Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Nitrogen dioxide(NO 2)is a prevalent air pollutant that poses significant threats to the environment and human health,emphasizing the urgent need for high-performance NO 2 sensors for effective environmental monitoring at room temperature.Sensors based on metal halide perovskites have emerged as promising candidates for gas detection at room temperature,but their long-term stability remains a major challenge.In this study,a methylamine thiocyanate(MT)-doped FA 0.8Cs 0.2PbI 2Br(PVK)gas sensor(MT-PVK)was prepared using a simple one-step spin-coating method and ethyl acetate(EA)anti-solvent extraction technique.The crystalline structure,chemical composition,and particle morphology of the MT-PVK thin film were characterized.The MT-PVK thin film was then utilized as a gas sensor for NO 2 detection at room temperature.The results demonstrated that the sensor exhibited outstanding selectivity and reversibility at low concentrations of NO 2 gas,with a detection limit as low as 33 ppb(10-9,nL/L).For 10 ppm(10-6,μL/L)NO 2,the sensor showed rapid response and recovery time of only 1.6 s and 27 s,outperforming most traditional metal oxide NO 2 sensors.Furthermore,compared to the original PVK,the MT molecules significantly enhanced the structural and sensing stability of the MT-PVK sensor under high humidity conditions(55%±5%).These findings suggested that MT-doped FA 0.8Cs 0.2PbI 2Br perovskite gas sensors offered a promising pathway for the development of rapid-response gas sensing technologies suitable for room temperature operation.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

According to the codon characteristics of the prokaryotic system,we synthesized the optimized Rv2628c-Rv1737c nucleic acid sequence and constructed the expression plasmid pET24a-Rv2628c-Rv1737c.After sequencing,expression in E.coli was induced.The fusion protein was found in inclusion bodies.After renaturation and affinity chromatography purifi-cation,the Rv2628c-Rv1737c recombinant protein,with a molecular weight of 57 kDa and a purity exceeding 90％,was ob-tained.The recombinant protein was used to stimulate PBMC cells from different patients,and the differences in IFN-γ mRNA expression were analyzed with q-PCR.The Rv2628c-Rv1737c fusion protein stimulated patients with TB,particularly latent TB infection(LTBI).The level of IFN-γ mRNA in PBMC cells was higher than that in healthy controls(P＜0.05).Mice immu-nized with BCG+Rv2628c-Rv1737c/DMT showed significant induction of high levels of IgG antibodies.Rv2628c-Rv1737c re-combinant protein,as a latent infection antigen,is recognized by PBMCs cells infected with TB,with strong immunogenicity,and thus may serve as a potential TB subunit vaccine target antigen.This protein may be used to prevent TB infection,particu-larly latent infection,and to perform laboratory diagnosis.

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3^rd to May 31^st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Young Adult ; China/epidemiology* ; COVID-19/genetics* ; Nucleic Acids ; Retrospective Studies

OBJECTIVE: To compare the effect of two different arthroscopic procedures, threading lasso fixation and full-thickness conversion, for repairing articular-sided partial-thickness supraspinatus tendon tear. METHODS: From July 2015 to November 2018, 21 patients with articular-sided partial-thickness supraspinatus tendon tears underwent arthroscopic modified threading lasso fixation repair(group A). There were 12 males and 9 females in the group, with an average age of(53.2±6.4)years old. Twenty-four patients with articular-sided partial-thickness supraspinatus tendon tears received arthroscopic full-thickness conversion repair(group B). In this group, there were 14 males and 10 females, with an average age of (55.7±5.2) years old. The American Shoulder and Elbow Surgeons (ASES) score and University of California Los Angeles (UCLA) shoulder score were used to evaluate preoperative and postoperative clinical function. MRI was used to examine the healing status of the reconstructed rotator cuff. RESULTS: All patients were followed up, and the duration ranged from 20 to 27 months, with a mean of (23.7±3.1) months. In threading lasso fixation group, ASES score and UCLA score increased from 50.6±6.4 and 15.6±2.7 preoperatively to 87.3±5.2 and 31.6±2.4 postoperatively. In full-thickness conversion group, ASES score and UCLA score increased from 52.3±5.6 and 16.8±2.4 scores to 90.1±4.8 and 32.1±2.8. There were also no significant differences in ASES score and Constant score between the two groups before and after operation. There were no significant differences in rotator cuff healing between the two groups(χ²=2.374, P=0.128). CONCLUSION For the treatment of articular-sided partial-thickness supraspinatus tendon tears both arthroscopic repairs employing threading lasso fixation and full-thickness conversion could achieve satisfactory clinical results, and there are no significant differences in clinical outcomes between the two techniques. Arthroscopic repair with threading lasso fixation is a novel transtendinous procedure in which integrity of the tendon can be preserved.
Arthroscopy/methods* ; Female ; Humans ; Male ; Middle Aged ; Rotator Cuff ; Rotator Cuff Injuries/surgery* ; Shoulder/surgery* ; Tendons

To provide accurate information for registration and safety evaluation of surgical robot, the pose repeatability measurement method was proposed. According to the terminal instrument of the master-slave surgical robot (such as high-frequency electric knife, ultrasonic knife), a suitable target ball fixture was designed. The node data at 10%, 50% and 100% rated speed were measured respectively. Through data analysis, the pose repeatability property of the tested samples at different speeds was obtained. It has high applicability and repeatability, and can meet the requirements of data traceability and registration testing.
Equipment Design ; Lasers ; Robotic Surgical Procedures ; Robotics ; Surgery, Computer-Assisted

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), which causes great economic losses. At the moment, no effective neutralizing antibody is available for scientific research and treatment. Therefore, developing a method for screening the neutralizing monoclonal antibodies is of great significance for the prevention and treatment of PRRSV and the screening of antigen sites. Monoclonal antibodies have been widely used in the treatment and diagnosis of many human and animal diseases. Therefore, screening effective neutralizing antibodies for different pathogens is an urgent task. Among the methods for monoclonal antibody screening, B cell immortalization is an effective method to obtain neutralizing monoclonal antibody. Specifically, in this study, the bcl-6 and bcl-xl genes were connected by f2a and then the yielded product was ligated to a vector for retrovirus packaging. The swine lymphocytes immunized with PRRSV were infected the yielded mature viruses and cultured in the complete medium containing CD40L and IL21 cytokines. Then, CD21 was used as the marker to screen B cells with the magnetic bead method. Finally, monoclonal B cells were obtained and the secretion of antibodies was tested. The results showed that the plasmid, either being transfected alone or with the packaged plasmids, could be expressed, and that the packaged retrovirus could infect the cells. Moreover, the infected lymphocytes secreted antibodies, so did the screened B cells. Therefore, the method for screening monoclonal antibody against PRRSV was successfully established.
Animals ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Humans ; Porcine Reproductive and Respiratory Syndrome/prevention & control* ; Porcine respiratory and reproductive syndrome virus/genetics* ; Swine