[Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study]. / ä¸åŒè§’åº¦æ³¨å ¥è‚ºè¡¨é¢æ´»æ€§ç‰©è´¨å¯¹æ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å’Œé¢ å† å‡ºè¡€çš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

[Platelet-rich Plasma Induces M2 Macrophage Polarization via Regulating AMPK Singling Pathway].

OBJECTIVE: To investigate the role of platelet-rich plasma (PRP) in inducing the M2 macrophage polarization via regulating AMPK singling pathway. METHODS: The expressions of M1 marker CD11c and M2 marker CD206 in macrophages of blank control group, LPS group, LPS+PRP group, and LPS+PRP+Compound C group were detected by flow cytometry. Western blot was used to observe the effects of PRP on the expression of AMPK-mTOR signaling pathway-related proteins at different times (12 h, 18 h and 24 h) after LPS treatment. RNA interference technology was used to silence the expression of AMPK in macrophages, and the expression of TGF-ß protein was subsequently examined by Western blot. RESULTS: LPS significantly reduced the expression of CD206 and increased the expression of CD11c (P <0.05). After the addition of PRP, the expression of CD206 was significantly increased (P <0.05), while the expression of CD11c was significantly decreased (P <0.05). Compared with LPS group, PRP treatment significantly increased the expressions of p-AMPK and p-ULK1 proteins at 12 h, 18 h and 24 h, while significantly decreased the expression of p-mTOR protein (P <0.05). After the addition of AMPK inhibitor Compound C, the expression of CD206 was significantly reduced (P <0.05) and the expression of CD11c was significantly increased compared with LPS+PRP group (P <0.05). After silencing the expression of AMPK in macrophages, the promotion effect of PRP on TGF-ß was significantly reduced (P <0.05). CONCLUSION: PRP can stimulate the transformation of macrophages to M2 type via AMPK signalling pathway.

N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry.

IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

Assessment and sero-diagnosis for coronaviruses with risk of human spillover.

Zoonotic coronaviruses (CoVs) caused major human outbreaks in the last two decades. One of the biggest challenges during future CoV disease is ensuring rapid detection and diagnosis at the early phase of a zoonotic event, and active surveillance to the zoonotic high-risk CoVs appears the best way at the present time to provide early warnings. However, there is neither an evaluation of spillover potential nor diagnosis tools for the majority of CoVs. Here, we analyzed the viral traits, including population, genetic diversity, receptor and host species for all 40 alpha- and beta-CoV species, where the human-infecting CoVs are from. Our analysis proposed 20 high-risk CoV species, including 6 of which jumped to human, 3 with evidence of spillover but not to human and 11 without evidence of spillover yet, which prediction were further supported by an analysis of the history of CoV zoonosis. We also found three major zoonotic sources: multiple bat-origin CoV species, the rodent-origin sub-genus Embecovirus and the CoV species AlphaCoV1. Moreover, the Rhinolophidae and Hipposideridae bats harbour a significantly higher proportion of human-threatening CoV species, whereas camel, civet, swine and pangolin could be important intermediate hosts during CoV zoonotic transmission. Finally, we established quick and sensitive serologic tools for a list of proposed high-risk CoVs and validated the methods in serum cross-reaction assays using hyper-immune rabbit sera or clinical samples. By comprehensive risk assessment of the potential human-infecting CoVs, our work provides a theoretical or practical basis for future CoV disease preparedness.

Cingulate cGMP-dependent protein kinase I facilitates chronic pain and pain-related anxiety and depression.

ABSTRACT: Patients with chronic pain often experience exaggerated pain response and aversive emotion, such as anxiety and depression. Central plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion, which has been reported to involve activation of NMDA receptors. Numerous studies have documented the key significance of cGMP-dependent protein kinase I (PKG-I) as a crucial downstream target for the NMDA receptor-NO-cGMP signaling cascade in regulating neuronal plasticity and pain hypersensitivity in specific regions of pain pathway, ie, dorsal root ganglion or spinal dorsal horn. Despite this, whether and how PKG-I in the ACC contributes to cingulate plasticity and comorbidity of chronic pain and aversive emotion has remained elusive. Here, we uncovered a crucial role of cingulate PKG-I in chronic pain and comorbid anxiety and depression. Chronic pain caused by tissue inflammation or nerve injury led to upregulation of PKG-I expression at both mRNA and protein levels in the ACC. Knockdown of ACC-PKG-I relieved pain hypersensitivity as well as pain-associated anxiety and depression. Further mechanistic analysis revealed that PKG-I might act to phosphorylate TRPC3 and TRPC6, leading to enhancement of calcium influx and neuronal hyperexcitability as well as synaptic potentiation, which results in the exaggerated pain response and comorbid anxiety and depression. We believe this study sheds new light on the functional capability of ACC-PKG-I in modulating chronic pain as well as pain-associated anxiety and depression. Hence, cingulate PKG-I may represent a new therapeutic target against chronic pain and pain-related anxiety and depression.

