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Abstract Numerous studies have attempted to identify potential biomarkers for early detection of bronchopulmonary dysplasia (BPD) in preterm infants using metabolomics techniques. However, the presence of consistent evidence remains elusive. Our study aimed to conduct a systematic review and meta-analysis to identify differences in small-molecule metabolites between BPD and non-BPD preterm infants. Through meticulous screening of numerous samples, we identified promising candidates, providing valuable insights for future research. We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Internet, Wan-fang database, Chinese Science and Technique Journal Database and Chinese Biomedical Literature Database from inception until January 16, 2024. Studies were comprehensively reviewed against inclusion criteria. We included case-control studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Newcastle-Ottawa scale. We compared the changes in metabolite levels between the BPD and non-BPD preterm infants. A meta-analysis was conducted on targeted metabolomics research data based on the strategy of standardized mean differences (MD) and 95% confidence intervals (CI).Fifteen studies (1357 participants) were included. These clinical-based metabolomics studies clarified 110 differential metabolites between BPD and non-BPD preterm infants. The meta-analysis revealed higher glutamate concentration in the BPD group compared to the non-BPD group (MD = 1, 95% CI 0.59 to 1.41, p

Abstract During each cell cycle, the process of DNA replication timing is tightly regulated to ensure the accurate duplication of the genome. The extent and significance of alterations in this process during malignant transformation have not been extensively explored. Here, we assess the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours. We find that 6%–18% of the cancer genome exhibits ART, with regions with a change from early to late replication displaying an increased mutation rate and distinct mutational signatures. Whereas regions changing from late to early replication contain genes with increased expression and present a preponderance of APOBEC3-mediated mutation clusters and associated driver mutations. We demonstrate that ART occurs relatively early during cancer evolution and that ART may have a stronger correlation with mutation acquisition than alterations in chromatin structure.

BackgroundPrematurity significantly impacts neonatal health worldwide, necessitating effective interventions to improve outcomes for these vulnerable infants. While breastfeeding has emerged as a cornerstone of preterm care, its precise impact on neurodevelopment remains a subject of ongoing inquiry and debate. This systematic review aims to investigate the existing evidence in this area.MethodsOn December 17, 2023, online databases including PubMed, The Cochrane Library, Embase, Web of Science, CNKI, VIP, CBM, and Wan Fang Data were searched. Comparisons were classified into several categories: never breastfeeding (Never-BF) versus exclusive breastfeeding, Never-BF versus any breastfeeding (Any-BF), predominant preterm formula (Pre-PTF) versus predominant breastfeeding (Pre-BF), and Pre-PTF versus predominant donor breast milk (Pre-DBM) groups. Randomized controlled trials and observational studies were analyzed separately through meta-analyses. Each study’s risk of bias was assessed, and the GRADE system was utilized to evaluate the certainty of the findings.ResultsSixteen studies met the inclusion criteria, comprising one RCT and 15 cohort studies. The key findings indicated that infants in the Any-BF groups demonstrated superior long-term cognitive scores compared to those in the Never-BF groups, particularly evident in infants assessed before 18 months in the Pre-BF groups versus Pre-PTF groups. A reduced risk of neurodevelopmental impairment was also observed in preterm infants in the Any-BF groups. Evidence regarding the effect of breastfeeding on motor development was inconclusive, except for potential motor improvement in extremely low birth weight infants in the Any-BF groups. Neither exclusive breastfeeding nor pre-DBM exhibited clear superiority over Pre-PTF in terms of neurodevelopmental outcomes for preterm infants. Caution is warranted due to potential publication bias impacting the assessment of breastfeeding’s impact on motor skills.ConclusionOur systematic review supports current recommendations for breastfeeding in preterm infants, emphasizing its positive effects on cognitive abilities and reduced risk of neurodevelopmental disorders. Further studies are needed to clarify if DHM provides neurodevelopmental benefits comparable to maternal milk, as current evidence does not sufficiently address this question. Additionally, future investigations should prioritize refining our understanding of the influence of breastfeeding on motor development in this vulnerable population.Systematic review registrationPROSPERO, identifier CRD42023492274, Available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023492274.

BackgroundTo analyze the characteristics of blood metabolites within 24 h after birth in preterm infants with bronchopulmonary dysplasia (BPD) and to identify biomarkers for predicting the occurrence of BPD.MethodsDried blood spots (DBS) were collected at birth from preterm infants with gestational age (GA) of less than 32 weeks in the cohort. The infants were divided into the BPD group and non-BPD group based on whether they eventually developed BPD. Dried blood spot filter papers were prepared from venous blood collected within the first 24 h of life. Metabolites were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed using the R software package.ResultsDBS samples from 140 infants with the GA

ObjectiveTo explore the risk factors of delivery room (DR) resuscitation and assess the association of DR resuscitation with neonatal outcomes in very preterm infants (VPIs).MethodsA multicenter retrospective cross-sectional study included VPIs with gestational age (GA)

Backgroundbacterial meningitis (BM) is more common in infants than at any other time in life and remains a devastating disease with considerable risk of death and morbidity. This article aims to gather the currently available evidence to perform a systematic review of clinical factors that may predict or be associated with BM death and/or sequelae in infants

