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Background: Extralobar pulmonary sequestration (ELS) with torsion is extremely rare, consequently, the diagnosis of ELS with torsion in children presents a challenge for clinicians. Herein, we report four cases of ELS with torsion that presented with abdominal pain, and further review the relevant literature to summarize the clinical features., Case Summary: Four children presented to our department with abdominal pain. All underwent chest computed tomography, which revealed an intrathoracic soft tissue mass with pleural effusion. All four children underwent thoracoscopic resection of the identified pulmonary sequestration, and the vascular pedicle was clipped and excised. None of the patients experienced any postoperative complications., Conclusion: Clinicians should consider the possibility of ELS with torsion in children presenting with abdominal pain as the chief complaint., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatitis C virus (HCV) infection affects men and women differently, yet few studies have investigated sex differences in long-term mortality risk among the HCV-infected population. We conducted a population-based study to elucidate all-cause and cause-specific mortality among men and women with HCV infection., Methods: The study population consisted of adult participants from the 1999-2018 National Health and Nutrition Examination Survey, including 945 HCV-infected and 44,637 non-HCV-infected individuals. HCV infection was defined as either HCV seropositivity or detectable HCV RNA. Participants were followed until the date of death or December 31, 2019, to determine survival status., Results: The HCV-infected population, both male and female, tended to be older, more likely to be Black, single, have lower income, lower BMI, higher prevalence of hypertension, and were more likely to be current smokers. During a median follow-up of 125.0 months, a total of 5,309 participants died, including 1,253 deaths from cardiovascular disease (CVD) and 1,319 deaths from cancer. The crude analysis showed that the risk of death from all causes and from cancer, but not from CVD, was higher in the HCV-infected population. After adjusting for potential confounders, we found that both HCV-infected men (HR 1.41, 95% CI 1.10-1.81) and women (HR 2.03, 95% CI 1.36-3.02) were equally at increased risk of all-cause mortality compared to their non-HCV infected counterparts (p for interaction > 0.05). The risk of cancer-related mortality was significantly increased in HCV-infected women (HR 2.14, 95% CI 1.01-4.53), but not in men, compared to non-HCV-infected counterparts. Among HCV-infected population, there was no difference in the risks of all-cause, CVD-related, or cancer-related death between men and women., Conclusion: Both men and women with HCV infection had an increased risk of death from all causes compared to their non-HCV infected counterparts, but we did not observe a significant sex difference., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos., 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 Masson SAS. All rights reserved.)

Introduction: Phosphodiesterase 9 (PDE9) has been demonstrated as a potential target for neurological disorders and cardiovascular diseases, such as Alzheimer's disease and heart failure. For the last few years, a series of PDE9 inhibitors with structural diversities have been developed and patented by researchers and pharmaceutical companies, providing insights into first-in-class therapies of PDE9 drug candidates., Area Covered: This review provides an overview of PDE9 inhibitors in patents from 2018 to the present., Expert Opinion: Only a few of the current PDE9 inhibitors are highly selective over other PDEs, which limits their application in pharmacological and clinical research. The design and development of highly selective PDE9 inhibitors remain the top priority in future research. The advantages of targeting PDE9 rather than other PDEs in treating neurodegenerative diseases need to be explained thoroughly. Besides, application of PDE9 inhibitor-based combination therapies sheds light on treating diabetes and refractory heart diseases. Finally, PDE9 inhibitors should be further explored in clinical indications beyond neurological disorders and cardiovascular diseases.

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t -test and Mann-Whitney U -test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z =-2.298, P <0.05; DM-SCIT: Z =-3.411, P <0.001); total ACT score (SM-SCIT: Z =-2.054, P <0.05; DM-SCIT: Z =-2.014, P <0.05) and total medication scores (SM-SCIT: Z =-3.799, P <0.000 1; DM-SCIT: Z =-3.474, P <0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t =-2.253, P <0.05). There was no significant change in sIgE in the SM-SCIT group ( P >0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z= -2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P <0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z =-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P <0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z =-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P <0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P <0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z =-1.988, -2.090, -2.497, -1.988, respectively, all P <0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r= -0.499, P <0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r =0.451, 0.420, 0.474, respectively; all P <0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Background: This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas., Methods: Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up., Results: The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4)., Conclusions: High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.

Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1., 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 © 2024 Tang, Jiang, Cao and Wan.)

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC 50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-β-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.

Active adjustable terahertz multifunctional devices are crucial for the application of terahertz technology. In this paper, we propose a composite metasurface structure based on an indium antimonide metal octagonal pattern, which achieves different functional switching by controlling the phase state of indium antimonide material under different ambient temperatures. When indium antimonide exhibits in the dielectric state, by stacking and encoding the unit cell, the designed metasurface has the functions of two-beam splitting beam superposition, vortex beam and quarter beam superposition, and dual vortex beam superposition for circularly polarized and linearly polarized wave incidence. When indium antimonide appears in the metallic state, the encoding metasurface alters the modulation function of incident circularly polarized and linearly polarized terahertz waves. This terahertz metasurface provides a new approach for the design of multifunctional devices that can flexibly regulate terahertz wave metasurfaces.

Background: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet., Objective: To investigate trial characteristics related to treatment effect estimates on CHM RCTs., Search Strategy: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021., Inclusion Criteria: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis., Data Extraction and Analysis: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively., Results: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates., Conclusion: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234., 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 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Two new monoterpene esters, illigerates H and I ( 1 and 2 ), and six known compounds actinodaphine ( 3 ), bulbocupnine ( 4 ), stephanine ( 5 ), hypserpanine B ( 6 ), betulinic acid ( 7 ) and gallic acid ( 8 ) were obtained from the root of Illigera paviflora Dunn. Their structures were elucidated by spectroscopic analysis. Anti-inflammatory and α-glucosidase inhibitory activity of some isolated compounds were assessed. Two monoterpenes 1 and 2 exhibited weak in vitro anti-inflammatory activity (IC 50 64.5 ± 5.3 and 79.2 ± 7.5 μM) while compounds 3-6 showed inhibition of α-glucosidase with IC 50 values ranged from 87.17 to 118.74 μM.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide., 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 Ltd. All rights reserved.)

Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. PDE1 (Phosphodiesterase 1) is a subfamily of the PDE super-enzyme families that can hydrolyze the second messengers cAMP and cGMP simultaneously. Previous research has shown that suppressing the gene expression of PDE1 can trigger apoptosis of human leukemia cells. However, no selective PDE1 inhibitors have been used to explore whether PDE1 is a potential target for treating AML. Based on our previously reported PDE9/PDE1 dual inhibitor 11a, a series of novel pyrazolopyrimidinone derivatives were designed in this study. The lead compound 6c showed an IC 50 of 7.5 nM against PDE1, excellent selectivity over other PDEs and good metabolic stability. In AML cells, compound 6c significantly inhibited the proliferation and induced apoptosis. Further experiments indicated that the apoptosis induced by 6c was through a mitochondria-dependent pathway by decreasing the ratio of Bcl-2/Bax and increasing the cleavage of caspase-3, 7, 9, and PARP. All these results suggested that PDE1 might be a novel target for AML., 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. Published by Elsevier Inc.)

Objective: To investigate the effect of adenovirus-mediated short hairpin RNA (shRNA) downregulating SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the apoptosis of human hepatic stellate cells LX-2 cultured in vitro. Methods: The recombinant adenovirus Ad-shRNA/SHP2 carrying shRNA targeted SHP2 and expressing green fluorescent protein (GFP), and the empty control virus Ad-GFP expressing GFP were transfected into LX-2 cells cultured in vitro. Real-time fluorescence quantitative PCR was used to detect SHP2 mRNA expression in LX-2 cells. Western blot was used to detect the protein expressions of SHP2, Bax, and Bcl-2 in LX-2 cells. TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry were used to detect apoptosis in LX-2 cells. Experimental group: (1) Control group: LX-2 cells were transfected with DMEM instead of adenovirus; (2) Ad-GFP group: transfected with empty virus Ad-GFP; (3) Ad-shRNA/SHP2 group: transfected with recombinant adenovirus Ad-shRNA/SHP2. The means between multiple groups were compared using a one-way ANOVA and the LSD test was used for inter group comparisons. Results: shRNA-targeted SHP2 significantly down-regulated the expression of SHP2 protein and mRNA in LX-2 cells ( P < 0.05). The TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry results showed that the apoptosis rate of LX-2 cells in the Ad-shRNA/SHP2 group (12.755%±1.606%, 19.340%±2.505%) ( P < 0.05) was significantly higher compared to the control group (3.077%±0.731%, 9.438%±0.804%) and the Ad-GFP group (3.250%±0.851%, 8.893%±1.982%), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Western blot analysis of Bax and Bcl-2 protein expression in LX-2 cells of each group revealed that the Bax protein expression was significantly higher in the Ad shRNA/SHP2 group (2.493 ± 0.203) ( P < 0.05) compared to the control group and Ad-GFP group (1.989 ± 0.147, 1.999 ± 0.162), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05), while the Bcl-2 protein was significantly decreased in the Ad-shRNA/SHP2 group (1.042±0.148) compared with the control group and the Ad-GFP group (1.707±0.146, 1.521±0.142), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Conclusions: SHP2 expression down-regulation induces apoptosis of human hepatic stellate cells LX-2 in vitro by reducing Bcl-2/Bax.

This study aimed to investigate the Mg × K product on the mortality risk of hemodialysis patients with concomitant hypokalemia and lower magnesium levels. This was a prospective observational study of patients in a HD center in southern Taiwan. A total of 444 HD patients were divided into 5 groups by the Mg × K product: group 1, bottom quintile, median Mg × K: 7.87, IQR: 7.03-8.12 (n = 89, age: 64 ± 13 years old); group 2, median Mg × K: 9.37, IQR: 8.97-9.86 (n = 89, age:62 ± 13 years old); group 3, median Mg × K: 10.95, IQR: 10.50-11.26 (n = 89, age:64 ± 13 years old); group 4, median Mg × K: 12.30, IQR: 11.87-12.82 (n = 89, 61 ± 12 years old); and group 5, top quintile, median Mg × K: 14.92, IQR:14.07-16.23 (n = 88, 62 ± 11 years old). The patients were followed up for 2 years to determine the risk of all-cause mortality. Patients with a lower Mg × K product had more comorbidities, malnutrition-inflammation status, and a higher mortality risk. Using multivariable Cox regression analysis, a higher Mg × K [HR, 0.89; 95%CI (0.81-0.98)] was found to be an independent predictor of better survival. HD patients with a lower Mg × K product had more comorbidities, a marked malnutrition-inflammation status, and were associated with long-term mortality. A higher Mg × K value is a favorable survival factor., (© 2023. The Author(s).)

Background: Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism., Methods: A high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC-MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator., Results: The expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC-MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin., Conclusions: Adipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation., (© 2023. The Author(s).)

