Highly Stretchable, Self-Healing, and Sensitive E-Skins at -78 °C for Polar Exploration.

Ultralow temperature-tolerant electronic skins (e-skins) can endow polar robots with tactile feedback for exploring in extremely cold polar environments. However, it remains a challenge to develop e-skins that enable sensitive touch sensation and self-healing at ultralow temperatures. Herein, we describe the development of a sensitive robotic hand e-skin that can stretch, self-heal, and sense at temperatures as low as -78 °C. The elastomeric substrate of this e-skin is based on poly(dimethylsiloxane) supramolecular polymers and multistrength dynamic H-bonds, in particular with quadruple H-bonding motifs (UPy). The structure-performance relationship of the elastomer at ultralow temperatures is investigated. The results show that elastomers with side-chain UPy units exhibit higher stretchability (∼3257%) and self-healing efficiency compared to those with main-chain UPy units. This is attributed to the lower binding energy variation and lower potential well. Based on the elastomer with side-chain UPy and man-made electric ink, a sensitive robotic hand e-skin for usage at -78 °C is constructed to precisely sense the shape of objects and specific symbols, and its sensation can completely self-recover after being damaged. The findings of this study contribute to the concept of using robotic hands with e-skins in polar environments that make human involvement limited, dangerous, or impossible.

Three-dimensional laser micromachining system with integrated sub-100†nm resolution in-situ measurement.

In this study, a three-dimensional (3D) laser micromachining system with an integrated sub-100 nm resolution in-situ measurement system was proposed. The system used the same femtosecond laser source for in-situ measurement and machining, avoiding errors between the measurement and the machining positions. It could measure the profile of surfaces with an inclination angle of less than 10°, and the measurement resolution was greater than 100 nm. Consequently, the precise and stable movement of the laser focus could be controlled, enabling highly stable 3D micromachining. The results showed that needed patterns could be machined on continuous surfaces using the proposed system. The proposed machining system is of great significance for broadening the application scenarios of laser machining.

LncRNA NEAT1 targets miR-125/ADAM9 mediated NF-κB pathway in inflammatory response of rosacea.

OBJECTIVE: To investigate the role of NEAT1 targeted regulation of miR-125/ADAM9 mediated NF-κB pathway in inflammatory response in rosacea. METHOD: HaCaT cell rosacea phenotype was induced by LL37. The connection targeted by NEAT1 and miR-125a-5p was confirmed by Double-Luciferase report analysis. qPCR was employed to assess the levels of expression for NEAT1, miR-125a-5p, and ADAM9 genes. The levels of expression for ADAM9/TLR2/NF-κB P65 pathway proteins in each batch of cells were determined by Western blotting. The levels of expression for inflammatory factors, including TNF-α, IL-1ß, IL-6, and IL-18, were measured through ELISA experimentation. RESULTS: LL37 could successfully induce HaCaT cells to exhibit rosacea phenotype. The luciferase report experiment confirmed that NEAT1 could target and bind miR-125a-5p and inhibit its expression. ADAM9 exhibited increased expression in LL37-induced HaCaT cells, showing a positive association with NEAT1 expression and inverse relationship with miR-125a-5p activation. LL37 treatment promoted the expression of ADAM9/TLR2/NF-κB P65 pathway proteins. Silencing ADAM9 can inhibit the inflammatory signaling pathway and reduce the level of TNF-α, IL-1ß, IL-6, and IL-18 in HaCaT cells. CONCLUSION: NEAT1 can suppress the production of miR-125a-5p and activate the TLR2/NF-κB inflammatory pathway mediated by ADAM9, thereby promoting the inflammatory response in rosacea.

Prevalence of multidrug-resistant bacterial infections in diabetic foot ulcers: A meta-analysis.

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.

Mechanical strength changes of combustible municipal solid waste components during their early pyrolysis stage and mechanism analysis.

