Melanin Nanoparticle-Modified Probiotics for Targeted Synergistic Therapy of Ulcerative Colitis.

Ulcerative colitis (UC) is a recurrent chronic mucosal inflammation disease whose most significant pathological characteristics are intestinal inflammation and damaged mucosal barrier induced by reactive oxygen/nitrogen species, abnormal immune microenvironment, and intestinal microecological imbalance. Oral probiotics are a living therapy for intestinal diseases, but their clinical application is hindered by poor bacterial biological activity and insufficient intestinal retention. Here, we developed a targeted oral formulation, functionalized probiotic Lf@MPB, with Lactobacillus fermentum (Lf) as the core and modified melanin nanoparticles (MNPs) on its surface through a click reaction of tricarboxyphenylboronic acid for synergistic therapy of UC. In vitro experiments showed that Lf@MPB not only possessed strong free radical scavenging ability, reduced cellular mitochondrial polarization, and inhibited apoptosis but also significantly enhanced the viability of Lf probiotics in simulated gastrointestinal fluid. Fluorescence imaging in vivo revealed the high accumulation of Lf@MPB at the site of intestinal inflammation in dextran sulfate sodium-induced UC mice. Moreover, in vivo results demonstrated that Lf@MPB effectively alleviated oxidative stress and inflammatory response and restored the intestinal barrier. In addition, 16S rRNA gene sequencing verified that Lf@MPB could increase the abundance and diversity of intestinal microbial communities and optimize microbial composition to inhibit the progression of UC. This work combines effective antioxidant and anti-inflammatory strategies with the oral administration of functionalized probiotics to provide a promising alternative for UC treatment.

Nanoconfinement steers nonradical pathway transition in single atom fenton-like catalysis for improving oxidant utilization.

The introduction of single-atom catalysts (SACs) into Fenton-like oxidation promises ultrafast water pollutant elimination, but the limited access to pollutants and oxidant by surface catalytic sites and the intensive oxidant consumption still severely restrict the decontamination performance. While nanoconfinement of SACs allows drastically enhanced decontamination reaction kinetics, the detailed regulatory mechanisms remain elusive. Here, we unveil that, apart from local enrichment of reactants, the catalytic pathway shift is also an important cause for the reactivity enhancement of nanoconfined SACs. The surface electronic structure of cobalt site is altered by confining it within the nanopores of mesostructured silica particles, which triggers a fundamental transition from singlet oxygen to electron transfer pathway for 4-chlorophenol oxidation. The changed pathway and accelerated interfacial mass transfer render the nanoconfined system up to 34.7-fold higher pollutant degradation rate and drastically raised peroxymonosulfate utilization efficiency (from 61.8% to 96.6%) relative to the unconfined control. It also demonstrates superior reactivity for the degradation of other electron-rich phenolic compounds, good environment robustness, and high stability for treating real lake water. Our findings deepen the knowledge of nanoconfined catalysis and may inspire innovations in low-carbon water purification technologies and other heterogeneous catalytic applications.

Association between triglyceride glucose index and cognitive decline: A meta-analysis.

BACKGROUND: The triglyceride glucose (TyG) index, a novel surrogate indicator for insulin resistance (IR), is believed to be associated with various diseases. However, its connection with cognitive decline remains controversy. METHODS: The PubMed, EMBASE, Cochrane Library, Web of Science, and Medline databases were systematically searched up to October 2023 to assess the association between the TyG index and the risk of cognitive decline. Effect estimates and 95 % confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Our review included 3 cohort studies and 9 case-control/cross-sectional studies with a total of 5,603,350 participants. In comparison to a low TyG index, a higher TyG index was connected to an elevated risk of cognitive decline (RR/HR = 1.14, 95 % CI [1.11, 1.17], P < 0.05; OR = 1.75, 95 % CI [1.34, 2.29], P < 0.05). Furthermore, the dose-response analysis from the case-control/cross-sectional studies revealed a 1.42 times higher risk of cognitive decline per 1 mg/dl increment of the TyG index (OR = 1.42, 95 % CI [1.19, 1.69], P < 0.05). LIMITATIONS: The inclusion of observational studies in the meta-analysis demonstrated a lower hierarchy of evidence compared to randomized controlled trials. Moreover, we incorporated a restricted number of studies and identified significant heterogeneity among them, potentially attributed to the presence of numerous confounding variables. CONCLUSION: TyG index is related to cognitive decline. In view of some of the limitations of this study, further research will be necessary to confirm this relationship.

