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Abstract Background Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain controversial. The aim of this meta-analysis was to evaluate the comparative effect of ADCs and other anti-HER2 therapy on progression-free survival (PFS) and overall survival (OS) for treatment of HER2-positive locally advanced or metastatic BC. Methods Relevant randomized controlled trials (RCTs) were retrieved from five databases. The risk of bias was assessed with the Cochrane Collaboration’s tool for RCTs by RevMan5.4 software. The hazard ratio (HR) and 95% confidence intervals (CIs) were extracted to evaluate the benefit of ADCs on PFS and OS in HER2-positive advanced BC by meta-analysis. Results Meta-analysis of six RCTs with 3870 patients revealed that ADCs significantly improved PFS (HR: 0.63, 95% CI: 0.49–0.80, P = 0.0002) and OS (HR: 0.79, 95% CI: 0.72–0.86, P

The utilisation of coated controlled-release fertilizers (CRFs) leads to the persistence of residual plastic films in agricultural soils, posing a potential threat to crop health. This study investigates the impacts of four residual films (0.39 %, w/w) derived from CRFs in soil, including petrochemical polyether, bio-based polyether, castor oil polyester, and wheat straw polyester polyurethane on wheat growth. This study found that PecPEUR significantly reduced wheat plant height, stem diameter, leaf area, and aboveground fresh weight by 24.8 %, 20.2 %, and 25.7 %. Through an in-depth exploration of transcriptomics and metabolomics, it has been discovered that all residual films disrupted glycolysis-related metabolic pathways in wheat roots, affecting seedling growth. Among them, PecPEUR significantly reduced the fresh weight of aboveground parts by 20.5 %. In contrast, polyester polyurethane residue had no discernible impact on aboveground wheat growth. This was attributed to the enrichment of wheat root genes in jasmonic acid and γ-aminobutyric acid metabolic pathways, thus mitigating oxidative stress, enhancing stress resistance, and ensuring normal plant growth. This study, for the first time, provides comprehensive insights into the effects of polyurethane film residue on wheat seedling growth, underscoring its potential as a promising alternative to conventional plastics in soil.

Abstract Background The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship between SHR and mortality in patients with diabetes or prediabetes is still unclear. This study aimed to investigate the predictive value of the SHR for all-cause and cardiovascular mortality in patients with diabetes or prediabetes. Methods This study included 11,160 patients diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2005–2018). The study endpoints were all-cause and cardiovascular mortality, and morality data were extracted from the National Death Index (NDI) up to December 31, 2019. Patients were divided into SHR quartiles. Cox proportion hazards regression was applied to determine the prognostic value of SHR. Model 1 was not adjusted for any covariates. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, BMI, smoking status, alcohol use, hypertension, CHD, CKD, anemia, and TG. Results During a mean follow-up of 84.9 months, a total of 1538 all-cause deaths and 410 cardiovascular deaths were recorded. Kaplan-Meier survival analysis showed the lowest all-cause mortality incidence was in quartile 3 (P

Abstract Background Infectious diseases are a serious threat to human especially since the COVID-19 outbreak has proved the importance and urgency of their diagnosis and treatment again. Metagenomic next-generation sequencing (mNGS) has been widely used and recognized in clinical and carried out localized testing in hospitals. Increasing the training of mNGS detection technicians can enhance their professional quality and more effectively realize the application value of the hospital platform. Methods Based on the initial theoretical understanding and practice of the mNGS platform for localization construction, we have designed a training program to enhance the ability of technicians to detect pathogens by utilizing mNGS, and hence to conduct training practices nationwide. Results Until August 30, 2022, the page views of online classes have reached 51,500 times and 6 of offline small-scale training courses have been conducted. A total of 67 trainees from 67 hospitals have participated in the training with a qualified rate of 100%. After the training course, the localization platform of 1 participating hospital has been put into use, 2 have added the mNGS localization platform for admission, among which 3 have expressed strong intention of localization. Conclusions This study focuses on the training procedures and practical experience of the project which is the first systematic standardized program of mNGS in the world. It solves the training difficulties in the current industry, and effectively promotes the localization construction and application of mNGS in hospitals. It has great development potential in the future and is worth further promotion.

The common carp (Cyprinus carpio) is a crucial freshwater species cultivated worldwide for food consumption. Female carp have better growth performance than males, which fascinates scholars to uncover the mechanism of gonadal differentiation and produce mono-sex populations. However, the mechanism of ovarian development at single-cell resolution is limited. Here, we conducted single-nucleus RNA sequencing in adolescent common carp ovaries. Our study obtained transcriptional profiles of 13,155 nuclei and revealed 13 distinct cell clusters in the ovaries, including three subtypes of germ cells and four subtypes of granulosa cells. We subsequently performed pseudotime trajectory analysis to delineate potential mechanisms underlying the development of germ cells and granulosa cells. We identified 1250 dynamic expression genes in germ cells and 1815 in granulosa cells (q-value < 0.01), including zp3, eif4a2 and aspm in germ cells and fshr and esr1 in granulosa cells. The functional annotation showed that dynamic expression genes in germ cells were involved in sperm–egg recognition and some terms related to meiosis, such as sister chromatid segregation and homologous recombination. Genes expressed dynamically in granulosa cells were related to the TGF-β signaling pathway, response to gonadotropin, and development of primary female sexual characteristics. In addition, the dynamic genes expressed in granulosa cells might relate to the complex communication between different cell types. In summary, our study provided a transcriptome profile of common carp ovaries at single-nucleus resolution, and we further revealed the potential cell type-specific mechanisms underlying oogenesis and the differentiation of granulosa cells, which will facilitate breeding all-female common carp populations.

