Jianpi Huayu Prescription Prevents Atherosclerosis by Improving Inflammation and Reshaping the Intestinal Microbiota in ApoE-/- Mice.

This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora.

The advantage of afforestation using native tree species to enhance soil quality in degraded forest ecosystems.

Different vegetation restoration methods have improved soil quality to varying degrees. This study, focused on the forest-grassland-desert transition zone in the Hebei-Inner Mongolia border region, and employed a systematic grid sampling method to establish fixed monitoring plots in the Saihanba Mechanized Forest Farm and the Ulan Buh Grassland. The differences in soil quality evolution across various vegetation restoration methods under the same climatic and soil historical conditions were analyzed, elucidating the roles of these vegetation restoration methods in degraded forest ecosystems, with the aim of providing a reference for ecological restoration under similar land conditions. This study used a grid method to establish sample points in the forest-grassland-desert transitional zone and assessed five methods of vegetation restoration sites: artificial forest composed of native species of Larix principis-rupprechtii (FL), artificial forest composed of exotic Pinus sylvestris var. mongolica (FP), natural secondary broad-leaved forest (FN), open grassland (GO), and enclosed grassland (GC). The differences in soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkaline hydrolysis nitrogen (AN), rapidly available phosphorus (AP) and rapidly available potassium (AK) among the different vegetation restoration sites were compared via variance analysis, and the soil quality index (SQI) was calculated to assess the soil quality at the sample points. The SOC, TN, and AN contents of forest soil were significantly greater than those of grassland, and the TN, TP, AN, AK, and SOC contents of FL, FN, and GC were significantly greater than those of FP and GO. Among them, the TN, TP, and SOC contents were the highest in the FL, reaching 2.74, 0.39, and 47.27 g kg-1, respectively. In terms of ecological stoichiometric characteristics, the average N:P ratio in the study area was 6.68, indicating a serious lack of N in the study area. Among the different types of restoration sites, the effect was stronger in the FP than in the FL, and the TN and AN contents were only 1.48 g kg-1 and 116.69 mg kg-1, respectively. The SQI in the FL was not significantly different from that in the FN or GC, but it was significantly greater than that in the FP and GO. These findings indicate that native tree species restoration in degraded forest ecosystems significantly improved soil quality, while the introduction of exotic tree species for afforestation had a minimal effect on improving soil quality.

Age-period-cohort analysis of global, regional, and national pancreatic cancer incidence, mortality, and disability-adjusted life years, 1990-2019.

BACKGROUND: Pancreatic cancer is one of the deadliest cancers in the world. In recent years, the incidence and mortality rates of pancreatic cancer have shown an increasing trend year by year. This study investigates the independent effects of age, period, and cohort on the global incidence, mortality, and disability-adjusted life years (DALYs) of pancreatic cancer from 1990 to 2019, and evaluates the differences in the burden of pancreatic cancer across regions with different Sociodemographic Index (SDI) levels. METHODS: Estimating the impact of age, period, and cohort on pancreatic cancer disease burden in different SDI regions using age-period-cohort modeling with data (with 95% uncertainty intervals [UI]) from the Global Burden of Disease (GBD) Study 2019 and net drift of age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) for pancreatic cancer in 120 countries. RESULTS: The number of new cases of pancreatic cancer worldwide increased from 197,348 (95% UI: 188,604,203,971) in 1990 to 530,297 (486,175,573,635) in 2019, the number of deaths increased from 198,051 (189,329 to 204,763) in 1990 to 531,107 (491,948 to 566,537) in 2019, and the number of DALY increased from 4,647,207 (4,465,440 to 4,812,129) in 1990 to 11,549,016 (10,777,405 to 1,238,912) in 2019. The ASIR of the average levels in global pancreatic cancer increased from 5.22 (4.97 to 5.40) per 100,000 population to 6.57 (6.00 to 7.09) per 100,000 population, the ASMR increased from 5.34 (5.07 to 5.52) per 100,000 population to 6.62 (6.11 to 7.06) per 100,000 population, and the ASDR increased from 115.47 (110.82 to 119.60) per 100,000 population to 139.61 (130.18 to 149.14) per 100,000 population. The incidence, mortality, and DALY rates of pancreatic cancer increase with age globally and across all SDI regions, peaking in the 85-89 age group. In high and high-middle SDI regions, the growth rate for males is higher than for females before the age of 85, while females have a higher growth rate after 85. The 75-79 age group exhibits the highest DALY rate in high and high-middle SDI regions, significantly higher than the global and other SDI regions. From 1990 to 2019, the period effects of pancreatic cancer incidence, mortality, and DALY rates have increased significantly worldwide, while remaining almost unchanged in high and high-middle SDI regions. In contrast, period effects have significantly increased in middle, low-middle, and low SDI regions. Cohort effects are more pronounced in middle, low-middle, and low SDI regions. CONCLUSIONS: With the aggravation of population aging, the incidence and mortality rates of pancreatic cancer in the world are increasing, and effective prevention and control measures can be achieved by reducing the exposure of risk factors. The APC model used in our analysis provides a novel approach to understanding the complex trends in the incidence, mortality, and disability-adjusted life years of pancreatic cancer. It can inform the development of targeted interventions to reduce the severe disease burden caused by pancreatic cancer.

