Critical roles of lncRNA-mediated autophagy in urologic malignancies.

Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play crucial roles in various cancers, including urologic malignancies. This article provides a summary of the latest research findings, suggesting that lncRNA-mediated autophagy could either suppress or promote tumors in prostate, kidney, and bladder cancers. The intricate network involving different lncRNAs, target genes, and mediated signaling pathways plays a crucial role in urological malignancies by modulating the autophagic process. Dysregulated expression of lncRNAs can disrupt autophagy, leading to tumorigenesis, progression, and enhanced resistance to therapy. Consequently, targeting particular lncRNAs that control autophagy could serve as a dependable diagnostic tool and a promising prognostic biomarker in urologic oncology, while also holding potential as an effective therapeutic approach.

[Noise exposure-induced stress response and its measurement methods].

Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be driven by changes in hormone secretion in animals. When animals face with noise stress, the neuroendocrine systems, mainly the hypothalamic-pituitary-adrenal (HPA) axis, are activated, which promotes the secretion and release of stress hormones, and then leads to a series of behavioral changes. The behavioral changes can be easily observed, but the changes in physiological indicators such as hormone levels need to be accurately measured. Currently, many studies have measured the variations of stress hormone levels in animals under different noise conditions. Taking glucocorticoid as an example, this paper summarizes the different measurement methods of stress hormones, especially the non-invasive measurement methods, and compares the advantages and shortcomings of them. It provides a variety of measurement choices for the study of related issues, and also helps us to further understand the sources of animal stress, in order to provide a better habitat for animals.

Design and Implementation of Electrochromic Smart Windows with Self-Driven Thermoelectric Power Generation.

Electrochromic smart windows can achieve controllable modulation of color and transmittance under an external electric field with active light and thermal control capabilities, which helps reduce energy consumption caused by building cooling and heating. However, electrochromic smart windows often rely on external power circuits, which greatly affects the independence and portability of smart windows. Based on this, an electrochromic smart window driven by temperature-difference power generation was designed and implemented. This smart window provides automatic and manual control of the reversible cycle of electrochromic glass from light blue to dark blue according to user requirements and changes in the surrounding environment, achieving adaptive adjustment of visual comfort and reducing energy consumption. The infrared radiation rejection (from 780 to 2500 nm) of the electrochromic smart window is as high as 77.3%, and its transmittance (from 380 to 780 nm) fluctuates between 39.2% and 56.4% with changes in working state. Furthermore, the temperature in the indoor simulation device with electrochromic glass as the window was 15 °C lower than that with ordinary glass as the window after heating with a 250 W Philips infrared lamp for ten minutes. After 2000 cycles of testing, the performance of the smart window was basically maintained at its initial values, and it has broad application prospects in buildings, vehicles, and high-speed rail systems.

A modified HSV-1 oncolytic virus reconciles antiviral and antitumor immunity via promoting IFNß expression and inhibiting PKR.

Type I interferon (IFN-I) is a potent immune modulator intricately involved in regulating tumor immunity. Meanwhile, the integrity of the IFN-I signaling pathway is essential for radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, the clinical application of IFN-I remains challenging due to its non-specific cytotoxicity and limited half-life. To overcome these limitations, we developed a gene delivery platform, CRISPR-V, enabling the rapid creation of novel HSV-1 oncolytic viruses. Utilizing this platform, we created an oncolytic virus, OVH-IFNß, in which the IFNß gene was incorporated into the HSV-1 genome. However, exogenous IFNß expression significantly inhibited OVH-IFNß replication. Through transcriptome data analyses, we identified several ISG genes inhibiting OVH-IFNß replication. By gene knockout and functional studies of the downstream effectors, we confirmed the prominent antiviral activities of protein kinase R (PKR). To balance the antitumor and antiviral immunity of IFNß, we developed a novel HSV-1 oncolytic virus, OVH-IFNß-iPKR, which can express IFNß while inhibiting PKR, leading to a potent antitumor immunity while reducing the antiviral capacity of IFNß. OVH-IFNß-iPKR shows a strong ability to induce immunogenic cell death and activate tumor-specific CD8+ T cells, leading to de novo immune responses and providing a novel strategy for tumor immunotherapy.