Ovarian mucinous tumors with sarcomatous mural nodules are rare. Sarcomatous nodules have a bad prognosis. Its diagnosis and treatment are controversial.It is still controversial whether malignant mural nodules represent a dedifferentiated form of mucinous tumors or collisional tumors. This is a case report of a 32-year-old female diagnosed with ovarian mucinous tumor recurred as a mucinous carcinoma combined with sarcomatoid and undifferentiated sarcoma mural nodules after surgery and chemotherapy. The primary lesion did not have a sarcomatous component after comprehensive sampling and repeated review, while the recurrent lesion had a predominantly sarcomatous component. The patient received a second operation and postoperative chemotherapy plus Anlotinib with no progression at 16 months of follow-up. Primary mucinous carcinoma and sarcomatous mural nodules revealed the same K-RAS mutation(c.35G>T, pG12V), TP53 mutation (c.817C>T, p.R273C), MLL2 mutation(c.13450C>T, p.R4484) and NF1 mutation(c.7876A>G, p.S2626G). We present a comprehensive analysis on morphologic characteristics, molecular detection results, clinical management, and prognosis of ovarian mucinous tumors with mural nodules of sarcomatoid and undifferentiated sarcoma. Mutation sharing between primary mucinous carcinoma and recurrent sarcomatous nodules supports monoclonal origin of primary and recurrent tumors, suggesting a tendency for sarcomatous differentiation during the progression of epithelial tumors. Malignant mural nodules represent dedifferentiation in mucinous ovarian tumors rather than collision of two different tumor types. Therefore, it is imperative to conduct comprehensive sampling, rigorous clinical examination, and postoperative follow-up in order to thoroughly evaluate all mural nodules of ovarian mucinous tumors due to their potential for malignancy and sarcomatous differentiation.

ABSTRACT: The Ca2+-selective epithelial channel TRPV5 plays a significant role in renal calcium reabsorption and improving osteoporosis (OP). In this study, we investigated the mechanisms of yak milk on osteoporosis mice in TRPV5-mediated Ca2+ reabsorption in the kidney. We observed that treatment of OP mice with yak milk reconstructed bone homeostasis demonstrated by increasing the levels of OPG as well as decreasing the levels of TRAP and ALP in serum. Additionally, yak milk reduced the level of parathyroid hormone (PTH) and elevated 1,25-(OH)2D3 and calcitonin (CT), and inhibited the excretion of Ca/Cr and Pi/Cr in OP mice, which explained by regulating hormone levels and thus enhance the renal Ca2+ reabsorption. Further analysis exhibited that yak milk upregulated the expression of TRPV5 protein and mRNA as well as calbindin-D28k in OP mice kidneys. Overall, these outcomes demonstrate that yak milk enhances renal Ca2+ reabsorption through the TRPV5 pathway synergistically with calbindin-D28k, thus ameliorating OP mice. This provides a new perspective for yak milk as a nutritional supplement to prevent osteoporosis.

ObjectiveTo analyze survival and morbidity among very preterm infants (VPIs) in Shenzhen and explore factors associated with survival without major morbidity.MethodsBetween January 2022 and December 2022, 797 infants were admitted to 25 neonatal intensive care units in Shenzhen with gestational age (GA)

Abstract The fabrication of one-dimensional (1D) magnetic systems on solid surfaces, although of high fundamental interest, has yet to be achieved for a crossover between two-dimensional (2D) magnetic layers and their associated 1D spin chain systems. In this study, we report the fabrication of 1D single-unit-cell-width CrCl3 atomic wires and their stacked few-wire arrays on the surface of a van der Waals (vdW) superconductor NbSe2. Scanning tunneling microscopy/spectroscopy and first-principles calculations jointly revealed that the single wire shows an antiferromagnetic large-bandgap semiconducting state in an unexplored structure different from the well-known 2D CrCl3 phase. Competition among the total energies and nanostructure-substrate interfacial interactions of these two phases result in the appearance of the 1D phase. This phase was transformable to the 2D phase either prior to or after the growth for in situ or ex situ manipulations, in which the electronic interactions at the vdW interface play a nontrivial role that could regulate the dimensionality conversion and structural transformation between the 1D-2D CrCl3 phases.

Understanding changes in ecosystem services (ESs) and quantitatively identifying the drivers that influence these changes are essential for achieving sustainable ecosystem development. In this study, multiple data sources and techniques, including meteorological data, land use/cover data, soil data, the InVEST model, and ArcGIS, were used to analyze the spatiotemporal variation characteristics of carbon storage, habitat quality, soil retention, water yield, and crop product supply in Xinghua City from 2000 to 2015. Additionally, we explored the causes of these changes and the interrelationships among these ESs. The results showed that: (1) During the study period, carbon storage and habitat quality declined, water yield fluctuated and increased, and soil retention had small interannual variations. The supply capacity of crop products first increased rapidly and then stabilized. (2) ESs were influenced by multiple drivers, with altitude having the strongest explanatory power for habitat quality and soil retention, and food production having the strongest explanatory power for crop product supply. (3) Relationships between different ESs were variable and changed over time. This study could enrich the understanding of spatial and temporal changes and drivers of ESs in the plain river network area, which has important implications for future land use planning and sustainable development of ESs.

Sugar plays an important role in apple fruit development, appearance and quality as well as contributing to a plant's water stress response. Trehalose and the trehalose biosynthetic metabolic pathways are part of the sugar signaling system in plants, which are important regulator of water stress response in apple. The effect of water stress treatments applied to apple trees and the corresponding effects of ABA on developmental fruit quality were examined for indicators of fruit quality during fruit development. The results indicated that the severe water stress treatment (W2) occurring after the last stage of fruit cell division caused a decrease in the color and size of fruit. The moderate water stress (W1) occurring after the last stage of fruit cell enlargement (S2) caused an increase in the content of fructose and sorbitol while the apple fruit shape was not affected. These changes in sugar are related to the activity of sugar metabolic enzymes. While the enzymatic activity of vacuolar acid invertase (vAINV) was higher, that of sucrose-phosphate synthase (SPS) was lower in water stress treated fruit throughout the developmental period. This indicates that enhanced sucrose degradation and reduced sucrose synthesis leads to an overall reduced sucrose content during times of drought. Thus, water stress reduced sucrose content. Whereas the content of endogenous trehalose and ABA were the highest in water stress treated fruit. A moderate water stress (W1) imposed on apple trees via water restriction (60%–65% of field capacity) after the fruit cell enlargement phase of fruit development yielded sweeter fruit of higher economic value.