Implementation of municipal solid waste (MSW) source segregation leads to a more convenient recycle of combustible MSW components. Textiles, plastics and papers are commonly available combustible components in MSW. Their shredding is conducive to resources recovery. But these components usually have high tensile strengths and are difficult to shred. To understand their mechanical strength changes in their early pyrolysis stage will help to address this problem. In this study, a universal electronic testing machine was used to determine the breaking strengths of the materials including cotton towel, polyethylene glycol terephthalate (PET), ivory board (IB), kraft paper (KP) and wool scarf in the temperature range of 30-250°C under N2 atmosphere, and the mechanisms of their strength changes were explored. The reaction force field molecular dynamics (ReaxFF-MD) simulation was used to explain the decomposition behaviours of different sugar groups of hemicellulose in cotton and paper and the change of van der Waals energy of wool during their early pyrolysis stages. The results showed that breaking strengths of all the combustible MSW components reduced as the temperature increased. The breaking strength of PET was found to have the highest descent rate with increasing temperature, then the descent rates of wool and cotton came as the second and third, respectively. Compared with cotton, the breaking strengths of KP and IB decreased more slowly. As the temperature increased, the breaking strength of cotton reduced mainly due to the decomposition of the glucuronic acid in hemicellulose, and the reduction was characterized by CO2 release. The breaking strength reduction of PET was caused by its molecular chain being relaxed. The breaking strength reduction of wool was firstly caused by the decrease in the van der Waals energy between its molecules, and then caused by molecular chain breaking. In addition, in order to understand the influence of material size on the breaking strength change during thermal treatment, the breaking strengths of cotton yarn bundles were correlated with their yarn number and temperature. This study lays the foundation for understanding changes in mechanical strengths of combustible MSW components during their early pyrolysis stage.

An Extreme-Environment-Resistant Self-Healing Anti-Icing Coating.

Anti-icing coatings on outdoor infrastructures and transportations inevitably suffer from surface injuries, especially in extreme weather events (e.g., freezing weather or acid rain). The coating surface damage can result in anti-icing performance loss or even icing promotion. The development of anti-icing coatings that enables self-healing in extreme conditions is highly desired but still challenging. Herein, an extreme-environment-resistant self-healing anti-icing coating is developed by integrating fluorinated graphene (FG) into a supramolecular polymeric matrix. The coating exhibits both anti-icing and deicing performance (ice nucleation temperature is ≈-30.3 °C; ice shear strength is ≈48.7 kPa), mainly attributable to the hydrophobic FG and silicone-based supramolecular material. Notably, owing to the crosslinking polymeric network with various dynamic bonds, this coating can sustain anti-icing/deicing performance after autonomous self-healing under harsh conditions including low temperature (-20 °C), strong acid (pH = 0), and strong alkali (pH = 14) environments. This coating paves the way to meet the anti-icing demand in open air, especially for the infrastructures in polar regions or acid/alkali environments.

Homeobox A4 suppresses vascular remodeling by repressing YAP/TEAD transcriptional activity.

The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes-associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD-mediated gene expressions involved in vascular pathophysiology remains to be elucidated. Here, we identified Homeobox A4 (HOXA4) as a potent repressor of YAP/TEAD transcriptional activity using lentiviral shRNA screen. Mechanistically, HOXA4 interacts with TEADs and attenuates YAP/TEAD-mediated transcription by competing with YAP for TEAD binding. We also clarified that the expression of HOXA4 is relatively abundant in the vasculature, especially in VSMCs. In vitro experiments in human VSMCs showed HOXA4 maintains the differentiation state of VSMCs via inhibition of YAP/TEAD-induced phenotypic switching. We generated Hoxa4-deficient mice and confirmed the downregulation of smooth muscle-specific contractile genes and the exacerbation of vascular remodeling after carotid artery ligation in vivo. Our results demonstrate that HOXA4 is a repressor of VSMC phenotypic switching by inhibiting YAP/TEAD-mediated transcription.

Development and initial validation of the Chinese Version of the Noise Exposure Questionnaire (C-NEQ).

