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Abstract This study compared the hospitalization expenses of patients with chronic bronchitis in a central province (Province A) in China to estimate the direct medical cost of the family. Our data included hospitalization records of 30,341 patients with chronic bronchitis from five urban general hospitals in Province A. Using descriptive statistics and regression analysis, we explored the relevant factors affecting hospitalization expenses. Our study results have indicated that from 2016 to 2020, the medical expenditure of patients with chronic bronchitis increased annually, with an average annual growth rate of 22.65%. Among all kinds of expenses, the hospitalization expenses, drug cost, bed cost, test cost and other cost of UEMI (Urban Employee Medical Insurance) are higher than that of other types of medical insurance. The check-up fees of CMI (Commercial Insurance) are lower than that of other types of insurance. Between 2016 and 2019, the average medical expenses per patient with chronic bronchitis increased by 44%, which is the highest average medical expenses among patients aged 60–70. And the highest average medical expenditure emerged when the number of service days is between 5 and 10 days. The increase in expenditure could be attributed to the rapid development of medical technology and the increasing medical demand of the people. Overall, the results of our study implied a significant increase in medical expenses for patients with chronic bronchitis from 2015 to 2020, indicating that chronic bronchitis could bring heavy economic pressures to patients, their families and society.

Abstract Obesity has become a global health problem. In recent years, the influence of dietary microbes in the obese population has attracted the attention of scholars. Our study aimed to investigate the link between live microbe intake and obesity in adults. Participants (aged over 20 years) for this study were from the 1999–2018 National Health and Nutrition Examination Survey (NHANES). Participants were categorised into low, medium and high dietary live microbe intake groups. Linear regression was used to analyse the link between live microbe intake and body mass index (BMI) and waist circumference (WC). Logistic regression was used to analyse the link between live microbe intake and obesity and abdominal obesity prevalence. Restricted cubic spline curves (RCS) were used to check whether there was a non-linear relationship between live microbe intake and obesity. A total of 42,749 participants were included in this study and the number of obese reached 15,463. We found that live microbe intake was negatively linked to BMI and WC. In models adjusted for all confounders, the high live microbe intake group had lower obesity (OR = 0.812, 95%CI: 0.754–0.873) and abdominal obesity prevalence (OR = 0.851, 95%CI: 0.785–0.923) than the lowest intake group. Upon further quantification of live microbe intake, we found similar results. RCS analyses showed that live microbe intake was nonlinearly negatively correlated with BMI, WC, obesity, and abdominal obesity prevalence (P for non-linearity

Abstract Purpose To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. Methods A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. Results Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P 0.05). Conclusion Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

IntroductionResearch increasingly links environmental exposure to toxic metals with health risks, yet the effect of combined metal exposure on Toxoplasma infection remains underexplored. This study investigates the relationship between concurrent heavy metal exposure and Toxoplasma infection in adults.MethodsWe analyzed data from 10,746 adults aged 20–80 from NHANES, with 1,869 positive for Toxoplasma gondii IgG. The study assessed associations between lead (Pb), cadmium (Cd), and mercury (Hg) with Toxoplasma infection risk using single-metal logistic regression, RCS analysis, WQS regression, and qgcomp models.ResultsEach metal showed an independent association with Toxoplasma infection risk. Pb had a non-linear association, while Hg had a linear one. Analysis of multiple metals indicated a positive correlation between heavy metal exposure and infection risk, particularly in younger and middle-aged adults, with Pb showing the strongest link.DiscussionOur findings reveal a significant association between heavy metal exposure and Toxoplasma infection risk, especially in younger demographics, with lead being a key factor. This highlights the importance of understanding environmental metal exposure’s impact on public health and informs the development of prevention strategies.

The ongoing evolution and immune escape of SARS-CoV-2, alongside the potential threat of SARS-CoV-1 and other sarbecoviruses, underscore the urgent need for effective strategies against their infection and transmission. This study highlights the discovery of nanobodies from immunized alpacas, which demonstrate exceptionally broad and potent neutralizing capabilities against the recently emerged and more divergent SARS-CoV-2 Omicron subvariants including JD.1.1, JN.1, KP.3, KP.3.1.1, as well as SARS-CoV-1 and coronaviruses from bats and pangolins utilizing receptor ACE2. Among these, Tnb04-1 emerges as the most broad and potent, binding to a conserved hydrophobic pocket in the spike's receptor-binding domain, distinct from the ACE2 binding site. This interaction disrupts the formation of a proteinase K-resistant core, crucial for viral-cell fusion. Notably, intranasal administration of Tnb04-1 in Syrian hamsters effectively prevented respiratory infection and transmission of the authentic Omicron XBB.1.5 subvariant. Thus, Thb04-1 holds promise in combating respiratory acquisition and transmission of diverse sarbecoviruses.

Proliferative vitreoretinopathy(PVR) is a type of fibrotic eye disease with a poor clinical prognosis. Increasing evidence has shown that the primary pathological mechanism of PVR is the epithelial-mesenchymal transition(EMT) of retinal pigment epithelium(RPE) cells. Histone deacetylase 3(HDAC3) is a crucial enzyme involved in regulating the acetylation level of proteins. Several studies have reported associations between HDAC3 levels and EMT in various tumors; however, the specific effect of HDAC3 on PVR remains largely unknown. The current study found that HDAC3 was highly expressed in both human PVR membranes and experimental PVR. In vivo, silencing HDAC3 in RPE cells reduced their ability to develop experimental PVR through suppression of EMT. In vitro, inhibition of HDAC3 in RPE cells suppressed EGF-mediated cell proliferation, migration, and EMT. Additionally, overexpression of HDAC3 in RPE cells promoted cell proliferation, migration, and EMT. Mechanistically, the results of chromatin immunoprecipitation(ChIP) and luciferase assays revealed a direct binding of the transcription factor MAZ to the promoter region of HDAC3, thereby promoting its transcription. Furthermore, It was demonstrated that HDAC3 facilitated EMT by interacting with AKT and contributing to its deacetylation. In summary, our findings indicated the involvement of HDAC3 in the EMT of RPE cells, as well as its role in PVR through the regulation of the AKT pathway. These results suggested that targeting HDAC3 could be a potential strategy for preventing and treating PVR.

AimsTo investigate levels of 25-hydroxyvitamin-D (25HVD), interleukin-17 (IL-17), IL-27, IL-35, and transforming growth factor β1 (TGF-β1) in chronic spontaneous urticaria (CSU) patients and their correlations with disease activity.MethodsAn observational, case-control study was conducted. Eighty-one CSU patients and fifty-eight healthy individuals were recruited into two groups. Serum levels of 25HVD, IL-17, IL-27, IL-35, TGF-β1 were determined via enzyme-linked immunosorbent assay (ELISA). Disease activity of CSU was assessed using urticaria activity score (UAS).ResultsSerum level of 25HVD was significantly lower in CSU group compared to control group (P < 0.001). Serum levels of IL-17 (P < 0.001), IL-27 (P < 0.001), TGF-β1 (P = 0.01) were significantly higher in CSU group than those in control group. In CSU group, the level of 25HVD was negatively associated with IgE (P < 0.01) and positively correlated with IL-35 (P < 0.01). In addition, serum level of IL-17 was negatively correlated with disease activity among female patients (P < 0.05).ConclusionDeficiency of 25HVD is associated with development of CSU, the underlying mechanism might be related with IL-35. Likewise, IL-17, IL-27, IL-35, and TGF-β1 might also contribute to development of CSU.

