Thrombomodulin Improves Cognitive Deficits in Heat-Stressed Mice.

BACKGROUND: Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed mice. METHODS: Adult male mice were exposed to HS (33 oC 2h daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble thrombomodulin (TM, 1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide, high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were measured biochemically. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined. RESULTS: Compared to controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice. CONCLUSIONS: The findings suggest that heat stress can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. Thrombomodulin, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.

Dynamic Interchain Motion in 1D Tetrathiafulvalene-Based Coordination Polymers for Highly Sensitive Molecular Recognition.

The application of electrically conductive 1D coordination polymers (1D CPs) in nanoelectronic molecular recognition is theoretically promising yet rarely explored due to the challenges in their synthesis and optimization of electrical properties. In this regard, two tetrathiafulvalene-based 1D CPs, namely [Co(m-H2TTFTB)(DMF)2(H2O)]n (Co-m-TTFTB), and {[Ni(m-H2TTFTB)(CH3CH2OH)1.5(H2O)1.5]·(H2O)0.5}n (Ni-m-TTFTB) are successfully constructed. The shorter S···S contacts between the [M(solvent)3(m-H2TTFTB)]n chains contribute to a significant improvement in their electrical conductivities. The powder X-ray diffraction (PXRD) under different organic solvents reveals the flexible and dynamic structural characteristic of M-m-TTFTB, which, combined with the 1D morphology, lead to their excellent performance for sensitive detection of volatile organic compounds. Co-m-TTFTB achieves a limit of detection for ethanol vapor down to 0.5 ppm, which is superior to the state-of-the-art chemiresistive sensors based on metal-organic frameworks or organic polymers at room temperature. In situ diffuse reflectance infrared Fourier transform spectroscopy, PXRD measurements and density functional theory calculations reveal the molecular insertion sensing mechanism and the corresponding structure-function relationship. This work expands the applicable scenario of 1D CPs and opens a new realm of 1D CP-based nanoelectronic sensors for highly sensitive room temperature gas detection.

Meta-analysis of the Selected Genetic Variants in Immune-Related Genes and Multiple Sclerosis Risk.

Previous studies have suggested that certain variants in immune-related genes may participate in the pathogenesis of multiple sclerosis (MS), including rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, rs16944 in the IL-1ß gene, rs2243250 in the IL-4 gene, and rs12722489 and rs2104286 in the IL-2Rα gene. However, the results remained inconclusive and conflicting. In view of this, a comprehensive meta-analysis including all eligible studies was conducted to investigate the association between these 8 selected genetic variants and MS risk. Up to June 2023, 64 related studies were finally included in this meta-analysis. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated by the random-effects model were used to evaluate the strength of association. Publication bias test, sensitivity analyses, and trial sequential analysis (TSA) were conducted to examine the reliability of statistical results. Our results indicated that rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, and rs12722489 and rs2104286 in the IL-2Rα gene may serve as the susceptible factors for MS pathogenesis, while rs16944 in the IL-1ß gene and rs2243250 in the IL-4 gene may not be associated with MS risk. However, the present findings need to be confirmed and reinforced in future studies.

Ensemble and Pre-Training Approach for Echo State Network and Extreme Learning Machine Models.

The echo state network (ESN) is a recurrent neural network that has yielded state-of-the-art results in many areas owing to its rapid learning ability and the fact that the weights of input neurons and hidden neurons are fixed throughout the learning process. However, the setting procedure for initializing the ESN's recurrent structure may lead to difficulties in designing a sound reservoir that matches a specific task. This paper proposes an improved pre-training method to adjust the model's parameters and topology to obtain an adaptive reservoir for a given application. Two strategies, namely global random selection and ensemble training, are introduced to pre-train the randomly initialized ESN model. Specifically, particle swarm optimization is applied to optimize chosen fixed and global weight values within the network, and the reliability and stability of the pre-trained model are enhanced by employing the ensemble training strategy. In addition, we test the feasibility of the model for time series prediction on six benchmarks and two real-life datasets. The experimental results show a clear enhancement in the ESN learning results. Furthermore, the proposed global random selection and ensemble training strategies are also applied to pre-train the extreme learning machine (ELM), which has a similar training process to the ESN model. Numerical experiments are subsequently carried out on the above-mentioned eight datasets. The experimental findings consistently show that the performance of the proposed pre-trained ELM model is also improved significantly. The suggested two strategies can thus enhance the ESN and ELM models' prediction accuracy and adaptability.

