Exploring the role of autophagy in psoriasis pathogenesis: Insights into sustained inflammation and dysfunctional keratinocyte differentiation.

Psoriasis is a common and prevalent chronic papulosquamous cutaneous disorder characterized by sustained inflammation, uncontrolled keratinocyte proliferation, dysfunctional differentiation, and angiogenesis. Autophagy, an intracellular catabolic process, can be induced in response to nutrient stress. It entails the degradation of cellular constituents through the lysosomal machinery, and its association with psoriasis has been well-documented. Nevertheless, there remains a notable dearth of research concerning the involvement of autophagy in the pathogenesis of psoriasis within human skin. This review provides a comprehensive overview of autophagy in psoriasis pathogenesis, focusing on its involvement in two key pathological manifestations: sustained inflammation and uncontrolled keratinocyte proliferation and differentiation. Additionally, it discusses potential avenues for disease management.

The identification of intact HIV proviral DNA from human cerebrospinal fluid.

We evaluated the HIV-1 DNA reservoir in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) in people with HIV (PWH) and associations to cognitive dysfunction. Using the intact proviral DNA assay (IPDA), an emerging technique to identify provirus that may be the source of viral rebound, we assessed HIV DNA in CSF and PBMC in PWH regardless of antiretroviral therapy (ART). CSF was used as a sampling surrogate for the central nervous system (CNS) as opposed to tissue. IDPA results (3' defective, 5' defective, and intact HIV DNA) were analyzed by compartment (Wilcoxon signed rank; matched and unmatched pairs). Cognitive performance, measured via a battery of nine neuropsychological (NP) tests, were analyzed for correlation to HIV DNA (Spearman's rho). 11 CSF and 8 PBMC samples from PWH were evaluated both unmatched and matched. Total CSF HIV DNA was detectable in all participants and was significantly higher than in matched PBMCs (p â€‹= â€‹0.0039). Intact CSF HIV DNA was detected in 7/11 participants and correlated closely with those in PBMCs but tended to be higher in CSF than in PBMC. CSF HIV DNA did not correlate with global NP performance, but higher values did correlate with worse executive function (p â€‹= â€‹0.0440). Intact HIV DNA is frequently present in the CSF of PWH regardless of ART. This further supports the presence of an HIV CNS reservoir and provides a method to study CNS reservoirs during HIV cure studies. Larger studies are needed to evaluate relationships with CNS clinical outcomes.

Technological Maturity of Aircraft-Based Methane Sensing for Greenhouse Gas Mitigation.

Methane is a major contributor to anthropogenic greenhouse gas emissions. Identifying large sources of methane, particularly from the oil and gas sectors, will be essential for mitigating climate change. Aircraft-based methane sensing platforms can rapidly detect and quantify methane point-source emissions across large geographic regions, and play an increasingly important role in industrial methane management and greenhouse gas inventory. We independently evaluate the performance of five major methane-sensing aircraft platforms: Carbon Mapper, GHGSat-AV, Insight M, MethaneAIR, and Scientific Aviation. Over a 6 week period, we released metered gas for over 700 single-blind measurements across all five platforms to evaluate their ability to detect and quantify emissions that range from 1 to over 1,500 kg(CH4)/h. Aircraft consistently quantified releases above 10 kg(CH4)/h, and GHGSat-AV and Insight M detected emissions below 5 kg(CH4)/h. Fully blinded quantification estimates for platforms using downward-facing imaging spectrometers have parity slopes ranging from 0.76 to 1.13, with R2 values of 0.61 to 0.93; the platform using continuous air sampling has a parity slope of 0.5 (R2 = 0.93). Results demonstrate that aircraft-based methane sensing has matured since previous studies and is ready for an increasingly important role in environmental policy and regulation.

Longitudinal Dynamics of Immune Response in Occupational Populations Post COVID-19 Infection in the Changning District of Shanghai, China.

