Differential Bioactivation Profiles of Different GS-441524 Prodrugs in Cell and Mouse Models: ProTide Prodrugs with High Cell Permeability and Susceptibility to Cathepsin A Are More Efficient in Delivering Antiviral Active Metabolites to the Lung.

We assessed factors that determine the tissue-specific bioactivation of ProTide prodrugs by comparing the disposition and activation of remdesivir (RDV), its methylpropyl and isopropyl ester analogues (MeRDV and IsoRDV, respectively), the oral prodrug GS-621763, and the parent nucleotide GS-441524 (Nuc). RDV and MeRDV yielded more active metabolite remdesivir-triphosphate (RDV-TP) than IsoRDV, GS-621763, and Nuc in human lung cell models due to superior cell permeability and higher susceptivity to cathepsin A. Intravenous administration to mice showed that RDV and MeRDV delivered significantly more RDV-TP to the lung than other compounds. Nevertheless, all four ester prodrugs exhibited very low oral bioavailability (<2%), with Nuc being the predominant metabolite in blood. In conclusion, ProTides prodrugs, such as RDV and MeRDV, are more efficient in delivering active metabolites to the lung than Nuc, driven by high cell permeability and susceptivity to cathepsin A. Optimizing ProTides' ester structures is an effective strategy for enhancing prodrug activation in the lung.

New insight into Ca2+ -permeable channel in plant immunity.

Calcium ions (Ca2+ ) are crucial intracellular second messengers in eukaryotic cells. Upon pathogen perception, plants generate a transient and rapid increase in cytoplasmic Ca2+ levels, which is subsequently decoded by Ca2+ sensors and effectors to activate downstream immune responses. The elevation of cytosolic Ca2+ is commonly attributed to Ca2+ influx mediated by plasma membrane-localized Ca2+ -permeable channels. However, the contribution of Ca2+ release triggered by intracellular Ca2+ -permeable channels in shaping Ca2+ signaling associated with plant immunity remains poorly understood. This review discusses recent advances in understanding the mechanism underlying the shaping of Ca2+ signatures upon the activation of immune receptors, with particular emphasis on the identification of intracellular immune receptors as non-canonical Ca2+ -permeable channels. We also discuss the involvement of Ca2+ release from the endoplasmic reticulum in generating Ca2+ signaling during plant immunity.

Preparation of mouse monoclonal antibodies against the ectodomain of Western equine encephalitis virus E2 (E2ecto) protein / 细胞与分子免疫学杂志

Objective To prepare mouse monoclonal antibodies against the ectodomain of E2 (E2ecto) glycoprotein of Western equine encephalitis virus (WEEV). Methods A prokaryotic expression plasmid pET-28a-WEEV E2ecto was constructed and transformed into BL21 (DE3) competent cells. E2ecto protein was expressed by IPTG induction and presented mainly as inclusion bodies. Then the purified E2ecto protein was prepared by denaturation, renaturation and ultrafiltration. BALB/c mice were immunized with the formulated E2ecto protein using QuickAntibody-Mouse5W as an adjuvant via intramuscular route, boosted once at an interval of 21 days. At 35 days post-immunization, mice with antibody titer above 1×104 were inoculated with E2ecto intraperitoneally, and spleen cells were fused with SP2/0 cells three days later. Hybridoma cells secreting specific monoclonal antibodies were screened by the limited dilution method, and ascites were prepared after intraperitoneal inoculation of hybridoma cells. The subtypes and titers of the antibodies in ascites were assayed by ELISA. The biological activity of the mAb was identified by immunofluorescence assay(IFA) on BHK-21 cells which were transfected with eukaryotic expression plasmid pCAGGS-WEEV-CE3E2E1. The specificity of the antibodies were evaluated with E2ecto proteins from EEEV and VEEV. Results Purified WEEV E2ecto protein was successfully expressed and obtained. Four monoclonal antibodies, 3G6G10, 3D7G2, 3B9E8 and 3D5B7, were prepared, and their subtypes were IgG2c(κ), IgM(κ), IgM(κ) and IgG1(κ), respectively. The titers of ascites antibodies 3G6G10, 3B9E8 and 3D7G2 were 105, and 3D5B7 reached 107. None of the four antibody strains cross-reacted with other encephalitis alphavirus such as VEEV and EEEV. Conclusion Four strains of mouse mAb specifically binding WEEV E2ecto are successfully prepared.