Hyperbaric oxygen preconditioning normalizes scrotal temperature, sperm quality, testicular structure, and erectile function in adult male rats subjected to exertional heat injury.

Testicular hyperthermia has been noted in men who work in high ambient temperatures. Scrotal temperatures above the normal range caused germ cell loss in the testes and resulted in male subfertility. In adult male rats, exercising at a higher environmental temperature (36 °C with relative humidity of 50%, 52 min) caused exertional heat stroke (EHS) characterized by scrotal hyperthermia, impaired sperm quality, dysmorphology in testes, prostates and bladders, and erectile dysfunction. Here, we aim to ascertain whether hyperbaric oxygen preconditioning (HBOP: 100% O2 at 2.0 atm absolute [ATA] for 2 h daily for 14 days consequently before the onset of EHS) is able to prevent the problem of EHS-induced sterility, testes, prostates, and bladders dysmorphology and erectile dysfunction. At the end of exertional heat stress compared to normobaric air (NBA or non-HBOP) rats, the HBOP rats exhibited lower body core temperature (40 °C vs. 43 °C), lower scrotal temperature (34 °C vs. 36 °C), lower neurological severity scores (2.8 vs. 5.8), higher erectile ability, (5984 mmHg-sec vs. 3788 mmHg-sec), higher plasma testosterone (6.8 ng/mL vs. 3.5 ng/mL), lower plasma follicle stimulating hormone (196.3 mIU/mL vs. 513.8 mIU/mL), lower plasma luteinizing hormone (131 IU/L vs. 189 IU/L), lower plasma adrenocorticotropic hormone (5136 pg/mL vs. 6129 pg/mL), lower plasma corticosterone (0.56 ng/mL vs. 1.18 ng/mL), lower sperm loss and lower values of histopathological scores for epididymis, testis, seminal vesicle, prostate, and bladder. Our data suggest that HBOP reduces body core and scrotal hyperthermia and improves sperm loss, testis/prostate/bladder dysmorphology, and erectile dysfunction after EHS in rats.

Polymorphism rs5780218, rs12998 and rs10158616 in KISS1 gene among the Hubei province Chinese girls with the central precocious puberty.

PURPOSE: Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. To elucidate the molecular genetic basis of CPP, we here investigated the effects of polymorphism rs5780218, rs12998 and rs10158616 in KISS1 gene on CPP susceptibility. METHODS: The three KISS1 gene polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing in 422 healthy Hubei Chinese girls and 384 Hubei Chinese girls with CPP. RESULTS: Single-locus analysis demonstrated that rs5780218 and rs12998 were significantly associated with CPP susceptibility in Hubei Chinese girls. Haplotype analysis exhibited that the AGG carrying the risk allele A of rs5780218 and the -GG carrying the protective allele - of rs5780218 were associated with increased and decreased CPP susceptibility in Hubei Chinese girls, respectively. The following meta-analysis confirmed the contribution of rs5780218 and rs12998 on CPP susceptibility in Chinese girls. CONCLUSIONS: rs5780218 and rs12998 in the KISS1 gene may participate in genetic susceptibility to CPP in Chinese girls, and the KISS1 gene rs5780218 may serve as a genetic biomarker of CPP. However, the present findings should be validated in future studies with larger sample sizes in other ethnic populations.

Prevalence and risk factors of subsyndromal delirium among postoperative patients: A systematic review and meta-analysis.

AIM: The aim of this study is to determine the prevalence and risk factors for subsyndromal delirium in the postoperative patient. DESIGN: A systematic review and meta-analysis. METHODS: The Review Manager 5.3 statistics platform and the Newcastle-Ottawa Scale were used for quality evaluation. DATA SOURCES: The following databases were searched: PubMed, Web of Science, EMBASE, The Cochrane Library, Scopus and EBSCO from January 2000 to December 2021. Additional sources were found by looking at relevant articles' citations. RESULTS: A total of 1744 titles were originally identified, and five studies including 962 patients were included in the systematic review, with a pooled prevalence of postoperative subsyndromal delirium (PSSD) of 30% (95% CI: 0.28-0.32). Significant risk variables for PSSD were older age, low levels of education (≤9 years), cognitive impairment, higher comorbidity score, and the duration of operation. CONCLUSION: PSSD is prevalent and is associated with a variety of risk factors as well as low academic performance. IMPACT: Identification and clinical management of patients with PSSD should be improved. Future research on PSSD risk factors should look at a wider range of intraoperative and postoperative risk factors that can be changed. PATIENT AND PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Regional effects of China's monetary policy during the economic transition period: Based on China's city classification system under the new normal.

