Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds.

Previously, we only apply a traditional Chinese medicine (TCM) Danshen-Chuanxiong-Honghua (DCH) for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA) for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO). We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg) and FA (100 mg/kg) improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds

Olfaction in Host Plant Selection of the Soybean Aphid Aphis glycines

Results from a behavioral study using a four-armed olfactometer (Vet et al, 1983) showed that alate and apterous virginopara of Aphis glycines were clearly attracted or arrested by volatiles from Glycine max, its secondary host plant, and Rhamnus davurica, its primary host plant. The attractiveness of G. max was greater than that of R. davurica. Chemical analysis indicated that there is some difference in the volatile profiles between these two plant species. The volatiles from two nonhost plant species Gossypium hirsutrm and Cucumis sativa, which are the most suitable host plants of another aphid A. gossypii closely related to A. glycines, were found to be neutral. However, the odors of Luffa cylindrical and Cucurbita pepo significantly repelled the alate virginopara of A. glycines. Thus, the olfactory response of A. glycines to these host and nonhost plants implies the evolutionary transition of A. glycines in host plant specificity. Blending the odors from nonhost plants Gossypium hirsutum, Luffa cylindrical and Cucurbita pepo with the attractive odor of host plant G. max blocked the attractiveness of the latter to the alate virginopara of A. glycines. It thus appeared that attractiveness of host plant to aphids can be disrupted by the presence of nonhost plant volatiles which have presumably masked the host plant odor, and the lack of attractiveness of the blended odors is caused by the change in volatile profile.Originating text in Chinese.Citation: Du, Yongjun, Yan, Fushun, Han, Xinli, Zhang, Guangxue. (1994). Olfaction in Host Plant Selection of the Soybean Aphid Aphis glycines. Kun chong xue bao. Acta entomologica Sinica, 37(4), 385-392

Neuron-Radial Glial Cell Communication via BMP/Id1 Signaling Is Key to Long-Term Maintenance of the Regenerative Capacity of the Adult Zebrafish Telencephalon

The central nervous system of adult zebrafish displays an extraordinary neurogenic and regenerative capacity. In the zebrafish adult brain, this regenerative capacity relies on neural stem cells (NSCs) and the careful management of the NSC pool. However, the mechanisms controlling NSC pool maintenance are not yet fully understood. Recently, Bone Morphogenetic Proteins (BMPs) and their downstream effector Id1 (Inhibitor of differentiation 1) were suggested to act as key players in NSC maintenance under constitutive and regenerative conditions. Here, we further investigated the role of BMP/Id1 signaling in these processes, using different genetic and pharmacological approaches. Our data show that BMPs are mainly expressed by neurons in the adult telencephalon, while id1 is expressed in NSCs, suggesting a neuron-NSC communication via the BMP/Id1 signaling axis. Furthermore, manipulation of BMP signaling by conditionally inducing or repressing BMP signaling via heat-shock, lead to an increase or a decrease of id1 expression in the NSCs, respectively. Induction of id1 was followed by an increase in the number of quiescent NSCs, while knocking down id1 expression caused an increase in NSC proliferation. In agreement, genetic ablation of id1 function lead to increased proliferation of NSCs, followed by depletion of the stem cell pool with concomitant failure to heal injuries in repeatedly injured mutant telencephala. Moreover, pharmacological inhibition of BMP and Notch signaling suggests that the two signaling systems cooperate and converge onto the transcriptional regulator her4.1. Interestingly, brain injury lead to a depletion of NSCs in animals lacking BMP/Id1 signaling despite an intact Notch pathway. Taken together, our data demonstrate how neurons feedback on NSC proliferation and that BMP1/Id1 signaling acts as a safeguard of the NSC pool under regenerative conditions

Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

<p>Abstract</p> <p>Background</p> <p>The incidence of dengue, an infectious disease caused by dengue virus (DENV), has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs) has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated.</p> <p>Results</p> <p>By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses.</p> <p>Conclusions</p> <p>Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.</p

Integrative analysis of different low-light-tolerant cucumber lines in response to low-light stress

IntroductionLow light stress inhibits plant growth due to a line of physiological disruptions in plants, and is one of the major barriers to protected cucumber cultivation in northern China.MethodsTo comprehensively understand the responses of cucumber seedlings to low-light stress, the low-light-tolerant line (M67) and The low-light-sensitive line (M14) were conducted for the analysis of photosynthetic phenotype, RNA sequencing (RNA-seq) and the expression level of photosynthesis-related genes in leaves under low-light stress and normal light condition (control).ResultsThe results showed that there was a sharp decrease in the photosynthate accumulation in the leaves of the sensitive line, M14, resulting in a large decrease in the photosynthetic rate (Pn) (with 31.99%) of leaves compared to that of the control, which may have been caused by damage to chloroplast ultrastructure or a decrease in chlorophyll (Chl) content. However, under the same low-light treatment, there was no large drop in the photosynthate accumulation and even no decrease in Pn and Chl content for the tolerant line, M67. Moreover, results of gene expression analysis showed that the expression level of genes CsPsbQ (the photosystem II oxygen-evolving enhancer protein 3 gene) and Csgamma (ATPase, F1 complex gene) in the M14 leaves decreased sharply (by 35.04% and 30.58%, respectively) compared with the levels in the M67 leaves, which decreased by 14.78% and 23.61%, respectively. The expression levels of genes involved in Chl synthesis and carbohydrate biosynthesis in the leaves of M14 decreased markedly after low-light treatment; in contrast, there were no sharp decreases or changes in leaves of M67.DiscussionOver all, the ability of cucumber to respond to low-light stress, as determined on the basis of the degree of damage in leaf structure and chloroplast ultrastructure, which corresponded to decreased gene expression levels and ATP phosphorylase activity, significantly differed between different low-light-tolerant lines, which was manifested as significant differences in photosynthetic capacity between them. Results of this study will be a reference for comprehensive insight into the physiological mechanism involved in the low-light tolerance of cucumber

