TRANSPARENT TESTA GLABRA1 regulates high-intensity blue light-induced phototropism by reducing CRYPTOCHROME1 levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

Prenatal and early childhood infections requiring hospitalization and risk of neurodevelopmental disorders in offspring: a population-based birth cohort study in Taiwan.

In utero and early childhood infections have been associated with an increased risk of neurodevelopmental disorders; however, the observed associations may be confounded by familial predispositions. This study examined the neurodevelopmental disorders attributable to maternal infections during pregnancy and early childhood infections during the first year of life, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), tic disorders, and mental retardation (MR). We performed population and sibling comparison analyses to account for unmeasured familial confounding factors. We conducted a register-based cohort study with 2,885,662 individuals (comprising 1,864,660 full siblings) born in Taiwan between 2001 and 2018 and followed up until 2021. We employed Cox regression analysis to assess the association between in utero and early childhood infections requiring hospitalization and the subsequent risk of neurodevelopmental disorders. In the population analyses, an offspring exposed to maternal infection had an increased risk for ASD (hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.13-1.26), ADHD (HR = 1.14, 95% CI: 1.11-1.18), and MR (HR = 1.21, 95% CI: 1.13-1.30). These associations attenuated toward null in the sibling analyses. Individuals exposed to early childhood infection had an increased risk for ASD (HR = 1.13, 95% CI: 1.10-1.16), ADHD (HR = 1.16, 95% CI: 1.15-1.18), tic disorders (HR = 1.12, 95% CI: 1.09-1.15), and MR (HR = 1.64, 95% CI: 1.60-1.69) in the population analyses; these associations were also significant for ASD (HR = 1.14, 95% CI: 1.07-1.21) and MR (HR = 1.52, 95% CI: 1.44-1.62) in the sibling analyses. The association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors. Conversely, infection in early childhood may be attributable to it being a sensitive period and may play a role in the subsequent risk of ASD and MR.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

CDPK protein in cotton: genomic-wide identification, expression analysis, and conferring resistance to heat stress.

BACKGROUND: Calcium-dependent protein kinase (CDPK) plays a key role in cotton tolerance to abiotic stress. However, its role in cotton heat stress tolerance is not well understood. Here, we characterize the GhCDPK gene family and their expression profiles with the aim of identifying CDPK genes associated with heat stress tolerance. RESULTS: This study revealed 48 GhCDPK members in the cotton genome, distributed on 18 chromosomes. Tree phylogenetic analysis showed three main clustering groups of the GhCDPKs. Cis-elements revealed many abiotic stress and phytohormone pathways conserved promoter regions. Similarly, analysis of the transcription factor binding sites (TFBDS) in the GhCDPK genes showed many stress and hormone related sites. The expression analysis based on qRT-PCR showed that GhCDPK16 was highly responsive to high-temperature stress. Subsequent protein-protein interactions of GhCDPK16 revealed predictable interaction with ROS generating, calcium binding, and ABA signaling proteins. Overexpression of GhCDPK16 in cotton and Arabidopsis improved thermotolerance by lowering ROS compound buildup. Under heat stress, GhCDPK16 transgenic lines upregulated heat-inducible genes GhHSP70, GHSP17.3, and GhGR1, as demonstrated by qRT-PCR analysis. Contrarily, GhCDPK16 knockout lines in cotton exhibited an increase in ROS accumulation. Furthermore, antioxidant enzyme activity was dramatically boosted in the GhCDPK16-ox transgenic lines. CONCLUSIONS: The collective findings demonstrated that GhCDPK16 could be a viable gene to enhance thermotolerance in cotton and, therefore, a potential candidate gene for improving heat tolerance in cotton.

The individual contributions of blaB, blaGOB and blaCME on MICs of ß-lactams in Elizabethkingia anophelis.

