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BACKGROUND: The lesions besides lateral ventricle and motor recovery following rehabilitation have hardly been studied. OBJECTIVE: To explore the relationship between the size, location of infarction beside the lateral ventricle and motor recovery following rehabilitation. METHODS: A prospective cohort of 55 patients submitted to a Rehabilitation Medical Center between January 2015 and June 2019 who suffered a single cerebral infarction beside the lateral ventricle were included in the study. The size and distance between the posterior margin and the frontal-middle line (FML) of the lesion were measured. Follow-up was conducted until the recovery was no longer progressing. Barthel index and Brunstrom stages were used to evaluate the outcome (full recovery, partial recovery and poor recovery). Variance analysis and nonparametric test were used for the comparison between groups. Multivariate logistic regression analysis was used to screen the factors affecting the outcomes. The Pearson correlation coefficient was used to compare the volume of infarction, behind the FML and the outcomes. RESULTS: Among the 55 patients, the outcome was full recovery (n = 28), partial recovery (n = 13) and poor recovery (n = 14). Multivariate logistic regression analysis showed that volume and location of the infarction were significantly correlated with the outcome (p = 0.039, 0.050). The lesion volume in the full recovery patients was significantly smaller than that in the poor recovery patients (p

MicroRNA (miRNA) and long noncoding RNA (lncRNA) are both regulators of cancer progression. This study sought to discuss the functional mechanism of miR-96-5p/lncRNA TRIM52 antisense RNA 1 (head-to-head; TRIM52-AS1) in cervical cancer (CC) cell resistance to cisplatin (DDP). DDP-resistant CC cell line was established using increasing concentrations of DDP, followed by transfection with miR-96-5p inhibitor, or si-TRIM52-AS1, or insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) overexpression vector. Expression levels of miR-96-5p, TRIM52-AS1, and IGF2BP2 were determined. Changes in IC50 value to DDP, cell proliferation, and apoptosis rate were evaluated by cell-counting kit-8 assay, colony formation, and flow cytometry. The bindings of miR-96-5p to IGF2BP2 and TRIM52-AS1 to IGF2BP2 were verified by dual-luciferase or RNA pull-down assays. These experiments revealed an up-expression of miR-96-5p and IGF2BP2 while an under-expression of TRIM52-AS1 in CC cells. After DDP treatment, miR-96-5p inhibition increased apoptosis and decreased proliferation and DDP resistance. miR-96-5p bound to TRIM52-AS1 and downregulated TRIM52-AS1 expression, and TRIM52-AS1 bound to IGF2BP2 to inhibit IGF2BP2 expression. TRIM52-AS1 inhibition or IGF2BP2 overexpression neutralized the inhibition of silencing miR-96-5p on CC cell resistance to DDP. Overall, miR-96-5p improved CC cell resistance to DDP by inhibiting TRIM52-AS1 and promoting IGF2BP2.

Treatment of bone defects still poses a great challenge in orthopedic clinics, and the vital role of periosteum in such processes has attracted widespread attention. However, studies focusing on the oxidative stress micro-environment with an artificial periosteum at the site of defect have been scarce. The intrinsic anti-oxidative properties and therapeutic potential for bone defects of metal-phenolic networks (MPNs) have provided a potential solution to this. Herein, we have developed a protocatechualdehyde + zinc ion (PCA+ZnⅡ) MPN coating on a thermoplastic polyurethane membrane with a one-pot method to fabricate a new-type of periosteum with meritorious biocompatibility and abilities of modulating oxidative stress condition and promoting osteogenesis and mineralization for better bone regeneration, which has shown to be a promising strategy for constructing artificial periosteum with various MPNs.

A new tyramine derivative, glycosamide A (1), together with two known amide alkaloids, N-benzoyltyramine methyl ether (2) and aurantiamide acetate (3), was isolated from the branches and leaves of Glycosmis craibii Tanaka. Their structures were elucidated through extensive 1D and 2D NMR and HR-ESI-MS spectroscopic analyses. All known compounds were isolated from the genus Glycosmis for the first time. Furthermore, the antiproliferative activities of all isolated alkaloids in vitro were evaluated. Compound 2 displayed weak antiproliferative activities against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW480.

Two new aldoximes A–B (1−2), and two known analogues (3−4), were identified from ethanolic extracts of Glycosmis craibii. The structures of new compounds 1−2 were unambiguously elucidated based on spectroscopic methods. All isolated aldoximes were evaluated for their anti-inflammatory activity in vivo. Compounds 1−4 displayed remarkable inhibitory effects against nitric oxide (NO) production stimulated by lipopolysaccharide in mouse macrophage RAW 264.7 cells with the IC50 values ranging from 2.38 ± 0.08–8.43 ± 0.21 μM.

There is increasing evidence that angiotensin (1-7) [Ang (1-7)] is an endogenous biologically active component of the renin-angiotensin system. However, the role of the Ang (1-7)-MasR axis in postresuscitation myocardial dysfunction (PRMD) and its associated mechanism are still unclear. In this study, we investigated the effect of the Ang (1-7)-MasR axis on myocardial injury after cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation. We established a model of oxygen/glucose deprivation-reperfusion in myocardial cells in vitro and a rat model of cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation in vivo. The cell apoptosis rate and the expression of the superoxide anion 3-nitrotyrosine were decreased in the Ang (1-7) group in vitro and in vivo. The mean arterial pressure was decreased, whereas +LVdp/dtmax and -LVdp/dtmax were increased in rats in the Ang (1-7) group. The mRNA and protein levels of Ang II type 1 receptor, MasR, phosphoinositide 3-kinase, protein kinase B, and endothelial nitric oxide synthase were increased in the Ang (1-7) group in vivo. These results indicate that the Ang (1-7)-MasR axis can alleviate PRMD by reducing myocardial tissue damage and oxidative stress through activation of the phosphoinositide 3-kinase-protein kinase B-endothelial nitric oxide synthase signaling pathway and provide a new direction for the clinical treatment of PRMD.

