.

INTRODUCTION: Endothelial progenitor cells (EPCs) dysfunction is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The transcription factor PU.1 is essential for the maintenance of stem/progenitor cell homeostasis. However, the role of PU.1 in COPD and its effects on EPC function and lung-homing, remain unclear. This study aimed to explore the protective activity of PU.1 and the underlying mechanisms in a cigarette smoke extract (CSE)-induced emphysema mouse model. METHODS: C57BL/6 mice were treated with CSE to establish a murine emphysema model and injected with overexpressed PU.1 or negative control adeno-associated virus. Morphometry of lung slides, lung function, and apoptosis of lung tissues were evaluated. Immunofluorescence co-localization was used to analyze EPCs homing into the lung. Flow cytometry was performed to detect EPC count in lung tissues and bone marrow (BM). The angiogenic ability of BM-derived EPCs cultured in vitro was examined by tube formation assay. We determined the expression levels of PU.1, ß-catenin, C-X-C motif ligand 12 (CXCL12), C-X-C motif receptor 4 (CXCR4), stem cell antigen-1 (Sca-1), and stemness genes. RESULTS: CSE exposure significantly reduced the expression of PU.1 in mouse lung tissues, BM, and BM-derived EPCs. PU.1 overexpression attenuated CSE-induced emphysematous changes, lung function decline, and apoptosis. In emphysematous mice, PU.1 overexpression markedly reversed the decreased proportion of EPCs in BM and promoted the lung-homing of EPCs. The impaired angiogenic ability of BM-derived EPCs induced by CSE could be restored by the overexpression of PU.1. In addition, PU.1 upregulation evidently reversed the decreased expression of ß-catenin, CXCL12, CXCR4, Scal-1, and stemness genes in mouse lung tissues, BM, and BM-derived EPCs after CSE exposure. CONCLUSIONS: PU.1 alleviates the inhibitory effects of CSE on EPC function and lung-homing via activating the canonical Wnt/ß-catenin pathway and CXCL12/CXCR4 axis. While further research is needed, our research may indicate a potential therapeutic target for COPD patients.

A nomogram model for predicting 5-year risk of prediabetes in Chinese adults.

Early identification is crucial to effectively intervene in individuals at high risk of developing pre-diabetes. This study aimed to create a personalized nomogram to determine the 5-year risk of pre-diabetes among Chinese adults. This retrospective cohort study included 184,188 participants without prediabetes at baseline. Training cohorts (92,177) and validation cohorts (92,011) were randomly assigned (92,011). We compared five prediction models on the training cohorts: full cox proportional hazards model, stepwise cox proportional hazards model, multivariable fractional polynomials (MFP), machine learning, and least absolute shrinkage and selection operator (LASSO) models. At the same time, we validated the above five models on the validation set. And we chose the LASSO model as the final risk prediction model for prediabetes. We presented the model with a nomogram. The model's performance was evaluated in terms of its discriminative ability, clinical utility, and calibration using the area under the receiver operating characteristic (ROC) curve, decision curve analysis, and calibration analysis on the training cohorts. Simultaneously, we also evaluated the above nomogram on the validation set. The 5-year incidence of prediabetes was 10.70% and 10.69% in the training and validation cohort, respectively. We developed a simple nomogram that predicted the risk of prediabetes by using the parameters of age, body mass index (BMI), fasting plasma glucose (FBG), triglycerides (TG), systolic blood pressure (SBP), and serum creatinine (Scr). The nomogram's area under the receiver operating characteristic curve (AUC) was 0.7341 (95% CI 0.7290-0.7392) for the training cohort and 0.7336 (95% CI 0.7285-0.7387) for the validation cohort, indicating good discriminative ability. The calibration curve showed a perfect fit between the predicted prediabetes risk and the observed prediabetes risk. An analysis of the decision curve presented the clinical application of the nomogram, with alternative threshold probability spectrums being presented as well. A personalized prediabetes prediction nomogram was developed and validated among Chinese adults, identifying high-risk individuals. Doctors and others can easily and efficiently use our prediabetes prediction model when assessing prediabetes risk.

Akkermansia muciniphila and its outer membrane protein Amuc_1100 prevent high-fat diet-induced nonalcoholic fatty liver disease in mice.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. A. muciniphila and its outer membrane protein Amuc_1100 ameliorate metabolic disorders, enteritis, depression, and other diseases in mice. The NAFLD mouse model was established by feeding a high-fat diet (HFD) for 10 weeks. To assess the effect of A. muciniphila and Amuc_1100 on NAFLD, we used atorvastatin, a common lipid-lowering drug, as a positive control. A. muciniphila and Amuc_1100 significantly reduced body weight and serum ALT and AST levels, and improved serum lipid levels in NAFLD mice, which had similar effects to Ator. In addition, A. muciniphila and Amuc_1100 decreased the concentration of LPS in the serum and upregulated the mRNA expression of the colonic tight junction proteins. In the liver, A. muciniphila and Amuc_1100 significantly reduced the mRNA expression levels of nodular receptor protein 3 (NLRP3) and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB), and the protein and mRNA expression levels inflammatory cytokines. At the genus level, Amuc_1100 treatment significantly reduced the abundance of Coriobacteriaceae_UCG-002 produced by the HFD. The abundances of Blautia, norank_f__Ruminococcaceae, Lachnoclostridium, GCA-900066575 and Lachnospiraceae_UCG-006 increased dramatically. Together, A. muciniphila and Amuc_1100 alleviate HFD-induced NAFLD by acting on the gut-liver axis and regulating gut microbes.

