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Min Yang, Mingyang GuoRheumatology Center, PLA General Hospital of Chengdu Military Area Command, Chengdu, Sichuan Province, PR ChinaAlthough treat-to-target goals for rheumatoid arthritis (RA) have been well-established through several guidelines in recent years, concerns regarding treat-to-prevent goals for RA remain unclear. RA patients are typically subjected to over- or under-treatment because it is difficult for clinicians to determine the prognosis of RA patients. This typically results in failure to select and identify patient subsets that should receive monotherapy or combination therapy to treat early RA. Understanding treat-to-prevent goals, as well as unfavorable prognoses, risk factors, and prediction methods for RA, is therefore critical for making treatment decisions. Rapid radiographic progression plays a central role in contributing to other composite RA indices, so this may be the best method for defining treat-to-prevent goals for RA. Accordingly, risk factors of rapid radiographic progression have been defined and two prediction models were retrospectively derived based on clinical trial data. Additional studies are required to develop risk models that can be used for accurate predictions.Keywords: rapid radiographic progression, prognosis, risk factors, prediction models

beta-Adrenoceptor activation increases intracellular cAMP levels and consequently induces exocytotic amylase release in parotid acinar cells. Phosphodiesterase (PDE) catalyses the hydrolysis of cAMP, which terminates the downstream signaling of this second messenger. We investigated the involvement of PDE4, a cAMP-PDE, in beta-adrenoceptor agonist-induced amylase release in mouse, rat and rabbit parotid acinar cells by using the specific PDE4 inhibitor rolipram. cAMP-PDE activity was detected in mouse, rat and rabbit parotid acinar cells. In the presence of rolipram, cAMP-PDE activity was reduced by about 31%, 38% and 33% in mouse, rat and rabbit parotid acinar cells, respectively. The increase in cAMP levels induced by the beta-adrenoceptor agonist isoproterenol was enhanced in the presence of rolipram in mouse, rat and rabbit parotid acinar cells. Isoproterenol-induced amylase release, but not constitutive amylase release, was also enhanced in the presence of rolipram in mouse, rat and rabbit parotid acinar cells. These results suggest that the rolipram-sensitive cAMP-PDE, PDE4, is involved in beta-adrenoceptor agonist-induced amylase release in parotid acinar cells. [ABSTRACT FROM AUTHOR]

Introduction: The role for routine thymectomy in patients with secondary or tertiary hyperparathyroidism (SHPT, THPT) is unclear. We aim to compare rates of recurrence and complications in patients who underwent subtotal parathyroidectomy with and without thymectomy., Methods: Patients who underwent surgery for renal HPT at a tertiary endocrine surgery center between 2010 and 2022 were reviewed. Presence of parathyroid tissue in resected tissue was identified through pathology reports. A multivariate logistic regression was used to compare baseline characteristics, recurrence rates and complications between those who did and did not undergo thymectomy., Results: Of 107 patients who underwent subtotal parathyroidectomy, 29 (27.1 ​%) underwent concomitant thymectomy. Recurrence occurred in 15 patients (14 ​%). Thymectomy did not affect recurrence (OR: 0.33, 95%CI: 0.06-1.28, p ​= ​0.14), but was associated with permanent hypoparathyroidism (OR: 4.62, 95%CI: 1.67-13.18, p ​= ​0.003). Fewer parathyroid specimens increased the odds of thymectomy (p ​= ​0.04). Parathyroid glands were found in 6 thymectomy samples (20.7 ​%)., Conclusion: Thymectomy at the time of subtotal parathyroidectomy for renal HPT was not associated with disease recurrence, but increased likelihood of permanent hypoparathyroidism., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRβ pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C 2 C 12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 μg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRβ as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRβ, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRβ pathway thereby influencing skeletal muscle development., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To evaluate the accuracy of artificial intelligence (AI)-based technology in recognizing tessellated fundus in students aged 7-14 years., Methods: A retrospective study was conducted to collect consecutive fundus photographs for visual function screening of students aged 7-14 years old in Haikou City from June 2018 to May 2019, and 1907 cases were included in the study. Among them, 949 cases were male and 958cases were female. The results were manually analyzed by two attending ophthalmologists to ensure the accuracy of the results. In case of discrepancies between the results analyzed by the two methods, the manual results were used as the standard. To assess the sensitivity and specificity of AI in recognizing tessellated fundus, a Kappa consistency test was performed comparing the results of manual recognition with those of AI recognition., Results: Among 1907 cases, 1782 cases, or 93.4%, were completely consistent with the recognition results of manual and AI; 125 cases, or 6.6%, were analyzed with differences. The diagnostic rates of manual and AI for tessellated fundus were 26.1% and 26.4%, respectively. The sensitivity, specificity and area of the ROC curve (AUC) of AI for recognizing tessellated fundus in students aged 7-14 years were 88.0%, 95.4% and 0.917, respectively. The results of test showed that that the manual and AI identification results were highly consistent (κ = 0.831, P = 0.000)., Conclusion: AI analysis has high specificity and sensitivity for tessellated fundus identification in students aged 7-14 years, and it is feasible to apply artificial intelligence to visual function screening in students aged 7-14 years., (© 2024. The Author(s).)

Purpose: To investigate the impact of obstructive sleep apnea (OSA) on postoperative delirium (PD), and evaluate the effectiveness of positive airway pressure (PAP) therapy on PD among OSA patients., Methods: We systematically searched Embase, Cochrane Library and PubMed databases from their establishment to November 27, 2022. A random-effects approach was employed to determine aggregated results. Subgroup and sensitivity analyses were carried out to investigate heterogeneity., Results: Sixteen eligible studies were included in the analysis. Thirteen studies revealed that OSA significantly elevated the likelihood of developing PD (OR = 1.71; 95%CI = 1.17 to 2.49; p = 0.005). Subgroup analysis according to delirium assessment scales showed that OSA did not exhibit an association with the incidence of PD assessed by the Confusion Assessment Method-Intensive Care Unit (OR = 1.14; 95%CI = 0.77 to 1.67; p = 0.51) but enhanced the likelihood of developing PD evaluated with other measurement scales (OR = 2.15; 95%CI = 1.44 to 3.19; p = 0.0002). Three additional studies explored the impact of PAP treatment on PD among OSA individuals, indicating no significant reduction in PD incidence with PAP use (OR = 0.58; 95%CI = 0.13 to 2.47; p = 0.46)., Conclusions: OSA may not be a risk factor for PD in critically ill patients in the intensive care unit, but may increase the likelihood of developing PD among individuals receiving regular care in the ward postoperatively. The efficacy of PAP therapy in decreasing PD incidence among OSA patients remains debatable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: This study investigated the separate impacts of diet and pre-operative antibiotics on gut microbiome and colonic anastomotic healing using a mouse model., Methods: Male C57BL/6J mice were fed either low-fat-high-fibre (SD) or high-fat-low-fiber (WD) groups for 6 weeks, then further received either pre-operative antibiotics or a control sham before a colonic anastomotic procedure was performed. After 7 days, the anastomosis was assessed and microbiota composition and biodiversity were analyzed in anastomotic tissue and stool., Results: WD-fed mice had shorter survival (5.2 ​± ​2.3 vs. 6.9 ​± ​2.3 days, p ​= ​0.022), increased weight loss (5.55 ​± ​3.80g vs. 2.65 ​± ​2.36g, p ​= ​0.03), and reduced biodiversity compared to SD-fed mice. Pre-operative antibiotics improved anastomotic healing scores (1.33 ​± ​0.65 vs. 2.08 ​± ​0.79, p ​= ​0.02) and reduced Enterococcus faecalis growth in tissue and stool (p ​= ​0.02, p ​= ​0.02). Improved anastomotic healing correlated with lower Enterococcus abundance (p ​= ​0.04) and higher collagen III and IV levels (p ​= ​0.01, 0.04) in anastomotic tissue., Conclusion: SD promotes enhanced post-operative recovery and increased microbiome biodiversity, while pre-operative antibiotics enhance anastomotic healing by suppressing Enterococcus faecalis growth, mitigating collagen III/IV degradation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals., Methods: We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis., Results: Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD., Conclusions: This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Tetrabromobisphenol A (TBBPA) is a global pollutant. When TBBPA is absorbed by the body through various routes, it can have a wide range of harmful effects on the body. Green tea polyphenols (GTPs) can act as antioxidants, resisting the toxic effects of TBBPA on animals. The effects and mechanisms of GTP and TBBPA on oxidative stress, inflammation and apoptosis in the mouse lung are unknown. Therefore, we established in vivo and in vitro models of TBBPA exposure and GTP antagonism using C57 mice and A549 cells and examined the expression of factors related to oxidative stress, autophagy, inflammation and apoptosis. The results of the study showed that the increase in reactive oxygen species (ROS) levels after TBBPA exposure decreased the expression of autophagy-related factors Beclin1, LC3-II, ATG3, ATG5, ATG7 and ATG12 and increased the expression of p62; oxidative stress inhibits autophagy levels. The increased expression of the pro-inflammatory factors IL-1β, IL-6 and TNF-α decreased the expression of the anti-inflammatory factor IL-10 and activation of the NF-κB p65/TNF-α pathway. The increased expression of Bax, caspase-3, caspase-7 and caspase-9 and the decreased expression of Bcl-2 activate apoptosis-related pathways. The addition of GTP attenuated oxidative stress levels, restored autophagy inhibition and reduced the inflammation and apoptosis levels. Our results suggest that GTP can attenuate the toxic effects of TBBPA by modulating ROS, reducing oxidative stress levels, increasing autophagy and attenuating inflammation and apoptosis in mouse lung and A549 cells. These results provide fundamental information for exploring the antioxidant mechanism of GTP and further for studying the toxic effects of TBBPA.