The study aimed to investigate the effects of galangin on learning and memory impairments and Akt/MEF2 D/Beclin-1 signaling pathway in APP/PS1 double-transgenic mice. The mice in this experiment were divided into the normal group, model group, low-(25 mg·kg~(-1)), medium-(50 mg·kg~(-1)), and high-dose(100 mg·kg~(-1)) galangin groups, donepezil(3 mg·kg~(-1)) group, Akt inhibitor(25 mg·kg~(-1)) group, and autophagy inhibitor(30 mg·kg~(-1)) group, with ten in each group, and administered with the corresponding drugs for 30 successive days. On the 24 th day of medication, the water maze and dark avoidance tests were performed. The levels of p-tau, β-amyloid peptide 1-42(Aβ_(42)), acetylcholinesterase(AChE), β-site amyloid precursor protein cleaving enzyme 1(BACE1), and amyloid precursor protein(APP) in hippocampus were detected by ELISA, the Beclin-1 mRNA expression by RT-PCR, the expression of Aβ_(42) and glial fibrillary acidic protein(GFAP) by immunohistochemistry, and the expression of myocyte enhancer factor 2 D(MEF2 D) by immunofluorescence assay. The pathological changes in hippocampus were observed after HE staining, and the expression of Akt, MEF2 D, and Beclin-1 in hippocampus were assayed by Western blot. These results showed that compared with the normal group, the model group exhibited prolonged swimming time, increased number of errors and electric shocks, up-regulated p-tau, Aβ_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened incubation period, decreased p-Akt and MEF2 D, and obvious hippocampal injury. Compared with the model group, donepezil and galangin shortened the swimming time, reduced the number of errors and electric shocks, down-regulated the expression of p-tau, Aβ_(42), APP, AChE, BACE1, GFAP, and Beclin-1, prolonged the incubation period, up-regulated p-Akt and MEF2 D, and improved the pathological changes in hippocampus. Compared with the autophagy inhibitor group, galangin prolonged the swimming time, elevated the number of errors and electric shocks, enhanced the expression of p-tau, Aβ_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened the incubation period, and diminished the expression of p-Akt and MEF2 D. In conclusion, galangin improves the learning and memory impairments and hippocampal neuron injury of APP/PS1 mice, which may be related to its regulation of Akt/MEF2 D/Beclin-1 signaling pathway.

Purpose: To describe the prevalence and analyse the associated factors of possible sarcopenia and sarcopenia among community-dwelling old adults in China, in order to provide effective strategies for early prevention and treatment of sarcopenia.Methods: This cross-sectional study evaluated community-dwelling old adults aged over 60 years. The basic information, morphological indices, body composition, physical activities were collected and assessed. Possible sarcopenia and sarcopenia were diagnosed by the criteria of Asian Working Group for Sarcopenia (AWGS) in 2019. A multivariate logistic regression model with stepwise method was employed to identify factors associated with possible sarcopenia and sarcopenia.Results: In total 729 old adults from Tianjin were included in this study. 81 participants were diagnosed with possible sarcopenia (prevalence of 11.11%). 75 participants were diagnosed with sarcopenia (prevalence of 10.29%). Age (odds ratio (OR):1.047, 95% confidence interval (CI): 1.055-1.090) and lower physical activities (low level OR:4.171, 95% CI:1.790-9.720; medium level OR:2.634, 95% CI:1.352-5.132) were significantly associated with possible sarcopenia. Age (OR:1.187, 95% CI:1.124-1.253), higher body fat percentage (OR:1.225, 95% CI:1.140-1.317), lower BMI (OR:0.424, 95% CI:0.346-0.519), lower mini-mental state examination (MMSE) scores (OR:0.865,95% CI:0.781-0.958) and low physical activities (OR:4.638, 95% CI:1.683-12.782) were significantly associated with sarcopenia.Conclusion: Possible sarcopenia and sarcopenia are prevalent among community-dwelling old adults in China. Ageing and lower physical activities were both associated with possible sarcopenia and sarcopenia. Old adults with sarcopenia more likely have higher body fat percentage, lower BMI and lower cognitive function compared with those without this condition.

In nursing education, the diversity of clinical scenarios is complex and dynamic, and it is a challenge for nursing students to learn this clinical knowledge in conventional teaching mechanisms. However, integrating information technology into teaching can promote diversity of learning environment. This study aimed to investigate the effectiveness of teaching mechanisms which combined clinical simulation scenario and Information Technology Integrated Instruction. This study applied innovative experimental teaching in medical–surgical and critical care nursing courses for nursing students in their fourth or fifth year at a five-year junior college. Instructional systems design was combined with clinical simulation scenarios and technology to develop multidimensional teaching strategies. Fifth-year students' overall OSCE mean score was considerably higher than that of fourth-year students; specifically, their scores on basic life support and care for subdural hemorrhage varied substantially. Compared with fourth-year students, fifth-year students performed considerably greater on situational awareness. The results of the present study can be used to develop nursing core competencies and improve the clinical care competency of nursing personnel.

Sing-Ong Lee,1 Li-Ping Huang,1 Chih-Shung Wong1– 3 1Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan; 2Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 3School of Medicine, Fu-Jen Catholic University, New Taipei, TaiwanCorrespondence: Chih-Shung Wong Department of AnesthesiologyCathay General Hospital, #280, Renai Road, Section 4, Taipei, TaiwanTel +886-2-27082121 Ext 3510Fax +886-2-87924835Email w82556@gmail.comPurpose: Perioperative pain management plays a critical role in the effort to promote enhanced recovery after surgery (ERAS). Pain is also the most concern for patients after laparoscopic cholecystectomy (LC). Naldebain (extended-release dinalbuphine sebacate, DS) is an oil-based formulation for intramuscular injection that has been designed for extended release and can be used for preoperative analgesia over a 7-day period. This study was aimed to compare the efficacy of DS injection with that of regular postoperative morphine administered when necessary for the management of post-laparoscopic cholecystectomy pain.Patients and Methods: Forty-four patients scheduled for elective laparoscopic cholecystectomy were included in this prospective study. The patients were allocated randomly into two groups, with equal numbers receiving preoperative DS versus post-operative morphine. A total of 21 and 22 patients completed the study within the preoperative DS and post-operative morphine group, respectively.Results: There were no statistically significant differences between two treatment groups with respect to length of surgery, anesthetics used during operation, or the average visual analog scale pain score in the post-operative anesthesia care unit (PACU), and at 4, 24, 48, and 72 hours post-procedure. Morphine was required only during the first postoperative day among those in the DS group. Safety was comparable in both DS and morphine groups.Conclusion: A single preoperative dose of DS provides sufficient analgesia along with a manageable safety profile and no interference with surgical anesthetics when compared to control cases that underwent surgery without preoperative DS treatment. This pilot study suggests that preoperative administration of DS is safe and may decrease the need for postoperative opioid use after laparoscopic cholecystectomy.Registration: ClinicalTrials.gov Identifier: NCT03713216.Keywords: nalbuphine, enhanced recovery after surgery, multimodal analgesia, preventive analgesia

A phytochemical investigation on the stems of Glycosmis puberula var. craibii led to the isolation of a new indole alkaloid (named glycosmiscrol A, 1), together with four known compounds (2–5). The new structure was elucidated by detailed analysis of comprehensive spectroscopic methods. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–5 showed significant antiproliferative effects with IC50 values ranging from 0.16 to 8.58 µM.

