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Larsucosterol, a potent endogenous epigenetic regulator, has been reported to play a significant role in lipid metabolism, inflammatory responses, and cell survival. The administration of larsucosterol has demonstrated a reduction in lipid accumulation within hepatocytes and the attenuation of inflammatory responses induced by lipopolysaccharide (LPS) and TNFα in macrophages, alleviating LPS- and acetaminophen (ATMP)-induced multiple organ injury, and decreasing mortalities in animal models. Results from phase 1 and 2 clinical trials have shown that larsucosterol has potential as a biomedicine for the treatment of acute and chronic liver diseases. Recent evidence suggests that larsucosterol is a promising candidate for treating alcohol-associated hepatitis with positive results from a phase 2a clinical trial, and for metabolic dysfunction-associated steatohepatitis (MASH) from a phase 1b clinical trial. In this review, we present a culmination of our recent research efforts spanning two decades. We summarize the discovery, physiological and pharmacological mechanisms, and clinical applications of larsucosterol. Furthermore, we elucidate the pathophysiological pathways of metabolic dysfunction-associated steatotic liver diseases (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and acute liver injuries. A central focus of the review is the exploration of the therapeutic potential of larsucosterol in treating life-threatening conditions, including acetaminophen overdose, endotoxin shock, MASLD, MASH, hepatectomy, and alcoholic hepatitis. [ABSTRACT FROM AUTHOR]

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, <5 years; A10, ~10 years; A15, ~15 years; A20, >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. [ABSTRACT FROM AUTHOR]

The first synthesis of unnatural β2,3,3‐amino acids with a spirocyclic backbone by one‐pot protocol has been presented. This reaction features wide functional group tolerance and feasibility of post‐functionalization of natural products and biologically important molecules. Novel dipeptide and tripeptide structures were assembled using this newly developed β2,3,3‐amino acid in high efficiency. The combination of C−H activation and C−C cleavage for the synthesis of β‐amino acids would trigger more promising synthetic routes for this compound. [ABSTRACT FROM AUTHOR]

Taking into account the effects of the immune response and delay, and complexity on HIV-1 transmission, a multiscale AIDS/HIV-1 model is formulated in this paper. The multiscale model is described by a within-host fast time model with intracellular delay and immune delay, and a between-host slow time model with latency delay. The dynamics of the fast time model is analyzed, and includes the stability of equilibria and properties of Hopf bifurcation. Further, for the coupled slow time model without an immune response, the basic reproduction number R 0 h is defined, which determines whether the model may have zero, one, or two positive equilibria under different conditions. This implies that the slow time model demonstrates more complex dynamic behaviors, including saddle-node bifurcation, backward bifurcation, and Hopf bifurcation. For the other case, that is, the coupled slow time model with an immune response, the threshold dynamics, based on the basic reproduction number R ˜ 0 h , is rigorously investigated. More specifically, if R ˜ 0 h < 1 , the disease-free equilibrium is globally asymptotically stable; if R ˜ 0 h > 1 , the model exhibits a unique endemic equilibrium that is globally asymptotically stable. With regard to the coupled slow time model with an immune response and stable periodic solution, the basic reproduction number R 0 is derived, which serves as a threshold value determining whether the disease will die out or lead to periodic oscillations in its prevalence. The research results suggest that the disease is more easily controlled when hosts have an extensive immune response and the time required for new immune particles to emerge in response to antigenic stimulation is within a certain range. Finally, numerical simulations are presented to validate the main results and provide some recommendations for controlling the spread of HIV-1. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A new type of experiment that aims to determine the optimal quantities of a sequence of factors is eliciting considerable attention in medical science, bioengineering, and many other disciplines. Such studies require the simultaneous optimization of both quantities and sequence orders of several components which are called quantitative-sequence (QS) factors. Given the large and semi-discrete solution spaces in such experiments, efficiently identifying optimal or near-optimal solutions by using a small number of experimental trials is a nontrivial task. To address this challenge, we propose a novel active learning approach, called QS-learning, to enable effective modeling and efficient optimization for experiments with QS factors. QS-learning consists of three parts: a novel mapping-based additive Gaussian process (MaGP) model, an efficient global optimization scheme (QS-EGO), and a new class of optimal designs (QS-design). The theoretical properties of the proposed method are investigated, and optimization techniques using analytical gradients are developed. The performance of the proposed method is demonstrated via a real drug experiment on lymphoma treatment and several simulation studies. for this article are available online. [ABSTRACT FROM AUTHOR]

Trichoderma harzianum is a well-known biological control strain and a mycoparasite of Rhizoctonia solani. To explore the mechanisms of mycoparasitism, the genome and transcriptome of T. harzianum T4 were both assembled and analyzed in this study. The genome of T. harzianum T4 was assembled into 106 scaffolds, sized 41.25 Mb, and annotated with a total of 8118 predicted genes. We analyzed the transcriptome of T. harzianum T4 against R. solani in a dual culture in three culture periods: before contact (BC), during contact (C), and after contact (AC). Transcriptome sequencing identified 1092, 1222, and 2046 differentially expressed genes (DEGs), respectively. These DEGs, which are involved in pathogen recognition and signal transduction, hydrolase, transporters, antibiosis, and defense-related functional genes, are significantly upregulated in the mycoparasitism process. The results of genome and transcriptome analysis indicated that the mycoparasitism process of T. harzianum T4 was very complex. T. harzianum successfully recognizes and invades host cells and kills plant pathogens by regulating various DEGs at different culture periods. The relative expression levels of the 26 upregulated DEGs were confirmed by RT-qPCR to validate the reliability of the transcriptome data. The results provide insight into the molecular mechanisms underlying T. harzianum T4's mycoparasitic processes, and they provide a potential molecular target for the biological control mechanism of T. harzianum T4. [ABSTRACT FROM AUTHOR]

Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is critical in maintaining Ca2+ homeostasis. The cysteine 674 (C674) is the key redox regulatory cysteine in regulating SERCA2 activity, which is irreversibly oxidized in the renal cortex of hypertensive mice. We have reported that the substitution of C674 by serine causes SERCA2 dysfunction and increases blood pressure by induction of endoplasmic reticulum stress (ERS). This study is to explore whether the dysfunction of SERCA2 causes hypertension by interrupting mitochondrial homeostasis and inducing oxidative stress. We used heterozygous SERCA2 C674S gene mutation knock-in (SKI) mice, where one copy of C674 was substituted by serine to represent partial C674 oxidation. In renal proximal tubule (RPT) cells, the substitution of C674 by serine decreased mitochondrial Ca2+ content, increased mitochondrial membrane potential, ATP content, and reactive oxygen species (ROS), which could be reversed by ERS inhibitor 4-phenylbutyric acid or SERCA2 agonist CDN1163. In SKI RPT cells, the redox modulator Tempol alleviated oxidative stress, downregulated the protein expression of ERS markers and soluble epoxide hydrolase, upregulated the protein expression of dopamine D1 receptor, and reduced Na+/K+- ATPase activity. In SKI mice, SERCA2 agonists CDN1163 and [6]-Gingerol, or the redox modulator Tempol increased urine output and lowered blood pressure. The irreversible oxidation of C674 is not only an indicator of increased ROS, but also further inducing oxidative stress to cause hypertension. Activation of SERCA2 or inhibition of oxidative stress is beneficial to alleviate hypertension caused by SERCA2 dysfunction. [Display omitted] • SERCA2 is the key to controlling mitochondrial homeostasis. • SERCA2 dysfunction causes hypertension by inducing oxidative stress in renal cortex. • Direct evidence of SERCA activators lower blood pressure caused by SERCA2 dysfunction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Trichoderma harzianum is a well-known biological control agent (BCA) that shows great potential in controlling many pathogenic fungi. To screen for genes associated with mycoparasitism, we sequenced and analyzed the transcriptome of T. harzianum T4 grown in dual culture with Colletotrichum musae. We analyzed differentially expressed genes (DEGs) of Trichoderma harzianum T4 in three different culture periods: before contact (BC), during contact (C) and after contact (AC). A total of 1453 genes were significantly differentially expressed compared to when T. harzianum T4 was cultured alone. During the three periods of double culture of T. harzianum T4 with C. musae, 74, 516, and 548 genes were up-regulated, respectively, and 11, 315, and 216 genes were down-regulated, respectively. The DEGs were screened using GO and KEGG enrichment analyses combined with differential expression multiples. Six gene categories related to mycoparasitism were screened: (a) pathogen recognition and signal transduction, (b) hydrolases, (c) ribosomal proteins and secreted proteins, (d) multidrug-resistant proteins and transporters, (e) heat shock proteins and detoxification, and (f) oxidative stress and antibiotics-related genes. The expression levels of 24 up-regulated genes during T. harzianum T4’s antagonistic interaction with C. musae were detected via real-time fluorescence quantitative PCR (RT-qPCR). This study provided information on the transcriptional expression of T. harzianum T4 against C. musae. These results may help us to further understand the mechanism of mycoparasitism, which can provide a potential molecular target for improving the biological control capacity of T. harzianum T4. [ABSTRACT FROM AUTHOR]

To assess the prevalence and exacerbating factors of intimate partner violence in people with human immunodeficiency virus (PWH) in China, we conducted a cross-sectional study, involving 2792 PWH in 4 provinces in China from 1 September 2020 to 1 June 2021. The categories of intimate partner violence (IPV) included physical violence, sexual violence, emotional abuse, and controlling behavior. The severity of a violent act was divided into mild, moderate, and severe. Among PWH, the prevalence of IPV was 15.4% (95% confidence interval, 14.1%–16.8%). The severity of physical violence was mainly moderate, and the severity of sexual violence, emotional abuse, and controlling behavior was mainly mild. The prevalence of IPV in men was higher than that in women. Results from the multivariable logistic regression showed that age, ethnic, registered residence, education, and duration of HIV antiretroviral therapy were factors related to IPV in PWH (P <.05). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tryptophan synthetase (TSase), which functions as a tetramer, is a typical enzyme with a substrate channel effect, and shows excellent performance in the production of non-standard amino acids, histamine, and other biological derivatives. Based on previous work, we fused a mutant CE protein (colistin of E. coli, a polypeptide with antibacterial activity) sequence with the sequence of TSase to explore whether its catalytic activity could be enhanced, and we also analyzed whether the addition of a DNA scaffold was a feasible strategy. Here, dCE (CE protein without DNase activity) protein tags were constructed and fused to the TrapA and TrapB subunits of TSase, and the whole cell was used for the catalytic reaction. The results showed that after the dCE protein tag was fused to the TrapB subunit, its whole cell catalytic activity increased by 50%. Next, the two subunits were expressed separately, and the proteins were bound in vitro to ensure equimolar combination between the two subunits. After the dCE label was fused to TrapB, the activity of TSase assembled with TrapA also improved. A series of experiments revealed that the enzyme fused with dCE9 showed higher activity than the wild-type protein. In general, the activity of assembly TSase was optimal when the temperature was 50 °C and the pH was about 9.0. After a long temperature treatment, the enzyme maintained good activity. With the addition of exogenous nucleic acid, the activity of the enzyme increased. The maximum yield was 0.58 g/L, which was almost three times that of the wild-type TSase (0.21 g/L). The recombinant TSase constructed in this study with dCE fusion had the advantages of higher heat resistance and higher activity, and confirmed the feasibility of adding a nucleic acid scaffold, providing a new idea for the improvement of structurally similar enzymes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims Chlamydospores are a special, differentiated type with high environmental resistance. Consequently, the chlamydospores of Trichoderma harzianum T4 can used to industrialize the latter. This study aimed to investigate the key factors affecting the sporulation type of T. harzianum T4 and the mechanisms underlying this effect. Methods and results In the liquid fermentation of T. harzianum T4, ammonium sulfate (AS) inhibited conidia formation and chlamydospore production. Fermentation tests revealed that acid stress induced sporulation type alteration. Transcriptomic analysis was used to evaluate the adaptation strategy and mechanism underlying spore type alteration under acid stress. The fermentation experiments involving the addition of amino acids revealed that branched-chain amino acids benefited conidia production, whereas β-alanine benefited chlamydospore production. Confocal microscope fluorescence imaging and chloroquine intervention demonstrated that vacuole function was closely related to chlamydospore production. Conclusion The sporulation type of T. harzianum T4 can be controlled by adjusting the fermentation pH. T. harzianum T4 cells employ various self-protection measures against strong acid stress, including regulating their metabolism to produce a large number of chlamydospores for survival. [ABSTRACT FROM AUTHOR]

Immune evasion is a major obstacle for pancreatic ductal adenocarcinoma (PDAC) therapy. Inhibition of autophagy can improve antigen presentation and enlarge immunogenic cell death (ICD) effect to generate a strong anti-tumor immune response. However, abundant extracellular matrix dominated by hyaluronic acid (HA) hinders the deep penetration of autophagy inhibitors and ICD inducers. Herein, an intelligent autophagy inhibitor hydroxychloroquine (HCQ) and chemotherapeutic drug doxorubicin (DOX) co-loaded "bulldozer" (HD@HH/EcN) driven by anoxic bacteria was constructed for PDAC chemo-immunotherapy. Results demonstrated that probiotic Escherichia coli 1917 (EcN) could carry hyaluronidases (HAases)-hybrided albumin nanoparticles (HD@HH) to reach PDAC tumor tissue quickly and accurately. Thereafter, HAases can efficiently cleave the tumor matrix barrier and promote HD@HH/EcN to accumulate at tumor hypoxic core significantly. After that, high level of glutathione (GSH) in tumor microenvironment (TME) induces intermolecular disulfide bond in HD@HH nanoparticles breakage, to precisely release HCQ and DOX. DOX can induce ICD effect. Meanwhile, HCQ can amplify DOX induced ICD effect by inhibiting tumor autophagy, which further increase cell surface expression of major histocompatibility complex class I (MHC-I) and augment recruitment of CD8+ T cell to improve immunosuppressive TME. This study provides a new strategy for PDAC chemo-immunotherapy. [Display omitted] • A "bulldozer" to actively seek PDAC tumor and cleave dense matrix barrier. • Enhance chemo-immunotherapy via autophagy regulation. • Disulfide bond reconstruction for efficient drug loading and TME-responsive drug release. [ABSTRACT FROM AUTHOR]

