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Research on the potential association between life-ever gallstones and depressive symptoms is limited. This study aims to evaluate whether the presence of gallstone disease is associated with depressive symptoms. In this cross-sectional study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 cycles. The presence of depressive symptoms and gallstone disease was assessed using questionnaire responses. Adjusted odds ratios (OR) were calculated using a multivariate logistic regression model, with adjustments made for age, sex, race, body mass index, history of cardiovascular disease, hypertension, arthritis, and pulmonary disease across different models. Subgroup and sensitivity analyses were conducted to ensure the stability of the results. This study included 6201 adults aged 20 years and above, with 539(8.7%) experiencing depressive symptoms. After adjusting for age, sex, race, body mass index, CVD history, hypertension, arthritis, pulmonary disease, depressive symptoms were possibly associated with life-ever gallstones (OR 1.37, 95% CI 0.91-2.08).When depressive symptoms were categorized as mild, moderate, moderately severe, and severe,life-ever gallstones was possibly associated with mild depressive symptoms (OR 1.12, 95% CI 0.81-1.56), moderate depressive symptoms (OR 1.37, 95% CI 0.89-2.12), moderately severe depressive symptoms (OR 1.93, 95% CI 0.93-3.99), and severe depressive symptoms (OR 0.67, 95% CI 0.16-2.88).As a continuous variable, life-ever gallstones was associated with the PHQ-9 score (OR 0.42, 95% CI 0.02-0.83). The results remained stable after multiple imputation for all missing data. This cross-sectional study demonstrates no significant association between life-ever gallstones and depressive symptoms in US adults., (© 2024. The Author(s).)

Broad-spectrum disease resistance (BSR) is crucial for controlling plant diseases and relies on immune signals that are subject to transcriptional and post-translational regulation. How plants integrate and coordinate these signals remains unclear. We show here that the rice really interesting new gene (RING)-type E3 ubiquitin ligase OsRING113 targets APIP5, a negative regulator of plant immunity and programmed cell death (PCD), for 26S proteasomal degradation. The osring113 mutants in Nipponbare exhibited decreased BSR, while the overexpressing OsRING113 plants showed enhanced BSR against Magnaporthe oryzae (M. oryzae) and Xanthomonas oryzae pv. oryzae (Xoo). Furthermore, APIP5 directly suppressed the transcription of the Bowman-Birk trypsin inhibitor genes OsBBTI5 and AvrPiz-t-interacting protein 4 (APIP4). Overexpression of these two genes, which are partially required for APIP5-mediated PCD and disease resistance, conferred BSR. OsBBTI5 and APIP4 associated with and stabilized the pathogenesis-related protein OsPR1aL, which promotes M. oryzae resistance. Our results identify an immune module with integrated and coordinated hierarchical regulations that confer BSR in plants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In underwater computational ghost imaging, the presence of scattering and absorption introduces significant degradation, leading to blurring and distortion of illuminating patterns. This work proposes an anti-degradation underwater computational ghost imaging (AUGI) method based on the physical degradation model of underwater forward degradation caused by scattering and absorption. Through AUGI, we can enhance the quality of a reconstructed image by about 10 % compared to differential ghost imaging (DGI) as measured by peak signal-to-noise ratio (PSNR) and structural similarity (SSIM), as a result of simulations. We experimentally demonstrate the superior effectiveness of this method in the artificial submarine environment. Additionally, benefitting from its simplicity, this method is expected to be applied across a wide range of underwater ghost imaging applications.

Selenium is an essential trace element closely related to human health; however, the relationship between blood selenium levels, diabetes, and heart failure remains inconclusive. Therefore, this study aimed to explore the relationship between blood selenium levels and the prevalence of diabetes as well as heart failure in American general adults aged 20 years or older. This study utilized data from four survey cycles from NHANES 2011-2020 pre. Blood selenium levels were considered as both a continuous variable and quartiles, and logistic regression was employed to investigate the associations between blood selenium levels with diabetes and heart failure. Nonlinear relationships were examined by restricted cubic spline regression. The analysis included a total of 16311 participants aged 20 years or older. After adjustment for all potential confounder, we found when the blood selenium levels increased by 10 ug/L, the average risk of diabetes increased by 4.2% (95% CI: 1.5%, 7.0%), and the average risk of heart failure decreased by 5.0% (95% CI: 0.1%, 9.8%). In addition, compared with the lowest reference group, blood selenium levels were significantly positively associated with risk of diabetes in participants in the fourth quartile (OR=1.458, 95% CI: 1.173, 1.812), while significantly negatively associated with the risk of heart failure in participants in the second, third and fourth quartiles (Q2, OR=0.677, 95% CI: 0.471, 0.974) (Q3, OR=0.609, 95% CI: 0.426, 0.870) (Q4, OR=0.653, 95% CI: 0.443, 0.961). There was a nonlinear and reverse L-shaped association between blood selenium and diabetes, while a negative dose-response association between blood selenium and heart failure. Furthermore, the association between blood selenium levels and heart failure was more pronounced in participants with poor glycemic control, rather than diabetic patients. High blood selenium levels may be positively related to diabetes, while low blood selenium levels may be associated to heart failure. Appropriate blood selenium levels may help prevent diabetes and heart failure., (© 2023. The Author(s).)

Introduction: Smoking significantly burdens human health, contributing to an increasing incidence of mortality and morbidity. This study aims to explore the prevalence of smoking, cessation, and the association between various risk factors and smoking intensity measured in pack-years among Chinese adults., Methods: During 2020-2021, the China Stroke High-risk Population Screening and Intervention Program (CSHPSIP) invited participants aged ≥40 years from 31 provinces in mainland China. This cross-sectional study presents the standardized prevalence of smoking and cessation across various demographics, including age, sex, residence, income, education level, BMI, and geographical region of residence. Multivariable logistic regression was used to examine the associations between smoking pack-years and related factors., Results: Among 524741 participants (mean age: 61.9 ± 10.9 years; 41.1% male; 58.9% female), standardized smoking prevalence was 19.3% (95% CI: 19.2-19.4), with men (37.2%; 95% CI: 37.0-37.4) displaying significantly higher rates than women (1.3%; 95% CI: 1.2-1.3). Smoking cessation rate stood at 11.2% (95% CI: 11.0-11.4), with 11.3% (95% CI: 11.1-11.5) for men and 8.4% (95% CI: 7.5-9.2) for women. Urban residents and those with advanced education had lower smoking rates and higher cessation rates. Additionally, the dose-response relationship indicated a more pronounced association between higher smoking pack-years and elevated health risks, including hypertension (AOR=1.30; 95% CI: 1.24-1.36), diabetes (AOR=1.26; 95% CI: 1.20-1.33), hyperlipidemia (AOR=1.22; 95% CI: 1.16-1.28), heart disease (AOR=1.40; 95% CI: 1.26-1.54), and stroke (AOR=1.23; 95% CI: 1.10-1.36)., Conclusions: This comprehensive study emphasizes the profound impact of smoking on health in Chinese adults, indicating the critical need for tailored cessation programs, particularly for middle-aged individuals, men, rural residents, and those with lower level of education., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Zeng Q. et al.)

The ubiquitin-proteasome system (UPS) plays crucial roles in cellular processes including plant growth, development, and stress responses. In this study, we report that a pair of E3 ubiquitin ligases, AvrPiz-t-interaction protein 6 (APIP6) and IPA1-interaction protein 1 (IPI1), intricately target early flowering3 (ELF3) paralogous proteins to control rice immunity and flowering. APIP6 forms homo-oligomers or hetero-oligomers with IPI1. Both proteins interact with OsELF3-2, promoting its degradation to positively control resistance against the rice blast fungus (Magnaporthe oryzae). Intriguingly, overexpression of IPI1 in Nipponbare caused significantly late-flowering phenotypes similar to the oself3-1 mutant. Except for late flowering, oself3-1 enhances resistance against M. oryzae. IPI1 also interacts with and promotes the degradation of OsELF3-1, a paralog of OsELF3-2. Notably, IPI1 and APIP6 synergistically modulate OsELF3s degradation, finely tuning blast disease resistance by targeting OsELF3-2, while IPI1 controls both disease resistance and flowering by targeting OsELF3-1. This study unravels multiple functions for a pair of E3 ligases in rice., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The incidence of skin trauma is high and the repair process is complex, often leading to poor healing and other issues, which can result in significant economic and social burdens. Traditional Chinese medicine (TCM) is a valuable resource with proven effectiveness and safety in wound repair, widely utilized in clinical practice. A systematic analysis of wound healing with a focus on TCM research progress holds both academic and clinical importance., Aim of the Review: This article reviews the research progress of TCM in promoting wound healing, and provides basic data for the development of innovative drugs that promote wound healing., Materials and Methods: This article provides a review of the literature from the past decade and conducts a thorough analysis of various databases that contain reports on the use of TCM for wound repair. The data for this systematic research was gathered from electronic databases including CNKI, SciFinder, and PubMed. The study explores and summarizes the research findings and patterns by creating relevant charts., Results: This study reviewed the mechanism of wound healing, experimental TCM methods to promote wound healing, the theory and mode of action of TCM to promote wound healing, the active ingredients of TCM that promote wound healing, the efficacy of TCM formulae to promote wound healing, and the potential toxicity of TCM and its antidotes. This study enriched the theory of TCM in promoting wound healing., Conclusion: Skin wound healing is a complex process that can be influenced by various internal and external factors. This article offers a theoretical foundation for exploring and utilizing TCM resources that enhance wound repair. By analyzing a range of TCM that promote wound healing, the article highlights the clinical importance and future potential of these medicines in promoting wound healing., 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.)