Abstract Background Mental health problems have become a public health problem that needs to be solved in China. However, medical resources for mental healthcare remain insufficient and unevenly distributed. The Chinese central government has taken many measures to address this issue over the last decade. This study aimed to evaluate the changes in equity in mental health bed allocation from 2011 to 2020. Methods The data of this study came from the China Health Statistical Yearbook (2012–2021) and the China National Administrative Division Information Platform. The annual growth rate was used to evaluate the time trends of mental health beds. The Lorenz curve, Gini coefficient and Theil index were used to assess equity in the demographic and geographical dimensions. The distribution of mental health beds was visualized on a map using geographic information system (GIS) software. Results The total number of mental health beds in China increased steadily from 2011 to 2020. At the national level, the Gini coefficient and Theil index all exhibited downward trends over time. The mental health bed allocation in terms of the demographic dimension was relatively equitable, with Gini values all less than 0.3; however, the Gini coefficients by geographical area were all more than 0.6, indicating inequity. Intraregional contribution rates were higher than interregional contribution rates, which were all above 60%. Conclusion The overall distribution equity of mental health beds improved from 2011 to 2020. The equity of mental health beds in terms of population size is superior to that in terms of geographical area. Intraregional differences are the main source of inequity. In particular, differences within the western region need to be given attention. Thus, the findings from this study emphasize that the demographic and geographical distributions and all influencing factors should be considered when the government makes mental health resource allocation policies.

The ETV6-RUNX1 chimeric- and native RUNX1-responsive regulomes in paediatric B-acute lymphoblastic leukemia (B-ALL) remain to be characterized. Here, the authors reveal functional antagonism between the two transcription factors predominantly for the regulation of cell cycle-associated pathways and dependency on native RUNX1 for tumorigenesis which can be targeted pharmacologically.

Expression cloning of fully human monoclonal antibodies (hmAbs) is seeing powerful utility in the field of vaccinology, especially for elucidating vaccine-induced B-cell responses and novel vaccine candidate antigen discovery. Precision of the hmAb cloning process relies on efficient isolation of hmAb-producing plasmablasts of interest. Previously, a novel immunoglobulin-capture assay (ICA) was developed, using single protein vaccine antigens, to enhance the pathogen-specific hmAb cloning output. Here, we report a novel modification of this single-antigen ICA using formalin-treated, fluorescently stained whole cell suspensions of the human bacterial invasive pathogens, Streptococcus pneumoniae and Neisseria meningitidis. Sequestration of IgG secreted by individual vaccine antigen-specific plasmablasts was achieved by the formation of an anti-CD45-streptavidin and biotin anti-IgG scaffold. Suspensions containing heterologous pneumococcal and meningococcal strains were then used to enrich for polysaccharide- and protein antigen-specific plasmablasts, respectively, during single cell sorting. Following application of the modified whole-cell ICA (mICA), ~61% (19/31) of anti-pneumococcal polysaccharide hmAbs were cloned compared to 14% (8/59) obtained using standard (non-mICA) methods – representing a ~4.4-fold increase in hmAb cloning precision. A more modest ~1.7-fold difference was obtained for anti-meningococcal vaccine hmAb cloning; ~88% of hmAbs cloned via mICA versus ~53% cloned via the standard method were specific for a meningococcal surface protein. VDJ sequencing revealed that cloned hmAbs reflected an anamnestic response to both pneumococcal and meningococcal vaccines; diversification within hmAb clones occurred by positive selection for replacement mutations. Thus, we have shown successful utilization of whole bacterial cells in the ICA protocol enabling isolation of hmAbs targeting multiple disparate epitopes, thereby increasing the power of approaches such as reverse vaccinology 2.0 (RV 2.0) for bacterial vaccine antigen discovery.

In this study, an ensemble forecasting model for in situ wind speed and wave height was developed using the Coupled Ocean–Atmosphere–Wave–Sediment Transport (COAWST) model. This model utilized four bias correction algorithms—Model Output Statistics (MOS), Back Propagation Neural Network (BPNN), Long Short-Term Memory (LSTM) neural network, and Convolutional Neural Network (CNN)—to construct ensemble forecasts. The training data were derived from the COAWST simulations of one year and observations from three buoy stations (Laohutan, Zhifudao, and Lianyungang) in the Yellow Sea and Bohai Sea. After the optimization of the bias correction model training, the subsequent evaluations on the ensemble forecasts showed that the in situ forecasting accuracy of wind speed and wave height was significantly improved. Although there were some uncertainties on bias correction performance levels for individual algorithms, the uncertainties were greatly reduced by the ensemble forecasts. Depending on the dynamic weight assignment, the ensemble forecasts presented a stable performance even when the corrected forecasts by three algorithms had an obvious negative bias. Specifically, the ensemble forecasting bias was found with a mean reduction of about 96%~99% and 91%~95% for wind speed and wave height, and a reduction of about 91%~98% and 16%~54% during the period of Typhoon “Muifa”. For the four correction algorithms, the performance of bias correction was not directly related to the algorithm complexity. However, the strategies with more complex algorithms (i.e., CNN) were more conservative, and simple algorithms (i.e., MOS) might have induced unstable performance levels despite their lower bias in some cases.

In this paper, the global exponential stability problem of the switched linear system with time-varying delays is considered. We establish a new stability criterion for the switched linear time-delay system under the Φ-dependent average dwell time technique. By adopting different grouping methods for subsystems, the corresponding stability criteria based on average dwell time and mode-dependent dwell time techniques can be unified to the new results. Finally, an example is given to illustrate the effectiveness of the obtained results.