Ant behavior relies on a collection of natural products, from following trail pheromones during foraging to warding off potential predators. How nervous systems sense these compounds to initiate a behavioral response remains unclear. Here, we used Caenorhabditis elegans chemotaxis assays to investigate how ant compounds are detected by heterospecific nervous systems. We found that C. elegans avoid extracts of the pavement ant ( Tetramorium immigrans ) and either osm-9 or tax-4 ion channels are required for this response. These experiments were conducted in an undergraduate laboratory course, demonstrating that new insights into interspecies interactions can be generated through genuine research experiences in a classroom setting., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Microplastics (MPs) are ubiquitous environmental contaminants that have negative impacts on health and safety. The gut microbiota plays multiple roles as a newly discovered virtual metabolic organ. The objective of this study was to investigate the potential of MPs to cause liver injury by disrupting the balance of gut microbiota. The results indicated that exposure to MPs resulted in liver damage and disrupted the homeostasis of gut microbiota. MPs significantly reduced the liver organ coefficient, leading to liver cell injury and impaired function. Additionally, there was an increase in the expression of fibril-related proteins, which positively correlated with MPs concentration. Furthermore, MPs increased the relative abundances of Desulfovibrio, Clostridia, Enterorhabdus, Bacteroides, and Gemella while decreasing the abundance of Dubosoella. Different concentrations of MPs exhibited varying effects on specific bacterial groups, however, both concentrations resulted in an increase in pathogenic bacteria and a decrease in beneficial bacteria, as well as alterations in microbial structure. Moreover, MPs induced oxidative stress, inflammation, apoptosis and necrosis in liver cells. The study found that MPs disrupted gut microbiota homeostasis and activated TLR2/NF-κB/NLRP3 pathway in the liver, providing a new insight into the mechanism underlying MPs-induced liver injury. These findings serve as a warning regarding environmental pollution caused by MPs., 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 © 2024 Elsevier B.V. All rights reserved.)

In this work, we reported a fluorescent probe Fur-SH, a derivative of benzofuranone, which was used to detect H 2 S in living cells and zebrafish. Based on the three structural characteristics of the probe, the effects of different structural modifications on the optical properties of the fluorophore were compared. Then, the fluorophore Fur-OH was synthesized by modifying diethylamino group with benzofuranone as the main skeleton. With 2,4-dinitrofluorobenzene as the recognition group and diethylamino as the electron donor, the push-pull electron effect occurred with nitro group, which led to fluorescence quenching, and an openable fluorescent probe Fur-SH was formed. The probe Fur-SH (λ ex  = 510 nm; λ em  = 570 nm) had the advantages of smaller full width at half maxima, rapid response (5 min) and wide pH window. The quantitative properties of the probe were excellent, reaching saturation at 50 equivalents of substrate. The probe Fur-SH showed high sensitivity to H 2 S, with LOD of 48.9 nM and LOQ of 50 nM. At present, the probe Fur-SH had been applied to fluorescence imaging of MCF-7 cells and zebrafish. By comparing the effects of different structures on the optical properties of fluorophores, this work was expected to be helpful to the development of fluorescent probes in the future., 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. Published by Elsevier B.V.)

The extensive application of Tetrabromobisphenol A (TBBPA) leads to the pollution of part of the water environment and brings great safety risks to aquatic animals. As a natural extract, tea polyphenols (TPs) have antioxidant and anti-inflammatory effects. Gills are one of the immune organs of fish and constitute the first line of defense of the immune system. However, it was unclear whether TPs could mitigate TBBPA-induced gills injury. Therefore, an animal model was established to investigate the effect of TPs on TBBPA-induced gills. The results indicated that TBBPA changed the coefficient and tissue morphology of carp gills. In addition, TBBPA induced oxidative stress and inflammation, leading to ferroptosis and apoptosis in carp gills. Dietary addition of TPs significantly improved the antioxidant capacity of carp, effectively inhibited the overexpression of TLR4/NF-κB and its mediated inflammatory response. Moreover, TPs restored iron metabolism, reduced the expression of pro-apoptotic factors thereby alleviating ferroptosis and apoptosis in carp gills. This study enriched the protective effect of TPs and provided a new way to improve the innate immunity of carp., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this work, a fluorescent probe, TPABF-HS, was developed for detecting hydrogen sulfide (H 2 S) using a human serum albumin (HSA)-binding-based approach for amplifying the fluorescence signal and extending the linear correlation range. Compared to the most recent probes for H 2 S, the most interesting feature of the detection system developed herein was the especially wide linear range (0-1000 μM (0-100 eq.)), which covered the physiological and pathological levels of H 2 S. TPABF-HS could be used in applications high sensitivity and selectivity with an LOD value of 0.42 μM. Further, site-competition experiments and molecular docking simulation experiments indicated that signal amplification was realized by the binding of the TPABF fluorophore to the naproxen-binding site of HSA. Moreover, the extension of the measurement span could allow for applications in living cells and Caenorhabditis elegans for imaging both exogenous and endogenous H 2 S. This work brings new information to the strategy of signal processing by exploiting fluorescent probes.

Two new quinoline alkaloids ( 1 - 2 ) together with twenty-two known alkaloids ( 3 - 24 ) were isolated and identified from Dictamnus dasycarpus Turcz. Compounds 6 - 7 , 9 , 11 , 15 - 16 , 19 and 24 were isolated from D. dasycarpus for the first time. The structures of all compounds were characterised by spectroscopic methods (1D, 2D NMR and HRESIMS). The anti-proliferative activity was mediated by the arrest of three human cancer cell lines (SW982, HepG2 and A549) of all the compounds that were evaluated by CCK-8 assay.