Monitoring the long-term changes in antibody and cellular immunity following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial for understanding immune mechanisms that prevent reinfection. In March 2023, we recruited 167 participants from the Changning District, Shanghai, China. A subset of 66 participants that were infected between November 2022 and January 2023 was selected for longitudinal follow-up. The study aimed to investigate the dynamics of the immune response, including neutralizing antibodies (NAbs), anti-spike (S)-immunoglobulin G (IgG), anti-S-IgM, and lymphocyte profiles, by analyzing peripheral blood samples collected three to seven months post infection. A gradual decrease in NAbs and IgG levels were observed from three to seven months post infection. No significant differences in NAbs and IgG titers were found across various demographics, including age, sex, occupation, and symptomatic presentation, across five follow-up assessments. Additionally, a strong correlation between NAbs and IgG levels was identified. Lymphocyte profiles showed a slight change at five months but had returned to baseline levels by seven months post infection. Notably, healthcare workers exhibited lower B-cell levels compared to police officers. Our study demonstrated that the immune response to SARS-CoV-2 infection persisted for at least seven months. Similar patterns in the dynamics of antibody responses and cellular immunity were observed throughout this period.

Autonomous navigation and collision prediction of port channel based on computer vision and lidar.

This study aims to enhance the safety and efficiency of port navigation by reducing ship collision accidents, minimizing environmental risks, and optimizing waterways to increase port throughput. Initially, a three-dimensional map of the port's waterway, including data on water depth, rocks, and obstacles, is generated through laser radar scanning. Visual perception technology is adopted to process and identify the data for environmental awareness. Single Shot MultiBox Detector (SSD) is utilized to position ships and obstacles, while point cloud data create a comprehensive three-dimensional map. In order to improve the optimal navigation approach of the Rapidly-Exploring Random Tree (RRT), an artificial potential field method is employed. Additionally, the collision prediction model utilizes K-Means clustering to enhance the Faster R-CNN algorithm for predicting the paths of other ships and obstacles. The results indicate that the RRT enhanced by the artificial potential field method reduces the average path length (from 500 to 430 m), average time consumption (from 30 to 22 s), and maximum collision risk (from 15 to 8%). Moreover, the accuracy, recall rate, and F1 score of the K-Means + Faster R-CNN collision prediction model reach 92%, 88%, and 90%, respectively, outperforming other models. Overall, these findings underscore the substantial advantages of the proposed enhanced algorithm in autonomous navigation and collision prediction in port waterways.

Mulberry (Morus alba L.) leaf powder modified the processing of meat alternatives: Principal component analysis from apparent properties to chemical bonds.

For texture control in plant-meat alternatives, the interrelationship between apparent characteristics and chemical bonds in high-fiber formulations remains unclear. The influence of mulberry leaf powder on apparent characteristics and chemical bonds of raw materials, block and strip products at addition amounts of 0.5-25% was analyzed. The results showed that 8% addition significantly increased the chewiness of the block by 98.12%. The strips' texture shows a downward trend, and the processing produced more redness and color difference. Additives promoted the formation of voids, lamellar and filamentous structures, and the strip produced more striped structures. Disulfide bonds significantly increased in the block, and the ß-turn in the secondary structure enhanced by 12.20%. The ß-turn transformed into a ß-sheet in strips. Principal component analysis revealed that the texture improvement was associated with producing disulfide bonds and ß-turn, providing a basis for high-fiber components to improve products' apparent characteristics by chemical bonds.

INHBA regulates Hippo signaling to confer 5-FU chemoresistance mediated by cellular senescence in colon cancer cells.

