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Abstract Although global vaccination campaigns alleviated the SARS-CoV-2 pandemic in terms of morbidity and mortality, the ability of the virus to originate mutants may reduce the efficacy of vaccines, posing a serious risk of a renewed pandemic. There is therefore a need to develop small molecules capable of targeting conserved viral targets, such as the main protease (Mpro). Here, a series of benzisoselenazolones and diselenides were tested for their ability to inhibit Mpro; then the most potent compounds were measured for antiviral activity in vitro, and the mechanism of action was investigated. Density functional theory calculations, molecular docking and molecular dynamics simulations were also used to elucidate the protein/drug interaction. Finally, a bio-organic model was established to study the reaction between selenorganic compounds and biologically relevant thiols to unveil possible metabolic pathways of such compounds. The overall results contribute to the identification of a series of novel Se-containing molecules active against SARS-CoV-2 and to the clarification of some important aspects in the mechanisms of action of such inhibitors targeting SARS-CoV-2 Mpro.

Abstract Material production and construction activities are key contributors to global carbon footprints, necessitating sustainable alternatives. This study aims to investigate the potential of integrating recycled materials as Supplementary Cementitious Materials (SCMs) in concrete production to mitigate the substantial carbon emissions of Singapore’s building and construction sector. The research focuses on Ground Granulated Blast-furnace Slag (GGBFS), waste glass powder, and calcined marine clay as alternative SCMs, aiming to reduce environmental impact and waste disposal emissions in Singapore. Employing a cradle-to-gate Life Cycle Assessment (LCA) methodology for 1 m3 of concrete with different grades, this study quantifies embodied carbon savings and assesses the feasibility of substituting these SCMs in concrete. The results reveal that substituting Ordinary Portland Cement (OPC) with GGBFS in concrete offers the most significant reduction, up to 56%, in 1 m3 of concrete. In contrast, the use of calcined marine clay and glass powder in concrete results in reductions of up to 21% and 16%, respectively. Two case studies were used to exemplify the impact of using SCM concrete at the project scale. Results indicate that up to 31% of the total embodied carbon could be saved in the building. Additionally, scenario analysis suggests that the total emissions from cementitious materials in Singapore could decrease by 20% through the incorporation of locally recycled marine clay and glass powder. This reduction could potentially reach 56% if the GGBFS supply is not constrained. To further enhance sustainability in Singapore’s construction sector, the study proposes sourcing GGBFS from neighboring countries to minimize transportation emissions and localizing the production and usage of calcined marine clay and glass powder. These measures can improve material circularity and significantly contribute to achieving carbon reduction targets.

Lung cancer remains as the leading cause of cancer-related fatalities globally, posing significant challenges to conventional treatment methods, particularly in advanced stages where limitations and adverse effects are prevalent. Nanotechnology offers promising solutions to enhance lung cancer therapy. Inorganic nanomaterials, such as metal nanoparticles, rare earth elements, and carbonaceous materials, exhibit unique properties that can address these challenges. Metal nanoparticles facilitate targeted drug delivery, biosensing, and imaging, while rare earth elements demonstrate selective cytotoxic effects and imaging capabilities. Carbonaceous materials find applications in biosensing and drug delivery, including carbon ion radiotherapy. These advancements in inorganic nanomaterials present an opportunity to revolutionize lung cancer treatment, potentially leading to improved outcomes and better patient well-being. This paper focuses on recent progress in utilizing inorganic nanomaterials for treating lung cancer, aiming to provide a clearer understanding of their benefits compared to conventional treatments, along with an in-depth examination of their associated limitations and adverse effects.

BackgroundSimple obesity has become an increasingly prevalent health concern among college students. Existing research indicates that traditional exercise methods may not sufficiently engage this population, particularly those facing barriers to regular physical activity. Thus, this study investigated how combining VR cycling with music influenced fat reduction in this population.MethodThis study recruited 78 Chinese college students with simple obesity (BMI ≥ 28 kg/m2) and randomly assigned them to either an experimental group (VR cycling combined with music, n = 41) or a control group (traditional cycling, n = 37). Both groups engaged in 12 weeks of cycling training, three times a week, for 45 min per session. Key physiological indicators, such as weight, BMI, waist circumference, and hip circumference, were measured at baseline, mid-intervention, and post-intervention.ResultsThe VR cycling with music group exhibited significant improvements in key physiological metrics compared to the control group. Notable changes included a 4.1% reduction in weight, a 2.8% decrease in BMI, and a 2.8% reduction in waist circumference. Hip circumference also decreased by 2.5%, while the waist-to-hip ratio dropped by 0.016 units. Furthermore, the intervention led to a 7.2% increase in vital capacity, with all outcomes showing statistical significance (p

BackgroundGlobally, there is an increasing trend in the incidence of premature births and low birth weight. Neonatal intensive care unit (NICU) care has become indispensable for these newborns. Nevertheless, this mode of care poses substantial economic, psychological, and health challenges to the families of preterm infants. Despite abundant evidence concerning the parents’ needs in the NICU, the needs of grandparents—vital family members—are frequently disregarded. This exploratory study aimed to assess the grandparents’ needs of preterm infants in the NICU, exploring the impact of demographic elements on these needs to offer guidance for clinical care practices.MethodsThis study employed a cross-sectional design and the Chinese version of the NICU Family Needs Inventory (NICU-FNI) to investigate the needs of grandparents. A total of 280 grandparents participated in the study, providing data by completing structured questionnaires related to their demographic profiles and needs. Statistical analyses were utilized to analyze the data, including descriptive statistics, chi-square tests, Pearson’s correlation, and multiple linear regression.ResultsSix items about Assurance emerged as significant among the top 10 important needs, with two items for Information, one for Proximity, and one for Support; among the least important needs, nine items related to Comfort and Support were identified. The subscale “Assurance” achieved the highest mean score of 4.07 ± 0.49, followed by the subscales of “Information” and “Proximity,” registering mean scores of 3.50 ± 0.47 and 3.50 ± 0.46, respectively. This explorative study identified a correlation between the needs for Assurance and employment status, place of residence, gestational age, and birth weight (p