BACKGROUND: With a high prevalence of noise-induced hearing loss (NIHL), the noise survey tools for identifying individuals with high risk of NIHL are still limited. This study was aimed to translate and develop a Chinese version of noise exposure questionnaire (C-NEQ), and validate its reliability and reproducibility. METHODS: This study was conducted from May 2020 to March 2021 in China. The questionnaire was translated from the original NEQ and adapted into Chinese culture using the method according to the International Test Committee. Content validity was evaluated by our expert group. Construct validity and reliability of the C-NEQ was determined through estimating the confirmatory factor analysis and Cronbach's alpha in a cross-sectional analysis among 641 Chinese speaking adults, respectively. The retest reproducibility of the C-NEQ was analyzed by using the intra-group correlation coefficient (ICC) in a follow-up analysis among 151 participants. RESULTS: The C-NEQ comprises ten items covering four domains: occupational, housework, transport and recreational noise exposure. The annual noise exposure (ANE) was calculated as the protocol of original NEQ. A total of 641 adult participants (aged 26.9 ± 10.1 years, 53.4% males) completed the C-NEQ. The average time for completing the C-NEQ was 4.4 ± 3.0 min. Content validity indicated high relevance of the C-NEQ. The confirmatory factor analysis indices illustrated that the items of the C-NEQ were suitable with the data in the study. For the internal reliability, the Cronbach's α coefficients of the total items and four domains (occupational, housework, transport, and recreational noise exposure) were 0.799, 0.959, 0.837, 0.825, and 0.803, respectively. Among them, 151 participants (aged 36.1 ± 11.1 years, 65.6% males) completed the retest of the C-NEQ 1 month after the first test. The ICC value of total ANEs between the first test and the second test was 0.911 (P < 0.001). CONCLUSIONS: In this study, we have validated the C-NEQ with adequate reliability and reproducibility for quantifying an individual's annual daily noise exposure, which provides an effective fast-screen tool for researches and clinics to identify those individuals with high risks of NIHL within the short time duration (no more than five minutes) among Chinese population.

Machine vision-based high-precision and robust focus detection for femtosecond laser machining.

We propose a machine vision-based focus detection method (MVFD) for femtosecond laser machining. By analyzing the laser focus pattern, the defocus direction and distance are obtained simultaneously. The proposed technique presents high precision with an average error of 0.047 µm and a root mean square error (RMSE) of 0.055 µm. Moreover, the method is robust and is less affected by the tilted sample. For the curved surface sample, the average error and RMSE are 0.093 and 0.145 µm, respectively. Thus, the proposed focus detection method can be easily combined with laser processing equipment, which is widely used in large-range and high-precision femtosecond laser processing.

LncRNA PICSAR binds to miR-485-5p and activates TGF-ß1/Smad to promote abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and excessive deposition of extracellular matrix (ECM).

The purpose of this study is to explore whether LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-ß1/Smad signaling pathway, influencing the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation. PICSAR and miR-485-5p expressions were detected by qPCR. Cell proliferation was examined by CCK-8. Protein expressions were determined by western blot. Immunofluorescence detected the Ki-67 expression. Dual-luciferase followed by immunoprecipitation was performed to verify the interaction between PICSAR and miR-485-5p. Interference with PICSAR inhibited the abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and the excessive deposition of ECM. It was also confirmed in our study that MiR-485-5p is a direct target of PICSAR in HSFs. Additionally, inhibition of miR-485-5p reversed the effect of PICSAR knockdown in HSFs. LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-ß1/Smad signaling pathway, promoting the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation.

Novel Nano Drug-Loaded Hydrogel Coatings for the Prevention and Treatment of CAUTI.

Catheter-associated urinary tract infection (CAUTI) is a prevalent type of hospital-acquired infection, affecting approximately 15% to 25% of patients with urinary catheters. Long-term use of the catheter can lead to colonization of microorganisms and biofilm formation, and may develop into bacterial CAUTI. However, the frequent replacement of catheters in clinical settings can result in tissue damage, inflammation, ulceration, and additional complications, causing discomfort and pain for patients. In light of these challenges, a novel nanodrug-supported hydrogel coating called NP-AM/FK@OMV-P/H has been developed in this study. Through in vitro experiments, it is confirmed that OMV nano-loaded liquid gel coating has an effective reaction against E.coli HAase and releases antibacterial drugs. This coating has also demonstrated strong inhibition of E.coli and has shown the ability to inhibit the formation of bacterial biofilm. These findings highlight the potential of the OMV nanoparticle gel coating in preventing and treating bacterial infections. Notably, NP-AM/FK@OMV-P/H has exhibited greater efficacy against multidrug-resistant E.coli associated with UTIs compared to coatings containing single antimicrobial peptides or antibiotics. Additionally, it has demonstrated good biosecurity. In conclusion, the NP-AM/FK@OMV-P/H coating holds great potential in providing benefits to patients with CAUTI.

An isothermal nucleic acid amplification-based enzymatic recombinase amplification method for dual detection of porcine epidemic diarrhea virus and porcine rotavirus A.