Colon cancer has become a global public health challenge, and 5-Fluorouracil (5-FU) chemoresistance is a major obstacle in its treatment. Chemoresistance can be mediated by therapy-induced cellular senescence. This study intended to investigate mechanisms of INHBA (inhibin A) in 5-FU resistance mediated by cellular senescence in colon cancer. Bioinformatics analysis of INHBA expression in colon cancer tissues, survival analysis, and correlation analysis of cellular senescence markers were performed. The effects of INHBA on the biological characteristics and 5-FU resistance of colon cancer cells were examined through loss/gain-of-function and molecular assays. Finally, a xenograft mouse model was built to validate the mechanism of INHBA in vivo. INHBA was upregulated in colon cancer and was significantly positively correlated with cellular senescence markers uncoupling protein 2 (UCP-2), matrix metalloproteinase-1 (MMP-1), dense and erect panicle 1 (DEP1), and p21. Cellular senescence in colon cancer mediated 5-FU resistance. Downregulation of INHBA expression enhanced 5-FU sensitivity in colon cancer cells, inhibited cell proliferation, promoted apoptosis, increased the proportion of cells in G0/G1 phase, and it resulted in a lower proportion of senescent cells and lower levels of the cellular senescence markers interleukin 6 (IL-6) and interleukin 8 (IL-8). Analysis of whether to use the pathway inhibitor Verteporfin proved that INHBA facilitated colon cancer cell senescence and enhanced 5-FU chemoresistance via inactivation of Hippo signaling pathway, and consistent results were obtained in vivo. Collectively, INHBA conferred 5-FU chemoresistance mediated by cellular senescence in colon cancer cells through negative regulation of Hippo signaling.

Examining the association between delay discounting, delay aversion and physical activity in Chinese adults with type-2 diabetes mellitus.

BACKGROUND: The role of physical activity in diabetes is critical, influencing this disease's development, man-agement, and overall outcomes. In China, 22.3% of adults do not meet the minimum level of physical activity recommended by the World Health Organization. Therefore, it is imperative to identify the factors that contributing to lack of physical activity must be identified. AIM: To investigate the relationship among delay discounting, delay aversion, glycated hemoglobin (HbA1c), and various levels of physical activity in Chinese adults diagnosed with type 2 diabetes mellitus (T2DM). METHODS: In 2023, 400 adults with T2DM were recruited from the People's Hospital of Linxia Hui Autonomous Prefecture of Gansu Province. A face-to-face questionnaire was used to gather demographic data and details on physical activity, delay discounting, and delay aversion. In addition, HbA1c levels were measured in all 400 participants. The primary independent variables considered were delay discounting and delay aversion. The outcome variables included HbA1c levels and different intensity levels of physical activity, including walking, moderate physical activity, and vigorous physical activity. Multiple linear regression models were utilized to assess the relationship between delay discounting, delay aversion, and HbA1c levels, along with the intensity of different physical activity measured in met-hours per week. RESULTS: After controlling for the sample characteristics, delay discounting was negatively associated with moderate physical activity (ß = -2.386, 95%CI: -4.370 to -0.401). Meanwhile, delay aversion was negatively associated with the level of moderate physical activity (ß = -3.527, 95% CI: -5.578 to -1.476) in the multiple linear regression model, with statistically significant differences. CONCLUSION: Elevated delay discounting and increased delay aversion correlated with reduced levels of moderate physical activity. Result suggests that delay discounting and aversion may influence engagement in moderate physical activity. This study recommends that health administration and government consider delay discounting and delay aversion when formulating behavioral intervention strategies and treatment guidelines involving physical activity for patients with T2DM, which may increase participation in physical activity. This study contributes a novel perspective to the research on physical activity in adults with T2DM by examining the significance of future health considerations and the role of emotional responses to delays.

Advancing insights into in vivo meningeal lymphatic vessels with stereoscopic wide-field photoacoustic microscopy.

Meningeal lymphatic vessels (mLVs) play a pivotal role in regulating metabolic waste from cerebrospinal fluid (CSF). However, the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo. Here, we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system, including mLVs and glymphatic pathways. The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm, facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma. Subsequently, using this imaging technique, we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20-40 min after injection, along with determining the flow direction from CSF to lymph nodes. Inspiringly, in the Alzheimer's disease (AD) mouse model, we observed that AD mice exhibit a ~ 70% reduction in drainage volume of mLVs compared to wild-type mice. With the development of AD, there is be continued decline in mLVs drainage volume. This finding clearly demonstrates that the AD mouse model has impaired CSF drainage. Our study opens up a horizon for understanding the brain's drainage mechanism and dissecting mLVs-associated neurological disorders.

Exploring the roles and potential therapeutic strategies of inflammation and metabolism in the pathogenesis of vitiligo: a mendelian randomization and bioinformatics-based investigation.

