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Objective: Rare disease Background: Primary hepatic neuroendocrine neoplasms (PHNEN) are exceedingly rare tumors with atypical clinical manifestations, accounting for less than 0.5% of all neuroendocrine tumors. Currently, there is a lack of consensus on their management, and guidelines do not recommend postoperative chemotherapy for patients with stage G1/G2 disease after curative resection. We present a case report of PHNEN, outlining its diagnostic challenges, treatment strategy, and clinical outcomes. Case Report: A 31-year-old man presented with jaundice and was initially diagnosed with suspected IgG4-related disease, which initially appeared to respond to steroid therapy, but manifested worsening jaundice 4 months after initial treatment. Subsequent evaluation revealed a PHNEN NET G2 with lymph node metastasis and invasion of the right hepatic artery; and involvement of the hepatic duct at the hepatic hilum, primarily the left hepatic duct. The patient underwent extended left hemi-hepatectomy with caudate lobe resection, bile duct resection, and lymphadenectomy, followed by reconstruction of the right hepatic artery. Postoperatively, the patient received adjuvant chemotherapy consisting of capecitabine (1000 mg bid D1-14) and temozolomide (200 mg qn D10-14) for 6 cycles. Currently, the patient remains disease free 43 months after treatment. Conclusions: PHNEN presents diagnostic challenges due to its rarity and lack of specific markers. Surgical resection remains the cornerstone of treatment, with chemotherapy being considered in select cases with high-risk features. Further research is needed to refine treatment approaches and improve outcomes for patients with PHNEN. [ABSTRACT FROM AUTHOR]

BACKGROUND: The ABO blood group is closely related to clinical blood transfusion, transplantation, and neonatal hemolytic disease. It is also the most clinically significant blood group system in clinical blood transfusion. OBJECTIVE: The purpose of this paper is to review and analyze the clinical application of the ABO blood group. METHODS: The most common ABO blood group typing methods in clinical laboratories are hemagglutination test and microcolumn gel test, while genotype detection is mainly adopted in clinical identification of suspicious blood types. However, in some cases, the expression variation or absence of blood type antigens or antibodies, experimental techniques, physiology, disease, and other factors affect the accurate determination of blood types, which may lead to serious transfusion reactions. RESULTS: The mistakes could be reduced or even eliminated by strengthening training, selecting reasonable identification methods, and optimizing processes, thereby improving the overall identification level of the ABO blood group. ABO blood groups are also correlated with many diseases, such as COVID-19 and malignant tumors. Rh blood groups are determined by the RHD and RHCE homologous genes on chromosome 1 and are classified as Rh negative or positive according to the D antigen., the agglutination method is often used in clinical settings, while genetic and sequencing methods are often used in scientific research. CONCLUSION: Accurate ABO blood typing is a critical requirement for the safety and effectiveness of blood transfusion in clinical practice. Most studies were designed for investigating rare Rh blood group family, and there is a lack of research on the relationship between Rh blood groups and common diseases. [ABSTRACT FROM AUTHOR]

The genus Cybister Curtis, 1827 is reviewed with respect to the fauna of China. A new species, Cybister (Melanectes) danxiaensis sp. nov. is described and illustrated. Altogether, 16 Cybister species are recorded from China, although the status of two of them remains in question. All species are diagnosed, with their habitus and male genitalia illustrated. Additional faunistic data from China are provided for the following species: C. guerini Aubé, 1838 from Hainan; C. lewisianus Sharp, 1873 from Guangdong and Hainan; C. limbatus (Fabricius, 1775) from Guangdong, Guangxi and Hainan; C. rugosus (W. S. Macleay, 1825) from Chongqing, Guangdong, Hubei, Hunan, Jiangxi, Yunnan, Zhejiang; C. tripunctatus lateralis (Fabricius, 1798) from Chongqing, Guangxi, Jiangxi, Shanghai; C. brevis Aubé, 1838 from Guizhou, Hunan, Zhejiang; and C. sugillatus Erichson, 1834 from Guangxi and Yunnan. An updated identifi cation key and distribution maps for all species are provided. Cybister lateralimarginalis torquatus (Fischer von Waldheim, 1829) is recorded for the fi rst time from Tajikistan and Uzbekistan. [ABSTRACT FROM AUTHOR]

Researchers from the world over are working to create prophylactic and therapeutic interventions to combat the COVID-19 global healthcare crisis. The current therapeutic options against the COVID-19 include repurposed drugs aimed at targets other than virus-specific proteins. Antibody-based therapeutics carry a lot of promise, and there are several of these candidates for COVID-19 treatment currently being investigated in the preclinical and clinical research stages around the world. The viral spike protein (S protein) appears to be the main target of antibody development candidates, with the majority being monoclonal antibodies. Several antibody candidates targeting the SARS-CoV-2 S protein include LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. These neutralizing antibodies will treat COVID-19 and possibly future coronavirus infections. Future studies should focus on effective immune-therapeutics and immunomodulators with the purpose of developing specific, affordable, and cost-effective prophylactic and treatment regimens to fight the COVID-19 globally. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is the most common complication of sepsis. MicroRNAs (miRNAs) play important roles in the sepsis-induced AKI. This paper aimed to explore the role of miRNA 181a-2-3p (miR-181a-2-3p) in the sepsis-induced AKI and the underlying mechanism. Our results revealed that miR-181a-2-3p showed low expression levels in patients with sepsis and mouse models undergoing cecal ligation and puncture (CLP). The addition of miR-181a-2-3p antagonists aggravated the sepsis-induced kidney injuries and inflammatory response in CLP mouse models, as suggested by hematoxylin and eosin (H&E) staining and quantitative real-time PCR (qRT-PCR). In addition, miR-181a-2-3p mimic alleviated the lipopolysaccharide (LPS)-induced inflammatory response, along with apoptosis of TCMK-1. Moreover, results from the GSE46955 data set indicated that GJB2 was highly expressed in septic patients but lowly expressed after recovery. Further, the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out, which confirmed that GJB2 was a target of miR-181a-2-3p, and overexpression of GJB2 reversed the antiinflammatory and antiapoptotic effects of miR-181a-2-3p mimic on the LPS-induced sepsis cell models. In conclusion, miR-181a-2-3p alleviates the inflammatory response and cell apoptosis of septic patients and animal models by upregulating GJB2 expression, which may provide a new therapeutic strategy for sepsis. [ABSTRACT FROM AUTHOR]

