Efficacy of Mid-Urethral Sling and Urethral Dilation for Stress Urinary Incontinence Combined with Urethral Stricture in Women.

OBJECTIVE: To investigate the potential clinical benefits of mid-urethral sling (MUS) and urethral dilatation (UD) operations for the treatment of stress urinary incontinence (SUI) combined with urethral stricture. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China, from January 2017 to 2022. METHODOLOGY: Patients with Qmax <15ml/s or PVR >50ml, and video urodynamic study (VUDS) capable of confirming the presence and position of urethral stricture were included. The clinical efficacy was evaluated by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaire, maximum flow rate (Qmax), and postvoid residual (PVR) urine. ICIQ-SF, Qmax, and PVR were measured presurgery, on postoperative 2-week, and 1-month postsurgery. RESULTS: There were total 19 patients with an average age of 61.37 ± 11.28 years (range 39-84) with SUI and urethral stricture. ICIQ-SF scores were decreased significantly at one month postoperatively compared with the preoperative [5.0 (0.0, 7.0) vs. 14.0 (13.0, 15.0), p <0.001]. Qmax was increased dramatically compared with the preoperative [21.3 (14.0, 28.4) vs. 13.0 (8.7,18.0), p <0.001], and PVR was decreased remarkably than the preoperative [0.0 (0.0,0.0) vs. 0.0 (0.0,60.0), p = 0.018]. Of 19 patients primarily managed with MUS and UD, two patients experienced recurrence requiring repetitive dilation till sling excision surgery was conducted, and improvement was evident in one patient after repeating UD. CONCLUSION: The overall incidence of SUI combined with urethral stricture in women is low. With a success rate of 89.5%, MUS and UD were effective therapies for the co-existence of SUI with urethral stricture, and repeated UD can be performed safely if necessary in long-term follow-up. KEY WORDS: Stress urinary incontinence, Urethral stricture, Mid-urethral sling, Urethral dilatation.

Rapid assessment of cosmic radiation exposure in aviation based on BP neural network method.

Cosmic radiation exposure is one of the important health concerns for aircrews. In this work, we constructed a back propagation neural network model for the real-time and rapid assessment of cosmic radiation exposure to the public in aviation. The multi-dimensional dataset for this neural network was created from modeling the process of cosmic ray transportation in magnetic field by geomagnetic cutoff rigidity method and air shower simulation by a Monte Carlo based Geant4 code. The dataset was characterized by parameters including cosmic ray energy spectrum, Kp-index, coordinated universal time, altitude, latitude, and longitude. The effective dose and dose rate was finally converted from the particle fluxes at flight position by the neural network. This work shows a good agreement with other models from International Civil Aviation Organization. It is also illustrated that the effective dose rate by galactic cosmic ray is <10 µSv h-1 and the value during ground level enhancement (GLE) 42 is 4 ~ 10 times larger on the routes calculated in this work. In GLE 69, the effective dose rate reaches several mSv h-1 in the polar region. Based on this model, a real-time warning system is achieved.

UBE2T mediates SORBS3 ubiquitination to enhance IL-6/STAT3 signaling and promote lung adenocarcinoma progression.

UBE2T is an oncogene in varying tumors, including lung adenocarcinoma (LUAD). SORBS3 is an important signaling regulatory protein that plays a crucial role in many cancers. This study aimed to investigate whether UBE2T promoted LUAD development by mediating the ubiquitination of SORBS3 and further explore its mechanism. Bioinformatics analysis was conducted to examine the expression of SORBS3 in LUAD tissues. Cell Counting Kit-8, Transwell, and flow cytometry were employed to analyze the cellular functions of SORBS3. Co-immunoprecipitation and ubiquitination analysis were employed to observe the correlation between UBE2T and SORBS3. In vitro and in vivo experiments verified the role of UBE2T in mediating SORBS3 ubiquitination to enhance interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling and promote LUAD development. We observed significant downregulation of SORBS3 in LUAD tissues and cells. Furthermore, SORBS3 inhibited the proliferation, migration, and invasion of LUAD cells, while facilitating apoptosis in vitro. UBE2T enhanced IL-6/STAT3 signaling by mediating ubiquitination and degradation of SORBS3, thereby promoting LUAD progression. Additionally, this mechanism was further validated in the xenograft animal model in vivo. This study confirmed that UBE2T-mediated SORBS3 ubiquitination enhanced IL-6/STAT3 signaling and promoted LUAD progression, providing a novel therapeutic target for LUAD.