We analyse the regional effects of China's monetary policy during the economic transition period based on the city classification system under the New Normal. Using panel vector autoregressive (PVAR) models, we examine the differences in the influence of a unified monetary policy on four types of Chinese cities: first-tier, quasi-first-tier, second-tier, and third-tier cities, from perspective of economic output. Based on a comparative analysis of the results of impulse response function and variance decomposition, we conclude that whether for quantitative monetary policy or price-based monetary policy, the degree to which economic growth responds to the unified monetary policy varies across the four types of cities in the short and long terms. With reference to China's economic transition under the New Normal, in the short term, this phenomenon probably relate to the varying degrees of financial marketization among the four city types; in the long run, this phenomenon may be attributed to the difference in the progress of industrial upgrading of these urban areas. Based on the analysis above, we suggest policy implications for Chinese cities based on the structural monetary policy, industrial upgrading, and market-oriented financial sector reforms.

Highly Efficient Electrochemical Nitrate Reduction to Ammonia in Strong Acid Conditions with Fe2 M-Trinuclear-Cluster Metal-Organic Frameworks.

Nitrate-containing industrial wastewater poses a serious threat to the global food security and public health safety. As compared to the traditional microbial denitrification, electrocatalytic nitrate reduction shows better sustainability with ultrahigh energy efficiency and the production of high-value ammonia (NH3 ). However, nitrate-containing wastewater from most industrial processes, such as mining, metallurgy, and petrochemical engineering, is generally acidic, which contradicts the typical neutral/alkaline working conditions for both denitrifying bacteria and the state-of-the-art inorganic electrocatalysts, leading to the demand for pre-neutralization and the problematic hydrogen evaluation reaction (HER) competition and catalyst dissolution. Here, we report a series of Fe2 M (M=Fe, Co, Ni, Zn) trinuclear cluster metal-organic frameworks (MOFs) that enable the highly efficient electrocatalytic nitrate reduction to ammonium under strong acidic conditions with excellent stability. In pH=1 electrolyte, the Fe2 Co-MOF demonstrates the NH3 yield rate of 20653.5 µg h-1 mg-1 site with 90.55 % NH3 -Faradaic efficiency (FE), 98.5 % NH3 -selectivity and up to 75 hr of electrocatalytic stability. Additionally, successful nitrate reduction in high-acidic conditions directly produce the ammonium sulfate as nitrogen fertilizer, avoiding the subsequent aqueous ammonia extraction and preventing the ammonia spillage loss. This series of cluster-based MOF structures provide new insights into the design principles of high-performance nitrate reduction catalysts under environmentally-relevant wastewater conditions.

Myocardial structure and functional alterations in a preclinical model of exertional heat stroke.

AIM: Relatively little information is available about the effect of an acute exertional heat stroke (EHS) on myocardium structure and function. Herein, we used a survival male rat model of EHS to answer the question. MAIN METHODS: Adult male Wistar rats underwent forced treadmill running at a 36 °C room temperature and 50 % relative humidity until EHS onset, characterized by hyperthermia and collapse. All rats that were followed for 14 days survived. Injury severity scores of both gastrocnemius and myocardium were determined histologically. Following an EHS event, pathological echocardiography, skeletal muscle and myocardial damage scores and indicators, myocardial fibrosis, hypertrophy, and autophagy were elucidated. KEY FINDINGS: Rats with EHS onset displayed skeletal muscle damage, elevated serum levels of skeletal muscle damage indicators (e.g., creatinine kinase, myoglobin, and potassium), and myocardial injury indicators (e.g., cardiac troponin I, creatinine kinase, and lactate dehydrogenase) returning to homeostasis within 3 days post-EHS. However, EHS-induced myocardial damage, pathological echocardiography, myocardial fibrosis, hypertrophy, and deposited misfolded proteins lasted up to 14 days post-EHS at least. SIGNIFICANCE: First, we provide evidence to confirm that despite the apparent return to homeostasis, underlying processes may still be ongoing after EHS onset. Second, we provide several key findings emphasizing the pathophysiology and risk factors of EHS, highlighting gaps in knowledge with the aim of stimulating future studies.

Spinel-Derived Formation and Amorphization of Bimetallic Oxyhydroxides for Efficient Electrocatalytic Biomass Oxidation.

