Search

Runing Fu,1,* Wenping Lian,1,* Bohao Zhang,2,* Gang Liu,3 Xinyu Feng,1 Yingjie Zhu,1 Jiuan Zhou,1 Xinyu Zhang,4 Shukai Wang,1 Huijuan Huo,1 Daxin Wang,1 Cui Liu,1 Saisai Gao,1 Yajie Ma,4 Mengle Peng1,* 1Department of Clinical Laboratory, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 3The Center of Meige Syndrome, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 4Department of Medical Affair, the Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengle Peng; Yajie Ma, Email pengmengle1990@126.com; szsyywk@sina.comPurpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers.Patient Data and Methods: Data from 448 consecutive patients with MS at the Third People’s Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model’s performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune‐inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application.Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk.Keywords: Meige syndrome, inflammatory marker, nomogram, LMR, SII

Lian W, Chen W. Drug Des Devel Ther. 2020;14:3385–3391. We, the Editor and Publisher of the journal Drug Design, Development and Therapy have retracted the published article. Following publication of the article, concerns were raised about the duplication of an image from Figure 4 with an image from an unrelated article. Specifically, The western blot image for Figure 4A, GAPDH, right, has been duplicated with a western blot image for Figure 2C, β-actin, from Feng Zhu, Shang-Nan Dai, Da-Lai Xu, Chao-Qun Hou, Tong-Tai Liu, Qiu-Yang Chen, Jun-Li Wu, Yi Miao, EFNB2 facilitates cell proliferation, migration, and invasion in pancreatic ductal adenocarcinoma via the p53/p21 pathway and EMT. Biomedicine & Pharmacotherapy. 2020;125:109972. https://doi.org/10.1016/j.biopha.2020.109972. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Peng Wang,1,2,* Yueying Fan,2,* Wenqin Lian,2,* Yingjun Su,3 Hou’an Xiao,1 Chiyu Jia2 1Department of Burns and Plastic and Cosmetic Surgery, Xi’an Ninth Hospital, Xi’an, People’s Republic of China; 2Department of Burns and Plastic and Wound Repair Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 3Department of Burns and Plastic Surgery, Plastic Surgery Hospital, Xi’an International Medical Center, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chiyu Jia, Department of Burns and Plastic and Wound Repair Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China, Email jiachiyu@qq.com Hou’an Xiao, Department of Burns and Plastic and Cosmetic Surgery, Xi’an Ninth Hospital, Xi’an, People’s Republic of China, Email xiaohouan@163.comObjective: To investigate the application of local rotation flaps for reconstruction of divided nevi of the penises in young male patients.Methods: A group of 8 patients of divided nevi of the penises who underwent wound reconstruction with local rotation flaps after surgical lesion removal was enrolled in a retrospective clinical study. Postoperative complication, sexual function and psychological traits were evaluated during the follow-up.Results: All patients, with ages ranged from 16 to 32 years (mean 23.25 years), were followed up for 6 to 48 months (mean 19.86 months). The patient’s average length of hospital stay was 7.85 day (7 to 15 days). The average dimension of the lesions was (2.31± 0.44) × (1.46± 0.48) cm2 on the glans and (1.38± 0.40) × (1.01± 0.46) cm2 on the inner prepuce plate. All patients had no postoperative infection and were satisfied with the postoperative outcome upon discharge. Five cases of benign intradermal nevi and 3 cases of compound nevi without malignant transformation were confirmed by pathological evaluation on the removed samples. The sexual function of all patients was unaffected postoperatively by male sexual function scale (BMSFI and IIEF-5) evaluation. The psychological status of depression, anxiety and stress was all improved after the surgical reconstruction confirmed by the psychological traits scale (DASS) evaluation.Conclusion: Reconstruction with the local rotation flap is a simple, safe and appropriate surgical procedure, achieves satisfactory cosmetic outcome, and maintains intact male sexual function when used for the repair of defect after removal of divided nevi of the penises.Keywords: divided nevi, local rotation flap, genital plastic surgery, postoperative, follow-up