Ethnopharmacological Relevance: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with limited therapy. Renshen Pingfei Formula (RPFF), a classic Chinese medicine derivative formula, has been shown to exert therapeutic effects on IPF., Aim of the Study: The study aimed to explore the anti-pulmonary fibrosis mechanism of RPFF through network pharmacology, clinical plasma metabolomics, and in vitro experiment., Methods: Network pharmacology was used to study the holistic pharmacological mechanism of RPFF in the treatment of IPF. The differential plasma metabolites for RPFF in the treatment of IPF were identified by untargeted metabolomics analysis. By integrated analysis of metabolomics and network pharmacology, the therapeutic target of RPFF for IPF and the corresponding herbal ingredients were identified. In addition, the effects of the main components of the formula, kaempferol and luteolin, which regulate the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ (PPAR-γ) pathway were observed in vitro according to the orthogonal design., Results: A total of 92 potential targets for RPFF in the treatment of IPF were obtained. The Drug-Ingredients-Disease Target network showed that PTGS2, ESR1, SCN5A, PPAR-γ, and PRSS1 were associated with more herbal ingredients. The protein-protein interaction (PPI) network identified the key targets of RPFF in IPF treatment, including IL6, VEGFA, PTGS2, PPAR-γ, and STAT3. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis acquired the main enriched pathways, and PPAR-γ involved in multiple signaling pathways, including the AMPK signaling pathway. Untargeted clinical metabolomics analysis revealed plasma metabolite variations in patients with IPF versus controls and before versus after RPFF treatment for patients with IPF. Six differential metabolites were explored as differential plasma metabolites for RPFF in IPF treatment. Combined with network pharmacology, a therapeutic target PPAR-γ of RPFF in IPF treatment and the corresponding herbal components were identified. Based on the orthogonal experimental design, the experiments showed that kaempferol and luteolin can decrease the mRNA and protein expression of α-smooth muscle actin (α-SMA), and the combination of lower dose can inhibit α-SMA mRNA and protein expression by promoting the AMPK/PPAR-γ pathway in transforming growth factor beta 1 (TGF-β1)-treated MRC-5 cells., Conclusions: This study revealed that the therapeutic effects of RPFF are due to multiple ingredients and have multiple targets and pathways, and PPAR-γ is one of therapeutic targets for RPPF in IPF and involved in the AMPK signaling pathway. Two ingredients of RPFF, kaempferol and luteolin, can inhibit fibroblast proliferation and the myofibroblast differentiation of TGF-β1, and exert a synergistic effect through AMPK/PPAR-γ pathway activation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Respiratory syncytial virus (RSV) infection in infants is a global health priority. We aimed to investigate the common manifestations of RSV infection by age group and human development index (HDI) level and to assess its association with the development of wheezing and recurrent wheezing illness., Methods: We searched the literature published between January 1, 2010 and June 2, 2022 in seven databases. Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children. Random- and fixed-effect models were used to estimate the effect size and their 95% confidence intervals. Subgroup analysis was conducted by age and HDI levels. This review was registered in PROSPERO (CRD42022379401)., Results: The meta-analysis included 47 studies. The top five manifestations were cough (92%), nasal congestion (58%), rhinorrhea (53%), shortness of breath (50%), and dyspnea (47%). The clinical symptoms were most severe in infants. In our analysis, compared to very high and high HDI countries, fewer studies in medium HDI countries reported related manifestations, and no study in low HDI countries reported that. The RSV-infected infants were more likely to develop wheezing than the non-infected infants [odds ratio (OR), 3.12; 95% CI, 2.59-3.76] and had a higher risk of developing wheezing illnesses after recovery (OR, 2.60; 95% CI, 2.51-2.70)., Conclusions: Cough and shortness of breath are common manifestations of RSV infection. More attention should be given to infants and areas with low HDI levels. The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness., (© 2023. The Author(s).)

Excessive application of chemical fertilizer has caused many problems in Angelica dahurica var. formosana planting, such as yield decline and quality degradation. In order to promote the green cultivation mode of A. dahurica var. formosana and explore rhizosphere fungus resources, the rhizosphere fungi with nitrogen fixation, phosphorus solubilization, potassium solubilization, iron-producing carrier, and IAA-producing properties were isolated and screened in the rhizosphere of A. dahurica var. formosana from the genuine and non-genuine areas, respectively. The strains were identified comprehensively in light of the morphological characteristics and ITS rDNA sequences, and the growth-promoting effect of the screened strains was verified by pot experiment. The results showed that 37 strains of growth-promoting fungi were isolated and screened from the rhizosphere of A. dahurica var. formosana, mostly belonging to Fusarium. The cultured rhizosphere growth-promoting fungi of A. dahurica var. formosana were more abundant and diverse in the genuine producing areas than in the non-genuine producing areas. Among all strains, Aspergillus niger ZJ-17 had the strongest growth promotion potential. Under the condition of no fertilization outdoors, ZJ-17 inoculation significantly promoted the growth, yield, and accumulation of effective components of A. dahurica var. formosana planted in the soil of genuine and non-genuine producing areas, with yield increases of 73.59% and 37.84%, respectively. To a certain extent, it alleviated the restriction without additional fertilization on the growth of A. dahurica var. formosana. Therefore, A. niger ZJ-17 has great application prospects in increasing yield and quality of A. dahurica var. formosana and reducing fertilizer application and can be actually applied in promoting the growth of A. dahurica var. formosana and producing biofertilizer.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis . An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo 2 (OAc) 4 -induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p -coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC 50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans - p -coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis - p -coumaroyl group., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Phosphodiesterase 1 (PDE1) is a subfamily of PDE super enzyme families that can hydrolyze cyclic adenosine monophosphate and cyclic guanosine monophosphate simultaneously. Currently, the number of PDE1 inhibitors is relatively few, significantly limiting their application. Herein, a novel series of quinolin-2(1 H )-ones were designed rationally, leading to compound 10c with an IC 50 of 15 nM against PDE1C, high selectivity across other PDEs, and remarkable safety properties. Furthermore, we used the lead compound 10c as a chemical tool to explore whether PDE1 could work as a novel potential target for the treatment of inflammatory bowel disease (IBD), a disease which is a chronic, relapsing disorder of the gastrointestinal tract inflammation lacking effective treatment. Our results showed that administration of 10c exerted significant anti-IBD effects in the dextran sodium sulfate-induced mice model and alleviated the inflammatory response, indicating that PDE1 could work as a potent target for IBD.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Introduction: Studies on association of α-klotho levels with mortality risk in general population are relatively scarce and inconclusive. Therefore, we conducted a population-based cohort study to investigate the relationship between soluble α-klotho and all-cause mortality in a nationally representative sample of middle-aged and older adults in the United States (U.S.)., Methods: The study population was 2007-2016 National Health and Nutrition Examination Survey (NHANES) participants, totaling 13,583 adults aged 40-79 years. Participants were divided into 7 groups by septile of α-klotho levels. We linked the NHANES data to the National Death Index to determine participants' survival status. End of follow-up was participants' death date or December 31, 2019., Results: We observed that males, current smokers, older age, higher body mass index, and lower estimated glomerular filtration rate correlated to lower α-klotho levels, while hepatitis C virus infection correlated to higher α-klotho. The population mortality rate was 11.8 per 10,000 person-months (1,490 deaths); group 1 (the first septile) had higher mortality risk compared with group 2 through group 7. By weighted Cox regression with adjustment for potential confounders, we found that group 2 through group 6, but not group 7, were associated with 25% to 35% lower risk of all-cause mortality compared with group 1. When compared with group 4, we observed that both group 1 (HR: 1.46, 95% CI 1.13-1.88) and group 7 (HR: 1.38, 95% CI 1.09-1.74) were associated with higher mortality risk., Conclusion: In summary, among middle-aged and older U.S. adults, we observed a non-linear association between soluble α-klotho and all-cause mortality, with individuals at the two extremes at increased risk of death., 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 Chuang, Wang, Huang and Jiang.)