Ethnopharmacological Relevance: Asthma is a chronic airway inflammatory disease that can lead to several complications caused by bacterial infections. However, recurrent attacks of the disease require long-term use of antibiotics, resulting in lung dysbiosis and poor outcomes. Daqing Formula (DQF) is a well-known herbal medicine in Pharmacopoeia of China, which is widely used for various stimuli-induced lower respiratory diseases, including asthma, bronchitis, and pneumonia. Thus, it has been demonstrated to be a plant-derived broad-spectrum antibiotic for treating and preventing various acute and chronic respiratory diseases., Aim of the Study: This study evaluated the efficacy and possible mechanism of DQF on allergic asthma and airway dysbiosis., Methods and Materials: The mice were co-challenged with ovalbumin and ampicillin to induce allergic asthma combined with airway dysbacteriosis. The populations of lung microbiota were detected by using 16s DNA sequencing. The levels of asthmatic markers in BALF were detected by ELISA. The levels of Th1/Th2 cytokines in splenic CD4 + cells of mice were analyzed by flow cytometry. The expressions of the GSK-3β signaling pathway in the lung tissues of asthmatic mice and eosinophils were detected by western blotting assay. The inhibition of DQF on the production of pro-inflammatory cytokines in eosinophils of asthmatic mice., Results: The results showed that treatment with DQF at 200-800 mg/kg doses significantly reduced the frequency of nasal rubbing and lung inflammation as well as the number of total cells, eosinophils, and macrophages in bronchoalveolar lavage fluid. It decreased the relative abundances of Streptococcus, Cuoriavidus, and Moraxella, increased Akkermansia and Prevotella&#95;6 in lung tissues of asthmatic mice, and inhibited the growth of Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae and their resistant strains in vitro. Furthermore, DQF reduced the levels of eotaxin, TSLP, IL-4, IL-5, IL-25, and IL-33, but enhanced IFN-γ and IL-12 in BALF. It elevated the population of Th1 cells, inhibited eosinophil activation, and downregulated the expressions of p-GSK-3β, p-p65, nuclear β-catenin, and p-STAT3 in the lung tissues of asthmatic mice., Conclusions: The results revealed that DQF reduced airway inflammation, ameliorated lung dysbiosis, shifted the Th1/Th2 balance, and inhibited eosinophil activation in asthmatic mice, indicating its potential for severe asthma treatment., 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.)

Background: Hypertension affects approximately 1 in 2 adults in the US. Home blood pressure (BP) monitoring programs are effective in the diagnosis and management of hypertension. Free clinics serve as an integral safety net for millions of uninsured and economically disadvantaged patients in the US. The feasibility and effects of a free home BP monitoring and follow-up program in a free clinic setting is not well characterized., Methods: This was a prospective study of the implementation of a pilot BP monitoring and follow-up program between March 2021 and August 2023 at 2 free clinics in the San Francisco Bay Area. A total of 78 hypertensive patients were enrolled in the program and given a free BP monitor. We surveyed via telephone the change in systolic and diastolic BPs and BP monitor use and comfort at 3 weeks. Volunteers in clinic roles involved in the BP monitoring program were surveyed to assess their time spent and perceptions of the program., Results: Of the 78 patients, 37 provided responses to the 3-week survey. A total of 36 of 37 (97%) patients reported using their BP monitor. A total of 35 patients reported using it at least once a week (95%), with the majority reporting at least four uses a week (68%). A total of 36 patients (97%) planned on continuing to use their BP monitor. At 3 weeks, the mean systolic and diastolic BP changed by -6.40 mmHg (95% CI, -10.8 to -2.01 mmHg; P = .00577) and -2.72 mmHg (95% CI, -5.62 to 0.188 mmHg; P = .0657), respectively. The time commitment for this program ranged from 130 ± 51 min for program leaders to 16 ± 14 min per week for patient-facing roles. All volunteer roles (patient-facing, phone follow-up, program leaders) expressed that they had a clear understanding of their responsibilities in the program (median 4 on Likert scale, IQR 3-5)., Conclusion: Home BP monitoring and follow-up is feasible to implement in free clinics, resulting in high rates of patient engagement among respondents. Our findings suggest that home BP monitoring and follow-up programs may be beneficial in vulnerable patient populations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The meta-analysis aimed to evaluate the efficacy of mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA) and explore the effect of different positions on MAD for OSA., Methods: The Embase, PubMed, Medline, and Cochrane Library databases were searched for relevant studies evaluating the effect of MAD on the treatment of OSA from database inception to November 2022. The Bayesian random-effects mode was used to calculate the pooled outcome. Subgroup analysis and sensitivity analysis were applied to investigate the heterogeneity., Results: A total of 6 studies enrolling 643 patients were eligible for further analysis. MAD treatment led to improvements in total apnea-hypopnea index (AHI) for both positional OSA(POSA) and Non-POSA groups, but there was no significant difference in the effect of MAD on Non-POSA and POSA (MD = -1.46,95%CI [-4.89,1.97], P = 0.40). In the supine position, AHI improvement after MAD treatment in POSA group was more than that in Non-POSA group by 15 events/hour in average (MD = 14.82, 95%CI [11.43,18.22], P＜0.00001), while in the non-supine position, the change of AHI in Non-POSA group was significantly better than that in POSA group by approximately 8 events/hour (MD = -7.55,95%CI[-10.73,-4.38],p < 0.00001)., Conclusion: MAD is more suitable for POSA compared to Non-POSA in patients with habitual sleep in the supine or supine predominant position. While for patients with habitual sleep in the non-supine position, MAD is an effective treatment option for Non-POSA., 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.)

Microplastics (MPs) are widely distributed pollutants in the environment and accumulate in the aquatic environment due to human activities. Carp, a common edible aquatic organism, has been found to accumulate MPs in body. MicroRNA (miRNAs) is a non-coding short RNA that regulates protein expression by binding to target genes in various physiological processes such as proliferation, differentiation and apoptosis. The ovary is a crucial role in carp reproduction. In this study, we established a model of carp exposed to polyethylene microplastics (PE-MPs) in the aquatic environment to investigate the specific mechanism of PE-MPs causing ovarian injury and the involvement of miR-132/calpain (CAPN) axis. H&E stained sections revealed that PE-PMs induced inflammation in ovarian tissues and impaired oocyte development. TUNEL analysis showed an increased rate of apoptosis in ovarian cells treated with PE-PMs. RT-PCR and Western Blot assays confirmed that exposure to PE-MPs significantly decreased miR-132 expression while increasing CAPN expression at both mRNA and protein levels. The concentration of calcium ions was significantly increased in tissues, leading to CAPN enzyme activity increase. The expression of mitochondrial damage-related genes (bax, AIF, cyt-c, caspase-7, caspase-9, and caspase-3) was higher while the expression of anti-apoptotic genes (bcl-2 and bcl-xl) was lower. Protein levels of bax, AIF, caspase-3, bcl-2 and bcl-xl changed accordingly with the genetic alterations. Additionally, we discovered that PE-MPs can activate the p65 factor through the TRAF6/NF-kB pathway resulting in elevated production of pro-inflammatory factors IL-6, IL-1β and TNF-a which contribute to ovarian inflammation development. This study investigates the impact of PE-MPs on carp ovarian function and provides insights into miRNAs' role and their target genes., 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.)

