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The research on coastal ecological carrying capacity holds great significance for the sustainable development of coastal areas and is a focal point of the United Nations Sustainable Development Goals (SDGs). This study coupled multi-source data and ecological analysis models to construct a multi-level evaluation system and analysis method for the coastal ecological carrying capacity of Shandong Province so as to realize the dynamic monitoring and evaluation of the coastal ecological carrying capacity of Shandong Province from 2010 to 2020. The results indicated: (1) The ecological carrying capacity of the coastal zone in Shandong Province showed a “U”-shaped development trend, with 2016 being a turning point. (2) The economic development–social support system gradually became the main force driving the overall improvement of coastal ecological carrying capacity. (3) The system coupling coordination degree of ecological carrying capacity in the coastal areas of Shandong Province showed a trend of first decreasing and then increasing, with a high level of internal coupling coordination of carrying capacity. (4) Per capita GDP, environmental protection investment, per capita water resources, and other indicators were the main factors driving the changes in the ecological carrying capacity of the coastal zone. This study aims to provide methodological reference and data support for coastal ecosystem monitoring, assessment, and climate change response.

Aiming to address the complexity and challenges of predicting pure electric vehicle (EV) sales, this paper integrates a time series model, support vector machine and combined model to forecast EV sales in China. Firstly, a seasonal autoregressive integrated moving average (SARIMA) model was constructed using historical EV sales data, and the model was trained on sales statistics to obtain forecasting results. Secondly, variables that were highly correlated with sales were analyzed using gray relational analysis (GRA) and utilized as input parameters for the support vector regression (SVR) model, which was constructed to optimize sales predictions for EVs. Finally, a combined model incorporating different algorithms was verified against market sales data to explore the optimal sales prediction approach. The results indicate that the SARIMA-GRA-SVR model with the squared prediction error and inverse method achieved the best predictive performance, with MAPE, MAE and RMSE values of 12%, 1.45 and 2.08, respectively. This empirical study validates the effectiveness and superiority of the SARIMA-GRA-SVR model in forecasting EV sales.

Nitric oxide (NO) is an important signaling molecule involved in regulating plant processes to cope with abiotic stress. S-allyl-L-cysteine (SAC) is known to induce NO synthesis in animals. However, it is unknown whether SAC can trigger NO biosynthesis, regulate Cd transport, or alleviate Cd stress in plants. After being sprayed with 0.2 mM SAC, rice seedlings had a NO content that was 1.8 times higher than that of the control (ctrl) group at the ninth hour, which then gradually decreased. The expressions of Cd uptake and transport genes in the roots (including OsNRAMP5, OsNRAMP1, and OsHMA2) were markedly downregulated by 27.2%, 24.8%, and 49.1%, respectively, 72 h after SAC spraying treatment. The Cd content in seedling roots’ cell wall (CW) components significantly increased by 43.5% compared to that of the ctrl group. The Cd content in the shoots and roots decreased by 49.0% and 29.8%, respectively. Cd stress in the seedlings was also substantially alleviated. In conclusion, spraying rice seedlings with SAC triggered an increase in NO synthesis, regulated the expression of genes related to Cd transport, increased Cd fixation in the root CW components, and reduced Cd accumulation in the roots and shoots.

Japanese encephalitis (JE) is a mosquito-borne infectious disease caused by the Japanese encephalitis virus (JEV). There is currently no effective treatment for JE, and all approved Japanese encephalitis vaccine products originated from the JEV genotype III (GIII). In recent years, JEV genotype I (GI) has gradually replaced GIII as the dominant genotype, and a new symptom of peripheral nerve injury (PNI) caused by JEV NX1889 strain has attracted wide attention, in which JEV envelope (E) protein may be involved in early peripheral nerve injury. Here, the envelope (E) gene of JEV GIb, NX1889 strain was cloned into pET-32a (+) plasmid, and then the E protein was successfully expressed as the high-yield inclusion body form in Escherichia coli (E. coli) BL21 (DE3). Subsequently, we successfully developed a simplified approach to generate soluble JEV E protein by solubilization, and a stepwise dialysis refolding approach with the introduction of a redox system. The refolding recombinant E protein was identified by anti-JEV-E polyclonal antibody and the serum anti-E titer of mice immunized with refolded E protein was higher than 1: 409,600, which proves it has highly immunoreactive. Moreover, the recombinant E protein could recognize antibodies in samples of multiple species and types, such as mice, rabbits, and humans. The approach described above is economical and does not require complex eukaryotic expression systems to produce immunoreactive JEV E protein, which may be of great significance for the diagnosis and pathogenesis of JEV GI strain.

Objectives: We aimed to estimate the effectiveness of telemedicine for the prevention of mother-to-child transmission (PMTCT) program of HIV in low- and middle-income countries (LMICs). Methods: We did a systematic literature search of 15 databases for articles published from database inception to October 26, 2022, and performed meta-analyses to estimate the pooled risk ratio of intervention effect (RR) and its 95% confidence interval (CI). We used subgroup analyses and meta-regressions to explore variation in the RRs. Funnel plots and Egger regression tests were also performed to assess publication bias. Results: Seventeen studies were included in the systematic review, with a total sample size of 9118 participants. We found that telemedicine was beneficial for early infant diagnosis (EID) in the sixth week (RR 1.04 [95% CI 1.00-1.09]), exclusive breastfeeding (RR 1.12 [95% CI 1.01-1.24]) and PMTCT retention (RR 1.34 [95% CI 1.16-1.55]). However, we did not find a significant effect of telemedicine on infant prophylaxis, HIV transmission, and ART adherence. Besides, the heterogeneity of ART adherence was associated with enrollment time, while retention was related to ART initiation. Conclusions: Our meta-analysis demonstrated the benefits of telemedicine in improving PMTCT, especially for EID, exclusive breastfeeding, and PMTCT retention.

The attractive properties of ye'elimite (C4A3$) are receiving particular attention in cement and repairing materials. The present paper aims to further explore the difference in hydration performance of different C4A3$ phases (o-C4A3$ and c-C4A3$) using the Ga-doping method. On this basis, C4A3-xGx$ specimens (noted as C4A3$, C4A2.3G0.7$, and C4A1.6G1.4$) were first synthesized and their hydration characteristics were systematically studied. Results showed that Ga-doping enhanced the hydration activity of ye'elimite. With increasing Ga3+ ions addition, the intensity of the initial peak gradually increased, but the duration of the induction period and the hydration heat development rate were gradually reduced. The conductivity and pore solution analysis also demonstrated a higher ion concentration precipitation at the early stage for cubic C4A1.6G1.4$ compared to pure C4A3$. The main hydration products of these specimens were AFt, AFm, and AH3 (gel). Moreover, the addition of Ga3+ ions improved the crystallinity of AFt and AFm with recorded a relatively higher decomposition temperature. Overall, this study demonstrated that the addition of Ga3+ ions can regulate the hydration characteristics of ye'elimite.