Introduction: Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism's pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets. Methods: Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed. Results: MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol's binding to IRF3, indicating a stable interaction. Conclusion: This study comprehensively elucidates inflammation, immune response, and metabolism's intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo's etiology, informing future research and drug development endeavors.

Mid-term prognosis of endoscopic debridement combined with percutaneous cutaneo-fascial suture for the treatment of Morel-Lavallée lesion: a minimum 3-year follow-up study.

PURPOSE: Morel-Lavallée lesion (MLL) is a closed soft-tissue degloving injurie resulting from shear forces. With the advent of endoscopic technology and advancements in surgical techniques, innovative solutions are now available. However, there are few data on mid-term results after treatment of MLL, especially regarding arthroscopic method. The objective of this study is to evaluate the clinical outcomes of endoscopic debridement combined with percutaneous cutaneo-fascial suture in treating MLL. METHODS: A single-center retrospective study was conducted at a university teaching hospital investigating patients who underwent arthroscopic management of Morel-Lavallée lesion between 2014 and 2020.Patient demographics, postoperative recovery time, peri- and postoperative complications were investigated. Mid-term follow up clinical and radiological examinations were performed. RESULTS: The retrospective study included 38 patients aged between 11 and 90 years, with an average age of 50.9 ± 16.9 years. These patients waited an average of 36.6±23.5days to return to work after operation. The average time to follow-up was from 3 to 9 years, averaging 5.0 ± 1.8 years. At the end of follow-up, only one complication of superficial skin necrosis occurred, accounting for 2.6%. The imaging assessment at the final follow-up indicated improvement over the postoperative period for all 38patients. CONCLUSION: In mid-term experience, endoscopic debridement combined with percutaneous cutaneo-fascial suture for MLL management is a safe and effective option.

Palladium/XuPhos-catalyzed enantioselective cascade Heck/intermolecular C(sp2)-H alkylation reaction.

Palladium-catalyzed enantioselective domino Heck/intramolecular C-H functionalization reaction, as a valuable strategy for creating molecular diversity, has remained a prominent challenge. Here, we describe a Pd/XuPhos catalyst for asymmetric domino Heck/intermolecular C-H alkylation of unactivated alkenes with diverse polyfluoro- and heteroarenes in a highly chemo- and enantioselective manner. This process enables efficient synthesis of various dihydrobenzofurans, indolines and indanes, which are of interest in pharmaceutical research and other areas. Late-stage modifications of the core structures of natural products are also well showcased. Moreover, synthetic transformations create a valuable platform for preparing a series of functionalized molecules. Several control experiments for mechanistic study are conducted to pursue a further understanding of the reaction.

Prevalence and molecular characterization of Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis in dairy cattle in Ningxia, northwestern China.

Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis are common intestinal pathogens that infect humans and animals. To date, research regarding these three protozoa in the Ningxia Hui Autonomous Region (Ningxia) has mostly been limited to a single pathogen, and comprehensive data on mixed infections are unavailable. This study aimed to evaluate the zoonotic potential of these three protozoa. In this study, small subunit ribosomal RNA (SSU rRNA) and 60 kDa glycoprotein (gp60) genes of Cryptosporidium; internal transcribed spacer (ITS) gene of E. bieneusi; and SSU rRNA, glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis were examined. DNA extraction, polymerase chain reaction, and sequence analysis were performed on fecal samples collected from 320 dairy cattle at three intensive dairy farms in Ningxia in 2021 to determine the prevalence and genetic characteristics of these three protozoa. The findings revealed that 61.56% (197/320) of the samples were infected with at least one protozoan. The overall prevalence of Cryptosporidium was 19.38% (62/320), E. bieneusi was 41.56% (133/320), and G. duodenalis was 29.38% (94/320). This study identified four Cryptosporidium species (C. bovis, C. andersoni, C. ryanae, and C. parvum) and the presence of mixed infections with two or three Cryptosporidium species. C. bovis was the dominant species in this study, while the dominant C. parvum subtypes were IIdA15G1 and IIdA20G1. The genotypes of E. bieneusis were J, BEB4, and I alongside the novel genotypes NX1-NX8, all belonging to group 2, with genotype J being dominant. G. duodenalis assemblages were identified as assemblages E, A, and B, and a mixed infection involving assemblages A + E was identified, with assemblage E being the dominant one. Concurrently, 11 isolates formed 10 different assemblage E multilocus genotypes (MLGs) and 1 assemblage A MLG and assemblage E MLGs formed 5 subgroups. To the best of our knowledge, this is the first report on mixed infection with two or three Cryptosporidium species in cattle in Ningxia and on the presence of the C. parvum subtype IIdA20G1 in this part of China. This study also discovered nine genotypes of E. bieneusis and novel features of G. duodenalis assemblages in Ningxia. This study indicates that dairy cattle in this region may play a significant role in the zoonotic transmission of Cryptosporidium spp., E. bieneusi, and G. duodenalis.

