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Abstract This study used the three-level EuroQol five-dimension questionnaire (EQ-5D-3L) to assess the quality of life (QOL) of Chinese Shidu parents (who have lost their only child) and conducted an in-depth investigation into the factors affecting their QOL using non-parametric tests and the Tobit regression model. A total of 651 Shidu parents were enrolled in this study. The questionnaire included a general information survey, the Geriatric Depression Scale-15 (GDS-15), the Social Support Rating Scale (SSRS), and the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L). The results revealed that approximately 60% of Shidu parents reported no problems in all five dimensions. Pain and discomfort were the most frequently reported problems among Shidu parents, affecting 23.35% of participants. The Tobit regression model revealed that GDS-15 scores, marital status, education, and self-reported health status were significantly associated with EQ-5D scores. Additionally, SSRS scores, GDS-15 scores, and self-reported health status were significantly associated with EQ-VAS scores. Based on the study's findings, relevant recommendations were proposed.

Abstract Enhancing infrared images is essential for detecting wind turbine blades using infrared technology. This paper introduces an Infrared Image Enhancement Method based on Adaptive Iterative Cutoff Threshold Difference Multi-Scale Top-Hat Transformation (AICT-DMTH) to address the challenge of low image clarity in infrared detection. The method involves performing a black-white difference top-hat transformation by utilizing structural elements of varying scales for dilation and erosion. Additionally, an iterative threshold method is applied to extract more detailed image features, followed by setting a cutoff constant to determine the final scale of the structural element. The effectiveness of the proposed method is evaluated both qualitatively and quantitatively, with infrared images from laboratory and wind farm settings enhanced and compared against existing methods. The experimental results indicate that the proposed method significantly improves the clarity of infrared images, demonstrating robustness in enhancing images from various environments.

Objective MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods We identified bta-miR-365-3p, which specifically targets the 3′ untranslated region (3′UTR) of the FK506-binding protein 5 (FKBP5), and verified its mechanisms for regulating expression and involvement in adipogenesis. Results In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-36 5-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by quantitative real-time polymerase chain reaction and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. Adenosine 5′-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

Abstract This research aims to scrutinize specific parametrized integral inequalities linked to 1, 2, 3, and 4-point Newton-Cotes rules applicable to local fractional differentiable generalized ( s , P ) $(s,P)$ -convex functions. To accomplish this objective, we introduce a novel integral identity and deduce multiple integral inequalities tailored to mappings within the aforementioned function class. Furthermore, we present an illustrative example featuring graphical representations and potential practical applications.

BackgroundTo address the growing burden of older adult care, the Chinese government has introduced a policy that integrates medical care with elder care, launching two batches of national pilot projects. A majority of the older adult population suffers from one or more chronic diseases, with many experiencing multiple chronic conditions, necessitating support from both elder care and medical services.MethodsUsing panel data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011 to 2020, this study employs the difference-in-difference (DID) model to analyze the impact of the integrated medical-nursing policy on the physical health of older patients with chronic diseases.ResultsThe study found that the average annual number of hospitalizations for older individuals with one or more chronic diseases was 0.276. The integrated medical-nursing policy reduced hospitalizations by 0.0405. Additionally, the average annual hospitalization rate for older individuals with two or more chronic diseases was 0.339, higher than the former group. The integrated medical-nursing policy reduced hospitalizations by 0.0738 in this group.ConclusionThe pilot study demonstrates that the implementation of the integrated medical-nursing policy has significantly improved the physical health of older patients with chronic diseases. The government should promote these policies on a larger scale, explore various forms of integrated medical care, and provide more comprehensive medical and elder care services for older patients with chronic diseases.

Objectives: Esophagogastric variceal bleeding (EVB) is one of the main causes of cirrhosis-related deaths, and endoscopic therapy is the first-line treatment of choice. However, the efficacy of prophylactic endotracheal intubation (PEI) before endoscopy remains controversial. Methods: Data were collected from 119 patients who underwent endoscopic confirmation of an EVB. Inverse probability of treatment weighting was applied to reduce bias between the two groups. The primary outcomes included rebleeding rates within 24 h and 6 weeks post-endoscopic surgery and 6-week mortality. Results: After endoscopic surgery, the rebleeding rate within 24 h in the PEI group was significantly lower than non-PEI group (1.2 % VS 12.6 %, P-value = 0.025). Although PEI did not reduce 6-week mortality, it significantly reduced the risk of rebleeding within 24 h (odds ratio [OR]: 0.89, 95 % confidence interval [CI]: 0.82–0.97, P = 0.008) and within 6 weeks (hazard ratio [HR]: 0.36, 95%CI: 0.14–0.90, P = 0.029). In multivariate regression analyses, maximum varices diameter >1.5 cm (OR: 1.23, 95 % CI: 1.09–1.37, P

Abstract Morchella spongiola is a highly prized mushroom for its delicious flavor and medical value and is one of the most flourishing, representative, and dominant macrofungi in the Qilian Mountains of the Qinghai-Tibet Plateau subkingdoms (QTPs). However, the understanding of M. spongiola remains largely unknown, and its taxonomy is ambiguous. In this study, we redescribed a unique species of M. spongiola, i.e., micromorphology, molecular data, genomics, and comparative genomics, and the historical biogeography of M. spongiola were estimated for 182 single-copy homologous genes. A high-quality chromosome-level reference genome of M. spongiola M12-10 was obtained by combining PacBio HiFi data and Illumina sequencing technologies; it was approximately 57.1 Mb (contig N50 of 18.14 Mb) and contained 9775 protein-coding genes. Comparative genome analysis revealed considerable conservation and unique characteristics between M. spongiola M12-10 and 32 other Morchella species. Molecular phylogenetic analysis indicated that M. spongiola M12-10 is similar to the M. prava/Mes-7 present in sandy soil near rivers, differentiating from black morels ~ 43.06 Mya (million years ago), and diverged from M. parva/Mes-7 at approximately 12.85 Mya (in the Miocene epoch), which is closely related to the geological activities in the QTPs (in the Neogene). Therefore, M. spongiola is a unique species rather than a synonym of M. vulgaris/Mes-5, which has a distinctive grey-brown sponge-like ascomata. This genome of M. spongiola M12-10 is the first published genome sequence of the species in the genus Morchella from the QTPs, which could aid future studies on functional gene identification, germplasm resource management, and molecular breeding efforts, as well as evolutionary studies on the Morchella taxon in the QTPs.

