Pro-resolving lipid mediator reduces amyloid-ß42-induced gene expression in human monocyte-derived microglia.

JOURNAL/nrgr/04.03/01300535-202503000-00031/figure1/v/2024-06-17T092413Z/r/image-tiff Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-ß. With this objective, we analyzed the relevance of human monocyte-derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-ß42-induced Alzheimer's disease-like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease-like neuroinflammation in human brain microglia after incubation with amyloid-ß42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-ß42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-ß42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-ß42-induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

Microstructure Evolution and Mechanical Properties of 7A52 Aluminum Alloy Thin Sheet Repaired with Friction Stir Surfacing.

A solid-state repair technique based on surface friction welding is investigated in depth to achieve excellent mechanical properties of damaged 7A52 aluminum alloy. The results show that the yield strength and tensile strength along the repair direction are 436 MPa and 502 MPa, respectively, at a rotational speed of 1400 rpm and a travel speed of 300 mm/min, which are about 157.9% and 129.7% of those before the defects were repaired, respectively, while the elongation is 17.2% compared to the base material. Perpendicular to the repair direction, the yield strength and tensile strength are 254 MPa and 432 MPa, which are 111.4% and 129.7% of those before the defects were repaired, respectively, while the elongation is 11.8% compared to the base material. The mechanical properties of the repaired areas are still improved compared to those of the defect-free sheets. On the one hand, this is attributed to the dynamic recrystallization of the nugget zone due to the thermo-mechanical coupling, resulting in the formation of a fine, equiaxed grain structure; on the other hand, the precipitated Mg2Si phase, which is incoherent within the base material, transforms into the Al12(Fe, Mn)3Si phase, as well as the precipitation of the Al6Mn phase and η' phase, resulting in the enhancement of the properties. The material fracture at the junction of the nugget zone and the heat-affected zone occurs after repair, which is attributed to the significant difference in the texture of the nugget zone and the heat-affected zone, as well as to the stress concentration at the junction.

Achieving Equiaxed Transition and Excellent Mechanical Properties in a Novel Near-ß Titanium Alloy by Regulating the Volume Energy Density of Selective Laser Melting.

This research investigated the relationship between volume energy density and the microstructure, density, and mechanical properties of the Ti-5Al-5Mo-3V-1Cr-1Fe alloy fabricated via the SLM process. The results indicate that an increase in volume energy density can promote a transition from a columnar to an equiaxed grain structure and suppress the anisotropy of mechanical properties. Specifically, at a volume energy density of 83.33 J/mm3, the average aspect ratio of ß grains reached 0.77, accompanied by the formation of numerous nano-precipitated phases. Furthermore, the relative density of the alloy initially increased and then decreased as the volume energy density increased. At a volume energy density of 83.33 J/mm3, the relative density reached 99.6%. It is noteworthy that an increase in volume energy density increases the ß grain size. Consequently, with a volume energy density of 83.33 J/mm3, the alloy exhibited an average grain size of 63.92 µm, demonstrating optimal performance with a yield strength of 1003.06 MPa and an elongation of 18.16%. This is mainly attributable to the fact that an increase in volume energy density enhances thermal convection within the molten pool, leading to alterations in molten pool morphology and a reduction in temperature gradients within the alloy. The reduction in temperature gradients promotes equiaxed grain transformation and grain refinement by increasing constitutive supercooling at the leading edge of the solid-liquid interface. The evolution of molten pool morphology mainly inhibits columnar grain growth and refines grain by changing the grain growth direction. This study provided a straightforward method for inhibiting anisotropy and enhancing mechanical properties.

Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3aR878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.

Comparison of accelerated and standard infliximab induction regimens in acute severe ulcerative colitis using propensity score analysis: a retrospective multicenter study in China.

