Heart/breathing rate ratio (HBR) as a predictor of mortality in critically ill patients.

Objectives: The early prediction of death is a challenge for medical staff. We evaluated the ability of the heart/breathing rate ratio (HBR) to predict mortality. Methods: This was a single-center retrospective observational study of adult patients who had fever with or without respiratory symptoms, who survived at least 2 h after visiting the hospital, and whose lactate levels and vital signs were tested. We evaluated the distribution of mortality at different HBR levels and compared HBR with lactate. Results: A total of 18,872 fever clinic visits were screened, and 183 patients whose lactate levels were tested were recruited. Patients who had HBR values lower than 4·5 or higher than 5·5 had greater mortality than patients who had HBR values between 4·5 and 5·5 (21·3 % vs. 3·4 %, p = 0·003; 28·9 % vs. 3·4 %, p < 0·001, respectively). In patients whose HBR was <5, the AUROC for HBR for mortality was 0·762 (95 % CI: 0.643-0·880), and that for lactate was 0·701 (95 % CI: 0·564-0·837). In patients whose HBR was ≥5, the AUROC for HBR for mortality was 0·721 (95 % CI: 0·584-0·857), and that for lactate was 0·742 (95 % CI: 0·607-0·848). Conclusions: HBR is helpful for stratifying mortality risk among critically ill patients in acute care clinics for infectious diseases.

Comparative chemical profiling of leaf essential oils from Cinnamomum kanehirae and related species using steam distillation and solvent extraction: Implications for plant-based classification.

Cinnamomum kanehirae Hayata, belonging to Lauraceae family, is an indigenous and endangered species of considerable economic importance in Taiwan. It plays a crucial role as the host for the economically valuable saprotrophic fungus, Taiwanofungus camphorates. However, accurate species identification poses a challenge due to the similarity in morphological features and frequent natural hybridization with closely related species. Acquiring high-quality and pure leaf oils becomes imperative for precise species identification and producing superior goods. In this study, our objective was to establish methodologies for analyzing the chemical composition of leaf essential oils and subsequently apply this knowledge to differentiate among three Cinnamomum species. Gas chromatography-mass spectrometry (GC/MS) was employed to scrutinize the chemical makeup of leaf essential oils from three closely related species: C. kanehirae, C. micranthum, and C. camphora. We utilized Steam Distillation (SD) and steam distillation-solvent extraction (SDSE) methods, with the SDSE-Hexane approach chosen for optimization, enhancing extraction efficiency and ensuring essential oil purity. Through the SDSE-Hexane method, we identified seventy-four compounds distributed across three major classes: monoterpenes hydrocarbons (0.0-7.0 %), oxygenated monoterpenes (3.8-90.9 %), sesquiterpenes hydrocarbons (0.0-28.3 %), and oxygenated sesquiterpenes (1.6-88.1 %). Our findings indicated the presence of more than one chemotype in both C. kanehirae and C. camphora, whereas no specific chemotype could be discerned in C. micranthum. Furthermore, clustering based on chemotypes allowed for the differentiation of samples from the three species. Notably, we demonstrated that the chemical compositions of grafted C. kanehirae remained largely unaffected by the rootstock. Conversely, natural hybrids between C. kanehirae and C. camphora exhibited profiles more closely aligned with C. kanehirae. The optimized extraction method and the chemotype-based classification system established in this study present valuable tools for essential oil preparation, species identification, and further exploration into the genetic variation of Cinnamomum.

Genetic diversities in wild and cultivated populations of the two closely-related medical plants species, Tripterygium Wilfordii and T. Hypoglaucum (Celastraceae).