Three new compounds from Anoectochilus roxburghii (Wall.) Lindl.

In this study, three new compounds, roxburic acid A (1) and two flavone glycosides isorhamnetin-3-O-α-L-rhamnosyl-(1→6)-ß-D-glucopyranose-(1→3)-ß-D-glucopyranoside (2), and kaempferol-7-O-ß-D-glucopyranosyl-(1→3)-ß-D-glucopyranoside (3) were isolated from an ethanol extract of the fresh Anoectochilus roxburghii (Wall.) Lindl., together with 10 known compounds (4-13). The structures of these compounds were comprehensively characterized by HR-ESI-MS, 1H NMR, 13C NMR, and 2 D-NMR. The DPPH free radical scavenging activity of the isolated compounds was evaluated, and the results showed that kaempferol-7-O-ß-D-glucopyranosyl- (1→3) -ß-D-glucopyranoside (3) and rutin (11) has the potential antioxidant activity with IC50 values of 139 µg/mL and 22.5 µg/mL respectively.

Cerebral Small Vessel Disease: A Bibliometric Analysis.

Cerebral small vessel disease is a common neurological disease, and its incidence is increasing year by year worldwide. In recent years, research on cerebral small vessel disease has gained more and more attention. Our research aims to visualize publications to identify the hotspots and frontiers of cerebral small vessel disease research, and to provide reference and guidance for further research. Publications related to cerebral small vessel disease were searched from the Web of Science Core Collection and screened according to inclusion criteria. CiteSpace 5.8.R3 was used to evaluate and visualize results, including generating web maps and analyzing annual publications, countries, institutions, bibliographic and co-cited references, and keywords; in this article, we use CiteSpace and VOSviewer for the 2012 Cerebral small vessel disease and bibliometric analysis from January 1, 2022 to April 30, 2022. A total of 3037 papers related to cerebral small vessel disease were retrieved, and the number of published papers showed a steady upward trend. Among them, Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration, the most symbolic references in the field of cerebral small vessel disease have been cited a total of 438 times. Stroke is the most active journal (227 articles) and USA publishes up to 800 articles. Harvard Med SchUniv Edinburgh (133 papers) and Charidimou (85 papers) are the institutions and authors who have made the most contributions in this field, respectively. Among the keywords, most of them are related to the pathogenesis of cerebral small vessel disease. After 2018, gut-brain axis and cortex are the keywords with the strongest number of cited outbreaks. There is increasing evidence that cerebral small vessel disease is a research frontier and may remain a research hotspot in the future.

QiShenYiQi Pill Ameliorates Cardiac Fibrosis After Pressure Overload-Induced Cardiac Hypertrophy by Regulating FHL2 and the Macrophage RP S19/TGF-ß1 Signaling Pathway.

Purpose: Heart failure (HF) is a leading cause of morbidity and mortality worldwide, and it is characterized by cardiac hypertrophy and fibrosis. However, effective treatments are not available to block cardiac fibrosis after cardiac hypertrophy. The QiShenYiQi pill (QSYQ) is an effective treatment for chronic HF. However, the underlying mechanism remains unclear. Methods: In the present study, a pressure overload-induced cardiac hypertrophy model was established in rats by inducing ascending aortic stenosis for 4 weeks. QSYQ was administered for 6 weeks, and its effects on cardiac fibrosis, myocardial apoptosis, RP S19 release, macrophage polarization, TGF-ß1 production, and TGF-ß1/Smad signaling were analyzed. In vitro studies using H9C2, Raw264.7, and RDF cell models were performed to confirm the in vivo study findings and evaluate the contribution to the observed effects of the main ingredients of QSYQ, namely, astragaloside IV, notoginsenoside R1, 3,4-dihydroxyl-phenyl lactic acid, and Dalbergia odorifera T. C. Chen oil. The role of four-and-a-half LIM domains protein 2 (FHL2) in cardiac fibrosis and QSYQ's effects were assessed by small interfering RNAs (siRNAs). Results: QSYQ ameliorated cardiac fibrosis after pressure overload-induced cardiac hypertrophy and attenuated cardiomyocyte apoptosis, low FHL2 expression, and TGF-ß1 release by the injured myocardium. QSYQ also inhibited the following: release of RP S19 from the injured myocardium, activation of C5a receptors in monocytes, polarization of macrophages, and release of TGF-ß1. Moreover, QSYQ downregulated TGF-ßR-II expression induced by TGF-ß1 in fibroblasts and inhibited Smad protein activation and collagen release and deposition. Conclusion: The results showed that QSYQ inhibited myocardial fibrosis after pressure overload, which was mediated by RP S19-TGF-ß1 signaling and decreased FHL2, thus providing support for QSYQ as a promising therapy for blocking myocardial fibrosis.