Replacing the oxygen evolution reaction (OER) with water-assisted oxidation of organic molecules represents a promising approach for achieving sustainable electrochemical biomass utilization. Among numerous OER catalysts, spinels have received substantial attention due to their manifold compositions and valence states, yet their application in biomass conversions remains rare. Herein, a series of spinels were investigated for the selective electrooxidation of furfural and 5-hydroxymethylfurfural, two model substrates for versatile value-added chemical products. Spinel sulfides universally exhibit superior catalytic performance compared to that of spinel oxides, and further investigations show that the replacement of oxygen with sulfur led to the complete phase transition of spinel sulfides into amorphous bimetallic oxyhydroxides during electrochemical activation, serving as the active species. Excellent values of conversion rate (100%), selectivity (100%), faradaic efficiency (>95%), and stability were achieved via sulfide-derived amorphous CuCo-oxyhydroxide. Furthermore, a volcano-like correlation was established between their BEOR and OER activities based on an OER-assisted organic oxidation mechanism.

Interface Modulation of Metal Sulfide Anodes for Long-Cycle-Life Sodium-Ion Batteries.

Although studies of transition metal sulfides (TMS) as anode materials for sodium-ion batteries are extensively reported, the short cycle life is still a thorny problem that impedes their practical application. In this work, a new capacity fading mechanism of the TMS electrodes is demonstrated; that is, the parasitic reaction between electrolyte anions (i.e., ClO4 - ) and metal sulfides yields non-conductive and unstable solid-electrolyte interphase (SEI) and meanwhile, corrosively turns metal sulfides into less-active oxides. This knowledge guides the development of an electrochemical strategy to manipulate the anion decomposition and construct a stable interface that prevents extensive parasitic reactions. It is shown that introducing sodium nitrate to the electrolyte radically changes the Na+ solvation structure by populating nitrate ions in the first solvation sheath, generating a stable and conductive SEI layer containing both Na3 N and NaF. The optimized interface enables an iron sulfide anode to stably cycle for over 2000 cycles with negligible capacity loss, and a similar enhancement in cycle performance is demonstrated on a number of other metal sulfides. This work discloses metal sulfides' cycling failure mechanism from a unique perspective and highlights the critical importance of manipulating the interface chemistry in sodium-ion batteries.

Uncovering the Inhibitory Molecular Mechanism of Pomegranate Peel to Urinary Bladder Urothelial Carcinoma Using Proteomics Techniques.

Pomegranate (Punica granatum L.) fruit demonstrates the repressive effectiveness of many tumors. Our previous studies showed that the PEP (pomegranate peel extract) E2 fraction obtained from the ethyl acetate layer of the pomegranate peel's ethanol extract exhibited the highest inhibitory activities to induce Urinary bladder urothelial carcinoma (UBUC) cell apoptosis. The ethyl acetate layer could lower the volume and weight of T24 tumors and initiate apoptosis in nude mice xenografted bladder tumors. In this study, we intended to clarify the inhibitory molecular process of Taiwanese local pomegranate peel to urinary bladder urothelial carcinoma using a proteomics strategy. Gel-based proteomics (two-dimensional gel electrophoresis coupled with tandem mass spectrometry) was used to get an insight into the molecular mechanisms initiated by PEPE2 to evoke bladder cancer cell apoptosis. We found eleven down-regulated and eight up-regulated proteins in PEPE2-treated T24 cells. Our results implied that these PEPE2-dysregulated proteins belong to cell apoptosis, cell proliferation, death receptor signaling, JAK/STAT signaling, the PPAR pathway, the PPARα/RXR α pathway, Rho family GTPase signaling, and RhoGDI signaling. In addition, HSP90 and PTP1B proteins, associated with apoptosis, were de-regulated in xenografted bladder tumors in nude mice fed with an ethyl acetate layer of ethanol extract. The findings above implied that pomegranate might be a potential chemopreventive resource for UBUC carcinogenesis.

Highly Selective Electrocatalytic Oxidation of Amines to Nitriles Assisted by Water Oxidation on Metal-Doped α-Ni(OH)2.

Selective oxidation to synthesize nitriles is critical for feedstock manufacturing in the chemical industry. Current strategies typically involve substitutions of alkyl halides with toxic cyanides or the use of strong oxidation reagents (oxygen or peroxide) under ammoxidation/oxidation conditions, setting considerable challenges in energy efficiency, sustainability, and production safety. Herein, we demonstrate a facile, green, and safe electrocatalytic route for selective oxidation of amines to nitriles under ambient conditions, assisted by the anodic water oxidation on metal-doped α-Ni(OH)2 (a typical oxygen evolution reaction catalyst). By controlling the balance between co-adsorption of the amine molecule and hydroxyls on the catalyst surface, we demonstrate that Mn doping significantly promotes the subsequent chemical oxidation of amines, resulting in Faradaic efficiencies of 96% for nitriles under ≥99% conversion. This anodic oxidation is further coupled with cathodic hydrogen evolution for overall atomic economy and additional green energy production.

