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Mutation of methylenetetrahydrofolate reductase (MTHFR) C677T leads to the decrease of folate utilization and the impairment of spermatogenesis. This study attempts to investigate the association between MTHFR C677T polymorphisms and nonobstructive oligozoospermia, asthenozoospermia or oligoasthenozoospermia in the Chinese population. The study cohort comprised 189 patients diagnosed with oligozoospermia, asthenozoospermia or oligoasthenozoospermia, and 626 controls based on clinical examinations. The MTHFR c.677 genotype of all subjects was determined by fluorescence staining in situ hybridization and the significance of different genotype frequencies was further analyzed by Chi-square test. The results showed that the frequency of MTHFR 677 CT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 33.3%, 38.3% and 44.0% respectively, whereas it was 47.3% in the control group. The P value of Chi-square test was 0.070, 0.103 and 0.654, respectively. The frequency of MTHFR 677 TT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 31.1%, 11.7% and 18.0% respectively, while that in the control group was 19.5%. The P value of Chi-square test was 0.061, 0.070 and 0.066, respectively. Collectively, there is a weak association between MTHFR C677T polymorphisms and oligozoospermia, asthenozoospermia or oligoasthenozoospermia within the current Chinese population cohort., (© 2024. The Author(s).)

Staphylococcus aureus inhabits diverse habitats including food waste and wastewater treatment plants. Cases of S. aureus-induced infection are commonly reported worldwide. The emergence of antimicrobial resistance (AMR) of S. aureus is a growing public health threat worldwide. Here, we longitudinally monitored global trends in antibiotic resistance genes (ARGs) of 586 S. aureus strains, isolated between 1884 and 2022. The ARGs in S. aureus exhibited a significant increase over time (P < 0.0001). Mobile genetic elements play a crucial role in the transfer of ARGs in S. aureus strains. The structural equation model results revealed a significant correlation between the human development index and rising antibiotic consumption, which subsequently leads to an indirect escalation of AMR in S. aureus strains. Lastly, a machine learning algorithm successfully predicted the AMR risk of global terrestrial S. aureus with over 70% accuracy. Overall, these findings provided valuable insights for managing AMR in S. aureus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Activated sludge (AS) plays a vital role in removing organic pollutants and nutrients from wastewater. However, the risks posed by horizontal gene transfer (HGT) between bacteria in AS are still unclear. Here, a total of 478 high-quality non-redundant metagenome-assembled genomes (MAGs) were obtained. >50 % and 5 % of MAGs were involved in at least one HGT and recent HGT, respectively. Most of the transfers (82.4 %) of antimicrobial resistance genes (ARGs) occurred among the classes of Alphaproteobacteria and Gammaproteobacteria. The bacteria involved in the transfers of virulence factor genes (VFGs) mainly include Alphaproteobacteria (42.3 %), Bacteroidia (19.2 %), and Gammaproteobacteria (11.5 %). Moreover, the number of ARGs and VFGs in the classes of Alphaproteobacteria and Gammaproteobacteria was higher than that in other bacteria (P < 0.001). Mobile genetic elements were important contributors to ARGs and VFGs in AS bacteria. These results have implications for the management of antimicrobial resistance and virulence in activated sludge microorganisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pyroptosis, a novel form of programmed cell death (PCD) discovered after apoptosis and necrosis, is characterized by cell swelling, cytomembrane perforation and lysis, chromatin DNA fragmentation, and the release of intracellular proinflammatory contents, such as Interleukin (IL) 8, IL-1β, ATP, IL-1α, and high mobility group box 1 (HMGB1). Our understanding of pyroptosis has increased over time with an increase in research on the subject: gasdermin-mediated lytic PCD usually, but not always, requires cleavage by caspases. Moreover, new evidence suggests that pyroptosis induction in tumor cells results in a strong inflammatory response and significant cancer regression, which has stimulated great interest among scientists for its potential application in clinical cancer therapy. It's worth noting that the side effects of chemotherapy and radiotherapy can be triggered by pyroptosis. Thus, the intelligent use of pyroptosis, the double-edged sword for tumors, will enable us to understand the genesis and development of cancers and provide potential methods to develop novel anticancer drugs based on pyroptosis. Hence, in this review, we systematically summarize the molecular mechanisms of pyroptosis and provide the latest available evidence supporting the antitumor properties of pyroptosis, and provide a summary of the various antitumor medicines targeting pyroptosis signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 You, Wang, Meng, Huang, Fang and Li.)

Vibrio parahaemolyticus is a common pathogen, and has emerged with multiple antimicrobial resistance (AMR). However, few studies have conducted large-scale investigations of AMR and virulence trends of V. parahaemolyticus worldwide. This study longitudinally monitored antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) trends of 1540 V. parahaemolyticus isolates isolated from 1951 to 2021. The number of ARGs in V. parahaemolyticus isolates distinctly increased over the years (P = 5.9e-10), while the number of VFGs decreased significantly (P < 2.2e-16). However, the number of VFGs of isolates isolated from humans has not changed significantly over the years (R = 0.013, P = 0.74), suggesting that the pathogenic risk to humans has not been reduced. Besides, mobile genetic elements are important contributors to ARGs in V. parahaemolyticus (R = 0.34, P < 2.2e-16), but have no promoting effect on VFGs (P = 0.50). The structural equation model illustrated that the human development index promoted the consumption of antibiotics, thereby indirectly promoting an increase in the AMR of the V. parahaemolyticus isolates. Finally, the random forest was performed to predict the ARG and VFG risks of global terrestrial V. parahaemolyticus isolates, and successfully map these threats with over 80% accuracy. This study aimed to evaluate the global risks posed by AMR and virulence, which helps to develop methods specifically targeting V. parahaemolyticus to mitigate these threats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Doxorubicin is one of the most classical chemotherapeutic drugs for the treatment of cancer. However, resistance to the cytotoxic effects of doxorubicin in tumor cells remains a major obstacle. Aberrant expression of long non-coding RNAs (lncRNAs) has been associated with tumorigenesis and development via regulation of chromatin remodeling, transcription, and post-transcriptional processing. Emerging studies have also revealed that dysregulation of lncRNAs mediates the development of drug resistance through multiple molecules and pathways. In this review, we focus on the role and mechanism of lncRNAs in the progress of doxorubicin resistance in various cancers, which mainly include cellular drug transport, cell cycle disorder, anti-apoptosis, epithelial-mesenchymal transition, cancer stem cells, autophagy, tumor microenvironment, metabolic reprogramming and signaling pathways. This review is aimed to provide potential therapeutic targets for future cancer therapy, especially for the reversal of chemoresistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Hu, Deng, Fang and Zeng.)

