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BackgroundReasonable and effective time allocation can promote the improvement of medical care service quality. This study aimed to translate, cross-culturally adapt and validate the Chinese Nursing Time Management Scale (NTMS).MethodsUsing a cross-sectional survey, 345 clinical nurses were selected from June to September 2023 for a general information questionnaire and Nursing Time Management Scale (NTMS) study. Item analysis, exploratory factor analysis and validation factor analysis were used to verify the reliability and validity of the Chinese version of Nursing Time Management Scale.ResultsThe Chinese version of the Nurses’ Time Management Competency Scale includes 17 entries in 3 dimensions: planning activities and setting goals, coordinating activities and procedures, and organizing nursing activities. The Cronbach’s alpha coefficient for the total scale was 0.966. Exploratory factor analysis showed that the cumulative variance contribution of the three male factors was 97.44%.ConclusionThe NTMS has acceptable validity and reliability and can be used to evaluate the nursing time management skills of Chinese clinical nurses.

Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

Epilepsy affects ∼ 65 million people worldwide. Status epilepticus can lead to life-threatening if untreated. In this study, peripheral blood mononuclear cells were isolated from a young patient patient bearing a Nitrogen Perntease Regulator Like 2 Protein (NPRL2) mutation and suffering from Epilepsy verified by clinical and genetic diagnosis. Induced pluripotent stem cells (iPSCs) were established by a non-integrative method, using plasmids carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSCs presented typical pluripotent cells morphology, normal karyotype, and potential to differentiate into three germ layers. Our approach offers a useful model to explore pathogenesis and therapy of Epilepsy.

Abstract Grassland provides multiple ecosystem services and plays a key role in preventing desert encroachment and maintaining oasis stability. In China, the area of cropland in oases has expanded significantly in recent decades, which results in a rapid increase in agricultural water demand and encroachment on grassland subsistence space. However, our knowledge about how the expansion of cropland affects oasis grasslands remains limited. We used machine learning, temporal segmentation of spectral trajectories, and maximum covariance analysis to generate an annual oasis grassland aboveground biomass (AGB) data set at 30‐m resolution from 1989 to 2021 based on multiple remotely sensed and ground observation data sets, and investigated the dynamics of grassland AGB under cropland expansion in oases. We found that overall oasis grassland AGB increased significantly (0.3 gm−2 yr−1, P

The symptoms and signs of infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are milder in children than in adults. However, in April 2020, British pediatricians first reported that coronavirus disease 2019 (COVID-19) may present as multisystem inflammatory syndrome in children and adolescents (MIS-C), similar to that observed in Kawasaki disease. MIS-C can be associated with multiple systemic injuries and even death in children. In addition to digestive system involvement, cardiac injury is prominent. This article reviews the pathogenesis, clinical manifestations, and treatment of cardiac injury caused by MIS-C, which may help clinicians in early diagnosis and timely commencement of treatment.

BackgroundCervical cancer is the fourth highest incidence of malignancy in the world and a common cause of cancer death in women. We assessed the trends of incidence and mortality and disability-adjusted life year (DALY) in China, England and India from 1990 to 2030.MethodData were obtained from the Global Burden of Disease (GBD) database. We collected the number and rate of incidence, death and DALY from 1990 to 2019 and calculated the estimated annual percentage change (EAPC). Further analysis was carried out by ages and years. We also collected attributable risk factors to cervical cancer. Finally, we utilized the Bayesian Age-Period-Cohort (BAPC) model to forecast trends in the rate of age-standardized incidence (ASIR) and age-standardized death (ASDR) the for the next decade.ResultGlobally, the incidence of cervical cancer cases increased from 335,641.56 in 1990 to 565,540.89 in 2019. In 2019, the ASIR and ASDR of cervical cancer were higher than those of India but lower than those of England. Furthermore, unsafe sex and smoking emerge as prominent risk factors for cervical cancer. Over the next decade, ASIR and ASDR are expected to decline in China and England, while India’s ASIR is still on an upward trend and ASDR is on a downward trend.ConclusionThe epidemiological data of cervical cancer in these three countries reflects the influence of different stages of development and healthcare systems. Trends over the next decade suggest that China and India still face a huge burden of cervical cancer. When England has made significant progress, China and India need to take more measures to improve the prevention and control of cervical cancer.

Sleep disturbances are highly prevalent during the COVID-19 pandemic, especially among older adults. We aimed to evaluate sleep heath during COVID-19 pandemic and assess the differences among geographical regions and pandemic periods. We searched three databases (PubMed, Embase, Web of Science) to find articles up to March 12, 2023. We included observational studies that reported the prevalence of sleep disturbances among adults aged 60 years or older in any setting. Two researchers independently reviewed the literature and retrieved the data. We used Der Simonian-Laird random effects meta-analyses to pool the data, followed by subgroup analysis, sensitivity analysis, and meta-regression. A total of 64 studies with 181,224 older adults during the pandemic were included. The prevalence of poor sleep quality, short sleep duration, long sleep duration, and insomnia symptoms were 47.12% (95% CI: 25.97%, 68.27%), 40.81% (95% CI: 18.49%, 63.12%), 31.61% (95% CI: 24.83%, 38.38%), and 21.15% (95% CI: 15.30%, 27.00%), respectively. The prevalence of sleep problems reported by self-constructed items was 26.97% (95% CI: 20.73%, 33.22%). When compared to America (64.13%), Europe (20.23%) and the Western Pacific (21.31%) showed a lower prevalence of sleep problems (all P

Abstract The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg and/or young ages, is still unresolved due to the lack of surrogate models. Here, we generate a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrate that human IFN stimulates gene expression profiles in huIFNAR peripheral blood mononuclear cells (PBMCs) are similar to those in human PBMCs, supporting the representativeness of this mouse model for functionally analyzing human IFN in vivo. Next, we reveal the tissue-specific gene expression atlas across multiple organs in response to human IFN treatment; this pattern has not been reported in healthy humans in vivo. Finally, by using the AAV-HBV model, we test the antiviral effects of human interferon. Fifteen weeks of human PEG-IFNα2 treatment significantly reduces HBsAg and HBeAg and even achieves HBsAg seroconversion. We observe that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon may be critical for HBsAg suppression. Our huIFNAR mouse can authentically respond to human interferon stimulation, providing a platform to study interferon function in vivo. PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieves HBsAg seroconversion.