Viral diarrhea is the predominant digestive tract sickness in piglings, resulting in substantial profit losses in the porcine industry. Porcine rotavirus A (PoRVA) and porcine epidemic diarrhea virus (PEDV) are the main causes of grave gastroenteritis and massive dysentery, especially in piglets. PoRVA and PEDV have high transmissibility, exhibit similar clinical symptoms, and frequently co-occur. Therefore, to avoid financial losses, a quick, highly efficient, objective diagnostic test for the prevention and detection of these diseases is required. Enzymatic recombinase amplification (ERA) is a novel technology based on isothermal nucleic acid amplification. It demonstrates high sensitivity and excellent specificity, with a short processing time and easy operability, compared with other in vitro nucleic acid amplification technologies. In this study, a dual ERA method to detect and distinguish between PEDV and PoRVA nucleic acids was established. The method shows high sensitivity, as the detection limits were 101 copies/µL for both viruses. To test the usefulness of this method in clinical settings, we tested 64 swine clinical samples. Our results were 100% matched with those acquired using a commercially available kit. Therefore, we have successfully developed a dual diagnostic ERA nucleic acids method for detecting and distinguishing between PEDV and PoRVA.

Demographic and zoological drivers of infectome diversity in companion cats with ascites.

Cats (Felidae) have become an integral part of many households. However, our understanding of the full spectrum of pathogens affecting cats (referred to as the infectome) is limited, mainly due to the inadequacy of commonly used diagnostic tools in capturing the complete diversity of potential pathogens and the prevalence of pathogen co-infections. In this study, we employed a meta-transcriptomic approach to simultaneously characterize the infectome contributing to different disease syndromes and to investigate spatial, demographic, and ecological factors influencing pathogen diversity and community composition in a cohort of 27 hospitalized cats and seven stray cats. We identified 15 species of pathogens, with Candidatus Rickettsia tarasevichiae and Tritrichomonas foetus representing potential spillover risks. Importantly, although most cases of ascites hyperplasia were explained by coinfection with multiple pathogens, we identified the potential novel clinical outcomes of M. aubagnense infection among cats. We demonstrated that the increase in infectome diversity can be explained by a variety of predictors including age growth, temperature increase, and a higher proportion of females, with age growth presenting the strongest effect. Fine-scale analysis indicated that a higher diversity of infectomes were harbored in young cats rather than adult ones. Our results demonstrated that most feline diseases are better explained by the presence of virus-bacteria or virus-virus coinfection. This study serves as a timely endorsement for clinical diagnosis by vets to consider the cause of a disease based on a panel of cryptical co-infecting pathogens rather than on individual infectious agents. IMPORTANCE: Frequent studies reported the risks of cats as an intermediate host of zoonotic pathogens (e.g., SARS-CoV-2). Cats have a physically close interaction with their owners through activities like petting, kissing, and being licked on the cheek and hands. However, there are still limited studies that systematically investigate the infectome structure of cats. In this study, we employed a meta-transcriptomics approach to characterize 15 species of pathogens in cats, with Candidatus Rickettsia tarasevichiae first characterizing infection in diseased cats. Most feline diseases were better explained by the presence of virus-bacteria or virus-virus coinfection. The increase in infectome diversity could be influenced by a variety of predictors including age growth, temperature increase, and a higher proportion of females. A higher diversity of pathogens was harbored in young cats rather than adults. Importantly, we showed the value of linking the modern influx of meta-transcriptomics with comparative ecology and demography and of utilizing it to affirm that ecological and demographic variations impact the total infectome.

Spider-silk-inspired strong and tough hydrogel fibers with anti-freezing and water retention properties.

Ideal hydrogel fibers with high toughness and environmental tolerance are indispensable for their long-term application in flexible electronics as actuating and sensing elements. However, current hydrogel fibers exhibit poor mechanical properties and environmental instability due to their intrinsically weak molecular (chain) interactions. Inspired by the multilevel adjustment of spider silk network structure by ions, bionic hydrogel fibers with elaborated ionic crosslinking and crystalline domains are constructed. Bionic hydrogel fibers show a toughness of 162.25 ± 21.99 megajoules per cubic meter, comparable to that of spider silks. The demonstrated bionic structural engineering strategy can be generalized to other polymers and inorganic salts for fabricating hydrogel fibers with broadly tunable mechanical properties. In addition, the introduction of inorganic salt/glycerol/water ternary solvent during constructing bionic structures endows hydrogel fibers with anti-freezing, water retention, and self-regeneration properties. This work provides ideas to fabricate hydrogel fibers with high mechanical properties and stability for flexible electronics.

Lactobacillus rhamnosus GG improves cognitive impairments in mice with sepsis.