Yu-Ping-Feng Formula Ameliorates Alveolar-Capillary Barrier Injury Induced by Exhausted-Exercise via Regulation of Cytoskeleton.

Background: Yu-ping-feng powder (YPF) is a compound traditional Chinese medicine extensively used in China for respiratory diseases. However, the role of YPF in alveolar-capillary barrier dysfunction remains unknown. This study aimed to explore the effect and potential mechanism of YPF on alveolar-capillary barrier injury induced by exhausted exercise. Methods: Male Sprague-Dawley rats were used to establish an exhausted-exercise model by using a motorized rodent treadmill. YPF at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Food intake-weight/body weight, blood gas analysis, lung water percent content, BALF protein concentration, morphological observation, quantitative proteomics, real-time PCR, and Western blot were performed. A rat pulmonary microvascular endothelial cell line (PMVEC) subjected to hypoxia was applied for assessing the related mechanism. Results: YPF attenuated the decrease of food intake weight/body weight, improved lung swelling and hemorrhage, alleviated the increase of lung water percent content and BALF protein concentration, and inhibited the impairment of lung morphology. In addition, YPF increased the expression of claudin 3, claudin 18, occludin, VE-cadherin, and ß-catenin, attenuated the epithelial and endothelial hyperpermeability in vivo and/or in vitro, and the stress fiber formation in PMVECs after hypoxia. Quantitative proteomics discovered that the effect of YPF implicated the Siah2-ubiquitin-proteasomal pathway, Gng12-PAK1-MLCK, and RhoA/ROCK, which was further confirmed by Western blot. Data are available via ProteomeXchange with identifier PXD032737. Conclusion: YPF ameliorated alveolar-capillary barrier injury induced by exhausted exercise, which is accounted for at least partly by the regulation of cytoskeleton.

Single-Cell Landscape of Lungs Reveals Key Role of Neutrophil-Mediated Immunopathology during Lethal SARS-CoV-2 Infection.

Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177high cluster that is undergoing respiratory burst and Stfahigh cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.

[Effects of nitrogen reduction combined with organic materials on crop yield, photosynthetic characteristics, and product quality of corn-cabbage rotation system]. / å‡æ°®é æ–½æœ‰æœºç‰©æ–™å¯¹çŽ‰ç±³-ç™½èœè½®ä½œç³»ç»Ÿä½œç‰©äº§é‡ã€å ‰åˆç‰¹æ€§å’Œäº§å“å“è´¨çš„å½±å“.