Lin Zhu,* Wanyi Lian,* Zhiwen Yao, Xiao Yang, Ziyi Wang, Yupei Lai, Shiting Xu, Bingcheng Zhao, Kexuan Liu Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kexuan Liu; Bingcheng Zhao, Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China, Tel/Fax +86 020 61641881, Email liukexuan705@163.com; zhaobch@mail2.sysu.edu.cnPurpose: Intestinal ischemia/reperfusion (I/R) injury is an unresolved clinical challenge due to its high prevalence, difficulty in diagnosis, and lack of clinically effective therapeutic agents. Ferroptosis is a novel form of cell-regulated death that has been shown to play a role in various I/R models and has been shown to be immune-related. Further unraveling the molecular mechanisms associated with ferroptosis and immunity in intestinal I/R injury may lead to the discovery of potentially effective drugs.Methods: We obtained differentially expressed mRNAs (DEGs) in mouse intestinal tissues following intestinal I/R injury or sham surgery. Then, we extracted ferroptosis-related DEGs (FRGs) and immune-related DEGs (IRGs) from the DEGs. In addition, we performed functional analysis of FRGs and IRGs. Next, we used transcriptome sequencing from patients with intestinal I/R injury to validate the results. Then, we constructed transcription factors (TFs)-gene networks and gene-drug networks using mouse and human co-expressed FRGs (coFRG) and mouse and human co-expressed IRGs (coIRG). We also analyzed the composition of immune cells to reveal correlations between FRGs signatures and immune cells in the mouse and human gut. Finally, we validated these results through animal experiments.Results: We extracted 61 FRGs and 294 IRGs from mouse samples and performed PPI and functional analyses. We extracted 45 FRGs and 200 IRGs from human samples for validation, and identified 24 coFRGs,100 coIRGs and 6 hub genes (HSPA5, GDF15, TNFAIP3, HMOX1, CXCL2 and IL6) in both. We also predicted potential TF-gene networks for coFRGs and coIRGs, as well as predicted gene-drug pairs for hub genes. In addition, we found that the immune cells were altered in the early stages of intestinal I/R injury and that FRGs were closely associated with immune cells in mice and humans. Finally, we validated the hub genes in mouse samples.Conclusion: In conclusion, we identified ferroptosis and immunity-related genes to predict their correlations in intestinal I/R injury. We also predicated potential TF-genes network and potential therapeutic targets (HSPA5, GDF15, TNFAIP3, HMOX1, CXCL2 and IL6) to provide clues for further investigation of intestinal I/R injury.Keywords: intestinal ischemia-reperfusion injury, ferroptosis, immunity, RNA-seq, bioinformatics

Weibin Lian,1,* Xiaohua Jiang,2,* Liangqiang Li,1,* Qinglan Wang,1 Chengye Hong,1 Peidong Yang,1 Debo Chen1 1Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 2Department of Orthopedics, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weibin Lian; Debo Chen Tel +86-15260819892; +86-13600738668Email weibinlian@fjmu.edu.cn; deboqz@163.comIntroduction: Recently, the significant regulatory effects of lncRNAs on the oncogenesis and growth of tumor have been demonstrated by an increasing number of research projects. A previous study showed that LL22NC03-N64E9.1 could promote the development of colorectal cancer, especially via enhanced cell proliferation. Similarly, this lncRNA should have comparable functions in breast cancer (BC), which requires in-depth investigation. Therefore, this study was designed to explore the correlation of LL22NC03-N64E9.1 with BC.Methods: qRT-PCR was used to assess the relative expression of LL22NC03-N64E9.1 in BC tissues. Cell viability examination and colony formation experiments were performed to investigate the role of LL22NC03-N64E9.1 in BC cell’s proliferation. Transwell assays were used to explore the effects of LL22NC03-N64E9.1 on BC cell’s migration. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of LL22NC03-N64E9.1 with target proteins and genes in BC cells.Results: We identified that LL22NC03-N64E9.1 is an oncogene, upregulated in BC, which was verified in a cohort of 48 pairs of BC tissues. Based on the loss-of-function experiments, silencing LL22NC03-N64E9.1 expression significantly inhibited malignancy progression. In terms of the mechanism, LL22NC03-N64E9.1 acted on the enhancer of zeste homolog 2 (EZH2) by direct binding, which promoted BC cell growth. Furthermore, in the promoters of KLF2, the trimethylation of H3K27 could be regulated by LL22NC03-N64E9.1 as the mediator.Conclusion: Relying on the LL22NC03-N64E9.1/EZH2/KLF2 pathway, the lncRNA LL22NC03-N64E9.1 was significantly associated with BC development and could, therefore, be a potential therapeutic target to block BC growth.Keywords: breast cancer, lncRNA, LL22NC03-N64E9.1, H3K27me3, KLF2