BACKGROUND: The sustainable supply of medicinal plants is important, and cultivating and domesticating them has been suggested as an optimal strategy. However, this can lead to a loss of genetic diversity. Tripterygium wilfordii Hook. f. is a medicinal plant commonly used in traditional Chinese medicine, but its wild populations are dwindling due to excessive harvesting. To protect the species and meet the increasing demand, it is urgent to cultivate it on a large scale. However, distinguishing between T. wilfordii and T. hypoglaucum, two similar species with different medicinal properties, is challenging. Therefore, it is crucial to understand the genetic diversity and population structure of these species for their sustainable utilization. RESULTS: In this study, we investigated the genetic diversity and population structure of the two traditional medicinal semiwoody vines plant species, Tripterygium wilfordii and T. hypoglaucum, including wild and cultivated populations using chloroplast DNA (cpDNA) sequences and microsatellite loci. Our results indicated that the two species maintain a high level of genetic divergence, indicating possible genetic bases for the different contents of bioactive compounds of the two species. T. wilfordii showed lower genetic diversity and less subdivided population structures of both markers than T. hypoglaucum. The potential factors in shaping these interesting differences might be differentiated pollen-to-seed migration rates, interbreeding, and history of population divergence. Analyses of cpDNA and microsatellite loci supported that the two species are genetically distinct entities. In addition, a significant reduction of genetic diversity was observed for cultivated populations of the two species, which mainly resulted from the small initial population size and propagated vegetative practice during their cultivation. CONCLUSION: Our findings indicate significant genetic divergence between T. wilfordii and T. hypoglaucum. The genetic diversity and population structure analyses provide important insights into the sustainable cultivation and utilization of these medicinal plants. Accurate identification and conservation efforts are necessary for both species to ensure the safety and effectiveness of crude drug use. Our study also highlighted the importance of combined analyses of different DNA markers in addressing population genetics of medicinal plants because of the contrasts of inheritance and rates of gene flow. Large-scale cultivation programs should consider preserving genetic diversity to enhance the long-term sustainability of T. wilfordii and T. hypoglaucum. Our study proposed that some populations showed higher genetic diversity and distinctness, which can be considered with priority for conservation and as the sources for future breeding and genetic improvement.

Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H: quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase / 中国天然药物

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.

Unveiling Cryptic Species Diversity and Genetic Variation of Lasiodiplodia (Botryosphaeriaceae, Botryosphaeriales) Infecting Fruit Crops in Taiwan.

The genus Lasiodiplodia, a member of the family Botryosphaeriaceae, is an important fungal disease genus in agriculture. However, the Lasiodiplodia species survey and genetic diversity in Taiwan remain unclear. This study aimed to investigate the Lasiodiplodia species associated with various fruit species to explore the cryptic Lasiodiplodia species diversity, validate species delimitation, and unveil cryptic genetic diversity. Overall, six Lasiodiplodia species were identified, with several new records of infection identified. Additionally, phylogenetic analyses indicated that the relations of all isolates of L. theobromae might be paraphyletic. They were grouped with L. brasiliense based on Automatic Barcode Gap Discovery (ABGD), Automatic Partitioning (ASAP) and structure-based clustering analyses. These analyses did not provide conclusive evidence for L. brasiliensis as a stable species. It may be necessary to gather more information to clarify the species delineation. The multiple new records of Lasiodiplodia species with high genetic diversity and differentiation revealed that the diversity of Lasiodiplodia in Taiwan was underestimated in the past. We found that L. theobromae has the highest number of haplotypes but the lowest number of haplotype and nucleotide diversities, indicating a recent population expansion. This was supported by the significant negative Tajima's D and Fu and Li's D* tests. The high genetic diversity, low gene flow, and host-associated differentiation of Lasiodiplodia species indicate that they might harbour powerful evolutionary potential in Taiwan. This study provided critical insights into genetic variation, host-associated differentiation, and demography of Lasiodiplodia species, which would be helpful for disease management of related pathogens.

Identification of three capsule depolymerases in a bacteriophage infecting Klebsiella pneumoniae capsular types K7, K20, and K27 and therapeutic application.