Jun B proto-oncogene (JunB) is a crucial member of dimeric activator protein-1 (AP-1) complex, which plays a significant role in various physiological processes, such as placental formation, cardiovascular development, myelopoiesis, angiogenesis, endochondral ossification and epidermis tissue homeostasis. Additionally, it has been reported that JunB has great regulatory functions in innate and adaptive immune responses by regulating the differentiation and cytokine secretion of immune cells including T cells, dendritic cells and macrophages, while also facilitating the effector of neutrophils and natural killer cells. Furthermore, a growing body of studies have shown that JunB is involved in tumorigenesis through regulating cell proliferation, differentiation, senescence and metastasis, particularly affecting the tumor microenvironment through transcriptional promotion or suppression of oncogenes in tumor cells or immune cells. This review summarizes the physiological function of JunB, its immune regulatory function, and its contribution to tumorigenesis, especially focusing on its regulatory mechanisms within tumor-associated immune processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ren, Cai, Yao and Fang.)

Shigella flexneri infection is the main cause of diarrhea in humans worldwide. The emergence of antimicrobial resistance (AMR) of S. flexneri is a growing public health threat worldwide, while large-scale studies monitoring the longitudinal AMR trends of isolates remain scarce. Here, the AMR gene (ARG) profiles of 717 S. flexneri isolates from 1920 to 2020 worldwide were determined. The results showed that the average number of ARGs in isolates has increased significantly, from 19.2 ± 2.4 before 1970 to 29.6 ± 5.3 after 2010. In addition, mobile genetic elements were important contributors to ARGs in S. flexneri isolates. The results of the structural equation model showed that the human development index drove the consumption of antibiotics and indirectly promoted the antibiotic resistance. Finally, a machine learning algorithm was used to predict the antibiotic resistance risk of global terrestrial S. flexneri isolates and successfully map the antibiotic resistance threats in global land habitats with over 80% accuracy. Collectively, this study monitored the longitudinal AMR trends, quantitatively surveilled the health risk of S. flexneri AMR, and provided a theoretical basis for mitigating the threat of antibiotic resistance.

Pit mud microbial consortia play crucial roles in the formation of Chinese strong-flavor baijiu's key flavor-active compounds, especially butyric and caproic acids. Clostridia , one of the abundant bacterial groups in pit mud, were recognized as important butyric and caproic acid producers. Research on the interactions of the pit mud microbial community mainly depends on correlation analysis at present. Interaction between Clostridium and other microorganisms and its involvement in short/medium-chain fatty acid (S/MCFA) metabolism are still unclear. We previously found coculture of two clostridial strains isolated from pit mud, Clostridium fermenticellae JN500901 ( C. 901) and Novisyntrophococcus fermenticellae JN500902 ( N. 902), could enhance S/MCFA accumulation. Here, we investigated their underlying interaction mechanism through the combined analysis of phenotype, genome, and transcriptome. Compared to monocultures, coculture of C. 901 and N. 902 obviously promoted their growth, including shortening the growth lag phase and increasing biomass, and the accumulation of butyric acid and caproic acid. The slight effects of inoculation ratio and continuous passage on the growth and metabolism of coculture indicated the relative stability of their interaction. Transwell coculture and transcriptome analysis showed the interaction between C. 901 and N. 902 was accomplished by metabolite exchange, i.e., formic acid produced by C. 901 activated the Wood-Ljungdahl pathway of N. 902, thereby enhancing its production of acetic acid, which was further converted to butyric acid and caproic acid by C. 901 through reverse β-oxidation. This work demonstrates the potential roles of mutually beneficial interspecies interactions in the accumulation of key flavor compounds in pit mud. IMPORTANCE Microbial interactions played crucial roles in influencing the assembly, stability, and function of the microbial community. The metabolites of pit mud microbiota are the key to flavor formation of Chinese strong-flavor baijiu. So far, researches on the interactions of the pit mud microbial community have been mainly based on the correlation analysis of sequencing data, and more work needs to be performed to unveil the complicated interaction patterns. Here, we identified a material exchange-based mutualistic interaction system involving two fatty acid-producing clostridial strains ( Clostridium fermenticellae JN500901 and Novisyntrophococcus fermenticellae JN500902) isolated from pit mud and systematically elucidated their interaction mechanism for promoting the production of butyric acid and caproic acid, the key flavor-active compounds of baijiu. Our findings provide a new perspective for understanding the complicated interactions of pit mud microorganisms.

