Dietary influences on urinary tract infections: unraveling the gut microbiota connection.

This study employs Mendelian randomization to investigate the causal relationships between dietary factors, gut microbiota, and urinary tract infections (UTIs). Our analysis revealed statistically significant associations, including high alcohol intake, cheese, and oily fish consumption with UTI risk, as well as links between UTI risk and specific gut microbiota, such as Prevotellaceae, Butyrivibrio, Anaerotruncus, and Dorea. Additionally, we observed associations with inflammatory markers, including C-Reactive Protein and Interleukin-6. Although the observed effects of these dietary factors on UTI risk are minimal and may limit their clinical relevance, these findings can still hold significant implications at the population level in public health. This research offers novel insights into the interplay between diet, gut microbiota, and UTI risk, laying a foundation for future studies. Further research is warranted to validate these associations and to explore the underlying mechanisms and their broader impact on public health.

Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer.

Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor-specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4-arm polyethylene glycol hydroxylamine (4-arm PEG-ONH2) through oxime bonds, which can be injected through a clinic-used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential.

Multicenter study on clinical outcomes and poor prognostic factors in patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment.

BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.

A Glucose-Responsive Hydrogel Inhibits Primary and Secondary BRB Injury for Retinal Microenvironment Remodeling in Diabetic Retinopathy.

Current diabetic retinopathy (DR) treatment involves blood glucose regulation combined with laser photocoagulation or intravitreal injection of vascular endothelial growth factor (VEGF) antibodies. However, due to the complex pathogenesis and cross-interference of multiple biochemical pathways, these interventions cannot block disease progression. Recognizing the critical role of the retinal microenvironment (RME) in DR, it is hypothesized that reshaping the RME by simultaneously inhibiting primary and secondary blood-retinal barrier (BRB) injury can attenuate DR. For this, a glucose-responsive hydrogel named Cu-PEI/siMyD88@GEMA-Con A (CSGC) is developed that effectively delivers Cu-PEI/siMyD88 nanoparticles (NPs) to the retinal pigment epithelium (RPE). The Cu-PEI NPs act as antioxidant enzymes, scavenging ROS and inhibiting RPE pyroptosis, ultimately blocking primary BRB injury by reducing microglial activation and Th1 differentiation. Simultaneously, MyD88 expression silence in combination with the Cu-PEI NPs decreases IL-18 production, synergistically reduces VEGF levels, and enhances tight junction proteins expression, thus blocking secondary BRB injury. In summary, via remodeling the RME, the CSGC hydrogel has the potential to disrupt the detrimental cycle of cross-interference between primary and secondary BRB injury, providing a promising therapeutic strategy for DR.

Transcutaneous oxygen tension-guided hyperbaric oxygen therapy for preventing skin necrosis after hyaluronic acid filler injections.

Introduction: Hyaluronic acid (HA) fillers, popular for facial cosmetic enhancements, pose risks of vascular complications like skin necrosis due to arterial blockage, necessitating effective treatments such as hyperbaric oxygen therapy (HBOT). Methodology: This study presents a series of cases where measurements of transcutaneous oxygen pressure (TcPO2) informed the application of HBOT for skin necrosis induced by HA. Clinical presentation and outcomes: In cases 1 and 3, following the injection of HA, potential skin necrosis was observed. In addition to standard treatment, TcPO2 revealed values below 40 mmHg, indicating tissue hypoxia. Treatment with HBOT increased TcPO2 levels to above 200 mmHg, suggesting that HBOT could correct the hypoxia. Monitoring TcPO2 levels also aided in determining the optimal time to discontinue HBOT. In cases 2 and 4, patients received standard treatment, resulting in TcPO2 levels above 40 mmHg, indicating adequate tissue oxygenation, and no additional HBOT was administered. All four patients mentioned above showed good clinical recovery. Conclusion: This study investigates the application of TcPO2 measurement technology in aiding decisions on whether to utilize HBOT in the treatment of complications arising from HA fillers, as well as in optimizing HBOT protocols.

Design and application of coal gangue sorting system based on deep learning.

