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Abstract Background Routinely collected health data (RCD) are important resource for exploring drug treatment effects. Adequate reporting of data source profiles may increase the credibility of evidence generated from these data. This study conducted a systematic literature review to evaluate the reporting characteristics of databases used by RCD studies to explore the effects of drug treatment. Methods Observational studies published in 2018 that used RCD to explore the effects of drug treatment were identified by searching PubMed. We categorized eligible reports into two groups by journal impact factor (IF), including the top 5 general medical journals (NEJM, Lancet, JAMA, BMJ and JAMA Internal Medicine) and the other journals. The reporting characteristics of the databases used were described and compared between the two groups and between studies citing and not citing database references. Results A total of 222 studies were included, of which 53 (23.9%) reported that they applied data linkage, 202 (91.0%) reported the type of database, and 211 (95.0%) reported the coverage of the data source. Only 81 (36.5%) studies reported the timeframe of the database. Studies in high-impact journals were more likely to report that they applied data linkage (65.1% vs. 20.2%) and used electronic medical records (EMR) (73.7% vs. 30.0%) and national data sources (77.8% vs. 51.3%) than those published in other medical journals. There were 137/222 (61.7%) cited database references. Studies with database-specific citations had better reporting of the data sources and were more likely to publish in high-impact journals than those without (mean IF, 6.08 vs. 4.09). Conclusions Some deficits were found in the reporting quality of databases in studies that used RCD to explore the effects of drug treatment. Studies citing database-specific references may provide detailed information regarding data source characteristics. The adoption of reporting guidelines and education on their use is urgently needed to promote transparency by research groups.

Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.

Abstract Background Because of the low regeneration efficiency and unclear underlying molecular mechanism, tooth regeneration applications are limited. In this study, we explored the influence of residual periodontal ligament on the dentin regeneration potential of dental pulp stem cells (DPSCs) in the jaw. Methods To establish a tooth regeneration model, the incisors of New Zealand white rabbits were extracted while preserving residual periodontal ligament, followed by the implantation of DPSCs. After 3 months, micro-computed tomography (micro-CT), stereomicroscopy and scanning electron microscopy (SEM) were used to observe the volume, morphology and microstructure of regenerated tissue. Histological staining and immunostaining analyses were used to observe the morphological characteristics and expression of the dentin-specific proteins DMP1 and DSPP. To explore the mechanism, DPSCs and periodontal ligament stem cells (PDLSCs) were cocultured in vitro, and RNA was collected from the DPSCs for RNA-seq and bioinformatic analysis. Results The results of micro-CT and stereomicroscopy showed that the number of sites with regeneration and the volume of regenerated tissue in the DPSCs/PDL group (6/8, 1.07 ± 0.93 cm3) were larger than those in the DPSCs group (3/8, 0.23 ± 0.41 cm3). The results of SEM showed that the regenerated dentin-like tissue in the DPSCs and DPSCs/PDL groups contained dentin tubules. Haematoxylin and eosin staining and immunohistochemical staining indicated that compared with the DPSCs group, the DPSCs/PDL group showed more regular regenerated tissue and higher expression levels of the dentin-specific proteins DMP1 and DSPP (DMP1: P = 0.02, DSPP: P = 0.01). RNA-seq showed that the coculture of DPSCs with PDLSCs resulted in the DPSCs differentially expressing 427 mRNAs (285 upregulated and 142 downregulated), 41 lncRNAs (26 upregulated and 15 downregulated), 411 circRNAs (224 upregulated and 187 downregulated), and 19 miRNAs (13 upregulated and 5 downregulated). Bioinformatic analysis revealed related Gene Ontology function and signalling pathways, including extracellular matrix (ECM), tumour necrosis factor (TNF) signalling and chemokine signalling pathways. Conclusions Residual periodontal ligament in the extraction socket promotes the dentin regeneration potential of DPSCs in the jaw. RNA-seq and bioinformatic analysis revealed that ECM, TNF signalling and chemokine signalling pathways may represent the key factors and signalling pathways.

The constitutive model plays a decisive role in the accuracy and reliability of the simulation results. Because the material flow characteristics obtained by the traditional experimental method are difficult to describe thermoplastic deformation behavior in the cutting process accurately, and the inverse identification is usually carried out based on a two-dimensional orthogonal cutting model, ignoring the actual cutting state, which leads to significant deviations in the results of parameter identification. Therefore, a three-dimensional (3-D) turning finite element simplified model which conforms to the actual cutting scenario was established. Based on this model, a coupling simulation was used to inverse identify the Johnson-Cook (J-C) parameters for turning 304 stainless steel. Firstly, the automatic finite element modeling and calculation of 3-D turning is implemented by Python. Then, the inverse identification framework was built based on the ISIGHT. The initial yield strength of J-C parameters was obtained from quasi-static compression experiments. With the objective function of minimizing the error between the experimental cutting force and the simulated cutting force, the inverse identification of J-C parameters (strain reinforcement factor, strain rate sensitivity, thermal softening index, and hardening index) was carried out by a multi-island genetic algorithm. Finally, compared with cutting forces, chip morphology, and residual stresses, the feasibility of the inverse identification method and the accuracy of the constitutive model is demonstrated, which also provides a reference for the optimal identification method of constitutive parameters of difficult-to-machine materials.

Nitrate reduction by napA (encodes periplasmic nitrate reductase) bacteria and nitrous oxide reduction by nosZ (encodes nitrous oxide reductase) bacteria play important roles in nitrogen cycling and removal in intensive aquaculture systems. This study investigated the diversity, dynamics, drivers, and assembly mechanisms of total bacteria as well as napA and nosZ denitrifiers in intensive shrimp aquaculture ponds over a 100-day period. Alpha diversity of the total bacterial community increased significantly over time. In contrast, the alpha diversity of napA and nosZ bacteria remained relatively stable throughout the aquaculture process. The community structure changed markedly across all groups over the culture period. Total nitrogen, phosphate, total phosphorus, and silicate were identified as significant drivers of the denitrifying bacterial communities. Network analysis revealed complex co-occurrence patterns between total, napA, and nosZ bacteria which fluctuated over time. A null model approach showed that, unlike the total community dominated by stochastic factors, napA and nosZ bacteria were primarily governed by deterministic processes. The level of determinism increased with nutrient loading, suggesting the denitrifying community can be manipulated by bioaugmentation. The dominant genus Ruegeria may be a promising candidate for introducing targeted denitrifiers into aquaculture systems to improve nitrogen removal. Overall, this study provides important ecological insights into aerobic and nitrous oxide-reducing denitrifiers in intensive aquaculture, supporting strategies to optimize microbial community structure and function.

BackgroundPresenteeism is a significant global public health problem, and nurses are a high-prevalence group of presenteeism, affecting not only nurses’ physical and mental health, work efficiency, and quality of work but even poses a serious threat to patient safety.ObjectiveThe categorization of presenteeism among ICU nurses is unclear. Our research aims to explore the subtypes of presenteeism among ICU nurses based on latent profile analysis, analyze the influencing factors of different subtypes, and provide a reference basis for developing targeted interventions to reduce the presenteeism rate.MethodsFrom January to February 2023, 509 ICU nurses in Sichuan Province, China, were selected as respondents and surveyed using the general information questionnaire, the presenteeism scale, and the perceived social support scale. Potential categories of presenteeism among ICU nurses were explored using potential profile analysis, and factors influencing the potential types of presenteeism among ICU nurses were investigated using the chi-square test and multivariate logistic regression analysis.ResultsThe best model was suggested to consist of three profiles: low presenteeism-normal coping group (18.3%), moderate presenteeism group (47.9%), and high presenteeism-work limitation group (33.8%). Multiple logistic regression results showed that secondary hospitals (OR = 0.116, p = 0.015), good physical health (OR = 0.084, p = 0.023), general physical health (OR = 0.016, p = 0.037), ICU human resource allocation = 1:2.5 to 3 (OR = 0.315, p = 0.007), and higher social support scores (OR = 0.975, p = 0.047) were more likely to be grouped into low presenteeism-normal coping group; married with no children (OR = 24.554, p = 0.005) were more likely to be grouped into moderate presenteeism group; and having experienced workplace violence in the past year (OR = 1.182, p = 0.049) were more likely to be grouped into high presenteeism-work limitation group.ConclusionThere is group heterogeneity in the presenteeism of ICU nurses, and nursing managers should develop targeted interventions to reduce the presenteeism rate of ICU nurses according to the characteristics and influencing factors of each type of presenteeism of ICU nurses.