Clostridium inhabiting pit mud (PM) is one of the important bacterial populations for synthesizing flavor compounds of Chinese strong-flavor baijiu. The long-term cereal fermentation with sorghum as the main raw material creates an environment rich in starch, ethanol, and organic acids (mainly lactic acid). However, the genetic factors underpinning Clostridium 's adaptation to PM remain poorly understood. Here, we performed comparative genomic analysis between 30 pit mud-associated (PMA) and 100 non-pit mud-associated (NPMA) Clostridium strains. Comparison analysis of the enrichment of KEGG pathways between PMA and NPMA Clostridium strains showed two-component system, flagellar assembly, and bacterial chemotaxis pathways related to environmental adaptation were enriched in PMA strains. The number of genes encoding alcohol dehydrogenase and l-lactate dehydrogenase in PMA Clostridium strains was significantly higher than that in NPMA, which is helpful for them to adapt to the ethanol- and lactic acid-rich environment. The analysis of carbohydrate-active enzymes demonstrated that glycoside hydrolases (GHs) was the most abundant family in all Clostridium strains, and genes encoding GH4 and GH13, involved in starch and sucrose metabolism, were enriched in PMA Clostridium . Horizontal gene transfer analysis revealed that multiple genes encoding the enzymes involved in carbohydrate and amino acid metabolism were transferred from Bacillus to Clostridium in pit mud. Most of the PMA Clostridium strains had good potential for butyric acid synthesis from ethanol, lactic acid, and starch. Collectively, this study furthers our understanding of the habitat adaptation and metabolic potential of PMA Clostridium strains. IMPORTANCE Pit mud is a typical artificial ecosystem for Chinese liquor production. Clostridium inhabiting pit mud plays essential roles in the flavor formation of strong-flavor baijiu. The relative abundance of Clostridium increased with pit mud quality, further influencing the quality of baijiu. So far, the ecological adaptation of Clostridium to a pit mud-associated lifestyle is largely unknown. Here, comparative genomic analysis of pit mud-associated (PMA) and non-pit mud-associated (NPMA) Clostridium strains was performed. We found genes related to the metabolism of starch, ethanol, and lactic acid were enriched in PMA Clostridium strains, which facilitated their adaptation to the unique brewing environment. In addition, horizontal gene transfer contributed to the adaptation of Clostridium to pit mud. Our findings provide genetic insights on PMA Clostridium strains' ecological adaptation and metabolic characteristics.

High-temperature Daqu, usually used as a fermentation starter for sauce-flavor Baijiu production, plays an essential role in the yield and flavor quality of Baijiu. The environmental heterogeneity of different locations in the workshop during fermentation led to the final production of Daqu with three different types (i.e., white, yellow, and black Daqu). How to use these three types of Daqu in Baijiu production mainly depends on the workers' experience so far. Here, we aimed to reveal the potential functions of different types of Daqu by comparing enzyme activity, volatile metabolites, and microbiota characteristics. White&#95;Qu exhibited the highest liquefaction and saccharification enzyme activities, while the highest neutral proteinase and cellulase enzyme activities were detected in black&#95;Qu. The total volatile content of yellow&#95;Qu and black&#95;Qu was roughly double that of white&#95;Qu, and multivariate analysis revealed distinct volatile dissimilarities across different types of Daqu. Significant differences in bacterial and fungal community structures, assembly patterns, and potential functional profiles were discovered among different types of Daqu. At the genus level, Oceanobacillus and Thermomyces dominated the white&#95;Qu microbiota, and the abundant microbes in yellow&#95;Qu and black&#95;Qu were scattered in Kroppenstedtia and Thermoascus. Bacterial and fungal communities were dominated by deterministic and stochastic assembly processes, respectively, suggesting that bacteria may be more affected by abiotic environmental factors and species interaction than fungi. Co-occurrence network analysis showed positive correlations characterized Daqu microbial networks, and network topological features indicated stronger interactions between bacterial taxa compared with fungal community. The Spearman correlation analysis revealed that four bacterial genera (Kroppenstedtia, Virgibacillus, Scopulibacillus, and Staphylococcus) and two fungal genera (Thermoascus and Aspergillus) exhibited positive correlations with almost all of the abundant volatiles. This work reveals that spatially varying environments lead to the microbiome and metabolome heterogeneity of high-temperature Daqu in the same workshop., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effeicacy of Yishen Huoxue decoction (YSHX) on renal fibrosis induced by unilateral ureteric obstruction (UUO), and on reactive oxygen species (ROS) homeostasis in human umbilical vein endothelial cells (HUVECs)., Methods: Forty male mice were randomly divided into six groups, sham group, UUO group, UUO+ resveratrol (RSV) (15 mg/kg) group, UUO + YSHX 20 mg/kg group (UUO + YSHX-L), UUO + YSHX 40 mg/kg group (UUO + YSHX-M), UUO + YSHX 80 mg/kg group (UUO + YSHX-H). Western blotting was used to measure protein expression levels. Reverse transcription-quantitative polymerase chain reaction was used to measure the mRNA expression. Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample. Cell apoptosis was measured by Annexin V/PI staining. Cell viability was measured using CCK-8/WST-8 assay., Results: YSHX treatment reduced α-SMA and Col-4 expressions, and increased CD31 and VE-cadherin expressions in UUO model mice. In vitro, YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions. YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor coactivator-1α (PGC-1α)/silent mating-type information regulation 2 homolog 3 (Sirt3) signaling., Conclusion: YSHX treatment reduced 109KJ UUO-induced renal injury and fibrosis. Furthermore, YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.