Abstract The middle and lower reaches of the Yangtze River serve as principal rice production bases in China, yet the biodiversity and ecological processes of bacterial communities in paddy soils are not well understood. This study explores the diversity, composition, ecological function, and assembly processes of abundant and rare bacterial communities in paddy soils. A total of 129 paddy soil samples from 43 sites along the middle and lower reaches of the Yangtze River were collected and analyzed using NovaSeq sequencing. The results showed that the dominant phylum for both abundant and rare taxa was Proteobacteria, with a greater relative abundance of the abundant taxa. The diversity of the abundant community was lower than that of the rare community. Soil properties and geographic variables explained more of the variation in the abundant community than in the rare community. The rare community exhibited a significant distance‐decay relationship. The assembly of the abundant community was more influenced by stochastic processes, although both the abundant and rare communities were governed by stochastic processes. It is concluded that both abundant and rare bacterial communities exhibit differing biogeographic patterns, yet they undergo similar ecological processes in the paddy soils along the middle and lower reaches of the Yangtze River. These observations offer a theoretical framework for a deeper comprehension of the function of both abundant and rare bacteria, as well as the development and preservation of soil bacterial diversity within agricultural ecosystems.

IntroductionArts therapies offer effective non-pharmacological intervention for Sleep Initiation and Maintenance Disorders (SIMDs), encompassing both passive and active modalities. This review assesses their effectiveness and ethical considerations, focusing on music therapy, meditation, and Tai Chi.MethodsFollowing PRISMA guidelines, a detailed search across PubMed, the Cochrane Library, Web of Science, and CNKI identified 17 relevant RCTs. Utilizing the Joanna Briggs Institute (JBI) quality criteria and the PICO(S) framework for data extraction ensured methodological integrity.ResultsAnalysis shows arts therapies significantly improve sleep quality. Music therapy and meditation yield immediate benefits, while Tai Chi and Qigong require longer commitment for significant outcomes. DiscussionThe link between SIMDs and mental health issues like anxiety, stress, and depression suggests arts therapies not only enhance sleep quality but also address underlying mental health conditions. The evidence supports a wider adoption of arts therapies in treating SIMDs due to their dual benefits.Systematic review registrationPROSPERO, ID: CRD42024506393.

Primary familial brain calcification (PFBC) is a rare genetic neurodegenerative disorder characterized by bilateral calcifications in the brain. PFBC may manifest with a broad spectrum of motor, cognitive, and neuropsychiatric symptoms. Several causal genes have been identified in PFBC, which are inherited as both autosomal dominant and autosomal recessive traits. Herein, we present the case of a Chinese family diagnosed with PFBC. The family members carry a rare heterozygous variant (p. R334Q) in exon 7 of platelet-derived growth factor receptor β (PDGFRB) gene. The platelet-derived growth factor-B/PDGF receptor β (PDGF-B/PDGFRβ) signaling pathway plays a crucial role in pericyte development in various organs and tissues. Notably, this variant uniquely coexists with nontraumatic osteonecrosis of the femoral head. Additionally, we reviewed previous studies on PFBC-causing variants in PDGFRB.

Abstract Ferroptosis is a newly discovered form of cell death that is featured in a wide range of diseases. Exosome therapy is a promising therapeutic option that has attracted much attention due to its low immunogenicity, low toxicity, and ability to penetrate biological barriers. In addition, emerging evidence indicates that exosomes possess the ability to modulate the progression of diverse diseases by regulating ferroptosis in damaged cells. Hence, the mechanism by which cell-derived and noncellular-derived exosomes target ferroptosis in different diseases through the system Xc−/GSH/GPX4 axis, NAD(P)H/FSP1/CoQ10 axis, iron metabolism pathway and lipid metabolism pathway associated with ferroptosis, as well as its applications in liver disease, neurological diseases, lung injury, heart injury, cancer and other diseases, are summarized here. Additionally, the role of exosome-regulated ferroptosis as an emerging repair mechanism for damaged tissues and cells is also discussed, and this is expected to be a promising treatment direction for various diseases in the future. Video Abstract

Abstract Purpose To investigate the optimal threshold for measuring thyroid volume in patients with Grave's hyperthyroidism (GH) by SPECT/CT. Materials and methods A 53 mL butterfly-shaped hollow container made of two 45-degree transparent elbows was put into a NEMA IEC phantom tank. The butterfly-shaped container and the tank were then filled with Na99mTcO4 of different radioactive concentrations, respectively, which could simulate thyroid gland with GH by different target-to-background ratios (T/B) (200:1, 600:1, 1000:1). The different T/B of planar imaging and SPECT/CT were acquired by a Discovery NM/CT 670 Pro SPECT/CT. With Thyroid software (Version 4.0) of GE-Xeleris workstation, the region of the thyroid gland in planar imaging was delineated. The thyroid area and average long diameter of both lobes were substituted into the Allen formula to calculate the thyroid volume. The calculation error was compared with the actual volume. Q-Metrix software was used to perform CT-based attenuation correction, scatter correction, resolution recovery. Ordered-subsets expectation maximization was used to reconstruct SPECT data. 20%, 25%, 30%, 40%, 50%, 60% thresholds were selected to automatically delineate the volume of interest and compared with the real volume, which determinated the optimal threshold. We measured the thyroid volume of 40 GH patients using the threshold and compared the volumes obtained by planar imaging and ultrasound three-dimensional. The differences of the volumes with different T/B and thresholds were compared by the ANOVA and least significant difference t test. The volumes delineated by SPECT/CT were evaluated using ANOVA, least significant difference t test, correlation analysis and, linear regression and Bland–Altman concordance test plot. The differences and consistency of thyroid volume were compared among the above three methods. Results There was no significant difference in the results between different T/B models (P > 0.05). The thyroid volume calculated by the planar imaging formula method was higher than the real volume, with an average overestimation of 22.81%. The volumes delineated by SPECT/CT threshold automatically decreased while the threshold increased. There were significant differences between groups with different thresholds (P 0.05). Thyroid volume measured by planar imaging method was significantly higher than ultrasound and SPECT/CT threshold automatic delineation method (P

Abstract The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.

To address the issue of measurement errors in ultrasonic water meters caused by various interfering factors during the flow calibration process, this study proposes a highly automated and intelligent ultrasonic water meter flow calibration system design. Firstly, by analyzing and studying the working principle of the water flow calibration device, and considering the actual flow calibration range, the calibration method that combines the master meter method and the dynamic weighing method is determined. To enhance the automation level of the flow calibration system, the flow calibration control algorithm is thoroughly analyzed and designed. Finally, a flow correction algorithm based on linear interpolation was designed and utilized for water meter flow calibration. Test data show that after the flow correction, the value error of the ultrasonic water meter in the “high area” is not more than 2%, in the “low area” it is not more than 3%, and the repeatability is less than 0.05%. Compared with manual calibration, the flow calibration system designed in this paper enables high-precision automated flow calibration of ultrasonic water meters, significantly enhancing detection efficiency and accuracy.