Effect of Gentianella acuta (Michx.) Hulten against the arsenic-induced development hindrance of mouse oocytes.

The current study was designed to investigate the alleviative effect of Gentianella acuta (Michx.) Hulten (G. acuta) against the sodium arsenite (NaAsO2)-induced development hindrance of mouse oocytes. For this purpose, the in vitro maturation (IVM) of mouse cumulus-oocyte complexes (COCs) was conducted in the presence of NaAsO2 and G. acuta, followed by the assessments of IVM efficiency including oocyte maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, redox regulation, epigenetic modification, DNA damage, and apoptosis. Subsequently, the alleviative effect of G. acuta intervention on the fertilization impairments of NaAsO2-exposed oocytes was confirmed by the assessment of in vitro fertilization (IVF). The results showed that the G. acuta intervention effectively ameliorated the decreased maturation potentials and fertilization deficiency of NaAsO2-exposed oocytes but also significantly inhibited the DNA damages, apoptosis, and altered H3K27me3 expression level in the NaAsO2-exposed oocytes. The effective effects of G. acuta intervention against redox dysregulation including mitochondrial dysfunctions, accumulated reactive oxygen species (ROS) generation, glutathione (GSH) deficiency, and decreased adenosine triphosphate (ATP) further confirmed that the ameliorative effects of G. acuta intervention against the development hindrance of mouse oocytes were positively related to the antioxidant capacity of G. acuta. Evidenced by these abovementioned results, the present study provided fundamental bases for the ameliorative effect of G. acuta intervention against the meiotic defects caused by the NaAsO2 exposure, benefiting the future application potentials of G. acuta intervention in these nutritional and therapeutic research for attenuating the outcomes of arseniasis.

Regioselective and Enantioselective Nickel-Catalyzed Intermolecular Reductive Coupling of Aliphatic Alkenes with Imines.

Unactivated aliphatic alkenes are particularly desirable as starting materials because they are readily accessible in large quantities, but the enantioselective intermolecular reductive coupling of unactivated alkenes with imines is challenging. In this paper, we report a method for nickel-catalyzed intermolecular reductive coupling reactions between aliphatic alkenes and imines to yield chiral amines with excellent enantioselectivities and good linear selectivities. The reaction conditions are compatible with a broad range of aliphatic alkenes, including those derived from bioactive molecules. The success of this method can be attributed to the use of newly developed monodentate chiral spiro phosphine ligands.

FOXA1/UBE2T Inhibits CD8+T Cell Activity by Inducing Mediates Glycolysis in Lung Adenocarcinoma.

BACKGROUND: Immune escape is a key factor influencing survival rate of lung adenocarcinoma (LUAD) patients, but molecular mechanism of ubiquitin binding enzyme E2T (UBE2T) affecting immune escape of LUAD remains unclear. The objective was to probe role of UBE2T in LUAD. METHODS: Bioinformatics means were adopted for analyzing UBE2T and forkhead box A1 (FOXA1) expression in LUAD tissues, the gene binding sites, the pathway UBE2T regulates, and the correlation between UBE2T and glycolysis genes. Dual luciferase and chromatin immunoprecipitation (ChIP) assays were conducted for validating the binding relationship between the two genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were employed to evaluate UBE2T, FOXA1, and programmed death ligand 1 (PD-L1) levels in cancer cells. MTT assay was conducted for detecting cell viability. Cytotoxicity assay detected CD8+T cell toxicity. Cytokine expression was assayed by enzyme linked immunosorbent assay (ELISA). Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were assayed by extracellular flow analyzer. Glycolytic gene expression was analyzed by qRT-PCR, and glycolysis-related indicators were detected by ELISA. Immunohistochemistry (IHC) detected CD8+T cell infiltration in tumor tissues. RESULTS: FOXA1 and UBE2T were up-regulated in LUAD, and a binding site existed between UBE2T and FOXA1. Overexpressing UBE2T could increase PD-L1 expression and inhibit toxicity of CD8+T cells to LUAD cells. Overexpressing UBE2T repressed CD8+T cell activity in LUAD by activating the glycolysis pathway, and the addition of glycolysis inhibitor 2-deoxy-d-glucose (2-DG) reversed the above results. Mechanistically, FOXA1 promoted the immune escape of LUAD by up-regulating UBE2T and thus mediating glycolysis. In vivo experiments revealed that UBE2T knockdown hindered tumor growth, inhibited PD-L1 expression, and facilitated CD8+T cell infiltration. CONCLUSION: FOXA1 up-regulated the expression of UBE2T, which activated glycolysis, and thus inhibited activity of CD8+T cells, causing immune escape of LUAD.

