Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

A novel costimulatory molecule gene-modified leukemia cell-derived exosome enhances the anti-leukemia efficacy of DC vaccine in mouse models.

OBJECTIVES: Leukemia cell-derived exosomes (LEXs), carrying leukemia cell-specific antigens, can serve as a source of antigen for dendritic cell (DC) vaccine loading. However, LEX-targeted DC-based vaccines have demonstrated limited antitumor immune effects in clinical trials, attributed to the low immunogenicity of LEXs and the scant levels of costimulatory molecules on DCs. The costimulatory molecules CD80 and CD86, which are crucial to DC function, play a significant role in enhancing immune efficacy. In this study, we explored the anti-leukemia immune response of costimulatory molecule gene-modified LEX-targeted DCs (LEX-8086) in vitro and in animal models. METHODS: DCs were incubated with LEX-8086 to produce LEX-8086-targeted DCs (DCsLEX-8086). ELISA, cytotoxicity assays and flow cytometry utilized to assess the antitumor efficacy of DCsLEX8086 in vitro. Flow cytometry was used to evaluate the immunomodulatory function of DCsLEX8086 in animal models. RESULTS: Our findings indicated that LEX-8086 enhanced the maturation and antigen-presenting ability of DCs. Immunization with DCsLEX8086 significantly activated CD8+ T cells and boosted the CTL response in vitro. More importantly, DCsLEX-8086 effectively suppressed tumor growth and exerted anti-leukemia effects in both prophylactic and therapeutic animal models. Furthermore, DCsLEX-8086 promoted the proportion of CD4+ T cells, CD8+ T cells and M1 macrophages in the tumor environments both prophylactically and therapeutically. Treatment with DCsLEX-8086 showed no significant difference in the levels of M2 macrophages but decreased the proportion of Tregs within the tumor bed during therapeutic experiments. CONCLUSION: The results suggested that DCsLEX-8086 induces a more effective anti-leukemia immunity compared to DCsLEX-null in vivo and in vitro. DCsLEX-8086 might achieve antitumor effects by elevating the numbers of CD4+ T cells, CD8+ T cells, and M1 macrophages in tumors. Our findings indicate that DCsLEX-8086 could be leveraged to develop a new, highly effective vaccine for anti-leukemia immunity.

One-Dimensional Copper-Doped Rb2AgI3 with Efficient Sky-Blue Emission as a High-Performance X-ray Scintillator.

Scintillators have garnered heightened attention for their diverse applications in medical imaging and security inspection. Nonetheless, commercial scintillators encounter challenges with costly rare-earth metals and toxic elements like thallium (Tl), driving the need for sustainable, cost-effective, and eco-friendly alternatives to meet contemporary X-ray detection demands. This study focuses on exploring the potential of Cu+-doped Rb2AgI3 as an effective metal halide (MH) scintillator. One-dimensional (1D) Rb2AgI3 and Cu+-doped Rb2AgI3 single crystals (SCs) were synthesized by using the conventional temperature-lowering crystallization method. When excited by UV light, Cu+-doped SCs emitted a broad sky-blue light at 490 nm with a high photoluminescence (PL) quantum yield (PLQY) of 76.48%. Remarkably, under X-ray excitation, these Cu+-doped SCs demonstrated an outstanding light yield of 36,293 photons MeV-1, a relatively low detection threshold of 1.022 µGyair s-1, and a rapid scintillation decay time of 465 ns. The prepared translucent scintillation film has good uniformity and flexibility, with a high spatial resolution of 10.2 lp mm-1. These results position Cu+-doped Rb2AgI3 as a leading candidate among promising X-ray scintillators, offering superior scintillation light yield, excellent stability, and nontoxicity.

Recent advances in predicting acute mountain sickness: from multidimensional cohort studies to cutting-edge model applications.