BACKGROUND: The blaB, blaGOB and blaCME genes are thought to confer ß-lactam resistance to Elizabethkingia anophelis, based on experiments conducted primarily on Escherichia coli. OBJECTIVES: To determine the individual contributions of ß-lactamase genes to increased MICs in E. anophelis and to assess their impact on the in vivo efficacy of carbapenem therapy. METHODS: Scarless gene deletion of one or more ß-lactamase gene(s) was performed in three clinical E. anophelis isolates. MICs were determined by broth microdilution. Hydrolytic activity and expressions of ß-lactamase genes were measured by an enzymatic assay and quantitative RT-PCR, respectively. In vivo efficacy was determined using Galleria mellonella and murine thigh infection models. RESULTS: The presence of blaB resulted in >16-fold increases, while blaGOB caused 4-16-fold increases of carbapenem MICs. Hydrolysis of carbapenems was highest in lysates of blaB-positive strains, possibly due to the constitutionally higher expression of blaB. Imipenem was ineffective against blaB-positive isolates in vivo in terms of improvement of the survival of wax moth larvae and reduction of murine bacterial load. The deletion of blaB restored the efficacy of imipenem. The blaB gene was also responsible for a >4-fold increase of ampicillin/sulbactam and piperacillin/tazobactam MICs. The presence of blaCME, but not blaB or blaGOB, increased the MICs of ceftazidime and cefepime by 8-16- and 4-8-fold, respectively. CONCLUSIONS: The constitutionally and highly expressed blaB gene in E. anophelis was responsible for increased MICs of carbapenems and led to their poor in vivo efficacy. blaCME increased the MICs of ceftazidime and cefepime.

Pulmonary rehabilitation improves exercise capacity, health-related quality of life, and cardiopulmonary function in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer significantly impairs exercise capacity and health-related quality of life (HRQL). Pulmonary rehabilitation (PR) has demonstrated positive effects on exercise capacity and HRQL in lung cancer patients. However, its impact on cardiopulmonary function needs further exploration. The aim of this study was to explore the effects of PR on cardiopulmonary function, exercise capacity and HRQL in patients with lung cancer. METHODS: Patients with lung cancer were enrolled in a 12-week PR program. Each participant underwent a thorough evaluation, which included spirometry, cardiopulmonary exercise testing, respiratory muscle strength test, and evaluation of HRQL using the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). RESULTS: Fifty-six patients completed the PR program. Following PR, exercise capacity significantly improved, as evidenced by increased peak oxygen uptake and work rate (both p < 0.05). Exertional symptoms were notably reduced, including leg soreness and dyspnea at peak exercise, accompanied by a decrease in the CAT score (all p < 0.05). Furthermore, improvements in cardiopulmonary function were observed, encompassing respiratory muscle strength, ventilatory equivalent, tidal volume, stroke volume index, and cardiac index at peak exercise (all p < 0.05). CONCLUSIONS: PR demonstrated notable enhancements in cardiopulmonary function, exertional symptoms, exercise capacity, and HRQL in patients with lung cancer.

Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501).

Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD.

Thiotepa-busulfan-fludarabine-based conditioning as a promising approach prior to allogeneic hematopoietic stem cell transplantation in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.

Human life expectancy and season of birth in Taiwan: A retrospective cohort study.

Prior research has indicated a correlation between the birth season and life expectancy; however, many of these studies did not sufficiently account for comorbidities. In this comprehensive investigation, we aimed to meticulously explore the association between the birth month and life expectancy, giving due consideration to comorbidities. We used a robust dataset derived from Taiwan's National Health Insurance Research Database (2000-2013), which allowed us to conduct a thorough examination. We divided our participants into four groups based on their season of birth: spring, summer, autumn, and winter. Propensity score matching was used to ensure an equitable distribution of demographic and clinical characteristics across the groups. Propensity scores were computed using logistic regression. Our model incorporated a broad range of demographic factors and comorbidities, providing rigorous adjustment for potential confounders. Our findings revealed a significantly increased risk of all-cause mortality among individuals born in spring, even after stringent adjustment for demographic factors and comorbidities. People born in spring demonstrated a 1.05-fold increase in the risk of all-cause mortality, with a hazard ratio of 1.05 and a 95% confidence interval of 1.01-1.09. Our study provides compelling evidence that helps understand the potential long-term impacts of a person's birth season, which acts as a proxy for pregnancy / early-life environmental exposure, on life expectancy. These findings underscore the crucial need for additional research to illuminate the underlying biological and environmental mechanisms linking the birth season and lifespan of a person. The elucidation of these links could guide the development of innovative health promotion and disease prevention strategies that are tailored to an individual's birth season.

