MicroRNA-21 in urologic cancers: from molecular mechanisms to clinical implications.

The three most common kinds of urologic malignancies are prostate, bladder, and kidney cancer, which typically cause substantial morbidity and mortality. Early detection and effective treatment are essential due to their high fatality rates. As a result, there is an urgent need for innovative research to improve the clinical management of patients with urologic cancers. A type of small noncoding RNAs of 22 nucleotides, microRNAs (miRNAs) are well-known for their important roles in a variety of developmental processes. Among these, microRNA-21 (miR-21) stands out as a commonly studied miRNA with implications in tumorigenesis and cancer development, particularly in urological tumors. Recent research has shed light on the dysregulation of miR-21 in urological tumors, offering insights into its potential as a prognostic, diagnostic, and therapeutic tool. This review delves into the pathogenesis of miR-21 in prostate, bladder, and renal cancers, its utility as a cancer biomarker, and the therapeutic possibilities of targeting miR-21.

A pilot study of optical coherence tomography-guided transbronchial biopsy in peripheral pulmonary lesions.

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPLs) remains challenging. Despite advancements in guided transbronchial biopsy (TBB) techniques, diagnostic yields haven't reached ideal levels. Optical coherence tomography (OCT) has been developed for application in pulmonary diseases, yet no data existed evaluating effectiveness in diagnosing PPLs. RESEARCH DESIGN AND METHODS: This study included patients who underwent OCT and radial endobronchial ultrasound (R-EBUS)-guided TBB. OCT and R-EBUS imaging features were analyzed to differentiate between benign and malignant PPLs and subtypes of lung cancer. RESULTS: A total of 89 patients were included in this study. The diagnostic yield of OCT-guided TBB stood at 56.18%, R-EBUS-guided TBB was 83.15% (P<0.01). The accuracy of OCT to judge the nature of lesions was 92.59%, while R-EBUS was 77.92%. The accuracy of OCT in predicting squamous carcinoma (SCC) and adenocarcinoma were both 91.30%. CONCLUSIONS: Although the diagnostic yield of OCT-guided TBB fell short of that achieved by R-EBUS, OCT possessed the capability to judge the nature of lesions and guide the pathological classification of malignant lesions. Further extensive prospective studies are necessary to thoroughly assess the characteristics of this procedure. CLINICAL TRIAL REGISTRATION: https://register.clinicaltrials.gov/ identifier is NCT06419114.

A study on the impact of open source metaverse immersive teaching method on emergency skills training for medical undergraduate students.

BACKGROUND: In recent years, the traditional simulation-based medical teaching approach has faced challenges in meeting the requirements of practical emergency medicine education. This study utilized open-source tools and software to develop immersive panoramic videos using virtual reality technology for emergency medical teaching. It aims to investigate the efficacy of this novel teaching methodology. This transformation shifted the focus from physical simulation to virtual simulation in medical education, establishing a metaverse for emergency medical teaching. METHODS: In accordance with the curriculum guidelines, the instructors produced panoramic videos demonstrating procedures such as spinal injury management, humeral fracture with abdominal wall intestinal tube prolapse, head and chest composite injuries, cardiopulmonary resuscitation, and tracheal intubation. Using Unity software, a virtual training application for bronchoscopy was developed and integrated into the PICO4 VR all-in-one device to create a metaverse teaching environment. Fourth-year medical undergraduate students were allocated into either an experimental group (n = 26) or a control group (n = 30) based on student IDs. The experimental group received instruction through the metaverse immersive teaching method, while the control group followed the traditional simulation-based medical teaching approach. Both groups participated in theoretical and practical lessons as usual. Subsequently, all students underwent a four-station Objective Structured Clinical Examination (OSCE) to assess the effectiveness of the teaching methods based on their performance. Additionally, students in the experimental group provided subjective evaluations to assess their acceptance of the new teaching approach. RESULTS: Before the training commenced, there were no significant statistical differences in the first aid test scores between the experimental and control groups. Following the training, the experimental group outperformed the control group in the four-station OSCE examination, with all P-values being less than 0.05. The satisfaction rate among the experimental group regarding the new teaching method reached 88.46%, reflecting levels of satisfaction and extreme satisfaction. CONCLUSION: The open-source metaverse immersive teaching method has demonstrated a positive impact on enhancing the emergency skills of medical undergraduate students, with a high level of acceptance among students. In comparison to traditional simulated medical teaching methods, this approach requires less time and space, incurring lower costs, and is deemed worthy of wider adoption.

Non-coding RNAs as regulators of autophagy in chondrocytes: Mechanisms and implications for osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA.

Rhodium-Catalyzed Regioselective [4 + 2] Cycloaddition of Ynamines and 2-(Cyanomethyl)phenylboronates.