Membrane fouling induces catastrophic loss of separation performance and seriously restricts the applications of reverse osmosis (RO) membranes. Inspired by the mussel structure, polydopamine (PDA) and cystamine molecules (CA) with excellent anti-fouling properties were used to prepare accessible, biocompatible, and redox-responsive coatings for RO membranes. The PDA/CA-coated RO membranes exhibit a superior water flux of 65 L m -2 h -1 with a favourable NaCl rejection exceeding 99%. The water permeability through the PDA/CA-coated membrane is much higher than that of most membranes with similar rejection rates. Due to the formed protective hydration layers by PDA/CA coatings, anti-fouling properties against proteins, polysaccharides and surfactants were evaluated separately, and ultralow fouling properties were demonstrated. Moreover, the disulfide linkages in CA molecules can cleave in a reducing environment, yielding the degradation of PDA/CA coatings, thereby removing the foulants deposited on the coatings. The degradation endows the coated membranes with satisfying longtime anti-fouling properties, where the flux recovery reaches up to 90%. The construction of redox-responsive smart coatings not only provided a promising route to alleviate membrane fouling but can also be upscaled for use in numerous practical applications like sensors, medical devices, and drug delivery.

Background: Cryptocaryon irritans, a common parasite in tropical and subtropical marine teleost fish, has caused serious harm to the marine aquaculture industry. Honokiol was proven to induce C. irritans tomont cytoplasm shrinkage and death in our previous study, but the mechanism by which it works remains unknown., Methods: In this study, the changes of apoptotic morphology and apoptotic ratio were detected by microscopic observation and AnnexinV-FITC/PI staining. The effects of honokiol on intracellular calcium ([Ca 2+ ] i ) concentration, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), quantity of DNA fragmentations (QDF) and caspase activities were detected by Fluo-3 staining, JC-1 staining, DCFH-DA staining, Tunel method and caspase activity assay kit. The effects of honokiol on mRNA expression levels of 61 apoptosis-related genes in tomonts of C. irritans were detected by real-time PCR., Results: The results of the study on the effects of honokiol concentration on C. irritans tomont apoptosis-like death showed that the highest levels of prophase apoptosis-like death rate (PADR), [Ca 2+ ] i concentration, ROS, the activities of caspase-3/9 and the lowest necrosis ratio (NER) were obtained at a concentration of 1 μg/ml, which was considered the most suitable for inducing C. irritans tomont apoptosis-like death. When C. irritans tomonts were treated with 1 μg/ml honokiol, the [Ca 2+ ] i concentration began to increase significantly at 1 h. Following this, the ROS, QDF and activities of caspase-3/9 began to increase significantly, and the ΔΨm began to decrease significantly at 2 h; the highest PADR was obtained at 4 h. The mRNA expression of 14 genes was significantly upregulated during honokiol treatment. Of these genes, itpr2, capn1, mc, actg1, actb, parp2, traf2 and fos were enriched in the pathway related to apoptosis induced by endoplasmic reticulum (ER) stress., Conclusions: This article shows that honokiol can induce C. irritans tomont apoptosis-like death. These results suggest that honokiol may disrupt [Ca 2+ ] i homeostasis in ER and then induce C. irritans tomont apoptosis-like death by caspase cascade or mitochondrial pathway, which might represent a novel therapeutic intervention for C. irritans infection., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Poly(ADP-ribose)polymerase family member 14 (PARP14), which is an intracellular mono(ADP-ribosyl) transferase, has been reported to promote post-stroke functional recovery, but its role in spinal cord injury (SCI) remains unclear. To investigate this, a T10 spinal cord contusion model was established in C57BL/6 mice, and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression. We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury, accompanied by obvious neuronal apoptosis, severe neuroinflammation, and slight bone loss. Furthermore, PARP14 levels were elevated in microglia after SCI, PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia (anti-inflammatory phenotype) to M1-polarized microglia (pro-inflammatory phenotype) that may have been mediated by the signal transducers and activators of transcription (STAT) 1/6 pathway. Next, microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γ and interleukin-4, respectively. The results showed that PARP14 knockdown promoted microglia M1 polarization, accompanied by activation of the STAT1 pathway. In addition, PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway. In conclusion, these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway., Competing Interests: None

Introduction: The prevalence of vitamin D deficiency varied among populations and regions worldwide. In addition, the association between vitamin D deficiency and health outcomes remained controversial. Our study aimed to investigate the prevalence of vitamin D deficiency and its association with mortality risk among non-institutional middle-aged and older adults in the United States., Method: The study population included 11,119 adult participants aged between 50 and 79 years in the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Vitamin D status was divided as ≤ 30 (severely deficient), 30.1-50 (moderately deficient), 50.1-75 (insufficient), 75.1-100 (sufficient), and > 100 nmol/L (very sufficient). NHANES data were linked to National Death Index to ascertain the survival status and cause of death., Results: The population aged 61.5 years (survey-weighted) and 47.9% were men. Among them, 4.6% were severely vitamin D deficient, 15.2% moderately deficient, and 33.6% insufficient. Individuals with higher vitamin D levels tended to be female, older, white people, non-smoker, non-single, more educated, with higher family income, and lower body mass index. During a median follow-up of 97.0 months, a total of 1,585 participants died (15.9 per 10,000 person-months). The crude analysis showed that vitamin D deficiency, but not vitamin D insufficiency, correlated to higher all-cause mortality risk. The association remained similar after adjusting for potential confounders, showing that vitamin D deficiency (HR: 1.38, 95% CI 1.15-1.66), but not vitamin D insufficiency (HR: 1.03, 95% CI 0.88-1.20), correlated to higher all-cause mortality risk. In addition, we showed that vitamin D deficiency was an independent risk factor for death from pneumonia (HR: 3.82, 95% CI 1.14-12.86) but not from cardiovascular diseases, cancer, or cerebrovascular diseases., Conclusion: In summary, among middle-aged and older adults in the United States, nearly 20% were vitamin D deficient. Vitamin D deficiency, but not vitamin D insufficiency, correlated to increased mortality risk., 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 Wang, Wang and Jiang.)

In the present study, the sputtered aluminum nitride (AlN) films were processed in a reactive pulsed DC magnetron system. We applied a total of 15 different design of experiments (DOEs) on DC pulsed parameters (reverse voltage, pulse frequency, and duty cycle) with Box-Behnken experimental method and response surface method (RSM) to establish a mathematical model by experimental data for interpreting the relationship between independent and response variables. For the characterization of AlN films on the crystal quality, microstructure, thickness, and surface roughness, X-ray diffraction (XRD), atomic force microscopy (AFM), and field emission-scanning electron microscopy (FE-SEM) were utilized. AlN films have different microstructures and surface roughness under different pulse parameters. In addition, in-situ optical emission spectroscopy (OES) was employed to monitor the plasma in real-time, and its data were analyzed by principal component analysis (PCA) for dimensionality reduction and data preprocessing. Through the CatBoost modeling and analysis, we predicted results from XRD in full width at half maximum (FWHM) and SEM in grain size. This investigation identified the optimal pulse parameters for producing high-quality AlN films as a reverse voltage of 50 V, a pulse frequency of 250 kHz, and a duty cycle of 80.6061%. Additionally, a predictive CatBoost model for obtaining film FWHM and grain size was successfully trained.