With the advancement of science and technology, coal-washing plants are transitioning to intelligent, information-based, and professional sorting systems. This shift accelerates the construction a modern economic system characterized by green and low-carbon development, thereby promoting the high-quality advancement of the coal industry. Traditional manual gangue picking and multi-axis robotic arm gangue selection currently suffer from low recognition accuracy, slow sorting efficiency, and high worker labor intensity. This paper proposes a deep learning-based, non-contact gangue recognition and pneumatic intelligent sorting system. The system constructs a dynamic database containing key feature information such as the target gangue's contour, quality, and center of mass. The system elucidates the relationships between ejection speed, mass, volume, angle of incidence, and the impact energy matching mechanism. Demonstration experiments using the system prototype for coal gangue sorting reveal that, compared to existing robotic arm sorting methods in coal washing plants, this system achieves a gangue identification accuracy exceeding 97%, a sorting rate above 91%, and a separation time of less than 3 s from identification to separation, thereby effectively enhancing raw coal purity.

Dynamic Covalent Hydrogel as a Single-Dose Vaccine Adjuvant for Sustained Antigen Release and Significantly Elevated Humoral Immunity.

Vaccine is the most important way for fighting against infection diseases. However, multiple injections and unsatisfied immune responses are the main obstacles for current vaccine application. Herein, a dynamic covalent hydrogel (DCH) is used as a single-dose vaccine adjuvant for eliciting robust and sustained humoral immunity. By adjusting the mass ratio of the DCH gel, 10-30 d constant release of the loaded recombinant protein antigens is successfully realized, and it is proved that sustained release of antigens can significantly improve the vaccine efficacy. When loading SARS-CoV-2 RBD (Wuhan and Omicron BA.1 strains) antigens into this DCH gel, an over 32 000 times and 8000 times improvement is observed in antigen-specific antibody titers compared to conventional Aluminum adjuvanted vaccines. The universality of this DCH gel adjuvant is confirmed in a Nipah G antigen test as well as a H1N1 influenza virus antigen test, with much improved protection of C57BL/6 mice against H1N1 virus infection than conventional Aluminum adjuvanted vaccines. This sustainably released, single-dose DCH gel adjuvant provides a new promising option for designing next-generation infection vaccines.

A life-threatening, massive subcutaneous hematoma caused by trauma in a patient with neurofibromatosis type 1: a case report and literature review.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that can give rise to the formation of vascular lesions in affected individuals. These lesions, whether occurring spontaneously or as a result of trauma, have the potential to cause severe and even fatal hemorrhage. Case description: We presented a case demonstrating the most extensive hematoma ever documented in a patient with NF1, resulting from a minor trauma. He experienced hemodynamic instability due to severe anemia. Arteriography revealed a rupture in the intercostal artery, which was successfully treated through interventional embolization to stop the hemorrhage. Additionally, we implemented a refined surgical approach, beginning with suturing, followed by the meticulous resection of necrotic and aberrant tissues, thereby markedly diminishing bleeding. Conclusion: Minor trauma may cause severe bleeding in patients with NF1, which can be life-threatening. Timely diagnosis of NF1 and effective hemostatic techniques are key to successful treatment.

Enhanced methane production from waste activated sludge by microbial electrolysis cell assisted anaerobic digestion: Fate and effect of humic substances.

Humic substances as major components of waste activated sludge are refractory to degrade and have inhibition in traditional anaerobic digestion (AD). This study for the first time investigated the feasibility and mechanism of microbial electrolysis cell assisted anaerobic digestion (MEC-AD) to break the recalcitrance and inhibition of humic substances. The cumulative methane production of AD decreased from 134.7 to 117.6 mL/g-VS with the addition of humic acids and fulvic acids at 25.2-102.1 mg/g-VS. However, 0.6 V MEC-AD maintained stable methane production (155.5-158.2 mL/g-VS) under the effect of humic substances. 0.6 V MEC-AD formed electrical stimulation on microbial cells, provided anodic oxidation and cathodic reduction transformation pathways for humic substances (acting as carbon sources and electron shuttles), and aggregated functional microorganisms on electrodes, facilitating the degradation of humic substances and generation of methane. This study provides a theoretical basis for improving the energy recovery and system stability of sludge treatment.

Effect of Regular Aerobic Exercise on Cognitive Function, Depression Level and Regulative Role of Neurotrophic Factor: A Prospective Cohort Study in the Young and the Middle-Aged Sample.

