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Abstract Silicon is expected to become the ideal anode material for the next generation of high energy density lithium battery because of its high theoretical capacity (4200 mAh g−1). However, for silicon electrodes, the initial coulombic efficiency (ICE) is low and the volume of the electrode changes by over 300% after lithiation. The capacity of the silicon electrode decreases rapidly during cycling, hindering the practical application. In this work, a slidable and highly ionic conductive flexible polymer binder with a specific single‐ion structure (abbreviated as SSIP) is presented in which polyrotaxane acts as a dynamic crosslinker. The ionic conducting network is expected to reduce the overall resistance, improve ICE and stabilize the electrode interface. Furthermore, the introduction of slidable polyrotaxane increases the reversible dynamics of the binder and improves the long‐term cycling stability and rate performance. The silicon anode based on SSIP provides a discharge capacity of ≈1650 mAh g−1 after 400 cycles at 0.5C with a high ICE of upto 92.0%. Additionally, the electrode still exhibits a high ICE of 87.5% with an ultra‐high Si loading of 3.84 mg cm−2 and maintains a satisfying areal capacity of 5.9 mAh cm−2 after 50 cycles, exhibiting the potential application of SSIP in silicon‐based anodes.

BackgroundAtrial fibrillation (AF) is an age-related disease, while telomeres play a central role in aging. But the relationship between AF and telomere length (LTL) is still controversial. This study aims to examine the potential causal association between AF and LTL by using Mendelian randomization (MR).MethodsBidirectional two-sample MR, expression and protein quantitative trait loci (eQTL and pQTL)-based MR were performed using genetic variants from United Kingdom Biobank, FinnGen, and a meta-analysis study, which comprised nearly 1 million participants in the Atrial Fibrillation Study and 470,000 participants in the Telomere Length Study. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, complementary analysis approaches and sensitivity analysis were applied.ResultsThe forward MR revealed a significant causal estimate for the genetically predicted AF with LTL shortening [IVW: odds ratio (OR) = 0.989, p = 0.007; eQTL-IVW: OR = 0.988, p = 0.005; pQTL-IVW: OR = 0.975, p

Artemisinin, an antimalarial traditional Chinese herb, is isolated from Artemisia annua. L, and has shown fewer side effects. Several pieces of evidence have demonstrated that artemisinin and its derivatives exhibited therapeutic effects on diseases like malaria, cancer, immune disorders, and inflammatory diseases. Additionally, the antimalarial drugs demonstrated antioxidant and anti-inflammatory activities, regulating the immune system and autophagy and modulating glycolipid metabolism properties, suggesting an alternative for managing kidney disease. This review assessed the pharmacological activities of artemisinin. It summarized the critical outcomes and probable mechanism of artemisinins in treating kidney diseases, including inflammatory, oxidative stress, autophagy, mitochondrial homeostasis, endoplasmic reticulum stress, glycolipid metabolism, insulin resistance, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, and acute kidney injury, suggesting the therapeutic potential of artemisinin and its derivatives in managing kidney diseases, especially the podocyte-associated kidney diseases.

Bat coronavirus RaTG13 shares about 96.2% nucleotide sequence identity with that of SARS-CoV-2 and uses human and Rhinolophus affinis (Ra) angiotensin-converting enzyme 2 (ACE2) as entry receptors. Whether there are bat species other than R. affinis susceptible to RaTG13 infection remains elusive. Here, we show that, among 18 different bat ACE2s tested, only RaACE2 is highly susceptible to transduction by RaTG13 S pseudovirions, indicating that the bat species harboring RaTG13 might be very limited. RaACE2 has seven polymorphic variants, RA-01 to RA-07, and they show different susceptibilities to RaTG13 S pseudovirions transduction. Sequence and mutagenesis analyses reveal that residues 34, 38, and 83 in RaACE2 might play critical roles in interaction with the RaTG13 S protein. Of note, RaACE2 polymorphisms have minimal effect on S proteins of SARS-CoV-2 and several SARS-CoV-2 related CoVs (SC2r-CoVs) including BANAL-20-52 and BANAL-20-236 in terms of binding, membrane fusion, and pseudovirus entry. Further mutagenesis analyses identify residues 501 and 505 in S proteins critical for the recognition of different RaACE2 variants and pangolin ACE2 (pACE2), indicating that RaTG13 might have not been well adapted to R. affinis bats. While single D501N and H505Y changes in RaTG13 S protein significantly enhance the infectivity and minimize the difference in susceptibility among different RaACE2 variants, an N501D substitution in SARS-CoV-2 S protein displays marked disparity in transduction efficiencies among RaACE2 variants with a significant reduction in infectivity on several RaACE2 variants. Finally, a T372A substitution in RaTG13 S protein not only significantly increases infectivity on all RaACE2 variants, but also markedly enhances entry on several bat ACE2s including R. sinicus YN, R. pearsonii, and R. ferrumeiqunum. However, the T372A mutant is about 4-fold more sensitive to neutralizing sera from mice immunized with BANAL-20-52 S, suggesting that the better immune evasion ability of T372 over A372 might contribute to the natural selective advantage of T372 over A372 among bat CoVs. Together, our study aids a better understanding of coronavirus entry, vaccine design, and evolution.

Sterol 14α-demethylase catalyzes lanosterol hydroxylation, which is one of the key reactions in the biosynthetic pathway of sterols. There is only one sterol 14α-demethylases gene named Erg11 in Saccharomyces cerevisiae genome. In this study, three sterol 14α-demethylases genes named AoErg11A, AoErg11B and AoErg11C were identified in Aspergillus oryzae genome through bioinformatics analysis. The function of these three genes were studied by yeast complementation, and the expression pattern/subcellular localization of these genes/proteins were detected. The results showed that the three AoErg11s were expressed differently at different growth times and under different abiotic stresses. All of the three proteins were located in endoplasmic reticulum. The AoErg11s could not restore the temperature-sensitive phenotype of S. cerevisiae erg11 mutant. Overexpression of the three AoErg11s affected both growth and sporulation, which may be due to the effect of AoErg11s on ergosterol content. Therefore, this study revealed the functions of three AoErg11s and their effects on the growth and ergosterol biosynthesis of A. oryzae, which may contribute to the further understanding of the ergosterol biosynthesis and regulation mechanism in this important filamentous fungus, A. oryzae.

BackgroundThere are controversies on the pathophysiological alteration in patients with atrial fibrillation (AF) undergoing pulmonary vein isolation using different energy sources.ObjectivesWe evaluated the changes in plasma proteins in acute phase post-ablation in patients receiving cryoballoon ablation, radiofrequency balloon ablation, or radiofrequency ablation.MethodsBlood samples from eight healthy controls and 24 patients with AF were taken on the day of admission, day 1, and day 2 post-ablation and analyzed by the Olink proximity extension assay. Proteins were identified and performed with enrichment analysis. Protein–protein interaction network and module analysis were conducted using Cytoscape software.ResultsOf 181 proteins, 42 proteins in the cryoballoon group, 46 proteins in the radiofrequency balloon group, and 43 proteins in the radiofrequency group significantly changed after ablation. Most of the proteins altered significantly on the first day after ablation. Altered proteins were mainly involved in cytokine–cytokine receptor interaction. Both balloon-based ablations showed a similar shift toward enhancing cell communication and regulation of signaling while inhibiting neutrophil chemotaxis. However, radiofrequency ablation presented a different trend. Seed proteins, including osteopontin, interleukin-6, interleukin-10, C-C motif ligand 8, and matrix metalloproteinase-1, were identified. More significant proteins associated with hemorrhage and coagulation were selected in balloon-based ablations by machine learning.ConclusionPlasma protein response after three different ablations in patients with AF mainly occurred on the first day. Radiofrequency balloon ablation shared similar alteration in protein profile as cryoballoon ablation compared with radiofrequency ablation, suggesting that lesion size rather than energy source is the determinant in pathophysiological responses to the ablation.

