Streptococcal arginine deiminase system defences macrophage bactericidal effect mediated by XRE family protein XtrSs.

The arginine deiminase system (ADS) has been identified in various bacteria and functions to supplement energy production and enhance biological adaptability. The current understanding of the regulatory mechanism of ADS and its effect on bacterial pathogenesis is still limited. Here, we found that the XRE family transcriptional regulator XtrSs negatively affected Streptococcus suis virulence and significantly repressed ADS transcription when the bacteria were incubated in blood. Electrophoretic mobility shift (EMSA) and lacZ fusion assays further showed that XtrSs directly bind to the promoter of ArgR, an acknowledged positive regulator of bacterial ADS, to repress ArgR transcription. Moreover, we provided compelling evidence that S. suis could utilize arginine via ADS to adapt to acid stress, while ΔxtrSs enhanced this acid resistance by upregulating the ADS operon. Moreover, whole ADS-knockout S. suis increased arginine and antimicrobial NO in the infected macrophage cells, decreased intracellular survival, and even caused significant attenuation of bacterial virulence in a mouse infection model, while ΔxtrSs consistently presented the opposite results. Our experiments identified a novel ADS regulatory mechanism in S. suis, whereby XtrSs regulated ADS to modulate NO content in macrophages, promoting S. suis intracellular survival. Meanwhile, our findings provide a new perspective on how Streptococci evade the host's innate immune system.

Control the greenhouse gas emission via mediating the dissimilatory iron reduction: Fulvic acid inhibit secondary mineralization of ferrihydrite.

Reducing methane emission is of great importance to control the global greenhouse effect. Dissimilatory iron reduction (DIR) coupling of organic matter decomposition may suppress methane production via reducing primary electron donors available for methanogenesis. However, during DIR, the amorphous iron oxides (e.g., ferrihydrite) are easy to transform into more stable crystalline iron minerals, which slowdowns the rate of DIR. Humic substance (HS) with redox activity has been extensively reported to facilitate DIR via "electron shuttles" mechanism, yet little known about the effect of HS on mediating the mineralization of iron oxides and the subsequent influences on DIR and methanogenesis. To clarify this, ferrihydrite and fulvic acid (FA) (as the model substance of HS) were supplied to anaerobic methanogenesis systems. Results showed that FA could significantly decrease the formation of crystalline iron oxides, enhance DIR rate by 13.72% and suppress methanogenesis by 25.13% compared to ferrihydrite supplemented only. By X-ray absorption spectra analysis, it was found that FA could complex with ferrihydrite via forming a Fe-C/O structure on the second shell of Fe atom. Quantum chemical calculation further confirmed that FA reduced the adsorption energy between Fe(II) and ferrihydrite. Our study suggested that rational use of HS to mediate mineralization pathway of iron oxides could efficiently improve the availability of iron oxides to drive DIR and control the conversion of organics into CH4 in natural or engineered systems.

Water pollution characteristics of inflowing rivers under different land-use patterns in the Daye Lake basin: pollution mode and management suggestions.

Land use/land cover (LULC) conditions can have a profound impact on the water quality of rivers, lakes, and other water bodies within a basin. Land use status of Daye Lake basin in 2019 has been shown by Landsat 8 OLI image, water quality of Daye Lake, and 12 inflowing rivers have been investigated once a month; this study provides a comprehensive analysis of the water pollution characteristics of the inflowing rivers and lake in the basin under different LULC patterns, and providing a reference for the scientific planning of land-use types in the basin and land use research in lake basins in subtropical areas. Pollutants are mainly introduced to Daye Lake from the west (such as Da Gang) and north (such as Linjiaju Gang), with concentrations gradually decreasing within the lake from west to east. Construction land is closely associated with the total nitrogen (TN), total phosphorus (TP), permanganate index (CODMn), and ammonia nitrogen (NH3-N) inputs to the basin, which can be trapped by vegetation. Agricultural dryland can contribute acid and dissolved oxygen (DO) to water. Precipitation can influence the input of pollutants, with a stronger effect on TN and weaker effect on TP. Pollutants accumulate from the inlets to the centre of the lake, with longer retention times during the dry season.

[Effect on the core symptoms in children with autism spectrum disorder treated with acupuncture at "ghost points" combined with the acupoints selected by syndrome differentiation].