Summary: Background: The spread of emerging SARS-CoV-2 immune escape sublineages, especially JN.1 and KP.2, has resulted in new waves of COVID-19 globally. The evolving memory B cell responses elicited by the parental Omicron variants to subvariants with substantial antigenic drift remain incompletely investigated. Methods: Using the single B cell antibody cloning technology, we isolated single memory B cells, delineated the B cell receptor repertoire and conducted the pseudovirus-based assay for recovered neutralizing antibodies (NAb) screening. We analyzed the cryo-EM structures of top broadly NAbs (bnAbs) and evaluated their in vivo efficacy (golden Syrian hamster model). Findings: By investigating the evolution of human B cell immunity, we discovered a new panel of bnAbs arising from vaccinees after Omicron BA.2/BA.5 breakthrough infections. Two lead bnAbs neutralized major Omicron subvariants including JN.1 and KP.2 with IC50 values less than 10 ng/mL, representing ultrapotent receptor binding domain (RBD)-specific class I bnAbs. They belonged to the IGHV3-53/3-66 clonotypes instead of evolving from the pre-existing vaccine-induced IGHV1-58/IGKV3-20 bnAb ZCB11. Despite sequence diversity, they targeted previously unrecognized, highly conserved conformational epitopes in the receptor binding motif (RBM) for ultrapotent ACE2 blockade. The lead bnAb ZCP3B4 not only protected the lungs of hamsters intranasally challenged with BA.5.2, BQ.1.1 and XBB.1.5 but also prevented their contact transmission. Interpretation: Our findings demonstrated that class I bnAbs have evolved an ultrapotent mode of action protecting against highly transmissible and broad Omicron escape variants, and their epitopes are potential targets for novel bnAbs and vaccine development. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Summary: Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up. Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m2 twice daily on days 1–14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051). Findings: As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1–39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6–14.6) in cohort A and 5.7 months (95% CI, 3.4–11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6–33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0–15.8) in cohort A and 5.7 months (95% CI, 3.4–11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy. Interpretation: These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases. Funding: National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.

Fine particulate matter (PM2.5) may disrupt women's reproductive hormones, posing potential reproductive risks. However, the exact compositions of PM2.5 responsible for these effects remain unclear. Our investigation explored the long-term impacts of PM2.5 constituents on reproductive hormones, based on a large longitudinal assisted reproductive cohort study in Anhui, China. We included 24,396 reproductive hormone samples from 19,845 women attending assisted reproductive technologies (ART) between 2014 and 2020. Using high-resolution gridded data (1-km resolution), we calculated the residence-specified PM2.5 constituents during the year before the month of hormone testing. Relationships between PM2.5 constituents [organic matter (OM), chloride (Cl-), sulfate (SO42-), ammonium (NH4+), black carbon, and nitrate] and reproductive hormones were investigated using the linear mixed model with subject-specific intercepts. The constituent-proportion model and the constituent-residual model were also constructed. Additionally, cubic spline analysis was used to examine the potential non-linear exposure-response relationship. We found that per interquartile range (IQR) increment in OM was associated with a 5.31 % (3.74 %, 6.89 %) increase in estradiol, and per IQR increment in Cl- and NH4+ were associated with 13.56 % (7.63 %, 19.82 %) and 9.07 % (4.35 %, 14.01 %) increases in luteinizing hormone. Conversely, per IQR increment in OM and Cl- were associated with −7.27 % (-9.34 %, −5.16 %) and −8.52 % (-10.99 %, −5.98 %) decreases in progesterone, and per IQR increment in SO42- was associated with a −9.15 % (-10.31 %, −7.98 %) decrease in testosterone. These associations were held in both proportional and residual models. Moreover, exposure-response curves for estradiol and progesterone with PM2.5 constituents exhibited approximately U-shaped. These results suggested that specific PM2.5 constituents might disrupt reproductive hormone homeostasis in women attending ART, providing new evidence for formulating PM2.5 pollution reduction strategies that could benefit women's reproductive health.

Abstract The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.

Efficient translation mediated by the 5′ untranslated region (5′ UTR) is essential for the robust efficacy of mRNA vaccines. However, the N1-methyl-pseudouridine (m1Ψ) modification of mRNA can impact the translation efficiency of the 5′ UTR. We discovered that the optimal 5′ UTR for m1Ψ-modified mRNA (m1Ψ–5′ UTR) differs significantly from its unmodified counterpart, highlighting the need for a specialized tool for designing m1Ψ–5′ UTRs rather than directly utilizing high-expression endogenous gene 5′ UTRs. In response, we developed a novel machine learning-based tool, Smart5UTR, which employs a deep generative model to identify superior m1Ψ–5′ UTRs in silico. The tailored loss function and network architecture enable Smart5UTR to overcome limitations inherent in existing models. As a result, Smart5UTR can successfully design superior 5′ UTRs, greatly benefiting mRNA vaccine development. Notably, Smart5UTR-designed superior 5′ UTRs significantly enhanced antibody titers induced by COVID-19 mRNA vaccines against the Delta and Omicron variants of SARS-CoV-2, surpassing the performance of vaccines using high-expression endogenous gene 5′ UTRs.

Recognising the variations in driving behaviour between taxis in the empty and carry conditions is pivotal for enhancing the accuracy of route travel time estimations using floating car data. However, existing methods largely overlook this distinction. In light of this, this study aims to harness these variations for more precise estimations. Utilising taxi data, we segmented the information by service conditions and executed distinct estimations for each segment. The route travel time was deduced through convolutional operation, complemented by a Markov chain model to discern correlations between travel times across various links. Our innovative approach realised a substantial enhancement in accuracy. Notably, when accounting for distinct service conditions, there was a reduction of 51.44% in mean absolute error and a 46.83% decline in maximum percentage error. By providing more accurate and reliable travel time predictions, our methodology enables better-informed traffic management decisions. Accurate travel time estimations are essential for optimising traffic signal timings, planning efficient routing strategies, and managing road network usage. These improvements in traffic management can lead to smoother traffic flow, reduced travel times, and ultimately, diminished congestion in urban areas.