In this paper, molybdenum disulfide was grown on the surface of iron-containing tailings by hydrothermal method, and a series of highly efficient activated persulfate (PMS) iron-based catalysts were successfully prepared. The results show that in the CTM 1–200/PMS system, the additional ratio of tailings and the hydrothermal temperature have important effects on the catalyst. The catalyst prepared under the conditions of CT:MoS2 (molar ratio 1:1) and hydrothermal temperature of 200 °C (CTM 1–200) had the best degradation effect on BPA, and the degradation effect was increased by four times. The reason for the improvement of degradation efficiency is that the introduction of MoS2 accelerates the REDOX cycle between Fe(II)/Fe(III), and the reduction of Fe(III) is mainly related to Mo(IV), while the reduction capacity of S is relatively weak. Molybdenum disulfide/iron tailing composite material provides a way for tailings to solve the problem of water pollution. HIGHLIGHTS Hydrothermal preparation of iron tailings supported MoS2 catalyst can effectively activate PMS to degrade BPA.; Mo element is harmless, solves resource waste of tailings, degrades BPA in wastewater and realizes ‘pollution control with waste’.; This study explores the synergistic reaction mechanism between MoS2 and iron tailings and proposes a REDOX reaction model in which MoS2 dual pathways accelerate the Fe(II)/Fe(III) cycle.;

Abstract Background BMP7 has been shown to have neuroprotective effects and to alleviate demyelination. However, its role in trigeminal neuralgia (TN) has not been well investigated. The current study aims to determine whether BMP7 plays a role in demyelination, its effects on pain behaviors and mechanism of action in rats with TN. Methods We used an infraorbital-nerve chronic-constriction injury (ION-CCI) to establish a rat model of TN. Adeno-associated viruses (AAVs) were injected into the rats to upregulate or downregulate BMP7. The mechanical withdrawal thresholds (MWT) of the injured rats were detected using Von Frey filaments. The changes in expression levels of BMP7 and oligodendrocyte (OL) markers were examined by western blotting, quantitative real-time PCR, immunofluorescence, and transmission electron microscopy. Results The ION-CCI induced mechanical allodynia, demyelination, and loss of OLs with a reduction of BMP7. Short-hairpin RNA (shRNA)-BMP7 that inhibited BMP7 expression also caused mechanical allodynia, demyelination, and loss of OLs, and its mechanism may be OL apoptosis. Overexpressing BMP7 in the trigeminal spinal subnucleus caudalis(VC) with AAV-BMP7 relieved all three phenotypes induced by the CCI, and its mechanism may be alleviating OLs apoptosis. Two signal pathways associated with apoptosis, STAT3 and p65, were significantly downregulated in the VC after CCI and rescued by BMP7 overexpression. Conclusion BMP7 can alleviate TN by reducing OLs apoptosis and subsequent demyelination. The mechanism behind this protection could be BMP7-mediated activation of the STAT3 and NF-κB/p65 signaling pathway and subsequent decrease in OL apoptosis. Importantly, our study presents clear evidence in support of BMP7 as a possible therapeutic target for the treatment of TN.

Highlights Heterostructure engineering is proposed to construct CoTe2/ZnTe heterostructures with built-in electric field. Conductive and elastic Ti3C2T x MXene is introduced to improve the conductivity and alleviate the volume change of CoTe2/ZnTe upon cycling. The resulting CoTe2/ZnTe/Ti3C2T x (CZT) demonstrates outstanding rate capability (137.0 mAh g−1 at 10 A g−1) and cycling stability (175.3 mAh g−1 after 4000 cycles at 3.0 A g−1). Moreover, the CZT-based full cells demonstrate excellent energy density (220.2 Wh kg−1) and power density (837.2 W kg−1).

Abstract Background Lung cancer is the leading cause of cancer related to mortality worldwide, and the main pathological type is lung adenocarcinoma (LUAD). Circular RNAs (circRNAs) have been reported to be modified by N6‐methyladenosine (m6A), which is involved in the progression of diverse tumors. However, the crosstalk between circRNAs and m6A modification has not been well elucidated in LUAD. Methods MeRIP‐seq and YTHDF2‐RIP‐seq datasets were explored to identify candidate circRNAs modified by YTHDF2. Dual‐luciferase reporter assay, RIP, and rescue assays were performed to explore the relationship between circFUT8 and its parent mRNA of FUT8. In vitro and in vivo experiments were utilized to uncover the function of circFUT8. Results In this study, we identified a novel m6A‐modified circFUT8, derived from exon 3 of FUT8, which was elevated in tumor tissues compared with adjacent noncancerous tissues. The m6A reader YTHDF2 recognized and destabilized circFUT8 in an m6A‐dependent manner. YTHDF2 also combined with the line form of FUT8 (mFUT8), and circFUT8 competitively interacted with YTHDF2, blunting its binding to mFUT8, to stabilize the mRNA level of FUT8. Additionally, circFUT8 sponged miR‐186‐5p to elevate the expression of mFUT8. Finally, we revealed that circFUT8 promoted the malignant progression of LUAD dependent on the oncogenic function of FUT8. Conclusions These findings identified a novel m6A‐modified circFUT8 recognized and destabilized by YTHDF2, which competitively interacted with YTHDF2 and miR‐186‐5p to stabilize FUT8 mRNA to promote malignant progression in LUAD.

Abstract Senescence is a hot topic nowadays, which shows the accumulation of senescent cells and inflammatory factors, leading to the occurrence of various senescence-related diseases. Although some methods have been identified to partly delay senescence, such as strengthening exercise, restricting diet, and some drugs, these only slow down the process of senescence and cannot fundamentally delay or even reverse senescence. Stem cell-based therapy is expected to be a potential effective way to alleviate or cure senescence-related disorders in the coming future. Mesenchymal stromal cells (MSCs) are the most widely used cell type in treating various diseases due to their potentials of self-replication and multidirectional differentiation, paracrine action, and immunoregulatory effects. Some biological characteristics of MSCs can be well targeted at the pathological features of aging. Therefore, MSC-based therapy is also a promising strategy to combat senescence-related diseases. Here we review the recent progresses of MSC-based therapies in the research of age-related diseases and the challenges in clinical application, proving further insight and reference for broad application prospects of MSCs in effectively combating senesce in the future.

As a member of the pattern recognition receptor (PRR) class, scavenger receptor class B type 1 (SRB1) plays a key role in innate immunity. Grass carp (Ctenopharyngodon idellus) ranks among the most extensively cultivated freshwater aquaculture species in China. However, little is known about the function of SRB1 in C. idellus. In this research study, a SRB1 gene was identified in C. idellus, named CiSRB1. The full-length cDNA of CiSRB1 is 2486 bp long, with an open reading frame (ORF) of 2486 bp encoding a 497 amino acid (aa) protein containing a conserved CD36 domain. The identified genomic DNA length of CiSRB1 is 20,042 bp, including 12 exons and 11 introns. The predictive analysis of protein interactions revealed that CiSRB1 could interact with the outer capsid proteins of typical GCRV strains. The tissue distribution of CiSRB1 exhibited age-dependent characteristics. CiSRB1 displayed the highest expression in the intestines and moderate levels in muscle, spleen, liver, and brain of one-year-old grass carp while maintaining relatively low levels in three-year-old grass carp. Following grass carp reovirus (GCRV) infection, notable upregulation of CiSRB1 transcripts was observed in major immune tissues (gills, intestines, spleen, and liver). Furthermore, significant differences were found between one-year-old and three-year-old grass carp, with lower CiSRB1 expression levels being detected in the older group. Additionally, a distinct response to GCRV infection was observed in one-year-old and three-year-old grass carp. It was found that one-year-old individuals had a mortality rate of up to 84% 6 days post-infection (dpi), whereas all three-year-old counterparts survived after GCRV infection. The analysis of GCRV copy numbers across tissues revealed substantially higher levels in one-year-old grass carp compared with their older counterparts, confirming the existence of age-dependent susceptibility to GCRV infection in grass carp. Combined with these results, it was speculated that the decline in cell-surface CiSRB1 expression with age may impede reovirus binding to host cells, potentially explaining why older grass carp demonstrated enhanced resistance to GCRV infection. This observation accentuates the importance of CiSRB1 in the context of GCRV infection and provides insights into age-dependent susceptibility to reovirus.

