Comparative effects of sacubitril/valsartan and ACEI/ARB on endothelial function and arterial stiffness in patients with heart failure: a protocol for systematic review and meta-analysis.

INTRODUCTION: Heart failure (HF) is a complex syndrome that affects millions of people worldwide and leads to significant morbidity and mortality. Sacubitril/valsartan, a combination drug consisting of a neprilysin inhibitor and an angiotensin receptor blocker (ARB), has shown a greater improvement in the prognosis of HF than ACE inhibitors (ACEI) or ARB. Recent studies have found that ACEI/ARB or sacubitril/valsartan can increase flow-mediated dilation (FMD) and reduce pulse wave velocity (PWV), which are independent predictors of cardiovascular events and HF prognosis. The purpose of this study is to assess and compare the effect of sacubitril/valsartan and ACEI/ARB on FMD and PWV using meta-analysis and further provide a reference for the role of sacubitril/valsartan in the treatment of HF. METHODS AND ANALYSIS: Clinical randomised controlled trials investigating the effect of sacubitril/valsartan and/or ACEI/ARB on FMD and PWV in patients with HF will be searched in the relevant database, including PubMed, Web of Science, Embase, Cochrane Library and China's National Knowledge Infrastructure up to January 2024. The outcomes of interest are changes in endothelial function assessed by FMD and changes in arterial stiffness assessed by PWV. The risk of bias was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB2.0). Review Manager V.5.3 software is used for meta-analysis data synthesis, sensitivity analysis, meta-regression analysis, subgroup analysis and risk of bias assessment. The reporting bias of studies will be evaluated using the funnel plot, in which symmetry will be assessed by Begg's and Egger's tests. The evidence quality of the included studies will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation. ETHICS AND DISSEMINATION: This study only analyses research data from the published literature and therefore does not require ethical approval. We will submit the systematic review to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42024538148.

Rapid Detection of Getah Virus Antibodies in Horses Using a Recombinant E2 Protein-Based Immunochromatographic Strip.

The prevalence and impact of Getah virus (GETV) are significant concerns in China. GETV can infect a wide range of animals, including horses, pigs, sheep, cattle, birds, and humans, resulting in substantial losses in the livestock and agricultural industries. GETV infection can cause the development of ulcers and inflammation in the mouth and gums of horses, which result in pain and discomfort and lead to symptoms such as reduced appetite, drooling, and difficulty chewing. As a result, there is a pressing need for efficient and rapid disease diagnosis methods. However, the currently available diagnostic methods have limitations in terms of operational time, equipment, and the experience of the individuals using them. In this study, a rapid, specific, and sensitive detection method was developed using a colloidal gold-based immunochromatographic strip (ICS) for the detection of antibodies against GETV in horses. To prepare the ICS, the antigen domain of the E2 glycoprotein of GETV was expressed using the Escherichia coli expression system after analysis with DNAstar v7.1 software. The nitrocellulose membrane was coated with rE2 protein or SPA to form the test line and control line, respectively. After optimizing the reaction conditions, the sensitivity, specificity, and repeatability of the strip were verified. The results showed that the test strip had a detection limit of up to 1:320 dilutions for GETV-positive serum, with no cross-reactivity observed with other equine-susceptible pathogens such as equine arteritis virus (EAV), equine herpesvirus-1 (EHV-I), equine infectious anemia virus (EIAV), equine influenza virus (EIV), African horse sickness virus (AHSV), and Japanese encephalitis virus (JEV). Furthermore, the ICS exhibited a concordance rate of 94.0% when testing 182 clinical serum samples compared to the virus neutralization test. Overall, this ICS diagnosis method will be an effective tool for the rapid detection of GETV in the field.

Epidermoid Cyst at the Root of the Sphenoidal Pterygoid Process: A Rare Case Report.