Purpose: Mild cognitive impairment (MCI) and depressive disorder (DD), which are associated with unhealthy lifestyles, are prevalent worldwide. This study aimed to investigate the effects of regular aerobic exercise on cognitive function, depression, and the regulatory role of neurotrophic growth factors for providing scientific basis in preventing MCI and DD in healthy individuals. Patients and Methods: Eighty members of the fitness center and 80 community residents were recruited, who were administered by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Patient Health Questionnaire (PHQ-9). Brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) in the peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Results: The RBANS and other factor scores, except for visuospatial abilities, were higher and PHQ-9 scores were lower in the study group than in the control group. The concentrations of BDNF and GDNF in the study group were higher than those in the control group. RBANS and its factor scores positively and PHQ-9 negatively correlated with BDNF and GDNF levels. Finally, multiple regression analysis showed that BDNF, as a predictor of RBANS, could explain 59.90% of its variance and that GDNF was a predictor of PHQ-9 could explain 12.30% of the variance. Conclusion: Regular aerobic exercise can improve cognitive function and depressive symptoms by increasing the BDNF and GDNF levels.

Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.

Liproxstatin-1 Alleviated Ischemia/Reperfusion-Induced Acute Kidney Injury via Inhibiting Ferroptosis.

Ferroptosis, as a novel regulable cell death, is characterized by iron overload, glutathione depletion, and an accumulation of lipid peroxides. Recently, it has been discovered that ferroptosis is involved in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and plays a crucial role in renal tubular cell death. In this study, we tried to investigate the effect and mechanism of liproxstatin-1 (Lip-1) in I/R-induced AKI and seek the key regulator of ferroptosis in I/R-induced AKI. Mice were administrated with clamping bilateral renal pedicles for 30 min. We found that early growth response 1 (EGR1) might be a key regulator of ferroptosis, and Lip-1 could suppress ferroptosis via EGR1. Meanwhile, Lip-1 could reduce macrophage recruitment and the release of inflammatory cytokines. These findings indicated that Lip-1 alleviated I/R-induced AKI via regulating EGR1, and it might pave the theoretical basis of a new therapeutic strategy for I/R-induced AKI.

Marked variations in diversity and functions of gut microbiota between wild and domestic stag beetle Dorcus Hopei Hopei.

BACKGROUND: Although stag beetles are a popular saprophytic insect, their gut microbiome has been poorly studied. Here, 16 S rRNA gene sequencing was employed to reveal the gut microbiota composition and functional variations between wild and domestic Dorcus hopei hopei (Dhh) larval individuals. RESULTS: The results indicated a significant difference between the wild and domestic Dhh gut microbiota., the domestic Dhh individuals contained more gut microbial taxa (e.g. genera Ralstonia and Methyloversatilis) with xenobiotic degrading functions. The wild Dhh possesses gut microbiota compositions (e.g. Turicibacter and Tyzzerella ) more appropriate for energy metabolism and potential growth. This study furthermore assigned all Dhh individuals by size into groups for data analysis; which indicated limited disparities between the gut microbiota of different-sized D. hopei hopei larvae. CONCLUSION: The outcome of this study illustrated that there exists a significant discrepancy in gut microbiota composition between wild and domestic Dhh larvae. In addition, the assemblage of gut microbiome in Dhh was primarily attributed to environmental influences instead of individual differences such as developmental potential or size. These findings will provide a valuable theoretical foundation for the protection of wild saprophytic insects and the potential utilization of the insect-associated intestinal microbiome in the future.

Noctiluca scintillans bloom alters the composition and carbohydrate utilization of associated bacterial community and enriches potential pathogenic bacterium Vibrio anguillarum.

Noctiluca scintillans (red) is a widely distributed heterotrophic dinoflagellate and a prominent red tide forming species. This study investigated the effects of Noctiluca blooms on marine microbial diversity and functionality using multi-omics approaches. Our findings revealed significant differences in the community composition of Noctiluca-associated bacteria compared to those associated with autotrophic plankton and free-living bacteria in the surrounding seawater. The dominant bacterial groups within the Noctiluca-associated community shifted at various bloom stages, which could be attributed to changes in prey composition of Noctiluca. During the non-bloom stage, Burkholderiaceae, Carnobacteriaceae, and Pseudomonadaceae dominated the community, while Vibrionaceae became dominant during the bloom stage, and Saprospiraceae, Crocinitomicaceae, and Pirellulaceae thrived during the post-bloom stage. Compared to the non-bloom stage, Noctiluca-associated bacterial community at the bloom stage exhibited significant down-regulation of genes related to complex carbohydrate metabolism, while up-regulation of genes related to glucose transportation and utilization. Furthermore, we identified Vibrio anguillarum, a potential pathogenic bacterium to marine fish, as a major component of the Vibrionaceae family during the bloom stage. The occurrence of V. anguillarum associated with Noctiluca blooms may be attributed to the increased availability of its preferred carbon sources and its high capabilities in glucose transportation, motility and chemotaxis. Moreover, the presence of Vibrio infection genes (hap, hlyA, rtxA) encoding vibriolysin, hemolysin, and RTX (Repeats-in-toxin) toxin in the V. anguillarum genome, with the hap gene showing high expression levels during Noctiluca blooms, indicates an elevated risk of infection. This study underscores the unique composition of the bacterial community associated with red tide forming heterotrophic dinoflagellates and suggests that Noctiluca cells may serve as reservoirs and vectors for pathogenic bacteria, potentially posing a threat to fish-farming and the health of other marine organisms.