Abstract Background There is a growing body of evidence suggesting that disturbance of the gut-brain axis may be one of the potential causes of major depressive disorder (MDD). However, the effects of antidepressants on the gut microbiota, and the role of gut microbiota in influencing antidepressant efficacy are still not fully understood. Results To address this knowledge gap, a multi-omics study was undertaken involving 110 MDD patients treated with escitalopram (ESC) for a period of 12 weeks. This study was conducted within a cohort and compared to a reference group of 166 healthy individuals. It was found that ESC ameliorated abnormal blood metabolism by upregulating MDD-depleted amino acids and downregulating MDD-enriched fatty acids. On the other hand, the use of ESC showed a relatively weak inhibitory effect on the gut microbiota, leading to a reduction in microbial richness and functions. Machine learning-based multi-omics integrative analysis revealed that gut microbiota contributed to the changes in plasma metabolites and was associated with several amino acids such as tryptophan and its gut microbiota-derived metabolite, indole-3-propionic acid (I3PA). Notably, a significant correlation was observed between the baseline microbial richness and clinical remission at week 12. Compared to non-remitters, individuals who achieved remission had a higher baseline microbial richness, a lower dysbiosis score, and a more complex and well-organized community structure and bacterial networks within their microbiota. These findings indicate a more resilient microbiota community in remitters. Furthermore, we also demonstrated that it was not the composition of the gut microbiota itself, but rather the presence of sporulation genes at baseline that could predict the likelihood of clinical remission following ESC treatment. The predictive model based on these genes revealed an area under the curve (AUC) performance metric of 0.71. Conclusion This study provides valuable insights into the role of the gut microbiota in the mechanism of ESC treatment efficacy for patients with MDD. The findings represent a significant advancement in understanding the intricate relationship among antidepressants, gut microbiota, and the blood metabolome. Additionally, this study offers a microbiota-centered perspective that can potentially improve antidepressant efficacy in clinical practice. By shedding light on the interplay between these factors, this research contributes to our broader understanding of the complex mechanisms underlying the treatment of MDD and opens new avenues for optimizing therapeutic approaches. Video Abstract

In this paper, we investigate a stochastic prey-predator model with Holling-type IV functional responses, anti-predatory behavior (referring to prey resistance to predator), gestation time delay of prey and Lévy noise. We investigate the existence and uniqueness of global positive solutions through Itô's formulation and Lyapunov's method. We also provide sufficient conditions for the persistence and extinction of prey-predator populations. Additionally, we examine the stability of the system distribution and validate our analytical findings through detailed numerical simulations. Our paper concludes with the implications of our results.

Abstract Background People in China and the countries in the Association of Southeast Asian Nations (ASEAN) are affected by neglected tropical diseases and malaria (NTDM). In this study, we aimed to assess the current status and trends of NTDM burden from 1990 to 2019 in China and ASEAN countries, and also explore the association of NTDM burden with socio-demographic index (SDI). Methods The data from the Global Burden of Diseases Study 2019 (GBD 2019) results were used. Absolute incidence and death number, and age-standardized incidence and mortality rate (ASIR and ASMR) of NTDM in China and ASEAN were extracted. The estimated annual percentage change (EAPC) and join-point regression in the rates quantified the trends. Nonlinear regression (second order polynomial) was used to explore the association between SDI and ASRs. Results The ASIR of NTDM increased in China, Philippines, Singapore and Brunei, at a speed of an average 4.15% (95% CI 3.83–4.47%), 2.15% (1.68–2.63%), 1.03% (0.63–1.43%), and 0.88% (0.60–1.17%) per year. Uptrends of ASIR of NTDM in recent years were found in China (2014–2017, APC = 10.4%), Laos (2005–2013, APC = 3.9%), Malaysia (2010–2015, APC = 4.3%), Philippines (2015–2019, APC = 4.2%), Thailand (2015–2019, APC = 2.4%), and Vietnam (2014–2017, APC = 3.2%, all P

Picea mongolica is a rare tree species in China, which is of great significance in combating desertification and improving the harsh ecological environment. Due to the low rate of natural regeneration, high mortality, and susceptibility to pests and cold springs, Picea mongolica has gradually become extinct. At present, somatic embryogenesis (SE) is the most effective method of micro-proliferation in conifers, but the induction rate of embryogenic callus (EC) is low, and EC is difficult to differentiate from non-embryonic callus (NEC). Therefore, the EC and NEC of Picea mongolica were compared from the morphology, histological, physiological, and transcriptional levels, respectively. Morphological observation showed that the EC was white and transparent filamentous, while the NEC was compact and brownish-brown lumpy. Histological analyses showed that the NEC cells were large and loosely arranged; the nuclei attached to the edge of the cells were small; the cytoplasm was low; and the cell gap was large and irregular. In the EC, small cells, closely arranged cells, and a large nucleus and nucleolus were observed. Physiological studies showed significant differences in ROS-scavenging enzymes between the EC and NEC. Transcriptome profiling revealed that 13,267 differentially expressed genes (DEGs) were identified, 3682 were up-regulated, and 9585 were down-regulated. In total, 63 GO terms had significant enrichment, 32 DEGs in plant hormone signal transduction pathway were identified, and 502 different transcription factors (TFs) were characterized into 38 TF families. Meanwhile, we identified significant gene expression trends associated with somatic embryo development in plant hormones (AUX/IAA, YUCCA, LEA, etc.), stress (GST, HSP, GLP, etc.), phenylpropanoid metabolism (4CL, HCT, PAL, etc.), and transcription factors (AP2/ERF, MYB, WOX, etc.). In addition, nine genes were chosen for RT-qPCR, and the results were consistent with RNA-Seq data. This study revealed the changes in morphology, histology, physiology, and gene expression in the differentiation of NEC into EC and laid the foundation for finding the key genes to promote EC formation.