The urgency of environmental sustainability has catalyzed a thorough reconsideration of traditional workspaces and their environmental impact, particularly concerning carbon footprint stemming from business-related travel and daily commutes. In response to these concerns, the innovative notion of the “Phygital Workspace” has arisen. Moreover, the advent of the COVID-19 pandemic has accelerated the proliferation of this technology. In a Phygital Workspace, physical and digital elements coexist and interact to enhance productivity, collaboration, and overall work experience. This integration is often facilitated using advanced digital technologies, such as Augmented Reality (AR), Virtual Reality (VR), Mixed Reality (MR), and other immersive or interactive tools. This conceptual framework sets the stage for the seamless integration of both physical and digital dimensions, empowered by the potential of Extended Reality (XR) technology. An integral part of this review involves the analysis of various workspace scenarios, and further examines the role of a Phygital Workspace plays in reducing carbon footprint within each context. The scenarios under examination include flexible workspace scenarios, field work scenarios, and hybrid work scenarios. XR technology’s contributions to reducing carbon footprint are evaluated by minimizing the need for physical travel, enabling remote collaboration, and enhancing workspace efficiency within these scenarios. Employing a systematic review methodology, this review considers the status of XR technology adoption in diverse business environments, pinpointing its strengths and limitations. The aim is to provide a solid foundation for the framework of a new typological work environment that leverages XR technology to effectively reduce the carbon footprint associated with travel. The framework comprises four key dimensions: XR Infrastructure, Collaborative Work Environment, Social Interaction Enhancement, and Environmental Impact Assessment. These dimensions collectively guide the development and implementation of sustainable Phygital Workspaces, catering to technological, social, and ecological considerations. It is an impassioned call for collaborative efforts among researchers, policymakers, and organizations to converge their expertise for a more environmentally conscious future of work.

The [2,3]- and [1,2]-sigmatropic rearrangement reactions between pyridotriazoles and sulfides catalyzed by rhodium(II) were investigated. The utilization of pyridotriazoles as the carbene precursors in this kind of reaction efficiently constructed the C(sp3)-S and C(sp3)-Se bond with broad substrate scope and great functional group tolerance.

ObjectiveThe purpose of this paper is to study the effects of cavitation models on the simulation of full-scale propeller cavitation. MethodsThe minimum rotational speed of the propeller required for cavitation is predicted by the Bernoulli equation, and the propeller's cavitation condition is observed by full-scale experiment. After determining the boundary layer mesh thickness and establishing the hydrodynamic model, meshes are generated. In the numerical simulation, the turbulence model is selected from either the standard \begin{document}$k - \varepsilon $\end{document} model or Realizable \begin{document}$k - \varepsilon $\end{document} model, and the cavitation model is selected from either the Schnerr−Sauer (S−S) model or the Zwart−Gerber−Belamri (ZGB) model. The maximum gas volume fraction on the surface of the propeller is tracked and recorded. In the meantime, the reliability of the numerical simulation is evaluated by observing the gas distribution on the surface of the propeller. And the simulation accuracy of the related models is compared. ResultsThe simulation results show that compared with the standard \begin{document}$k - \varepsilon $\end{document} turbulence model, the cavitation region obtained with the Realizable \begin{document}$k - \varepsilon $\end{document} model is significantly more consistent with the experimental results. By monitoring the maximum gas volume fraction on propeller's surface, it is found that the choice of turbulence model has little effect on the cavitation intensity, and the cavitation intensity obtained by S−S model is significantly higher than that obtained by the ZGB model. ConclusionsThis study shows that the turbulence model has a great influence on the area of the cavitation region, and cavitation models have a great influence on cavitation intensity. In terms of the simulation of propeller cavitation, the accuracy of the Realizable \begin{document}$k - \varepsilon $\end{document} model is higher than that of the standard \begin{document}$k - \varepsilon $\end{document} model.

Abstract Background Embryo aneuploidy is a main of principal reason of pregnancy loss, in vitro fertilization (IVF) failure and birth defects in offspring. Previous researchs have demonstrated that Y chromosome AZFc microdeletion was associated with reproduction outcomes, however, the relationship between Y chromosome AZFc microdeletion and embryo aneuploidy remains unexplored. Methods This retrospective cohort study enrolled 513 patients with 603 cycles in the reproductive center of Nanjing Maternity and Child Health Care Hospital from January 1, 2016 to June 30, 2022. The study cohort was divided into two groups: the AZFc microdeletion group, comprising 53 patients and 58 cycles, and the control group, comprising 460 patients and 545 cycles. Statistical methods including restricted cubic spline and generalized estimating equation (GEE) were employed to evaluate the relationship between Y chromosome AZFc microdeletion and embryo euploidy. Results 294 and 2833 blastocysts were selected as AZFc microdeletion group and control group, respectively. Patients with Y chromosome AZFc microdeletion had significantly higher embryo aneuploid rate (33.0% vs. 27.3%, P

Although early diagnosis and therapeutic advances have transformed the living quality and outcome of cancer patients, the poor prognosis for metastatic patients has not been significantly improved. Mechanisms underlying the complexity of metastasis cannot be simply determined by the straightforward ‘cause‐and‐effect relationships’. We have developed a ‘dry‐lab‐driven knowledge discovery and wet‐lab validation’ approach to embrace the complexity of cancer and metastasis. We have revealed for the first time that polymetastatic (POL) melanoma cells can utilize both the secretory protein pathway (S100A11–Sec23a) and the exosomal crosstalk (miR‐487a‐5p) to transfer their ‘polymetastatic competency’ to the oligometastatic (OL) melanoma cells, via synergistic co‐targeting of the tumor‐suppressor Nudt21. The downstream deregulated glycolysis was verified to regulate metastatic colonization efficiency. Further, two gene sets conferring independent prognosis in melanoma were identified, which have the potential for clinical translation and merit future clinical validation.

Abstract Nonfused ring electron acceptors (NFREAs) are promising candidates for future commercialization of organic solar cells (OSCs) due to their simple synthesis. Still, the power conversion efficiencies (PCEs) of NFREA‐based OSCs have large room for improvement. In this work, by merging end group halogenation and side chain engineering, we developed four A–D–A'–D–A type NFREAs, which we refer to as EH‐4F, C4‐4F, EH‐4Cl, and C4‐4Cl. Single crystal X‐ray diffraction revealed that multiple intermolecular S···F interactions between cyclopentadithiophene and 5,6‐difluoro‐3‐(dicyanomethylene)indanone could cause an unfavorable dimer formation, leading to ineffective π–π stackings in EH‐4F and C4‐4F, whereas no such dimer was found in EH‐4Cl and C4‐4Cl after replacing with 5,6‐dichloro‐3‐(dicyanomethylene)indanone. Moreover, although the shorter n‐butyl side chain resulted in a closer molecular packing in C4‐4Cl, EH‐4Cl (2‐ethylhexyl substitution) with proper crystallinity exhibited enhanced face‐on orientation in thin film, which is favorable for vertical charge transport and further reducing charge recombination. As a result, a PCE of 13.0% is obtained for EH‐4Cl‐based OSC with a fill factor of 0.70. This work highlights the importance of molecular packing and orientation control toward future high‐performance A–D–A'–D–A type NFREAs.