Aiming at the challenge of high-precision and high-reliability simulation of urban medium- and high-pressure natural gas pipeline networks, the model establishment is analyzed in detail, solution algorithm and optimization process in gas pipeline network simulation, and designs a modeling and solution method that is easy to analyze and implement to solve the complexity problem of existing natural gas pipeline network simulation algorithms. First, a steady-state simulation model was established, and the nonlinear equations were converted to linear equations using Newton’s iterative method. Then, Kirchhoff’s law and the nodal pipe segment correlation matrix are applied to establish the system of equations. Finally, by combining the iterative process of Newton’s method with the “numerical table” method, a simple calculation method based on the contribution value is established. To solve the sensitivity problem of Newton’s iterative method, the advantages of Multilayer Perceptron (MLP) in data prediction are utilized in this work. A new initial value prediction algorithm of Newton’s iterative method is proposed based on the multilayer perceptron in the real-time simulation system of gas pipeline network. In the simulation of a complex natural gas network with 134 nodes and a total length of 35.843 kilometers, the results show that the average number of iterations of the Newton’s iterative method after inputting the predicted values is reduced by 87.51% and the computation time of the simulation system is reduced by 47.32%. In addition, the absolute error between the pressure values calculated by our proposed algorithm and the pressure values calculated by the commercial software TGNET software is within 1.3% for a single point, and the average absolute error for multiple points is within 0.9%. The experimental results demonstrate the advantages of the proposed algorithm in terms of real-time, effectiveness and stability.

Abstract Background The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model. Methods The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by flow cytometry, and the levels of cytokines in cell supernatants or in sera of mice were measured (ELISA). The therapeutic effect of EgCF on sepsis was evaluated by observing the survival rates of mice for 72 h after CLP, and the pathological injury to the liver, kidney, and lung was measured under a microscope. The expression of TLR-2/MyD88 in tissues was measured by western blot to determine whether TLR-2/MyD88 is involved in the sepsis-induced inflammatory signaling pathway. Results In vitro culture with BMDMs showed that EgCF promoted macrophage polarization to M2 type and inhibited lipopolysaccharide (LPS)-induced M1 macrophages. EgCF treatment provided significant therapeutic effects on CLP-induced sepsis in mice, with increased survival rates and alleviation of tissue injury. The EgCF conferred therapeutic efficacy was associated with upregulated anti-inflammatory cytokines (IL-10 and TGF-β) and reduced pro-inflammatory cytokines (TNF-α and INF-γ). Treatment with EgCF induced Arg-1-expressed M2, and inhibited iNOS-expressed M1 macrophages. The expression of TLR-2 and MyD88 in EgCF-treated mice was reduced. Conclusions The results demonstrated that EgCF confers a therapeutic effect on sepsis by inhibiting the production of pro-inflammatory cytokines and inducing regulatory cytokines. The anti-inflammatory effect of EgCF is carried out possibly through inducing macrophage polarization from pro-inflammatory M1 to regulatory M2 phenotype to reduce excessive inflammation of sepsis and subsequent multi-organ damage. The role of EgCF in regulating macrophage polarization may be achieved by inhibiting the TLR2/MyD88 signaling pathway. Graphical Abstract

Abstract Background Congenital antithrombin deficiency is an autosomal dominant disease that results in deep venous thrombosis and pulmonary embolism, which is mainly caused by mutations in the antithrombin gene (SERPINC1). Since SERPINC1 is highly susceptible to alterations, severe structural and functional changes that promote thrombosis may occur. Clinical presentations vary from different alterations. We report a pregnant case with novel mutation in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Case presentation We report a case of a 36-year-old pregnant patient who was diagnosed with congenital antithrombin deficiency for carrying a novel heterozygous mutation, NM_000488:exon5:c.T9 38 C:p. M313T in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Thrombolytic with alteplase and anticoagulant therapies with low-molecular-weight heparin and warfarin were administrated. After confirming the genetic analysis and the termination of pregnancy, rivaroxaban was administrated, and the thrombosis reduced. Conclusions Our study enriched the mutation database of SERPINC1 gene, provided some new theoretical basis for gene diagnosis and genetic counseling of patients with transient antithrombin deficiency. While it still needs for subsequent exploration of molecular pathogenesis.

Abstract Background Pseudorabies virus (PRV) causes substantial losses in the swine industry worldwide. Attenuated PRV strains with deletions of immunomodulatory genes glycoprotein E (gE), glycoprotein I (gI) and thymidine kinase (TK) are candidate vaccines. However, the effects of gE/gI/TK deletions on PRV-host interactions are not well understood. Methods To characterize the impact of gE/gI/TK deletions on host cells, we analyzed and compared the transcriptomes of PK15 cells infected with wild-type PRV (SD2017), PRV with gE/gI/TK deletions (SD2017gE/gI/TK) using RNA-sequencing. Results The attenuated SD2017gE/gI/TK strain showed increased expression of inflammatory cytokines and pathways related to immunity compared to wild-type PRV. Cell cycle regulation and metabolic pathways were also perturbed. Conclusions Deletion of immunomodulatory genes altered PRV interactions with host cells and immune responses. This study provides insights into PRV vaccine design.

Background: A COVID-19 outbreak in the rural areas of Shijiazhuang City was attributed to the complex interactions among vaccination, host, and non-pharmaceutical interventions (NPIs). Herein, we investigated the epidemiological characteristics of all reported symptomatic cases by picking Shijiazhuang City, Hebei Province in Northern China as research objective. In addition, we established an age-group mathematical model to perform the optimal fitting and to investigate the dynamical profiles under three scenarios. Methods: All reported symptomatic cases of Shijiazhuang epidemic (January 2-February 3, 2021) were investigated in our study. The cases were classified by gender, age group and location, the distributions were analyzed by epidemiological characteristics. Furthermore, the reported data from Health Commission of Hebei Province was also analyzed by using an age-group mathematical model by two phases and three scenarios. Results: Shijiazhuang epidemic caused by SARS-CoV-2 wild strain was recorded with the peak 84 cases out of 868 reported symptomatic cases on January 11, 2021, which was implemented with strong NPIs by local government and referred as baseline situation in this study. The research results showed that R0 under baseline situation ranged from 4.47 to 7.72, and Rt of Gaocheng Distinct took 3.72 with 95% confidence interval from 3.23 to 4.35 on January 9, the declining tendencies of Rt under baseline situation were kept till February 3, the value of Rt reached below 1 on January 19 and remained low value up to February 3 for Gaocheng District and Shijiazhuang City during Shijiazhuang epidemic. This indicated Shijiazhuang epidemic was under control on January 19. However, if the strong NPIs were kept, but remote isolation operated on January 11 was not implemented as of February 9, then the scale of Shijiazhuang epidemic reached 9,482 cases from age group who were 60 years old and over out of 31,017 symptomatic cases. The investigation also revealed that Shijiazhuang epidemic reached 132,648 symptomatic cases for age group who were 60 years old and over (short for G2) under risk-based strategies (Scenario A), 58,048 symptomatic cases for G2 under late quarantine strategies (Scenario B) and 207,124 symptomatic cases for G2 under late quarantine double risk strategies (Scenario C), and that the corresponding transmission tendencies of Rt for three scenarios were consistently controlled on Jan 29, 2021. Compared with baseline situation, the dates for controlling Rt below 1 under three scenarios were delayed 10 days. Conclusions: Shijiazhuang epidemic was the first COVID-19 outbreak in the rural areas in Hebei Province of Northern China. The targeted interventions adopted in early 2021 were effective to halt the transmission due to the implementation of a strict and village-wide closure. However we found that age group profile and NPIs played critical rules to successfully contain Shijiazhuang epidemic, which should be considered by public health policies in rural areas of mainland China during the dynamic zero-COVID policy.

