Platelet factors ameliorate thoracic aortic aneurysm and dissection by inhibiting the FGF-FGFR cascade activation in aortic-endothelial cell.

Thoracic aortic aneurysm and dissection (TAAD) is closely associated with vascular endothelial dysfunction. Platelet factor 4 (PF4) is crucial for maintaining vascular endothelial cell homeostasis. However, whether PF4 can influence the progression of TAAD remains unknown. In the present study, we constructed a liposome-encapsulated PF4 nanomedicine and verified its effect on BAPN-induced TAAD in vivo. We found that liposome PF4 nanoparticles (Lipo-PF4), more effectively than PF4 alone, inhibited the formation of TAAD. In vitro, PF4 improved endothelial cell function under pathological conditions by inhibiting migratory and angiogenic abilities of human aortic endothelial cells (HAECs). Mechanically, PF4 inhibited the development of TAAD and improved HAECs function by combining with heparin sulfate and blocking fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) signaling. Taken together, we developed a nano-drug (Lipo-PF4) that effectively ameliorates the progression of TAAD by improving endothelial function. Lipo-PF4 is expected to be a therapeutic option for TAAD in the future.

HSP90AA1 is an unfavorable prognostic factor for hepatocellular carcinoma and contributes to tumorigenesis and chemotherapy resistance.

Hepatocellular carcinoma (HCC) is still one of the leading causes of tumor-related deaths. Accumulating evidence indicates that immunogenic cell death (ICD) could occur in tumor cells. However, ICD-related studies are limited in HCC. This study collected HCC RNA sequencing data from the Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R software was used to analyze the expression of ICD in HCC and to screen essential genes with prognostic value. qRT-PCR and WB determined the mRNA and protein expressions of hub gene. Cell viability assay, Clonal formation assay, and Live/dead staining assay were employed to determine the gene functions. After cross-analysis of differentially expressed genes (DEGs) and ICD-related genes (ICDRGs), 7 differentially expressed ICDRGs were identified in HCC. Of them, HSP90AA1, with the most excellent prognostic value in HCC, was selected, whose expression was also validated in public cohorts, cell lines, and clinical tissue samples. High HSP90AA1 expression indicated an inferior prognosis of HCC, and HSP90AA1 knockdown significantly suppressed cell viability and chemotherapy resistance of HCC. ICD-related gene HSP90AA1 was an unfavorable factor for HCC, and high HSP90AA1 expression contributed to tumor cell survival and chemotherapy resistance.

Biochar enhances Cd mineralization through microbially induced carbonate precipitation as a soil remediation strategy for rice paddies.

Microbial induced carbonate precipitation (MICP) is a promising technique for remediating Cd-contaminated soils. However, the high cost and potential disruption to soil micro-ecology due to the excessive urea addition remain significant challenges, limiting the broader application of MICP technology in agricultural soils. This study aims to improve the efficiency of Cd immobilization by MICP under low urea levels by investigating the stimulatory effect of porous materials on urease secretion by ureolytic bacteria. Results demonstrate that these materials, including biochar, activated carbon, zeolite, and oyster shell, can stimulate the growth of ureolytic bacteria strain kp-22, but not diatomite. Urease activity was greatly improved within 12 hours, and the Cd removal rate reached over 82.12% within 0.5 hours. Notably, biochar supported urealytic bacterium strain kp-22 (BCM) can steadily remove Cd in solution, with the Cd removal rate remaining close to 99% even after multiple additions of Cd. XRD analysis shows that Cd was removed by BCM due to the formation of CdCO3. Soil experiment reveals that BCM significantly decreased the bioavailable Cd content in both flooded and unflooded paddy soils, even when the urea addition was at a dosage suitable for agricultural production. 16S rRNA gene sequencing shows that the disturbance caused by BCM to the soil bacterial community was lower than that caused by strain kp-22 alone. These findings offer new insights into enhancing the efficiency of MICP for Cd remediation, increasing the potential for broader application of MICP technology in sustainable agriculture.

Burden of biliary tract carcinoma in China (1990-2021): Findings from the 2021 Global Burden of Disease Study.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.

Stress-mediated Activation of Ferroptosis, Pyroptosis, and Apoptosis Following Mild Traumatic Brain Injury Exacerbates Neurological Dysfunctions.