• D. magna ingested the used microplastics (MPs, 32–38 μm), but S. kingi did not. • MPs affected anti-oxidant traits, behavior, and grazing rate of D. magna. • MPs changed life-history and inhibited population growth of D. magna. • MPs suppressed D. magna through resource and apparent competition. • MPs' risks have been underestimated without multiscale risk assessment. Although many studies have reported the negative effects of microplastics on aquatic organisms, most research is focused on individual scales. Individual studies highlight harm mechanisms, but understanding broader ecological effects necessitates evidence from multiscale perspectives, particularly those based on interspecific interactions. Therefore, in this study, we investigated the impacts of different microplastic concentrations (0, 0.4, 2, and 10 mg/L) on individual characteristics (physiology, behavior, and grazing rate) and population dynamics of two cladoceran species Daphnia magna and Scapholeberis kingi , and their interrelationships within communities in the absence and presence of predators (larvae of Agriocnemis pygmaea). We used 32–38 μm polyethylene microplastics; these particles were detected in the guts of D. magna , especially at higher concentrations, but were not found in S. kingi. Consequently, with increasing microplastic concentrations, the grazing and reproductive capacity of D. magna diminished, weakening their dominance in the coexistence system without damselfly larvae. Additionally, as microplastic concentration increased, D. magna faced greater oxidative damage and a reduction in mobility, making this species more susceptible to predation by damselfly larvae and less dominant in the predator-inhabited coexistence system. This study reveals the mechanism by which asymmetric impacts of microplastics on individual traits altered interspecific competition between zooplankton species, thereby illuminating the role of microplastics in altering zooplankton communities. [Display omitted] [ABSTRACT FROM AUTHOR]

• The activity of BN was highly improved by modulating the crystallinity of BN. • The high crystallinity could probably reduce the energy barrier for the activation of adsorbed O 2. • The activation of adsorbed O 2 is related to the formation of active site. In this work, we optimized the catalytic performances of h-BN in propane oxidative dehydrogenation by modulating the catalyst crystallinity. The propane conversion rate per unit specific surface area of the catalyst (-mol C 3 H 8 /m2/s) was improved by almost ten times by modulating the crystallinity of BN catalyst, gaining a propylene productivity of about 3.10 μmol g cat−1 s−1. The reaction activity presented a negative relationship with the specific surface area but positively related to the crystallinity of BN. High degree of crystallinity is proved to be beneficial for the binding of O 2 to BN by the O 2 -TPD results and zeta potentials of BN-T, which could probably reduce the energy barrier for the activation of O 2 and the formation of active sites. Additionally, the increase in propane conversion with the increase of reaction temperature tends to be gentle when the reaction temperature is above 530 °C, and it is almost equal to zero for O 2 /C 3 H 8 value increasing from 1.30 to 2.00, indicating an energy-efficient and economical route to convert C 3 H 8 over BN catalyst with high crystallinity. [ABSTRACT FROM AUTHOR]

Gene-environment interaction is identified as the determinant in anxiety. ABO blood types represent a part of the genetic phenotype. Therefore, we assume ABO blood types correlate with preoperative anxiety. This cross-sectional study enrolled 352 patients with different ABO blood types, scheduled for elective surgery between 2018 and 2019 in the First Affiliated Hospital of Shihezi University. HADS (hospital anxiety and depression scale) scores and VA (visual analogue scales for anxiety) scores were all used to assess the preoperative anxiety in the A, B, AB, and O groups. Bivariate correlation and logistic regression were performed to identify relationships between preoperative anxiety and related variables. A significant difference in VA and HADS-A (anxiety) scores was found between the AB and other groups. The ratio of preoperative anxiety was 3.73 (95% CI [confidence interval]: 2.32-6.00, P<0.001) times in female than in male; 0.36 (95% CI: 0.21-0.63, P<0.001) times in ASA (American Society of Anesthesiologists) grade II than in grade I; 0.41 (95% CI: 0.20-0.86, P<0.05) times in ASA grade III than in grade I; 1.25 (95% CI: 1.1-1.41, P<0.001) times in higher VAS (visual analogue scales for pain) scores than in lower VAS scores; and 0.28 (95% CI: 0.16-0.49, P<0.01) times in non-AB blood type than in AB blood type. Differences in ABO blood types were found in preoperative anxiety, and the AB group displayed a high preoperative anxiety level. ABO blood types, sex, ASA grade, and VAS were associated with preoperative anxiety. This trial is registered with ChiCTR1800019390. [ABSTRACT FROM AUTHOR]

In this work, a variety of microporous carbon nanospheres (MCNs) were synthesized by the in-situ approach, and used as metal-free catalysts for direct propane dehydrogenation (DPDH). Pristine MCNs showed excellent catalytic performances for DPDH with initial propane conversion of 26% and propylene selectivity of 87%–88%. Phosphorus (P) modifications with different P sources put different effects on the catalytic performances of MCNs in DPDH, i.e., triethyl phosphate exhibited a positive, while (NH 4) 2 HPO 4 and H 3 PO 4 showed a negative effect on the catalytic performances for the in-situ doping carbon catalysts. The amount of surface oxygenic groups and the graphitization extent of carbon materials are two important factors influencing the catalytic performances of MCNs in DPDH. These results indicate that P modification is an effective way to adjust the catalytic performances of MCNs in DPDH. While, except the dopant itself, the interaction between the dopant and other materials during the synthesis process also influences the surface oxygenic groups and the graphitization degree of carbon materials. Image 1 [ABSTRACT FROM AUTHOR]

Objective: To explore the application effects of information technology (IT) on emergency laboratory testing procedures. Methods: In this study, IT-based optimisation of the emergency laboratory testing process was implemented between October and December 2021. Thus, the emergency laboratory test reports from January to September 2021 were placed into the pre-optimised group, while those from January to September 2022 were categorised into the post-optimised group. Besides, the emergency laboratory test report time, emergency laboratory test report time limit coincidence rate, error rate, and employee and patient satisfaction levels in individual months and across the whole period were described. Moreover, changes in the above indicators before and after the implementation of IT-based optimisation were explored and the application effects of IT-based optimisation were also evaluated. Results: The emergency laboratory test report times after the implementation of IT-based optimisation were shorter than those before IT-based optimisation (P < 0.05). The total number of laboratory test items before and after information optimization amounted to 222,139 and 259,651, respectively. Also, IT-based optimisation led to an increase in the emergency laboratory test report time limit coincidence rate from 98.77% to 99.03% (P < 0.05), while the emergency laboratory test report error rate fell from 0.77‱ to 0.15‱ (P < 0.05). Additionally, IT-based optimisation resulted in increases in both employee satisfaction, from 80.65% to 93.55% (N = 31, P > 0.05), and patient satisfaction, from 93.06% to 98.44% (P < 0.05). Conclusion: The automation and IT-based optimisation of the emergency laboratory testing process significantly reduces the emergency laboratory test report time and error rate. Additionally, IT-driven optimization enhances the alignment of emergency laboratory test report deadlines and enhances the overall quality and safety of emergency laboratory testing. [ABSTRACT FROM AUTHOR]

