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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.

Nitrogen‐doped hard carbon on Ni foam (NC/NF) with numerous active sites, expanded interlayer distance (0.49 nm), and highly ordered pseudo‐graphic structure is synthesized by a melamine‐assisted hydrothermal pretreatment and subsequent pyrolysis procedure. The high content configurations of pyrrolic‐nitrogen and pyridinic‐nitrogen in NC/NF could provide abundant active sites and defects for efficient Na+ adsorption/desorption and improved transport kinetics. The obvious flocculent structures on carbon surface, corresponding to the highly ordered pseudo‐graphic structure, could enhance the transport kinetics for electrons. The strong electrostatic repulsion of pyrrolic‐nitrogen could expand interlayer distance, facilitating Na+ insertion/extraction process. The balance between high nitrogen content and sufficient graphitization degree comes into strong carbon frameworks with enhanced structural stability and electronic conductivity. When served as free‐standing anodes for sodium‐ion batteries (SIBs), NC/NF presents high rate capability of 128.5 mAh g−1 at 10 A g−1, and excellent cycling stability of 225.4 mAh g−1 after 1000 cycles under high current density of 5 A g−1. These results demonstrate a new light to prepare advanced anodes for SIBs. [ABSTRACT FROM AUTHOR]

Antibodies and antigen-binding fragments (Fabs) can be used to modify the surface of nanoparticles for enhanced target binding. In our previous work, site-specific conjugation of Fabs to polymeric micelles using conventional methods was limited to approximately 30% efficiency, possibly due to steric hindrance related to macromolecular reactants. Here, we report a new method that enables conjugation of Fabs onto a micelle surface in a controlled manner with up to quantitative conversion of nanoparticle reactive groups. Variation of (i) PEG spacer length in a heterofunctionalized cross-linker and (ii) Fab/polymer feed ratios resulted in production of nanoparticles with a range of Fab densities on the surface up to the theoretical maximum value. The biological impact of variable Fab density was evaluated in vitro with respect to cell uptake and cytotoxicity of a drug-loaded (SN38) targeted polymeric micelle bearing anti-EphA2 Fabs. Fab conjugation increased cell uptake and potency compared with non-targeted micelles, although a Fab density of 60% resulted in decreased uptake and potency of the targeted micelles. Altogether, our findings demonstrate that conjugation strategies can be optimized to allow control of Fab density on the surface of nanoparticles and also that Fab density may need to be optimized for a given cell-surface target to achieve the highest bioactivity. [ABSTRACT FROM AUTHOR]

"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]

Cover Feature: Nitrogen-Doped Hard Carbon on Nickel Foam as Free-Standing Anodes for High-Performance Sodium-Ion Batteries (ChemElectroChem 3/2020) B The Cover Feature b illustrates a nitrogen-doped hard carbon on Ni foam as a free-standing anode for sodium-ion batteries. Nitrogen-doped carbon, free-standing anodes, sodium-ion batteries, high rate performance, long cycling life. [Extracted from the article]

This paper describes the fate of a nitrobenzene-degrading bacterium, Klebsiella oxytoca NBA-1, which was isolated from a pharmaceutical wastewater treatment facility. The 90-day survivability of strain NBA-1 after exposure to sludge under anaerobic and aerobic conditions was investigated. The bacterium was inoculated into sludge amended with glucose and p -chloronitrobenzene ( p -CNB) to compare the bacterial community variations between the modified sludge and nitrobenzene amendment. The results showed that glucose had no obvious effect on nitrobenzene biodegradation in the co-metabolism process, regardless of the presence/absence of oxygen. When p -CNB was added under anaerobic conditions, the biodegradation rate of nitrobenzene remained unchanged although p -CNB inhibited the production of aniline. The diversity of the microbial community increased and NBA-1 continued to be one of the dominant strains. Under aerobic conditions, the degradation rate of both nitrobenzene and p -CNB was only 20% of that under anaerobic conditions. p -CNB had a toxic effect on the microorganisms in the sludge so that most of the DGGE (denaturing gradient gel electrophoresis) bands, including that of NBA-1, began to disappear under aerobic conditions after 90 days of exposure. These data show that the bacterial community was stable under anaerobic conditions and the microorganisms, including NBA-1, were more resistant to the adverse environment. [ABSTRACT FROM AUTHOR]

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]