Comparison of Demographic and Clinical Characteristics of Taiwan Biobank Participants with Nonparticipants.

BACKGROUND: This study investigated fundamental demographic variables within the Taiwan Biobank (TWBB) and compared them with national demographic statistics. Additionally, a matched cohort analysis compared TWBB participants with nonparticipants to uncover disparities in sociodemographic and clinical characteristics. METHODS: A total of 128,663 individuals aged 30 to 70 without cancer were recruited within the TWBB, and 514,652 nonparticipants matched by age and sex were randomly selected from the National Health Insurance claims database. Sociodemographic variables, healthcare utilization metrics, underlying medical conditions, and subsequent mortality and cancer risk were analyzed. RESULTS: TWBB participants were more likely to be female, older, married, higher educated, with higher incomes, and urban residency. Healthcare utilization metrics showed minimal differences. Pre-cohort entry, TWBB participants had a higher prevalence of certain medical conditions, such as peptic ulcer disease, osteoarthritis, osteoporosis, and uterine leiomyoma in females. During follow-up periods, elevated mortality rates were observed among TWBB participants but decreased cancer risk. CONCLUSION: The TWBB cohort exhibits disparities in sociodemographic and health-related attributes compared to the general population, comprising older, females, married, higher educated, higher income, and predominantly in urban areas. While mortality rates are slightly elevated within the TWBB cohort, cancer incidence rates are lower. Despite limitations in representativeness, the TWBB's size and exposure measures offer valuable insights into associations between exposures and health conditions.

Fibrocyte: A missing piece in the pathogenesis of fibrous epulis.

OBJECTIVES: To explore the role of fibrocytes in the recurrence and calcification of fibrous epulides. METHODS: Different subtypes of fibrous epulides and normal gingival tissue specimens were first collected for histological and immunofluorescence analyses to see if fibrocytes were present and whether they differentiated into myofibroblasts and osteoblasts upon stimulated by transforming growth factor-ß1 (TGF-ß1). Electron microscopy and elemental analysis were used to characterize the extracellular microenvironment in different subtypes of fibrous epulides. Human peripheral blood mononuclear cells (PBMCs) were subsequently isolated from in vitro models to mimic the microenvironment in fibrous epulides to identify whether TGF-ß1 as well as the calcium and phosphorus ion concentration in the extracellular matrix (ECM) of a fibrous epulis trigger fibrocyte differentiation. RESULTS: Fibrous epulides contain fibrocytes that accumulate in the local inflammatory environment and have the ability to differentiate into myofibroblasts or osteoblasts. TGF-ß1 promotes fibrocytes differentiation into myofibroblasts in a concentration-dependent manner, while TGF-ß1 stimulates the fibrocytes to differentiate into osteoblasts when combined with a high calcium and phosphorus environment. CONCLUSIONS: Our study revealed fibrocytes play an important role in the fibrogenesis and osteogenesis in fibrous epulis, and might serve as a therapeutic target for the inhibition of recurrence of fibrous epulides.

Constrictive pericarditis in a patient with fiberglass lung disease: a case report.

BACKGROUND: Fiberglass has a larger aerodynamic diameter and is less likely to be inhaled into the lungs. Further, it will be cleared even if it is mechanically broken into smaller pieces and inhaled into the lungs. Fiberglass lung disease has been well documented if long term exposure but was thought reversible and would not cause severe diseases. The diagnosis of fiberglass lung disease depends on exposure history and histopathological findings. However, the exact occupational exposure history is often difficult to identify because mixed substance exposure often occurs and fiberglass disease is not as well-known as asbestosis. CASE PRESENTATION: A 66-year-old man had unexplained transudative pericardial effusion requiring pleural pericardial window operation twice at another medical center where asbestosis was told because of his self-reported long-term asbestosis exposure and the histopathological finding of a ferruginous body in his lung. Constrictive pericarditis developed two years later and resulted in congestive heart failure. Radical pericardiectomy combined with lung biopsy was performed following chest computed tomography imaging and the transudative nature of pericardial effusion not compatible with asbestosis. However, the histopathologic findings of his lung and pericardium at our hospital only showed chronic fibrosis without any asbestosis body. The patient's lung was found to be extremely fragile during a lung biopsy; histopathologic specimens were reviewed, and various fragments of fiberglass were found in the lung and pericardium. The patient's occupational exposure was carefully reevaluated, and he restated that he was only exposed to asbestosis for 1-2 years but was heavily exposed to fiberglass for more than 40 years. This misleading exposure history was mainly because he was only familiar with the dangers of asbestos. Since most fiberglass lung diseases are reversible and the symptoms of heart failure resolve soon after surgery, only observation was needed. Ten months after radical pericardiectomy, his symptoms, pleural effusion, and impaired pulmonary function eventually resolved. CONCLUSION: Fiberglass could cause inflammation of the pericardium, resulting in pericardial effusion and constrictive pericarditis, which could be severe and require radical pericardiectomy. Exact exposure history and histopathological examinations are the key to diagnosis.