The absolute exponential stability problem for the continuous-time and discrete-time, respectively, switching positive nonlinear time-delay system is investigated under the nonlinearity of systems satisfying a certain sector condition in this paper. Two multiple co-positive Lyapunov-Krasovskii functionals (MCLKF) of such systems are constructed for the continuous-time and discrete-time contexts respectively. By using the MCLKF and the $\Phi $ -dependent average dwell time switching strategy, more general stability conditions compatible with some existing works are established. Furthermore, the obtained results are generalized to other types of systems. A numerical example, finally, implies the validity and significance of the results proposed.

Faba bean (Vicia faba L.) is an important food and feed legume crop in the world. The root rot complex caused by various pathogens is a main constraint in faba bean production. In April 2021, a severe disease of faba bean with symptoms of black necrosis on roots occurred in experimental fields at the Linxia Institute of Agricultural Sciences, Gansu Province, China. This study aimed to identify the pathogen and evaluate the resistance of faba bean cultivars. The pathogen was isolated from infected soils, and five representative isolates were identified as Berkeleyomyces rouxiae based on morphological characteristics, pathogenicity, and molecular phylogenetic analyses. A host range test showed that chickpea, common bean, cowpea, mung bean, rice bean, lentil, and hyacinth bean were susceptible hosts of the faba bean isolate, whereas adzuki bean, pea, and soybean were non-susceptible hosts, and maize and wheat were non-hosts. Identification of resistance among 36 faba bean cultivars was carried out, and six cultivars were found to be moderately resistant to B. rouxiae. In this study, we first reported black root rot on faba bean caused by B. rouxiae, confirmed and expanded the host range of B. rouxiae, and identified resistant faba bean cultivars.

Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. The effects of sex on intestinal microbiota after IOP absorption was determined. In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases.

Diabetic foot ulcers are one of the most severe complications of diabetes that have imposed great financial and psychological burdens on diabetic patients. A Nocardia rubra cell wall skeleton (Nr-CWS) can be externally applied to accelerate wound healing. However, its clinical application has not yet been reported. Herein, we report two patients with diabetic foot ulcers treated with Nr-CWS. After wound debridement, the wound was covered with a sterile cotton ball infiltrated with an Nr-CWS that was diluted with 2.0 mL of saline. The covers were changed every two days until complete wound healing occurred. The two wounds healed after 3 and 12 weeks, respectively. This article aims to provide a new treatment for diabetic foot ulcers, with the hope that physicians may consider an Nr-CWS as a complementary method for the treatment of chronic wounds.

In order to extend the basic theory of nonlinear discrete boundary value problems,this paper studied the sufficient conditions for the existence of positive solutions for a class of nonlinear second-order difference equations with three-point boundary value problems.Firstly,the expressions of the solutions for the corresponding three-point boundary value problems for second-order difference equations were given and their properties were proved; Secondly,by constructing suitable cone and integral operator in Banach space and utilizing Krasnoselskii's fixed point theorem in cones,the sufficient conditions for the existence of positive solutions of three-point boundary value problems for nonlinear second-order difference equations were obtained under the condition that the nonlinear term was allowed to change sign.Finally,two examples were given to illustrate the validity of the main theorems and results.The results show that the conditions of the theorem are proved and the discrete boundary value problems satisfies the existence condition of positive solutions.The method is effective in the theoretical proof of the second-order discrete boundary value problem,and has reference for the study of the nonlinear high-order multi-point discrete boundary value problems.

BackgroundAccording to clinical study results, immune checkpoint blockade (ICB) treatment enhances the survival outcome of patients with clear cell renal cell carcinoma (ccRCC). Previous research has divided ccRCC patients into immune subtypes with distinct ICB response rates. However, the study on the association between lncRNAs and ccRCC immune subtypes is lacking.MethodsDifferentially expressed lncRNAs/mRNAs between two major immune subgroups were calculated. A weighted gene co-expression network analysis (WGCNA) was conducted to establish the lncRNA-mRNA co-expression network and select the key lncRNAs. Then, prognostic lncRNAs were selected from the network by the bioinformatics method. Next, the risk-score was estimated by lncRNA expression and their coefficients. Finally, a nomogram based on lncRNAs and clinical parameters was created to predict the prognosis of ccRCC.ResultsLncRNAs and mRNAs associated with ccRCC immune subtypes were identified. The lncRNAs and mRNAs from a gene module closely linked to the immune subtype were used to construct a network. The KEGG pathways enriched in the network were related to immune system activation processes. These 8 lncRNAs (AL365361.1, LINC01934, AC090152.1, PCED1B-AS1, LINC00426, AC007728.2, AC243829.4, and LINC00158) were found to be positively correlated with immune cells of the tumor microenvironment. The C-index of the nomogram was 0.777, and the calibration curve data suggests that the nomogram has a high degree of discriminating capacity.ConclusionIn summary, we discovered core lncRNAs linked with immune subtypes and created corresponding lncRNA–mRNA networks. These lncRNAs are anticipated to have predictive significance for ccRCC and may provide insight into novel biomarkers for the disease.

The effects of different strain levels applied through high-pressure torsion (HPT) deformation following annealing on the microstructural evolution, thermal stability, and mechanical properties of Al-4Mg-0.3Cu alloy were investigated. The results reveal that Cu-segregated grain boundaries (GBs) were generated in the ultrafine-grained Al-4Mg-0.3Cu alloy with high angle grain boundaries. By contrast, the phenomenon of Cu segregation was not found in micron-scale and submicron-scale grains with low-angle grain boundaries. The mechanism of Cu segregation in ultrafine-grained Al-4Mg-0.3Cu alloy was discussed. After heat treatment, Cu segregation induced the precipitation of the dense Al2CuMg phase at GBs, which strongly inhibit grain growth and improve thermal stability. Stress–strain curves of as-cast, 5-turn, and 10-turn HPT samples showed that fracture strength significantly increased, attributed to grain size refinement, dislocation density increase, and Cu segregation at GBs. After heat treatment, 5-turn and 10-turn HPT samples demonstrate an enhanced elongation to fracture with a slight reduction of fracture strength.