ABSTRACT Screening for active tuberculosis (TB) among individuals with latent tuberculosis infection (LTBI) is important for the initiation and evaluation of TB preventive treatment. The performances of different tools and their combinations had rarely been studied in community-level screening among individuals with LTBI in China. This study aimed to explore appropriate algorithms for screening for active TB among individuals with LTBI in rural China. Three sputum samples were collected from each participant for smear microscopy, culture, and an Xpert MTB/RIF assay. Chest digital radiography and TB symptoms were investigated as well. The performances of different testing algorithms were compared with that of sputum culture as the gold standard. Overall, 1,564 study participants with LTBI were investigated, with a final diagnosis of 20 TB cases by sputum culture. Compared with other tests, the Xpert MTB/RIF assay detected 80.00% (95% confidence interval [CI], 58.40% to 91.93%) of culture-positive cases, with the highest sensitivity. When tests were combined using “or,” “and,” or “step” algorithms, the highest sensitivity reached 90.00% (95% CI, 69.90% to 97.21%) for the combination of the Xpert MTB/RIF assay and chest radiography, but the positive predictive value (PPV) decreased to 22.22% (95% CI, 14.54% to 32.41%). The Xpert MTB/RIF assay alone showed the best agreement with sputum culture, with a kappa value of 0.840. Pathogen molecular detection alone showed good performance compared to the other algorithms, for ruling out active TB in general LTBI, but the high cost might be a challenge for scaling it up. Identifying those with a high risk for progression to TB more precisely and establishing a cost-effective screening algorithm deserve further exploration. IMPORTANCE Enhancing community-wide active case screening in target LTBI populations is important for achieving the early treatment of active TB, and ruling active TB out is a prerequisite for initiating preventive treatment. The current study evaluated the performances of multiple tests and their combinations in screening for active TB among individuals with LTBI at the community level. Compared with the classical “TB symptoms and chest radiography” algorithm, the application of Xpert MTB/RIF improved the sensitivity from 45% to 80%. When the Xpert MTB/RIF assay was combined with chest radiography, the sensitivity was further improved to 90.00%, which achieved the World Health Organization (WHO) target product profiles. However, the algorithm requires caution as the PPV decreased from 88.89% for Xpert MTB/RIF alone to 22.22% for the combination. Xpert MTB/RIF alone offered remarkable sensitivity without compromising the PPV but would have major resource implications. Thus, identifying target populations for LTBI treatment more precisely and developing cost-effective and high-throughput screening tools and algorithms deserve further efforts.

Abstract Objective Obstructive sleep apnoea (OSA) is one cause of pulmonary hypertension (PH) and can also emerge along with PH. The clinical diagnosis and treatment of OSA in patients with PH are still controversial. The purpose of this clinical observation study was to observe and summarize the incidence and clinical characteristics of OSA in patients with PH and to explore possible predictors of PH combined with OSA. Methods Patients with PH diagnosed by right heart catheterization who underwent overnight cardiorespiratory monitoring from December 2018 to December 2020 were enrolled. OSA was defined as an apnoea–hypopnoea index of ≥ 5/h with ≥ 50% of apnoeic events being obstructive. Baseline clinical characteristics and parameters were collected to compare PH patients with and without OSA. Logistic regression analysis was run to determine the risk factors for OSA in PH patients. Results A total of 35 (25%) of 140 patients had OSA. OSA is relatively frequent in patients with PH, especially in patients with chronic thromboembolic pulmonary hypertension and patients with lung disease– or hypoxia-associated PH. The patients who had OSA were mostly male and had a higher age and a lower daytime arterial oxygen pressure. Logistic regression analysis found that older age, male sex, and lower daytime arterial blood oxygen pressure correlated with OSA in PH patients. Conclusion OSA is common in patients with PH. Lower daytime arterial oxygen pressure is a risk factor for OSA in older male patients with PH.

AIM:To compare the effect of self-crosslinking sodium hyaluronic gel, Nasopore, and gelatin sponge in endonasal endoscopic dacryocystorhinostomy(En-DCR).METHODS:Totally 72 patients(90 eyes)of chronic dacryocystitis admitted to our hospital from June 2019 to June 2020, and randomly divide them into three groups. Self-crosslinking sodium hyaluronic gel(group A), Nasopore(group B), and gelfoam(group C)were used during the En-DCR. Comfort level, bleeding, complication and epiphora, lacrimal situation were observed 2wk, 1, 2, 3, 6mo after surgery. Comparison of cure rate and effective rate.RESULTS: The patients were followed up for 6mo after operation. The cure rate of lacrimal system reconstruction was 97% in group A, 89% in group B and 94% in group C. There was no meaningful statistical difference among the three groups(P>0.05). The effective rate of lacrimal system reconstruction was 91% in group A, 56% in group B and 87% in group C(P0.0167). Postoperative comfort level was better and bleeding was more severe in the group of A than in group B(P

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important and major player in the pathophysiology of hypercholesterolemia and atherosclerosis. Recently, PCSK9 has been implicated in the pathogenesis of inflammatory diseases. Whether PCSK9 is involved in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to investigate the relationship between PCSK9 and IPAH. Serum PCSK9, interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), interleukin‐1 β (IL‐1β), and monocyte chemotactic protein‐1 (MCP‐1) were measured by enzyme linked immunosorbent assay. Transthoracic echocardiography was performed among 40 IPAH patients and 20 control subjects. Hemodynamic data were collected via right heart catheterization in patients with IPAH. Serum PCSK9, TNF‐α, IL‐6, IL‐1β, and MCP‐1 levels were significantly higher in IPAH patients than in control subjects (p

To solve the problem of mode competition in high-order working modes, this paper presents a fast design method based on the TM31-2π mode for the dumbbell shaped extended interaction cavity. Based on the equivalent circuit theory, the high-frequency characteristics of the structure are studied. In addition, we propose a W-band continuous wave sheet beam extended interaction klystron high-frequency circuit. The circuit was driven by a 20 kV and 0.85 A sheet electron beam, with a 3.2 × 0.3 mm2 section. The beam was focused by a 0.8 T permanent magnet system. The high-frequency system adopts five dumbbell shaped five-gap cavities, and the output system adopts a symmetrical output waveguide. The 3D particle-in-cell simulation shows that more than 1.5 kW power can be obtained at an input power of 0.12 W, and the electron efficiency and gain are 9.2% and 41.2 dB, respectively.