Background: The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients, and to explore risk factors and concrete accelerated regimens for them. Methods: Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at Day 14) rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjustment for potential confounders. The dose-response relationship was explored by plotting restricted cubic splines. Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes. A systematic review and meta-analysis was also performed. Results: A total of 76 patients were analysed: 29 received standard and 47 received accelerated induction. The accelerated group had a higher 90-day colectomy rate (17.8% vs 0%, P = 0.019) and lower clinical remission rate (27.7% vs 65.5%, P = 0.001). After adjusting for propensity score and institution, there was no significant difference in colectomy or clinical remission rates (both P > 0.05). Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, with no improvement observed for increasing cumulative infliximab dosage within 28 days. Multivariate logistic regression analyses revealed C-reactive protein of >10 mg/L at infliximab initiation (odds ratio = 5.00, 95% confidence interval: 1.27-24.34) as an independent risk factor for no clinical remission. Meta-analysis also revealed no significant difference in colectomy rates at 3 months (P = 0.54). Conclusions: After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients. Early administration of an intensified dosage within 5 days may be beneficial. Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.

Exploration of the sensitization effect of Chaihu Shugan powder on chemotherapy for triple-negative breast cancer and its active ingredients.

Chemotherapy plays a crucial role in the clinical treatment of triple-negative breast cancer (TNBC), but drug resistance limits its clinical application. The active ingredients of Chaihu Shugan Powder (CSP; Bupleurum Liver-Coursing Powder), quercetin and luteolin, both belong to flavonoid compounds and have significant anti-tumor potential, which can promote chemotherapy sensitivity. However, the correlation between the two and TNBC paclitaxel (PTX) chemotherapy sensitivity is unknown. We collected herbal components of CSP from the TCMSP database, and screened effective molecules and corresponding targets. STRING database was utilized to construct a protein-protein interaction network combining effective molecules and target genes. The top 50 nodes ranked by affinity were chosen for subsequent functional analysis, and the drug-active ingredient-gene interaction network was established using Cytoscape software. Molecular docking was used to determine the small molecules that target TNBC PTX resistance. The "clusterProfiler" package was utilized for GO and KEGG enrichment analyses on the top 50 genes to determine the pathways affected by CSP. Cell counting and colony formation assays evaluated cell viability, IC50 values, and proliferation capacity. Flow cytometry tested PTX intracellular accumulation. Western blot assayed the expression of TNF pathway-related proteins. Active ingredients of CSP, quercetin and luteolin, could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization. Quercetin and luteolin repressed the TNF signaling pathway and promoted PTX chemotherapy sensitization. Quercetin and luteolin could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization through the TNF signaling pathway. Therefore, the use of quercetin and luteolin plus PTX treatment provides a prospective strategy for TNBC treatment.

Effect of biochar-derived DOM on contrasting redistribution of chromate during Schwertmannite dissolution and recrystallization.

Biochar-derived dissolved organic matter (BDOM), is extensively involved in the recrystallization of minerals and the speciation alteration of associated toxic metals. This study investigates how BDOM extracted from tobacco petiole (TP) or tobacco stalk (TS) biochar influences the speciation repartitioning of Cr(VI) in environments impacted by acid mine drainage (AMD), focusing on interactions with secondary minerals during Schwertmannite (Sch) dissolution and recrystallization. TP-BDOM, rich in lignin-like substances, slowed down the Cr-Sch dissolution and Cr release under acidic conditions compared to TS-BDOM. TP-BDOM's higher O/C component exerts a delayed impact on Cr-Sch stability and Cr(VI) reduction. In-situ ATR-FTIR and 2D-COS analysis showed that carboxylic and aromatic N-OH groups in BDOM could interact with Cr-Sch surfaces, affecting sulfate and Cr(VI) release. It was also observed that slight recrystallization occurred from Cr-Sch to goethite, along with increased Cr incorporation into secondary minerals within TS-BDOM. This enhances our understanding of BDOM's role in Cr(VI) speciation changes in AMD-contaminated sites.

A Novel Inhalable Nanobody Targeting IL-4Rα for the Treatment of Asthma.