Epidermoid cysts of the skull base are rare. We present the case of a woman with an epidermoid cyst at the root of the sphenoidal pterygoid process. She experienced tightness of the forehead skin without headache. Computed tomography (CT) scan revealed a hypodense lesion at the base of the skull in the right middle cranial fossa, which had partly eroded the pterygoid root. Magnetic resonance imaging (MRI) scan revealed a soft cystic mass that eroded the pterygoid root with hypo-/iso-intense on T1-weighted images, hyperintense on T2-weighted images, inhomogeneous hyperintense on diffusion-weighted images, a slightly low apparent diffusion coefficient, and no enhancement, suggesting a diagnosis of an epidermoid cyst. Surgical excision was performed using a nasal endoscope via the pterygoid process-root approach. A histopathological examination confirmed the diagnosis of an epidermoid cyst. At the 6-month follow-up, no recurrence was found on MRI or nasal endoscopy, and the symptoms of forehead tightness disappeared. In conclusion, epidermoid cysts at the root of the sphenoidal pterygoid process are exceptionally rare. Preoperative MRI and CT scans are necessary for the correct diagnosis and differentiation of other low-growing lesions. Nasal endoscopy is crucial for surgical excision and postoperative follow-up for potential recurrence.

The role of potassium ion channels in chronic sinusitis.

Chronic sinusitis is a common inflammatory disease of the nasal and sinus mucosa, leading to symptoms such as nasal congestion, runny nose, decreased sense of smell, and headache. It often recurs and seriously affects the quality of life of patients. However, its pathological and physiological mechanisms are not fully understood. In recent years, the role of potassium ion channels in the regulation of mucosal barrier function and inflammatory cell function has received increasing attention. In chronic sinusitis, there are often changes in the expression and function of potassium channels, leading to mucosal damage and a stronger inflammatory response. However, the related research is still in its early stages. This article will review the role of the potassium channel in the pathological and physiological changes of chronic sinusitis. The studies revealed that BK/TREK-1 potassium channel play a protective role in the nasal mucosal function through p38-MAPK pathway, and KCa3.1/Kv1.3 enhance the inflammatory response of Chronic rhinosinusitis by regulating immune cell function, intracellular Ca2+ signaling and ERK/MAPK/NF-κB pathway. Because ion channels are surface proteins of cell membranes, they are easier to intervene with drugs, and the results of these studies may provide new effective targets for the prevention and treatment of chronic sinusitis.

Robust bifunctionality in an oxygen electrode via core-shell heterostructure construction.

A Co-CoSe core-shell heterostructure encapsulated into nitrogen-doped carbon nanotubes enables superior zinc air battery performance (172 mW cm-2) and stability (970 h). The enhanced bifunctionality and stability originates from the modulated d band center and confinement effect, respectively.

METTL3-induced circ_0008345 contributes to the progression of colorectal cancer via the microRNA-182-5p/CYP1A2 pathway.

BACKGROUND: Circular RNA (circRNAs) have been found to play major roles in the progression of colorectal cancer (CRC). However, the functions of circ_0008345 (transcribed by PTK2) in regulating CRC development remain undefined. In this study, we aimed to explore the roles and underlying mechanisms of circ_0008345 in CRC. METHODS: RNase R-treated total cellular RNA was used to verify the circular structure of circ_0008345, and a subcellular fractionation assay was performed to detect the subcellular localization of circ_0008345. RNA pull-down and dual-luciferase assays were used to verify the binding relation between microRNA (miR)-182-5p and circ_0008345 and/or CYP1A2. Colony formation assay, EdU, and Transwell assays were performed to detect the biological behavior of CRC cells in vitro, and CRC cells were injected into mice to observe the tumor formation. m6A immunoprecipitation was used to detect the m6A modification of circ_0008345 in CRC cells. RESULTS: Circ_0008345, upregulated in CRC tissues and cells, was mainly present in the cytoplasm. Circ_0008345 bound to miR-182-5p, and miR-182-5p targeted CYP1A2, an oncogene in CRC. The colony formation, mobility, EdU-positive cell rate in vitro, and tumor growth in mice were inhibited after the knockdown of circ_0008345. However, the suppressing effects of sh-circ_0008345 on CRC and CYP1A2 expression were significantly reversed after further knockdown of miR-182-5p. METTL3 was the m6A modifier mediating circ_0008345 expression, and the suppression of METTL3 reduced the expression of circ_0008345. CONCLUSIONS: METTL3-dependent m6A methylation upregulated circ_0008345, which blocked the inhibitory effect of miR-182-5p on CYP1A2, thereby exacerbating the malignant phenotype of CRC cells.

Modulation in work function of CoTe as bifunctional electrocatalyst for rechargeable zinc air battery.