Background: Glaucoma is a leading cause of blindness strongly associated with psychiatric disorders, but the causal association between glaucoma and psychiatric disorders remains uncertain because of the susceptibility of observational studies to confounding and reverse causation. This study aims to explore the potential causal association between glaucoma and three highly related psychiatric disorders (Depression, Insomnia, and Schizophrenia) in the European and East Asian populations using a two-sample Mendelian randomization analysis.Methods: Instrumental variables (IVs) of depression, insomnia, and schizophrenia in the European population were obtained after strict filtering. Summary-level data for glaucoma and glaucoma subtypes (primary open-angle glaucoma and primary closed-angle glaucoma) were obtained as outcomes. The inverse variance weighting (IVW) method was used as the primary method. Additionally, the causal effect was evaluated in the East Asian population using the same methods to validate analysis results. The robustness of these results was confirmed using heterogeneity, pleiotropy, and Steiger directionality test.Results: The primary MR results indicated that genetically driven psychiatric disorders were not causally associated with glaucoma (Depression: odds ratio (OR): 1.15, 95% confidence interval (CI): 0.93–1.42, p = 0.20; Insomnia: OR: 1.14, 95% CI: 0.63–2.05, p = 0.66; Schizophrenia: OR: 1.00, 95% CI: 0.93–1.08, p = 0.95), either with the risk of glaucoma subtypes in the European population. Meanwhile, results in the East Asian population were consistent with the results among the European population (Depression: OR = 1.38, CI 0.75–2.53, p = 0.30; Insomnia: OR = 0.99, CI 0.83–1.18, p = 0.93; Schizophrenia: OR = 1.06, CI 0.94–1.20, p = 0.34) with similar causal estimates in direction. Consistency was obtained by corroborating with other supporting methods. Besides, the robustness of the results was proved and the directionality test confirmed our estimation of potential causal direction (p < 0.001).Conclusion: This study found a non-causal association between psychiatric disorders and the risk of glaucoma in the European and East Asian populations, which contradicts many existing observational reports, indicating that increased psychiatric disorders in glaucoma patients were more likely modifiable rather not inheritable.

Abstract Advanced persistent threat (APT) attacks are malicious and targeted forms of cyberattacks that pose significant challenges to the information security of governments and enterprises. Traditional detection methods struggle to extract long-term relationships within these attacks effectively. This paper proposes an APT attack detection model based on graph convolutional neural networks (GCNs) to address this issue. The aim is to detect known attacks based on vulnerabilities and attack contexts. We extract organization-vulnerability relationships from publicly available APT threat intelligence, along with the names and relationships of software security entities from CVE, CWE, and CAPEC, to generate triple data and construct a knowledge graph of APT attack behaviors. This knowledge graph is transformed into a homogeneous graph, and GCNs are employed to process graph features, enabling effective APT attack detection. We evaluate the proposed method on the dataset constructed in this paper. The results show that the detection accuracy of the GCN method reaches 95.9%, improving by approximately 2.1% compared to the GraphSage method. This approach proves to be effective in real-world APT attack detection scenarios.

Bacillus cereus is responsible for 1.4–12% food poisoning outbreaks worldwide. The safety concerns associated with the applications of B. cereus in health and medicine have been controversial due to its dual role as a pathogen for foodborne diseases and a probiotic in humans and animals. In this study, the pathogenicity of B. cereus GW-01 was assessed by comparative genomic, and transcriptome analysis. Phylogenetic analysis based on a single-copy gene showed clustering of the strain GW-01, and 54 B. cereus strains from the NCBI were classified into six major groups (I–VI), which were then associated with the source region and sequence types (STs). Transcriptome results indicated that the expression of most genes related with toxins secretion in GW-01 was downregulated compared to that in the lag phase. Overall, these findings suggest that GW-01 is not directly associated with pathogenic Bacillus cereus and highlight an insightful strategy for assessing the safety of novel B. cereus strains.

Abstract Locomotor activities can enhance learning, but the underlying circuit and synaptic mechanisms are largely unknown. Here we show that locomotion facilitates aversive olfactory learning in C. elegans by activating mechanoreceptors in motor neurons, and transmitting the proprioceptive information thus generated to locomotion interneurons through antidromic-rectifying gap junctions. The proprioceptive information serves to regulate experience-dependent activities and functional coupling of interneurons that process olfactory sensory information to produce the learning behavior. Genetic destruction of either the mechanoreceptors in motor neurons, the rectifying gap junctions between the motor neurons and locomotion interneurons, or specific inhibitory synapses among the interneurons impairs the aversive olfactory learning. We have thus uncovered an unexpected role of proprioception in a specific learning behavior as well as the circuit, synaptic, and gene bases for this function.