In silico genome-wide analysis of homeodomain-leucine zipper transcription factors in Cannabis sativa L.

HD-Zip (Homeodomain-Leucine Zipper) is a family of transcription factors unique to higher plants and plays a vital role in plant growth and development. Increasing research results show that HD-Zip transcription factors are widely involved in many life processes in plants. However, the HD-Zip transcription factor for cannabis, a valuable crop, has not yet been identified. The sequence characteristics, chromosome localization, system evolution, conservative motif, gene structure, and gene expression of the HD-Zip transcription factor in the cannabis genome were systematically studied. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify its function. The results showed that cannabis contained 33 HD-Zip gene members. The number of amino acids is 136-849aa, the isoelectric point is 4.54-9.04, and the molecular weight is 23264.32-93147.87Da. Many cis-acting elements are corresponding to hormone and abiotic stress in the HD-Zip family promoter area of cannabis. Sequencing of the transcriptome at 5 tissue sites of hemp, stems, leaves, bracts, and seeds showed similar levels of expression of 33 members of the HD-Zip gene family at 5 tissue sites. Bioinformatics results show that HD-Zip expression is tissue-specific and may be influenced by hormones and environmental factors. This lays a foundation for further research on the gene function of HD-Zip.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Identification and validation of immune-related genes in osteoarthritic synovial fibroblasts.

Objective: OA was generally considered as a non-inflammatory disease dominated by articular cartilage degeneration. However, the role of synovitis in OA pathogenesis has received increasing attention. Recent studies support that OA patients have a pro-inflammatory/catabolic synovial environment similar to RA patients, promoting the occurrence and development of OA. Therefore, we investigated the co-immune-related genes and pathways of OA and RA to explore whether part of the pathogenesis of RA synovitis can be used to explain OA synovitis. Methods: Data of GSE29746 and GSE12021 were downloaded from the Gene Expression Omnibus (GEO) database. Compared with control group, differentially expressed genes (DEGs) of OA and RA groups were screened separately by R software, Venny website was used to screen co-DEGs. Metascape was used to screen the common enriched terms and pathways between OA and RA. STRING website and Cytoscape software were used to map protein-protein interaction (PPI) networks and screen co-hub genes. GSE29746 was selected as the test dataset, and GSE12021 as the validation dataset for validate the co-hub genes. The results were validated by western blotting (WB) and real-time quantitative polymerase chain reaction (qPCR) of clinical synovial samples. Results: We identified 573 OA-related DEGs, 148 RA-related DEGs, and 52 co-DEGs, revealing 14 common enriched terms, most of which were related to immune inflammation. IL7R was the only upregulated co-hub gene between OA and RA in the PPI network, consistent with the validation dataset. IL7R was highly expressed in clinical osteoarthritic synovial samples (P < 0.001). Conclusion: Our findings suggested that IL7R is a critical co-DEG in OA and RA and confirmed the involvement of immune inflammation in disease pathogenesis. Furthermore, it confirms the role of IL7R in synovial inflammation in RA and OA synovitis and provides evidence for further investigation of OA immune inflammation.

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation.