Associations between temporal eating patterns and body composition in young adults: a cross-sectional study.

PURPOSE: The aim of this study was to examine the associations between body composition and temporal eating patterns, including time of first eating occasion, time of last eating occasion, eating window, and eating jet lag (the variability in meal timing between weekdays and weekends). METHODS: A total of 131 participants were included in the study. Temporal eating pattern information was collected through consecutive 7-day eat timing questionnaires and photographic food records. Body composition was assessed by bioelectrical impedance analysis. Multiple linear regression models were used to evaluate the relationships of temporal eating patterns with body composition, and age was adjusted. Eating midpoint was additionally adjusted in the analysis of eating window. RESULTS: On weekdays, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with lower body fat percentage. On weekends, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with higher FFMI. Longer first eating occasion jet lag was associated with lower lean mass. CONCLUSION: Our study suggested that earlier and more regular eating patterns may have a benefit on body composition.

A qualitative study on inner experience of self-management behavior among elderly patients with type 2 diabetes in rural areas.

BACKGROUND: As a chronic metabolic disease, diabetes poses a serious threat to human health and has become a major public health problem in China and worldwide. In 2020, 30% of Chinese people (aged ≥ 60 years) reported having diabetes mellitus. Moreover, individuals with diabetes living in rural areas face a significantly higher mortality risk compared to those in urban areas. In this study, we explored the inner experience of self-management behaviors in elderly patients with type 2 diabetes in rural areas to inform targeted interventions. METHODS: A phenomenological research design was used to explore the inner experience of self-management in rural elderly diabetes. Ten elderly diabetic patients were sampled from December 2022 to March 2023 in rural areas of Yangcheng County, Jincheng City, ShanXi Province, China. The seven-step Colaizzi phenomenological was used to analyze the interview data and generate themes. RESULTS: Four themes emerged: "Insufficient self-management cognition", "Negative self-management attitude", "Slack self-management behavior", and "No time for self-management". CONCLUSION: The level of self-management among elderly patients with type 2 diabetes in rural areas is low. Healthcare professionals should develop targeted interventions aimed at enhancing their cognitive levels, modifying their coping styles, and improving their self-management abilities to improve their quality of life.

PUMC-MB1 is a novel group 3 medulloblastoma preclinical model, sensitive to PI3K/mTOR dual inhibitor.

PURPOSE: Medulloblastoma (MB), a common and heterogeneous posterior fossa tumor in pediatric patients, presents diverse prognostic outcomes. To advance our understanding of MB's intricate biology, the development of novel patient tumor-derived culture MB models with necessary data is still an essential requirement. METHODS: We continuously passaged PUMC-MB1 in vitro in order to establish a continuous cell line. We examined the in vitro growth using Cell Counting Kit-8 (CCK-8) and in vivo growth with subcutaneous and intracranial xenograft models. The xenografts were investigated histopathologically with Hematoxylin and Eosin (HE) staining and immunohistochemistry (IHC). Concurrently, we explored its molecular features using Whole Genome Sequencing (WGS), targeted sequencing, and RNA sequecing. Guided by bioinformatics analysis, we validated PUMC-MB1's drug sensitivity in vitro and in vivo. RESULTS: PUMC-MB1, derived from a high-risk MB patient, displayed a population doubling time (PDT) of 48.18 h and achieved 100% tumor growth in SCID mice within 20 days. HE and Immunohistochemical examination of the original tumor and xenografts confirmed the classification of PUMC-MB1 as a classic MB. Genomic analysis via WGS revealed concurrent MYC and OTX2 amplifications. The RNA-seq data classified it within the Group 3 MB subgroup, while according to the WHO classification, it fell under the Non-WNT/Non-SHH MB. Comparative analysis with D283 and D341med identified 4065 differentially expressed genes, with notable enrichment in the PI3K-AKT pathway. Cisplatin, 4-hydroperoxy cyclophosphamide/cyclophosphamide, vincristine, and dactolisib (a selective PI3K/mTOR dual inhibitor) significantly inhibited PUMC-MB1 proliferation in vitro and in vivo. CONCLUSIONS: PUMC-MB1, a novel Group 3 (Non-WNT/Non-SHH) MB cell line, is comprehensively characterized for its growth, pathology, and molecular characteristics. Notably, dactolisib demonstrated potent anti-proliferative effects with minimal toxicity, promising a potential therapeutic avenue. PUMC-MB1 could serve as a valuable tool for unraveling MB mechanisms and innovative treatment strategies.