Background: Insufficient clinicians' auscultation ability delays the diagnosis and treatment of valvular heart disease (VHD); artificial intelligence provides a solution to compensate for the insufficiency in auscultation ability by distinguishing between heart murmurs and normal heart sounds. However, whether artificial intelligence can automatically diagnose VHD remains unknown. Our objective was to use deep learning to process and compare raw heart sound data to identify patients with VHD requiring intervention. Methods: Heart sounds from patients with VHD and healthy controls were collected using an electronic stethoscope. Echocardiographic findings were used as the gold standard for this study. According to the chronological order of enrollment, the early-enrolled samples were used to train the deep learning model, and the late-enrollment samples were used to validate the results. Results: The final study population comprised 499 patients (354 in the algorithm training group and 145 in the result validation group). The sensitivity, specificity, and accuracy of the deep-learning model for identifying various VHDs ranged from 71.4 to 100.0%, 83.5–100.0%, and 84.1–100.0%, respectively; the best diagnostic performance was observed for mitral stenosis, with a sensitivity of 100.0% (31.0–100.0%), a specificity of 100% (96.7–100.0%), and an accuracy of 100% (97.5–100.0%). Conclusions: Based on raw heart sound data, the deep learning model effectively identifies patients with various types of VHD who require intervention and assists in the screening, diagnosis, and follow-up of VHD.

Background: The tissue response viewer (TRV) is a multiparametric index that incorporates time, power, tissue pressure, impedance, and wall thickness data during radiofrequency catheter ablation (RFCA) and is used to predict the transmurality of lesions. This study aimed to evaluate the feasibility and accuracy of the TRV in a porcine model. Methods: Twelve pigs underwent preablation high-density voltage and activation mapping of two atria, and both were repeated after linear RFCA. Intentional gaps were kept in the left atrium (LA) and were touched up in the right atrium (RA). Standard and high powers were, respectively, performed in the LA ablation. Six pigs were immediately sacrificed for pathological examination after the mapping and ablation procedure (acute study). Another six pigs were kept for 4 weeks before remapping and pathological examination (chronic study). Results: All animals completed the planned procedure. The TRV function showed a sensitivity of 97.1% and a specificity of 76.9% in the acute study, and a sensitivity of 95.9% and a specificity of 72.5% in the chronic study to predict the transmural lesion. All positive and negative predictive values were over 80%. In addition, the TRV achieved higher sensitivity (92.3% vs. 85.0%) and specificity (88.2% vs. 78.9%) to predict the transmural lesion in LA ablation with high power compared with standard ablation. Conclusions: This study presents the histopathological validation of TRV to predict transmural lesions. The use of TRV may guide a more individual ablation and a more precise touch-up of gaps for atrial arrhythmias.

Bartonella species are fastidious, aerobic bacteria that are transmitted by blood-sucking arthropods. Bartonella spp. are responsible for cat scratch disease, Carrion’s disease, bacillary angiomatosis and trench fever. On the other hand, Bartonella vinsonii is rarely reported in the literature and there exist a few reports of systemic infection caused by Bartonella vinsonii in patients with acquired immunodeficiency syndrome. A 31-year-old male (diagnosed with AIDS six years ago) had persistent fever and ulceration in the right knee. The elevated levels of inflammatory markers suggested an infectious aetiology. Despite the negative findings of blood culture, metagenomic Next-Generation Sequencing of plasma detected Bartonella vinsonii. The polymerase chain reaction of whole blood and Sanger sequencing confirmed the mNGS findings. Immunohistochemical staining had later suggested bacillary angiomatosis, which was consistent with Bartonella infection. Following antibiotic treatment, the ulcers subsided significantly, but a high fever persisted. The patient died due to sudden respiratory failure.