Anchoring flap suture technique to repair a wound with exposed bone after hip disarticulation: a case report and brief review of the literature.

BACKGROUND: In specific clinical scenarios characterized by poor tissue conditions surrounding a wound, achieving stable flap fixation with standard sutures can be challenging. The anchoring flap suture technique, which is commonly used for soft tissue-to-bone attachment in cases of injury, may be an alternative and effective approach. CASE REPORT: This report describes the successful application of the anchoring flap suture technique to repair a wound with exposed bone in a 39-year-old female patient. She presented with a 7% TBSA wound of the left trunk following hip disarticulation. After 4 operations, a wound with exposed iliac bone remained. Given the compromised condition of the tissues surrounding the exposed bone, the authors opted to anchor a local flap directly to the exposed bone. Steady flap fixation was achieved using the anchoring flap suture method, resulting in complete healing of that wound. Remarkably, no short- or long-term complications associated with the flap were observed. Three months after hospital discharge, the patient regained mobility, walking on 1 leg with the assistance of a 4-legged walker. CONCLUSION: The anchoring flap suture technique seems to be a reliable and effective treatment option, particularly in cases in which inadequate soft tissue precludes the use of traditional flap fixation using standard sutures.

Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development.

The mutation of MET plays a crucial role in the initiation of cancer, while the Hedgehog (Hh) pathway also plays a significant role in cell differentiation and the maintenance of tumor stem cells. Conventional chemotherapy drugs are primarily designed to target the majority of cell populations within tumors rather than tumor stem cells. Consequently, after a brief period of remission, tumors often relapse. Moreover, the exclusive targeting of tumor stemness cell disregards the potential for other tumor cells to regain stemness and acquire drug resistance. As a result, current drugs that solely target the HGF/c-MET axis and the Hh pathway demonstrate only moderate efficacy in specific types of cancer. Mounting evidence indicates that these two pathways not only play important roles in cancer but also exert significant influence on the development of resistance to single-target therapies through the secretion of their own ligands. In this comprehensive review, we analyze and compare the potential impact of the Hh pathway on the tumor microenvironment (TME) in HGF/c-MET-driven tumor models, as well as the interplay between different cell types. Additionally, we further substantiate the potential and necessity of dual-pathway combination therapy as a critical target in MET addicted cancer treatment. Video Abstract.

The Epidemiological Analysis of COVID-19 Outbreaks in Nursing Homes during the Period of Omicron Variant Predominance.

BACKGROUND: The main purpose of this study was to evaluate the epidemic trend and risk factors associated with COVID-19 outbreaks in nursing homes during the period of Omicron variant predominance. METHODS: The study analyzed the risk factors associated with SARS-CoV-2 infection and death among the 327 residents and 129 healthcare workers (HCWs) in three hospital-affiliated nursing homes through a multivariate Cox regression model. RESULTS: The rates of receiving a COVID-19 booster dose were 70.3% for the residents and 93.0% for the healthcare workers (HCWs), respectively. A number of asymptomatic individuals, including 54 (16.5%) residents and 15 (11.6%) HCWs, were detected through mass screening surveillance tests. The COVID-19 infection rates during the outbreaks were 41.6% among residents and 48.1% among HCWs, respectively. The case fatality rate among residents was 10.3%. None of the HCWs were hospitalized or died. The multivariate Cox regression model showed that the risk of COVID-19 infection increased in males (HR 2.46; 95% CI 1.47-4.11; p = 0.001), Barthel index ≥ 61 (HR 1.93; 95% CI 1.18-3.17; p = 0.009), and dementia (HR 1.61; 95% CI 1.14-2.27; p = 0.007). The risk of COVID-19 death increased with pneumonia (HR 11.03; 95% CI 3.02-40.31; p < 0.001), hospitalization (HR 7.18; 95% CI 1.97-26.25; p = 0.003), and admission to an intensive care unit (HR 8.67; 95% CI 2.79-26.89; p < 0.001). CONCLUSIONS: This study highlighted the high infection rates with a substantial proportion of asymptomatic infections for both residents and HCWs, as well as a high case fatality rate for the residents among nursing homes during the Omicron epidemic period. We suggest implementing mass screening through regular surveillance testing as an effective strategy for early detection of COVID-19 and for preventing transmission during an epidemic period. Pneumonia is the primary risk associated with COVID-19 death. Early detection and prompt treatment of pneumonia for vulnerable residents in nursing homes are crucial to protect them from potential mortality.