Yeast ß-glucan promotes antiviral type I interferon response via dectin-1.

Pseudorabies virus (PRV), an alphaherpesvirus, is a neglected zoonotic pathogen. Dectin-1 sensing of ß-glucan (BG) induces trained immunity, which can possibly form a new strategy for the prevention of viral infection. However, alphaherpesvirus including PRV have received little to no investigation in the context of trained immunity. Here, we found that BG pretreatment improved the survival rate, weight loss outcomes, alleviated histological injury and decreased PRV copy number of tissues in PRV-infected mice. Type I interferons (IFNs) including IFN-α/ß levels in serum were significantly increased by BG. However, these effects were abrogated in the presence of Dectin-1 antagonist. Dectin-1-mediated effect of BG was also confirmed in porcine and murine macrophages. These results suggested that BG have effects on type I IFNs with antiviral property involved in Dectin-1. In piglets, oral or injected immunization with BG and PRV vaccine could significantly elevated the level of PRV-specific IgG and type I IFNs. And it also increased the antibody levels of porcine reproductive and respiratory syndrome virus vaccine and classical swine fever vaccine that were later immunized, indicating a broad-spectrum effect on improving vaccine immunity. On the premise that the cost was greatly reducing, the immunological effect of oral was better than injection administration. Our findings highlighted that BG induced type I IFNs related antiviral effect against PRV involved in Dectin-1 and potential application value as a feed additive to help control the spread of PRV and future emerging viruses.

Research on the evolutionary control of unsafe behavior of construction personnel based on multi-field coupled-homogeneous analysis model.

Unsafe behavior among construction personnel poses significant risks in petroleum engineering construction projects. This study addresses this issue through the application of a multi-field coupled homogeneous analysis model. By conducting case analyses of petroleum engineering construction accidents and utilizing the WSR methodology, the influencing factors of unsafe behaviors among construction personnel are systematically categorized into organizational system factors, equipment management factors, and construction personnel factors. Subsequently, employing Risk coupling theory, the study delves into the analysis of these influencing factors, discussing their coupling mechanisms and classifications, and utilizing the N-K model to elucidate the coupling effect among them. Furthermore, a novel approach integrating coupling analysis and multi-agent modeling is employed to establish an evolutionary model of construction personnel's unsafe behavior. The findings reveal that a two-factor control method, concurrently reinforcing equipment and construction personnel management, significantly mitigates unsafe behavior. This study provides valuable insights into the evolution of unsafe behavior among construction personnel and offers a robust theoretical framework for targeted interventions. Significantly, it bears practical implications for guiding safety management practices within petroleum engineering construction enterprises. By effectively controlling unsafe behaviors and implementing targeted safety interventions, it contributes to fostering sustainable development within the petroleum engineering construction industry.