Abstract Background The KODEX-EPD system is a novel, dielectric three-dimensional mapping system. We aim to illustrate the feasibility, safety, and outcomes of ablation using the KODEX-EPD system. Methods A total of 272 patients with supraventricular arrhythmias were enrolled and underwent catheter ablation using the KODEX-EPD system from October 2020 to July 2021. The feasibility, safety, and ablation outcomes were analyzed. Results Of the enrolled patients, 15 (5.4%) had atrial tachycardia (AT), 88 (31.4%) had atrioventricular reentrant tachycardia (AVRT), 141 (50.4%) had atrioventricular nodal reentrant tachycardia (AVNRT), 34 (12.1%) had atrial fibrillation (AF), and 9 (3.2%) had atrial flutter (AFL). All AF patients included were first-do-pulmonary vein isolation (PVI); there were 26 paroxysmal AF and 8 persistent AF. All patients achieved immediate success of ablation. The mean follow-up duration was 11.8 ± 2.4 months. One patient (1.1%) in the AVRT subgroup and two patients (1.4%) in the AVNRT subgroup experienced recurrence. When considering a three-month blanking time, the estimated freedom of AF at one-year post-ablation with and without AADs was 75.7% and 70.4%, respectively. The Kaplan–Meier analysis showed no significant difference in the overall AF recurrence (log-rank; P = 0.931) or AAD-free AF recurrence (log-rank; P = 0.841) between RFCA and cryoablation. One patient had mild pulmonary embolism. None of the patients died or had a cerebrovascular event in the periprocedural period. Conclusions This retrospective, two-center study demonstrated that catheter ablation of supraventricular arrhythmias using the KODEX-EPD system is feasible, safe, and effective. Trial registration Retrospectively registered.

Background: Immune checkpoint inhibitors (ICIs) have been an emerging treatment strategy for advanced triple-negative breast cancer (TNBC). Some studies have shown that high expression of programmed death-ligand 1 (PD-L1) can achieve a better response of clinical efficacy. However, the efficacy of ICIs in advanced TNBC remains controversial. In this meta-analysis, we evaluated the correlation of PD-L1 expression with the efficacy of ICIs in patients with advanced TNBC.Methods: We conducted a systematic search using four databases until March 2022 to obtain eligible randomized controlled trials (RCTs). The quality of the studies was assessed by the Cochrane risk of bias tool. Hazard ratio (HR) was extracted to evaluate the relationship between PD-L1 expression and progression-free survival (PFS) or overall survival (OS) in patients with advanced TNBC.Results: Five randomized controlled clinical trials (RCTs) with 3104 patients were included in this meta-analysis. The results demonstrated that ICIs could significantly improve the OS (HR 0.77, 95% CI 0.60–0.98, p = 0.03) in PD-L1 positive TNBC group. In the subgroup analysis, longer OS was observed (HR: 0.70, 95% CI: 0.60–0.82, p = 0.00001) in PD-L1 positive TNBC patients receiving ICIs alone or ICIs combined with nab-paclitaxel. In terms of PFS, PFS was significantly improved (HR: 0.68, 95% CI: 0.58–0.79, p < 0.00001) in PD-L1 positive patients receiving first-line ICIs and chemotherapy compared to those with ICIs alone. No significant improvement was observed for OS or PFS in PD-L1 negative group.Conclusion: Our study indicated significant improvement for OS in advanced TNBC with ICIs therapy in the PD-L1 positive status, and ICIs alone or ICIs combined with nab-paclitaxel might be a excellent choice in terms of OS. Although PFS has no significant benefit in PD-L1 positive patients, the subgroup analysis showed that ICIs combined with chemotherapy could achieve the PFS benefit in the first-line treatment. However, further clinical studies are needed to validate our conclusions due to limited relevant research.

Abstract The absolute dominant species that infests wild population of Przewalski’s horse (Equus przewalskii) is Gasterophilus pecorum, and feces of released Przewalski’s horse, a habitat odor, plays an important role in mating and ovipositing locations of G. pecorum. To screen out unique volatiles for attracting G. pecorum, volatiles from fresh feces of released horses at stages of pre-oviposition (PREO), oviposition (OVIP), and post-oviposition (POSO) of G. pecorum, and feces with three different freshness states (i.e., Fresh, Semi-fresh, and Dry) at OVIP were collected by dynamic headspace adsorption and determined by automatic thermal desorption GC–MS. Results show that there were significant differences in fecal volatiles within both test conditions. Of the five most abundant volatiles from the five individual samples, the most important volatile was ammonium acetate at OVIP/Fresh, followed by acetophenone (Semi-fresh), toluene (PREO, OVIP and POSO), butanoic acid (OVIP and Semi-fresh), acetic acid (PREO, POSO and Semi-fresh), 1,6-octadiene,3,7-dimethyl-,(S)- (PREO, OVIP and POSO), 1,5,9-undecatriene,2,6,10-trimethyl-,(Z)- (PREO and Semi-fresh) and caprolactam (all conditions), which seem to be critical substances in oviposition process of G. pecorum. The findings may be beneficial to development of G. pecorum attractants, facilitating prevention and control of infection by G. pecorum to released Przewalski’s horse.

Abstract Background It is important to recognize the coronavirus disease 2019 (COVID-19) patients in severe conditions from moderate ones, thus more effective predictors should be developed. Methods Clinical indicators of COVID-19 patients from two independent cohorts (Training data: Hefei Cohort, 82 patients; Validation data: Nanchang Cohort, 169 patients) were retrospected. Sparse principal component analysis (SPCA) using Hefei Cohort was performed and prediction models were deduced. Prediction results were evaluated by receiver operator characteristic curve and decision curve analysis (DCA) in above two cohorts. Results SPCA using Hefei Cohort revealed that the first 13 principal components (PCs) account for 80.8% of the total variance of original data. The PC1 and PC12 were significantly associated with disease severity with odds ratio of 4.049 and 3.318, respectively. They were used to construct prediction model, named Model-A. In disease severity prediction, Model-A gave the best prediction efficiency with area under curve (AUC) of 0.867 and 0.835 in Hefei and Nanchang Cohort, respectively. Model-A’s simplified version, named as LMN index, gave comparable prediction efficiency as classical clinical markers with AUC of 0.837 and 0.800 in training and validation cohort, respectively. According to DCA, Model-A gave slightly better performance than others and LMN index showed similar performance as albumin or neutrophil-to-lymphocyte ratio. Conclusions Prediction models produced by SPCA showed robust disease severity prediction efficiency for COVID-19 patients and have the potential for clinical application.