Forskolin is an effective therapeutic small molecule for the treatment of hypertrophic cardiomyopathy through ADCY6/cAMP/PKA pathway.

Hypertrophic cardiomyopathy (HCM) arises from a pathogenic variant in the gene responsible for encoding the myocardium-associated protein. Forskolin (FSK), a labdane diterpene isolated from Sphingomonas capillaris, exhibits diverse pharmacological effects, including bronchospasm relief, intraocular pressure reduction, and glaucoma treatment. However, whether FSK could regulate HCM and its associated mechanism remains unclear. Here, we discovered that FSK could mitigate cardiac hypertrophy in two HCM mouse models (Myh6R404Q and Tnnt2R109Q) in vivo. Additionally, FSK could prevent norepinephrine (NE)-induced cardiomyocyte hypertrophy in vitro. It reversed cardiac dysfunction, reduced enlarged cell size, and downregulated the expression of hypertrophy-related genes. We further demonstrated that FSK's mechanism in alleviating HCM relied on the activation of ADCY6. In conclusion, our findings demonstrate that FSK alleviates hypertrophic cardiomyopathy by modulating the ADCY6/cAMP/PKA pathway, suggesting that FSK holds promise as a therapeutic agent for HCM.

Towards Lightweight Super-Resolution with Dual Regression Learning.

Deep neural networks have exhibited remarkable performance in image super-resolution (SR) tasks by learning a mapping from low-resolution (LR) images to high-resolution (HR) images. However, the SR problem is typically an ill-posed problem and existing methods would come with several limitations. First, the possible mapping space of SR can be extremely large since there may exist many different HR images that can be super-resolved from the same LR image. As a result, it is hard to directly learn a promising SR mapping from such a large space. Second, it is often inevitable to develop very large models with extremely high computational cost to yield promising SR performance. In practice, one can use model compression techniques to obtain compact models by reducing model redundancy. Nevertheless, it is hard for existing model compression methods to accurately identify the redundant components due to the extremely large SR mapping space. To alleviate the first challenge, we propose a dual regression learning scheme to reduce the space of possible SR mappings. Specifically, in addition to the mapping from LR to HR images, we learn an additional dual regression mapping to estimate the downsampling kernel and reconstruct LR images. In this way, the dual mapping acts as a constraint to reduce the space of possible mappings. To address the second challenge, we propose a dual regression compression (DRC) method to reduce model redundancy in both layer-level and channel-level based on channel pruning. Specifically, we first develop a channel number search method that minimizes the dual regression loss to determine the redundancy of each layer. Given the searched channel numbers, we further exploit the dual regression manner to evaluate the importance of channels and prune the redundant ones. Extensive experiments show the effectiveness of our method in obtaining accurate and efficient SR models.

Organ-Specific Gene Expression Control Using DNA Origami-Based Nanodevices.

Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.

Effect of Metaldehyde on Survival, Enzyme Activities, and Histopathology of the Apple Snail Pomacea canaliculata (Lamarck 1822).

Pomacea canaliculata, as an invasive exotic species in Asia, can adversely affect crop yields, eco-environment, and human health. Application of molluscicides containing metaldehyde is one effective method for controlling P. canaliculata. In order to investigate the effects of metaldehyde on adult snails, we conducted acute toxicological experiments to investigate the changes in enzyme activities and histopathology after 24 h and 48 h of metaldehyde action. The results showed that the median lethal concentrations (LC) of metaldehyde on P. canaliculata were 3.792, 2.195, 1.833, and 1.706 mg/L at exposure times of 24, 48, 72, and 96 h, respectively. Treatment and time significantly affected acetylcholinesterase (AChE), glutathione S-transferase (GST), and total antioxidant capacity (TAC) activity, with sex significantly affecting AChE, GST, and TAC activity and time significantly affecting carboxylesterase (CarE). In addition, the interaction of treatment and time significantly affected the activity of GST, CarE and TAC. In addition, histopathological changes occurred in the digestive glands, gills and gastropods of apple snail exposed to metaldehyde. Histological examination of the digestive glands included atrophy of the digestive cells, widening of the hemolymph gap, and an increase in basophils. In treated snails, the hemolymph gap in the gills was widely dilated, the columnar cells were disorganized or even necrotic, and the columnar muscle cells in the ventral foot were loosely arranged and the muscle fibers reduced. The findings of this study can provide some references for controlling the toxicity mechanism of invasive species.