Aims: Changes in litter chemistry and stoichiometry following N enrichment have important consequences on litter decomposition and plant-mediated nutrient cycling. Our knowledge about the responses of litter stoichiometry at different biological organization levels to N enrichment remains poorly understood. Moreover, whether the impacts of N enrichment on stoichiometric ratios in litter would depend on ecosystem management strategies remains unknown. Methods: We examined the effects of N addition and mowing on C:N:P stoichiometry in standing litter at plant organ, species, functional group, and community levels in a semi-arid grassland of northern China, taking advantage of a field experiment that has been running for seven years. Results: Nitrogen addition altered biomass allocation between different organs and among different plant functional groups, with consequences on litter stoichiometry at community level. N addition had no impacts on litter C concentration, increased litter N, and N:P ratio, and decreased litter C:N ratio from plant organ to community. The impacts of N addition on litter P and C:P depended on the identity of plant species and functional group. Mowing did not affect litter nutrient characters across all organization levels. Furthermore, no interactive effects between N addition and mowing on litter nutrient characters were observed from plant organ to community levels. Conclusions: We conclude that N deposition will enhance litter quality even in the heavily-used grasslands with shifts in biomass allocation and species composition, which may contribute to the enhancement of plant-mediating nutrient cycling. [ABSTRACT FROM AUTHOR]

Disruption of FOXP2 , a gene encoding a forkhead domain transcription factor, may cause a severe developmental disorder of verbal communication, especially vocalization. In insectivorous bats, accelerated evolution of FoxP2 supports a previously proposed hypothesis that this gene plays a role in sensorimotor coordination. In order to validate this hypothesis, it is necessary to examine the expression of FoxP2 in the relevant sensorimotor structures involved in echolocation behavior. Here, we present the detailed spatial expression pattern of FoxP2 in the mature brain of Rhinolophus ferrumequinum using immunohistochemistry. FoxP2 expression was found in many regions of the bat brain. The homologous pattern of FoxP2 expression in this bat argues for the role of the gene in motor-related circuits. In addition, FoxP2 was strongly expressed in many regions related to echolocation such as the inferior colliculus, superior colliculus, periaqueductal gray, paralemniscal nucleus, nuclei of the lateral lemniscus, parabrachial nucleus and ambiguous nucleus. Overall, our findings imply that FoxP2 plays an important role in echolocation. [ABSTRACT FROM AUTHOR]

Litter quality plays an important role in determining litter decomposition and nutrient cycling in terrestrial ecosystems. We investigated the main and interactive effects of nitrogen (N) addition and mowing on litter quality (%N, lignin, cellulose, and hemicellulose concentrations and lignin:N ratio) of four dominant species in a temperate steppe in northern China. In addition to species-specific impacts, both N addition and mowing can alter community composition by changing relative dominance of individual species, with consequences on litter decomposition. Nitrogen addition significantly increased N concentration of shoot litters at species- and community-level, while mowing did not affect N concentration. Nitrogen addition decreased concentrations of lignin, cellulose, hemicellulose, and lignin:N ratio at both species- and community-level. Mowing decreased lignin and cellulose concentrations, increased hemicellulose concentrations, and did not affect lignin:N ratio at species-level. Mowing decreased cellulose concentrations but did not alter lignin and hemicellulose concentrations, and lignin:N ratio at the community level. Furthermore, mowing did not alter the impacts of N addition on litter quality at both organization levels. Our results suggested that both N addition and mowing can influence litter quality by affecting individual species litter quality and community structure, and thus regulate the processes of litter decomposition and nutrient cycling in grassland ecosystems through a plant-mediated pathway. Importantly, our results showed that the role of annual mowing as a widely-used ecosystem management strategy globally appears to be limited in mediating the impacts of N deposition on plant-mediated nutrient cycling. [ABSTRACT FROM AUTHOR]

Background Sepsis has high morbidity and mortality. The aim of this study was to investigate whether emodin, an anthraquinone derived from Chinese herb, exerts protective effects on lung injury in rat model of sepsis. Materials and methods Forty-eight male Wistar rats were randomly divided into four groups ( n = 12): normal group, sham-operated group, cecal ligation and puncture (CLP) model group, and emodin-treated group. Saline or emodin (25 mg/kg) was injected intraperitoneally 0.5 h before CLP. The rats were sacrificed 48 h after CLP. Lung wet-to-dry weight ratio and pathologic changes in the lung were examined, the contents of malondialdehyde and myeloperoxidase in lung tissue were detected, serum tumor necrosis factor alpha and interleukin 6 levels were measured by enzyme-linked immunosorbent assay, and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was detected by Western blot analysis. Results Compared with control group, CLP group exhibited higher wet-to-dry weight ratio and water content in the lung ( P < 0.01), but these indexes were reduced and pathologic changes in the lung were relieved in the emodin-treated group. In addition, lung malondialdehyde and myeloperoxidase contents, serum levels of tumor necrosis factor alpha and interleukin 6, and phosphorylation of p38 MAPK increased in the CLP group but decreased in the emodin-treated group ( P < 0.05). Conclusions Emodin exerts protective effects on lung injury in septic rats, which is related to the inhibition of p38 MAPK pathway and the reduction of oxidative stress and inflammation response during sepsis. [ABSTRACT FROM AUTHOR]

To achieve simultaneous biological nitrogen and phosphorus removal, a pilot-scale sequencing batch reactor–biofilm (SBR–BF) system was explored. SBR–BF system was started up with two phases, which were anaerobic/aerobic and anaerobic/aerobic/anoxic, to enrich phosphate accumulating organisms (PAOs) and denitrifying phosphate accumulating organisms (DNPAOs), and to form system of suspended activated sludge and attached biofilm. Operation cycle of SBR–BF system was adjusted as fill 5 min, anaerobic 90 min, aerobic 210 min, anoxic 90 min, settle 30 min, draw 15 min and idle 40 min, and average removal of chemical oxygen demand, total nitrogen and total phosphorus respectively reached 95%, 94%, and 97% during stable operation for 3 months. Analysis of a typical wastewater treatment cycle testified that DNPAOs played an important role for phosphate uptake and denitrification under aerobic and anoxic conditions. The SBR–BF system not only provided good living conditions for PAOs, DNPAOs, nitrifying bacteria and denitrifying bacteria which had different generation times, but also prevented the competition for carbon source between different bacteria. [ABSTRACT FROM AUTHOR]

Emerging evidence has revealed a negative correlation between Forkhead box-O (FOXO) expression and prostate cancer grade and spread, indicating its role as a suppressor of prostate cancer metastasis. However, there is still incomplete understanding about the role of FOXO transcription factors in prostate cancer progression. In this investigation, we demonstrate that FOXO3a significantly inhibits the expression β-catenin in prostate cancer cells. The mechanism of inhibiting β-catenin expression involves the FOXO3a-mediated transactivated microRNA-34b/c, which consequently suppressed β-catenin mRNA expression by targeting the untranslated regions (UTRs) of β-catenin. Additionally, FOXO3a can directly bind to β-catenin, and competes with TCF for interaction with β-catenin, thereby inhibiting β-catenin/TCF transcriptional activity and reducing the expression of β-catenin target genes. Furthermore, prostate cancer cells expressing FOXO3a shRNAs display mesenchymal characteristics, including enhanced cell migration and differential regulation of the EMT markers, whereas knockdown of β-catenin results in reversal of shFOXO3a-mediated EMT phenotypic changes. Collectively, these observations demonstrated that FOXO3a inhibits malignant phenotypes that are dependent on β-catenin-dependent modulation of EMT-related genes, and provided fresh insight into the mechanisms by which a FOXO3a-miR-34b/c axis restrains canonical β-catenin signaling cascades in prostate cancer cell. [ABSTRACT FROM AUTHOR]