High-altitude illnesses, encompassing a spectrum of health threats including Acute Mountain Sickness (AMS), pose significant challenges to individuals exposed to high altitude environments, necessitating effective prophylaxis and immediate management. Given the variability in individual responses to these conditions, accurate prediction of high-altitude illnesses onset is of paramount importance. This review systematically consolidates recent advancements in research on predicting AMS by evaluating existing cohort data, predictive models, and methodologies, while also delving into the application of emerging technologies. Through a thorough analysis of scholarly literature, we discuss traditional prediction methods anchored in physiological parameters (e.g., heart rate, respiratory frequency, blood pressure) and biochemical markers, as well as the integration and utility of novel technologies such as biosensors, genetic testing, and artificial intelligence within high-altitude prediction research. While conventional pre-diction techniques have been extensively used, they are often constrained by limitations in accuracy, reliability, and multifactorial influences. The advent of these innovative technologies holds promise for more precise individual risk assessments and personalized preventive and therapeutic strategies across various forms of AMS. Future research endeavors must pivot decisively towards the meticulous identification and stringent validation of innovative predictive biomarkers and models. This strategic re-direction should catalyze intensified interdisciplinary cooperation to significantly deepen our mechanistic insights into the pathogenesis of AMS while refining existing prediction methodologies. These groundbreaking advancements harbor the potential to fundamentally transform preventive and therapeutic frameworks for high-altitude illnesses, ultimately securing augmented safety standards and wellbeing for individuals operating at elevated altitudes with far-reaching global implications.

Application of plant-derived products as adjuvants for immune activation and vaccine development.

Vaccines are one of the most important means to prevent and control the epidemic of infectious diseases. Commercial vaccines not only include corresponding antigens, but also need vaccine adjuvants. Immune adjuvants play an increasingly important role in the research, development and manufacture of vaccines. Adjuvants combined with antigens can improve the stability, safety and immune efficiency of vaccines. Some substances that can enhance the immune response have been found in nature(mainly plants) and used as adjuvants in vaccines to improve the immune effect of vaccines. These plant-derived immune adjuvants often have the advantages of low toxicity, high stability, low price, etc., providing more possibilities for vaccine development. We summarized and analyzed the advantages, application research, particulate delivery systems, existing problems and future research focus of botanical adjuvant. It is hoped to provide new ideas for the research and development of immune adjuvants in the future.

Exposure to Chloropropanols and Their Fatty Acid Esters and Glycidyl Fatty Acid Esters in the Sixth Total Diet Study - China, 2016-2019.

What is already known about this topic?: Chloropropanols, along with their fatty acid esters and glycidyl fatty acid esters (GEs), are prevalent contaminants in a variety of processed foods, posing potential health risks to humans. What is added by this report?: In the Sixth China Total Diet Study (TDS), 3-monochloropropane-1,2-diol esters (3-MCPD esters) and GEs were identified as the predominant chloropropanols and their esters in composite food samples. Vegetables (47.0%) and cereals (15.4%) were the major contributors to exposure among the 12 food categories evaluated. What are the implications for public health practice?: The Sixth China TDS highlighted concerns regarding potential health risks associated with dietary exposure to GEs. This study underscores the need for further attention in devising practical strategies to mitigate dietary exposure to GEs.

Material and Microstructure Analysis of Wood Color Paintings from Shaanxi Cangjie Temple, China.

Cangjie Temple was built to commemorate Cangjie, the legendary inventor of Chinese characters. It stands as one of the few remaining temples in China dedicated to the invention and creation of writing. In this study, the material properties of wooden paintings from the Cangjie temple were characterized using Polarized Light Microscopy (PLM), Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (SEM-EDS), Micro-confocal Raman Spectroscopy, X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Pyrolysis-Gas Chromatography-Mass Spectrometry (Py-GC/MS). It was confirmed that the pigments of the paintings included cinnabar, lapis lazuli, lead white, Paris green, and carbon black. The proteinaceous glue was used as an adhesive in the pigment samples, with tung oil likely being utilized as a primer for the wooden structures before painting. This study not only provides valuable data support for the conservation and restoration of the architectural features of Cangjie Temple but also provides useful reference for the maintenance and inheritance of similar ancient buildings.