We, the Editors and Publisher of the journal Annals of Medicine, have retracted the following article:Bing-yaoPang, Yan Leng, Xiaoli Wang, Yi-qiang Wang & Li-hong Jiang (2023) A meta-analysis and of clinical values of 11 blood biomarkers, such as AFP, DCP, and GP73 for diagnosis of hepatocellular carcinoma, Annals of Medicine, 55:1, 42-61, DOI: http://doi.org/10.1080/07853890.2022.2153163Since publication, concerns have been raised about the integrity of the data presented in the article. When approached for an explanation, the authors have been unable to provide sufficient details to address the concerns raised. In addition, it has come to our attention that the authorship list for this manuscript was significantly changed after the submission of the article. We have contacted the authors for a full explanation but have not received a satisfactory explanation.As determining authorship and verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed.We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Abstract Background Low-pass genome sequencing (LP GS) has shown distinct advantages over traditional methods for the detection of mosaicism. However, no study has systematically evaluated the accuracy of LP GS in the detection of mosaic aneuploidies and copy number variants (CNVs) in prenatal diagnosis. Moreover, the influence of sequencing depth on mosaicism detection of LP GS has not been fully evaluated. Methods To evaluate the accuracy of LP GS in the detection of mosaic aneuploidies and mosaic CNVs, 27 samples with known aneuploidies and CNVs and 1 negative female sample were used to generate 6 simulated samples and 21 virtual samples, each sample contained 9 different mosaic levels. Mosaic levels were simulated by pooling reads or DNA from each positive sample and the negative sample according to a series of percentages (ranging from 3 to 40%). Then, the influence of sequencing depth on LP GS in the detection of mosaic aneuploidies and CNVs was evaluated by downsampling. Results To evaluate the accuracy of LP GS in the detection of mosaic aneuploidies and CNVs, a comparative analysis of mosaic levels was performed using 6 simulated samples and 21 virtual samples with 35 M million (M) uniquely aligned high-quality reads (UAHRs). For mosaic levels > 30%, the average difference (detected mosaic levels vs. theoretical mosaic levels) of 6 mosaic CNVs in simulated samples was 4.0%, and the average difference (detected mosaic levels vs. mosaic levels of Y chromosome) of 6 mosaic aneuploidies and 15 mosaic CNVs in virtual samples was 2.7%. Furthermore, LP GS had a higher detection rate and accuracy for the detection of mosaic aneuploidies and CNVs of larger sizes, especially mosaic aneuploidies. For depth evaluation, the results of LP GS in downsampling samples were compared with those of LP GS using 35 M UAHRs. The detection sensitivity of LP GS for 6 mosaic aneuploidies and 15 mosaic CNVs in virtual samples increased with UAHR. For mosaic levels > 30%, the total detection sensitivity reached a plateau at 30 M UAHRs. With 30 M UAHRs, the total detection sensitivity was 99.2% for virtual samples. Conclusions We demonstrated the accuracy of LP GS in mosaicism detection using simulated data and virtual samples, respectively. Thirty M UAHRs (single-end 35 bp) were optimal for LP GS in the detection of mosaic aneuploidies and most mosaic CNVs larger than 1.48 Mb (Megabases) with mosaic levels > 30%. These results could provide a reference for laboratories that perform clinical LP GS in the detection of mosaic aneuploidies and CNVs.

Abstract Background Enterovirus 71(EV71)-associated hand, foot and mouth disease (HFMD) decreased dramatically in Beijing from 2009 to 2019. This study was to investigate the epidemiological characteristics, evolutionary dynamics, geographic diffusion pathway, and other features of EV71 in Beijing, China. Methods We conducted a retrospective study of EV71-associated HFMD and its causative agent in Beijing, China, from 2009 to 2019. Phylogenetic and phylogeographic methods based on the EV71 genome were used to determine the evolution features, origin, and spatiotemporal dynamics. Positive selection sites in the VP1 gene were identified and exhibited in the tertiary structure. Bayesian birth-death skyline model was used to estimate the effective reproductive number (Re). Results EV71-associated HFMD decreased greatly in Beijing. From 2009 to 2019, EV71 strains prevalent in Beijing shared high homology in each gene segment and evolved with a rate of 4.99*10− 3 substitutions per site per year. The genetic diversity of EV71 first increased and peaked in 2012 and then decreased with fluctuations. The time to the most recent common ancestor (TMRCA) of EV71 in Beijing was estimated around 2003 when the EV71 strains were transmitted to Beijing from east China. Beijing played a crucial role in seeding EV71 to central China as well. Two residues (E145Q/G, A293S) under positive selection were detected from both the VP1 dataset and the P1 dataset. They were embedded within the loop of the VP1 capsid and were exposed externally. Mean Re estimate of EV71 in Beijing was about 1.007. Conclusion In recent years, EV71 was not the primary causative agent of HFMD in Beijing. The low Re estimate of EV71 in Beijing implied that strategies for preventing and controlling HFMD were performed effectively. Beijing and east China played a crucial role in disseminating EV71 to other regions in China.

Oxidative stress is a pivotal stimulating factor in neurocyte apoptosis and has been involved in the pathogenesis of Parkinson’s disease (PD). In this study, we have demonstrated that the improvement in the motor disorder of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/Pro-induced mice caused by b-Ecdysterone (b-Ecd) treatment is due to its antioxidant properties. Using open field, rotarod, and pole climbing tests, we have found that b-Ecd alleviates motor disorder in MPTP/Pro-induced mice and ultimately reduces the impairment of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra (SN). Notably, these effects of b-Ecd were not observed in Nrf2-KO mice. In addition, b-Ecd significantly reduced the formation of ROS and the level of MDA, blocked the increase of LPO, and partially reversed the GSH/GSSG ratio in MPTP/Pro-induced WT mice; however, these results were also not observed in MPTP/Pro-induced Nrf2-KO mice. Mechanistically, b-Ecd enhanced the expression levels of heme oxygenase 1 (HO-1) and GCLc, but not NQO1 (NAD(P)H quinone dehydrogenase 1) and GCLm expression. Interestingly, b-Ecd failed to increase the protein and mRNA levels of HO-1 and GCLc in Nrf2-KO mice, suggesting that b-Ecd attenuates oxidative stress through an Nrf2-dependent mechanism. Furthermore, b-Ecd promoted the expressions of PI3K/Akt phosphorylation (activity) and GSK-3b phosphorylation (inactivity). Conversely, administration of b-Ecd markedly decreased Fyn phosphorylation levels. Collectively, our findings suggest that b-Ecd focuses on Nrf2 in reducing MPTP/Pro-induced oxidative stress and subsequent motor deficits by inhibiting its nuclear export through PI3K/Akt/GSK-3b/Fyn pathway regulation. These further indicate that b-Ecd may be an absorbing therapeutic agent for PD.