MicroRNAs (miRNAs) consist of a large family of small, non-coding RNAs with the ability to result in gene silencing post-transcriptionally. With recent advances in research technology over the past several years, the physiological and pathological potentials of miRNAs have been gradually uncovered. MiR-149-5p, a conserved miRNA, was found to regulate physiological processes, such as inflammatory response, adipogenesis and cell proliferation. Notably, increasing studies indicate miR-149-5p may act as an important regulator in solid tumors, especially cancers in reproductive system and digestive system. It has been acknowledged that miR-149-5p can function as an oncogene or tumor suppressor in different cancers, which is achieved by controlling a variety of genes expression and adjusting downstream signaling pathway. Moreover, the levels of miR-149-5p are influenced by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there is blank about systematic function and mechanism of miR-149-5p in human cancers. In this review, we firstly summarize the present comprehension of miR-149-5p at the molecular level, its vital role in tumor initiation and progression, as well as its potential roles in monitoring diverse reproductive and digestive malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ren, Yao, Cai, Cai, Su and Fang.)

A Gram-stain-negative, coccus-shaped, obligately anaerobic, non-motile and non-spore-forming bacterium, designated strain JN500902 T , was isolated from the mud in a fermentation cellar used continuously over 30 years for Chinese strong-flavour baijiu production. Colonies were white, circular, convex and smooth-edged. Growth was observed at 20-40 °C (optimum, 37 °C), at pH 5.0-10 (optimum, pH 7.5), with 0-2 % (w/v) NaCl and with 0-4 % (v/v) ethanol. The Biolog assay demonstrated positive reactions of strain JN500902 T in the metabolism of l-fucose and pyruvate. The predominant cellular fatty acids (>10 %) consisted of C 16 : 0 and C 14 : 0 . The major end metabolites of strain JN500902 T were acetic acid and ethanol when incubated anaerobically in liquid reinforced clostridial medium. Acetate was the major organic acid end product. The complete genome size of strain JN500902 T was 3 420 321 bp with 3327 identified genes. The G+C content was 43.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain JN500902 T with the family Lachnospiraceae , having low sequence similarity (92.8 %) to the nearest type strain, Syntrophococcus sucromutans DSM 3224 T and forming a clearly distinct branch. Core genome phylogenetic analysis of the isolate and 134 strains belonging to the family Lachnospiraceae also revealed that strain JN500902 T was well-separated from other genera of this family as a monophyletic clade. The average nucleotide identity and amino acid identity values between strain JN500902 T and 134 Lachnospiraceae strains were less than 74 and 65 %, respectively. Considering its polyphasic characteristics, strain JN500902 T represents a novel genus and species within the family Lachnospiraceae , for which the name Novisyntrophococcus fermenticellae gen. nov., sp. nov. is proposed. The type strain is JN500902 T (=CICC 24502 T =JCM 33939 T ).

Zhejiang Rosy Vinegar (ZRV) is a traditional condiment in Southeast China, produced using semi-solid-state fermentation techniques under an open environment, yet little is known about the functional microbiota involved in the flavor formation of ZRV. In this study, 43 kinds of volatile flavor substances were identified by HS-SPME/GC-MS, mainly including ethyl acetate (relative content at the end of fermentation: 1104.1 mg/L), phenylethyl alcohol (417.6 mg/L) and acetoin (605.2 mg/L). The most abundant organic acid was acetic acid (59.6 g/L), which kept rising during the fermentation, followed by lactic acid (7.0 g/L), which showed a continuously downward trend. Amplicon sequencing analysis revealed that the richness and diversity of bacterial community were the highest at the beginning and then maintained decreasing during the fermentation. The predominant bacteria were scattered in Acetobacter (average relative abundance: 63.7%) and Lactobacillus (19.8%). Both sequencing and culture-dependent analysis showed Lactobacillus dominated the early stage (day 10 to 30), and Acetobacter kept highly abundant from day 40 to the end. Spearman correlation analysis displayed that the potential major groups involved in the formation of flavor compounds were Acetobacter and Lactobacillus, which were also showed strong relationships with other bacteria through co-occurrence network analysis (edges attached to Acetobacter: 61.7%; Lactobacillus: 14.0%). Moreover, structural equation model showed that the contents of ethanol, titratable acid and reducing sugar were the major environmental factors playing essential roles in influencing the succession of bacterial community and their metabolism during the fermentation. Overall, these findings illuminated the dynamic profiles of bacterial community and flavor compounds and the potential functional microbes, which were expected to help us understand the formation of flavor substances in ZRV., (Copyright © 2021 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) are a type of small non-coding RNAs that play an essential role in numerous biological processes by regulating the post-transcriptional expression of target genes. Recent studies have demonstrated that miR-192-5p, a member of the miR-192 family, partakes in several human diseases, especially various cancers, including cancers of the lung, liver, and breast. Importantly, the levels of miR-192-5p are abundant in biofluids, including the serum and urine, and the exosomal levels of miR-192-5p in circulation can aid in the diagnosis and prognosis of various diseases, such as chronic hepatitis B (CHB) infection disease. Notably, recent studies suggest that miR-192-5p is regulated by long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there are no comprehensive overviews on the role of miR-192-5p in human diseases. This review discusses the significant studies on the role of miR-192-5p in various human diseases, with special emphasis on the diseases of the respiratory and digestive systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ren, Yao, Cai and Fang.)