Nitrogen reduction combined with organic materials is an important measure to achieve or even increase crop yield retention at the background of fertilizer reduction. We conducted a pot experiment to explore the effects of nitrogen reduction combined with organic materials on yield, photosynthetic characteristics, and product quality of agricultural products of maize-cabbage rotation system in yellow soil area of Guizhou. There were five treatments, including no fertilizer (CK), conventional fertilizer (CF), nitrogen reduction (20%, the same below) combined with biochar (RF+B), nitrogen reduction combined with rapeseed cake (RF+O), and nitrogen reduction combined with both biochar and rapeseed cake (RF+BO). Leaf photosynthetic characteristics were measured in maize (seedling stage, jointing stage, heading stage, and mature stage) and cabbage (seedling stage, growing stage and harvest stage). The biological characters, yield and quality indices were investigated in the harvest period. Compared with CF, RF+BO significantly enhanced the yield of corn and cabbage by 9.7% and 39.2%, respectively, while RF+O had no effect, and RF+B did not affet maize yield. RF+BO improved the biological properties of maize and cabbage, including the 100-kernel weight of maize, and plant height, maximum leaf length and total biomass of cabbage. Furthermore, the green holding period and high photosynthetic duration of maize and cabbage were prolonged, among which, maize leaf SPAD was increased respectively by 42.7%, 11.0%, 12.8%, and 30.3% at seedling, jointing, heading, and mature stages, the cabbage leaf SPAD was increased by 13.5%, 9.2%, and 30.3% in seedling, growing and harvest stages, respectively. The net photosynthetic rate (Pn) of maize was increased by 11.1%, 10.9%, and 119.8% in seedling, jointing, and mature stages, while that of cabbage was increased by 12.7% and 14.6% in growing and harvest stages, respectively. The stomatal conductance (gs) of maize was increased by 58.3% and 41.7% in jointing and harvest stages, while that of cabbage was increased by 10%, 64.7%, and 19.2% in seedling, growing, and harvest stages, respectively. The transpiration rate (Tr) of maize was increased by 55.0%, 10.6%, 14.0%, and 143.9% in seedling, jointing, heading, and mature stages, respectively, while that of cabbage was increased by 26.1% in growing stage. The nutritional quality of maize and cabbage was significantly improved. The contents of reducing sugar, starch, and crude protein in maize were increased by 16.2%, 3.5% and 20.3%. The contents of Vc, amino acid, and reducing sugar in cabbage were increased by 26.3%, 21.0% and 27.8%, separately. In conclusion, 20% nitrogen reduction combined with biochar and rapeseed cake had positive effects on crop growth, yield increase, green retention period, high photosynthetic duration, and agricultural product quality improvement in Guizhou yellow soil maize-cabbage rotation system, the overall effect of which was the best. Nitrogen reduction combined with single organic material overally did not affect crop yield, photosynthetic characteristics, and quality.

Thioether-based recyclable metal-organic frameworks for selective and efficient removal of Hg2+ from water.

Hg2+ is highly toxic and hazardous and widely found in polluted water. To remove mercury ions from wastewater, there is an urgent need to investigate and develop new adsorbents. Herein, we synthesized three novel thioether-based metal-organic frameworks (MOFs) through a facile diffusion method or a solvothermal strategy, i.e. [(ZnCl2)3(L1)2·χ(solvent)]n (1), [(Cu2I3O2)4(CH4N0.5)4(L1)4(DMA)4·3(H2O)·χ(solvent)]n (2) and [(CuBr2)2(L2)2 CH3CN·χ(solvent)]n (3), where L1 = 1,3,5-tris((pyridin-4-ylthio)methyl)benzene and L2 = 2,4,6-trimethoxy-1,3,5-tris((pyridin-4-ylthio)methyl)benzene. The obtained thioether-based MOFs were characterized by single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis and thermogravimetric analysis. Further studies revealed that they could remove Hg2+ from water. They have high adsorptivity (up to 362 mg g-1) and are highly efficient in removing Hg2+ (up to 95%). Besides, these MOFs can be recycled and can selectively remove Hg2+ from water in the presence of other metal ions. Consequently, these MOFs are highly promising candidates for the selective absorption and removal of mercury ions from water.

Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: a Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments.

BACKGROUND/AIMS: The purpose of this study was to probe the clinico-pathological significance and the underlying mechanism of miR-30d-5p expression in non-small cell lung cancer (NSCLC). METHODS: We initially examined the level of miR-30d-5p expression in NSCLC and non-cancer tissues using RT-qPCR. Then, a series of validation analyses including a meta-analysis of data from microarray chips in Gene Expression Omnibus (GEO), data mining of the cancer genome atlas (TCGA) and an integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies were performed to examine the clinico-pathological value of miR-30d-5p expression in NSCLC. In vitro experiments were further conducted to investigate the impact of miR-30d-5p on NSCLC cell growth. The molecular mechanism by which miR-30d-5p regulates the pathogenesis of NSCLC was probed through a bioinformatics analysis of its target genes. Moreover, dual luciferase reporter assay was conducted to verify the targeting regulatory relationship between miR-30d-5p and CCNE2. RESULTS: Based on results from RT-qPCR, GEO meta-analysis, TCGA data mining and the integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies, miR-30d-5p expression was decreased in NSCLC tissues, and patients with NSCLC who presented with lower miR-30d-5p expression tended to display an advanced clinical progression. Significant pathways including the Mucin type O-glycan biosynthesis pathway, cell cycle pathway and cysteine and methionine metabolism pathway (all P< 0.05) revealed potential roles of the target genes of miR-30d-5p in the oncogenesis of NSCLC. Results from in vitro experiments indicated that miR-30d-5p could attenuate proliferation and viability of NSCLC cells. Among the 12 identified hub genes, nine genes including E2F3, CCNE2, SKP2, CDK6, TFDP1, LDHA, GOT2, DNMT3B and ST6GALNAC1 were validated by Pearson's correlation test and the human protein atlas (HPA) database as targets of miR-30d-5p with higher probability. Specifically, dual luciferase reporter assay confirmed that CCNE2 was directly targeted by miR-30d-5p. CONCLUSION: In summary, miR-30d-5p expression is decreased in NSCLC, and it might play the role as tumor suppressor in NSCLC by regulating target genes.