ABSTRACT Bacterial spores are metabolically dormant, resistant to microbicides, and vectors of food spoilage and diseases, while germinated spores are easy to kill. Consequently, understanding germination mechanisms may facilitate the development of “germinate-to-eradicate” strategies. Spores germinate in response to many compounds (called germinants). They can also retain the memory of a germinant exposure, such that a second exposure triggers more efficient germination, but how is not clear. A recent high-profile paper [Science (2022) 378:43] suggested that increasing spore electrochemical potential is how memory is “stored” based on measurements of Bacillus subtilis spores’ accumulation of the dye thioflavin-T after germinant exposure. Indeed, we found that wild-type spores of three Bacillus and one Clostridioides species all exhibited this early thioflavin-T accumulation during nutrient pulses. However, our data indicate that inferring spores’ electrochemical potential from thioflavin-T accumulation is problematic. We found that B. subtilis spores lacking their proteinaceous coat exhibited memory but did not accumulate thioflavin-T prior to germinant addition or during nutrient pulses. Furthermore, wild-type Bacillus spores germinating with dodecylamine, which also elicits memory, showed no thioflavin-T accumulation. Finally, we found that thioflavin-T accumulation by a germinating spore is outside the spore core at early stages but inside the spore core as germination proceeds. These findings suggest that thioflavin-T accumulation during the early stages of germination is due to its binding to one or more protein in the spore coat rather than to changes in spores’ electrochemical potential; thus, thioflavin-T is not a potentiometric dye for the study of spore memory of germinant pulses. IMPORTANCE Bacillus and Clostridium spores cause food spoilage and disease because of spores’ dormancy and resistance to microbicides. However, when spores “come back to life” in germination, their resistance properties are lost. Thus, understanding the mechanisms of spore germination could facilitate the development of “germinate to eradicate” strategies. One germination feature is the memory of a pulsed germinant stimulus leading to greater germination following a second pulse. Recent observations of increases in spore binding of the potentiometric dye thioflavin-T early in their germination of spores led to the suggestion that increasing electrochemical potential is how spores “remember” germinant pulses. However, new work finds no increased thioflavin-T binding in the physiological germination of Coatless spores or of intact spores germinating with dodecylamine, even though spore memory is seen in both cases. Thus, using thioflavin-T uptake by germinating spores to assess the involvement of electrochemical potential in memory of germinant exposure, as suggested recently, is questionable.

BackgroundTranscranial magnetic stimulation (TMS), as a non-invasive neuromodulation technique, has been widely used in the treatment of Parkinson’s disease (PD). The increasing application of TMS has promoted an increasing number of clinical studies. In this paper, a bibliometric analysis of existing studies was conducted to reveal current research hotspots and guide future research directions.MethodRelevant articles and reviews were obtained from the Science Citation Index Expanded of Web of Science Core Collection database. Data related to publications, countries, institutions, authors, journals, citations, and keywords in the studies included in the review were systematically analyzed using VOSviewer 1.6.18 and Citespace 6.2.4 software.ResultA total of 1,894 papers on the topic of TMS in PD between 1991 and 2022 were analyzed and visualized to identify research hotspots and trends in the field. The number of annual publications in this field of study has increased gradually over the past 30 years, with the number of annual publications peaking in 2022 (n = 150). In terms of publications and total citations, countries, institutions, and authors from North America and Western Europe were found to make significant contributions to the field. The current hotspot focuses on the effectiveness of TMS for PD in different stimulation modes or different stimulated brain regions. The keyword analysis indicates that the latest research is oriented to the mechanism study of TMS for motor symptoms in PD, and the non-motor symptoms are also receiving more attention.ConclusionOur study offers insights into the current hotspots and emerging trends of TMS in the rehabilitation of PD. These findings may serve as a guide for future research and the application of TMS for PD.

Percutaneous closure has emerged as the standard treatment for secundum-type atrial septal defects (ASDs). However, there is a rare but serious complication of occluder device migration and embolization to the heart chambers or distal vasculature during or shortly after implantation. Although this occurrence is extremely rare, it can have disastrous consequences. Fortunately, advancements in equipment and technology have facilitated the transition from surgical procedures to percutaneous techniques for removing embolized occluder devices. In this report, we present a case in which an Amplatzer septal occluder (ASO) device embolized to the descending thoracic aortic isthmus two days after implantation. The device was successfully retrieved using a percutaneous technique, and another ASO device was subsequently redeployed to the ASD. Regrettably, the patient experienced an intraoperative cardiac arrest. Despite prompt rescue efforts and recovery of vital signs, the patient still suffered postoperative sequelae. The main reason for occluder device migration in this case may have been the undersizing of the ASO device due to the operator's lack of caution.

Understanding the mechanism of detoxification initiation in arthropods after pesticide exposure is crucial. Although the identity of transcription factors that induce and regulate the expression of detoxification genes in response to pesticides is beginning to emerge, whether transcription factors directly interact with xenobiotics is unclear. The findings of this study revealed that a nuclear hormone receptor, Tetranychus cinnabarinus hormone receptor (HR) TcHR96h, regulates the overexpression of the detoxification gene TcGSTm02, which is involved in cyflumetofen resistance. The nuclear translocation of TcHR96h increased after cyflumetofen exposure, suggesting direct binding with cyflumetofen. The direct binding of TcHR96h and cyflumetofen was supported by several independent proteomic assays that quantify interactions with small molecules. Together, this study proposes a model for the initiation of xenobiotic detoxification in a polyphagous agricultural pest. These insights not only provide a better understanding of the mechanisms of xenobiotic detoxification and metabolism in arthropods, but also are crucial in understanding adaptation in polyphagous herbivores.

We report a case of primary cutaneous γδT cell lymphoma complicated with hemophagocytic lymphohistiocytosis. A 33-year-old female presented with nodule on her left arm for 1 month and erythema on her both legs for a week. Physical examination revealed redness and swelling of the left upper arm with nodule sized 6.8 cm, accompanied with elevated skin temperature and tenderness. A sinus with yellow exudate was observed in the center of the lesion. There were more than 10 red nodular plaques in various sizes with unclear boundaries and tenderness around the ankles. Histology showed atypical lymphoid infiltrate in the dermis. Immunohistochemistry showed positive for CD3, CD5, CD8, Granzyme B, TIA-1, TCRγδ and Ki67(90%). Bone marrow aspiration showed abnormal maturation of granulocytes, erythroid hyperplasia and hemophagocytosis by reticular cells. TCRG gene rearrangement showed clonal amplification peak in the target band. PET-CT revealed multiple lymphadenopathy in her body. The diagnosis was primary cutaneous Gamma-Delta T-Cell lymphoma with hemophagocytic lymphohistiocytosis. After 2 weeks of CHOP+VP-16 combined with chemotherapy, patient's body temperature became normal, and the skin lesions gradually subsided. During the regular follow-up, the patient's symptoms recurred many times, and new skin lesions repeatedly developed, without significant improvement after the treatments with different chemotherapy. One year later, patient received hematopoietic stem cell transplantation, and her condition became stable. Currently the patient is still under follow-up.

Abstract Background China has a double burden of diabetes mellitus and tuberculosis. Diabetes mellitus and tuberculosis are both important risk factors for Aspergillus infection. Aspergillus lentulus is an emerging fungal pathogen in China and invasive aspergillosis due to A. lentulus is associated with high mortality. Case presentation A 79-year-old man was admitted to our hospital, complaining of a 7-day history of fever. Five days before admission, he was diagnosed with pulmonary infection at a local hospital, but his symptoms did not relieve after antibiotic therapy. The patient was diagnosed with diabetes mellitus two months ago. About 20 days ago, he began to present chest tightness and shortness of breath after physical activity. After admission, he developed continuous fever and rapid respiratory deterioration, and finally died after his family abandoned treatment. Pulmonary coinfection with M. tuberculosis and A. lentulus was identified by metagenome next-generation sequencing (mNGS) from bronchoalveolar lavage fluid. Conclusions Clinicians and laboratories should be alert to the emerging A. lentulus infection in China due to its drug-resistance and high mortality. In comparison with conventional methods, mNGS has a great advantage for the diagnosis of mixed pulmonary infection.