Enhancing rice panicle branching and grain yield through tissue-specific brassinosteroid inhibition.

Crop yield potential is constrained by the inherent trade-offs among traits such as between grain size and number. Brassinosteroids (BRs) promote grain size, yet their role in regulating grain number is unclear. By deciphering the clustered-spikelet rice germplasm, we show that activation of the BR catabolic gene BRASSINOSTEROID-DEFICIENT DWARF3 (BRD3) markedly increases grain number. We establish a molecular pathway in which the BR signaling inhibitor GSK3/SHAGGY-LIKE KINASE2 phosphorylates and stabilizes OsMADS1 transcriptional factor, which targets TERMINAL FLOWER1-like gene RICE CENTRORADIALIS2. The tissue-specific activation of BRD3 in the secondary branch meristems enhances panicle branching, minimizing negative effects on grain size, and improves grain yield. Our study showcases the power of tissue-specific hormonal manipulation in dismantling the trade-offs among various traits and thus unleashing crop yield potential in rice.

[Epidemiological Characteristics of Lung Cancer Incidence 
in the Tumor Registration Area of Gansu Province from 2010 to 2019].

BACKGROUND: Lung cancer is the malignant tumor with the highest incidence rate and the heaviest disease burden in China. In recent years, lung cancer has shown a high incidence trend, seriously affecting the health of the population. In this paper, we analyze the characteristics of lung cancer incidence in 2019 and the trend of incidence rate from 2010-2019 in the tumor registration area of Gansu province, in order to provide a reference basis for the development of lung cancer prevention and control strategies in Gansu province. METHODS: By analyzing the cases of lung cancer incidence in the tumor registration area of Gansu province in 2019, we calculated the incidence rate, medium incidence rate, world incidence rate and other related indexes; we used Joinpoint to calculate the annual percentage change (APC) for trend analysis. RESULTS: In 2019, a total of 3757 new cases of lung cancer were reported in Gansu province, accounting for 14.96% of all new malignant tumors. The incidence rate, medium incidence rate and world incidence rate and world rate of lung cancer were 40.52/105, 25.78/105, 25.86/105; and the cumulative rate of 0-74 years old, and the truncation rate of 35-64 years old were 3.23%, 40.03/105, respectively. The incidence of lung cancer rises with age, and is high in the age group of 40 years and above, and the incidence peaks in the male and female populations in the group of 75 years and above, and the group of 80 years and above, respectively. The crude incidence rate of lung cancer in the tumor registration area of Gansu province from 2010-2019 showed an overall increasing trend, and the rate of increase was relatively fast, with an APC 5.39% (P<0.05); Separately, according to gender, urban and rural areas, the incidence of lung cancer in all populations showed an increasing trend, and the APC of male, female, urban and rural populations were 4.98%, 6.39%, 6.26%, and 4.64%, respectively (all P<0.05). According to the trend analysis of lung cancer incidence rate by age group, only lung cancer incidence in the age group of 65 years and above increased at an annual average rate of 4.15% (P<0.05). CONCLUSIONS: The incidence rate of lung cancer in the tumor registration area of Gansu province from 2010 to 2019 shows a rising trend year by year, and there are differences in the incidence of lung cancer in people of different genders, regions and age groups, so comprehensive prevention and control work should be carried out for the key populations of lung cancer incidence.

The clustering status of detached gastric cancer cells inhibits anoikis-induced ferroptosis to promote metastatic colonization.

BACKGROUND AND PURPOSE: Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis. METHODS: GC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan-Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients. RESULTS: Detached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan-Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression. CONCLUSIONS: Our study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential. Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.

Preparation, characterization and application of a composite bioflocculant.