Revealing the role of regulatory T cells in the tumor microenvironment of lung adenocarcinoma: a novel prognostic and immunotherapeutic signature.

Background: Regulatory T cells (Tregs), are a key class of cell types in the immune system. In the tumor microenvironment (TME), the presence of Tregs has important implications for immune response and tumor development. Relatively little is known about the role of Tregs in lung adenocarcinoma (LUAD). Methods: Tregs were identified using but single-cell RNA sequencing (scRNA-seq) analysis and interactions between Tregs and other cells in the TME were investigated. Next, we used multiple bulk RNA-seq datasets to construct risk models based on marker genes of Tregs and explored differences in prognosis, mutational landscape, immune cell infiltration and immunotherapy between high- and low-risk groups, and finally, qRT-PCR and cell function experiments were performed to validate the model genes. Results: The cellchat analysis showed that MIF-(CD74+CXCR4) pairs play a key role in the interaction of Tregs with other cell subpopulations, and the Tregs-associated signatures (TRAS) could well classify multiple LUAD cohorts into high- and low-risk groups. Immunotherapy may offer greater potential benefits to the low-risk group, as indicated by their superior survival, increased infiltration of immune cells, and heightened expression of immune checkpoints. Finally, the experiment verified that the model genes LTB and PTTG1 were relatively highly expressed in cancer tissues, while PTPRC was relatively highly expressed in paracancerous tissues. Colony Formation assay confirmed that knockdown of PTTG1 reduced the proliferation ability of LUAD cells. Conclusion: TRAS were constructed using scRNA-seq and bulk RNA-seq to distinguish patient risk subgroups, which may provide assistance in the clinical management of LUAD patients.

Dysregulations of metabolites and gut microbes and their associations in rats with noise induced hearing loss.

Background: Noise exposure could lead to hearing loss and disorders of various organs. Recent studies have reported the close relations of environmental noise exposure to the metabolomics dysregulations and gut microbiota disturbance in the exposers. However, the associations between gut microbial homeostasis and the body metabolism during noise-induced hearing loss (NIHL) were unclear. To get a full understanding of their synergy in noise-associated diseases, it is essential to uncover their impacts and associations under exposure conditions. Methods: With ten male rats with background noise exposure (≤ 40 dB) as controls (Ctr group), 20 age- and weight-matched male rats were exposed to 95 dB Sound pressure level (SPL) (LN group, n = 10) or 105 dB SPL noise (HN group, n = 10) for 30 days with 4 h/d. The auditory brainstem response (ABR) of the rats and their serum biochemical parameters were detected to investigate their hearing status and the potential effects of noise exposure on other organs. Metabolomics (UPLC/Q-TOF-MS) and microbiome (16S rDNA gene sequencing) analyses were performed on samples from the rats. Multivariate analyses and functional enrichments were applied to identify the dysregulated metabolites and gut microbes as well as their associated pathways. Pearson correlation analysis was performed to investigate the associations of the dysregulations of microbiota and the metabolites. Results: NIHL rat models were constructed. Many biochemical parameters were altered by noise exposure. The gut microbiota constitution and serum metabolic profiles of the noise-exposed rats were also dysregulated. Through metabolomics analysis, 34 and 36 differential metabolites as well as their associated pathways were identified in LN and HN groups, respectively. Comparing with the control rats, six and 14 florae were shown to be significantly dysregulated in the LN group and HN group, respectively. Further association analysis showed significant correlations between differential metabolites and differential microbiota. Conclusion: There were cochlea injuries and abnormalities of biochemical parameters in the rats with NIHL. Noise exposure could also disrupt the metabolic profiles and the homeostatic balance of gut microbes of the host as well as their correlations. The dysregulated metabolites and microbiota might provide new clues for prevention of noise-related disorders.

Aberrant reward dynamics in depression with anticipatory anhedonia.

OBJECTIVE: Previous studies have shown that anticipatory anhedonia is linked to abnormal reward processing. The present study aimed to explore the underlying neural mechanism of the influence of anticipatory anhedonia symptoms on reward processing. METHODS: Electrophysiological activities in the anticipatory and consummatory phase were recorded during the Monetary Incentive Delay (MID) task in 24 depressed high anticipatory anhedonia (HAA) patients, 25 depressed low anticipatory anhedonia (LAA) patients, and 29 healthy controls (HC). RESULTS: We suggested a significant condition × group interaction effect on feedback-related negativity (FRN) amplitudes during the consummatory phase, a smaller FRN in reward cue trails compared with neutral cue trail was revealed in the HC and LAA group, but such reward-related effect was not found in the HAA group. In addition, we found significant correlations between FRN, fb-P3 and cue-N1, cue-N2 in the HC group, besides, significant correlations between FRN, fb-P3 and cue-P2 was also revealed in the HC and LAA group. However, no significant correlation was found in HAA patients. CONCLUSIONS: Our results suggest that the link between the anticipatory and consummatory phase was interrupted in depressed HAA patients, which may be driven by the aberrant consummatory reward processing. SIGNIFICANCE: The current study is the first one to demonstrate the influence of anticipatory anhedonia symptom on the association between anticipatory and consummatory phase of reward process.