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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).)

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.)

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.

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.)

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.)

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.

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.

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.