SmI2-mediated reductive cyclization of ß-arylthio ketones: a facile and diastereoselective synthesis of thiochroman derivatives.

SmI2-mediated reductive cyclization of ß-arylthio ketones to generate thiochroman derivatives is not a generally observed process and the reported examples are limited to geminal disubstitution in the substrates. The results of the current study show that the cyclization also occurs when other substitution patterns are present, affording a general approach to dihydrothiochroman-ols in good yields and high degrees of diastereoselectivity. Besides, the halogen substitution on ß-aryl is tolerated in most cases here although reductive dehalogenation has been reported to predominate in the reductive cyclization process. Dihydrothiochroman-4-ols were readily oxidized to thiochroman-4-ols in almost quantitative yields.

Human papillomavirus as a potential risk factor for gastric cancer: a meta-analysis of 1,917 cases.

BACKGROUND: Human papillomaviruses (HPVs) are causally associated with the tumorigenesis of several classes of cancers. However, the prevalence of HPV in gastric cancer (GC) has not yet been systematically reviewed. Hence, a meta-analysis was conducted to estimate the HPV prevalence in patients with GC, and its potential etiologic significance was assessed. METHODS: The pooled HPV prevalence and 95% confidence intervals (CIs) were estimated among all GC patients. Heterogeneity was described by using the I2 statistic. Sources of heterogeneity were explored by meta-regression and stratified analyses. The meta-influence was applied to evaluate the influence of a single study on the pooled estimates. Odds ratios (ORs) and 95% CIs were computed for case-control studies. For research providing clinicopathological parameters of age, sex, pathological, differentiated, and clinical stages, and HPV subtypes, the corresponding pooled ORs and 95% CIs were also calculated. RESULTS: Thirty studies were included in the current meta-analysis, involving 1,917 patients with GC and 576 controls. The pooled HPV prevalence was 28.0% (95% CI: 23.2%, 32.7%) among all the patients with GC, and the I2 was 96.9% (P<0.001). A pooled OR of 7.388 (95% CI: 3.876, 14.082) was achieved based on 15 case-control studies (I2=56.7%, P=0.004). Moreover, the HPV prevalence was significantly higher in patients from China than in those from non-Chinese regions (31% vs 9%, I2=95.0%, P<0.001). The pooled prevalence of HPV16 was 21% in GC tissues, and the pooled prevalence of HPV18 was 7% with an OR of 3.314 (95% CI =1.617, 6.792). HPV16 was 3 times more frequently detected than HPV18. CONCLUSION: HPV could play a potential role in the pathogenesis of GC. A causal relationship can be confirmed only by detecting HPV in the cells of GC precursor lesions (gastric dysplasia or adenoma). In addition, this study might be beneficial for expounding the potential etiologic significance of molecular mechanism of gastric tumorigenesis and providing opinions regarding precautionary measures.

Sequencing analysis and characterization of the plasmid pBIF10 isolated from Bifidobacterium longum.

A resident plasmid, pBIF10, was isolated from Bifidobacterium longum B200304, and the full-length sequence of pBIF10 was analyzed. In this sequence, we identified at least 17 major open reading frames longer than 200 bp. A tetracycline resistance gene, tetQ, was identified and verified to confer antibiotic resistance to tetracycline. The plasmid replicon with replication protein B gene (repB) and a typical iteron was identified in pBIF10. An artificial clone vector was constructed with the replicon of pBIF10; the results showed that repB controlled plasmid replication in other bifidobacteria host cells at low transformation frequency. Taken together, the analysis and characterization of pBIF10 provided necessary information for the understanding of antibiotic resistance mediated by a plasmid in a Bifidobacterium strain. GC% and repB sequence analyses indicated that pBIF10 was a molecular hybrid of at least 2 other bacterial genera plasmids.