Abstract Glycyrrhiza polysaccharide (GCP) is a natural plant active polysaccharide extracted from traditional Chinese medicine licorice. In this research, we studied the antiviral activity of glycyrrhiza polysaccharide against porcine reproductive and respiratory syndrome virus (PRRSV), a virus of the Arteriviridae family, with a high rate of variation and has caused huge economic losses to the pig industry in various countries since its discovery. Our results show that GCP can inhibit PRRSV replication in a dose-dependent manner. Furthermore, GCP could inhibit the mRNA expression of receptor genes CD163 and NF-κB p65 and promote the mRNA expression of the SLA-7 gene. Because of these results, GCP can be used as a candidate drug to prevent and treat PRRS.

Abstract Objective To investigate the risk factors of left ventricular diastolic dysfunction in maintenance hemodialysis (MHD) patients. Method We retrospectively collected data from 363 hemodialysis patients who were on dialysis for at least 3 months at January 1, 2020. According to the echocardiogram results, these patients were divided into left ventricular diastolic dysfunction (LVDD) group and non-LVDD group. The differences in basic data, cardiac structure and functiona between the two groups were analyzed. Logistic regression analysis was used to analyze the risk factors of cardiac diastolic dysfunction in MHD patients. Results Compared with the non-LVDD group, patients in the LVDD group were older, with an increased proportion of coronary heart disease, more prone to chest tightness, shortness of breath. Simultaneously, they had a significantly increased (p

BackgroundBy comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized.MethodsFrom January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed.ResultsThere were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group.ConclusionThe lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

Background: The tuberculin-purified protein derivative (PPD) test is commonly used as a screening tool for tuberculosis (TB). However, the traditional judgment standard of the PPD test is influenced by subjective factors, which can lead to less accurate and intuitive test results. Objectives: To evaluate the accuracy of ultrasonography as a novel auxiliary judgment method for the tuberculin-PPD test and its clinical application. Design: This study was designed as a comparative study following the STROBE guidance. Methods: From February to May 2022, 208 patients with active tuberculosis infection were enrolled. Manual judgment and ultrasonography were employed in a double-blind-utilized manner, and the PPD examination results were recorded. Kappa statistic was performed to measure the concordance between the two diagnostic methods. Fisher’s exact test was used for the analyses of the PPD test results of all 208 active tuberculosis infection patients’ PPD results. Results: There was a significant difference between the two methods in the PPD result judgment ( p

Cell type epigenetic and topographic information of primate brain is lacking. Here, authors identified transcriptional regulatory network, gradient expression pattern and disease vulnerability at cell type level in PFC, M1 and V1 of monkey brain by snRNAseq, snATAC-seq and Stereo-seq.

Summary: Obesity and type 2 diabetes (T2D) remain major global healthcare challenges, and developing therapeutics necessitates using nonhuman primate models. Here, we present a transcriptomic and proteomic atlas of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues such as the liver and kidney. Immune-response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Moreover, we highlight some potential therapeutic targets, including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our study provides a resource for exploring the complex molecular mechanism of obesity and T2D and developing therapies for these diseases, with limitations including lack of hypothalamus, isolated islets of Langerhans, longitudinal data, and body fat percentage.

Noble metal-free electrocatalysts have received widespread attention in a hydrogen evolution reaction (HER) due to the importance of renewable energy development. Herein, a Co2P/CoP heterojunction embedded on an N-doped carbon (Co2P/CoP/NC) electrocatalyst was prepared via an in situ pyrolysis method. The as-prepared electrocatalyst exhibited efficient electrocatalytic activity for HER in an acidic solution. The Co2P/CoP/NC catalyst displayed an overpotential of 184 mV at 10 mA cm−2 and a low Tafel slope of 82 mV dec−1, which could be attributed to the tight Co2P/CoP heterojunction and the synergetic effect of Co2P/CoP and N-doped carbon. In addition, the electrochemical active surface area of Co2P/CoP/NC was 75.2 m2 g−1, which indicated that more active regions can be applied for the HER process. This report may pave a new way for the design of efficient and low-cost N-doped-carbon-supported 3d transition metal phosphide electrocatalysts.

BackgroundIncreased rates of methicillin-resistant Staphylococcus aureus (MRSA) antibiotic resistance and the associated morbidity have increased dermatologists' attention to skin and soft tissue MRSA infections. However, the clinical characterization of MRSA skin and soft tissue infections (SSTIs) in Southwest China is lacking, which precludes optimal prevention and treatment of these infections.ObjectivesThis study was conducted to characterize the prevalence, clinical comorbidities and antibiotic susceptibility of MRSA isolates from SSTIs, including community-associated (CA) and healthcare-associated (HA) isolates.MethodsIn the Dermatology Inpatient Department of the First Affiliated Hospital of Guangxi Medical University, a retrospective study was conducted on data, including patient demographics and clinical information, from culture-confirmed S. aureus isolated from skin and soft tissue between January 1, 2015, and December 31, 2021. Isolate susceptibility to 13 antibiotics was determined using the Vitek 2 system.ResultsFrom among 864 S. aureus strains, we identified 283 MRSA (32.75%) isolates comprising 203 CA-MRSA and 80 HA-MRSA isolates. The average rate of CA-MRSA isolation for MRSA SSTIs was 71.73%. The HA-MRSA isolation rate for MRSA SSTIs increased significantly. HA-MRSA-infected patients were older. The most common dermatological presentation of CA-MRSA infection was staphylococcal scalded skin syndrome, while the comorbidity severe drug eruption was significantly associated with HA-MRSA infection. One CA-MRSA strain was resistant to linezolid, and one HA-MRSA strain had an intermediate phenotype for vancomycin; both strains had low sensitivity to clindamycin and erythromycin (3.70%~19.40%). However, HA-MRSA isolates were more susceptible to trimethoprim/sulfamethoxazole.ConclusionsCA-MRSA is a predominant pathogen causing SSTIs, and HA-MRSA infection incidence is increasing gradually. Both strains showed increasing antibiotic resistance. Our data on MRSA susceptibility may guide dermatologist antibiotic treatment decisions. Dermatologists should consider these identified comorbidities of MRSA SSTIs when patients are admitted and initiate early prevention and treatment of MRSA.