BACKGROUND: Inhalable biologics represent a promising approach to improve the efficacy and safety of asthma treatment. Although several monoclonal antibodies (mAbs) targeting IL-4Rα have been approved or are undergoing clinical trials, the development of inhalable mAbs targeting IL-4Rα presents significant challenges. OBJECTIVE: Capitalizing on the distinctive advantages of nanobodies (Nbs) in maintaining efficacy during storage and administration, we sought to develop a novel inhalable IL-4Rα Nb for effectively treating asthma. METHODS: Three IL-4Rα immunized Nb libraries were utilized to generate specific and functional IL-4Rα Nbs. LQ036, a bivalent Nb comprising two HuNb103 units, was constructed with a high affinity and specificity for hIL-4Rα. The efficacy, pharmacokinetic and safety of inhaled LQ036 were evaluated in B-hIL4/hIL4Ra humanized mice. RESULTS: LQ036 inhibited secreted embryonic alkaline phosphatase (SEAP) reporter activity, TF-1 cell proliferation, and suppressed pSTAT6 in T cells from asthma patients. Crystal structure analysis revealed a binding region similar to Dupilumab but with higher affinity, leading to better efficacy in blocking the signaling pathway. HuNb103 competed with IL-4 and IL-13 for IL-4Rα binding. Additionally, LQ036 significantly inhibited OVA-specific IgE levels in serum, CCL17 levels in BALF, bronchial mucous cell hyperplasia, and airway goblet cell hyperplasia in B-hIL4/hIL4Ra humanized mice. Inhaled LQ036 exhibited favorable pharmacokinetics, safety and tissue distribution, with higher concentrations observed in the lungs and bronchi. CONCLUSION: These findings from preclinical studies establish the safety and efficacy of inhaled LQ036, underscoring its potential as a pioneering inhalable biologic therapy for asthma.

[Screening of Highly Hazardous Pollutants in Groundwater of Beijing].

Groundwater contaminants pose a great threat to water safety and human health. Therefore, in this study, the traditional hazard assessment method was improved and a comprehensive system covering hazard assessment, screening, and characterization by combining the toxicological priority index (Tox Pi) framework; absorption, distribution, metabolism, and excretory (ADME) analysis; and bipartite network analysis was constructed. Then, the system was applied to hazard assessment and toxic pollutants screening from the 234 hydrophobic organic contaminants (HOCs) identified in the groundwater of Beijing. First, the top 20 pollutants with hazard potential were screened out using the Tox Pi method. Subsequently, 17 high-priority HOCs were further identified based on the ADME property analysis. Then, the molecular targets of these 17 high-priority HOCs were characterized through systematic bipartite network analysis. Finally, ten HOCs with high hazard were screened through correlation and weighted average analysis, and it was revealed that their toxic effects were mainly concentrated in the endocrine-disrupting effect, carcinogenic effect, and genetic toxicity. This study provides technical support for the prevention of regional groundwater contaminants.

Functional Characterization of the Soybean Glycine max Actin Depolymerization Factor GmADF13 for Plant Resistance to Drought Stress.