BACKGROUND: Klebsiella pneumoniae capsular types K1, K2, K5, K20, K54, and K57 are prevalent hypervirulent types associated with community infections, and worrisomely, hypervirulent strains that acquired drug resistance have been found. In the search for alternative therapeutics, studies have been conducted on phages that infect K. pneumoniae K1, K2, K5, and K57-type strains and their phage-encoded depolymerases. However, phages targeting K. pneumoniae K20-type strains and capsule depolymerases capable of digesting K20-type capsules have rarely been reported. In this study, we characterized a phage that can infect K. pneumoniae K20-type strains, phage vB_KpnM-20. METHODS: A phage was isolated from sewage water in Taipei, Taiwan, its genome was analyzed, and its predicted capsule depolymerases were expressed and purified. The host specificity and capsule-digesting activity of the capsule depolymerases were determined. The therapeutic effect of the depolymerase targeting K. pneumoniae K20-type strains was analyzed in a mouse infection model. RESULTS: The isolated Klebsiella phage, vB_KpnM-20, infects K. pneumoniae K7, K20, and K27-type strains. Three capsule depolymerases, K7dep, K20dep, and K27dep, encoded by the phage were specific to K7, K20, and K27-type capsules, respectively. K20dep also recognized Escherichia coli K30-type capsule, which is highly similar to K. pneumoniae K20-type. The survival of K. pneumoniae K20-type-infected mice was increased following administration of K20dep. CONCLUSIONS: The potential of capsule depolymerase K20dep for the treatment of K. pneumoniae infections was revealed using an in vivo infection model. In addition, K7dep, K20dep, and K27dep capsule depolymerases could be used for K. pneumoniae capsular typing.

A cross-sectional study of the association between heavy metals and pan-cancers associated with sex hormones in NHANES 1999-2018.

Given the complexity of tumorigenesis, numerous studies have also shown that excessive exposure to heavy metals increases the risk of cancers and disrupts the secretion of sex hormones. However, the specific effects of heavy metals on cancers remain to be proven. To confirm the association between heavy metals and pan-cancer sex hormone levels among adults, 94,337 individuals from the National Health and Nutrition Examination Survey were assessed. We examined the associations between pan-cancers associated with sex hormones (ovarian, testicular, breast, and prostate cancers) and heavy metals in blood/urine. The methods (the WQS (weighted quantile sums) and SVYGLM (survey generalized linear model) regressions) were used to evaluate the association between sex hormone-related cancers and each metal category by incorporating covariates. To evaluate the overall effect of heavy metals and detect the dose-response relationship between the prevalence of pan-cancers associated with sex hormones and heavy metals, RCS (restricted cubic splines) were applied. Environmental exposure to heavy metals may be associated with pan-cancers associated with sex hormones in adults in the USA. Prostate cancer was inversely associated with blood cadmium while positively associated with blood lead, urinary tin, and thallium. Breast cancer was inversely associated with blood lead. Ovarian cancer was positively associated with blood cadmium. We also found a non-linear dose-response relationship between pan-cancers associated with sex hormones and heavy metals, which was non-parametric, using RCS models. The OR for breast cancer decreased along with the increase in lead concentration under approximately 20 µg/dl, while the OR for prostate cancer increased between urine thallium levels of approximately 0.17-1.1 ng/ml. Pan-cancers associated with sex hormones are associated with exposure to heavy metals. Considering the design of the NHANES study, further studies need to be conducted on other nationally representative surveys.

Work-Related Factors Associated With the Pelvic Floor Dysfunction Among a Sample of Female Nurses in China.

BACKGROUND: Female nurses are a high-risk group for pelvic floor dysfunction (PFD). Predictors of female nurses' PFD among work-related factors are not well known. The aim of this study was to investigate the prevalence of PFD and its association with workplace conditions among female nurses in China. METHODS: An online cross-sectional survey was conducted in May 2021. A sample of 380 registered nurses working in six tertiary hospitals in Nanjing, China participated. Data on individual characteristics, work-related factors, the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7 were used. FINDINGS: The overall prevalence of PFD among nurses was 83.9%, with 43.9% of participants experiencing pelvic organ prolapse, 66.6% experiencing anorectal dysfunction and 60.5% experiencing lower urinary tract symptoms. In terms of work-related factors, PFD was associated with heavy lifting, pushing, and carrying at work, delayed toileting at work and fluid intake. Female nurses with PFD reported lower quality of life (QoL) relative to nurses without PFD. CONCLUSIONS/APPLICATION TO PRACTICE: Our findings provide initial insights into workplace conditions that promote PFD among female nurses. Occupational health nurses should consider providing educational information for female workers who are potentially at risk for PFD and consider integrating screening of PFD into practice.

Adverse effects of inadequate sleep duration patterns during pregnancy on toddlers suspected developmental delay: A longitudinal study.