Ferroptosis: An Emerging Target for Bladder Cancer Therapy.

Bladder cancer (BC), as one of the main urological cancers in the world, possesses the abilities of multiple-drug resistance and metastasis. However, there remains a significant gap in the understanding and advancement of prognosis and therapeutic strategies for BC. Ferroptosis, a novel type of iron-dependent regulated cell death, depends on lipid peroxidation, which has been proven to have a strong correlation with the development and treatment of BC. Its mechanism mainly includes three pathways, namely, lipid peroxidation, the antioxidant system, and the iron overload pathway. In this review, we reviewed the mechanism of ferroptosis, along with the related therapeutic targets and drugs for BC, as it might become a new anticancer treatment in the future.

Branched-chain keto-acid dehydrogenase kinase regulates vascular permeability and angiogenesis to facilitate tumor metastasis in renal cell carcinoma.

Branched-chain keto-acid dehydrogenase kinase (BCKDK) is the rate-limiting enzyme of branched-chain amino acid (BCAA) metabolism. In the last six years, BCKDK has been used as a kinase to promote tumor proliferation and metastasis. Renal cell carcinoma (RCC) is a highly vascularized tumor. A high degree of vascularization promotes tumor metastasis. Our objective is to explore the relationship between BCKDK and RCC metastasis and its specific mechanism. In our study, BCKDK is highly expressed in renal clear cell carcinoma and promotes the migration of clear cell renal cell carcinoma (ccRCC). Exosomes from ccRCC cells can promote vascular permeability and angiogenesis, especially when BCKDK is overexpressed in ccRCC cells. BCKDK can also augment the miR-125a-5p expression in ccRCC cells and derived exosomes, thereby decreasing the downstream target protein VE-cadherin level, weakening adhesion junction expression, increasing vascular permeability, and promoting angiogenesis in HUVECs. The novel BCKDK/Exosome-miR-125a-5p/VE-cadherin axis regulates intercellular communication between ccRCC cells and HUVECs. BCKDK plays a critical role in renal cancer metastasis, may be used as a molecular marker of metastatic ccRCC, and even may become a potential target of clinical anti-vascular therapy for ccRCC.

BCKDK regulates breast cancer cell adhesion and tumor metastasis by inhibiting TRIM21 ubiquitinate talin1.

Breast cancer is the most common malignant cancer in women worldwide. Cancer metastasis is the major cause of cancer-related deaths. BCKDK is associated with various diseases, including proliferation, migration, and invasion in multiple types of human cancers. However, the relevance of BCKDK to the development and progression of breast cancers and its function is unclear. This study found that BCKDK was overexpressed in breast cancer, associated with poor prognosis, and implicated in tumor metastasis. The downregulation of BCKDK expression inhibited the migration of human breast cancer cells in vitro and diminished lung metastasis in vivo. BCKDK perturbed the cadherin-catenin complex at the adherens junctions (AJs) and assembled focal adhesions (FAs) onto the extracellular matrix, thereby promoting the directed migration of breast cancer cells. We observed that BCKDK acted as a conserved regulator of the ubiquitination of cytoskeletal protein talin1 and the activation of the FAK/MAPK pathway. Further studies revealed that BCKDK inhibited the binding of talin1 to E3 ubiquitin ligase-TRIM21, leading to the decreased ubiquitination/degradation of talin1. In conclusion, identifying BCKDK as a biomarker for breast cancer metastasis facilitated further research on diagnostic biomarkers. Elucidating the mechanism by which BCKDK exerted its biological effect could provide a new theoretical basis for developing new markers for breast cancer metastasis and contribute to developing new therapies for the clinical treatment of breast cancer patients.