Abstract Background Leukemias driven by activated, chimeric FGFR1 kinases typically progress to AML which have poor prognosis. Mouse models of this syndrome allow detailed analysis of cellular and molecular changes occurring during leukemogenesis. We have used these models to determine the effects of leukemia development on the immune cell composition in the leukemia microenvironment during leukemia development and progression. Methods Single cell RNA sequencing (scRNA-Seq) was used to characterize leukemia associated neutrophils and define gene expression changes in these cells during leukemia progression. Results scRNA-Seq revealed six distinct subgroups of neutrophils based on their specific differential gene expression. In response to leukemia development, there is a dramatic increase in only two of the neutrophil subgroups. These two subgroups show specific gene expression signatures consistent with neutrophil precursors which give rise to immature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Analysis of gene expression in these precursor cells identified pathways that were specifically upregulated, the most pronounced of which involved matrix metalloproteinases Mmp8 and Mmp9, during leukemia progression. Pharmacological inhibition of MMPs using Ilomastat preferentially restricted in vitro migration of neutrophils from leukemic mice and led to a significantly improved survival in vivo, accompanied by impaired PMN-MDSC recruitment. As a result, levels of T-cells were proportionally increased. In clinically annotated TCGA databases, MMP8 was shown to act as an independent indicator for poor prognosis and correlated with higher neutrophil infiltration and poor pan-cancer prognosis. Conclusion We have defined specific leukemia responsive neutrophil subgroups based on their unique gene expression profile, which appear to be the precursors of neutrophils specifically associated with leukemia progression. An important event during development of these neutrophils is upregulation MMP genes which facilitated mobilization of these precursors from the BM in response to cancer progression, suggesting a possible therapeutic approach to suppress the development of immune tolerance.

The primary objective of this study was to determine the antimicrobial resistance (AMR) profile of common mastitis pathogens on large Chinese dairy farms. A total of 673 isolates, including Staphylococcus aureus (14.41%, 97/673), coagulase-negative staphylococci (CNS, 52.30%, 352/673), Streptococcus agalactiae (5.64%, 38/673), non-agalactiae streptococci (7.42%, 50/673), Acinetobacter spp. (7.72%, 52/673), Escherichia spp. (6.39%, 43/673), and Klebsiella spp. (6.09%, 41/673), were collected from 15 large Chinese dairy farms in 12 provinces. The AMR profiles were measured using a microdilution method. Our results showed that more than 75% of Staph. aureus (87/97) and CNS (291/352) were resistant to penicillin (PEN). More than 30% of Escherichia spp. (15/43) showed resistance to ampicillin (AMP). However, less than 10% CNS and non-agalactiae streptococci showed resistance to amoxicillin/clavulanate (AMC; 1/352; 0/50), cephalexin (LEX; 1/352; 0/50), ceftiofur (EFT; 10/352; 0/50), and rifaximin (RIX; 21/352; 2/50); less than 10% Staph. aureus showed resistance to AMC (1/97), oxacillin (OX; 3/97), LEX (1/97), EFT (2/97), and RIX (2/97); less than 10% Strep. agalactiae showed resistance to PEN (3/38), AMC (0/38), LEX (0/38), EFT (0/38), and RIX (0/38); and less than 10% Escherichia spp. showed resistance to AMC (1/43) and EFT (4/43). These results suggested that most mastitis pathogens were susceptible to most antimicrobials with exceptions of Staph. aureus tested against penicillin or ampicillin and CNS against penicillin or oxacillin. To control the AMR threat in Chinese dairy farms, a nationwide surveillance program for AMR of bovine mastitis pathogens is needed.

Abstract Respiratory sensitivity and pneumonia are possible outcomes of the coronavirus (COVID-19). Surface characteristics like temperature and sunshine affect how long the virus survives. This research article analyzes COVID-19 mathematical model behavior based on symptomatic and non-symptomatic individuals. In the reproductive model, the best result indicates the intensity of the epidemic. Our model remained stable at a certain point under controlled conditions after we evaluated a specific element. This approach is in place of traditional approaches such as Euler’s and Runge–Kutta’s. An unusual numerical approach known as the non-standard finite difference (NSFD) scheme is used in this article. This numerical approach gives us positivity. A dependable numerical analysis allowed us to evaluate different approaches and verify our theoretical results. Unlike the widely used Euler and RK4 approaches, we investigated the benefits of implementing NSFD schemes. By numerically simulating COVID-19 in a variety of scenarios, we demonstrated how our theoretical concepts work. The simulation findings support the usefulness of both approaches.

This paper introduces a novel parametrized integral identity that forms the basis for deriving a comprehensive class of generalized fractional integral inequalities. Building on recent advancements in fractional calculus, particularly in conformable fractional integrals, our approach offers a unified framework for various known inequalities. The novelty of this work lies in its ability to generate new and more general inequalities, including Hermite–Hadamard-, Maclaurin-, and corrected Maclaurin-type inequalities, by selecting specific parameter values. These results extend the scope of fractional integral inequalities and provide new insights into their structure. To demonstrate the practical applicability and accuracy of the theoretical findings, we present a detailed numerical example along with graphical representations.

Abstract Objective The aim of this study was to assess whether coronavirus disease 2019 (COVID‐19) infection during pregnancy is a risk factor for hypertensive disorders of pregnancy. Methods A retrospective evaluation was conducted on obstetric patients who gave birth between March 2020 and December 2021 at an academic urban referral center. The patients were categorized as COVID‐19‐positive or COVID‐19‐negative during pregnancy. The primary outcome was the development of a hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery, mode of delivery, maternal death, maternal intensive care unit (ICU) admission, neonatal ICU admission, intrauterine fetal demise/stillbirth, fetal growth restriction and prolonged hospital stay. χ2 tests, Fisher's exact tests, Student's two‐sample tests and multiple logistic regressions were used to evaluate the association between COVID‐19 status and outcomes. Results Of 2760 reviewed charts, 2426 (87.9%) met the inclusion criteria. Of 2426 patients, 203 were COVID‐positive and 2223 were COVID‐negative. There were no significant demographic differences between the two groups. After adjusting for confounding effects, COVID‐19 was determined to be a risk factor for combined hypertensive disorders of pregnancy (odds ratio [OR] 1.93, 95% confidence interval [CI]: 1.39–2.66) and pre‐eclampsia specifically (OR 2.01, 95% CI 1.38–2.88). COVID‐19 infection during pregnancy was weakly associated with an increased risk of caesarean delivery (p = 0.046) on univariate analysis but not on multivariate analysis, whereas it was associated with an increased risk of maternal ICU admission (p = 0.003), and prolonged hospital stay (p

Reliable material parameters, correct boundary condition settings, and a reasonably simplified numerical model are key to obtain reliable and reasonable analysis results. A new finite element analysis model for the HgCdTe infrared focal plane array detector is presented, which includes the core column. The thermal stress and strain of the new model and current model are analyzed, and their distribution laws are obtained. The results are compared, and the reasons are analyzed, which can provide some references for the simulation of infrared detector package structure.

This paper introduces new versions of Hermite–Hadamard, midpoint- and trapezoid-type inequalities involving fractional integral operators with exponential kernels. We explore these inequalities for differentiable convex functions and demonstrate their connections with classical integrals. This paper validates the derived inequalities through a numerical example with graphical representations and provides some practical applications, highlighting their relevance to special means. This study presents novel results, offering new insights into classical integrals as the fractional order β approaches 1, in addition to the fractional integrals we examined.