Background Causes of voriconazole-related visual adverse events (VVAE) remained controversial. Objectives We aimed to explore the relationship between voriconazole serum concentrations and VVAE as well as the potential influence of transient receptor potential melastatin 1 (TRPM1) on VVAE. Patients/methods This prospective observational cohort study was done in two stages. Patients who received voriconazole for invasive fungal diseases were consecutively enrolled. Correlations between voriconazole trough levels and VVAE were explored in 76 patients. Genotyping was further conducted for 17 tag SNPs of TRPM1 in a larger population of 137 patients. Genotype distributions were compared between patients with and without VVAE. Result Of the 76 patients, a total of 229 steady-state voriconazole trough levels were evaluated, 69.9% of which were within the target range (1-5.5 mg/L). No correlations were found between voriconazole trough levels and VVAE. Of the total 137 patients, VVAE occurred in 37 (27.0%) patients, including visual hallucination (13.9%, 19/137) and visual disturbances (19.0%, 26/137). Significant difference in TRPM1 genotype distribution was only observed in patients with visual hallucination but not with visual disturbances. We found that rs890160 G/T genotype was under-presented (OR, 0.11; 95% CI, 0.01-0.84; P = .011) and rs1378847 C/C genotype was more frequently detected (OR, 8.89; 95% CI, 1.14-69.02; P = .013) in patients with visual hallucination when compared with those without. Conclusion Transient receptor potential melastatin 1 was genetically associated with voriconazole-related visual hallucination. The correlation was failed to found between voriconazole trough levels and VVAE.

In plants, submergence from flooding causes hypoxia, which impairs energy production and affects plant growth, productivity, and survival. In Arabidopsis, hypoxia induces nuclear localization of the group VII ethylene-responsive transcription factor RELATED TO AP2.12 (RAP2.12), following its dissociation from the plasma membrane-anchored ACYL-COA BINDING PROTEIN1 (ACBP1) and ACBP2. Here, we show that polyunsaturated linolenoyl-CoA (18:3-CoA) regulates RAP2.12 release from the plasma membrane. Submergence caused a significant increase in 18:3-CoA, but a significant decrease in 18:0-, 18:1-, and 18:2-CoA. Application of 18:3-CoA promoted nuclear accumulation of the green fluorescent protein (GFP) fusions RAP2.12-GFP, HYPOXIA-RESPONSIVE ERF1-GFP, and RAP2.3-GFP, and enhanced transcript levels of hypoxia-responsive genes. Plants with decreased ACBP1 and ACBP2 (acbp1 ACBP2-RNAi, produced by ACBP2 RNA interference in the acbp1 mutant) had reduced tolerance to hypoxia and impaired 18:3-CoA-induced expression of hypoxia-related genes. In knockout mutants and overexpression lines of LONG-CHAIN ACYL-COA SYNTHASE2 (LACS2) and FATTY ACID DESATURASE 3 (FAD3), the acyl-CoA pool size and 18:3-CoA levels were closely related to ERF-VII-mediated signaling and hypoxia tolerance. These findings demonstrate that polyunsaturation of long-chain acyl-CoAs functions as important mechanism in the regulation of plant hypoxia signaling, by modulating ACBP-ERF-VII dynamics.

The present study explored the effect and mechanism of repeatedly steamed and sundried Rehmanniae Radix Praeparata(RRP) in delaying brain aging in ovariectomized mice. After ovariectomy, the mice were randomly divided into a model group, an estradiol valerate group(0.3 mg·kg~(-1)), and low-(1.0 g·kg~(-1)), medium-(2.0 g·kg~(-1)), and high-dose(4.0 g·kg~(-1)) RRP groups, and a sham operation group was also set up, with 15 mice in each group. One week after the operation, intragastric administration was carried out for 15 consecutive weeks. The step-down test and Morris water maze test were used to detect the behavioral changes of mice. HE staining and Nissl staining were used to observe the morphological changes of mouse brain tissues. Immunohistochemistry was used to detect the expression of Aβ and ER_β in mouse brain tissues. The serum estrogen levels and cholinesterase and cholinesterase transferase levels in brain tissues of mice were detected by assay kits. The extracted hippocampal protein was detected by the Nano-ESI-LC-MS system, identified by the Protein Discovery, and analyzed quantitatively and qualitatively by the SIEVE. The PANTHER Classification System was used for GO analysis and KEGG pathway enrichment analysis of the differential proteins. Compared with the sham operation group, the model group showed decreased learning and memory ability, shortened step-down latency(Plt;0.05), prolonged escape latency(Plt;0.05), reduced platform crossings and residence time in the target quadrant, scattered nerve cells in the hippocampus with enlarged intercellular space, increased expression of Aβ-positive cells(Plt;0.05), declining expression of ER_β-positive cells and estrogen level(Plt;0.05), and weakened cholinergic function(Plt;0.05). Compared with the model group, the RRP groups showed improved learning and memory ability, prolonged step-down latency(Plt;0.05), increased estrogen level(Plt;0.05), neatly arranged nerve cells in the hippocampus with complete morphology, declining Aβ-positive cells, and elevated expression of ER_β-positive cells. A total of 146 differential proteins were screened out by proteomics, and KEGG pathway enrichment yielded 75 signaling pathways. The number of proteins involved in the dopaminergic synapse signaling pathway was the largest, with 13 proteins involved. In summary, RRP can delay brain aging presumedly by increasing the level of estrogen, mediating the dopaminergic synapse signaling pathway, and improving cholinergic function.

