Association of Myostatin With Complications and Cognition in Lung Cancer Patients With Sarcopenia.

INTRODUCTION: The risk of surgery and postoperative complications increases greatly in frail older patients with sarcopenia. The purpose of this study is to explore the correlation between myostatin (MSTN) levels and cognitive function and postoperative pulmonary complications (PPCs) in older patients undergoing thoracoscopic lobectomy and to determine whether MSTN could be used to predict the risk of postoperative complications and cognitive impairment. METHODS: A prospective observational study was conducted at the First Affiliated Hospital of Bengbu Medical College, China, between January 2023 and June 2023. The risk factors of PPCs and postoperative cognitive impairment were studied using backward stepwise logistic regression analysis. The independent factors were formed into a linear regression equation to construct a risk score model for each patient. The 122 patients who participated in the study were divided into two groups, a low-level group and a high-level group, based on an MSTN level cut-off; the preoperative MSTN cut-off values was 25.55 ng/mL for cognitive dysfunction and 22.29 ng/mL for PPCs. The PPCs and cognitive function of the groups were compared. RESULTS: Preoperative MSTN was confirmed as a risk factor for postoperative cognitive dysfunction and PPCs. After surgery, the proportion of patients with cognitive impairment in the high-level group was significantly higher than in the low-level group (P < 0.001). In the high-level group, the incidence of respiratory tract infections was 17.9% higher (P = 0.021), hypoxaemia was 20.5% higher (P = 0.001) and respiratory failure was 14.4% higher (P = 0.012) than in the low-level group. In addition, a high level of MSTN increased the length of hospital stay (P < 0.001) and decreased the Barthel Index score (P < 0.001). CONCLUSIONS: The study findings suggest that MSTN could be used as an index to predict complications and cognitive impairment after thoracoscopic lobectomy in older patients with sarcopenia and to provide evidence for reducing postoperative cognitive impairment and PPCs.

The glycolysis-related AMPK/ULK signaling pathway mediates the inhibitory effect of adiponectin in prostate cancer cells.

OBJECTIVE: Reduced adiponectin (ADPN) levels have been implicated in the pathogenesis of prostate cancer (PCa). The role of glycolysis in cancer development and treatment has attracted increasing attention. The present study aimed to elucidate its impact on PCa and to explore the mechanistic involvement of glycolysis. METHODS: An RM-1 cell xenograft model of Adpn-knockout mice was used to corroborate the effects of glycolysis, AMP-activated protein kinase (AMPK) signaling, and autophagy on tumor xenograft progression. The effect of ADPN on PCa cells was evaluated using the Cell Counting Kit-8 (CCK-8), lactate levels, and flow cytometry. The expression of glycolysis-related genes was detected using real-time RT-PCR in LNCaP and PC-3 cells after incubation with ADPN. Autophagic flux after ADPN treatment was quantified by chloroquine intervention and confocal analysis of mRFP-GFP-LC3. Alterations in the levels of adiponectin receptor 1 (AdipoR1), AMPK, Unc-51-like kinase 1 (ULK1), autophagy-related protein 7 (ATG7), p62, and microtubule-associated protein 1 light chain 3 beta (LC3B) were assessed after incubation of LNCaP cells with ADPN. RESULTS: Proteomic analysis of xenograft tumors demonstrated significant upregulation of glycolysis in Adpn-/- mice. Lower levels of ADPN accelerated tumor xenograft growth, diminished p-AMPKα/AMPKα ratio and LC3B II/I ratio, and elevated levels of proliferating cell nuclear antigen (PCNA) within the tumor microenvironment. ADPN inhibited proliferation and glycolysis and potentiated apoptosis in both cell lines. Expression of glycolysis-related genes decreased after ADPN treatment. Autophagic flux was elevated, as evidenced by changes in autophagy-related proteins and confocal microscopy analysis of mRFP-GFP-LC3. It led to the suppression of p62 while inducing phosphorylation of AMPKα and upregulating AdipoR1, ULK1, ATG7, and LC3B II/I ratio. CONCLUSION: ADPN inhibited the proliferation and progression of PCa cell-derived tumor xenografts by inhibiting glycolysis. Specifically, ADPN effectively inhibits glycolysis and activates the downstream AMPK/ULK1 signaling pathway to suppress proliferation of PCa cells.