Abiotic stress significantly affects plant growth and has devastating effects on crop production. Drought stress is one of the main abiotic stressors. Actin is a major component of the cytoskeleton, and actin-depolymerizing factors (ADFs) are conserved actin-binding proteins in eukaryotes that play critical roles in plant responses to various stresses. In this study, we found that GmADF13, an ADF gene from the soybean Glycine max, showed drastic upregulation under drought stress. Subcellular localization experiments in tobacco epidermal cells and tobacco protoplasts showed that GmADF13 was localized in the nucleus and cytoplasm. We characterized its biological function in transgenic Arabidopsis and hairy root composite soybean plants. Arabidopsis plants transformed with GmADF13 displayed a more robust drought tolerance than wild-type plants, including having a higher seed germination rate, longer roots, and healthy leaves under drought conditions. Similarly, GmADF13-overexpressing (OE) soybean plants generated via the Agrobacterium rhizogenes-mediated transformation of the hairy roots showed an improved drought tolerance. Leaves from OE plants showed higher relative water, chlorophyll, and proline contents, had a higher antioxidant enzyme activity, and had decreased malondialdehyde, hydrogen peroxide, and superoxide anion levels compared to those of control plants. Furthermore, under drought stress, GmADF13 OE activated the transcription of several drought-stress-related genes, such as GmbZIP1, GmDREB1A, GmDREB2, GmWRKY13, and GmANK114. Thus, GmADF13 is a positive regulator of the drought stress response, and it may play an essential role in plant growth under drought stress conditions. These results provide new insights into the functional elucidation of soybean ADFs. They may be helpful for breeding new soybean cultivars with a strong drought tolerance and further understanding how ADFs help plants adapt to abiotic stress.

LAMC2 regulates the proliferation, invasion, and metastasis of gastric cancer via PI3K/Akt signaling pathway.

OBJECTIVES: Gastric cancer (GC) is a prevalent malignant tumor widely distributed globally, exhibiting elevated incidence and fatality rates. The gene LAMC2 encodes the laminin subunit gamma-2 chain and is found specifically in the basement membrane of epithelial cells. Its expression is aberrant in multiple types of malignant tumors. This research elucidated a link between LAMC2 and the clinical characteristics of GC and investigated the potential involvement of LAMC2 in GC proliferation and advancement. MATERIALS AND METHODS: LAMC2 expressions were detected in GC cell lines and normal gastric epithelial cell lines via qRT-PCR. Silencing and overexpression of the LAMC2 were conducted by lentiviral transfection. A xenograft mouse model was also developed for in vivo analysis. Cell functional assays were conducted to elucidate the involvement of LAMC2 in cell growth, migration, and penetration. Further, immunoblotting was conducted to investigate the impact of LAMC2 on the activation of signal pathways after lentiviral transfection. RESULTS: In the findings, LAMC2 expression was markedly upregulated in GC cell lines as opposed to normal gastric epithelial cells. In vitro analysis showed that sh-LAMC2 substantially inhibited GC cell growth, migration, and invasion, while oe-LAMC2 displayed a contrasting effect. Xenograft tumor models demonstrated that oe-LAMC2 accelerated tumor growth via high expression of Ki-67. Immunoblotting analysis revealed a substantial decrease in various signaling pathway proteins, PI3K, p-Akt, and Vimentin levels upon LAMC2 knockdown, followed by increased E-cadherin expression. Conversely, its overexpression exhibited contrasting effects. Besides, epithelial-mesenchymal transition (EMT) was accelerated by LAMC2. CONCLUSION: This study provides evidence indicating that LAMC2, by stimulating signaling pathways, facilitated EMT and stimulated the progression of GC cells in laboratory settings and mouse models. Research also explored that the abnormal LAMC2 expression acts as a biomarker for GC.

Arsenic redistribution associated with Fe(II)-induced jarosite transformation in the presence of polygalacturonic acid.