Plant-derived exosome-like nanoparticles (ELNs) have been proposed as a novel therapeutic tool for preventing human diseases. However, the number of well-verified plant ELNs remains limited. In this study, the microRNAs in ELNs derived from fresh Rehmanniae Radix, a well-known traditional Chinese herb for treating inflammatory and metabolic diseases, were determined by using microRNA sequencing to investigate the active components in the ELNs and the protection against lipopolysaccharide (LPS)-induced acute lung inflammation in vivo and in vitro. The results showed that rgl-miR-7972 (miR-7972) was the main ingredient in ELNs. It exerted stronger protective activities against LPS-induced acute lung inflammation than catalpol and acteoside, which are two well-known chemical markers in this herb. Moreover, miR-7972 decreased the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide (NO) in LPS-exposed RAW264.7 cells, thereby facilitating M2 macrophage polarization. Mechanically, miR-7972 downregulated the expression of G protein-coupled receptor 161 (GPR161), activating the Hedgehog pathway, and inhibited the biofilm form of Escherichia coli via targeting virulence gene sxt2. Therefore, miR-7972 derived from fresh R. Radix alleviated LPS-induced lung inflammation by targeting the GPR161-mediated Hedgehog pathway, recovering gut microbiota dysbiosis. It also provided a new direction for gaining novel bioactivity nucleic acid drugs and broadening the knowledge on cross-kingdom physiological regulation through miRNAs., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Microplastics (MPs), a new class of pollutant that threatens aquatic biodiversity, are becoming increasingly prevalent around the world. Fish growth may be severely inhibited by microplastics, resulting in severe mortality. Exposure to microplastics increases the likelihood of intestinal injuries, but the underlying mechanisms remain equivocal. The objective of this study was to investigate the potential toxic mechanisms underlying microplastic-induced intestinal injury in fish and to assist researchers in identifying novel therapeutic targets. In this study, a model of carp exposed to microplastics was established successfully. Histological observation showed that exposure to polyethylene microplastics caused damage to the intestinal mucosal surface and a significant increase in goblet cells, which aggregated on the surface of the mucosa. The mucosal layer was observed to fall off. Lymphocytes in the intestinal wall proliferated and aggregated. TUNEL staining showed that apoptosis occurred in the group exposed to microplastics. The qPCR results showed that the expression of Ferroptosis apoptotic factors COX-2 and ACSL4 was upregulated, while the expression of TFRC, FIH1, SLC7A11, and GPX4 was downregulated. The NF-κB pathway (p-p65, IκBα), inflammatory cytokines (TNF-α, IL-8, IL-6) and apoptosis genes (Bax, Caspase3) were upregulated. Semi-quantitative detection of related proteins by Western blotting was consistent with the gene expression results. In addition, the ELISA assay showed that lipid peroxidation and inflammatory cytokines (TNF-α, IL-1β, IL-6) were increased in the microplastic exposed group. To conclude, lipid peroxidation induced by microplastics activates the NF-κB pathway and causes ferroptosis, ultimately resulting in intestinal damage and cellular apoptosis., 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.)

Objectives: Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China., Methods: A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types., Results: The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008)., Conclusions: Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

A lack of the trace element zinc (Zn) in freshwater environments causes slow growth and malnutrition and affects the normal biological functions of organisms. In this study, a Zn deficiency model of grass carp hepatocytes was established with TPEN. Acetylcysteine (NAC) was used as an inhibitor. TPEN was added to L8824 cell culture medium, and LDH, AST, ALT, and AKP activities were enhanced in a Zn-deficient environment, leading to abnormal hepatopancreas function. Fluorescence microscopy showed an increase in ROS levels, and antioxidant enzyme activity assays revealed that SOD, CAT, GSH-PX, and T-AOC activities were decreased, indicating oxidative stress caused by Zn deficiency. The RT‒PCR results showed that the mRNA expression of GRP78, PERK, EIF2α, ATF4, and Chop was increased due to the addition of TPEN. Calcium kits showed increased Ca 2+ levels. The RT‒PCR results showed that the mRNA expression levels of Caspase-12, Caspase-9, Caspase-3, and PARP apoptotic were increased due to the addition of TPEN. RT‒PCR and ELISA showed that the expression levels of interleukin-1β (IL-1β), interleukin-8 (IL-8), tumour necrosis factor (TNF-α), and inducible nitric oxide synthase (iNOS) were increased. This led to the conclusion that Zn deficiency in the freshwater environment caused inflammation and apoptosis in hepatocytes in grass carp. For the first time, apoptosis caused by endoplasmic reticulum stress in grass carp hepatocytes due to Zn deficiency was studied in the context of Ca 2+ . The present study provided some insight into the adverse effects of Zn deficiency in freshwater environments on fish., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Selenium (Se), one of the essential trace elements of fish, regulates immune system function and maintains immune homeostasis. Muscle is the important tissue that generate movement and maintain posture. At present, there are few studies on the effects of Se deficiency on carp muscle. In this experiment, carps were fed with dietary with different Se content to successfully establish a Se deficiency model. Low-Se dietary led to the decrease of Se content in muscle. Histological analysis showed that Se deficiency resulted in muscle fiber fragmentation, dissolution, disarrangement and increased myocyte apoptosis. Transcriptome revealed a total of 367 differentially expressed genes (DEGs) were screened, including 213 up-regulated DEGs and 154 down-regulated DEGs. Bioinformatics analysis showed that DEGs were concentrated in oxidation-reduction process, inflammation and apoptosis, and were related to NF-κB and MAPKs pathways. Further exploration of the mechanism showed that Se deficiency led to excessive accumulation of ROS, decreased the activity of antioxidant enzymes, and also resulted in increased expression of the NF-κB and MAPKs pathways. In addition, Se deficiency significantly increased the expressions of TNF-α, IL-1β and IL-6, and the pro-apoptotic factors BAX, p53, caspase-7 and caspase-3, while decreased the expressions of anti-apoptotic factors Bcl-2 and Bcl-xl. In conclusion, Se deficiency reduced the activities of antioxidant enzymes and led to excessive accumulation of ROS, which caused oxidative stress and affected the immune function of carp, leading to muscle inflammation and apoptosis., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with NAFLD is rapidly increasing because of the obesity epidemic. There are currently no approved drugs that prevent or treat NAFLD. Recent evidence shows that bavachin, a flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and insulin sensitivity during preadipocyte differentiation, but the effect of bavachin on glucose and lipid metabolism remains unclear. In the current study we investigated the effects of bavachin on obesity-associated NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with bavachin (20 μM) significantly suppressed PA/OA or high glucose/high insulin-induced increases in the expression of fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore, bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3β, improving the insulin signaling activity in the cells. In HFD-induced obese mice, administration of bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in body weight, liver weight, blood glucose, and liver and serum triglyceride contents. Moreover, bavachin administration significantly alleviated hepatic inflammation and ameliorated HFD-induced glucose intolerance and insulin resistance. We demonstrated that bavachin protected against HFD-induced obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that bavachin repressed the expression of lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion, bavachin attenuates hepatic steatosis and obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that bavachin is a potential drug for NAFLD therapy., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Selecting suitable promoters to drive gene overexpression can provide significant insight into the development of engineered bacteria. In this study, we analyzed the transcriptome data of Burkholderia pyrrocinia JK-SH007 and identified 54 highly expressed genes. The promoter sequences were located using genome-wide data and scored using the prokaryotic promoter prediction software BPROM to further screen out 18 promoter sequences. We also developed a promoter trap system based on two reporter proteins adapted for promoter optimization in B. pyrrocinia JK-SH007: firefly luciferase encoded by the luciferase gene set ( Luc ) and trimethoprim ( TP )-resistant dihydrofolate reductase ( TP r ). Ultimately, eight constitutive promoters were successfully inserted into the probe vector and transformed into B. pyrrocinia JK-SH007. The transformants were successfully grown on Tp antibiotic plates, and firefly luciferase expression was determined by measuring the relative light unit (RLU). Five of the promoters (P4, P9, P10, P14, and P19) showed 1.01-2.51-fold higher activity than the control promoter λ phage transcriptional promoter (PRPL). The promoter activity was further validated via qPCR analysis, indicating that promoters P14 and P19 showed stable high transcription levels at all time points. Then, GFP and RFP proteins were overexpressed in JK-SH007. In addition, promoters P14 and P19 were successfully used to drive gene expression in Burkholderia multivorans WS-FJ9 and Escherichia coli S17-1. The two constitutive promoters can be used not only in B. pyrrocinia JK-SH007 itself to gene overexpression but also to expand the scope of application.