Black shoot blight disease caused by Erwinia pyrifoliae has serious impacts on quality and yield in pear production in Korea; therefore, rapid and accurate methods for its detection are needed. However, traditional detection methods require a great deal of time and fail to achieve absolute quantification. In the present study, we developed a droplet digital polymerase chain reaction (ddPCR) method for the detection and absolute quantification of E. pyrifoliae using a pair of species-specific primers. The detection range was 103–107 copies/ml (DNA templates) and cfu/ml (cell culture templates). This new method exhibited good linearity and repeatability and was validated by absolute quantification of E. pyrifoliae DNA copies from samples of artificially inoculated immature pear fruits. Here, we present the first study of ddPCR assay for the detection and quantification of E. pyrifoliae. This method has potential applications in epidemiology and for the early prediction of black shoot blight outbreaks.

Occlusion handling is crucial for improving the performance of convolutional neural networks (CNNs) in real-world remote sensing images, which are often captured in complex and unconstrained environments. In particular, occlusion scene classification has received significant attention due to its usefulness in various remote sensing tasks. However, existing methods are limited by their dependence on close-world learning, which assumes that all test cases are included in the training set. This is problematic because occlusion is too complex to be thoroughly annotated. To address this issue, we propose a novel contrastive learning-based CNN that can classify out-of-distribution occluded scenes without the need for occlusion annotation. Our approach uses a two-branch subnetwork to learn representations of unoccluded anchor images and occlusion-augmented images. We then employ cascade supervised contrastive learning to make the network's representations invariant to occlusion. Unlike standard contrastive learning, our method leverages category information to avoid incompact intraclass distribution and uses a cascade strategy to hierarchically learn occlusion-invariant representations. Finally, we use a multilayer perceptron to classify the learned representations and assess representation quality. We evaluate our method on the UAVDT dataset and two simulated datasets, and the results demonstrate that our approach accurately characterizes occluded objects and achieves more precise classification in occlusion scenarios.

Abstract Background and objective Liver fibrosis has been considered a predictor of cardiovascular disease. This study aimed to evaluate whether the degree of liver fibrosis is related to post-stroke depression (PSD) at 3 months follow-up. Methods We prospectively and continuously enrolled patients with first-ever ischemic stroke from June 2020 to January 2022. Liver fibrosis was measured after admission by calculating the Fibrosis-4 index (FIB-4) and stratified into two categories ( 7 were further evaluated using the Chinese version of the structured clinical interview of DSM-IV, for diagnosing PSD at 3 months. Results A total of 326 patients (mean age 66.6 years, 51.5% male) were recruited for the study. As determined by the FIB-4 score, 80 (24.5%) patients had advanced liver fibrosis. During the follow-up, PSD was observed in 91 patients, which accounted for 27.9% (95% confidence interval [CI] 25.5%–30.5%) of the cohort. The prevalence of advanced liver fibrosis was higher in PSD patients than those without PSD (40.0% versus 24.0%; P = 0.006). After adjustment for covariates in the multivariate logistic analysis, advanced fibrosis was significantly associated with PSD (odds ratio [OR], 1.88; 95% CI, 1.03–3.42; P = 0.040). Similar results were found when the FIB-4 was analyzed as a continuous variable. Conclusions This study found that advanced liver fibrosis was associated with an increased risk of 3-month PSD. FIB-4 score may be valuable for screening depressive symptoms in ischemic stroke patients.

Objectives In this work, the influence of the initial heeling angle on the roll motion response of a ship in random beam wave is studied. MethodsSpecifically, the path integration method is applied to solve the Fokker-Planck equation, which governs the probability properties of the stochastic differential equation for the roll motion. The probability distributions of the roll motion response can then be obtained. ResultsThe results show that the initial heeling angle has limited influence on the roll motion response spectrum, but the probability density function of the roll motion response and distribution of extreme roll motion response can be significantly influenced by the heeling angle. As a result, the safety and stability of the ship will deteriorate dramatically. ConclusionsThe path integration method can be effective for studying the characteristics of ship roll motion under random waves.

Abstract Background The purpose of this study was to investigate the fracture strength and stress distribution of four ceramic restorations. Methods Forty human mandibular first molars were collected and randomized into four groups after establishing the distal defect: full crown group with 4 mm axial wall height (AWH) (FC4); short AWH crown group with 2 mm AWH (SC2); occlusal veneer group with 0 mm AWH (OV0); occlusal distal veneer group with only the distal surface prepared, and 4 mm AWH (OD4). The teeth were prepared according to the groups and the ceramic restorations were completed using celtra duo ceramic blocks. The ceramic thickness of the occlusal surface is about 1.5 mm and the edge is about 1 mm. The failure load values and fracture modes of each group were detected by mechanical test in vitro. According to the groups to establish three-dimensional finite element analysis (FEA) models, a 600 N loading force was applied vertically using a hemispherical indenter with a diameter of 6 mm. and compare the stress distribution under the condition of different restorations. Results In vitro mechanical tests showed that the failure load values were SC2 (3232.80 ± 708.12 N) > OD4 (2886.90 ± 338.72 N) > VO0 (2133.20 ± 376.15 N) > FC4(1635.40 ± 413.05 N). The failure load values of the short AWH crown and occlusal distal veneer were significantly higher than that of occlusal veneer and full crown (P VO0 (214.3 MPa) > OD4 (197.9 MPa) > SC2 (163.1 MPa). The stress of enamel was concentrated in the area where the remaining enamel was thinner, the maximum von Mises stress values was OD4 (246.2 MPa) ≈ FC4 (212.4 MPa) > VO0 (61.8 MPa) ≈ SC2 (45.81 MPa). The stress of dentin is concentrated in the root furcation and the upper third region of the root. However, stress concentration was observed at the tooth cervix in the full crown. Conclusion Under certain conditions, the occlusal distal veneer shows better performance than the full crown.

Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis (Mtb). Clarithromycin (CTY), an analog of erythromycin (ERY), is more potent against multidrug-resistance (MDR) TB. ERY and CTY were previously reported to bind to the nascent polypeptide exit tunnel (NPET) near peptidyl transferase center (PTC), but the only available CTY structure in complex with D. radiodurans (Dra) ribosome could be misinterpreted due to resolution limitation. To date, the mechanism of specificity and efficacy of CTY for Mtb remains elusive since the Mtb ribosome-CTY complex structure is still unknown. Here, we employed new sample preparation methods and solved the Mtb ribosome-CTY complex structure at 3.3Å with cryo-EM technique, where the crucial gate site A2062 (E. coli numbering) is located at the CTY binding site within NPET. Two alternative conformations of A2062, a novel syn-conformation as well as a swayed conformation bound with water molecule at interface, may play a role in coordinating the binding of specific drug molecules. The previously overlooked C–H hydrogen bond (H-bond) and π interaction may collectively contribute to the enhanced binding affinity. Together, our structure data provide a structural basis for the dynamic binding as well as the specificity of CTY and explain of how a single methyl group in CTY improves its potency, which provides new evidence to reveal previously unclear mechanism of translational modulation for future drug design and anti-TB therapy. Furthermore, our sample preparation method may facilitate drug discovery based on the complexes with low water solubility drugs by cryo-EM technique.