The sluggish kinetics and inferior stability of oxygen electrocatalyst in rechargeable zinc air battery (ZAB) hamper its industrialization. In this work, we activate cobalt telluride (CoTe) by introduction of metallic cobalt (Co) to modulate the work function to facilitate the electron transfer from Co to CoTe during oxygen catalysis; additionally, the three-dimensional porous carbon nanosheets (3DPC) are invited to reduce the resistance towards electrolyte/oxygen diffusion. Thereby, Co-CoTe@3DPC only demands 280 mV overpotential to reach 10 mA cm-2 under alkaline oxygen evolution reaction (OER) condition, relatively lower than commercial iridium oxides (IrO2); besides, the operando electrochemical impedance spectroscopy (EIS) indicates a better resistance towards surface reconstruction than Co@3DPC leading to a superior stability. A Pt-like oxygen reduction reaction (ORR) performance, half-wave potential associated with kinetic current density, is achieved for Co-CoTe@3DPC. A maximum power density of 203 mW cm-2 is achieved and sustains for 800 h. Furthermore, the all-solid-state ZAB offers 97 mW cm-2. Theoretical calculation suggests that the incorporation of metallic Co to CoTe maintains the superb ORR activity and promotes the OER catalysis.

Porcine reproductive and respiratory syndrome virus nsp4-mediated ß2M downregulation contributes to SLA-I decrease and virus infection in vivo and in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient antigen presentation and subsequent low levels of cellular PRRSV-specific immunity as well as persistent viremia. We previously observed that the non-structural protein 4 (nsp4) of PRRSV contributed to inhibition of the ß2-microglobulin (ß2M) and SLA-I expression in cells. Here, we constructed a series of nsp4 mutants with different combination of amino acid mutations to attenuate the inhibitory effect of nsp4 on ß2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of ß2M and SLA-I expression, but the recombinant PRRSV harboring these nsp4 mutants failed to be rescued with exception of the rPRRSV-nsp4-mut10 harboring three amino acid mutations. However, infection of rPRRSV-nsp4-mut10 not only enhanced ß2M and SLA-I expression in both cells and pigs but also promoted the DCs to active the CD3+CD8+T lymphocytes more efficiently, as compared with its parental PRRSV (rPRRVS-nsp4-wt). These data suggested that the inhibition of nsp4-mediated ß2M downregulation improved ß2M/SLA-I expression in pigs.

Two Enterococcus faecium Isolates Demonstrated Modulating Effects on the Dysbiosis of Mice Gut Microbiota Induced by Antibiotic Treatment.

Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.

Development and biological characterization of an infectious cDNA clone of NADC34-like PRRSV.

Introduction: Porcine Reproductive and Respiratory Syndrome virus (PRRSV) causes high abortion rates in gestating sows and stillbirths, as well as high piglet mortality, seriously jeopardizing the pig industry in China and worldwide. Methods: In this study, an infectious clone containing the full-length genome of NADC34-like PRRSV was constructed for the first time using reverse genetic techniques. The gene was amplified segmentally onto a plasmid, transfected into BHK-21 cells, and the transfected supernatant was harvested and transfected into PAM cells, which showed classical cytopathic effects (CPE). Results: The virus rJS-KS/2021 was successfully rescued which could be demonstrated by Western Blot and indirect immunofluorescence assays. Its growth curve was similar to the original strain. Replace the 5'UTR and 3'UTR of rJS-KS/2021 with 5'UTR and 3'UTR of HP-PRRSV (strain SH1) also failed to propagate on MARC-145. Discussion: In this study, an infectious clone of NADC34-like was constructed by reverse genetics, replacing the UTR and changing the cellular tropism of the virus. These findings provide a solid foundation for studying the recombination of different PRRSVs and the adaption of PRRSVs on MARC-145 in the future.

Immunogenicity and Protective Capacity of Sugar ABC Transporter Substrate-Binding Protein against Streptococcus suis Serotype 2, 7 and 9 Infection in Mice.

Background:Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis.

A superior zinc-air battery performance achieved by CoO/Fe3O4 heterostructured nanosheets.

CoO/Fe3O4 nanosheets exhibit a superior rechargeable zinc-air battery (ZAB) performance of 276 mW cm-2 and stability over 600 h. The all-solid-state ZAB also affords a high power density of 107 mW cm-2.

Corrigendum: A metagenomic analysis of mosquito virome collected from different animal farms at Yunnan-Myanmar border of China.

[This corrects the article DOI: 10.3389/fmicb.2020.591478.].