Obscured Contribution of Oxygenated Intermediate-Volatility Organic Compounds to Secondary Organic Aerosol Formation from Gasoline Vehicle Emissions.

Secondary organic aerosol (SOA) formation from gasoline vehicles spanning a wide range of emission types was investigated using an oxidation flow reactor (OFR) by conducting chassis dynamometer tests. Aided by advanced mass spectrometric techniques, SOA precursors, including volatile organic compounds (VOCs) and intermediate/semivolatile organic compounds (I/SVOCs), were comprehensively characterized. The reconstructed SOA produced from the speciated VOCs and I/SVOCs can explain 69% of the SOA measured downstream of an OFR upon 0.5-3 days' OH exposure. While VOCs can only explain 10% of total SOA production, the contribution from I/SVOCs is 59%, with oxygenated I/SVOCs (O-I/SVOCs) taking up 20% of that contribution. O-I/SVOCs (e.g., benzylic or aliphatic aldehydes and ketones), as an obscured source, account for 16% of total nonmethane organic gas (NMOG) emission. More importantly, with the improvement in emission standards, the NMOG is effectively mitigated by 35% from China 4 to China 6, which is predominantly attributed to the decrease of VOCs. Real-time measurements of different NMOG components as well as SOA production further reveal that the current emission control measures, such as advances in engine and three-way catalytic converter (TWC) techniques, are effective in reducing the "light" SOA precursors (i.e., single-ring aromatics) but not for the I/SVOC emissions. Our results also highlight greater effects of O-I/SVOCs to SOA formation than previously observed and the urgent need for further investigation into their origins, i.e., incomplete combustion, lubricating oil, etc., which requires improvements in real-time molecular-level characterization of I/SVOC molecules and in turn will benefit the future design of control measures.

Transcriptomics to evaluate the influence mechanisms of ethanol on the ester production of Wickerhamomyces anomalus with the induction of lactic acid.

Wickerhamomyces anomalus is one of the most important ester-producing strains in Chinese baijiu brewing. Ethanol and lactic acid are the main metabolites produced during baijiu brewing, but their synergistic influence on the growth and ester production of W. anomalus is unclear. Therefore, in this paper, based on the contents of ethanol and lactic acid during Te-flavor baijiu brewing, the effects of different ethanol concentrations (3, 6, and 9% (v/v)) combined with 1% lactic acid on the growth and ester production of W. anomalus NCUF307.1 were studied and their influence mechanisms were analyzed by transcriptomics. The results showed that the growth of W. anomalus NCUF307.1 under the induction of lactic acid was inhibited by ethanol. Although self-repair mechanism of W. anomalus NCUF307.1 induced by lactic acid was initiated at all concentrations of ethanol, resulting in significant up-regulation of genes related to the Genetic Information Processing pathway, such as cell cycle-yeast, meiosis-yeast, DNA replication and other pathways. However, the accumulation of reactive oxygen species and the inhibition of pathways associated with carbohydrate and amino acid metabolism may be the main reason for the inhibition of growth in W. anomalus NCUF307.1. In addition, 3% and 6% ethanol combined with 1% lactic acid could promote the ester production of W. anomalus NCUF307.1, which may be related to the up-regulation of EAT1, ADH5 and TGL5 genes, while the inhibition in 9% ethanol may be related to down-regulation of ATF2, EAT1, ADH2, ADH5, and TGL3 genes.

Hydrogen peroxide enhanced glow-type chemiluminescence of hydrazine hydrate modified carbon quantum dots-potassium persulfate system.