Ex vivo-expanded mesenchymal stem cells (MSCs) have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative, multipotential, and immunomodulatory capacities. However, the exact characteristics of MSCs remain largely unknown. By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton’s jelly, we revealed five distinct subpopulations. The developmental trajectory of these five MSC subpopulations was mapped, revealing a differentiation path from stem-like active proliferative cells (APCs) to multipotent progenitor cells, followed by branching into two paths: 1) unipotent preadipocytes or 2) bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondrocytes. The stem-like APCs, expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES, uniquely exhibited strong proliferation and stemness signatures. Remarkably, the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3+ T cell proliferation in vitro, supporting the role of this population in immunoregulation. In summary, our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation. Our findings advance the definition of MSCs by identifying the specific functions of their heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of their functional subpopulations.

Background. Asthma is a chronic inflammatory disease with structural changes in the lungs defined as airway remodelling. Mast cell responses are important in asthma as they, upon activation, release mediators inducing bronchoconstriction, inflammatory cell recruitment, and often remodelling of the airways. As guinea pigs exhibit anatomical, physiological, and pharmacological features resembling human airways, including mast cell distribution and mediator release, we evaluated the effect of extracts from two common allergens, house dust mite (HDM) and cat dander (CDE), on histopathological changes and the composition of tryptase- and chymase-positive mast cells in the guinea pig lungs. Methods. Guinea pigs were exposed intranasally to HDM or CDE for 4, 8, and 12 weeks, and airway histology was examined at each time point. Hematoxylin and eosin, Picro-Sirius Red, and Periodic Acid-Schiff staining were performed to evaluate airway inflammation, collagen deposition, and mucus-producing cells. In addition, Astra blue and immunostaining against tryptase and chymase were used to visualize mast cells. Results. Repetitive administration of HDM or CDE led to the accumulation of inflammatory cells into the proximal and distal airways as well as increased airway smooth muscle mass. HDM exposure caused subepithelial collagen deposition and mucus cell hyperplasia at all three time points, whereas CDE exposure only caused these effects at 8 and 12 weeks. Both HDM and CDE induced a substantial increase in mast cells after 8 and 12 weeks of challenges. This increase was primarily due to mast cells expressing tryptase, but not chymase, thus indicating mucosal mast cells. Conclusions. We here show that exposure to HDM and CDE elicits asthma-like histopathology in guinea pigs with infiltration of inflammatory cells, airway remodelling, and accumulation of primarily mucosal mast cells. The results together encourage the use of HDM and CDE allergens for the stimulation of a clinically relevant asthma model in guinea pigs.

Background and objectiveA considerable number of pregnant women who were supplemented with folate and vitamin B12 were selected as major participants in studying the one-carbon metabolic (OCM) pathway. Our study aimed to explore the effects of OCM-related indicators on pregnancy-induced hypertension (PIH) and preeclampsia (PE) in pregnant women with folate and vitamin B12 supplementation.Subjects and methodsA total of 1,178 pregnant women who took multivitamin tablets containing 800 μg folate and 4 μg vitamin B12 daily from 3 months before pregnancy to 3 months after pregnancy were enrolled in this study. These pregnant women were classified into three groups: the normotensive group (n = 1,006), the PIH group (n = 131), and the PE group (n = 41). The information on age, weight, body mass index (BMI), number of embryos, gravidity, parity, and OCM-related indicators (serum level of homocysteine, folate, and vitamin B12; MTHFR C677T genotype) was collected.ResultsThe accuracy of the prediction model based on the screened independent risk factors (hyperhomocysteine, OR = 1.170, 95% CI = 1.061–1.291; high folate status, OR = 1.018, 95% CI = 0.999–1.038; and high BMI, OR = 1.216, 95% CI = 1.140–1.297) for PIH in subjects with MTHFR CC genotype (AUC = 0.802) was obviously higher than that in subjects with MTHFR CT, TT genotype (AUC = 0.684,0.685, respectively) by receiver operating characteristic curve analysis. The homocysteine level of the PIH group was significantly higher than that of the normotensive group only in subjects with the MTHFR CC genotype (p = 0.005). A negative correlation between homocysteine and folate appeared in subjects with MTHFR CT + TT genotype (p = 0.005). A model including multiple embryos, nulliparas, and lower folate could predict the process from PIH to PE (AUC = 0.781, p < 0.0001).ConclusionThe prediction model composed of homocysteine, folate, and BMI for PIH was suitable for subjects with MTHFR CC genotype in pregnant women with supplementation of folate and vitamin B12. Lower folate levels could be an independent risk factor in developing the process from PIH to PE.