Background: The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising therapeutic strategy. Forsythoside B (FB) is a phenylethanoid glycoside isolated from Forsythiae fructus, which has been reported to have anti-inflammatory effects. However, the mechanism of the neuroprotective effect of FB on CIRI remains unclear., Methods: Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). FB was administered intraperitoneally for 3 days prior to MCAO/R. Cerebral infarct volume and neurological deficit score were used as indices to evaluate MCAO/R injury. The serum levels of inflammatory factors and antioxidant enzymes were measured. The activation of silent information regulator 2 homolog 1 (Sirt1) and the inhibition of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) pathway were assessed through western blot and immunohistochemistry analysis. Furthermore, the rats were treated with Sirt1 shRNA 3 days before MCAO/R by stereotactical injection into the ipsilateral hemispheric region to assess the impact of Sirt1 knockdown on the protection of FB during MCAO/R., Results: FB reduced cerebral infarct volume and neurological deficit score in MCAO/R rats. FB reduced pathological changes and cell apoptosis in the hippocampal CA1 region and cortex on the ischemic side of rats. FB inhibited the serum levels of inflammatory factors and increased the activities of antioxidant enzymes. Further study showed that FB inhibited the activation of the NLRP3 pathway and induced Sirt1 activation., Conclusion: FB demonstrated neuroprotective and anti-inflammatory effects by inhibiting the NLRP3 pathway through Sirt1 activation in CIRI., Competing Interests: The authors declare that there are no conficts of interest, (Copyright: © 2024 Li 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 observe the clinical effect of prophylaxis on migraine without aura differentiated as liver yang hyperactivity undergoing acupuncture at the points selected using the "seven lines of the neck" method., Methods: Fifty-eight patients with migraine without aura of liver yang hyperactivity at remission stage were randomly divided into an observation group (29 cases, 3 cases dropped out) and a control group (29 cases, 4 cases dropped out). In the observation group, acupuncture was delivered at Dazhui (GV 14), Fengfu (GV 16), bilateral Fengchi (GB 20), Gongxue (Extra), etc., selected using the "seven lines of the neck" method. In the control group, conventional acupuncture was applied to ashi point, Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5) and others on the affected side. The treatment was given once every other day or every two days, 3 interventions weekly, for consecutive 8 weeks. Before treatment, after 4 and 8 weeks of treatment, and after 4 weeks of treatment completion (follow-up visit), the days of migraine episodes, the frequency of migraine episodes, the score of visual analogue scale (VAS) for pain intensity, and the score of migraine specific quality of life questionnaire (MSQ) were observed in the patients of the two groups. Before treatment and after 8 weeks of treatment, the score of TCM syndrome was observed. After 4 and 8 weeks of treatment and after 4 weeks of treatment completion (follow-up visit), the response rates of 50% reduction in the days and the frequency of migraine episodes were calculated in the two groups., Results: After 4 and 8 weeks of treatment and during follow-up visit, the days and the frequency of migraine episodes were decreased ( P <0.01) and VAS scores were declined ( P <0.01) when compared with those before treatment in the two groups. The days and the frequency of migraine episodes in the observation group were lower during the follow-up visit ( P <0.05) and VAS scores were lower after 8 weeks of treatment and during the follow-up visit ( P <0.05) when compared with those in the control group. After 4 and 8 weeks of treatment, and during follow-up visit, the scores of "role function-preventive" and "emotional function" of MSQ were increased in comparison with those before treatment in the observation group ( P <0.05). After 8 weeks of treatment and during the follow-up visit, the scores of "role function-restrictive" of MSQ were increased in comparison with those before treatment in the observation group ( P <0.05), and the scores of "role function-restrictive" "role function-preventive" and "emotional function" were higher when compared with those before treatment in the control group ( P <0.05). After 8 weeks of treatment, the scores of TCM syndrome were decreased in comparison with those before treatment in the two groups ( P <0.01). In the observation group, the response rate of 50% reduction in the days of migraine episodes after 8 weeks of treatment and that of the frequency of migraine episodes during the follow-up visit were higher than those of the control group ( P <0.05)., Conclusion: Acupuncture at the points selected using the "seven lines of the neck" method can reduce the days and frequency of migraine episodes and pain intensity, ameliorate the syndrome of TCM and improve the quality of life of the patients with migraine without aura of liver yang hyperactivity.

Background: Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception., Methods: Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals., Results: Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants]., Conclusion: Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear., 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 Tian, Zhang, Liao, Yang, Hong, Shi, Yan, Pan, Zhang, Meng, Robinson, Bai and Gang.)

The rapid and ultra-sensitive detection of trace elements in liquid is a primary concern for researchers. In this study, a partial Leidenfrost effect superhydrophobic (PLSHB) array surface was used for rapid in situ evaporation enrichment of sample droplets. Within 4 min, a 50 μL droplet sample was completely evaporated, resulting in all solutes in it being concentrated within a circular range measuring approximately 350 μm in diameter, without the formation of a coffee ring structure. The limits of detection for six metals (Pb, Ba, Be, Mn, Cr, Cu) in water were determined to be as follows: 0.82 μgL -1 , 0.27 μgL -1 , 0.033 μgL -1 , 0.136 μgL -1 , 0.241 μgL -1 , and 0.083 μgL -1 . Furthermore, laser-induced breakdown spectroscopy (LIBS) was employed to detect the enriched solutes from ten liquid samples with identical concentrations on the PLSHB array surface; these measurements exhibited a relative standard deviation (RSD) of only 3.7%. Spike experiments involving the addition of the aforementioned six metals into drinking water demonstrated recovery rates ranging from 85.7% to 117.7%. Therefore, the application potential of PLSHB array surface enhanced LIBS for rapid, stable, and ultra-sensitive detection and analysis of trace metal elements across various fields such as industry, environmental science, and biomedicine might be highly promising., 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.)

Background: Urinary incontinence (UI) might be linked to suicidal ideation, but we do not yet have all the relevant details. This study aimed to dig deeper into the connection between UI and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES)., Methods: We examined 31,891 participants aged ≥ 20 years from NHANES 2005-2018 who provided complete information. We used standardized surveys to check for UI and signs of suicidal ideation. To better understand this relationship, we used statistical tools such as multivariable logistic regression, subgroup analysis, and sensitivity analyses., Results: Among the 31,891 participants, 28.9% reported UI and 10.7% reported suicidal ideation. Those with UI exhibited a significantly greater incidence of suicidal ideation (15.5%) than did those without UI (8.8%, P < 0.001). After adjusting for various factors, including age, sex, marital status, socioeconomic status, educational level, lifestyle factors, and chronic comorbidities, UI remained significantly associated with suicidal ideation (OR:1.54, 95% CI = 1.39-1.7, P < 0.001). Among all types of UI, MUI participants were more likely to experience suicidal ideation. Compared with no UI, higher odds of suicidal ideation suffered from MUI (OR:2.11, 95%CI:1.83-2.44, P < 0.001), SUI (OR:1.4, 95%CI:1.19-1.65, P < 0.001), UUI(OR:1.37,95%CI:1.16-1.62, P < 0.001) after full adjustment. With the exception of individuals living with a partner, the remaining subgroups exhibited a positive correlation between urinary incontinence and suicidal ideation, considering that factors such as age, sex, and prevalent comorbidities such as hypertension, depression, and diabetes did not reveal any statistically significant interactions (all P > 0.05). Sensitivity analyses, incorporating imputed missing covariates, did not substantially alter the results (OR: 1.53, 95% CI: 1.4-1.68, P < 0.001)., Conclusion: Urinary incontinence may correlate with increased suicidal ideation risk, priority screening for suicidal ideation and timely intervention are essential for individuals with urinary incontinence, but prospective studies are needed to verify the results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pan 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.)