[Display omitted] • Unique gut microbiome of autism with gastrointestinal symptoms at an early age. • Gut microbiota biomarkers for early recognition of autism. • Possibility to stratify autism based on enterotypes. • Foundation for early intervention targeted gut microbiome in autism. Gastrointestinal (GI) disorders are widely recorded in autism spectrum disorder (ASD), and ASD with GI symptoms is a vital subtype of this disease. Growing evidence suggests altered gut microbiota biomarkers in ASD, but little is known about the gut microbiota of individuals with ASD with GI Symptoms, particularly in early childhood. In our study, the gut microbiota of 36 individuals with ASD along with GI symptoms and 40 typically developing (TD) children were compared using 16S rRNA gene sequencing. The microbial diversity and composition were found to differ between the two groups. Compared to TD, the gut microbiota of ASD patients with GI symptoms exhibited decreased alpha diversity and depletion of butyrate-producing bacteria (e.g., Faecalibacterium and Coprococcus). In addition, microbial functional analysis showed abnormality in several gut metabolic models and gut brain models of ASD with GI symptoms, including short-chain fatty acid (SCFA) synthesis/degradation and neurotoxin-related p-cresol degradation, which are closely associated with ASD-related behaviors in animal models. Furthermore, we constructed a Support Vector Machine classification model, which robustly discriminated individuals with ASD and GI symptoms from TD individuals in a validation set (AUC = 0.88). Our findings provide a deep insight into the roles of the disturbed gut ecosystem in individuals with ASD and GI symptoms aged 3–6 years. Our classification model supports gut microbiota as a potential biomarker for the early identification of ASD and interventions targeting particular gut-beneficial microbiota. [ABSTRACT FROM AUTHOR]

In complex industrial environments, the vibration signal of the rolling bearing is covered by noise, which makes fault diagnosis inaccurate. In order to overcome the effect of noise on the signal, a rolling bearing fault diagnosis method based on the WOA-VMD (Whale Optimization Algorithm-Variational Mode Decomposition) and the GAT (Graph Attention network) is proposed to deal with end effect and mode mixing issues in signal decomposition. Firstly, the WOA is used to adaptively determine the penalty factor and decomposition layers in the VMD algorithm. Meanwhile, the optimal combination is determined and input into the VMD, which is used to decompose the original signal. Then, the Pearson correlation coefficient method is used to select IMF (Intrinsic Mode Function) components that have a high correlation with the original signal, and selected IMF components are reconstructed to remove the noise in the original signal. Finally, the KNN (K-Nearest Neighbor) method is used to construct the graph structure data. The multi-headed attention mechanism is used to construct the fault diagnosis model of the GAT rolling bearing in order to classify the signal. The results show an obvious noise reduction effect in the high-frequency part of the signal after the application of the proposed method, where a large amount of noise was removed. In the diagnosis of rolling bearing faults, the accuracy of the test set diagnosis in this study was 100%, which is higher than that of the four other compared methods, and the diagnosis accuracy rate of various faults reached 100%. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A single feature cannot show the operational state of a bearing during its entire life cycle. Therefore, a rolling bearing performance deterioration prediction method based on an SAE and the TCN-attention model is proposed. The SAE method is used to fuse the time-domain indicator and the frequency-domain indicator to construct the performance degradation characteristic indicator. The evaluation indices are used to comprehensively evaluate multiple performance degradation indices, and the fused feature indices together, to filter out the features that have a good overall performance. Attention is added to the TCN model, and the output state weight of the TCN model is calculated through a scoring function to increase the important information weight and the prediction accuracy. The appropriate network structure and parameter configuration are determined, and the rolling bearing performance degradation prediction model is established. A validation is performed using publicly available datasets from the University of Cincinnati and XJTU-SY. The results show that the method is more sensitive to the critical information part of the long time series than the other models. At the same time, the average absolute error and the root mean square error are minimized, the accuracy of the rolling bearing performance degradation prediction is high, and the model has a strong robustness and generalization abilities. Additionally, the model has practical engineering value for predicting the health status of equipment. [ABSTRACT FROM AUTHOR]

Drought is the major abiotic stress that limits apple productivity and quality. To date, many important and divergent regulatory functions of miR156/SBP genes in plant growth and development have been well understood. However, little is known about the role of apple miR156 in response to abiotic stress. To better understand the functions of MdmiR156 in abiotic stress tolerance, we constructed the overexpression (OE) and short tandem target mimic (STTM) vector of MdmiR156n and performed its functional analysis through the characterization of transgenic apple calli and Arabidopsis thaliana plants. In this study, MdmiR156n overexpression significantly increased the length of primary roots and the number of lateral roots in transgenic Arabidopsis plants under drought stress. In addition, MdmiR156n transgenic Arabidopsis and apple calli had a lower electrolyte leakage rate and less cell membrane damage than WT and STTM156 after drought stress. Further studies showed that MdmiR156n overexpression promoted the accumulation of flavonoids and scavenging of reactive oxygen species (ROS) under drought conditions in transgenic apple calli and A. thaliana plants. Taken together, overexpression MdmiR156n enhances drought tolerance by regulating flavonoid synthesis and ROS signaling cascades in apple calli and A. thaliana. [ABSTRACT FROM AUTHOR]

Maximin distance designs have attracted increasing attention in computer experiments owing to their appealing space‐filling properties. The quality of these designs is typically evaluated by comparing their separation distance with the associated upper bound. Nevertheless, deriving tight upper bounds for the separation distance of designs remains a challenging problem that has been infrequently addressed in the literature. In this study, we obtain a new upper bound for the separation distance of certain classes of five‐level U‐type designs. We also investigate the characteristics of maximin distance U‐type designs and show the optimality of some existing orthogonal designs. Based on these theoretical results, we develop an efficient algorithm for searching maximin distance U‐type designs. Numerical studies and comparisons are given to show the superior performance of the obtained designs. [ABSTRACT FROM AUTHOR]

Protective coatings are effective in stabilizing Zn metal anodes. Nevertheless, the diverse features of the coating material increase the interface's complexity and often conceal the real mechanism of how the coating functions on electrode behavior. Moreover, the lack of precise regulation for a targeting feature results in ostensible correlations between structure and function, which sets great obstacles for further improving Zn anode performance. Herein, sepiolite, a hydrated mineral, and its derived materials to protect the Zn anode is introduced. By precisely tailoring different kinds of water molecules, the crystal/chemical states of the coating material is managed to regulate. Their impacts on Zn anode kinetics are revealed by experiments and DFT calculations, which indicate major interactions of Zn with the water molecules or the oxygens on the silicate backbone before/after the removal of zeolitic/coordinated water, and an important role of the structural water (Mg‐OH hydroxyl group) on the structural stability. The Sep‐OH sample with good stability and desired interaction with Zn shows the best performance in terms of uniforming Zn depositions, inhibiting side reactions and reducing polarizations. The tailoring of water molecules in mineral materials provides a new example for investigating and improving the Zn anodes and other similar electrodes. [ABSTRACT FROM AUTHOR]

