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ObjectiveTo compare the efficacy of robotic-assisted single-incision-plus-one-port laparoscopic choledochal cyst excision (R-SILC + 1) and single-incision laparoscopic choledochal cyst (SILC) in treating pediatric choledochal cyst (CDC).MethodsWe retrospectively analyzed the clinical data of patients diagnosed with CDC in our hospital from June 2021 to October 2023. Among them, patients underwent either R-SILC + 1 or SILC procedures. Demographic parameters, operative details, and postoperative outcomes were studied.ResultsA total of forty-nine patients were included, with 23 children undergoing R-SILC + 1 and 26 children undergoing SILC. There were no statistically significant differences in demographic data, postoperative pain scores, and postoperative complication rates between the two groups (all p > 0.05). Compared with the SILC group, the R-SILC + 1 group demonstrated less intraoperative bleeding volume (10.4 ± 3.6 vs. 15.0 ± 3.6 ml, p

ObjectiveThe aim of the study was to develop a prediction nomogram based on clinical factors to assess the risk of postoperative complications in children with congenital choledochal cyst.MethodsThe clinical data from 131 children who underwent choledochal cyst resection and Roux-en-Y hepaticojejunostomy in our hospital between January 2016 and December 2022 were retrospectively analyzed. The general information, clinical symptoms, procedure, biochemical indicators, and imaging data were recorded. A prolonged hospital stay induced by postoperative complications or a follow-up over 6 months was assessed as the event outcome. A logistics regression analysis was performed to screen for risk factors with statistical significance in inducing postoperative complications. Then, with the dataset split into the training group and internal validation group, the nomogram for the prediction of postoperative complications was developed based on a computer algorithm. In addition, the receiver operating characteristic (ROC) curve and calibration curve were performed for nomogram verification.ResultsOf 131 children, the multivariate logistics regression analysis suggested that age ≤2 years [odds ratio (OR) 0.93; 95% confidence interval (CI) 0.15–5.65; p = 0.938], Todani classification type 1 (OR 36.58; 95% CI 4.14–871.74; p = 0.005), cyst wall thickness >0.4 cm (OR 10.82; 95% CI 2.88–49.13; p

The coronavirus disease of 2019 (COVID-19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can result in severe health complications. In addition to physical preventative measures, pharmaceutical intervention is also crucial. Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS-CoV-2 and other coronaviruses. In this study, we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels, as well as molecular separation and characterization, to screen and identify natural products with antiviral activity. Using this workflow, we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods. We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS-CoV-2 infection and receptor binding domain - human angiotensin-converting enzyme 2 (RBD-hACE2) binding in vitro. Following charge- and size-based characterization of the active compounds through filtration and chromatographic fractionation, mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition. Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID-19 and other diseases.

TiC/Ti6Al4 V titanium matrix composites were prepared by synthesising TiC particles using SLM technology to study the microstructure evolution of Ti6Al4 V alloy and TiC/Ti6Al4 V composites during isothermal deformation at 900°C and 1s−1 and the strengthening mechanism of TiC particles. The formation of TiC particles resulted in a yield strength of the composites 78 MPa higher than that of the Ti6Al4 V alloy. The acicular martensite coarsened after 15% deformation of the composite with recrystallisation beginning after 45% deformation. The lath-like α structure was refined, with dislocation slips in the α lath during the deformation of the composite. The TiC particles accumulate dislocations, transforming into subgrain boundaries to promote recrystallisation. The composite material is mainly based on grain refinement supplemented by Orowan strengthening by TiC particles.

ObjectiveThe purpose of this study is to compare the intraoperative and postoperative outcomes of a trans-umbilical single-site plus one robot-assisted surgery and a trans-umbilical single-site laparoscopic surgery in the treatment of choledochal cysts.MethodsWe retrospectively analyzed clinical data from 49 children diagnosed with choledochal cysts who were admitted to our hospital between June 2020 and December 2023. Among these patients, 24 underwent a trans-umbilical single-site plus one Da Vinci robot-assisted surgery (the robot group) and 25 underwent a trans-umbilical single-site laparoscopic-assisted surgery (the laparoscopic group). We compared differences in intraoperative and postoperative outcomes between the two groups.ResultsThere was no significant difference between the two groups of patients in terms of gender, age, weight, clinical symptoms, maximum cyst diameter, type, postoperative complications, and facial expression, leg movement, activity, crying, and comfortability (FLACC) scoring (p > 0.05). Compared with the patients in the laparoscopic group, those in the robot group had less intraoperative bleeding [10 (8–12) vs. 15 (11.5–18) ml, p

Abstract Targeting cancer‐specific metabolic processes is a promising therapeutic strategy. Here, this work uses a compound library that directly inhibits metabolic enzymes to screen the potential metabolic targets in lung adenocarcinoma (LUAD). SHIN1, the specific inhibitor of serine hydroxymethyltransferase 1/2 (SHMT1/2), has a highly specific inhibitory effect on LUAD cells, and this effect depends mainly on the overexpression of SHMT2. This work clarifies that mitogen‐activated protein kinase 1 (MAPK1)‐mediated phosphorylation at Ser90 is the key mechanism underlying SHMT2 upregulation in LUAD and that this phosphorylation stabilizes SHMT2 by reducing STIP1 homology and U‐box containing protein 1 (STUB1)‐mediated ubiquitination and degradation. SHMT2‐Ser90 dephosphorylation decreases S‐adenosylmethionine levels in LUAD cells, resulting in reduced N6‐methyladenosine (m6A) levels in global RNAs without affecting total protein or DNA methylation. Methylated RNA immunoprecipitation sequencing (MeRIP‐Seq) and RNA sequencing (RNA‐Seq) analyses further demonstrate that SHMT2‐Ser90 dephosphorylation accelerates the RNA degradation of oncogenic genes by reducing m6A modification, leading to the inhibition of tumorigenesis. Overall, this study elucidates a new regulatory mechanism of SHMT2 during oncogenesis and provides a theoretical basis for targeting SHMT2 as a therapeutic target in LUAD.