Most known chemiluminescence (CL) systems are flash-type that generate weak luminescence and decline quickly after dozens of seconds, while the glow-type CL systems have stable emission for an extended period to achieve accurate quantitation. In this work, a long-term CL system based on hydrazine-hydrate (N2H4·H2O) modified carbon quantum dots (N-CQDs) as a luminescent probe, with K2S2O8 and H2O2 as co-reactants, was proposed. The CL emission enhanced by H2O2 increased 18-fold more than that of N-CQDs and K2S2O8 direct reaction, and decayed by 5% of the maximum intensity over 700 s. In the reaction system, K2S2O8 and H2O2 co-reactants can promote each other to continuously generate corresponding radicals (•OH, O2•-, 1O2), which in turn trigger the CL emission of N-CQDs. This phenomenon was identified as the primary cause for the production of persistent CL. In addition, a stable and selective CL sensor based on the N-CQDs-K2S2O8-H2O2 CL enhancing system was developed for ascorbic acid quantitation in the linear range from 0.1 to 10.0 mM with a detection limit of 0.036 mM. The method has been applied to the analysis of tablet samples and holds potential in pharmaceutical analysis field.

Inhibition of STAT3-NF-κB pathway facilitates SSPH I-induced ferroptosis in HepG2 cells.

Hepatocellular carcinoma (HCC), a highly lethal solid tumor, has shown responsiveness to ferroptosis inducers, presenting new avenues in cancer treatment. Our study focuses on the roles of STAT3 and Nf-κB in regulating ferroptosis, particularly their interaction in this process. Using HepG2 cells, we employed specific inhibitors (Stattic for STAT3 and Bay11-7082 for Nf-κB) and a ferroptosis inducer, SSPH I, to dissect their collective impact on ferroptosis. Our findings reveal that inhibiting STAT3 and Nf-κB enhances ferroptosis and cytotoxicity induced by SSPH I. This is mechanistically linked to alterations in iron metabolism-related proteins and GPX4 resulting from SSPH I action, which consequently triggers a STAT3-dependent activation of Nf-κB. The inhibition of STAT3 and Nf-κB led to increased intracellular ROS, MDA, and Fe2+, along with significant GSH depletion, thereby intensifying lipid peroxidation and iron overload in HepG2 cells. This study offers a deeper understanding of the ferroptosis mechanisms in HCC. It highlights the therapeutic potential of targeting STAT3 and Nf-κB pathways to enhance the efficacy of ferroptosis-based treatments.

Cost-Effectiveness Analysis of Regorafenib versus Other Third-Line Treatments for Metastatic Colorectal Cancer.

Background: Regorafenib, a novel multikinase inhibitor, has been approved by the US Food and Drug Administration as a standard treatment choice for metastatic colorectal cancer (mCRC). Nonetheless, its substantial cost places a significant burden on social health resources and patients. However, the cost-effectiveness (CE) of regorafenib compared to other third-line therapies is still undetermined. Objective: This study aims to assess the CE of regorafenib compared to other third-line therapies for the treatment of mCRC. Methods: We conducted a comprehensive literature search in PubMed, Medline, Scopus, Embase, Cochrane Library, as well as nine other databases to identify relevant studies published up to October 2023, focusing on patients with mCRC and examining the cost-effectiveness of regorafenib. Following the screening and extraction of pertinent data, the study quality was assessed using the Quality of Health Economic Studies (QHES) checklist. Results: The literature search yielded 751 records, and after applying the inclusion criteria, 13 studies from 7 different countries were included. Of these, 7 studies evaluated the cost-effectiveness of regorafenib compared to trifluridine/tipiracil (TAS-102), 3 studies compared regorafenib with best supportive care (BSC), and 3 studies compared regorafenib with fruquintinib, serplulimab, and regorafenib dose optimization (ReDo).The quality of the included studies was high with an average QHES scores of 85.62. Regorafenib standard dose proves to be less cost-effective than alternative third-line therapies. Implementing a dose optimization strategy could potentially rectify this disparity and enhance the cost-effectiveness of regorafenib. Conclusion: The use of the standard dose of regorafenib is generally regarded as not cost-effective when compared to other third-line therapies for patients with mCRC. However, implementing a dose-escalation strategy may enhance regorafenib's cost-effectiveness. Consequently, significant price reductions or optimizing the dose of regorafenib are required to achieve cost-effectiveness.

Clinicopathological significance and prognostic analysis of p21 and EGFR in colorectal cancer: a retrospective analysis on 12 319 cases in China.