Increasing evidence indicates the adverse effect of air pollution exposure during pregnancy on neurologic development among children. However, the impact on neurobehavioral development in fetus remains unknown. In 2017, a total of 1193 mother–newborns pairs were enrolled in a birth cohort study in Changsha, China. Exposures to PM 2.5 , PM 10, SO 2 , CO and NO 2 were determined by using inverse distance weighted method based on local monitoring station data. Neurobehavioral measure was administered at 48–72 h postpartum by utilizing the neonatal behavioral neurological assessment (NBNA). Basic information and covariates were collected by face to face interview. Generalized linear regression and multivariable restricted cubic spline function were performed to explore the trimester-specific association and dose-response relationship of maternal air pollution exposure with NBNA score, respectively. In adjusted three-pollutant model, PM 2.5 exposure in trimester 2 was negatively associated with behavior score (β, −0.003; 95% CI, −0.006, −0.001) and the inverse relation was more pronounced in male infants. In addition, PM 2.5 level in the 2nd trimester was negatively related to activetone score (β, −0.012; 95% CI, −0.021, −0.002) in a dose-dependent manner for both genders. Collectively, our results demonstrated that prenatal exposure to PM 2.5 was linked to poor neurobehavioral performance of newborns. The second trimester was the most sensitive time window for the developments of behavior and activetone, and male subject was more vulnerable as compared to females. • Prenatal exposure to PM 2.5 was associated with poor neurobehavioral performance of newborns. • The second trimester was the most sensitive time window for behavioral and activetone development. • Male newborns were more vulnerable to the influence of PM 2.5 as compared to females. [ABSTRACT FROM AUTHOR]

Development of three-dimensional self-assembled hollow nanoarchitectures combining functional shells and inner voids is an important approach for realizing high-rate and long-life battery electrodes. As a potential high-performance anode for sodium-ion batteries (SIBs), (1 1 0)-bridged nanoblocks self-assembled VS 4 hollow microspheres (PNBH-VS 4) are controllably synthesized by a facile one-step hydrothermal method. The (1 1 0)-bridged structure constructs the Na+ conducting channels and e− transfer paths among nano-grains and nanoblocks, and the self-assembled hollow structure presents the double space physical entrapment effect for the excessive volume change of nanoblocks, which synergistically improve the Na+ storage kinetics and structure stability. When employed as an anode for SIBs, PNBH-VS 4 electrode exhibits the superior rate capability and long cycling life, outperforming those of the ever-reported VS 4 -based anode materials. At 0.2, 0.5, 1.0 and 2.0 A g−1, the capacity can reach 629, 564, 428 and 400 mAh g−1 after 250, 200, 350 and 700 cycles, respectively. Even at 5.0 A g−1, the capacity can still stabilize at 309 mAh g−1 after 1000 long cycles. In addition, it is revealed that PNBH-VS 4 electrode undertakes the insertion and conversion reaction in the potential range of 0.50–3.00 and 0.05–0.50 V, respectively, where the main capacity contribution originates from the insertion reaction. Meanwhile, PNBH-VS 4 electrode exhibits better insertion reversibility at lower current densities and conversion reversibility at higher current densities during cycling, respectively. [ABSTRACT FROM AUTHOR]

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.)

Background: Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of premature infants. Connective tissue growth factor (CTGF) plays an important role in tissue development and remodeling. We have previously shown that targeted overexpression of CTGF in alveolar type II epithelial cells results in BPD-like pathology and activates β-catenin in neonatal mice., Methods: Utilizing this transgenic mouse model and ICG001, a specific pharmacological inhibitor of β-catenin, we tested the hypothesis that β-catenin signaling mediates the effects of CTGF in the neonatal lung. Newborn CTGF mice and control littermates received ICG001 (10 mg/kg/dose) or placebo (dimethyl sulfoxide, equal volume) by daily i.p. injection from postnatal day 5 to 15. Alveolarization, vascular development, and pulmonary hypertension (PH) were analyzed., Results: Administration of ICG001 significantly downregulated expression of cyclin D1, collagen 1a1, and fibronectin, which are the known target genes of β-catenin signaling in CTGF lungs. Inhibition of β-catenin signaling improved alveolar and vascular development and decreased pulmonary vascular remodeling. More importantly, the improved vascular development and vascular remodeling led to a decrease in PH., Conclusion: β-Catenin signaling mediates the autocrine and paracrine effects of CTGF in the neonatal lung. Inhibition of CTGF-β-catenin signaling may provide a novel therapy for BPD.

Background: Overexpression of connective tissue growth factor (CTGF) in alveolar type II epithelial (AT II) cells disrupts alveolar structure, causes interstitial fibrosis, and upregulates integrin-linked kinase (ILK). Whether CTGF-ILK signaling induces epithelial to mesenchymal transition (EMT) in AT II cells is unknown., Methods: Transgenic mice with targeted overexpression of CTGF in AT II cells were generated utilizing the surfactant protein C (SP-C) gene promoter and doxycycline-inducible system. AT II cells were isolated from 4-wk-old CTGF-overexpressing (CTGF+) mice and control littermates, and cultured on Matrigel. Cells were transfected with ILK siRNA, and cell morphology and expression of cell differentiation markers were analyzed., Results: The AT II cells from the control lungs grew in clusters and formed alveolar-like cysts and expressed SP-C. In contrast, the cells from CTGF+ lungs were spread and failed to form alveolar-like cysts. These cells expressed higher levels of CTGF, α smooth muscle actin (α-SMA), fibronectin and vimentin, the mesenchymal markers, suggesting EMT-like changes. Transfection with ILK siRNA not only dramatically attenuated ILK expression, but also decreased α-SMA expression as well as reversed cell morphological changes in CTGF+ AT II cells., Conclusion: Overexpression of CTGF induces EMT in mouse primary AT II cells and this is mediated by ILK.