ObjectiveTo evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics in unvaccinated children aged < 12 y with vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China.MethodsA total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Realtime PCR positive and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; the effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis.ResultsThe Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84(1.32,2.71)×10^9/L vs. 1.31(0.94,1.85)×10^9/L; pp< 0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13(0.00,0.09) vs. 0.12(0.03,0.41), pp pp=0.13).ConclusionChildren aged < 12y may be critical hidden spreaders, which indicates an urgent need of vaccination for this particular population.

Phosphatidic acid (PA) is an important lipid essential for several aspects of plant development and biotic and abiotic stress responses. We previously suggested that submergence induces PA accumulation in Arabidopsis thaliana; however, the molecular mechanism underlying PA-mediated regulation of submergence-induced hypoxia signaling remains unknown. Here, we showed that in Arabidopsis, loss of the phospholipase D (PLD) proteins PLDα1 and PLDδ leads to hypersensitivity to hypoxia, but increased tolerance to submergence. This enhanced tolerance is likely due to improvement of PA-mediated membrane integrity. PA bound to the mitogen-activated protein kinase 3 (MPK3) and MPK6 in vitro and contributed to hypoxia-induced phosphorylation of MPK3 and MPK6 in vivo. Moreover, mpk3 and mpk6 mutants were more sensitive to hypoxia and submergence stress compared with wild type, and fully suppressed the submergence-tolerant phenotypes of pldα1 and pldδ mutants. MPK3 and MPK6 interacted with and phosphorylated RELATED TO AP2.12, a master transcription factor in the hypoxia signaling pathway, and modulated its activity. In addition, MPK3 and MPK6 formed a regulatory feedback loop with PLDα1 and/or PLDδ to regulate PLD stability and submergence-induced PA production. Thus, our findings demonstrate that PA modulates plant tolerance to submergence via both membrane integrity and MPK3/6-mediated hypoxia signaling in Arabidopsis.

BACKGROUND Cryptococcal meningitis (CM)-associated immune reconstitution inflammatory syndrome (IRIS) is associated with high mortality, the epidemiology and pathophysiology of which is poorly understood, especially in non-HIV populations. OBJECTIVES We aim to explore the incidence, clinical risk factors, immunological profiles and potential influence of leukotriene A4 hydroxylase (LTA4H) on non-HIV CM IRIS populations. METHODS In this observational cohort study, 101 previously untreated non-HIV CM patients were included. We obtained data for clinical variables, 27 cerebrospinal fluid (CSF) cytokines levels and LTA4H genotype frequencies. Changes of CSF cytokines levels before and at IRIS occurrence were compared. RESULTS Immune reconstitution inflammatory syndrome was identified in 11 immunocompetent males, generating an incidence of 10.9% in non-HIV CM patients. Patients with higher CrAg titres (> 1:160) were more likely to develop IRIS, and titre of 1:1280 is the optimum level to predict IRIS occurrence. Baseline CSF cytokines were significantly higher in IRIS group, which indicated a severe host immune inflammation response. Four LTA4H SNPs (rs17525488, rs6538697, rs17525495 and rs1978331) exhibited significant genetic susceptibility to IRIS in overall non-HIV CM, while five cytokines were found to be associated with rs1978331, and baseline monocyte chemotactic protein 1 (MCP-1) became the only cytokine correlated with both IRIS and LTA4H SNPs. CONCLUSIONS Our study suggested that non-HIV CM patients with high fungal burden and severe immune inflammation response were more likely to developed IRIS. LTA4H polymorphisms may affect the pathogenesis of IRIS by regulating the level of baseline CSF MCP-1.

BACKGROUND Tomato chlorosis virus (ToCV) is mainly vectored by Bemisia tabaci in China, which has a worldwide distribution, and greatly reduces the yields of tomato and other vegetables. At present, control of ToCV has been focused mainly by the use of insecticides to control whitefly populations. Transcriptome sequencing showed high expression of the B. tabaci Bta11975 gene, an α-glucosidase (AGLU) during ToCV acquisition by whitefly Mediterranean (MED) species. To investigate the role of Bta11975 gene in ToCV acquisition and transmission by B. tabaci MED, we used RNA interference (RNAi) to reduce the expression of the Bta11975 gene. RESULTS The relative expression of the Bta11975 gene was correlated with the ToCV content in B. tabaci. The AGLU is highly expressed in primary salivary gland and gut. After the Bta11975 gene was silenced, the gene expression of B. tabaci was reduced and B. tabaci mortality was increased. Besides, ToCV acquisition by B. tabaci at 48 and 72 h AAP was reduced, and ToCV transmission was significantly reduced by 25 or 50 of B. tabaci. CONCLUSIONS These results indicate that suppression of expression of the Bta11975 gene in B. tabaci MED by RNAi can reduce acquisition and transmission of ToCV by B. tabaci MED.

Tomato chlorosis virus(ToCV), is one of the most devastating cultivated tomato viruses, seriously threatened the growth of crops worldwide. As the vector of ToCV, the whiteflyBemisia tabaciMediterranean (MED) is mainly responsible for the rapid spread of ToCV. The current understanding of tomato plant responses to this virus andB. tabaciis very limited. To understand the molecular mechanism of the interaction between tomato, ToCV andB. tabaci, we adopted a next-generation sequencing approach to decipher miRNAs and mRNAs that are differentially expressed under the infection ofB. tabaciand ToCV in tomato plants. Our data revealed that 6199 mRNAs were significantly regulated, and the differentially expressed genes were most significantly associated with the plant-pathogen interaction, the MAPK signaling pathway, the glyoxylate, and the carbon fixation in photosynthetic organisms and photosynthesis related proteins. Concomitantly, 242 differentially expressed miRNAs were detected, including novel putative miRNAs. Sly-miR159, sly-miR9471b-3p, and sly-miR162 were the most expressed miRNAs in each sample compare to control group. Moreover, we compared the similarities and differences of gene expression in tomato plant caused by infection or co-infection ofB. tabaciand ToCV. Taken together, the analysis reported in this article lays a solid foundation for further research on the interaction between tomato, ToCV andB. tabaci, and provide evidence for the identification of potential key genes that influences virus transmission in tomato plants.