Summary: Cerebellar involvement in both motor and non-motor functions manifests in specific regions of the human cerebellum, revealing the functional heterogeneity within it. One compelling theory places the heterogeneity within the cerebellar functional hierarchy along the sensorimotor-association (SA) axis. Despite extensive neuroimaging studies, evidence for the cerebellar SA axis from different modalities and scales was lacking. Thus, we establish a significant link between the cerebellar SA axis and spatio-molecular profiles. Utilizing the gene set variation analysis, we find the intermediate biological principles the significant genes leveraged to scaffold the cerebellar SA axis. Interestingly, we find these spatio-molecular profiles notably associated with neuropsychiatric dysfunction and recent evolution. Furthermore, cerebello-cerebral interactions at genetic and functional connectivity levels mirror the cerebral cortex and cerebellum’s SA axis. These findings can provide a deeper understanding of how the human cerebellar SA axis is shaped and its role in transitioning from sensorimotor to association functions.

The Bacillus velezensis strain NBNZ-0060 was isolated from the bottom sediment samples of the lake Jin in Wuhan, China. This strain is an aerobic denitrifying bacterium and able to promote growth of submerged macrophytes. The 3,929,784 bp entire genome contains 3,781 coding sequences (CDS), 27 rRNAs, 85 tRNAs, 5 ncRNAs, with an average G + C content of 46.5%. The average nucleotide identity and digital DNA-DNA values between strain NBNZ-0060 and Bacillus velezensis NRRL B-41580T were 98.28% and 84.5%, respectively. The genome data have been deposited in NCBI with the accession number CP133277.1.

While virtual reality(VR) technology enhances learning, it also places new demands on medical learning evaluation. Verifying the occurrence of learning is a primary issue. To design and implement practical and feasible VR-based learning evaluation based on the immersive learning evaluation framework, the Substitution-Augmentation-Modification-Redefinition (SAMR) model, a VR-based learning evaluation framework, was constructed. This framework included competency, learning objectives, assessment tasks, evaluation data, criteria, and feedback. A comprehensive application pathway was developed, utilizing technological integration frameworks. This pathway includes the selection and implementation processes to offer teachers theoretical direction on evaluating medical learning using VR. Finally, this study performed a learning evaluation utilizing VR. The findings revealed that using VR for evaluation can create a deeply engaging and interactive environment. Participants reported feeling a strong sense of being present in the virtual environment and expressed high acceptance and satisfaction with the VR evaluation process. Furthermore, they believed that VR evaluation offers a comprehensive and practical means of assessing cognitive abilities and receiving feedback. These findings establish that VR evaluation optimise learning assessment and showcase the feasibility of the assessment framework and application path.

Background: The burden of neonatal infections in low- and middle-income countries and territories (LMICs) is a critical public health challenge, while our understanding of specific burden and secular trends remains limited. Methods: We gathered annual data on 15 types of neonatal infections in LMICs from 1990 to 2019 from the Global Burden of Disease 2019. Numbers, rates, percent changes, and estimated annual percentage changes of incidence and deaths were calculated. We also explored the association between disease burden, socio-demographic index (SDI), and universal health coverage index (UHCI). Results: Enteric infections and upper respiratory infections owned the top highest incidence rates for neonates in 2019. Neonatal sepsis and other neonatal infections, as well as otitis media, demonstrated an increasing trend of incidence across all 3 low- and middle-income regions. The top 3 causes of neonatal mortality in 2019 were neonatal sepsis and other neonatal infections, lower respiratory infections, and enteric infections. Between 1990 and 2019, all of the neonatal infection-related mortality rates suggested an overall decline. Sex differences could be found in the incidence and mortality of some neonatal infections, but most disease burdens decreased more rapidly in males. SDI and UHCI were both negatively associated with most of the disease burden, but there were exceptions. Conclusions: Our study serves as a vital exploration into the realities of neonatal infectious diseases in LMICs. The identified trends and disparities not only provide a foundation for future research but also underscore the critical need for targeted policy initiatives to alleviate on a global scale.

As a key component of rotating machinery power transmission system, rolling bearings in gas turbines are often required to serve in complex working conditions such as the high speed, the heavy load, the variable load, the variable rotational speed, and so on. The signals of bearing failures are easily drowned out by strong background noise and disturbances of related components. In the mechanical transmission system, the signals of bearing failures are easily submerged by the strong background noise and the disturbance of related components, especially for the composite bearing failures, which seriously hinders the effective identification of the vibration characteristics of the bearing operating state and increases the difficulty of fault diagnosis. In order to investigate the impact of interference on the bearing, through the establishment of rolling bearing composite fault vibration model, analyze the relationship between the vibration signals caused by different types of bearing failures and the corresponding vibration characteristics, to reveal the transmission system of the parts of the perturbation of the main multi-interference factors on the bearing fault signal influence law. The experimental verification shows that disturbance yp(t) caused by the sum of gear meshing frequency, and installation errors of the shaft, and coupling in the transmission system and background noise ni(t), which makes the fault frequency relatively weak and difficult to observe, and makes it difficult to accurately separate the fault information of the bearing. It provides a theoretical basis to solve the problem of damage identification and fault diagnosis of rolling bearings under multi-interference state.

Aims: Association between perceived discrimination and depression has been demonstrated in some sources of discrimination, such as age, sex, and race. However, the effects of perceived discrimination both in any domain and each domain on development of depression are still unclear. We aimed to estimate the association of any and each domain of perceived discrimination with the risk of depression among US older adults. Methods: We did a population-based cohort study using eight waves (from 2006 to 2020) of data from the Health and Retirement Study (HRS), a nationally representative study of US older adults aged 51 years and above. Perceived discrimination was measured by the shortened 5-item version of Williams’ discrimination scale, including five domains (less courtesy, service setting, not smart, threatened or harassed, and medical setting). Depressive symptoms were assessed with shortened 8-item version of the Center for Epidemiological Depression scale (8-item CES-D). Cox proportional hazards models were used to estimate the crude and adjusted hazards ratio (HRs) and their 95 % confidence intervals (CIs) between perceived discrimination and risk of depression, after controlling for potential confounders. Results: A total of 18502 participants were included in our final analyses. 42.8 % of them had any perceived discrimination at baseline, and the most prevalent perceived discrimination was feeling less courtesy, which was observed in 5893 people (31.6 %). During a median of 9.8 years follow-up, 44.7 % of participants developed depression. The risk of depression was 46 % (adjusted HR: 1.46, 95 % CI: 1.39–1.52) higher among people with perceived discrimination than those without. The associations between perceived discrimination in each domain and risk of depression were all prominent. Conclusions: Both any and each domain of perceived discrimination were associated with an increased risk of depression. Considering the high prevalence of perceived discrimination and the following poor health outcomes, our findings suggested the integrated measures of providing public education and diversified communication to reduce discrimination, as well as accessible emotional supports to prevent depression are urgently needed.