Kobresia humilis is a major species in the alpine meadow communities of the Qinghai-Tibet Plateau (QTP); it plays a crucial role in maintaining the ecological balance of these meadows. Nevertheless, little is known about the rhizosphere fungi associated with K. humilis on the Qinghai Tibet Plateau. In this study, we used Illumina Miseq to investigate the fungal diversity, community structure, and ecological types in the root and rhizosphere soil of K. humilis across eight areas on the QTP and analyzed the correlation between rhizosphere fungi of K. humilis and environmental factors. A total of 19,423 and 25,101 operational taxonomic units (OTUs) were obtained from the roots and rhizosphere soil of K. humilis. These were classified into seven phyla, 25 classes, 68 orders, 138 families, and 316 genera in the roots, and nine phyla, 31 classes, 76 orders, 152 families, and 407 genera in the rhizosphere soil. There were 435 and 415 core OTUs identified in root and rhizosphere soil, respectively, which were categorized into 68 and 59 genera, respectively, with 25 shared genera. Among them, the genera with a relative abundance >1% included Mortierella, Microscypha, Floccularia, Cistella, Gibberella, and Pilidium. Compared with the rhizosphere soil, the roots showed five differing fungal community characteristics, as well as differences in ecological type, and in the main influencing environmental factors. First, the diversity, abundance, and total number of OTUs in the rhizosphere soil of K. humilis were higher than for the endophytic fungi in the roots by 11.85%, 9.85%, and 22.62%, respectively. The composition and diversity of fungal communities also differed between the eight areas. Second, although saprotroph-symbiotrophs were the main ecological types in both roots and rhizosphere soil; there were 62.62% fewer pathotrophs in roots compared to the rhizosphere soil. Thirdly, at the higher altitude sites (3,900–4,410 m), the proportion of pathotroph fungi in K. humilis was found to be lower than at the lower altitude sites (3,200–3,690 m). Fourthly, metacommunity-scale network analysis showed that during the long-term evolutionary process, ZK (EICZK = 1) and HY (EICHY = 1) were critical sites for development of the fungal community structure in the roots and rhizosphere soil of K. humilis, respectively. Fifthly, canonical correspondence analysis (CCA) showed that key driving factors in relation to the fungal community were longitude (R2 = 0.5410) for the root community and pH (R2 = 0.5226) for the rhizosphere soil community. In summary, these results show that K. humilis fungal communities are significantly different in the root and rhizosphere soil and at the eight areas investigated, indicating that roots select for specific microorganisms in the soil. This is the first time that the fungal distribution of K. humilis on the QTP in relation to long-term evolutionary processes has been investigated. These findings are critical for determining the effects of environmental variables on K. humilis fungal communities and could be valuable when developing guidance for ecological restoration and sustainable utilization of the biological resources of the QTP.

Background: Lansoprazole, a proton-pump inhibitor (PPI), is the primary therapy for peptic ulcers (PU). Potassium competitive acid blockers (P-CAB) offer an alternative for acid suppression. However, the efficacy and safety of P-CABs versus lansoprazole in the management of PU has not been evaluated.Methods: Five databases were searched for randomized clinical trials in English until 31 August 2023. Data extraction provided outcome counts for ulcer healing, recurrent NSAID-related ulcer, and adverse events. The pooled effect, presented as rate difference (RD), was stratified by ulcer location, follow-up time, and the types of P-CAB, along with their corresponding 95% confidence intervals (95% CI).Results: The pooled healing rates of peptic ulcers were 95.3% (1,100/1,154) and 95.0% (945/995) for P-CABs and lansoprazole, respectively (RD: 0.4%, 95% CI: −1.4%–2.3%). The lower bounds of the 95% CI fell within the predefined non-inferiority margin of −6%. In subgroup analyses base on ulcer location, and follow-up time also demonstrated non-inferiority. The drug-related treatment-emergent adverse events (TEAEs) did not differ significantly among groups (RR: 0.997, 95% CI: 0.949–1.046, p = 0.893). However, P-CAB treatment was associated with an increased risk of the serious adverse events compared to lansoprazole (RR: 1.325, 95% CI: 1.005–1.747, p = 0.046).Conclusion: P-CABs demonstrated non-inferiority to lansoprazole in the management of peptic ulcer. The safety and tolerability profile are comparable, with similar TEAEs rates. However, P-CABs appear to have a higher risk of serious adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=458361 Identifier: PROSPERO (No. CRD42023458361).

In recent years, with the rapid development of molecular biology techniques such as polymerase chain reaction and molecular biochip, the etiological diagnosis of viral encephalitis has a very big step forward. At present, the etiological examination of viral meningitis mainly includes virus isolation, serological detection and molecular biological nucleic acid detection. This article reviews the progress in etiological diagnosis of viral meningitis.

Summary: Congenital heart defects (CHDs) are frequent in children with Down syndrome (DS), caused by trisomy of chromosome 21. However, the underlying mechanisms are poorly understood. Here, using a human-induced pluripotent stem cell (iPSC)-based model and the Dp(16)1Yey/+ (Dp16) mouse model of DS, we identified downregulation of canonical Wnt signaling downstream of increased dosage of interferon (IFN) receptors (IFNRs) genes on chromosome 21 as a causative factor of cardiogenic dysregulation in DS. We differentiated human iPSCs derived from individuals with DS and CHDs, and healthy euploid controls into cardiac cells. We observed that T21 upregulates IFN signaling, downregulates the canonical WNT pathway, and impairs cardiac differentiation. Furthermore, genetic and pharmacological normalization of IFN signaling restored canonical WNT signaling and rescued defects in cardiogenesis in DS in vitro and in vivo. Our findings provide insights into mechanisms underlying abnormal cardiogenesis in DS, ultimately aiding the development of therapeutic strategies.

Background Adoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC). A patient with HNSCC received autologous tumor-infiltrating lymphocytes (TILs) labeled with a perfluorocarbon (PFC) nanoemulsion cell tracer. Nanoemulsion, released from apoptotic cells, clears through the reticuloendothelial system, particularly the Kupffer cells of the liver, and fluorine-19 (19F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF.Methods Autologous TILs were isolated from a patient in their late 50s with relapsed, refractory human papillomavirus-mediated squamous cell carcinoma of the right tonsil, metastatic to the lung. A lung metastasis was resected for T cell harvest and expansion using a rapid expansion protocol. The expanded TILs were intracellularly labeled with PFC nanoemulsion tracer by coincubation in the final 24 hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver 19F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant.Results We show that it is feasible to PFC-label ~7×1010 TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining >90% cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo 19F MRS measurements in the liver, we estimate that ~30% cell equivalents of adoptively transferred F-TILs have become apoptotic by 22 days post-transfer.Conclusions Survival of the primary cell therapy product is likely to vary per patient. A non-invasive assay of ACF over time could potentially provide insight into the mechanisms of response and non-response, informing future clinical studies. This information may be useful to developers of cytotherapies and clinicians as it opens an avenue to quantify cellular product survival and engraftment.

Building upon previous research in conformable fractional calculus, this study introduces a novel identity. Using this identity as a foundation, we derive a set of conformable fractional Milne-type inequalities specifically designed for differentiable convex functions. The obtained results recover some existing inequalities in the literature by fixing some parameters. These novel contributions aim to enrich the analytical tools available for studying convex functions within the realm of conformable fractional calculus. The derived inequalities reflect an inherent symmetry characteristic of the Milne formula, further illustrating the balanced and harmonious mathematical structure within these frameworks. We provide a thorough example with graphical representations to support our findings, offering both numerical insights and visual confirmation of the established inequalities.

