Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study.

Introduction: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation. Methods: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments. Results: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland. Conclusion: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

Associations between frailty, depression and risk of hospitalisation for infection: A large prospective cohort study.

BACKGROUND: There is a considerable lack of epidemiological evidence on whether frailty, and frailty comorbid depression could increase the risk of infections in older adults. This study aimed to examine the prospective association between frailty, depression, and risk of infections. METHODS: A total of 308,892 eligible participants were included. Linked hospital admission records (HES) were used to identify a primary or secondary diagnosis of depression, and infection. Frailty was assessed by Fried frailty phenotype indicators. Cox proportional hazard model was conducted to examine the associated risk between frailty, depression, comorbid frailty and depression and risk of incident infections. Results were stratified by age and gender. RESULTS: During the follow-up, 74,749 (24.19 %) incident any infection cases were identified, the incidence density of any infection was 17.29/1000 person years. Frailty alone (HR = 1.38, 95 % CI: 1.33-1.43), depression alone (HR = 1.90, 95 % CI: 1.86-1.94), and comorbid frailty and depression (HR = 1.91, 95 % CI: 1.82-1.99) were associated with greater risks of any infections relative to participants with neither frailty nor depression. The associations between frailty alone, depression alone, comorbid frailty and depression, and any infections/most infection subtypes were significant for all age strata in both male and female. LIMITATIONS: Frailty phenotype was assessed through the adapted Fried criteria, based on a mix of self-reported and objective measurements. CONCLUSION: Frailty, depression, and comorbid frailty and depression were significantly associated with increased risk of incident infections.

The effect of PAP on UACR and metabolic indexes in patients with MS and OSAHS.

PURPOSE: To investigate the effects of positive airway pressure (PAP) device on urinary albumin to creatinine ratio (UACR) and metabolic indexes in patients with metabolic syndrome (MS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: This study is a retrospective cohort study. Grouped according to whether to use PAP treatment, there were 25 cases in the PAP group and 44 cases in the no OSAHS treatment group. The PAP group received positive airway pressure device and routine treatment of MS. The no OSAHS treatment group received routine treatment of OSAHS and MS. The treatment period is 3 months. RESULTS: 1. The PAP group demonstrated significant reductions in Body Mass Index (BMI), Waist circumference (WC), Neck circumference (NC), Visceral fat area (VFA), Fasting C peptide (FCP), high-sensitivity C-reactive protein (hs-CRP), and UACR compared to the no OSAHS treatment group, with significant differences (P all <0.05). Among them, the UACR in the PAP group decreased significantly (from 86.05(52.55,131.61)mg/g to 16.76(8.70,25.12)mg/g, P<0.001). 2. Linear regression analysis using the decrease in UACR values as the dependent variable demonstrated a positive linear relationship with the decrease in BMI, VFA, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Furthermore, multiple linear regression analysis indicated that the decrease in VFA (B=0.537 [95% confidence interval, 0.084 to 0.989]; P = 0.021) and HOMA-IR (B=1.000 [95% confidence interval, 0.082 to 1.917]; P = 0.033) values independently correlated with decrease in UACR values. CONCLUSIONS: PAP treatment can reduce UACR in patients with MS and OSAHS, and has the effect of improving metabolic disorders. The decrease of UACR in patients may be related to the decrease of visceral fat and the improvement of insulin resistance.

Alleles on locus chromosome 4B from different parents confer tiller number and the yield-associated traits in wheat.

Pleiotropy is frequently detected in agronomic traits of wheat (Triticum aestivum). A locus on chromosome 4B, QTn/Ptn/Sl/Sns/Al/Tgw/Gl/Gw.caas-4B, proved to show pleiotropic effects on tiller, spike, and grain traits using a recombinant inbred line (RIL) population of Qingxinmai × 041133. The allele from Qingxinmai increased tiller numbers, and the allele from line 041133 produced better performances of spike traits and grain traits. Another 52 QTL for the eight traits investigated were detected on 18 chromosomes, except for chromosomes 5D, 6D, and 7B. Several genes in the genomic interval of the locus on chromosome 4B were differentially expressed in crown and inflorescence samples between Qingxinmai and line 041133. The development of the KASP marker specific for the locus on chromosome 4B is useful for molecular marker-assisted selection in wheat breeding.

Mapping QTLs for adult-plant resistance to powdery mildew and stripe rust using a recombinant inbred line population derived from cross Qingxinmai × 041133.

