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The microbial community structure and diversity of Jiang-flavor Daqu (TS, WS, WM, MH and DJ) from different areas of Maotai town were analyzed by using the third-generation nanopore sequencing platform, and its physicochemical indexes and characteristic flavor substances were measured. The results showed that there were some similarities and differences between Daqu in different areas of Maotai town. In terms of microbial community structure, Bacillus, Saccharopolyspora, Weissella, Staphylococcus and Streptomyces were the common dominant bacterial genera in the five Daqu samples. Among them, Bacillus was the absolute dominant bacteria in MH and DJ. Aspergillus and Penicillium were the common dominant fungal genera, and the proportions of Lichtheimia and Saccharomycopsis in TS, WM and MH were significantly higher than those in DJ and WS. Compared with TS and WM, network correlation analysis showed that MH, DJ and WS had stronger interactions among dominant bacteria. In addition, redundancy analysis (RDA) showed that Weissella was positively correlated with esterification power, liquefaction power, saccharification power, acetic acid, ethyl acetate, ethyl lactate and n-pentanol. Lichtheimia was positively correlated with liquefaction power, saccharification power, acetic acid, isovaleric acid, 2,3-butanediol, phenylacetaldehyde and dibutyl phthalate. Saccharomycopsis was positively correlated with esterification power and ethyl acetate. Bacillus was positively correlated with 2,3,5,6-tetramethylpyrazine, propionic acid, isovaleric acid, dibutyl phthalate, 2,3-butanediol and phenacetaldehyde.

"The authors declare no competing interests." now reads: "JPdRV, WDD and RWK are co-founders and managing members of InflamaCORE, LLC and have licensed patents on inflammasome proteins as biomarkers of injury and disease as well as on targeting inflammasome proteins for therapeutic purposes. JPdRV, WDD and RWK are Scientific Advisory Board Members of ZyVersa Therapeutics.". [Extracted from the article]

Tumor-associated macrophages (TAMs) play a dual role in tumors. However, the factors which drive the function of TAMs in cholangiocarcinoma remain largely undefined. SHH signaling pathway and endoplasmic reticulum stress (ERS) indicators were detected in clinical tissues and cholangiocarcinoma cell lines. TAMs were co-cultured with cholangiocarcinoma cells under conditions of hypoxia/normoxia. Polarized TAMs were counted by flow cytometry, and TGF-β1 levels in cell supernatants were detected by ELISA. The effects of glioma-associated oncogene GLI2 on TAMs themselves and cholangiocarcinoma cells were examined by conducting interference and overexpression assays. The SHH signaling pathway and ERS were both activated in tumor tissues or tumor cell lines under conditions of hypoxia. In co-culture experiments, the presence of cholangiocarcinoma cells increased the proportion of M2-polarized TAMs and the secretion of TGF-β1 by TAMs, while knockdown of SHH expression reversed those increases. Overexpression of GLI2 in TAMS or stimulation of TAMS with Hh-Ag1.5 increased their levels of TGF-β1 expression. Furthermore, under co-culture conditions, interference with GLI2 expression in TAMs reduced the tumor cell migration, invasion, and ER homeostasis induced by Hh-Ag1.5-pretreated TAMs. Under conditions of hypoxia, the presence of cholangiocarcinoma cells promoted the expression of GLI2 and TGF-β1 in Tams, and in turn, TAMs inhibited the apoptosis and promoted the migration and invasion of cholangiocarcinoma cells. In vivo, an injection of cholangiocarcinoma cells plus TAMs contributed to the growth, EMT, and ER homeostasis of tumor tissue, while an injection of TAMs with GLI2 knockdown had the opposite effects. Cholangiocarcinoma cells regulated TAM polarization and TGF-β1 secretion via a paracrine SHH signaling pathway, and in turn, TAMs promoted the growth, EMT, and ER homeostasis of cholangiocarcinoma cells via TGF-β1. [Display omitted] • Hypoxia increases SHH level in tumor microenvironment. • Cancer cell derived SHH modulates TAMs polarization and promotes transcriptional expression of TGF-β1. • TGF-β1 secreted by TAMs further activates SHH/GLI2 signaling in cholangiocarcinoma cells. • SHH/GLI2-TGF-β1 loop maintains epithelial-mesenchymal transition and endoplasmic reticulum homeostasis in cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI) are among the most common morbidities affecting preterm infants. Although BPD is a predictor of poor NDI, it is currently uncertain how BPD contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are involved in inter-organ communication in diverse pathological processes. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly and activation of inflammatory response. We assessed expression profiles of alveolar macrophage (AM) markers, CD11b, CD11c, and CD206, and ASC in EVs isolated from the plasma of preterm infants at risk for BPD at 1 week of age. We found that infants on higher fraction inspired oxygen (FiO 2 ) therapy (HO 2 , ≥30%) had increased levels of AM-derived EV-ASC compared with infants on lower FiO 2 (LO 2 , <30%). To assess the function of these EVs, we performed adoptive transfer experiments by injecting them into the circulation of newborn mice. We discovered that mice that received EVs from infants on HO 2 had increased lung inflammation, decreased alveolarization, and disrupted vascular development, the hallmarks of BPD. Importantly, these EVs crossed the blood-brain barrier and the EVs from infants on HO 2 caused inflammation, reduced cell survival, and increased cell death with features of pyroptosis and necroptosis in the hippocampus. These results highlight a novel role for AM-derived EV-ASC in mediating the lung-to-brain crosstalk that is critical in the pathogenesis of BPD and brain injury and identify potential novel targets for preventing and treating BPD and brain injury in preterm infants.