BackgroundPeanut is an important source of dietary protein for human beings, but it is also recognized as one of the eight major food allergens. Binding of IgE antibodies to specific epitopes in peanut allergens plays important roles in initiating peanut-allergic reactions, and Ara h 2 is widely considered as the most potent peanut allergen and the best predictor of peanut allergy. Therefore, Ara h 2 IgE epitopes can serve as useful biomarkers for prediction of IgE-binding variations of Ara h 2 and peanut in foods. This study aimed to develop and validate an IgE epitope-specific antibodies (IgE-EsAbs)-based sandwich ELISA (sELISA) for detection of Ara h 2 and measurement of Ara h 2 IgE-immunoreactivity changes in foods.MethodsDEAE-Sepharose Fast Flow anion-exchange chromatography combining with SDS-PAGE gel extraction were applied to purify Ara h 2 from raw peanut. Hybridoma and epitope vaccine techniques were employed to generate a monoclonal antibody against a major IgE epitope of Ara h 2 and a polyclonal antibody against 12 IgE epitopes of Ara h 2, respectively. ELISA was carried out to evaluate the target binding and specificity of the generated IgE-EsAbs. Subsequently, IgE-EsAbs-based sELISA was developed to detect Ara h 2 and its allergenic residues in food samples. The IgE-binding capacity of Ara h 2 and peanut in foods was determined by competitive ELISA. The dose-effect relationship between the Ara h 2 IgE epitope content and Ara h 2 (or peanut) IgE-binding ability was further established to validate the reliability of the developed sELISA in measuring IgE-binding variations of Ara h 2 and peanut in foods.ResultsThe obtained Ara h 2 had a purity of 94.44%. Antibody characterization revealed that the IgE-EsAbs recognized the target IgE epitope(s) of Ara h 2 and exhibited high specificity. Accordingly, an IgE-EsAbs-based sELISA using these antibodies was able to detect Ara h 2 and its allergenic residues in food samples, with high sensitivity (a limit of detection of 0.98 ng/mL), accuracy (a mean bias of 0.88%), precision (relative standard deviation < 16.50%), specificity, and recovery (an average recovery of 98.28%). Moreover, the developed sELISA could predict IgE-binding variations of Ara h 2 and peanut in foods, as verified by using sera IgE derived from peanut-allergic individuals.ConclusionThis novel immunoassay could be a user-friendly method to monitor low level of Ara h 2 and to preliminary predict in vitro potential allergenicity of Ara h 2 and peanut in processed foods.

Abstract Background Visualizing genome coverage is of vital importance to inspect and interpret various next-generation sequencing (NGS) data. Besides genome coverage, genome annotations are also crucial in the visualization. While different NGS data require different annotations, how to visualize genome coverage and add the annotations appropriately and conveniently is challenging. Many tools have been developed to address this issue. However, existing tools are often inflexible, complicated, lack necessary preprocessing steps and annotations, and the figures generated support limited customization. Results Here, we introduce ggcoverage, an R package to visualize and annotate genome coverage of multi-groups and multi-omics. The input files for ggcoverage can be in BAM, BigWig, BedGraph and TSV formats. For better usability, ggcoverage provides reliable and efficient ways to perform read normalization, consensus peaks generation and track data loading with state-of-the-art tools. ggcoverage provides various available annotations to adapt to different NGS data (e.g. WGS/WES, RNA-seq, ChIP-seq) and all the available annotations can be easily superimposed with ‘ + ’. ggcoverage can generate publication-quality plots and users can customize the plots with ggplot2. In addition, ggcoverage supports the visualization and annotation of protein coverage. Conclusions ggcoverage provides a flexible, programmable, efficient and user-friendly way to visualize and annotate genome coverage of multi-groups and multi-omics. The ggcoverage package is available at https://github.com/showteeth/ggcoverage under the MIT license, and the vignettes are available at https://showteeth.github.io/ggcoverage/ .

AlCrFeNi multi-component alloys with excellent mechanical properties have been designed and extensively investigated in recent years. The massive fabrication of sheets will be an effective way for industrial application, where hot rolling is the inevitable process. After hot rolling, the mechanical properties could be further tailored. In this study, the effects of heat treatments on a dual-phase Al17Cr10Fe36Ni36Mo1 hot-rolled plate were systematically investigated, including: (i) annealing (700 °C, 850 °C, 1000 °C and 1150 °C for 1 h, respectively), (ii) solution and single aging (1150 °C for 1 h and 700 °C for 4 h), (iii) solution and double aging (1150 °C for 1 h, 700 °C for 4 h and 650 °C for 1 h). The B2 precipitates with varied morphologies were observed in the FCC matrix of the hot-rolled alloy after a heat treatment range from 700 °C to 1000 °C for 1 h, and the BCC particles in the B2 matrix were dissolved when the heat treatment temperature was higher than 1000 °C. The hot-rolled alloy heat treated at 700 °C for 1 h had the highest yield strength, and the hot-rolled alloy treated at 1150 °C for 1 h showed the lowest yield strength. After a solution at 1150 °C for 1 h, aging at 700 °C for 4 h and 650 °C for 1 h, the L12 phase and BCC particles were precipitated in the FCC and B2 matrices, and B2 nanoprecipitates were observed around the FCC grain boundaries. The solution and double aging alloy exhibit the tensile strength of 1365.7 ± 9.5 MPa, a fracture elongation of 14.2 ± 1.5% at 20 °C, a tensile strength of 641.4 ± 6.0 MPa, and a fracture elongation of 16.9 ± 1.0% at 700 °C, showing great potential for application.

Abstract Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial cells after ventricular resection and endothelium-specific overexpression of dominant-negative Xenopus Brg1 (dn-xbrg1) inhibited myocardial proliferation and heart regeneration and increased cardiac fibrosis. RNA-seq and ChIP-seq analysis revealed that endothelium-specific overexpression of dn-xbrg1 changed the levels of H3K4me3 modifications in the promoter regions of the zebrafish genome and induced abnormal activation of Notch family genes upon injury. Mechanistically, Brg1 interacted with lysine demethylase 7aa (Kdm7aa) to fine-tune the level of H3K4me3 within the promoter regions of Notch family genes and thus regulated notch gene transcription. Together, this work demonstrates that the Brg1-Kdm7aa-Notch axis in cardiac endothelial cells, including the endocardium, regulates myocardial proliferation and regeneration via modulating the H3K4me3 of the notch promoters in zebrafish.