A recombinant inbred line (RIL) population derived from wheat landrace Qingxinmai and breeding line 041133 exhibited segregation in resistance to powdery mildew and stripe rust in five and three field tests, respectively. A 16K genotyping by target sequencing (GBTS) single-nucleotide polymorphism (SNP) array-based genetic linkage map was used to dissect the quantitative trait loci (QTLs) for disease resistance. Four and seven QTLs were identified for adult-plant resistance (APR) against powdery mildew and stripe rust. QPm.caas-1B and QPm.caas-5A on chromosomes 1B and 5A were responsible for the APR against powdery mildew in line 041133. QYr.caas-1B, QYr.caas-3B, QYr.caas-4B, QYr.caas-6B.1, QYr.caas-6B.2, and QYr.caas-7B detected on the five B-genome chromosomes of line 041133 conferred its APR to stripe rust. QPm.caas-1B and QYr.caas.1B were co-localized with the pleiotropic locus Lr46/Yr29/Sr58/Pm39/Ltn2. A Kompetitive Allele Specific Polymorphic (KASP) marker KASP_1B_668028290 was developed to trace QPm/Yr.caas.1B. Four lines pyramiding six major disease resistance loci, PmQ, Yr041133, QPm/Yr.caas-1B, QPm.caas-2B.1, QYr.caas-3B, and QPm.caas-6B, were developed. They displayed effective resistance against both powdery mildew and stripe rust at the seedling and adult-plant stages.

A membrane associated tandem kinase from wild emmer wheat confers broad-spectrum resistance to powdery mildew.

Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36, originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance.

Affiliate stigma and its association with family burden among family members of people living with schizophrenia in China.

PURPOSE: Understanding affiliate stigma and its impact on family of people living with schizophrenia (PLS) in China is important for culturally informed intervention. This study aims to describe the pattern of affiliate stigma of family members of PLS in China and investigated the association between affiliate stigma and family burden. METHODS: PLS and their family members dwelling in community were randomly recruited from four cities across China and completed measures of affiliate stigma and family burden. Linear regression analyses were used to determine the association between affiliate stigma and family burden. RESULTS: A total of 493 dyads of family member and PLS were include in this study. The mean affiliate stigma in family members was 2.21 (SD = 0.61). The vast majority of family members reported the feeling of inferiority, helpless and sad because of their family members' schizophrenia, but few family members refusing to communicate or contact with the PLS. The mean score of overall family burden was 22.25 (SD = 14.90), with 98 % of participants reported moderate or severe burden. A higher level of affiliate stigma was associated with more family burden (b = 7.837, 95CI: 5.240 to 8.747). Affiliate stigma was significantly associated with family daily activities, entertainment activities, family relationship, physical health and mental health of family members, but not family economic burden. CONCLUSION: A higher level of affiliate stigma was associated with more family burden among family with PLS. Anti-stigma intervention of mental illness should be consider not only PLS but also their family members.

Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader.

The process of induced pluripotent stem cells (iPSCs) reprogramming involves several crucial events, including the mesenchymal-epithelial transition (MET), activation of pluripotent genes, metabolic reprogramming, and epigenetic rewiring. Although these events intricately interact and influence each other, the specific element that regulates the reprogramming network remains unclear. Dux, a factor known to promote totipotency during the transition from embryonic stem cells (ESC) to 2C-like ESC (2CLC), has not been extensively studied in the context of iPSC reprogramming. In this study, we demonstrate that the modification of H3K18la induced by Dux overexpression controls the metabolism-H3K18la-MET network, enhancing the efficiency of iPSC reprogramming through a metabolic switch and the recruitment of p300 via its C-terminal domain. Furthermore, our proteomic analysis of H3K18la immunoprecipitation experiment uncovers the specific recruitment of Brg1 during reprogramming, with both H3K18la and Brg1 being enriched on the promoters of genes associated with pluripotency and epithelial junction. In summary, our study has demonstrated the significant role of Dux-induced H3K18la in the early reprogramming process, highlighting its function as a potent trigger. Additionally, our research has revealed, for the first time, the binding of Brg1 to H3K18la, indicating its role as a reader of histone lactylation.

Flavor formation of tilapia byproduct hydrolysates in Maillard reaction.