With the expansion of mpox virus infection from endemic to a global epidemic in 2022, the WHO declared that the mpox event constituted a Public Health Emergency of International Concern. Due to the high degree of gene sequence similarity among orthopox viruses and cross-reactive antibodies induced by orthoviruses, smallpox vaccination may affect the immune response induced by mpox virus infection. The analysis of the protective effects of smallpox vaccination against mpox virus infection will help define the focus of prevention and control. In this review, we clarify the protection of the smallpox vaccine against mpox virus infection by analyzing the correlation between smallpox vaccination, immune response status, and clinical data and providing evidence for the prevention, control, and strategies of mpox epidemics.

Background: Compared with children and immunocompromised patients, Adenovirus pneumonia in immunocompetent adults is less common. Evaluation of the applicability of severity score in predicting intensive care unit (ICU) admission of Adenovirus pneumonia is limited., Methods: We retrospectively reviewed 50 Adenovirus pneumonia inpatients in Xiangtan Central Hospital from 2018 to 2020. Hospitalized patients with no pneumonia or immunosuppression were excluded. Clinical characteristics and chest image at the admission of all patients were collected. Severity scores, including Pneumonia severity index (PSI), CURB-65, SMART-COP, and PaO2/FiO2 combined lymphocyte were evaluated to compare the performance of ICU admission., Results: Fifty inpatients with Adenovirus pneumonia were selected, 27 (54%) non-ICU and 23 (46%) ICU. Most patients were men (40 [80.00%]). Age median was 46.0 (IQR 31.0-56.0). Patients who required ICU care (n = 23) were more likely to report dyspnea (13[56.52%] vs 6[22.22%]; P = 0.002) and have lower transcutaneous oxygen saturation ([90% (IQR, 90-96), 95% (IQR, 93-96)]; P = 0.032). 76% (38/50) of patients had bilateral parenchymal abnormalities, including 91.30% (21/23) of ICU patients and 62.96% (17/27) of non-ICU patients. 23 Adenovirus pneumonia patients had bacterial infections, 17 had other viruses, and 5 had fungi. Coinfection with virus was more common in non-ICU patients than ICU patients (13[48.15%]VS 4[17.39%], P = 0.024), while bacteria and fungi not. SMART-COP exhibited the best ICU admission evaluation performance in Adenovirus pneumonia patients (AUC = 0.873, p < 0.001) and distributed similar in coinfections and no coinfections (p = 0.26)., Conclusions: In summary, Adenovirus pneumonia is not uncommon in immunocompetent adult patients who are susceptible to coinfection with other etiological illnesses. The initial SMART-COP score is still a reliable and valuable predictor of ICU admission in non-immunocompromised adult inpatients with adenovirus pneumonia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Seasonal influenza has a high disease burden, and children infected with influenza are prone to multiple complications. Influenza vaccination is effective in preventing infection and reducing risks of severe diseases and complications. Influenza vaccines are trivalent and quadrivalent, depending on the components of the vaccine. According to the hemagglutinin content, it can be divided into full dose and half dose of influenza vaccine for children. The findings from clinical trials and real-world studies suggested, the full-dose influenza vaccine as in adults has the same safety profile and higher immunogenicity in children aged 6 to 35 months. The application of full-dose influenza vaccine in children aged 6 to 35 months can greatly improve the flexibility and convenience of vaccination, and help reduce the workload in the process.

Purpose: To investigate the application value of nitrous oxide/oxygen inhalation comfort technique during tooth extraction in elderly patients with hypertension under electrocardiographic(ECG) monitoring., Methods: According to the inclusion and exclusion criteria, sixty elderly patients (over 65 years old) with hypertension for tooth extraction were randomly divided into 2 groups: the experimental group(nitrous oxide/oxygen inhalation combined with ECG monitoring group, n=30) and the control group (routine ECG monitoring group, n=30). Mean arterial pressure (MAP) and heart rate (HR) at T0 (baseline values before surgery), T1 (on local anesthesia), T2 (during operation) and T3(5 minutes after operation) were recorded. SPSS 25.0 software package was used for statistical analysis., Results: There was no significant difference in MAP and HR at each time point in the experimental group(P＞0.05). There was no significant difference in MAP and HR at T0 and T3 time points in the control group(P＞0.05). At other time points, MAP and HR were significantly different (P＜0.05). There was no significant differences in MAP and HR between the two groups at T0 and T3(P＞0.05). MAP and HR at T1 and T2 in the experimental group were significantly less than those in the control group(P＜0.05)., Conclusions: Nitrous oxide/oxygen inhalation comfort technology can stabilize patients' emotions and maintain stable blood pressure and heart rate in elderly patients with hypertension during tooth extraction, thus improving the safety of tooth extraction.

Human Respiratory Syncytial Virus (HRSV) is a serious threat to the population health. The elderly are one of the susceptible populations. The prevalence of HRSV in the elderly is generally higher than that in other age groups except children, which has gradually attracted attention in recent years. This paper reviewed the prevalence, common complications and major complications of HRSV in the elderly, briefly expounded the economic burden of HRSV infection, and proposed that attention should be paid to the disease burden of the elderly after HRSV infection, timely treat common complications, so as to reduce the occurrence of adverse survival outcomes and provide scientific evidence for the prevention and control of HRSV infection in the elderly.

Human respiratory syncytial virus (HRSV) is one of the main pathogen causing severe acute lower respiratory tract infections in infants and the elderly, with high incidence rate and mortality worldwide. Vaccine is one of the important measure to prevent infection, transmission and severe disease of HRSV, but currently there is no officially approved preventive vaccine for prevention of HRSV in the world. This paper reviews and analyzes the current research and development progress of HRSV vaccine, summarizes the design routes of different types of HRSV preventive vaccines, and discusses the difficulties and challenges in vaccine research and development, in order to provide reference for the research and development of HRSV vaccine and the development of clinical trials.