Jarosite exists widely in acid-sulfate soil and acid mine drainage polluted areas and acts as an important host mineral for As(V). As a metastable Fe(III)-oxyhydoxysulfate mineral, its dissolution and transformation have a significant impact on the biogeochemical cycle of As. Under reducing conditions, the trajectory and degree of abiotic Fe(II)-induced jarosite transformation may be greatly influenced by coexisting dissolved organic matter (DOM), and in turn influencing the fate of As. Here, we explored the impact of polygalacturonic acid (PGA) (0-200 mg·L-1) on As(V)-coprecipitated jarosite transformation in the presence of Fe(II) (1 mM) at pH 5.5, and investigated the repartitioning of As between aqueous and solid phase. The results demonstrated that in the system without both PGA and Fe(II), jarosite gradually dissolved, and lepidocrocite was the main transformation product by 30 d; in Fe(II)-only system, lepidocrocite appeared by 1 d and also was the mainly final product; in PGA-only systems, PGA retarded jarosite dissolution and transformation, jarosite might be directly converted into goethite; in Fe(II)-PGA systems, the presence of PGA retarded Fe(II)-induced jarosite dissolution and transformation but did not alter the pathway of mineral transformation, the final product mainly still was lepidocrocite. The retarding effect on jarosite dissolution enhanced with the increase of PGA content. The impact of PGA on Fe(II)-induced jarosite transformation mainly was related to the complexation of carboxyl groups of PGA with Fe(II). The dissolution and transformation of jarosite drove pre-incorporated As transferred into the phosphate-extractable phase, the presence of PGA retarded jarosite dissolution and maintained pre-incorporated As stable in jarosite. The released As promoted by PGA was retarded again and almost no As was released into the solution by the end of reactions in all systems. In systems with Fe(II), no As(III) was detected and As(V) was still the dominant redox species.

Chromatin accessibility during human first-trimester neurodevelopment.

The human brain develops through a tightly organized cascade of patterning events, induced by transcription factor expression and changes in chromatin accessibility. Although gene expression across the developing brain has been described at single-cell resolution1, similar atlases of chromatin accessibility have been primarily focused on the forebrain2-4. Here we describe chromatin accessibility and paired gene expression across the entire developing human brain during the first trimester (6-13 weeks after conception). We defined 135 clusters and used multiomic measurements to link candidate cis-regulatory elements to gene expression. The number of accessible regions increased both with age and along neuronal differentiation. Using a convolutional neural network, we identified putative functional transcription factor-binding sites in enhancers characterizing neuronal subtypes. We applied this model to cis-regulatory elements linked to ESRRB to elucidate its activation mechanism in the Purkinje cell lineage. Finally, by linking disease-associated single nucleotide polymorphisms to cis-regulatory elements, we validated putative pathogenic mechanisms in several diseases and identified midbrain-derived GABAergic neurons as being the most vulnerable to major depressive disorder-related mutations. Our findings provide a more detailed view of key gene regulatory mechanisms underlying the emergence of brain cell types during the first trimester and a comprehensive reference for future studies related to human neurodevelopment.

Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo.

Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.

Transfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing.

Nanopore direct RNA sequencing (DRS) has emerged as a powerful tool for RNA modification identification. However, concurrently detecting multiple types of modifications in a single DRS sample remains a challenge. Here, we develop TandemMod, a transferable deep learning framework capable of detecting multiple types of RNA modifications in single DRS data. To train high-performance TandemMod models, we generate in vitro epitranscriptome datasets from cDNA libraries, containing thousands of transcripts labeled with various types of RNA modifications. We validate the performance of TandemMod on both in vitro transcripts and in vivo human cell lines, confirming its high accuracy for profiling m6A and m5C modification sites. Furthermore, we perform transfer learning for identifying other modifications such as m7G, Ψ, and inosine, significantly reducing training data size and running time without compromising performance. Finally, we apply TandemMod to identify 3 types of RNA modifications in rice grown in different environments, demonstrating its applicability across species and conditions. In summary, we provide a resource with ground-truth labels that can serve as benchmark datasets for nanopore-based modification identification methods, and TandemMod for identifying diverse RNA modifications using a single DRS sample.

Deep-eutectic-solvent modulation of self-assembled multi-responsive films based on polyvinyl alcohol/cellulose nanocrystal and grape skin red for highly sensitive food monitoring.