Zygote arrest-1 (Zar1) and Wilms’ tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation. Here, Lczar1 and Lcwt1b were identified in Asian seabass (Lates calcarifer), a hermaphrodite fish, as the valuable model for studying sex differentiation. The cloned cDNA fragments of Lczar1 were 1192 bp, encoding 336 amino acids, and contained a zinc-binding domain, while those of Lcwt1b cDNA were 1521 bp, encoding a peptide of 423 amino acids with a Zn finger domain belonging to Wt1b family. RT-qPCR analysis showed that Lczar1 mRNA was exclusively expressed in the ovary, while Lcwt1b mRNA was majorly expressed in the gonads in a higher amount in the testis than in the ovary. In situ hybridization results showed that Lczar1 mRNA was mainly concentrated in oogonia and oocytes at early stages in the ovary, but were undetectable in the testis. Lcwt1b mRNA was localized not only in gonadal somatic cells (the testis and ovary), but also in female and male germ cells in the early developmental stages, such as those of previtellogenic oocytes, spermatogonia, spermatocytes and spermatids. These results indicated that Lczar1 and Lcwt1b possibly play roles in gonadal development. Therefore, the findings of this study will provide a basis for clarifying the mechanism of Lczar1 and Lcwt1b in regulating germ cell development and the sex reversal of Asian seabass and even other hermaphroditic species.

Abstract Globally, cervical cancer, whose etiologic factor is Human papillomavirus (HPV), is the third most common cancer among women. In cervical cancer screening, HPV testing is important. However, the prevalence of HPV in northern Guangdong Province has not been conclusively determined. A total of 100,994 women attending Yuebei People's Hospital Affiliated to Shantou University Medical College between 2012 and 2020 were recruited. HPV was tested by a polymerase chain reaction (PCR)-based hybridization gene chip assay. The prevalence of HPV among these women was established to be19.04%. Peak prevalence was observed in women aged 40–49 (7.29%). Besides, the prevalence of single-type HPV infection (14.46%) was significantly high, compared to multiple-type infection (4.58%) (p

Abstract Objectives The present study aimed to identify the gender-specific trajectories of grip strength using group-based trajectories, explore the interaction between grip strength and physical activity on depression, and investigate the association of physical activity with the change in depression by different grip strength groups among middle-aged and older European adults. Methods A total of 14,098 participants aged 50 years or older from the Survey of Health, Ageing and Retirement in Europe 2007–2019 were included in this study. Group-based trajectory modeling was used to identify the low, middle and high group of grip strength by gender. Generalized estimated equations were fitted to analyze the interaction effect. The data of wave 2-wave 5 and wave 2-wave 7 were chosen to conduct sensitivity analyses. Results Significant interactions between grip strength group and physical inactivity were found (x 2 interaction = 11.16, P = 0.004). Significant interactions between physical inactivity and time on depression were identified in low (x 2 interaction = 27.83, P

This article is concerned with the existence of entire solutions for the following complex second order partial differential-difference equation $ \left(\frac{\partial^2 f(z_1, z_2)}{\partial z_1^2}+\frac{\partial^2 f(z_1, z_2)}{\partial z_2^2}\right)^{l}+f(z_1+c_1, z_2+c_2)^{k} = 1, $ where $ c_1, c_2 $ are constants in $ \mathbb{C} $ and $ k, l $ are positive integers. In addition, we also investigate the forms of finite order transcendental entire solutions for several complex second order partial differential-difference equations of Fermat type, and obtain some theorems about the existence and the forms of solutions for the above equations. Meantime, we give some examples to explain the existence of solutions for some theorems in some cases. Our results are some generalizations of the previous theorems given by Qi [23], Xu and Cao [35], Liu, Cao and Cao [17].

BackgroundTofu whey wastewater (TWW) is the wastewater of tofu processing, which is rich in a variety of nutrients. Rhodotorula glutinis can make full use of TWW to ferment and reproduce yeast cells, produce carotenoids and other nutrients, improve the utilization value of TWW, and reduce environmental pollution and resource waste.MethodsIn this study, the nutrient composition changes of TWW treated by Rhodotorula glutinis were analyzed to reformulate TWW medium, and the optimal composition and proportion of TWW medium that can improve the biomass and carotenoids production of Rhodotorula glutinis were explored. Meanwhile, the Rhodotorula glutinis liquid obtained under these conditions was used to prepare biological feed for laying hens, and the effect of Rhodotorula glutinis growing on TWW as substrate on laying performance and egg quality of laying hens were verified.ResultsThe results showed that the zinc content of TWW after Rhodotorula glutinis fermentation increased by 62.30%, the phosphorus content decreased by 42.31%, and the contents of vitamin B1, B2 and B6 increased to varying degrees. The optimal fermentation conditions of Rhodotorula glutinis in the TWW medium were as follow: the initial pH was 6.40, the amount of soybean oil, glucose and zinc ions was 0.80 ml/L, 16.32 g/L, and 20.52 mg/L, respectively. Under this condition, the biomass of Rhodotorula glutinis reached 2.23 g/L, the carotenoids production was 832.86 μg/g, and the number of effective viable yeast count was 7.08 × 107 cfu/ml. In addition, the laying performance and egg quality of laying hens fed Rhodotorula glutinis biological feed were improved.DiscussionIn this study, we analyzed the composition changes of TWW, optimized the fermentation conditions of Rhodotorula glutinis in TWW medium, explored the influence of Rhodotorula glutinis utilizing TWW on laying layers, and provided a new idea for the efficient utilization of TWW.

Hypoxia is an important tumor feature and hypoxia-inducible factor 1 (HIF-1) is a master regulator of cell response to hypoxia. Mouse double minute 2 homolog (MDM2) promotes cancer cell survival in retinoblastoma (RB), with the underlying mechanism remaining elusive. In this study, we investigated the role of MDM2 and its relation to HIF-1α in RB. Expression analysis on primary human RB samples showed that MDM2 expression was positively correlated with that of HIF-1α while negatively correlated with von Hippel-Lindau protein (pVHL), the regulator of HIF-1α. In agreement, RB cells with MDM2 overexpression showed increased expression of HIF-1α and decreased expression of pVHL, while cells with MDM2 siRNA knockdown or MDM2-specific inhibitor showed the opposite effect under hypoxia. Further immuno-precipitation analysis revealed that MDM2 could directly interact with pVHL and promotes its ubiquitination and degradation, which consequently led to the increase of HIF-1α. Inhibition of MDM2 and/or HIF-1α with specific inhibitors induced RB cell death and decreased the stem cell properties of primary RB cells. Taken together, our study has shown that MDM2 promotes RB survival through regulating the expression of pVHL and HIF-1α, and targeting MDM2 and/or HIF-1α represents a potential effective approach for RB treatment.

This article is to describe the entire solutions of some partial differential-difference equations and systems. Some theorems about the forms of transcendental entire solutions with finite order for several high-order partial differential-difference equations (or systems) of the Fermat type with two complex variables are obtained. Moreover, some examples are provided to explain that our results are precise to some extent.