A rhodium-catalyzed [4 + 2] cycloaddition of ynamines and 2-(cyanomethyl)phenylboronates has been developed, leading to efficient and excellent regioselective synthesis of valuable indole-linked aromatic compounds in a concise and flexible approach. Interestingly, this strategy was successful in the construction of C···N axially chiral indoles with high enantiocontrol by the introduction of a new phosphoramidite ligand (Xie-Phos).

Autophagy in erectile dysfunction: focusing on apoptosis and fibrosis.

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.

Exploring ABHD5 as a Lipid-Related Biomarker in Idiopathic Pulmonary Fibrosis: Integrating Machine Learning, Bioinformatics, and In Vitro Experiments.

Recent studies increasingly suggest a connection between lipids and idiopathic pulmonary fibrosis (IPF). This study was aimed at exploring potential lipid-related biomarkers for IPF and uncovering the mechanisms underlying pulmonary fibrosis. IPF-related datasets were retrieved from the GEO database, and the ComBat algorithm was used to merge multiple datasets and eliminate batch effects. Weighted gene co-expression network analysis (WGCNA) was utilized to identify modules and genes associated with IPF. Potential hub genes were determined by intersecting these genes with lipid-related genes from the GeneCards database. A machine learning-based integrative approach was developed to construct diagnostic and prognostic signatures, which were validated across several datasets. Additionally, single-cell sequencing data was used to validate the expression differences of core IPF-related genes across various cell types. The effect of ABHD5 on fibroblasts was assessed using the cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and cell scratch assays. The expression levels of fibrotic factors were measured using real-time quantitative polymerase chain reaction and western blot analysis. WGCNA identified a red module potentially related to IPF, and the intersection with lipid-related genes yielded 51 hub genes. These genes were used to build diagnostic and prognostic models that demonstrated robust validation capabilities across multiple datasets. Single-cell sequencing analysis revealed low expression of ABHD5 in the lung tissues of IPF patients, with a higher proportion of fibroblasts exhibiting low ABHD5 expression. Cell experiments showed that under the influence of TGF-ß1, knockdown of ABHD5 slightly promoted fibroblast proliferation. Additionally, fibroblasts with low ABHD5 expression exhibited enhanced migratory capabilities and secreted more fibrotic factors. Lipid-related diagnostic and prognostic models for IPF were developed, and ABHD5 may serve as a potential biomarker. Low ABHD5 expression could potentially accelerate the progression of pulmonary fibrosis.

Fast and non-invasive identification of Baijiu based on Tyndall effect and chemometrics.

The value of Baijiu is affected by its flavor, age, and adulteration. Therefore, a simple and rapid identification method is crucial for the market. In this study, we present a rapid, non-intrusive identification technique for Baijiu utilizing the Tyndall effect combined with chemometrics analysis. Our experiment begins illuminating Baijiu with a 405 nm wavelength laser and recording the resulting bright light path due to the Tyndall effect. To further analyze the color and brightness information, Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), Hierarchical Cluster Analysis (HCA), and Multilayer Perceptron (MLP) were employed. This study establishes correlations between the brightness of the Tyndall light path and seven trace flavor compounds in Baijiu. The findings demonstrate that this method effectively identifies the flavor, age cellar, and adulteration of Baijiu and also quantitatively detects the concentrations of flavor compounds. Additionally, an analysis platform was developed to enable the rapid identification of Baijiu.

Entropy drives the ligand recognition in G-protein-coupled receptor subtypes.

Achieving ligand subtype selectivity within highly homologous subtypes of G-protein-coupled receptor (GPCR) is critical yet challenging for GPCR drug discovery, primarily due to the unclear mechanism underlying ligand subtype selectivity, which hampers the rational design of subtype-selective ligands. Herein, we disclose an unusual molecular mechanism of entropy-driven ligand recognition in cannabinoid (CB) receptor subtypes, revealed through atomic-level molecular dynamics simulations, cryoelectron microscopy structure, and mutagenesis experiments. This mechanism is attributed to the distinct conformational dynamics of the receptor's orthosteric pocket, leading to variations in ligand binding entropy and consequently, differential binding affinities, which culminate in specific ligand recognition. We experimentally validated this mechanism and leveraged it to design ligands with enhanced or ablated subtype selectivity. One such ligand demonstrated favorable pharmacokinetic properties and significant efficacy in rodent inflammatory analgesic models. More importantly, it is precisely due to the high subtype selectivity obtained based on this mechanism that this ligand does not show addictive properties in animal models. Our findings elucidate the unconventional role of entropy in CB receptor subtype selectivity and suggest a strategy for rational design of ligands to achieve entropy-driven subtype selectivity for many pharmaceutically important GPCRs.

Programmable Chemical Reactions Enable Ultrastrong Soft Pneumatic Actuation.