Enterotoxigenic Escherichia coli (ETEC) strains that produce various adhesins and one or two enterotoxins are the leading causes of children's diarrhea and travelers' diarrhea. MecVax, a multivalent ETEC vaccine candidate, consists of two proteins, an adhesin multiepitope fusion antigen (MEFA) that stimulates antibodies to the seven most important ETEC adhesins (CFA/I and CS1-CS6) and a toxoid fusion antigen which stimulates antibodies against ETEC enterotoxins (heat-labile toxin and heat-stable toxin). CFA MEFA-II, another polyvalent MEFA protein, has been demonstrated to stimulate antibodies to another five important ETEC adhesins (CS7, CS12, CS14, CS17, and CS21). We hypothesize that MecVax coverage and efficacy can be expanded if MecVax could stimulate antibodies to all 12 adhesins. In this study, we supplemented MecVax with CFA MEFA-II, examined broad immunity to the 12 targeted ETEC adhesins and 2 ETEC toxins (STa, LT) in mice, and assessed mouse antibody functions for inhibiting the adherence of the 12 adhesins and neutralizing the enterotoxicity of 2 toxins, thus assessing the potential application of a broadly protective pan-ETEC vaccine. Mice intramuscularly immunized with MecVax and CFA MEFA-II developed robust antibody responses to the 12 ETEC adhesins and 2 toxins; furthermore, mouse serum antibodies showed functional activities against the adherence from each of the targeted adhesins and the enterotoxicity of either toxin. Data also indicated that CFA MEFA-II was antigenically compatible with MecVax. These results demonstrated that the inclusion of CFA MEFA-II further expands MecVax broad immunogenicity and protection coverage, suggesting the feasibility of developing a vaccine against all important diarrheal ETEC strains.IMPORTANCEThere are no vaccines licensed for Enterotoxigenic Escherichia coli (ETEC), a leading cause of children's diarrhea and the most common cause of travelers' diarrhea. Since ETEC strains produce over 25 adhesins and 2 distinctive enterotoxins, heterogeneity is a key obstacle to vaccine development. MecVax, a multivalent ETEC vaccine candidate, induces protective antibodies against the seven most important adhesins (CFA/I and CS1-CS6) associated with two-thirds of ETEC clinical cases. However, ETEC prevalence shifts chronically and geographically, and other adhesins are also associated with clinical cases. MecVax would become a pan-ETEC vaccine if it also protects against the remaining important adhesins. This study demonstrated that MecVax supplemented with adhesin protein CFA MEFA-II induces functional antibodies against 12 important ETEC adhesins (CFA/I, CS1-CS7, CS12, CS14, CS17, and CS21), enabling the development of a more broadly protective ETEC vaccine and further validating the application of the MEFA vaccinology platform for multivalent vaccine development., Competing Interests: The senior authors are the inventors of MecVax and are continuously working on the research and development of this ETEC vaccine candidate.

Objective: To investigate the therapeutic effect of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive positive pressure ventilation (NPPV) on patients with pulmonary edema caused by seawater drowning., Methods: A retrospective analysis method was used. Based on the Utstein database of emergency drowning in the First Hospital of Qinhuangdao, the clinical data of patients with seawater drowning pulmonary edema admitted to the emergency medicine department of the First Hospital of Qinhuangdao from January 1, 2019 to December 31, 2022 were collected. The patients were divided into NPPV group and HFNC group according to different ventilation methods. The general data, endotracheal intubation rate in 7 days, arterial blood gas analysis indexes [arterial partial pressure of oxygen (PaO 2 ), arterial partial pressure of carbon dioxide (PaCO 2 ), arterial oxygen saturation (SaO 2 )] and hemodynamic indexes (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, blood lactic acid) before and after treatment, length of stay in intensive care unit (ICU), oxygen therapy comfort of the two groups were compared., Results: A total of 54 patients were enrolled, including 21 patients in the NPPV group and 33 patients in the HFNC group. There were no significant differences in gender, age, state of consciousness and other general information between the two groups. Compared with NPPV group, the rate of endotracheal intubation in HFNC group within 7 days was significantly lower [24.2% (8/33) vs. 33.3% (7/21), P < 0.05]. Before treatment, there were no significant differences in arterial blood gas analysis and hemodynamics between the two groups. After treatment, the above indexes in both groups were significantly improved compared with those before treatment, and PaO 2 , SaO 2 , systolic blood pressure, diastolic blood pressure and mean arterial pressure in HFNC group were significantly higher than those in NPPV group [PaO 2 (mmHg, 1 mmHg≈0.133kPa): 93.56±6.37 vs. 82.14±6.25, SaO 2 : 1.02±0.09 vs. 0.95±0.11, systolic blood pressure (mmHg): 117.37±8.43 vs. 110.42±8.38, diastolic blood pressure (mmHg): 79.43±7.61 vs. 72.21±4.32, mean arterial pressure (mmHg): 92.34±6.32 vs. 85.12±5.38], PaCO 2 , heart rate and blood lactic acid were significantly lower than those in NPPV group [PaCO 2 (mmHg) : 34.26±5.63 vs. 37.24±6.22, heart rate (times/min): 73.38±7.56 vs. 86.25±5.41, blood lactic acid (mmol/L): 1.38±0.36 vs. 2.25±1.14], and the differences were statistically significant (all P < 0.05). In addition, the length of ICU stay in HFNC group was significantly shorter than that in NPPV group (days: 13.30±2.38 vs. 16.27±4.26), and the comfort rate of oxygen therapy was significantly higher than that in NPPV group [66.7% (22/33) vs. 42.8% (9/21)], with statistical significance (all P < 0.05)., Conclusions: HFNC can improve the oxygenation of patients with pulmonary edema caused by seawater drowning, improve hemodynamics, reduce the rate of tracheal intubation, shorten the length of ICU stay, and improve the comfort of oxygen therapy, which has certain clinical application value.

Ethnopharmacological Relevance: Acute lung injury (ALI) is a life-threatening condition with high morbidity and mortality, underscoring the urgent need for novel treatments. Monochasma savatieri Franch. (LRC) is commonly used clinically to treat wind-heat cold, bronchitis, acute pneumonia and acute gastroenteritis. However, its role in the treatment of ALI and its mechanism of action are still unclear., Aim of the Study: This study aimed to demonstrate the pharmacological effects and underlying mechanisms of LRC extract, and provide important therapeutic strategies and theoretical basis for ALI., Materials and Methods: In this study, a research paradigm of integrated pharmacology combining histopathological analysis, network pharmacology, metabolomics, and biochemical assays was used to elucidate the mechanisms underlaying the effects of LRC extract on LPS-induced ALI in BALB/c mice., Results: The research findings demonstrated that LRC extract significantly alleviated pathological damage in lung tissues and inhibited apoptosis in alveolar epithelial cells, and the main active components were luteolin, isoacteoside, and aucubin. Lung tissue metabolomic and immunohistochemical methods confirmed that LRC extract could restore metabolic disorders in ALI mice by correcting energy metabolism imbalance, activating cholinergic anti-inflammatory pathway (CAP), and inhibiting TLR4/NF-κB signaling pathway., Conclusions: This study showed that LRC extract inhibited the occurrence and development of ALI inflammation by promoting the synthesis of antioxidant metabolites, balancing energy metabolism, activating CAP and suppressing the α7nAChR-TLR4/NF-κB p65 signaling pathway. In addition, our study provided an innovative research model for exploring the effective ingredients and mechanisms of traditional Chinese medicine. To the best of our knowledge, this is the first report describing the protective effects of LRC extract in LPS-induced ALI mice., 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: Exposome recognizes that humans are constantly exposed to multiple environmental factors, and elucidating the health effects of complex exposure mixtures places greater demands on analytical methods., Objects: We aimed to explore the association between mixed exposure to metals and hyperuricemia (HUA), and highlight the potential of explainable machine learning (EML) and causal mediation analysis (CMA) for application in the analysis of exposome data., Methods: Pre-pandemic data from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 and a total of 13780 individuals were included. We first used traditional statistical models (multiple logistic regression (MLR) and restricted cubic spline regression (RCS)) and EML to explore associations between mixed metals exposures and HUA, followed by the CMA using the 4-way decomposition method to analyze the interaction and mediation effects among BMI or estimated glomerular filtration rate (eGFR), metals and HUA., Results: The prevalence of HUA was 18.91% (2606/13780). The MLR showed that mercury (Q4 vs Q1: OR = 1.08, 95% CI:1.02-1.14) and lead (Q4 vs Q1: OR = 1.23, 95% CI:1.13-1.34) were generally positively associated with HUA. Higher concentrations of lead, mercury, selenium and manganese were associated with the increased odds of HUA, and BMI and eGFR were the top two variables attributable to the risk of developing HUA in the EML. Subgroup analyses from the MLR and EML consistently demonstrated the positive relationship between exposure to lead, mercury and selenium in participants with BMI <25 kg/m 2 and BMI ≥30 kg/m 2 . BMI mediated 32.12% of the association between lead exposure and HUA, and the interaction between BMI and lead accounted for 3.88% of the association in the CMA., Conclusions: Heavy metals can increase the HUA risk and BMI or eGFR can mediate and interact with metals to cause HUA. Future studies based on exposome can attempt to utilize the EML and CMA., 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.)