Regional characterization of meteorological and agricultural drought in Baluchistan province, Pakistan.

Drought is a complex natural hazard that occurs when a region experiences a prolonged period of dry conditions, leading to water scarcity and negative impacts on the environment. This study analyzed the recurrence of drought and wet spells in Baluchistan province, Pakistan. Reconnaissance Drought Index (RDI), Standardized Precipitation Evapotranspiration Index (SPEI), and Vegetation Condition Index (VCI) were used to analyze droughts in Baluchistan during 1986-2021. Statistical analysis i.e. run theory, linear regression, and correlation coefficient were used to quantify the trend and relationship between meteorological (RDI, SPEI) and agricultural (VCI) droughts. The meteorological drought indices (1, 3, 6, and 12-month RDI and SPEI) identified severe to extreme drought spells during 1986, 1988, 1998, 2000-2002, 2004, 2006, 2010, 2018-2019, and 2021 in most meteorological stations (met-stations). The Lasbella met-station experienced the most frequent extreme to severe droughts according to both the 12-month RDI (8.82%) and SPEI (15.38%) indices. The Dalbandin met-station (8.34%) follows closely behind for RDI, while Khuzdar (5.88%) comes in second for the 12-month SPEI. VCI data showed that Baluchistan experienced severe to extreme drought in 2000, 2001, 2006, and 2010. The most severe drought occurred in 2000 and 2001, affecting 69% of the study region. A positive correlation was indicated between meteorological (RDI, SPEI) and agricultural drought index (VCI). The multivariate indices can provide valuable knowledge about drought episodes and preparedness to mitigate drought impacts.

Predicting the Risk of Postoperative Delirium in Elderly Patients Undergoing Hip Arthroplasty: Development and Assessment of a Novel Nomogram.

OBJECTIVE: To construct and internally validate a nomogram that predicts the likelihood of postoperative delirium in a cohort of elderly individuals undergoing hip arthroplasty. METHODS: Data for a total of 681 elderly patients underwent hip arthroplasty were retrospectively collected and divided into a model (n = 477) and a validation cohort (n = 204) according to the principle of 7:3 distribution temporally. The assessment of postoperative cognitive function was conducted through the utilization of The Confusion Assessment Method (CAM). The nomogram model for postoperative cognitive impairments was established by a combination of Lasso regression and logistic regression. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance. RESULTS: The nomogram utilized various predictors, including age, body mass index (BMI), education, preoperative Barthel Index, preoperative hemoglobin level, history of diabetes, and history of cerebrovascular disease, to forecast the likelihood of postoperative delirium in patients. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.836 (95% CI: 0.797-0.875) for the training set and 0.817 (95% CI: 0.755-0.880) for the validation set. The calibration curves for both sets indicated a good agreement between the nomogram's predictions and the actual probabilities. CONCLUSION: The use of this novel nomogram can help clinicians predict the likelihood of delirium after hip arthroplasty in elderly patients and help prevent and manage it in advance.

A Study on the Aesthetic Parameters and Proportions of the External Contour for Minimally Invasive Facial Injection.

OBJECTIVE: The aim of this study was to further guide the diagnosis and treatment programs for clinical facial contouring with injectable fillers by studying the facial contour parameters and proportion preferences consistent with Asian aesthetics. METHODS: A total of 89 subjects (42 males and 47 females aged 20-60 years) who met the inclusion criteria were enrolled in this study. The subjects were grouped by age, sex, and external contour attractiveness score, and the external contour aesthetic parameters and proportions of the subjects in different groups were measured and analysed. RESULTS: The upper facial breadth and lower facial breadth decreased with age, with significant differences between the 50-60-year age group and other age groups (P < 0.01). The nasomental angle showed a decreasing trend with age, with significant differences between the 40-49-year age group and the 20-29-year and 30-39-year age groups (P < 0.05). Males and females were significantly different in calva height, total head height, lower facial height, and calva height to total head height ratio (P < 0.05). With increasing age, the external contour attractiveness scores of males and females both showed decreasing trends, with significant differences between the 50-60-year age group and other age groups (P < 0.05). CONCLUSION: The calva height and the cranioauricular angle have a significant impact on external contour attractiveness. In general, temporal depression, cheek sagging, lateral cheek depression, and an ill-defined mandibular border will occur due to ageing, collagen loss, ligament laxity and sagging, and soft tissue atrophy and sagging, reducing the attractiveness of the external contour. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