In order to study vibro-acoustic characteristics between composite laminated rotationally stiffened plate and acoustic cavities in the coupled system, first-order shear deformation theory (FSDT) and modified Fourier series are used to construct a unified analysis model. The involved coupled systems primarily encompass three types: the coupled system between composite laminated rotationally stiffened plate and cylindrical-cylindrical cavities, spherical-cylindrical cavities, and conical-cylindrical cavities. First, the first-order shear deformation theory and the modified Fourier series are applied to construct the allowable displacement function of the composite laminated rotationally stiffened plate and the allowable sound pressure function of the acoustic cavities. Second, the energy functionals for the structural domain and the acoustic field domain are established, respectively. According to the continuity condition of the particle vibration velocity at the coupling boundary between the composite, laminated cylindrical shell and the enclosed cavity, the coupling potential energy between the stiffened plate and two acoustic cavities is introduced to obtain the energy functional of the coupled system. Third, the Rayleigh-Ritz method is utilized to solve the energy functional and, when combined with artificial virtual spring technology, the suggested theory may be used to study the vibro-acoustic characteristics of a coupled system with arbitrary elastic boundary conditions. Finally, based on validating the fast convergence and correctness of the model, this paper will analyze the impact of crucial parameters on vibro-acoustic characteristics. Furthermore, by incorporating internal point forces and point-sound source stimulation, a steady-state response analysis of the coupled system will be conducted. This research can give a theoretical foundation for the vibration and noise reduction of a vibro-acoustic coupling system.

We present a systematic study of the putative hot gas corona around late-type galaxies (LTGs) residing in the Virgo cluster, based on archival Chandra observations. Our sample consists of 21 nearly edge-on galaxies representing a range of star formation rate (SFR) of 0.2–3 M _⊙ yr ^−1 and a range of stellar mass ( M _* ) of (0.2–10) × 10 ^10 M _⊙ , the majority of which have not been explored with high-sensitivity X-ray observations so far. Significant extraplanar diffuse X-ray (0.5–2 keV) emission is detected in only three LTGs, which are also the three galaxies with the highest SFR. A stacking analysis is performed for the remaining galaxies without individual detection, dividing the whole sample into two subsets based on SFR, stellar mass, or specific SFR. Only the high-SFR bin yields a significant detection, which has a value of L _X ∼ 3 × 10 ^38 erg s ^−1 per galaxy. The stacked extraplanar X-ray signals of the Virgo LTGs are consistent with the empirical L _X –SFR and L _X – M _* relations found among highly inclined disk galaxies in the field, but appear to be systematically lower than those of a comparison sample of simulated star-forming galaxies in clusters identified from the Illustris-TNG100 simulation. The apparent paucity of hot gas coronae in the sampled Virgo LTGs might be understood as the net outcome of the long-lasting effect of ram pressure stripping exerted by the hot intracluster medium and in-disk star-forming activity acting on shorter timescales. A better understanding of the roles of environmental effects in regulating the hot gas content of cluster galaxies invites sensitive X-ray observations for a large sample of galaxies.

Drug combination therapy is a highly effective approach for enhancing the therapeutic efficacy of anti-cancer drugs and overcoming drug resistance. However, the innumerable possible drug combinations make it impractical to screen all synergistic drug pairs. Moreover, biological insights into synergistic drug pairs are still lacking. To address this challenge, we systematically analyzed drug combination datasets curated from multiple databases to identify drug pairs more likely to show synergy. We classified drug pairs based on their MoA and discovered that 110 MoA pairs were significantly enriched in synergy in at least one type of cancer. To improve the accuracy of predicting synergistic effects of drug pairs, we developed a suite of machine learning models that achieve better predictive performance. Unlike most previous methods that were rarely validated by wet-lab experiments, our models were validated using two-dimensional cell lines and three-dimensional tumor slice culture (3D-TSC) models, implying their practical utility. Our prediction and validation results indicated that the combination of the RTK inhibitors Lapatinib and Pazopanib exhibited a strong therapeutic effect in breast cancer by blocking the downstream PI3K/AKT/mTOR signaling pathway. Furthermore, we incorporated molecular features to identify potential biomarkers for synergistic drug pairs, and almost all potential biomarkers found connections between drug targets and corresponding molecular features using protein-protein interaction network. Overall, this study provides valuable insights to complement and guide rational efforts to develop drug combination treatments.

ABSTRACT Anopheles mosquitoes are the primary vectors for the transmission of malaria parasites, which poses a devastating burden on global public health and welfare. The recent invasion of Anopheles stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. To address this issue, we developed a new approach for mosquito larvae control using gut microbiota-mediated RNA interference (RNAi). We engineered a mosquito symbiotic gut bacterium, Serratia fonticola, by deleting its RNase III gene to produce double-stranded RNAs (dsRNAs) in the mosquito larval gut. We found that the engineered S. fonticola strains can stably colonize mosquito larval guts and produce dsRNAs dsMet or dsEcR to activate RNAi and effectively suppress the expression of methoprene-tolerant gene Met and ecdysone receptor gene EcR, which encode receptors for juvenile hormone and ecdysone pathways in mosquitoes, respectively. Importantly, the engineered S. fonticola strains markedly inhibit the development of A. stephensi larvae and leads to a high mortality, providing an effective dsRNA delivery system for silencing genes in insects and a novel RNAi-mediated pest control strategy. Collectively, our symbiont-mediated RNAi (smRNAi) approach offers an innovative and sustainable method for controlling mosquito larvae and provides a promising strategy for combating malaria. IMPORTANCE Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. RNA interference (RNAi) is a promising approach that uses dsRNA to silence specific genes in pests. This study presents the use of a gut symbiotic bacterium, Serratia fonticola, as an efficient delivery system of dsRNA for RNAi-mediated pest control. The knockout of RNase III, a dsRNA-specific endonuclease gene, in S. fonticola using CRISPR-Cas9 led to efficient dsRNA production. Engineered strains of S. fonticola can colonize the mosquito larval gut and effectively suppress the expression of two critical genes, Met and EcR, which inhibit mosquito development and cause high mortality in mosquito larvae. This study highlights the potential of exploring the mosquito microbiota as a source of dsRNA for RNAi-based pest control.

BackgroundHistory of first-degree relatives with colorectal cancer is one of the most important and common risk factors for colorectal cancer in China. Most chronic diseases, such as malignancies, are preventable by adopting health-promoting behaviors and other approaches. However, the relationships among factors affecting the health-promoting lifestyles of first-degree relatives with colorectal cancer have not been sufficiently studied. This study aimed to test the mediation effects of Health belief in the relationship between health-promoting lifestyle and health information literacy among first-degree relatives with colorectal cancer.MethodsA cross-sectional descriptive design was conducted using convenience sampling of 856 first-degree relatives of CRC patients attending three tertiary care hospitals in Nanchong and Deyang of China from December 2020 to December 2022. Questionnaires were used to collect data on the participants’ demographic information, the colorectal cancer health beliefs, the health promotion lifestyle, and the health information literacy. Data were analyzed with descriptive statistics, one-way ANOVA, Pearson’s correlation coefficients, and mediation analysis using SPSS 25.0 program and its macro-program PROCESS.ResultsThe findings indicated health information literacy was less, health belief was at the medium level, and performance of health promotion behavior was average for first-degree relatives of colorectal cancer. Whereas first-degree relatives of colorectal cancer health-promotion lifestyle had a positive correlation with health beliefs (r = 0.376, p

Background: Kidney renal clear cell carcinoma (KIRC) is an immunogenic tumor, and immune infiltrates are relevant to patients’ therapeutic response and prognosis. NDUFS1, the core subunit of mitochondrial complex I, has been reported to be associated with KIRC patients’ prognosis. However, the upstream regulator for NDUFS1 and their correlations with immune infiltration remain unclear.Methods: The expression of NDUFS genes in KIRC and their influences on patients’ survival were investigated by UALCAN, ENCORI, Oncomine, TIMER as well as Kaplan-Meier Plotter. miRNAs regulating NDUFS1 were predicted and analyzed by TargetScan and ENCORI. The correlations between NDUFS1 expression and immune cell infiltration or gene marker sets of immune infiltrates were analyzed via TIMER. The overall survival in high/low NDUFS1 or hsa-miR-320b expressed KIRC patients with or without immune infiltrates were analyzed via Kaplan-Meier Plotter. The combined NDUFS1 expression and/or CD4+ T cell infiltration on KIRC patients’ overall survival were validated by multiplexed immunofluorescence (mIF) staining in tissue microarray (TMA). Furthermore, the influences of NDUFS1 expression on the chemotaxis of CD4+ T cells to KIRC cells were performed by transwell migration assays.Results: We found that the low expression of NDUFS1 mRNA and protein in KIRC was correlated with unfavorable patients’ survival and poor infiltration of CD4+ T cells. In patients with decreased CD4+ T cell infiltration whose pathological grade less than III, TMA mIF staining showed that low expression of NDUFS1 had significantly poor OS than that with high expression of NDUFS1 did. Furthermore, hsa-miR-320b, a possible negative regulator of NDUFS1, was highly expressed in KIRC. And, low NDUFS1 or high hsa-miR-320b consistently correlated to unfavorable outcomes in KIRC patients with decreased CD4+ T cell infiltration. In vitro, NDUFS1 overexpression significantly increased the chemotaxis of CD4+ T cell to KIRC cells.Conclusion: Together, NDUFS1, upregulated by decreased hsa-miR-320b expression in KIRC patients, might act as a biomarker for CD4+ T cell infiltration. And, the combination of NDUFS1 with CD4+ T cell infiltration predicts favorable prognosis in KIRC.