Background: We aimed to assess the overall effect of pelvic muscle training (PFMT) on patients with pelvic organ prolapse (POP) based on eligible randomized controlled trials (RCT)., Methods: We searched the following databases, such as PubMed, Cochrane, and Embase, to identify eligible RCT based on the index words updated to December 2018. We also searched the publications related to the present study. Odds rations (OR), and mean difference (MD) along with 95% confidence interval (95% CI) were used to analyze the main outcomes., Results: In this meta-analysis, 15 RCTs were included with a total of 1309 patients in the PFMT group and a total of 1275 patients in the control group. The overall results showed no significant difference in the incidence of add 2 POP-Q stages (RR: 0.55, 95%CI: 0.19-1.63), add 1 POP-Q stages (RR: 1.04, 95%CI: 0.69-1.57), no POP-Q stages change (RR: 0.94, 95%CI: 0.81-1.09), reduce 2 POP-Q stages (RR: 1.72, 95%CI: 0.79-3.76), self-reported same symptom change (RR: 0.70, 95%CI: 0.45-1.09), and self-reported worse symptom change (RR: 0.67, 95%CI: 0.22-2.03) between the 2groups. Besides, the incidence of reduce 1 POP-Q stages was significantly higher in the PFMT group than that of the control group (RR: 1.80, 95%CI: 1.20-2.69), and the PFMT significantly changed the self-reported symptoms with better outcomes when compared with the control group (RR: 2.90, 95%CI: 1.72-4.89). However, after the therapy, the PFMT group decreased the POP-SS (SMD: -0.24, 95%CI: -0.71-0.22), POPDI-6 (SMD: -0.14, 95%CI: -0.43-0.15), CRADI-8 (SMD: -0.03, 95%CI: -0.16-0.11), and UDI-6 (SMD: -0.17, 95%CI: -0.43-0.10) versus the control group, but without statistical significance., Conclusion: PMFT showed better effect in reducing 1 POP-Q stages, changing the self-reported symptoms with better outcomes, decreasing the score of POP-SS, POPDI-6, CRADI-8, and UDI-6 in women with POP versus the control group. However, more high-quality multicenter RCTs with a larger sample size are needed to confirm the present conclusions., (Copyright © 2020 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

We numerically investigate the nonequilibrium behaviors of classic particles with competing interactions confined in a two-dimensional logarithmic trap. We reveal a quench-induced surprising dynamics exhibiting rich dynamic patterns depending upon confinement strength and trap size, which is attributed to the time-dependent competition between interparticle repulsions and attractions under a circular confinement. Moreover, in the collectively diffusive motions of the particles, we find that the emergence of dynamic structure transformation coincides with a diffusive mode transition from superdiffusion to subdiffusion. These findings are likely useful in understanding the pattern selection and evolution in various chemical and biological systems in addition to modulated systems, and add a new route to tailoring the morphology of pattern-forming systems.

We propose a confinement model and study numerically the structural properties of particles with competing interactions in logarithmic traps (i.e., the confinement potential is a logarithmic function). A rich variety of cluster structures are observed as a function of trap steepness, trap size, and particle density. In addition to the consistent results with previous studies for a harmonic confinement, we observe some new stable structures, including a hybrid cluster structure consisting of clumps surrounded by a circular stripe, parallel stripes, or homogeneous voids surrounded by a ringlike arrangement of clumps, and a gear-like cluster with fringed outer rims evenly arranged along the circumference. Our work reveals that such self-organized structures arise due to the radial density reconfiguration in a finite confined system corresponding to the unconstrained systems, which is controlled by the interplay between the long-range repulsions and the attractions to the minimum of the confinement potential. Such results are likely relevant in understanding the structural properties of confined mermaid systems.

Objectives: The objective of the current study was to evaluate the doses of vancomycin used to obtain therapeutic drug concentrations in pediatric patients on extracorporeal membrane oxygenation (ECMO), using new ECMO technologies., Methods: This was a single-center, retrospective study of patients treated with vancomycin while receiving ECMO using low-volume circuit technology., Results: A total of 28 patients were included in the analysis of the primary endpoint. Patients had a median age of 6 weeks (0-11 years) and a median weight of 3.45 kg (2.44-37.2 kg). Ultrafiltration was used in 89.3% of patients at initiation of ECMO regardless of baseline renal function, resulting in a median urine output of 2 mL/kg/hr at the time of the final vancomycin dose. Most patients started vancomycin at the same time as ECMO. The median total daily dose was 30 mg/kg/day. The median total daily dose in a subset of patients less than one year of age was 20 mg/kg/day. Nearly all patients had at least 1 therapeutic trough serum vancomycin concentration. A total of 16 patients completed their vancomycin course using an interval of every 12 hours or shorter. Half-life was calculated in a subset of 11 patients and the mean was found to be 12.3 ± 2.8 hours., Conclusions: An initial dosing interval of every 12 hours to provide a total daily dose of 30 mg/kg/day is a possible option in pediatric patients on ECMO provided that renal function is normal at baseline. Monitoring of serum vancomycin concentrations for adjustment of dosing is required throughout therapy and is still warranted., Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Background: Activation and consumption of platelets (PLT) and clotting factors along with hemolysis occurs when blood contacts the extracorporeal life support (ECLS) circuit and its components., Study Design and Methods: The objective was to examine the effects of reducing ECLS circuit volume by decreasing tubing length and changing components on blood product usage in neonatal and pediatric patients. Blood product administration was analyzed in 40 consecutive patients who required ECLS for respiratory or cardiac failure before (PRE) and after (POST) changes in circuit design and components., Results: The total circuit volume was reduced from 500 mL (PRE) to 275 mL (POST). In the POST group, total blood product volume usage was 58% lower compared to the PRE group (81 mL/kg/day vs. 191 mL/kg/day, p = 0.003), 65% lower for fresh-frozen plasma (FFP; 15 mL/kg/day vs. 43 mL/kg/day, p = 0.001), and PLT volumes trended lower. In the subgroup of infants with respiratory or cardiac failure, there was a 55% reduction of a total blood product replacement (61 mL/kg/day vs. 136 mL/kg/day, p = 0.008), red blood cell (RBC) use was 61% lower (28 mL/kg/day vs. 71 mL/kg/day, p < 0.049), and there was a 73% reduction in FFP use (11 mL/kg/day vs. 41 mL/kg/day, p < 0.001). In the subgroup of postoperative infants, there was a 25% decrease in RBC use (86 mL/kg/day vs. 115 mL/kg/day, p = 0.03)., Conclusion: Decreasing the ECLS circuit volume by reducing the tubing length and changing the components was associated with a significant reduction in blood product usage., (© 2017 AABB.)