Background: Acute graft versus host disease (aGVHD) remains a leading cause of transplant-related mortality following allogeneic haematopoietic cell transplantation(allo-HCT). Although previous studies indicated that mesenchymal stem cells (MSCs) may be a salvage therapeutic agent for aGVHD, the mechanism is not yet fully clear. Human amniotic mesenchymal stem cells (hAMSCs) is a novel MSCs, compared with bone marrow mesenchymal stem cells, it has the advantage of being non-invasive, and also has stronger proliferation ability than that of BM-MSCs and equivalent immune regulation ability as BM-MSCs. The aim of this study was to explore the therapeutic efficacy and underlying mechanisms of human amniotic mesenchymal stem cells transplantation for the humanized aGVHD mouse model.Methods: We established a humanized aGVHD mouse model by transplanting human peripheral blood mononuclear cells (PBMCs) into NOD-PrkdcscidIL2rγnull (NPG) mice, hAMSCs collected from discarded placenta of healthy pregnant women after delivery. Mice were divided into control group (untreated), aGVHD group, and hAMSCs treatment group, the hAMSCs labeled with GFP were administered to aGVHD mice to explore the homing ability of hAMSCs. T effector and Treg cell levels and cytokines of each group in target organs were detected by flow cytometry and cytometric bead array (CBA) respectively.Results: We successfully established a humanized aGVHD mouse model using NPG mice. The hAMSCs have the ability to inhibit aGVHD in this mouse model through reduced villous blunting and lymphocyte infiltration into the lamina propria of the gut while reducing vascular endothelialitis and lymphocyte infiltration into the parenchyma of the liver and lung. hAMSCs suppressed xenogenesis CD3+CD4+ T and CD3+CD8+ T cell expression and increased the proportion of Treg cells, and besides, hAMSCs can reduce the levels of IL-17A, INF-γ, TNF, and IL-2 in aGVHD target organs.Conclusions: The NPG murine environment was capable of activating human T cells to produce aGVHD pathology to mimic aGVHD as in humans. The hAMSCs controlled aGVHD by decreasing inflammatory cytokine secretion within target organs by modulating the balance of Treg and T effector cells in humanized mice.

Let q be a power of 2, and let $${\mathbb {F}}_q$$ be the finite field with q elements. The quadratic forms graph, denoted by Q(n, q) where $$n\ge 2$$ , has all quadratic forms on $${\mathbb {F}}_q^n$$ as vertices and two vertices f and g are adjacent if $$\mathrm{rk}(f-g) = 1$$ or 2. A graph G is called a pseudo-core if every endomorphism of G is either an automorphism or a colouring. A graph G is a core if every endomorphism of G is an automorphism. We prove that Q(n, q) is a pseudo-core and Q(2m, q) is a core. Moreover, we gave the smallest eigenvalue of Q(n, q).

Let Z p s be the residue class ring of integers modulo p s , where p is a prime number and s is a positive integer. We study subspaces and Grassmann graphs for Z p s n . A Grassmann graph for Z p s n , denoted by G d ( n , m , p s ) ( G d for short), has all m-subspaces of Z p s n as its vertices, and two distinct vertices are adjacent if their intersection is of dimension > m − d , where m n and 2 ≤ d ≤ m + 1 . We give the clique number and geometric structures of maximum cliques of G d , etc. By these results, we obtain the Erdős–Ko–Rado theorem for Z p s n and some bounds of the independence number of G d . We also show that an optimal Grassmannian code for Z p s n is a largest independent set of G d . A p s -Kneser graph over Z p s , denoted by Z p s K n : m where n ≥ 2 m ≥ 4 , is the complement of G m ( n , m , p s ) . Finally, we prove that Z p s K n : m is a core when n > 2 m ≥ 4 , and give some estimations for the chromatic number and clique number of Z p s K n : m .

A graph G is called a pseudo-core if every endomorphism of G is either an automorphism or a colouring. A graph G is a core if every endomorphism of G is an automorphism. Let F q be the finite field with q elements where q is a power of an odd prime number. The quadratic forms graph, denoted by Quad ( n , q ) where n ≥ 2 , has all quadratic forms on F q n as vertices and two vertices f and g are adjacent whenever rk ( f − g ) = 1 or 2. We prove that every Quad ( n , q ) is a pseudo-core. Further, when n is even, Quad ( n , q ) is a core. When n is odd, Quad ( n , q ) is not a core. On the other hand, we completely determine the independence number of Quad ( n , q ) .

Natural circulation (NC) loops were widely used in many fields, but still limited in the instability of the loop. The instability characteristics of NC are not fully understood, such as oscillation boundary, amplitude and frequency. To understand the oscillation characteristics, experiments of two-phase natural circulation were performed for R134a in a single loop. Two types of the oscillation were observed and identified by the characteristic frequency in their oscillation spectra. The characteristic frequencies and amplitudes of the oscillations were affected by the system pressure, the heating power and the evaporator inlet subcooling. For the type 1 oscillation, with the increase of the heating power, the main characteristic frequency increased, while the oscillation amplitude decreased; with the increase of the system pressure, the oscillation frequency decreased; with the increase of the subcooling, the frequency decreased. For the type 2 oscillation, with the increase of the heating power, the main characteristic frequency increased, the oscillation amplitude increased; with the increase of subcooling, the frequency decreased, and the amplitude increased. An instability map was built based on the dimensionless numbers: the subcooling number N_sub versus the phase change number N_pch. The stable region of the system was wider at low subcooling condition. Two types of the oscillation may occur at the same time, and the stable region disappeared when subcooling number higher than 3. Combining dimensionless analysis and spectrum analysis, we divided the two-phase natural circulation into five regions in the instability map. Through the oscillation spectrum, this study provided a deep perspective for the instability of two-phase natural circulation. Also, the experimental results of this study can lay the foundation for future research.