10-HCPT is a topoisomerase I inhibitor effective in the treatment of liver cancer but its use is hampered by its resistance. The expression of hypoxia-inducible factor-1α (HIF-1α) is reportedly upregulated in liver cancer tissues, which is directly linked to the resistance of 10-HCPT. While BBR can significantly decrease the level of HIF-1α according to the literature report. Thus, the aim of this study was to prepare a novel intravenous 10-HCPT-BBR-loaded lipid microsphere (LM) and evaluate their synergistic effect on liver cancer treatment. The optimal preparation mainly included 10.0% oil phase (medium-chain triglyceride:long-chain triglyceride = 1:1), emulsifier (egg lecithin E80 and pluronic F68), antioxidant (0.02% NaHSO3), and pH regulator (0.1 mol/L Hcl). Then, the behaviors of BBR-10-HCPT loaded LM in vitro and in vivo were systematically investigated. In vitro, it showed an obvious sustained-release effect in different release mediums, good physicochemical stability at accelerated and long-term storage conditions, and great anti-proliferative capability toward human liver cancer Hep-3B cells. In vivo, the prepared LM exhibited a longer half-life and higher AUC compared to BBR injection and 10-HCPT injection. More importantly, it was found that The LM was distributed more in the liver, spleen, and tumors, but less in the lungs and heart, especially in the lung. And then, it showed significant inhibition of tumor growth against nude mouse with Hep-3B tumor, and the tumor inhibition rate reached 91.55%. Thus, the data obtained in our study suggested that BBR combined with 10-HCPT can raise curative effect and reduce the toxicity of 10-HCPT.

The microbiota and its metabolites play an important role in regulating the host metabolism and immunity. However, the underlying mechanism is still not well studied. Thus, we conducted the LC-MS/MS analysis and RNA-seq analysis on Equus przewalskii with and without horse botfly infestation to determine the metabolites produced by intestinal microbiota in feces and differentially expressed genes (DEGs) related to the immune response in blood and attempted to link them together. The results showed that parasite infection could change the composition of microbial metabolites. These identified metabolites could be divided into six categories, including compounds with biological roles, bioactive peptides, endocrine-disrupting compounds, pesticides, phytochemical compounds, and lipids. The three pathways involving most metabolites were lipid metabolism, amino acid metabolism, and biosynthesis of other secondary metabolites. The significant differences between the host with and without parasites were shown in 31 metabolites with known functions, which were related to physiological activities of the host. For the gene analysis, we found that parasite infection could alarm the host immune response. The gene of “cathepsin W” involved in innate and adaptive immune responses was upregulated. The two genes of the following functions were downregulated: “protein S100-A8” and “protein S100-A9-like isoform X2” involved in chemokine and cytokine production, the toll-like receptor signaling pathway, and immune and inflammatory responses. GO and KEGG analyses showed that immune-related functions of defense response and Th17 cell differentiation had significant differences between the host with and without parasites, respectively. Last, the relationship between metabolites and genes was determined in this study. The purine metabolism and pyrimidine metabolism contained the most altered metabolites and DEGs, which mainly influenced the conversion of ATP, ADP, AMP, GTP, GMP, GDP, UTP, UDP, UMP, dTTP, dTDP, dTMP, and RNA. Thus, it could be concluded that parasitic infection can change the intestinal microbial metabolic activity and enhance immune response of the host through the pathway of purine and pyrimidine metabolism. This results will be a valuable contribution to understanding the bidirectional association of the parasite, intestinal microbiota, and host.

Abstract Background This paper is to describe percutaneous endoscopy in the treatment of lumbar spinal stenosis secondary to ligamentum flavum hypertrophy targeted and to investigate the efficacy and safety of percutaneous endoscopy in the treatment of this kind of lumbar spinal stenosis in elderly patients. Method A retrospective analysis of 40 elderly patients with lumbar spinal stenosis secondary to ligamentum flavum hypertrophy admitted between January 2016 and January 2018 was performed. According to different surgical methods, they were divided into two groups: the control group and the endoscopy group (interlaminar approach), 20 people per group. There were 9 males and 11 females in the control group; the age of patients was 65.65 ± 4.44 years, and the average disease duration was 4.55 ± 1.85 years. Besides, there were 10 males and 10 females in the endoscopy group; the age of patients was 67.30 ± 4.23 years, and the average disease duration was 4.95 ± 2.04 years. Collect and count surgical-related indicators, preoperative and postoperative radiologic findings, incision visual analog scale (VAS), lumbar and leg pain VAS, lumbar Japanese Orthopaedic Association (JOA), and Oswestry disability index (ODI) scores of all patients. Result A series of surgical indicators (including the operation time, the quantity of bleeding, and postoperative hospital stay) in the endoscopy group was significantly lower than that in the control group (p < 0.05). The incision VAS score in the endoscopy group was also significantly lower than that in the control group at each time after surgery (p < 0.05). Besides, compared with the control group, in the endoscopy group, the leg pain VAS score and lumbar ODI score after surgery were significantly decreased (p < 0.05). Compared with the control group, in the endoscopy group, the lumbar JOA score was significantly higher (p < 0.05). Conclusion Percutaneous endoscopic technique is a small trauma, quick recovery, safe, and effective minimally invasive surgery for patients with lumbar spinal stenosis secondary to ligamentum flavum hypertrophy.