BackgroundChildren with autism spectrum disorders (ASDs) suffer from sleep disorders to a considerable degree; however, there is no safe and effective treatment available in clinical practice. The objective of the trial is to assess the clinical effectiveness of auricular plaster therapy (APT) in treating sleep disorders in children with ASD.MethodThis is a single-center, patient-assessor blind, randomized controlled trial. A total of 44 preschool children with sleep disorders with ASD will be included in this study. Eligible participants will be randomly assigned to either the auricular plaster group or the sham auricular plaster group in a 1:1 ratio. Participants in the different groups will receive APT or sham APT, respectively, for a total of 30 sessions over 30 days. The primary outcome includes the Children's Sleep Habits Questionnaire (CSHQ), while secondary outcomes include the Autism Behavior Checklist (ABC) and polysomnography (PSG) for total sleep time, sleep latency, awakening duration, and sleep structures. The CSHQ and ABC will be assessed at baseline, 10, 20, 30, 60, 90, and 120 days after randomization, whereas PSG will be assessed at baseline and 30 days after randomization. The follow-up period will be scheduled to be 60, 90, and 120 days after randomization.DiscussionThe results of this study may provide evidence of the efficacy of APT, as well as offer new alternatives for the treatment of sleep disorders in children with ASD.Trial registrationCHiCTR.org.cn (ChiCTR2100048257). Registered on July 5, 2021.

ObjectiveThis study aimed to investigate the diagnostic efficacy of computed tomography (CT)-guided transthoracic lung core needle biopsy combined with aspiration biopsy and the clinical value of this combined routine microbial detection.Materials and methodsWe retrospectively collected the electronic medical records, CT images, pathology, and other data of 1085 patients with sequential core needle biopsy and aspiration biopsy of the same lung lesion under CT guidance in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to January 2021. GenXpert MTB/RIF detection and BD BACTEC™ Mycobacterium/fungus culture were applied to identifying the microbiological results of these patients. We then compared the positive diagnostic rate, false negative rate, and diagnostic sensitivity rate of three methods including core needle biopsy alone, aspiration biopsy alone, and both core needle biopsy and aspiration biopsy.ResultsThe pathological results of cutting histopathology and aspiration of cell wax were examined for 1085 patients. The diagnostic rates of cutting and aspiration pathology were 90.1% (978/1085) and 86.3% (937/1085), respectively, with no significant difference (P > 0.05). Considering both cutting and aspiration pathologies, the diagnostic rate was significantly improved, up to 98% (1063/1085) (P < 0.001). A total of 803 malignant lesions were finally diagnosed (803/1085, 74.0%). The false negative rate by cutting pathology was 11.8% (95/803), which was significantly lower than that by aspiration biopsy [31.1% (250/803), P < 0.001]. Compared with core needle biopsy alone, the false negative rate of malignant lesions decreased to 5.6% (45/803) (P < 0.05). Next, the aspirates of the malignant lesions highly suspected of corresponding infection were cultured. The results showed that 16 cases (3.1%, 16/511) were infected with Mycobacterium tuberculosis complex, Aspergillus niger, and Acinetobacter baumannii, which required clinical treatment. 803 malignant tumors were excluded and 282 cases of benign lesions were diagnosed, including 232 cases of infectious lesions (82.3%, 232/282). The diagnostic rate of Mycobacterium/fungus culture for infectious lesions by aspiration biopsy (47.4%) was significantly higher than that by lung core needle biopsy (22.8%; P < 0.001). The diagnostic rate of aspiration biopsy combined with core needle biopsy was 56% (130/232). The parallel diagnostic rate of aspirated biopsy for GenXpert detection and Mycobacterium/fungal culture combined with core needle biopsy was 64.7% (150/232), which was significantly higher than that of lung core needle biopsy alone (P < 0.001). Finally, pulmonary tuberculosis was diagnosed in 90 cases (38.8%) of infectious lesions. Compared with the sensitivity of core needle biopsy to detect tuberculosis (27.8%, 25/90), the sensitivity of aspirating biopsy for GenXpert detection and Mycobacterium/fungal culture was significantly higher, at 70% (63/90) and 56.7% (51/90), respectively. Although there was no significant difference in the sensitivity of aspirated biopsy for GenXpert and Mycobacterium/fungal culture to detect pulmonary tuberculosis, the sensitivity was significantly increased to 83.3% (P < 0.05) when the two tests were combined. Moreover, when aspirated biopsies were combined with GenXpert detection, Mycobacterium/fungus culture, and core needle biopsy, the sensitivity was as high as 90% (81/90).ConclusionCT-guided lung aspiration biopsy has a significant supplementary effect on core needle biopsies, which is indispensable in clinical application. Additionally, the combination of aspiration biopsy and core needle biopsy can significantly improve the diagnostic rate of benign and malignant lesions. Aspiration biopsy showed that pulmonary malignant lesions are complicated with pulmonary tuberculosis, aspergillus, and other infections. Finally, the diagnostic ability of lung puncture core needle biopsy and aspiration biopsy combined with routine microbial detection under CT positioning in the diagnosis of pulmonary infectious diseases was significantly improved.