Tomato chlorosis virus (ToCV), is one of the most devastating cultivated tomato viruses, seriously threatened the growth of crops worldwide. As the vector of ToCV, the whitefly Bemisia tabaci Mediterranean (MED) is mainly responsible for the rapid spread of ToCV. The current understanding of tomato plant responses to this virus and B. tabaci is very limited. To understand the molecular mechanism of the interaction between tomato, ToCV and B. tabaci, we adopted a next-generation sequencing approach to decipher miRNAs and mRNAs that are differentially expressed under the infection of B. tabaci and ToCV in tomato plants. Our data revealed that 6199 mRNAs were significantly regulated, and the differentially expressed genes were most significantly associated with the plant-pathogen interaction, the MAPK signaling pathway, the glyoxylate, and the carbon fixation in photosynthetic organisms and photosynthesis related proteins. Concomitantly, 242 differentially expressed miRNAs were detected, including novel putative miRNAs. Sly-miR159, sly-miR9471b-3p, and sly-miR162 were the most expressed miRNAs in each sample compare to control group. Moreover, we compared the similarities and differences of gene expression in tomato plant caused by infection or co-infection of B. tabaci and ToCV. Taken together, the analysis reported in this article lays a solid foundation for further research on the interaction between tomato, ToCV and B. tabaci, and provide evidence for the identification of potential key genes that influences virus transmission in tomato plants.

Four antibiotics[azithromycin (AZM), sulfamethoxazole (SMZ), ciprofloxacin (CIP), and tetracycline (TCY)], and the antibiotic resistance genes (ARGs)[sulfonamides (

Taking windfall woods of以伊犁南部山区雪岭云杉风倒木为对象,研究了1.3、5、10、15、20 m树高处树轮圆盘样品的最大密度、最小密度、早材平均密度、晚材平均密度4种树轮密度年表,结合当地气象观测资料进行相关分析,研究树干不同高度树轮密度对气候要素的响应特征。结果表明: 同一树高下4种密度参数在整体上表现出较高的相关性,其中10、15、20 m树高相对显著;不同树高处晚材平均密度的一致性相对较好;不同树高处树轮密度对气候要素的响应存在差异,15 m树高处最大密度、晚材平均密度对上年7—9月、当年5—9月平均气温具有较好的响应。因此,在1.3 m处采集雪岭云杉样本存在对气温响应估计偏低的可能。.

To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.

We conducted a systematic literature review to obtain risk population-based fungal disease incidence or prevalence data from China. Data were categorized by risk factors and extrapolated by using most recent demographic figures. A total of 71,316,101 cases (5.0% of the population) were attributed to 12 risk factors and 17 fungal diseases. Excluding recurrent Candida vaginitis (4,057/100,000 women) and onychomycosis (2,600/100,000 persons), aspergillosis (317/100,000 persons) was the most common problem; prevalence exceeded that in most other countries. Cryptococcal meningitis, an opportunistic infection, occurs in immunocompetent persons almost twice as often as AIDS. The pattern of fungal infections also varies geographically; Talaromyces marneffei is distributed mainly in the Pearl River Basin, and the Yangtze River bears the greatest histoplasmosis burden. New host populations, new endemic patterns, and high fungal burdens in China, which caused a huge impact on public health, underscore the urgent need for building diagnostic and therapeutic capacity.

A phytochemical investigation on the stems of

Background Noninvasive monitoring of fetal development and the early detection of pregnancy-associated complications is challenging, largely due to the lack of information about the molecular spectrum during pregnancy. Recently, cell-free DNA in plasma was found to reflect the global nucleosome footprint and status of gene expression, and showed potential for noninvasive health monitoring during pregnancy. Objective(s) We aimed to test the relationships between plasma cell-free DNA profiles and pregnancy biology, and evaluate the use of cell-free DNA profile as a non-invasive method for physiological and pathological status monitoring during pregnancy. Study Design We used genome cell-free DNA sequencing data generated from non-invasive prenatal testing in a total of 2937 pregnant women. For each physiological and pathological conditions, features of cell-free DNA profile were identified using the discovery cohort, and support vector machines classifiers were built and evaluated using independent training and validation cohorts. Results We established nucleosome occupancy profiles at transcription start sites in different gestational trimesters, demonstrated the relationships between gene expression and cell-free DNA coverage at transcription start sites, and showed that the cell-free DNA profiles at transcription start sites represented the biological processes of pregnancy. In addition, using cell-free DNA data, nucleosome profiles of transcription factor binding sites were identified to reflect transcription factor footprint, which may help to reveal the molecular mechanisms underlying pregnancy. Finally, by using machine learning models on low coverage non-invasive prenatal testing data, we evaluated the use of cell-free DNA nucleosome profiles for distinguishing gestational trimesters, fetal gender, and fetal trisomy 21, and highlighted its potential utility for predicting physiological and pathological fetal conditions by using low coverage non-invasive prenatal testing data. Conclusion(s) Our analyses profiled nucleosome footprints and regulatory networks during pregnancy and established a noninvasive, proof-of-principle methodology for health monitoring during pregnancy.

In order to effectively improve the effect of blended learning, the paper describes a blended learning oriented full-dimensional teaching method. The author first analyzed the characteristics and applicability of each teaching activity involved in blended learning from both the teaching process and teaching method dimensions. On this basis, the authors put forward the corresponding methods for designing teaching activities and organizing teaching materials. Then, the paper takes practice in the course of "object-oriented programming" as an example, and analyzes the practical effect of the full-dimensional teaching method. The results show that the proposed blended learning oriented full-dimensional teaching method can meet the students' individual learning needs, enhance students' learning enthusiasm and initiative, as well as realize the overall improvement of students' learning effect.

SPOC (Small Private Online Course) teaching mode is a combination mode of online and offline teaching mode. It is the mainstream teaching mode at home and abroad, and also an effective teaching mode to effectively improve the quality of education. Based on the course of "Object-Oriented Programming" in the Software College of Northeast University, this paper applies the theories of SPOC teaching mode to construct and apply SPOC course. In the construction of this course, the emphasis is on leading the high-quality resources inside and outside the school into the course, so as to integrate the contents of inside and outside the school, and the integration of excellent courses at home and abroad. From the implementation effect, this kind of teaching mode can effectively improve students' participation in the classroom, enhance students' interests in extracurricular learning, effectively promote students' studying independently ability, and also greatly promote the improvement of teaching quality.