We investigate a space‐filling criterion based on L2‐type discrepancies, namely the uniform projection criterion, aiming at improving designs' two‐dimensional projection uniformity. Under a general reproducing kernel, we establish a formula for the uniform projection criterion function, which builds a connection between rows and columns of the design. For the commonly used discrepancies, we further use this formula to represent the two‐dimensional projection uniformity in terms of the Lp‐distances of U‐type designs. These results generalize existing works and reveal new links between the two seemingly unrelated criteria of projection uniformity and the maximin Lp‐distance for U‐type designs. We also apply the obtained results to study several families of space‐filling designs with appealing projection uniformity. Because of good projected space‐filling properties, these designs are well adapted for computer experiments, especially for the case where not all the input factors are active. [ABSTRACT FROM AUTHOR]

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 < 0.05). The effect of FMT on alleviating the reduction of intestinal TJPs was also proved by immunohistochemistry analysis and mRNA expression levels. Moreover, the abundance of health-threatening bacteria, belonging to phylum Proteobacteria, family Enterobacteriaceae and Tannerellaceae, genus Escherichia-Shigella, Sphingomonas, Collinsella, etc., were significantly increased, whereas beneficial bacteria, belonging to phylum Firmicutes, family Lactobacillaceae, genus Lactobacillus were decreased in the gut of infected mice. Furthermore, we sought to investigate the association of clinical symptoms with FMT treatment with modulation in gut microbiota. According to beta diversity, the microbial community of gut microbiota results reflected the similarities between non-infected and FMT groups. The improvement of the intestinal microbiota in FMT group was characterized by the significant high level of beneficial microorganisms with the synergistic decrease of Escherichia-Shigella, Acinetobacter, and other taxa. Conclusion: The findings suggest a beneficial host-microbiome correlation following fecal microbiota transplanatation for controlling gut infections and pathogens-associated diseases. [ABSTRACT FROM AUTHOR]

Immunotherapy shows great promise in the treatment of hepatocellular carcinoma (HCC), however, the low response rate of HCC patients to immunotherapy caused by inadequately immunogenic and immunosuppressive tumor microenvironment (TME) is a huge challenge. Herein, a donut‐like multifunctional polysaccharide nanoplatform (GH‐PID) is constructed from doxorubicin/aldehyde hyaluronan nanoring, indocyanine green/hydroxyethyl chitosan nanocomplex, and HCC‐bitargeted galactosamine‐hyaluronan conjugate via a facile self‐assembly process. The GH‐PID nanodonuts exhibit excellent HCC‐targeted ability and synergetic photochemotherapy effect with a coefficient index of about 0.44. Moreover, near infrared laser‐irradiated GH‐PID nanodonuts show robust therapeutic efficacy in HCC mouse models by virtue of photochemotherapy‐augmented immunogenic cell death (ICD) effect. The remarkable ICD in combination with programmed death‐1 antibody efficiently eradicates primary tumors and inhibits distant tumor growth and lung metastasis of HCC by maturing dendritic cells, increasing CD8+ T cell infiltration, suppressing the expansion and trafficking of immunosuppressive myeloid‐derived suppressor cells, and ameliorating immunosuppressive TME. This study provides a facile and versatile strategy to construct polysaccharide nanodonuts integrating multifunctionality and highly efficient HCC‐targeted ability, and the nanodonuts‐based ICD inducer holds great promise for potentiating systemic antitumor immunity and programmed death‐1/programmed death‐ligand 1 blockade efficacy. [ABSTRACT FROM AUTHOR]

Taking into account the effects of the heterogeneity of the population and media coverage on disease transmission, in this paper, a hybrid HIV/AIDS model with age-structure, self-protection awareness and media coverage is formulated, which is made up of five partial differential equations (PDEs) and one ordinary differential equation (ODE). We establish the existence of the solution associated with the hybrid system and prove that the solution is unique, bounded and positive utilizing the semigroup approach. Based on the basic reproduction number R 0 , the threshold dynamics of this model are rigorously investigated, that is, there always is a unique disease-free steady state E 0 and it is globally stable when R 0 < 1 , that is, the disease dies out. Further, there exists a unique endemic steady state E * and it is locally stable when R 0 > 1 and some additional technical conditions are met. In addition, the uniform persistence of this hybrid system is demonstrated for R 0 > 1 , which means that the disease remains at the endemic level for a long time, which is not discussed in other age-structured infectious disease articles. Numerical simulations are also given to explain the main theoretical results, which suggest that age variability is a non-negligible factor in HIV/AIDS transmission, that is, the moment and scale of HIV/AIDS outbreaks are diverse for people of different ages, and media coverage can encourage people to take steps to avoid potential infection and control the spread of the disease. [ABSTRACT FROM AUTHOR]

The ability to precisely control the subcellular distribution of luminous materials presents unprecedented advantages for understanding cell biology and disease therapy. We introduce a luminescence tool for subcellular distribution imaging and differentiation of live and dead cells, utilizing cationic organoplatinum(II) complexes that exhibit well‐defined monomeric to aggregate nanostructures along with concentration‐dependent switchable luminescence from green to red due to assembly via PtII⋅⋅⋅PtII and π–π stacking interactions. One of the complexes was chosen to demonstrate the unique lysosome‐to‐nucleus subcellular re‐distribution and imaging capability in live and dead cells, respectively, which represents the first example to discriminate the subcellular localization of platinum(II) complexes through differential luminescence response. These new findings facilitate the fundamental understanding of self‐assembly behaviors of platinum(II) complexes for potential subcellular detection assays. [ABSTRACT FROM AUTHOR]

The ability to precisely control the subcellular distribution of luminous materials presents unprecedented advantages for understanding cell biology and disease therapy. We introduce a luminescence tool for subcellular distribution imaging and differentiation of live and dead cells, utilizing cationic organoplatinum(II) complexes that exhibit well‐defined monomeric to aggregate nanostructures along with concentration‐dependent switchable luminescence from green to red due to assembly via PtII⋅⋅⋅PtII and π–π stacking interactions. One of the complexes was chosen to demonstrate the unique lysosome‐to‐nucleus subcellular re‐distribution and imaging capability in live and dead cells, respectively, which represents the first example to discriminate the subcellular localization of platinum(II) complexes through differential luminescence response. These new findings facilitate the fundamental understanding of self‐assembly behaviors of platinum(II) complexes for potential subcellular detection assays. [ABSTRACT FROM AUTHOR]

[Display omitted] • NaTi 2 (PO 4) 3 /carbon is rationally designed from an all-integrated framework precursor. • Precursor is a citric acid-organic phosphonic acid skeleton chelating with Ti. • NaTi 2 (PO 4) 3 /carbon shows high capacity and superior rate capability for SIBs. • NaTi 2 (PO 4) 3 /carbon delivers an ultrastable cycling performance. Finding suitable hosts for Na+ ion storage holds the key to achieving large-scale applications of sodium-ion batteries (SIBs). NaTi 2 (PO 4) 3 is widely considered to be an advanced anode material for SIBs, because of its 3D open framework, high theoretical capacity, and good thermodynamic stability. However, the instability of electrolyte/electrode interface and intrinsic low electronic conductivity of NaTi 2 (PO 4) 3 lead to the poor cycling and rate performance. In this work, an all-integrated framework with chelating Ti in a cross-linked citric acid-organic phosphonic acid skeleton is fabricated as a precursor for the synthesis of NaTi 2 (PO 4) 3 /carbon composite. The generated interconnected carbon provides extensive support for NaTi 2 (PO 4) 3 crystal. These unique structure delivers a high reversible capacity (225.8 mAh g−1 at 0.2 A g−1), good rate performance (219.7 mAh g−1 at 0.4 A g−1, and 189.6 mAh g−1 at 1 A g−1), and superb long-term cycling stability (156.0 mAh g−1 at 2 A g−1 after 4000 cycles). It is believed that this facile and effective strategy can shed light on the development of advanced phosphate electrode materials for SIBs. [ABSTRACT FROM AUTHOR]