The classical Kalman filter (KF) can estimate the structural state online in real time. However, the classical KF presupposes that external excitations are known. The existing methods of Kalman filter with unknown inputs (KF-UI) have limitations that require observing the acceleration response at the excitation point or assuming the unknown force. To surmount the above defects, an innovative modal Kalman filter with unknown inputs (MKF-UI) is proposed in this paper. Modal transformation and modal truncation are used to reduce the dimensionality of the structural state, and the accelerations at the excitation positions do not need to observe. Besides, the proposed MKF-UI does not require the assumption of unknown external excitation. Therefore, the proposed approach is suitable for the generalized identification of dynamic structural states and unknown loadings. The effectiveness and feasibility of the proposed identification approach are ascertained by some numerical simulation examples.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease caused by the PRRS virus that leads to reproductive disorders and severe dyspnoea in pigs, which has serious economic impacts. One of the reasons PRRSV cannot be effectively controlled is that it has developed countermeasures against the host immune response, allowing it to survive and replicate for long periods. Transcription Factors acts as a bridge in the interactions between the host and PRRSV. PRRSV can create an environment conducive to PRRSV replication through transcription factors acting on miRNAs, inflammatory factors, and immune cells. Conversely, some transcription factors also inhibit PRRSV proliferation in the host. In this review, we systematically described how PRRSV uses host transcription factors such as SP1, CEBPB, STATs, and AP-1 to escape the host immune system. Determining the role of transcription factors in immune evasion and understanding the pathogenesis of PRRSV will help to develop new treatments for PRRSV.

Summary: Hepatocellular carcinoma (HCC) is the most common liver cancer with a high rate of metastasis. However, the molecular mechanisms that drive metastasis remain unclear. We combined single-cell transcriptomic, proteomic, and chromatin accessibility data to investigate how heterogeneous phenotypes contribute to metastatic potential in five HCC cell lines. We confirmed that the prevalence of a mesenchymal state and levels of cell proliferation are linked to the metastatic potential. We also identified a rare hypoxic subtype that has a higher capacity for glycolysis and exhibits dormant, invasive, and malignant characteristics. This subtype has increased metastatic potential. We further identified a robust 14-gene panel representing this hypoxia signature and this hypoxia signature could serve as a prognostic index. Our data provide a valuable data resource, facilitate a deeper understanding of metastatic mechanisms, and may help diagnosis of metastatic potential in individual patients, thus supporting personalized medicine.

This study proposed an extended multi–layer heat transfer model to simulate skin burns of firefighters during firefighting. The proposed model takes into account the effect of fabric movement frequencies, fabric movement amplitudes and human body movement speeds on the heat transfer between the skin and the heat source under low–level radiative exposure. The simulation performance was validated against the simulations in the published literature in terms of the heat transfer in the multi–layer fabric system, skin temperature and skin burns. The results indicated that the fabric periodic movement caused by human body movement decreased the time to skin burns and the skin temperature increased with increasing fabric movement amplitude. During firefighting, the time to 2nd degree burn was 33.3–35.2% shorter at medium human body movement speed than at low and high movement speeds. Furthermore, at low movement speeds, the time to 2nd degree burn was negatively associated with fabric movement amplitude, whereas it was delayed by 12.9–29.8% at the fabric movement amplitude of 2.5 mm at medium and high human body movement speeds. This research provides foundational knowledge for the development of a new generation of firefighters’ protective clothing (FPC) and the assessment of skin burns in firefighters.

Acupuncture treatment is based on acupoint stimulation; however, the biological basis is not understood. We stimulated one acupoint with catgut embedding for 8 weeks and then used isobaric tags for relative and absolute quantitation to screen proteins with altered expression in adjacent acupoints of Sprague Dawley rats. We found that kininogen expression was significantly upregulated in the stimulated and the nonstimulated adjacent acupoints along the same meridian. The enhanced kininogen expression was meridian dependent and was most apparent among small vessels in the subcutaneous layer. Enhanced signals of nitric oxide synthases, cGMP-dependent protein kinase, and myosin light chain were also observed at the nonstimulated adjacent acupoints along the same meridian. These findings uncover biological changes at acupoints and suggest the critical role of the kininogen–nitric oxide signaling pathway in acupoint activation.

The metabolism disorders are a common convergence of Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM). The characteristics of AD are senile plaques and neurofibrillary tangles (NFTs) composed by deposits of amyloid−β (Aβ) and phosphorylated tau, respectively. Advanced glycation end−products (AGEs) are a stable modification of proteins by non−enzymatic reactions, which could result in the protein dysfunction. AGEs are associated with some disease developments, such as diabetes mellitus and AD, but the effects of the glycated γ2 subunit of AMPK on its activity and the roles in AD onset are unknown. Methods: We studied the effect of glycated γ2 subunit of AMPK on its activity in N2a cells. In 3 × Tg mice, we administrated L−arginine once every two days for 45 days and evaluated the glycation level of γ2 subunit and function of AMPK and alternation of pathologies. Results: The glycation level of γ2 subunit was significantly elevated in 3 × Tg mice as compared with control mice, meanwhile, the level of pT172−AMPK was obviously lower in 3 × Tg mice than that in control mice. Moreover, we found that arginine protects the γ2 subunit of AMPK from glycation, preserves AMPK function, and improves pathologies and cognitive deficits in 3 × Tg mice. Conclusions: Arginine treatment decreases glycated γ2 subunit of AMPK and increases p−AMPK levels in 3 × Tg mice, suggesting that reduced glycation of the γ2 subunit could ameliorate AMPK function and become a new target for AD therapy in the future.

Abstract Exploring earth-abundant and noble metal-free catalysts for water electrolysis is pivotal in renewable hydrogen production. Herein, a highly active electrocatalyst of nitrogen-doped porous carbon nanosheets coupled with Mo2C nanoparticles (Mo2C/NPC) was synthesized by a novel method with high BET surface area of 1380 m2 g−1 using KOH to activate carbon composite materials. The KOH plays a key role in etching out MoS2 to produce Mo precursor; simultaneously, it corrodes carbon to form porous structure and produce reducing gas such as H2 and CO. The resulting Mo2C/NPC hybrid demonstrated superior HER activity in acid solution, with the overpotential of 166 mV at current density of 10 mA cm−2, onset overpotential of 93 mV, Tafel slope of 68 mV dec−1, and remarkable long-term cycling stability. The present strategy may provide a promising strategy to fabricate other metal carbide/carbon hybrids for energy conversion and storage.