Micromixing, the mixing at the molecularscale, is believed toplay a substantial role in many industrial processes. In this work,a novel surface-modified nickel foam packing (SNP) loaded in a rotatingpacked bed (RPB) reactor was first proposed to improve the micromixingefficiency studied by adopting the iodide–iodate reaction asa working system. Experimental results showed that the RPB reactorwith the SNP presented better micromixing efficiency, compared tothe RPB reactor with the nonmodified nickel foam packing (NNP) ortraditional stainless steel wire mesh packing (SWP). It could be foundthat the segregation index (XS) decreasedas the rotational speed and liquid flow rate each increased, whileit increased with increasing acid concentration and volumetric ratio.Moreover, the micromixing time (tm) wascalculated using an incorporation model based on the experimentaldata. Compared with NNP or SWP, the minimum tmvalue of SNP (tm= 3.28 ms) isless than that of NNP (tm= 5.68 ms) orSWP (tm= 8.67 ms). [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding α-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. IDUA consists of a TIM barrel domain containing the catalytic site, a β-sandwich domain and a fibronectin-like domain. Structures of IDUA bound to iduronate analogs illustrate the Michaelis complex and reveal a 2,5B conformation in the glycosyl-enzyme intermediate, which suggest a retaining double displacement reaction involving the nucleophilic Glu299 and the general acid/base Glu182. Unexpectedly, the N-glycan attached to Asn372 interacts with iduronate analogs in the active site and is required for enzymatic activity. Finally, these IDUA structures and biochemical analysis of the disease-relevant P533R mutation have enabled us to correlate the effects of mutations in IDUA to clinical phenotypes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether a two-hit acute lung injury (ALI) model is better than a one-hit model in simulating ALI, and to evaluate the inflammatory response in the lungs in these two models using micro-positron emission tomography (microPET) with [18F]fluorodeoxyglucose (FDG). Sprague Dawley rats were divided into four groups; rats in the lipopolysaccharide (LPS; n=10) and LPS-HCl (n=10) groups were challenged by the intraperitoneal administration of 5 mg/kg LPS, while rats in the normal saline (NS; n=3) and HCl (n=10) groups received the same volume of normal saline solution. Sixteen hours following the administration, the rats in the HCl and LPS-HCl groups received an acid instillation (IT) of 0.5 ml/kg HCl (pH=1.2), while the rats in the remaining two groups received the same volume of normal saline solution. The mean arterial blood pressure (MAP) and blood gas concentrations were measured in all four groups. MicroPET was performed 4 h following HCl IT and the lungs were excised for histopathological examination. The rats in the LPS-HCl group exhibited a higher arterial PaO2 and a lower arterial PaCO2 compared with the rats in the remaining groups. The MAP decreased markedly in the LPS-HCl group, but remained stable in the LPS, HCl and NS groups. MicroPET results identified that the region of interest ratio in the LPS-HCl group (9.00±1.41) was significantly higher compared with those in the LPS (4.01±0.60) and HCl (3.33±0.55) groups (P<0.01). In addition, histological examination showed that the mean lung injury score in the LPS-HCl group (12.70±0.95) was significantly higher compared with those in the HCl (8.40±1.26) and LPS (7.00±0.82) groups (P<0.01). The present study demonstrates that LPS pretreatment significantly magnifies and prolongs the inflammatory response to subsequent acid IT in the lungs. Moreover, it is simpler to induce ALI using the two-hit model than with the one-hit model, and [18F]FDG microPET is a useful tool for evaluating the inflammatory reaction during ALI. [ABSTRACT FROM AUTHOR]

Objective Epidemiologic findings are inconsistent concerning the association between cesarean section (C-section) and celiac disease in offspring. Methods We performed a systematic literature search of PubMed and Embase databases until July 2021. A meta-analysis was performed for each outcome in which a summary odds ratio (OR) was calculated while taking heterogeneity into account. Results A total of 11 observational were identified for the literature review. We found that C-section was not associated with an increase in the risk of CD (OR = 1.03, 95% CI, 0.95–1.12; p = .501). In subgroup analyses, the association remained insignificant for both infants born after elective C-section (OR 1.05; 0.95–1.16; p = .329) and emergency C-section (OR 1.06; 1–1.13; p = .051). Conclusions Our results indicate that C-section is not associated with CD in offspring. [ABSTRACT FROM AUTHOR]

Abstract: The Gaussian function or kernel () based algorithms are popularly applied in various computational biology researches. It is well known for its outstanding capability of measuring the remote similarity between any two samples in a mapped space. The Gaussian kernel can not only be used in unsupervised fields but also in supervised cases. Despite the success of the Gaussian kernel in bioinformatics applications, the scalar parameter β is demonstrated to have significant influences on final results. There are no good methods to determine optimal values of β until now since they vary in different applications, which are usually identified by trial and error tests achieved by a global grid search in a pre-defined potential rage. This global grid search approach is heavily limited by the difficulty for setting proper start and end edges of the range, grid scales, as well as the huge search computational complexity in both cases of large dataset size and complicated learning algorithms. To deal with these problems, we present a systematic protocol consisting of two data-driven approaches to derive optimal choices for the Gaussian kernel parameter in bioinformatics studies, one for unsupervised cases and the other for supervised applications. The advantage of the two methods is that they only depend on the original dataset. The corresponding experiments on 6 datasets demonstrate the robustness and efficacy of the proposed approaches. An online calculator is implemented at: http://www.csbio.sjtu.edu.cn/bioinf/GFO/ for free academic use. [Copyright &y& Elsevier]

Polymorphisms in the human catechol-O-methyltransferase (COMT) gene have been widely studied for their role in pain and analgesia. In this study, sensitivity to potassium iontophoresis, visual analog scale measurements for fixed twofold pain threshold stimulation and pain threshold changes induced by transcutaneous electrical acupoint stimulation (TEAS) were assessed in a population of healthy Chinese males. These results were correlated with the alleles of six single nucleotide polymorphisms (SNP) or diplotypes of common haplotypes designated as low pain sensitive, average pain sensitive, and high pain sensitive in the COMT gene of these subjects. Our results reveal that the alleles of each SNP are not significantly correlated with pain perception except for the rs4633 allele in the 2 Hz TEAS session (P < 0.05). In addition, the six diplotypes of COMT haplotypes, which cover 92.5% of the Chinese population, are also not correlated with pain perception. Moreover, there were no significant differences in pain threshold changes induced by 2 and 100 Hz TEAS among the diplotypes of each SNP or the various haplotypes. These results suggest that COMT activity do not play a significant role in pain perception and TEAS-induced analgesia in the Chinese Han male population. [ABSTRACT FROM AUTHOR]