ABSTRACTThe emergence and nosocomial spread of the multidrug-resistant Candida auris pose a severe public health threat. Most C. auris clinical isolates are fluconazole resistant. In this study, we conduct transposon-mediated screens to profile genes whose inactivation causes fluconazole resistance in C. auris. We discover that mutation of genes encoding the Ubr2/Mub1 ubiquitin-ligase complex results in high fluconazole resistance by stabilizing the transcription activator, Rpn4. Global transcriptomic analysis, quantitative PCR, and combinatorial gene deletion reveal that Rpn4 causes fluconazole resistance by upregulating four efflux pump genes, SNQ21, SNQ22, MDR1, and CDR1, increasing efflux activity of the cell. Rpn4 autoactivates its own expression by binding to a PACE element in its promoter, forming a positive autoregulatory loop. Rpn4 also promotes CDR1 expression by binding to a PACE element in the CDR1 promoter. Furthermore, using the published genome sequence data of 304 clinical isolates, we identified a UBR2 A316T mutation in isolates from clades I and III. Although complementation of the ubr2Δ mutant with the UBR2A316T allele resulted in increased susceptibility to fluconazole, the UBR2A316T mutant was still more resistant to fluconazole compared to wild type, suggesting that acquisition of the mutation is sufficient to confer an increase in fluconazole resistance. In conclusion, this study identifies Rpn4 as a critical transcription factor that regulates fluconazole resistance via the Rpn4-efflux pump axis in C. auris.IMPORTANCECandida auris is a recently emerged pathogenic fungus of grave concern globally due to its resistance to conventional antifungals. This study takes a whole-genome approach to explore how C. auris overcomes growth inhibition imposed by the common antifungal drug fluconazole. We focused on gene disruptions caused by a “jumping genetic element” called transposon, leading to fluconazole resistance. We identified mutations in two genes, each encoding a component of the Ubr2/Mub1 ubiquitin-ligase complex, which marks the transcription regulator Rpn4 for degradation. When either protein is absent, stable Rpn4 accumulates in the cell. We found that Rpn4 activates the expression of itself as well as the main drug efflux pump gene CDR1 by binding to a PACE element in the promoter. Furthermore, we identified an amino acid change in Ubr2 in many resistant clinical isolates, contributing to Rpn4 stabilization and increased fluconazole resistance.

ABSTRACTThe hot deformation behavior of the Mg-Gd-Y-Zn-Zr alloy formed by CMT arc additive under 400°C, 0.1 s−1, and 50% deformation were systematically studied by means of hot compression test, constitutive equation, numerical simulation and microscopic structure. After deformation, twinning appeared in the microstructure. A large number of high-density dislocations and stacking faults were distributed around it. This was the thermal stress generated during the compression process, causing the deformation of the grains and stress concentration within the grains. The deformation at the center of the specimen was severe, the grains were elongated, and the equivalent stress was high. The simulated peak stress was close to the experimental value. The effect of the high-temperature deformation on the crystal slip was independent of the deformation region. The slip occurred along the {10-10} crystal plane and the crystal direction with the deformation, which was related to the Hcp structure of the alloy.

Photothermal immunochromatographic sensor is an emerging detection technology, and it is important to develop new sensing probes with excellent photothermal performance to improve its detection performance. In the present study, a novel photothermal sensing probe based on violet phosphorus nanosheets with satisfactory photothermal conversion efficiency (31.1 %) was reported for the first time. A photothermal immunochromatographic sensor using the above probe was applied for visual and photothermal detection of diethylstilbestrol. The diethylstilbestrol concentration was inversely proportional to photothermal sensing signal and showed a good linear correlation in the range of 0.75 ∼ 50 μg·L−1. After optimizing, the visual and photothermal detection limits were 6 μg·L−1 and 0.56 μg·L−1, respectively. The recovery rates in tap water, milk and pork samples ranged from 82.2 % to 115.2 %, with a coefficient of variation (CV) ranging from 2.0 % to 10.8 %. This work not only structured a new type of photothermal probe, but also expanded the application range of violet phosphorus.

Summary: The majority of activated ovarian follicles undergo atresia during reproductive life in mammals, and only a small number of follicles are ovulated. Though hormone treatment has been widely used to promote folliculogenesis, the molecular mechanism behind follicle selection and atresia remains under debate due to inconsistency among investigation models. Using a high-throughput molecular pathology strategy, we depicted a transcriptional atlas of mouse follicular granulosa cells (GCs) under physiological condition and obtained molecular signatures in healthy and atresia GCs during development. Functional results revealed hypoxia-inducible factor 1 (HIF1) as a major effector downstream of follicle-stimulating hormone (FSH), and HIF1 activation is essential for follicle growth. Energy shortage leads to prevalent AMP-activated protein kinase (AMPK) activation and drives follicular atresia. FSHR-mTOR-HIF1 signaling helps follicles escape from the atresia fate, while energy stress persists. Our work provides a comprehensive understanding of the molecular network behind follicle selection and atresia under physiological condition.

Abstract Background The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. Results We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period. Conclusions Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19. Video Abstract

The Mg-Gd-Y-Zn-Zr alloy components were fabricated by cold metal transfer (CMT) based wire arc additive manufacturing (WAAM). The heat transfer and equiaxed grain growth in the weld pool bonding zone of the alloy were investigated through macro-micro numerical simulation. The results shows, the morphology of the molten pool in the bonding area is ellipsoid with a major semi-axis of 13 mm and a semi-minor axis of 6 mm. The size of the molten pool increases with increasing temperature. With the increase in the number of layers of material added, the high temperature zone is enlarged continuously. This is due to the weakening of the heat dissipation of the substrate and the preheating effect of the first material added on the subsequent material added. The phase field model of equiaxed grain growth during the solidification process of the CMT arc welding pool, was established. The growth of equiaxed crystals in the bonding region temperature gradients of 4.9 °C/m and 3.6 °C/m, the propulsion velocity of 1.5 m/min and 2.3 m/min were simulated, respectively. The further away the molten pool from the keyhole center, the smaller the temperature gradient, the faster the dendrite growth speed, and the more vigorous the dendrite morphology. The unique layered processing method and Marangoni effect of the melting pool in the bonding zone of CMT-WAAM arc additive promote the β-Mg24(Gd,Y)5 and RE-rich phases of body-centered cubic structure. These precipitated phases are evenly distributed at the grain boundaries, it hinders the migration of grain boundarie st, which in turn inhibits grain growth.