Background: Dietary magnesium intake inversely correlated to risk of death in general population. However, it is relatively unknown whether the beneficial effect remains significant in individuals with diabetes. Our study purpose is to evaluate the association of dietary magnesium intake with mortality risk in diabetic population., Methods: The study population is recruited from 2003-2014 National Health and Nutrition Examination Survey, totaling 2,045 adults with diabetes being included. Participants were divided based on glycohemoglobin (HbA1c < 7% and ≥ 7%) and daily dietary magnesium intake (≤ and > 250mg/day) ascertained by 24-hour dietary recall interviews., Results: The average age of the study population was 52.9±10.1 years, with 49.1% being male. During a median follow-up of 77.0 months (interquartile range: 45.0-107.0 months), a total of 223 participants died (1.5 per 1000 person-months). Our results showed that individuals with lower dietary magnesium intake (≤250mg/day) had higher risk of all-cause (HR: 1.56, 95% CI: 1.13-2.16) and other-cause (non-cardiovascular and non-cancer) mortality (HR: 1.68, 95% CI: 1.09-2.60), while cardiovascular and cancer-related mortality were similar compared with individuals with magnesium intake > 250mg/day. We also showed that the risk of all-cause (HR: 1.86, 95% CI: 1.33-2.60) and other-cause mortality (HR: 2.03, 95% CI: 1.29-3.19) were higher in individuals with poorly controlled diabetes (HbA1c ≥7.0%) compared with HbA1c <7.0%; however, the association attenuated in the subgroup of higher magnesium intake (>250mg/day). When combining HbA1c and dietary magnesium intake, we showed that individuals with HbA1c ≥ 7% and dietary magnesium intake ≤ 250 mg/day had higher all-cause and other-cause (non-cardiovascular and non-cancer) mortality risk compared with those with HbA1c < 7% and/or dietary magnesium intake > 250 mg/day., Conclusion: Higher magnesium intake may help reduce mortality risk in individuals with diabetes and attenuate mortality risk of poor diabetic control., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Serum prealbumin level is slightly higher, whereas albumin is lower in peritoneal dialysis (PD) than hemodialysis (HD) patients. It is unknown whether albumin to prealbumin ratio (APR) is associated with mortality risk among PD patients. This study aimed to evaluate the clinical implications of APR and its prediction value on long-term outcomes of PD patients., Methods: The study population were prevalent PD patients at a tertiary hospital. Based on APR, a total of 220 PD patients were divided into 3 groups: group 1: top tertile, median APR: 121.1; IQR:109.5-131.9 (n = 73, male: 37%; age: 59±13); group 2: middle tertile, median APR: 97.1; IQR 93.5-100.0 (n = 73, male:37%; age: 54±14), and group3: bottom tertile, median APR: 81.3; IQR:76.8-85.0 (n = 74, male:38%; 54±11). Patients were followed up for a maximum of 5 years. Outcome of interest was all-cause mortality., Results: Group 1 was characterized by older age, higher prevalence of diabetes, lower nPCR, higher Davies score and hs-CRP level. APR positively correlated to hs-CRP (β = 0.149, p = 0.045), but negatively correlated to nPCR (β = -0.161, p = 0.034). Hyperprealbuminemia, accounting for 0%, 23.3%, and 82.4% in groups 1,2, and 3, was associated with a lower risk for mortality (HR:0.41, 95%CI = 0.23-0.73). The cumulative survival is significantly lower in group 1 than the other two groups. By multivariable Cox regression, APR (HR:1.02; 95%CI:1.01-1.03) was found to be an independent predictor of long-term mortality., Conclusion: PD patients with high APR are characterized by having more comorbidities and marked malnutrition-inflammation status, and are associated with long-term mortality, whereas hyperprealbuminemia and lower APR are favorable prognostic factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the recognition of acute respiratory infection (ARI) by a pretrained model based on electronic medical records (EMRs). Methods: 38 581 EMRs were obtained from Chongqing University Three Gorges Hospital in December 2021. Bidirectional encoder representation from transformers (BERT) pretrained model was used to identify ARI in EMRs. The results of medical professionals were considered as the gold standard to calculate the sensitivity, specificity, Kappa value, and area under the curve of the receiver operating characteristic (AUC). Results: There were 3 817 EMRs in the test set, with 1 200 ARIs. A total of 1 205 cases were determined as ARI by the model, with a sensitivity of 92.67% (1 112/1 200) and a specificity of 96.45% (2 524/2 617). The model identified ARI with similar accuracy in males and females (AUCs 0.95 and 0.94, respectively), and was more accurate in identifying ARI cases in those aged less than 18 than in adults 18-59 and adults 60 and older (AUCs 0.94, 0.89 and 0.94, respectively). The current model had a better identification of ARIs in outpatient patients than that in hospitalized patients, with AUCs of 0.74 and 0.95, respectively. Conclusion: The use of the BERT pretrained model based on EMRs has a good performance in the recognition of ARI cases, especially for the outpatients and juveniles. It shows a great potential to be applied to the monitoring of ARI cases in medical institutions.

Since the global pandemic of COVID-19, different countries have implemented various prevention and control measures, which has affected the epidemic characteristics of respiratory infectious diseases such as influenza. From 2020 to 2021, the level of influenza activity was relatively low, but it is necessary to be alert that with the adjustment of national prevention and control measures, influenza may have a relatively strong epidemic rebound. In order to deal with influenza epidemic, experts were organized to publish a series of influenza studies in this issue, suggesting that influenza prevention and control cannot be underestimated during the COVID-19 pandemic. It is suggested to carry out research on the interaction between COVID-19 and influenza to explore the epidemic characteristics of the disease, develop new technologies and tools to improve the efficiency of monitoring and early warning, identify obstacles to vaccination, promote the scientific implementation of intervention measures, and achieve joint prevention and control of multiple diseases.