Abstract Persistent infection with high-risk types Human Papillomavirus could cause diseases including cervical cancers and oropharyngeal cancers. Nonetheless, so far there is no effective pharmacotherapy for treating the infection from high-risk HPV types, and hence it remains to be a severe threat to the health of female. Based on drug repositioning strategy, we trained and benchmarked multiple machine learning models so as to predict potential effective antiviral drugs for HPV infection in this work. Through optimizing models, measuring models’ predictive performance using 182 pairs of antiviral-target interaction dataset which were all approved by the United States Food and Drug Administration, and benchmarking different models’ predictive performance, we identified the optimized Support Vector Machine and K-Nearest Neighbor classifier with high precision score were the best two predictors (0.80 and 0.85 respectively) amongst classifiers of Support Vector Machine, Random forest, Adaboost, Naïve Bayes, K-Nearest Neighbors, and Logistic regression classifier. We applied these two predictors together and successfully predicted 57 pairs of antiviral-HPV protein interactions from 864 pairs of antiviral-HPV protein associations. Our work provided good drug candidates for anti-HPV drug discovery. So far as we know, we are the first one to conduct such HPV-oriented computational drug repositioning study.

IntroductionMorchella has become a research hotspot because of its wide distribution, delicious taste, and phenotypic plasticity. The Qinghai-Tibet Plateau subkingdoms (QTPs) are known as the cradle of Ice age biodiversity. However, the diversity of Morchella in the QTPs has been poorly investigated, especially in phylogenetic diversity, origin, and biogeography.MethodsThe genealogical concordance phylogenetic species recognition (GCPSR, based on Bayesian evolutionary analysis using sequences from the internal transcribed spacer (ITS), nuclear large subunit rDNA (nrLSU), translation elongation factor 1-α (EF1-α), and the largest and second largest subunits of RNA polymerase II (RPB1 and RPB2)), differentiation time estimation, and ancestral region reconstruction were used to infer Morchella’s phylogenetic relationships and historical biogeography in the QTPs.ResultsFirstly, a total of 18 Morchella phylogenetic species are recognized in the QTPs, including 10 Elata clades and 8 Esculenta clades of 216 individuals Secondly, the divergences of the 18 phylogenetic species were 50.24–4.20 Mya (Eocene-Pliocene), which was closely related to the geological activities in the QTPs. Furthermore, the ancestor of Morchella probably originated in the Northern regions (Qilian Shan, Elata cade) and southwestern regions (Shangri-La, Esculenta clade) of QTPs and might have migrated from North America (Rufobrunnea clade) via Beringian Land Bridge (BLB) and Long-Distance Dispersal (LDD) expansions during the Late Cretaceous. Moreover, as the cradle of species origin and diversity, the fungi species in the QTPs have spread out and diffused to Eurasia and South Africa starting in the Paleogene Period.ConclusionThis is the first report that Esculenta and Elata clade of Morchella originated from the QTPs because of orogenic, and rapid differentiation of fungi is strongly linked to geological uplift movement and refuge in marginal areas of the QTPs. Our findings contribute to increasing the diversity of Morchella and offer more evidence for the origin theory of the QTPs.

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2–5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

Objectives: Non-invasive prenatal testing (NIPT) has been widely used in recent years. According to clinical experience from all hospitals providing prenatal screening services in Beijing, we explored the feasibility of using NIPT for the analysis of common foetal aneuploidies among pregnancies.Methods: In total, 68,763 maternal blood samples were collected from January 2020 to December 2020 at the Beijing prenatal diagnosis agency. Cases with positive screening results by NIPT detection were validated using prenatal diagnosis.Results: In total, 920 cases had a high-risk NIPT result, and 755 cases were shown to be truly positive by a chromosome karyotyping analysis; the prenatal diagnosis rate was 82.07% (755/920). Of the920 cases, there were 164 cases of T21, 70 cases of T18, 38 cases of T13, 360 cases of SCAs and 288 cases of other chromosomal abnormalities. The positive rates of T21, T18, T13, and SCAs were 0.24% (164/68,763), 0.10% (70/68,763), 0.06% (38/68,763) and 0.52% (360/68,763), respectively. The sensitivity and specificity were 98.17% and 99.92% for T21, 96.15% and 99.93% for T18, and 100% and 99.95% for T13, respectively. The PPVs of T21,T18,T13 and SCAs were65.24% (107/164), 35.71% (25/70), 18.42% (7/38) and 31.39% (113/360), respectively. For all indications, there were more higher T21/18/13 in the high-risk group than in the low-risk group (comprising only cases of voluntary request), with a positive rate of 0.46% vs. 0.27% (p < 0.001), sensitivity of 99.16% vs. 91.30% (p = 0.02) and PPV of 56.73%vs.32.81% (p = 0.001), but there was no significant difference in specificity between the groups (p = 0.71). The detection indication with the highest PPV (100%) by NIPT was ultrasound structural abnormalities and ultrasound soft marker abnormalities for T21 and ultrasound structural abnormalities and NT thickening for T18 and T13. The PPVs of different clinical indications of T21 (p = 0.002), T13 (p = 0.04) and SACs (p = 0.02) were statistically significant.Conclusion: The high specificity, efficiency and safety (non-invasiveness) of NIPT can effectively improve the detection rate of common chromosomal aneuploidy, thereby reducing the occurrence of birth defects. We should encourage pregnant women with NIPT-high-risk results to undergo a prenatal diagnosis to determine whether the foetus has chromosomal abnormalities. More importantly, the screening efficiency of NIPT in the low-risk group was significantly lower than that in the high-risk group. Therefore, the use of NIPT in low-risk groups should be fully promoted, and socioeconomic benefits should be considered.

Given the rising popularity of post-retirement work and its potential benefits for older adults’ mental health, this study examined older adults’ adaptation ability as a conditional factor for the impact of post-retirement work on depression. Quantitative data from 1433 working older adults and 1433 non-working older adults were analyzed using the PROCESS macro in SPSS to test a moderated regression model with adaptation ability as the moderator. Results showed that older adults with lower adaptation ability demonstrated significantly lower depression if they worked (vs. did not work). Older adults with higher adaptation ability exhibited significantly higher depression if they worked (vs. did not work). These findings were subsequently verified with a robustness check. Overall, post-retirement work did not prevent depression for the entire sample; working only alleviated depression among older adults with limited adaptation ability. Older adults with stronger adaptation ability could better maintain their mental health by staying retired. This study fills a knowledge gap regarding the relationship between post-retirement work and mental health. Implications for aging societies are also discussed.

By making use of the Nevanlinna theory and difference Nevanlinna theory of several complex variables, we investigate some properties of the transcendental entire solutions for several systems of partial differential difference equations of Fermat type, and obtain some results about the existence and the forms of transcendental entire solutions of the above systems, which improve and generalize the previous results given by Cao, Gao, Liu [5,24,39]. Some examples are given show that there exist some significant differences in the forms of transcendental entire solutions with finite order of the systems of equations with between several complex variables and a single complex variable.