The Maillard reaction (MR) of tilapia byproduct protein hydrolysates was investigated for the use of byproduct protein as a food ingredient and to mask its fishy odor and bitter flavor. The flavor differences in tilapia byproduct hydrolysates before and after the MR were analyzed to explore the key flavor precursor peptides and amino acids involved in MR. The results suggested that eight key volatile substances, including 2,5-dimethylpyrazine, 2-pentylfuran, hexanal, octanal, nonanal, (E)-2-decenal, decanal, and 1-octen-3-ol contributed most to the MR products group (ROAV > 1). Ten volatile compounds, including 1-octen-3-ol, hexanal, 2-pentylfuran, 2,5-dimethylpyrazine, methyl decanoate, and 2-octylfuran, were the flavor markers that distinguished the different samples (VIP > 1). The four most consumed peptides were VAPEEHPTL, GPIGPRGPAG, KSADDIKKAF, and VWEGQNIVK. Umami peptides and bitter free amino acids (FAAs) were the key flavor precursor peptide and FAAs, respectively. Overall, the hydrolysates of tilapia byproducts with flavor improved by MR are a promising strategy for the production of flavorings.

Neutrophil to lymphocyte ratio may predict efficacy of anti-PD-1 inhibitors in advanced EGFR-mutant non-small cell lung cancer: retrospective cohort study.

This study aimed to investigate the associations between the clinical characteristics and effectiveness of anti-PD-1 inhibitors in patients with EGFR-sensitive mutations, aiming to identify the potential subgroup of patients who might benefit from anti-PD-1 inhibitor treatment. Patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-sensitive mutations who received subsequent anti-PD-1 inhibitors in combination with chemotherapy/antiangiogenic agents or alone after progression to tyrosine kinase inhibitors (TKIs) were screened. Clinical characteristics, including hematological parameters, were investigated for potential correlations with clinical outcomes. Subgroup and multivariate analyses were used for further confirmation of the relationship. Kaplan-Meier curves and Cox survival regression models using the log-rank test were used for progression-free survival (PFS) and overall survival (OS) assessments between the groups. Multiple regression analysis was performed using the standard regression coefficient values. The Wilcoxon test was used for the analysis of the variation in NLR. P ≤ 0.05 was considered to indicate statistical significance. This study was a retrospective study. Twenty-two patients met the inclusion criteria and were included in the study. The median PFS was 3.05 months (95% CI, 2.9-10.2 months). The median OS was 7.30 months (95% CI, 5.2-18.1 months). PFS in low neutrophil to lymphocyte ratio (NLR ≤ 4) was significantly longer than high NLR (NLR > 4, 5.7 months versus 2.0 months, HR, 0.35, 95% CI, 0.08-0.63, P = 0.0083). The OS in the low NLR group was also significantly better than that in the high NLR group (OS, 21.3 months versus 5.0 months, HR, 0.33; 95% CI, 0.09-0.74; P = 0.0163). In the multivariate analysis, NLR was the only significant factor for OS benefits (ß = 3.535, 95% CI, 1.175-10.636, P = 0.025). Further investigation revealed that front-line TKIs exposure may contribute to the elevation or decrease of NLR, and finally lead to different efficacy outcomes by anti-PD-1 inhibitors. The findings suggest that a portion of advanced NSCLC patients with low NLR characteristics (NLR ≤ 4), even those harboring EGFR-sensitive mutations, could benefit from anti-PD-1 inhibitors as further line treatment after progression to EGFR-TKIs.

Isolation and characterization of natural nano starch from amaranth starch.

Nano starch exhibits many advantages for application in diverse fields. Amaranth starch consisted of starch particle aggregates, isolated amaranth starch, and few natural nano starch (NNS), while NNS (0.92 ± 0.12 µm) was successfully isolated for the first time. Compared with the isolated amaranth starch, NNS showed smaller particle size but larger molecular weight, suggesting that the molecules arranged densely. NNS had a weak A-type crystal structure because of its more content of short starch chains, but higher amylose content resulted in the increase of its gelatinization temperature. The special NNS, owning several different physicochemical properties from amaranth starch, can open new ways for the production and application of nano biomass materials.

Knowledge, attitudes and practices towards advance directives among clinical nurses: Multicenter cross-sectional survey.