Background: Previous investigation has demonstrated that CD4+ T cells play a crucial role in effective immunity against Helicobacter pylori (H.pylori) infection. It has been well proved that Lpp20 is one of major protective antigens that induce immune responses after H.pylori invades host. Therefore it is valuable to identify CD4+ T cell epitopes on Lpp20, which is uncharacterized. Methods: Putative epitopes of H-2d restricted CD4+ T cell on Lpp20 of H.pylori were predicted by the SYFPEITHI algorithm and then eight hypothetical epitope peptides were synthesized. After BALB/c mice were primed with recombinant Lpp20, splenic CD4+ T cells were isolated and stimulated with synthesized peptides to measure T cell proliferation and MHC restriction. Cytokine profile was determined by ELISA and real-time PCR. Two identified epitopes were used to immunize mice to investigate CD4+ T cell response by flow cytometry. Results: Two of eight peptides were able to stimulate CD4+ T cell proliferation and were mapped to residues 83-97aa and 58-72aa on Lpp20 respectively. These two peptides additively stimulated Th1 cells to secrete IFN-γ. The percentage of CD4+ T cell from mice immunized with two identified epitopes respectively was higher than the control group. Conclusion: The identification and characterization of two CD4+ T cell epitopes of Lpp20 helps understand the protective immunity of Lpp20 in H.pylori infection and design effective epitope vaccines against H.pylori. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis ( Mtb) acyl-CoA carboxylase is involved in the biosynthesis of mycolic acids, which are a key component of the bacillus cell wall. The Mtb genome encodes six acyl-CoA carboxylase β subunits (ACCD1-6), three of which (ACCD4-6) are essential for survival of the pathogen on minimal medium. Mtb ACCD6 has been expressed, purified and crystallized. The two forms of Mtb ACCD6 crystals belonged to space groups P41212 and P212121 and diffracted to 2.9 and 2.5 Å resolution, respectively, at a synchrotron-radiation source. [ABSTRACT FROM AUTHOR]

Abstract: The Gaussian kernel function implicitly defines the feature space of an algorithm and plays an essential role in the application of kernel methods. The parameter of Gaussian kernel function is a scalar that has significant influences on final results. However, until now, it is still unclear how to choose an optimal kernel parameter. In this paper, we propose a novel data-driven method to optimize the Gaussian kernel parameter, which only depends on the original dataset distribution and yields a simple solution to this complex problem. The proposed method is task irrelevant and can be used in any Gaussian kernel-based approach, including supervised and unsupervised machine learning. Simulation experiments demonstrate the efficacy of the obtained results. A user-friendly online calculator is implemented at: www.csbio.sjtu.edu.cn/bioinf/kernel/ for public use. [Copyright &y& Elsevier]

Eleven compounds, [Zn(L1)2(bbmi)] (1), [Zn(HL2)2(bbmi)] (2), [Zn0.5(L3)(bbmi)0.5] (3), [Zn0.5(L4)(bbmi)0.5(H2O)] (4), [Zn(L5)2(bbmi)] (5), [Zn(L6)(bbmi)] (6), [Zn(L7)(bbmi)0.5(H2O)] (7), [Zn(L8)(bbmi)0.5(H2O)] (8), [Ag2(L6)(bbmi)(H2O)] (9), [Ag(L9)0.5(bbmi)0.5]·2H2O (10) and [Ag2.5(L10)(bbmi)2]·0.5(OH)·0.5(EtOH)·1.5H2O (11), where bbmi = 1,1′-(1,4-butanediyl)bis(2-methylbenzimidazole), HL1= benzoic acid, H2L2= salicylic acid, HL3= p-nitrobenzoic acid, HL4= nicotinic acid, HL5= 3,5-dinitrobenzoic acid, H2L6= o-phthalic acid, H2L7= m-phthalic acid, H2L8= fumaric acid, H2L9= p-phthalic acid and H2L10= 5-aminoisophthalic acid, have been synthesized and characterized. Compounds 1–5and 10display one-dimensional chain structures. These chains are connected through intermolecular interactions to form 2D supramolecular structures, respectively. The layers of 2are further connected through C–Hπ interactions to yield a 3D supramolecular structure. There exist weak AgAg interactions in 10, which also contribute to the stabilization of the supramolecular layer. Compound 6exhibits a diamondoid network. Compound 7shows a 2D (4,4) layer. The structure of 8is a 3D α-Po framework. Compound 9displays a 2D layer structure. Furthermore, the π–π interactions among the bbmi ligands link the layers into a 3D supramolecular framework. Compound 11shows a ladder structure. The AgAg and π–π interactions further connect the ladders to form a 2D supramolecular assembly. The thermal stabilities of 4and 7–11and the luminescent properties of 1, 3–5and 7–11in the solid state are also discussed. [ABSTRACT FROM AUTHOR]

The gene product of the open reading frame Rv3340 from Mycobacterium tuberculosis is annotated as encoding a probable O-acetylhomoserine (OAH) sulfhydrylase (MetC), an enzyme that catalyzes the last step in the biosynthesis of methionine, which is an essential amino acid in bacteria and plants. Following overexpression in Escherichia coli, the M. tuberculosis MetC enzyme was purified and crystallized using the hanging-drop vapor-diffusion method. Native diffraction data were collected from crystals belonging to space group P21 and were processed to a resolution of 2.1 Å. [ABSTRACT FROM AUTHOR]

Branched amino-acid biosynthesis is important to bacterial pathogens such as Mycobacterium tuberculosis ( Mtb), a microorganism that presently causes more deaths in humans than any other prokaryotic pathogen (). In this study, the molecular cloning, expression, purification, crystallization and preliminary crystallographic analysis of recombinant IlvH, the small regulatory subunit of acetohydroxylic acid synthase (AHAS) in Mtb, are reported. AHAS carries out the first common reaction in the biosynthesis of valine, leucine and isoleucine. AHAS is an essential enzyme in Mtb and its inactivation leads to a lethal phenotype [Sassetti et al. (2001), Proc. Natl Acad. Sci. USA, 98, 12712-12717]. Thus, inhibitors of AHAS could potentially be developed into novel anti- Mtb therapies. [ABSTRACT FROM AUTHOR]

A new coordination polymer [Ni(L)(Hbtec)] ( 1) was obtained from the reaction of NiSO·6HO, macrocyclic ligand 3,6,9,17,20,23-hexaaza-29,30-dihydroxy-13,27-di- tert-butyl-tricyclo[23,3,1,1]triaconta-1(28),11,13,15(30),25,26-hexaene (HL), and 1,2,4,5-benzenetetracarboxylic acid (Hbtec) in methanol. Its structure was determined by X-ray diffraction analysis. The crystal is monoclinic C2/ c space group with cell parameters a = 20.4923(3) Å, b = 14.2389(3) Å, c = 14.5130(2) Å, β = 97.441(2)°, V = 4199.05(12) Å, and Z = 8. The X-ray analysis shows that each Ni (II) cation is six-coordinated by an ON donor set. The macrocyclic complex [NiL] are bridged by Hbtec anions to form 1D chains, which are further joined via N-H···O hydrogen bonds to yield a 3D supramolecular structure. Thermogravimetric analysis (TGA) for the complex is discussed. Graphical Abstract: The macrocyclic complexes [NiL] are bridged by Hbtec anions to form 1D chains, which are further joined via N-H···O hydrogen bonds to yield a 3D supramolecular structure.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We study gluon condensate in a pion superfluid by calculating the equation of state of the system in the Nambu-Jona-Lasinio model. While in mean-field approximation the growing pion condensate leads to an increasing gluon condensate, meson fluctuations reduce the gluon condensate, and the broken scalar symmetry can be smoothly restored at finite isospin density. [ABSTRACT FROM AUTHOR]

