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Background: Bladder cancer is characterized by a high recurrence rate and mortality, posing a significant challenge to clinical management. Recently, cuproptosis, a novel form of regulated cell death, has been identified as a potential target for therapeutic intervention in various diseases. The contribution of cuproptosis-related microRNAs (miRNAs) in bladder cancer pathogenesis, however, remains largely unexplored. Therefore, the current study aims to construct a miRNA signature related to cuproptosis for predicting the prognosis and facilitating personalized therapeutic strategies in bladder cancer patients.

Methods: In this study, we retrieved transcriptomic data and clinical information pertaining to bladder cancer from publicly available databases, including the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified a set of 19 cuproptosis-related genes through a comprehensive review of relevant literature. Using multivariate Cox regression and LASSO analysis, we constructed a cuproptosis-related miRNA prognostic signature. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were used to validate the accuracy of prediction. Additionally, we developed a nomogram incorporating clinical characteristics and the miRNA signature to further assess its prognostic value. We evaluated the tumor microenvironment (TME) of every patient using immune ESTIMATE, CIBERSORT, and ssGSEA algorithms. We also investigated the differences in tumor mutation burden (TMB) and drug sensitivity between two groups. Finally, we validated the prognostic value of this miRNA signature using the OncomiR dataset.

Results: We developed a panel of eight cuproptosis-associated miRNAs to serve as a prognostic signature. The predictive validity of this signature was determined using Kaplan-Meier and ROC curves, and was found to be acceptable in both the TCGA training, test and total dataset. The prognostic value of this signature was confirmed by univariate and multivariate Cox regression analysis, indicating its applicability as a prognostic factor. The immune cell infiltration was significantly associated with an immunosuppressive phenotype of TME in the high-risk group of patients; meanwhile, patients in the high-risk group had a lower TMB resulted in shorter survival. Notably, higher estimate scores and IC50 value for chemotherapy drugs were observed in the high-risk group, indicating poor response to immune therapy and chemotherapy.

Background: Frequently, the women affected by the genitourinary syndrome of menopause experience genitourinary dysfunctions that profoundly influence their overall health. Even though the symptoms do not jeopardize the women's lives, the urinary and sexual dysfunctions significantly impact their quality of life. Isolated treatments focused on the main causes of the dysfunctions, such as pelvic floor muscle training (PFMT) and photobiomodulation have shown significant improvements in genitourinary dysfunctions. So, the association of PFMT with photobiomodulation may generate additional effects in the genitourinary area. This study aims to create a PFMT protocol isolated and associated with photobiomodulation therapy in women affected by the genitourinary syndrome of menopause.

Methods: It is a randomized, controlled, double-blind clinical trial protocol study that will include women experiencing genitourinary symptoms related to menopause, sexually active, never practiced pelvic floor muscle exercise or photobiomodulation treatment, and do not use hormone replacement therapy for at least 3 months. The randomization will allocate the women to three groups: PFMT group, PFMT associated with active intracavitary photobiomodulation group, and PFMT associated with sham intracavitary photobiomodulation group. A total of 16 sessions will be conducted twice a week. The assessments will occur before interventions, after the sixteenth session, and 1 month after the sixteenth session (follow-up). The evaluation will include the pelvic floor muscle vaginal manometry as the primary outcome. Also, the international consultation on incontinence questionnaire-short form, the female sexual function index, the Utian Quality of Life scale, the patient global impression of improvement, the modified Oxford scale, and the vaginal health index will be the secondary outcomes.

Discussion: Despite there are gold standard treatments such as PFMT, to alleviate genitourinary symptoms, interventions mirroring clinical practice are needed. This study protocol might show a groundbreaking and viable method to potentiate the effects of a gold-standard treatment associated with photobiomodulation.

Conclusion: We expect this protocol to demonstrate that the use of PFMT and photobiomodulation strategies is feasible and able to potentiate the recovery of women affected by the genitourinary syndrome of menopause. The Ethics Committee of the Federal University of Rio Grande do Norte approved the study (n° 6.038.283), and the clinical trials platform registered the protocol (n° RBR-5r7zrs2).