OBJECTIVE: To explore the effect on the core symptoms in children with autism spectrum disorder (ASD) treated with acupuncture at "ghost points", combined with the acupoints selected by syndrome differentiation. METHODS: A total of 124 ASD children were divided into a control group and a treatment group according to random number table, 62 cases in each group. In the control group, the routine rehabilitation treatment was provided in all of children, while in the treatment group, acupuncture was exerted at "ghost points", combined with the acupoints selected by syndrome differentiation. Acupuncture treatment was conducted for 15 min each time, 5 days weekly, for 3 months totally. Before and after treatment, the children were assessed with autism spectrum rating scale (ASRS) in two groups. RESULTS: After treatment, the total score (T-score) of ASRS and the score of each sub-scale, e.g. peer socialization, adult socialization, social/emotional reciprocity, atypical language, stereotypy, repetitive behavior, sensory sensitivity, attention/self-regulation were all reduced remarkably as compared with those before treatment in intra-group comparison (P<0.05, P<0.01). Compared with the control group, the scores aforementioned were all significantly reduced in the treatment group (P<0.05). CONCLUSION: Acupuncture at "ghost poitns" combined with the acupoints selected by syndrome differentiation effectively relieves the core symptoms of ASD in children and improves the holistic therapeutic effect.

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.

BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

[The Therapeutic Effect of Acupuncture on Cerebral Palsy in Children with Language Retardation Using the Midnight-noon Ebb-flow Method Combined with Syndrome Differentiation].

OBJECTIVE: To determine the clinical effect of acupuncture treatment on cerebral palsy in children with language retardation using the Midnight-noon Ebb-flow method combined with syndrome differentiation. METHODS: One hundred and thirty-six children with cerebral palsy and language retardation were randomly divided into control group and treatment group. The control group received routine treatment for language rehabilitation, while the treatment group received acupuncture treatment using the Midnight-noon Ebb-flow method combined with syndrome differentiation for 3 months based on language rehabilitation. The children were assessed by sign-significate relations for language comprehension and language expression before and after treatment. RESULTS: After treatment, the development quotient scores for language comprehension and language expression were (60.37±4.64) and (51.13±3.81) in the control group, and (73.54±4.73) and (64.08±3.93) in the treatment group, and the differences were statistically significant compared with those before treatment in the same one group, respectively(P<0.05, P<0.01). The effects of the treatment group were statistically better than those of the control group (P<0.05). CONCLUSIONS: Acupuncture treatment using the Midnight-noon Ebb-flow method combined with syndrome differentiation has a better therapeutic effect in improving language comprehension and language expression, and promoting language development in children with cerebral palsy.

Cultural influences behind cholera transmission in the Far North Region, Republic of Cameroon: a field experience and implications for operational level planning of interventions.

INTRODUCTION: In recent years, the Far North Region of Cameroon has experienced serious and recurrent cholera outbreaks. Yet, understanding of cultural influences on outbreaks and spread remain poorly understood. This qualitative study explored cultural influences on cholera exposure in this region. METHODS: Interviews and group discussions were conducted in two phases. Phase I involved key informants and phase II included focus group and household discussions. Thematic techniques including word repetition, key-indigenous-terms, and key-words-in-context were used for qualitative data analysis. RESULTS: Key informants attributed cholera etiology to dirt and spread through water (caneri) and food (group eating or faire-un-rond) while group discussions attributed it to a reprimand from god and transmission through the air. Participants suggested that funerals, weddings, open defecation, and mountaintop burial might influence cholera exposure and facilitate its spread. Hospital avoidance and non-adherence with cholera treatment regimens were linked to favorable beliefs about traditional medicine (rural-urban mentality confrontation). Furthermore, a multiplicity of ethnic languages, mistrust of message sources, culture of dependency and sentimental animal husbandry were barriers to the reception of public health messages. CONCLUSION: Many participants had limited scientific knowledge about cholera etiology and transmission. The cultural practice of mountain burial seemed to explain the high cholera attack rate in the mountainous terrain compared to the floodplains. Cultural factors are likely to play important roles in the exposure to and spread of cholera. Understanding cultural context, individual and community perceptions of risk and disease may help public health agencies in response to outbreak prevention and control.

[Observation on Effectiveness of Acupuncture Treatment of Children with Spastic Cerebral Palsy by Stimulating Acupoints Selected According to the Day to Match the Heavenly Stems and Earthly Branches].