Named Entity Recognition (NER) is a fundamental but crucial task in natural language understanding, aiming at identifying entity mentions from free text. Current methods mainly use sequence-labeling and span-based models, where the former ignores the importance of token interaction, and the latter pays little attention to the global inter-dependency among entity tokens. In this work, we propose a novel NER model that consists of two branches: a Token-Pair Interaction Module (TPIM) and a U-shaped Network. The TPIM models head-tail relations between token pairs while capturing intrinsic token connectivity within entity boundaries. The U-shaped Network is employed to capture the contextual dependency in the token-pair relation matrix. Furthermore, we build a typical domain-specific entity dataset CCAEE based on real-world applications in the chemical accident domain. The experimental results on CCAEE and CLUENER datasets demonstrate the effectiveness of our proposed model.

Wireless sensor networks (WSNs) are gaining traction in the realm of network communication, renowned for their adaptability, configuration, and flexibility. The forthcoming network traffic within WSNs can be forecasted through temporal sequence models. In this correspondence, we present a method (TSENet) that can accurately predict the traffic in the cellular network. TSENet is composed of transformers and self-attention network. We have designed a temporal transformer module specifically for extracting temporal features. This module accomplishes this by modeling the traffic flow within each grid of the communication network at both near-term and periodical intervals. Simultaneously, we amalgamate the spatial features of each grid with information from its correlated grids, generating spatial predictions within the spatial transformer. Furthermore, we employ self-attention aggregation to capture dependencies between external factor features and cellular data features. Empirical assessments performed on a genuine cellular traffic dataset offer compelling evidence substantiating the efficacy of TSENet.

Using metal additive manufacturing processes can make up for traditional forging technologies when forming complex-shaped parts. At the same time, metal additive manufacturing has a fast forming speed and excellent manufacturing flexibility, so it is widely used in the aerospace industry and other fields. The fatigue strength of metal additive manufacturing is related to the microstructure of the epitaxially grown columnar grains and crystallographic texture. The crystal plasticity finite element method is widely used in the numerical simulation of the microstructure and macro-mechanical response of materials, which provides a strengthening and toughening treatment and can reveal the inner rules of material deformation. This paper briefly introduces common metal additive manufacturing processes. In terms of additive manufacturing fatigue, crystal plasticity simulations are summarized and discussed with regard to several important influencing factors, such as the microstructure, defects, surface quality, and residual stress.

ObjectiveTo investigate the clinical effect of the da Vinci robotic-assisted laparoscopic pyeloureteroplasty (RALP) in treating pediatric ureteropelvic junction obstruction (UPJO).MethodsWe retrospectively analyzed clinical data from 32 children with UPJO who suffered from RALP in our hospital from October 2020 to February 2023, compared with those treated with common laparoscopy at the same time. After the establishment of the robotic arm, a mesenteric approach was performed after entering the abdominal cavity to focus on the lesion site. The dilated renal pelvis was then cut and the stenotic ureter was removed; the anastomosis and the incision were sutured by layer.ResultsA total of 62 children (44 boys and 20 girls) with a median age of 14 months (ranging from 3 to 38 months) were included. All 62 cases had hydronephrosis caused by unilateral UPJO, and the surgery was successfully completed without conversion to open. All intraoperative blood losses amounted to less than 10 ml. In the RALP group, the average operative duration was 131.28 min (ranging from 108 to 180 min). The average catheter time was 3.66 days (ranging from 2 to 7 days). The average hematuria time was 3.84 days (ranging from 2 to 6 days). The average postoperative hospital stay was 7.8 days (ranging from 6 to 12 days). The average hospitalization costs were 59,048.31 yuan (ranging from 50,484 to 69,977 yuan). The double-J tube was removed 1 month after surgery. Only one patient suffered from complications, developing a urinary tract infection 4 weeks after surgery, and was cured with the administration of oral cefaclor anti-inflammatory drugs for 3 days. All patients were followed up for 2–28 months, with a median follow-up time of 12 months. The thickness of the renal cortex was increased after surgery [(1.95 ± 0.24) vs. (4.82 ± 0.50)] cm, and the isotope renograms revealed a definite recovery of the split renal function [(28.32 ± 1.95) vs. (37.01 ± 2.71)]%.ConclusionThe robotic-assisted laparoscopic pyeloureteroplasty (RALP) in the treatment of children with upper ureteral obstruction has overall clinical efficiency. With technological advancements and an increased number of experienced surgeons, robotic surgery may become a new trend in surgery.

With the development of network technology and computer intelligent monitoring technology, a large number of video data came into being. In view of the analysis of specific targets in video, the traditional artificial analysis method can not meet the existing needs. In volleyball teaching in college physical education, because each student has different movements, intelligent processing of video data has become a key issue. Through collecting and sorting out the relevant research results on behavior recognition, it is found that in the research of deep learning, the algorithm structure applied in this paper is representative, and its strong learning ability, especially compared with the traditional algorithm, can more accurately identify human movements, natural language processing and so on, but the research on volleyball action recognition is still less. Therefore, this paper constructs a data set, improves the convolution neural network model, subsequently, new models are constructed through the neural network structure to improve the accuracy of the nonlinear expression and optimize the content of the input data. In order to more accurately analyze the effectiveness of this algorithm, the new data are obtained by grouping the volleyball games in college sports courses. Compared with the original paper, the accuracy of the improved 3D network is improved by 3.3%–88.5%, and the complexity is reduced by 33.6%.

Background: Alkaline pectate lyase plays an important role in papermaking, biological refining and wastewater treatment, but its industrial applications are largely limited owing to its low activity and poor alkali resistance.Methods: The alkaline pectate lyase BspPel from Bacillus RN.1 was heterologously expressed in Escherichia coli BL21 (DE3) and its activity and alkali resistance were improved by loop replacement. Simultaneously, the effect of R260 on enzyme alkaline tolerance was also explored.Results: Recombinant pectate lyase (BspPel-th) showed the highest activity at 60°C and pH 11.0, and showed significant stability over a wide pH range (3.0–11.0). The specific enzyme activity after purification was 139.4 U/mg, which was 4.4 times higher than that of the wild-type enzyme. BspPel-th has good affinity for apple pectin, since the Vmax and Km were 29 μmol/min. mL and 0.46 mol/L, respectively. Molecular dynamics simulation results showed that the flexibility of the loop region of BspPel-th was improved.Conclusion: The modified BspPel-th has considerable potential for industrial applications with high pH processes.