ObjectiveDiabetes mellitus is the leading cause of death worldwide, and multiple risk factors associated with diabetes mortality.MethodsEmploying spatial statistics, we characterized the spatial distribution and patterns of diabetes mortality, and revealed the spatial relationship between diabetes mortality and 11 socioeconomic and environmental risk factors at the country level, from 1990 to 2019.ResultsGlobally, significantly high rates of diabetes mortality were primarily clustered in countries with limited land areas or located on islands, such as Fiji, Kiribati, Eswatini, and Trinidad and Tobago. Countries with weaker economic independence are more likely to have higher diabetes mortality rates. In addition, the impact of socioeconomic and environmental factors was significant at the country level, involving health expenditure, number of physicians, household and ambient air pollution, smoking, and alcohol consumption. Notably, the spatial relationship between diabetes mortality and ambient air pollution, as well as alcohol consumption, showed negative correlations. Countries with high diabetes mortality rates generally had lower levels of ambient air pollution and alcohol consumption.ConclusionThe study highlights the spatial clustering of diabetes mortality and its substantial variation. While many risk factors can influence diabetes mortality, it’s also essential to consider the level of these factors at the country level. Tailoring appropriate interventions based on specific national circumstances holds the potential to more effectively mitigate the burden of diabetes mortality.

BackgroundPerchlorates, nitrates, and thiocyanates are prevalent environmental chemicals. Their potential association with arthritis remains unexplored. This study aimed to investigate the link between perchlorate, nitrate, and thiocyanate exposure and arthritis, as well as the potential role of inflammation in this context.MethodsUtilizing the National Health and Nutrition Examination Survey (NHANES) data spanning from 2005 to 2016, the study enrolled 6597 participants aged 20-59 (young and middle-aged), of which 1045 had arthritis. Employing multivariate logistic regression modeling, multiple linear regression models, restricted cubic spline analysis, Bayesian kernel machine regression (BKMR) modeling, and mediation analysis, we assessed these relationships.ResultsThere was a significant positive association between elevated urinary thiocyanate levels and arthritis risk [1.19 (1.11, 1.28)]. This association held true across subgroups of osteoarthritis (OA) [1.24 (1.10, 1.40)] and rheumatoid arthritis (RA) [1.33 (1.15, 1.55)]. Thiocyanate levels displayed a dose-dependent relationship with arthritis risk, showing a linear trend (nonlinear P > 0.05). Conversely, perchlorate and nitrate did not exhibit associations with arthritis risk. BKMR outcomes highlighted a positive correlation between a mixture of perchlorate, nitrate, and thiocyanate and arthritis risk, with thiocyanate being the predominant predictors. Moreover, BKMR and generalized linear model analyses unveiled no significant synergistic effect of urinary perchlorate, nitrate, and thiocyanate on arthritis risk. Furthermore, thiocyanate exposure has been linked to elevated levels of inflammatory indicators (white blood cell, neutrophils, lymphocytes, and systemic immune-inflammatory index (SII)).ConclusionHeightened thiocyanate exposure may be linked to elevated arthritis risk, either single or in combined effects. Additionally, thiocyanate exposure is associated with heightened inflammation levels.

Abstract As climate conditions deteriorate, human health faces a broader range of threats. This study aimed to determine the risk of death from metabolic syndrome (MetS) due to meteorological factors. We collected daily data from 2014 to 2020 in Wuhu City, including meteorological factors, environmental pollutants and death data of common MetS (hypertension, hyperlipidemia and diabetes), as well as a total number of 15,272 MetS deaths. To examine the relationship between meteorological factors, air pollutants, and MetS mortality, we used a generalized additive model (GAM) combined with a distributed delay nonlinear model (DLNM) for time series analysis. The relationship between the above factors and death outcomes was preliminarily evaluated using Spearman analysis and structural equation modeling (SEM). As per out discovery, diurnal temperature range (DTR) and daily mean temperature (T mean) increased the MetS mortality risk notably. The ultra low DTR raised the MetS mortality risk upon the general people, with the highest RR value of 1.033 (95% CI: 1.002, 1.065) at lag day 14. In addition, T mean was also significantly associated with MetS death. The highest risk of ultra low and ultra high T mean occured on the same day (lag 14), RR values were 1.043 (95% CI: 1.010, 1.077) and 1.032 (95% CI: 1.003, 1.061) respectively. Stratified analysis’s result showed lower DTR had a more pronounced effect on women and the elderly, and ultra low and high T mean was a risk factor for MetS mortality in women and men. The elderly need to take extra note of temperature changes, and different levels of T mean will increase the risk of death. In warm seasons, ultra high RH and T mean can increase the mortality rate of MetS patients.

ObjectivesThis study aims to carry out systematic research on the hydrodynamic performance of a small unmanned catamaran. MethodsBased on STAR-CCM+ numerical simulation software, the hydrodynamic performance of a small unmanned catamaran in a hydrostatic state and self-propelled state under different Froude (Fr) numbers is numerically simulated. The unsteady RANSE model is selected and the Dynamic Fluid Body Interaction (DFBI) model and overset grid function are used to simulate the trim and heave of the catamaran. A body-force propeller is used to replace the propeller effect. The empirical formula of the friction resistance coefficient is used to verify the simulation results of the hydrostatic state. The self-propelled experimental results are then compared to the simulation results of the self-propelled state to verify the accuracy of the simulation results. ResultsWhen the propeller speed is 3 000 r/min, the difference in total resistance between the self-propelled and hydrostatic states of the small unmanned catamaran is 21.099%. Under different propeller rotation speeds, the relative errors of the thrust between the simulation and experimental results of the self-propelled catamaran is less than 10%. ConclusionsThe comparison between the simulation results and experimental results verifies the reliability of the simulation. The hydrodynamic performance of the self-propelled ship hull studied by the volume method is quite different from that under hydrostatic conditions. The numerical method can provide valuable references for further predicting the hydrodynamic performance of small unmanned catamarans.

Abstract Background We aimed to establish risk factors for stroke-associated pneumonia (SAP) following intracerebral hemorrhage (ICH) and develop an efficient and convenient model to predict SAP in patients with ICH. Methods Our study involved 1333 patients consecutively diagnosed with ICH and admitted to the Neurology Department of the First Affiliated Hospital of Wenzhou Medical University. The 1333 patients were randomly divided (3:1) into the derivation cohort (n = 1000) and validation Cohort (n = 333). Variables were screened from demographics, lifestyle-related factors, comorbidities, clinical symptoms, neuroimaging features, and laboratory tests. In the derivation cohort, we developed a prediction model with multivariable logistic regression analysis. In the validation cohort, we assessed the model performance and compared it to previously reported models. The area under the receiver operating characteristic curve (AUROC), GiViTI calibration belt, net reclassification index (NRI), integrated discrimination index (IDI) and decision curve analysis (DCA) were used to assess the prediction ability and the clinical decision-making ability. Results The incidence of SAP was 19.9% and 19.8% in the derivation (n = 1000) and validation (n = 333) cohorts, respectively. We developed a nomogram prediction model including age (Odds Ratio [OR] 1.037, 95% confidence interval [CI] 1.020–1.054), male sex (OR 1.824, 95% CI 1.206–2.757), multilobar involvement (OR 1.851, 95% CI 1.160–2.954), extension into ventricles (OR 2.164, 95% CI 1.456–3.215), dysphagia (OR 3.626, 95% CI 2.297–5.725), disturbance of consciousness (OR 2.113, 95% CI 1.327–3.362) and total muscle strength of the worse side (OR 0.93, 95% CI 0.876–0.987). Compared with previous models, our model was well calibrated and showed significantly higher AUROC, better reclassification ability (improved NRI and IDI) and a positive net benefit for predicted probability thresholds between 10% and 73% in DCA. Conclusions We developed a simple, valid, and clinically useful model to predict SAP following ICH, with better predictive performance than previous models. It might be a promising tool to assess the individual risk of developing SAP for patients with ICH and optimize decision-making.