Background: Malnutrition-inflammation-atherosclerosis (MIA) syndrome is caused by the inflammatory cytokines in end stage renal disease (ESRD) patients, and MIA complex-related factors may be associated with hypomagnesemia and mortality. However, the association between serum magnesium level and mortality for dialysis patients is still not clear. Additionally, no meta-analysis has investigated the impact of serum magnesium on peritoneal dialysis and hemodialysis, separately., Methods: We searched published studies in PubMed, Embase, Cochrane, Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews through April 2022. Studies associated with serum magnesium and all-cause mortality or cardiovascular (CV) mortality in ESRD on kidney replacement therapy (KRT) patients were included. A hazard ratio (HR) with 95% confidence intervals (CI) was used to report the outcomes., Results: Twenty-one studies involving 55,232 patients were included. Overall, there was a significant association between hypomagnesemia and all-cause mortality for dialysis patients (HR: 1.67, 95% CI [1.412-2.00], p < 0.001; certainty of evidence: moderate) using a mixed unadjusted and adjusted HR for analysis. There was also a significantly increased risk of CV mortality for individuals with hypomagnesemia compared with the non-hypomagnesemia group (HR 1.56, 95% CI [1.08-2.25], p < 0.001; certainty of evidence: moderate). In addition, a subgroup analysis demonstrated that hypomagnesemia was associated with a high risk of both all-cause mortality and CV mortality (all-cause mortality, HR:1.80, 95% CI [1.48-2.19]; CV mortality, HR:1.84, 95% CI [1.10-3.07]) in hemodialysis (HD) patients, but not in participants receiving peritoneal dialysis (PD; all-cause mortality, HR:1.26, 95% CI [0.84-1.91]; CV mortality, HR:0.66, 95% CI [0.22-2.00]). The systematic review protocol was prespecified and registered in PROSPERO [CRD42021256187]., Conclusions: Hypomagnesemia may be a significant risk factor for all-cause mortality and CV mortality in KRT patients, especially in those receiving hemodialysis. However, because of the limited certainty of evidence, more studies are required to investigate this association., Competing Interests: The authors declare that they have no competing interests., (© 2022 Huang et al.)

Objective: To explore changes of C-terminal cleavage epitope of type Ⅱ collagen 3/4 fragment in cartilage metabolism (Col2-3/4Clong mono or C2C), carboxyl-terminal telopeptide of type Ⅱ collagen (CTX-Ⅱ) and knee joint function before and after osteotomy of fibula in patients with knee osteoarthritis., Methods: From January 2019 to March 2020, 65 patients with knee osteoarthritis who underwent fibular osteotomy treatment accompanied with medial pain were selected, including 25 males and 40 females, aged from 44 to 70 years old with an average of (56.20±10.05) years old;25 patients were gradeⅠ, 19 patients with gradeⅡ, 17 patients with grade Ⅲ, and 4 patients with grade Ⅳ according to Kellgren-Lawrence grading. The content of CTX-Ⅱ and C2C in knee joint fluid, serum interleukin 1β ( IL-1β), tumor necrosis factor-α (TNF-α) before osteotomy and 6 months after osteotomy were detected. Visual analogue scale(VAS) was used to evaluate degree of pain relief, American Knee Society Score (KSS) and Hospital for Special Surgery (HSS) were applied to evaluate recovery of knee joint function., Results: Sixty-five patients were followed up from 6 to 18 months with an average of(12.4±3.6) months. VAS, KSS and HSS score at 6 months after osteotomy were better than that of before osteotomy( P <0.05). Serum IL-1β, TNF-α and content of CTX-Ⅱand C2C of knee joint fluid at 6 months after osteotomy were lower than those before osteotomy( P <0.05)., Conclusion: Fibula osteotomy could relieve pain of knee osteoarthritis, maintain balance of joint stress, reduce organism inflammatory response, improve cartilage metabolism, reduce decomposition of articular cartilage, and reduce level of CTX-Ⅱand C2C, which is benefit for regeneration of articular cartilage and promote recovery of knee joint function.

Chlorophenols are widely used in industry and are known environmental pollutants. The degradation of chlorophenols is important for environmental remediation. In this study, we evaluated the biodegradation of 2-chlorophenol using crude laccase produced by Myrothecium verrucaria. Atmospheric and room temperature plasma technology was used to increase laccase production. The culture conditions of the M-6 mutant were optimized. Our results showed that corn stover could replace glucose as a carbon source and promote laccase production. The maximum laccase activity of 30.08 U/mL was achieved after optimization, which was a 19.04-fold increase. The biodegradation rate of 2-chlorophenol using crude laccase was 97.13%, a positive correlation was determined between laccase activity and degradation rate. The toxicity of 2-CP was substantially reduced after degradation by laccase solution. Our findings show the feasibility of the use of corn stover in laccase production by M. verrucaria mutant and the subsequent biodegradation of 2-chlorophenol using crude laccase., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Medical students learning to use artificial intelligence for medical practices is likely to enhance medical services. However, studies in this area have been lacking. The present study investigated medical students' perceptions of and behavioral intentions toward learning artificial intelligence (AI) in clinical practice based on the theory of planned behavior (TPB). A sum of 274 Year-5 undergraduates and master's and doctoral postgraduates participated in the online survey. Six constructs were measured, including (1) personal relevance (PR) of medical AI, (2) subjective norm (SN) related to learning medical AI, (3) perceived self-efficacy (PSE) of learning medical AI, (4) basic knowledge (BKn) of medical AI, (5) behavioral intention (BI) toward learning medical AI and (6) actual learning (AL) of medical AI. Confirmatory factor analysis and structural equation modelling were employed to analyze the data. The results showed that the proposed model had a good model fit and the theoretical hypotheses in relation to the TPB were mostly confirmed. Specifically, (a) BI had a significantly strong and positive impact on AL; (b) BI was significantly predicted by PR, SN and PSE, whilst BKn did not have a direct effect on BI; (c) PR was significantly and positively predicted by SN and PSE, but BKn failed to predict PR; (d) both SN and BKn had significant and positive impact on PSE, and BKn had a significantly positive effect on SN. Discussion was conducted regarding the proposed model, and new insights were provided for researchers and practitioners in medical education.

Although the automatic speech recognition (ASR) technology is increasingly used for commercial purposes, its impact on language learning has not been extensively studied. Underpinned by the sociocultural theory, the present work examined the effects of leveraging ASR technology to support English vocabulary learning in a tertiary flipped setting. A control group and an experimental group of college students participated in a 14-week study. Both groups had their English classes in a flipped fashion, but the experimental group was assigned with ASR-assisted oral tasks for pre-class self-learning. The pre- and post-intervention in-class task performance of both groups was audio-recorded and transcribed for data analysis. The triadic complexity-accuracy-fluency (CAF) framework was adopted to evaluate the participants' vocabulary learning. The between- and within-subjects effects were examined mainly through procedures of MANCOVA and mixed-design repeated measures ANCOVA. Results showed that on all the metrics of lexical complexity and speed fluency, the experimental group outperformed the control group, and had significant growth over time. On the other hand, the control group only improved significantly overtime on the G-index. On lexical accuracy, there was no significant difference between the two groups, and the within-subjects effect was not significant for either group. The findings lent some support to Skehan's Trade-off Hypothesis and discussions were conducted regarding the triarchic CAF framework., 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 Jiang, Jong, Wu, Shen, Chai, Lau and Huang.)