AimsThe incidence of atrioventricular nodal reentrant tachycardia (AVNRT) is higher in pulmonary arterial hypertension (PAH) patients than in the general population. AVNRT is reportedly associated with a larger coronary sinus (CS) ostium (CSo). However, the correlation between AVNRT and CSo size in PAH patients is poorly investigated. We aimed to investigate the impact of CSo size on AVNRT and identify its risk factors in PAH.Methods and ResultsOf 102 PAH patients with catheter ablation of supraventricular tachycardia (SVT), twelve with a confirmed AVNRT diagnosis who underwent computed tomographic angiography were retrospectively enrolled as the study group. The control group (PAH without SVT, n = 24) was matched for sex and BMI at a 2:1 ratio. All baseline and imaging data were collected. Mean pulmonary artery pressure was not significantly different between the two groups (65.3 ± 16.8 vs. 64.5 ± 17.6 mmHg, P = 0.328). PAH patients with AVNRT were older (45.9 ± 14.8 vs. 32.1 ± 7.6 years, P = 0.025), had a larger right atrial volume (224.4 ± 129.6 vs. 165.3 ± 71.7 cm3, P = 0.044), larger CSo in the left anterior oblique (LAO) plane (18.6 ± 3.3 vs. 14.8 ± 4.0 mm, P = 0.011), and larger CSo surface area (2.08 ± 1.35 vs. 1.45 ± 0.73 cm2, P = 0.039) and were more likely to have a windsock-shape CS (75% vs. 16.7%, P = 0.001) than those without AVNRT. A linear correlation was shown between CSo diameter in the LAO-plane and the atrial fractionation of the ablation target for AVNRT (R2 = 0.622, P = 0.012).ConclusionAnatomical dilation of the CSo is a risk factor for AVNRT development in patients with PAH.

Background: Little is known about the differences among ventricular arrhythmias (VAs) ablated in different subregions of the aortic sinuses of Valsalva (ASVs). We aim to investigate the distribution, precordial electrocardiographic patterns, and bipolar electrogram characteristics of VAs ablated in different subregions of the ASVs.Methods: We divided the right ASV and the left ASV into a total of 6 subregions and studied 51 idiopathic VAs ablated first time successfully in the ASVs.Results: These 51 VAs were inhomogeneously distributed among the 6 subregions, which comprised the right-lateral ASV (1/51), the right-anterior ASV (11/51), the regions along the right (13/51) and left (9/51) sides of the ASV junction, the left-anterior ASV (5/51), and the left-lateral ASV (12/51). Fractionated potentials were dominant (39/51, 76%) among the 3 types of target electrograms. From the right-lateral ASV to the left-lateral ASV, the percentage of fractionated potentials gradually decreased from 100 to 59%. A precordial rebound notch in V3-V4 or V4-V5 had sensitivity of 90.9%, specificity of 85.0%, and negative predictive value (NPV) of 97.1% to predict VAs ablated in the right-anterior ASV. A precordial rebound notch in V2-V3 had sensitivity of 50.0%, specificity of 94.9%, and NPV of 86.0% to predict VAs ablated in the left-lateral ASV.Conclusion: VA targets were mainly distributed in the anterior and the left-lateral ASVs. Fractionated potentials were common among target electrograms, especially in theright-anterolateral ASV. Precordial electrocardiographic rebound notch has high predictive accuracy in identifying different subregions of the ASVs as target ablation sites.