Abstract Background Prevalent single-cell transcriptomic profiling (scRNA-seq) methods are mainly based on the synthesis and enrichment of full-length double-stranded complementary DNA. These approaches are challenging to generate accurate quantification of transcripts when their abundance is low or their full-length amplifications are difficult. Results Based on our previous finding that Tn5 transposase can directly cut-and-tag DNA/RNA hetero-duplexes, we present SHERRY2, a specifically optimized protocol for scRNA-seq without second-strand cDNA synthesis. SHERRY2 is free of pre-amplification and eliminates the sequence-dependent bias. In comparison with other widely used scRNA-seq methods, SHERRY2 exhibits significantly higher sensitivity and accuracy even for single nuclei. Besides, SHERRY2 is simple and robust and can be easily scaled up to high-throughput experiments. When testing single lymphocytes and neuron nuclei, SHERRY2 not only obtained accurate countings of transcription factors and long non-coding RNAs, but also provided bias-free results that enriched genes in specific cellular components or functions, which outperformed other protocols. With a few thousand cells sequenced by SHERRY2, we confirmed the expression and dynamics of Myc in different cell types of germinal centers, which were previously only revealed by gene-specific amplification methods. Conclusions SHERRY2 is able to provide high sensitivity, high accuracy, and high throughput for those applications that require a high number of genes identified in each cell. It can reveal the subtle transcriptomic difference between cells and facilitate important biological discoveries.

Introduction: β-Alanine is the only β-amino acid in nature; it is widely used in food additives, medicines, health products, and surfactants. To avoid pollution caused by traditional production methods, the synthesis of β-alanine has been gradually replaced by microbial fermentation and enzyme catalysis, which is a green, mild, and high-yield biosynthesis method.Methods: In this study, we constructed an Escherichia coli recombinant strain for efficient β-alanine production using glucose as the raw material. The microbial synthesis pathway of L-lysine-producing strain, Escherichia coli CGMCC 1.366, was modified using gene editing by knocking out the aspartate kinase gene, lysC. The catalytic efficiency and product synthesis efficiency were improved by assembling key enzymes with cellulosome.Results: By-product accumulation was reduced by blocking the L-lysine production pathway, thereby increasing the yield of β-alanine. In addition, catalytic efficiency was improved by the two-enzyme method to further increase the β-alanine content. The key cellulosome elements, dockerin (docA) and cohesin (cohA), were combined with L-aspartate-α-decarboxylase (bspanD) from Bacillus subtilis and aspartate aminotransferase (aspC) from E.coli to improve the catalytic efficiency and expression level of the enzyme. β-alanine production reached 7.439 mg/L and 25.87 mg/L in the two engineered strains. The β-alanine content reached 755.465 mg/L in a 5 L fermenter.Discussion: The content of β-alanine synthesized by constructed β-alanine engineering strains were 10.47 times and 36.42 times higher than the engineered strain without assembled cellulosomes, respectively. This research lays the foundation for the enzymatic production of β-alanine using a cellulosome multi-enzyme self-assembly system.

Background: L-lysine is widely used in the feed, food, and pharmaceutical industries, and screening for high L-lysine-producing strains has become a key goal for the industry.Methods: We constructed the rare L-lysine codon AAA by corresponding tRNA promoter replacement in C. glutamicum. Additionally, a screening marker related to the intracellular L-lysine content was constructed by converting all L-lysine codons of enhanced green fluorescent protein (EGFP) into the artificial rare codon AAA. The artificial EGFP was then ligated into pEC-XK99E and transformed into competent Corynebacterium glutamicum 23604 cells with the rare L-lysine codon. After atmospheric and room-temperature plasma mutation and induction culture, 55 mutants (0.01% of total cells) with stronger fluorescence were sorted using flow cytometry, and further screened by fermentation in a 96-deep-well plate and 500 mL shaker.Results: The fermentation results showed that the L-lysine production was increased by up to 9.7% in the mutant strains with higher fluorescence intensities, and that the highest screening positive rate was 69%, compared with that in the wild-type strain.Conclusion: The application of artificially constructed rare codons in this study represents an efficient, accurate, and simple method for screening other amino acid-producing microorganisms.

Dual-phase high-entropy alloys with excellent room temperature and high-temperature properties have been widely studied as potential high-temperature structural materials. However, interface weakening causes its high-temperature performance to decline at higher temperatures, severely limiting further development. In this study, a series of Al17Cr10Fe36Ni36Mo1Hfx (x = 0, 0.03, 0.15, 0.3, 0.5, and 0.8 at%) alloys were prepared to study the effect of Hf content on the microstructure and mechanical properties of the matrix alloy. The results indicate that with the addition of the Hf, the Hf-rich phase began to precipitate at the interface and inside the B2 phase in the matrix alloy. In contrast, the morphology of both the FCC and B2 phases had no noticeable change. With the increase in Hf content, the high-temperature strength and ductility of the alloy first increased and then decreased, while the room temperature performance remained almost unchanged. Benefiting from the hindrance of the Hf-rich phase to grain boundary sliding and dislocation movement during high-temperature deformation, the tensile strength, yield strength, and plasticity of the matrix alloy increased from 474 MPa, 535 MPa, and 8.7% to 816 MPa, 923 MPa, and 42.0% for the Al17Cr10Fe36Ni36Mo1Hf0.5 alloys, respectively. This work provides a new path for designing a high-entropy alloy with excellent high-temperature mechanical properties.

In this paper, the research status of three types of wheel-rail interaction force measuring approaches, that is, IWS, ground measurement method and indirect measurement method, are summarized systematically. According to the measuring locations, the IWS can be determined by measuring the bending strain of the axle, as well as the strain of the wheel web. The measuring principle, bridge assembly method, calibration test and sensing technology of IWS are introduced respectively. This paper introduces the ground measurement method of measuring·wheel-rail force by arranging sensors on the rail and other track components to test their response, and the indirect methods for wheel-rail forces measurement are reviewed, which is derived from inertial force and suspension force of wheelset according to the force states of the wheelset. The advantages and disadvantages of the IWS, the ground measurement method and the indirect measurement method are analyzed. The investigation results show that the measuring principle of the IWS is relatively mature, and its measurement accuracy mainly depends on the manufacturing technology, bench calibration and signal acquisition. Future development of the IWS tend to realize the non-destructive, wireless, continuous and accurate measurement of the wheel-rail forces and contact points locations.