Background: This study aims to evaluate the short-term efficacy of concurrent chemoradiotherapy (CCRT) in primary fallopian tube carcinoma (PFTC) using magnetic resonance diffusion-weighted imaging (MR-DWI)., Patients and Methods: Total abdominal irradiation was performed for 61 PFTC patients after surgery, and paclitaxel and carboplatin were used for CCRT. According to the response evaluation criteria in solid tumors (RECIST1.1), patients were divided into a sensitive (n = 36) and a resistant group (n = 25). Pearson correlation analysis was conducted to assess the correlations of tumor regression rate with apparent diffusion coefficient (ADC)pre, ADCpost, and ∆ADCpost. The efficacy of CCRT in PFTC using MR-DWI was evaluated by ROC curve, logistic regression analysis, Kaplan-Meier survival curve, and Cox regression model., Results: The ADCpre in both the sensitive and the resistant group was negatively associated with the tumor regression rate (r = -0.508), while the ADCpost (r = 0.454) and ∆ADCpost (r = 0.769) were positively associated with the tumor regression rate (all p < 0.05). Histopathological type, FIGO stage, lymphatic metastasis, tumor regression rate, ADCpre, ADCpost, and ∆ADCpost were confirmed as key factors for CCRT in PFTC (all p < 0.05)., Conclusion: Our retrospective study demonstrates the predictive value of MR-DWI in CCRT for PFTC patients., (© 2017 S. Karger GmbH, Freiburg.)

Inspired by recent experimental fabrication of mono-halogenated versions of Metal-Organic Framework MOF-5 (i.e., X-MOF-5, X = F to I) and some experimentally known fully halogenated MOF compounds, we systematically studied frameworks incorporating full halogenation of the BDC linkers of the prototypical Iso-Reticular Metal-Organic Framework (IRMOF) series, exemplified by MOF-5. Using quantum chemistry calculations, we find that halogenation leads to a 90° rotation of the aryl group, which is mainly ascribed to overcrowding between halogen atoms and the carboxyl and benzene ring and strong repulsion among in-plane atoms/groups. The 90° configuration decreases the repulsion, and maximizes the stabilization energy, and is therefore more stable than 0° configuration. We find that the band gap can be tuned from 4.1 to 1.5 eV as we go from F, Cl, Br, to I. This extends the optical response of these experimentally accessible materials through the visible and infrared region. We have also considered a broader range of new materials that substitute various metals for Zn. Totally, 70 materials were systematically examined computationally including (M 4 O)(BDC-Z 4 ) 3 (M = Zn, Cd, Be, Mg, Ca, Sr, Ba; Z = H, F, Cl, Br, I). For the full range of materials, we calculate band gaps of 4.2 to 1.0 eV, corresponding to a threshold of absorption of 290-1240 nm. Four selected materials were tested for stability using short 5 ps molecular dynamics simulations up to 600 K. The new materials with the smallest band gaps could potentially be used in near-infrared (NIR) light-emitting devices. Other properties, e.g., bulk moduli, formation energy, chemical bonding, and optical properties, were also investigated. The present results may provide new materials for use as novel photocatalysts, photoactive materials for photovoltaic cells, or functional devices in nanoelectronics and optoelectronics.

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) gene family has been well-studied in Arabidopsis and play crucial roles in the diverse growth and development processes including establishment and maintenance of boundary of developmental lateral organs. In this study we identified and characterized 38 LBD genes in Lotus japonicus (LjLBD) and 57 LBD genes in Medicago truncatula (MtLBD), both of which are model legume plants that have some specific development features absent in Arabidopsis. The phylogenetic relationships, their locations in the genome, genes structure and conserved motifs were examined. The results revealed that all LjLBD and MtLBD genes could be distinctly divided into two classes: Class I and II. The evolutionary analysis showed that Type I functional divergence with some significantly site-specific shifts may be the main force for the divergence between Class I and Class II. In addition, the expression patterns of LjLBD genes uncovered the diverse functions in plant development. Interestingly, we found that two LjLBD proteins that were highly expressed during compound leaf and pulvinus development, can interact via yeast two-hybrid assays. Taken together, our findings provide an evolutionary and genetic foundation in further understanding the molecular basis of LBD gene family in general, specifically in L. japonicus and M. truncatula., Competing Interests: The authors have declared that no competing interests exist.

We have demonstrated a flexible resistive random access memory unit with trilayer structure by atomic layer deposition (ALD). The device unit is composed of Al2O3/HfO2/Al2O3-based functional stacks on TiN-coated Si substrate. The cross-sectional HRTEM image and XPS depth profile of Al2O3/HfO2/Al2O3 on TiN-coated Si confirm the existence of interfacial layers between trilayer structures of Al2O3/HfO2/Al2O3 after 600°C post-annealing. The memory units of Pt/Al2O3/HfO2/Al2O3/TiN/Si exhibit a typical bipolar, reliable, and reproducible resistive switching behavior, such as stable resistance ratio (>10) of OFF/ON states, sharp distribution of set and reset voltages, better switching endurance up to 10(3) cycles, and longer data retention at 85°C over 10 years. The possible switching mechanism of trilayer structure of Al2O3/HfO2/Al2O3 has been proposed. The trilayer structure device units of Al2O3/HfO2/Al2O3 on TiN-coated Si prepared by ALD may be a potential candidate for oxide-based resistive random access memory.