Adipose stem cell-derived exosomes promote wound healing by regulating the let-7i-5p/GAS7 axis.

BACKGROUND: Injury to skin tissue is devastating for human health, making it imperative to devise strategies for hastening wound healing. Normal wound healing is a complex process comprising overlapping steps, including hemostasis, inflammatory response, proliferation, and matrix remodeling. This study investigated the effects of adipose stem cell-derived exosomes (ADSC-exos) on wound healing and the underlying mechanisms. METHODS: In vitro hydrogen peroxide (H2O2)-treated human keratinocyte (HaCaT) cell lines and in vivo animal wound models were established for this purpose. The cell migration was assessed using transwell and wound healing assays, while exosome biomarker expressions were studied using western blot. Moreover, adipose stem cells were identified using flow cytometry, alizarin red S and oil red O staining, and transmission electron microscopy. RESULTS: Results indicated that H2O2 treatment inhibited the cell viability and migration of HaCaT cells while being promoted by ADSC-exos. Mechanistic investigations revealed that microRNA-let-7i-5p (let-7i-5p) in ADSC-exos was carried into the HaCaT cells, inhibiting the expression of growth arrest-specific-7 (GAS7). Rescue experiments further verified these results, which indicated that GAS7 overexpression reversed the effect of let-7i-5p on the viability and migration of HaCaT cells, suggesting ADSC-exos promoted wound healing via the let-7i-5p/GAS7 axis. CONCLUSION: Adipose stem cell-derived-exos enhanced the viability and migration of HaCaT via carrying let-7i-5p and targeting GAS7, ultimately promoting wound healing in rats.

Clinical characteristics and risk factors associated with bone erosion in patients with tophi.

INTRODUCTION: If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. METHODS: A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. RESULTS: Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. CONCLUSIONS: Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.

Hash Encoding and Brightness Correction in 3D Industrial and Environmental Reconstruction of Tidal Flat Neural Radiation.

We present an innovative approach to mitigating brightness variations in the unmanned aerial vehicle (UAV)-based 3D reconstruction of tidal flat environments, emphasizing industrial applications. Our work focuses on enhancing the accuracy and efficiency of neural radiance fields (NeRF) for 3D scene synthesis. We introduce a novel luminance correction technique to address challenging illumination conditions, employing a convolutional neural network (CNN) for image enhancement in cases of overexposure and underexposure. Additionally, we propose a hash encoding method to optimize the spatial position encoding efficiency of NeRF. The efficacy of our method is validated using diverse datasets, including a custom tidal flat dataset and the Mip-NeRF 360 dataset, demonstrating superior performance across various lighting scenarios.

Stratifying ICIs-responsive tumor microenvironment in HCC: from parsing out immune-hypoxic crosstalk to clinically applicable MRI-radiomics models.

BACKGROUND: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC). METHODS: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability. RESULTS: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75). CONCLUSION: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification.

The HIF-1α/EGF/EGFR Signaling Pathway Facilitates the Proliferation of Yak Alveolar Type II Epithelial Cells in Hypoxic Conditions.