Abstract Background Gluteal muscle contracture (GMC) is a notable problem in some developing countries and includes features such as a snapping sound of the hip, abnormal gait, and unusual posture when patients squat with the knees together. Arthroscopic release can not only resolve symptoms, as previously reported, but can also greatly improve accompanying patellofemoral instability. This study was conducted to evaluate the effect of arthroscopic release of GMC on patellofemoral instability and its underlying mechanism. Methods A total of nearly 500 patients who underwent arthroscopic release of GMC over 2.5 years were filtered, and 54 patients were enrolled in the study. The selected research subjects all had combined patellofemoral instability preoperatively. The Lysholm scores and CT scans of the knee were evaluated pre- and postoperatively. Results The mean follow-up time was 12.2 months. All of the surveyed patients had satisfactory clinical outcomes for hip snapping sounds and abnormal gait. In addition, a significant difference (p

Wind loads on structures are difficult to directly measure, so it is practical to identify structural wind loads based on the measurements of structural responses. However, this inversed problem is challenging compared with conventional load identification as wind loads are time-space coupled and spatially distributed dynamic loads on structures. An improved method is proposed for identifying wind loads on structures using only partial measurements of structural acceleration responses in this paper. First, the wind loads on a structure are decomposed by proper orthogonal decomposition as a series of time-space decoupled sub-distributed dynamic loads with independent basic spatial distribution functions and time history functions. Herein, structural modes are adopted as the basic spatial distribution functions and structural modes of discretized and continuous structural systems are investigated. Then, a history function of the decomposed wind load is identified in the modal domain based on modal Kalman filter with unknown inputs, which is proposed by the authors. Finally, the distributed wind loads are reconstructed for discrete or continuous structural systems. The feasibility of the proposed algorithm is verified by two numerical examples of identification of wind loads on a discrete shear frame and a wind turbine tower, respectively.

Inaccurate mass estimates have been recognized as an important source of uncertainty in structural identification, especially for large-scale structures with old ages. Over the past decades, some identification algorithms for structural states and unknown parameters, including unknown mass, have been proposed by researchers. However, most of these identification algorithms are based on the simplified mechanical model of chain-like structures. For a chain-like structure, the mass matrix and its inverse matrix are diagonal matrices, which simplify the difficulty of identifying the structure with unknown mass. However, a structure with a non-diagonal mass matrix is not of such a simple characteristic. In this paper, an online joint state-parameter identification algorithm based on an Unscented Kalman filter (UKF) is proposed for a structure with a non-diagonal mass matrix under unknown mass using only partial acceleration measurements. The effectiveness of the proposed algorithm is verified by numerical examples of a beam excited by wide-band white noise excitation and a two-story one-span plane frame structure excited by filtered white noise excitation generated according to the Kanai–Tajimi power spectrum. The identification results show that the proposed algorithm can effectively identify the structural state, unknown stiffness, damping and mass parameters of the structures.

An 83-year old Alzheimer's disease (AD) male patient donated his Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system used to reprogram PBMCs with the human OKSM transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency markers and by the ability of the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a normal karyotype. Our model might offer a good platform to further study the pathological mechanisms, to identify early biomarkers, and also for drug testing studies in AD.

A 32-year old Bipolar Disorder (BD) male patient donated his Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system used to reprogram PBMCs with the human OKSM transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency markers and by the ability of the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a normal karyotype. Our model might offer a good platform to further study the pathological mechanisms, to identify early biomarkers, and also for drug testing studies in BD.Resource tableUnlabelled TableUnique stem cell line identifierTUSMi005-AAlternative name(s) of stem cell lineN/AInstitutionTongji University School of Medicine, Shanghai, Peoples R ChinaContact information of distributorYing Wang, wangying_csu@126.comType of cell lineiPSCOriginHumanAdditional origin infoAge: 32Sex: maleEthnicity: Chinese HanCell sourcePeripheral blood mononuclear cells (PBMCs)ClonalityClonalMethod of reprogrammingTransgene free, Episomal plasmidsGenetic modificationNOType of modificationN/AAssociated diseaseBipolar Disorder (BD)Gene/locusSLC1A3/chr 5p13.2: 36679820, rs117588697 A-G,MAPT/chr 17q21.31:44073818, rs577501443 G-A,SIRT1/chr 10q21.3: 67864422, rs12415800 G-AMethod of modificationN/AName of transgene or resistanceN/AInducible/constitutive systemN/ADate archived/stock date08th July,2018Cell line repository/bankhPSCreg, https://hpscreg.eu/user/cellline/edit/TUSMi005-AEthical approvalParticipants informed consent obtained/Ethics Review Board-competent authority approval obtained (EC. D(BG).016.01.1).