Intestinal microbiota is involved in immune response and metabolism of the host. The frequent use of anthelmintic compounds for parasite expulsion causes disturbance to the equine intestinal microbiota. However, most studies were on the effects of such treatment on the intestinal bacterial microbes; none is on the entire microbial community including archaea and eukaryotic and viral community in equine animals. This study is the first to explore the differences of the microbial community composition and structure in Przewalski's horses prior to and following anthelmintic treatment, and to determine the corresponding changes of their functional attributes based on metagenomic sequencing. Results showed that in archaea, the methanogen of Euryarchaeota was the dominant phylum. Under this phylum, anthelmintic treatment increased the Methanobrevibacter genus and decreased the Methanocorpusculum genus and two other dominant archaea species, Methanocorpusculum labreanum and Methanocorpusculum bavaricum. In bacteria, Firmicutes and Bacteroidetes were the dominant phyla. Anthelmintic treatment increased the genera of Clostridium and Eubacterium and decreased those of Bacteroides and Prevotella and dominant bacteria species. These altered genera were associated with immunity and digestion. In eukaryota, anthelmintic treatment also changed the genera related to digestion and substantially decreased the relative abundances of identified species. In virus, anthelmintic treatment increased the genus of unclassified_d__Viruses and decreased those of unclassified_f__Siphoviridae and unclassified_f__Myoviridae. Most of the identified viral species were classified into phage, which were more sensitive to anthelmintic treatment than other viruses. Furthermore, anthelmintic treatment was found to increase the number of pathogens related to some clinical diseases in horses. The COG and KEGG function analysis showed that the intestinal microbiota of Przewalski's horse mainly participated in the carbohydrate and amino acid metabolism. The anthelmintic treatment did not change their overall function; however, it displaced the population of the functional microbes involved in each function or pathway. These results provide a complete view on the changes caused by anthelmintic treatment in the intestinal microbiota of the Przewalski's horses.

Abstract Aims We aim to understand bird richness and variation in species composition (beta diversity) along a 630 km riparian landscape in the Altai Mountains of China and to test whether vegetation cover is the main explanation of species diversity. Methods We selected nine regions along a gradient of natural vegetation change. Bird surveys and environmental measurements were conducted at 10 points in each of the nine regions. We collected environmental land cover variables such as wood cover (area proportion of trees and shrubs with saplings in habitats; here trees are woody plant with a single trunk and higher than 3 m, shrubs and saplings are distinguished from trees by their multiple trunks and shorter height) and tree cover, and two climate factors which were Annual Mean Temperature (AMT) and Annual Precipitation (AP). We used Liner Regression Models to explore the correlation between bird species richness and environmental variables. We used Sørensen's dissimilarity index to measure birds' beta diversity, and quantified the contribution of environmental variables to this pattern using a Canonical Correspondence Analysis (CCA). Results Wood cover was the strongest predictor of overall, insectivore, and omnivore bird richness. Regions with wood cover contained more bird species. Beta diversity was overall high in the studied regions, and turnover components occupied a major part of beta diversity. Wood cover and AP were significant predictors of bird species composition explaining 33.24% of bird beta diversity together. Conclusions Wood vegetation including trees, shrubs, and saplings, rather than only trees, contains high bird richness. High beta diversity suggests that expansion of the existing nature reserves is needed in the riparian landscapes to capture the variation in bird species composition. Thus all wood cover in the overall riparian landscapes of Altai Mountains should be protected from farming and grazing to improve bird conservation outcomes. OPEN RESEARCH BADGES This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at Raw bird data in this study: osf.io/78qcw; Raw environment data: osf.io/qr5cw.

Soluble synaptotoxic aggregates of the main pathological proteins of Alzheimer's disease, amyloid β-protein (Aß) and tau, have rapid and potent inhibitory effects on long-term potentiation (LTP). Although the promotion of synaptic weakening mechanisms, including long-term depression (LTD), is posited to mediate LTP inhibition by Aß, little is known regarding the action of exogenous tau on LTD. The present study examined the ability of different assemblies of full-length human tau to affect LTD in the dorsal hippocampus of the anaesthetized rat. Unlike Aß, intracerebroventricular injection of soluble aggregates of tau (SτAs), but not monomers or fibrils, potently increased the threshold for LTD induction in a manner that required cellular prion protein. However, MTEP, an antagonist of the putative prion protein coreceptor metabotropic glutamate receptor 5, did not prevent the disruption of synaptic plasticity by SτAs. In contrast, systemic treatment with Ro 25–6981, a selective antagonist at GluN2B subunit-containing NMDA receptors, reduced SτA-mediated inhibition of LTD, but not LTP. Intriguingly, SτAs completely blocked Aß-facilitated LTD, whereas a subthreshold dose of SτAs facilitated Aß-mediated inhibition of LTP. Overall, these findings support the importance of cellular prion protein in mediating a range of, sometimes opposing, actions of soluble Aß and tau aggregates with different effector mechanisms on synaptic plasticity.

Located on the southwest slope and plain areas of the Altai Mountains in China, this study aims to explore bird composition variation (beta diversity) in mountain landscape (metacommunity M), riparian landscape (metacommunity R), desert landscape (metacommunity D) and across the three landscapes (metacommunity A), and to assess how patch connectivity with environmental and spatial factors influence species distributional patterns across multiple metacommunities. In 78 transect lines over the study area, 9724 detections of 139 bird species were detected. We calculated the beta diversity, its turnover and nestedness components in four metacommunities. We used the variation partitioning method to investigate the relative importance between the environment, spatial variation and locality connectivity in driving bird community composition variation. We found high beta diversities with a small contribution of nestedness components in all four metacommunities. When only a single set of predictors is contained in the model, the predictor that best explains the variation of bird community composition is connectivity in metacommunity M, R and D and spatial predictor in metacommunity A. In all three sets of predictors, 73.8~85.4% of variations of community composition can be explained in the four metacommunities, and connectivity always contributed the most. High beta diversity and a high turnover component imply that regional-scale conservation efforts should be thought of as preserving overall biodiversity. A conservation strategy is to keep stepping-stone habitats with good connectivity in the middle of the riparian landscape. Along with the Altai-Sayan biodiversity ecoregion, the desert and riparian environments are essential for birds residing in the mountainous terrain. Furthermore, they should be regarded as integral parts of the ecoregion.