Interkingdom Hormonal Regulations between Plants and Animals Provide New Insight into Food Safety.

Food safety has become an attractive topic among consumers. Raw material production for food is also a focus of social attention. As hormones are widely used in agriculture and human disease control, consumers' concerns about the safety of hormone agents have never disappeared. The present review focuses on the interkingdom regulations of exogenous animal hormones in plants and phytohormones in animals, including physiology and stress resistance. We summarize these interactions to give the public, researchers, and policymakers some guidance and suggestions. Accumulated evidence demonstrates comprehensive hormonal regulation across plants and animals. Animal hormones, interacting with phytohormones, help regulate plant development and enhance environmental resistance. Correspondingly, phytohormones may also cause damage to the reproductive and urinary systems of animals. Notably, the disease-resistant role of phytohormones is revealed against neurodegenerative diseases, cardiovascular disease, cancer, and diabetes. These resistances derive from the control for abnormal cell cycle, energy balance, and activity of enzymes. Further exploration of these cross-kingdom mechanisms would surely be of greater benefit to human health and agriculture development.

Investigation and analysis of pin-point damage and damage growth characteristics in KDP and DKDP crystals.

In this paper, we report the damage and damage growth in potassium dihydrogen phosphate and its deuterated analog crystals. A time-resolved shadow imaging system was used to investigate the damage behavior in the bulk and on the rear surface. The damage images show differences in the damage sizes of the crystals with different deuterization rates. Theoretical simulations demonstrated that this may be due to differences in the crystallographic defects. The experimental results showed that the development of crystal damage was not only manifested as the expansion of damage on the rear surface of the crystal but also as an increase in pin-point density and size within the crystal. Crystals with higher deuterization rates had higher probability of the increasing of initial damage size, rather than the increasing of pin-point density.

[Spatial Distribution of Soil Heavy Metals and Regional Control Strategies in China at Province Level].

It is important to understand the spatial distribution characteristics and health risks of soil heavy metals for the implementation of soil pollution control measures in different levels and regions. Based on the data of 706 core studies in the last 20 years, the spatial distribution characteristics, accumulation degree, and health risks of soil heavy metals in China were analyzed at the provincial level. The results showed that the soil heavy metals had obvious spatial differences on the provincial scale, with an overall trend of "high in the south and low in the north and high in the east and low in the west." The content of heavy metals in the soil of agricultural land and construction land was high, and the rate of exceeding the standard was higher than that of other land types. Soil heavy metal concentrations in most areas of China were higher than the regional background values and were highly cumulative. The accumulation indices were:Cd(1.80)>Pb(0.23)>Cu(0.17)>Zn(-0.05)>As(-0.56)>Cr(-0.69), with more than 85% of the provincial soils reaching moderate levels of Cd pollution. Non-ferrous metal resource-based provinces such as Yunnan, Guizhou, Guangxi, Hunan, and Jiangxi generally had higher soil heavy metal levels than those in other provinces, and local children faced higher cancer risks. Soil pollution in coastal areas such as Fujian, Zhejiang, Jiangsu, and Tianjin mainly originated from industrial production and urbanization construction. High intensity agricultural utilization was an important cause of soil heavy metal accumulation in Henan, Shandong, and Anhui.

Efficacy of intravascular ultrasound versus coronary angiographic guided drug-eluting stent implantation in the treatment of left main coronary artery disease: a meta-analysis / 中华心血管病杂志

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.

Role of Histone Modifications and 12/15-lipoxygenase Metabolic Pathway in the Development of Diabetic Kidney Disease / 中山大学学报(医学科学版)

Diabetic kidney disease （DKD） is one of the most common microvascular complications in patients with diabetes. DKD is also the main cause of end-stage renal failure， with very complex pathogenesis. A large number of experiments have confirmed that epigenetic mechanisms， including histone chemical modifications and lipid metabolites 12/15-lipoxygenase （12/15-LO）， are involved in regulating the characteristic pathophysiological process of DKD， based on which， this review further explores the pathogenesis of DKD and provides the new research direction for DKD treatment.