Results demonstrated that in meat quail, three genotypes (AA, BB and AB) were detected at locus A and B in MyoG gene. Locus A is significantly correlated with weight and body length of meat quail (P

To distinguish Methicillin-Resistant Staphylococcus aureus (MRSA) from Methicillin-Sensitive Staphylococcus aureus (MSSA) in the protein sequences level, test the susceptibility to antibiotic of all Staphylococcus aureus isolates from Quanzhou hospitals, define the virulence factor and molecular characteristics of the MRSA isolates. MRSA and MSSA Pfam protein sequences were used to extract feature vectors of 188D, n-gram and 400D. Weka software was applied to classify the two Staphylococcus aureus and performance effect was evaluated. Antibiotic susceptibility testing of the 81 Staphylococcus aureus was performed by the Mérieux Microbial Analysis Instrument. The 65 MRSA isolates were characterized by Panton-Valentine leukocidin (PVL), X polymorphic region of Protein A (spa), multilocus sequence typing test (MLST), staphylococcus chromosomal cassette mec (SCCmec) typing. After comparing the results of Weka six classifiers, the highest correctly classified rates were 91.94, 70.16, and 62.90% from 188D, n-gram and 400D, respectively. Antimicrobial susceptibility test of the 81 Staphylococcus aureus: Penicillin-resistant rate was 100%. No resistance to teicoplanin, linezolid, and vancomycin. The resistance rate of the MRSA isolates to clindamycin, erythromycin and tetracycline was higher than that of the MSSAs. Among the 65 MRSA isolates, the positive rate of PVL gene was 47.7% (31/65). Seventeen sequence types (STs) were identified among the 65 isolates, and ST59 was the most prevalent. SCCmec type III and IV were observed at 24.6 and 72.3%, respectively. Two isolates did not be typed. Twenty-one spa types were identified, spa t437 (34/65, 52.3%) was the most predominant type. MRSA major clone type of molecular typing was CC59-ST59-spa t437-IV (28/65, 43.1%). Overall, 188D feature vectors can be applied to successfully distinguish MRSA from MSSA. In Quanzhou, the detection rate of PVL virulence factor was high, suggesting a high pathogenic risk of MRSA infection. The cross-infection of CA-MRSA and HA-MRSA was presented, the molecular characteristics were increasingly blurred, HA-MRSA with typical CA-MRSA molecular characteristics has become an important cause of healthcare-related infections. CC59-ST59-spa t437-IV was the main clone type in Quanzhou, which was rare in other parts of mainland China.

The extended Kalman filter is a useful tool in the research of structural health monitoring and vibration control. However, the traditional extended Kalman filter approach is only applicable when the information of external inputs to structures is available. In recent years, some improved extended Kalman filter methods applied with unknown inputs have been proposed. The authors have proposed an extended Kalman filter with unknown inputs based on data fusion of partially measured displacement and acceleration responses. Compared with previous approaches, the drifts in the estimated structural displacements and unknown external inputs can be avoided. The feasibility of proposed extended Kalman filter with unknown inputs has been demonstrated by some numerical simulation examples. However, experimental validation of the proposed extended Kalman filter with unknown inputs has not been conducted. In this paper, an experiment is conducted to validate the effectiveness of the proposed approach. A five-story shear building model subjected to an unknown external excitation of wide-band white noise is conducted. Moreover, the data fusion of partially measured strain and acceleration responses from the building is adopted as it is difficult to accurately measure structural displacement in practice. Identified results show that the recently proposed extended Kalman filter with unknown inputs can be applied to identify structural parameters, structural states, and the unknown inputs in real time.

Commercial diol chain extenders generally could only form two urethane bonds, while abundant hydrogen bonds were required to construct self-healing thermoplastic polyurethane elastomers (TPU). Herein, two diol chain extenders bis(2-hydroxyethyl) (1,3-pheny-lene-bis-(methylene)) dicarbamate (BDM) and bis(2-hydroxyethyl) (methylenebis(cyclohexane-4,1-diy-l)) dicarbamate (BDH), containing two carbamate groups were successfully synthesized through the ring-opening reaction of ethylene carbonate (EC) with 1,3-benzenedimetha-namine (MX-DA) and 4, 4′-diaminodicyclohexylmethane (HMDA). The two chain extenders were applied to successfully achieve both high strength and high self-healing ability. The BDM-1.7 and BDH-1.7 elastomers had high comprehensive self-healing efficiency (100%, 95%) after heated treatment at 60 °C, and exhibited exceptional comprehensive mechanical performances in tensile strength (20.6 ± 1.3 MPa, 37.1 ± 1.7 MPa), toughness (83.5 ± 2.0 MJ/m3, 118.8 ± 5.1 MJ/m3), puncture resistance (196.0 mJ, 626.0 mJ), and adhesion (4.6 MPa, 4.8 MPa). The peculiar mechanical and self-healing properties of TPUs originated from the coexisting short and long hard segments, strain-induced crystallization (SIC). The two elastomers with excellent properties could be applied to engineering-grade fields such as commercial sealants, adhesives, and so on.

Due to the unpredictability of seismic excitation, the data-driven damage identification method, which only depends on the monitoring response data, has a good development prospect in structural health monitoring. In recent years, damage identification methods based on transmissibility function (TF) and Mahalanobis squared distance (MSD) have been widely studied. However, the existing methods are only applicable to damage warning. To overcome this limitation, an improved method for structural damage localization is proposed. Strain TF is used to eliminate the influence of unknown ambient excitation and unknown seismic excitation, which is more sensitive to local damage than traditional TF based on acceleration and displacement data. The MSD of strain TF is employed to construct a novel damage indicator that is used to identify the damage location. Two numerical simulations have been conducted to verify the feasibility of the method for damage localization and good anti-noise performance. In the case of the multi-damage condition, the novel damage indicator is performed to estimate the severity of damage to some extent.