BACKGROUND: Although studies have reported the effects of inadequate sleep on maternal health, few have examined the relationships of maternal sleep patterns with fetal health and early childhood development. This study investigated maternal sleep duration patterns from early pregnancy to 3-years postpartum and their effects on birth outcomes and child development. METHODS: This study recruited pregnant women and their partners during prenatal visits at five selected hospitals in the Taipei area; follow-up lasted from July 2011 to April 2021. A total of 1178 parents completed self-reported assessments from early pregnancy until childbirth and 544 completed eight assessments up to 3-years postpartum. Generalized estimated equation models were used for analyses. RESULTS: Group-based trajectory modeling was used to identify four trajectories of sleep duration patterns. Although maternal sleep duration was not associated with birth outcomes, maternal "short decreasing" and "stably short" sleep patterns were associated with a higher risk of suspected overall developmental delay and language developmental delay, respectively. Furthermore, an "extremely long decreasing" pattern was associated with a higher risk of suspected overall developmental delay, [adjusted odds ratio (aOR) = 2.97, 95% confidence interval (CI):1.39-6.36)], gross motor delay, (aOR = 3.14, 95% CI: 1.42-6.99) and language developmental delay (aOR = 4.59, 95% CI:1.62-13.00). The results were significant for the children of multiparous women. CONCLUSIONS: We identified a U-shaped distribution of risk between offspring developmental delay and maternal prenatal sleep duration, with the highest risk levels on both ends of the maternal prenatal sleep duration pattern. Interventions for maternal sleep are relatively straightforward to implement and should thus be a key part of standard prenatal care.

1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/ß-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

Principles of extramural health care for chronic wounds in China / 中华创伤杂志(英文版)

Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.

Analysis of expression of m 6A regulators in colorectal tumor samples based on TCGA and GEO databases / 中国基层医药

Objective:To detect the expression of N6-methyladenosine (m 6A) regulators in colorectal tumor samples and its clinical significance. Methods:From September to December 2021, the data regarding the expression of m 6A regulators in colorectal tumor samples were collected using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and the expression of m 6A regulators was compared between different clinical pathological characteristics and between different molecular subtypes. Survival analysis was conducted in patients with colorectal cancer with different m 6A expression levels. Results:In TCGA, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) were higher in colorectal tumor samples than normal tissue samples (TCGA-COAD: IGF2BP3: 12.80 vs. 204.46, logFC = 4.00, P = 0.003; YTHDF1: 2 347.56 vs. 3712.77, logFC = 0.66, P < 0.001; TCGA-READ: IGF2BP1: 6.20 vs. 359.32, logFC = 5.82, P = 0.007; YTHDF1: 2 470.10 vs. 4 369.09, logFC = 0.82, P = 0.020). The intersection of TCGA and GEO databases showed that methyltransferase like 14 (METTL14), YTH domain m 6A RNA binding protein 3 (YTHDF3), and α-ketoglutarate dependent dioxygenase AlkB homolog 5 (ALKBH5) were downregulated in colorectal tumor samples compared with normal tissue samples (TCGA-COAD: METTL14: 1 051.56 vs. 711.40, logFC = -0.56, P < 0.001; YTHDF3:4 613.85 vs. 3 155.05, logFC = -0.55, P < 0.001, ALKBH5: 4 250.10 vs. 2 555.55, logFC = -0.73, P < 0.001; TCGA-READ vs. METTL14: 1 113.3 vs. 674.36, logFC = -0.72, P < 0.001; YTHDF3: 5 034.30 vs. 3 331.95, logFC = -0.60, P = 0.004; ALKBH5: 4 902.20 vs. 2 529.71, logFC = -0.95, P < 0.001; GEO-CRC vs. METTL14: 6.58 vs. 6.33, logFC = -0.06, P < 0.001; YTHDF3: 6.28 vs. 6.20, logFC = -0.02, P = 0.002; ALKBH5: 5.07 vs. 4.98, logFC = -0.02, P < 0.001). In colorectal tumor samples of different molecular subtypes, IGF2BP2, HNRNPC, TP53 and YTHDF2 expression was low in KRAS (IGF2BP2: 48.53 vs. 44.04, t = 2.64, P = 0.008; HNRNPC: 121.30 vs. 112.60, t = 2.32, P = 0.020; TP53: 65.30 vs. 60.26, t = 2.11, P = 0.034; YTHDF2: 54.07 vs. 51.19; t = 1.97, P = 0.048). Different clinical pathological characteristics showed that IGF2BP1 was higher in colorectal cancer with positive lymph nodes (8.97 vs. 6.11, W = 20 008, P = 0.002), distant metastasis (8.94 vs. 6.41, W = 19 104, P = 0.009), or stage Ⅲ-Ⅳ (7.46 vs. 7.13, W = 8 779, P = 0.025) than normal tissue. ALKBH5 overexpression, advanced age, presence of vascular invasion, and late pathological staging were significantly related to a short survival period (high ALKBH5 expression vs. low ALKBH5 expression: 5.85 years vs. not available, HR: 1.63, 95% CI: 1.071-2.491, P = 0.021; > 68 years vs. < 68 years: 6.78 years vs. not available, HR: 1.59, 95% CI: 1.049-2.422, P = 0.047; stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 4.55 years vs. 8.33 years, HR: 2.89, 95% CI: 1.895-4.425, P < 0.001; presence of vein invasion vs. absence of vein invasion: 5.48 years vs. not available, HR: 2.82, 95% CI: 1.672-4.783, P < 0.001). Conclusion:Some of the m 6A regulators are associated with the biological characteristics and prognosis of colorectal cancer.

nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story / 神经科学通报·英文版

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.

Effects of host proteins interacting with non-structural protein nsp9 of porcine epidemic diarrhea virus on viral replication / 生物工程学报

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic virus that can cause acute intestinal infectious diseases in both piglets and fattening pigs. The virus encodes at least 16 non-structural proteins, including nsp9, which has been shown to bind to single-stranded RNA. However, its function and mechanism remain unclear. In this study, we aimed to identify potential host proteins that interact with PEDV nsp9 using immunoprecipitation combined with mass spectrometry. The interactions were then confirmed by co-immunoprecipitation (Co-IP) and confocal laser scanning fluorescence techniques. The results showed that nsp9 interacts with HSPA8, Tollip, HSPA9 and TOMM70. Among them, overexpression of HSPA8 resulted in caused first upregulated and then down-regulated expression of nsp9, and promoted the proliferation of PEDV. Overexpression of Tollip significantly upregulated the expression of nsp9 and inhibited the proliferation of PEDV. Overexpression of TOMM70 significantly reduced the expression of nsp9, but did not show significant effect on the proliferation of PEDV. Overexpression of HSPA9 did not show significant effect on the expression of nsp9 and the proliferation of PEDV. These findings may facilitate further investigating the role of nsp9-interacting proteins in PEDV infection.

nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story / 神经科学通报·英文版

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Effect of dissolved solids released from biochar on soil microbial metabolism.

Dissolved solids released from biochar (DSRB), including organic and inorganic compounds, may affect the role of biochar as a soil amendment. In this study, the effects of DSRB on soil microbe metabolism, especially CO2 fixation, were evaluated in liquid soil extract. DSRB were found to be released in large amounts (289.05 mg L-1 at 1 hour) from biochar over a short period of time before their rate of release slowed to a gradual pace. They increased the microbial biomass and provided energy and reducing power to microbes, while reducing their metabolic output of extracellular proteins and polysaccharides. DSRB inputs led to the redistribution of metabolic flux in soil microorganisms and an increased organic carbon content in the short term. This content gradually decreased as it was utilized. DSRB did not improve microbial CO2 fixation but, rather, enhanced its release, while promoting specific soil microorganism genera, including Cupriavidus, Flavisolibacter, and Pseudoxanthomonas. These heterotrophic genera may compete with autotrophic microorganisms for nutrients but have positive synergistic relationships with autotrophs during CO2 fixation. These results demonstrated that reducing the DSRB in biochar can improve its role as a soil amendment by enhancing soil carbon storage and CO2 fixation capabilities.

[Advances in N-methyl-D-aspartate Receptor Signaling Pathway and Mechanism of the Pathway-mediated Apoptosis].

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.

Advances in N-methyl-D-aspartate Receptor Signaling Pathway and Mechanism of the Pathway-mediated Apoptosis / 中国医学科学院学报

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.