Abstract Background Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression. Methods The structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed. Results This study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability. Conclusion We delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells. Video Abstract

Abstract Melatonin is a functionally conserved broad-spectrum physiological regulator found in most biological organisms in nature. Enrichment of tomato fruit with melatonin not only enhances its agronomic traits but also provides extra health benefits. In this study, we elucidate the full melatonin biosynthesis pathway in tomato fruit by identifying biosynthesis-related genes that encode caffeic acid O-methyltransferase 2 (SlCOMT2) and N-acetyl-5-hydroxytryptamine-methyltransferases 5/7 (SlASMT5/7). We further reveal that red light supplementation significantly enhances the melatonin content in tomato fruit. This induction relies on the “serotonin—N-acetylserotonin—melatonin” biosynthesis route via the SlphyB2-SlPIF4-SlCOMT2 module. Based on the regulatory mechanism, we design a gene-editing strategy to target the binding motif of SlPIF4 in the promoter of SlCOMT2, which significantly enhances the production of melatonin in tomato fruit. Our study provides a good example of how the understanding of plant metabolic pathways responding to environmental factors can guide the engineering of health-promoting foods.

Abstract Ferroptosis is a recently recognized form of regulated cell death, characterized by iron-dependent accumulation of lipid peroxidation. Ample evidence has depicted that ferroptosis plays an essential role in the cause or consequence of human diseases, including cancer, neurodegenerative disease and acute kidney injury. However, the exact role and underlying mechanism of ferroptosis in fibrotic kidney remain unknown. Acyl-CoA synthetase long-chain family member 4 (ACSL4) has been demonstrated as an essential component in ferroptosis execution by shaping lipid composition. In this study, we aim to discuss the potential role and underlying mechanism of ACSL4-mediated ferroptosis of tubular epithelial cells (TECs) during renal fibrosis. The unbiased gene expression studies showed that ACSL4 expression was tightly associated with decreased renal function and the progression of renal fibrosis. To explore the role of ACSL4 in fibrotic kidney, ACSL4 specific inhibitor rosiglitazone (ROSI) was used to disturb the high expression of ACSL4 in TECs induced by TGF-β, unilateral ureteral obstruction (UUO) and fatty acid (FA)-modeled mice in vivo, and ACSL4 siRNA was used to knockdown ACSL4 in TGF-β-induced HK2 cells in vitro. The results demonstrated that inhibition and knockdown of ACSL4 effectively attenuated the occurrence of ferroptosis in TECs and alleviated the interstitial fibrotic response. In addition, the expression of various profibrotic cytokines all decreased after ROSI-treated in vivo and in vitro. Further investigation showed that inhibition of ACSL4 obviously attenuates the progression of renal fibrosis by reducing the proferroptotic precursors arachidonic acid- and adrenic acid- containing phosphatidylethanolamine (AA-PE and AdA-PE). In conclusion, these results suggest ACSL4 is essential for tubular ferroptotic death during kidney fibrosis development and ACSL4 inhibition is a viable therapeutic approach to preventing fibrotic kidney diseases.

Abstract Background Assisted reproductive technologies (ART) have increased the incidence of multiple births, which can have a negative impact on maternal and offspring health. The study aimed to investigate the association between genetically predicted multiple birth and the risk of 42 common diseases of the nervous, psychiatric, cardiovascular, respiratory, digestive, and endocrine systems. Methods The study utilized two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between genetically predicted multiple birth and the genetically predicted risk of diseases. The study used the FinnGen and UK Biobank datasets for analysis. Results The study found no significant causal relationship between multiple birth and psychiatric disorders. However, the lower limits of the 95% confidence intervals for bipolar affective disorder and anxiety disorders were not robust, indicating a need for further investigation. The study found that multiple birth may be a strong risk factor for infantile cerebral palsy, and caution is necessary in both natural and ART multiple births. The study revealed a potential causal relationship between multiple birth and coronary heart disease, ischemic heart disease, and deep vein thrombosis, which may be related to abnormal intrauterine environments in multiple pregnancies. Surprisingly, multiple birth appears to have a protective effect against some respiratory diseases, such as chronic obstructive pulmonary disease and asthma. Conclusions The study highlights the need for caution regarding the risk of infantile cerebral palsy, cardiovascular diseases, and psychiatric disorders in multiple birth. Our study can lead to the development of preventive strategies and improved clinical management for affected infants.

Cultivated peanut (Arachis hypogaea L.) is a key oil- and protein-providing legume crop of the world. It is full of nutrients, and its nutrient profile is comparable to that of other nuts. Peanut is a unique plant as it showcases a pegging phenomenon, producing flowers above ground, and after fertilization, the developing peg enters the soil and produces seeds underground. This geocarpic nature of peanut exposes its seeds to soil pathogens. Peanut seeds are protected by an inedible pericarp and testa. The pericarp- and testa-specific promoters can be effectively used to improve the seed defense. We identified a pericarp- and testa-abundant expression gene (AhN8DT-2) from available transcriptome expression data, whose tissue-specific expression was further confirmed by the qRT-PCR. The 1827bp promoter sequence was used to construct the expression vector using the pMDC164 vector for further analysis. Quantitative expression of the GUS gene in transgenic Arabidopsis plants showed its high expression in the pericarp. GUS staining showed a deep blue color in the pericarp and testa. Cryostat sectioning of stained Arabidopsis seeds showed that expression is only limited to seed coat (testa), and staining was not present in cotyledons and embryos. GUS staining was not detected in any other tissues, including seedlings, leaves, stems, and roots, except for some staining in flowers. Under different phytohormones, this promoter did not show an increase in expression level. These results indicated that the AhN8DT-2 promoter drives GUS gene expression in a pericarp- and testa-specific manner. The identified promoter can be utilized to drive disease resistance genes, specifically in the pericarp and testa, enhancing peanut seed defense against soil-borne pathogens. This approach has broader implications for improving the resilience of peanut crops and other legumes, contributing to sustainable agricultural practices and food security.

Abstract Docosahexaenoic acid (DHA) supplementation is recommended for women during pregnancy because of its neurological, visual, and cognitive effects. Previous studies have suggested that DHA supplementation during pregnancy may prevent and treat certain pregnancy complications. However, there are contradictions in the current related studies, and the specific mechanism by which DHA acts remains unclear. This review summarizes the research on the relationship between DHA intake during pregnancy and preeclampsia, gestational diabetes mellitus, preterm birth, intrauterine growth restriction, and postpartum depression. Furthermore, we explore the impact of DHA intake during pregnancy on the prediction, prevention, and treatment of pregnancy complications as well as its impact on offspring neurodevelopment. Our results suggest that there is limited and controversial evidence for the protective effect of DHA intake on pregnancy complications, with the exception of preterm birth and gestational diabetes mellitus. However, additional DHA supplementation may improve long-term neurodevelopmental outcomes in the offspring of women with pregnancy complications.