Background: To achieve favorable hemodynamics, the number of balloon pulmonary angioplasty (BPA) sessions varied significantly among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Increased BPA sessions burdened patients financially and psychologically. We aim to identify baseline characteristics that could predict early BPA response. Methods: Consecutive patients who were diagnosed with inoperable CTEPH and received BPA between May 2018 and October 2021 at Fuwai Hospital were retrospectively collected. Patients were categorized into ‘Early BPA responders’ or ‘Non-early BPA responders’ according to the hemodynamic outcome within the first three BPA sessions. Results: In total, 101 patients were included into analysis. At baseline, non-early BPA responders had lower female proportion, longer disease duration, and poorer laboratory test results compared with early responders, whereas hemodynamics were comparable. After the first three BPA sessions, hemodynamic improvement was more significant in early responders. Incidence of complication was comparable between the two groups. Multivariable logistic analysis identified that female sex (odds ratio [OR]: 7.155, 95% confidence interval [CI]: 1.323-38.692, p = 0.022), disease duration (OR: 0.851, 95% CI: 0.727-0.995, p = 0.043), baseline total bilirubin (OR: 0.934, 95% CI: 0.875-0.996, p = 0.038), and baseline NT-proBNP (OR: 0.473, 95% CI: 0.255-0.879, p = 0.018) were independently associated with early BPA response. Combination of these four parameters could predict 90% early BPA response. Conclusions: Patients with shorter disease duration, female sex, lower baseline NT-proBNP, and lower baseline total bilirubin are more likely to achieve early hemodynamic response to BPA. Moreover, early hemodynamic response was not accompanied with increased incidence of procedure-related complications.

Podocyte injury is a common cause of proteinuric kidney diseases. Uncontrollable progressive podocyte loss accelerates glomerulosclerosis and increases the risk of end-stage renal disease. To date, owing to the complex pathological mechanism, effective therapies for podocyte injury have been limited. Accumulating evidence supports the indispensable role of autophagy in the maintenance of podocyte homeostasis. A variety of natural compounds and their derivatives have been found to regulate autophagy through multiple targets, including promotes nuclear transfer of transcription factor EB and lysosomal repair. Here, we reviewed the recent studies on the use of natural compounds and their derivatives as autophagy regulators and discussed their potential applications in ameliorating podocyte injury. Several known natural compounds with autophagy-regulatory properties, such as quercetin, silibinin, kaempferol, and artemisinin, and their medical uses were also discussed. This review will help in improving the understanding of the podocyte protective mechanism of natural compounds and promote their development for clinical use.

ObjectivesThis study aimed to explore the effect of maternal iodine status on the brain development of offspring in rats. Since in human studies, the interference of environmental factors and other nutrients cannot be removed.Materials and methodsA total of 48 female Wistar rats were randomly divided into four groups: low iodine (LI), normal iodine (NI), 10-fold high iodine (10HI), and 50-fold high iodine (50HI). The rats were killed on the 15th day of pregnancy and lactation after collecting 24-h urine. The iodine concentration in 24-h urine, blood, and placenta of pregnant rats, and 24-h urine, milk, blood, and mammary glands of lactating rats was determined by inductively coupled plasma mass spectrometry. The thyroid hormone of pregnant and lactating rats was detected by chemiluminescence. The offspring were subjected to the Morris water maze on the 10th day after birth. Serum was collected to detect the thyroid hormone of offspring. The protein expression of neuroendocrine-specific protein (NSP)-A and brain-derived neurotrophic factor (BDNF) in the offspring brain were studied.ResultsIodine storage in the placenta during pregnancy and mammary glands during lactation was positively correlated with iodine intake, and iodine storage in the placenta and mammary glands in the 50HI group was significantly higher than that in the NI group (P = 0.045 and P = 0.040). Compared with the NI group, the offspring thyroid-stimulating hormone (TSH) level was significantly higher in the 10HI group (P = 0.046), and the FT4 level was significantly lower in the 50HI group (P = 0.032). The Morris water maze showed that LI and 50HI groups required longer time and distance to find the platform than the NI group (P < 0.001). The platform crossing numbers in the LI and 50HI groups decreased significantly (P < 0.001). The expression of NSP-A in offspring brain was lower in the 10HI and 50HI groups than in the NI group (P = 0.026 and P = 0,008). BDNF expression levels were significantly lower in the LI, 10HI, and 50HI groups than in the NI group (P < 0.001).ConclusionMaternal iodine intake affects iodine storage in the placenta and lactating mammary gland, which in turn affects thyroid function and BDNF and NSP-A expression in the offspring.

Silicon carbide wafer serves as an ideal substrate material for manufacturing semiconductor devices, holding immense potential for the future. However, its ultra-hardness and remarkable chemical inertness pose significant challenges for the surface processing of wafers, and a highly efficient and damage-free method is required to meet the processing requirements. In this study, atmospheric plasma processing was used to conduct point-residence experiments on silicon carbide wafers by varying process parameters such as Ar, CF4, and O2 flow rate, as well as processing power and the distance between the plasma torch and the workpiece. We investigate the effects of these on the surface processing function of atmospheric plasma etching and technique for surface modification of silicon carbide wafers, evaluating the material removal rates. Then, according to the experimentally derived influence law, suitable parameter ranges were selected, and orthogonal experiments were designed to determine the optimal processing parameters that would enable rapid and uniform removal of the wafer surface. The results indicate that the volume removal rate of the plasma on the silicon carbide wafer achieves its maximum when the input power is 550 W, the processing distance between the plasma torch and workpiece is 3.5 mm, and when the Ar, CF4, and O2 flow rates are 15 SLM, 70 SCCM, and 20 SCCM, respectively.

The inflammatory and insulinemic potentials of diets have been associated with colorectal cancer risk. However, it is unknown whether the plasma metabolite profiles related to inflammatory diets, or to insulinemic diets, underlie this association. The aim of this study was to evaluate the association between metabolomic profile scores related to the food-based empirical dietary inflammatory patterns (EDIP), the empirical dietary index for hyperinsulinemia (EDIH), and plasma inflammation (CRP, IL-6, TNFα-R2, adiponectin) and insulin (C-peptide) biomarkers, and colorectal cancer risk. Elastic net regression was used to derive three metabolomic profile scores for each dietary pattern among 6840 participants from the Nurses’ Health Study and Health Professionals Follow-up Study, and associations with CRC risk were examined using multivariable-adjusted logistic regression, in a case-control study of 524 matched pairs nested in both cohorts. Among 186 known metabolites, 27 were significantly associated with both the EDIP and inflammatory biomarkers, and 21 were significantly associated with both the EDIH and C-peptide. In men, odds ratios (ORs) of colorectal cancer, per 1 standard deviation (SD) increment in metabolomic score, were 1.91 (1.31–2.78) for the common EDIP and inflammatory-biomarker metabolome, 1.12 (0.78–1.60) for EDIP-only metabolome, and 1.65 (1.16–2.36) for the inflammatory-biomarkers-only metabolome. However, no association was found for EDIH-only, C-peptide-only, and the common metabolomic signatures in men. Moreover, the metabolomic signatures were not associated with colorectal cancer risk among women. Metabolomic profiles reflecting pro-inflammatory diets and inflammation biomarkers were associated with colorectal cancer risk in men, while no association was found in women. Larger studies are needed to confirm our findings.