Comparison of efficacy and safety of rituximab at different doses in the treatment of idiopathic membranous nephropathy / 中华肾脏病杂志

It was a retrospective cohort study. Patients diagnosed with idiopathic membranous nephropathy (IMN) and received rituximab (RTX) alone for one course of treatment during hospitalization in the Department of Nephrology of the First Hospital of Jilin University from March 2020 to March 2022 were enrolled. The patients were divided into 1 g standard treatment group (once 1 g every 2 weeks for twice) and 375 mg/m 2 experimental treatment group (375 mg/m 2 once a week for 4 weeks) according to the different methods of drug administration, and the efficacy and safety of different doses of RTX in the treatment of IMN were compared between the two groups to provide a reference for optimizing the clinical treatment protocol. The patients were followed up regularly for more than 9 months after treatment and the data were complete. A total of 69 patients were included with age of (51.7±11.8) years old, and 46 males (66.7%). There were 31 patients in the 1 g standard treatment group and 38 patients in the 375 mg/m 2 experimental treatment group. The proportion of first-treatment patients in the 1 g standard treatment group was higher than that in the 375 mg/m 2 experimental treatment group (87.1% vs. 65.8%, χ2=4.174, P=0.041). There were no statistically significant differences in the general data, clinical characteristics and baseline laboratory parameters between the two groups (all P>0.05). At the end of 3 months of treatment, 22 patients (31.9%) experienced remission, including 9 patients (29.0%) in the 1 g standard treatment group and 13 patients (34.2%) in the 375 mg/m 2 experimental treatment group ( χ2=0.211, P=0.646). At 6 months, 30 patients (43.5%) experienced remission, including 12 patients (38.7%) in the 1 g standard treatment group and 18 patients (47.4%) in the 375 mg/m 2 experimental treatment group ( χ2=0.521, P=0.470). At 9 months, 38 patients (55.1%) achieved remission, including 18 patients (58.1%) in the 1 g standard treatment group and 20 patients (52.6%) in the 375 mg/m 2 experimental treatment group ( χ2=0.204, P=0.652). At 9 months, the 24 h urine protein of 1 g standard treatment group and 375 mg/m 2 experimental treatment group decreased by 7.93 (6.24, 8.46) g and 7.45 (5.66, 8.67) g (both P<0.05), respectively, and serum albumin increased by 16.4 (15.5, 17.5) g/L and 15.5 (9.0, 15.8) g/L (both P<0.05), respectively, from the baseline value. Kaplan-Meier survival analysis result showed that there was no significant difference in the time of phospholipase A2 receptor titer decreasing to <5 RU/ml between the two groups (Log-rank χ2=3.653, P=0.056). Twenty-three non-serious adverse events occurred in the 1 g standard treatment group, involving 16 patients, and 10 non-serious adverse events occurred in the 375 mg/m 2 experimental treatment group, involving 10 patients. There was better safety in the 375 mg/m 2 experimental treatment group than that in the 1 g standard treatment group ( Fisher value=8.593, P=0.015). Both 375 mg/m 2 regimen and 1 g regimen of RTX in IMN patients are effective in relieving proteinuria and elevating serum albumin. The 375 mg/m 2 regimen of RTX has a lower incidence of adverse events compared with the 1 g regimen.

Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

A surface-receptor-coupled G protein regulates plant immunity through nuclear protein kinases.

Plants employ cell-surface-localized pattern recognition receptors (PRRs) to recognize immunogenic patterns and activate defenses. How these receptors regulate immune signaling in the nucleus is not well understood. Our previous studies showed that BIK1, a central kinase associated with PRRs, phosphorylates a plant-specific Gα protein called extra-large G protein 2 (XLG2) to positively regulate immunity. Here, we show that this phosphorylation promotes XLG2 nuclear translocation, which is essential for antibacterial immunity. XLG2 interacts with nuclear-localized MUT9-like kinases (MLKs) to regulate transcriptome programming. MLKs negatively regulate plant immunity in a kinase activity-dependent manner, whereas XLG2 promotes defense gene expression and antibacterial immunity likely by inhibiting MLK kinase activity. A C-terminal motif in MLKs is essential for the interaction with XLG2, and this motif is required for the XLG2-mediated defense activation. Together, our findings reveal a previously unknown pathway and mechanisms by which cell surface receptors regulate transcriptome during pathogen invasion.

Genomic characterization and phylogenetic analysis of a novel Nairobi sheep disease genogroup Orthonairovirus from ticks, Southeastern China.