Evidence against a role for jaagsiekte sheep retrovirus in human lung cancer

Background: Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats that can be transmitted by aerosols produced by infected animals. Virus entry into cells is initiated by binding of the viral envelope (Env) protein to a specific cell-surface receptor, Hyal2. Unlike almost all other retroviruses, the JSRV Env protein is also a potent oncoprotein and is responsible for lung cancer in animals. Of concern, Hyal2 is a functional receptor for JSRV in humans. Results: We show here that JSRV is fully capable of infecting human cells, as measured by its reverse transcription and persistence in the DNA of cultured human cells. Several studies have indicated a role for JSRV in human lung cancer while other studies dispute these results. To further investigate the role of JSRV in human lung cancer, we used highly-specific mouse monoclonal antibodies and a rabbit polyclonal antiserum against JSRV Env to test for JSRV expression in human lung cancer. JSRV Env expression was undetectable in lung cancers from 128 human subjects, including 73 cases of bronchioalveolar carcinoma (BAC; currently reclassified as lung invasive adenocarcinoma with a predominant lepidic component), a lung cancer with histology similar to that found in JSRV-infected sheep. The BAC samples included 8 JSRV DNA-positive samples from subjects residing in Sardinia, Italy, where sheep farming is prevalent and JSRV is present. We also tested for neutralizing antibodies in sera from 138 Peruvians living in an area where sheep farming is prevalent and JSRV is present, 24 of whom were directly exposed to sheep, and found none. Conclusions: We conclude that while JSRV can infect human cells, JSRV plays little if any role in human lung cancer

Multidimensional risk factor analysis of acute low back pain progressing to chronicity: a longitudinal cohort study protocol

IntroductionApproximately 40% of patients with acute low back pain (LBP) develop chronic low back pain, which significantly increases the risk of poor prognosis. To reduce the risk of acute LBP becoming chronic, effective preventive strategies are needed. Early identification of risk factors for the development of chronic LBP can help clinicians choose appropriate treatment options and improve patient outcomes. However, previous screening tools have not considered medical imaging findings. The aim of this study is to identify factors that can predict the risk of acute LBP becoming chronic based on clinical information, pain and disability assessment, and MRI imaging findings. This protocol describes the methodology and plan for investigating multidimensional risk factors for acute LBP becoming chronic, in order to better understand the development of acute LBP and prevent chronic LBP.MethodsThis is a prospective multicenter study. We plan to recruit 1,000 adult patients with acute low back pain from four centers. In order to select four representative centers, we find the larger hospitals from different regions in Yunnan Province. The study will use a longitudinal cohort design. Patients will undergo baseline assessments upon admission and will be followed up for 5 years to collect the time of chronicity and associated risk factors. Upon admission, patients will be collected detailed demographic information, subjective and objective pain scores, disability scale, and lumbar spine MRI scanning. In addition, patient’s medical history, lifestyle, psychological factors will be collected. Patients will be followed up at 3 months, 6 months, 1 year, 2 years and up for 5 years after admission to collect the time of chronicity and associated factors. Multivariate analysis will be used to explore the multidimensional risk factors affecting the chronicity of acute LBP patients (such as age, gender, BMI, degree of intervertebral disc degeneration, etc.), and survival analysis will be performed to explore the impact of each factor on the time of chronicity.Ethics and disseminationThe study has been approved by the institutional research ethics committee of each study center (main center number: 2022-L-305). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders

Critical Epitopes in the Nucleocapsid Protein of SFTS Virus Recognized by a Panel of SFTS Patients Derived Human Monoclonal Antibodies

BACKGROUND: SFTS virus (SFTSV) is a newly discovered pathogen to cause severe fever with thrombocytopenia syndrome (SFTS) in human. Successful control of SFTSV epidemic requires better understanding of the antigen target in humoral immune responses to the new bunyavirus infection. METHODOLOGY/PRINCIPAL FINDINGS: We have generated a combinatorial Fab antibody phage library from two SFTS patients recovered from SFTSV infection. To date, 94 unique human antibodies have been generated and characterized from over 1200 Fab antibody clones obtained by screening the library with SFTS purified virions. All those monoclonal antibodies (MAbs) recognized the nucleocapsid (N) protein of SFTSV while none of them were reactive to the viral glycoproteins Gn or Gc. Furthermore, over screening 1000 mouse monoclonal antibody clones derived from SFTSV virions immunization, 462 clones reacted with N protein, while only 16 clones were reactive to glycoprotein. Furthermore, epitope mapping of SFTSV N protein was performed through molecular simulation, site mutation and competitive ELISA, and we found that at least 4 distinct antigenic epitopes within N protein were recognized by those human and mouse MAbs, in particular mutation of Glu10 to Ala10 abolished or significantly reduced the binding activity of nearly most SFTS patients derived MAbs. CONCLUSIONS/SIGNIFICANCE: The large number of human recombinant MAbs derived from SFTS patients recognized the viral N protein indicated the important role of the N protein in humoral responses to SFTSV infection, and the critical epitopes we defined in this study provided molecular basis for detection and diagnosis of SFTSV infection