A Peritrophin-44 gene in Litopenaeus vannamei is involved in disease resistance.

Peritrophic membrane (PM) is a pellicle structure present in the midgut of some invertebrates, such as insects and crustaceans. It could isolate harmful components and pathogens in food from intestinal epithelial cells; and it also plays a role in improving digestion and absorption efficiency. So PM is important for survival of its owner. In current study, 44 PM proteins were identified in Litopenaeus vannamei by PM proteome analysis. Among these PM proteins, the Peritrophin-44 homologous protein (LvPT44) was further studied. Chitin-binding assay indicated that LvPT44 could bind to colloidal chitin, and immunoeletron microscopy analysis shown that it was located to PM of L. vannamei. Furthermore, LvPT44 promoter was found to be activated by L. vannamei STAT and c-Jun. Besides, LvPT44 was induced by ER-stress as well as white spot syndrome virus infection. Knocked-down expression of LvPT44 by RNA inference increased the cumulative mortality of shrimp that caused by ER-stress or white spot syndrome virus. These results suggested that LvPT44 has an important role in disease resistance.

Simultaneous application of oral and intravaginal probiotics for Helicobacter pylori and its antibiotic-therapy-induced vaginal dysbacteriosis.

Helicobacter pylori is a prevalent bacterial pathogen globally, implicated in various gastrointestinal disorders. Current recommended antibiotic therapies for H. pylori infection have been proven to be therapeutically insufficient, with low eradication rates and high recurrence rates. Emerging evidence suggests that antibiotic therapy for H. pylori can lead to gastrointestinal and subsequent vaginal dysbiosis, posing challenges for conventional antibiotic approaches. Thus, this article proposes a novel probiotic therapy involving simultaneous oral and intra-vaginal probiotic administration alongside antibiotics for H. pylori treatment, aiming to enhance eradication rates and mitigate dysbiosis. We begin by providing an overview of gastrointestinal and vaginal microbiota and their interconnectedness through the vagina-gut axis. We then review the efficacy of current antibiotic regimens for H. pylori and discuss how antibiotic treatment impacts the vaginal microenvironment. To explore the feasibility of this approach, we evaluate the effectiveness of oral and intra-vaginal probiotics in restoring normal microbiota in the gastrointestinal and vaginal tracts, respectively. Additionally, we analyze the direct mechanisms by which oral and intra-vaginal probiotics act on their respective tracts and discuss potential cross-tract mechanisms. Considering the potential synergistic therapeutic effects of probiotics in both the gastrointestinal and vaginal tracts, dual-channel probiotic therapy holds promise as a more effective approach for H. pylori eradication and dysbiosis mitigation, presenting a novel concept in the collaborative treatment of gastrointestinal and genital disorders.

Comparison of the burden of digestive diseases between China and the United States from 1990 to 2019.

Introduction: China has experienced unprecedented transformations unseen in a century and is gradually progressing toward an emerging superpower. The epidemiological trends of digestive diseases in the United States (the US) have significant prescient effects on China. Methods: We extracted data on 18 digestive diseases from the Global Burden of Diseases 2019 Data Resource. Linear regression analysis conducted by the JoinPoint software assessed the average annual percentage change of the burden. We performed subgroup analyses based on sex and age group. Results: In 2019, there were 836.01 and 180.91 million new cases of digestive diseases in China and the US, causing 1558.01 and 339.54 thousand deaths. The age-standardized incidence rates of digestive diseases in China and the US were 58417.87/100,000 and 55018.65/100,000 respectively, resulting in age-standardized mortality rates of 81.52/100,000 and 60.88/100,000. The rates in China annually decreased by 2.149% for mortality and 2.611% for disability-adjusted life of year (DALY). The mortality and DALY rates of the US, respectively, had average annual percentage changes of -0.219 and -0.251. Enteric infections and cirrhosis and other chronic liver diseases accounted for the highest incidence and prevalence in both counties, respectively. The burden of multiple digestive diseases exhibited notable sex disparities. The middle-old persons had higher age-standardized prevalence rates. Conclusion: China bore a greater burden of digestive diseases, and the evolving patterns were more noticeable. Targeted interventions and urgent measures should be taken in both countries to address the specific burden of digestive diseases based on their different epidemic degree.