Horse botflies have been a threat to the Przewalski's horses in the Kalamaili Nature Reserve in Xinjiang of China since their reintroduction to the original range. As larvae of these parasites could infest the intestine of a horse for months, they could interact with and alter the structure and composition of its intestinal microbiota, affecting adversely its health. Nonetheless, there are no such studies on the rewilded Przewalski's horses yet. For the first time, this study characterizes the composition of the intestinal microbiota of 7 rewilded Przewalski's horses infected severely by Gasterophilus pecorum following and prior to their anthelmintic treatment. Bioinformatics analyses of the sequence data obtained by amplicon high throughput sequencing of bacterial 16S rRNA genes showed that G. pecorum infestation significantly increased the richness of the intestinal microbial community but not its diversity. Firmicutes and Bacteroidetes were found the dominant phyla as in other animals, and the parasitic infestation decreased the F/B ratio largely by over 50%. Large reduction in relative abundances of the two genera Streptococcus and Lactobacillus observed with G. pecorum infestation suggested possible changes in colic and digestion related conditions of the infected horses. Variations on the relative abundance of the genus groups known to be pathogenic or symbiotic showed that adverse impact of the G. pecorum infestation could be associated with reduction of the symbiotic genera Lactobacillus and Bifidobacterium that are probiotics and able to promote immunity against parasitic infection.

Abstract The pandemic of novel coronavirus disease 2019 (COVID‐19) seriously threatened the public health all over the world. A colloidal gold immunochromatography assay for IgM/IgG antibodies against the receptor‐binding domain of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) S1 protein was established to assess its rapid diagnostic value. We first designed and manufactured all contents of the test cassette of SARS‐CoV‐2 rapid test kit: the colloidal gold‐labeled mouse‐antihuman lgM/lgG antibody, the recombinant SARS‐CoV‐2 antigen, the nitrocellulose membrane control line, and specimen diluents. Furthermore, reverse transcription‐polymerase chain reaction (RT‐PCR) assay, colloidal gold immunochromatography assay, serological validation of cross reaction with other common viruses, and clinical validation were performed. The kit was finally evaluated by 75 serum/plasma samples of SARS‐CoV‐2 infection cases and 139 healthy samples as control, with the result of that the sensitivity, specificity, and accuracy for IgM were 90.67%, 97.84%, and 95.33%, whereas for IgG were 69.33%, 99.28%, and 88.79%, respectively; the combination of IgM and IgG could improve the value: 92.00%, 97.12%, and 95.33%, respectively. Therefore, the rapid detection kit has high sensitivity and specificity, especially for IgM&IgG, showing a critical value in clinical application and epidemic control of COVID‐19.

(1) Background: The panoramic view of a novel wide-band dielectric mapping system could show the individual anatomy. We aimed to compare the feasibility, efficacy and safety of the panoramic view guided approach for ablation of AVNRT with the conventional approach. (2) Methods: Ablation distributions in eight patients were retrospectively analyzed using the panoramic view. The para-slow-pathway (para-SP) region was divided into three regions, and the region that most frequently appeared with the appropriate junctional rhythm or eliminated the slow-pathway was defined as the adaptive slow-pathway (aSP) region. Twenty patients with AVNRT were then ablated in the aSP region under the panoramic view and compared with 40 patients using the conventional approach. (3) Results: Thirty ablation points were analyzed. The majority of effective points (95.0%) were located in the inferior and anterior portions of the para-SP region and defined as the aSP region. Baseline characteristics, fluoroscopic duration, and mean number of ablations were similar among the two groups. The panoramic view group had a significantly higher percentage of appropriate junctional rhythm (81.9% ± 26.0% vs. 55.7% ± 30.5%, p = 0.002) than the conventional group. (4) Conclusions: The use of the panoramic view for AVNRT ablation achieved similar clinical endpoints with higher ablation efficiency than the conventional approach.

Pro-inflammatory mechanisms have recently emerged as an important component of early Alzheimer's disease (AD) pathogenesis. A particularly attractive therapeutic strategy is to selectively prevent the disruptive effects of activation of the innate immune system in the brain at an early transitional stage by reducing the production or directly neutralizing pro-inflammatory cytokines, in particular IL-1β and TNF-α. Here we tested their in vivo effects on synaptic plasticity deficits, which provide sensitive and robust measures of synaptic failure, in a rat model of AD amyloidosis. Using electrophysiological techniques we longitudinally studied the effects of the NLRP3 inflammasome inhibitor Mcc950, the IL-1 receptor antagonist (anakinra) and an anti-TNF-α agent (etanercept) in awake freely moving transgenic rats overexpressing AD associated β-amyloid precursor protein at a pre-plaque stage of amyloidosis. Repeated treatment with Mcc950 reversibly abrogated the inhibition of long-term potentiation. The IL-1 receptor antagonist and etanercept also had a similar beneficial effect on the deficit in synaptic plasticity. Our findings support the clinical development of Mcc950 and clinically available IL-1- and TNF-α-neutralizing agents in early AD.