Abstract: Based on the classical flow stress–dislocation density relation and kinetics of dynamic recrystallization (DRX), a model was developed to determine flow stress of magnesium alloy at hot deformation condition. The proposed model is capable of predicting the flow behavior of work hardening and dynamic recovery (DRV) region as well as the softening caused by DRX. To establish the model, the double-differentiation method was used to identify the critical strain for initiation of DRX, and the DRV parameter Ω was evaluated from the work-hardening behavior prior to critical strain. The net softening attributable to DRX was defined as the difference between the DRV and experimental curves, and Avrami equation was employed to represent this softening behavior. The flow stress curves of ZK60 magnesium alloy predicted by the developed model are in good agreement with experimental results, which confirms the validity of the model. [Copyright &y& Elsevier]

In this paper, by improving a line search criterion to yield steplength, and designing a hybrid conjugate parameter to construct sufficient descent direction, we propose a generalized hybrid conjugate gradient projection method for solving large-scale monotone nonlinear equations with convex constraints. For the proposed method, we prove its global convergence under some mild conditions, and study its convergence rate. Numerical comparisons with two existing methods show that our method is promising for solving large-scale nonlinear constrained equations. Furthermore, the experiment results of dealing with image restoration problems also verify that the proposed method is effective. [ABSTRACT FROM AUTHOR]

Abstract: The 3C-like main proteinase of the severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV Mpro, is widely considered to be a major drug target for the development of anti-SARS treatment. Based on the chemical structure of a lead compound from a previous screening, we have designed and synthesized a number of non-peptidyl inhibitors, some of which have shown significantly improved inhibitory activity against SARS-CoV Mpro with IC50 values of ∼60nM. In the absence of SARS-CoV Mpro crystal structures in complex with these synthetic inhibitors, molecular docking tools have been employed to study possible interactions between these inhibitors and SARS-CoV Mpro. The docking results suggest two major modes for the initial binding of these inhibitors to the active site of SARS-CoV Mpro. They also establish a structural basis for the ‘core design’ of these inhibitors by showing that the 3-chloropyridine functions common to all of the present inhibitors tend to cluster in the S1 specificity pocket. In addition, intrinsic flexibility in the S4 pocket allows for the accommodation of bulky groups such as benzene rings, suggesting that this structural plasticity can be further exploited for optimizing inhibitor–enzyme interactions that should promote a tighter binding mode. Most importantly, our results provide the structural basis for rational design of wide-spectrum antiviral drugs targeting the chymotrypsin-like cysteine proteinases from coronaviruses and picornaviruses. [Copyright &y& Elsevier]

White organic light emitting diodes (WOLEDs) with copper phthalocyanine (CuPc), 4,4',4''-tris(N-3-methylphenyl-N-phenyl-amino) triphenylamine (m-MTDATA), tungsten oxide (WO3) and molybdenum oxide (MoOx) as buffer layers have been investigated. The MoOx based device shows superior performance with low driving voltage, high power efficiency and much longer lifetime than those with other buffer layers. For the Cell using MoOx as buffer layer and 4,7-diphenyl-1,10-phenanthroline (Bphen) as electron transporting layer (ETL), at the luminance of 1000 cd m[?]2, the driving voltage is 4.9 V, which is 4.2 V, 2 V and 0.7 V lower than that of the devices using CuPc (Cell-CuPc), m-MTDATA (Cell-m-MTDATA) and WO3 (Cell-WO3) as buffer layers, respectively. Its power efficiency is 7.67 Lm W[?]1, which is 2.37 times higher than that of Cell-CuPc and a little higher than that of Cell-m-MTDATA. The projected half-life under the initial luminance of 100 cd m[?]2 is 55 260 h, which is more than 4.6 times longer than that of Cell-m-MTDATA and Cell-CuPc. The superior performance of Cell-MoOx is attributed to its high hole injection ability and the stable interface between MoOx and organic material. The work function of MoOx has been measured by the contact potential difference method. The J-V curves of 'hole-only' devices indicate that a small hole injection barrier between MoOx/N,'-bis(naphthalene-1-y1)-N, N'-bis(phenyl)-benzidine (NPB) leads to a strong hole injection, resulting in a low driving voltage and a high stability. [ABSTRACT FROM AUTHOR]

Chronic alcohol drinking has been associated with the development of a number of abnormalities, including neuron-behavioral disorders, liver, pancreas, and heart-related diseases and inflammation and immune disorders. Because diverse mechanisms are involved in the development of these disorders, the commonly used receptor- or enzyme-specific drugs do not provide comprehensive protection against the adverse effects of alcoholism. This study describes possible therapeutic potency of puerarin (PU) from kudzu root, polyenylphosphatidylcholine from soy (SPCh), and curcumin (CU) from turmeric against alcohol''s addiction-related and inflammatory-related abnormalities in alcohol-preferring P rats receiving free choice water and 15 ethanol in water. P-rats were fed once daily either the vehicle (for control) or different doses of PU, SPCh, CU, PU SPCh, or PU CU. The rats were divided in two groups one received water alone, and the other free choice water and ethanol. Four rats from each group were fitted with electroencephalogram (EEG) electrodes for EEG recording. After 70 days of alcohol drinking, alcohol was withdrawn for 2 weeks, and the withdrawal symptoms were assessed. This study showed that alcohol drinking for 70 days (1) caused liver inflammation characterized by elevated tumor necrosis factor-α, interleukin-1β, and matrix metalloproteinase-9 expression and (2) dysregulated lipopolysaccharide (LPS)-induced pleurisy. Alcohol withdrawal after 70 days of drinking generated severe withdrawal symptoms including seizure-type EEG activity. PU suppressed the addiction-mediated abnormalities but did not affect the inflammation-related abnormalities, while SPCh or CU suppressed only the inflammation-related abnormalities in alcohol-drinking rats subjected to LPS-induced pleurisy. A combination of PU with SPCh or CU suppressed both the addiction-related and inflammation-related abnormalities of alcohol drinking. Therefore, a mixture consisting of PU and either SPCh or CU may provide alternative therapy for alcohol-related disorders. [ABSTRACT FROM AUTHOR]