AIMS AND OBJECTIVES: This study aimed to describe the knowledge, attitudes and practices (KAP) of nurses in implementing advance directives (ADs) for older patients and analyze the influencing factors before the establishment of the first advance directives act in China. DESIGN: Multicenter cross-sectional survey. The standards for reporting the STROBE checklist are used. METHODS: This cross-sectional study developed a self-designed structured questionnaire to assess nurses' knowledge, attitudes and practices about ADs. Nurses were recruited by stratified random sampling through the Nursing Departments of 12 hospitals in southwest China and were asked to fill out the questionnaire face to face about knowledge, attitudes and practices. Data were analyzed following descriptive statistics, rank-sum test and multiple linear regression. RESULTS: This study included 950 nurses. The study found that nurses were extremely supportive of ADs. Unmarried nurses had better knowledge of ADs than married ones. Nevertheless, there was a discrepancy between the participants' knowledge, attitude and practice. The participants' practice was lower (4.3%) compared with their attitude (81.9%) and knowledge (42.2%). Knowledge on, attitudes towards and standardized procedures for ADs in the workplace affected nursing practice. CONCLUSIONS: The study recommends that courses on ADs and appropriate support from medical institutions should be provided to nurses to increase their knowledge and confidence in implementing ADs. Healthcare professionals should be sufficiently equipped to implement ADs and handle their execution appropriately to provide adequate end-of-life care corresponding to patients' wishes. RELEVANCE TO CLINICAL PRACTICE: The study results inform rich insights as it discusses the numerous interrelating factors influencing these three fundamental aspects that affect the success of any AD policy by surveying the knowledge, attitudes and practices of clinical nurses. Furthermore, our results hint at distinct areas of improvement in the nursing practice to facilitate the wider implementation and acceptance of ADs in China. PATIENT OR PUBLIC CONTRIBUTION: This study involved no patient.

Factors controlling the heavy metal ion activity in soil contaminated by microplastics with different mulch durations: Partial least squares path model.

Film covers have been widely applied worldwide. However, the effects of long-term plastic film mulching use on heavy metal (HM) activity in soil remain unclear. This study focused on farmland in the upstream part of the Pearl River in China and collected 103 soil samples after 2, 5, and 15 years of plastic film mulching. The main environmental factors controlling microplastics (MPs), plasticizer phthalic acid esters (PAEs), HM pollution characteristics, and HM activity were analyzed. The results showed that Polyethylene (PE) and di(2-ethylhexyl) dicyclohexyl phthalate (DCHP) were the main MPs and PAEs, respectively. The abundance of MPs and the concentrations of free HM ions (Cd, Cu, and Ni) in the soil solution increased with increasing plastic film mulching duration. The Partial Least Squares Path Model (PLS-PM) indicated that after plastic film mulching, soil chemical properties (pH/amorphous Fe) and biological properties (Dissolved organic carbon/ Easily oxidizable carbon/Microbial biomass carbon) were the main controlling factors for free and complexed HM ions (Cd, Pb, Cu, and Ni). These results suggest that, after plastic film mulching, MPs indirectly regulate HM activity by altering soil properties. This study provides a new perspective for the management of MPs and HM activities in agricultural ecosystems.

Drug resistance and genetic diversity of clinical strains of Helicobacter pylori in the Qiannan Prefecture and Guiyang City,and their relationships with diseases / 中国人兽共患病学报

To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6％(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4％in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

Patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia: mediation effects of potentially harmful behavior, affiliate stigma, and social support.

Evidence on the associations between patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia is lacking. This study aimed at explore the underlying mechanisms between patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia. A cross-sectional study was carried out in four Chinese cities (Wuhan, Changsha, Guangzhou, and Shenzhen), between April, 2021 and March, 2022. A total of 493 patients and their family caregivers were invited to report related data. The Zarit burden interview, WHODAS 2.0, the Potentially harmful behavior scale, the Affiliate Stigma Scale, and the Multidimensional Scale of perceived social support were used to collect data. Linear regression analysis and bootstrapping analysis were conducted. The adjusted regression results showed that patients' disability (B = 0.616; 95% CI: 0.479-0.753), potentially harmful behavior on caregivers (B = 0.474; 95% CI: 0.232-0.716), and caregiver's low social support (B = -0.079; 95% CI: -0.158- -0.002), high level of affiliate stigma (B = 13.045; 95% CI: 10.227-15.864) were associated with higher level of caregiver burden (p < 0.05). In the mediation model, the direct path from patient's disability to caregiver burden (B = 0.428, ß = 0.371, p < 0.001) was significant and positive. Patient's disability was indirectly associated with caregiver burden through patient's potentially harmful behavior, caregiver's affiliate stigma, and social support, the standardized regression coefficients ranged from 0.026-0.049 (p < 0.05). Patient's potentially harmful behavior, caregiver's affiliate stigma, and social support mediated the relationship between patients' disability and caregiver burden. Future intervention studies designed to target these three factors may be beneficial for family caregivers of persons living with schizophrenia.