The increasing prevalence and transmission of tick-borne diseases, especially those emerging ones, have posed a significant threat to public health. Thus, the discovery of neglected pathogenic agents carried and transmitted by ticks is urgently needed. Using unbiased high-throughput sequencing, a novel Orthonairovirus designated as Meihua Mountain virus (MHMV), was identified in bloodsucking ticks collected from cattle and wild boars in Fujian province, Southeastern China. The full-length genome was determined by RT-PCR and RACE. Genomic architecture of MHMV shares typical features with orthonairoviruses. Phylogenetic analyses suggested that MHMV is clustered into the Nairobi sheep disease (NSD) genogroup of the genus Orthonairovirus and is closely related to the Hazara virus. The RdRp, GPC, and N protein of MHMV shares 62.3%-83.5%, 37.1%-66.1%, and 53.4%-77.3% amino acid identity with other NSD genogroup viruses, respectively, representing a novel species. The overall pooled prevalence of MHMV in ticks was 2.53% (95% CI: 1.62%-3.73%, 22 positives of 134 tick pools), with 7.38% (95% CI: 3.84%-12.59%, 11 positives of 18 pools) in Haemaphysalis hystricis, 6.02% (95% CI: 1.85%-14.22%, four positives of eight pools) in H. formosensis, 25.03% (95% CI: 9.23%-54.59%, six positive of eight pools) in Dermacentor taiwanensis, and 0.16% (95% CI: 0.01%-0.72%, one positive of 100 pools) in Rhipicephalus microplus. This study presented the first report of tick-carried Orthonairovirus in Fujian province and highlighted the broad geographic distribution and high genetic diversity of orthonairoviruses in China.

The relationship between blood pressure variability and ST-T change of electrocardiogram and the severity of acute cerebral infarction and their influence on prognosis / 中国医师进修杂志

Objective:To investigate the relationship between blood pressure variability and ST-T changes of electrocardiogram and the severity of acute cerebral infarction (ACI) and their influence on the prognosis.Methods:A total of 80 ACI patients who diagnosed and treated from February 2018 to February 2020 in Ningbo Medical Center Li Huili Hospital were selected as the research subjects. According the National Institutes of Health Stroke Scale (NIHSS) score, they were divided into mild group (0-15 scores, 31 cases) and moderate group (16-30 scores, 27 cases), severe group (31-45 scores, 22 cases), the changes of ischemic ST-T and blood pressure variation were compared among the three groups, the correlation between ST-T changes, blood pressure variation and disease severity were analyzed by Kendall (tau-b) method. According the results of Modified Rankin Scale(mRS), the ACI patients were divided into the good prognosis group (mRS≤2 scores, 63 cases) and the poor prognosis group (mRS>2 scores, 17 cases). The Logistic regression model was used to analyze the risk factors affecting the prognosis.Results:The ST-T changes among the mild group, moderate group and severe group had significant differences ( P<0.05); the persistent ST-T changes rate in the mild group, moderate group was lower than that in the severe group: 3.23%(1/31), 14.81%(4/27) vs. 59.09%(13/22), P<0.05. The daytime mean systolic blood pressure standard deviation (dSBPSD), nocturnal systolic blood pressure standard deviation (nSBPSD) in the severe group were significantly higher than those in the mild group and moderate group: (14.41 ± 3.22) mmHg (1 mmHg = 0.133 kPa) vs. (11.54 ± 3.02), (12.95 ± 4.52) mmHg;(13.19 ± 3.52) mmHg vs. (10.02 ± 1.65), (11.45 ± 2.45) mmHg, there were statistical differences ( P<0.05). The results of Kendall(tau-b) correlation analysis showed that dSBPSD, dDBPSD, nSBPSD and ischemic ST-T were positively correlated with severity ( r = 0.275, 0.251, 0.334, 0.440; P<0.05). Logistic regression analysis showed that age>70 years old, complete anterior circulation infarction/partial anterior circulation infarction of Oxfordshire Community Stroke Project (OCSP) classification, severe/moderate disease severity, large infarct/small infarct size, persistent ST changes/transient ST-T changes, as well as high levels of 24 h mean systolic blood pressure, 24 h systolic standard deviation, 24 h mean diastolic blood pressure and 24 h diastolic standard deviation were risk factors for poor prognosis in ACI patients. Conclusions:The ST-T changes and blood pressure variability of ACI patients will change with the severity of the disease. Monitoring the changes is helpful to provide an important reference for prognostic judgment.