People living with human immunodeficiency virus (HIV) are more likely to develop tuberculosis (TB), and their co-infection (HIV-TB) increases the risk of death. We aimed to describe the global trends, regional differences and age distribution of HIV-TB. Annual new cases, age-standardized incidence rates (ASRs) and age-specific incidence rates with 95% uncertainty intervals (UIs) of HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis without extensive drug resistance (HIV-MDR-TB) and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) during 1990–2019 were collected from the Global Burden of Disease Study 2019. To reveal the trends of HIV-TB by region and age, the percentage change of new cases and estimated annual percentage change (EAPC) of ASRs were calculated. The ASR of HIV-XDR-TB increased significantly by an average of 14.77% (95% CI: 11.05%–18.62%) per year during 1990–2019 worldwide, while the ASRs of HIV-DS-TB and HIV-MDR-TB decreased after 2005. HIV-XDR-TB was a great threat to Eastern Europe for the largest number of new cases (792, 95% UI: 487–1167) and the highest ASR (0.34 per 100,000 population, 95% UI: 0.21–0.50). In addition, Oceania had the largest rise in ASRs of HIV-MDR-TB (EAPC = 22.56, 95% CI: 18.62–26.64) and HIV-XDR-TB (EAPC = 32.95, 95% CI: 27.90–38.20) during 1990–2019. Recently, age-specific incidence rates of HIV-XDR-TB increased in all age groups, especially in the 50–69 age groups among high, low-middle and low Socio-Demographic Index regions. Additionally, the proportion of patients aged <15 years was nearly 10% of new cases in sub-Saharan Africa in 2019, which was higher than in other regions. HIV-infected drug-resistant TB is common in Oceania and Eastern Europe. Moreover, HIV-XDR-TB among elderly people became increasingly prevalent. In the future, the collaboration of management for HIV and TB should be intensified in Oceania and Eastern Europe, and more concerns need to be paid in elderly people. [ABSTRACT FROM AUTHOR]

An experimental Warn-on-Forecast System (WoFS) ensemble data assimilation (DA) and prediction system at 1-km grid spacing is developed and tested using two landfalling tropical cyclone (TC) events, one springtime severe thunderstorm event, and one summertime flash flood event. To evaluate the impact of DA at 1-km grid spacing, two experiments are conducted. One experiment, namely, the WoFS-1km, generates 3-h ensemble forecasts from the 1-km WoFS analyses while another experiment, namely, the Downscaled-1km, generates 3-h ensemble forecasts from downscaled 3-km analyses. With 1-km DA, the two landfalling TC events and the summertime event show some improvement in predicting high reflectivity, while the springtime event performs worse. Meanwhile, WoFS-1km is slightly better at predicting heavier precipitation (>20 mm h−1) with lower bias. However, heavy precipitation spatial placement error is only mitigated in one TC event and the summertime event with 1-km DA but is neutral or worse in the other two events. Object-based verification for rotation objects indicates that WoFS-1km performs better in one of the TC events, but worse in the springtime event with lower probability of detection and higher false alarm ratio due to fewer strong rotation objects being generated. The forecast skill of WoFS-1km for the springtime event is degraded mainly because the convective cores do not sufficiently develop as the forecast advances. The conditional benefits from 1-km DA in this study highlights the need for evaluation of a larger sample of convective storm cases and further development of the system. [ABSTRACT FROM AUTHOR]

Trichoderma strains have been successfully used in plant disease control. However, the poor stress resistance of mycelia and conidia makes processing and storage difficult. Furthermore, they cannot produce chlamydospores in large quantities during fermentation, which limits the industrialization process of chlamydospore preparation. It is important to explore an efficient liquid fermentation strategy for ensuring chlamydospore production in Trichoderma harzianum. We found that the addition of mannitol, glycine betaine, and N-acetylglucosamine (N-A-G) during liquid fermentation effectively increases the yield of chlamydospores. Furthermore, we provided evidence that chlamydospores have stronger tolerance to high temperature, ultraviolet, and hypertonic stress after the addition of mannitol and trehalose. Lipids are an important component of microbial cells and impact the stress resistance of microorganisms. We studied the internal relationship between lipid metabolism and the stress resistance of chlamydospores by detecting changes in the lipid content and gene expression. Our results showed that mannitol and trehalose cause lipid accumulation in chlamydospores and increase the unsaturated fatty acid content. In conclusion, we verified that these exogenous regulators increase the production of chlamydospores and enhance their stress resistance by regulating lipid metabolism. In addition, we believe that lipid metabolism is an important part of the chlamydospore production process and impacts the stress resistance of chlamydospores. Our findings provide clues for studying the differentiation pathway of chlamydospores in filamentous fungi and a basis for the industrial production of chlamydospores. [ABSTRACT FROM AUTHOR]