Composite flocculant PAFS-PDM was prepared from Polymeric aluminium ferric sulphate (PAFS) and Poly (diallyl dimethyl ammonium chloride) (PDM) in this study. A bacterium was selected from the soil near the shale gas exploitation platform as a bioflocculant-producing bacterium, and polysaccharide was extracted and combined with PAFS-PDM to obtain composite bioflocculant (CBF) to treat shale gas fracturing flowback fluid. The prepared CBF was characterized and the results showed that the prepared PAFS-PDM contained aluminium-iron hydroxyl polymer, which was a cationic flocculant. By measuring the turbidity removal rate and chemical oxygen demand (COD) removal efficiency, the function mechanism of CBF on the shale gas fracturing flowback fluid was discussed. The results showed that CBF had a stable treatment effect on fracturing flowback fluid when the pH value was about 7.0. With the increase of dosage, the coagulation efficiency increased first and then decreased. When the dosage of the CBF was 2500 mg·L-1, the treatment effect of shale gas fracturing flowback fluid was the best, and COD removal rate reached 89.43%. Through Zeta potential analysis, it was concluded that one of the coagulation mechanisms was electrical neutralization. According to the characterization results, it could be concluded that both adsorption bridging and charge neutralization mechanisms played important roles in the treatment of shale gas fracturing flowback fluids.

Effects of feeding different levels of dietary corn silage on growth performance, rumen fermentation and bacterial community of post-weaning dairy calves.

OBJECTIVE: The objective of this study was to evaluate the growth performance, rumen fermentation parameters and bacterial community of post-weaning dairy calves in response to five diets varying in corn silage (CS) inclusion. METHODS: A total of forty Holstein weaned bull calves (80±3 days of age;128.2±5.03 kg at study initiation) were randomized into five groups (8 calves/group) with each receiving one of five dietary treatments offered as total mixed ration in a 123-d feeding study. Dietary treatments were control diet (CON; 0% CS dry matter [DM]); Treatment 1 (T1; 27.2% CS DM); Treatment 2 (T2; 46.5% CS DM); Treatment 3 (T3; 54.8% CS DM); and Treatment 4 (T4; 67.2% CS DM) with all diets balanced for similar protein and energy concentration. RESULTS: Results showed that calves offered CS had greater average daily gain, body length and chest depth growth, meanwhile altered rumen fermentation indicated by decreased rumen acetate concentrations. Principal coordinate analysis showed the rumen bacterial community structure was affected by varying CS inclusion diets. Bacteroidetes and Firmicutes were the predominant bacterial phyla in the calf rumens across all treatments. At the genus level, the abundance of Bacteroidales_RF16_group was increased, whereas Unclassified_ Lachnospiraceae was decreased for calves fed CS. Furthermore, Spearman's correlation test between the rumen bacteria and rumen fermentation parameters indicated that Bacteroidales_RF16_group and Unclassified Lachnospiraceae were positively correlated with propionate and acetate, respectively. CONCLUSION: The results of the current study suggested that diet CS inclusion was beneficial for post-weaning dairy calf growth, with 27.2% to 46.5% CS of diet DM recommended to achieve improved growth performance. Bacteroidales_RF16_group and Unclassified Lachnospiraceae play an important role in the rumen fermentation pattern for post-weaning calves fed CS.

Perioperative chemotherapy versus adjuvant chemotherapy treatment for resectable locally advanced gastric cancer: a retrospective cohort study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. METHODS: Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan-Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P < 0.001). NAC did not affect postoperative complications or AC-related grade 3/4 adverse events. Patients in NSA group achieved significantly longer OS (P = 0.021) and DFS (P = 0.002). The Cox regression model showed that NAC was independently associated with better OS (HR 0.245, P = 0.039) and DFS (HR 0.591, P = 0.031). CONCLUSIONS: Compared with SA, the administration of NSA was considered safe and feasible for achieving higher R0 resection rate without increasing the postoperative complications or AC-related grade 3/4 adverse events, and NAC was independently associated with better OS and DFS for resectable LAGC.

Years lived with disability of cancer in China: findings from disability weights measurement with a focus on the effect of disease burden.