Preliminary results of domestic surgical robot-assisted remote nephrectomy based on 5G communication technology / 中华泌尿外科杂志

Objective:To explore the feasibility and safety of long-distance urological nephrotomy with the support of 5G communication technology by using the domestic robot.Methods:Clinical data of the patients with remote robot-assisted laparoscopic nephrectomy, which were completed from March to April 2021 by the Affiliated Hospital of Qingdao University (as the host hospital where the main operating system located) were retrospectively analyzed. There were 3 patients, including 2 males and 1 female.The average age was 61 (49-73) years, and the average body mass index was 23.73 (20.00-27.76) kg/m 2. One patient had a ASA classification of grade 2, and the other 2 patients had grade 3. All patients met the surgical criteria for non-functional nephrectomy. The chief surgeon who performing the telesurgery was located at the Affiliated Hospital of Qingdao University. The surgeon remotely controlled the bedside operating system (slave system) in 3 local hospitals located in other cities in Shandong Province (network communication distances of 82.5, 141 and 229 km, respectively) by manipulating the master system located in Qingdao. Images and operating instructions during surgery were transmitted using 5G wireless communication technology. Intraoperative network conditions, robot operation, and patient perioperative data were summarized. Results:All 3 tele-nephrectomies were successfully completed. The average network signal latency time was 27.3 (23-30) ms, with no packet loss, and the average total latency time was 177.3(173-180) ms. The mean resection time was 79.3 (52-111) min, and the average intraoperative blood loss was 31.1 (15.6-41.9) ml. There were no network related adverse events occurred during the operation, and the robot-related adverse events occured 3 times, all three of which were characterized by inconsistent master and slave movements of the manipulator arm and the bedside robotic arm. None of these adverse events affected the successful performance of the telesurgery. The mean postoperative exhaust time was 60.5 (38.5-78.0) h. The mean postoperative VAS score at 24 hours was 3.7 (3-4). The Clavien-Dindo classification were all grade I. No significant abnormality was found on the 30th day after surgery, and the patients recovered well at the follow-up until 6 months postoperatively.Conclusions:It is safe and feasible to perform remote robot-assisted laparoscopic nephrectomy based on 5G communication technology with no serious adverse events or surgical complications.However, the conclusion needs to be further verified by large sample and multi-center prospective study.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Thyroid Nodule Classification in Ultrasound Images by Fusion of Conventional Features and Res-GAN Deep Features.

In spite of the gargantuan number of patients affected by the thyroid nodule, the detection at an early stage is still a challenging task. Thyroid ultrasonography (US) is a noninvasive, inexpensive procedure widely used to detect and evaluate the thyroid nodules. The ultrasonography method for image classification is a computer-aided diagnostic technology based on image features. In this paper, we illustrate a method which involves the combination of the deep features with the conventional features together to form a hybrid feature space. Several image enhancement techniques, such as histogram equalization, Laplacian operator, logarithm transform, and Gamma correction, are undertaken to improve the quality and characteristics of the image before feature extraction. Among these methods, applying histogram equalization not only improves the brightness and contrast of the image but also achieves the highest classification accuracy at 69.8%. We extract features such as histograms of oriented gradients, local binary pattern, SIFT, and SURF and combine them with deep features of residual generative adversarial network. We compare the ResNet18, a residual convolutional neural network with 18 layers, with the Res-GAN, a residual generative adversarial network. The experimental result shows that Res-GAN outperforms the former model. Besides, we fuse SURF with deep features with a random forest model as a classifier, which achieves 95% accuracy.

Responses of greenhouse gas emissions to residue returning in China's croplands and influential factors: A meta-analysis.

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.

Safety and Effectiveness of Orthopaedic Medical Staff in Providing Support in Combating the COVID-19 Pandemic: A Retrospective Investigation from Wuhan, China.