Nearly half of mild traumatic brain injury (mTBI) patients continue to experience residual neurological dysfunction, which may be attributed to exposure to stress. Ferroptosis, a newly discovered form of cell death, is increasingly recognized for its involvement in the pathophysiology of TBI. Understanding the mechanisms by which stress influences mTBI, particularly through ferroptosis, is crucial for the effective treatment and prevention of mTBI patients who are sensitive to stressful events. In our study, a mouse mTBI model was established. An acute restraint stress (RS) and a chronic unpredictable mild stress (CUMS) model then were applied to make acute and chronic stress, respectively. We found acute RS significantly delayed the recovery of reduced body weight and short-term motor dysfunctions and exacerbated cell insults and blood-brain barrier leakage caused by mTBI. Further studies revealed that acute RS exacerbates neuronal ferroptosis, pyroptosis, and apoptosis by promoting iron overloading in the neocortex following mTBI. Interestingly, the inhibition of ferroptosis with iron chelators, including deferoxamine and ciclopirox, reversed pyroptosis and apoptosis. Moreover, CUMS aggravated neurological dysfunctions (motor function, cognitive function, and anxiety-like behavior) and exacerbated brain lesion volume. CUMS also exacerbates ferroptosis, pyroptosis, and apoptosis by intensifying iron deposition, along with decreasing the expression of neuronal brain-derived neurotrophic factor and glucocorticoid receptor in the neocortex post mTBI. These effects were also mitigated by iron chelators. Our findings suggest that alleviating ferroptosis induced by iron deposition may represent a promising therapeutic approach for mTBI patients who have experienced stressful events.

Targeted regulation of 5-aminolevulinic acid enhances flavonoids, anthocyanins and proanthocyanidins accumulation in Vitis davidii callus.

BACKGROUND: Spine grape (Vitis davidii) is a promising source of high-quality anthocyanins, with vast potential for application in food, pharmaceutical, and cosmetic industries. However, their availability is limited by resource constraints. Plant cell culture has emerged as a valuable approach for anthocyanin production and serves as an ideal model to investigate the regulation of anthocyanin biosynthesis. Elicitors are employed to achieve targeted enhancement of anthocyanin biosynthesis. The present study investigated the impact of 5-aminolevulinic acid (ALA) as an elicitor on the accumulation of anthocyanins and flavonoids during spine grape callus growth. Specifically, we examined the effects of ALA on anthocyanin and its component accumulation in callus, and biosynthetic anthocyanin gene expression. RESULTS: ALA at 25 µg/L increased the biomass of spine grape callus. ALA induction enhanced the levels of flavonoids, anthocyanins and proanthocyanidins in callus, with maximum values reaching 911.11 mg/100 g DW, 604.60 mg/100 g DW, and 5357.00 mg/100 g DW, respectively, after callus culture for 45 days. Notably, those levels were 1.47-, 1.93- and 1.83-fold higher than controls. ALA induction modulated the flavonoid profile, and among 97 differential flavonoid metabolites differing from controls, 77 were upregulated and 20 were downregulated. Six kinds of anthocyanins, namely cyanidin (8), delphinidin (6), peonidin (5), malvidin (4), petunidin (3) and pelargonidin (3), were detected in callus, with peonidin most abundant. Compared with controls, anthocyanin components were increased in ALA-treated callus. The key genes PAL1, PAL2, PAL4, CHI, CHS3, F3'H, F3H, FLS, DFR, UFGT, MYBA1, LDOX, OMT3, GT1 and ACT involved in anthocyanin biosynthesis were upregulated following ALA treatment, resulting in anthocyanin accumulation. CONCLUSION: This study revealed a novel mode of ALA-mediated promotion of plant anthocyanin biosynthesis and accumulation at the cellular level, and a strategy for enhancing anthocyanin content in spine grape callus. The findings advance commercial-scale production of anthocyanins via spine grape callus culture. we also explored the accumulation patterns of flavonoids and anthocyanins under ALA treatment. Augmentation of anthocyanins coincided with elevated expression levels of most genes involved in anthocyanin biosynthesis within spine grape callus following ALA treatment.