ETS1-mediated Regulation of SOAT1 Enhances the Malignant Phenotype of Oral Squamous Cell Carcinoma and Induces Tumor-associated Macrophages M2-like Polarization.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer that poses a substantial threat to human life and quality of life globally. Lipid metabolism reprogramming significantly influences tumor development, affecting not only tumor cells but also tumor-associated macrophages (TAMs) infiltration. SOAT1, a critical enzyme in lipid metabolism, holds high prognostic value in various cancers. This study revealed that SOAT1 is highly expressed in OSCC tissues and positively correlated with M2 TAMs infiltration. Increased SOAT1 expression enhanced the capabilities of cell proliferation, tumor sphere formation, migration, and invasion in OSCC cells, upregulated the SREBP1-regulated adipogenic pathway, activated the PI3K/AKT/mTOR pathway and promoted M2-like polarization of TAMs, thereby contributing to OSCC growth both in vitro and in vivo. Additionally, we explored the upstream transcription factors that regulate SOAT1 and discovered that ETS1 positively regulates SOAT1 expression levels. Knockdown of ETS1 effectively inhibited the malignant phenotype of OSCC cells, whereas restoring SOAT1 expression significantly mitigated this suppression. Based on these findings, we suggest that SOAT1 is regulated by ETS1 and plays a pivotal role in the development of OSCC by facilitating lipid metabolism and M2-like polarization of TAMs. We propose that SOAT1 is a promising target for OSCC therapy with tremendous potential.

Core microbiome-associated proteins associated with ulcerative colitis interact with cytokines for synergistic or antagonistic effects on gut bacteria.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with a loss or an imbalance of host-microorganism interactions. However, such interactions at protein levels remain largely unknown. Here, we applied a depletion-assisted metaproteomics approach to obtain in-depth host-microbiome association networks of IBD, where the core host proteins shifted from those maintaining mucosal homeostasis in controls to those involved in inflammation, proteolysis, and intestinal barrier in IBD. Microbial nodes such as short-chain fatty-acid producer-related host-microbial crosstalk were lost or suppressed by inflammatory proteins in IBD. Guided by protein-protein association networks, we employed proteomics and lipidomics to investigate the effects of UC-related core proteins S100A8, S100A9, and cytokines (IL-1ß, IL-6, and TNF-α) on gut bacteria. These proteins suppressed purine nucleotide biosynthesis in stool-derived in vitro communities, which was also reduced in IBD stool samples. Single species study revealed that S100A8, S100A9, and cytokines can synergistically or antagonistically alter gut bacteria intracellular and secreted proteome, with combined S100A8 and S100A9 potently inhibiting beneficial Bifidobacterium adolescentis. Furthermore, these inflammatory proteins only altered the extracellular but not intracellular proteins of Ruminococcus gnavus. Generally, S100A8 induced more significant bacterial proteome changes than S100A9, IL-1ß, IL-6, and TNF-α but gut bacteria degrade significantly more S100A8 than S100A9 in the presence of both proteins. Among the investigated species, distinct lipid alterations were only observed in Bacteroides vulgatus treated with combined S100A8, S100A9, and cytokines. These results provided a valuable resource of inflammatory protein-centric host-microbial molecular interactions.

PPP2R1A silencing suppresses LUAD progression by sensitizing cells to nelfinavir-induced apoptosis and pyroptosis.