Pulmonary arterial hypertension (PAH) is a progressive disease in which pulmonary arterial (PA) endothelial cell (EC) dysfunction is associated with unrepaired DNA damage. BMPR2 is the most common genetic cause of PAH. We report that human PAEC with reduced BMPR2 have persistent DNA damage in room air after hypoxia (reoxygenation), as do mice with EC-specific deletion of Bmpr2 (EC-Bmpr2 -/- ) and persistent pulmonary hypertension. Similar findings are observed in PAEC with loss of the DNA damage sensor ATM, and in mice with Atm deleted in EC (EC-Atm -/- ). Gene expression analysis of EC-Atm -/- and EC-Bmpr2 -/- lung EC reveals reduced Foxf1, a transcription factor with selectivity for lung EC. Reducing FOXF1 in control PAEC induces DNA damage and impaired angiogenesis whereas transfection of FOXF1 in PAH PAEC repairs DNA damage and restores angiogenesis. Lung EC targeted delivery of Foxf1 to reoxygenated EC-Bmpr2 -/- mice repairs DNA damage, induces angiogenesis and reverses pulmonary hypertension., (© 2023. The Author(s).)

There are no vaccines licensed against enterotoxigenic Escherichia coli (ETEC), a leading cause of children's diarrhea and the most common cause of travelers' diarrhea. Multivalent vaccine candidate MecVax unprecedentedly targets two ETEC enterotoxins (heat-stable toxin, STa; heat-labile toxin, LT) and the seven most prevalent ETEC adhesins (colonization factor antigen, CFA/I, coli surface antigens, CS1-CS6) and has been demonstrated preclinically to protect against STa- and LT-mediated ETEC clinical diarrhea and prevent intestinal colonization from ETEC strain H10407 (CFA/I, STa, LT). However, it is unattested whether MecVax broadly protects against intestinal colonization from ETEC strains producing the other six adhesins (CS1-CS6) also targeted by this product. In this study, we immunized rabbits with MecVax and challenged them with heterogeneous ETEC strains that express CS1-CS6 adhesins to evaluate MecVax's efficacy against bacterial intestinal colonization, thus providing broad vaccine protection against ETEC infection. Data revealed that rabbits intramuscularly immunized with MecVax developed robust responses to both ETEC enterotoxins (STa, LT) and seven adhesins (CFA/I, CS1-CS6), and when challenged with ETEC isolates expressing CS1/CS3, CS2/CS3, CS4/CS6, CS5/CS6, or CS6 adhesin, the immunized rabbits prevented over two logs (>99%) of bacteria from colonization in small intestines. Additionally, compared to a CFA-toxoid fusion protein, which is another potential ETEC vaccine antigen to target two ETEC enterotoxins and the seven adhesins, MecVax exhibited better protection against ETEC intestinal colonization. These results, in conjunction with the protection data from early studies, evidenced that MecVax is broadly protective, validating MecVax's candidacy as an effective vaccine against ETEC-associated diarrhea and accelerating ETEC vaccine development., Competing Interests: The senior author has the patent for the development of a protein-based vaccine for ETEC.

Potent usage of the multi-scale light field information for salient object detection (SOD) is the essential requirement of three-dimensional (3D) SOD. On this basis, a light field 3D-SOD scheme is proposed that employs the pixel mapping algorithm to achieve a more distinct representation of spatial and angular information in the four-dimensional (4D) light field, collaboratively mining the global saliency cues via the co-salient object detection (CoSOD) network. Compared with the previous method, our scheme filters out most of the noise by thoroughly leveraging the global dependence of the 4D light field, offering significant enhancements in saliency extraction performance and efficiency. Additionally, the 3D reconstruction results demonstrate the integral retention of the spatial and angular information of the original light field.

Objective: To establish a machine learning model to predict the risk of early neurological deterioration (END) based on the clinical and laboratory data of patients with acute ischemic stroke (AIS) before intravenous thrombolysis., Methods: The clinical data of AIS patients who received intravenous thrombolytic with recombinant tissue plasminogen activator (rt-PA) at the Stroke Center of the First Hospital of Qinhuangdao City from January 2019 to July 2022 were retrospectively analyzed. Patients were divided into END group and non-END group according to whether END appeared after intravenous thrombolytic. Clinical data of patients at admission were collected, including demographic characteristics, clinical evaluation, comorbidification, drug use history, laboratory tests, etc. Univariate and multivariate Logistic regression analysis were performed to screen out the independent predictors of the END of AIS patients after intravenous thrombolytic. The study subjects were randomly divided into a training set and a test set in a 7 : 3 ratio. Four machine learning prediction models, including Logistic regression (LR), K-nearest neighbor (KNN), support vector machine (SVM) and random forest (RF), were established based on independent predictors. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive ability of each model in END., Results: A total of 704 patients were enrolled, of whom 99 were identified as END and 605 as non-END. Univariate and multivariate Logistic regression analysis was used to screen out the National Institutes of Health stroke scale [NIHSS, odds ratio (OR) = 1.049, 95% confidence interval (95%CI) was 1.015-1.082, P = 0.004], systolic blood pressure (OR = 1.013, 95%CI was 1.004-1.022, P = 0.004), lymphocyte percentage (LYM%, OR = 0.903, 95%CI was 0.853-0.953, P < 0.001), platelet to lymphocyte ratio (PLR, OR = 1.007, 95%CI was 1.002-1.014, P = 0.013) were the independent predictors of END in AIS patients after intravenous thrombolysis. The area under the curve (AUC) of LR, KNN, SVM, and RF machine learning models in the test dataset were 0.789 (95%CI was 0.675-0.902), 0.797 (95%CI was 0.685-0.910), 0.851 (95%CI was 0.751-0.952) and 0.809 (95%CI was 0.699-0.919), respectively. The RF model had the highest sensitivity (95.7%). The accuracy (0.736), specificity (72.0%) and AUC of SVM model were the highest, and its overall prediction ability was better than the other three models., Conclusions: Machine learning models have a potential role in early predicting the risk of END after intravenous thrombolysis in AIS patients, and can provide help in clinical decision-making for intravenous thrombolysis.

X-ray detectors have numerous applications in medical imaging, industrial inspection, and crystal structure analysis. Gallium oxide (Ga 2 O 3 ) shows potential as a material for high-performance X-ray detectors due to its wide bandgap, relatively high mass attenuation coefficient, and resistance to radiation damage. In this study, we present Sn-doped Ga 2 O 3 microwire detectors for solar-blind and X-ray detection. The developed detectors exhibit a switching ratio of 1.66 × 10 2 under X-ray irradiation and can operate stably from room temperature to 623 K, which is one of the highest reported operating temperatures for Ga 2 O 3 X-ray detectors to date. These findings offer a promising new direction for the design of Ga 2 O 3 -based X-ray detectors.

