ObjectiveThe study explores the influence of voluntary wheel running on the behavioral abnormalities and the activation state of the hypothalamic-pituitary-adrenal (HPA) axis in autism spectrum disorder (ASD) rats through gut microbiota. MethodsSD female rats were selected and administered either400 mg/kg of valproic acid (VPA) solution or an equivalent volume of saline via intraperitoneal injection on day 12.5 of pregnancy. The resulting offspring were divided into 2 groups: the ASD model group (PASD, n=35) and the normal control group (PCON, n=16). Behavioral assessments, including the three-chamber social test, open field test, and Morris water maze, were conducted on postnatal day 23. After behavioral testing, 8 rats from each group (PCON, PASD) were randomly selected for serum analysis using enzyme-linked immunosorbent assay (ELISA) to measure corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) concentration, to evaluate the functional state of the HPA axis in rats. On postnatal day 28, the remaining 8 rats in the PCON group were designated as the control group (CON, n=8), and the remaining 27 rats in the PASD group were randomly divided into 4 groups: ASD non-intervention group (ASD, n=6), ASD exercise group (ASDE, n=8), ASD fecal microbiota transplantation group (FMT, n=8), and ASD sham fecal microbiota transplantation group (sFMT, n=5). The rats in the ASD group and the CON group were kept under standard conditions, while the rats in the ASDE group performed 6 weeks of voluntary wheel running intervention starting on postnatal day 28. The rats in the FMT group were gavaged daily from postnatal day 42 with 1 ml/100 g fresh fecal suspension from ASDE rats which had undergone exercise for 2 weeks, 5 d per week, continuing for 4 weeks. The sFMT group received an equivalent volume of saline. After the interventions were completed, behavioral assessments and HPA axis markers were measured for all groups. ResultsBefore the intervention, the ASD model group exhibited significantly reduced social ability, social novelty preference, spontaneous activity, and exploratory interest, as well as impaired spatial learning, memory, and navigation abilities compared to the normal control group (P<0.05). Serum concentration of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the PASD group were significantly higher than those in the PCON group (P<0.05). Following 6 weeks of voluntary wheel running, the ASDE group showed significant improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, spatial learning, memory, and navigation skills compared to the ASD group (P<0.05), with a significant decrease in serum CORT concentration (P<0.05), and a downward trend in CRH and ACTH concentration. After 4 weeks of fecal microbiota transplantation in the exercise group, the FMT group showed marked improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, as well as spatial learning, memory, and navigation abilities compared to both the ASD and sFMT groups (P<0.05). In addition, serum ACTH and CORT concentration were significantly reduced (P<0.05), and CRH concentration also showed a decreasing trend. ConclusionExercise may improve ASD-related behaviors by suppressing the activation of the HPA axis, with the gut microbiota likely playing a crucial role in this process.

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

ObjectivesBased on the changes of lung lesions in patients with COVID-19 at different stages， a nomogram model describing CT image features was established by radiomics method to explore its efficacy in predicting the progression of the disease. MethodsThis retrospective study enrolled 136 patients with COVID-19 pneumonia who received at least two CTs including three cohorts （training cohort and validation cohort 1 and 2）. Patients in the training cohort were divided into three groups according to time between onset of fever symptoms and the first CT. The clinical manifestations and CT features of each group were analyzed and compared. A nomogram to predict disease progression was constructed according to the CT features of the patients， and its performance was evaluated. ResultsThe training cohort consisted of 41 patients.A nomogram was generated to predict disease progression based on three CT features： irregular strip shadow， air bronchial sign， and the proportion of lesions with irregular shape ≥50%. AUC（95%CI）=0.906（0.817，0.995）.The C index of the training cohort was 0.906， and the C index of the internal verification was 0.892. AUC（95%CI）of the validation cohort 1 （34 cases） =0.889（0.793，0.984）；AUC（95%CI）of the validation cohort 2 （61 cases）=0.876（0.706，1.000）.The calibration curves show that the predicted values of the nomogram are in good agreement with the observed values. ConclusionThe nomogram model based on CT radiomics can predict the outcome of lung lesions in patients with high sensitivity and specificity.According to the changes of CT image characteristics of patients with COVID-19， lung lesions will be improved when the proportion of irregular cable shadow， air bronchogram and irregular lesions is greater than 50%.