Background: Survivors of sepsis may encounter cognitive impairment following their recovery from critical condition. At present, there is no standardized treatment for addressing sepsis-associated encephalopathy. Lactobacillus rhamnosus GG (LGG) is a prevalent bacterium found in the gut microbiota and is an active component of probiotic supplements. LGG has demonstrated to be associated with cognitive improvement. This study explored whether LGG administration prior to and following induced sepsis could ameliorate cognitive deficits, and explored potential mechanisms. Methods: Female C57BL/6 mice were randomly divided into three groups: sham surgery, cecal ligation and puncture (CLP), and CLP+LGG. Cognitive behavior was assessed longitudinally at 7-9d, 14-16d, and 21-23d after surgery using an open field test and novel object recognition test. The impact of LGG treatment on pathological changes, the expression level of brain-derived neurotrophic factor (BDNF), and the phosphorylation level of the TrkB receptor (p-TrkB) in the hippocampus of mice at two weeks post-CLP (16d) were evaluated using histological, immunofluorescence, immunohistochemistry, and western blot analyses. Results: The CLP surgery induced and sustained cognitive impairment in mice with sepsis for a minimum of three weeks following the surgery. Compared to mice subjected to CLP alone, the administration of LGG improved the survival of mice with sepsis and notably enhanced their cognitive functioning. Moreover, LGG supplementation significantly alleviated the decrease in hippocampal BDNF expression and p-TrkB phosphorylation levels caused by sepsis, preserving neuronal survival and mitigating the pathological changes within the hippocampus of mice with sepsis. LGG supplementation mitigates sepsis-related cognitive impairment in mice and preserves BDNF expression and p-TrkB levels in the hippocampus.

CRISPR-Cas9-guided amplification-free genomic diagnosis for familial hypercholesterolemia using nanopore sequencing.

Familial hypercholesterolemia is an inherited disorder that remains underdiagnosed. Conventional genetic testing methods such as next-generation sequencing (NGS) or target PCR are based on the amplification process. Due to the efficiency limits of polymerase and ligase enzymes, these methods usually target short regions and do not detect large mutations straightforwardly. This study combined the long-read nanopore sequencing and CRISPR-Cas9 system to sequence the target DNA molecules without amplification. We originally designed and optimized the CRISPR-RNA panel to target the low-density lipoprotein receptor gene (LDLR) and proprotein convertase subtilisin/kexin type 9 gene (PCSK9) from human genomic DNA followed by nanopore sequencing. The average coverages for LDLR and PCSK9 were 106× and 420×, versus 1.2× for the background genome. Among them, continuous reads were 52x and 307x, respectively, and spanned the entire length of LDLR and PCSK9. We identified pathogenic mutations in both coding and splicing donor regions in LDLR. We also detected an 11,029 bp large deletion in another case. Furthermore, using continuous long reads generated from the benchmark experiment, we demonstrated how a false-positive 670 bp deletion caused by PCR amplification errors was easily eliminated.

Pathogenicity and horizontal transmission evaluation of a novel isolated African swine fever virus strain with a three-large-fragment-gene deletion.

African swine fever has caused substantial economic losses to China`s pig industry in recent years. Currently, the highly pathogenic African swine fever virus strain of genotype II is predominantly circulating in China, accompanied by a series of emerging isolates displaying unique genetic variations. The pathogenicity of these emerging strains is still unclear. Recently, a novel ASFV strain with a distinguishable three-large-fragment gene deletion was obtained from the field specimens, and its in vivo pathogenicity and transmission were evaluated in this study. The animal experiment involved inoculating a high dose of YNFN202103 and comparing its effects with those of the highly pathogenic strain GZ201801_2. Results showed that pigs infected by YNFN202103 exhibited significantly prolonged onset and survival time, lower viremia levels, and less severe histopathological lesions compared to GZ201801_2. These findings contributed valuable insights into the pathogenicity and transmission of ASFV and its prevention and eradication strategies in practical settings.

KUS121, a VCP modulator, has an ameliorating effect on acute and chronic heart failure without calcium loading via maintenance of intracellular ATP levels.