Benchmarking the CoW with the TopCoW Challenge: Topology-Aware Anatomical Segmentation of the Circle of Willis for CTA and MRA.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.

Voluntary running wheel exercise induces cognitive improvement post traumatic brain injury in mouse model through redressing aberrant excitation regulated by voltage-gated sodium channels 1.1, 1.3, and 1.6.

Traumatic brain injury (TBI) leads to disturbed brain discharge rhythm, elevated excitability, anxiety-like behaviors, and decreased learning and memory capabilities. Cognitive dysfunctions severely affect the quality of life and prognosis of TBI patients, requiring effective rehabilitation treatment. Evidence indicates that moderate exercise after brain injury decreases TBI-induced cognitive decline. However, the underlying mechanism remains unelucidated. Our results demonstrate that TBI causes cognitive impairment behavior abnormalities and overexpression of Nav1.1, Nav1.3 and Nav1.6 proteins inside the hippocampus of mice models. Three weeks of voluntary running wheel (RW) exercise treatments before or/and post-injury effectively redressed the aberrant changes caused by TBI. Additionally, a 10% exercise-conditioned medium helped recover cell viability, neuronal sodium current and expressions of Nav1.1, Nav1.3 and Nav1.6 proteins across cultured neurons after injury. Therefore, the results validate the neuroprotection induced by voluntary RW exercise treatment before or/and post-TBI. The RW exercise-induced improvement in cognitive behaviors and neuronal excitability could be associated with correcting the Nav1.1, Nav1.3, and Nav1.6 expression levels. The current study proves that voluntary exercise is an effective treatment strategy against TBI. The study also highlights novel potential targets for rehabilitating TBI, including the Navs proteins.

Hepatocellular carcinoma immune prognosis score predicts the clinical outcomes of hepatocellular carcinoma patients receiving immune checkpoint inhibitors.

OBJECTIVE: The predictive biomarkers of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) still need to be further explored. This study aims to establish a new immune prognosis biomarker to predict the clinical outcomes of hepatocellular carcinoma patients receiving immune checkpoint inhibitors. METHODS: The subjects of this study were 151 HCC patients receiving ICIs at Harbin Medical University Cancer Hospital from January 2018 to December 2021. This study collected a wide range of blood parameters from patients before treatment and used Cox's regression analysis to identify independent prognostic factors in blood parameters, as well as their ß coefficient. The hepatocellular carcinoma immune prognosis score (HCIPS) was established through Lasso regression analysis and COX multivariate analysis. The cut-off value of HCIPS was calculated from the receiver operating characteristic (ROC) curve. Finally, the prognostic value of HCIPS was validated through survival analysis, stratified analyses, and nomograms. RESULTS: HCIPS was composed of albumin (ALB) and thrombin time (TT), with a cut-off value of 0.64. There were 56 patients with HCIPS < 0.64 and 95 patients with HCIPS ≥ 0.64, patients with low HCIPS were significantly related to shorter progression-free survival (PFS) (13.10 months vs. 1.63 months, P < 0.001) and overall survival (OS) (14.83 months vs. 25.43 months, P < 0.001). HCIPS has also been found to be an independent prognostic factor in this study. In addition, the stratified analysis found a significant correlation between low HCIPS and shorter OS in patients with tumor size ≥ 5 cm (P of interaction = 0.032). The C-index and 95% CI of the nomograms for PFS and OS were 0.730 (0.680-0.779) and 0.758 (0.711-0.804), respectively. CONCLUSIONS: As a new score established based on HCC patients receiving ICIs, HCIPS was significantly correlated with clinical outcomes in patients with ICIs and might serve as a new biomarker to predict HCC patients who cloud benefit from ICIs.