Background: Hyperoxia-induced neonatal lung injury is associated with activation of Wnt/β-catenin signaling. Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are Wnt coreceptors that bind to Wnt ligands and mediate canonical Wnt/β-catenin signaling. We hypothesized that inhibition of LRP5/6 by their universal inhibitor, Mesd, would attenuate hyperoxia-induced lung injury., Methods: Newborn rat pups were randomly exposed to normoxia or hyperoxia at 90% FiO2 and injected intraperitoneally with placebo or Mesd every other day for 14 d. On day 15, phosphorylation of LRP5/6 (pLRP5/6), expression of Wnt/β-catenin target genes, cyclin D1 and Wnt-induced signaling protein-1 (WISP-1), right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), pulmonary vascular remodeling, alveolarization, and vascularization were measured., Results: Hyperoxia exposure markedly induced pLRP5/6, cyclin D1, and WISP-1 expression in the lungs of placebo animals, but they were significantly attenuated by the administration of Mesd. Mesd also significantly attenuated hyperoxia-induced pulmonary hypertension (PH) and pulmonary vascular remodeling. However, there was no effect on alveolarization or vascularization after Mesd administration., Conclusion: This study demonstrates that LRP5/6 mediates pulmonary vascular remodeling and PH in hyperoxia-induced neonatal lung injury, thereby suggesting a potential therapeutic target to alleviate PH in neonates with severe bronchopulmonary dysplasia.

Introduction: Oxygen exposure plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD). The phosphodiesterase inhibitor pentoxifylline (PTX) has anti-inflammatory and antifibrotic effects in multiple organs. It was hypothesized that PTX would have a protective effect on hyperoxia-induced lung injury (HILI)., Methods: Newborn Sprague-Dawley rats were exposed to >95% oxygen (O(2)) and injected subcutaneously with normal saline (NS) or PTX (75 mg/kg) twice a day for 9 d. NS-injected, room air-exposed pups were controls. At days 4 and 9, lung tissue was collected to assess edema, antioxidant enzyme (AOE) activities, and vascular endothelial growth factor (VEGF) expression. At day 9, pulmonary macrophage infiltration, vascularization, and alveolarization were also examined., Results: At day 9, treatment with PTX significantly increased survival from 54% to 88% during hyperoxia. Treatment with PTX significantly decreased lung edema and macrophage infiltration. PTX treatment increased lung AOE activities including those of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Furthermore, PTX treatment also increased the gene expression of VEGF189 and VEGF165, increased VEGF protein expression, and improved pulmonary vascularization., Discussion: These data indicate that the reduced lung edema and inflammation, increased AOE activities, and improved vascularization may be responsible for the improved survival with PTX during hyperoxia. PTX may be a potential therapy in reducing some of the features of BPD in preterm newborns.

The pathological hallmarks of bronchopulmonary dysplasia (BPD), one of the most common long-term pulmonary complications associated with preterm birth, include arrested alveolarization, abnormal vascular growth, and variable interstitial fibrosis. Severe BPD is often complicated by pulmonary hypertension characterized by excessive pulmonary vascular remodeling and right ventricular hypertrophy that significantly contributes to the mortality and morbidity of these infants. Connective tissue growth factor (CTGF) is a multifunctional protein that coordinates complex biological processes during tissue development and remodeling. We have previously shown that conditional overexpression of CTGF in airway epithelium under the control of the Clara cell secretory protein promoter results in BPD-like architecture in neonatal mice. In this study, we have generated a doxycycline-inducible double transgenic mouse model with overexpression of CTGF in alveolar type II epithelial (AT II) cells under the control of the surfactant protein C promoter. Overexpression of CTGF in neonatal mice caused dramatic macrophage and neutrophil infiltration in alveolar air spaces and perivascular regions. Overexpression of CTGF also significantly decreased alveolarization and vascular development. Furthermore, overexpression of CTGF induced pulmonary vascular remodeling and pulmonary hypertension. Most importantly, we have also demonstrated that these pathological changes are associated with activation of integrin-linked kinase (ILK)/glucose synthesis kinase-3β (GSK-3β)/β-catenin signaling. These data indicate that overexpression of CTGF in AT II cells results in lung pathology similar to those observed in infants with severe BPD and that ILK/GSK-3β/β-catenin signaling may play an important role in the pathogenesis of severe BPD.