This study evaluated the ability of a high-voltage electrostatic field (HVEF) treatment to extend the shelf life of tomatoes. Tomatoes were exposed to HVEF treatment for different lengths of time, and the physicochemical properties of tomatoes and bioactive compounds were monitored during 28 days of storage at 4 °C. The results indicated that the quality parameters of tomatoes were better maintained during storage by the HVEF treatment relative to the control treatment, extending their shelf life by 14–28 days. The HVEF treatment mitigated losses in firmness, weight, color changes, and bioactive substances, such as total phenolic content, total flavonoid content, ascorbic acid, and lycopene. The activity of pectin-degrading enzymes was also inhibited. The best exposure times for the HVEF treatment were 90 and 120 min. While the measured parameters decreased in both the control and HVEF treatment groups, the decrease in all of these measured parameters was significantly less (p < 0.05) in the optimum HVEF treatment groups than in the control. While the physicochemical properties may vary between different tomato varieties, the HVEF treatment of harvested tomatoes for 90 or 120 min can mitigate the degradation of quality parameters and loss of bioactive compounds incurred during the postharvest storage of tomatoes, thus maintaining their commercial value.

Joint deflection during curved pipe jacking in power tunnels poses a significant risk of structural failure due to the resulting eccentric and diagonal loading on the pipes. This study investigated the axial stress and strain characteristics of reinforced-concrete pipes under varying joint deflection angles and jacking forces, using a combined approach of experimental model testing and finite element method (FEM) numerical simulations. The experimental setup replicated curved pipe jacking conditions, allowing for the measurement of strains and deformation under controlled loading. Numerical simulations, validated against experimental data, provided detailed insights into the stress distribution patterns. The results revealed distinct stress states in different pipe sections. The pipe closest to the jacking force (3# pipe) experienced eccentric loading, leading to localized stress concentrations and inelastic strain on the inner wall at the point of eccentricity, indicating vulnerability to compressive failure. The middle pipe section (2# pipe) underwent complex diagonal loading, resulting in the development of inelastic strain on both the inner and outer walls at specific orientations, highlighting a risk of both compressive and shear failure modes. The study also demonstrated that the magnitude of the axial jacking force and the degree of joint deflection significantly influence the stress distribution and the extent of inelastic strain. These findings provide important information for optimizing the design and construction of curved pipe jacking projects in power tunnels. The identified failure mechanisms and the influence of key parameters on pipe behavior can inform strategies to mitigate the risk of structural failure, improve the resilience of pipe systems, and enhance the overall safety and reliability of underground power tunnel infrastructure.

Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively). Both PV2 wtVLP and sVLP are efficiently produced in Pichia pastoris yeast. The PV2 sVLP displays higher levels of D-antigen and significantly enhanced thermostability than the wtVLP. Unlike the wtVLP, the sVLP elicits neutralizing antibodies in mice at levels comparable to those induced by inactivated polio vaccine. The addition of an aluminum hydroxide adjuvant to sVLP results in faster induction and a higher magnitude of neutralizing antibodies. Furthermore, our cryo-EM structural study of both sVLP and wtVLP reveals a native conformation for the sVLP and a non-native expanded conformation for the wtVLP. Our work not only validates the yeast-produced PV2 sVLP as a promising vaccine candidate with high production potential but also sheds light on the structural mechanisms that underpin the assembly and immunogenicity of the PV2 sVLP. These findings may expedite the development of sVLP-based PV vaccines.

In order to accurately obtain the seedling emergence rate of breeding sunflower and to assess the quality of sowing as well as the merit of sunflower varieties, a method of extracting the sunflower seedling emergence rate using multi-source remote sensing information from unmanned aerial vehicles is proposed. Visible and multispectral images of sunflower seedlings were acquired using a UAV. The thresholding method was used to segment the excess green image of the visible image into vegetation and non-vegetation, to obtain the center point of the vegetation to generate a buffer, and to mask the visible image to achieve weed removal. The components of color models such as the hue–saturation value (HSV), green-relative color space (YCbCr), cyan-magenta-yellow-black (CMYK), and CIELAB color space (L*A*B) models were compared and analyzed. The A component of the L*A*B model was preferred for the optimization of K-means clustering to segment sunflower seedlings and mulch using the genetic algorithm, and the segmentation accuracy was improved by 4.6% compared with the K-means clustering algorithm. All told, 10 geometric features of sunflower seedlings were extracted using segmented images, and 10 vegetation indices and 48 texture features of sunflower seedlings were calculated based on multispectral images. The Pearson’s correlation coefficient method was used to filter the three types of features, and the geometric feature set, the vegetation index set, the texture feature set, and the preferred feature set were constructed. The construction of a sunflower plant number estimation model using the crested porcupine optimizer–support vector machine is proposed and compared with the sunflower plant number estimation models constructed based on decision tree regression, BP neural network, and support vector machine regression. The results show that the accuracy of the model based on the preferred feature set is higher than that of the other three feature sets, indicating that feature screening can improve the accuracy and stability of models; assessed using the CPO-SVR model, the accuracy of the preferred feature set was the highest, with an R² of 0.94, an RMSE of 5.16, and an MAE of 3.03. Compared to the SVR model, the value of the R2 is improved by 3.3%, the RMSE decreased by 18.3%, and the MAE decreased by 18.1%. The results of the study can be cost-effective, accurate, and reliable in terms of obtaining the seedling emergence rate of sunflower field breeding.