Exploring the association between triglyceride-glucose index and thyroid function.

BACKGROUND: Thyroid dysfunction is associated with abnormal glucose-insulin homeostasis, and the triglyceride-glucose (TyG) index has been recommended as a convenient surrogate of insulin resistance (IR). This study aimed to investigate the relationship between TyG and thyroid function in the US population. METHODS:  We analyzed data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2012 in a cross-sectional manner. Aside from conventional thyroid parameters, our study evaluated the central sensitivity to thyroid hormones (THs) using the thyroid feedback quantile-based index (TFQI), thyrotropin resistance index (TT4RI), and thyrotropin index (TSHI). To evaluate peripheral sensitivity to THs, we calculated the ratio of free triiodothyronine (FT3) to free thyroxine (FT4) and the sum activity of peripheral deiodinases (SPINA-GD). In the 1848 adults, multivariable linear regression, subgroup, and interaction analyses were employed to estimate the association between TyG and thyroid parameters. The nonlinear relationship was addressed by smooth curve fittings and generalized additive models. RESULTS: After adjusting covariates, we demonstrated a significant negative association between TyG and FT4 (ß = - 0.57, p < 0.001), and a positive relationship between TyG and thyroid-stimulating hormone (ß = 0.34, p = 0.037), as well as TgAb (ß = 17.06, p = 0.005). Subgroup analysis indicated that the association between TyG and TgAb was more pronounced in the female subjects (ß = 32.39, p < 0.001, p for interaction = 0.021). We also confirmed an inverse correlation between TyG and central sensitivity to THs, as assessed by TSHI and TT4RI (ßTSHI = 0.12, p < 0.001; ßTT4RI = 2.54, p = 0.023). In terms of peripheral sensitivity to THs, we found a significant positive correlation between TyG and FT3/FT4 (ß = 0.03, p = 0.004), and SPINA-GD (ß = 2.93, p = 0.004). CONCLUSION: The present study established a noteworthy association between TyG and thyroid parameters, indicating a strong link between IR and thyroid dysfunction. Further investigations are warranted to validate these results.

Microplastic pollution in organic farming development cannot be ignored in China: Perspective of commercial organic fertilizer.

Commercial organic fertilizer, an essential fertilizer for developing organic farming in China, has been identified as a potentially important source of microplastics (MPs) on farmland. However, little is known about the occurrence of MPs in commercial organic fertilizers and their potential ecological risks nationwide. Here, stereoscopy and laser-infrared imaging spectrometry were used to comprehensively investigate the abundance, size, type and morphology of MPs in commercial organic fertilizers collected from mainland China, assess the ecological risks, and predict MP contamination. Commercial organic fertilizers contained many MPs (8.88 ×103 to 2.88 ×105 items/kg), especially rich in small-size MPs (<100 µm), accounting for 76.53%. The highest MP pollution load value was observed in fertilizers collected from East China. Chlorinated polyethylene, polyurethane, polyethylene and polypropylene were the dominant MPs with the shape of film and fragment, concentrated in small sizes (<100 µm). The risk index (H-index) of the MPs was used to quantify the ecological risk of the MPs in the different samples, and most of the fertilizers were at level Ⅲ with high risk. Predictably, 2.32 × 1013 - 2.81 × 1016 MPs will accumulate in orchard soils after five years of fertilization, especially in South, Southwest and East China. This study provides primary scientific data on MP pollution in commercial fertilizer and the health development of organic farming.

Prognostic value of nutritional and inflammatory markers in patients with hepatocellular carcinoma who receive immune checkpoint inhibitors.