Objective: DNA methylation plays a potential role in the pathogenesis of Alzheimer’s disease (AD). However, little is known about the global changes of blood leukocyte DNA methylome profiles from Chinese patients with mild cognitive impairment (MCI) and with AD, or the specific DNA methylation-based signatures associated with MCI and AD. In this study, we sought to dissect the characteristics of blood DNA methylome profiles in MCI- and AD-affected Chinese patients with the aim of identifying novel DNA methylation biomarkers for AD.Methods: In this study, we profiled the DNA methylome of peripheral blood leukocytes from 20 MCI- and 20 AD-affected Chinese patients and 20 cognitively healthy controls (CHCs) with the Infinium Methylation EPIC BeadChip array.Results: We identified significant alterations of the methylome profiles in MCI and AD blood leukocytes. A total of 2,582 and 20,829 CpG sites were significantly and differentially methylated in AD and MCI compared with CHCs (adjusted p < 0.05), respectively. Furthermore, 441 differentially methylated positions (DMPs), aligning to 213 unique genes, were overlapped by the three comparative groups of AD versus CHCs, MCI versus CHCs, and AD versus MCI, of which 6 and 5 DMPs were continuously hypermethylated and hypomethylated in MCI and AD relative to CHCs (adjusted p < 0.05), respectively, such as FLNC cg20186636 and AFAP1 cg06758191. The DMPs with an area under the curve >0.900, such as cg18771300, showed high potency for predicting MCI and AD. In addition, gene ontology and pathway enrichment results showed that these overlapping genes were mainly involved in neurotransmitter transport, GABAergic synaptic transmission, signal release from synapse, neurotransmitter secretion, and the regulation of neurotransmitter levels. Furthermore, tissue expression enrichment analysis revealed a subset of potentially cerebral cortex-enriched genes associated with MCI and AD, including SYT7, SYN3, and KCNT1.Conclusion: This study revealed a number of potential biomarkers for MCI and AD, also highlighted the presence of epigenetically dysregulated gene networks that may engage in the underlying pathological events resulting in the onset of cognitive impairment and AD progression. Collectively, this study provides prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course.

Abstract Oocyte maturation arrest is one of the important causes of female infertility, but the genetic factors remain largely unknown. PABPC1L, a predominant poly(A)‐binding protein in Xenopus, mouse, and human oocytes and early embryos prior to zygotic genome activation, plays a key role in translational activation of maternal mRNAs. Here, we identified compound heterozygous and homozygous variants in PABPC1L that are responsible for female infertility mainly characterized by oocyte maturation arrest in five individuals. In vitro studies demonstrated that these variants resulted in truncated proteins, reduced protein abundance, altered cytoplasmic localization, and reduced mRNA translational activation by affecting the binding of PABPC1L to mRNA. In vivo, three strains of Pabpc1l knock‐in (KI) female mice were infertile. RNA‐sequencing analysis showed abnormal activation of the Mos‐MAPK pathway in the zygotes of KI mice. Finally, we activated this pathway in mouse zygotes by injecting human MOS mRNA, and this mimicked the phenotype of KI mice. Our findings reveal the important roles of PABPC1L in human oocyte maturation and add a genetic potential candidate gene to be screened for causes of infertility.

Legume-rhizobial symbiotic nitrogen fixation is the most efficient nitrogen assimilation system in the ecosystem. In the special interaction between organ–root nodules, legumes supply rhizobial carbohydrates for their proliferation, while rhizobials provide host plants with absorbable nitrogen. Nodule initiation and formation require a complex molecular dialogue between legumes and rhizobia, which involves the accurate regulation of a series of legume genes. The CCR4–NOT complex is a conserved multi-subunit complex with functions regulating gene expression in many cellular processes. However, the functions of the CCR4–NOT complex in rhizobia–host interactions remain unclear. In this study, we identified seven members of the NOT4 family in soybean and further classified them into three subgroups. Bioinformatic analysis showed that NOT4s shared relatively conserved motifs and gene structures in each subgroup, while there were significant differences between NOT4s in the different subgroups. Expression profile analysis indicated that NOT4s may be involved in nodulation in soybean, as most of them were induced by Rhizobium infection and highly expressed in nodules. We further selected GmNOT4-1 to clarify the biological function of these genes in soybean nodulation. Interestingly, we found that either GmNOT4-1 overexpression or down-regulation of GmNOT4-1 by RNAi or CRISPR/Cas9 gene editing would suppress the number of nodules in soybean. Intriguingly, alterations in the expression of GmNOT4-1 repressed the expression of genes in the Nod factor signaling pathway. This research provides new insight into the function of the CCR4–NOT family in legumes and reveals GmNOT4-1 to be a potent gene for regulating symbiotic nodulation.

Abstract To evaluate and establish a prediction model of the outcome of induced labor based on machine learning algorithm. This was a cross-sectional design. The subjects were divided into primipara and multipara, and the risk factors for the outcomes of induced labor were assessed by multifactor logistic regression analysis. The outcome model of labor induced with oxytocin (OT) was constructed based on the four machine learning algorithms, including AdaBoost, logistic regression, naive Bayes classifier, and support vector machine. Factors, such as accuracy, recall, precision, F1 value, and receiver operating characteristic curve, were used to evaluate the prediction performance of the model, and the clinical application of the model was verified. A total of 907 participants were included in this study. Logistic regression algorithm obtained better results in both primipara and multipara groups compared to the other three models. The accuracy of the model for the prediction of “successful induction of labor” was 94.24% and 96.55%, and that of “failed induction of labor” was 65.00% and 66.67% in the primipara and the multipara groups, respectively. This study established a prediction model of OT-induced labor based on the Logistic regression algorithm, with rapid response, high accuracy, and strong extrapolation, which was critical for obstetric clinical nursing.

Abstract Background Previous studies on European (EUR) samples have obtained inconsistent results regarding the genetic correlation between type 2 diabetes mellitus (T2DM) and Schizophrenia (SCZ). A large-scale trans-ethnic genetic analysis may provide additional evidence with enhanced power. Objective We aimed to explore the genetic basis for both T2DM and SCZ based on large-scale genetic analyses of genome-wide association study (GWAS) data from both East Asian (EAS) and EUR subjects. Methods A range of complementary approaches were employed to cross-validate the genetic correlation between T2DM and SCZ at the whole genome, autosomes (linkage disequilibrium score regression, LDSC), loci (Heritability Estimation from Summary Statistics, HESS), and causal variants (MiXeR and Mendelian randomization, MR) levels. Then, genome-wide and transcriptome-wide cross-trait/ethnic meta-analyses were performed separately to explore the effective shared organs, cells and molecular pathways. Results A weak genome-wide negative genetic correlation between SCZ and T2DM was found for the EUR (rg = − 0.098, P = 0.009) and EAS (rg =- 0.053 and P = 0.032) populations, which showed no significant difference between the EUR and EAS populations (P = 0.22). After Bonferroni correction, the rg remained significant only in the EUR population. Similar results were obtained from analyses at the levels of autosomes, loci and causal variants. 25 independent variants were firstly identified as being responsible for both SCZ and T2DM. The variants associated with the two disorders were significantly correlated to the gene expression profiles in the brain (P = 1.1E-9) and pituitary gland (P = 1.9E-6). Then, 61 protein-coding and non-coding genes were identified as effective genes in the pituitary gland (P

The steering system noise is one of the main noise sources in submarine stealth condition. Combined with the composition of the steering system, the noise source of each component is sorted out systematically, and corresponding vibration and noise reduction design measures are proposed. As the main noise source of the steering system, emphasis is placed on analyzing the noise mechanism of the rudder hydraulic system, which is divided into two categories and six types according to steady state and transient operating conditions. Finally, it is pointed out that the new type electro-hydraulic steering gear, based on direct drive servo control principle, is the future development trend.