The accurate estimation of soil plant analytical development (SPAD) values in cotton under various intercropping patterns with soybean is crucial for monitoring cotton growth and determining a suitable intercropping pattern. In this study, we utilized an unmanned aerial vehicle (UAV) to capture visible (RGB) and multispectral (MS) data of cotton at the bud stage, early flowering stage, and full flowering stage in a cotton–soybean intercropping pattern in the Yellow River Delta region of China, and we used SPAD502 Plus and tapeline to collect SPAD and cotton plant height (CH) data of the cotton canopy, respectively. We analyzed the differences in cotton SPAD and CH under different intercropping ratio patterns. It was conducted using Pearson correlation analysis between the RGB features, MS features, and cotton SPAD, then the recursive feature elimination (RFE) method was employed to select image features. Seven feature sets including MS features (five vegetation indices + five texture features), RGB features (five vegetation indices + cotton cover), and CH, as well as combinations of these three types of features with each other, were established. Voting regression (VR) ensemble learning was proposed for estimating cotton SPAD and compared with the performances of three models: random forest regression (RFR), gradient boosting regression (GBR), and support vector regression (SVR). The optimal model was then used to estimate and visualize cotton SPAD under different intercropping patterns. The results were as follows: (1) There was little difference in the mean value of SPAD or CH under different intercropping patterns; a significant positive correlation existed between CH and SPAD throughout the entire growth period. (2) All VR models were optimal when each of the seven feature sets were used as input. When the features set was MS + RGB, the determination coefficient (R2) of the validation set of the VR model was 0.902, the root mean square error (RMSE) was 1.599, and the relative prediction deviation (RPD) was 3.24. (3) When the features set was CH + MS + RGB, the accuracy of the VR model was further improved, compared with the feature set MS + RGB, the R2 and RPD were increased by 1.55% and 8.95%, respectively, and the RMSE was decreased by 7.38%. (4) In the intercropping of cotton and soybean, cotton growing under 4:6 planting patterns was better. The results can provide a reference for the selection of intercropping patterns and the estimation of cotton SPAD.

In order to improve the accuracy of multispectral image inversion of soil and plant analytical development (SPAD) of the cotton canopy, image segmentation methods were utilized to remove the background interference, such as soil and shadow in UAV multispectral images. UAV multispectral images of cotton bud stage canopies at three different heights (30 m, 50 m, and 80 m) were acquired. Four methods, namely vegetation index thresholding (VIT), supervised classification by support vector machine (SVM), spectral mixture analysis (SMA), and multiple endmember spectral mixture analysis (MESMA), were used to segment cotton, soil, and shadows in the multispectral images of cotton. The segmented UAV multispectral images were used to extract the spectral information of the cotton canopy, and eight vegetation indices were calculated to construct the dataset. Partial least squares regression (PLSR), Random forest (FR), and support vector regression (SVR) algorithms were used to construct the inversion model of cotton SPAD. This study analyzed the effects of different image segmentation methods on the extraction accuracy of spectral information and the accuracy of SPAD modeling in the cotton canopy. The results showed that (1) The accuracy of spectral information extraction can be improved by removing background interference such as soil and shadows using four image segmentation methods. The correlation between the vegetation indices calculated from MESMA segmented images and the SPAD of the cotton canopy was improved the most; (2) At three different flight altitudes, the vegetation indices calculated by the MESMA segmentation method were used as the input variable, and the SVR model had the best accuracy in the inversion of cotton SPAD, with R2 of 0.810, 0.778, and 0.697, respectively; (3) At a flight altitude of 80 m, the R2 of the SVR models constructed using vegetation indices calculated from images segmented by VIT, SVM, SMA, and MESMA methods were improved by 2.2%, 5.8%, 13.7%, and 17.9%, respectively, compared to the original images. Therefore, the MESMA mixed pixel decomposition method can effectively remove soil and shadows in multispectral images, especially to provide a reference for improving the inversion accuracy of crop physiological parameters in low-resolution images with more mixed pixels.

This paper presents, for the first time, the consideration of three-dimensional (3D) oblique incident P and SV waves in calculating the 3D seismic response of a lined tunnel embedded in a half-space by the 2.5D finite/infinite element method (FIEM). Firstly, the applicability of the 2.5D FIEM for 3D seismic analysis is summarized. With the exact solutions obtained for the free field in the Appendix, the equivalent seismic forces are rationally computed for the near-field boundary, considering the horizontal and vertical excitations of the Chi-Chi Earthquake. By performing seismic analysis of the half space embedded with a tunnel using the 2.5D FIEM, the time-domain responses of the tunnel are obtained. The accuracy of the present solutions is verified against those of de Barros and Luco. Conclusions drawn from the parametric study include: (1) Stress concentration for the principal stress under oblique incident seismic waves occurs at the polar angles of 0° (vault), 90°, 180° (inverted arch), and 270° of the lining wall. (2) The vault and inverted arch are the weakest parts of the tunnel during earthquakes. (3) The accelerations of the tunnel during earthquakes can be regarded as of the rigid body type. (4) The responses of the tunnel lining caused by SV waves of an earthquake are much more critical than those by P waves. (5) For arbitrary seismic waves, the maximum longitudinal acceleration azmax is of the same order of magnitude as the maximum horizontal acceleration axmax.

Abstract Background With the widespread spread of carbapenem-resistant gram-negative bacteria (CR-GNB) in medical facilities, the carriage of CR-GNB among critically ill patients has become a significant concern in intensive care units (ICU). This study aimed to develop a scoring system to identify CR-GNB carriers upon ICU admission. Methods Consecutive critically ill patients admitted to the ICU of Shanghai Ruijin Hospital between January 2017 and December 2020 were included. The patients were then divided into training and testing datasets at a 7:3 ratio. Parameters associated with CR-GNB carriage were identified using least absolute shrinkage and selection operator regression analysis. Each parameter was assigned a numerical score ranging from 0 to 100 using logistic regression analysis. Subsequently, a four-tier risk-level system was developed based on the cumulative scores, and assessed using the area under the receiver operating characteristic curve (AUC). Results Of the 1736 patients included in this study, the prevalence of CR-GNB carriage was 10.60%. The clinical scoring system including seven variables (neurological disease, high-risk department history, length of stay ≥ 14 days, ICU history, invasive mechanical ventilation, gastrointestinal tube placement, and carbapenem usage) exhibited promising predictive capabilities. Patients were then stratified using the scoring system, resulting in CR-GNB carriage rates of 2.4%, 12.0%, 36.1%, and 57.9% at the respective risk levels (P

Abstract Background Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment. Methods The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts-AES by intraperitoneal injection. The therapeutic effect of Ts-AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts-AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts-AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts-AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts-AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry. Results We observed that treatment with Ts-AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts-AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro. Conclusions Our results demonstrate that Ts-AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts-AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases. Graphical Abstract

Abstract Background The Inonotus obliquus mushroom, a wondrous fungus boasting edible and medicinal qualities, has been widely used as a folk medicine and shown to have many potential pharmacological secondary metabolites. The purpose of this study was to supply a global landscape of genome-based integrated omic analysis of the fungus under lab-growth conditions. Results This study presented a genome with high accuracy and completeness using the Pacbio Sequel II third-generation sequencing method. The de novo assembled fungal genome was 36.13 Mb, and contained 8352 predicted protein-coding genes, of which 365 carbohydrate-active enzyme (CAZyme)-coding genes and 19 biosynthetic gene clusters (BCGs) for secondary metabolites were identified. Comparative transcriptomic and proteomic analysis revealed a global view of differential metabolic change between seed and fermentation culture, and demonstrated positive correlations between transcription and expression levels of 157 differentially expressed genes involved in the metabolism of amino acids, fatty acids, secondary metabolites, antioxidant and immune responses. Facilitated by the widely targeted metabolomic approach, a total of 307 secondary substances were identified and quantified, with a significant increase in the production of antioxidant polyphenols. Conclusion This study provided the comprehensive analysis of the fungus Inonotus obliquus, and supplied fundamental information for further screening of promising target metabolites and exploring the link between the genome and metabolites.