Ferroelectricity-Driven Self-Powered Weak Temperature and Broadband Light Detection in MoS2/CuInP2S6/WSe2 van der Waals Heterojunction Nanoarchitectonics.

Two-dimensional ferroelectric materials enrich the modulation degrees of freedom in self-powered van der Waals temperature/light detectors by incorporating pyroelectric and bulk photovoltaic effects. However, in addition to the low polarization, the practical applications of these materials are limited due to the significant challenge posed by their ultrathin nature, which affects their polarization stability. In this report, we introduce a design for a dual heterostructure-stabilized van der Waals heterojunction that addresses this challenge by improving the performance and extending the operational lifetime of self-powered van der Waals temperature/light detectors. The design is demonstrated using the MoS2/CuInP2S6 (CIPS)/WSe2 van der Waals heterojunction, which exhibits sensitivity to small temperature changes induced by weak light across the ultraviolet to mid-infrared spectrum. It can generate a noticeable pyroelectric current without the need for an external voltage, and its pyroelectric coefficient exceeds 130 and 978 µC/m2 K for 45 and 70 nm CIPS, respectively. The heterojunction offers high detection accuracy, with a temperature variation sensitivity as small as 0.1 K and an optical power intensity detection range from low to 1 µW/cm2. Additionally, the heterojunction exhibits exceptional detectivity (D*) for different light wavelengths. Remarkably, the self-powered detection performance remains stable for months without obvious degradation in the natural environment. These results offer a promising solution for high-performance, self-sustaining temperature/light detection applications and pave the way for the development of future ferroelectricity-driven photodetection technologies.

Alterations of lower respiratory tract microbiome and short-chain fatty acids in different segments in lung cancer: a multiomics analysis.

Introduction: The lower respiratory tract microbiome is widely studied to pinpoint microbial dysbiosis of diversity or abundance that is linked to a number of chronic respiratory illnesses. However, it is vital to clarify how the microbiome, through the release of microbial metabolites, impacts lung health and oncogenesis. Methods: In order to discover the powerful correlations between microbial metabolites and disease, we collected, under electronic bronchoscopy examinations, samples of paired bronchoalveolar lavage fluids (BALFs) from tumor-burden lung segments and ipsilateral non-tumor sites from 28 lung cancer participants, further performing metagenomic sequencing, short-chain fatty acid (SCFA) metabolomics, and multiomics analysis to uncover the potential correlations of the microbiome and SCFAs in lung cancer. Results: In comparison to BALFs from normal lung segments of the same participant, those from lung cancer burden lung segments had slightly decreased microbial diversity in the lower respiratory tract. With 18 differentially prevalent microbial species, including the well-known carcinogens Campylobacter jejuni and Nesseria polysaccharea, the relative species abundance in the lower respiratory tract microbiome did not significantly differ between the two groups. Additionally, a collection of commonly recognized probiotic metabolites called short-chain fatty acids showed little significance in either group independently but revealed a strong predictive value when using an integrated model by machine learning. Multiomics also discovered particular species related to SCFAs, showing a positive correlation with Brachyspira hydrosenteriae and a negative one with Pseudomonas at the genus level, despite limited detection in lower airways. Of note, these distinct microbiota and metabolites corresponded with clinical traits that still required confirmation. Conclusions: Further analysis of metagenome functional capacity revealed that genes encoding environmental information processing and metabolism pathways were enriched in the lower respiratory tract metagenomes of lung cancer patients, further supporting the oncogenesis function of various microbial species by different metabolites. These findings point to a potent relationship between particular components of the integrated microbiota-metabolites network and lung cancer, with implications for screening and diagnosis in clinical settings.

Quantification and characterization of microplastics in farmland soils of Jiangsu Province, East China.