Abstract Background Osteosarcopenia is a syndrome with a concomitant presence of both sarcopenia and osteopenia/osteoporosis. It increases the risk of frailty, falls, fractures, hospitalization, and death. Not only does it burden the lives of older adults, but it also increases the economic burden on health systems around the world. This study aimed to review the prevalence and risk factors of osteosarcopenia to generate important references for clinical work in this area. Methods Pubmed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, CBM, and VIP databases were searched from inception until April 24th, 2022. The quality of studies included in the review was evaluated using the NOS and AHRQ Scale. Pooled effects of the prevalence and associated factors were calculated using random or fixed effects models. Egger’s test, Begg’s test, and funnel plots were used to test the publication bias. Sensitivity analysis and subgroup analysis were conducted to identify the sources of heterogeneity. Statistical analysis was performed using Stata 14.0 and Review Manager 5.4. Results A total of 31 studies involving 15,062 patients were included in this meta-analysis. The prevalence of osteosarcopenia ranged from 1.5 to 65.7%, with an overall prevalence of 21% (95% CI: 0.16–0.26). The risk factors for osteosarcopenia were female (OR 5.10, 95% CI: 2.37–10.98), older age (OR 1.12, 95% CI: 1.03–1.21), and fracture (OR 2.92, 95% CI: 1.62–5.25). Conclusion The prevalence of osteosarcopenia was high. Females, advanced age, and history of fracture were independently associated with osteosarcopenia. It is necessary to adopt integrated multidisciplinary management.

Abstract Soil microbial community composition plays a key role in the decomposition of organic matter, while the quality of exogenous organic matter (EOM: rice straw, roots and pig manure) can influence soil chemical and biological properties. However, the evidences of the effect of combination of crop residues and pig manure on the changes in soil microbial community and enzymes activities are scarce. A greenhouse pot experiment was conducted to investigate the potential effect of EOM by analyzing soil properties, enzyme activities and microbial communities. The experiment consisted of eight treatments: CK (control), S (1% (w/w) rice straw), R (1% (w/w) rice root), SR (1% (w/w) rice straw + 1% (w/w) rice root), and added 1% (w/w) pig manure to CK, S, R and SR, respectively. Results showed that the straw treatment significantly increased the microbial biomass (carbon and nitrogen) and total carbon and nitrogen contents, cellulase and β-1,4-glucosidase activities, bacteria (i.e., gram-positive bacteria and gram-negative bacteria) PLFAs contents relative to CK regardless of whether pig manure was added. Moreover, the interaction between crop residues (e.g., straw and roots) and pig manure significantly influenced the contents of microbial biomass nitrogen and microbial biomass phosphorus, and the ratio of gram-positive bacteria to gram-negative bacteria. Redundance analysis confirmed that pH, nitrate nitrogen, ammonium nitrogen and dissolve organic carbon contents were significantly associated with soil microbial community under crop residues without pig manure addition. Furthermore, the experiment results showed that pig manure application not only provided more abundant nutrients (C, N and P) but also induced higher microbial and enzymatic activity compared with no pig manure addition. Our findings suggest that the combination of above-ground straw and pig manure is a better option for improving the functions of soil ecosystem.

Traditional univariate drought indices may not be sufficient to reflect comprehensive information on drought. Therefore, this paper proposes a new composite drought index that can comprehensively characterize meteorological and hydrological drought. In this study, the new drought index was established by combining the standardized precipitation index (SPI) and the standardized baseflow index (SBI) for the Jiaojiang River Basin (JRB) using the copula function. The prediction model was established by training random forests on past data, and the driving force behind the combined drought index was explored through the LIME algorithm. The results show that the established composite drought index combines the advantages of SPI and SBI in drought forecasting. The monthly and annual droughts in the JRB showed an increasing trend from 1991 to 2020, but the temporal characteristics of the changes in each subregion were different. The accuracies of the trained random forest model for heavy drought in Baizhiao (BZA) and Shaduan (SD) stations were 83% and 88%, respectively. Furthermore, the Local Interpretable Model-Agnostic Explanations (LIME) interpretation identified the essential precipitation, baseflow, and evapotranspiration features that affect drought. This study provides reliable and valid multivariate indicators for drought monitoring and can be applied to drought prediction in other regions.

Auxins play crucial regulatory roles in plants coping with cadmium (Cd) stress. However, the regulatory mechanism by which auxins alleviate Cd toxicity in tomato seedlings remains unclear. Here, we demonstrate that exposure to Cd stress leads to dynamic changes in the auxin response in tomato roots, characterized by an initial increase followed by a subsequent weakening. Under Cd stress, tomato seedlings show primary root- and hypocotyl-growth inhibition, accompanied by the accumulation of Cd and reactive oxygen species (ROS) in the roots. The exogenous application of 1-naphthylacetic acid (NAA) does not mitigate the inhibitory effect of Cd toxicity on primary root growth, but it does significantly enhance lateral root development under Cd stress. Auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA) and 2,3,5-triiodobenoic acid (TIBA), aggravate the growth inhibition of primary roots caused by Cd stress. Additionally, lateral root development was inhibited by NPA. However, applying auxin synthesis inhibitors L-kynurenine (kyn) and yucasin alleviated the tomato root growth inhibition caused by Cd stress; between them, the effect of yucasin was more pronounced. Yucasin mitigates Cd toxicity in tomato seedlings by reducing Cd2+ absorption and auxin accumulation, strengthening ROS scavenging, and reducing cell death in roots. These observations suggest that yucasin potentially mitigates Cd toxicity and improves the tolerance of tomato seedlings to Cd stress.

Baseflow is the part of streamflow that is mainly replenished by groundwater. The protection of the biological environment and the growth of its water resources greatly depend on the spatial and temporal evolution of baseflow. Therefore, the Baizhiao (BZA) and Shaduan (SD) catchments of the Jiaojiang River Basin (JRB) in the Zhejiang province of China were selected as study areas. The ABCD model and Eckhardt method were used to calculate baseflow and baseflow index (BFI). The temporal and spatial evolution patterns of baseflow were analyzed through statistical analysis and the Mann–Kendall test. The results showed that the ABCD model performs well in simulating overall hydrological processes on the monthly streamflow at BAZ and SD stations with NSE (Nash–Sutcliffe Efficiency) values of 0.82 and 0.83 and Pbias (Percentage Bias) values of 9.2% and 8.61%, respectively. The spatial–temporal distribution of the BFI indicates the higher baseflow contribution in upstream areas compared to downstream areas at both stations. The baseflow and BFI had significant upward trends at the BZA and SD stations in the dry season, while their trends were not uniform during the wet period. These findings are essential guidance for water resource management in the JRB regions.