In this paper, the research on the fatigue damage mechanism of tire rubber materials is the core, from designing fatigue experimental methods and building a visual fatigue analysis and testing platform with variable temperature to fatigue experimental research and theoretical modeling. Finally, the fatigue life of tire rubber materials is accurately predicted by using numerical simulation technology, forming a relatively complete set of rubber fatigue evaluation means. The main research is as follows: (1) Mullins effect experiment and tensile speed experiment are carried out to explore the standard of the static tensile test, and the tensile speed of 50 mm/min is determined as the speed standard of plane tensile, and the appearance of 1 mm visible crack is regarded as the standard of fatigue failure. (2) The crack propagation experiments were carried out on rubber specimens, and the crack propagation equations under different conditions were constructed, and the relationship between temperature and tearing energy was found out from the perspective of functional relations and images, and the analytical relationship between fatigue life and temperature and tearing energy was established. Thomas model and thermo-mechanical coupling model were used to predict the life of plane tensile specimens at 50 °C, and the predicted results were 8.315 × 105 and 6.588 × 105, respectively, and the experimental results were 6.42 × 105, with errors of 29.5% and 2.6%, thus verifying the accuracy of thermo-mechanical coupling model.

Abstract Background Identifying and prioritizing at-risk populations is critical for pediatric tuberculosis control. We aimed to identify a latent tuberculosis infection (LTBI) screening strategy that is appropriate for the Chinese context among children with different TB exposure levels and to explore its clinical importance. Methods During 2013–2015, we enrolled hospitalized children with suspected respiratory infectious disease (RID) for LTBI screening using the tuberculin skin test (TST) and interferon-γ release assay (IGRA) T-SPOT.TB as part of a work up for their RID. Participants with confirmed diagnosis were classified into three subgroups according to level of exposure to TB: no reported contact risk, with household contact risk, and with non-household contact risk. Results A total 6202 children (median age: 4.76 years; interquartile range: 1.0–8.0 years) were enrolled. Children with no reported contact risk had the lowest proportions of positive results for the IGRA (0.7%) and TST (3.3%). The proportion of positive results for each test was higher for household contacts than non-household contacts. The TST positive proportion was much higher than that for the IGRA in all three groups. Children with IGRA+/TST+ results had larger indurations than those with IGRA− /TST+ results (15 mm vs. 13 mm, P = 0.02). For IGRA, older age (> 5 years) and non-household or household contact risk were associated with a positive result. Conclusions Positive IGRA results in children with a contact risk can serve as a critical reference for LTBI management. IGRA can be used, in preference to TST, for Chinese children with a TB exposure risk.

Ultrasonic surface rolling technology is a new mechanical surface treatment technology that can improve the surface integrity, increase the amplitude and depth of the residual compressive stress layer and improve the fatigue property of metal materials. In this paper, the effect of ultrasonic rolling on the surface layer's microstructure and properties of Ti6Al4V alloys is investigated. The microstructure, surface roughness, surface topography, microhardness and residual stress were used to characterise the surface-modified layer. Specimens treated by ultrasonic surface rolling obtained the smallest surface roughness (0.231 μm) and largest plastic deformation depth (304.38 μm), simultaneously, under sixteen processing stage numbers. The rule of surface compressive residual stress distribution had a similar tendency to the law of surface microhardness distribution. Furthermore, the grain size of the strengthened surface layer decreased, the texture type changed and the Schmidt factor increased compared with the matrix. The increase of microhardness and residual stress is due to grain refinement and dislocation strengthening.

Abstract Background The role of sexually transmitted infections (STIs) in semen parameters and male infertility is still a controversial area. Previous studies have found bacterial infection in a minority of infertile leukocytospermic males. This study aims to investigate the prevalence of STIs in semen from subfertile men with leukocytospermia (LCS) and without leukocytospermia (non-LCS) and their associations with sperm quality. Methods Semen samples were collected from 195 men who asked for a fertility evaluation. Infection with the above 6 pathogens was assessed in each sample. Sperm quality was compared in subfertile men with and without LCS. Results The LCS group had significantly decreased semen volume, sperm concentration, progressive motility, total motility and normal morphology. The infection rates of Ureaplasma urealyticum (Uuu), Ureaplasma parvum (Uup), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), herpes simplex virus-2 (HSV-2) and Neisseria gonorrhoeae (NG) were 8.7 %, 21.0 %, 8.2 %, 2.1 %, 3.6 %, 1.0 and 0 %, respectively. The STI detection rates of patients with LCS were higher than those of the non-LCS group (52.3 % vs. 39.3 %), although there was no statistically significant difference between the two groups (P = 0.07). All semen parameters were not significantly different between LCS with STIs and without STIs, except the semen volume in the MG-infected patients with LCS was significantly lower than that in the noninfected group. Conclusions LCS was associated with a reduction in semen quality, but was not associated with STIs.

Neutrophils have been recognized to play an important role in the pathogenesis of tuberculosis in recent years. Interferon-induced blood transcriptional signatures in ATB are predominantly driven by neutrophils. In this study, we performed global RNA-seq on peripheral blood neutrophils from active tuberculosis patients (ATB, n=15); latent tuberculosis infections (LTBI, n=22); and healthy controls (HC, n=21). The results showed that greater perturbations of gene expression patterns happened in neutrophils from ATB individuals than HC or those with LTBI, and a total of 344 differentially expressed genes (DEGs) were observed. Functional enrichment analysis showed that besides the interferon signaling pathway, multiple pattern recognition receptor pathways were significantly activated in ATB, such as NOD-like receptors and Toll-like receptors. Meanwhile, we also observed that the expression of genes related to endocytosis, secretory granules, and neutrophils degranulation were downregulated. Our data also showed that the NF-κB signaling pathway might be inhibited in patients with ATB, which could increase Mycobacterium tuberculosis survival and lead to active tuberculosis status. Furthermore, we validated the accuracy of some differentially expressed genes in an independent cohort using quantitative PCR, and obtained three novel genes (RBM3, CSRNP1, SRSF5) with the ability to discriminate active tuberculosis from LTBI and HC.

Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising results in improving the prognosis of cancer patients. The goal of this meta-analysis was to determine the impact of probiotic use on the survival of cancer patients treated with ICIs.Methods: Before 3 March 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, Google Scholar, and Clinical trials.gov databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were the primary endpoints.Results: A total of 6 studies met the inclusion criteria, and 1,123 patients were included. Meta-analysis showed a trend for probiotic use to prolong PFS (HR: 0.585, 95% CI: 0.328–1.045, p = 0.070) and increase DCR (HR: 1.868, 95% CI: 0.890–3.922, p = 0.099), although it was of borderline statistical significance. We also found that probiotics significantly improved OS (HR: 0.526, 95% CI: 0.341–0.812, p = 0.004) and ORR (OR: 2.831, 95% CI: 1.578–5.076, p < 0.001) in ICI-treated cancer patients. Besides, subgroup analysis showed that non-small cell lung cancer (NSCLC) patients treated with ICIs in combination with probiotics would achieve significantly longer PFS (HR: 0.532, 95% CI: 0.354–0.798, p = 0.002) and OS (HR: 0.528, 95% CI: 0.306–0.912, p = 0.022), as well as higher ORR (OR: 2.552, 95% CI: 1.279–5.091, p = 0.008) and DCR (OR: 2.439, 95% CI: 1.534–3.878, p < 0.001). Sensitivity analysis showed that the above results are stable and reliable. The publication bias test confirmed that there was no publication bias in these results.Conclusion: Current evidence reveals that probiotics can improve the efficacy of ICI treatment in NSCLC patients.Systematic Review Registeration:https://www.crd.york.ac.uk/prospero/, identifier CRD42022316104.