With the rapid development of computer technology and network communication technology, copyright protection caused by widely spread digital media has become the focus of attention in various fields. For digital media watermarking technology research emerge in endlessly, but the results are not ideal. In order to better realize the copyright identification and protection, based on the embedded intelligent edge computing detection technology, this paper studies the zero watermark copyright protection algorithm of digital media. Firstly, this paper designs an embedded intelligent edge detection module based on Sobel operator, including image line buffer module, convolution calculation module and threshold processing module. Then, based on the embedded intelligent edge detection module, the Arnold transform of image scrambling technology is used to preprocess the watermark, and finally a zero watermark copyright protection algorithm is constructed. At the same time, the robustness of the proposed algorithm is tested. The image is subjected to different proportion of clipping and scaling attacks, different types of noise, sharpening and blur attacks, and the detection rate and signal-to-noise ratio of each algorithm are calculated respectively. The performance of the watermark image processed by this algorithm is evaluated subjectively and objectively. Experimental data show that the detection rate of our algorithm is the highest, which is 0.89. In scaling attack, the performance of our algorithm is slightly lower than that of Fourier transform domain algorithm, but it is better than the other two algorithms. The Signal to Noise Ratio of the algorithm is 36.854% in P6 multiplicative noise attack, 39.638% in P8 sharpening edge attack and 41.285% in fuzzy attack. This shows that the algorithm is robust to conventional attacks. The subjective evaluation of 33% and 39% of the images is 5 and 4. The mean values of signal to noise ratio, peak signal to noise ratio, mean square error and mean absolute difference are 20.56, 25.13, 37.03 and 27.64, respectively. This shows that the watermark image processed by this algorithm has high quality. Therefore, the digital media zero watermark copyright protection algorithm based on embedded intelligent edge computing detection is more robust, and its watermark invisibility is also very superior, which is worth promoting.

Background Adoptive cell therapy (ACT) using genetically modified T cells has evolved into a promising treatment option for patients with cancer. However, even for the best-studied and clinically validated CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, many patients face the challenge of lack of response or occurrence of relapse. There is increasing need to improve the efficacy of ACT so that durable, curative outcomes can be achieved in a broad patient population.Methods Here, we investigated the impact of indomethacin (indo), a non-steroidal anti-inflammatory drug (NSAID), on the efficacy of ACT in multiple preclinical models. Mice with established B-cell lymphoma received various combinations of preconditioning chemotherapy, infusion of suboptimal dose of tumor-reactive T cells, and indo administration. Donor T cells used in the ACT models included CD4+ T cells expressing a tumor-specific T cell receptor (TCR) and T cells engineered to express CD19CAR. Mice were monitored for tumor growth and survival. The effects of indo on donor T cell phenotype and function were evaluated. The molecular mechanisms by which indo may influence the outcome of ACT were investigated.Results ACT coupled with indo administration led to improved tumor growth control and prolonged mouse survival. Indo did not affect the activation status and tumor infiltration of the donor T cells. Moreover, the beneficial effect of indo in ACT did not rely on its inhibitory effect on the immunosuppressive cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2) axis. Instead, indo-induced oxidative stress boosted the expression of death receptor 5 (DR5) in tumor cells, rendering them susceptible to donor T cells expressing TNF-related apoptosis-inducing ligand (TRAIL). Furthermore, the ACT-potentiating effect of indo was diminished against DR5-deficient tumors, but was amplified by donor T cells engineered to overexpress TRAIL.Conclusion Our results demonstrate that the pro-oxidative property of indo can be exploited to enhance death receptor signaling in cancer cells, providing rationale for combining indo with genetically modified T cells to intensify tumor cell killing through the TRAIL-DR5 axis. These findings implicate indo administration, and potentially similar use of other NSAIDs, as a readily applicable and cost-effective approach to augment the efficacy of ACT.

The Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and its ultraviolet (UV) radiation is much greater than that of other regions in the world. Yellow mushroom (Floccularia luteovirens) is a unique and widely distributed edible fungus on the QTP. However, the molecular mechanism of F. luteovirens’s response to strong UV radiation remains unclear. Herein, we reported the 205 environmental adaptation and information processing genes from genome of F. luteovirens. In addition, we assembled the RNA sequence of UV-affected F. luteovirens at different growth stages. The results showed that in response to strong UV radiation, a total of 11,871 significantly different genes were identified, of which 4,444 genes in the vegetative mycelium (VM) stage were significantly different from the young fruiting bodies (YFB) stage, and only 2,431 genes in the YFB stage were significantly different from fruiting bodies (FB) stage. A total of 225 differentially expressed genes (DEGs) were found to be involved in environmental signal transduction, biochemical reaction preparation and stress response pathway, pigment metabolism pathway, and growth cycle regulation, so as to sense UV radiation, promote repair damage, regulate intracellular homeostasis, and reduce oxidative damage of UV radiation. On the basis of these results, a molecular regulation model was proposed for the response of F. luteovirens to strong UV radiation. These results revealed the molecular mechanism of adaptation of F. luteovirens adapting to strong UV radiation, and provided novel insights into mechanisms of fungi adapting to extreme environmental conditions on the QTP; the production the riboflavin pigment of the endemic fungi (Yellow mushroom) in the QTP was one of the response to extreme environment of the strong UV radiation.

Abstract Two-dimensional (2D) semiconductors beyond graphene represent the thinnest stable known nanomaterials. Rapid growth of their family and applications during the last decade of the twenty-first century have brought unprecedented opportunities to the advanced nano- and opto-electronic technologies. In this article, we review the latest progress in findings on the developed 2D nanomaterials. Advanced synthesis techniques of these 2D nanomaterials and heterostructures were summarized and their novel applications were discussed. The fabrication techniques include the state-of-the-art developments of the vapor-phase-based deposition methods and novel van der Waals (vdW) exfoliation approaches for fabrication both amorphous and crystalline 2D nanomaterials with a particular focus on the chemical vapor deposition (CVD), atomic layer deposition (ALD) of 2D semiconductors and their heterostructures as well as on vdW exfoliation of 2D surface oxide films of liquid metals.

Continuous cropping often leads to an unbalanced soil microbial community, which in turn negatively affects soil functions. However, systematic research of how these effects impact the bacterial composition, microbial functional traits, and soil metabolites is lacking. In the present study, the rhizosphere soil samples of Tibetan barley continuously monocropped for 2 (CCY02), 5 (CCY05), and 10 (CCY10) years were collected. By utilizing 16S high-throughput sequencing, untargeted metabolomes, and quantitative microbial element cycling smart chips, we examined the bacterial community structure, soil metabolites, and bacterial functional gene abundances, respectively. We found that bacterial richness (based on Chao1 and Phylogenetic Diversity [PD] indices) was significantly higher in CCY02 and CCY10 than in CCY05. As per principal component analysis (PCA), samples from the continuous monocropping year tended to share more similar species compositions and soil metabolites, and exhibited distinct patterns over time. The results of the Procrustes analysis indicated that alterations in the soil metabolic profiles and bacterial functional genes after long-term continuous cropping were mainly mediated by soil microbial communities (P

Abstract Background Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China’s primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages. Methods We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months’ post-trial long-term follow-up. Discussion Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs. Trial registration ISRCTN, ID: ISRCTN96892547 . Registered on 18 August 2019.