The emergence of immune checkpoint inhibitors (ICIs) has provided a new treatment option for patients with hepatocellular carcinoma (HCC). However, further evaluation is needed for determining biomarkers for the use of ICIs. The present study evaluated the prognostic value of certain nutritional and inflammatory markers in patients with HCC who received ICIs. In the present study, the clinical data of 151 patients with HCC who received ICIs at Harbin Medical University Cancer Hospital from January 2019 to December 2021 were collected. The blood parameters of all patients before treatment were collected to evaluate certain nutritional and inflammatory markers, including the prognostic nutrition index (PNI), nutritional risk index (NRI), geriatric NRI (GNRI), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and advanced lung cancer inflammation index (ALI). Patients were grouped using the cut-off value calculated using receiver operating characteristic (ROC) curves, and the relationship between these biomarkers and prognosis was evaluated through survival analysis. Furthermore, the prognostic value of these biomarkers was assessed through multivariate Cox regression analysis and construction of nomograms. Finally, time-ROC curves were plotted to compare the differences in predicting prognosis between the biomarkers. In the preliminary survival analysis, all inflammatory and nutritional markers included in the present study were significantly associated with the prognosis of HCC in patients who received ICIs. Similar results were obtained in a subgroup analysis of patients with different Barcelona Clinic Liver Cancer (BCLC) stages. Multivariate Cox regression analysis demonstrated that GNRI, PNI, BCLC stage and Tumor-Node-Metastasis (TNM) stage were significantly associated with progression-free survival (PFS), whereas GNRI, BCLC stage and TNM stage were also significantly associated with overall survival (OS). Furthermore, the time-ROC curves indicated that nutritional indicators had a higher prognostic value in all indexes, especially GNRI. The C-index (95% confidence interval) of the nomograms for predicting the survival probability of patients who received ICIs were 0.801 (0.746-0.877) and 0.823 (0.761-0.898) for PFS and overall OS, respectively, which also showed high accuracy. In conclusion, the present study demonstrated that PNI, GNRI, NRI, SII, SIRI and ALI were all related to the efficacy of ICIs in HCC and could serve as non-invasive biomarkers for ICI treatment effectiveness. Moreover, compared with inflammatory markers, nutritional markers had greater predictive ability, with GNRI being the biomarker with the best prognostic value.

Analysis on EZH2: mechanism identification of related CeRNA and its immunoassay in hepatocellular carcinoma.

OBJECTIVE: To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed. METHODS: First, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed. RESULTS: Seven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p-EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression. CONCLUSION: This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.

LaVO4: Eu3+ nano-islands onto silica for achieving fluorescence enhancement and their detection of Fe3+ ions and anti-counterfeiting applications.

Rare earth (RE) composite fluorescent materials are favored by researchers in the field of anti-counterfeiting and ion sensing due to their fascinating optical properties. Ultra-small RE fluorescent nanoparticles are anchored on inorganic carriers by a simple preparation method to improve luminous intensity and hydrophilicity, which has not been explored yet. Herein, LaVO4: Eu3+ nano-islands anchored on silica with high fluorescence intensity and easy formation of stable colloidal solution is designed. Through a simple and mild hydrothermal approach, ultra-small LaVO4: Eu3+ nano-islands are highly dispersed on the surface of hierarchical hollow silica sphere (HHSS) to expose more luminescent centers. Remarkably, the stable HHSS@LaVO4: Eu3+ colloidal solution displayed highly sensitive and selective sensor for Fe3+ ions. The "island-sea synergy" structure formed by the LaVO4: Eu3+ nano-islands and the surrounding silica surface makes HHSS@LaVO4: Eu3+ to be an outstanding sensor for the effective detection of iron ions in water. In addition, HHSS@LaVO4: Eu3+ phosphor exhibit unique properties for anti-counterfeiting and encryption applications. These findings provide a promising strategy for the carrierisation of RE luminescent materials to improve optical properties and enable broader applications.

Magnetic functionalized graphene oxide combined with ultra-high performance liquid chromatography for trace detection of succinate dehydrogenase inhibitor fungicides in food.