Aims: Although alcohol drinking impairs the blood-rain barrier (BBB). the underlying mechanism is not fully understood. Thus, the effects of chronic ethanol drinking on the BBB were studied in vivo, Methods: Alcohol-preferring rats were given for 70 days free choice water and 15% ethanol. Then, they received LPS by i.p. injection. Effiux of [144C]sucrose or [14C]dextran was measured by their microinjection into the brain. Endothelial cells and neurons were isolated from the brain and analysed for mitugen-activated protein kinase (MAPK) and the tight-junction (TJ) protein phosphorylation, NFkB activation, mRNA levels of TJ proteins, inducible nitric oxide synthase, tumour necrosis factor α, intuerleukin-1 β (IL-1β) IL-10 CASPASE-8 and DNA damage. Results: LPS transiently increased [14C]sucrose efflux in water drinking, while it caused a lasting increase in [14C]sucrose and [14C]dextran efflux in ethanol-drinking rats. The time-course of changes in the TJ correlated with (i) an increase in extracellular signal-regulated kinase (ERK), p38mapk Jun-N-terminal Kinase (JNK), and TJ protein phosphorylation, (ii) RelA-p50 and p50-p50 activation, and (iii) a decrease in the TJ proteins' mRNA levels in endothelial cells and neurons. Apoptotic cells were detected in water drinking and LPS (WC-LPS) neurons at 24 h after LPS exposure. Neurons from Et-LPS rats did not exhibit apoptosis. Conclusions: LPS injection in WC-LPS rats transiently disrupted the BBB. Lack of JNK activation and CASPASE-8 may be responsible for lack of apoptusis in endothelial cells and vice versa in neurons. Chronic alcohol drinking in ethanol drinking and LPS (Et-LPS) rats augmented and dysregulated the LPS-induced BBB abnormalities but suppressed apoptusis in neurons. [ABSTRACT FROM AUTHOR]

Abstract: The 3C-like main peptidase 3CLpro is a viral polyprotein processing enzyme essential for the viability of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). While it is generalized that 3CLpro and the structurally related 3Cpro viral peptidases cleave their substrates via a mechanism similar to that underlying the peptide hydrolysis by chymotrypsin-like serine proteinases (CLSPs), some of the hypothesized key intermediates have not been structurally characterized. Here, we present three crystal structures of SARS 3CLpro in complex with each of two members of a new class of peptide-based phthalhydrazide inhibitors. Both inhibitors form an unusual thiiranium ring with the nucleophilic sulfur atom of Cys145, trapping the enzyme''s catalytic residues in configurations similar to the intermediate states proposed to exist during the hydrolysis of native substrates. Most significantly, our crystallographic data are consistent with a scenario in which a water molecule, possibly via indirect coordination from the carbonyl oxygen of Thr26, has initiated nucleophilic attack on the enzyme-bound inhibitor. Our data suggest that this structure resembles that of the proposed tetrahedral intermediate during the deacylation step of normal peptidyl cleavage. [Copyright &y& Elsevier]

Abstract: We have solved the crystal and molecular structures of hepatitis A viral (HAV) 3C proteinase, a cysteine peptidase having a chymotrypsin-like protein fold, in complex with each of three tetrapeptidyl-based methyl ketone inhibitors to resolutions beyond 1.4 Å, the highest resolution to date for a 3C or a 3C-Like (e.g. SARS viral main proteinase) peptidase. The residues of the β-hairpin motif (residues 138–158), an extension of two β-strands of the C-terminal β-barrel of HAV 3C are critical for the interactions between the enzyme and the tetrapeptide portion of these inhibitors that are analogous to the residues at the P4 to P1 positions in the natural substrates of picornaviral 3C proteinases. Unexpectedly, the Sγ of Cys172 forms two covalent bonds with each inhibitor, yielding an unusual episulfide cation (thiiranium ring) stabilized by a nearby oxyanion. This result suggests a mechanism of inactivation of 3C peptidases by methyl ketone inhibitors that is distinct from that occurring in the structurally related serine proteinases or in the papain-like cysteine peptidases. It also provides insight into the mechanisms underlying both the inactivation of HAV 3C by these inhibitors and on the proteolysis of natural substrates by this viral cysteine peptidase. [Copyright &y& Elsevier]

Hepatitis A virus (HAV) 3C proteinase is a member of the picornain cysteine proteases responsible for the processing of the viral polyprotein, a function essential for viral maturation and infectivity. This and its structural similarity to other 3C and 3C-like proteases make it an attractive target for the development of antiviral drugs. Previous solution NMR studies have shown that a Cys24Ser (C24S) variant of HAV 3C protein, which displays catalytic properties indistinguishable from the native enzyme, is irreversibly inactivated by N-benzyloxycarbonyl-l-serine-β-lactone (1a) through alkylation of the sulfur atom at the active site Cys172. However, crystallization of an enzyme–inhibitor adduct from the reaction mixture followed by X-ray structural analysis shows only covalent modification of the ε2-nitrogen of the surface His102 by the β-lactone with no reaction at Cys172. Re-examination of the heteronuclear multiple quantum coherence (HMQC) NMR spectra of the enzyme–inhibitor mixture indicates that dual modes of single covalent modification occur with a ≥3:1 ratio of S-alkylation of Cys172 to N-alkylation of His102. The latter product crystallizes readily, probably due to the interaction between the phenyl ring of the N-benzyloxycarbonyl (N-Cbz) moiety and a hydrophobic pocket of a neighboring protein molecule in the crystal. Furthermore, significant structural changes are observed in the active site of the 3C protease, which lead to the formation of a functional catalytic triad with Asp84 accepting one hydrogen bond from His44. Although the 3C protease modified at Cys172 is catalytically inactive, the singly modified His102 Nε2-alkylated protein displays a significant level of enzymatic activity, which can be further modified/inhibited by N-iodoacetyl-valine-phenylalanine-amide (IVF) (in solution and in crystal) or excessive amount of the same β-lactone inhibitor (in solution). The success of soaking IVF into HAV 3C–1a crystals demonstrates the usefulness of this new crystal form in the study of enzyme–inhibitor interactions in the proteolytic active site. [Copyright &y& Elsevier]

B ackground Carrageenin (CAR) injection into the pleural cavity causes local inflammation called carrageenin-induced pleurisy (CAR-IP). Inflammation onset is characterized by an activation of pro-inflammatory NFκB, RelA-p50, while inflammation resolution is characterized by an activation of an anti-inflammatory NFκB, p50-p50, that re-establishes homeostasis, an essential process for an organism's survival. Although chronic alcohol intake disrupts inflammation, the mechanism behind the development of inflammatory disorder in alcoholics is not yet known. Therefore, the aim of this investigation was to study the effects of ethanol intake on CAR-IP and NFκB activation in pleural fluid neutrophils in P rats. Methods Alcohol-preferring, P rats were given free choice of alcohol (15% ethanol) and water or water alone (for control) for 15 days. Then, each rat was injected with 0.2 ml of 2% CAR into the pleural cavity under light ether anesthesia. At different time intervals after the CAR injection, rats were anesthetized and their blood and pleural fluid samples were collected. Pleural fluid inflammatory cells were identified with Turk's or Wright-Giemsa staining. Different cell types were sorted using a fluorescence-activated cell sorter. Pleural fluid neutrophils were examined for apoptosis and activation of the two NFκB subspecies. Results In control rats, fluid began to accumulate in the pleural cavity 0.5 h after, which peaked 24 h after, CAR injection. Then, the values declined gradually. The increase in pleural fluid correlated with RelA-p50 activation, while the decline in pleural fluid correlated with p50-p50 activation and apoptosis in neutrophils. In alcohol-drinking rats, pleural fluid remained elevated for up to 6 days after CAR injection. Neutrophils from alcohol-drinking rats exhibited suppressed apoptosis, augmented RelA-p50 activation, and suppressed p50-p50 activation. Conclusions Alcohol intake prolonged inflammation in P rats. An alcohol-induced upregulation of RelA-p50 activation and downregulation of p50-p50 activation may be causally related to the alcohol-induced inflammation dysregulation. [ABSTRACT FROM AUTHOR]