Multiple omics integration analysis reveals the regulatory effect of chitosan oligosaccharide on testicular development.

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

Acute mountain sickness on Jade Mountain: Results from the real-world practice (2018-2019).

Acute mountain sickness (AMS) is initiated in response to a hypoxic and hypobaric environment at a high altitude. The precise prevalence of AMS in Jade Mountain climbers remained largely unknown, particularly data obtained from real medical consultations. An overnight stay at the Pai-Yun Lodge (3402 m) is usually required before an ascent of the Jade Mountain. Since 2004, a Pai-Yun Clinic has been established in the Pai-Yun Lodge. The Pai-Yun Clinic provided regular and emergency medical service every weekend. We conducted a retrospective study by using medical records from the Pai-Yun Clinic between 2018 and 2019. A total of 1021 patients were enrolled, with 56.2 % males. Different age groups were 3.2 %, 54.5 %, 37.9 %, and 4.4 % in <20, 20-39, 40-59, and ≥60 years, respectively. There were 582 (57.0 %) patients diagnosed to have AMS (230 [39.5 %] were mild type and 352 [60.5 %] were severe type). The factors associated with AMS development included young age, absence of climbing history (>3000 m) within the last 3 months, first climbing (>3000 m) experience, taking preventive medication, low oxygen saturation, and a high Lake Louise AMS score (LLAMSS). The factors associated with AMS severity included absence of taking preventive medication, low oxygen saturation, and a high LLAMSS. Approximately 15 % of Jade Mountain climbers needed medical service, of which 60 % had AMS. 60 % of patients with AMS must require oxygen supply or medication prescription. Oxygen saturation measure and LLAMSS evaluation are reasonable tools to predict the occurrence and severity of AMS on Jade Mountain.

Ultrasound-based radiomics-clinical nomogram for noninvasive prediction of residual cancer burden grading in breast cancer.

PURPOSE: To assess the predictive value of an ultrasound-based radiomics-clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. METHODS: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. RESULTS: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound-based radiomics-clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. CONCLUSIONS: Ultrasound-based radiomics-clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.

Genome-wide characterization of microsatellites in cobia Rachycentron canadum (Linnaeus, 1766): Survey and analysis of their abundance and diversity.

The cobia Rachycentron canadum, mainly distributed in the warm waters of tropical and subtropical regions around the world, remains a fish of considerable economic importance. Detailed diversity and the number of microsatellite sequences in the cobia genome are still unintelligible. The primary aim of this work was to identify and quantify the miscellaneous SSR sequences in the cobia genome. More than 280,000 sequences were sequenced and screened using next-generation sequencing technology and microsatellite identification. Perfect mononucleotide repeats, dinucleotide microsatellites, and trinucleotide microsatellites contain (A)10 /(T)10 , (AC)6 /(TG)6 , and (AAT)5-32 as the largest number of motifs in each type of microsatellite, respectively. The tetranucleotide and pentanucleotide microsatellites (TTM and PTM) consist of the largest number of motifs of both (ATCT)5-32 and (TCAT)5-31 in TTMs, and (CTCTC)5-9 in PTMs, whereas the hexanucleotide microsatellites are rarely observed in the cobia genome. All c. 38000 sequences of composite microsatellites are extremely diverse, including compound (11.71%), interrupted compound (71.77%), complex (0.45%), and interrupted complex (16.07%). In this study, we developed a convenient and useful recording system for writing down and categorizing diverse composite microsatellite types. This system will provide great support for exploring repeat origins, evolutionary mechanisms, and the application of polymorphic microsatellites.