Background: Tetanus, diphtheria, acellular pertussis, inactivated polio (Tdap-IPV) vaccines administered during pregnancy protect young infants from Bordetella pertussis (B. pertussis) infection. Whilst the impact of maternal Tdap-IPV vaccination on infants’ humoral response to subsequent pertussis immunisation has been investigated, little is known about any impact on innate responses. Methods: We investigated the immune response to B. pertussis in mothers and infants from Tdap-IPV-vaccinated and unvaccinated pregnancies, utilising a whole blood assay and flow cytometric phenotyping of neonatal natural killer (NK) cells, monocytes and dendritic cells. Blood was collected from mother and umbilical cord at birth, and from infants at seven weeks (one week pre-primary pertussis immunisation) and five months of age (one month post-primary pertussis immunisation). 21 mothers and 67 infants were studied. Findings: Vaccinated women had elevated pro-inflammatory cytokine responses to B. pertussis. At birth, babies of vaccinated women had elevated IL-2 and IL-12 responses, elevated classical monocyte proportions, and reduced monocyte and NK cell cytokine responses. The elevated IL-2 response persisted to seven weeks-of-age, when lower IL-10 and IL-13 responses were also seen. One-month post-primary pertussis vaccination, infants from vaccinated pregnancies still had lower IL-10 responses to B. pertussis, as well as lower IL-4. Interpretation: This study suggests that pertussis vaccination during pregnancy impacts infant cellular immune responses, potentially contributing to the modification of antibody responses already reported following primary immunisation against B. pertussis. Funding: National Institute for Health Research Imperial Biomedical Research Centre and IMmunising PRegnant women and INfants neTwork (funded by the GCRF Networks in Vaccines R&D).

Advances in crop breeding techniques and economic evaluation are critical to ensuring and improving crop yields and sustainable development. Based on the provincial data on food legumes breeding (FLB) in China from 2001 to 2020, the research and development (R&D) expenditure distribution, FLB contribution rate, and R&D expenditure on FLB were estimated. The economic benefits of output per unit area and R&D expenses were evaluated, and relevant policy suggestions were put forward. The study found that: (i) the R&D expenditure on FLB’s showed a significant upward trend, and the development can be divided into a starting, stable, and rapid growth period. There were significant differences in R&D expenditures across eight provinces of China with relatively high R&D expenditures for FLB; (ii) the R&D expenditure on FLB had a significant lag in the improvement of per mu yield (1 mu = 0.067 hectares). For every 10,000 yuan increase in R&D funding for FLB, the yield per mu will increase by 0.145 kg/mu in the next five years, and the regional spillover effect of breeding costs is significant; and (iii) the marginal revenue of R&D expenditures FLB from 2008 to 2020 is 34.91 yuan, that is, every 1 yuan invested in breeding R&D can bring a short-term marginal revenue of 34.91 yuan and a long-term marginal revenue of 337.23 yuan. Based on the above analysis, some recommendations were proposed and discussed, including further increasing the R&D investment of FLB, strengthening industry–university–research cooperation in breeding, improving the breeding research system, and promoting the multi-dimensional development of FLB industry–university–research services.

Cervical spondylosis (CS), which is resulted from degeneration of cervical intervertebral disc, is a common disease seriously threatening human health and quality of life. However, there is still no effective clinic strategies for the treatment of this disease. The acupoint stimulation with needle-scalpel is a widely used approach to treat orthopedic diseases. In the present study, we evaluated the therapeutic effects of acupoint stimulation around neck with needle-scalpel on delaying the degeneration of cervical intervertebral discs and hopefully provided an approach for the precaution and early intervention of CS. We firstly established a rat model of CS by cervical static-dynamic imbalance to mimics disc degeneration and then stimulated the acupoints around neck with needle-scalpel. The cervical intervertebral disc samples were collected to measure type I and II collagen by quantitative PCR (qPCR), immunohistochemistry, and western blot. The changes in micro-structure and ultra-structure of nucleus pulposus were analyzed under the optical microscope and electron microscope respectively. Acupoint stimulation with needle-scapelon increased type I collagen production and decreased type II collagen production, and improved the micro-structure and ultra-structure of nucleus pulposus. Our results suggest that acupoint stimulation around neck with needle-scapelon could inhibit intervertebral disc degeneration through modulating the extracellular matrix collagen system and improving the changed structure of nucleus pulposus.