Microplastics have been recognized as a widespread new pollutant in nature and have induced an increase in the occurrence of a variety of diseases in carp. An animal model of microplastic ingestion was successfully established in an aqueous environment. The gut microbiota was analysed using a metagenomic approach. The results showed a significant reduction in the relative abundances of Lactococcus garvieae, Bacteroides&#95;paurosaccharolyticus, and Romboutsia&#95;ilealis after PS-MPs treatment. The 16S Silva database was used to predict and analyse the known genes. Intestinal flora disorders related to infectious diseases, cancers, neurodegenerative diseases, endocrine and metabolic diseases, cardiovascular diseases, and other diseases were found. The intake of PS-MPs resulted in damage to carp intestinal tissue and apoptosis of intestinal epithelial cells. The levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α were significantly increased with the intake of PS-MPs. The gene and protein levels of GRP78, Caspase-3, Caspase-7, Caspase-9, Caspase-12, PERK, IRE1, and ATF6 were further examined in PS group. The occurrence of ERS and apoptosis in carp intestines was confirmed. These results suggest that the accumulation of PS-MPs in the aquatic environment can disturb the carp gut microbiota and induce ERS, apoptosis, and inflammation in the intestinal tissue., 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.)

Microplastics (MPs) have attracted widespread attention as an emerging environmental pollutant. Especially in aquatic ecosystems, the harm of MPs to aquatic animals has increasingly become a severe environmental problem. In this study, we constructed a carp polystyrene microplastics (PS-MPs) exposure model to explore the damage and mechanism of PS-MPs exposure to carp myocardial tissue. The results of H&E, TUNEL, and AO/EB staining showed that PS-MPs exposure could induce inflammation, apoptosis, and necrosis in carp myocardial tissue and cardiomyocytes. In addition, our study explored the targeting relationship between PS-MPs and TLR4 and found that PS-MPs exposure could significantly increase the expression of TLR4 pathway-related factors. As the concentration of PS-MPs increased, the NF-κB pathway and inflammation-related factors increased dose-dependent. In addition, myocardial injury induced by exposure to PS-MPs was predominantly apoptotic, accompanied by necrosis. In short, our data suggest that PS-MPs cause damage to myocardial tissue via the TLR4\NF-κB pathway. The above findings enrich the theory of toxicological studies on PS-MPs and provide an essential reference for aquaculture., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Selenium (Se) is one of the essential trace elements in animal organisms with good antioxidant and immune-enhancing abilities. In this study, we investigated the effect and mechanism of Se deficiency on skeletal muscle cell differentiation. A selenium-deficient skeletal muscle model was established. The skeletal muscle tissue and blood Se content were significantly reduced in the Se deficiency group. HE staining showed that the skeletal muscle tissue had a reduced myofiber area and nuclei and an increased myofascicular membrane with Se deficiency. The TUNEL test showed massive apoptosis of skeletal muscle cells in Se deficiency. With Se deficiency, reactive oxygen species (ROS) and malondialdehyde (MDA) increased, and the activities of glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and catalase (CAT) were inhibited. In in vitro experiments, microscopic observations showed that the low-Se group had reduced C2C12 cell fusion and a reduced number of differentiated myotubes. In addition, qPCR results showed that differentiation genes (Myog, Myod, Myh2, Myh3, and Myf5) were significantly reduced in the low Se group. Meanwhile, Western blot analysis showed that the levels of differentiation proteins (Myog, Myod, and Myhc) were significantly reduced in the low-Se group. This finding indicates that Se deficiency reduces the expression of skeletal muscle cell differentiation factors. All the above data suggest that Se deficiency can lead to oxidative stress in skeletal muscle, resulting in a reduction in the differentiation capacity of muscle cells., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Selenium (Se) is a vital trace element in the regulation of inflammation and antioxidant reactions in both animals and humans. Se deficiency is rapidly affecting lung function. The present study investigated the molecular mechanism of Se deficiency aggravates reactive oxygen species (ROS)-induced inflammation, leading to fibrosis in lung. Mice fed with different concentrations of Se to establish the model. In the Se-deficient group, the ROS and malondialdehyde (MDA) was increased, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) reduced. The histopathological observation showed that Se deficiency lead to lung texture damage with varying degrees of degeneration, necrosis, shedding of some alveolar epithelial cells, and inflammatory cell infiltration. Immunohistochemistry showed that the expression of α-smooth muscle actin (α-SMA) increased. The fibrosis index was verified with Sirius red staining. The ELISA and qPCR results showed that the inflammatory cytokines (TNF-α and IL-1β) and ECM (collagen I, collagen IV, fibronectin, and laminin) were increased with ROS increasing, which was induced by Se deficiency. The results displayed that oxidative stress with Se deficiency led to an increase in tissue inhibitors of metalloproteinase (TIMPs), but a decrease in matrix metalloproteinases (MMPs). All the results indicated that Se deficiency induced excessive ROS accumulation to generate inflammation, which disrupted ECM homeostasis and aggravated fibrosis in the lung., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polystyrene microplastics (PS-MPs) affect the immune defense function on carp (Cyprinus carpio). The PS-MPs model of carp was established by feeding with PS-MPs particle size of 8 µm and concentration of 1000 ng/L water. Hepatopancreas function test revealed the activities of AKP, ALT, AST and LDH abnormal increase. PS-MPs induced tissue damage and lead to abnormal hepatopancreas function. The PS-MPs also induced a oxidative stress with the antioxidant enzymes SOD, CAT, GSH-PX, and T-AOC activities decreasing and reactive oxygen species (ROS) excessive accumulation. PS-MPs activated the Toll like receptor-2 (TLR2) signaling pathway. The mRNA and protein expressions of TLR2, Myeloid differentiation primary response 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), NF-κB p65, Tumor necrosis factor (TNF-α), Interleukin-1β (IL-1β), Inducible Nitric Oxide Synthase (iNOS), and cycooxygenase 2(COX2) was revealed increased in both hepatopancreas and hepatocytes with the qPCR and Western blotting analysis mode. ELISA showed the expressions of TNF-α, IL-1β, iNOS, and COX2 inflammatory molecule were increased in both hepatopancreas and hepatocytes. The results showed that PS-MPs caused a serious injure in the hepatopancreas and brought serious effects on the inflammatory response of carp. The present study displayed the harm caused by PS-MPs in freshwater fish, and provided some suggestions and references for toxicological studies of microplastics in freshwater environment., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from children aged 8 days to 7 years in Urumqi, China, between 2014 to 2021, during which PCV13 was introduced in the private sector's immunization program and COVID-19 control was administrated in the last 2 years., Methods: Serotypes of S. pneumoniae isolates were determined by Quellung reaction, and their susceptibility against 14 antimicrobials were tested. According to the start year of PCV13 administration (2017) and COVID-19 control (2020), the study period was divided into three stages: 2014-2015, 2018-2019, and 2020-2021., Results: A total of 317 isolates were involved in this study. The most common serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A(5.0%). The coverage rate of both PCV13 and PCV15 was 83.0%. The coverage of PCV20 was a little higher at 85.2%. The resistance rate against penicillin was 28.6% according to the breakpoints of oral penicillin, which would reach up to 91.8% based on the breakpoints of parenteral penicillin for meningitis. The resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were 95.9%, 90.2%, 88.9%, and 78.8%, respectively. The PCV13 isolate was more resistant to penicillin than the non-PCV13 ones. There was not any significant change found in the serotype distribution since the PCV13 introduction and the COVID-19 control. The resistance rate against oral penicillin slightly elevated to 34.5% in 2018-2019 from 30.7% in 2014-2015 and then decreased significantly to 18.1% in 2020-2021 ( χ 2 = 7.716, P < 0.05), while the resistance rate to ceftriaxone (non-meningitis) continuously declined from 16.0% in 2014-2015 to 1.4% in 2018-2019 and 0% in 2020-2021 (Fisher = 24.463, P < 0.01)., Conclusion: The common serotypes of S. pneumoniae isolated from children in Urumqi were types 19F, 19A, 23F, 6B, and 6A, which we found to have no marked change since the PCV13 introduction and the COVID-19 control However, the resistance rate to oral penicillin and ceftriaxone significantly declined in the COVID-19 control stage., 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 Guo, Shi, Gao, Tian, Yuan, Yang, Wumaier, Cao, Abulimiti, Zhang and Yao.)