Small Intestinal Endocrine Cell Derived Exosomal ACE2 Protects Islet ß-Cell Function by Inhibiting the Activation of NLRP3 Inflammasome and Reducing ß-Cell Pyroptosis.

Background: The "gut-islets axis" is an important endocrine signaling axis that regulates islets function by modulating the gut microbiota and endocrine metabolism within the gut. However, the specific mechanisms and roles of the intestine in islets regulation remain unclear. Recent studies investigated that exosomes derived from gut microbiota can transport signals to remotely regulate islets ß-cell function, suggesting the possibility of novel signaling pathways mediated by gut exosomes in the regulation of the "gut-islet axis.". Methods: The exosomes were isolated from the intestinal enteroendocrine cell-line STC-1cells culture supernatants treated with palmitate acid (PA) or BSA. Metabolic stress models were established by separately subjecting MIN6 cells to PA stimulation and feeding mice with a high-fat diet. Intervention with exosomes in vitro and in vivo to assess the biological effects of exosomes on islets ß cells under metabolic stress. The Mas receptor antagonist A779 and ACE2ko mice were used to evaluate the role of exosomal ACE2. Results: We found ACE2, a molecule that plays a crucial role in the regulation of islets function, is abundantly expressed in exosomes derived from STC-1 under physiological normal condition (NCEO). These exosomes cannot only be taken up by ß-cells in vitro but also selectively transported to the islets in vivo. Following intervention with NCEXO, both Min6 cells in a lipotoxic environment and mice on a high-fat diet exhibited significant improvements in islets ß-cell function and ß-cell mass. Further investigations demonstrated that these protective effects are attributed to exosomal ACE2, as ACE2 inhibits NLRP3 inflammasome activation and reduces ß-cell pyroptosis. Conclusion: ACE2-enriched exosomes from the gut can selectively target islets, subsequently inhibiting NLRP3 inflammasome activation and ß cell pyroptosis, thereby restoring islets ß cell function under metabolic stress. This study provides novel insights into therapeutic strategies for the prevention and treatment of obesity and diabetes.

Enhanced long-term potentiation in the anterior cingulate cortex of tree shrew.

Synaptic plasticity is a key cellular model for learning, memory and chronic pain. Most previous studies were carried out in rats and mice, and less is known about synaptic plasticity in non-human primates. In the present study, we used integrative experimental approaches to study long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of adult tree shrews. We found that glutamate is the major excitatory transmitter and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid (AMPA) receptors mediate postsynaptic responses. LTP in tree shrews was greater than that in adult mice and lasted for at least 5 h. N-methyl-d-aspartic acid (NMDA) receptors, Ca2+ influx and adenylyl cyclase 1 (AC1) contributed to tree shrew LTP. Our results suggest that LTP is a major form of synaptic plasticity in the ACC of primate-like animals. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Cortical nitric oxide required for presynaptic long-term potentiation in the insular cortex.

Nitric oxide (NO) is a key diffusible messenger in the mammalian brain. It has been proposed that NO may diffuse retrogradely into presynaptic terminals, contributing to the induction of hippocampal long-term potentiation (LTP). Here, we present novel evidence that NO is required for kainate receptor (KAR)-dependent presynaptic form of LTP (pre-LTP) in the adult insular cortex (IC). In the IC, we found that inhibition of NO synthase erased the maintenance of pre-LTP, while the induction of pre-LTP required the activation of KAR. Furthermore, NO is essential for pre-LTP induced between two pyramidal cells in the IC using the double patch-clamp recording. These results suggest that NO is required for homosynaptic pre-LTP in the IC. Our results present strong evidence for the critical roles of NO in pre-LTP in the IC. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

Clinical significance of serum Ck18-M65 and M30 levels in patients with chronic hepatitis B combined with nonalcoholic steatohepatitis and liver fibrosis.