The effects of the different feeding systems, graze feeding (GSF), time-limited graze feeding (GF), and stall-feeding (SF)) on the fatty acid content, metabolites, and genes expression of the longissimus dorsi (LD) in Tan lambs were investigated in the present study. Thirty-nine 4-month-old male Tan lambs with similar body weight (24.91 ± 1.74 kg) were selected and divided into the three feeding systems (n = 13) randomly. Lambs were slaughtered after 83 days of the feeding trails, and LD muscle samples were collected for further analysis. The results indicated that different feeding systems have no significant effect on short-chain fatty acids in Tan lambs (p > 0.05). However, the total saturated fatty acids (∑SFA) and monounsaturated fatty acids (∑MUFA) in the GSF and GF groups were lower than those in the SF group (p < 0.001). The total polyunsaturated fatty acids (∑PUFA) in the GSF group were higher than those in the GF and SF groups (p < 0.001). Moreover, in the comparison of both GF vs GSF groups and SF vs GSF groups, metabolomic analysis showed that metabolites such as cis-(6,9,12)-linolenic acid, arachidic acid, acetylcarnitine, and L-carnitine with lower concentration were significantly enriched in the biosynthesis of unsaturated fatty acid pathway (p < 0.05), but metabolites such as phosphorylcholine, glycerophosphocholine, cytidine 5’-diphosphocholine, and glycerol-3-phosphate with higher concentrations were enriched in the glycerophospholipid metabolism pathway. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of the results indicated that in the comparison of the GSF group with the SF group, differentially expressed genes (DEGs) such as LIPC, ERFE, FABP3, PLA2R1, LDLR, and SLC10A6, were enriched in the steroid biosynthesis and cholesterol metabolism pathways. In addition, differential metabolites and genes showed a significant correlation with the content of ∑SFA, ∑MUFA, and ∑PUFA in lamb meat (p < 0.05). These findings demonstrated that the feeding system was an important factor in regulating fatty acid content by affecting lipid-metabolism-related metabolites and gene expression in muscle, and graze-feeding system provided lamb meat with higher ∑PUFA content than time-limited-grazing and stall-feeding systems.

Insomnia is a common sleep disorder that is closely associated with the occurrence and deterioration of cardiovascular disease, depression and other diseases. The evaluation of pharmacological treatments for insomnia brings significant clinical implications. In this study, a total of 20 patients with mild insomnia and 75 healthy subjects as controls (HC) were included to explore alterations of electroencephalogram (EEG) complexity associated with insomnia and its pharmacological treatment by using multi-scale permutation entropy (MPE). All participants were recorded for two nights of polysomnography (PSG). The patients with mild insomnia received a placebo on the first night (Placebo) and temazepam on the second night (Temazepam), while the HCs had no sleep-related medication intake for either night. EEG recordings from each night were extracted and analyzed using MPE. The results showed that MPE decreased significantly from pre-lights-off to the period during sleep transition and then to the period after sleep onset, and also during the deepening of sleep stage in the HC group. Furthermore, results from the insomnia subjects showed that MPE values were significantly lower for the Temazepam night compared to MPE values for the Placebo night. Moreover, MPE values for the Temazepam night showed no correlation with age or gender. Our results indicated that EEG complexity, measured by MPE, may be utilized as an alternative approach to measure the impact of sleep medication on brain dynamics.

Trehalose-6-phosphate (Tre6P) is a precursor of trehalose, which is widespread in nature and greatly influences plant growth and development. Tre6P acts as a signal of carbon availability in many plants, but little is known about the function of Tre6P in rosaceous plants, which have specific sorbitol biosynthesis and transportation pathways. In the present study, Tre6P levels and Sorbitol:Tre6P ratios were analyzed in apple (Malus domestica, Borkh. cv. Gala). Tre6P levels were positively correlated with sorbitol content but negatively correlated with sucrose, glucose, and fructose content in developing fruit. However, under sorbitol-limited conditions, Tre6P levels were positively correlated with both sorbitol and sucrose. In the presence of different exogenous sugar supply, Tre6P levels increased corresponding with sorbitol, but this was not the case with sucrose. In addition, Tre6P content and sorbitol:Tre6P ratios were more highly correlated with ADP-glucose levels under sorbitol-limited conditions and fruit development stages, respectively. These results suggest that Tre6P is more closely related to sorbitol than other soluble sugars and has an important role in influencing carbon metabolism in apple.

The microstructures and mechanical properties of the as-cast Mg-5.5Zn-1Y-0.5Zr based alloys with 0-1 wt pct stannum (Sn) micro addition were investigated. The results indicate that Sn has an obvious effect on refining microstructures, which is related to the variations of the hindering effect to grain growth and constitutional supercooling resulted from the segregated Sn atoms at advancing solid/liquid interfaces. Tensile tests indicate that the alloys exhibit excellent increasing strength but decreasing elongation with increasing Sn content, which is attributed to the improved grain bonding strength.

Effects of different potassium (K) levels, which were K0 (no fertilizer), K1 (71.5 g KCl plant−1 year−1), K2 (286.7 g KCl plant−1 year−1), and K3 (434 g KCl plant−1 year−1), were evaluated based on sugar and organic acid metabolism levels from 70–126 days after bloom (DAB) in the developing fruit of potted five-year-old apple (Malus domestica, Borkh.) trees. The results indicate that K fertilization promoted greater fruit mass, higher Ca2+ and soluble solid levels, and lower titratable acid levels, as well as increased pH values at harvest. With the application of different levels of K fertilizer, fructose, sorbitol, glucose and sucrose accumulation rates significantly changed during fruit development. Fruit in the K2 group had higher fructose, sucrose and glucose levels than those in other treatment groups at 126 DAB. These changes in soluble sugar are related to the activity of metabolic enzymes. Sucrose synthase (SS) and sorbitol dehydrogenase (SDH) activity in the K2 treated fruit was significantly higher than those in other treatment groups from 70–126 DAB. Malate levels in K-supplemented fruit were notably lower than those in non K-supplemented fruit, and K3 treated fruit had the lowest malate levels during fruit development. Cytosolic malic enzyme (ME) and phosphoenolpyruvate carboxykinase (PEPCK) activity significantly increased in fruit under the K2 treatment during 112–126 DAB and 98–126 DAB, respectively. In addition, Ca2+ concentration increased with increasing K fertilization levels, which promoted a maximum of 11.72 mg g−1 dry weight in apple fruit. These results show that K levels can alter soluble sugar and malate levels due to the interaction between sugars and acid-metabolic enzymes in fruit.