The rhizomes of Alpinia officinarum Hance (known as the smaller galangal) have been used as a traditional medicine for over 1000 years. Nevertheless, little research is available on the bacteriostatic activity of the herb rhizomes. In this study, we employed, for the first time, a chloroform and methanol extraction method to investigate the antibacterial activity and components of the rhizomes of A. officinarum Hance. The results showed that the growth of five species of pathogenic bacteria was significantly inhibited by the galangal methanol-phase extract (GMPE) (p < 0.05). The GMPE treatment changed the bacterial cell surface hydrophobicity, membrane fluidity and/or permeability. Comparative transcriptomic analyses revealed approximately eleven and ten significantly altered metabolic pathways in representative Gram-positive Staphylococcus aureus and Gram-negative Enterobacter sakazakii pathogens, respectively (p < 0.05), demonstrating different antibacterial action modes. The GMPE was separated further using a preparative high-performance liquid chromatography (Prep-HPLC) technique, and approximately 46 and 45 different compounds in two major component fractions (Fractions 1 and 4, respectively) were identified using ultra-HPLC combined with mass spectrometry (UHPLC-MS) techniques. o-Methoxy cinnamaldehyde (40.12%) and p-octopamine (62.64%) were the most abundant compounds in Fractions 1 and 4, respectively. The results of this study provide data for developing natural products from galangal rhizomes against common pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Aiming to resolve the problem of redundant information concerning rolling bearing degradation characteristics and to tackle the difficulty faced by convolutional deep learning models in learning feature information in complex time series, a prediction model for remaining useful life based on multiscale fusion permutation entropy (MFPE) and a multiscale convolutional attention neural network (MACNN) is proposed. The original signal of the rolling bearing was extracted and decomposed by resonance sparse decomposition to obtain the high-resonance and low-resonance components. The multiscale permutation entropy of the low-resonance component was calculated. Moreover, the locally linear-embedding algorithm was used for dimensionality reduction to remove redundant information. The multiscale convolution module was constructed to learn the feature information at different time scales. The attention module was used to fuse the feature information and input it into the remaining useful life prediction module for evaluation. The appropriate network structure and parameter configuration were determined, and a multiscale convolutional attention neural network was designed to determine the remaining useful life prediction model. The results show that the method demonstrates effectiveness and superiority in degrading the feature information representation and improving the remaining useful life prediction accuracy compared with other models. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a prevalent organic pollutant found in wastewater environment, is notorious for its resistance to natural degradation, raising significant ecological and human health concerns. In this study, a "signal-on" photoelectrochemical aptasensing system was designed for detecting BPA in real water samples with high specificity and sensitivity. One-dimensional (1D) β-FeOOH nanobelts were synthesized on a two-dimensional (2D) porous carbon nitride (g-C 3 N 4) through an in-situ growth procedure. The β-FeOOH/g-C 3 N 4 nanocomposites demonstrated superior photoelectric conversion efficiency due to several factors: (i) The 1D nanobelt-like structure of β-FeOOH shortens the charge transfer path within the nanocomposite, enabling directional and rapid migration of photoinduced charges from the interior to the surface. (ii) β-FeOOH possesses strong visible absorption capabilities, enhancing the utilization of g-C 3 N 4 under photoexcitation, resulting in the generation of numerous photo-induced carriers. (iii) The in-situ formation of the β-FeOOH/g-C 3 N 4 heterojunction establishes an intimate interfacial contact, facilitating the rapid separation and transfer of charges between β-FeOOH and g-C 3 N 4. A photoelectrochemical aptasensing platform based on the photoactive material of β-FeOOH/g-C 3 N 4 detects BPA with reduced photocurrent owing to the presence of BPA-aptamer macromolecules on the electrode surface. This BPA detection system exhibits excellent linearity over a wide concentration range from 10 pM to 10 nM, with high sensitivity (a detection limit of 3.5 pM), stability, specificity, and repeatability. Furthermore, this research offers a straightforward and rapid sensing platform for monitoring BPA enriched water environments. • 1D-FeOOH nanobelts on 2D g-C 3 N 4 was designed to detect trace Bisphenol A. • The efficiency of photoelectric conversion was enhanced by the unique structure. • The BPA detection system exhibits excellent linearity and high sensitivity. [ABSTRACT FROM AUTHOR]

Depression is a psychiatric disorder associated with multiple factors including microglia-mediated neuroinflammation. Although atractylodin exerted a variety of biological activities, however the effect of atractylodin on neuroinflammation-related depression was still unclear. In this study, the lipopolysaccharide (LPS)-induced mouse model was used to explore the antidepressant effects and molecular mechanisms of atractylodin. The results showed that atractylodin increased sugar preference, also reduced immobility time in FST and TST. Further study showed atractylodin reduced the oxidative stress and the activation of microglia in mouse hippocampus, also inhibited the level of cytokine release, especially IL-1β. The results of western blotting showed that atractylodin significantly inhibited the expression of NLRP3 and pro-IL1β via inhibition of NF-κB pathway. Our studies showed that atractylodin upregulated BDNF/Akt pathway in mouse hippocampus. Therefore, this study firstly indicated that atractylodin can ameliorate lipopolysaccharide-induced depressive-like behaviors in mice through reducing neuroinflammation and neuronal damage, and its molecular mechanism may be associated with the decrease of the expression of NLRP3 inflammasome and upregulation of BDNF/Akt pathway. • Atractylodin ameliorated lipopolysaccharide-induced depressive-like behaviors in mice. • Atractylodin significantly reduced the oxidative stress. • Atractylodin significantly inhibited the expression of NLRP3 and Pro-IL1β. • Atractylodin significantly inhibited NF-κB signaling pathway. • Atractylodin increased BDNF/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Water-nitrate coupling is explored under farmland and apple orchards • Large water deficit and nitrate accumulation are observed under apple orchards • Water deficit and nitrate accumulation are spatiotemporally asynchronous • Soil properties significantly affect water-nitrate coupling in deep soils Understanding the relationship between water and nitrate in soils is critical to agricultural production and aquifer vulnerability assessments, especially in regions with intensive agricultural activities and thick unsaturated zones. Deep soils usually record long-term variations in coupling water and nitrate processes, influenced by multiple environmental factors. As such, this study aims to investigate water and nitrate-nitrogen (NO 3 –−N) contents and their relationships in soil profiles of 13–23 m deep under farmland and neighboring apple orchards with different ages. Soil properties were considered to explore the individual effect of a single factor or combined effects of multiple factors by wavelet analysis and partial least squares path models. Compared with farmland, apple orchards had large water deficit and NO 3 –−N accumulation due to root water uptake and synthetic fertilizer inputs, with high spatiotemporal asynchrony in deep unsaturated zones. Specifically, water deficit and NO 3 –−N accumulation were respectively observed in relatively stable (5–15 m) and active layers (0–5 m, spatial asynchrony), with higher water deficit rates under young apple trees (e.g., 12 and 22 years old) but larger NO 3 –−N accumulation rates under old apple trees (e.g., 23–32 years old, temporal asynchrony), respectively. Under farmland and orchard, soil texture-organic carbon regulated soil water movement, while soil water-organic carbon affected nitrate transport and transformation processes, which further altered soil pH and electric conductivity conditions in deep vadose zones. The growth of apple trees leads to asynchronous water depletion and fertilizer accumulation in soils, and the > 20 years apple trees are limited by insufficient water despite the excessive fertilizer. The dried soil layers not only reduce potential groundwater recharge, but also prolong the residence time of nitrate bombs in thick unsaturated zones. This study provides essential information for sustainable management of vegetation and water resources, and benefits the complicated hydrological and biogeochemical cycles in thick vadose zones. [ABSTRACT FROM AUTHOR]

Space-filling designs are crucial for computer experiments. The quality of a space-filling design can be appropriately reflected by its stratification properties. In a recent paper, Tian and Xu (Biometrika 109(2):489–501, 2022) introduced the concept of a space-filling pattern to properly characterize a design’s stratification properties on various grids. In this study, we generalize the space-filling pattern using arbitrary orthonormal contrasts. We also propose a new pattern called the two-dimensional projection pattern to capture the stratification properties of balanced designs in two dimensions more comprehensively. We derive some theoretical results for both patterns and show that they are easier to compute and apply to a wider range of designs. We further show the use of the two patterns in constructing space-filling designs based on existing strong orthogonal arrays. [ABSTRACT FROM AUTHOR]