[Objective] Overhaul operations for urban rail transit vehicles pose challenges and bottlenecks in the organization of maintenance work. Currently, there is a lack of systematic exploration of the overhaul contents and process design tailored for maintenance. [Method] Analyzing and refining the process design for the advanced overhaul schedule of urban rail transit vehicles is essential to improving the rationality of maintenance work arrangement, and effectively address the increased maintenance work demands resulting from the expansion of line network mileage and passenger flow volume. Based on existing research achievements regarding maintenance facility layout and maintenance task sequence optimization, the current urban rail transit vehicle overhaul situation is analyzed. Features such as shift repairs between lines, concentrated component-specific repairs, and diverse maintenance strategies in the overhaul operations are summarized. Subsequently, the process characteristics of the overhaul are outlined from the perspectives of process flow, maintenance strategies, and allocation of maintenance resources. Furthermore, a flexible process for overhaul is proposed, including the introduction of parallel operations in the process flow, adjustment of maintenance strategies based on the operational capacity of the maintenance line, and the separation of maintenance equipment and personnel in the allocation of maintenance resources. A computational example analysis is carried out based on the actual overhaul process of a 6-car formation urban rail transit train. [Result & Conclusion] Under a fixed process flow, the overhaul time required for synchronous maintenance strategy is 25 days. By applying flexible process, the required maintenance time is reduced to only 17.5 days, resulting in a 7.5-day reduction in maintenance time compared to the fixed process. The reduction in maintenance time stems from the introduction of parallel operations and the avoidance of executing synchronous overhaul strategy for the entire vehicle when the maintenance facility capacity is insufficient. The computational example results indicate that applying flexible process can effectively shorten the overhaul time of trains, thereby enhancing the maintenance efficiency of urban rail transit vehicles.

AbstractBackground Corona Virus Disease 2019 (COVID-19) has a significant impact on sleep quality. However, the effects on sleep quality in the post-COVID-19 pandemic era remain unclear, and there is a lack of a screening tool for Chinese older adults. This study aimed to understand the prevalence of poor sleep quality and determine sensitive variables to develop an effective prediction model for screening sleep problems during infectious diseases outbreaks.Materials and Methods The Peking University Health Cohort included 10,156 participants enrolled from April to May 2023. The Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality. The data were randomly divided into a training-testing cohort (n = 7109, 70%) and an independent validation cohort (n = 3027, 30%). Five prediction models with 10-fold cross validation including the Least Absolute Shrinkage and Selection Operator (LASSO), Stochastic Volatility Model (SVM), Random Forest (RF), Artificial Neural Network (ANN), and XGBoost model based on the area under curve (AUC) were used to develop and validate predictors.Results The prevalence of poor sleep quality (PSQI >7) was 30.69% (3117/10,156). Among the generated models, the LASSO model outperformed SVM (AUC 0.579), RF (AUC 0.626), ANN (AUC 0.615) and XGBoost (AUC 0.606), with an AUC of 0.7. Finally, a total of 12 variables related to sleep quality were used as parameters in the prediction models. These variables included age, gender, ethnicity, educational level, residence, marital status, history of chronic diseases, SARS-CoV-2 infection, COVID-19 vaccination, social support, depressive symptoms, and cognitive impairment among older adults during the post-COVID-19 pandemic. The nomogram illustrated that depressive symptoms contributed the most to the prediction of poor sleep quality, followed by age and residence.Conclusions This nomogram, based on twelve-variable, could potentially serve as a practical and reliable tool for early identification of poor sleep quality among older adults during the post-pandemic period.

ABSTRACTObjectives: High reactive oxygen species (ROS) levels lead to cell death, and the testes are among the most vulnerable organs to oxidative damage. Rg1, an active ingredient extracted from the natural medicine ginseng, has potential anti-inflammatory, antioxidant and antiapoptotic properties. Our previous studies showed that Rg1 can effectively improve spermatogenic function in mice, but the specific mechanism remains unclear. The purpose of this study was to investigate the effect of Rg1 on oxidative stress and spermatogonium apoptosis in D-gal-induced testicular toxicity and elucidate the associated mechanism.Methods: Male C57BL/6 mice at 6–8 weeks of age were intraperitoneally injected with D-gal (200 mg/kg) for 42 days to establish a testicular injury model, and on day 16, 40 mg/kg Rg1-rich saline was injected intraperitoneally. Concurrently, we established an in vitro model of D-gal-damaged spermatogonia, which was treated with Rg1.Results: We found that treatment with the ginsenoside Rg1 reduced D-gal-induced oxidative stress and spermatogonium apoptosis in vivo and in vitro. Mechanistically, we found that Rg1 activated Akt/bad signaling and reduced D-gal-induced spermatogonium apoptosis.Discussion: We provide evidence showing that the antioxidant effect of Rg1 is mediated by the Akt/GSK-3β/NRF2 axis. Based on these findings, we consider Rg1 a potential treatment for testicular oxidative damage.

AbstractGadolinium-based MR cisternography has been mainly applied in clinical evaluation of cerebrospinal fluid leaking, that is conducted by intrathecal administration of contrast media. Recently, we have reported one novel technique of intrathecal targeted drug delivery with prepontine cisternal routine to treat orofacial cancer pain. The aim of this study was to examine the distribution pattern of this intrathecal drug delivery strategy. Here, we introduce one case who suffered severe orofacial pain caused by sublingual gland tumor, and successfully attenuated by prepontine cisternal administration of analgesic agents. To assess the distribution of intrathecal drugs, postoperative MR images of brain, cervical, thoracic, and lumbar segments in axial, coronal, and sagittal planes were obtained after application of gadolinium. The perfusion rate of contrast medium was set at 0.01 mmol per hour for 24 hours prior to MR scanning. In the T1-weighted images, we can identify contrast spread not only locating around the site of the intrathecal catheter tip, but also concentrated to the lateral sides. None obvious side effect was found after intrathecal injection of contrast media. Thus, our finding demonstrated the local distribution phenomenon of intrathecal drugs through prepontine cisternal access, and the bilateral perfusion pattern may provide insights underlying the analgesic mechanism of trigeminal pain provided by this novel intrathecal therapy. Gadolinium-based MR cisternography may serve as a potential tool to confirm the therapeutic effect of intrathecal targeted drug delivery via prepontine cisternal routine in orofacial pain management.

Accurate and continuous meteorological observation data are necessary in researches of weather forecast and climate prediction， also homogeneity long-series data are necessary in climate change researches.In order to make knowledge of the continuity of the observation data at new and old stations and investigate the potential impact on the long-term data from the change of site location， two indexes of the difference and the standard deviation （SD） of the difference were calculated based on 1a comparative observation records from 15 relocated meteorological sites in Gansu Province to investigate the impact of station relocation on the observation of meteorological elements.The SNHT method was used to test the homogenization of the old and new observations from 2 sites， Zhangye station and Ningxian station， as well as the impact of station relocation on long-series data.The first one has the longest distance change between old and new locations， and the second one has the biggest altitude change.According to the results from the difference and the SD of the difference， the air temperature at new stations is lower than the old ones， and the wind speed is higher at the new sites， and the relative humidity at new stations is generally higher than the old sites.Also， the impact from station relocation on the mean air temperature and the minimum temperature is greater than that on the maximum temperature.those sites with the biggest difference in the mean air temperature and the minimum temperature among all the 15 sites got the relatively longest migrating distance and greatest altitude change.The relationship between two indexes， the absolute difference and the standard deviation of the difference， and the distance and altitude difference of the sites relocated indicated that there is bigger influence from the altitude change on the maximum temperature and average wind speed.while the migration distance produced a bigger influence on the average temperature， minimum temperature and relative humidity.According to the homogeneity test results from selected stations， the big straight-line distance （altitude） change during the relocation will have an impact on the homogeneity of the temperature data.But whether there existed a threshold for this impact or there are some other which will enforce this impact needed to be further researched.It is expected that the possible impact from station relocation on the observations could be paid attention when scientific researchers and business personnel use the meteorological data.