Objective:. He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia, and the causative gene locus was mapped to chromosome 10q11.2. The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency. Methods:. Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated. The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants. The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows–Wheeler Aligner software, Sequence Alignment/Map tools and ANNOVAR tool. In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression. R environment was used to conduct t-tests. The study protocol was approved by the Research Ethics Committee of Bio-X Institutes, Shanghai Jiao Tong University (M2011004). Results:. The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1α as the molecular etiology of the disease. The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12, at which time the primary teeth should have been replaced with permanent teeth. Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity. Conclusion:. c.-144 C>A variant of PRKG1α involving odontoclast-associated root resorption is responsible for He-Zhao deficiency, unlike other forms of hypodontia, which typically involve odontoblast dysfunction.

Objective:. The majority of non-small cell lung cancer (NSCLC) cases remain undiagnosed until advanced stages of the disease. Accumulating studies have highlighted the utility of palliative care as an effective treatment option, which relieves patients’ suffering by activating placebo effect in the body. To evaluate the clinical significance of palliative care, data from NSCLC drug-randomized controlled trials (RCTs) were collected and the effects of placebo treatment examined. Methods:. PubMed (MEDLINE), Scopus, Web of Science, and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020. Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included. The quality of included studies was assessed using the Jadad method. Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo, that is, the primary and secondary outcome measures, were subsequently performed using either Bayesian or conventional models. Results:. Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study. Low risk of bias was observed for all five included studies using the Cochrane method. Following placebo treatment, controlled disease rate of 24.1% (95% credible interval [CrI], –0.126–0.609) and dropout rate of 2.1% (95% CrI, 0.007–0.039) were calculated, with a dose reduction rate of 3.0% (95% CrI, 0.017–0.045). Compared with active drug treatment, the placebo treatment group had a risk ratio of 0.81 (95% confidence interval, 0.68-0.97) and 0.85 (95% confidence interval, 0.76–0.96) for the achievement of progression-free survival and overall survival, respectively. Conclusion:. In NSCLC drug RCTs, placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events, although the therapeutic responses could not be precisely determined. The results suggest that under specific circumstances, palliative care which can activate placebo effect may have similar effects as active drugs (such as erlotinib, vandetanib, or pemetrexed) in terms of prolonging survival time.

Establishing a material constitutive model reflecting the mechanical behavior of metal materials in the cutting process is the basis of cutting finite element simulation, and has an important guiding role in accurately describing the cutting thermo-mechanical coupling state variables and further optimizing process parameters. This paper proposes a reverse identification method of material constitutive parameters based on co-simulation. The influence of mass scaling factor, mesh size, and Johnson-Cook (J-C) constitutive parameters on cutting force was analyzed, and orthogonal cutting experiments were carried out for two difficult-to-machine materials, die steel H13 and titanium alloy Ti-6Al-4V. ABAQUS is redeveloped based on Python, and then the J-C constitutive parameters are directly optimized for the first time with the minimum error between the finite element simulation value and the experimental value of the cutting force as the objective function, the least square identification of J-C constitutive parameters based on co-simulation is realized by combining genetic algorithm. The results show that the reasonable setting of mass scaling factor and mesh size can significantly reduce the time of simulation calculation and improve the optimization efficiency of constitutive parameters. The yield stress, hardening coefficient, strain rate coefficient, hardening coefficient and softening coefficient of materials have different effects on cutting force, which is the key to effective inverse identification of constitutive parameters. Compared with different J-C parameters reported in the literature, it is found that the constitutive parameters obtained by inverse identification based on co-simulation are more accurate, and the prediction of residual stress and serrated chip characteristics also has good accuracy. This study provides a reference for the optimization of constitutive parameters, and the research results provide a new scheme for the efficient construction of material mechanical behavior required for cutting finite element simulation.

Abstract Background The purpose of this study was to evaluate the distributions of vaginal microbiome dysbiosis and human papillomavirus (HPV) subtypes in infertile women and explore the correlations of HPV infection and vaginal microbiome dysbiosis with infertility. Methods In total, 1464 women aged 18–50 years were included in this study; 649 participants were included in the infertility group, and 815 participants were included in the normal group. The participants were tested for HPV, and their vaginal microecology was examined. The χ2 test and Spearman regression were used for statistical analysis, and binary logistic regression was performed to identify the risk factors for infertility. Results The patients in the infertility group were younger than those in the normal group, and the proportions of bacterial vaginosis and vaginal imbalance in the infertility group were significantly higher than those in the normal group. The incidence proportions of high-risk HPV types in the infertility group were significantly higher than those in the normal group, and the proportions of high-risk subtytes HPV16, HPV39, HV52, HPV56, and HPV68 were significantly higher in the infertility group than in the normal group. However, there were no significant differences in the incidences of low-risk HPV types. The incidence proportions of vaginal flora imbalance and HPV infection in the infertility group were significantly higher than those in the normal group. HPV16, HPV33, HPV51, HPV52and HPV58 infections were independent risk factors for infertility. Conclusions Vaginal microecological imbalance and HPV infection are directly related to infertility, and precautions should be taken.

The Cryo-EM structures reported in this work reveal how heparin incorporates into α-syn fibril formation to determine fibril polymorphs. This highlights the role of biological polymers in the conformational selection and neuropathological regulation of amyloid fibrils.

The infiltration and cooling effect of lubricant droplets in the cutting zone largely depend on setting minimum quantity lubricant (MQL) system parameters appropriately. The study determines the optimal spray angle and spray distance relying on the geometric position relationship between the nozzle and the overall cutting zone. A numerical model that combines computational fluid dynamics (CFD) and discrete phase model (DPM) is presented to simulate droplet transport process for dynamic milling and one-tooth milling by flow field distribution and droplet characteristics. The influences of different spray distances and spray angles on the infiltration process and cutting tool temperature are analyzed. The experiments aimed at verifying the results of the analysis are conducted by measuring cutting force, cutting temperature, surface roughness, surface microtopography and tool wear. The result indicates that the spray distance has a significant impact on the jet divergence, and insufficient lubrication or excessive lubrication is effectively avoided with the optimal cutting distance. Spraying in the direction of cutting-out promotes the accessibility of the lubricant and greater concentration of droplets in the cutting zone, especially later in the cutting process, which results in increased infiltration, reduced friction, and improved heat dissipation. Moreover, experiments demonstate that the optimal state of jetting in the direction of cutting-out is 46 °C lower than that of dry cutting, the surface roughness is reduced by 19.8%, and the wear amount is reduced by roughly 34%. This study has a better understanding of the setting of spray distance and spray angle in MQL milling and the development of equipment, which provides theoretical guidance for the optimization of MQL system parameters in practical applications.

Abstract Recipients after hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy are at increased risk for unfavorable outcomes after SARS-CoV-2 infection. The efficacy of COVID-19 vaccines remains undetermined in this vulnerable population, we therefore conducted a pooled analysis to evaluate the immune response after vaccination. A total of 46 studies were finally included, comprising 4757 HSCT and 174 CAR-T recipients. Our results indicated that HSCT and CAR-T recipients had an attenuated immune response to SARS-CoV-2 vaccination compared with healthy individuals, while time interval between transplant and vaccination, immunosuppressive therapy (IST) and lymphocyte counts at vaccination significantly affected the humoral response in HSCT recipients. In addition, seroconversion was significantly higher in patients with BCMA-based CAR-T than those with CD19-based CAR-T. Thus, an adapted vaccination strategy for HSCT and CAR-T recipients may be required, and further research on the effect of a booster dose of COVID-19 vaccine and the role of cellular response after vaccination is warranted.