BackgroundIdentifying host plasma exosome proteins associated with host response to latent tuberculosis infection (LTBI) treatment might promote our understanding of tuberculosis (TB) pathogenesis and provide useful tools for implementing the precise intervention.MethodsBased on an open-label randomized controlled trial (RCT) aiming to evaluate the short-course regimens for LTBI treatment, plasma exosomes from pre- and post-LTBI treatment were retrospectively detected by label-free quantitative protein mass spectrometry and validated by a parallel reaction monitoring method for participants with changed or not changed infection testing results after LTBI treatment. Eligible participants for both screening and verification sets were randomly selected from the based-RCT in a 1:1 ratio by age and gender. Reversion was defined as a decrease in IFN-γ levels from >0.70 IU/ml prior to treatment to 0.20 IU/ml within 1 week of treatment. The predictive ability of the candidate proteins was evaluated by receiver operating characteristic (ROC) analysis.ResultsTotally, two sample sets for screening (n = 40) and validation (n = 60) were included. Each of them included an equal number of subjects with persistent positive or reversed QuantiFERON-TB Gold In-Tube (QFT) results after LTBI. A total of 2,321 exosome proteins were detected and 102 differentially expressed proteins were identified to be associated with QFT reversion. Proteins with high confidence and original values intact were selected to be further verified. Totally, 9 downregulated proteins met the criteria and were validated. After verification, C4BPA and S100A9 were confirmed to be still significantly downregulated (fold change

Aims: Impairment of right ventricle-to-pulmonary artery coupling (RV-PA coupling) is a major determinant of poor prognosis in patients with pulmonary hypertension. This study sought to evaluate the ability of an echo-derived metric of RV-PA coupling, the ratio between tricuspid annular plane systolic excursion (TAPSE), and pulmonary artery systolic pressure (PASP) and to predict adverse clinical outcomes in chronic thromboembolic pulmonary hypertension (CTEPH). Methods and results: A total of 205 consecutive patients with confirmed CTEPH were retrospectively recruited from Fuwai Hospital between February 2016 and November 2020. Baseline echocardiography, right heart catheterization, and cardiopulmonary exercise testing were analyzed. Patients with lower TAPSE/PASP had a significantly compromised echocardiographic and hemodynamic status and exercise capacity at baseline. The TAPSE/PASP ratio correlated significantly with hemodynamic parameters, including pulmonary vascular resistance ( r = −0.48, p

Artificial intelligence is increasingly being used on the clinical electrocardiogram workflows. Few electrocardiograms based on artificial intelligence algorithms have focused on detecting myocardial ischemia using long-term electrocardiogram data. A main reason for this is that interference signals generated from daily activities while wearing the Holter monitor lowered the ability of artificial intelligence to detect myocardial ischemia. In this study, an automatic system combining denoising and segmentation modules was developed to detect the deviation of the ST-segment and J point. We proposed a ECG Bidirectional Transformer network that applied in both denoising and segmentation tasks. The denoising model achieved RMSEde, SNRimp, and PRD values of 0.074, 10.006, and 16.327, respectively. The segmentation model achieved precision, sensitivity (recall), and F1-score of 96.00, 93.06, and 94.51%, respectively. The system’s ability to distinguish the depression and elevation of the ST-segment and J point was also verified by cardiologists as well. From our ECG dataset, 103 patients with ST-segment depression and 10 patients with ST-segment elevation were detected with positive predictive values of 80.6 and 60% respectively. Using Holter ECG and transformer-based deep neural networks, we can detect subtle ST-segment changes in noisy ECG signals. This system has the potential to improve the efficacy of daily medicine and to provide a broader population-level screening for asymptomatic myocardial ischemia.

ABSTRACT Tuberculosis (TB) remains one of the deadliest communicable diseases. Biomarkers predicting the risk of active disease development from latent tuberculosis infection (LTBI) are urgently needed for precise intervention. This study aimed to identify potential circulating microRNAs (miRNAs) playing such a role in Chinese population. Based on a prospective study aiming to track the development of active TB among rural residents with LTBI, the baseline levels of circulating miRNAs were retrospectively compared between those who developed TB (case group) and those age-gender matched controls remain free of TB (contraol group) during the follow-up. Agilent human miRNA microarray were used to select differently expressed circulating miRNAs and verified by subsequent real-time quantitative PCR (RT-qPCR). Six candidate miRNAs were expressed at statistically significant levels between the two groups at the baseline, as determined by microarray. Following verification among 150 study participants by RT-qPCR, the levels of hsa-miR-16-5p (P < 0.001) and hsa-miR-451a (P < 0.001) were found to be significantly lower in case group compared to control group. The combined areas under curves (AUCs) and precision-recall curves (PRCs) were 0.84, 0.86 and 0.85, 0.87 for hsa-miR-16-5p and hsa-miR-451a, respectively. hsa-miR-451a combined with body mass index (BMI) and prior history of TB presented the best performance, with a sensitivity of 80.82% and an acceptable specificity of 79.22%. After adjusting the two co-variables, the AUC of hsa-miR-451a was 0.78. Circulating levels of hsa-miR-451a showed potential to predict development of active TB from LTBI in a Chinese population. Further studies are warranted to verify these findings in varied study settings. IMPORTANCE Approximately a quarter of the world population are infected with M. tuberculosis and about 5% to 10% of these might develop active disease in their lifetime. Preventive treatment could effectively protect individuals at a high risk of developing active disease from LTBI, and is regarded as a critical component of End TB Strategies. Biomarkers which could accurately identify high-risk population and predict the risk of disease development are urgently needed for developing local guidelines of LTBI management and precise intervention. A nested case-control study was designed to explore possible microRNAs related with TB occurrence based on a previous prospective study, which aimed to track the development of active TB among rural residents with LTBI. The baseline circulating levels of hsa-miR-16-5p and hsa-miR-451a were significantly lower in TB cases compared to those in LTBI controls. Further receiver operator characteristic (ROC) curve analysis found that hsa-miR-451a showed considerable potential to predict the development of active TB from LTBI.

Abstract Background Dogs are domesticated wolves. Change of living environment, such as diet and veterinary care may affect the gut bacterial flora of dogs. The aim of this study was to assess the gut bacterial diversity and function in dogs compared with captive wolves. We surveyed the gut bacterial diversity of 27 domestic dogs, which were fed commercial dog food, and 31 wolves, which were fed uncooked meat, by 16S rRNA sequencing. In addition, we collected fecal samples from 5 dogs and 5 wolves for shotgun metagenomic sequencing to explore changes in the functions of their gut microbiome. Results Differences in the abundance of core bacterial genera were observed between dogs and wolves. Together with shotgun metagenomics, the gut microbiome of dogs was found to be enriched in bacteria resistant to clinical drugs (P

Abstract Background The development of atrial fibrillation (AF) following valvular heart disease (VHD) remains a common disease and is associated with substantial adverse complications. However, valid molecular diagnostic and therapeutic tools for post-VHD AF have not been fully established. This study was conducted to discover the molecular mechanisms and immune microenvironment underlying AF following VHD. Methods Gene expression profiles of the GSE41177 dataset were assessed to construct a protein–protein interaction network, and then, autophagy-related hub genes were identified. In addition, to determine the functions of immune cell infiltration in valvular AF, we used the CIBERSORT algorithm to estimate the composition of 22 immune cell types in valvular heart disease. Finally, correlation analysis was carried out to identify the relationship between differentially expressed autophagy-related genes (DEARGs) and significant immune cell subpopulations to reveal potential regulatory pathways. Results A total of 153 DEARGs were identified in AF-VHD patients compared with controlled donors. Moreover, we screened the top ten hub nodes with the highest degrees through a network analysis. The ten hub nodes were considered hub genes related to AF genesis and progression. Then, we revealed six significant immune cell subpopulations through the CIBERSORT algorithm. Finally, correlation analysis was performed, and six DEARGs (BECN1, GAPDH, ATG7, MAPK3, BCL2L1, and MYC) and three immune cell subpopulations (T cells CD4 memory resting, T cells follicular helper, and neutrophils) were identified as the most significant potential regulators. Conclusion The DEARGs and immune cells identified in our study may be critical in AF development following VHD and provide potential predictive markers and therapeutic targets for determining a treatment strategy for AF patients.

Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully understood, pulmonary vasoconstriction, vascular remodeling, immune and inflammatory responses, and thrombosis are thought to be involved in the development and progression of PAH. In the era of non-targeted agents, PAH had a very dismal prognosis with a median survival time of only 2.8 years. With the deep understanding of the pathophysiological mechanism of PAH as well as advances in drug research, PAH-specific therapeutic drugs have developed rapidly in the past 30 years, but they primarily focus on the three classical signaling pathways, namely the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. These drugs dramatically improved pulmonary hemodynamics, cardiac function, exercise tolerance, quality of life, and prognosis in PAH patients, but could only reduce pulmonary arterial pressure and right ventricular afterload to a limited extent. Current targeted agents delay the progression of PAH but cannot fundamentally reverse pulmonary vascular remodeling. Through unremitting efforts, new therapeutic drugs such as sotatercept have emerged, injecting new vitality into this field. This review comprehensively summarizes the general treatments for PAH, including inotropes and vasopressors, diuretics, anticoagulants, general vasodilators, and anemia management. Additionally, this review elaborates the pharmacological properties and recent research progress of twelve specific drugs targeting three classical signaling pathways, as well as dual-, sequential triple-, and initial triple-therapy strategies based on the aforementioned targeted agents. More crucially, the search for novel therapeutic targets for PAH has never stopped, with great progress in recent years, and this review outlines the potential PAH therapeutic agents currently in the exploratory stage to provide new directions for the treatment of PAH and improve the long-term prognosis of PAH patients.

Objective The aim of this study was to compare the clinical efficacy of percutaneous endoscopic interlaminar discectomy (PEID) and percutaneous endoscopic transforaminal discectomy (PETD) in treating L5/S1 disc herniation. Methods A retrospective analysis of 76 patients with L5/S1 intervertebral disc herniation was performed. There were two surgical treatment groups: one with patients receiving PEID and the other with patients receiving PETD. The two groups were compared by length of surgery, times of intraoperative X‐ray exposure, postoperative time in bed, length of hospital stay, operative complications, patient's assessment of pain using a visual analogue scale (VAS), and disability using the Oswestry disability index (ODI) before and after surgery. Results Subjects in the PEID group were in surgery for 60.90 ± 13.11 min and needed intraoperative X‐ray exposure 4.10 ± 1.09 times. Patients in this group were ambulatory by 7.52 ± 1.08 h after surgery and were hospitalized for 5.05 ± 0.92 days. In contrast, patients in the PETD group were in surgery for 84.06 ± 15.58 min and needed intraoperative X ray exposure 12.81 ± 8.46 times. These patients were ambulatory by 7.06 ± 0.91 h after surgery and remained in the hospital for 4.94 ± 0.80 days. Based on these data, operation time and fluoroscopy time were significantly less (P

Abstract Background As the largest group of mammalian species, which are also widely distributed all over the world, rodents are the natural reservoirs for many diverse zoonotic viruses. A comprehensive understanding of the core virome of diverse rodents should therefore assist in efforts to reduce the risk of future emergence or re-emergence of rodent-borne zoonotic pathogens. Results This study aimed to describe the viral range that could be detected in the lungs of rodents from Mainland Southeast Asia. Lung samples were collected from 3284 rodents and insectivores of the orders Rodentia, Scandentia, and Eulipotyphla in eighteen provinces of Thailand, Lao PDR, and Cambodia throughout 2006–2018. Meta-transcriptomic analysis was used to outline the unique spectral characteristics of the mammalian viruses within these lungs and the ecological and genetic imprints of the novel viruses. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time in these species, and viruses related to known pathogens were characterized for their genomic and evolutionary characteristics, host species, and locations. Conclusions These results expand our understanding of the core viromes of rodents and insectivores from Mainland Southeast Asia and suggest that a high diversity of viruses remains to be found in rodent species of this area. These findings, combined with our previous virome data from China, increase our knowledge of the viral community in wildlife and arthropod vectors in emerging disease hotspots of East and Southeast Asia. Video abstract

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22–28, whereas HCoV-OC43 antibody titres increased until days 15–21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, −229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1–21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1–10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.

Heavy metal resistant bacteria play an important role in the metal biogeochemical cycle in soil, but the benefits of microbial oxidation for plants and soil have not been well-documented. The purpose of this study was to explore the contribution of two Bacillus spp. to alleviate the antimony (Sb) toxicity in plants, and, then, to propose a bioremediation method for Sb contaminated soil, which is characterized by environmental protection, high efficiency, and low cost. This study explored the effects of Bacillus cereus HM5 and Bacillus thuringiensis HM7 inoculation on Broussonetia papyrifera and soil were evaluated under controlled Sb stressed conditions (0 and 100 mmol/L, antimony slag) through a pot experiment. The results show that the total root length, root volume, tips, forks, crossings, and root activities of B. papyrifera with inoculation are higher than those of the control group, and the strains promote the plant absorption of Sb from the soil environment. Especially in the antimony slag treatment group, B. cereus HM5 had the most significant effect on root promotion and promoting the absorption of Sb by B. papyrifera. Compared with the control group, the total root length, root volume, tips, forks, crossings, and root activities increased by 64.54, 70.06, 70.04, 78.15, 97.73, and 12.95%, respectively. The absorption of Sb by root, stem, and leaf increased by 265.12, 250.00, and 211.54%, compared with the control group, respectively. Besides, both B. cereus HM5 and B. thuringiensis HM7 reduce the content of malondialdehyde, proline, and soluble sugars in plant leaves, keeping the antioxidant enzyme activity of B. papyrifera at a low level, and alleviating lipid peroxidation. Principal component analysis (PCA) shows that both B. cereus HM5 and B. thuringiensis HM7 are beneficial to the maintenance of plant root functions and the improvement of the soil environment, thereby alleviating the toxicity of Sb. Therefore, B. cereus HM5 and B. thuringiensis HM7 in phytoremediation with B. papyrifera is a promising inoculant used for bacteria-assisted phytoremediation on Sb contaminated sites.