In Hawai’i, ecosystem conservation practitioners are increasingly considering the potential ecohydrological benefits from applied conservation action to mitigate the degrading impacts of runoff on native and restored ecosystems. One determinant of runoff is excess rainfall events where rainfall rates exceed the infiltration capacity of soils. To help understand runoff risks, we calculated the probability of excess rainfall events across the Hawaiian landscape by comparing the probability distributions of projected rainfall frequency and land-cover-specific infiltration capacity. We characterized soil infiltration capacity based on different land cover types (bare soil, grasses, and woody vegetation) and compared them to the frequency of large rainfall events under current and future climate scenarios. We then mapped the potential risk of excess rainfall across the main Hawaiian Islands. Our results show that land cover type has a very large effect on runoff risk as excess rainfall conditions are 234% more likely in bare soil and 75% more likely in grasslands compared to woody forests and shrublands. In contrast, projected shifts in rainfall intensity by end-of-century show little impact on these probabilities and thus, the risk of runoff. This indicates that the probability of excess rainfall is primarily driven by differences in land cover and not by current or potential shifts in rainfall patterns across the Hawaiian landscape. The ability to estimate the risk of potentially ecologically and economically costly runoff based on changes of land cover is useful for managers focused on invasive species control and restoration planning, especially for native and endemic ecosystems unique to the State of Hawai’i.

Abstract Background Multimorbidity of non-communicable diseases (NCDs) is increasingly prevalent among older adults around the world, leading a higher risk of household catastrophic health expenditure (CHE). As current powerful evidence was insufficient, we aimed to estimate the association between multimorbidity of NCDs and the risk of CHE in China. Methods We designed a cohort study using data investigated in 2011–2018 from the China Health and Retirement Longitudinal Study, which is a nationally-representative study covering 150 counties of 28 provinces in China. We used mean ± standard deviation (SD) and frequencies and percentages to describe baseline characteristics. Person χ2 test was employed to compare the differences of baseline characteristics between households with and without multimorbidity. Lorenz curve and concentration index were used to measure the socioeconomic inequalities of CHE incidence. Cox proportional hazards models were applied to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between multimorbidity and CHE. Results Among 17,708 participants, 17,182 individuals were included for the descriptive analysis of the prevalence of multimorbidity in 2011, and 13,299 individuals (8029 households) met inclusion criteria and were included in the final analysis with a median of 83 (interquartile range: 25–84) person-months of follow-up. 45.1% (7752/17,182) individuals and 56.9% (4571/8029) households had multimorbidity at baseline. Participants with higher family economic level (aOR = 0.91, 95% CI: 0.86–0.97) had lower multimorbidity prevalence than those with lowest family economic level. 82.1% of participants with multimorbidity did not make use of outpatient care. The CHE incidence was more concentrated among participants with higher socioeconomic status (SES) with a concentration index of 0.059. The risk of CHE was 19% (aHR = 1.19, 95% CI: 1.16–1.22) higher for each additional NCD. Conclusions Approximately half of middle-aged and older adults in China had multimorbidity, causing a 19% higher risk of CHE for each additional NCD. Early interventions for preventing multimorbidity among people with low SES could be intensified to protect older adults from financial hardship. In addition, concerted efforts are needed to increase patients’ rational healthcare utilization and strengthen current medical security for people with high SES to reduce economic disparities in CHE.

Objectives: To assess the duration of viable virus shedding and polymerase chain reaction (PCR) positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract. Methods: We systematically searched PubMed, Cochrane, and Web of Science for original articles reporting the duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract from November 11, 2021 to December 11, 2022. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42022357349). We used the DerSimonian-Laird random-effects meta-analyses to obtain the pooled value and the 95% confidence intervals. Results: We included 29 studies and 230,227 patients. The pooled duration of viable virus shedding of the SARS-CoV-2 Omicron variant in the upper respiratory tract was 5.16 days (95% CI: 4.18-6.14), and the average duration of PCR positivity was 10.82 days (95% CI: 10.23-11.42). The duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in symptomatic patients was slightly higher than that in asymptomatic patients, but the difference was not significant (P >0.05). Conclusion: The current study improves our understanding of the status of the literature on the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract. Our findings have implications for pandemic control strategies and infection control measures.

The Chinese Loess Plateau has undergone extensive revegetation to restore degraded land and enhance carbon sequestration. However, soil organic carbon (SOC) sequestrated in the soil profiles of deep-rooted plants has not been fully studied. Here, we investigated the SOC within a 0–23 m profile in farmlands and apple orchards converted from farmlands with different ages (A5, 20 years) and the controlling factors on three loess tablelands (Changwu, Qingyang, and Luochuan). The results show that SOC stocks among farmlands and orchards showed no significant difference (p = 0.88); however, SOC stocks showed a trend with tree ages, i.e., a decrease for A5 and A10 but an increase for A15 and A20. For the vertical variability, the SOC stock was the highest within 0–1 m, regardless of the standing age; however, the SOC stock in this layer only accounted for 8.8% of the total SOC stock (97.93 ± 9.18 kg m−2). Climate accounted for 82% of the variations and controlled the changes in SOC in the 0–1 m range, while soil texture dominated the SOC in the soil below 1 m, accounting for 57% of the SOC variations. The variations in SOC in the thick, unsaturated zones provide implications for future land use management and the sustainability of apple orchards in arid regions.

Objective: This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. Methods: This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. Results: The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. Conclusions: Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

High-density building environments and fast-paced working conditions in cities pose health challenges for office workers. Office-type pocket parks assume the social responsibility of providing restorative environments for office workers, and the soundscape is an essential element of such environments. However, there is limited research on soundscape restoration in office-type pocket parks. Therefore, this study focused on soundscape restoration in office-type pocket parks. First, on-site investigations explored the spatial characteristics of 55 office-type pocket parks while analysing the soundscape features of 12 representative parks. Notably, significant correlations emerged among the perceptual parameters of the soundscape. Subsequently, three dimensions were extracted through an experimental study on the restoration levels of soundscape elements in office-based pocket parks: attractiveness, coordination, and disengagement. Finally, this study explored the impact of spatial enclosures and interface characteristics on soundscape restoration levels. This revealed that the restorative effect of negative sounds, such as traffic, air-conditioning, and speech, is significantly negatively correlated with spatial enclosure. Therefore, the greater the enclosure, the lower the restorative effect of the soundscape. Birdsongs significantly enhance the attractiveness of grey spaces, whereas small fountain sounds are most coordinated in blue spaces. This study provides a reference for the design of soundscapes in pocket parks to build healthy, restorative urban environments.