Tropical montane ecosystems are the centers of biodiversity, and Janzen proposed that mountain climate variability plays a key role in sustaining this biodiversity. We test this hypothesis for soil bacteria and fungi along a 265–1,400 m elevational gradient on Hainan Island of tropical China, representing diverse vegetation types from deciduous monsoon forest to cloud forest. We found that bacterial and fungal diversity declined as elevation increased, and the dissimilarity of both groups increased with increasing separation in elevation, although changes in bacteria were larger than in fungi. Seasonal alterations and the range of soil moisture in the growing season were found to be the dominant drivers of fungal richness and Shannon diversity, whereas soil pH was the major driver of bacterial diversity. Dissimilarities of bacterial and fungal communities were best predicted by climate, particularly seasonal changes in soil temperature, with weaker influences of soil physicochemistry and vegetation. The dominant effect of seasonality in soil temperature was further detected in cloud forests, which harbored a higher proportion of unique bacterial species and dissimilarity of bacterial and fungal communities. Our findings suggest that local-climate variability plays a crucial role in structuring the distribution of soil microbial communities along a tropical montane gradient, which generally supports Janzen’s hypothesis. Such a sensitivity to climatic variability suggests that soil microbial communities along tropical montane gradients may shift in response to future climate scenarios.

In most organisms, the whole genome is maintained throughout the life span. However, exceptions occur in some species where the genome is reduced during development through a process known as programmed DNA elimination (PDE). In the human and pig parasite Ascaris, PDE occurs during the 4 to 16 cell stages of embryogenesis, when germline chromosomes are fragmented and specific DNA sequences are reproducibly lost in all somatic cells. PDE was identified in Ascaris over 120 years ago, but little was known about its molecular details until recently. Genome sequencing revealed that approximately 1,000 germline-expressed genes are eliminated in Ascaris, suggesting PDE is a gene silencing mechanism. All germline chromosome ends are removed and remodeled during PDE. In addition, PDE increases the number of chromosomes in the somatic genome by splitting many germline chromosomes. Comparative genomics indicates that these germline chromosomes arose from fusion events. PDE separates these chromosomes at the fusion sites. These observations indicate that PDE plays a role in chromosome karyotype and evolution. Furthermore, comparative analysis of PDE in other parasitic and free-living nematodes illustrates conserved features of PDE, suggesting it has important biological significance. We summarize what is known about PDE in Ascaris and its relatives. We also discuss other potential functions, mechanisms, and the evolution of PDE in these parasites of humans and animals of veterinary importance.

The parasitic nematode Ascaris lacks piRNAs. Here the authors compare Argonaute proteins and small RNAs from C. elegans and Ascaris, expanding our understanding of the conservation, divergence, and flexibility of Argonautes and small RNA pathways in nematodes.

Strain rate and temperature are influential factors that significantly impact the mechanical properties of long glass fiber-reinforced polypropylene composites. This study aims to investigate the tensile properties of these composites, analyzing the effects of temperature, strain rate, and their interplay on variables such as tensile stress, tensile strength, fracture stress, and fracture morphology through a series of comprehensive tensile experiments. The experimental results demonstrate a notable increase in both tensile strength and tensile fracture stress when the temperature is set at 25 °C, accompanied by strain rates of 10−4, 10−3, 10−2, and 10−1 s−1. Conversely, a significant decrease is observed in the aforementioned properties when the strain rate is fixed at 10−4, while varying temperatures of −25 °C, 0 °C, 25 °C, 50 °C, and 75 °C are applied. At lower temperatures, cracks manifest on the fracture surface, while matrix softening occurs at higher temperatures. Additionally, in the context of strain rate–temperature coupling, the decreasing trend of both tensile strength and tensile fracture stress decelerates as the temperature ranges from −25 °C to 75 °C at a strain rate of 10−1, compared to 10−4 s−1. These findings highlight the significant influence of both strain rate and temperature on high fiber content long glass fiber-reinforced polypropylene composites.

Microglial abnormalities may contribute to neurodevelopmental disorders. PTEN is implicated as a susceptibility gene for autism spectrum disorders and its germline ablation in mice causes behavioral abnormalities. Here we find postnatal PTEN deletion in microglia causes deficits in sociability and novel object recognition test. Mutant mice harbor markedly more activated microglia that manifest enhanced phagocytosis. Interestingly, two-week postponement of microglia PTEN ablation leads to no social interaction defects, even though mutant microglia remain abnormal in adult animals. Disturbed neurodevelopment caused by early PTEN deletion in microglia is characterized by insufficient VGLUT1 protein in synaptosomes, likely a consequence of enhanced removal by microglia. In correlation, in vitro acute slice recordings demonstrate weakened synaptic inputs to layer 5 pyramidal neurons in the developing cortex. Therefore, microglial PTEN safeguards integrity of neural substrates underlying sociability in a developmentally determined manner.

Esophageal squamous-cell carcinomas (ESCC) have poor prognosis, and detailed molecular profiles are necessary to identify prognostic markers. Here the authors analyse 60 ESCC patient samples using scRNA-seq, TCR-seq and genomics; they find mucosal immunity markers associated with survival and immunosuppressive microenvironments.

The major pathologic hallmark of the alcoholic liver disease (ALD) is the representation of chronic alcohol-induced hepatocyte lipid accumulation. This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia (ACT) in chronic alcohol-induced liver injury mice, establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks. In long-term alcohol consumption mice, the significantly lost body weight, increased organ indexes, hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration, showing its hepatoprotective property. ACT suppressed the triglyceride, total cholesterol and low-density lipoprotein levels, and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice. Combining with the pathological observations, ACT displayed an anti-steatosis effects to restrain the progress of ALD. Based on proteomic analysis and enzyme-linked immunosorbent assay, ACT had been confirmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species. According to further data, ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1α and NF-κB signaling. In summary, ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.