Wei Lian, Wensheng Chen Department of Gastroenterology, Southwest Hospital of Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wensheng ChenDepartment of Gastroenterology, Southwest Hospital of Army Medical University, Gaotanyanzheng Street, Shapingba District, Chongqing 400038, People’s Republic of ChinaEmail wensheng_c1241@126.comBackground: Cyanidin-3-O-glucoside (C3G) is an important anthocyanin that can modulate digestive system functioning. Inflammation associated with severe acute pancreatitis (SAP) induces H2S production, which impairs the gastrointestinal (GI) system. We investigated the effects of C3G in attenuating SAP-associated colonic motility loss by examining the H2S level and activity of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.Methods: A rat model of SAP was induced using sodium taurocholate, and the effect of C3G on colonic mobility, H2S production, and the inflammatory response was investigated. AMPK/mTOR pathway changes were detected to assess the pathways by which H2S influences colonic mobility in SAP-model rats. The mechanism underlying H2S function was further examined by subjecting colonic muscle cells (CMCs) to C3G, SAP plasma and an AMPK activator.Results: Administering C3G improved colonic motility but suppressed the inflammatory response and H2S production in the SAP-model rats, which was associated with inhibiting the AMPK/mTOR pathway. Furthermore, activating the AMPK/mTOR pathway in CMCs promoted inflammation but suppressed Ca2+ levels, even after administering C3G.Conclusion: Administering C3G may improve SAP-associated colonic mobility by inhibiting the H2S-mediated AMPK/mTOR pathway.Keywords: AMP-activated protein kinase, AMPK, cyanidin-3-O-glucoside, colonic motility, severe acute pancreatitis, hydrogen sulfide

Chuanwu Cao,* Shilong Han,* Yifeng Yuan, Yongfa Wu, Weishuai Lian, Xiaojun Zhang, Long Pan, Maoquan Li Department of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University, Shanghai 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maoquan LiDepartment of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University, 301 Middle Yan Chang Road, Shanghai 200072, People’s Republic of ChinaTel +86-021-66313506Email cjr.limaoquan@vip.163.comBackground: Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported.Objective: To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion.Materials and methods: In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation.Results: Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 “sponging,” which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype.Conclusion: Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.Keywords: hsa_circ_0000291, miR-183, integrin beta 1, proliferation and migration, gastric cancer

Xiaoxiao Hu,1,* Weishuai Lian,1,* Xiaojun Zhang,2,* Xue Yang,3,* Jinxia Jiang,4 Maoquan Li1 1Department of Interventional Vascular Surgery, The Tenth People’s Hospital affiliated to Tongji University, Tongji University School of Medicine, Shanghai, 200072, China; 2Department of Interventional Catheter, The Tenth People’s Hospital affiliated to Tongji University, Shanghai, 200072, China; 3Department of Anesthesiology, Eastern Hospital Affiliated to Tongji University, Shanghai, 200120, China; 4Department of Emergency, The Tenth People’s Hospital affiliated to Tongji University, Shanghai, 200072, China *These authors contributed equally to this work Background: Diabetes mellitus, one of the most prevalent chronic metabolic diseases, causes many complications. Among the complications, one of the most common chronic complications is diabetic foot ulcers (DFUs).Objective: This study was conducted to investigate the efficacy of negative pressure wound therapy using vacuum-assisted closure (VAC) combined with photon therapy for the management of DFUs.Patients and methods: The study included a total of 69 patients with DFUs during the period from January 2014 to December 2015. All patients were diagnosed with DFUs with Wagner’s stage 2 or 3 and were divided into two groups – the VAC group in which patients received only VAC and the combined group in which patients received both VAC and photon therapy. Data on duration of the treatment, pre- and postoperative wound surface areas, dressing changing times, pain conditions assessed using visual analog scale scores, recurrence rate and amputation rate were collected.Results: Among all patients, 35 patients were divided into the VAC group and 34 patients into the combined group. Areas of foot ulcers for all patients ranged from 5 to 100 cm2. The treatment duration, dressing changing times and the peak value of visual analog scale scores were all significantly lower in the combined group compared with the VAC group (P

Marine protected areas (MPAs) can facilitate recovery of diminished stocks by protecting reproductive adults. To effectively augment fisheries, however, reproductive output must increase within the bounds of MPAs so that larvae can be exported to surrounding areas and seed the region. In response to dramatic declines of rockfishes (Sebastes spp.) in southern California by the late 1990s two large MPAs, the Cowcod Conservation Areas (CCAs), were established in 2001. To evaluate whether the CCAs affected rockfish productivity we evaluated the dynamics of 8 species that were, and 7 that were not, historically targeted by fishing. Abundances of 6/8 targeted and 4/7 non-targeted species increased regionally from 1998 to 2013. These upturns were probably affected by environmental conditions in addition to changes in fishing pressure as the presence of most species correlated negatively with temperature, and temperature was lower than the historic average in 11/15 years. Seventy-five per cent of the targeted, but none of the non-targeted species increased at a greater rate inside than outside the CCAs while controlling for environmental factors. Results indicate that management actions, coupled with favourable environmental conditions, facilitated the resurgence of multiple rockfish species that were targeted by intense fishing effort for decades.