Abstract Due to quick response and large quantity of electric motor torque, the traction wheels of battery electric vehicle are easy to slip during the initial phase of starting. In this paper, a sliding mode control approach of acceleration slip regulation is designed to prevent the slip of the traction wheels. The wheel slip ratio is used as the state variable for the formulation of system dynamics model. The fuzzy algorithm is utilized to adjust the switch function of sliding mode controller. After stability and robustness analysis, the sliding mode control law is transferred into C code and downloaded into vehicle control unit, which is validated under wet and dry road conditions. The experimental results with a small overshoot and a quick response during starting indicate that the sliding mode controller has good control effect on the slip ratio regulation. This article proposes an acceleration slip regulation method that improves the safety during acceleration for battery electric vehicle.

Abstract. Vaccines are one of the biggest successes in modern history and are particularly important in light of the multiple ongoing epidemics. Recently, vaccines have protected peoples’ health and lives around the world during the coronavirus disease 2019 pandemic. Different types of vaccines have their own characteristics and advantages and are used in the context of different epidemics. Responses to vaccination are also different, and can include adverse reactions and absent responses. These individual differences are thought to be influenced by host genes. In this review, we first discuss vaccine types and characteristics. Second, we discuss different responses to vaccination, primarily focusing on the association between genetic variation and inter-individual differences.

Background: Eponyms are ubiquitous in dermatology; however, their usage trends have not been studied. Objective: To characterize the usage of eponyms in dermatology from 1880 to 2020. Methods: Candidate eponyms were collected from a textbook and an online resource. A subset of these eponyms was deemed to be dermatology-focused by a panel of experienced dermatologists. Python scripts were used to permute eponyms into multiple variations and automatically search PubMed using BioPython’s Entrez library. Results: The dermatologist panel designated 373 of 529 candidate eponyms as dermatology-focused. These eponyms were permuted into 3159 variations and searched in PubMed. The highest occurring dermatology-focused eponyms (DFEs) in the year 2020 included Leishmania, Behçet syndrome, Kaposi sarcoma, Langerhans cell histiocytosis, and Mohs surgery. Increased DFE usage in the general medical literature parallels the overall increase in the use of other eponyms in the medical literature. However, in the most cited dermatology journals, DFE usage did not increase in the past decade. There were several eponyms with decreased usage. Limitations: This study is limited to the publications in PubMed; only titles and abstracts could be queried. Conclusion: DFEs are increasing in usage in the general medical literature, but the usage of eponyms in the most cited dermatology journals has plateaued.

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children.MethodsSix candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA.ResultsThe frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P

Lipopeptide-19, a HIV fusion inhibitor (LP-19), has showed potent anti-HIV activity. However, there is still limited information of the antiviral activity against different subtype clinical isolates and the drug resistance barrier of LP-19. Therefore, 47 HIV clinical isolates were selected for this study. The viral features were identified, in which 43 strains are CCR5 tropisms, and 4 strains are CCR5/CXCR4 tropisms, and there are 6 subtype B’, 15 CRF01_AE, 14 CRF07_BC, 2 CRF08_BC and 10 URF strains. These 47 viruses were used to detected and analyze the inhibitory activities of LP-19. The results showed that the average 50% inhibitory concentration (IC50) and 90% inhibitory concentration (IC90) of LP-19 were 0.50 nM and 1.88 nM, respectively. The average IC50 of LP-19 to B’, CRF01_AE, CRF07_BC, CRF08_BC, and URF strains was 0.76 nM, 0.29 nM, 0.38 nM, 0.85 nM, and 0.44 nM, respectively. C34 and Enfuvirtide (T-20), two fusion inhibitors, were compared on the corresponding strains simultaneously. The antiviral activity of LP-19 was 16.7-fold and 86-fold higher than that of C34 and T-20. The antiviral activity of LP-19, C34, and T-20 were further detected and showed IC50 was 0.15 nM, 1.02 nM, and 66.19 nM, respectively. IC50 of LP-19 was about 7-fold and 441-fold higher compared to C34 and T-20 against HIV-1 NL4-3 strains. NL4-3 strains were exposed to increasing concentrations of LP-19 and C34 in MT-2 cell culture. The culture virus was sequenced and analyzed. The results showed that A243V mutation site identified at weeks 28, 32, 38, and 39 of the cell culture in the gp41 CP (cytoplasmic domain) region. NL4-3/A243V viruses containing A243V mutation were constructed. Comparing the antiviral activities of LP-19 against HIV NL4-3 to HIV strains (only 1.3-fold), HIV did not show drug resistance when LP-19 reached 512-fold of the initial concentration under the drug pressure for 39 weeks. This study suggests that LP-19 has broad-spectrum anti-HIV activity, and high drug resistance barrier.

The abundant unconventional oil ores (about 70% of total world oil) are playing an increasingly important role in global energy supply. To obtain asphalt in unconventional oil ores, different methods, including hot water-based extraction, pyrolysis and solvent extraction, were used to recover asphalt from oil ores (i.e., Canadian, Indonesian, and Iranian oil ores). It is found that asphalt recovery obtained by solvent extraction is the highest. Multi-staged single solvent extraction was used to recover asphalt from oil ores (i.e., toluene, tetrahydrofuran: THF, xylene, petroleum: PE, ethanol), resulting in a cumulative asphalt recovery over 98% at ambient conditions by using toluene. Take Iranian oil ores with the highest oil content (83.79 wt%) as an example, great asphalt recovery was obtained by using multi-staged composite solvents extraction (i.e., toluene@xylene, toluene@THF, toluene@PE, toluene@ethanol). It is also found that introduction of toluene in the composite solvents can significantly increase the ability of single solvent’s (xylene, THF, PE and ethanol) asphalt recovery. After solvent extraction, the solvent recovery was more than 95%. This finds suggest that solvent extraction method would be potential choice to recover asphalt from unconventional oil ores, and it possesses great prospect of industrial application in the future.

IntroductionThe application of phosphorus (P) fertilizer can promote photosynthesis in forage grasses and accelerate their establishment.MethodsTo improve the utilization efficiency of P fertilizer for bluegrass (Poa L.) in alpine regions, the effects of P fertilizer on their growth, and carbon (C), nitrogen (N) and P distribution in their different organs of them are tested at six P fertilization levels (3, 6, 9, 12, 15, 18 g·m−2).Results(1) The nutrient content in each organ of bluegrass varies during different growth stages, with the lowest nutrient content occurring in the wilt stage. (2) The response of the nutrient content and ratio of each organ of bluegrass to different P fertilization levels varies. When the P application rate was 15 g·m−2, the contents of N and P in roots were the highest, and their C/N and C/P ratios were the lowest. When the P application rate was 12 g·m−2, the contents of N and P in the stems were the highest, and their C/N and C/P ratios were the lowest. When the P application rate was 9 g·m−2, the contents of N and P in leaves were the highest, and their C/N and C/P ratios were the lowest. When the P application rate was 6 g·m−2 the contents of N and P in the panicle were the highest, and their C/N and C/P ratios were the lowest.DiscussionThese results provide a better understanding of the effect of P fertilization in the nutrient partitioning pattern of perennial forage plant organs in alpine regions. The information from this study can support a more reasonable P fertilization for the establishment of early grassland. For example, in artificial forage grassland, the application of low-concentration P fertilizer (6~9 g·m−2) can promote the nutrient content in spikes and stems of forage grass; for ecological management, the application of high-concentration P fertilizer (15 g·m−2) can promote the nutrient content in roots and enhance the ecological benefits of forage grassland.