Soft pneumatic actuation is widely used in wearable devices, soft robots, artificial muscles, and surgery machines. However, generating high-pressure gases in a soft, controllable, and portable way remains a substantial challenge. Here, a class of programmable chemical reactions that can be used to controllably generate gases with a maximum pressure output of nearly 6 MPa is reported. It is proposed to realize the programmability of the chemical reaction process using thermoelectric material with programmable electric current and employing preprogrammed reversible chemical reactants. The programmable chemical reactions as soft pneumatic actuation can be operated independently as miniature gas sources (∼20-100 g) or combined with arbitrary physical structures to make self-contained machines, capable of generating unprecedented pressures of nearly 6 MPa or forces of about 18 kN in a controllable, portable, and silent manner. Striking demonstrations of breaking a brick, a marble, and concrete blocks, raising a sightseeing car, and successful applications in artificial muscles and soft assistive wearables illustrate tremendous application prospects of soft pneumatic actuation via programmable chemical reactions. The study establishes a new paradigm toward ultrastrong soft pneumatic actuation.

Size Dependence of Ultrafast Electron Transfer from Didodecyl Dimethylammonium Bromide-Modified CsPbBr3 Nanocrystals to Electron Acceptors.

Charge transfer efficiencies in all-inorganic lead halide perovskite nanocrystals (NCs) are crucial for applications in photovoltaics and photocatalysis. Herein, CsPbBr3 NCs with different sizes are synthesized by varying the ligand contents of didodecyl dimethylammonium bromide at room temperature. Adding benzoquinone (BQ) molecules leads to a decrease in the PL intensities and PL decay times in NCs. The electron transfer (ET) efficiency (ηET) increases with NC size in complexes of CsPbBr3 NCs and BQ molecules (NC-BQ complexes), when the same concentration of BQ is maintained, as investigated by transient photobleaching and photoluminescence spectroscopies. Controlling the same number of attached BQ acceptor molecules per NC induces the same ηET in NC-BQ complexes even though with different NC sizes. Our findings provide new insights into ultrafast charge transfer behaviors in perovskite NCs, which is important for designing efficient light energy conversion devices.

LATA1, a RING E3 ligase, modulates the tiller angle by affecting auxin asymmetric distribution and content in rice.

The tiller angle is an important agronomic trait that determines plant architecture and grain yield in rice (Oryza sativa L.). However, the molecular regulation mechanism of the rice tiller angle remains unclear. Here, we identified a rice tiller angle gene, LARGE TILLER ANGLE 1 (LATA1), using the MutMap approach. LATA1 encodes a C3H2C3-type RING zinc finger E3 ligase and the conserved region of the RING zinc finger is essential for its E3 activity. LATA1 was highly expressed in the root and tiller base and LATA1-GFP fusion protein was specifically localized to the nucleus. The mutation of LATA1 significantly reduced indole-3-acetic acid content and attenuated lateral auxin transport, thereby resulting in defective shoot gravitropism and spreading plant architecture in rice. Further investigations found that LATA1 may indirectly affect gravity perception by modulating the sedimentation rate of gravity-sensing amyloplasts upon gravistimulation. Our findings provide new insights into the molecular mechanism underlying the rice tiller angle and new genetic resource for the improvement of plant architecture in rice.

A Real-world Study of Denosumab For Reducing Refracture Risk after Percutaneous Vertebral Augmentation.

OBJECTIVE: To investigate the use of anti-osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real-world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real-world scenarios to enhance the management of bone health in OVCF patients. METHODS: This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55-90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on-treatment and off-treatment groups according to whether they received a second dose of denosumab, with follow-up beginning on the index day (225 days after the first denosumab dose). In this study, the off-treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti-osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed. RESULTS: A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on-treatment group than in the off-treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on-treatment group than in the off-treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti-osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%-15% taking oral bisphosphonates. CONCLUSION: Postmenopausal women have a high refracture rate and a low proportion of anti-osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.

The Effects of Different Dietary Patterns on Bone Health.

Bone metabolism is a process in which osteoclasts continuously clear old bone and osteoblasts form osteoid and mineralization within basic multicellular units, which are in a dynamic balance. The process of bone metabolism is affected by many factors, including diet. Reasonable dietary patterns play a vital role in the prevention and treatment of bone-related diseases. In recent years, dietary patterns have changed dramatically. With the continuous improvement in the quality of life, high amounts of sugar, fat and protein have become a part of people's daily diets. However, people have gradually realized the importance of a healthy diet, intermittent fasting, calorie restriction, a vegetarian diet, and moderate exercise. Although these dietary patterns have traditionally been considered healthy, their true impact on bone health are still unclear. Studies have found that caloric restriction and a vegetarian diet can reduce bone mass, the negative impact of a high-sugar and high-fat dietary (HSFD) pattern on bone health is far greater than the positive impact of the mechanical load, and the relationship between a high-protein diet (HPD) and bone health remains controversial. Calcium, vitamin D, and dairy products play an important role in preventing bone loss. In this article, we further explore the relationship between different dietary patterns and bone health, and provide a reference for how to choose the appropriate dietary pattern in the future and for how to prevent bone loss caused by long-term poor dietary patterns in children, adolescents, and the elderly. In addition, this review provides dietary references for the clinical treatment of bone-related diseases and suggests that health policy makers should consider dietary measures to prevent and treat bone loss.