AIMS: Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations. METHODS: This study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses. RESULTS: Differential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage and BRAF gene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates. CONCLUSION: p21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study's findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.

Association between long-term visit-to-visit blood pressure variability and depression among Chinese middle-aged and older adults.

BACKGROUND: Whether there is a longitudinal association between long-term blood pressure variability (BPV) and subsequent depression among Chinese adults remains inconclusive. METHODS: This study utilized data from a nationwide cohort of the China Health and Retirement Longitudinal Study, which included participants aged > 45 years without prevalent psychiatric or memory-related diseases. The intra-individual coefficient of variation (CV) and standard deviation (SD) across 3 visits from 2011 to 2015 were used to examine the long-term variability in systolic BP (SBP) and diastolic BP (DBP). The depressive symptoms were examined using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10), and moderate-to-severe depression was defined as CES-D-10 ≥ 15. RESULTS: A total of 5,249 participants (mean age: 61.4 ± 8.1 years, 46.5% were men) were included in the current analysis. Individuals in the highest quartile of both BP CV and SD were independently correlated with a higher total CES-D-10 score compared to those in the lowest quartile after multivariable adjustment. 1,070 participants (20.4%) had moderate-to-severe depression during the 3-year follow-up period. Participants in the Q4 of SBP and DBP CV had 1.23-fold higher odds (95% CI: 1.01, 1.49) and 1.20-fold higher odds (95% CI: 1.01, 1.41) of moderate-to-severe depression compared to those in Q1. Subgroup analyses revealed that men with higher BP CVs had a greater risk of severe depressive symptoms (p for SBP CV-by-sex interaction = 0.050, p for SBP CV-by-sex interaction = 0.025). CONCLUSIONS: Depression was common among Chinese middle-aged and older adults and long-term visit-to-visit BPV was positively associated with depressive symptoms, highlighting the importance of implementing intensive prevention strategies for depression and enhancing blood pressure monitors in China.

Knowledge, attitude, practice and illness perception toward subarachnoid hemorrhage prevention and management among intracranial aneurysm patients.

OBJECTIVE: This study aims to explore the knowledge, attitude, practice and illness perception toward prevention and management of subarachnoid hemorrhages (SAH) among intracranial aneurysm (IA) patients. METHODS: A cross-sectional study was conducted between March 2023 and June 2023; demographic characteristics and KAP scores were collected by a self-administered questionnaire and analyzed by linear regression and path analysis. RESULTS: A total of 455 patients with IA were included, of them 26.37% experienced SAH before. Mean knowledge, attitude and practice scores were 16.60 ± 5.86, 16.39 ± 1.84, and 35.07 ± 3.51, respectively. The linear regression showed ethnic minority, married, education, family members in healthcare system, monthly per capita household income, experience ruptured intracranial aneurysms, smoking, hypertension, hyperlipidemia, diabetes, and aortic lesion were associated with knowledge scores. Age, ethnic minority, urban residence, education, family members in healthcare system, monthly per capita household income, duration of IA ≥6 months, experience ruptured intracranial aneurysms, smoking, diabetes, and aortic lesion were associated with attitude scores. Age, urban residence, monthly per capita household income, duration of IA ≥6 months, experience of ruptured intracranial aneurysms, smoking, diabetes, and aortic lesion were associated with practice scores. According to the path analysis, knowledge directly affected illness perception (ß=0.156, P<0.001) and attitude (ß=0.708, P<0.001), while attitude (ß=0.909, P<0.001) and illness perception (ß=0.039, P=0.027) affected practice. CONCLUSIONS: Patients had positive attitudes towards SAH prevention and management, but a substantial knowledge gap was found along with notably delayed medical help-seeking behavior.

Nanoscale zero-valent iron reverses resistance of Pseudomonas aeruginosa to chloramphenicol.