The soil ecosystem plays a significant role in the dynamics of microplastics. Qualitative and quantitative analyses of microplastics in six farmland plots from the cities of Nanjing, Suzhou, and Xuzhou were conducted by using laser infrared imaging system (LDIR). The results showed that the abundance of microplastics in farmland soils in Jiangsu Province ranged from 667-9333 items/kg, and the difference between the abundance of microplastics in soils from open-field cultivation and greenhouse farming was not significant. The vertical distribution characteristics showed that the abundance of microplastic decreased significantly with the increase of soil depth. However, there was no significant difference in particle size between top soil (0-5 cm) and deep soil (10-20 cm). Fragments were the most common microplastic form in soil samples (94.6%), with polyvinyl chloride (PVC) being the main polymer type, followed by polyethylene terephthalate (PET). Compared with previous studies conducted in China, the abundance of microplastics in farmland soils in Jiangsu Province was at moderate level but was notably higher than other places within the Yangtze River Delta region. The conclusions drawn from this paper provided important reference data for future assessment of microplastic pollution in agricultural fields. Furthermore, they establish a fundamental groundwork for understanding the migration patterns of MPs in soil environments.

Upregulation of Pin1 contributes to alleviation of cognitive dysfunction in diabetic mice.

OBJECTIVE: This study aimed to explore the molecular mechanism underlying the role of Pin1 in cognitive dysfunction in diabetic mice. METHODS: Using a streptozotocin-induced diabetic mouse model, an adeno-associated virus carrying the Pin1 gene was used to upregulate Pin1 expression in the hippocampus of diabetic mice. Animal behavior tests and molecular biology techniques were further used to explore the role of Pin1 in cognitive dysfunction in diabetic mice. RESULTS: Our study demonstrated that upregulation of Pin1 expression increased the phosphorylation of AKT and insulin receptor substrate 1 downstream signaling molecules of the IR-IGF1R pathway, increased the phosphorylation of GSK-3ß, and concomitantly decreased the phosphorylation of Tau in the hippocampus of diabetic mice, thereby improving the ultrastructural pathology of the hippocampus and further alleviating diabetes-related cognitive impairment. CONCLUSION: Pin1 can improve cognitive dysfunction in diabetic mice.

Exploration of a novel prognostic model based on nomogram in non-small cell lung cancer patients with distant organ metastasis: implications for immunotherapy.

Background: Evidence for the effects of immunotherapy in non-small cell lung cancer (NSCLC) patients with distant organ metastasis is insufficient, and the predictive efficacy of established markers in tissue and blood is elusive. Our study aimed to determine the prognostic factors and develop a survival prognosis model for these patients. Methods: A total of 100 advanced NSCLC patients with distant organ metastases, who received single or combination immune checkpoint inhibitors (ICIs) in Xijing Hospital between June 2018 and June 2021, were enrolled for retrospective analysis. The major clinicopathological parameters were collected, and associated survival outcomes were followed up by telephone or inpatient follow-up for nearly 3 years to assess prognoses. The survival prognosis model was established based on univariate and multivariate Cox regression analyses to determine the candidate prognostic factors. Results: From the start of immunotherapy to the last follow-up, 77 patients progressed and 42 patients died, with a median follow-up of 18 months [95% confidence interval (CI): 15-19.9]. The median progression-free survival (PFS) and overall survival (OS) were 8 months (95% CI: 5.6-10.4) and 21 months (95% CI: 8.9-33.1), respectively. Multivariate Cox proportional hazards analysis showed Eastern Cooperative Oncology Group performance status (ECOG PS), body mass index (BMI), age-adjusted Charlson comorbidity index (ACCI), lactate dehydrogenase (LDH), and absolute neutrophil count (ANC) were correlated significantly with OS. Based on these five predictive factors, a nomogram and corresponding dynamic web page were constructed with a concordance index (C-index) of 0.81 and a 95% CI of 0.778-0.842. Additionally, the calibration plot and time-receiver operating characteristic (ROC) curve validated the precision of the model at 6-, 12-, and 18-month area under the curves (AUCs) reached 0.934, 0.829, and 0.846, respectively. According to the critical point of the model, patients were further divided into a high-risk total point score (TPS) >258, middle-risk (204< TPS ≤258), and low-risk group (TPS ≤204), and significant OS differences were observed among the three subgroups (median OS: 4.8 vs. 13.0 vs. 32.9 months). Conclusions: A feasible and practical model based on clinical characteristics has been developed to predict the prognosis of NSCLC patients with distant organ metastasis undergoing immunotherapy.