Heat shock protein 71 restricts mutation of porcine reproductive and respiratory syndrome virus nsp2 in vitro.

porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV) infection, is an important swine infectious disease that causes substantial losses worldwide each year. PRRSV is a positive-sense single-stranded RNA virus that is highly susceptible to mutation and recombination, making vaccine and drug research for the disease extremely difficult. In this study, the binding of PRRSV nsp2 to HSP71 protein was detected by using the IP/MS technique. And the inhibitory effect of HSP71 on nsp2 antagonistic activity was validated by measuring NF-kB luciferase reporter. According to stress from inhibitory effects, the amino acid variation profile of PRRSV nsp2 under HSP71 stress was further analyzed using second-generation sequencing. Surprisingly, the results indicated that HSP71 pressure limits the random mutations of PRRSV nsp2 and maintains the dominant PRRSV strain within the population. Mutant strain showed weaker antagonistic activity and replication capability in cell. These results imply the binding of HSP71 with PRRSV nsp2 may lead to maintain the stability of highly virulent strains of PRRSV.

Detection and Phylogenetic Analysis of Caprine Arthritis Encephalitis Virus Using TaqMan-based qPCR in Eastern China.

Caprine arthritis encephalitis is an infectious disease caused by the caprine arthritis encephalitis virus that infects goats, sheep, and other small ruminants. An outbreak of CAEV could be extremely harmful to the goat farming industry and could cause severe economic losses. We designed specific primers and probes for the gag gene and established a TaqMan real-time quantitative polymerase chain reaction assay. This method's correlation coefficient (R2) was >0.999, and the sensitivity of the assay to the plasmid-carried partial gag gene was approximately 10 copies/µL, 1000 times higher than that of conventional PCR. No specific fluorescence was detected for other sheep viruses. Using this method, we tested 776 asymptomatic sheep blood samples and 4 neurodegenerative sheep brain samples from six farms in eastern China, and the positivity rate was 0.77% (6/780). The gag gene was partially sequenced in the three positive samples and compared with the sequences from other representative strains in GenBank. The results revealed that all three strains belonged to the B1 subtype and were most closely related to the strains from Shanxi and Gansu, previously isolated in China, with their homology ranging from 97.7% to 98.9%. These results suggest that the designed RT-qPCR assay can be used to detect subclinical CAEV in sheep and that the virus is still present in eastern China.

Short Communication: Mosquito Histone 2A Protein Facilitate Japanese Encephalitis Virus Infection in the Mosquito.

Japanese encephalitis virus is mainly prevalent in the tropical and subtropical regions of Asia and Oceania. Through immunoprecipitation-mass spectrometry analysis using monoclonal antibodies targeting JEV E protein, we found that mosquito Histone 2A protein could bind to JEV particles. The binding of H2A and JEV was detected in the salivary gland and supernatant of mosquito cells. Furthermore, RNA interference experiments in vitro and in vivo confirmed that H2A protein promotes JEV infection in mosquitoes. In summary, we found that mosquito H2A is a factor that supports JEV infection and can potentially facilitate cross-species transmission of JEV.

Photo- and Oxygen- Synergistically Controlled Selective Expression of Organic Phosphorescence Units.

Dynamic control of ultralong organic room-temperature phosphorescence (UORTP) is a charming target. Herein, we report a stimuli-responsive phosphorescence unit 7H-indolo[2,3-c]quinoline (NBCz) and its derivatives (PCBNBCz, FSO2NBCz, and N2BCzSO2NBCz) that show photo- and oxygen- synergistically induced afterglow activation and afterglow color change in the PMMA film. PCBNBCz and FSO2NBCz feature a donor-acceptor (D-A) structure, and N2BCzSO2NBCz features acceptor-bridged two different phosphorescence units (NBCz and N2BCz). The photoactivated UORTP of PCBNBCz and FSO2NBCz arises from the photoinduced consumption of oxygen in the PMMA film. It is clear that the phosphorescence unit NBCz contributes to subsequent photoinduced UORTP color change because the NBCz-doped PMMA film shows the same UORTP color change process. ESR and HRMS measurements confirmed that oxidation of NBCz occurs at the nitrogen atom of the quinoline ring via photogenerated superoxide radicals, which results in the UORTP color change. TDDFT calculations proved that after oxidation of NBCz, the T1 energy level declines significantly. Furthermore, photocontrolled selective expression of phosphorescence units is achieved in the case of N2BCzSO2NBCz. After further UV irradiation, oxidation of NBCz happened, and the oxidized form N2BCzSO2NBCz-O emitted the intrinsic orange UORTP of NBCz-O selectively and screened the intrinsic yellowish-green UORTP of N2BCz. Finally, multilevel photolithography can be demonstrated based on the photoactivated UORTP and the photoinduced UORTP color change. This work may give a deep insight into organic phosphorescence and pave a simple way for the development of stimulus-responsive smart UORTP materials.