Background Cryptococcal meningitis (CM) is a significant source of mortality, the pathogenesis of which has not been fully understood, especially in non-HIV infected populations. We aimed to compare single nucleotide polymorphisms (SNPs) of Toll-like receptor (TLR) in non-HIV CM patients with those of healthy controls, and to assess the links among TLR SNPs, cytokine concentrations in cerebrospinal fluid (CSF), and clinical severity. Methods This observational cohort study was done in 2 stages: a discovery stage and a validation stage. We conducted a case-control genetic association study between 159 non-HIV CM patients and 468 healthy controls. TLR SNPs significantly related to susceptibility were further validated in a second cohort of 583 subjects from a certain district. Cytokine concentrations in CSF were used to evaluate the in situ immune response of CNS after infection. Correlations among TLR SNPs, CSF cytokine concentrations, and clinical severity were validated in a third prospective cohort of 99 previously untreated non-HIV CM patients. Logistic regression model was used to determine the independent predictors for disease severity. Findings In the discovery stage, the genotype distributions of 8 TLR SNPs in non-HIV CM patients exhibited a significant difference in comparison with controls, of which 3 SNPs remained statistically significant in patients without predisposing factors. In the validation stage, 5 of the 8 nominated TLR SNPs were found to influence CSF cytokine expression. Eighteen cytokines were significantly up-regulated in severely ill patients, among which 12 were affected by TLR2 rs3804099. The rs3804099 was also found in relation to disease severity. High IL-10 levels in CSF (OR 2*97, 95% CI 1*49-5*90; p=0*002) was suggested as an independent predictor for severity after adjusted for possible confounders. Interpretation TLR participate in both the occurrence and the pathogenesis of non-HIV CM. The in situ immune responses of CM were under genetic influence of TLR and contributed to disease severity. Our findings inform of an opportunity for early evaluation and treatment of non-HIV CM. TLR might also become a potential target on which to base host-directed immunotherapy. Funding: National Natural Science Foundation of China and National Key Basic Research Program of China (973 Program). Declaration of Interest: We declare no competing interests. Ethical Approval: Ethical approval was obtained from the medical ethics committee of Huashan Hospital, Mengchao Hepatobiliary Hospital, Fujian HIV/AIDS Diagnosis and Treatment Center, and No. 476 Hospital of Fuzhou General Hospital.

Plants accumulate the lipids phosphatidic acid (PA), diacylglycerol (DAG), and triacylglycerol (TAG) during cold stress, but how plants balance the levels of these lipids to mediate cold responses remains unknown. The enzymes ACYL-COENZYME A:DIACYLGLYCEROL ACYLTRANSFERASE (DGAT) and DIACYLGLYCEROL KINASE (DGK) catalyze the conversion of DAG to TAG and PA, respectively. Here, we show that DGAT1, DGK2, DGK3, and DGK5 contribute to the response to cold in Arabidopsis (Arabidopsis thaliana). With or without cold acclimation, the dgat1 mutants exhibited higher sensitivity upon freezing exposure compared with the wild type. Under cold conditions, the dgat1 mutants showed reduced expression of C-REPEAT/DRE BINDING FACTOR2 and its regulons, which are essential for the acquisition of cold tolerance. Lipid profiling revealed that freezing significantly increased the levels of PA and DAG while decreasing TAG in the rosettes of dgat1 mutant plants. During freezing stress, the accumulation of PA in dgat1 plants stimulated NADPH oxidase activity and enhanced RbohD-dependent hydrogen peroxide production compared with the wild type. Moreover, the cold-inducible transcripts of DGK2, DGK3, and DGK5 were significantly more up-regulated in the dgat1 mutants than in the wild type during cold stress. Consistent with this observation, dgk2, dgk3, and dgk5 knockout mutants showed improved tolerance and attenuated PA production in response to freezing temperatures. Our findings demonstrate that the conversion of DAG to TAG by DGAT1 is critical for plant freezing tolerance, acting by balancing TAG and PA production in Arabidopsis.

We investigate the generalized bilinear forms graph Γ d over a residue class ring Z p s . The graph Γ d is a connected vertex-transitive graph, and we completely determine its independence number, clique number, chromatic number and maximum cliques. We also prove that cores of both Γ d and its complement are maximum cliques. The graph Γ d is useful for error-correcting codes. We show that there is a largest independent set of Γ d which is a linear MRD code over Z p s .

Our previous work showed that polysaccharide isolated from Portulaca oleracea L. (POP) has an insulinotropic effect. The voltage-gated Na+ channel (VGSC) in the excitement phase plays an important role. This work aims to study the effect of POP on the voltage-gated Na+ channel current (INa) and its channel dynamic characteristics in insulin-secreting β-cell line (INS-1) cells of rat. Our results revealed that POP can inhibit the amplitude of INa and improve cell survival in a concentration-dependent manner. POP concentration of 0.5 mg mL−1 reduced the amplitude of INa, suppressed the INa of steady-state activation, shifted the steady-state inactivation curves of INa to negative potentials, prolonged the time course of INa recovery from inactivation, and enhanced the activity-dependent attenuation of INa. Furthermore, 0.5 mg mL−1 POP or low concentration of tetrodotoxin (TTX, a VGSC-specific blocker) partially inhibited INa and also improved insulin synthesis and cell survival. Collectively, these results revealed that POP protects INS-1 cells and enhances the insulin synthesis in INS-1 cells, and the mechanism through the partial inhibition on INa channel is strongly recommended.

Background/Aims: Islet beta cells (β-cells) are unique cells that play a critical role in glucose homeostasis by secreting insulin in response to increased glucose levels. Voltage-gated ion channels in β-cells, such as K + and Ca 2+ channels, contribute to insulin secretion. The response of voltage-gated Na + channels (VGSCs) in β-cells to the changes in glucose levels remains unknown. This work aims to determine the role of extracellular glucose on the regulation of VGSC. Methods: The effect of glucose on VGSC currents ( I Na ) was investigated in insulin-secreting β-cell line (INS-1) cells of rats using whole-cell patch clamp techniques, and the effects of glucose on insulin content and cell viability were determined using Enzyme-Linked Immunosorbent Assay (ELISA) and Methylthiazolyldiphenyl-tetrazolium Bromide (MTT) assay methods respectively. Results: Our results show that extracellular glucose application can inhibit the peak of I Na in a concentration-dependent manner. Glucose concentration of 18 mM reduced the amplitude of I Na , suppressed the I Na of steady-state activation, shifted the steady-state inactivation curves of I Na to negative potentials, and prolonged the time course of I Na recovery from inactivation. Glucose also enhanced the activity-dependent attenuation of I Na and reduced the fraction of activated channels. Furthermore, 18 mM glucose or low concentration of tetrodotoxin (TTX, a VGSC-specific blocker) partially inhibited the activity of VGSC and also improved insulin synthesis. Conclusion: These results revealed that extracellular glucose application enhances the insulin synthesis in INS-1 cells and the mechanism through the partial inhibition on I Na channel is involved. Our results innovatively suggest that VGSC plays a vital role in modulating glucose homeostasis.