In recent years, as more and more fossil species of berothids from Myanmar have been reported, the species and morphological diversity of Berothidae continues to increase. Herein, one new species of Berothidae, Aggregataberotha paucipunctata sp. nov., and one new genus, Sejunctaberotha gen. nov., with three new species (Sejunctaberotha sphaerica gen. et sp. nov., Sejunctaberotha tenuis gen. et sp. nov. and Sejunctaberotha transversa gen. et sp. nov.) are described from mid-Cretaceous Myanmar amber. A. paucipunctata sp. nov. is assigned to Aggregataberotha Wang, Huang & Wang, 2022, based on the characteristics of the similar female terminalia and wing venation, but can be different from A. punctate regarding the pale pterostigma and a few detailed features of wing venation. Additionally, representatives of Sejunctaberotha gen. nov. are remarkably different from the representatives of the other genera within Berothidae in the configuration of wing venation. For example, Sejunctaberotha gen. nov. has simple subcostal veinlets, obviously free Sc and RA at the apex present both in fore- and hindwings, a single ra-rp crossvein connecting the RA with RP3, a single rp-m crossvein locating before the origin of the MP, a simple CuP and no gradate veins. Interestingly, in one of the specimens of Sejunctaberotha gen. nov., a pair of spherical bulges was found at the end of the antennae. The new genus Sejunctaberotha gen. nov. suggests that Berothidae had a higher potential diversification during the Mesozoic Era.

Key Clinical Message Coronavirus disease 2019 (COVID‐19) is known to trigger systemic inflammation and elicit immune responses, which may disrupt the delicate balance of cytokines involved in psoriatic regulation. Compared to other therapies in dermatology, biologics used for immune‐mediated dermatological diseases have been more extensively studied during the COVID‐19 pandemic. Herein, we report a case of flare‐up of previously well‐controlled psoriasis shortly after infection with COVID‐19, with treatment transition from secukinumab to adalimumab.

This study aims to investigate the effect of limestone filler, sulfate concentration and temperature on the thaumasite sulfate attack (TSA) in Portland cement (PC)-calcium aluminate cement (CAC)-gypsum ternary system. The compressive strength of mortar was tested, while X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were used to analyze the deteriorated products. The results indicate that the ternary system with limestone filler is susceptible to TSA. The higher the limestone content, the higher the TSA is in systems with MgSO4 solution of less than 5%. When the limestone filler content is 10% or 20%, the sulfate attack is mainly presented as gypsum sulfate attack. When the concentration of MgSO4 solution increases, the corrosion is diminished. The ternary system exposed to low concentration MgSO4 solution of 5% is prone to form thaumasite. The lower the temperature, the more vulnerable the system is to TSA. The mortar at 5 °C under 5% MgSO4 solution is rarely damaged and thaumasite could easily be detected.

Radiometric correction is one of the most important preprocessing parts of unmanned aerial vehicle (UAV) multispectral remote sensing data analysis and application. In this article, a back propagation (BP) neural network-based radiometric correction method (BPNNRCM) considering optimal parameters was proposed. First, we used different UAV multispectral sensors (K6 equipped on the DJI M600, D-MSPC2000 equipped on the FEIMA D2000) to collect training, validation, testing and cross-validation data. Second, the radiometric correction results of BP neural network with different input variables and hidden layer node number were compared to select the best combination of input parameters and hidden layer node number. Finally, the radiometric correction accuracy and robustness of BP neural network considering the optimal parameters were verified. When the number of nodes in the input layer was five (digital number, UAV sensor height, wavelength, solar altitude angle, and temperature) and the number of nodes in the hidden layer was eight, the BP neural network had the best comprehensive performance in training time of train set and accuracy of validation/test set. In the aspect of accuracy and robustness, the absolute errors of test and cross-validation images' surface reflectance obtained by the BPNNRCM were all less than 0.054. The BPNNRCM had smaller average absolute error (0.0141), mean squared error (0.0003), mean absolute error (0.0141) and mean relative error (7.1%) comparing with empirical line method and radiative transfer model. In general, the research results of this article prove the feasibility and prospect of BPNNRCM for radiometric correction of UAV multispectral images.

Abstract Background Electromagnetic induction has recently been considered as an important factor affecting the activity of neurons. However, as an important form of intervention in epilepsy treatment, few people have linked the two, especially the related dynamic mechanisms have not been explained clearly. Methods Considering that electromagnetic induction has some brain area dependence, we proposed a modified two-compartment cortical thalamus model and set eight different key bifurcation parameters to study the transition mechanisms of epilepsy. We compared and analyzed the application and getting rid of memristors of single-compartment and coupled models. In particular, we plotted bifurcation diagrams to analyze the dynamic mechanisms behind abundant discharge activities, which mainly involved Hopf bifurcations (HB), fold of cycle bifurcations (LPC) and torus bifurcations (TR). Results The results show that the coupled model can trigger more discharge states due to the driving effect between compartments. Moreover, the most remarkable finding of this study is that the memristor shows two sides. On the one hand, it may reduce tonic discharges. On the other hand, it may cause new pathological states. Conclusions The work explains the control effect of memristors on different brain regions and lays a theoretical foundation for future targeted therapy. Finally, it is hoped that our findings will provide new insights into the role of electromagnetic induction in absence seizures.

Excessive cell-free DNA (cfDNA) released by damaged or apoptotic cells can cause inflammation, impacting the progression of rheumatoid arthritis (RA). cfDNA scavengers, such as cationic nanoparticles (NPs), have been demonstrated as an efficient strategy for treating RA. However, most scavengers are limited by unfavorable biocompatibility and poor scavenging efficacy. Herein, by exploiting the favorable biocompatibility, biodegradability and bioadhesion of polydopamine (P), we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfDNA for RA therapy. Results showed that DPs endowed with superior binding affinity of cfDNA and little cytotoxicity, which effectively inhibited lipopolysaccharide (LPS) stimulated inflammation in vitro, resulting in the relief of joint swelling, synovial hyperplasia and cartilage destruction in RA rats. Significantly, DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfDNA binding affinity, leading to excellent RA therapeutic effect among all of the treated groups, which was even close to normal rats. These finding provides a novel strategy for the treatment of cfDNA-associated diseases.

Abstract Melanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine phosphatase non-receptor type7 (PTPN7), a phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.

Abstract Background Metastatic melanoma has a high mortality rate and poor survival. This is associated with efficient metastatic colonization, but the underlying mechanisms remain elusive. Communication between cancer stem cells (CSCs) and cancer cells plays an important role in metastatic dissemination. Whether cancer stem cells can alter the metastatic properties of non-CSC cells; and whether exosomal crosstalk can mediate such interaction, have not been demonstrated in melanoma prior to this report. Results The results revealed that exosomes secreted by highly metastatic melanoma CSCs (OL-SCs) promoted the invasiveness of the low metastatic melanoma cells (OL) and accelerated metastatic progression. miR-1268a was up-regulated in cells and exosomes of OL-SCs. Moreover, OL-SCs-derived exosomal miR-1268a, upon taking up by OL cells, promoted the metastatic colonization ability of OL cells in vitro and in vivo. In addition, the pro-metastatic activity of exosomal miR-1268a is achieved through inhibition of autophagy. Conclusion Our study demonstrates that OL cells can acquire the “metastatic ability” from OL-SCs cells. OL-SCs cells achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-1268a, to the targeted OL cells which in turn augments metastatic colonization by inactivating the autophagy pathway in OL cells.