OBJECTIVE: To evaluate the clinical effectiveness of acupuncture in the treatment of spastic cerebral palsy (CP) children by stimulating acupoints selected according to the day to match the heavenly stems and earthly branches (Ziwu Liu-zhu Najia Zhenfa). METHODS: A total of 130 CP patients were randomized into a control group and a treatment group (n=65 in each). Both groups were given with routine rehabilitation therapy, while the treatment group additionally received 3 months' acupuncture intervention. All patients were assessed before and after treatment with gross motor function measure (GMFM-88), mo-dified Ashworth scale (MAS) and activities of daily living (ADL) in cerebral palsy. RESULTS: After the treatment, the control group scored (25.12±2.74) points in GMFM-88, (1.53±0.71) points in MAS, (19.25±5.08) points in ADL, while the treatment group were respectively (31.87±2.58) points in GMFM-88, (1.07±0.74) points in MAS, (25.67±6.15) points in ADL. Both groups experienced significant improvement in increasing GMFM-88 and ADL scores, and reducing MAS score compared to those before treatment (P<0.05, P<0.01), and the effects of the treatment group were evidently superior to those of the control group in increasing GMFM-88 and ADL scores, and reducing MAS score (P<0.05). CONCLUSIONS: The "Ziwu Liuzhu Najia Zhenfa" acupuncture achieved greater improvement in gross motor function and reduction in muscular tone and enhancement of capacity of daily living activity.

Synthesis, molecular docking and biological evaluation of 3-arylfuran-2(5H)-ones as anti-gastric ulcer agent.

3-Arylfuran-2(5H)-one derivatives show good antibacterial activity and were determined as tyrosyl-tRNA synthetase (TyrRS) inhibitors. In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to treat infections caused by Helicobacter pylori. Twenty 3-arylfuran-2(5H)-ones were synthesized and evaluated for anti-H. pylori, antioxidant and anti-urease activities which are closely interconnected with H. pylori infection. The results displayed that some of the compounds show excellent antioxidant activity, and good anti-H. pylori and urease inhibitory activities. Out of these compounds, 3-(3-methylphenyl)furan-2(5H)-one (b9) showed the most potent antioxidant activity (IC50=8.2 µM) and good anti-H. pylori activity (MIC50=2.6 µg/mL), and it can be used as a good candidate for discovering novel anti-gastric ulcer agent.

Structural and Functional Diversity of Peptide Toxins from Tarantula Haplopelma hainanum (Ornithoctonus hainana) Venom Revealed by Transcriptomic, Peptidomic, and Patch Clamp Approaches.

Spider venom is a complex mixture of bioactive peptides to subdue their prey. Early estimates suggested that over 400 venom peptides are produced per species. In order to investigate the mechanisms responsible for this impressive diversity, transcriptomics based on second generation high throughput sequencing was combined with peptidomic assays to characterize the venom of the tarantula Haplopelma hainanum. The genes expressed in the venom glands were identified, and the bioactivity of their protein products was analyzed using the patch clamp technique. A total of 1,136 potential toxin precursors were identified that clustered into 90 toxin groups, of which 72 were novel. The toxin peptides clustered into 20 cysteine scaffolds that included between 4 and 12 cysteines, and 14 of these groups were newly identified in this spider. Highly abundant toxin peptide transcripts were present and resulted from hypermutation and/or fragment insertion/deletion. In combination with variable post-translational modifications, this genetic variability explained how a limited set of genes can generate hundreds of toxin peptides in venom glands. Furthermore, the intraspecies venom variability illustrated the dynamic nature of spider venom and revealed how complex components work together to generate diverse bioactivities that facilitate adaptation to changing environments, types of prey, and milking regimes in captivity.

The association between hantavirus infection and selenium deficiency in mainland China.

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.

A silica-gold-silica nanocomposite for photothermal therapy in the near-infrared region.

The focus of this work was to study the photothermal effect of a silica-gold-silica nanocomposite in the near-infrared (NIR) region. The NIR region is considered a biological window because living cells and tissues have low light scattering and adsorption in this region. Both a laser source and a tungsten lamp source were used in this study. The critical parameters for photothermal efficiency, including nancomposite concentration and irradiation time, were evaluated. The penetration of the nanocomposites into mammalian cells was also investigated. With laser irradiation, the nanocomposite showed a significant photothermal effect in the NIR region. The maximal temperature that the nanocomposites could reach was 51.9 °C. Vybrant assays showed that 5 min of laser irradiation along with the nanocomposite caused target cell death through both apoptosis (59%) and necrosis (31%), while controls showed minimal effects. The nanocomposite may be a potential light-absorbing agent for NIR fluorescence-guided photothermal therapy.