Highly pathogenic viruses from family Phenuiviridae , which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes., Importance: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

Objective: To investigate the association of metals/metalloids exposure with risk of liver disfunction among occupational population in Hunan Province, and to explore the potential dose-response relationship., Methods: In 2017, a mining area in Hunan Province was chosen as the research site, and eligible workers were recruited as study subjects. General demographic characteristics, levels of 23 metals/metalloids in plasma and urine, and liver function index(total bilirubin(TBIL), alanine amino transferase(ALT), globulin(GLB) and γ-glutamyl transferase(GGT)) were obtained by questionnaire, physical examination and laboratory tests. Participants were followed up in 2018, 2019 and 2020 respectively. Cox proportional risk model was used to evaluate the relationship between metal/metalloids exposure and risk of liver disfunction, and dose-response relationship curves were plotted by using the restricted cubic spline function., Results: A total of 891 employees were recruited in the study, 576(65.0%)were aged ≤45 years, 832(93.4%) were male and 530(59.5%) worked as smelters. After adjusting various factors such as age, gender, BMI, type of work, education, smoking, alcohol consumption, diet, stress, medical history, exercise and tea consumption, positive correlations were found between plasma tungsten(HR=4.90, 95%CI 1.17-20.48) and urinary barium(HR=1.07, 95%CI 1.02-1.12) levels with abnormally elevated TBIL levels. Additionally, a significant association was observed between plasma thallium and the risk of elevated ALT levels(HR=11.15, 95%CI 1.97-63.29)., Conclusion: Plasma tungsten and thallium, along with barium found in urine, are risk factors for the development of abnormally elevated liver function indices in occupational groups.

Objective: To investigate the association between levels of twenty-three plasma metals/metalloids and the risk of arrhythmia among occupational population., Methods: In 2017, a total of 765 workers aged 18 and above were recruited from a non-ferrous metal factory. The general demographic characteristics were obtained by using questionnaire. Plasma metal/metalloid levels were determined by inductively coupled plasma mass spectrometry(ICP-MS). Participants were followed up in 2018, 2019 and 2020 respectively. After the elements that may affect the incidence of arrhythmia were screened out by least absolute shrinkage and selection operator(LASSO) regression, Cox regression model was used to analyze the relationship between levels of selected elements and risk of arrhythmia occurrence, Quantile g-computation model was used to analyze the effect of element mixture exposure on arrhythmia, and the dose-response curve was estimated by using restricted cubic spline(RCS) function., Results: Of all the research subjects, 386(50.5%) were ≤45 years old; 401(52.4%) had 20 years or more of work experience; 712(93.1%) subjects were male workers. The incidence of arrhythmia was 17.6%. After adjusting for age, seniority, gender, body mass index(BMI), marital status, education level, smoking, drinking, drinking tea, regular exercise, chronic diseases(hypertension, hyperlipidemia), sleep quality and psychological stress, chromium, molybdenum and antimony increased the risk of arrhythmia with HR(95%CI) values of 1.22(1.11-1.34), 1.51(1.20-1.90) and 2.38(1.03-5.49), respectively, while barium reduced the risk of arrhythmia with HR(95%CI) value of 0.98(0.95-1.00)., Conclusion: Chromium, molybdenum and antimony are the risk factors while barium is the protective factor for arrhythmia.