Cinnamyl alcohol dehydrogenase (CAD) is a crucial enzyme in the final stage of lignin monomer biosynthesis. This study focuses on the CAD gene family within Gossypium hirsutum. Through comprehensive genomic analysis, we identified 29 GhiCAD genes within the Gossypium hirsutum genome using a bioinformatics approach. Phylogenetic analysis revealed that the GhiCAD family can be categorized into four subgroups, which are closest to the evolutionary relationship with Arabidopsis thaliana. There are multiple cis-acting elements on the promoters of GhiCAD genes associated with abiotic stress responses. Some GhiCAD genes demonstrated high expression in various tissues like root, leaf, and sepal, as well as in fiber and ovule at different developmental stages (10 days post anthesis (DPA), 15 DPA, 20 DPA, 25 DPA). The transcript levels of GhiCAD23 were notably elevated when exposed to PEG treatment and drought stress (DS). GhiCAD23 is also co-expressed with many known drought response genes, suggesting its involvement in the plant's reaction to DS. Employing virus-induced gene silencing (VIGS) technology to silence the GhiCAD23 gene, it was found that silencing GhiCAD23 reduced the tolerance of cotton to DS. Under DS, the relative leaf water content, superoxide dismutase (SOD), and catalase (CAT) enzyme activities of the GhiCAD23-silenced cotton plants were decreased by 31.84%, 30.22% and 14.19%, respectively, while malondialdehyde (MDA) was increased by 72.16% compared with the control cohort. Drought promotes the accumulation of lignin, and it was found that silencing the GhiCAD23 reduces lignin accumulation in cotton under DS. The analysis of phenotypic and physiological indicators indicates that GhiCAD23 is vital in cotton's resistance to DS. This investigation provides an important reference for future comprehensive exploration of the GhiCAD23 gene's function in cotton's DS response mechanism.

Background: Bacteria can develop resistance to various antibiotics under selective pressure, leading to multifaceted changes in resistance mechanisms. Transcriptomic sequencing allows for the observation of transcriptional level alterations in cells under antibiotic stress. Understanding the bacterial response to such stress is essential for deciphering their strategy against drug-resistant antibiotics and identifying potential targets for antibiotic development.

Methods: This study using wild-type (WT) Escherichia coli (E. coli) discovered that continuous in vitro induction screening for imipenem-resistant strains resulted in bacteria with enhanced biofilm-forming ability and mutations in antibiotic target sites. Transcriptomic sequencing of the resistant bacteria revealed significant changes in carbon and amino acid metabolism, nutrient assimilation, substance transport, nucleotide metabolism, protein biosynthesis, and cell wall biosynthesis. The up-regulated drug efflux genes were disrupted using gene knockout technology. Drug sensitivity tests indicated that drug efflux has a minimal effect on imipenem resistance.

Results: This suggests a strategy for E. coli drug resistance involving the reduction of unnecessary substance synthesis and metabolism, coupled with an increase in activities that aid in resisting foreign threats.

Background: The rapid pace of knowledge production has introduced a phenomenon termed "knowledge anxiety", a psychological state where researchers feel inadequate in keeping up with emerging information. This state can negatively affect productivity and mental well-being, yet there is no comprehensive tool to measure knowledge anxiety across different research domains.

Methods: We employed a mixed-methods approach to develop a multidimensional scale for assessing knowledge anxiety. Initial items were generated through a literature review and qualitative interviews with 313 researchers. After pilot testing, the main study involved 26 participants. The scale was refined through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to ensure its structural validity and reliability.

Results: EFA resulted in a 16-item scale with four distinct factors: cognitive, emotional, behavioral, and capability-related anxieties. CFA confirmed a strong model fit, with standardized factor loadings between 0.549 and 0.887. The scale demonstrated high reliability, with a composite Cronbach's alpha of 0.883.

Conclusions: This newly developed scale offers a reliable and valid measure of knowledge anxiety, providing researchers with a valuable tool to assess the psychological impacts of knowledge overload.

The pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae) is a serious insect pest of cotton crop. The studies to evaluate the impact of abiotic factors on cotton pests' biology are limited. The current study was undertaken to determine the impact of abiotic factors (temperature, humidity, photoperiod) and an insecticide (lambda-cyhalothrin) on the biological aspects of P. gossypiella. The results revealed that all the treatments showed a significant impact on different life parameters of P. gossypiella. The temperature exposure at 27 °C revealed a total life span of about 33 days. Maximum mortality for larvae (51.11%), pupae (59.04%) and adults (61.92%) were recorded at 33 °C exposure. Both low and high humidity levels caused negative impacts on life parameters of P. gossypiella. The life span was completed in about 30 days at 60% relative humidity (RH). Maximum mortality for larvae (75.00%) and pupae (49.59%) were recorded at 80% RH level exposure, while adult mortality was maximum (63.09%) at 40% RH level followed by 80% RH level (55.52%). The P. gossypiella exhibited a life span of about 32 days at 14:10 light-dark period. The larval mortality was maximum (14.83%) at 12:12 light-dark period while pupal (47.36%) and adult (48.84%) mortality was maximum at 16:08 light-dark period. Lambdacyhalothrin (LC) showed dose dependent negative impacts on biological aspects of P. gossypiella. The P. gossypiella exhibited a life span of about 26 days at 0.5 ppm LC concentration. The P. gossypiella exposure to highest concentration (LC) revealed maximum mortality of larval (80.22%), pupal (64.63%) and adult (70.74%) stages. Conclusively, the best suited abiotic factor ranges were 27 °C (temperature), 60% (RH) and 14:10 (light-dark) which can be used for successful rearing and bioassay activities of P. gossypiella.

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, characterized by significant individual variations in treatment response. Predicting treatment response remains a formidable challenge. This study aims to identify predictors within the synovium associated with the response to JAK inhibitor therapy in RA patients, employing a retrospective approach.

Methods: A retrospective analysis was conducted on 27 RA patients who underwent synovial biopsy and received JAK inhibitor therapy for at least three months at our center, from January to November 2023. These patients had comprehensive clinical records. Based on their response to JAK inhibitor therapy, as measured by the ACR20 criteria, they were categorized into non-responder and responder groups. We compared clinical data (including sex, age, disease duration), laboratory findings (RF, ACPA, ESR, CRP, etc.), DAS28-CRP scores, and synovial pathology features-such as synovial lining hyperplasia, neovascularization, stromal activation, inflammatory infiltration, and the expression of CD3, CD20, CD68, and CD138 markers in the synovium-between the two groups.

Results: The rate of non-responder to JAKi was found to be 33.3% (nine cases out of a total of 27 patients). Non-responders, when compared to responders, exhibited longer disease duration, more pronounced synovial neovascularization alongside reduced infiltration of labeled CD20+ and CD138+ cells in the synovium. Multivariate regression analysis identified synovial neovascularization and disease duration as independent predictors of a poor response to JAK inhibitor treatment.

Conclusions: The presence of vascular phenotype with low inflammation within the synovium of RA patients is an indicator of poor response to JAK inhibitor therapy, highlighting its potential as a predictive marker for treatment outcomes.

Ecological niche modeling (ENM) is a valuable tool for inferring suitable environmental conditions and estimating species' geographic distributions. ENM is widely used to assess the potential effects of climate change on species distributions; however, the choice of modeling algorithm introduces substantial uncertainty, especially since future projections cannot be properly validated. In this study, we evaluated the performance of seven popular modeling algorithms-Bioclim, generalized additive models (GAM), generalized linear models (GLM), boosted regression trees (BRT), Maxent, random forest (RF), and support vector machine (SVM)-in transferring ENM across time, using Mexican endemic rodents as a model system. We used a retrospective approach, transferring models from the near past (1950-1979) to more recent conditions (1980-2009) and vice versa, to evaluate their performance in both forecasting and hindcasting. Consistent with previous studies, our results highlight that input data quality and algorithm choice significantly impact model accuracy, but most importantly, we found that algorithm performance varied between forecasting and hindcasting. While no single algorithm outperformed the others in both temporal directions, RF generally showed better performance for forecasting, while Maxent performed better in hindcasting, though it was more sensitive to small sample sizes. Bioclim consistently showed the lowest performance. These findings underscore that not all species or algorithms are suited for temporal projections. Therefore, we strongly recommend conducting a thorough evaluation of the data quality-in terms of quantity and potential biases-of the species of interest. Based on this assessment, appropriate algorithm(s) should be carefully selected and rigorously tested before proceeding with temporal transfers.