In this study, an efficient, sensitive, and convenient magnetic solid-phase extraction method combined with ultra-high performance liquid chromatography-tandem mass spectrometry (MSPE-UHPLC-MS/MS) was developed for the simultaneous determination of 19 succinate dehydrogenase inhibitor fungicide residues in six different food matrices The synthesized tetraethylenepentamine magnetic graphene oxide nanocomposite showed the advantages of good dispersibility, large specific surface area (113.93 m2 /g) and large pore volume (0.25 cm3 /g), making it an ideal succinate dehydrogenase inhibitor pretreatment adsorbent. The MSPE-UHPLC-MS/MS method showed linearity in the range of 5.0-800.0 µg/kg, with a correlation coefficient (R2 ) > 0.99, and a limit of quantification of 5 µg/kg. The recovery of succinate dehydrogenase inhibitor fungicides was in the range of 71.2%-119.4%. The MSPE method is simple, rapid, and efficient, making it an ideal alternative to sample pretreatment in the determination of trace succinate dehydrogenase inhibitor fungicides in complex matrices.

Clinical plasma cells-related genes to aid therapy in colon cancer.

The tumor immune microenvironment (TIME) of colon cancer (CC) has been associated with extensive immune cell infiltration (IMI). Increasing evidence demonstrated that plasma cells (PC) have an extremely important role in advance of antitumor immunity. Nonetheless, there is a lack of comprehensive analyses of PC infiltration in clinical prognosis and immunotherapy in CC. This study systematically addressed the gene expression model and clinical information of CC patients. Clinical samples were obtained from the TCGA (The Cancer Genome Atlas) databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), GSVA, and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were employed to research the potential mechanism and pathways. Immunophenoscore (IPS) was obtained to evaluate the immunotherapeutic significance of risk score. Half maximal inhibitory concentration (IC50) of chemotherapeutic medicine was predicted by employing the pRRophetic algorithm. A total of 513 CC samples (including 472 tumor samples and 41 normal samples) were collected from the TCGA-GDC database. Significant black modules and 313 candidate genes were considered PC-related genes by accessing WGCNA. Five pivotal genes were established through multiple analyses, which revealed excellent prognostic. The underlying correlation between risk score with tumor mutation burden (TMB) was further explored. In addition, the risk score was obviously correlated with various tumor immune microenvironment (TIME). Also, risk CC samples showed various signaling pathways activity and different pivotal sensitivities to administering chemotherapy. Finally, the biological roles of the CD177 gene were uncovered in CC.

The combination of circulating IgM and geriatric nutritional risk index predicts the prognostic of hepatocellular carcinoma patients who underwent immune checkpoint inhibitors.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown promise in hepatocellular carcinoma (HCC) treatment. With the increasing use of ICIs in cancer treatment, identifying biomarkers that can predict the prognosis of patients receiving ICIs is of great importance. We aimed to investigate the potential of circulating immunoglobulins and the combination of Geriatric Nutritional Risk Index (GNRI) with IgM to predict prognosis in patients with HCC who received ICIs. METHODS: Clinical and pathological data were collected from 101 patients with HCC who were administered ICIs and underwent circulating immunoglobulin testing between January 2018 and December 2021. Survival analysis, Cox regression analysis, and nomogram construction were performed to evaluate the prognostic value of the indicators. RESULTS: In the preliminary survival analysis, we observed a significant correlation between patient prognosis and IgM levels. Patients with low IgM had shorter survival times. Upon combining the GNRI with IgM, patients with low GNRI and IgM levels had shorter progression-free survival (PFS) and overall survival (OS) (P < 0.001). Additionally, GNRI-IgM had the highest area under the curve (AUC) and was identified as an independent prognostic marker in this study. The C-indices of the nomograms for PFS and OS were 0.797 (0.734-0.860) and 0.827 (0.778-0.876), respectively. CONCLUSIONS: IgM was significantly associated with the prognosis of patients with HCC receiving ICIs. The combination of the GNRI with IgM provided superior prognostic value and served as an independent prognostic marker. The GNRI-IgM can be used to effectively identify patients with HCC who are responsive to ICIs.