Lung adenocarcinoma is a major public health problem with the low 5-year survival rate (15%) among cancers. Aberrant alterations of meiotic genes, which have gained increased attention recently, might contribute to elevated tumor risks. However, systematic and comprehensive studies based on the relationship between meiotic genes and LUAD recurrence and treatment response are still lacking. In this manuscript, we first confirmed that the meiosis related prognostic model (MRPM) was strongly related to LUAD progression via LASSO-Cox regression analyses. Furthermore, we identified the role of PPP2R1A in LUAD, which showed more contributions to LUAD process compared with other meiotic genes in our prognostic model. Additionally, repression of PPP2R1A enhances cellular susceptibility to nelfinavir-induced apoptosis and pyroptosis. Collectively, our findings indicated that meiosis-related genes might be therapeutic targets in LUAD and provided crucial guidelines for LUAD clinical intervention.

Cambium Reactivation Is Closely Related to the Cell-Cycle Gene Configuration in Larix kaempferi.

Dormancy release and reactivation in temperate trees are mainly controlled by temperature and are affected by age, but the underlying molecular mechanisms are still unclear. In this study, we explored the effects of low temperatures in winter and warm temperatures in spring on dormancy release and reactivation in Larix kaempferi. Further, we established the relationships between cell-cycle genes and cambium cell division. The results showed that chilling accelerated L. kaempferi bud break overall, and the longer the duration of chilling is, the shorter the bud break time is. After dormancy release, warm temperatures induced cell-cycle gene expression; when the configuration value of the cell-cycle genes reached 4.97, the cambium cells divided and L. kaempferi reactivated. This study helps to predict the impact of climate change on wood production and provides technical support for seedling cultivation in greenhouses.

Lineage-specific gene duplication and expansion of DUF1216 gene family in Brassicaceae.

Proteins containing domain of unknown function (DUF) are prevalent in eukaryotic genome. The DUF1216 proteins possess a conserved DUF1216 domain resembling to the mediator protein of Arabidopsis RNA polymerase II transcriptional subunit-like protein. The DUF1216 family are specifically existed in Brassicaceae, however, no comprehensive evolutionary analysis of DUF1216 genes have been performed. We performed a first comprehensive genome-wide analysis of DUF1216 proteins in Brassicaceae. Totally 284 DUF1216 genes were identified in 27 Brassicaceae species and classified into four subfamilies on the basis of phylogenetic analysis. The analysis of gene structure and conserved motifs revealed that DUF1216 genes within the same subfamily exhibited similar intron/exon patterns and motif composition. The majority members of DUF1216 genes contain a signal peptide in the N-terminal, and the ninth position of the signal peptide in most DUF1216 is cysteine. Synteny analysis revealed that segmental duplication is a major mechanism for expanding of DUF1216 genes in Brassica oleracea, Brassica juncea, Brassica napus, Lepidium meyneii, and Brassica carinata, while in Arabidopsis thaliana and Capsella rubella, tandem duplication plays a major role in the expansion of the DUF1216 gene family. The analysis of Ka/Ks (non-synonymous substitution rate/synonymous substitution rate) ratios for DUF1216 paralogous indicated that most of gene pairs underwent purifying selection. DUF1216 genes displayed a specifically high expression in reproductive tissues in most Brassicaceae species, while its expression in Brassica juncea was specifically high in root. Our studies offered new insights into the phylogenetic relationships, gene structures and expressional patterns of DUF1216 members in Brassicaceae, which provides a foundation for future functional analysis.

A novel mutation in the ABCC8 gene causing maturity-onset diabetes of the young: A case report.

A 34-year-old woman was diagnosed with type 1 diabetes mellitus and treated with insulin for 24 years. The patient has a family history of diabetes in three consecutive generations. Her Whole exon sequencing showed a heterozygous mutation in the ABCC8 gene, and it also found some of her relatives to carry this mutation. She was diagnosed with MODY12 and received glimepiride therapy with the achievement of good glycaemic control.

Analysis of Characteristics of Endometrial Carcinoma in Peri- and Postmenopausal Women with Abnormal Uterine Bleeding.