Background: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB). Objective: To determine the significance of Th2/Th1 ratio and concentration of PD-L1 in the pleural effusions for prediction of MDR-TB. Methods: We measured the ratio of Th2 to Th1 T cells from pleural effusions in 373 tuberculous pleuritis patients. We also measured the concentration of programmed death ligand-1 (PD-L1) in the pleural effusions of these patients. Afterwards, we determined the optimal cut-off value for predicting the occurrence of multi-drug resistant tuberculous based on the Youden index, diagnostic evaluation test, and receiver operation curve. Multiple logistic analysis was employed to identify the independent risk factors for MDR-TB occurrence. Results: The area under the curve (AUC) of the Th2 to Th1 ratio was 0.66 and the concentration of PD-L1 was 0.71. Based on the combined detection of PD-L1 concentration in pleural effusion and the Th2 to Th1 ratio, our AUC was 0.81 and had a specificity of 0.92. Only a combined detection was able to identify patients developing multidrug-resistant tuberculosis. Multiple logistic analysis showed that a high concentration of PD-L1 and a high Th2 to Th1 T ratio in pleural effusions were indicative of an immunocompromised status. Therefore, these measurements might be independent risk factors for the occurrence of multidrug-resistant tuberculous. Conclusion: Evaluation of immune status based on PD-L1 pleural concentration and Th2 to Th1 ratio might predict the risk of MDR-TB occurrence.

Abstract Nanoscale Au-ZnO heterostructures were fabricated on 4-in. SiO2/Si wafers by the atomic layer deposition (ALD) technique. Developed Au-ZnO heterostructures after post-deposition annealing at 250 °C were tested for amperometric hydrogen peroxide (H2O2) detection. The surface morphology and nanostructure of Au-ZnO heterostructures were examined by field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), etc. Additionally, the electrochemical behavior of Au-ZnO heterostructures towards H2O2 sensing under various conditions is assessed by chronoamperometry and electrochemical impedance spectroscopy (EIS). The results showed that ALD-fabricated Au-ZnO heterostructures exhibited one of the highest sensitivities of 0.53 μA μM−1 cm−2, the widest linear H2O2 detection range of 1.0 μM–120 mM, a low limit of detection (LOD) of 0.78 μM, excellent selectivity under the normal operation conditions, and great long-term stability. Utilization of the ALD deposition method opens up a unique opportunity for the improvement of the various capabilities of the devices based on Au-ZnO heterostructures for amperometric detection of different chemicals. Graphical abstract

Sickle cell disease (SCD) is an inherited blood disorder caused by a mutation in the HBB gene leading to hemoglobin S production and polymerization under hypoxia conditions leading to vaso-occlusion, chronic hemolysis, and progressive organ damage. This disease affects ~100,000 people in the United States and millions worldwide. An effective therapy for SCD is fetal hemoglobin (HbF) induction by pharmacologic agents such as hydroxyurea, the only Food and Drug Administration-approved drug for this purpose. Therefore, the goal of our study was to determine whether salubrinal (SAL), a selective protein phosphatase 1 inhibitor, induces HbF expression through the stress-signaling pathway by activation of p-eIF2α and ATF4 trans-activation in the γ-globin gene promoter. Sickle erythroid progenitors treated with 24μM SAL increased F-cells levels 1.4-fold (p = 0.021) and produced an 80% decrease in reactive oxygen species. Western blot analysis showed SAL enhanced HbF protein by 1.6-fold (p = 0.0441), along with dose-dependent increases of p-eIF2α and ATF4 levels. Subsequent treatment of SCD mice by a single intraperitoneal injection of SAL (5mg/kg) produced peak plasma concentrations at 6 hours. Chronic treatments of SCD mice with SAL mediated a 2.3-fold increase in F-cells (p = 0.0013) and decreased sickle erythrocytes supporting in vivo HbF induction.

The COVID-19 pandemic broke the normal of school education and sounded the horn for future education reform. This paper designs the online and offline mixed teaching mode of the SPOC platform in the postpandemic era according to the actual situation of teaching at application-oriented colleges and universities, and the blended teaching mode is applied to real teaching scenarios. The teaching effect and students’ behaviors are analyzed in such scenarios. Empirical research shows that the situational teaching model based on mixed SPOC for course design, teaching resources are more abundant, and task assessments are more reasonable. Through the questionnaire survey, about 95% of the students think that the learning mode based on SPOC has improved their learning interest, autonomous learning ability, and problem-solving ability, which is much higher than the assessment of traditional courses. The exploratory practice has shown that the online and offline blended teaching mode based on SPOC can dramatically improve teaching quality.

The Fuyun Fault is a typical intraplate, slow-slipping fault, but has been repeatedly ruptured by surface wave magnitude (Ms) ≥ 8.0 earthquakes. The 11 August 1931 Ms 8.0 Fuyun earthquake resulted in more than 10,000 casualties in the sparsely populated Fuyun area. Cosmogenic 10Be dating of offset landforms produced by prehistoric Ms ≥ 8.0 earthquakes yields an average recurrence interval of 9,700 ± 3,300 years, much longer than previously estimated 2,000–4,500 years, clouding our understanding of the timing and recurrence behavior of past earthquakes originating from the Fuyun Fault. Reflection seismic data reveal widely distributed subaquatic faults in Yileimu Lake, implying high sensitivity of the lake sediments to paleoearthquakes originating from the Fuyun Fault. Two new long sediment cores (Y20A: 267 cm; Y20B: 890 cm) together with previously published two short cores (Y19: 71 cm; Y20: 31.5 cm) from the depocenter and nearshore zone of Yileimu Lake are used for stratigraphic correlations and analyses of sedimentary structures, grain-size distributions, magnetic susceptibility, elemental composition and carbon content. The mass-wasting deposits with underlying soft-sediment deformation structures (SSDS) in the Y20B core indicate six siliciclastic-enriched sandy sediment fluxes from earthquake-triggered landslides of granitic rocks, and isolated SSDS record three additional earthquake-induced in situ deformations. Turbidite-like deposits with sorting indices >3 and Si contents >700 counts per second (cps) are comparable to those of the seismic mass-wasting deposits, and are thus interpreted as seismites from earthquake-induced re-deposition of nearshore sediments. There are a total of 20 seismic events recorded by the Y20B core. Seismic intensity calculation results, combined with historical seismic data, provide potential magnitudes of Ms ≥ 8.0, Ms ≥ 7.0, and Ms ≥ 5.5 for the earthquake-triggered mass-wasting deposits, SSDS, and turbidite-like seismites, respectively, in Yileimu Lake, generally consistent with previously published magnitude thresholds. Radiocarbon dating and stratigraphic correlations constrain the timing of these past earthquakes to ∼28 cal kyr BP. This unique, long lacustrine paleoseismic record suggests a weakly periodic pattern with recurrence intervals between 2,317 and 7,830 years and an average of 5,303 years for potential Ms ≥ 8.0 earthquakes, and reveals an unprecedented high frequency of potential Ms ≥ 7.0 earthquakes originating from the Fuyun Fault in the last 5 kyr, demonstrating the urgent need for an improved assessment of seismic hazards and risks in the Fuyun Fault zone.