In this paper, we use Bananch's contraction mapping principle and Schauder’s fixed point theorem to study the existence and uniqueness of solutions for nonlocal boundary value problems of fractional differential equations with the nonlinear term dependent in a fractional derivative of lower order on infinite intervals,  Dα0+u(t)=f(t,u(t),Dα-10+u(t)),t∈J,u(0)=0,Dα-10+u(∞)=∑ m-2 t=1 βiu(ηi)  and extend the existing relevant conclusions. We have given some examples to demonstrate the correctness of the main results.

In our study, the effects of water stress on photosynthesis and photosynthetic electron transport chain (PETC) were studied in several ways, including monitoring the change of gas exchange parameters, modulated chlorophyll fluorescence, rapid fluorescence induction kinetics, reactive oxygen species (ROS), antioxidant enzyme activities and D1 protein levels in apple leaves. Our results show that when leaf water potential (ψw) is above –1.5 MPa, the stomatal limitation should be the main reason for a drop of photosynthesis. In this period, photosynthetic rate (PN), stomatal conductance (Gs), transpiration rate (E) and intercellular CO2 concentration (Ci) all showed a strong positive correlation with ψw. Modulated chlorophyll fluorescence parameters related to photosynthetic biochemistry activity including maximum photochemical efficiency (Fv/Fm), actual photochemical efficiency of PSII (ΦPSII), photochemical quenching coefficient (qP) and coefficient of photochemical fluorescence quenching assuming interconnected PSII antennae (qL) also showed a strong positive correlation as ψw gradually decreased. On the other hand, in this period, Stern-Volmer type non-photochemical quenching coefficient (NPQ) and quantum yield of light-induced non-photochemical fluorescence quenching [Y(NPQ)] kept going up, which shows an attempt to dissipate excess energy to avoid damage to plants. When ψw was below –1.5 MPa, PN continued to decrease linearly, while Ci increased and a ‘V’ model presents the correlation between Ci and ψw by polynomial regression. This implies that, in this period, the drop in photosynthesis activity might be caused by non-stomatal limitation. Fv/Fm, ΦPSII, qP and qL in apple leaves treated with water stress were much lower than in control, while NPQ and Y(NPQ) started to go down. This demonstrates that excess energy might exceed the tolerance ability of apple leaves. Consistent with changes of these parameters, excess energy led to an increase in the production of ROS including H2O2 and O2•−. Although the activities of antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) increased dramatically and ascorbate peroxidase (APX) decreased in apple leaves with drought stress, it was still not sufficient to scavenge ROS. Consequently, the accumulation of ROS triggered a reduction of net D1 protein content, a core protein in the PSII reaction center. As D1 is responsible for the photosynthetic electron transport from plastoquinone A (QA) to plastoquinone B (QB), the capacity of PETC between QA and QB was considerably downregulated. The decline of photosynthesis and activity of PETC may result in the shortage of adenosine triphosphate (ATP) and limitation the regeneration of RuBP (Jmax), a key enzyme in CO2 assimilation. These are all non-stomatal factors and together contributed to decreased CO2 assimilation under severe water stress.

Background: Autosomal dominant optic atrophy (ADOA) is usually caused by mutations in the essential gene, OPA1. This encodes a ubiquitous protein involved in mitochondrial dynamics, hence tissue specificity is not understood. Dysregulated mitophagy (mitochondria recycling) is implicated in ADOA, being increased in OPA1 patient fibroblasts. Furthermore, autophagy may be increased in retinal ganglion cells (RGCs) of the OPA1Q285STOP mouse model.Aims: We developed a mouse model for studying mitochondrial dynamics in order to investigate mitophagy in ADOA.Methods: We crossed the OPA1Q285STOP mouse with our RedMIT/GFP-LC3 mouse, harboring red fluorescent mitochondria and green fluorescent autophagosomes. Colocalization between mitochondria and autophagosomes, the hallmark of mitophagy, was quantified in fluorescently labeled organelles in primary cell cultures, using two high throughput imaging methods Imagestream (Amnis) and IN Cell Analyzer 1000 (GE Healthcare Life Sciences). We studied colocalization between mitochondria and autophagosomes in fixed sections using confocal microscopy.Results: We validated our imaging methods for RedMIT/GFP-LC3 mouse cells, showing that colocalization of red fluorescent mitochondria and green fluorescent autophagosomes is a useful indicator of mitophagy. We showed that colocalization increases when lysosomal processing is impaired. Further, colocalization of mitochondrial fragments and autophagosomes is increased in cultures from the OPA1Q285STOP/RedMIT/GFP-LC3 mice compared to RedMIT/GFP-LC3 control mouse cells that were wild type for OPA1. This was apparent in both mouse embryonic fibroblasts (MEFs) using IN Cell 1000 and in splenocytes using ImageStream imaging flow cytometer (Amnis). We confirmed that this represents increased mitophagic flux using lysosomal inhibitors. We also used microscopy to investigate the level of mitophagy in the retina from the OPA1Q285STOP/RedMIT/GFP-LC3 mice and the RedMIT/GFP-LC3 control mice. However, the expression levels of fluorescent proteins and the image signal-to-background ratios precluded the detection of colocalization so we were unable to show any difference in colocalization between these mice.Conclusions: We show that colocalization of fluorescent mitochondria and autophagosomes in cell cultures, but not fixed tissues from the RedMIT/GFP-LC3, can be used to detect mitophagy. We used this model to confirm that mitophagy is increased in a mouse model of ADOA. It will be useful for cell based studies of diseases caused by impaired mitochondrial dynamics.