Key messages: Genetic analysis revealed that CmCLV3 is a candidate gene for the variation in melon carpel number. Carpel number (CN) is an important trait in melon. Three-CN melon fruit is oval, while 5-CN melon fruit has a round or flat shape. Herein, a genetic analysis of a population in which the CN locus was segregated indicated that 3-CN is controlled by a major dominant effective gene. Bulked segregant analysis and initial linkage mapping placed the CN locus in a 6.67 Mb region on chromosome 12, and it was narrowed to 882.19 kb with molecular markers and recombinant plants. Fine mapping with a large F2 population containing 1026 individuals further narrowed the locus to an 83.98 kb region harboring five annotated genes. Gene structure alignment between the parental lines revealed MELO3C035640.2 (annotated as CLAVATA3, CmCLV3) as the best candidate gene for the CN trait. CmCLV3 was more highly expressed in 3- than 5-CN lines and specifically expressed in terminal buds rather than in young leaves, hypocotyls, and roots. The CmCLV3 coding region was cloned from eight 3- or 5-CN melon accessions, and a nonsynonymous SNP site was highly correlated with CN variation. This SNP site was also related to CN variations among 40 melon lines according to their resequencing data, causing a helix alteration in the CmCLV3 protein. Promoter region sequence alignment and activity analysis showed that, unlike in cucumber and tomato, CmCLV3 promoter variation and activity were not the main reasons for CN alteration. Overall, this study provides a genetic resource for melon fruit development research and molecular breeding tools for melon CN improvement. [ABSTRACT FROM AUTHOR]

Objective. To study the mechanism of chronic obstructive pulmonary disease (COPD) in diagnosing alveolar factors and analyze the effect of miR-149-3p on alveolar inflammatory factors and the expression of surfactant protein D (SP-D) and SP-A on the lung surface mediated by Wnt pathway. Methods. Patients with stable COPD were taken as the research subjects, and healthy volunteers as the control group. Cardiac color Doppler ultrasound was adopted to measure the ventricular structure of patients. The ultrasound simulation method was introduced in the ultrasound imaging. The ultrasound image was processed based on the intelligent ultrasound simulation algorithm. The changes in the structure of the left and right ventricles were analyzed and compared in the two groups. The expression changes of miR-149-3p, Wnt1, β-catenin, RhoA, and Wnt5a in lung tissues of mice in three groups were detected, as well as the content of tumor necrosis factor- (TNF-) α, IL-1β, interleukin (IL-6), nuclear factor kB (NF-kB), and other inflammatory factors in bronchoalveolar tissues of mice in three groups. Results. The position where the attenuation ratio was less than 0.92 in the experiment under the ultrasonic simulation algorithm had a gray value of 50. Compared with the control group, the right ventricular mass index of patients with stable COPD was statistically considerable (P < 0.05). In patients with stable COPD, the overall right ventricular longitudinal strain, right ventricular diastolic longitudinal strain rate (RV DLSR), right ventricular diastolic circumferential strain rate, and right ventricular longitudinal displacement were significantly impaired (P < 0.05). The content of miR-149-3p in the lung tissue of the model group was dramatically inferior to that of the control group and the interference group (P < 0.05). The contents of Wnt1, β-catenin, RhoA, and Wnt5a in the lung tissue of the model group were dramatically superior to those of the control group (P < 0.05). In addition, the expressions of TNF-α, IL-1β, IL-6, and NF-kB in the alveolar lavage fluid of the model group were statistically different from those of control group (P < 0.05). The expression levels of SP-D and surfactant protein A (SP-A) in the COPD group were also statistically different from those of control group (P < 0.05). Conclusion. miR-149-3p regulated the expression of Wnt1, β-catenin, RhoA, and Wnt5a, which also affected the signal transmission of the Wnt pathway, causing changes in the expression of alveolar inflammatory factors. Eventually, it affected the development of COPD. [ABSTRACT FROM AUTHOR]

Uniform designs have been widely applied in engineering and sciences' innovation. When a lot of quantitative factors are investigated with as few runs as possible, a supersaturated uniform design with good overall and projection uniformity is needed. By combining combinatorial methods and stochastic algorithms, such uniform designs with flexible numbers of columns are constructed in this article under the wrap-around L 2 -discrepancy. Compared with the existing designs, the new designs and their two-dimensional projections not only have less aberration, but also have lower discrepancy. Furthermore, some novel theoretical results on the minimum-aberration, uniform and uniform projection designs are obtained. [ABSTRACT FROM AUTHOR]

Space-filling designs are widely used in both computer and physical experiments. Column-orthogonality, maximin distance, and projection uniformity are three basic and popular space-filling criteria proposed from different perspectives, but their relationships have been rarely investigated. We show that the average squared correlation metric is a function of the pairwise L2-distances between the rows only. We further explore the connection between uniform projection designs and maximin L1-distance designs. Based on these connections, we develop new lower and upper bounds for column-orthogonality and projection uniformity from the perspective of distance between design points. These results not only provide new theoretical justifications for each criterion but also help in finding better space-filling designs under multiple criteria. for this article are available online. [ABSTRACT FROM AUTHOR]

For more than a decade many researchers have been developing new ways to produce laminated composites. In this paper, aluminum/titanium/steel multi-laminated composites were fabricated by the cross accumulative roll bonding (CARB) process, and effects of different rolling passes on microstructure, and mechanical properties were investigated. As the number of rolling passes increased, in spite of having no voids and cracks, more instabilities were observed on titanium and steel layers. With regard to mechanical properties, by increasing the rolling passes, the values of ultimate and yield strength, as well as elongation fell, because of the non-uniform distribution of hard layers within the aluminum matrix. Based on scanning electron microscopy (SEM) images, both ductile and cleavage modes of fracture were observed on fracture surfaces. Furthermore, with an increase in the number of rolling passes, the values of fracture toughness pertaining to the crack initiation declined on account of the increased probability of delamination. Plus, the trend of the R-curves was mainly downward due to the growing number of interfaces within the matrix by increasing the number of passes; nonetheless, the upward trend of these curves may be attributed to the ductile Al matrix in which the path of cracks can be bridged. Also, based on the results of wear tests, different wear mechanisms such as adhesion, abrasion, and delamination were observed, and with an increase in the number of rolling passes, the amount of weight loss showed a decline which was due to the rise of hardness concerning the strain-hardened layers. [ABSTRACT FROM AUTHOR]

Purpose: The International Federation of Gynecology and Obstetrics (FIGO) stage remains the standard staging system for the assessment of endometrial cancer (EC) prognosis. Thus, we aim to identify the significant genes or biomarkers associated with the stage of endometrial cancer, which may also help reveal the mechanism of EC progression and assess the prognosis of patients with EC. Materials and methods: We compared the mRNA expression levels of EC patients with stages I and II as well as stages III and IV in the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) of EC patients at different stages were selected by volcano plot and Venn analysis. Gene Ontology (GO) and Pathways were applied to analyze the identified genes. Protein protein interaction (PPI) network was employed to identify the correlation. The survival analyses based on TCGA database were conducted for further screening. The Human Protein Atlas, quantitative PCR and immunohistochemistry were utilized to confirm the differences in expression of DEGs in endometrial cancer samples at different FIGO stages. Results: CKMT1A was identified as a candidate gene. Through survival analyses, we found that CKMT1A may be a poor prognostic factor in the overall survival of endometrial cancer patients. GO and Pathways revealed that CKMT1A is closely associated with the metabolic process. More importantly, Human Protein Atlas and quantitative PCR confirmed the differences in expression of CKMT1A in endometrial cancer samples at different FIGO stages. Conclusion: In summary, this study shows that CKMT1A is a newly identified essential tumor progression regulator of endometrial cancer, which may give rise to novel therapeutic strategies in the management of endometrial cancer patients to prolong its prognosis and prevent tumor progression. [ABSTRACT FROM AUTHOR]