The levels of amino acid metabolites in serum induce the pathogenesis of atopic dermatitis by mediating the inflammatory protein S100A12.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting tens of millions of people globally. The causal relationship between metabolites and AD pathology has not yet been formally indicated, and the mediating mechanism by which metabolites affect AD has not yet been explored. This study aimed to determine the genetic relationship between metabolites and AD and to determine the pathways through which amino acid metabolites affect AD. Meta-analysis integrates the results of multiple GWAS analyses using METAL software. Using bidirectional two-sample Mendelian randomization (MR), we analyzed the causal relationships between metabolites and AD. The principal MR test of causal effects was conducted using inverse-variance weighted regression, and we used reverse MR analysis to exclude reverse causality. We also performed the MR-PRESSO test to detect and correct for possible pleiotropic effects, and used the Cochran Q test to assess heterogeneity. Two-step MR was utilized to analyze the mediating factors between amino acid metabolites and the onset of AD. The correlation between mediating factors (inflammatory protein S100A12) and immune cell infiltration was analyzed using the edgeR and GSVA software packages. Using single-cell sequencing data from skin tissues of patients with AD, we studied the regulatory role of the S100A12 gene in immune cells. Multiple drug databases and macromolecular docking were used to search for S100A12-targeting drugs. Bidirectional two-sample MR analyses indicated that twenty-two metabolites and one inflammatory protein (S100A12) were significantly associated with AD pathogenesis. S100A12 is a mediator of amino acid metabolites (N6-methyllysine; N2-acetyl,N6,N6-dimethyllysine and N6,N6-dimethyllysine) that are genetically associated with AD. S100A12 was positively correlated with the infiltration of multiple immune cell types in lesional AD skin. The amino acid metabolites N6-methyllysine; N2-acetyl,N6,N6-dimethyllysine and N6,N6-dimethyllysine influence AD pathogenesis by mediating S100A12 expression.

Outcome and Survival Analysis of Multicenter Lung Metastasectomy for Primary Liver Tumor with Pulmonary Metastasis.

Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes.

Quaternary Chiral Phthalides Enabled by Dirhodium(II)/Phosphine Catalyzed Asymmetric Carbonyl Addition Cascade.

The catalytic asymmetric synthesis of chiral phthalides has garnered considerable interest. However, the construction of phthalides with a chiral quaternary carbon stereocenter still remains challenging. In this study, we developed a new strategy toward catalytic asymmetric synthesis of chiral 3,3-disubstituted phthalides via a dirhodium(II)/phosphine-catalyzed carbonyl addition cascade, yielding phthalides with up to 97% ee values. The reaction proceeded through dirhodium(II)/phosphine-catalyzed asymmetric carbonyl addition of arylboronic acids to isoquinoline-1,3,4(2H)-triones, followed by base-mediated ring contraction.

Promotion of polyhydroxyalkanoates-producing granular sludge formation by lactic acid using anaerobic dynamic feeding process.

To promote the formation of granular sludge with high polyhydroxyalkanoates (PHAs) synthesis ability, an anaerobic dynamic feeding process (AnDF) was proposed. This process combines the feast-famine mode with an anaerobic plug flow feeding process and involving variations in cycle length and settling time. The effects of lactic acid (LA) content (0 %, 20 %, and 40 % COD) on sludge granulation and PHAs production were investigated using three AnDF reactors (R1, R2, and R3). The results showed that the AnDF process feeding with LA not only effectively promoted sludge granulation but also improved its PHAs synthesis ability. The granules were quickly observed in R3 after 50 days of cultivation, with an average diameter of 0.69 mm. The maximum PHAs content reached 47.0 wt% in R3, representing a 30.09 % increase compared to R1. Additionally, extracellular polymeric substances (EPS)-producing bacteria observed in granular sludge may be the prime drivers of the formation of PHAs-producing granular sludge (PHAGS), which was defined as granular sludge with an average particle size larger than 0.30 mm and PHAs content above 40 % cell dry weight (CDW) of sludge samples.

Effect of phosphate-mineralized bacteria on multi-metals migration behavior in vanadium tailing slags: Coexistence of immobilization and mobilization.

Biomineralization techniques have been utilized to remediate heavy metals (HMs) contaminated environments. However, the effect of microbial-induced phosphate precipitation (MIPP) on HMs behavior in vanadium tailing slags has not been revealed. This study is the first to report the influence of MIPP on multiple HMs including Cd, Cu, Pb and Zn in the slags with and without soil mixing. The results showed that MIPP exhibited excellent ability for Cd immobilization, Cd immobilization rate reached 43.41 % under the optimal parameters within 7 days. Cd immobilization performance was significantly improved and sustained after the slags were covered with soil, resulting from better colonization of phosphate mineralizing bacteria in slag-soil mixtures. Surprisingly, DTPA-Cu, Zn and Pb contents in slags were all increased to varying degrees after MIPP treatment. Leaching solution mineralization tests further suggested that MIPP significantly reduced the concentration of Cd2+, Pb2+, Ca2+, Mg2+ and Al3+, but barely changed Cu2+ and Zn2+ concentrations. Characterization analysis confirmed that formation of phosphates including Cd(PO4)2 and dissolution of minerals including PbZnSiO2 were the reason for HMs immobilization and mobilization in vanadium tailing slags. This study provides new insights for understanding biomineralization technology and using MIPP to remediate HMs contaminated mine waste.