Disability weights are crucial for quantifying health loss associated with non-fatal outcomes and were not well assessed in different countries, especially for specific cancer. Therefore, this study aimed to identify disability weights with a focus on specific cancer in a large Chinese population. Two types of web surveys were conducted, and 254 health states, including 30 new states for specific cancer, were investigated using paired comparison methods. The years lived with disability (YLDs) of cancer were calculated as the sum of the prevalence of each sequela of cancer multiplied by its relative disability weight. In total, 44,069 participants were eligible for the disability weights study. The disability weights of 254 health states were estimated. Among those, the disability weights of 18 specific cancer types varied greatly at diagnosis and primary treatment stage, with the value ranging from 0.619 (95% uncertainty interval (UI) 0.606-0.632) for brain cancer to 0.167 (95% UI 0.158-0.176) for oropharyngeal cancer. The discrepancy in YLDs calculated by different disability weights was high, and the largest gap for all cancer combined was approximately 30.14%. When calculated using the cancer-specific disability weights, a total of 1,967,830 (95% UI 1,928,880-2,008,060) YLDs of cancer were recorded in China. The disability weights of cancer varied greatly among cancer types and populations, which had considerable influence on the estimation of the disease burden. Cancer-specific disability weights could provide a more accurate evaluation of the cancer burden.

Crystallinity engineering for overcoming the activity-stability tradeoff of spinel oxide in Fenton-like catalysis.

A precise modulation of heterogeneous catalysts in structural and surface properties promises the development of more sustainable advanced oxidation water purification technologies. However, while catalysts with superior decontamination activity and selectivity are already achievable, maintaining a long-term service life of such materials remains challenging. Here, we propose a crystallinity engineering strategy to break the activity-stability tradeoff of metal oxides in Fenton-like catalysis. The amorphous/crystalline cobalt-manganese spinel oxide (A/C-CoMnOx) provided highly active, hydroxyl group-rich surface, with moderate peroxymonosulfate (PMS)-binding affinity and charge transfer energy and strong pollutant adsorption, to trigger concerted radical and nonradical reactions for efficient pollutant mineralization, thereby alleviating the catalyst passivation by oxidation intermediate accumulation. Meanwhile, the surface-confined reactions, benefited from the enhanced adsorption of pollutants at A/C interface, rendered the A/C-CoMnOx/PMS system ultrahigh PMS utilization efficiency (82.2%) and unprecedented decontamination activity (rate constant of 1.48 min-1) surpassing almost all the state-of-the-art heterogeneous Fenton-like catalysts. The superior cyclic stability and environmental robustness of the system for real water treatment was also demonstrated. Our work unveils a critical role of material crystallinity in modulating the Fenton-like catalytic activity and pathways of metal oxides, which fundamentally improves our understanding of the structure-activity-selectivity relationships of heterogeneous catalysts and may inspire material design for more sustainable water purification application and beyond.

Gastric cancer-associated long non-coding RNA profiling and noninvasive biomarker screening based on a high-risk population cohort.

BACKGROUND: Effective noninvasive biomarkers of gastric cancer (GC) are critical for early detection and improvement of prognosis. We performed genome-wide long non-coding RNA (lncRNA) microarray analysis to identify and validate novel GC biomarkers depending on a high-risk population cohort. METHODS: LncRNA profiles were described using the Human LncRNA Microarray between GC and control plasma samples. The differential candidate lncRNAs were validated in two stages by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We further evaluated the joint effect between the GC-associated lncRNA and Helicobacter pylori (H. pylori) infection on the risk of cardia and non-cardia GC, respectively. RESULTS: Different lncRNA expression profiles were identified between GC and control plasma with a total of 1206 differential lncRNAs including 470 upregulated and 736 downregulated in GC compared with the control group. The eight significantly upregulated lncRNAs (RP11-521D12.1, AC011995.3, RP11-5P4.3, RP11-244 K5.6, RP11-422 J15.1, CTD-2306 M5.1, CTC-428G20.2, and AC009133.20) in GC cases both in the present study and a similar microarray screening study by our collaborative team were selected for a two-stage validation. After the large sample size validation, the subjects with higher expression of RP11-244 K5.6 showed a significantly increased risk of GC with an adjusted odds ratio (OR) as 2.68 and 95% confidence interval (CI) as 1.15-6.24. Joint effects between RP11-244 K5.6 expression and H. pylori infection on the risk of GC were evaluated with no statistical significance. CONCLUSIONS: Our study found different lncRNA expression profiles between GC and control plasma and preliminarily identified RP11-244 K5.6 as a potential noninvasive biomarker for GC screening.

Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Preoperative chemotherapy has been increasingly used in locally advanced gastric cancer (LAGC). However, the prognostic factors are still insufficient. This study aimed to investigate the prognostic significance of pathological response of the primary tumor to neoadjuvant chemotherapy (NACT) and the lymph node status after NACT. METHODS: Data from 160 patients with LAGC treated with NACT followed by gastrectomy and met the inclusion criteria between March 2016 and December 2019 were retrospectively reviewed. Pathological evaluation after NACT was based on the grade of pathological response of the primary tumor and the status of lymph node. Survival curves for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: Among 160 selected cases, 90 had pathological response (PR), while 70 had no pathological response (nPR) to NACT. Smaller tumor size was presented in PR group, which also had lower level of signet ring cell features, compared to nPR group (all p < 0.05). Based on the status of lymph nodes, nodal status (-) group showed smaller tumor size, lower depth of tumor invasion, better differentiated degree, lower level of signet ring cell features, lower rate of lymphatic and venous invasion and less advanced ypTNM stage (all p < 0.05). Survival was equivalent between PR and nPR group (all p > 0.05), while patients with no lymph node metastasis had better DFS than that with lymph node metastasis (HR 0.301, 95% CI 0.194-0.468, p = 0.002). Multivariable Cox regression analysis identified that lymph node status after NACT was an independent prognostic factor associated with survival (OS: hazard ratio 1.756, 95% CI 1.114-3.278, p = 0.029; DFS: hazard ratio 1.901, 95% CI 1.331-3.093, p = 0.012). CONCLUSION: Lymph node status is a potential independent prognostic factor for LAGC patients treated with NACT and may be more efficient than pathological response in primary tumor.

Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma.

Introduction: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. Methods: In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was composed by a stepwise ordinal logistic model in the discovery population. The receiver operating characteristic (ROC) curve with the bootstrapping procedure was used to assess the performance of the glycan score. Results: In the discovery population, the adjusted OR of GP20 (digalactosylated monosialylated biantennary with core and antennary fucose), IGP33 (the ratio of all fucosylated monosyalilated and disialylated structures), IGP44 (the proportion of high mannose glycan structures in total neutral IgG glycans), IGP58 (the percentage of all fucosylated structures in total neutral IgG glycans), IGP75 (the incidence of bisecting GlcNAc in all fucosylated digalactosylated structures in total neutral IgG glycans), and the glycan score are 4.03 (95% CI: 3.03-5.36, P<0.001), 0.69 (95% CI: 0.55-0.87, P<0.001), 0.56 (95% CI: 0.45-0.69, P<0.001), 0.52 (95% CI: 0.41-0.65, P<0.001), 7.17 (95% CI: 4.77-10.79, P<0.001), and 2.86 (95% CI: 2.33-3.53, P<0.001), respectively. Individuals in the highest tertile of the glycan score own an increased risk (OR: 11.41), compared with those in the lowest. The average multi-class AUC are 0.822 (95% CI: 0.786-0.849). Findings are verified in the validation population, with an average AUC of 0.807 (95% CI: 0.758-0.864). Discussion: Our study demonstrated that IgG N-glycans and the proposed glycan score appear to be promising predictive markers for ESCC, contributing to the early prevention of esophageal cancer. From the perspective of biological mechanism, IgG fucosylation and mannosylation might involve in the carcinogenesis progression of ESCC, and provide potential therapeutic targets for personalized interventions of cancer progression.

Molecular insights into effects of PBAT microplastics on latosol microbial diversity and DOM chemodiversity.

The impact of biodegradable microplastics on the microbial community and dissolved organic matter (DOM) in latosol has not been well reported. In this study, an incubation experiment at 25 ºC for 120 days using latosol amended with low (5%) and high (10%) concentrations of polybutylene adipate terephthalate (PBAT) microplastics was carried out to explore the impacts of PBAT microplastics on soil microbial communities and DOM chemodiversity, and the intrinsic interactions between their shifts. The main bacterial and fungal phyla in soil, namely Chloroflexi, Actinobacteria, Chytridiomycota, and Rozellomycota showed a nonlinear relationship with PBAT concentration and played a pivotal role in shaping DOM chemodiversity. A higher decreased levels of lignin-like compounds and increased levels of protein-like and condensed aromatic compounds in the 5% treatment were observed than that in the 10% treatment. Furthermore, a higher increase relative abundance of CHO compounds in the 5% treatment than in the 10% treatment was ascribed to its higher oxidation degree. Co-occurrence network analysis suggested that bacteria formed more complex relationships with DOM molecules than fungi did, indicating their critical roles in DOM transformation. Our study has important implications for understanding the potential influence of biodegradable microplastics on carbon biogeochemical roles in soil.