A graph G is a core if every endomorphism of G is an automorphism. Let $$J_q(n,m)$$ be the Grassmann graph with parameters q, m, n. We prove that many Grassmann graphs are cores, and both $$J_2(2k,2)$$ and $$J_q(2^k,2)$$ are not cores. We also obtain the independence number of $$J_q(n,2)$$ . In further to study cores and coding theory, it is important to estimate the upper bound of the independence number of $$J_q(n,m)$$ . Using a vertex-transitive subgraph of $$J_q(n,m)$$ , we obtain upper bounds on the independence number of $$J_q(n,m)$$ , which are also an improvement of bounds for the size of constant dimension codes in a 2011 paper of Etzion and Vardy.

We investigate the bilinear forms graph Γ over the residue class ring modulo p s (where p is a prime number and s is a positive integer). First, we prove that the bilinear forms graph Γ is a connected vertex transitive graph. When p > 2 , Γ is distance-regular if and only if s = 1 . Next, we completely determine the valency of a vertex, the clique number, the independence number and the chromatic number of the bilinear forms graph Γ, respectively. Finally, we show that both Γ and the complement of Γ are not cores and their cores are complete.

Cordycepin has important neuroprotective effects in hypoxic or ischemic insult. However, the direct electrophysiological evidence of cordycepin's neuroprotection from hypoxic or ischemic insult remains unknown. Hence, in this study, the electrophysiological mechanism by which cordycepin protects against ischemic and hypoxic damages has been studied using an energy-deprivation injury model through whole-cell patch clamp techniques. Results revealed that cordycepin (80µM) significantly delayed hypoxia-induced membrane depolarization, including cordycepin reduced slope, and extended the duration of slow depolarization, prolonged the ability to generate spontaneous action potential (AP) firing, delayed the onset of rapid depolarization, and maintained the more hyperpolarized membrane potential after rapid depolarization. Additionally, cordycepin also delayed the hypoxia-induced decrease in the evoked AP amplitude. Furthermore, cordycepin can rescue the neuronal electrophysiological function after the 5min hypoxia pretreatment insult as seen the recovery on the evoked spike amplitude, membrane potential, and evoked AP latency during reoxygenation of hippocampal slices with cordycepin. Collectively, the results in this study provide direct evidence demonstrating the important neuroprotective effects of cordycepin against the hypoxic insult via improvement of the neuronal electrophysiological function, and the mechanism underlying the anti hypoxia-induced membrane depolarization is strongly recommended.

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A1R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

Cryptococcosis is one of the most common opportunistic infections in both immunocompetent and immunocompromised hosts. Although the cryptococcal antigen (CrAg) lateral flow assay (LFA) has been widely used in clinical settings due to its high sensitivity and specificity, the diagnostic value of a low CrAg LFA titers remains unclear. In this study, we performed a retrospective analysis of 149 HIV-negative patients with low CrAg LFA titers (≤1:10) in a Chinese tertiary hospital from January 2013 to December 2017, to evaluate the diagnostic value of low CrAg LFA titers in serum and cerebrospinal fluid (CSF) at different thresholds. Sensitivity and specificity of low CrAg LFA titers in patients with definitive diagnoses of cryptococcosis were 39.6% (95% CI, 29.7–50.1%) and 100% (95% CI, 69.2–100%), respectively, at a threshold of 1:10 in serum. A sensitivity of 72.9% (95% CI, 62.9–81.5%) and a decreased specificity of 70.0% (95% CI, 34.8–93.3%) were observed at a threshold of 1:5 in serum. No false-positive cases were identified in patients with low CrAg titers in CSF and all positive predictive values (PPVs) were 100%. Among the cases with low serum CrAg titers, lumbar puncture was performed in 97 patients and positive CSF CrAg titers were reported in 6 patients. In conclusion, the results of this study imply that low CrAg LFA titer, either in serum or CSF, is crucial for early diagnosis of cryptococcosis in HIV-negative patients, and lumbar puncture is recommended to be performed routinely for CSF testing when a positive low serum titer is reported. Cryptococcal meningitis should be considered seriously when the CSF CrAg titer is positive.

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1, AGD, sperm count, and mean DFI in the F2, and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1, sperm count in the F2, and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system.

The aim of the study was to elucidate the involvement of cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in the pathogenesis of primary focal hyperhidrosis (PFH). The hyperhidrosis mouse model was constructed using pilocarpine injection. The expression levels of CHRNA1 in sweat gland tissues of PFH patients and hyperhidrosis mice were compared using Western blots and quantitative real-time PCR (qRT-PCR) analyses. Sweat secretion in hyperhidrosis mice treated with small-interfering RNA (siRNA) targeting CHRNA1 (si-CHRNA1) or non-specific siRNA were compared. Sweat secretory granules in the sweat gland cells of hyperhidrosis mice were examined using transmission electron microscopy. The serum level of acetylcholine was measured using enzyme-linked immunosorbent assay, while markers associated with PFH, including Aquaporin 5 (AQP5) and Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), were assessed using immunohistochemical assay and Western blots. Brain-derived neurotrophic factor (BDNF) and Neuregulin 1 (NRG-1) in sympathetic ganglia axons of hyperhidrosis mice were quantified using Western blots. CHRNA1 up-regulation is a characteristic of the sweat glands of PFH patients and Hyperhidrosis mice. Silencing CHRNA1 decreased sweat secretion and the number of sweat secretory granules of hyperhidrosis mice. Serum acetylcholine, as well as AQP5 and CACNA1C expression in the sweat glands, was reduced by siCHRNA1. BDNF1 and NRG-1 levels in the sympathetic ganglia axons were also attenuated by siCHRNA1 treatment. CHRNA1 up-regulation is a potential biomarker of PFH and downregulating CHRNA1 could alleviate the symptoms of PFH through inactivating the sympathetic system.