Abstract Background Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology. Methods HLP hamster model was induced by high-fat diet. Hematoxylin—eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology. Results The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP. Conclusions In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

BackgroundPrevious observational studies have reported the striking association between ankylosing spondylitis (AS) and psoriasis, but the causal relationship between the two diseases remains unclear.MethodsTwo-sample Mendelian randomization (MR) analysis with methods of inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode was conducted to evaluate the bidirectional causal associations between AS and psoriasis. Effective single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) were selected as instrumental variables (IVs). Sensitivity analyses were also applied to verify whether heterogeneity and pleiotropy can bias the results.ResultWe found positive causal effects of genetically increased AS risk on psoriasis (IVW: OR = 1.009, 95% CI = 1.005–1.012, p = 8.07E-07). Comparable outcomes were acquired by MR-Egger regression, weighted median, and weighted mode approaches. Nevertheless, we did not find significant causal effects of psoriasis on AS (IVW: OR = 1.183, 95% CI = 0.137–10.199, p = 0.879). The sensitivity analyses showed that the horizontal pleiotropy was unlikely to skew the causality. The leave-one-out analysis demonstrated that no single SNP can drive the MR estimates. No evidence of heterogeneity was found between the selected IVs.ConclusionOur findings provide evidence that AS has positive causal effects on the risk of psoriasis in the European population.

Precise identification of spatial unit functional features in the city is a pre-condition for urban planning and policy-making. However, inferring unknown attributes of urban spatial units from data mining of spatial interaction remains a challenge in geographic information science. Although neural-network approaches have been widely applied to this field, urban dynamics, spatial semantics, and their relationship with urban functional features have not been deeply discussed. To this end, we proposed semantic-enhanced graph convolutional neural networks (GCNNs) to facilitate the multi-scale embedding of urban spatial units, based on which the identification of urban land use is achieved by leveraging the characteristics of human mobility extracted from the largest mobile phone datasets to date. Given the heterogeneity of multi-modal spatial data, we introduced the combination of a systematic data-alignment method and a generative feature-fusion method for the robust construction of heterogeneous graphs, providing an adaptive solution to improve GCNNs’ performance in node-classification tasks. Our work explicitly examined the scale effect on GCNN backbones, for the first time. The results prove that large-scale tasks are more sensitive to the directionality of spatial interaction, and small-scale tasks are more sensitive to the adjacency of spatial interaction. Quantitative experiments conducted in Shenzhen demonstrate the superior performance of our proposed framework compared to state-of-the-art methods. The best accuracy is achieved by the inductive GraphSAGE model at the scale of 250 m, exceeding the baseline by 25.4%. Furthermore, we innovatively explained the role of spatial-interaction factors in the identification of urban land use through the deep learning method.

Cadmium (Cd) is one of the major pollutants in the aquatic environment, and it can easily accumulate in aquatic animals and result in toxic effects by changing the metabolism of the body, causing a serious impact on the immune system, reproductive system, and the development of offspring. The clam Meretrix meretrix is one of the commercially important species that is cultivated in large-scale aquaculture in China. To elucidate the underlying molecular mechanisms of Cd2+ in the developmental processes, fertilized eggs and larvae of M. meretrix at different developmental stages were exposed to Cd2+ (27.2 mg L−1 in natural seawater) or just natural seawater without Cd2+ (control), and high-throughput transcriptome sequencing and immunohistochemistry techniques were used to analyze the toxic effects of Cd on larvae at different early developmental stages. The results revealed 31,914 genes were differentially expressed in the different stages of M. meretrix development upon treatment with Cd2+. Ten of these genes were differentially expressed in all stages of development examined, but they comprised only six unigenes (CCO, Ndh, HPX, A2M, STF, and pro-C3), all of which were related to the oxidative stress response. Under Cd exposure, the expression levels of CCO and Ndh were significantly upregulated in D-shaped and pediveliger larvae, while pro-C3 expression was significantly upregulated in the fertilized egg, D-shaped larva, and pediveliger. Moreover, HPX, A2M, and STF expression levels in the fertilized egg and pediveliger larvae were also significantly upregulated. In contrast, CCO, Ndh, HPX, A2M, STF, and pro-C3 expression levels in the postlarva were all downregulated under Cd exposure. Besides the genes with changes in expression identified by the transcriptome, the expression of two other oxidative stress-related genes (MT and Nfr2) was also found to change significantly in the different developmental stages of M. meretrix upon Cd exposure, confirming their roles in combating oxidative stress. Overall, the findings of this study indicated that Cd would interfere with cellular respiration, ion transport, and immune response through inducing oxidative stress, and changes in the expression of oxidative stress-related genes might be an important step for M. meretrix to deal with the adverse effects of Cd at different stages of its development.

The liver plays a vital role in metabolism, synthesis, and detoxification, but it is susceptible to damage from various factors such as viral infections, drug reactions, excessive alcohol consumption, and autoimmune diseases. This susceptibility is particularly problematic for patients requiring medication, as drug-induced liver injury often leads to underestimation, misdiagnosis, and difficulties in treatment. Acetaminophen (APAP) is a widely used and safe drug in therapeutic doses but can cause liver toxicity when taken in excessive amounts. This study aimed to investigate the hepatotoxicity of APAP and explore potential treatment strategies using a mouse model of APAP-induced liver injury. The study involved the evaluation of various natural products for their therapeutic potential. The findings revealed that natural products demonstrated promising hepatoprotective effects, potentially alleviating liver damage and improving liver function through various mechanisms such as oxidative stress and inflammation, which cause changes in signaling pathways. These results underscore the importance of exploring novel treatment options for drug-induced liver injury, suggesting that further research in this area could lead to the development of effective preventive and therapeutic interventions, ultimately benefiting patients with liver injury caused by medicine.

Objectives Autoimmune diseases are a kind of chronic diseases for which the immune system loses tolerance to autoantigens. This meta-analysis’ purpose is to determine whether there exists a correlation between IL-23R polymorphism and common autoimmune diseases like ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Methods We searched the relevant literatures up to September 2021 and used different effect models for meta-analysis. 95% confidence interval (95% CI) and odds ratio (OR) were used to determine the relationship between rs10889677 (A/C) polymorphism and AS as well as RA. Finally, to promote the reliability of results, the trial sequential analysis (TSA) has also been applied and we searched the data related to autoimmune diseases (AS, RA) on genome-wide association studies (GWAS). Results Generally, 31 studies were included. Rs10889677 (A/C) was significantly correlated with the susceptibility to AS and RA among the general individuals (p