BackgroundMandibular sagittal split ramus osteotomy (SSRO) is a routine surgery to correct mandibular deformities, such as mandibular retrusion, protrusion, deficiency, and asymmetry. However, nonunion/malunion of the fragments and relapse caused by fixation failure after SSRO are major concerns. Rigid fixation to maintain postosteotomy segmental stabilization is critical for success. Additionally, understanding the biomechanical characteristics of different fixation methods in SSRO with large advancements is extremely important for clinical guidance. Therefore, the aim of the present study was to evaluate the biomechanical characteristics of different SSRO methods by finite element analysis.MethodsSSRO finite element models with 5-, 10-, 15-, and 20-mm advancements were developed. Seven fixation methods, namely, two types of bicortical screws, single miniplate, dual miniplates, grid plate, dual L-shaped plates, and hybrid fixation, were positioned into the SSRO models. Molar and incisal biomechanical loads were applied to all models to simulate bite forces. We then investigated the immediate postoperative stability from four aspects, namely, the stability of the distal osteotomy segment, osteotomy regional stability, stress distribution on the mandible, and implant stress performance.ResultsThe stability of the distal osteotomy segment and osteotomy region decreased when the advancement increased. All seven fixation methods displayed favorable biomechanical stability under minor advancement (5 mm). With large advancements, bicortical screws, dual miniplates, and grid plates provided better stability. The von Mises stress was concentrated around the screws close to the osteotomy region for the proximal segment for all fixation methods, and the von Mises stress on implants increased with larger advancements. With small advancements, five fixation methods endured tolerable maximum stresses of

Lysine crotonylation is a newly discovered post-translational modification (PTM) with key roles in various important regulatory pathways. Despite its functional significance, there is limited knowledge about crotonylation in fungi. Trichophyton rubrum is the most common fungal pathogen in human infection and is considered a model organism of dermatophytes and human pathogenic filamentous fungi. In this study, we obtained a proteome-wide crotonylation profile of T. rubrum, leading to the identification of 14,019 crotonylated sites on 3144 proteins. The crotonylated proteins were significantly involved in translation and in various metabolic and biosynthetic processes. Some proteins related to fungal pathogenicity were also found to be targets of crotonylation. In addition, extensive crotonylation was found on histones, suggesting a role in epigenetic regulation. Furthermore, about half of the crotonylated proteins were specific to either the conidial or the mycelial stage, and functional enrichment analysis showed some differences between the two stages. The results suggest that the difference in crotonylation between the two stages is not due to differences in protein abundance. Crosstalk of crotonylation with acetylation, propionylation, and succinylation suggests distinct regulatory roles. This study is the first crotonylation analysis in dermatophytes and human pathogenic filamentous fungi. These results represent a solid foundation for further research on PTM regulatory mechanisms in fungi and should facilitate improved antifungal strategies against these medical important species.

BackgroundThe aim of this study is to investigate the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in assessing the poor outcomes of adult patients with acute myocarditis.MethodsA total of 170 adult patients with available NT-proBNP information were included in the study. They were grouped according to quartiles of NT-proBNP concentrations at admission. Baseline and follow-up information was collected. Thirty-day major adverse cardiac events (MACE) were death and heart transplantation. Long-term MACE included all-cause death, heart transplantation, re-hospitalization due to heart failure, sustained ventricular arrhythmia, and myocarditis relapse.ResultsDuring a median follow-up of 3.8 years, patients in the highest NT-proBNP quartile suffered from the highest risk both of 30-day and long-term MACE (P < 0.001 by log-rank test). Multivariate analysis showed that apart from left ventricular ejection fraction (LVEF), an increased baseline NT-proBNP > 3,549 pg/mL (hazard ratio 3.535, 95% CI 1.316–9.499, P = 0.012) and NT-proBNP > 7,204 pg/mL (hazard ratio 22.261, 95% CI 1.976–250.723, P = 0.012) was independent predictor of long-term and 30-day MACE, respectively.ConclusionsHigher baseline NT-proBNP level was an independent predictor of poor outcomes in adult patients with acute myocarditis. Therefore, NT-proBNP may serve as a useful biomarker for risk stratification in acute myocarditis patients.

Retinal vein occlusion(RVO)is divided into branch retinal vein occlusion and central retinal vein occlusion. It is characterized by retinal vein dilatation and tortuosity, blood flow stasis, bleeding and edema. It is often accompanied by macular edema(ME)and neovascularization. Neovascular glaucoma is the most serious complications. RVO is the second most common cause of visual loss classified under retinal vascular disorders after diabetic retinopathy. So far, the number of patients suffering from retinal vein occlusion has increased, but the pathogenesis of retinal vein occlusion has not been fully understood and there are no treatments that are very long-lasting. The research of animal models on the pathogenesis and treatment of the RVO is very important. Therefore, this article gives a briefly review to the animals and model making methods used in retinal vein occlusion experiments, and discusses the advantages and disadvantages of various RVO animal models.

Abstract The optimized strategy to further increase the success rate of ablation for ventricular arrhythmias (VAs) from the right ventricular outflow tract (RVOT) is challenging. Recent studies have shown that the pulmonary sinus cusp (PSC) region may be the origin of certain RVOT VAs. We evaluated the efficacy of preferential ablation below the pulmonary valve (PV) and alternated radiofrequency delivery in the PSC using remote magnetic navigation (RMN). Sixty-five (65) consecutive patients experiencing VAs with RVOT-like appearance were included in this study. Mapping and ablation were preferentially performed below the PV. Ablation in the PSC would only be attempted when intensified ablation below the PV could not eliminate VAs. Finally, if ablation in the RVOT region failed, the aortic sinus cusp (ASC) would be mapped. Sixty-one (61) of 65 (93.8%) patients achieved procedural success. Except 7 cases of which the VAs were ablated in the ASC, the rest 54 VAs were thought to be originate from the RVOT region. Fifty (50) of 54 VAs were successfully ablated below the PV, and in the presence of a local special signal in the bipolar electrogram a more aggressive ablation was required. Subsequent ablation in the PSC with assistance of the RMN system achieved success in the remaining 4 patients. No complications occurred in this study. Our strategy of using RMN-guided ablation below the PV for VAs of RVOT origin was proved to be effective. PSC mapping and ablation using a magnetic catheter may provide the optimal strategy for treating these types of arrhythmias.

Here, using a humanized phage display library with recombinant SARS- CoV-2 receptor binding domain (RBD) proteins, the authors identify a number of single domain antibodies (sdAbs) that neutralize SARS-CoV-2 in vitro by inhibiting the interaction of the RDB with the host entry receptor ACE2.

Objective The short-term clinical effects of two kinds of normal temperature flow root sealers (the calcium silicate-based sealer iRoot SP and the siloxane-based sealer GuttaFlow2) combined with single point filling technology and a frequently-used sealing agent (AH Plus) combined with continuous wave hot tooth filling technology were evaluated. Methods A total of 279 teeth (656 root canals) were randomly divided into three groups: the iRoot SP group, GuttaFlow2 group and AH plus group. We recorded the filling time of each root canal, collected a digital dental film to evaluate the filling effect of each root canal, and conducted a follow-up visit one week and one month after the operation to record the incidence of pain. We used SPSS 18.0 to analyze the above data. Results There was no significant difference in the root canal filling effect among the three groups (P > 0.05). There was no significant difference in the filling time between the iRoot SP group and the GuttaFlow2 group (P > 0.05), but the filling time was significantly shorter in the AH Plus group (P < 0.05). There was no significant difference in the postoperative pain between the iRoot SP group and the GuttaFlow2 group (P > 0.05), and the incidence of pain in the iRoot SP group and the GuttaFlow2 group was lower than that in the AH Plus group (P < 0.05). Conclusions GuttaFlow2 and iRoot SP combined with single point filling technology can save filling time and obtain good clinical effects compared with frequently-used hot tooth filling technology and the incidence of postoperative pain was low.