The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing.

Poor wound healing in individuals with diabetes has long plagued clinicians, and immune cells play key roles in the inflammation, proliferation and remodeling that occur in wound healing. When skin integrity is damaged, immune cells migrate to the wound bed through the actions of chemokines and jointly restore tissue homeostasis and barrier function by exerting their respective biological functions. An imbalance of immune cells often leads to ineffective and disordered inflammatory responses. Due to the maladjusted microenvironment, the wound is unable to smoothly transition to the proliferation and remodeling stage, causing it to develop into a chronic refractory wound. However, chronic refractory wounds consistently lead to negative outcomes, such as long treatment cycles, high hospitalization rates, high medical costs, high disability rates, high mortality rates, and many adverse consequences. Therefore, strategies that promote the rational distribution and coordinated development of immune cells during wound healing are very important for the treatment of diabetic wounds (DW). Here, we explored the following aspects by performing a literature review: 1) the current situation of DW and an introduction to the biological functions of immune cells; 2) the role of immune cells in DW; and 3) existing (or undeveloped) therapies targeting immune cells to promote wound healing to provide new ideas for basic research, clinical treatment and nursing of DW.

Boosting the performance of single-atom catalysts via external electric field polarization.

Single-atom catalysts represent a unique catalytic system with high atomic utilization and tunable reaction pathway. Despite current successes in their optimization and tailoring through structural and synthetic innovations, there is a lack of dynamic modulation approach for the single-atom catalysis. Inspired by the electrostatic interaction within specific natural enzymes, here we show the performance of model single-atom catalysts anchored on two-dimensional atomic crystals can be systematically and efficiently tuned by oriented external electric fields. Superior electrocatalytic performance have been achieved in single-atom catalysts under electrostatic modulations. Theoretical investigations suggest a universal "onsite electrostatic polarization" mechanism, in which electrostatic fields significantly polarize charge distributions at the single-atom sites and alter the kinetics of the rate determining steps, leading to boosted reaction performances. Such field-induced on-site polarization offers a unique strategy for simulating the catalytic processes in natural enzyme systems with quantitative, precise and dynamic external electric fields.

Single-Atom Tailoring of Two-Dimensional Atomic Crystals Enables Highly Efficient Detection and Pattern Recognition of Chemical Vapors.

Low-dimensional semiconductor materials, such as single-walled carbon nanotubes, two-dimensional (2D) atomic crystals, and organic frameworks, have been widely adapted as ideal platforms to construct various chemo/biosensors with satisfying sensitivity. However, the general drawbacks in chemiresistive devices, including high operation temperatures, low response to low-polarity molecules, and poor selectivity, have limited their real-world applications. In this study, 2D materials (graphene, MoS2, and WSe2) were systematically functionalized with series of monodispersed single atomic sites (Pt, Co, and Ru) through a facile approach to construct single-atom sensors (SASs) for the detection of VOCs at room temperature. The structural and catalytic characteristics of SAs successfully translated into enhanced gas-sensing performance, with a 1-2 orders of magnitude increase in relative response to ethanol (@5 ppm) and acetone (@20 ppm) vapors (in all M-2D SASs as compared to pristine substrates), high selectivity to VOCs against relative humidity (M-WSe2 SASs), and fast response/recovery time (11/58 s for Pt-Graphene and 22/48 s for Pt-MoS2 to 50 ppm ethanol, 9/57 s for Pt-Graphene and 15/75 s for Pt-MoS2 to 200 ppm acetone) that are several times faster than the pristine 2D materials. Density functional theory (DFT) calculations revealed the signaling mechanism in SASs, and the data were further trained to build machine learning (ML) models for predicting the adsorption energies and sensing performance using the features of adsorption heights, metal charge, and charge transfer between the adsorbed VOCs and SASs sites. Finally, the rich combination of the metal single atoms and 2D atomic crystal supports were converted to cross-sensitive SA sensor array that allows for detection and identification of different VOCs.

The ATO/miRNA-885-5p/MTPN axis induces reversal of drug-resistance in cholangiocarcinoma.