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 6.4 million deaths worldwide. The prevalent comorbidity between hypertension and severe COVID-19 suggests common genetic factors may affect the outcome of both diseases. As both hypertension and severe COVID-19 demonstrate sex-biased prevalence, common genetic factors between the two diseases may display sex-biased differential associations. By evaluating COVID-19 association signals of 172-candidate hypertension single nucleotide polymorphisms (SNPs) derived from more than 1 million European individuals in two sex-stratified severe COVID-19 genome-wide association studies from UK BioBank with European ancestry, we revealed one functional cis expression quantitative trait locus of SPEG (rs12474050) showing sex-biased association with severe COVID-19 in women. The risk allele rs12474050*T associates with higher blood pressure. In our study, we found it is significantly correlated with lower SPEG expression in muscle-skeletal but with higher expression in both brain cerebellum and cerebellar hemisphere. Additionally, nominal significances were detected for the association between rs12474050*T and lower SPEG expression in both heart left ventricle and atrial appendage; among these tissues, the SPEG expression is nominally significantly higher in females than in males. Further analysis revealed SPEG is mainly expressed in cardiomyocytes in heart and is upregulated upon SARS-CoV-2 infection, with significantly higher upregulation of SPEG only observed in female but not in male COVID-19 patients compared to both normal female and male individuals, suggesting upregulation of SPEG is a female-specific protective mechanism against COVID-19 induced heart damage. Taken together, our analyses suggest the involvement of SPEG in both hypertension and severe COVID-19 in women, which provides new insights for sex-biased effect of severe COVID-19 in women., 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 Luo, Shen, Li, Wu, Yang, Guo, Chen, Shen, Zhang, Gao, Nie, Wu, Mou, Zhang and Cheng.)

Microplastics cause varying degrees of damage to aquatic organisms. Exposure to microplastics contaminated water, the gills are among the first tissues, after the skin, to be affected by microplastics. As an essential immune organ, prolonged stimulation by microplastics disrupts immune function not only in the gills but throughout the body, yet the underlying mechanisms remain elusive. A model of gill injury from exposure to polyethylene (PE) microplastics was developed in this study. H&E staining revealed that polyethylene microplastics caused gill inflammation, vascular remodeling, and mucous cell proliferation. An increase in collagen indicates severe tissue damage. Additional analysis showed that polyethylene microplastics profoundly exacerbated oxidative stress in the gills. TUNEL assay demonstrated cell apoptosis induced by polyethylene microplastic. The mRNA levels were subsequently quantified using RT-PCR. The results showed that polyethylene microplastics increased the expression of the nuclear factor-κB (NF-κB) pathway (NF-κB p65, IKKα, IKKβ) and apoptosis biomarkers (p53, caspase-3, caspase-9, and Bax). Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes, which is an influential component of innate immunity, were overactive. What's more, the pro-inflammatory factors (TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-1β) that induce immune disorder also increased significantly, while the anti-inflammatory factors (IL-4, IL-10) decreased significantly. These results suggested that oxidative stress acted as an activation signal of apoptosis triggered by the NF-κB pathway and activating the NLRP3 inflammasome to promote inflammatory immune responses. The present study provided a different target for the prevention of toxin-induced gill injury under polyethylene microplastics., 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. All authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in FISH & Shellfish Immunology., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Intestinal microbiota dysbiosis is a well established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an effective UC treatment strategy. Berberine (BBR), an alkaloid extracted from several Chinese herbs, is a common traditional Chinese medicine. To establish the efficacy and mechanism of action of BBR, we constructed a UC model using healthy adult shorthair cats to conduct a systematic study of colonic tissue pathology, inflammatory factor expression, and gut microbiota structure. We investigated the therapeutic capacity of BBR for regulating the gut microbiota and thus work against UC in cats using 16S rRNA genes amplicon sequencing technology. Our results revealed that dextran sulfate sodium (DSS)-induced cat models of UC showed weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by supplementation with BBR. A 16S rRNA gene-based microbiota analysis demonstrated that BBR could significantly benefit gut microbiota. Western blot, quantitative PCR, and enzyme-linked immunosorbent assays (ELISAs) showed that in DSS-induced cat models, the expression of the inflammatory factors was increased, activating the JAK2/STAT3 signaling pathway, and treatment with BBR reversed this effect. The myosin light chain (MLC) phosphorylation in the smooth muscle of the intestines is associated with motility of inflammation-related diarrhea in cats. This study used gut flora analyses to demonstrate the anti-UC effects of BBR and its potential therapeutic mechanisms and offers novel insights into the prevention of inflammatory diseases using natural products. IMPORTANCE Ulcerative colitis (UC) is common in clinics. Intestinal microbiota disorder is correlated with ulcerative colitis. Although there are many studies on ulcerative colitis in rats, there are few studies on colitis in cats. Therefore, this study explored the possibility of the use of BBR as a safe and efficient treatment for colitis in cats. The results demonstrated the therapeutic effects of BBR on UC based on the state of the intestinal flora. The study found BBR supplementation to be effective against dextran sulfate sodium (DSS)-induced colitis, smooth muscle damage, and gut microbiota dysbiosis.

Cysteine (Cys), one of the biological thiols, which plays critical roles in biological system regulating the balance of redox homeostasis. In order to monitor the level of Cys in the living cells and organisms, a chromogenic fluorescence probe Rhocl-Cys based on Rhodamine chloride exhibiting the preferable performance of fluorescence turn-on response reacting with Cys was presented. Rhocl-Cys responded rapidly to Cys within 20 min, and had stable fluorescence intensity within pH 6.0-10.0, high selectivity towards Cys and the anti-inference capability with a low detection limit of 0.80 μM. In particular, Rhocl-Cys could qualitatively and quantitatively monitor the level of endogenous and exogenous Cys in living cells and successfully apply to zebrafish detecting Cys. Therefore, these results might further provide the basis exploring the role of Cys in biological system and facilitate as clinical diagnostic molecular tools., 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 © 2022 Elsevier B.V. All rights reserved.)