Abstract Aim There is no conclusive evidence which one is the optimal methodology for enhancing the quality and efficacy of learning for medical students. Therefore, this systematic review and network meta-analysis aims to evaluate and prioritize various teaching strategies in medical education, including simulation-based learning (SBL), flipped classrooms (FC), problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL), and bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary (BOPPPS). Methods We conducted a comprehensive systematic search of PubMed, Embase, Web of Science, the Cochrane Library, and some key medical education journals up to November 31, 2023. The following keywords were searched in MeSH: (“medical students”) AND (“problem-based learning” OR “problem solving”) AND (“Randomized Controlled Trials as Topic”). Two authors independently carried out data extraction and quality assessment from the final selection of records following a full-text assessment based on strict eligibility criteria. Pairwise and network meta-analyses were then applied to calculate pooled standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) using a random-effects model. Statistical analysis was performed by R software (4.3.1) and Stata 14 software. Results A total of 80 randomized controlled trials with 6,180 students were included in the study. Compared to LBL, CBL (SMD = 1.19; 95% CI 0.49–1.90; p

Abstract Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and EGFR-TKI combination treatments have become the standard first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC) patients. However, the best option has yet to be determined. This study compares the efficacy and safety of various first-line EGFR-TKI monotherapies and combination treatments for advanced EGFR-mutated NSCLC. Methods We searched PubMed, Embase, the Cochrane Central Register of Controlled Clinical Trials databases, and several international conferences to identify randomized controlled trials reporting on first-line EGFR-TKI treatments for patients with advanced EGFR-mutated NSCLC. The study quality was assessed using the revised tool for risk of bias in randomized trials. The efficacy and safety outcomes of the included treatments were compared by network meta-analysis based on a frequentist approach. Results We identified 26 trials (8,359 patients) investigating 14 treatment groups, including first, second, and third-generation EGFR-TKIs and their combination treatments. Osimertinib plus chemotherapy and lazertinib plus amivantamab showed the highest efficacy in improving progression-free survival. New third-generation EGFR-TKIs demonstrated comparable efficacy to osimertinib alone but did not surpass it. Subgroup analyses revealed slight variation in treatment efficacy based on mutation types and patient demographics. Combination treatments were associated with a higher incidence of adverse events. Conclusion These results reveal that osimertinib plus chemotherapy and lazertinib plus amivantamab are superior first-line options for patients with advanced EGFR-mutated NSCLC. However, these combinations are associated with higher adverse event rates.

Abstract Background Currently, there is a lack of research on multi-drug resistant Pseudomonas aeruginosa (MDR-PA) isolation in bronchiectasis-related hemoptysis. The aim of this study to analyze the risk factors for recurrent hemoptysis following bronchial artery embolization (BAE) and compare the recurrent hemoptysis-free rates between MDR-PA, non-MDR-PA, and non-PA isolation. Methods A retrospective study was performed of patients diagnosed with idiopathic bronchiectasis-related recurrent hemoptysis who underwent BAE at an university-affiliated hospital. Patients were categorized based on PA susceptibility tests into non-PA, non-MDR-PA, and MDR-PA groups. Univariate and multivariate Cox regression were conducted to identify independent risk factors for recurrent hemoptysis. The Kaplan-Meier curves was conducted to compare recurrent hemoptysis-free rates after BAE for non-PA, non-MDR-PA, and MDR-PA. Results A total of 432 patients were included. 181 (41.90%) patients experienced recurrent hemoptysis during a median follow-up period of 25 months. MDR-PA isolation (adjusted hazard ratio (aHR) 2.120; 95% confidence interval (CI) [1.249, 3.597], p = 0.005) was identified as an independent risk factor for recurrent hemoptysis. Antibiotic treatment (aHR 0.666; 95% CI [0.476, 0.932], p = 0.018) reduced the risk of recurrent hemoptysis. The cumulative recurrent hemoptysis-free rates for non-PA, non-MDR-PA, and MDR-PA were as follows: at 3 months, 88.96%, 88.24%, and 75.86%, respectively; at 1 year, 73.13%, 69.10%, and 51.72%; and at 3 years, 61.91%, 51.69%, and 41.10% (p = 0.034). Conclusion MDR-PA isolation was an independent risk factor of recurrent hemoptysis post-BAE. Reducing the occurrence of MDR-PA may effectively decrease the recurrence rates of hemoptysis.