Objective: To analyze the menstrual characteristics of endometrial carcinoma and investigate whether abnormal uterine bleeding in the perimenopausal period differs from postmenopausal bleeding. Methods: We conducted a retrospective analysis of 928 cases of endometrial carcinoma in patients admitted from January 2016 to December 2022. We gathered fundamental clinical data and analyzed distinct clinical risk factors between the perimenopausal and postmenopausal groups. Furthermore, we computed the statistical variances in menarche, regular menstrual cycles, and the duration of abnormal uterine bleeding. Results: Perimenopausal patients with endometrial carcinoma exhibit similar factors to postmenopausal patients, especially if they have a history of menstrual cycles lasting more than 30 years, hypertension, abnormal uterine bleeding for over 1 year, and a high risk of endometrial carcinoma. Early intervention for abnormal uterine bleeding during the perimenopausal stage can prevent up to 80% of women from developing endometrial carcinoma. Conclusion: Perimenopause women experiencing abnormal uterine bleeding should be mindful of the risk of endometrial carcinoma, as this awareness can substantially decrease the occurrence of the disease.

Effective health management strategies for patients undergoing valve replacement: a bibliometric analysis of the current research status and future directions.

Background: Valvular heart disease is a major health concern worldwide. The effective management of patients undergoing valve replacement determines their prognosis. Bibliometric analysis of studies on managing patients with artificial heart valves has not been previously performed. Methods: This study analyzed 2,771 publications related to patient management after valve replacement published in the Web of Science Core Collection database between January 1, 2013, and December 31, 2022. Bibliometric analysis was performed using CiteSpace and VOSviewer considering countries, institutions, authors, journals, references, and keywords. Results: The countries with the most significant contributions in this field were the United States of America (USA), Germany, and Italy. Leon MB from Columbia University, USA was the most influential author. Transcatheter aortic valve replacement was a current research hotspot, while anticoagulation management was a key area of interest. Combining anticoagulation therapy with internet-linked tools and portable health devices may offer new research avenues. Frailty assessment and intervention were potential future research areas. Conclusions: This bibliometric analysis provides clinicians and researchers with useful insights for developing novel ideas and directions to manage the health of patients undergoing valve replacement.

GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas.

Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, the most common malignancy of the central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior treatment outcomes or disease relapse, likely because of poor chemosensitivity of glioma cells due to a robust DNA damage response (DDR). GINS2, a subunit of DNA helicase, contributes to maintaining genomic stability and is highly expressed in various cancers, promoting their development. Here, we report that GINS2 was upregulated in TMZ-treated glioma cells and co-localized with γH2AX, indicating its participation in TMZ-induced DDR. Furthermore, GINS2 regulated the malignant phenotype and TMZ sensitivity of glioma cells, mostly by promoting DNA damage repair by affecting the mRNA stability of early growth response factor 1 (EGR1), which in turn regulates the transcription of epithelial cell-transforming sequence 2 (ECT2). We constructed a GINS2-EGR1-ECT2 prognostic model, which accurately predicted patient survival. Further, we screened Palbociclib/BIX-02189 which dampens GINS2 expression and synergistically inhibits glioma cell proliferation with TMZ. These findings delineate a novel mechanism by which GINS2 regulates the TMZ sensitivity of glioma cells and propose a promising combination therapy to treat glioma.

The Research Trend of Soft Tissue Filler Injection from 2000 to 2022: A Bibliometric and Visualized Analysis.

Background: The demand for soft tissue filler injections has experienced a significant increase in recent years. Therefore, this study used bibliometric analysis to identify prominent research areas and emerging trends within the field. Methods: Publications concerning research on soft tissue filler injections were collected from the Web of Science Core Collection database. Subsequently, VOSviewer 1.6.18 and CiteSpace 6.2.R4 software were used to analyze the co-authorship, co-occurrence, and citations of countries, institutions, authors, hotspot keywords, and journals associated with these studies. Results: A total of 1370 records pertaining to filler injection research conducted between 2000 and 2022 were identified. The United States (524 publications) emerged as the country with the highest number of publications in this field, with Mayo Clinic (37 publications) making the most substantial contribution. Dermatologic Surgery emerged as the leading journal in this field, publishing the highest number of research articles (151 publications) and also being the most frequently co-cited. Cotofana proved to be the most prolific author with 51 publications, and Lemperle emerged as the most frequently co-cited author with 628 citations (including total link strength: 6587). The most popular keywords, in descending order of popularity, were "dermal filler," "injection," "soft-tissue augmentation," "complications," and "hyaluronic acid." Conclusions: The findings of this study offer a comprehensive overview of the main directions in filler injection research. Furthermore, they underscore the imperative of intensifying efforts to prevent complications linked to filler injections.