Eight new steroids, designated mantuoluosides A-H (1-8), were obtained from the enrichment of steroids of the Datura stramonium L. using HPD-BJQH macroporous resin. Their respective structures were elucidated based on spectroscopic methods and comparison data with literature. The anti-inflammatory activities of these compounds were evaluated on (LPS)-induced RAW264.7 cells with inhibition ratio. It was found that most isolates showed potential anti-inflammatory activity with varying degrees of inhibition rate in a concentration-dependent manner at non-cytotoxic concentrations., (Copyright © 2022. Published by Elsevier B.V.)

The trace element selenium (Se) plays an indispensable role in the growth of humans and animals due to its antioxidant function. Mastitis is one of the most important diseases affecting the dairy industry in the world. In recent years, long non-coding RNAs (lncRNAs) have been implicated in a series of cellular processes and disease development processes. RNA-sequencing technology was used to characterize lncRNA profiles and compared transcriptomic dynamics among the control group, the LPS group, and the Se-treated group to highlight the potential roles and functions of lncRNAs in the mammary epithelial cells of dairy cows. We identified 14 specific lncRNAs related to Se and their predicted target genes. KEGG and GO functional annotation was used to elucidate their biological function and the pathways in which they may be involved. The present study provides novel insights for exploring the molecular markers for the protection of Se against mastitis in dairy cows., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

N6-methyladenine (m6A) is one of the most common RNA epigenetic modifications in all higher eukaryotes. Increasing evidence demonstrated that m6A-related proteins, acted as oncogenes or tumor suppressors, are abnormally expressed in the cell lines and tissues of non-small cell lung cancer (NSCLC). In addition, lung as the special immune organ contacts with the outer environments and thereby inevitably suffers from different types of microbial pathogen attack. Those microbial pathogens affect the development, progression, and clinical outcomes of NSCLC via altering host m6A modification to disrupt pulmonary immune homeostasis and increase the susceptibility; conversely, host cells modulate m6A modification to repress bacterial colonization. Therefore, m6A harbors the potential to be the novel biomarkers and targets for predicting poor prognosis and chemotherapy sensitivity of patients with lung cancer. In this paper, we provided an overview of the biological properties of m6A-modifying enzymes, and the mechanistic links among lung microbiota, m6A modification and NSCLC. Although the flood of novel m6A-related inhibitors represents many dramatic improvements in NSCLC therapy, their efficacy and toxicity in NSCLC are explored to address these pivotal gaps in the field., 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 Qiu, He, Zhong, Guo and Yu.)

Zinc (Zn) is an essential trace element for the body. Studies have confirmed that Zn deficiency can cause oxidative stress. The purpose of the present study was designed to investigate the effect of Zn on fibrosis in lung of mice and its mechanism. Mice were fed with different Zn levels dietary, then we found that the Zn-deficient diet induced a decrease of Zn level in lung tissue. The results also revealed the alveolar structure hyperemia and an inflammatory exudated in the alveolar cavity. Moreover, immunohistochemical results showed that the expression of α-smooth muscle actin (α-SMA) increased. And the Sirius red staining indicated an increase in collagen with Zn deficiency. Furthermore, oxygen radicals (ROS) levels were significantly increased, and the antioxidants were significantly decreased. Meanwhile, inflammatory factors (TNF-α and IL-1β) were remarkably increased, and the ELISA results showed that collagen I, III, and IV and fibronectin (FN) were increased. In addition, the expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) were detected by qPCR. The results showed that the expression of TIMPs was increased but the expression of MMPs was decreased. The results of the experiment in vitro were consistent with that in vivo. All the results indicated that Zn deficiency aggravated the oxidative stress response of lung tissue to induce inflammation, leading to fibrosis in lung., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect ( p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2 . Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation., 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 Luo, Luo, Li, Chen, Wu, Chen, Shen, Li, Guo, Yin, Zhang and Cheng.)

Multi-mycotoxin contamination of barley reduces malt quality and also poses serious health risks to both humans and animals. Among the detected mycotoxins in barley, Fusarium and Alternaria toxins represent severe food safety issues due to their widespread prevalence and strong synergistic toxicity. In this study, the effects of Fusarium and Alternaria fungi and their related toxins were investigated using simulated malting process conditions for contaminated barley samples. The dynamic changes of the fungal community and their associated mycotoxins were analyzed via high-throughput sequencing and UHPLC-q-trap-MS/MS, respectively. The results showed significant differences in the fungal communities between barley grains and their associated malt samples. These differences were noted for the following: fungal community diversity, dominant flora and the fungal structures at phylum, genus, and family level. Additionally, significant changes in the levels of alternariol monomethyl ether, tentoxin, zearalenone, and 15Acetyl-Deoxynivelenone were observed (p < 0.05) during the malting process. These results provide valuable information for strategies aimed at controlling fungal infections and the presence of mycotoxins in malt, so as to ensure food safety and human health., (Copyright © 2022. Published by Elsevier B.V.)

Ammonia (NH 3 ), an air pollutant in the living environment, has many toxic effects on various tissues and organs. However, the underlying mechanisms of NH 3 -induced tracheal cell autophagy remains poorly understood. In present study, chickens and LMH cells were used as NH 3 exposure models to investigate toxic effects. The change of tracheal tissues ultrastructure showed that NH 3 exposure induced autolysosomes. The differential expression of 12 circularRNAs (circRNAs) was induced by NH 3 exposure using circRNAs transcriptome analysis in broiler tracheas. We further found that circ-IFNLR1 was down-regulated, and miR-2188-5p was up-regulated in tracheal tissues under NH 3 exposure. Bioinformatics analysis and dual luciferase reporter system showed that circ-IFNLR1 bound directly to miR-2188-5p and regulated each other, and miR-2188-5p regulated RNF182. Overexpression of miR-2188-5p caused autophagy and its inhibition partially reversed autophagy in LMH cells which were caused by ammonia stimulation or knockdown of circ-IFNLR1. The expressions of three autophagy-related genes (LC3, Beclin 1, and BNIP3) were observably up-regulated. Our results indicated that NH 3 exposure caused autophagy through circ-IFNLR1/miR-2188-5p/RNF182. These results provided new insights for the study of ammonia on environmental toxicology on ceRNA and circRNAs in vivo and vitro., (© 2021 International Union of Biochemistry and Molecular Biology.)