Atomic layer deposition (ALD) is a powerful deposition technique for constructing uniform, conformal, and ultrathin films in microelectronics, photovoltaics, catalysis, energy storage, and conversion. The possible pathways for silicon dioxide (SiO2) ALD using silicon tetrachloride (SiCl4) and water (H2O) without a catalyst have been investigated by means of density functional theory calculations. The results show that the SiCl4 half-reaction is a rate-determining step of SiO2 ALD. It may proceed through a stepwise pathway, first forming a Si-O bond and then breaking Si-Cl/O-H bonds and forming a H-Cl bond. The H2O half-reaction may undergo hydrolysis and condensation processes, which are similar to conventional SiO2 chemical vapor deposition (CVD). In the H2O half-reaction, there are massive H2O molecules adsorbed on the surface, which can result in H2O-assisted hydrolysis of the Cl-terminated surface and accelerate the H2O half-reaction. These findings may be used to improve methods for the preparation of SiO2 ALD and H2O-based ALD of other oxides, such as Al2O3, TiO2, ZrO2, and HfO2.

Plasma-enhanced atomic layer deposition (PE-ALD) has been applied to prepare high-quality ultrathin films for microelectronics, catalysis, and energy applications. The possible pathways for SiO2 PE-ALD using aminosilanes and O2 plasma have been investigated by density functional theory calculations. The silane half-reaction between SiH4 and surface -OH is very difficult and requires a high activation free energy of 57.8 kcal mol(-1). The introduction of an aminosilane, such as BDMAS, can reduce the activation free energy to 11.0 kcal mol(-1) and the aminosilane plays the role of a self-catalyst in Si-O formation through the relevant half-reaction. Among the various species generated in O2 plasma, (3)O2 is inactive towards surface silane groups, similar to ordinary oxygen gas. The other three species, (1)O2, (1)O, and (3)O, can strongly oxidize surface silane groups through one-step or stepwise pathways. In the (3)O pathway, the triplet must be converted into the singlet and follow the (1)O pathway. Meanwhile, both (1)O and (3)O can decay to (1)O2 and enter into the relevant oxidation pathway. The concept of self-catalysis of aminosilanes may be invoked to design and prepare more effective Si precursors for SiO2 ALD. At the same time, the mechanism of strong surface oxidation by O2 plasma may be exploited in the PE-ALD preparation of other oxides, such as Al2O3, HfO2, ZrO2, and TiO2.

The interaction between 8-azaguanine (8-Azan) and bovine serum albumin (BSA) in Tris-HCl buffer solutions at pH 7.4 was investigated by means of fluorescence and ultraviolet-visible (UV-Vis) spectroscopy. At 298 K and 310 K, at a wavelength of excitation (λ (ex)) of 282 nm, the fluorescence intensity decreased significantly with increasing concentrations of 8-Azan. Fluorescence static quenching was observed for BSA, which was attributed to the formation of a complex between 8-Azan and BSA during the binding reaction. This was illuminated further by the UV-Vis absorption spectra and the decomposition of the fluorescence spectra. The thermodynamic parameters ∆G, ∆H, ∆S were calculated. The results showed that the forces acting between 8-Azan and BSA were typical hydrophobic forces, and that the interaction process was spontaneous. The interaction distance r between 8-Azan and BSA, evaluated according to fluorescence resonance energy transfer theory, suggested that there is a high possibility of energy transfer from BSA to 8-Azan. Theoretical investigations based on homology modeling and molecular docking suggested that binding between 8-Azan and BSA is dominated by hydrophilic forces and hydrogen bonding. The theoretical investigations provided a good structural basis to explain the phenomenon of fluorescence quenching between 8-Azan and BSA.

The reaction of trimethylsilyl-substituted sulfonium ylides with organoboranes (Ph(3)B, Et(3)B) has been studied and although homologated products were obtained in good yield (after oxidation to the corresponding alcohols), the enantiomeric excesses were low with our camphor-based chiral sulfide (up to 40% ee, cf. corresponding phenyl-substituted sulfonium ylides gave >95% ee). Cross-over experiments were conducted to ascertain the nature of this difference in selectivity. Thus, aryl- and silyl-substituted sulfonium ylides (1 equiv.) were (separately) reacted with Et(3)B (1.5 equiv.) followed by Ph(3)B (1.5 equiv.) The experiments were repeated changing the order of addition of the two boranes. It was found that the aryl-substituted sulfonium ylide only trapped the first borane that was added indicating that ate complex formation was non-reversible and so was the selectivity determining step. In contrast the silyl-substituted sulfonium ylide only trapped Ph(3)B (it is more reactive than Et(3)B) indicating that ate complex formation was reversible and so 1,2-migration was now the selectivity determining step. The reactions have been studied computationally and the experimental observations have been reproduced. They have further revealed that the cause of reversibility in the case of the silyl-substituted sulfonium ylides results from ate complex formation being less exothermic and a higher barrier to 1,2-migration.

Asymmetric lithiation of substituted benzylamines, N-Boc-pyrrolidine, or N-Boc-indoline using Beak's methodology was followed by electrophilic quench with trialkylboranes. The resulting borate intermediates rearrange with concomitant C-N bond breakage to give, after oxidation, chiral secondary alcohols with high enantioselectivity.