BACKGROUND: Gastric cancer (GC) is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis. Resveratrol, a non-flavonoid polyphenolic compound found in a variety of Chinese medicinal materials, has shown excellent anti-GC effect. However, its exact mechanisms of action in GC have not been clarified. AIM: To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms. METHODS: Action targets of resveratrol and GC-related targets were screened from public databases. The overlapping targets between the two were confirmed using a Venn diagram, and a "Resveratrol-Target-GC" network was constructed using Cytoscape software version 3.9.1. The protein-protein interaction (PPI) network was constructed using STRING database and core targets were identified by PPI network analysis. The Database for Annotation, Visualization and Integrated Discovery database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A "Target-Pathway" network was created by using Cytoscape 3.9.1. The RNA and protein expression levels of core target genes were observed using the Cancer Genome Atlas and the Human Protein Atlas databases. DriverDBv3 and Timer2.0 databases were used for survival and immune infiltration analysis. Subsequently, the findings were further verified by molecular docking technology and in vitro experiments. RESULTS: A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases, and 181 intersection targets between the two were screened by Venn diagram. The top 20 core targets were identified by PPI network analysis of the overlapping targets. GO function analysis mainly involved protein binding, identical protein binding, cytoplasm, nucleus, negative regulation of apoptotic process and response to xenobiotic stimulus. KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, ErbB signaling pathway, etc. FBJ murine osteosarcoma viral oncogene homolog (FOS) and matrix metallopeptidase 9 (MMP9) were selected by differential expression analysis, and they were closely associated with immune infiltration. Molecular docking results showed that resveratrol docked well with these two targets. Resveratrol treatment arrested the cell cycle at the S phase, induced apoptosis, and weakened viability, migration and invasion in a dose-dependent manner. Furthermore, resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression. CONCLUSION: The anti-GC effects of resveratrol are related to the inhibition of cell proliferation, migration, invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

US oil and gas system emissions from nearly one million aerial site measurements.

As airborne methane surveys of oil and gas systems continue to discover large emissions that are missing from official estimates1-4, the true scope of methane emissions from energy production has yet to be quantified. We integrate approximately one million aerial site measurements into regional emissions inventories for six regions in the USA, comprising 52% of onshore oil and 29% of gas production over 15 aerial campaigns. We construct complete emissions distributions for each, employing empirically grounded simulations to estimate small emissions. Total estimated emissions range from 0.75% (95% confidence interval (CI) 0.65%, 0.84%) of covered natural gas production in a high-productivity, gas-rich region to 9.63% (95% CI 9.04%, 10.39%) in a rapidly expanding, oil-focused region. The six-region weighted average is 2.95% (95% CI 2.79%, 3.14%), or roughly three times the national government inventory estimate5. Only 0.05-1.66% of well sites contribute the majority (50-79%) of well site emissions in 11 out of 15 surveys. Ancillary midstream facilities, including pipelines, contribute 18-57% of estimated regional emissions, similarly concentrated in a small number of point sources. Together, the emissions quantified here represent an annual loss of roughly US$1 billion in commercial gas value and a US$9.3 billion annual social cost6. Repeated, comprehensive, regional remote-sensing surveys offer a path to detect these low-frequency, high-consequence emissions for rapid mitigation, incorporation into official emissions inventories and a clear-eyed assessment of the most effective emission-finding technologies for a given region.

Amyloid ß oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction.

BACKGROUND: Although abnormal accumulation of amyloid beta (Aß) protein is thought to be the main cause of Alzheimer's disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid ß induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aß deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding. METHODS: Two-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aß oligomer stereotactic injection model was established to explain the relationship between Aß and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms. RESULTS: Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aß-injected model, suggesting a direct relationship between Aß and vascular dysfunction. Pericytes showed impaired features including low PDGFRß expression and increased pro-inflammatory chemokines secretion under the administration of Aß in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. CONCLUSIONS: Our results provide new insights into the pathogenic mechanism underlying Aß-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.

Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma.

BACKGROUND: Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets. MATERIALS AND METHODS: In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining. RESULTS: lncRNA BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). CONCLUSIONS: lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.