Herpes simplex virus type 2 (HSV-2) is a common human pathogen that establishes lifelong latency in neurons of the nervous system. The number of severe central nervous system infections caused by the virus has increased recently. However, the pathogenesis of HSV-2 infection in the nervous system is not fully understood. Here, we demonstrated global proteomic changes in the brain tissue in BALB/c mice vaginally infected with HSV-2. Data are available via ProteomeXchange with identifier PXD034186. A total of 249 differentially expressed proteins were identified in infected brain tissue. The GO and KEGG enrichment analysis of these proteins indicated that they were mainly involved in the regulation of synapse formation and synaptic excitability. In addition, genes affecting autophagy, the development of other neurodegenerative diseases, and signaling pathways relevant to other neurologic diseases were identified. Additional experiments, comparing the brain tissue of asymptomatic and symptomatic mice showed a differential expression of proteins involved in synapse formation and synaptic transmission. Others were involved in autophagy, addiction, and signaling pathways of other neurologic diseases. These results suggest that changes in synaptic structure and function, as well as autophagy, may be related to the development of neurologic abnormalities that follow HSV-2 infection. We also identified a protein GluN2A encoded by Grin2a was continuously expressed at high levels after infection. We propose that GluN2A may be a key molecule in the pathogenesis of HSV-2-induced neurologic diseases.

A film cooling hole is an efficient and reliable cooling method, which is widely used in aeroengine turbine blades to effectively improve the thrust–weight ratio of the engine. Electrical discharge machining is the most common manufacturing process for film cooling holes. Due to the rapid quenching after high-temperature melting, a certain thickness of the recast layer will be formed in the vicinity of the hole wall. The microstructure of the recast layer is considered to be an important factor affecting the performance of single-crystal blades. Generally, the recast layer has been thought of as one of the main reasons for the failure of turbine blades. Accordingly, the formation of the recast layer is an important and interesting issue to be revealed. In this work, the recast layer formed using electrical discharge machining on a single-crystal superalloy is studied with TEM. It is found that the recast layer is in the state of supersaturated solution with a single-crystal structure epitaxially grown from the matrix, and many dislocations were observed therein.

This paper studies motor structures and optimization methods for space robots, proposing an optimized stepped rotor bearingless switched reluctance motor (BLSRM) to solve the poor self-starting ability and significant torque fluctuation issues in traditional BLSRMs. Firstly, the advantages and disadvantages of the 12/14 hybrid stator pole type BLSRM were analyzed, and a stepped rotor BLSRM structure was designed. Secondly, the particle swarm optimization (PSO) algorithm was improved and combined with finite element analysis for motor structure parameter optimization. Subsequently, a performance analysis of the original and new motors was conducted using finite element analysis software, and the results showed that the stepped rotor BLSRM had an improved self-starting ability and significantly reduced torque fluctuation, verifying the effectiveness of the proposed motor structure and optimization method.

Abstract Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF (n = 29) and FD (n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30–50 cells (5 000–10 000 µm2) per sample. We found that the rate of recurrent CNAs in OF cases was much higher (44.8%, 13 of 29) than that in FD cases (3.6%, 1 of 28). Sixty-nine percent (9 of 13) of the CNA-containing OF cases involved segmental amplifications and deletions on Chrs 7 and 12. We also identified eight CNA-associated genes (HILPDA, CALD1, C1GALT1, MICALL2, PHF14, AIMP2, MDM2, and CDK4) with amplified expression, which was consistent with the copy number changes. We further confirmed a jaw lesion with a previous uncertain diagnosis due to its ambiguous morphological features and the absence of GNAS mutation as OF based on the typical Chr 12 amplification pattern in its CNA profile. Moreover, analysis of a set of longitudinal samples collected from an individual with a cellular lesion in suspicion of OF at the first surgery, recurrence and the latest malignant transformation revealed identical CNA patterns at the three time points, suggesting that copy number profiling can be used as an important tool to identify borderline lesions or lesions with malignant potential. Overall, CNA profiling of fibro-osseous lesions can greatly improve differential diagnosis between OF and FD and help predict disease progression.

Abstract Grainyhead-like 1 (GRHL1) is a transcription factor involved in embryonic development. However, little is known about the biological functions of GRHL1 in cancer. In this study, we found that GRHL1 was upregulated in non-small cell lung cancer (NSCLC) and correlated with poor survival of patients. GRHL1 overexpression promoted the proliferation of NSCLC cells and knocking down GRHL1 inhibited the proliferation. RNA sequencing showed that a series of cell cycle-related genes were altered when knocking down GRHL1. We further demonstrated that GRHL1 could regulate the expression of cell cycle-related genes by binding to the promoter regions and increasing the transcription of the target genes. Besides, we also found that EGF stimulation could activate GRHL1 and promoted its nuclear translocation. We identified the key phosphorylation site at Ser76 on GRHL1 that is regulated by the EGFR-ERK axis. Taken together, these findings elucidate a new function of GRHL1 on regulating the cell cycle progression and point out the potential role of GRHL1 as a drug target in NSCLC.

Summary: With the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle-encapsulated, nucleoside-unmodified mRNA (mRNA-LNP) vaccine encoding the trimerized receptor-binding domain (RBD trimer) and showed its robust capability in inducing broad and protective immune responses against wild-type and major variants of concern (VOCs) in the mouse model of SARS-CoV-2 infection. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling. Monoclonal antibodies isolated from vaccinated animals demonstrated broad and potent neutralizing activity against VOCs tested. Structure analysis of one representative antibody identified a novel epitope with a high degree of conservation among different variants. Collectively, these results demonstrate that the RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and beyond.

The fuel energy consumption of heater accounts for a large proportion of the total energy consumption ofcrude oil pipeline transportation. Energy-saving coating can increase the tube blackness and wall reflectivity of the heaterwithout changing its structure, and then improve its thermal efficiency. Thus, it can be widely used in various heaters. Inthe application test of thin-film ceramic coating with high emissivity, thermal test with positive and negative balance wasadopted. The thermal test was conducted to the heater at 45% and 75% load before and after coating respectively, and theresults indicate that the energy-saving efficiency of heater under the two load conditions is excellent, reaching 4.59% and5.72% respectively. Therefore, the thin film ceramic coating with high emissivity can improve the efficiency and reduce theunit energy consumption of the heater, and thus, it has significant economic benefits and is suitable for popularization andapplication.