The reactions of aryl-stabilized sulfur ylides with organoboranes has been studied under a variety of conditions. At 5 or -78 degrees C, the reaction with Et3B gave a mixture of the first and second homologation products, but at -100 degrees C, only the first homologation product was obtained even with just 1.1 equiv of Et3B. Under these optimized conditions, the chiral sulfur ylides (derived from camphor sulfonic acid) with different aryl groups were reacted with Et3B to give the corresponding alcohols (95-98% yield, 96-98% ee) and amines (74-77% yield, >98% ee). The origin of the high enantioselectivity is discussed. The use of nonsymmetrical 9-BBN derivatives was also explored. It was found that whereas primary alkyl substituents gave mixtures of products derived from competing migration of the boron substituent and the boracycle, all other groups resulted in either exclusive migration of the boron substituent (Ph, hexenyl, i-Pr) or exclusive migration of the boracycle (hexynyl, cyclopropyl). The factors responsible for the outcome of the reactions involving a hindered (i-Pr) and an unhindered (propynyl) substituent were studied by DFT calculations. This revealed that, in the case of an unhindered substituent, the conformation of the ate complex is the dominant factor whereas, in the case of a hindered substituent, the barriers to interconversion between the conformers of the ate complex and subsequent migration control the outcome of the reaction.

Calculations show that the unexpected low phenyl migratory aptitude observed in reactions of mixed alkyl-aryl boranes with benzylic sulfur ylides can be attributed to (1) a conformational issue, (2) the reduction of the usual neighbouring effect of the phenyl in the transition state by the benzylic nature of the migrating terminus, (3) steric hindrance suffered by the larger phenyl group migrating to the hindered migrating terminus and this despite (4) the increase in the barrier to alkyl migration by the presence of a 'non-migrating' phenyl on the boron atom.

The reactions of aryl-stabilized sulfonium ylides with trialkyl/triarylboranes have been investigated. Clean monohomologation of the boranes with only a small amount of the higher homologation products (<10%) was observed. The homologation products were isolated as the alcohols (treatment with H2O2/NaOH) and amines (treatment with NH2OSO3H). Although the reactions were conveniently conducted at 5 degrees C, the ylide reaction with tributylborane was very fast even at -78 degrees C (complete after 15 min). Use of chiral sulfides rendered the reactions asymmetric, and high enantioselectivity (>95% ee) was observed in all cases. The ylide-borane reaction was applied to short syntheses of the anti-inflammatory agents neobenodine and cetirizine, both of which contain a chiral diarylmethylalkoxy and diarylmethylamino moiety, respectively.

Density-functional method with different basis sets was applied to the study of the highly efficient and low sensitive explosive 3-nitro-1,2,4-triazole-5-one (NTO) in both gaseous dimer and its bulk state. The binding energies have been corrected for the basis set superposition errors. Six stable dimers (II-VII) were located. The corrected binding energy of the most stable dimer VII is predicted to be -53.66 kJ/mol at the B3LYP/6-311++G(**) level. It was found that the structures of the more stable dimers (V-VII) are through the hydrogen bonding interaction between the carbonyl oxygen and the azole hydrogen of 3-nitro-1,2,4-triazole-5-one. The changes of Gibbs free energies (DeltaG) in the processes from the monomer to the dimers at 298.15 K are 8.51, 0.90, 0.35, -8.74, -10.67, and -11.06 kJ/mol for dimers from II to VII, respectively. Dimers V-VII, possessing cyclic structures, can be spontaneously produced from the isolated monomer at room temperature. The lattice energy is -156.14 kJ/mol, and this value becomes to -150.43 kJ/mol when a 50% correction of the basis set superposition error was adopted. The frontier bands are quite flat. Judged from the value of band gap of 4.0 eV, it may be predicted that 3-nitro-1,2,4-triazole-5-one is an insulator. Most atoms in NTO, with the exception of C(5) atom and the nitro atoms, make up the upper valence bands. In contrast, the lower conduction bands mainly consist of the nitro N and O atoms. The population of the C-NO(2) bond is much less than those of the other bonds and the detonation may be initiated by the breakdown of this bond., ((c) 2004 American Institute of Physics.)

Using data from the evaluation of the Fast Track intervention, this article illustrates three methods for handling attrition. Multiple imputation and ignorable maximum likelihood estimation produce estimates that are similar to those based on listwise-deleted data. A panel selection model that allows for selective dropout reveals that highly aggressive boys accumulate in the treatment group over time and produces a larger estimate of treatment effect. In contrast, this model produces a smaller treatment effect for girls. The article's conclusion discusses the strengths and weaknesses of the alternative approaches and outlines ways in which researchers might improve their handling of attrition.

[reaction: see text] Cyclopropanation of allylic tertiary amines using the Simmons-Smith reagent has been achieved by employing chelating groups in close proximity to the amine. The chelating groups promote cyclopropanation at the expense of N-ylide formation. Using pseudoephedrine as the chelating group, high diastereoselectivity is observed.

[reaction: see text] Zinc-complexed methylene ammonium ylides are formed from tertiary amines and the Simmons-Smith reagent. These stable entities can be activated with n-BuLi to allow reactions typical of ammonium ylides such as [2,3] rearrangements. In the case of oxazolidine 12, ylide formation, activation, and subsequent [2,3] rearrangement was highly efficient and occurred with very high diastereoselectivity.

A mouse targeted for a Y Chromosome gene has not been reported. Because the Y Chromosome is present in only one copy, and most of its genes are critical for germ cell development, such a mouse would likely be infertile. Thus, we describe a new reproductive strategy to enable transmission of targeted Y Chromosome genes to subsequent generations. The strategy uses two segregating copies of Y Chromosome genes to mimic the autosomal condition. To achieve this, we developed a new embryonic stem cell line from the XYSxr(a) mouse, which carries a duplication of the gene-rich Y Chromosome short arm. Importantly, we demonstrate germ line transmission of the YSxr(a) chromosome and describe this significant new tool as a practical solution to enable reproduction in mice targeted for Y Chromosome genes., (Copyright 2002 Wiley-Liss, Inc.)