Research progress of sorafenib drug delivery system in the treatment of hepatocellular carcinoma: An update.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.

Identification of hub genes and gene modules associated with Behçet's disease by weighted gene co-expression network analysis of neutrophil transcriptome.

OBJECTIVES: Behçet's disease (BD) is a chronic inflammatory condition with recurrent skin lesions, uveitis, and oral and genital ulcers. Neutrophils are important in the pathogenis of BD, but their molecular mechanisms are unclear. METHODS: We performed weighted gene co-expression network analysis on the transcriptome of neutrophils from 10 BD patients and 10 healthy controls to identify hub genes and gene modules associated with BD. RESULTS: We found eight co-expression modules with different biological functions. The turquoise module was involved in response to hydrogen peroxide and reactive oxygen species, the blue module was involved in response to external stimulus and inflammatory response, and the brown module was involved in the type I interferon signaling pathway. We further identified hub genes and transcription factors in each module by using module membership and gene significance. CONCLUSIONS: Our results reveal novel gene modules and hub genes that are associated with neutrophil activation and dysfunction in BD, which could serve as potential biomarkers and therapeutic targets for this disease.

Effect of no-touch versus conventional technique on arteriovenous fistula outcomes: a randomised controlled trial.

BACKGROUND: Autologous arteriovenous fistulae (AVFs) are the best type of vascular access in patients with kidney failure. However, the conventional technique has a high failure rate. We performed a randomised controlled trial to investigate whether the no-touch technique has a higher maturation and patency rate than that of the conventional technique for creating AVFs. METHODS: This study was a single-centre randomised controlled trial involving patients with kidney failure requiring an AVF for haemodialysis access. A total of 179 patients undergoing their first radial artery-cephalic fistula were randomized 1:1 to the no-touch technique (n = 90) or conventional technique (n = 89). The maturation and patency rate of the two techniques were compared and analysed. RESULTS: The preoperative baseline data showed no differences between groups. When comparing the no-touch technique to the conventional technique, the maturation rate was 93% vs. 89% and the 1-year primary function patency was 72% vs. 62%, respectively. Factors associated with AVF failure included age > 55 years (OR = 2.417, 95% CI 1.242-4.703), female sex (OR = 2.149, 95% CI 1.099-4.202), and vein diameter ≤ 1.8 mm (OR = 3.664, 95% CI 1.714-7.832). For patients with small veins the maturation rate was 92.98% vs. 80% and the 1-year primary function patency was 68.42% vs. 40% for the no-touch technique and conventional technique, respectively. CONCLUSIONS: The no-touch technique has a higher maturation and patency rate than the conventional technique for creating an autologous AVF, especially in patients with small veins. This technique may provide a better outcome for patients with small cephalic veins.

A gain-of-function mutation in BnaIAA13 disrupts vascular tissue and lateral root development in Brassica napus.

Rapeseed (Brassica napus) is an important oilseed crop worldwide. Plant vascular tissues are responsible for material transport and provide mechanical support. The lateral roots (LRs) absorb sufficient water and nutrients. The genetic basis of vascular tissues and LRs development in rapeseed remains unknown. This study characterized an EMS-mutagenized rapeseed mutant, T16, which showed dwarf stature, reduced LRs, and leaf wilting. Scanning electron microscopy observations showed that the internode-cell shortened. Observations of the tissue sections revealed defects in the development of vascular bundles in the stems and petioles. Genetic analysis revealed that the phenotypes of T16 were controlled by a single semi-dominant nuclear gene. Map-based cloning and genetic complementarity confirmed that BnaA03.IAA13 is the functional gene, a G-to-A mutation in second exon changed the glycine at the 79th position to glutamic acid, disrupting the conserved degron motif VGWPP. Transcriptome analysis in roots and stems showed that auxin and cytokinin signaling pathways were disordered in T16. Evolutionary analysis showed that AUXIN/INDOLE-3-ACETIC ACID was conserved during plant evolution. The heterozygote of T16 significantly reduced the plant height while maintaining other agronomic traits. Our findings provide novel insights into the regulatory mechanisms of vascular tissues and LRs development, and provide a new germplasm resource for rapeseed breeding.