OBJECTIVE: To evaluate whether it is safe and effective for orthopaedic medical staff to provide support to the work against COVID-19. METHODS: One hundred and twenty-two orthopaedic medical staff from the orthopaedic center of Zhongnan Hospital of Wuhan University were included in this retrospective investigation. A total of 43 surgeons and 69 nurses provided medical support in the treatment of COVID-19 patients from 1 January 2020 to 8 April 2020 in four different hospitals in Wuhan. We collected data on the age, gender, and body temperature of orthopaedic medical staff, as well as the results for their chest CT scans, SARS-CoV-2 RNA, SARS-CoV-2 IgM and SARS-CoV-2 IgG tests, and training and examinations on COVID-19 knowledge. We also collected data on the time span of work, the number of infected staff during the support period, the number of COVID-19 patients the surgeons treated and the cure rate, the performance of the surgeons as assessed by the specialists and patients, and the number of infected staff during the pandemic. RESULTS: Among the 49 surgeons and 73 nurses, 43 surgeons and 69 nurses provided support against COVID-19. A total of 12 surgeons and 11 nurses provided support in the fields of respiration, intensive care, and emergency. A total of 34 surgeons and 58 nurses worked in the designated wards restructured for COVID-19 in the orthopaedic building. The average time span of work for the surgeons and nurses was 14.78 ± 3.64 days and 24.77 ± 7.58 days, respectively. No staff were infected during the support period. Over 1000 patients were received in the fever clinic by orthopaedic surgeons. The overall number of the treated hospitalized patients was 622. Among these patients, 226 cases were mild, 318 were mild to moderate, and 58 were severe or critical. The cure rate was 96.01%, 99.37%, and 52.00% respectively. The performance of the surgeons was scored 87.02 ± 3.17 and 90.69 ± 3.58 by the specialists and the patients, respectively. During the whole pandemic, 3 surgeons and 3 nurses who did not participate in the support work were infected in the early stages. The morbidity of all the orthopaedic staff was 4.92% during the whole pandemic, while no one was infected during the support work. CONCLUSION: Our investigation indicated that although they worked outside their specialty, it was safe and effective for the orthopaedic staff to provide medical support in the work against COVID-19 with adequate precautions and proper training.

Review about risk factors and treatment in retinal artery occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinal artery occlusion(RAO)is an ophthalmic emergency, including central retinal artery occlusion(CRVO), branch retinal artery occlusion(BRVO), ciliary retinal artery occlusion and retinal capillary microartery occlusion. The progression is fast and the prognosis is poor, with many risks involved, and there is still lack of standard treatment procedures. At present, the modern treatment procedures include traditional treatments, <i>e.g.</i> lowering intraocular pressure, high flow oxygen inhalation, blood vessels dilatation, antiplatelet aggregation, and other active treatments like thrombolysis, hyperbaric oxygen therapy and arterial intervention. This review summarizes recent advancement about risk factors and treatment in RAO.

Increased TRIM5 is associated with a poor prognosis and immune infiltration in glioma patients / 生物医学工程学杂志

Tripartite motif 5 (TRIM5) plays a significant function in autophagy and involves in immune and tumor processes. While the function of TRIM5 remains poorly understood in glioma. We purpose to evaluate the possible prognostic role of TRIM5 in glioma via bioinformatics analyses. The database clinical samples of glioma in this study included low grade glioma (LGG) and glioblastoma multiforme (GBM). TRIM5 expression in glioma tissues were explored in Oncomine, GEPIA and The Cancer Genome Atlas (TCGA) databases. Survival analysis and the multivariate Cox regression analysis of TRIM5 based on TCGA were used to evaluate the prognostic role of TRIM5. The protein networks of TRIM5 was detected by STRING database. KEGG enrichment analyses were performed to predict the potential molecular pathways of TRIM5 in glioma. In addition, immune infiltration analysis was conducted by CIBERSORT and TIMER databases. We found that TRIM5 was strongly increased in glioma samples compared with normal samples in Oncomine, GEPIA and TCGA databases. Higher TRIM5 was significantly contributed to worse overall survival (OS) in LGG+GBM patients and LGG patients, while was no correlated with OS of GBM patients. Interaction networks analysis identified that IRF3, IRF7, OAS1, OAS2, OAS3, OASL, GBP1, PML, BTBD1 and BTBD2 proteins were contacted with TRIM5. Moreover, KEGG revealed that apoptosis and cancer- and immune-related pathways were enriched with elevated TRIM5. Specifically, TRIM5 could influence the immune infiltration levels, such as activated NK cells, monocytes, activated mast cells and macrophages in glioma. In conclusion, our data indicated that TRIM5 was upregulated in glioma tissues and associated with poor prognosis and immune infiltration. TRIM5 may be acted as a biomarker in prognosis and immunotherapy guidance of glioma.