In this study, we aimed to explore the clinical significance of serum CK18-M65 and CK18-M30 levels in patients with chronic hepatitis B (CHB) complicated by nonalcoholic steatohepatitis (NASH) and liver fibrosis. The observation and control groups comprised 133 patients with CHB complicated by NASH and 50 healthy patients from our hospital, respectively. Liver function indices, including alanine aminotransferase, glutamic aminotransferase, γ-glutamyltransferase, total bilirubin, total protein, and total cholesterol, were determined using an automatic biochemical analyzer. Hyaluronic acid, type III procollagen, type IV collagen, laminin, and CK18-M65 and M30 levels were detected using ELISA. Serum CK18-M65 and M30 levels in patients with CHB complicated by NASH were positively correlated with the liver fibrosis stage (P < .05). While serum CK18-M65 demonstrated a low diagnostic value for liver fibrosis in the S0-1 stage, it exhibited good diagnostic value for S2-3 stage liver fibrosis. Serum CK18-M30 displayed good diagnostic value for S0-1 and S2-3 hepatic fibrosis, particularly for S2-3 hepatic fibrosis. Elevated serum CK18-M65 and CK18-M30 levels in patients with CHB complicated with NASH suggest their potential utility in evaluating the progression of liver fibrosis in this population. In particular, CK18-M30 exhibits superior diagnostic efficiency.

Characterization of Humicola pulvericola First Isolated from a Patient with Keratitis Clinical Case.

Infection caused by the Humicola sp is extremely rare. We report the first case of fungal keratitis caused by Humicola pulvericola (H. pulvericola) in a 63-year-old man with a history of exposed to hot oil two weeks ago who developed keratitis. Direct examination of confocal microscopy and corneal scrapings showed fungal hyphae and isolates were identified by morphology and by sequencing the internal transcribed spacer region of ribosomal DNA. The in vitro antifungal susceptibilities of the case strain were tested for five antifungal agents. The results showed that the infectious agent was resistant towards fluconazole, caspofungin and amphotericin B; itraconazole and voriconazole were highly effective against H. pulvericola. He was diagnosed with H. pulvericola keratitis and treated with oral itraconazole and natamycin eyedrops. After one month of treatment, the lesion gradually improved, with the best-corrected visual acuity improving to 0.8.

Nature's carriers: leveraging extracellular vesicles for targeted drug delivery.

With the rapid development of drug delivery systems, extracellular vesicles (EVs) have emerged as promising stars for improving targeting abilities and realizing effective delivery. Numerous studies have shown when compared to conventional strategies in targeted drug delivery (TDD), EVs-based strategies have several distinguished advantages besides targeting, such as participating in cell-to-cell communications and immune response, showing high biocompatibility and stability, penetrating through biological barriers, etc. In this review, we mainly focus on the mass production of EVs including the challenges and strategies for scaling up EVs production in a cost-effective and reproducible manner, the loading and active targeting methods, and examples of EVs as vehicles for TDD in consideration of potential safety and regulatory issues associated. We also conclude and discuss the rigor and reproducibility of EVs production, the current research status of the application of EVs-based strategies to targeted drug delivery, clinical conversion prospects, and existing chances and challenges.

Mullite-like SmMn2O5-Derived Composite Oxide-Supported Ni-Based Catalysts for Hydrogen Production by Auto-Thermal Reforming of Acetic Acid.

The x%Ni/Sm2O3-MnO (x = 0, 10, 15, 20) catalysts derived from SmMn2O5 mullite were prepared by solution combustion and impregnation method; auto-thermal reforming (ATR) of acetic acid (HAc) for hydrogen production was used to explore the metal-support effect induced by Ni loadings on the catalytic reforming activity and product distribution. The 15%Ni/Sm2O3-MnO catalyst exhibited optimal catalytic performance, which can be due to the appropriate Ni loading inducing a strong metal-support interaction to form a stable Ni/Sm2O3-MnO active center, while side reactions, such as methanation and ketonization, were well suppressed. According to characterizations, Sm2O3-MnO mixed oxides derived from SmMn2O5 mullite were formed with oxygen vacancies; nevertheless, loading of Ni metal further promoted the formation of oxygen vacancies, thus enhancing adsorption and activation of oxygen-containing intermediate species and resulting in higher reactivity with HAc conversion near 100% and hydrogen yield at 2.62 mol-H2/mol-HAc.