The present study explored the drying effect of new spiral vibration drying technology on Chinese medicinal pills with Liuwei Dihuang Pills, Zhuanggu Guanjie Pills, and Muxiang Shunqi Pills as model drugs. With the drying uniformity, drying time, energy consumption, pill split, dissolution time, and change of index components as evaluation indicators, the drying effect of spiral vibration drying technology on model drugs was evaluated and compared with traditional drying methods, such as hot air drying and vacuum drying in the oven. The dynamic changes of moisture in Liuwei Dihuang Pills with different drying time were investigated. Compared with the traditional drying methods in the oven(hot air drying and vacuum drying) at 80 ℃, the spiral vibration drying only took 80 min, shortened by 80%, with 10%-13% energy consumed. The results showed that the moisture of Liuwei Dihuang Pills was negatively related to the drying time. By virtue of multi-layer countercurrent drying and super resonant fluidization techniques, the new spiral vibration drying technology can significantly improve the drying quality of Chinese medicinal pills, improve the drying efficiency, and enhance the manufacturing capacity of Chinese medicinal pills. This study is expected to provide references for the innovation and development of new drying technology of Chinese medicinal pills.
China ; Desiccation ; Physical Therapy Modalities ; Technology ; Vibration

Objective: This study aimed to assess the technical feasibility, efficacy, and safety of the safe triangular working zone (STWZ) approach applied in percutaneous vertebroplasty (PV) for spinal metastases involving the posterior part of the vertebral body. Materials and Methods: We prospectively enrolled 87 patients who underwent PV for spinal metastasis involving the posterior part of the vertebral body, with or without the STWZ approach, from January 2019 to April 2022. Forty-nine patients (27 females and 22 males; mean age ± standard deviation [SD], 57.2 ± 11.6 years; age range, 31–76 years) were included in group A (with STWZ approach), accounting for 54 vertebrae. Thirty-eight patients (18 females and 20 males; 59.1 ± 10.9 years; 29–81 years) were included in group B (without STWZ approach), accounting for 57 vertebrae. Patient demographics, procedure-related variables, and pain relief as assessed using the visual analog scale (VAS) were collected at different time points. Tumor recurrence in the vertebrae after PV was analyzed using Kaplan–Meier curves. Results: The STWZ approach was successful from T1 to L5 without severe complications. Cement filling was satisfactory in 47/54 (87.0%) and 25/57 (43.9%) vertebrae in groups A and B, respectively (v< 0.001). Cement leakage was not significantly different between groups A and B (p= 1.000). Mean VAS score ± SD before and 1 week and 1, 3, 6, 9, and 12 months after PV were 7.6 ± 1.8, 4.2 ± 2.0, 2.7 ± 1.9, 1.9 ± 1.5, 1.7 ± 1.4, 1.7 ± 1.1, and 1.6 ± 1.3, respectively, in group A and 7.2 ± 1.7, 4.0 ± 1.3, 3.4 ± 1.6, 2.4 ± 1.2, 1.8 ± 1.0, 1.4 ± 0.5, and 1.7 ± 0.9, respectively, in group B. Kaplan–Meier analysis showed a lower tumor recurrence rate in group A than in group B (p = 0.001). Conclusion The STWZ approach may represent a new, safe, alternative/auxiliary approach to target the posterior part of the vertebral body in the PV for spinal metastases.

OBJECTIVE: To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons. METHODS: The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway. RESULTS: MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01). CONCLUSION TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.
Animals ; Beclin-1 ; Brain Ischemia/metabolism* ; Glucose ; Infarction, Middle Cerebral Artery/drug therapy* ; Mammals/metabolism* ; Neuroprotection ; Neuroprotective Agents/therapeutic use* ; Oxygen ; Panax notoginseng ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Reperfusion Injury/metabolism* ; Saponins/therapeutic use* ; TOR Serine-Threonine Kinases/metabolism*

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology* ; Heroin ; Humans ; Illicit Drugs ; Methamphetamine/adverse effects* ; Substance Abuse Detection

Aim To investigate the protective effect of bicyclol on tumor necrosis factor-α/D-galactosamine (TNF-α/D-GalN) induced liver injury and its possible mechanisms. Methods Male C57 mice were given 50, 100, and 200 mg · kg