PURPOSE: Cholangiocarcinoma (CCA) is the second most malignant tumor of the hepatobiliary system. Due to its cumbersome early diagnosis and rapid progression, chemotherapy has become the main treatment option. Primary drug resistance is a major cause of the poor efficacy of chemotherapeutic drugs. Therefore, it is considered urgent to explore new drugs to overcome primary drug resistance of CCA. METHODS: Western blot and qRT-PCR assays were used to assess the expression of myotrophin (MTPN) and microRNA-885-5p (miR-885-5p) in CCA tissues and cells. The viability of CCA cells treated with arsenic trioxide (ATO), 5-fluorouracil (5-Fu) and cisplatin (CDDP) was analyzed using a CCK-8 assay. A luciferase reporter assay was used to assess the interaction between miR-885-5p and MTPN. Kaplan-Meier analyses were used for survival assessments. RESULT: We found that ATO can reduce the resistance of CCA cells to 5-Fu and CDDP and promote the killing effect of 5-Fu and CDDP. Low-dose ATO showed an anti-drug-resistance effect through up-regulation of the expression of miR-885-5p. Combined with sequencing results and database predictions, we found that MTPN may serve as a direct target of miR-885-5p. After MTPN knockdown, the sensitivity of CCA cells to 5-FU and CDDP was increased. Finally, we found that ATO can reverse chemotherapy resistance induced by overexpression of MTPN. CONCLUSION: Our data indicate that the ATO/miR-885-5p/MTPN axis may serve as a target for improving the sensitivity of CCA cells to chemotherapy.

Exertional heat stroke on fertility, erectile function, and testicular morphology in male rats.

The association of exertional heat stroke (EHS) and testicular morphological changes affecting sperm quality, as well as the association of EHS and hypothalamic changes affecting sexual behavior, has yet to be elucidated. This study aimed to elucidate the effects of EHS on fertility, erectile function, and testicular morphology in male rats. Animals were exercised at higher room temperature (36 ℃ relative humidity 50%) to induce EHS, characterized by excessive hyperthermia, neurobehavioral deficits, hypothalamic cell damage, systemic inflammation, coagulopathy, and multiple organ injury. In particular, EHS animals had erectile dysfunction (as determined by measuring the changes of intracavernosal pressure and mean arterial pressure in response to electrical stimulation of cavernous nerves). Rats also displayed testicular temperature disruption, poorly differentiated seminiferous tubules, impaired sperm quality, and atrophy of interstitial Leydig cells, Sertoli cells, and peri-tubular cells in the testicular tissues accompanied by no spermatozoa and broken cells with pyknosis in their seminal vesicle and prostatitis. These EHS effects were still observed after 3 days following EHS onset, at least. Our findings provide a greater understanding of the effect of experimentally induced EHS on masculine sexual behavior, fertility, stress hormones, and morphology of both testis and prostate.

The diagnostic value of exosomal miRNAs in human bile of malignant biliary obstructions.

BACKGROUND: Diagnosis of malignant biliary obstruction is complicated and lacks accuracy. Exosomes may be secreted by malignant tumors; intact miRNAs from exosomes might serve as potential biomarkers for the disease. AIM: To identify exosomal microRNAs in human bile among benign and malignant biliary obstructions. METHODS: Bile samples were collected from patients undergoing therapeutic endoscopic retrograde cholangiopancreatography for biliary obstruction. Exosome microRNAs were determined by RNA-sequencing in the discovery cohort, which comprising benign (n = 5) cases and malignant biliary obstruction (n = 5) cases. Then, the diagnostic performance of the two up-regulated microRNAs (mir-483-5p and mir-126-3p) of bile exosomes was verified by analysis of 82 patients with a diagnosis of malignant (n=37) or nonmalignant (n=45) biliary obstruction. RESULTS: In both cohorts, the expressions of mir-483-5p and mir-126-3p were significantly higher in bile exosomes samples from patients with malignant biliary obstructions than controls. In the verification cohort, the two miRNAs can distinguished the benign and malignant groups with high diagnostic accuracy and specificity; the diagnostic values of the two microRNAs were better than serum carbohydrate antigen 19-9 (CA19-9), area under the curve (AUC) were 0.81 and 0.74. CONCLUSION: The expression of exosomal mir-483-5p and mir-126-3p in the bile samples discriminates between patients with malignant and nonmalignant biliary obstructions. CLINICAL TRIAL REGISTRATION NO: NCT03102268.