Synergistic effects of biochar derived from different sources on greenhouse gas emissions and microplastics mitigation during sewage sludge composting.

This study aimed to investigate the effects of biochar derived from different sources (wheat straw, sawdust and pig manure) on greenhouse gas and microplastics (MPs) mitigation during sewage sludge composting. Compared to the control, all biochar significantly reduced the N2O by 28.91-41.23%, while having no apparent effect on CH4. Sawdust biochar and pig manure biochar significantly reduced the NH3 by 12.53-23.53%. Adding biochar decreased the global warming potential during composting, especially pig manure biochar (177.48 g/kg CO2-eq.). The concentration of MPs significantly increased in the control (43736.86 particles/kg) compared to the initial mixtures, while the addition of biochar promoted the oxidation and degradation of MPs (15896.06-23225.11 particles/kg), with sawdust biochar and manure biochar were more effective. Additionally, biochar significantly reduced the abundance of small-sized (10-100 µm) MPs compared to the control. Moreover, biochar might regulate specific microbes (e.g., Thermobifida, Bacillus and Ureibacillus) to mitigate greenhouse gas emissions and MPs degradation.

BTF3 promotes proliferation and glycolysis in hepatocellular carcinoma by regulating GLUT1.

Hepatocellular carcinoma (HCC) is a grievous tumor with an increasing incidence worldwide. Basic transcription factor 3 (BTF3) is discovered to regulate the expression of glucose transporter 1 (GLUT1), which benefits glycolysis, a momentous signature of tumors, through transactivation of the forkhead box M1 (FOXM1) expression. BTF3 is highly expressed in HCC. However, whether BTF3 promotes GLUT1 expression through FOXM1 to modulate glycolysis in HCC remains unclear. The expression profile of BTF3 were determined by online database, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. The role and mechanism of BTF3 in the proliferation and glycolysis of HCC cells were examined by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, XF96 Extracellular Flux analyzer, spectrophotometry and western blot analysis. In addition, the direct interaction between BTF3 and FOXM1 was verified by dual-luciferase reporter and co-immunoprecipitation assays. Moreover, the role of BTF3 was also explored in a xenografted mice model. The expression of BTF3 was increased in HCC cells and tumor tissues. Knockdown of BTF3 reduced the cell viability, Edu positive cells, extracellular acidification rate (ECAR), glucose consumption and lactate production in both Huh7 and HCCLM3 cells. The expressions of FOXM1 and GLUT1 were increased in HCC tissues, which were positively correlated with the BTF3 expression. Moreover, a direct interaction existed between BTF3 and FOXM1 in HCC cells. Downregulation of BTF3 decreased the relative protein levels of FOXM1 and GLUT1, which were rescued with overexpression of FOXM1 in both cells. More importantly, overexpression of FOXM1 restored the cell viability, ECAR, glucose consumption and lactate production in both Huh7 and HCCLM3 cells transfected with siBTF3#1. Furthermore, inhibition of BTF3 decreased tumor weight and volume, and the relative level of BTF3, FOXM1, GLUT1 and Ki-67 in tumor tissues from mice xenografted with Huh7 cells. BTF3 enhanced the cell proliferation and glycolysis through FOXM1/GLUT1 axis in HCC.

Toward Earth system modeling with resolved clouds and ocean submesoscales on heterogeneous many-core HPCs.

With the aid of the newly developed 'Sunway' heterogeneous-architecture supercomputer, which has world-leading HPC (high-performance computer) capability, a series of high-resolution coupled Earth system models (SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been developed. These models can meet the needs of multiscale interaction studies with different computational costs. Here we describe the progress of SW-HRESMs development, with an overview of the major advancements made by the international Earth science community in HR-ESMs. We also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean, stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions, and paving the way for further model development to resolve finer scales with even higher resolution and more realistic physics. Finally, in addition to increasing model resolution, the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discussed, laying out the major scientific directions of such a huge modeling advancement.