[Efficacy and safety of combination of sorafenib and transarterial chemoembolization in treating primary hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of the combination of sorafenib and transarterial chemoembolization (TACE)in the treatment of primary hepatocellular carcinoma (HCC). METHODS: The clinical data of 10 patients with unresectable HCC treated by sorafenib combined with TACE in the Department of Radiology, the First Hospital of China Medical University were retrospectively analyzed. The efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors assessment. Survival was analyzed by Kaplan-Meier method. Safety was evaluated according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0. RESULTS: Among the 10 patients, 2 achieved complete response, 3 achieved partial response, 3 achieved stable disease, and 2 experienced progressive disease. The median overall survival of the cohort was 29.5 months. Different degree of adverse drug reactions (ADRs) occurred in 9 patients but all were at grade 3 or lower. The most common ADRs were hand-foot skin reaction (7/10) and diarrhea (6/10). CONCLUSION: The combination of sorafenib and TACE is an effective and safe treatment for HCC.

A turn-on fluorescent nanoprobe for selective determination of selenium(IV).

A turn-on fluorescent nanoprobe was developed for selective determination of selenium(IV). A trace amount of selenium, as an essential nutrient, plays an important role in human health. It has been proven that a selenium deficiency will result in serious health problems. The developed nanoprobe is capable of in situ detection of selenium with target-induced signaling, and no separation step is needed. The nanoprobe consists of a silica nanoparticle core and a coating layer containing selenium(IV)-induced fluorescent molecules, 3,3'-diaminobenzidine (DAB). The nanoprobes have no fluorescence signals if they are not exposed to selenium(IV). However, the nanoprobes will be "turned on", with fluorescence, when they bind to the targets of selenium(IV). With this strategy, the selenium(IV) are first collected and enriched on a small domain of the nanoprobes. Then, with an excitation at 420 nm, the nanoprobes emit fluorescence signals at 530 nm. The fluorescence intensity is proportional to the selenium concentration. A fluorescence microscope was used to monitor the process of enriching and collecting of the selenium(IV) by the nanoprobes. The optimal conditions for the determination of selenium(IV) using the nanoprobe were investigated including pH, solvent, and linear range. The interference from common metal ions was studied as well. This study is expected to shed light on how to design turn-on fluorescent nanoprobes for in situ monitoring of a wide variety of targets in biological processes.

[Study of the Tangut Prescription Sanxiandan unearthed in Heishuicheng].

Prescriptions (ИHB.NO.4384) in the10th Volume of Heishuicheng Manuscripts Collected in Russia covered 9 pages. The 4(th) and the 7(th) pages recorded a prescription with no name and composed of Radix Aconiti, Atractylodes lan and Foeniculumvulgare. By checking Chinese Medical books, the name of this prescription was probably Sanxiandan and it may have been recorded in Chenshi Jingyanfang for the first time. Chenshi Jingyanfang is not extant now but its narrative style, which is different from that of the Tangut prescription, could be speculated upon from other literature that mentioned it. So those Tangut prescriptions could have been compiled according to some Chinese Medical books after Chunyou Periods.

[Analysis of severe complications after transcatheter arterial chemoembolization for primary hepatocellular carcinoma].

OBJECTIVE: To investigate the cause and treatment as well as prevention measures of rarely occurring severe complications after transcatheter arterial chemoembolization (TACE) for primary hepatic carcinoma. METHODS: 573 consecutive patients with primary hepatic carcinoma underwent a total of 1252 TACE procedures from January 2005 to July 2007. All the patients who developed complications after TACE received imaging and biochemical examinations. The cause, treatment and preventive measures of the complications in the 573 cases were analyzed. RESULTS: There were upper gastrointestinal hemorrhage in 3 cases, hepatic failure in 4, pulmonary embolism in 1, cholecystitis in 4, hepatic encephalopathy in 2, gastric perforation in 1, and intrahepatic biloma in 2 cases. Two patients died of the complications: 1 of hepatic failure and 1 of gastric perforation. CONCLUSION: The rarely occurring severe complications after transcatheter arterial chemoembolization for primary hepatic carcinoma is correlated with poor hepatic function and portal hypertension before therapy, overdose and reflux of chemotherapeutic agents or allotopic chemoembolism, etc. It can be reduced or prevented through careful selection of proper cases before the treatment, close observation, and protection of hepatic function and gastric mucosa after treatment.