In this study, Chen and colleagues present genomic sequences of 102 SARS-CoV-2 isolates collected in Beijing. They look closely at genomic variation between isolates that arose as a result of domestic and global transmission. Their data suggest that SARS-CoV-2 genomes have a high mutational tolerance, which may have potential implications for the development of vaccines.

The multistep processes involved in the evolution of inflammation to invasive esophageal squamous cell carcinoma (ESCC) is unclear. Here, the authors report a mouse model of ESCC and the role of interplay between carcinogen-transformed epithelial cells and their microenvironment in ESCC development.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations—K417N, E484K, and N501Y—found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.

Abstract Background Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in TSC1 and TSC2. However, in 10%–15% of patients with clinically confirmed TSC, no TSC1/TSC2 variants are identified by panel sequencing or multiplex ligation‐dependent probe amplification (MLPA). Methods We analyzed eight fetuses with CR and their families. No TSC1/TSC2 variants had previously been identified for six of these fetuses, and we suspected the other two families of gonadal mosaicism. We performed next‐generation sequencing (NGS) using CR tissue, umbilical cord tissue, and parental blood. All positive results, involving two paternal semen, were verified by droplet digital polymerase chain reaction (ddPCR). Results Four fetuses carried low‐level mosaic variants (0.05%–14.89%), and two only exhibited somatic mosaic variants in the CR tissue (15.76% and 37.69%). Two fathers had gonadal mosaicism (9.07% and 4.86%). We identified nine pathogenic variants in eight fetuses, including one fetus with a second‐hit variant. Conclusion The fetuses assessed in this study carried low‐level and somatic mosaic variants, and CR tissue from one fetus exhibited a second‐hit variant. Heterozygous gonadal variants can exist in patients with low‐level mosaicism. Combining NGS with ddPCR improves the accuracy of prenatal TSC diagnosis.

Summary: Bicuspid aortic valve (BAV) with ∼1%–2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA). Mouse and human studies indicate LVOTO is genetically heterogeneous with a complex genetic etiology. Homozygous mutation in the Pcdha protocadherin gene cluster in mice can cause BAV, and also HLHS and other LVOTO phenotypes when accompanied by a second mutation. Here we show two common deletion copy number variants (delCNVs) within the PCDHA gene cluster are associated with LVOTO. Analysis of 1,218 white individuals with LVOTO versus 463 disease-free local control individuals yielded odds ratios (ORs) at 1.47 (95% confidence interval [CI], 1.13–1.92; p = 4.2 × 10−3) for LVOTO, 1.47 (95% CI, 1.10–1.97; p = 0.01) for BAV, 6.13 (95% CI, 2.75–13.7; p = 9.7 × 10−6) for CoA, and 1.49 (95% CI, 1.07–2.08; p = 0.019) for HLHS. Increased OR was observed for all LVOTO phenotypes in homozygous or compound heterozygous PCDHA delCNV genotype comparison versus wild type. Analysis of an independent white cohort (381 affected individuals, 1,352 control individuals) replicated the PCDHA delCNV association with LVOTO. Generalizability of these findings is suggested by similar observations in Black and Chinese individuals with LVOTO. Analysis of Pcdha mutant mice showed reduced PCDHA expression at regions of cell-cell contact in aortic smooth muscle and cushion mesenchyme, suggesting potential mechanisms for BAV pathogenesis and aortopathy. Together, these findings indicate common variants causing PCDHA deficiency play a significant role in the genetic etiology of common and rare LVOTO-CHD.

Aiming at exploring the material removal mechanism for sapphire using diamond abrasive grains at the microscopic level, this paper modeled and analyzed the microscopic yield behavior of diamond abrasive grains in the FAP grinding process of sapphire. Molecular dynamics were used to simulate the effects of abrasive particle size on the cutting force, potential energy, and temperature in the Newtonian zone during micro-cutting. The effect of different abrasive particle sizes on material removal was analyzed through experiments. The simulation results show that the abrasive particle radius was 12 Å, the micro-cutting force reached more than 3500 nN, while the cutting force with an abrasive particle radius of 8 Å only reached 1000 nN. Moreover, the potential energy, cutting force, and temperature in the Newtonian zone between the sapphire crystal atoms also increased. The results showed that the material removal rate saw a nonlinear increasing trend with the increase in particle sizes, while the surface roughness showed an approximately linear increase. Both of them showed a similar trend. The experimental results lay a theoretical basis for the selection of the lapping process parameters in sapphire.

For the analysis on the deformation of flexible ring gears in spur gear pairs, the complete flexible ring is discretized, and the boundary condition is added to the connecting points to develop a calculation method for the flexible deformation. The ovality index is used to describe the deformation degree of flexible ring gears, then the influences of ring-gear width and the spalling defects on the flexible deformation of ring gears are discussed. The result shows that the flexible deformation of ring gears is caused by the gear pair meshing force, and the deformed shape is close to an ellipse. In the single-tooth meshing interval of gear pairs, the main form of deformation is being stretched, and while in the double-tooth meshes, the main form is bending deformation. When the width of the ring gear rims is increased, the flexible deformation of the ring gears can be effectively suppressed, and the vibration amplitude of the gear pairs can be reduced. Additionally, when there is a localized spalling fault on gear pairs, the sudden changes in the deformation of flexible ring gears are generated by the shock of the meshing force. Finally, through the finite element analysis model and the experiment, the mathematical model of gear pairs with flexible rings is confirmed.

Herpes simplex virus type 2 (HSV2), a pathogen that causes genital herpes lesions, interferes with the host immune system via various known and unknown mechanisms. This virus has been used to study viral antigenic composition. Convalescent serum from HSV2-infected patients was used to identify viral antigens via 2-D protein electrophoresis and immunoblotting. The serum predominantly recognized several capsid scaffold proteins encoded by gene UL26.5, mainly ICP35. This protein has been primarily reported to function temporarily in viral assembly but is not expressed in mature virus particles. Further immunological studies suggested that this protein elicits specific antibody and cytotoxic T lymphocyte (CTL) responses in mice, but these responses do not result in a clinical protective effect in response to HSV2 challenge. The data suggested that immunodominance of ICP35 might be used to design an integrated antigen with other viral glycoproteins.

Objectives To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.Design A nationally representative retrospective study.Setting Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.Participants Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measures In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).Results A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.Conclusions The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.