To enhance the mechanics performance, sensitivity and response range of multi-responsive photonic films, herein, a facile method for fabricating multi-responsive films is demonstrated using the evaporative self-assembly of a mixture of grape skin red (GSR), cellulose nanocrystal (CNC), polyvinyl alcohol (PVA) and deep eutectic solvent (DES). The prepared materials exhibited excellent thermal stability, strain properties, solvent resistance, ultraviolet (UV) resistance and antioxidant activity. Compared to a pure PVA film, the presence of GSR strengthened the antioxidant property of the film by 240.1 % and provided excellent UV barrier capability. The additional cross-linking of DES and CNC promoted more efficient phase fusion, yielding a film strain of 41.5 %. The addition of hydrophilic compound GSR, wetting and swelling due to the DES and the surface inhomogeneity of the films rendered the multi-responsive films high sensitivity, wide response range and multi-cyclic stability in environments with varying pH and humidity. A sample application showed that a PVA/CNC/DES film has the potential to differentiate between fresh, sub-fresh and fully spoiled shrimps. The above results help in designing intelligent thin film materials that integrate antioxidant properties, which help in monitoring the changes in food freshness and food packaging.

Analyzing the expression and clinical significance of CENPE in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a prevalent type of malignant gastrointestinal tumor. Many studies have shown that CENPE acts as an oncogene in some cancers. However, its expression level and clinical value in GC are not clear. METHODS: Obtaining clinical data information on gastric adenocarcinoma from TCGA and GEO databases. The gene expression profiling interaction analysis (GEPIA) was used to evaluate the relationship between prognosis and CENPE expression in gastric cancer patients. Utilizing the UALCAN platform, the correlation between CENPE expression and clinical parameters was examined. Functions and signaling pathways of CENPE were analyzed using the Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The association between immunological infiltrating cells and CENPE expression was examined using TIMER2.0. Validation was performed by real-time quantitative PCR (qPT-PCR) and immunohistochemical analysis. RESULTS: According to the analysis of the GEPIA database, the expression of CENPE is increased in gastric cancer tissues compared to normal tissues. It was also found to have an important relationship with the prognosis of the patient (p<0.05). The prognosis was worse and overall survival was lower in individuals with increased expression of CENPE. In line with the findings of the GEPIA, real-time fluorescence quantitative PCR (qPT-PCR) confirmed that CENPE was overexpressed in gastric cancer cells. Furthermore, It was discovered that H. pylori infection status and tumor grade were related to CENPE expression. Enrichment analysis revealed that CENPE expression was linked to multiple biological functions and tumor-associated pathways. CENPE expression also correlated with immune-infiltrating cells in the gastric cancer microenvironment and was positively connected to NK cells and mast cells. According to immunohistochemical examination, paracancerous tissues had minimal expression of CENPE, but gastric cancer showed significant expression of the protein. CONCLUSIONS: According to our findings, CENPE is substantially expressed in GC and may perhaps contribute to its growth. CENPE might be a target for gastric cancer therapy and a predictor of a bad prognosis.

Global Atlas of Methane Metabolism Marker Genes in Soil.

Methane, a greenhouse gas, plays a pivotal role in the global carbon cycle, influencing the Earth's climate. Only a limited number of microorganisms control the flux of biologically produced methane in nature, including methane-oxidizing bacteria, anaerobic methanotrophic archaea, and methanogenic archaea. Although previous studies have revealed the spatial and temporal distribution characteristics of methane-metabolizing microorganisms in local regions by using the marker genes pmoA or mcrA, their biogeographical patterns and environmental drivers remain largely unknown at a global scale. Here, we used 3419 metagenomes generated from georeferenced soil samples to examine the global patterns of methane metabolism marker gene abundances in soil, which generally represent the global distribution of methane-metabolizing microorganisms. The resulting maps revealed notable latitudinal trends in the abundances of methane-metabolizing microorganisms across global soils, with higher abundances in the sub-Arctic, sub-Antarctic, and tropical rainforest regions than in temperate regions. The variations in global abundances of methane-metabolizing microorganisms were primarily governed by vegetation cover. Our high-resolution global maps of methane-metabolizing microorganisms will provide valuable information for the prediction of biogenic methane emissions under current and future climate scenarios.