Abstract Patient similarity search is an essential task in healthcare. Recent studies adopted electronic health records (EHRs) to learn patient representations for measuring the clinical similarities. These methods outperformed traditional methods, by capturing more information from various sources consisting of multi-modal EHRs, external knowledge and correlations among medical concepts. They often concerned certain type of data without taking full advantage of various information. We propose a graph representation learning framework, denoted by One-Size-Fits-Three (OSFT), that takes into account fusion-attention, neighbor-attention and global-attention from three types of information. Extensive experiments are conducted on two real datasets of MIMIC-III and MIMIC-IV, and the results verified the effectiveness and generality of our framework. When compared with baselines on patient similarity search, our framework achieved good effectiveness and comparative efficiency. The results provide new insights about whether the use of various information can better measure the patient similarity. The source codes are available at https://github.com/emmali808/ADDS/tree/master/EHRDeepHelper .

Liner companies have responded to escalating trade conflicts and the impact of the COVID-19 pandemic by forming alliances and implementing streamlined approaches to manage empty containers, which has strengthened the resilience of their supply chains. Meanwhile, shippers have grown more sensitive during these turbulent times. Motivated by the market situation, we investigate a liner alliance shipping network design problem considering the choice inertia of shippers and empty container relocation. To address this problem, we propose a bilevel programming model. The upper model aims to maximize the alliance's profit by optimizing the alliance's shipping network and fleet design scheme. The lower model focuses on optimizing the slot allocation scheme and the empty container relocation scheme. To ensure the sustainable operation of the alliance, we develop an inverse optimization model to allocate profits among alliance members. Furthermore, we design a differential evolution metaheuristic algorithm to solve the model. To validate the effectiveness of the proposed model and algorithm, numerical experiments are conducted using actual shipping data from the Asia-Western Europe shipping route. The results confirm the validity of the proposed model and algorithm, which can serve as a crucial decision-making reference for the daily operations of a liner shipping alliance.

Abstract Targeted public health interventions for an emerging epidemic are essential for preventing pandemics. During 2020-2022, China invested significant efforts in strict zero-COVID measures to contain outbreaks of varying scales caused by different SARS-CoV-2 variants. Based on a multi-year empirical dataset containing 131 outbreaks observed in China from April 2020 to May 2022 and simulated scenarios, we ranked the relative intervention effectiveness by their reduction in instantaneous reproduction number. We found that, overall, social distancing measures (38% reduction, 95% prediction interval 31-45%), face masks (30%, 17-42%) and close contact tracing (28%, 24-31%) were most effective. Contact tracing was crucial in containing outbreaks during the initial phases, while social distancing measures became increasingly prominent as the spread persisted. In addition, infections with higher transmissibility and a shorter latent period posed more challenges for these measures. Our findings provide quantitative evidence on the effects of public-health measures for zeroing out emerging contagions in different contexts.

Abstract Background Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear. Methods Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups. Results (1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF. Conclusion (1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.

Abstract Carmustine (BCNU), a vital type of chloroethylnitrosourea (CENU), inhibits tumor cells growth by inducing DNA damage at O 6 position of guanine and eventually forming dG-dC interstrand cross-links (ICLs). However, the clinical application of BCNU is hindered to some extent by the absence of tumor selectivity, poor stability and O 6-alkylguanine-DNA alkyltransferase (AGT) mediated drug resistance. In recent years, tumor microenvironment has been widely utilized for advanced drug delivery. In the light of the features of tumor microenvironment, we constructed a multifunctional hypoxia/esterase-degradable nanomicelle with AGT inhibitory activity named HACB NPs for tumor-targeting BCNU delivery and tumor sensitization. HACB NPs was self-assembled from hyaluronic acid azobenzene AGT inhibitor conjugates, in which O 6-BG analog acted as an AGT inhibitor, azobenzene acted as a hypoxia-responsive linker and carboxylate ester bond acted as both an esterase-sensitive switch and a connector with hyaluronic acid (HA). The obtained HACB NPs possessed good stability, favorable biosafety and hypoxia/esterase-responsive drug-releasing ability. BCNU-loaded HACB/BCNU NPs exhibited superior cytotoxicity and apoptosis-inducing ability toward the human uterine cervix carcinoma HeLa cells compared with traditional combined medication of BCNU plus O 6-BG. In vivo studies further demonstrated that after a selective accumulation in the tumor site, the micelles could respond to hypoxic tumor tissue for rapid drug release to an effective therapeutic dosage. Thus, this multifunctional stimulus-responsive nanocarrier could be a new promising strategy to enhance the anticancer efficacy and reduce the side effects of BCNU and other CENUs.

Numerous social media platforms have evolved into fertile grounds for the proliferation of irrational information, expanding the avenues of information dissemination. This paper initially utilized the Weibo and Bilibili social platforms as exemplars and devised a cross-platform two-layer network SEIaIbR-FXYaYbZ dissemination model grounded in classical infectious disease models. Subsequently, this research computed the model equilibrium point, basic reproduction number, and information entropy through dynamic equations. Finally, the model equations were fitted to real cases to determine optimal parameter solutions and conduct simulation analysis. The simulation results reveal that: (i) information entropy values on both platforms are low, with irrational information predominantly influencing public opinion; (ii) concerning various types of information, the augmentation of rational information results in a reduction of irrational information, while the quantity of rational information remains largely unaffected by changes in the quantity of irrational information; (iii) examining different platforms for information dissemination, alterations in the circulation rate and quantity of rational information on the Weibo platform impact the quantity of rational and irrational information on the Bilibili platform, while those changes on the Bilibili platform exert minimal influence on public opinion information on the Weibo platform. The results and corresponding strategies obtained from this study on the cross-platform dissemination of rational and irrational information on Weibo and Bilibili can provide a reference for relevant departments to guide the rational development of online information and enhance the effective management of public opinion in social media platforms.

Summary: The global burden of diseases and injuries poses complex and pressing challenges. This study analyzed 369 diseases and injuries attributed to 84 risk factors globally from 1990 to 2019, projecting trends to 2040. In 2019, global risks caused 35 million deaths. Non-communicable diseases were responsible for 8.2 million deaths, primarily from air pollution (5.5 million). Cardiovascular disease from air pollution had a high age-standardized disability-adjusted life year rate (1,073.40). Communicable, maternal, neonatal, and nutritional diseases caused 1.4 million deaths, mainly due to unsafe water and sanitation. Occupational risks resulted in 184,269 transport-related deaths. Behavioral risks caused 21.6 million deaths, with dietary factors causing 6.9 million cardiovascular deaths. Diabetes linked to sugar-sweetened beverages showed significant growth (1990–2019). Metabolic risks led to 18.6 million deaths. Projections to 2040 indicated persistent challenges, emphasizing the urgent need for targeted interventions and policies to alleviate the global burden of diseases and injuries.