We explore cell heterogeneity during spontaneous and transcription-factor-driven commitment for network inference in hematopoiesis. Since individual genes display discrete OFF states or a distribution of ON levels, we compute and combine pairwise gene associations from binary and continuous components of gene expression in single cells. Ddit3 emerges as a regulatory node with positive linkage to erythroid regulators and negative association with myeloid determinants. Ddit3 loss impairs erythroid colony output from multipotent cells, while forcing Ddit3 in granulo-monocytic progenitors (GMPs) enhances self-renewal and impedes differentiation. Network analysis of Ddit3-transduced GMPs reveals uncoupling of myeloid networks and strengthening of erythroid linkages. RNA sequencing suggests that Ddit3 acts through development or stabilization of a precursor upstream of GMPs with inherent Meg-E potential. The enrichment of Gata2 target genes in Ddit3-dependent transcriptional responses suggests that Ddit3 functions in an erythroid transcriptional network nucleated by Gata2.

Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify the cell surface antigen CD9 as a positive marker that provides a simple alternative for hematopoietic stem cell isolation at high purity. Crucially, CD9 affords the capture of all hematopoietic stem cells in murine bone marrow in the absence of contaminating populations that lack authentic stem cell function. Using CD9 as a tool to subdivide hematopoietic stem-cell-containing populations, we provide evidence for heterogeneity at the cellular, functional, and molecular levels.

We consider the sixth-order $m$-point boundary-value problem $$displaylines{ u^{(6)}(t)=fig(u(t), u''(t), u^{(4)}(t)ig),quad tin(0,1),cr u(0)=0, quad u(1)=sum_{i=1}^{m-2}a_iu(eta_i),cr u''(0)=0, quad u''(1)=sum_{i=1}^{m-2}a_iu''(eta_i),cr u^{(4)}(0)=0, quad u^{(4)}(1)=sum_{i=1}^{m-2}a_iu^{(4)}(eta_i), }$$ where $f: mathbb{R}imes mathbb{R}imes mathbb{R} o mathbb{R}$ is a sign-changing continuous function, $mgeq3$, $eta_iin(0,1)$, and $a_i>0$ for $i=1,2,dots,m-2$ with $sum_{i=1}^{m-2}a_i

In this article, we consider the existence of positive solutions for a class of boundary value problems with integral boundary conditions on infinite intervals $$displaylines{ (varphi_{p}(x'(t)))'+phi(t)f(t,x(t),x'(t))=0, quad 01$. By applying the Avery-Peterson fixed point theorem in a cone, we obtain the existence of three positive solutions to the above boundary value problem and give an example at last.

Using the Leggett-Williams fixed point theorem in cones, we prove the existence of at least three positive solutions to the nonlinear $n$-th order $m$-point boundary-value problem $$displaylines{ Delta^{n}u(k)+a(k)f(k,u)=0, quad kin {0,N},cr u(0)=0,; Delta u(0)=0, dots, Delta^{n-2}u(0)=0,quad u(N+n)=sum_{i=1}^{m-2}alpha_iu(xi_i). }$$

We discuss a class of singular boundary value problems of fractional q-difference equations. Some existence and uniqueness results are obtained by a fixed point theorem in partially ordered sets. Finally, we give an example to illustrate the results.

We consider the fourth-order difference equation: Δ(z(k+1)Δ3u(k-1))=w(k)f(k,u(k)), k∈{1,2,…,n-1} subject to the boundary conditions: u(0)=u(n+2)=∑i=1n+1g(i)u(i), aΔ2u(0)-bz(2)Δ3u(0)=∑i=3n+1h(i)Δ2u(i-2), aΔ2u(n)-bz(n+1)Δ3u(n-1)=∑i=3n+1h(i)Δ2u(i-2), where a,b>0 and Δu(k)=u(k+1)-u(k) for k∈{0,1,…,n-1}, f:{0,1,…,n}×[0,+∞)→[0,+∞) is continuous. h(i) is nonnegative i∈{2,3,…,n+2}; g(i) is nonnegative for i∈{0,1,…,n}. Using fixed point theorem of cone expansion and compression of norm type and Hölder’s inequality, various existence, multiplicity, and nonexistence results of positive solutions for above problem are derived, which extends and improves some known recent results.

We establish the existence of triple positive solutions of an m-point boundary value problem for the nonlinear singular second-order differential equations of mixed type with a p-Laplacian operator by Leggett-William fixed point theorem. At last, we give an example to demonstrate the use of the main result of this paper. The conclusions in this paper essentially extend and improve the known results.

This paper investigates the existence and nonexistence of positive solutions for a class of fourth-order nonlinear differential equation with integral boundary conditions. The associated Green's function for the fourth-order boundary value problems is first given, and the arguments are based on Krasnoselskii's fixed point theorem for operators on a cone.

By using a fixed point theorem in a cone and the nonlocal third-order BVP's Green function, the existence of at least one positive solution for the third-order boundary-value problem with the integral boundary conditions x′′′(t)+f(t,x(t),x′(t))=0, t∈J, x(0)=0, x′′(0)=0, and x(1)=∫01g(t)x(t)dt is considered, where f is a nonnegative continuous function, J=[0,1], and g∈L[0,1]. The emphasis here is that f depends on the first-order derivatives.

We consider the multi-point discrete boundary value problem with one-dimensional p-Laplacian operator Δ(ϕp(Δu(t−1))+q(t)f(t,u(t),Δu(t))=0, t∈{1,…,n−1} subject to the boundary conditions: u(0)=0, u(n)=∑i=1m−2aiu(ξi), where ϕp(s)=|s|p−2s,p>1,ξi∈{2,…,n−2} with 1

We consider the existence of countably many positive solutions for nonlinear nth-order three-point boundary value problem u(n)(t)+a(t)f(u(t))=0, t∈(0,1), u(0)=αu(η), u′(0)=⋯=u(n−2)(0)=0, u(1)=βu(η), where n≥2,α≥0,β≥0,0

By using the Leray-Schauder continuation theorem, we establish the existence of solutions for m-point boundary value problems on a half-line x″(t)+f(t,x(t),x′(t))=0, 0