This study aimed to investigate the underlying mechanisms of cerebral ischemia-reperfusion injury (CIRI) in mice using CIR and hypoxia/reoxygenation (H/R) cell models. The study evaluated brain tissue weight, pathological injury, and changes in the expression levels of TIMP2, p-ERK1/2 and NLRP3-mediated pyroptosis-related proteins in brain tissues and hippocampal neurons of CIR mice using established methods such as dry/wet weight measurement, HE staining, qPCR, TUNEL assay, and Western blotting. The results demonstrated a significant increase in brain water content and neuronal apoptosis rate in the experimental groups compared with those in the control group. In particular, the I/R+TIMP2 group showed the highest increase. Additionally, the control group exhibited a clear brain tissue structure, neatly and densely arranged cells with normal morphology, and evenly stained and clear hippocampal tissues. However, the I/R group showed hippocampal structure disorders, interstitial edema, deep nuclear staining, karyopyknosis, and karyorrhexis in brain tissues. The study results further revealed that TIMP2 could aggravate the pathological damage of brain tissues in the I/R+TIMP2 group compared with the I/R group and significantly reduced it in the TIMP2-KD group. Furthermore, the Western blotting results demonstrated that the protein expression levels of TIMP2, p-ERK1/2, t-ERK1/2, NLRP3, IL-1β, IL-18, GSDMD, Caspase-1, and ASC in brain tissues and hippocampal neurons were significantly higher in the experimental groups than those in the control group. The I/R+TIMP2 group displaying the highest increase and the TIMP2-KD group showing a significant decrease. In conclusion, TIMP2 can contribute to the occurrence and progression of CIRI by activating NLRP3-mediated pyroptosis.

Cameras with rolling shutters (RSs) dominate consumer markets but are subject to distortions when capturing motion. Many methods have been proposed to mitigate RS distortions for applications such as vision-aided odometry and three-dimensional (3D) reconstruction. They usually need known line delay d between successive image rows. To calibrate d, several methods have been proposed that often involve complex procedures. This Letter proposes an easy RS calibration method by using an off-the-shelf light-emitting diode (LED) panel, using the fact that the RS causes the blinking LED columns to appear slanted in images by a static camera. The calibration starts with extracting the LED lights and then rectifies the images to remove the lens distortion and misalignment between the camera and the LED panel. Next, blocks of slanted bright LEDs are recognized and their inclination leads to the line delay estimate. Our method needs not to move the camera, adjust the ambient light, or calibrate camera intrinsic parameters beforehand, and it can usually estimate the line delay given two LED panel images in one second. Extensive tests with industrial cameras and consumer cameras of wide-angle and fish-eye lenses validate its competitive accuracy relative to the established methods.

High-quality imaging with reduced optical complexity has been extensively investigated owing to its promising future in academic and industrial research. However, the practical performance of most imaging systems has encountered a bottleneck posed by optics rather than electronics. Here, we propose a digital lens (DL) to compensate for the chromatic aberration induced by physical optical elements, while the residual wavelength-independent degradation is tackled through a self-designed neural network. By transforming physical aberration correction to an algorithm-based computational imaging task, the proposed DL enables our framework to reduce optical complexity and achieve achromatic imaging in the analog domain. Real experiments have been conducted with an off-the-shelf single lens and recovered images show up to 14.62 dB higher peak signal-to-noise ratio (PSNR) than the original chromatic input. Furthermore, we run a comprehensive ablation study to highlight the contribution of embedding the proposed DL, which shows a 4.83 dB PSNR improvement compared with the methods without DL. Technically, the proposed method can be an alternative for future applications that require both simple optics and high-fidelity visualization.

Pyroptosis is a form of cell death triggered by the innate immune system that has been implicated in the pathogenesis of sepsis and acute lung injury. At the cellular level, pyroptosis is characterized by cell swelling, membrane rupture, and release of inflammatory cytokines, such as IL-1β. However, the role of endogenous lipids in pyroptosis remains underappreciated. We discovered that 4-hydroxynonenal (HNE), a major endogenous product of lipid peroxidation, inhibited pyroptosis and inflammasome activation. HNE at physiological concentrations (3 µM) blocked nigericin and ATP-induced cell death, as well as secretion of IL-1β, by mouse primary macrophages and human peripheral blood mononuclear cells. Treatment with HNE, or an increase of endogenous HNE by inhibiting glutathione peroxidase 4, reduced inflammasome activation in mouse models of acute lung injury and sepsis. Mechanistically, HNE inhibited the NLRP3 inflammasome activation independently of Nrf2 and NF-κB signaling, and had no effect on the NLRC4 or AIM2 inflammasome. Furthermore, HNE directly bound to NLRP3 and inhibited its interaction with NEK7. Our findings identify HNE as a novel, endogenous inhibitor of the NLRP3 inflammasome., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Large DOF (depth-of-field) with high SNR (signal-noise-ratio) imaging is a crucial technique for applications from security monitoring to medical diagnostics. However, traditional optical design for large DOF requires a reduction in aperture size, and hence with a decrease in light throughput and SNR. In this paper, we report a computational imaging system integrating dual-aperture optics with a physics-informed dual-encoder neural network to realize prominent DOF extension. Boosted by human vision mechanism and optical imaging law, the dual-aperture imaging system is consisted of a small-aperture NIR camera to provide sharp edge and a large-aperture VIS camera to provide faithful color. To solve the imaging inverse problem in NIR-VIS fusion with different apertures, a specific network with parallel double encoders and the multi-scale fusion module is proposed to adaptively extract and learn the useful features, which contributes to preventing color deviation while preserving delicate scene textures. The proposed imaging framework is flexible and can be designed in different protos with varied optical elements for different applications. We provide theory for system design, demonstrate a prototype device, establish a real-scene dataset containing 3000 images, perform elaborate ablation studies and conduct peer comparative experiments. The experimental results demonstrate that our method effectively produces high-fidelity with larger DOF range than input raw images about 3 times. Without complex optical design and strict practical limitations, this novel, intelligent and integratable system is promising for variable vision applications such as smartphone photography, computational measurement, and medical imaging.

The collagen from jellyfish has many beneficial effects, including antioxidant, anti-inflammatory and immune-modulatory activities. However, whether jellyfish collagen hydrolysate (JCH) has any effects on high-fat diet-induced obesity remains unknown. Consequently, we in the present study orally administrated JCH in high-fat diet-fed mice to explore its effects on body weight gain, inflammatory and oxidative status, and cecum microbe composition. The results showed that oral administration of JCH prevented the body weight gain in high-fat diet-treated mice. Meanwhile, glucose, triglycerides, and total cholesterol level in serum were maintained by JCH administration. Furthermore, JCH administration alleviated oxidative stress by increasing the GSH content and decreasing the level reactive oxygen species in the liver and improved inflammatory response by decreasing the expression of TNF- α , IL-1 β , and IL-8 gene in the liver and ileum. Importantly, JCH administration helps recover the alteration of microbiota composition induced by high-fat diet, and the genus Romboutsia may critically involve in the beneficial effects of JCH administration. In conclusion, our results indicated that JCH could be potentially used for the prevention and treatment of diet-induced obesity., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Zhe Lv et al.)

Phenolamide (PA) metabolites play important roles in the interaction between plants and pathogens. The putrescine hydroxycinnamoyl transferase genes OsPHT3 and OsPHT4 positively regulate rice cell death and resistance to Magnaporthe oryzae. The bZIP transcription factor APIP5, a negative regulator of cell death and rice immunity, directly binds to the OsPHT4 promoter to regulate putrescine-derived PAs. Whether other hydroxycinnamoyl transferase (HT) genes also participate in APIP5-mediated immunity remains unclear. Surprisingly, we find that genes encoding agmatine hydroxycinnamoyl transferases OsAHT1 and OsAHT2, tryptamine hydroxycinnamoyl transferases OsTBT1 and OsTBT2, and tyramine hydroxycinnamoyl transferases OsTHT1 and OsTHT2, responsible for the biosynthesis of polyamine-derived PAs are all up-regulated in APIP5-RNAi transgenic plants compared with segregated wild-type rice. Furthermore, both OsAHT1/2 and OsTBT1/2 are induced during M. oryzae infection, showing expression patterns similar to those previously reported for OsTHT1/2 and OsPHT3/4. Transgenic plants overexpressing either OsAHT2-GFP or OsTBT1-GFP show enhanced resistance against M. oryzae and accumulated more PA metabolites and lignin compared with wild-type plants. Interestingly, as demonstrated for OsPHT4, APIP5 directly binds to the promoters of OsAHT1/2, OsTBT1/2, and OsTHT1/2, repressing their transcription. Together, these results indicate that the HT genes are common targets of APIP5 and that PAs play critical roles in rice immunity., Competing Interests: Conflict of interest The authors have declared no competing interests., (Copyright © 2022 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. All rights reserved.)