Poliovirus RNA replication is initiated when a molecule of UMP is covalently linked to the hydroxyl group of a tyrosine in the terminal protein VPg. This reaction can be reproduced in vitro with an assay that utilizes two purified viral proteins, RNA polymerase 3D[sup pol] and viral protein 3CD[sup pro], synthetic VPg, UTP, and Mg[sup 2+]. The template for the reaction is either poliovirus RNA or transcripts of a small RNA hairpin, termed cre(2C), located in the coding sequence of protein 2C[sup ATPase]. The products of the reaction are VPgpU and VPgpUpU, the primers used by 3D[sup pol] for RNA synthesis. With mutant template RNAs in this assay we determined the precise initiation site. Our results indicate that 1) 3D[sup pol] does not possess strict specificity toward the nucleotide it links to VPg, 2) A-5 of the conserved ¹GXXXAAAXXXXXXA[sup 14] sequence in the loop is the template nucleotide for the linkage of both the first and second UMPs to VPg, 3) VPgpUpU is synthesized by a "slideback" mechanism, and 4) A-6 provides specificity to the reaction during the slide-back step and also modulates the uridylylation reaction. In additional experiments we determined the effect of mutations in the [sup 5]AAA[sup 7] sequence of cre(2C) on viral growth, RNA replication, and on the activity of the 2C[sup ATPase] protein. Furthermore, we observed that the spacing between G-1 and A-5 and the size of the loop affect the yield but not the nature of the VPglinked products. [ABSTRACT FROM AUTHOR]

BaCrO4 and SrCrO4 photocatalyst powders were prepared by the solid state reaction method. They were characterized by powder X-ray diffraction, UV–Vis diffuse reflection spectroscopy and photocatalytic activity measurements in case of sacrificial reagents CH3OH and AgNO3 under UV and visible light irradiation (λ>420 nm), respectively. The band gaps of BaCrO4 and SrCrO4 were determined as 2.63 and 2.44 eV. Due to the decrease of the ionic radius of the cation, the photocatalyst SrCrO4 showed much lower photocatalytic activity than BaCrO4 in evolving H2 from CH3OH/H2O solution. The difference in their photocatalytic activity is ascribed to the special electronic structures of BaCrO4 and SrCrO4. [Copyright &y& Elsevier]

Calcineurin (CN) is a highly abundant phosphatase in the brain and it is the only Ca2+- and calmodulin-dependent protein serine/threonine phosphatase. There is considerable evidence to suggest that CN plays an essential role in activity-dependent modulation of synaptic efficacy. It has been shown recently that inhibitors of CN, such as CsA or FK506, impair memory formation in day-old chicks. In our present study, extract of Fructus cannabis (EFC) with activation of CN, extracted from Chinese traditional medicine, was used to determine the effects on memory and immunity. In the step-down-type passive avoidance test, the plant extract (0.2 g/kg) significantly improved amnesia induced by chemical drugs in mice, and greatly enhanced the ability of cell-mediated type hypersensitivity and nonspecific immune responses in normal mice. The present study provided pharmacological evidence for Chinese herbal medicine screening from molecular model. [Copyright &y& Elsevier]

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis and limited treatment. As a major component of the tumor microenvironment, tumor-associated macrophages (TAMs) play an important role in facilitating the aggressive behavior of TNBC. This study aimed to explore the novel mechanism of TAMs in the regulation of epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties in TNBC. Methods: Expression of the M2-like macrophage marker CD163 was evaluated by immunohistochemistry in human breast cancer tissues. The phenotype of M2 macrophages polarized from Tohoku-Hospital-Pediatrics-1 (THP1) cells was verified by flow cytometry. Transwell assays, wound healing assays, western blotting, flow cytometry, ELISA, quantitative polymerase chain reaction (qPCR), luciferase reporter gene assays, and immunofluorescence assays were conducted to investigate the mechanism by which TAMs regulate EMT and CSC properties in BT549 and HCC1937 cells. Results: Clinically, we observed a high infiltration of M2-like tumor-associated macrophages in TNBC tissues and confirmed that TAMs were associated with unfavorable prognosis in TNBC patients. Moreover, we found that conditioned medium from M2 macrophages (M2-CM) markedly promoted EMT and CSC properties in BT549 and HCC1937 cells. Mechanistically, we demonstrated that chemokine (C–C motif) ligand 2 (CCL2) secretion by TAMs activated Akt signaling, which in turn increased the expression and nuclear localization of β-catenin. Furthermore, β-catenin knockdown reversed TAM-induced EMT and CSC properties. Conclusions: This study provides a novel mechanism by which TAMs promote EMT and enhance CSC properties in TNBC via activation of CCL2/AKT/β-catenin signaling, which may offer new strategies for the diagnosis and treatment of TNBC. 5r3JY8ktnQBgogUH1DXeQZ Video Abstract [ABSTRACT FROM AUTHOR]

Aims: The stoichiometric traits of litter play an important role in driving litter decomposition and ecosystem nutrient cycling. While the impacts of nitrogen (N) deposition on the species-level litter stoichiometric traits have been well addressed, we know little about that at community-level, which is supposed to be driven by both intra-specific variation and changes in community composition. Methods: We examined the effects of N deposition on litter phosphorus (P) concentration and N:P ratio at both species- and community-level in a semi-arid grassland of northern China. We further decomposed the community-level variations of litter nutritional traits into intra- and inter-specific variation. Results: Nitrogen addition, especially at high rates, substantially changed community composition. Litter P concentrations and N:P ratios significantly varied among different species. Litter P concentrations and N:P ratios at both species- and community-level were positively correlated with N addition rates. Biomass-weighted community-level N:P ratios were more sensitive to N addition than the non-weighted ones, indicating that community composition strengthened the positive impacts of N addition on litter N:P ratios. There was positive co-variation between intra- and inter-specific variation for litter N:P ratio, indicating the consistency of community composition and intra-specific variation in their effects on litter N:P ratio. Conclusions: Our results indicated that the imbalance of N and P following N enrichment would be much larger than the expectation based on the findings from species-level, and thus highlight the importance of changes in community composition in driving the responses of community-level litter N:P stoichiometry to N deposition in the semi-arid grassland. [ABSTRACT FROM AUTHOR]