Background: The Chinese government has taken action to prevent cervical cancer by implementing the National Cervical Cancer Screening Programme in Rural Areas (NACCSPRA), which was launched in 2009. Numerous studies have demonstrated that long-term cervical cancer screening alters human papillomavirus (HPV) infection rates and cervical disease detection. Nearly 80 million women have been screened over 10 years, representing <30% of the target population; however, in some rural areas, such as Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County, and Jingning County of Zhejiang Province, programs for prevention and treatment of cervical cancer have been implemented. Numerous studies have demonstrated that long-term cervical cancer screening alters rates of human papillomavirus (HPV) infection and cervical disease detection. In this study, we aimed to determine the infection rates of high-risk HPV (hrHPV) and the detection rate of cervical lesions; and changes in factors associated with cervical cancer, to provide scientific data to inform efforts to eliminate cervical cancer in rural areas., Methods: This was a cross-sectional, population-based, and multi-center survey. Populations from three rural areas of China (Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County and Jingning County of Zhejiang Province) were selected and 9,332 women aged 20-64 years old were invited to participate in cervical cancer screening by both cytology and HPV testing. The outcomes assessed were: infection rates with hrHPV, HPV16, 18, 16/18, and other 12 hrHPV types (HPV 31,33,35,39,45,51,52,56,58,59,66 and 68); detection rates of cytological and histological lesions; and factors associated with HPV infection., Results: A total of 9,217 women aged 45.62 ± 8.02 years were included in this study. Infection rates with hrHPV, HPV 16, 18, 16/18, and other 12 hrHPV types were 16.3%, 3.0%, 1.5%, 4.3%, and 13.6%, respectively. There were significant differences among the age-specific HPV infection rates ( P < 0.05). Infection rates with hrHPV, 16, 18, 16/18, and the other 12 hrHPV types showed a single peak infection mode, with a peak age of 56-65 years old. Age, marital status, number of live births, education level, reproductive disease history, and a history of alcohol consumption were risk factors for hrHPV infection. The detection rate of cytological abnormalities was 12.98% in the study and was higher in women older than 56 years old. The detection rates of cervical intraepithelial neoplasia CIN2+ and CIN3+ in the population were 1.45% and 0.77%, respectively. The highest incidence rates of CIN2+ and CIN3+ were 32.12% and 17.51%, respectively, in the 41-45 years old group., Conclusion: Infection rates with hrHPV, HPV16, and cervical lesions among our screening population were lower than the mean level in rural areas of China. Infection rates with hrHPV, HPV16, 18, and 16/18 showed a single-peak infection pattern, with the peak age of infection being 56-65 years old. Risk factors for hrHPV infection were age, history of alcohol consumption, marital status, reproductive diseases, education level, and the number of live births. Based on these data, we recommend that cervical cancer screening be offered to women older than 30 years in rural areas, particularly those aged 41-45 years., Competing Interests: Y-LQ and WC received grants from the Ministry of Science and Technology of the People's Republic of China during the conduct of the study, and personal fees and non-financial support from Roche. The remaining 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 Yu, Jiang, Dang, Feng, Bangura, Chen and Qiao.)

Background: Whether there is difference in kidney disease risk between chronic hepatitis C virus (HCV) infection and resolved HCV infection remains inconclusive. Additionally, the impact of different HCV genotypes on kidney disease risk is relatively unknown. Accordingly, we conducted a population-based cross-sectional study to investigate the association of HCV infection status and genotype on kidney disease risk., Methods: The study population were adult participants of 1999-2018 National Health and Nutrition Examination Survey in the United States. Chronic and resolved infection were defined as HCV seropositivity with and without detectable HCV RNA, respectively. HCV genotypes were classified into genotype 1, genotype 2, and other genotypes. Prevalent estimated glomerular filtration rate < 60 ml/min/1.73 m2 or urinary albumin creatinine ratio ≥ 30 mg/g was defined as kidney disease., Results: The average age of study population (n = 44,998) was 46.7±17.0 years with 49.8% being males. Compared with individuals without HCV infection (n = 44,157), those with resolved (n = 255) or chronic HCV infection (n = 586) had higher prevalence of kidney disease: 14.8%, 23.5%, and 20.1%, respectively (p<0.001). After adjusting for potential confounders, we found that both resolved (adjusted OR: 1.40, 95% CI: 1.02-1.93) and chronic HCV infection (adjusted OR: 1.26, 95% CI: 1.01-1.57) correlated to increased kidney disease risk compared with no HCV infection. Additionally, individuals with HCV genotype 1 (adjusted OR: 1.41, 95% CI: 1.09-1.82) but not genotype 2 or other genotypes had greater kidney disease risk compared with no HCV infection. Furthermore, we observed that genotype 1 had 2-fold higher kidney disease risk (adjusted OR: 2.20, 95% CI: 1.07-4.53) compared with non-genotype 1 HCV infection., Conclusion: Both resolved and chronic HCV infection, particularly genotype 1, were associated with higher kidney disease risk., Competing Interests: The authors declared no conflict of interest

STEM education has been regarded as an important educational initiative for cultivating students' twenty-first century skills. The present work aimed to explore ways to promote students' twenty-first century skills through an integrated STEM-based curriculum. Specifically, we designed and implemented an 8-week crossover program of STEM and community service education. In this program, students learned about STEM domain knowledge and community service issues. They then applied the knowledge to solve authentic problems faced by Hong Kong community-housing residents from disadvantaged groups. A mixed-method approach was employed to evaluate the effectiveness of the program in enhancing students' twenty-first century skills and attitudes, including (i) creative thinking, (ii) collaboration, (iii) perseverance, as well as their (iv) STEM career interests. The research participants were 121 secondary students from a government-subsidized school. The quantitative results showed that the participants' creative thinking, collaboration, and perseverance improved alongside their STEM career interests. These findings were further supported by the data gathered through focus-group interviews. This study provides theoretical and practical insights into the integration of STEM education with community service learning., 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 Huang, Jong, King, Chai and Jiang.)