Background: Ubiquitination is essential for many cellular processes in eukaryotes, including 26S proteasome-dependent protein degradation, cell cycle progression, transcriptional regulation, and signal transduction. Although numerous ubiquitinated proteins have been empirically identified, their cognate ubiquitin E3 ligases remain largely unknown., Results: Here, we generate a complete ubiquitin E3 ligase-encoding open reading frames (UbE3-ORFeome) library containing 98.94% of the 1515 E3 ligase genes in the rice (Oryza sativa L.) genome. In the test screens with four known ubiquitinated proteins, we identify both known and new E3s. The interaction and degradation between several E3s and their substrates are confirmed in vitro and in vivo. In addition, we identify the F-box E3 ligase OsFBK16 as a hub-interacting protein of the phenylalanine ammonia lyase family OsPAL1-OsPAL7. We demonstrate that OsFBK16 promotes the degradation of OsPAL1, OsPAL5, and OsPAL6. Remarkably, we find that overexpression of OsPAL1 or OsPAL6 as well as loss-of-function of OsFBK16 in rice displayed enhanced blast resistance, indicating that OsFBK16 degrades OsPALs to negatively regulate rice immunity., Conclusions: The rice UbE3-ORFeome is the first complete E3 ligase library in plants and represents a powerful proteomic resource for rapid identification of the cognate E3 ligases of ubiquitinated proteins and establishment of functional E3-substrate interactome in plants., (© 2022. The Author(s).)

As a kind of photodetector, position-sensitive-detectors (PSDs) have been widely used in noncontact photoelectric positioning and measurement. However, fabrications and applications of solar-blind PSDs remain yet to be harnessed. Herein, we demonstrate a solar-blind PSD developed from a graphene/Ga 2 O 3 Schottky junction with a 25-nanometer-thick Ga 2 O 3 film, in which the absorption of the nanometer-thick Ga 2 O 3 is enhanced by multibeam interference. The graphene/Ga 2 O 3 junction exhibits a responsivity of 48.5 mA/W and a rise/decay time of 0.8/99.8 μs at zero bias. Moreover, the position of the solar-blind spot can be determined by the output signals of the PSD. Using the device as a sensor of noncontact test systems, we demonstrate its application in measurement of angular, displacement, and light trajectory. In addition, the position-sensitive outputs have been used to demodulate optical signals into electrical signals. The results may prospect the application of solar-blind PSDs in measurement, tracking, communication, and so on.

Ethnopharmacological Relevance: The combination of Coptis chinensis (RC) and Dolomiaea souliei (VR) has long been used as a classic herb pair for the treatment of gastrointestinal diseases, but the underlying mechanisms remain unknown., Materials and Methods: In this study, the rationality of evidence-based RC and VR combination was explored from the perspective of metabolism, gut microbiota and gastrointestinal function., Results: After 5 weeks treatment, VR extracts (700 mg/kg) and RC alkaloids (800 mg/kg) showed no toxic effect on mice. However, RC administration significantly decreased the body weight of mice. Gastric emptying, gastrointestinal motility function and the absorption of FITC dextran were retarded in the mice of RC group, taking RC along with low dose VR (RC-VRL) and high dose VR (RC-VRH) reversed the impaired gastrointestinal function caused by RC. RC administration significantly increased villus height/crypt depth value. Notably, VR administration increased the number of crypts in mice ileum and reduced villus height/crypt depth value in VR and RC combination group. RC treatment significantly increased the expression of occludin compared to NC group; RC-VRL treatment reversed this tendency. While, VR administration increased ZO1 expression by 99.4% compared to NC mice. As for gut microbiota, RC gavage decreased the gut microbiota diversity, but gut microbiota in VR group was similar to NC group, and VR and RC combination increased gut microbiota diversity. RC administration obviously increased the proportion of Akkermansia muciniphila, Bacteroides thetaiotaomicron, Parabacteroides distasonis, and Escherichia coli, compared to NC mice. VR treatment increased the richness of Bacteroides thetaiotaomicron, Parabacteroides distasonis. RC-VRL and RC-VRH treatment dose-dependently increased the richness of Rikenellaceae RC9, Lactobacillus, and decreased the abundance of Psychrobacter, Bacteroides and Ruminococcus in mice. Serum metabolomic analysis revealed that RC gavage significantly down regulated 76 metabolites and up regulated 31 metabolites. VR treatment significantly down regulated 30 metabolites and up regulated 12 metabolites. Weight loss caused by RC may attribute to the elevated methylxanthine level in mice. The potential adverse effects caused by high dose RC intake may partially alleviate by high serum contents of adenosine, inosine and urolithin A resulted from VR coadministration., Conclusion: VR may alleviate RC caused "fluid retention" via normalizing gastrointestinal function, gut microbiota and modulating the perturbed metabolism., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background cGMP-hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP-dependent protein kinase I (PKGI)-dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men. Methods and Results AAA was induced in C57BL/6J male mice by periaortic elastase in combination with blocking elastin/collagen formation via 3-aminopropionitrile fumarate salt for 35 days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre-existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA. Conclusions Sildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.

The transcription regulator ID2 plays an essential role in the development and differentiation of immune cells. Here, we report that ID2 also negatively regulates antiviral innate immune responses. During viral infection of human epithelial cells, ID2 bound to TANK-binding kinase 1 (TBK1) and to inhibitor of nuclear factor κB kinase ε (IKKε). These interactions inhibited the recruitment and activation of interferon (IFN) regulatory factor 3 (IRF3) by TBK1 or IKKε, leading to a reduction in the expression of IFN-β1 ( IFNB1 ). IFN-β induced the nuclear export of ID2 to form a negative feedback loop. Knocking out ID2 in human cells enhanced innate immune responses and suppressed infection by different viruses, including SARS-CoV-2. Mice with a myeloid-specific deficiency of ID2 produced more IFN-α in response to viral infection and were more resistant to viral infection than wild-type mice. Our findings not only establish ID2 as a modulator of IRF3 activation induced by TBK1 and/or IKKε but also introduce a mechanism for cross-talk between innate immunity and cell development and differentiation.

Phenolamides (PAs), a diverse group of specialized metabolites, including hydroxycinnamoylputrescine (HP), hydroxycinnamoylagmatine, and hydroxycinnamoyltryptamine, are important in plant resistance to biotic stress. However, the genes involved in the biosynthesis and modulation of PAs have not been fully elucidated. This study identified an HP biosynthetic gene cluster in rice (Oryza sativa) comprising one gene (OsODC) encoding a decarboxylase and two tandem-duplicated genes (OsPHT3 and OsPHT4) encoding putrescine hydroxycinnamoyl acyltransferases coexpressed in different tissues. OsODC catalyzes the conversion of ornithine to putrescine, which is used in HP biosynthesis involving OsPHT3 and OsPHT4. OsPHT3 or OsPHT4 overexpression causes HP accumulation and cell death and putrescine hydroxycinnamoyl acyltransferases (PHT) activity-dependent resistance against the fungal pathogen Magnaporthe oryzae. OsODC overexpression plants also confer enhanced resistance to M. oryzae. Notably, the basic leucine zipper transcription factor APIP5, a negative regulator of cell death, directly binds to the OsPHT4 promoter, repressing its transcription. Moreover, APIP5 suppression induces OsPHT4 expression and HP accumulation. Comparative genomic analysis revealed that the HP biosynthetic gene cluster is conserved in monocots. These results characterized a previously unidentified monocot-specific gene cluster that is involved in HP biosynthesis and contributes to defense and cell death in rice., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.)