Abstract Background There are few data available on the prevalence, incidence, and residual risk of transfusion-transmitted HBV (TT-HBV) infections among Chinese blood donors. This study investigated the demographic characteristics of blood donors, as well as the prevalence, incidence, and residual risk (RR) of TT-HBV infections in six large blood centers in different regions of China. Methods The demographic characteristics and HBV screening test results of blood donors from six blood centers in different regions in China were collected and analyzed. The hepatitis B surface antigen (HBsAg) yield approach was used to estimate the incidence of HBV. Then, the RR of TT-HBV infections was evaluated using the incidence-window period model. Results The majority of donors were between 18 and 35 years old (including 35), with the exception of the Changzhi Blood Center where a majority of donors were between 35 and 55 years old (including 55). The prevalences of HBV were 0.13%, 0.078%, 0.16%, 0.07%, 0.20%, 0.25% in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. The estimated corresponding incidences were 213.44, 161.59, 989.80, 278.05, 125.31 and 352.19 per 105 person-years. Using an infectious window period of 59 days, the RR for HBV was estimated to be 34.14, 25.85, 158.35, 44.48, 20.04 and 56.35 per 105 person-years in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. Conclusion Despite the introduction of more sensitive assays in blood screening, our data revealed that the current residual risk of TT-HBV infection was still high (overall 56.53 per 105 py). A continuous monitoring of the residual risk of transfusion-transmitted infections is crucial for safe blood management.

How endogenously produced soluble amyloid ß-protein (Aß) affects synaptic plasticity in vulnerable circuits should provide insight into early Alzheimer’s disease pathophysiology. McGill-R-Thy1-APP transgenic rats, modeling Alzheimer’s disease amyloidosis, exhibit an age-dependent soluble Aß-mediated impairment of the induction of long-term potentiation (LTP) by 200 Hz conditioning stimulation at apical CA3-to-CA1 synapses. Here, we investigated if synaptic weakening at these synapses in the form of activity-dependent persistent reversal (depotentiation) of LTP is also altered in pre-plaque rats in vivo. In freely behaving transgenic rats strong, 400 Hz, conditioning stimulation induced stable LTP that was NMDA receptor- and voltage-gated Ca2+ channel-dependent. Surprisingly, the ability of novelty exploration to induce depotentiation of 400 Hz-induced LTP was impaired in an Aß-dependent manner in the freely behaving transgenic rats. Moreover, at apical synapses, low frequency conditioning stimulation (1 Hz) did not trigger depotentiation in anaesthetized transgenic rats, with an age-dependence similar to the LTP deficit. In contrast, at basal synapses neither LTP, induced by 100 or 200 Hz, nor novelty exploration-induced depotentiation was impaired in the freely behaving transgenic rats. These findings indicate that activity-dependent weakening, as well as strengthening, is impaired in a synapse- and age-dependent manner in this model of early Alzheimer’s disease amyloidosis.

1: Understanding species diversity patterns is important for conservation planning. We studied birds’ alpha and beta diversity along vegetation gradients in three watersheds in the Altai Mountains, a global biodiversity hotspot; and tested whether environment-based hypotheses could explain these patterns. 2: In Daxiaodonggou (DXDG), Jiadengyu (JDY) and Liangheyuan (LHY) watersheds, alpha diversity varied strongly along elevational vegetation zones. In DXDG, bird species richness displayed a double-hump pattern and increased slightly at the highest elevations. In JDY and LHY, bird species richness increased gradually with elevation but dipped in certain vegetation zones. The Shannon-Wiener index and Simpson's index showed consistent patterns in each watershed, and were higher in forest habitats. Bird species richness was affected by Human Footprint Index, elevation, temperate and precipitation in LHY, but only affected by Compound Topographic Index in JDY, and only affected by elevation in DXDG. 3: High beta diversity and high turnover component were found in all of the three watersheds, revealing distinct bird assemblages between various vegetation types. In contrast to previous studies, beta diversity of the Altai Mountains was not lower than those reported in tropical mountains. Simplified models by Canonical Correspondence Analysis explained 34–41% variation of bird species composition along vegetation zones among three watersheds, and environmental factors in the three models were inconsistent. Mantel test revealed beta diversity of the bird communities were lower in the two vegetation zones with more similar environmental conditions. 4: The variety of bird diversity patterns and various influential environmental factors among longitudinally-separated watersheds in the Altai Mountains indicate the complexity of environmental filtering mechanics. Though some vegetation zones contain higher bird species richness than others, high species composition turnover in the whole area suggests conservation strategies should consider multiple watersheds and multiple vegetation types in the Altai Mountains when aiming to conserve avian diversity. Keywords: Bird, Alpha diversity, Beta diversity, Elevation, Vegetation zone