Summary: The continuous regeneration of spermatogonial stem cells (SSCs) underpins spermatogenesis and lifelong male fertility, but the developmental origins of the SSC pool remain unclear. Here, we document that hnRNPU is essential for establishing the SSC pool. In male mice, conditional loss of hnRNPU in prospermatogonia (ProSG) arrests spermatogenesis and results in sterility. hnRNPU-deficient ProSG fails to differentiate and migrate to the basement membrane to establish SSC pool in infancy. Moreover, hnRNPU deletion leads to the accumulation of ProSG and disrupts the process of T1-ProSG to T2-ProSG transition. Single-cell transcriptional analyses reveal that germ cells are in a mitotically quiescent state and lose their unique identity upon hnRNPU depletion. We further show that hnRNPU could bind to Vrk1, Slx4, and Dazl transcripts that have been identified to suffer aberrant alternative splicing in hnRNPU-deficient testes. These observations offer important insights into SSC pool establishment and may have translational implications for male fertility.

Background Ovarian cancer (OC) is the most lethal malignancy in women owing to its diagnosis only at the advanced stage. Elucidation of its molecular pathogenesis may help identify new tumor markers and targets for therapy. Circular RNAs (circRNAs) are stable, conserved, and functional biomolecules that can be used as effective biomarkers for various cancers. Methods In this study, a potential circRNA related to early diagnosis of OC, circMAN1A2, was analyzed. Overexpression/knockdown of circMAN1A2 in OC cells was used to decipher its effects on cell proliferation with a Cell Counting Kit-8, 5-ethynyl-2’-deoxyuridine (EdU), cell cycle, clone formation, and wound healing assay. RNA pull-down and Dual luciferase assay were used to explain the underlying mechanism by which circMAN1A2 regulates OC cell proliferation. In vivo, the effect of circMAN1A2 in OC was evaluated using nude mouse xenograft experiments. Results CircMAN1A2 was highly expressed in OC and promoted proliferation, clone formation, and tumorigenicity of OC cells. In addition, we found that circMAN1A2 acted as a sponge for microRNA (miR)-135a-3p; miR-135a-3p directly targeted the 3’ untranslated region of interleukin 1 receptor accessory protein (IL1RAP) in OC cells, thereby regulating the phosphorylation of transforming growth factor-beta activated kinase 1 (TAK1), which resulted in promotion of OC cell growth. Conclusions CircMAN1A2 promotes OC cell proliferation by inhibiting the miR-135a-3p/IL1RAP/TAK1 axis. In conclusion, circMAN1A2 may be a biomarker for early detection of OC and a target for subsequent therapy.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

Enantiornithines were the dominant birds of the Mesozoic, but understanding of their diet is still tenuous. We introduce new data on the enantiornithine family Bohaiornithidae, famous for their large size and powerfully built teeth and claws. In tandem with previously published data, we comment on the breadth of enantiornithine ecology and potential patterns in which it evolved. Body mass, jaw mechanical advantage, finite element analysis of the jaw, and traditional morphometrics of the claws and skull are compared between bohaiornithids and living birds. We find bohaiornithids to be more ecologically diverse than any other enantiornithine family: Bohaiornis and Parabohaiornis are similar to living plant-eating birds; Longusunguis resembles raptorial carnivores; Zhouornis is similar to both fruit-eating birds and generalist feeders; and Shenqiornis and Sulcavis plausibly ate fish, plants, or a mix of both. We predict the ancestral enantiornithine bird to have been a generalist which ate a wide variety of foods. However, more quantitative data from across the enantiornithine tree is needed to refine this prediction. By the Early Cretaceous, enantiornithine birds had diversified into a variety of ecological niches like crown birds after the K-Pg extinction, adding to the evidence that traits unique to crown birds cannot completely explain their ecological success.

Global warming has evolved into a global environmental concern. Despite the significant impact of rivers on greenhouse gas (GHG) emissions, there remains a lack of wide quantification of emissions at high temporal resolution. This research investigated the characteristics of the CO2 exchange flux (FCO2) and CH4 exchange flux (FCH4) at the interface of water and gas, as well as the primary determinants that impact these fluxes, at both the seasonal and 24-h scales, in the Inner Mongolia section of the Yellow River (IMYR). FCO2 was 52.52 ± 78.26 mmol·m−2·d−1 in summer, which was higher than autumn (30.81 ± 51.24 mmol·m−2·d−1) and spring (-96.09 ± 264.31 mmol·m−2·d−1). FCH4 peaked in summer (928.45 ± 513.31 μmol·m−2·d−1) and declined in the fall (326.76 ± 576.31 μmol·m−2·d−1). The lowest FCH4 was recorded in spring (61.75 ± 190.26 μmol·m−2·d−1). Wind speed (WS) and organic carbon mineralisation were the primary determinants of FCO2 at the seasonal scale, whereas temperature and dissolved oxygen (DO) were the primary determinants of FCH4. Monitoring FCO2 and FCH4 at night revealed higher average levels than during the day. FCO2 was regulated by levels of dissolved inorganic carbon (DIC) and total phosphorus (TP) levels over a 24-h period, whereas FCH4 was regulated by levels of dissolved oxygen (DO) and total nitrogen (TN). Throughout the majority of the time period, the IMYR river segment emits carbon dioxide (CO2) and methane (CH4) to the atmosphere. Due to the fact that emission patterns and driving mechanisms of riverine CO2 and CH4 differ across time scales, it is necessary to conduct more precise observations with high spatial and temporal resolution in order to acquire the most reliable data and comprehend more targeted approaches to carbon emission reduction.

Idiopathic granulomatous mastitis (IGM) is a noncancerous, chronic inflammatory disorder of breast with unknown causes, posing significant challenges to the quality of life due to its high refractoriness and local aggressiveness. The typical symptoms of this disease involve skin redness, a firm and tender breast mass and mastalgia; others may include swelling, fistula, abscess (often without fever), nipple retraction, and peau d’orange appearance. IGM often mimics breast abscesses or malignancies, particularly inflammatory breast cancer, and is characterized by absent standardized treatment options, inconsistent patient response and unknown mechanism. Definite diagnosis of this disease relies on core needle biopsy and histopathological examination. The prevailing etiological theory suggests that IGM is an autoimmune disease, as some patients respond well to steroid treatment. Additionally, the presence of concurrent erythema nodosum or other autoimmune conditions supports the autoimmune nature of the disease. Based on current knowledge, this review aims to elucidate the autoimmune-favored features of IGM and explore its potential etiologies. Furthermore, we discuss the immune-mediated pathogenesis of IGM using existing research and propose immunotherapeutic strategies for managing this condition.