Observation on conditions and related factors of Keshan disease in Shandong province, 1990-2007 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To observe the serial changes of condition and related factors of Keshan disease (KSD) and provide the scientific basis for disease control and further research.</p><p><b>METHODS</b>The villages in KSD epidemic area of Juxian, Yishui, Pingyi, Zoucheng counties were selected. Since 1990, every five-year was counted as a stage. For the first to third stage, 3-14 year-old residents and over 14 year-old suspicious patients were selected as surveillance subjects. And in the fourth stage, all residents were selected as surveillance subjects. The same group of surveillance subjects in each stage were observed consecutively for 5 years. Surveillance contents included physical checkup, electrocardiogram (ECG) and Xray. At the same time, the selenium (Se) concentration in hair, wheat, corn and sweet potato was measured. The economic income and grain availability were also investigated.</p><p><b>RESULTS</b>Totally, 14,510 cases were visited during 18 years. The incidence of KSD was 3.02% in the first stage, 2.31% in the second stage, 3.57% in the third stages and 3.65% in the fourth stage. Totally, 14,510 cases were examined by ECG, 809 cases showed the abnormal ECG and the total incidence of abnormal ECG was 5.49%. The incidence of abnormal ECG was 3.52% -5.24% from 1990 to 2004 but was 10.97%-10.91% from 2005 to 2007. 732 of hair samples, 701 of wheat samples, 615 of corn samples and 643 of sweet potato samples were collected and the Se concentration was determined by the fluorescent method. Se levels in hair samples had increased (P < 0.05) year by year but Se levels in food have not changed significantly. The economic income and grain availability had increased gradually from 535.8 yuan and 254.6 kg per person in 1990 to 2968.0 yuan and 602.0 kg per person in 2007.</p><p><b>CONCLUSION</b>The condition of KSD was in a stable situation in Shandong Province. Related factors improvement should be an important environmental condition.</p>

[Effect of jiuxinfumai injection on L-type calcium currents in single guinea pig ventricular myocytes].

OBJECTIVE: To determine the effect of 311 and 417, both active ingredients isolated from Jiuxinfumai injection (Citrus Aurantium) on L-type calcium currents (I(Ca-L)) in ventricular myocytes of guinea pigs. METHODS: Single myocytes were dissociated by enzymatic dissociation method. The whole-cell patch-clamp recording technique was used to record the change of calcium current after the administration of 311and 417. RESULTS: 311 (10, 25, 50, 100 mmol/L) increased the (I(Ca-L)) by 8.27%, 27.29%, 41.01%, and 48.74% (P < 0.05), respectively. 417 (10, 25, 50, 100 mmol/L) increased the (I(Ca-L)) by 10.05%, 30.12%, 43.05%, and 51.90% (P < 0.05), respectively. Both 311 and 417 changed the (I(Ca-L)) significantly in a concentration-dependent manner. They did not change the shape of I-V cruves. CONCLUSION: 311 and 417 can increase I(I(Ca-L)) n ventricular myocytes of guinea pigs in a dose-response manner.

An aqueous extract of Rubus chingii fruits protects primary rat hepatocytes against tert-butyl hydroperoxide induced oxidative stress.

Different in vitro free radical generating systems were used to assess the antioxidative activity of aqueous extracts of the five herbal components of Wu-zi-yan-zong-wan, a traditional Chinese medicinal formula with a long history of use for tonic effects. Fructus Rubi [Rubus chingii (Rosaceae) fruits] was found to be the most potent. It was further investigated using the primary rat hepatocyte system. tert-Butyl hydroperoxide (t-BHP) was used to induce oxidative stress. Being a short chain analog of lipid hydroperoxide, t-BHP is metabolized into free radical intermediates by the cytochrome P450 system in hepatocytes, which in turn, initiate lipid peroxidation, glutathione depletion and cell damage. Pre-treatment of hepatocytes with Fructus Rubi extract (50 microg/ml to 200 microg/ml) for 24 h significantly reversed t-BHP-induced cell viability loss, lactate dehydrogenase leakage and the associated glutathione depletion and lipid peroxidation. The amount of reactive oxygen species formed was also decreased as visualized by the fluorescence probe 2',7'-dichlorofluorescin diacetate. These results suggested that Fructus Rubi was useful in protecting against t-BHP-induced oxidative damage and may also be capable of attenuating cytotoxicity of other oxidants.