Photomemories offer great opportunities for multifunctional integration of optical sensing, data storage, and processing into one single device. However, little attention has been paid to photomemories working in the solar-blind region so far, which may have unique advantages of insusceptibility to ambient light and higher capacity. Herein, we propose and demonstrate a Ga 2 O 3 based solar-blind photomemory array with logic, arithmetic, and optoelectronic memory functions. The device shows n-type field effect-transistor performance with an on/off ratio as high as 10 6 , a responsivity of 8 × 10 3 A W -1 , and a detectivity of 1.42 × 10 14 Jones, all of which are amongst the best values ever reported for Ga 2 O 3 based photodetectors. Based on the trapping and de-trapping process of holes in Ga 2 O 3 , multilevel data storage can be realized from the device. Simultaneously, the optical and electrical mixed basic logic of reconfigurable "AND" and "OR" operations have been realized in a single cell through the co-regulation of solar-blind light and the grid voltage. In addition, the photomemory can perform counting and addition operations, and the photomemory array can be utilized to realize solar-blind image storage. The results suggest that Ga 2 O 3 may have potential applications in high-performance information storage, computing, and communications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating pandemic worldwide. Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic, and scientists all over the world have made great efforts to this end. However, manipulation of the SARS-CoV-2 should be performed in the biosafety level 3 laboratory. This makes experiments complicated and time-consuming. Therefore, a safer system for working with this virus is urgently needed. Here, we report the construction of plasmid-based, non-infectious SARS-CoV-2 replicons with turbo-green fluorescent protein and/or firefly luciferase reporters by reverse genetics using transformation-associated recombination cloning in Saccharomyces cerevisiae. Replication of these replicons was achieved simply by direct transfection of cells with the replicon plasmids as evident by the expression of reporter genes. Using SARS-CoV-2 replicons, the inhibitory effects of E64-D and remdesivir on SARS-CoV-2 replication were confirmed, and the half-maximal effective concentration (EC 50 ) value of remdesivir and E64-D was estimated by different quantification methods respectively, indicating that these SARS-CoV-2 replicons are useful tools for antiviral drug evaluation., (© 2021. Wuhan Institute of Virology, CAS.)

ε-poly-L-lysine (ε-PL) is a naturally occurring poly(amino acid) of varying polymerization degree, which possesses excellent antimicrobial activity and has been widely used in food and pharmaceutical industries. To provide new perspectives from recent advances, this review compares several conventional and advanced strategies for the discovery of wild strains and development of high-producing strains, including isolation and culture-based traditional methods as well as genome mining and directed evolution. We also summarize process engineering approaches for improving production, including optimization of environmental conditions and utilization of industrial waste. Then, efficient downstream purification methods are described, including their drawbacks, followed by the brief introductions of proposed antimicrobial mechanisms of ε-PL and its recent applications. Finally, we discuss persistent challenges and future perspectives for the commercialization of ε-PL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Zhang, Zhang, Rao, Xu, Mao and Chen.)

Hepatitis C virus (HCV) infection induces the degradation and decreases the secretion of apolipoprotein B (ApoB). Impaired production and secretion of ApoB-containing lipoprotein is associated with an increase in hepatic steatosis. Therefore, HCV infection-induced degradation of ApoB may contribute to hepatic steatosis and decreased lipoprotein secretion, but the mechanism of HCV infection-induced ApoB degradation has not been completely elucidated. In this study, we found that the ApoB level in HCV-infected cells was regulated by proteasome-associated degradation but not autophagic degradation. ApoB was degraded by the 20S proteasome in a ubiquitin-independent manner. HCV induced the oxidation of ApoB via oxidative stress, and oxidized ApoB was recognized by the PSMA5 and PSMA6 subunits of the 20S proteasome for degradation. Further study showed that ApoB was degraded at endoplasmic reticulum (ER)-associated lipid droplets (LDs) and that the retrotranslocation and degradation of ApoB required Derlin-1 but not gp78 or p97. Moreover, we found that knockdown of ApoB before infection increased the cellular lipid content and enhanced HCV assembly. Overexpression of ApoB-50 inhibited lipid accumulation and repressed viral assembly in HCV-infected cells. Our study reveals a novel mechanism of ApoB degradation and lipid accumulation during HCV infection and might suggest new therapeutic strategies for hepatic steatosis., Competing Interests: The authors have declared that no competing interests exist.

The hormone melatonin is synthesized from serotonin by two enzymatic reactions (AANAT and ASMT/HIOMT) in the pineal gland following a circadian rhythm with low levels during the day and high levels at night. The robust nightly peak of melatonin secretion is an output signal of the circadian clock to the whole organism. However, so far the regulatory roles of endogenous melatonin in mammalian biological rhythms and physiology processes are poorly understood. Here, we establish congenic mouse lines (>N10 generations) that are proficient or deficient in melatonin synthesis (AH+/+ or AH-/- mice, respectively) on the C57BL/6J genetic background by crossing melatonin-proficient MSM/Ms with C57BL/6J. AH+/+ mice displayed robust nightly peak of melatonin secretion and had significantly higher levels of pineal and plasma melatonin vs AH-/- mice. Using this mice model, we investigated the role of endogenous melatonin in regulating multiple biological rhythms, physiological processes, and rhythmic behaviors. In the melatonin-proficient (AH+/+) mice, the rate of re-entrainment of wheel-running activity was accelerated following a 6-hour phase advance of dark onset when comparted with AH-/- mice, suggesting a role of endogenous melatonin in facilitating clock adjustment. Further in the AH+/+ mice, there was a significant decrease in body weight, gonadal weight and reproductive performance, and a significant increase in daily torpor (a hypothermic and hypometabolic state lasting only hours during adverse conditions). Endogenous melatonin, however, had no effect in the modulation of the diurnal rhythm of 2-[ 125 I]-iodomelatonin receptor expression in the SCN, free-running wheel behavior in constant darkness, life span, spontaneous homecage behaviors, and various types of social-emotional behaviors. The findings also shed light on the role of endogenous melatonin in mice domestication and provide new insights into melatonin's action in reducing energy expenditure during a food shortage. In summary, the congenic mice model generated in this study offers a significant advantage toward understanding of the role of endogenous melatonin in regulating melatonin receptor-mediated rhythm behaviors and physiological functions., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Large depth-of-field (DOF) imaging with a high resolution is useful for applications ranging from robot vision to bio-imaging. However, it is challenging to construct an optical system with both a high resolution and large DOF. The common solution is to design relatively complex optical systems, but the setup of such systems is often bulky and expensive. In this paper, we propose a novel, compact, and low-cost method for large-DOF imaging. The core concept is to (1) design an aspherical lens with a depth-invariant point spread function to enable uniform image blurring over the whole depth range and (2) construct a deep learning network to reconstruct images with high fidelity computationally. The raw images captured by the aspherical lens are deblurred by the trained network, which enables large-DOF imaging at a smaller F number. Experimental results demonstrate that our end-to-end computational imager can achieve enhanced imaging performance. It can reduce loss by up to 46.5% compared to inherited raw images. With the capabilities of high-resolution and large-DOF imaging, the proposed method is promising for applications such as microscopic pathological diagnosis, virtual/augmented reality displays, and smartphone photography.

Background: Subjects with low bone mineral density and osteoporosis are more likely to suffer osteoporotic fractures during their lifetime. Polymorphisms in osteoprotegerin (OPG) gene are found to be associated with low bone mineral density and osteoporosis risk but their association with fracture risk is inconclusive. Here, we performed a meta-analysis to investigate the relationship between OPG polymorphisms with susceptibility to osteoporotic fractures., Methods: Eligible studies investigating the association between common OPG polymorphisms (A164G, T245G, T950C, and G1181C) and risk of osteoporotic fracture were retrieved from PubMed, EMBASE, Web of Science, and the Cochrane Library. Odds ratio (OR) and the 95% confidence interval (CI) were calculated in the allelic, dominant, recessive, and homozygous model. Subgroup analyses of vertebral fractures, Caucasians, and postmenopausal women were also performed., Results: A total of 14 studies comprising 5459 fracture cases and 9860 non-fracture controls were included. A163G was associated with fracture risk in dominant (OR = 1.29, 95%CI 1.11-1.50), recessive (OR = 1.64, 95%CI 1.10-2.44), and homozygous model (OR = 1.73, 95%CI 1.16-2.59). T245G was significantly correlated with susceptibility to fractures in all genetic models. Subjects with CC genotype of T950C had a reduced risk of fracture compared to those with CT or TT genotypes (OR = 0.81, 95%CI 0.70-0.94, P = .004). Subgroup analysis showed that A163G and T245G but not T950C and G1181C were associated with vertebral fracture risk., Conclusion: OPG A163G and T245G polymorphisms were risk factors of osteoporotic fractures while T950C had a protective role. These polymorphisms can be used as predictive markers of fractures., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abdominal aortic aneurysm (AAA) is characterized by aorta dilation due to wall degeneration, which mostly occurs in elderly males. Vascular aging is implicated in degenerative vascular pathologies, including AAA. Cyclic nucleotide phosphodiesterases, by hydrolyzing cyclic nucleotides, play critical roles in regulating vascular structure remodeling and function. Cyclic nucleotide phosphodiesterase 1C (PDE1C) expression is induced in dedifferentiated and aging vascular smooth muscle cells (SMCs), while little is known about the role of PDE1C in aneurysm. We observed that PDE1C was not expressed in normal aorta but highly induced in SMC-like cells in human and murine AAA. In mouse AAA models induced by Angiotensin II or periaortic elastase, PDE1C deficiency significantly decreased AAA incidence, aortic dilation, and elastin degradation, which supported a causative role of PDE1C in AAA development in vivo. Pharmacological inhibition of PDE1C also significantly suppressed preestablished AAA. We showed that PDE1C depletion antagonized SMC senescence in vitro and/or in vivo, as assessed by multiple senescence biomarkers, including senescence-associated β-galactosidase activity, γ-H2AX foci number, and p21 protein level. Interestingly, the role of PDE1C in SMC senescence in vitro and in vivo was dependent on Sirtuin 1 (SIRT1). Mechanistic studies further showed that cAMP derived from PDE1C inhibition stimulated SIRT1 activation, likely through a direct interaction between cAMP and SIRT1, which leads to subsequent up-regulation of SIRT1 expression. Our findings provide evidence that PDE1C elevation links SMC senescence to AAA development in both experimental animal models and human AAA, suggesting therapeutical significance of PDE1C as a potential target against aortic aneurysms., Competing Interests: The authors declare no competing interest.