Angiotensin converting enzyme is involved in the cardiac hypertrophy induced by sinoaortic denervation in rats.

INTRODUCTION: The present study was designed to test the hypothesis that local angiotensin converting enzyme (ACE) was involved in the cardiac hypertrophy induced by sinoaortic denervation (SAD) in rats. METHODS: Experiment 1: Six weeks after SAD of rats, components of renin-angiotensin system (RAS) in left ventricles were assayed by quantitative real-time PCR and Western blotting analysis. Experiment 2: Rats were divided into five groups treated as follows: (1) sham-operated group; (2) SAD group; (3) SAD group treated with angiotensin II type 1 receptor (AT1R) antagonist losartan (10 mg·kg(-1)·day(-1), orally); (4) SAD group treated by ACE inhibitor ramipril (1 mg·kg(-1)·day(-1), orally); (5) SAD group treated by ramipril and the B2-kinin receptor selective antagonist HOE-140 (0.25 mg·kg(-1)·day(-1), subcutaneously). RESULTS: SAD led to augmentation of the mRNA levels and protein expression of left ventricular ACE and AT1R. Both losartan and ramipril ameliorated SAD-induced left ventricular hypertrophy. Both losartan and ramipril abated oxidative stress, suppressed inflammation, and reduced expression TGFß-R in left ventricles. In addition, the protective effect of ramipril could be abolished by HOE-140. CONCLUSION: Local ACE is involved in the left ventricular hypertrophy induced by sinoaortic denervation in rats, via both angiotensin II/AT1R and bradykinin/B2R pathways.

AG4, a compound isolated from Radix Ardisiae Gigantifoliae, induces apoptosis in human nasopharyngeal cancer CNE cells through intrinsic and extrinsic apoptosis pathways.

3ß-O-{α-L-Pyran rhamnose-(1→3)-[ß-D-xylopyranose-(1→2)]-ß-D-glucopyranose-(1→4)-[ß-D-lucopyranose-(1→2)]-α-L-pyran arabinose}-cyclamiretin A (AG4) is a saponin component obtained from the Giantleaf Ardisia Rhizome (Rhizoma Ardisiae Gigantifoliae). The present study aimed to investigate the antitumor potential of AG4 and its possible mechanisms in human nasopharyngeal carcinoma cells (CNE). We exposed tumor cells to AG4 to investigate which cell line was the most sensitive to AG4. Cell viability was assessed using the MTT reduction assay, and the effects of AG4 on apoptosis, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and cell cycle were detected using a flow cytometer; the glutathione, superoxide dismutase and malondialdehyde activities were measured using colorimetric methods. The relative expressions of Bax, Bad, Bid, Bcl-2, and Fas mRNA were calculated using the (Equation is included in full-text article.)comparative method by real-time PCR studies and protein was detected by western blotting. AG4 markedly inhibited the growth of CNE cells by decreasing cell proliferation, inducing apoptosis, and blocking the cell cycle in the S phase. The release of caspase-3, caspase-8, and caspase-9 was stimulated by AG4 in CNE, and the decreased proliferation induced by AG4 was blocked by the inhibitor of pan caspase (Z-VAD-FMK). Moreover, the MMP was decreased in AG4-treated cells, and AG4-induced cell apoptosis was accompanied by a rapid and lasting increase in ROS, which was abolished by N-acetyl-L-cysteine (NAC); glutathione, superoxide dismutase, and malondialdehyde were regulated by AG4. AG4 inhibited Bcl-2 mRNA and protein expression and stimulated Bax, Bad, Bid, Fas mRNA, and protein expression in CNE cultures, suggesting an effect at the transcriptional and protein level. In addition, both the FasL inhibitor (AF-016) and the Bcl-2 family inhibitor (GX15-070) could prevent the cell apoptosis induced by AG4. The findings suggested that AG4-induced apoptosis in CNE cells involved a death receptor pathway and a Bcl-2 family-mediated mitochondrial signaling pathway by decreasing the MMPs in an ROS-dependent manner and regulating genes and proteins relative to apoptosis; also, regulation of cell cycles may also play a role in the antitumor mechanism of AG4.

Efficacy and safety of sorafenib for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. METHODS: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. RESULTS: Results reported from 6 RCTs involving 2,748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96-1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. CONCLUSIONS: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.