Change point analysis has been useful for practical data analytics. In this paper, we provide a new R package, onlineBcp, based on an online Bayesian change point detection algorithm. This R package conveniently outputs the maximum posterior probabilities of multiple change points, loci of change points, basic statistics for segments separated by identified change points, confidence interval for each unknown segment mean and a plot displaying the segmented data. Practically, missing value pre-treatment of the data, before the change point detection algorithm is implemented, is built in this package. In addition, the Kolmogorov–Smirnov test for checking the normality assumption on each segment, post-change point detection, is included as an option in the package for the ease of data analytic and assumption checking flow. When additional data come in, the package provides a function to combine changes identified based on prior data and changes identified based on additional data and thus provides a fast detection of change points in the data stream when new batches of data are collected.

Drug combination therapies can improve drug efficacy, reduce drug dosage, and overcome drug resistance in cancer treatments. Current research strategies to determine which drug combinations have a synergistic effect rely mainly on clinical or empirical experience and screening predefined pools of drugs. Given the number of possible drug combinations, the speed, and scope to find new drug combinations are very limited using these methods. Due to the exponential growth in the number of drug combinations, it is difficult to test all possible combinations in the lab. There are several large-scale public genomic and phenotypic resources that provide data from single drug-treated cells as well as data from small molecule treated cells. These databases provide a wealth of information regarding cellular responses to drugs and offer an opportunity to overcome the limitations of the current methods. Developing a new advanced data processing and analysis strategy is imperative and a computational prediction algorithm is highly desirable. In this paper, we developed a computational algorithm for the enrichment of synergistic drug combinations using gene regulatory network knowledge and an operational module unit (OMU) system which we generate from single drug genomic and phenotypic data. As a proof of principle, we applied the pipeline to a group of anticancer drugs and demonstrate how the algorithm could help researchers efficiently find possible synergistic drug combinations using single drug data to evaluate all possible drug pairs.

Background: In China, congenital heart disease (CHD) is the most common birth defect type, with approximately 13,000 new cases annually. This study aimed to investigate high-risk factors, prenatal screening and prenatal diagnosis as a basis for clinical decisions.Methods: All CHD cases identified from 2018 to 2020 were obtained from the Beijing city birth defect surveillance system and prenatal diagnosis institutions. The prenatal CHD diagnosis was confirmed by fetal echocardiography and amniotic fluid or cord blood genetic examination. Chi-square, odds ratio (OR), 95% confidence interval (CI), and univariate and multivariate logistic analyses were used to explore the high-risk factors, prenatal screening and prenatal diagnosis of CHD. Results: In total, 6,786/594,860 fetuses with CHD were diagnosed by prenatal echocardiography. The average incidence of CHD was 11.4 per 1,000 births, with an increase of 30.7 per 1,000 births from 2018 to 2020 (P < 0.05); the average incidence of complex CHD (CCHD) was 2.02 per 1,000 births, with no significant change from 2018 to 2020 (P > 0.05). Women age ≥35 years (OR 1.06, 95% CI 0.77–1.46) was at higher risk of having babies with CHD than women aged 21–34 years. Overall, CHD incidence increased with maternal age (OR1.03, 95% CI 1.02–1.03). Additionally, women who had a non-local household registration (OR 1.16, 95% CI 1.10–1.22) or had diabetes mellitus (DM) (OR 1.16, 95% CI 0.96–1.25) were at higher risk of CHD. As an independent factor, CCHD was related to maternal age, DM, fetal gender, and maternal education level (all P < 0.05). The prenatal ultrasound screening detection rate of CCHD was 97.59%, which was far higher than that of total CHD (51.67%) (P < 0.001). The prenatal ultrasound diagnosis rate of CCHD was higher than that of simple CHD (P < 0.001), but the coincidence rate in the ultrasound diagnosis of CCHD was lower than that of simple CHD (P < 0.001). Prenatal genetic testing revealed chromosomal abnormalities in 25.62% (279/1089) of CHD cases with indications for a prenatal diagnosis.Conclusions: Maternal age, household registration and DM were related to CHD occurrence. Prenatal ultrasound screening is a highly effective method for CCHD diagnosis, and CHD fetuses should be closely evaluated to exclude chromosomal abnormalities.

Tectonic and climatic process controlling gravel accumulation in tectonically active regions is the subject of active debate. In this study, the formation mechanism of a gravel layer in the Diexi lacustrine section, eastern Tibetan Plateau, was investigated using mutually validated dating methods and detailed analysis of sedimentary processes. Optically stimulated luminescence (OSL) and accelerator mass spectrometry (AMS) 14C dating show that the gravel layer in the Diexi section accumulated at approximately 16.79 ka BP. The sedimentary characteristics of the gravel layer and the contact between upper and lower strata indicate that the formation of the Diexi gravel layer was triggered by an earthquake rather than by a debris flow caused by torrential rain. And the result based on the intensity attenuation model are consistent with the characteristics of frequent large earthquakes in Diexi area. Detailed analysis of satellite images and sedimentary characteristics of the gravel layer provide evidence for an ancient landslide, which may be related to the gravel layer at Muer village (to the north of the Diexi section). Overall, this study reconstructs a gravel event at approximately 16.79 ka BP and has important theoretical and practical significance for understanding the formation mechanism of gravel deposits and analysing seismic events through gravel accumulation.

Objectives: The COVID-19 pandemic caused by the novel SARS-CoV-2 coronavirus has drastically altered the global realities. Harnessing national scale data from the COVID-19 pandemic may better inform policy makers in decision making surrounding the reopening of society. We examined country-level, daily-confirmed, COVID-19 case data from the World Health Organization (WHO) to better understand the comparative dynamics associated with the ongoing global pandemic at a national scale. Study design: Observational study. Methods: We included data from 20 countries in Europe, the Americas, Africa, Eastern Mediterranean and West Pacific regions, and obtained the aggregated daily new case data for the European Union including 27 countries. We utilized an innovative analytic approach by applying statistical change point models, which have been previously employed to model volatility in stock markets, changes in genomic data, and data dynamics in other scientific disciplines, to segment the transformed case data. This allowed us to identify possible change or turning points as indicated by the dynamics of daily COVID-19 incidences. We also employed B-spline regression models to express the estimated (predicted) trend of daily new incidences for each country’s COVID-19 disease burden with the identified key change points in the model. Results: We identified subtle, yet different change points (translated to actual calendar days) by either the mean and variance change point model with small p-values or by a Bayesian online change point algorithm with large posterior probability in the trend of COVID-19 incidences for different countries. We correlated these statistically identified change points with evidence from the literature surrounding these countries’ policies regarding opening and closing of their societies in an effort to slow the spread of COVID-19. The days when change points were detected were ahead of the actual policy implementation days, and in most of the countries included in this study the decision lagged the change point days too long to prevent potential widespread extension of the pandemic. Conclusions: Our models describe the behavior of COVID-19 prevalence at a national scale and identify changes in national disease burden as relating to chronological changes in restrictive societal activity. Globally, social distancing measures may have been most effective in smaller countries with single governmental and public health organizational structures. Further research examining the impact of heterogeneous governmental responses to pandemic management appears warranted.