Alpha-ketoglutaric acid (α-KG), as an intermediate product of the tricarboxylic acid cycle, plays a crucial role in peptide and amino acid synthesis. In order to reduce costs and improve efficiency in the oxidative production of α-ketoglutaric acid, this study successfully synthesized and expressed L-glutamate oxidase (LGOXStr) from Streptomyces viridosporus R111 and catalase (KatGEsc) from Escherichia coli H736. Two immobilization methods and the conditions for one-step whole-cell catalysis of α-ketoglutaric acid were investigated. α-Ketoglutaric acid has broad applications in the pharmaceutical, food, and chemical industries. The specific research results are as follows: (1) By fusing the sfGFP tag, L-glutamate oxidase (LGOXStr r) and catalase (KatGEsc) were successfully anchored to the outer membrane of Escherichia coli cells, achieving one-step whole-cell catalysis of α-ketoglutaric acid with a conversion efficiency of up to 75%. (2) Through the co-immobilization of LGOXStr and KatGEsc, optimization of the preparation parameters of immobilized cells, and exploration of the immobilization method using E.coli@ZIF-8, immobilized cells with conversion rates of over 60% were obtained even after 10 cycles of reuse. Under the optimal conditions, the production rate of α-ketoglutaric acid reached 96.7% in a 12 h reaction, which is 1.1 times that of E. coli@SA and 1.29 times that of free cells.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

This study identified 13 GhTIR1/AFB members in G. hirsutum through bioinformatics methods and divided them into three subgroups by phylogenetic tree analysis. Motif and gene structure analysis showed that the genes in this family were highly conserved. Promoter cis-acting element analysis found that the promoters of GhTIR1/AFBs contained a large number of cis-acting elements in response to growth and development and abiotic stress. Further RT-qPCR results showed that GhTIR1/AFB genes responded to various abiotic stresses such as IAA, ABA, cold, and heat, and the expression levels of each gene changed obviously, especially Gh_D08G0763 (GhTIR1), which responded significantly to cold injury. Using VIGS (virus-induced gene silencing) technology to silence Gh_D08G0763 in the cold-tolerant cotton variety ZM36, it was found that the resistance of ZM36 to cold damage was significantly reduced. The physiological response mechanism of the Gh_D08G0763 in resisting cold damage was further analyzed through trypan blue staining of leaves and determination of enzyme activity levels. This study provided effective genetic resources for cotton cold-tolerance breeding.

DNA polymerases are important enzymes that synthesize DNA molecules and therefore are critical to various scientific fields as essential components of in vitro DNA synthesis reactions, including PCR. Modern diagnostics, molecular biology, and genetic engineering require DNA polymerases with improved performance. This study aimed to obtain and characterize a new CL7-Taq fusion DNA polymerase, in which the DNA coding sequence of Taq DNA polymerase was fused with that of CL7, a variant of CE7 (Colicin E7 DNase) from Escherichia coli. The resulting novel recombinant open reading frame was cloned and expressed in E. coli. The recombinant CL7-Taq protein exhibited excellent thermostability, extension rate, sensitivity, and resistance to PCR inhibitors. Our results showed that the sensitivity of CL7-Taq DNA polymerase was 100-fold higher than that of wild-type Taq, which required a template concentration of at least 1.8 × 105 nM. Moreover, the extension rate of CL7-Taq was 4 kb/min, which remarkably exceeded the rate of Taq DNA polymerase (2 kb/min). Furthermore, the CL7 fusion protein showed increased resistance to inhibitors of DNA amplification, including lactoferrin, heparin, and blood. Single-cope human genomic targets were readily available from whole blood, and pretreatment to purify the template DNA was not required. Thus, this is a novel enzyme that improved the properties of Taq DNA polymerase, and thus may have wide application in molecular biology and diagnostics.

Rolling bearing is one of the core components in rotating machinery, and its running status directly affects the operation of the whole equipment. Faults of rolling bearings in the actual working process are often multiple faults. To effectively separate fault sources, the blind source separation method is used for the compound fault diagnosis of rolling bearings. Because of the impact of the number of artificially limited decompositions and quadratic penalty factor on VMD in the decomposition process, and the slow convergence and low accuracy in the objective function of traditional FastICA operation, the VMD algorithm based on the energy loss coefficient and the information entropy is proposed, which adaptively determines the number of modal components and the quadratic penalty factor; The Tukey M estimation is selected as the objective convergence function of the FastICA algorithm to improve its robustness. First, VMD is used to decompose the signal; Secondly, the original signal and the decomposed IMF component are reconstructed, the covariance matrix and the singular value decomposition are constructed, the number of fault sources is estimated by the proximity dominance method, and the decomposed IMF components are filtered through correlation analysis and kurtosis index to build a multi-channel feature set; Finally, the constructed multi-channel feature set is input to the FastICA algorithm based on the Tukey M estimation for the separation of fault source signals to achieve composite fault diagnosis. The compound fault experiment shows that the proposed method in this paper can effectively realize the blind source separation of rolling bearing fault features to realize the compound fault diagnosis in different positions.

B-lymphocytopenia among myelosuppression is the most intractable side effect of chemotherapy. Here, we investigated ways to alleviate 5-fluorouracil-caused stress hematopoietic impairment. We found that intraperitoneally injected ASP (Angelica sinensis polysaccharides) (100 mg/kg per day), one main active ingredient of Angelica sinensis, for consecutive 7 days, significantly recovered mouse bone marrow pro-B and pre-B cells, reversed the capacity of CFU-PreB colony forming, thus alleviating B cell reduction in the spleen and peripheral blood, as well as ameliorating immunoglobin from spleen and serum. The mechanism is related to the protective effects of ASP on IL-7 producing cells, including perivascular Leptin+ and CXCL12+ mesenchymal stem and progenitor cells (MSPCs), thus promoting IL-7 production, and activating IL-7R-mediated STAT5, PI3K-AKT signaling, including survival signals and EBF1, PAX5 transcription factor expression. Additionally, ASP’s IL-7 promoting effect was demonstrated to be associated with maintaining osteogenesis/adipogenesis balance of MSPCs via the NRF2 antioxidant pathway. Collectively, our findings indicate that ASP reverse stress B-lymphocytopenia via improving Nrf2 signaling, promoting IL-7 production in MSPCs, and subsequently maintaining survival, proliferation, and differentiation of B cell progenitors, which may represent a promising therapeutic strategy.