Design, synthesis and biological evaluation of a novel PSMA-PI3K small molecule drug conjugate.

Small molecule drug conjugates are an emerging targeted therapy for cancer treatment. Building upon the overexpressed prostate-specific membrane antigen (PSMA) in prostate cancer, we herein report the design and synthesis of a novel PSMA-PI3K small molecule drug conjugate 1. Conjugate 1 demonstrates potent inhibition against PI3K with an IC50 value of 0.40 nM and simultaneously targets PSMA, giving rise to selective growth inhibition activity for PSMA-positive cancer cells. Conjugate 1 also potently inhibits the phosphorylation of PI3K main downstream effectors and arrests the cell cycle in the G0/G1 phase in PSMA-positive 22Rv1 prostate cancer cells. Further in vivo evaluation shows that conjugate 1 has favorable efficacy and tolerability in a 22Rv1 xenograft model, demonstrating its potential application in targeted cancer therapy.

Cross-modal group-relation optimization for visible-infrared person re-identification.

Visible-infrared person re-identification (VIPR) plays an important role in intelligent transportation systems. Modal discrepancies between visible and infrared images seriously confuse person appearance discrimination, e.g., the similarity of the same class of different modalities is lower than the similarity between different classes of the same modality. Worse still, the modal discrepancies and appearance discrepancies are coupled with each other. The prevailing practice is to disentangle modal and appearance discrepancies, but it usually requires complex decoupling networks. In this paper, rather than disentanglement, we propose to measure and optimize modal discrepancies. We explore a cross-modal group-relation (CMGR) to describe the relationship between the same group of people in two different modalities. The CMGR has great potential in modal invariance because it considers more stable groups rather than individuals, so it is a good measurement for modal discrepancies. Furthermore, we design a group-relation correlation (GRC) loss function based on Pearson correlations to optimize CMGR, which can be easily integrated with the learning of VIPR's appearance features. Consequently, our CMGR model serves as a pivotal constraint to minimize modal discrepancies, operating in a manner similar to a loss function. It is applied solely during the training phase, thereby obviating the need for any execution during the inference phase. Experimental results on two public datasets (i.e., RegDB and SYSU-MM01) demonstrate that our CMGR method is superior to state-of-the-art approaches. In particular, on the RegDB dataset, with the help of CMGR, the rank-1 identification rate has improved by more than 7% compared to the case of not using CMGR.

For aqueous/soil cadmium immobilization under acid attack, does the hydroxyapatite converted from Pseudochrobactrum sp. DL-1 induced vaterite necessarily show higher stability?

Microbial induced carbonate precipitation (MICP) technology was widely applied to immobilize heavy metals, but its long-term stability is tough to maintain, particularly under acid attack. This study successfully converted Pseudochrobactrum sp. DL-1 induced vaterite (a rare crystalline phase of CaCO3) to hydroxyapatite (HAP) at 30 â„ƒ. The predominant conversion mechanism was the dissolution of CdCO3-containing vaterite and the simultaneous recrystallization of Ca4.03Cd0.97(PO4)3(OH)-containing HAP. For aqueous Cd immobilization, stability test at pH 2.0-10.0 showed that the Cd2+ desorption rate of Cd-adsorbed vaterite (3.96-4.35 ‱) were 7.13-20.84 times greater than that of Cd-adsorbed HAP (0.19-0.61 ‱). For soil Cd immobilization under 60 days of acid-rain erosion, the highest immobilization rate (51.00 %) of exchangeable-Cd and the lowest dissolution rate (-0.18 %) of carbonate-Cd were achieved with 2 % vaterite, while the corresponding rates were 16.78 % and 1.31 % with 2 % HAP, respectively. Furthermore, vaterite outperformed HAP in terms of soil ecological thorough evaluation. In conclusion, for Cd immobilization by MICP under acid attack, DL-1 induced vaterite displayed direct application value due to its exceptional stability in soil and water, while the mineral conversion strategy we presented is useful for further enhancing the stability in water.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

Catalpol attenuates hepatic glucose metabolism disorder and oxidative stress in triptolide-induced liver injury by regulating the SIRT1/HIF-1α pathway.