Marine biogenic calcium carbonate production plays a role in the exchange of CO₂ between ocean and atmosphere. The effect of increased CO₂ on calcification and on the resulting chemistry of shells and skeletons, however, is only partly understood. Foraminifera are among the main marine CaCO₃ producers and the controls on element partitioning and isotope fractionation is the subject of many recent investigations. The enzyme carbonic anhydrase (CA) was, for example, shown to be vital for CaCO₃ deposition in benthic foraminifera and indicates their ability to manipulate their intracellular inorganic carbon chemistry. Here, we tested whether CA affects the partitioning of Na, Mg and Sr in the perforate, large benthic, symbiont-bearing foraminifer Amphistegina lessonii by addition of the inhibitor acetazolamide (AZ). The effect of dissolved CO₂ on the effect of CA on element partitioning was also determined using a culturing setup with controlled atmospheric carbon dioxide levels (400-1,600 ppm). Results show that inhibition by AZ reduces calcification greatly and that CO₂ has a small, but positive effect on the amount of calcite formed during the incubations. Furthermore, the inhibition of CA activity has a positive effect on element partitioning, most notably Mg. This may be explained by a (n indirect) coupling of inorganic carbon uptake and inward calcium ion pumping.

Background: Exercise in humid and hot environments (HHEs) may result in decreased perception, motor performance, and memory owing to endogenous heat production and exogenous load. However, whether a single bout of exercise (SBOE) intensity affects the magnitude of changes in the levels of hemocytes remains controversial. In this article, we aimed to investigate the effects of a SBOE of varying intensities on blood cells in HHE.

Methods: Thirty-two volunteers were randomly divided into a quiet control group (QC), 55% VO₂max intensity exercise group (HHE55%), 70% VO₂max intensity exercise group (HHE70%), and 85% VO₂max intensity exercise group (HHE85%). The participants in the exercise groups were assigned to perform an SBOE on the treadmill under HHE conditions for 30 min, whereas participants in the QC remained still under HHE conditions for 30 min (temperature: 28-32 °C, relative humidity: 85-95%).

Results: The net body mass (NBM), perfusion index (PI), mean corpuscular volume (MCV), platelet (PLT), and plateletcrit (PCT) values were affected significantly by the exercise intensity (P < 0.01) the hemoglobin (HGB) and neutrophil count (NE) were affected significantly by exercise intensity (P < 0.05). After an SBOE, compared with that before exercise, the sublingual temperature (ST) of all groups, the NBM and MCV of all exercise groups, the PI of the HHE55% and HHE70% groups, the HGB, hematocrit (HCT), and NE of the HHE70% group, the red blood cell count (RBC), PLT, and PCT of the HHE70% and HHE85% groups, and the white blood cell count (WBC) of HHE85% changed very significantly (P < 0.01). The PCT of QC, blood oxygen saturation (SaO₂), and soluble transferrin receptor (sTfR) levels in the HHE55% group, the lymphocyte count (LY) in the HHE70% group, and the HGB and HCT in the HHE85% group changed significantly (P < 0.05).

Conclusion: Low- and moderate-intensity SBOE in HHE could increase the serum EPO and serum sTfR levels and decrease the serum IL-3 levels. Conversely, a high-intensity load could increase the risk of inflammation. Therefore, low-intensity exercise may be more appropriate for an SBOE in HHE.