BackgroundPrevious research has linked polymorphisms in the SIRT1 gene to depressive symptoms, particularly in Chinese individuals. However, it is not clear how personality traits may contribute to this association.MethodsTo explore the potential mediating effect of personality traits, we utilized a mediation model to examine the relationship between the SIRT1 rs12415800 polymorphism and depressive symptoms in 787 Chinese college students. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, while personality traits were measured using the Big Five Inventory (BFI).ResultsOur analysis indicated a significant association between the SIRT1 rs12415800 polymorphism and depressive symptoms, with this relationship partially mediated by the personality traits of neuroticism and conscientiousness. Specifically, individuals who were heterozygous for the rs12415800 polymorphism and had higher levels of conscientiousness were less likely to experience depressive symptoms. Conversely, those who were homozygous for the rs12415800 polymorphism and had higher levels of neuroticism were more likely to experience depressive symptoms.ConclusionOur results suggest that personality traits, particularly neuroticism and conscientiousness, may play a critical role in the association between the SIRT1 rs12415800 polymorphism and depressive symptoms among Chinese college students. These findings highlight the importance of considering both genetic factors and personality traits when exploring the etiology of depressive symptoms in this population.

Summary: N6-methyladenosine (m6A) modification controls cell fate determination. Here, we show that liquid-liquid phase separation (LLPS) of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a pivotal m6A “reader” protein, promotes the transdifferentiation of spermatogonial stem cells (SSCs) into neural stem cell-like cells by activating the IκB-nuclear factor κB (NF-κB)-CCND1 axis. The inhibition of IκBα/β mRNA translation mediated by YTHDF1 LLPS is the key to the activation of the IκB-NF-κB-CCND1 axis. Disrupting either YTHDF1 LLPS or NF-κB activation inhibits transdifferentiation efficiency. Moreover, overexpression of the YTH domain of YTHDF1 inhibits the activation of the IκB-NF-κB-CCND1 axis by promoting IκBα/β mRNA translation. Overexpression of the tau-YTH fusion protein reactivates IκB-NF-κB-CCND1 axis by inhibiting the translation of IκBα/β mRNAs, and tau LLPS is observed, which can restore transdifferentiation efficiency. Our findings demonstrate that the protein-RNA LLPS plays essential roles in cell fate transition and provide insights into translational medicine and the therapy of neurological diseases.

BackgroundThe creation of an atrial shunt is a novel approach for the management of heart failure (HF), and there is a need for advanced methods for detection of cardiac function response to an interatrial shunt device. Ventricular longitudinal strain is a more sensitive marker of cardiac function than conventional echocardiographic parameters, but data on the value of longitudinal strain as a predictor of improvement in cardiac function after implantation of an interatrial shunt device are scarce. We aimed to investigate the exploratory efficacy of the D-Shant device for interatrial shunting in treating heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), and to explore the predictive value of biventricular longitudinal strain for functional improvement in such patients.MethodsA total of 34 patients were enrolled (25 with HFrEF and 9 with HFpEF). All patients underwent conventional echocardiography and two-dimensional speckle tracking echocardiogram (2D-STE) at baseline and 6 months after implantation of a D-Shant device (WeiKe Medical Inc., WuHan, CN). Left ventricular global longitudinal strain (LVGLS) and right ventricular free wall longitudinal strain (RVFWLS) were evaluated by 2D-STE.ResultsThe D-Shant device was successfully implanted in all cases without periprocedural mortality. At 6-month follow-up, an improvement in New York Heart Association (NYHA) functional class was observed in 20 of 28 patients with HF. Compared with baseline, patients with HFrEF showed significant reduced left atrial volume index (LAVI) and increased right atrial (RA) dimensions, as well as improved LVGLS and RVFWLS, at 6-month follow-up. Despite reduction in LAVI and increase in RA dimensions, improvements in biventricular longitudinal strain did not occur in HFpEF patients. Multivariate logistic regression demonstrated that LVGLS [odds ratio (OR): 5.930; 95% CI: 1.463–24.038; P = 0.013] and RVFWLS (OR: 4.852; 95% CI: 1.372–17.159; P = 0.014) were predictive of improvement in NYHA functional class after D-Shant device implantation.ConclusionImprovements in clinical and functional status are observed in patients with HF 6 months after implantation of a D-Shant device. Preoperative biventricular longitudinal strain is predictive of improvement in NYHA functional class and may be helpful to identify patients who will experience better outcomes following implantation of an interatrial shunt device.

A precise transfer matrix was employed to analyze the free vibration characteristics of a cord-reinforced air spring with winding formation under preload conditions. The air spring was abstracted as a rotary combined shell structure with variable winding trajectory characteristics. The rotary structure, which consisted of cylindrical and toroidal shells, was analyzed for its shell pre-stress under preload conditions. The shell pre-stress was combined with the theory of thin shells to create the rotary shell vibration control equations under preload effect. The Helmholtz equation was used to analyze the influence of sound pressure inside shells under the fluid–structure coupling boundary conditions. The rotary shell transfer matrix was derived from the variable winding trajectory equation, geometrical equation, and physical equation of shells. Under the continuous conditions of state vector between the cylindrical and toroidal shells, the shells were combined into a rotary combined shell structure to obtain its total free vibration equation. The shell boundary conditions were considered to solve the natural frequency of the air spring. The calculation results were compared with the prototype test and simulation results to verify the effectiveness and accuracy of the theoretical model. On this basis, we explored the influence of axial half wave number, circumferential wave number, geometrical structure, and material characteristics on the free vibration characteristics of the air spring. The research findings would provide important and significant guidance for the structural design of cord-reinforced air springs with winding formation.

BackgroundThe non-invasive cerebellar stimulation (NICS) is a neural modulation technique, which shows the therapeutic and diagnostic potentials for rehabilitating brain functions in neurological or psychiatric diseases. There is a rapid growth in the clinical research related to NICS in recent years. Hence, we applied a bibliometric approach to analyze the current status, the hot spots, and the trends of NICS visually and systematically.MethodsWe searched the NICS publications from the Web of Science (Wos) between 1995 and 2021. Both VOSviewer (1.6.18) and Citespace (Version 6.1.2) software were used to generate the co-occurrence or co-cited network maps about the authors, institutions, countries, journals, and keywords.ResultsA total of 710 articles were identified in accordance with our inclusion criteria. The linear regression analysis shows a statistical increase in the number of publications per year on NICS research over time (p < 0.001). The Italy and University College London ranked the first in this field with 182 and 33 publications, respectively. Koch, Giacomo was the most prolific author (36 papers). The journal of Cerebellum, Brain stimulation and Clinical neurophysiology were the most three productive journals to publish NICS-related articles.ConclusionOur findings provide the useful information regarding to the global trends and frontiers in NICS field. Hot topic was focused on the interaction between the transcranial direct current stimulation and functional connectivity in the brain. It could guide the future research and clinical application of NICS.

Staphylococcus aureus (SA) is representative of gram-positive bacteria. Sanguinarine chloride hydrate (SGCH) is the hydrochloride form of sanguinarine (SG), one of the main extracts of Macleaya cordata (M. cordata). There are few reports on its antibacterial mechanism against SA. Therefore, in this study, we investigated the in vitro antibacterial activity and mechanism of SGCH against SA. The inhibitory zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were measured, and the bactericidal activity curve was plotted. In addition, the micromorphology, alkaline phosphatase (AKP) activity, Na+K+, Ca2+Mg2+-adenosine triphosphate (ATP) activity, intracellular reactive oxygen species (ROS), and fluorescein diacetate (FDA) were observed and detected. The results showed that the inhibitory zone of SGCH against SA was judged as medium-sensitive; the MIC and MBC were 128 and 256 μg/mL, respectively; in the bactericidal activity curve, SGCH with 8 × MIC could completely kill SA within 24 h. SGCH was able to interfere with the integrity and permeability of the SA cell wall and membrane, as confirmed by the scanning electron microscopy (SEM) images, the increase in extracellular AKP and Na+ K+, Ca2+ Mg2+-ATP activities as well as the fluorescein diacetate (FDA) staining experiment results. Moreover, a high concentration of SGCH could induce SA to produce large amounts of ROS. In summary, these findings revealed that SGCH has a preferable antibacterial effect on SA, providing an experimental and theoretical basis for using SG as an antibiotic substitute in animal husbandry and for the clinical control and treatment of diseases caused by SA.