AIMS: As heart failure (HF) progresses, ATP levels in myocardial cells decrease, and myocardial contractility also decreases. Inotropic drugs improve myocardial contractility but increase ATP consumption, leading to poor prognosis. Kyoto University Substance 121 (KUS121) is known to selectively inhibit the ATPase activity of valosin-containing protein, maintain cellular ATP levels, and manifest cytoprotective effects in several pathological conditions. The aim of this study is to determine the therapeutic effect of KUS121 on HF models. METHODS AND RESULTS: Cultured cell, mouse, and canine models of HF were used to examine the therapeutic effects of KUS121. The mechanism of action of KUS121 was also examined. Administration of KUS121 to a transverse aortic constriction (TAC)-induced mouse model of HF rapidly improved the left ventricular ejection fraction and improved the creatine phosphate/ATP ratio. In a canine model of high frequency-paced HF, administration of KUS121 also improved left ventricular contractility and decreased left ventricular end-diastolic pressure without increasing the heart rate. Long-term administration of KUS121 to a TAC-induced mouse model of HF suppressed cardiac hypertrophy and fibrosis. In H9C2 cells, KUS121 reduced ER stress. Finally, in experiments using primary cultured cardiomyocytes, KUS121 improved contractility and diastolic capacity without changing peak Ca2+ levels or contraction time. These effects were not accompanied by an increase in cyclic adenosine monophosphate or phosphorylation of phospholamban and ryanodine receptors. CONCLUSIONS: KUS121 ameliorated HF by a mechanism totally different from that of conventional catecholamines. We propose that KUS121 is a promising new option for the treatment of HF.

Evidence-based complementary and alternative medicine conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility: A systematic review and meta-analysis.

BACKGROUND: Chinese medicinal retention enemas have gradually attracted the attention of clinicians as an alternative approach for tubal obstructive infertility. The purpose of this study was to investigate the efficacy and safety of conventional surgery combined with traditional Chinese medicinal retention enemas for the treatment of tubal obstructive infertility. MATERIALS AND METHODS: Eight electronic databases were searched from their inception to November 30, 2022. To assess the efficacy and safety of different treatments, following outcomes were measured: clinical pregnancy rate, clinical total effective rate, incidence of ectopic pregnancy, the improvement of Traditional Chinese Medicinal (TCM) symptoms, the improvement of the signs of obstructive tubal infertility and side effects. RESULTS: A total of 23 Randomized Controlled Trials (RCTs) with 1909 patients met the inclusion criteria. The pooled results showed a higher pregnancy rate in the experimental group than in the control group (RR 1.75, 95% CI [1.58, 1.94], Z = 10.55, P<0.00001). The clinical total effective rate in the experimental group was higher than that in the control group (RR 1.28, 95% CI [1.23, 1.34], Z = 11.07, P<0.00001). The incidence of ectopic pregnancy in the experimental group was lower than that in the control group (RR 0.40, 95% CI [0.20, 0.77], Z = -2.73, P = 0.01). CONCLUSION: Based on current evidence, we concluded that conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility was superior to conventional surgery alone in improving the clinical pregnancy rate, improving clinical total effective rate, improving TCM symptoms, improving the signs of obstructive tubal infertility and lowering the incidence of ectopic pregnancy. However, further clinical trials with high-quality methodologies need to be conducted.

Rapid visual detection of the allergen Dermatophagoides farinae in house dust by loop-mediated isothermal amplification.

Dermatophagoides farinae is considered to be an important factor causing some allergic diseases, such as urticaria, allergic rhinitis, asthma, and other interrelated diseases. Avoiding exposure to allergens is the most effective way to reduce allergic reactions. In this study, we successfully established a loop-mediated isothermal amplification (LAMP) method for the detection of D. farinae DNA target internal transcribed spacer (ITS) and D. farinae 1 allergen (Der f 1) genes. The turbidity-monitoring system and visual fluorescent reagents were used to verify the test results of LAMP assay. Following optimization of the primers and reaction temperatures, the amplification sensitivity, specificity, and efficiency of the method for detecting D. farinae were assessed. There was no cross-reaction with other arthropod species that are commonly found in indoor environmental dust, such as Dermatophagoides pteronyssinus, Alophagoides ovatus, Periplaneta americana, Anopheles sinensis, and Musca domestica. Furthermore, the sensitivity of LAMP assay for detecting D. farinae DNA was 10 times greater than that of conventional PCR. The positive detection rate by the LAMP method was greater than the conventional PCR for both single D. farinae mites and D. farinae mites in indoor dust. A new type of LAMP method for D. farinae based on the Der f 1 and ITS genes was, therefore, successfully established. This study is the first time to detect the D. farinae allergen using LAMP assay. This assay could be useful as a model for the rapid detection of allergens produced by other house dust mites in the future.