Physical distancing has been an important policy to mitigate the spread of the novel coronavirus disease 2019 (COVID-19) in public settings. However, the current 1-2 m physical distancing rule is based on the physics of droplet transport and could not directly translate into infection risk. We therefore revisit the 2-m physical distancing rule by developing an infection-risk-based model for human speaking. The key modeling framework components include viral load, droplets dispersion and evaporation, deposition efficiency, viral dose-response rate and infection risk. The results suggest that the one-size-fits-all 2-m physical distancing rule derived from the pure droplet-physics-based model is not applicable under some realistic indoor settings, and may rather increase transmission probability of diseases. Especially, in thermally stratified environments, the infection risk could exhibit multiple peaks for a long distance beyond 2 m. With Sobol's sensitivity analysis, most variance of the risk is found to be significantly attributable to the variability in temperature gradient, exposure time and breathing height difference. Our study suggests there is no such magic 2 m physical distancing rule for all environments, but it needs to be used alongside other strategies, such as using face cover, reducing exposure time, and controlling the thermal stratification of indoor environment., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Psoroptes ovis var. cuniculi infestation rapidly causes skin lesion, cutaneous inflammatory and subsequent adaptive immune response in rabbits. To success feeding and survive on the host skin, this mite should product bioactive molecules to confront host tissue repair and immune defense, but these molecules of this mite remains mostly unknown. Serpins have been proved to involve in diverse biological functions including parasite reproduction, survival and modulating host defense. Limited information is currently available on serpins from Psoroptes mites. Herein, we identified four novel serpins (PsoSP3-PsoSP6) in P. ovis var. cuniculi using bioinformatics and molecular biology techniques. Sequence analysis revealed that PsoSP3-PsoSP6 comprised the common features of typical serpins superfamily including serpin domains, signature or the reactive centre loop (RCL) domain. The recombinant PsoSP4-PsoSP6 (rPsoSP4-rPsoSP6) revealed variable potency inhibition on trypsin, chymotrypsin and elastase except for rPsoSP3 in inhibitory activity assays. By quantitative RT-PCR, the expressions of PsoSP3 and PsoSP4 were higher in juvenile mites (larva and nymph) than in adult mites, however, PsoSP5 and PsoSP6 appeared near-exclusive expression in adult female mites. Immunolocalization showed that native PsoSP4 protein was localized in uterus, whilst native PsoSP3, PsoSP5 and PsoSP6 were specifically localized in the ovarian nutritive cell (ONC) in ovary. Our findings indicated that PsoSP3-PsoSP6 might play critical roles in development and reproduction physiologies. rPsoSP4-rPsoSP6 might participate in modulating host inflammation, immune response and tissue repair., (Copyright © 2021 Elsevier B.V. All rights reserved.)

With the rapid development of electronic devices and wireless communication tools, it is urgent to design and fabricate low-cost, lightweight and effective electromagnetic absorption materials to solve interference of electromagnetic waves. Herein, a new strategy toward porous carbon/graphite nanosheet/ferromagnetic nanoparticle (PC/GNS/Fe) composites was designed to investigate the influence of crystalline carbon on electromagnetic wave absorption. To begin with, graphite nanosheets (GNSs) were incorporated into the porous polyimide by in situ polymerization, and Fe were added as a magnetic particle source and an agent to regulate the pore size. A series of PC/GNS/Fe composite absorbents were obtained. The direct carbonization of porous polymer precursors was beneficial to the design of the pore structure of materials. A hierarchically porous structure derived from the phase separation process was well maintained in the polyimide pyrolysis process. The results demonstrated that the presence of crystalline carbon could influence the reflection loss value and the frequency range. Hence, the absorbing performance can be optimized by adjusting the pore structure and the content of crystalline carbon in materials, which is conducive to obtaining electromagnetic wave absorption materials with excellent comprehensive performance.

Enterovirus 71 (EV71) is the major causative pathogen of hand, foot, and mouth disease. The lack of understanding of the virus's pathogenesis hinders the development of anti-virus drugs and the control of EV71 infection. Our previous studies have demonstrated that both mitochondria and endoplasmic reticulum (ER) were altered significantly in EV71 infected cells, but the mechanism is still unclear. In this study, we investigated the effects of EV71 infection on the expression of INF2, a key regulator factor in ER-Mitochondria communication and mitochondrial fission. We found that INF2 was cleaved in EV71 infected RD cells. The INF2 cleavage occurred at Aspartic 1,051 of INF2 and is mediated by activated caspases, predominantly by activated caspase-2. The subcellular localization of INF2 and caspase-2 was significantly altered in infected cells. We speculate that caspase-2-mediated INF2 cleavage is involved in forming viral replication organelles (ROs) and is a positive feedback regulatory mechanism of mitochondrial disorders caused by EV71 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Zhang, Yu, Zhu, Tang, Huang and Zhao.)

Objective: To analyze the distribution and composition characteristics of jellyfish stings in various coastal baths in Qinhuangdao City from 2017 to 2019, and to provide scientific basis for the prevention, control and early warning of jellyfish stings., Methods: Statistics and analysis of the age, gender, time of stings, location of injury, first symptoms, and playing time in the sea at the time of the sting, etc. of people with jellyfish stings in various bathing beaches along the coast of Qinhuangdao from 2017 to 2019 (July to August) were conducted., Results: The number of jellyfish stings in the coastal bathing beaches of Qinhuangdao City in 2017, 2018, and 2019 was decreasing year by year, with 1 890, 492, and 171 cases respectively. Among them, Qianshuiwan Bathing Beach and Dongshan Bathing Beach had more stings (60.90% and 35.08% respectively in 2017, 24.39% and 64.23% respectively in 2018, 16.96% and 16.42% respectively in 2019). There was no significant change in the gender and age distribution of jellyfish stings each year [57.99% males in 2017, with a median age of 13 (8, 31) years old; 63.21% males in 2018, with a median age of 25 (8, 29) years old; and 59.65% males in 2019, with a median age of 12 (7, 31) years old]. Stings were mainly located at the lower limbs (the proportion of lower limb injuries: 46.54% in 2018, 45.61% in 2019), followed by upper limbs (upper arm, elbow, forearm), trunk, etc. The first symptom was mainly pain (89.43% in 2018, 38.29% in 2019), followed by rash (64.43% in 2018, 59.43% in 2019), numbness, blisters, etc. Sting incidents mainly occurred from 13:00 to 17:59 (the proportion of sting incidents in this time period in 2018 and 2019 were 68.09% and 52.63%, respectively)., Conclusions: Jellyfish stings in coastal baths in Qinhuangdao City are mainly distributed in Qianshuiwan Baths and Dongshan Baths. The management of these sea areas should be strengthened, and scientific publicity and medical rescue should be strengthened to prevent jellyfish stings in peak hours and related baths.