Abstract. Background. Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods. We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results. Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion. A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Abstract Background Dynamically changed levels of serum cytokines might predict the development of active TB from latent tuberculosis infection (LTBI) and monitor preventive treatment effectiveness. The aim of the study was to identify potential serum cytokines associated with LTBI treatment which might predict active disease development in a Chinese population. Methods Based on a randomized controlled trial aiming to explore short-course regimens for LTBI treatment, the dynamic changes of serum cytokines determined by bead-based multiplex assays were investigated for the participants who developed active TB during follow-up and age and gender matched controls stayed healthy. Results Totally, 21 patients diagnosed with active tuberculosis (TB) during the 2-year follow-up (12 from treated groups and 9 from untreated controls) and 42 age and gender matched healthy controls (24 from treated groups and 18 from untreated controls) were included in the study. Before treatment, serum IL-1ra was statistically higher among those who developed active disease during follow-up as compared with those stayed healthy. As for treated participants, the levels of IL-1ra were significantly lower after treatment in comparison with those before treatment both in active TB group (p = 0.002) and non-TB group (p = 0.009). For untreated participants, the levels of IL-1ra were not statistically different between different time points both in active TB group (p = 0.078) and non-TB group (p = 0.265). Conclusion Our results suggested that declined serum level of IL-1ra was associated with LTBI treatment. Further studies are needed to verify whether it could be used to evaluate LTBI treatment and to predict active disease development.

Abstract Background Human epididymis protein 4 (HE4) was proved to be a novel biomarker for left heart failure. The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure. Methods 55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded. Results Serum levels of HE4 were significantly higher in IPAH patients than healthy controls (6.9 ± 2.2 vs 4.4 ± 0.9 ng/ml, p 6.5 ng/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC] = 0.81). Multivariate Cox regression analysis demonstrated that HE4 (χ2: 5.10; hazard ratio [HR] = 1.26; 95% confidence interval: 1.03 to 1.55, p 6.5 ng/ml had a worse 2-year survival rate than those with HE4 ≤ 6.5 ng/ml (58.9% vs 96.2%, p

Abstract Background Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS‐CoV‐2 was a need to explore the possible age‐related phenomena with non‐human primate models. Methods Three 3‐5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS‐CoV‐2, and then analyzed by clinical signs, viral replication, chest X‐ray, histopathological changes and immune response. Results Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS‐CoV‐2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. Conclusion SARS‐CoV‐2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS‐CoV‐2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS‐CoV‐2 infection.

SARS-CoV-2 has spread globally. Here, the authors characterize the entry pathway of SARS-CoV-2, show that the SARS-CoV-2 spike protein is less stable than that of SARS-CoV, and show limited cross-neutralization activities between SARS-CoV and SARS-CoV-2 sera.

ABSTRACTThe lung microbiome plays an important role in the pathophysiological processes associated with pulmonary tuberculosis (PTB). However, only a few studies using 16S rDNA amplicon sequencing have been reported, and the interactions between Mycobacterium tuberculosis (MTB) and the lung microbiome remain poorly understood. Patients with respiratory symptoms and imaging abnormalities compatible with tuberculosis (TB) were enrolled. We analyzed the lung microbiome in bronchoalveolar lavage (BAL) samples from 30 MTB-positive (MTB+) subjects and 30 MTB negative (MTB-) subjects by shotgun metagenomic sequencing. Alpha diversity tended to be lower in the MTB+ group than in the MTB- group. There was a significant difference in beta diversity between the MTB+ and MTB- subjects. MTB+ lung samples were dominated by MTB, while MTB- samples were enriched with Streptococcus, Prevotella, Nesseria, Selenomonas and Bifidobacterium, which more closely resemble the microbial composition of a healthy lung. Network analysis suggested that MTB could greatly impact the microbial community structure. MTB+ and MTB- communities showed distinct functional signatures. Fungal communities were also found to be associated with the presence or absence of MTB. Furthermore, it was confirmed that 16S rDNA amplicon sequencing underrepresents Mycobacterium. This pilot study is the first to explore the interplay between MTB and the host microbiome by using metagenomic sequencing. MTB dominates the lung microbiome of MTB+ subjects, while MTB- subjects have a Streptococcus-enriched microbiome. The 16S approach underrepresents Mycobacterium and is not the best way to study the TB-associated microbiome.

ABSTRACTEnzymes from the purine salvage pathway in Mycobacterium tuberculosis (Mtb) have been regarded as an attractive target for the development of anti-bacterial drugs. Although this pathway has not been extensively studied in Mtb, it has been identified as essential for growth and survival. Glycinamide-RNase-transformylase T (PurT) is found only in some specific bacteria including Mtb and utilizes ATP-dependent ligation to catalyze the formylation of 5′-phosphoribosyl-glycinamide (GAR) in the third reaction of the de novo purine salvage pathway. In the study, we determined the crystal structure of MtbPurT at a resolution of 2.79 Å. In contrast to Pyrococcus horikoshii OT3 PurT (phBCCPPurT), MtbPurT exhibits an “open” conformation, which results in a broader ATP-binding pocket and thus might facilitate the entry and exit of the cofactor. Additionally, active site superposition with E.coli PurT (EcPurT) showed that residues involved in the ATP-binding site in MtbPurT exhibited structural similarity but had notable difference in the GAR-binding site. The loop 383-389 in MtbPurT was much shorter and shifted 5.7 Å away from the phosphate of the GAR substrate. The different GAR-binding mode might result in a large conformational change in MtbPurT, and would provide a possible opportunity for anti-TB drug development.

Abstract Background Many studies have shown the potential therapeutic effect of acupuncture on allergic rhinitis. Most of these studies were limited by low-quality evidence. Preliminary experiments showed that the use of acupuncture at three nasal acupoints plus acupoint application (AAP) achieves a more persistent effect in the treatment of perennial allergic rhinitis than acupuncture alone. In this study, a multicenter, single-blind, randomized controlled trial will be performed, in which acupuncture at nonmeridian acupoints and sham AAP will be used as the control group to evaluate the effect of AAP through long-term observation. Methods The trial is designed on the basis of the Consolidated Standards of Reporting Trials 2010 guidelines and Standards for Reporting Interventions in Controlled Trials of Acupuncture. A total of 120 participants with perennial allergic rhinitis will be randomly assigned to a treatment or control group. A specially appointed investigator will be in charge of randomization. The participants in the treatment group will be treated with acupuncture at EX-HN3, LI20, and EX-HN8 thrice per week for a total of 12 sessions. In addition, they will undergo AAP at DU14, BL13, EX-BI, and RN22. The participants in the control group will be treated with sham AAP. The primary outcome will be the change in the Total Nasal Symptom Score from baseline to the completion of 4-week treatment. Secondary outcomes include changes in visual analog scale and total non-nasal symptom scores from baseline to the second and fourth weeks of treatment, as well as 1, 3, and 6 months after the completion of treatment. Peripheral blood IL-4, IL-5, IL-6, IL-8, and IL-10 levels will be measured, and any side effects related to treatment will be observed and recorded. Discussion It is expected that this randomized clinical trial will provide evidence to determine the effects of AAP compared with acupuncture at nonmeridian acupoints and sham AAP, particularly the long-term effect. These findings will help improve the clinical application of this technique. Trial registration Acupuncture-Moxibustion Clinical Trial Registry AMCTR-ICR-18000179 . Registered on 12 April 2018.