Head and neck cancer (HNC) is one of the most common cancers on the planet, with approximately 600,000 new cases diagnosed and 300,000 deaths every year. Research into the biological basis of HNC has advanced slowly over the past decades, which has made it difficult to develop new, more effective treatments. The patient-derived organoids (PDOs) are made from patient tumor cells, resembling the features of their tumors, which are high-fidelity models for studying cancer biology and designing new precision medicine therapies. In recent years, considerable effort has been focused on improving "organoids" technologies and identifying tumor-specific medicine using head and neck samples and a variety of organoids. A review of improved techniques and conclusions reported in publications describing the application of these techniques to HNC organoids is presented here. Additionally, we discuss the potential application of organoids in head and neck cancer research as well as the limitations associated with these models. As a result of the integration of organoid models into future precision medicine research and therapeutic profiling programs, the use of organoids will be extremely significant in the future., 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 Qi, Tan, Zhang, Zhou, Chen, Zha, Wang and Wen.)

Backgrounds and Aims: Pain is the main reason for hysteroscopy failure. In day-surgical settings, hysteroscopy procedures are commonly performed with the patient under sedation. Hypoxia is the most common adverse event during sedation and can lead to severe adverse events. This study aimed to compare the incidence of hypoxia when using high-flow nasal oxygen (HFNO) with that when using regular nasal oxygen in patients undergoing hysteroscopy with sedation., Materials and Methods: In this single-center, prospective, randomized, single-blinded study, 960 female patients undergoing elective diagnostic or operative hysteroscopy were randomly enrolled into the following two groups: the regular nasal group [O 2 (3-6 L/min) covered by an HFNO] and the HFNO group [O 2 (30-60 L/min)] from September 2021 to December 2021. All women were sedated with propofol (1.5 mg/kg) and remifentanil (1.5 μg/kg) in the operating room. The primary outcome was the incidence of hypoxia (75% ≤ SpO 2 < 90%, < 60 s)., Results: HFNO decreased the incidence of hypoxia (75% ≤ SpO 2 < 90%, < 60 s), subclinical respiratory depression (90% ≤ SpO 2 < 95%) and severe hypoxia (SpO 2 < 75% for any duration or 75% ≤ SpO 2 < 90% for ≥ 60 s) from 24.38 to 0.83%, from 11.25 to 1.46% and from 3.75 to 0%, respectively ( P < 0.001)., Conclusion: In procedures conducted to treat female infertility, HFNO can reduce hypoxia during hysteroscopy in patients sedated with propofol, and it can prevent the occurrence of subclinical respiratory depression and severe hypoxia., 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 © 2022 Tang, Huang, Chai, Zhang, Zhang, Chen, Su and Huang.)

Background: The role of caudal-related homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the mRNA (message RNA) expression of CDX2 in NSCLC, and to determine its relationship with miR-744 (microRNA744) and its potential as a biomarker of NSCLC., Methods: MiR-744 is overexpressed in A549, H460, and H1299 cell lines. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression. A chromatin immunoprecipitation (ChIP) essay was performed to determine the CDX2 binding sites. We then conducted a luciferase reporter essay to analyze interaction between MiR-744 and 3'UTRs (the 3' untranslated sequences). The migration and Boyden chamber method were used to study cell mobility., Results: In this study, we found that ectopic CDX2 increased the expression of miR-744, while the attenuation of CDX2 reduced the expression of miR-744 by qRT-PCR. Chromatin immunoprecipitation experiments confirmed that CDX2 directly binds to the promoter of miR-744. The luciferase reporter assay further verified the binding sites of -347 to -358 bp in the most likely promoter like sequence of miR-744. CDX2-induced up-regulation of miR-744 can significantly promote the migration and invasion of NSCLC cells, while overexpression CDX2 is sufficient to rescue the migration and invasion capacity of these cells following knockdown of miR-744., Conclusions: In summary, our results confirmed for the first time the regulatory mechanism of CDX2 on miR-744 transcription and provided a potential mechanism for CDX2 as an oncogene in lung cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4526). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)