Triptolide (TP), known for its effectiveness in treating various rheumatoid diseases, is also associated with significant hepatotoxicity risks. This study explored Catalpol (CAT), an iridoid glycoside with antioxidative and anti-inflammatory effects, as a potential defense against TP-induced liver damage. In vivo and in vitro models of liver injury were established using TP in combination with different concentrations of CAT. Metabolomics analyses were conducted to assess energy metabolism in mouse livers. Additionally, a Seahorse XF Analyzer was employed to measure glycolysis rate, mitochondrial respiratory functionality, and real-time ATP generation rate in AML12 cells. The study also examined the expression of proteins related to glycogenolysis and gluconeogenesis. Using both in vitro SIRT1 knockout/overexpression and in vivo liver-specific SIRT1 knockout models, we confirmed SIRT1 as a mechanism of action for CAT. Our findings revealed that CAT could alleviate TP-induced liver injury by activating SIRT1, which inhibited lysine acetylation of hypoxia-inducible factor-1α (HIF-1α), thereby restoring the balance between glycolysis and oxidative phosphorylation. This action improved mitochondrial dysfunction and reduced glucose metabolism disorder and oxidative stress caused by TP. Taken together, these insights unveil a hitherto undocumented mechanism by which CAT ameliorates TP-induced liver injury, positioning it as a potential therapeutic agent for managing TP-induced hepatotoxicity.

Eu/Tb-MOF as fluorescence sensors for the detection homocysteine in human serum performance and mechanistic investigation.

Abnormal homocysteine (Hcy) levels in human serum have been associated with serious or vital diseases, making the reliable and easy detection of Hcy important to clinical analysis and biological study. In this work, five phosphorescent Ir(C^N)2(N^N) complexes (Irn) having aldehyde group were synthesized as probes (C^N and N^N denoted ligands). A discussion was conducted on their molecular structure, electronic structure, photophysical parameters, and Hcy sensing ability, revealing the correlations between their molecular structures and performances. Irn emission was enhanced (by âˆ¼ two folds) and blue-shifted (by 100 nm) after meeting Hcy (free state), via a cyclization reaction between the -CHO group (from Irn) and Hcy. In addition, using RE(BTC) as a supporting material (RE = Tb and Eu), the Ir(III) probe was loaded onto a supporting material of RE(BTC) (H3BTC = 1, 3, 5-benzenetricarboxylic acid). The emission color was changed by increasing Hcy concentration. Straight working curves were obtained with LOD (limit of detection) of 1.9 µM and a response time of ∼200 s. The novelty of this work was the combination of Irn with RE(BTC), which offered enhanced and blue-shifted emission upon Hcy via a cyclization reaction. This demonstrated a high level of sensitivity towards homocysteine detection.

Enhancing H2-driven CO2 biomethanation performance in bidirectional flow tidal bioreactor by reducing liquid film resistance and heterogeneity.

This study presents a bidirectional flow tidal bioreactor designed to enhance H2-driven CO2 biomethanation. The bioreactor alternated biofilms between immersion in nutrient solution and exposure to H2/CO2, creating alternating dry and wet states. This tidal operation minimized liquid film thickness during dry periods and ensured uniform nutrient distribution during wet periods. Bidirectional H2/CO2 supply was used to reduce biofilm thickness heterogeneity across the reactor height. CO2 biomethanation remained stable with an empty bed residence time of 9.7 min, achieving a methane (CH4) formation rate of 26.8 Nm3 CH4/(m3·d). The product gas contained 95.0 ± 2.5 % CH4, with a H2/CO2 conversion efficiency of 90.8 %. Tidal operation mitigated the buildup of dissolved and suspended organics, such as organic acids and detached biofilms. Dominant bacteria in biofilms included fermentative species like Petrimonas and H2-utilizing homoacetogens like Sporomusa. Enriched hydrogenotrophic methanogens, particularly Methanobacterium, were observed. Overall, this study highlights the bioreactor's effectiveness in improving CO2 biomethanation.

Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer.

Magnesium (Mg) deficiency is associated with increased risk and malignancy in colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here, we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p upregulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1-ACTN4 interaction by decreasing DBN1S142p, which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.