Zero-valent iron (ZVI) has been extensively studied for its capacity to remove various contaminants in the environments. However, whether ZVI affects bacterial resistance to antibiotics has not been fully explored. Herein, it was unexpected that, compared with microscale ZVI (mZVI), nanoscale ZVI (nZVI) facilitated the susceptibility of Pseudomonas aeruginosa (P. aeruginosa) to chloramphenicol (CAP), with a decrease in the minimal inhibitory concentration (MIC) of about 60 %, demonstrating a nanosize-specific effect. nZVI enhanced CAP accumulation in P. aeruginosa via inhibitory effect on efflux pumps activated by MexT, thus conferring the susceptibility of P. aeruginosa to CAP. Circular dichroism spectroscopy revealed that the structure of MexT was changed during the evolution. More importantly, molecular dynamic simulations uncovered that, once the structure of MexT changed, it would be more likely to interact with nZVI, resulting in more serious changes in its secondary structure, which was consistent with the increasing susceptibility of P. aeruginosa to CAP. Collectively, this study elucidated the size-specific effect and the underlying mechanism of ZVI on the bacterial evolution of susceptibility toward antibiotics, highlighting the potentials of nZVI-based technologies on the prevention of bacterial resistance to antibiotics, one of the most important issue for globally public health.

Rapid determination of starch and alcohol contents in fermented grains by hyperspectral imaging combined with data fusion techniques.

Starch and alcohol serve as pivotal indicators in assessing the quality of lees fermentation. In this paper, two hyperspectral imaging (HSI) techniques (visible-near-infrared (Vis-NIR) and NIR) were utilized to acquire separate HSI data, which were then fused and analyzed toforecast the starch and alcohol contents during the fermentation of lees. Five preprocessing methods were first used to preprocess the Vis-NIR, NIR, and the fused Vis-NIR and NIR data, after which partial least squares regression models were established to determine the best preprocessing method. Following, competitive adaptive reweighted sampling, successive projection algorithm, and principal component analysis algorithms were used to extract the characteristic wavelengths to accurately predict the starch and alcohol levels. Finally, support vector machine (SVM)-AdaBoost and XGBoost models were built based on the low-level fusion (LLF) and intermediate-level fusion (ILF) of single Vis-NIR and NIR as well as the fused data. The results showed that the SVM-AdaBoost model built using the LLF data afterpreprocessing by standard normalized variable was most accurate for predicting the starch content, with an R P 2 $\ R_P^2$ of 0.9976 and a root mean square error of prediction (RMSEP) of 0.0992. The XGBoost model built using ILF data was most accurate for predicting the alcohol content, with an R P 2 $R_P^2$ of 0.9969 and an RMSEP of 0.0605. In conclusion, the analysis of fused data from distinct HSI technologies facilitates rapid and precise determination of the starch and alcohol contents in fermented grains.

[Mechanism of Fuzheng Huayu Tablets against hepatic fibrosis based on transcriptome and single-cell sequencing].

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Peptostreptococcus anaerobius mediates anti-PD1 therapy resistance and exacerbates colorectal cancer via myeloid-derived suppressor cells in mice.

Bacteria such as the oral microbiome member Peptostreptococcus anaerobius can exacerbate colorectal cancer (CRC) development. Little is known regarding whether these immunomodulatory bacteria also affect antitumour immune checkpoint blockade therapy. Here we show that administration of P. anaerobius abolished the efficacy of anti-PD1 therapy in mouse models of CRC. P. anaerobius both induced intratumoral myeloid-derived suppressor cells (MDSCs) and stimulated their immunosuppressive activities to impair effective T cell responses. Mechanistically, P. anaerobius administration activated integrin α2ß1-NF-κB signalling in CRC cells to induce secretion of CXCL1 and recruit CXCR2+ MDSCs into tumours. The bacterium also directly activated immunosuppressive activity of intratumoral MDSCs by secreting lytC_22, a protein that bound to the Slamf4 receptor on MDSCs and promoted ARG1 and iNOS expression. Finally, therapeutic targeting of either integrin α2ß1 or the Slamf4 receptor were revealed as promising strategies to overcome P. anaerobius-mediated resistance to anti-PD1 therapy in CRC.