The yak is a unique creature that thrives in low-oxygen environments, showcasing its adaptability to high-altitude settings with limited oxygen availability due to its unique respiratory system. However, the impact of hypoxia on alveolar type II (AT2) epithelial cell proliferation in yaks remains unexplored. In this study, we investigated the effects of different altitudes on 6-month-old yaks and found an increase in alveolar septa thickness and AT2 cell count in a high-altitude environment characterized by hypoxia. This was accompanied by elevated levels of hypoxia-inducible factor-1α (HIF-1α) and epidermal growth factor receptor (EGFR) expression. Additionally, we observed a significant rise in Ki67-positive cells and apoptotic lung epithelial cells among yaks inhabiting higher altitudes. Our in vitro experiments demonstrated that exposure to hypoxia activated HIF-1α, EGF, and EGFR expression leading to increased proliferation rates among yak AT2 cells. Under normal oxygen conditions, activation of HIF-1α enhanced EGF/EGFR expressions which subsequently stimulated AT2 cell proliferation. Furthermore, activation of EGFR expression under normoxic conditions further promoted AT2 cell proliferation while simultaneously suppressing apoptosis. Conversely, inhibition of EGFR expression under hypoxic conditions had contrasting effects. In summary, hypoxia triggers the proliferation of yak AT2 cells via activation facilitated by the HIF-1α/EGF/EGFR signaling cascade.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

Multicomponent chitosan complex/polyvinyl alcohol blended film with full-band UV-shielding performance and excellent antioxidant property for active food packaging.

Utilizing renewable natural resources to construct multifunctional packaging materials is critical to achieving sustainable development in the food packaging industry. In this study, we crafted transparent films with comprehensive UV-shielding and antioxidant properties by blending a multicomponent chitosan complex with polyvinyl alcohol (PVA), subsequently applied to preserve peanut butter. The multicomponent chitosan complex, synthesized from chitosan, ferulic acid (FA), and 5-oxo-3,5-dihydro-2H-thiazolo [3,2-a] pyridine-7-carboxylic acid (TPCA) through direct heating in water, served as the foundation. This chitosan complex was seamlessly blended with PVA, resulting in the creation of a transparent film through the solvent casting method. A meticulous investigation into the chemical structure and physicochemical properties of the blended films was conducted. The FA and TPCA components exhibited robust ultraviolet absorption properties, conferring virtually complete full-band ultraviolet shielding ability to the blend film. Additionally, FA endowed the blended film with significant antioxidant activity. The effectiveness of the chitosan complex/PVA blended film in preserving peanut butter from oxidative spoilage was demonstrated, showcasing its robustness in food preservation. Our research underscores the significance of creating advanced packaging materials from sustainable sources.

TEAD4: A key regulator of tumor metastasis and chemoresistance - Mechanisms and therapeutic implications.

Cancer metastasis is a complex process influenced by various factors, including epithelial-mesenchymal transition (EMT), tumor cell proliferation, tumor microenvironment, and cellular metabolic status, which remains a significant challenge in clinical oncology, accounting for a majority of cancer-related deaths. TEAD4, a key mediator of the Hippo signaling pathway, has been implicated in regulating these factors that are all critical in the metastatic cascade. TEAD4 drives tumor metastasis and chemoresistance, and its upregulation is associated with poor prognosis in many types of cancers, making it an attractive target for therapeutic intervention. TEAD4 promotes EMT by interacting with coactivators and activating the transcription of genes involved in mesenchymal cell characteristics and extracellular matrix remodeling. Additionally, TEAD4 enhances the stemness of cancer stem cells (CSCs) by regulating the expression of genes associated with CSC maintenance. TEAD4 contributes to metastasis by modulating the secretion of paracrine factors and promoting heterotypic cellular communication. In this paper, we highlight the central role of TEAD4 in cancer metastasis and chemoresistance and its impact on various aspects of tumor biology. Understanding the mechanistic basis of TEAD4-mediated processes can facilitate the development of targeted therapies and combination approaches to combat cancer metastasis and improve treatment outcomes.

Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance.