Application of eHealth Tools in Anticoagulation Management After Cardiac Valve Replacement: Scoping Review Coupled With Bibliometric Analysis.

BACKGROUND: Anticoagulation management can effectively prevent complications in patients undergoing cardiac valve replacement (CVR). The emergence of eHealth tools provides new prospects for the management of long-term anticoagulants. However, there is no comprehensive summary of the application of eHealth tools in anticoagulation management after CVR. OBJECTIVE: Our objective is to clarify the current state, trends, benefits, and challenges of using eHealth tools in the anticoagulation management of patients after CVR and provide future directions and recommendations for development in this field. METHODS: This scoping review follows the 5-step framework developed by Arksey and O'Malley. We searched 5 databases such as PubMed, MEDLINE, Web of Science, CINAHL, and Embase using keywords such as "eHealth," "anticoagulation," and "valve replacement." We included papers on the practical application of eHealth tools and excluded papers describing the underlying mechanisms for developing eHealth tools. The search time ranged from the database inception to March 1, 2023. The study findings were reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). Additionally, VOSviewer (version 1.6.18) was used to construct visualization maps of countries, institutions, authors, and keywords to investigate the internal relations of included literature and to explore research hotspots and frontiers. RESULTS: This study included 25 studies that fulfilled the criteria. There were 27,050 participants in total, with the sample size of the included studies ranging from 49 to 13,219. The eHealth tools mainly include computer-based support systems, electronic health records, telemedicine platforms, and mobile apps. Compared to traditional anticoagulation management, eHealth tools can improve time in therapeutic range and life satisfaction. However, there is no significant impact observed in terms of economic benefits and anticoagulation-related complications. Bibliometric analysis suggests the potential for increased collaboration and opportunities among countries and academic institutions. Italy had the widest cooperative relationships. Machine learning and artificial intelligence are the popular research directions in anticoagulation management. CONCLUSIONS: eHealth tools exhibit promise for clinical applications in anticoagulation management after CVR, with the potential to enhance postoperative rehabilitation. Further high-quality research is needed to explore the economic benefits of eHealth tools in long-term anticoagulant therapy and the potential to reduce the occurrence of adverse events.

Centimeter-Sized Single Crystals of Tetrahedral Manganese (II) Halide Hybrids for Wide-Color Gamut Backlighting Displays.

Phosphors with narrow-band green emissions and high photoluminescent quantum efficiency (PLQY) are significantly required for backlighting displays with wider color gamut. In this work, two centimeter-sized manganese (II) halide single crystals TMG2 MnCl4 and TMG2 MnBr4 (TMG = 1,1,3,3-tetramethylguanidine) are synthesized, exhibiting bright narrow-band green emissions with high PLQYs up to 62% and 90%, respectively. The narrow-band green light emission is located at 520 nm with a full-width at half-maximum (FWHM) of only 57 nm. The photoluminescence mechanisms of two single crystals are elaborated. Two white-light-emitting diodes for backlighting displays (BD-WLEDs) based on them are fabricated, exhibiting the widest color gamut of 122% National Television Standards Committee (NTSC), and a luminous efficacy reached ≈93 lm W-1 with excellent luminescence stability at high temperatures. These properties indicate the potential applications of tetrahedral manganese (II) hybrids in wide-color gamut backlighting displays.

Comprehensive analysis reveals hub genes associated with immune cell infiltration in allergic rhinitis.