Abstract Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of various diseases, such as infectious diseases, autoimmune disorders, metabolic diseases, and cancers. In this context, IRFs display a dichotomous nature, functioning as both tumor suppressors and promoters, contingent upon the specific disease milieu. Post-translational modifications of IRFs, including phosphorylation and ubiquitination, play a crucial role in modulating their function, stability, and activation. As prospective biomarkers and therapeutic targets, IRFs present promising opportunities for disease intervention. Further research is needed to elucidate the precise mechanisms governing IRF regulation, potentially pioneering innovative therapeutic strategies, particularly in cancer treatment, where the equilibrium of IRF activities is of paramount importance.

Abstract Background Global warming has greatly increased the impact of high temperatures on crops, resulting in reduced yields and increased mortality. This phenomenon is of significant importance to the rose flower industry because high-temperature stress leads to bud dormancy or even death, reducing ornamental value and incurring economic losses. Understanding the molecular mechanisms underlying the response and resistance of roses to high-temperature stress can serve as an important reference for cultivating high-temperature-stress-resistant roses. Results To evaluate the impact of high temperatures on rose plants, we measured physiological indices in rose leaves following heat stress. Protein and chlorophyll contents were significantly decreased, whereas proline and malondialdehyde (MDA) contents, and peroxidase (POD) activity were increased. Subsequently, transcriptomics and metabolomics analyses identified 4,652 common differentially expressed genes (DEGs) and 57 common differentially abundant metabolites (DAMs) in rose plants from four groups. Enrichment analysis showed that DEGs and DAMs were primarily involved in the mitogen-activated protein kinases (MAPK) signaling pathway, plant hormone signal transduction, alpha-linolenic acid metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis. The combined analysis of the DEGs and DAMs revealed that flavonoid biosynthesis pathway-related genes, such as chalcone isomerase (CHI), shikimate O-hydroxycinnamoyl transferase (HCT), flavonol synthase (FLS), and bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase (DFR), were downregulated after heat stress. Moreover, in the MAPK signaling pathway, the expression of genes related to jasmonic acid exhibited a decrease, but ethylene receptor (ETR/ERS), P-type Cu + transporter (RAN1), ethylene-insensitive protein 2/3 (EIN2), ethylene-responsive transcription factor 1 (ERF1), and basic endochitinase B (ChiB), which are associated with the ethylene pathway, were mostly upregulated. Furthermore, heterologous overexpression of the heat stress-responsive gene RcHSP70 increased resistance to heat stress in Arabidopsis thaliana. Conclusion The results of this study indicated that the flavonoid biosynthesis pathway, MAPK signaling pathway, and plant hormones may be involved in high-temperature resistance in roses. Constitutive expression of RcHSP70 may contribute to increasing high-temperature tolerance. This study provides new insights into the genes and metabolites induced in roses in response to high temperature, and the results provide a reference for analyzing the molecular mechanisms underlying resistance to heat stress in roses.

Abstract In the realm of reservoir development, the optimization of well placement constitutes a cornerstone challenge with significant implications that directly determine the recovery rate and economic benefits of oil and gas production. This research proposes a novel approach to optimizing well placement in reservoirs by integrating reservoir numerical simulations with intelligent optimization algorithms. The quintessence of this inquiry revolves around the strategic placing of wells amidst the complex geological fabric of reservoirs, where the objective function landscape often manifests with non-smooth, multimodal characteristics. To address those issues, the Weighted Mapping of Productivity Potential (WMPP) technique, fortified by the Simulated Annealing algorithm to judiciously ascertain specific weighting coefficients for the computation of WMPP across reservoirs is introduced in this study. Furthermore, an emblematic carbonate reservoir model serves to corroborate the adaptability and viability of WMPP for well placement optimization, underscoring its efficacy as a swift, economically viable instrument for the delineation of prospective reservoir zones and the guidance of drilling initiatives. The optimization results show that the well placement scheme guided by WMPP, which required 7 fewer wells than the oil initially in place (OOIP)-based scheme, improved 21.74% oil production over the twenty years production period. This comprehensive workflow proffers invaluable insights and benchmarks for the formulation of well placement strategies, with the proposed methodology, in its apparent simplicity, showcasing remarkable efficiency.