Isorhamnetin Regulates Programmed Death Ligand-1 Expression by Suppressing the EGFR-STAT3 Signaling Pathway in Canine Mammary Tumors.

Programmed death ligand-1 (PD-L1) is highly expressed in a variety of cancer cells and suggests a poorer prognosis for patients. The natural compound isorhamnetin (ISO) shows promise in treating cancers and causing damage to canine mammary tumor (CMT) cells. We investigated the mechanism of ISO in reducing PD-L1 expression in CMT cells. Clustered, regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) was used to mediate CD274 knockout in U27 cells. Then, monoclonal cells were screened and cultured. Nucleotide sequencing and expression of PD-L1 were detected. Additionally, we examined cell migration, invasion, and damage. Immunofluorescent staining of PD-L1 was examined in U27 cells. The signaling pathways were measured by Western blotting. Murine xenotransplantation models and murine immunocompetent allograft mammary tumor models were established to evaluate the effect of ISO therapy. Expression of Ki-67, caspase3, and PD-L1 were analyzed by immunohistochemistry. A pull-down assay was used to explore which proteins could bind to ISO. Canine EGFR protein was purified and used to detect whether it directly binds to ISO using a surface plasmon resonance assay. ISO inhibited the EGFR-STAT3-PD-L1 signaling pathway and blocked cancer growth, significantly increasing the survival rate of healthy cells. The cell membrane receptor EGFR was identified as a direct target of ISO. ISO could be exploited as an antineoplastic treatment of CMT by targeting EGFR to suppress PD-L1 expression.

Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

Effects of Nitric Oxide on Bladder Detrusor Overactivity through the NRF2 and HIF-1α Pathways: A Rat Model Induced by Metabolic Syndrome and Ovarian Hormone Deficiency.

Metabolic syndrome (MetS) includes cardiovascular risk factors like obesity, dyslipidemia, hypertension, and glucose intolerance, which increase the risk of overactive bladder (OAB), characterized by urgency, frequency, urge incontinence, and nocturia. Both MetS and ovarian hormone deficiency (OHD) are linked to bladder overactivity. Nitric oxide (NO) is known to reduce inflammation and promote healing but its effect on bladder overactivity in MetS and OHD is unclear. This study aimed to investigate NO's impact on detrusor muscle hyperactivity in rats with MetS and OHD. Female Sprague-Dawley rats were divided into seven groups based on diet and treatments involving L-arginine (NO precursor) and L-NAME (NOS inhibitor). After 12 months on a high-fat, high-sugar diet with or without OVX, a cystometrogram and tracing analysis of voiding behavior were used to identify the symptoms of detrusor hyperactivity. The MetS with or without OHD group had a worse bladder contractile response while L-arginine ameliorated bladder contractile function. In summary, MetS with or without OHD decreased NO production, reduced angiogenesis, and enhanced oxidative stress to cause bladder overactivity, mediated through the NF-kB signaling pathway, whereas L-arginine ameliorated the symptoms of detrusor overactivity and lessened oxidative damage via the NRF2/HIF-1α signaling pathway in MetS with or without OHD-induced OAB.

Effectiveness of Mobile Application Disease Self-Management Programme on Mental Health and Self-Management of Patients With Hypertension: A Randomised Controlled Trial.

BACKGROUND: Hypertension is a chronic disease that consumes considerable medical resources. AIM: The aim of this study is to evaluate a model able to develop and assess the effectiveness of a mobile application disease self-management programme regarding mental health and self-management for patients with hypertension. METHODS: A randomised controlled trial and single-blind random assignment was employed to group the participants. A total of 100 patients were collected from the cardiology clinic of a teaching hospital in Taiwan. There were 50 participants in each group: the mobile application group (experimental group) and the routine care (control group). The primary outcome measures were mental health and self-management. RESULTS: This study discovered that the intervention improved the mental health and self-management of the experimental group. The results for the experimental group revealed significantly improved effects and outcomes superior to those of the control group. CONCLUSIONS: The study results verified that a mobile application disease self-management programme could improve the mental health and disease self-management of patients with hypertension.