Introduction: In many countries, there are waits for elective (planned) surgery. In these settings, processes for triaging patients are applied to determine how long patients wait for their surgery. There are very few instances that evaluate the effectiveness of surgical triage processes., Methods: A sample of patients from four acute care hospitals in Vancouver, Canada, completed a number of patient-reported outcomes shortly after being registered on the surgical wait list. Patients' diagnosis was used to triage and determine their expected wait for surgery. The associations between patient-reported outcomes with surgical triage were measured., Results: The mean wait times for participants were similar across wait times categories. Participants whose expected waits for surgery were the longest reported successively lower levels of self-rated health (p < 0.01) and successively higher levels of pain (p < 0.01.) There was no difference in symptoms of anxiety among participants expected to wait the longest., Discussion: The diagnosis-based system for prioritizing patients found higher levels of pain and lower health status among those expected to wait the longest for their surgery. Screening waiting patients for treatable mental health conditions should be implemented and the process of surgical triage could be redesigned to allow for a broader set of attributes of health to determine how long a patient waits for their elective surgery., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

H 2 S has been reported to play essential roles in a variety of physiological and pathological procedures. In this work, a novel fluorescent probe, Rho-HS, for detecting H 2 S was developed by introducing the ortho-halogen to activate the least reactive recognition group 2,4-dinitrophenyl moiety. In combination of the structures from both Rhodamine B and fluorescein, Rho-HS could generate both the colorimetric and fluorescent responses. This feature was not frequently achieved and could lead to the quantitative and convenient for the end-user. In comparison with recent probes for H 2 S, the major advantages of Rho-HS included suiting wide pH range (6.0-10.0), relatively rapid response (within 15 min) and the high selectivity among the competing species including the biothiols. With low cytoxicity, Rho-HS was further applied in the biological imaging in living MCF-7 cells and Caenorhabditis elegans. We hope that the designing strategy in this work might provide useful information for more preferable implements in this field., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The assembly of two tripyridinium-tricarboxylate ligands and different metal ions leads to seven isostructural MOFs, which show novel 2D→2D supramolecular entanglement featuring catenane-like interlocking of tricyclic cages. The MOFs show tripyridinium-afforded and metal-modulated photoresponsive properties. The MOFs with d 10 metal centers (1-Cd, 1-Zn, 2-Cd, 2-Zn) show fast and reversible photochromism and concomitant fluorescence quenching, 1-Ni displays slower photochromism but does not fluoresce, and 1-Co and 2-Co are neither photochromic nor fluorescent. It is shown here that the network entanglement dictates donor-acceptor close contacts, which enable fluorescence originated from interligand charge transfer. The contacts also allow photoinduced electron transfer, which underlies photochromism and concomitant fluorescence response. The metal dependence in fluorescence and photochromism can be related to energy transfer through metal-centered d-d transitions. In addition, 1-Cd is demonstrated to be a potential fluorescence sensor for sensitive and selective detection of UO 2 2+ in water., (© 2021 Wiley-VCH GmbH.)

Corneal alkali burn, one of the most serious ophthalmic emergencies, is difficult to be cured by conservative treatments. It is well known that oxidative stress, inflammation and neovascularization are the main causes of corneal damage after alkali burn, but its underlying mechanism remains to be elucidated. Here, we reported that the expression and phosphorylation (Ser616) of mitochondrial fission protein Drp1 were up-regulated at day 3 after alkali burn, while mitochondrial fusion protein Mfn2 was down-regulated. The phosphorylation of ERK1/2 in corneas was increased at day 1, 3, 7 and peaked at day 3 after alkali burn. In human corneal epithelial cells (HCE-2), NaOH treatment induced mitochondrial fission, intracellular ROS production and mitochondrial membrane potential disruption, which was prevented by Drp1 inhibitor Mdivi-1. In corneas, Mdivi-1 or knockdown of Drp1 by Lenti-Drp1 shRNA attenuated alkali burn-induced ROS production and phosphorylation of IκBα and p65. In immunofluorescence staining, it was detected that Mdivi-1 also prevented NaOH-induced nuclear translocation of p65 in HCE-2 cells. Moreover, the expression of NADPH oxidase NOX2 and NOX4 in corneas peaked at day 7 after alkali burn. Mdivi-1, Lenti-Drp1 shRNA or the mitochondria-targeted antioxidant mito-TEMPO efficiently alleviated activation of NF-κB, expression of NOX2/4 and inflammatory cytokines including IL-6, IL-1β and TNF-α in corneas after alkali burn. In pharmacological experiments, both Mdivi-1 and NADPH oxidases inhibitor Apocynin protected the corneas against alkali burn-induced neovascularization. Intriguingly, the combined administration of Mdivi-1 and Apocynin had a synergistic inhibitory effect on corneal neovascularization after alkali burn. Taken together, these results indicate that Drp1-dependent mitochondrial fission is involved in alkali burn-induced corneal injury through regulating oxidative stress, inflammatory responses and corneal neovascularization. This might provide a novel therapeutic target for corneal injury after alkali burn in the future., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the negative feedback regulation from rat hippocampus on hypothalamic-pituitary-adrenal (HPA) axis under high temperature and high humidity stress., Methods: Thirty (30) SD male rats were randomly divided into three groups: control group, high temperature and high humidity group, drug intervention group. The rats in control group were kept in the environment with temperature of 24 ± 1°C and humidity of 50 ± 5%, without any stimulation. The rats in the other groups were exposed to high temperature and high humidity environment for 4 h each day, with temperature of 35±1 °C and humidity of 85±5%. The rats in drug intervention group were intragastrically administered with the glucocorticoid receptor antagonist mifepristone. The administration was continued for 3 weeks. After 3 weeks, the serum levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by ELISA.The protein and mRNA levels of corticosteroid receptors (MR), glucocorticoid receptors (GR) and inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid 1 (TRPV1) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in hippocampus were determined by immunohistochemistry and in situ hybridization, respectively. The apoptosis of hippocampal cells was examined with TUNEL apoptosis staining., Results: After stimulation with high temperature and high humidity stress for 3 weeks, the serum levels of CRH, ACTH and CORT in the high temperature and high humidity group were significantly increased compared to that of control group; the levels of these indicators in drug intervention group were decreased compared to that of high temperature and high humidity group (P<0.05). In high temperature and high humidity group, the protein and mRNA levels of MR, GR, iNOS in hippocampus of rats were significantly increased compared with that of control group (p<0.05); and the levels of these indicators in drug intervention group were lower than that of high temperature and high humidity group (p<0.05). In addition, compared with the control group, the TRPV1 protein level in hippocampus of rats in high temperature and high humidity group was not significantly changed (p>0.05), while the TRPV1 mRNA level was significantly increased (p<0.05). Neither the protein nor mRNA levels of 11β-HSD1 showed significant difference compared to control group (p>0.05). The apoptosis of hippocampus cells in the high temperature and high humidity group was significantly increased compared with that of control group (p<0.05); and it was lower in the drug intervention group than that of in high temperature and high humidity group while the result was not significant (p>0.05)., Conclusion: High temperature and high humidity stress may up-regulate the local expression of iNOS in hippocampus and decrease the activity of glucocorticoids (GC) receptor, then the effective binding of GR-GC would be decreased and the negative feedback regulation of hippocampus on HPA axis would be inhibited. The glucocorticoid receptor antagonist can improve the negative feedback regulation of hippocampus on HPA axis in rat.

Long noncoding RNAs (lncRNAs) have been reported to participate in regulating many biological processes, including immune response to influenza A virus (IAV). However, the association between lncRNA expression profiles and influenza infection susceptibility has not been well elucidated. Here, we analyzed the expression profiles of lncRNAs, miRNAs, and mRNAs among IAV-infected adult rat (IAR), normal adult rat (AR), IAV-infected junior rat (IJR), and normal junior rat (JR) by RNA sequencing. Compared with differently expressed lncRNAs (DElncRNAs) between AR and IAR, 24 specific DElncRNAs were found between IJR and JR. Then, based on the fold changes and P value, the top 5 DElncRNAs, including 3 upregulated and 2 downregulated lncRNAs, were chosen to establish a ceRNA network for further disclosing their regulatory mechanisms. To visualize the differentially expressed genes in the ceRNA network, GO and KEGG pathway analysis was performed to further explore their roles in influenza infection of junior rats. The results showed that the downregulated DElncRNA-target genes were mostly enriched in the IL-17 signaling pathway. It indicated that the downregulated lncRNAs conferred the susceptibility of junior rats to IAV via mediating the IL-17 signaling pathway., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Fen-Sheng Qiu et al.)