Abstract Background Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia. Methods We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer’s disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses. Results 155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer’s disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18–1.48]) but a reduced risk of Alzheimer’s disease (0.92 [0.84–1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65–1.96]), vascular dementia (2.95 [2.53–3.45]) and Alzheimer’s disease (1.46 [1.26–1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25–3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer’s disease (0.83 [0.75–0.91]) and all-cause dementia (0.9 [0.84–0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1–1.39]) but not Alzheimer’s disease (1.0 [0.91–1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer’s disease were only present in those without MASLD (0.78 [0.67–0.91]). Conclusions MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.

Abstract Background Several antifungal agents are available for primary therapy in patients with invasive aspergillosis (IA). Although a few studies have compared the effectiveness of different antifungal agents in treating IA, there has yet to be a definitive agreement on the best choice. Herein, we perform a network meta-analysis comparing the efficacy of different antifungal agents in IA. Methods We searched PubMed, Embase, and the Cochrane Central Register of Controlled Clinical Trials databases to find studies (both randomized controlled trials [RCTs] and observational) that reported on treatment outcomes with antifungal agents for patients with IA. The study quality was assessed using the revised tool for risk of bias and the Newcastle Ottawa scale, respectively. We performed a network meta-analysis (NMA) to summarize the evidence on antifungal agents’ efficacy (favourable response and mortality). Results We found 12 studies (2428 patients) investigating 11 antifungal agents in the primary therapy of IA. There were 5 RCTs and 7 observational studies. When treated with monotherapy, isavuconazole was associated with the best probability of favourable response (SUCRA, 77.9%; mean rank, 3.2) and the best reduction mortality against IA (SUCRA, 69.1%; mean rank, 4.1), followed by voriconazole and posaconazole. When treated with combination therapy, Liposomal amphotericin B plus caspofungin was the therapy associated with the best probability of favourable response (SUCRA, 84.1%; mean rank, 2.6) and the best reduction mortality (SUCRA, 88.2%; mean rank, 2.2) against IA. Conclusion These findings suggest that isavuconazole, voriconazole, and posaconazole may be the best antifungal agents as the primary therapy for IA. Liposomal amphotericin B plus caspofungin could be an alternative option.

Abstract Dapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut microbiota through the metabolic conversion of choline and phosphatidylcholine. Ferroptosis may offer novel therapeutic avenues for the management of diabetes and myocardial ischemia–reperfusion injury (IRI). However, the precise mechanism underlying ferroptosis in cardiomyocytes and the specific role of TMAO generated by gut microbiota in the therapeutic approach for DM and myocardial IRI utilizing DAPA need to be further explored. Nine male SD rats with specific pathogen-free (SPF) status were randomly divided equally into the normal group, the DM + IRI (DIR) group, and the DAPA group. The diversity of the gut microbiota was analyzed using 16S rRNA gene sequencing. Additionally, the Wekell technique was employed to measure the levels of TMAO in the three groups. Application of network pharmacology to search for intersection targets of DAPA, DIR, and ferroptosis, and RT-PCR experimental verification. Ultimately, the overlapping targets that were acquired were subjected to molecular docking analysis with TMAO. The changes of Bacteroidetes and Firmicutes in the gut microbiota of DIR rats were most significantly affected by DAPA. Escherichia-Shigella and Prevotella_9 within the phylum Bacteroidetes could be identified as the primary effects of DAPA on DIR. Compared with the normal group, the TMAO content in the DIR group was significantly increased, while the TMAO content in the DAPA group was decreased compared to the DIR group. For the network pharmacology analysis, DAPA and DIR generated 43 intersecting target genes, and then further intersected with ferroptosis-related genes, resulting in 11 overlapping target genes. The mRNA expression of ALB, HMOX1, PPARG, CBS, LCN2, and PPARA decreased in the DIR group through reverse transcription polymerase chain reaction (RT-PCR) validation, while the opposite trend was observed in the DAPA group. The docking score between TMAO and DPP4 was − 5.44, and the MM-GBSA result of − 22.02 kcal/mol. It epitomizes the finest docking performance among all the target genes with the lowest score. DAPA could reduce the levels of metabolite TMAO produced by gut microbiota, thereby regulating related target genes to decrease ferroptosis in DIR cardiomyocytes.