Development of Colloidal Gold-Based Immunochromatographic Strips for Rapid Detection and Surveillance of Japanese Encephalitis Virus in Dogs across Shanghai, China.

Japanese encephalitis virus (JEV) causes acute encephalitis in humans and is of major public health concern in most Asian regions. Dogs are suitable sentinels for assessing the risk of JEV infection in humans. A neutralization test (NT) or an enzyme-linked immunosorbent assay (ELISA) is used for the serological detection of JEV in dogs; however, these tests have several limitations, and, thus, a more convenient and reliable alternative test is needed. In this study, a colloidal gold immunochromatographic strip (ICS), using a purified recombinant EDIII protein, was established for the serological survey of JEV infection in dogs. The results show that the ICSs could specifically detect JEV antibodies within 10 min without cross-reactions with antibodies against other canine viruses. The test strips could detect anti-JEV in serum with dilution up to 640 times, showing high sensitivity. The coincidence rate with the NT test was higher than 96.6%. Among 586 serum samples from dogs in Shanghai examined using the ICS test, 179 (29.98%) were found to be positive for JEV antibodies, and the high seropositivity of JEV in dogs in China was significantly correlated with the season and living environment. In summary, we developed an accurate and economical ICS for the rapid detection of anti-JEV in dog serum samples with great potential for the surveillance of JEV in dogs.

Characterization of Sensitivity of Time Domain MEMS Accelerometer.

This paper characterizes the sensitivity of a time domain MEMS accelerometer. The sensitivity is defined by the increment in the measured time interval per gravitational acceleration. Two sensitivities exist, and they can be enhanced by decreasing the amplitude and frequency. The sensitivity with minor nonlinearity is chosen to evaluate the time domain sensor. The experimental results of the developed accelerometer demonstrate that the sensitivities span from -68.91 µs/g to -124.96 µs/g and the 1σ noises span from 8.59 mg to 6.2 mg (amplitude of 626 nm: -68.91 µs/g and 10.21 mg; amplitude of 455 nm: -94.51 µs/g and 7.76 mg; amplitude of 342 nm: -124.96 µs/g and 6.23 mg), which indicates the bigger the amplitude, the smaller the sensitivity and the bigger the 1σ noise. The adjustable sensitivity provides a theoretical foundation for range self-adaption, and all the results can be extended to other time domain inertial sensors, e.g., a gyroscope or an inclinometer.

Suppressive Photochromism and Promotive Mechanochromism of Rhodamine Mechanophore by the Strategy of Poly(methyl acrylate)/Polyurethane Interpenetrating Polymer Network.

As molecular design and the structure-property relationships of photochemical molecules established in the literature serve as a convenient reference for mechanophore exploration, many typical mechanophores suffer undesired responses to UV light or even sunlight in bulk polymers. We developed a strategy of a poly(methyl acrylate)/polyurethane (PMA/PU) interpenetrating polymer network (IPN) to suppress the photochromic property of the mechanophore and promote its mechanochromic property. A widely used rhodamine mechanophore (Rh-2OH) was first incorporated into polyurethane (P1). Then P1 was swollen in methyl acrylate and photopolymerized to prepare a PMA2.8/PU IPN (P2). Different from photo/force-responsive P1, P2 selectively responded to force because the low free volume in IPN greatly hinders photoisomerization of the rhodamine spirolactam, suggesting that a simple IPN strategy successfully resolves the giant problem of nonselective response to photo/force for photochromic mechanophores. Moreover, PMA/PU IPN enhanced the mechanical property, resulting in a higher mechanochemical activation ratio than PU, and the prestretching effect of PMA/PU IPN promoted the force sensitivity of rhodamine mechanophores significantly. We believe that the strategy can be applied to other mechanophores, promoting their application in more complicated environments.