Objectives: Allergic rhinitis (AR) refers to a form of respiratory inflammation that mainly affects the sinonasal mucosa. The purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of AR. Methods: We performed a comprehensive analysis of two gene expression profiles (GSE50223 and GSE50101, a total of 30 patients with AR and 31 healthy controls). CIBERSORT was used to evaluate the immune cell infiltration levels. Weighted gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status, and enrichment analyses including gene ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene set variation analysis, were performed to analyze the potential mechanisms in AR. A protein-protein interaction network was constructed to investigate the hub genes, and consensus clustering was conducted to identify the molecular subtypes of AR. Results: Compared to the healthy controls, patients with AR had high abundance levels and proportions of CD4+ memory-activated T cells. One hundred and eight immune-related differentially expressed genes were identified. Enrichment analysis suggested that AR was mainly related to leukocyte cell-cell adhesion, cytokine-cytokine receptor interaction, T-cell activation, and T-cell receptor signaling pathway. Ten hub genes, including TYROBP, CSF1R, TLR8, FCER1G, SPI1, ITGAM, CYBB, FCGR2A, CCR1, and HCK, which were related to immune response, might be crucial to the pathogenesis of AR. Three molecular subtypes with significantly different immune statuses were identified. Conclusion: This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.

BDH1-mediated LRRC31 regulation dependent on histone lysine ß-hydroxybutyrylation to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the most common form of lung cancer, with a consistently low 5-year survival rate. Therefore, we aim to identify key genes involved in LUAD progression to pave the way for targeted therapies in the future. BDH1 plays a critical role in the conversion between acetoacetate and ß-hydroxybutyrate. The presence of ß-hydroxybutyrate is essential for initiating lysine ß-hydroxybutyrylation (Kbhb) modifications. Histone Kbhb at the H3K9 site is attributed to transcriptional activation. We unveiled that ß-hydroxybutyrate dehydrogenase 1 (BDH1) is not only conspicuously overexpressed in LUAD, but it also modulates the overall intracellular Kbhb modification levels. The RNA sequencing analysis revealed leucine-rich repeat-containing protein 31 (LRRC31) as a downstream target gene regulated by BDH1. Ecologically expressed BDH1 hinders the accumulation of H3K9bhb in the transcription start site of LRRC31, consequently repressing the transcriptional expression of LRRC31. Furthermore, we identified potential BDH1 inhibitors, namely pimozide and crizotinib, which exhibit a synergistic inhibitory effect on the proliferation of LUAD cells exhibiting high expression of BDH1. In summary, this study elucidates the molecular mechanism by which BDH1 mediates LUAD progression through the H3K9bhb/LRRC31 axis and proposes a therapeutic strategy targeting BDH1-high-expressing LUAD, providing a fresh perspective for LUAD treatment.

Estimation of regional meteorological aridity and drought characteristics in Baluchistan province, Pakistan.

Droughts and prevailing arid conditions have a significant impacts on the natural environment, agriculture, and human life. To analyze the regional characteristics of drought in Baluchistan province, the aridity index (AI) and standardized potential evapotranspiration index (SPEI) were used in. The study analyzed the rainfall, temperature, and potential evapotranspiration (PET) data and the same were used for the calculation of AI as well as SPEI to find out the drought spells during the study period. The linear regression and Mann-Kendall test were applied to calculate the trend in AI as well as in SPEI results. The AI results revealed that most of the meteorological stations are arid and semi-arid, where the highest increasing aridity is noted at Kalat (0.0065/year). The results of the SPEI at 1 and 6-months identified the extreme to severe drought spell during 1998-2002 in all meteorological stations of Baluchistan province. The distinct drought spells identified from the SPEI results were in the years 1998-2003, 2006-2010, 2015-2016 and 2019. The drought frequency results showed highest frequency percentage at Lasbella (46%) of extreme to severe drought. The Mann-Kendall trend results showed negative trend in monthly AI and 1-month SPEI results and most significant trend was observed in April and October months, this shows that aridity and drought in the region are decreasing to some extent except Dalbandin and Lasbella observed increasing trend in winter season (November to January months) and Kalat met-station observed increasing trend in June. Prior investigation and planning of drought situations can help in controlling the far-reaching consequences on environment and human society.