Pathological pain, a multifaceted and debilitating ailment originating from injury or post-injury inflammation of the somatosensory system, poses a global health challenge. Despite its ubiquity, reliable therapeutic strategies remain elusive. To solve this problem, resveratrol, a naturally occurring nonflavonoid polyphenol, has emerged as a potential beacon of hope owing to its anti-inflammatory, antioxidant, and immunomodulatory capabilities. These properties potentially position resveratrol as an efficacious candidate for the management of pathological pain. This concise review summaries current experimental and clinical findings to underscore the therapeutic potential of resveratrol in pathological pain, casting light on the complex underlying pathophysiology. Our exploration suggests that resveratrol may exert its analgesic effect by the modulating pivotal signaling pathways, including PI3K/Akt/mTOR, TNFR1/NF-κB, MAPKs, and Nrf2. Moreover, resveratrol appears to attenuate spinal microglia activation, regulate primary receptors in dorsal root sensory neurons, inhibit pertinent voltage-gated ion channels, and curb the expression of inflammatory mediators and oxidative stress responses. The objective of this review is to encapsulate the pharmacological activity of resveratrol, including its probable signaling pathways, pharmacokinetics, and toxicology pertinent to the treatment of pathological pain. Hopefully, we aim to map out promising trajectories for the development of resveratrol as a potential analgesic.

METTL3-Mediated STING Upregulation and Activation in Kupffer Cells Contribute to Radiation-Induced Liver Disease via Pyroptosis.

PURPOSE: Radiation therapy is a vital adjuvant treatment for liver cancer, although the challenge of radiation-induced liver diseases (RILDs) limits its implementation. Kupffer cells (KCs) are a crucial cell population of the hepatic immune system, and their biologic function can be modulated by multiple epigenetic RNA modifications, including N6-methyladenosine (m6A) methylation. However, the mechanism for m6A methylation in KC-induced inflammatory responses in RILD remains unclear. The present study investigated the function of m6A modification in KCs contributing to RILD. METHODS AND MATERIALS: Methylated RNA-immunoprecipitation sequencing and RNA transcriptome sequencing were used to explore the m6A methylation profile of primary KCs isolated from mice after irradiation with 3 × 8 Gy. Western blotting and quantitative real-time PCR were used to evaluate gene expression. DNA pulldown and chromatin immunoprecipitation assays were performed to verify target gene binding and identify binding sites. RESULTS: Methylated RNA-immunoprecipitation sequencing revealed significantly increased m6A modification levels in human KCs after irradiation, suggesting the potential role of upregulated m6A in RILD. In addition, the study results corroborated that methyltransferase-like 3 (METTL3) acts as a main modulator to promote the methylation and gene expression of TEAD1, leading to STING-NLRP3 signaling activation. Importantly, it was shown that IGF2BP2 functions as an m6A "reader" to recognize methylated TEAD1 mRNA and promote its stability. METTL3/TEAD1 knockdown abolished the activation of STING-NLRP3 signaling, protected against RILD, and suppressed inflammatory cytokines and hepatocyte apoptosis. Moreover, clinical human normal liver tissue samples collected after irradiation showed increased expression of STING and interleukin-1ß in KCs compared with nonirradiated samples. Notably, STING pharmacologic inhibition alleviated irradiation-induced liver injury in mice, indicating its potential therapeutic role in RILD. CONCLUSIONS: The results of our study reveal that TEAD1-STING-NLRP3 signaling activation contributes to RILD via METTL3-dependent m6A modification.

Photothermally driven decoupling of gas evolution at the solid-liquid interface for boosted photocatalytic hydrogen production.

The slow mass transfer, especially the gas evolution process at the solid-liquid interface in photocatalytic water splitting, restricts the overall efficiency of the hydrogen evolution reaction. Here, we report a novel gas-solid photocatalytic reaction system by decoupling hydrogen generation from a traditional solid-liquid interface. The success relies on annealing commercial melamine sponge (AMS) for effective photothermal conversion that leads to rapid water evaporation. The vapor flows towards the photocatalyst covering the surface of the AMS and is split by the catalyst therein. This liquid-gas/gas-solid coupling system avoids the formation of photocatalytic bubbles at the solid-liquid interface, leading to significantly improved mass transfer and conversion. Utilizing CdS nanorods anchored by highly dispersed nickel atoms/clusters as a model photocatalyst, the highest hydrogen evolution rate from water splitting reaches 686.39 µmol h-1, which is 5.31 times that of the traditional solid-liquid-gas triphase system. The solar-to-hydrogen (STH) efficiency can be up to 2.06%. This study provides a new idea for the design and construction of efficient practical photocatalytic systems.