Summary: Background: Heterologous vaccine schedules have been recommended to provide superior immunity and protection against emergent SARS-CoV-2 variants of concern. We aimed to evaluate the safety, immunogenicity, and efficacy of an mRNA COVID-19 vaccine RQ3013 compared with adenoviral vectored vaccine Ad5-nCoV and protein subunit vaccine ZF2001 as the fourth dose in adults primed with three doses of inactivated vaccines in China. Methods: We conducted a double-blinded, randomised, controlled, phase 3b trial among healthy Chinese adults at Lancang County, Yunnan, China. Adults who had received three doses of inactivated COVID-19 vaccines at least 6 months prior were randomly allocated (3:1:1) to receive heterologous boosters with RQ3013, Ad5-nCoV, or ZF2001. We assessed safety within 28 days post boost and the serum geometric mean titres (GMTs) of neutralising antibodies (NAbs) against the live SARS-CoV-2 omicron variant BA.5 on day 14 post-boost. We used Poisson regression to assess the vaccine efficacy against the first episode of virologically confirmed symptomatic COVID-19 occurring at least 7 days post boost. Subgroup analyses categorized by age and sex were also performed for safety and immunogenicity outcomes. This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2200065281) and is now complete. Findings: Between December 12 and December 18, 2022, a total of 1382 adults were screened, and 1250 were enrolled and randomly assigned to receive one dose of RQ3013 (n = 750), Ad5-nCoV (n = 250), or ZF2001 (n = 250). Although solicited adverse reactions within 28 days post boost were more frequent in the RQ3013 group (175 [23.3%]) compared to the control groups (24 [9.6%] in both the Ad5-nCOV and ZF2001 groups, P 0.05). On day 14 post-boost, RQ3013 (GMT 69.14, 95% CI 47.90–99.81) elicited 4.8-fold and 5.6-fold higher concentrations of NAbs against BA.5 than did Ad5-nCoV (14.37, 7.78–26.56) and ZF2001 (12.21, 5.13–29.06), respectively. On day 28 post-boost, RQ3013 demonstrated a relative efficacy of 62.2% (95% CI 13.7–83.1, P = 0.02) compared to Ad5-nCoV, and of 69.0% (33.5–85.7, P = 0.002) compared to ZF2001. Interpretation: The administrations of all the three heterologous boosters were well tolerated. The heterologous prime-boost regimen with RQ3013 elicited superior immune responses and demonstrated better protection against symptomatic SARS-CoV-2 infections compared with Ad5-nCoV or ZF2001, supporting the use of RQ3013 as a booster vaccination in adults. Funding: Yunnan Province Science and Technology Department (grant no.202302AA310047).

In this study, authors identified neutralizing antibodies by isolating B cells from SARS-CoV-2 Delta infected patients and detect altered structural features, likely introduced by somatic hypermutation, that are involved in epitope binding and increase neutralization breadth against virus variants.

Abstract Background Given the crucial role of gut microbiota in animal and human health, studies on modulating the intestinal microbiome for therapeutic purposes have grasped a significant attention, of which the role of fecal microbiota transplantation (FMT) has been emphasized. Methods In the current study, we evaluated the effect of FMT on gut functions in Escherichia coli (E. coli) infection by using mice model. Moreover, we also investigated the subsequently dependent variables of infection, i.e., body weight, mortality, intestinal histopathology, and the expression changes in tight junction proteins (TJPs). Results The FMT effectively decreased weight loss and mortality to a certain extent with the restoration of intestinal villi that resulted in high histological scores for jejunum tissue damage (p

Future search algorithm imitates the person living life. If one person finds that his life is not good, he will try to change his living life, and he will imitate a more successful person. To overcome insufficient performances of the basic Future search algorithm, this paper proposed an improved Future search algorithm based on the sine cosine algorithm (FSASCA). The proposed algorithm uses sine cosine algorithm to loop-progressive find the best solution. The searching method of the sine cosine algorithm can make the feasible solution to be re-positioned around another feasible solutions, which can make the proposed algorithm have a strong exploitation ability. Four coefficient factors are added in the basic FSA, and new update methods are introduced in the searching phase. To verify the searching and optimization performances of the proposed algorithm in this paper, this paper also gives data calculation results, Wilcoxon rank sum test, iteration figures, box plot figures, and searching path figures. Experimental results showed that FSASCA has a better iteration speed, the convergence precision, the solving accuracy, the strong competitive, and the high balance.

Recent studies have shown that, in addition to direct predation, fear of predators alters the physiological behavior of prey. Based on this fact, this paper investigates a three-species food chain based on ratio-dependent and Beddington-DeAngelis type functional responses, which incorporates fear effects and two gestation delays. The positivity, boundedness and existence of equilibrium points of the system are investigated, and the local stability behavior of the equilibrium points and the occurrence of Hopf-bifurcation when the time lag parameters exceed the critical values are studied by analyzing the corresponding characteristic equations. The main results show that Hopf-bifurcation occurs when the time delay parameters attain the thresholds. Finally, numerical simulations are performed to verify our main results.

Abstract The SPL gene is a plant-specific transcription factor involved in the regulation of plant growth and development, which have been identified in woody plants. The process of floral bud differentiation affects the timing of flowering and fruit set and regulates plant growth, however, the mechanism of regulation of flower development by SPL genes is less studied. In this study, 56 VcSPL genes were identified in the tetraploid blueberry. The VcSPL gene family was classified into six subfamilies, and analysis of cis-elements showed that VcSPL genes were regulated by light, phytohormones (abscisic acid, MeJA), and low temperature. In the evolutionary analysis, segmental replication may play an important role in VcSPL gene amplification. Interestingly, we also studied diploid blueberry (Bilberry), in which 24 SPL genes were identified, and 36 homologous pairs were found, suggesting a high degree of convergence in the syntenic relationship between blueberry (Vaccinium corymbosum L) and bilberry (Vaccinium darrowii). Based on the expression profile, VcSPL genes were expressed at high levels in flowers, shoots, and roots, indicating a diversity of gene functions. Then we selected 20 differentially-expressed SPL genes to further investigate the role of VcSPL in floral induction and initiation. It showed that the genes VcSPL40, VcSPL35, VcSPL45, and VcSPL53 may play a crucial role in the blueberry floral transition phase (from vegetative growth to flower initiation). These results provided important information for understanding and exploring the role of VcSPLs in flower morphogenesis and plant growth.

Abstract Aim Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions. Subjects and method In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data. Results The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries. Conclusion The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Intrathecal targeted drug delivery provides effective relief for cancer-related pain. However, its validation in management of craniofacial pain remains much less widely practiced, mainly due to the localized diffusion of analgesic agent with current approach. Here, we report our experience of prepontine cisternal routine for placement and implantation of intrathecal targeted drug delivery in two cases of cancer-related craniofacial pain. Lumbar cannulation was applied and the intrathecal catheter tip was positioned at the prepontine cistern under fluoroscopic guidance during the surgical implantation. Postoperative imaging confirmed that the catheter tip was successfully placed in the prepontine cisternal space. Satisfactory control of pain was achieved after intrathecal therapy, with significant reduction of background and breakthrough cancer pain. None obvious complications were observed in this study. Thus, our novel intrathecal routine may provide an alternative option for craniofacial pain caused by tumor, who were insufficiently treated by oral analgesic agents.