The phenolic extracts of walnut cultivars with a red pellicle (HWE), a purple pellicle (ZWE) and a yellow pellicle (WWE) were compared. The total contents of phenolics, flavonoids and condensed tannins, as well as in vitro antioxidant activities (ABTS and DPPH) of the phenolic extracts were evaluated. The results showed that 25 phenolic compounds were identified in three colored walnuts. The HWE contained the highest contents of total phenolics and condensed tannins, while the ZWE contained the highest content of flavonoids. The DPPH and ABTS assays indicated that the phenolic extracts of colored-walnut pellicles showed a higher free radical scavenging ability than butylated hydroxytoluene (BHT) at the same concentration. Phenolic extracts of colored walnuts were also evaluated as natural antioxidants in walnut oil, substituting for BHT. The efficacy of phenolic extracts in walnut oil preservation was evaluated using accelerated storage (60 °C) for 12 days. After accelerated storage, walnut oil enriched with the phenolic extracts kept better qualities, with significantly lower peroxides, p-anisidine, and TOTOX values. The volatiles were measured and identified using the headspace solid phase micro-extraction gas chromatography to further assess oil quality. Aldehydes such as hexanal and 2-heptenal were identified as representative oxidative volatiles. Hexanal and 2-heptenal content indicated that adding phenolic extracts could prevent flavor deterioration of the oil. This study suggested that phenolic extracts of walnut pellicles could offer an effective alternative to synthetic antioxidants for walnut oil preservation. [ABSTRACT FROM AUTHOR]

To alleviate the instability of renewable energy generation and reduce the cost of energy storage, a wind-photovoltaic-hybrid energy storage project that combines hydrogen storage and electric thermal storage has been developed. Selecting the appropriate location is essential. Therefore, a two-stage decision framework is proposed to select the optimal site. In the first stage, geographic information system is used to assess the suitability of the study area and identify potential locations. In the second stage, the large-scale group decision-making method is employed for further evaluation. Considering the uncertainty of information, the probabilistic linguistic term sets are used to describe evaluation information. Then, experts are clustered via transitive closure algorithm, the weights of the experts and the subgroups are calculated according to the similarity and the importance of experts, and the size of subgroups, respectively. Furthermore, the weight of the criteria is calculated by maximum deviation method. Finally, the improved tomada de decisaointerativa e multicritévio method is used to rank the feasible sites. To verify the practicability of the method, an empirical study is conducted in Inner Mongolia Autonomous Region. Through sensitivity and comparative analyses, site A 3 is identified as the optimal location, which facilitates the layout of wind-photovoltaic-hybrid energy storage projects. [ABSTRACT FROM AUTHOR]

To alleviate the instability of renewable energy generation and reduce the cost of energy storage, a wind-photovoltaic-hybrid energy storage project that combines hydrogen storage and electric thermal storage has been developed. Selecting the appropriate location is essential. Therefore, a two-stage decision framework is proposed to select the optimal site. In the first stage, geographic information system is used to assess the suitability of the study area and identify potential locations. In the second stage, the large-scale group decision-making method is employed for further evaluation. Considering the uncertainty of information, the probabilistic linguistic term sets are used to describe evaluation information. Then, experts are clustered via transitive closure algorithm, the weights of the experts and the subgroups are calculated according to the similarity and the importance of experts, and the size of subgroups, respectively. Furthermore, the weight of the criteria is calculated by maximum deviation method. Finally, the improved tomada de decisaointerativa e multicritévio method is used to rank the feasible sites. To verify the practicability of the method, an empirical study is conducted in Inner Mongolia Autonomous Region. Through sensitivity and comparative analyses, site A 3 is identified as the optimal location, which facilitates the layout of wind-photovoltaic-hybrid energy storage projects. [ABSTRACT FROM AUTHOR]

The water and organic carbon stored within unsaturated zones are crucial in terrestrial ecosystems; however, the coupling effects of deep soil water and organic carbon are still poorly documented. To explore the water-carbon coupling effects within soils under tree plantations, we investigated the water and organic carbon content to 20 m deep under cultivated farmland and orchards with apple trees of varying ages (5, 10, 15, 20, and 24 years) in the loess-covered region of China. A conditional process model was used to explore the impacts of vegetation and edaphic factors on the water-carbon coupling processes. Compared with farmland, young apple orchards (0–10 years) showed lower water deficit, but the soil water storage reduced by 21%− 32% under old apple orchards (15–24 years). The organic carbon content exhibited negligible variation among apple trees of different ages. However, the water-carbon coupling effects varied with apple tree ages. A positive correlation existed between water storage and organic carbon density under young apple orchards (p < 0.05), but a negative correlation was found between water deficit and organic carbon sequestration under old apple orchards (p < 0.01). The conditional process model suggested that the water-carbon coupling relationship under young apple orchards was primarily controlled by clay content due to lower root biomass, while that under old apple orchards was concurrently shaped by silt content and coarse roots because of the developed root system of apple trees. This study offers novel insights into the sustainable management of agriculture and tree plantations in regions with deep-rooted vegetation and thick unsaturated zones. [Display omitted] • We analyzed water and carbon coupling effects within 0–20 m under apple orchards. • Apple trees triggered large water deficit but little organic carbon variation. • Soil texture led to positive water and carbon effects under young apple orchards. • Plant root caused negative water and carbon effects under old apple orchards. [ABSTRACT FROM AUTHOR]

Background: The characterization of colonization and dynamic changes related to gut microorganisms might be vital, as it presents an opportunity to quantify the co-variation between stocking densities and gut microbiome of dynamic distribution. The objective of this study was to determine the stocking density on physiological performance and dynamic distribution of gut microbiome (including bacterial and fungal communities) of Langya laying hens in the two development stages. Methods: A randomized design with 2 × 3 factorial controls consisting of two development stages (24, 43 weeks-old) with three different stocking densities was performed. Three different stocking densities were allocated to a total of 300 11-week-old Langya laying hens (450 cm2/bird, 675 cm2/bird, 900 cm2/bird). Three housing densities were accomplished by raising different chickens per cage with the same floor size. The dependent variables of stocking densities at each sampling point were; growth performance, organs index, egg quality and the changes of dynamic gut bacterial and fungal communities in the cecum. Results: Results showed that the stocking density didn't affect liver index, eggshell thickness, breaking shell strength and egg shape index. Hens from the highest stocking density had the lowest body weight, fallopian tube index, egg weight and yolk colour score. Except for the yolk colour score, the measurement changes caused by age followed the opposite pattern as stocking density. We observed a substantial rise in taxa linked with health threats when stocking density was increased, including Talaromyces, Oscillospiraceae_UCG-002, Oscillospira, and Dielma. The opposite was observed with Bacteroides, Bifidobacterium, Lachnoclostridium, Eisenbergiella, and Kurtzmaniella. Also, most taxa were linked to polymicrobial infection in clinical cases, especially species whose percentage declined as the hens aged, such as Terrisporobacter, Faecalicoccus, Dialister, Cylindrocarpon etc. Whereas Sellimonas, Mitsuokella, Eurotium, Wardomyces and Cephalotheca had the opposite trend. Conclusion: We speculated that excessive high density drove the abundance of bacteria and fungi connected with health problems. Where the gut microecology gradually reach a mature and balance status with age. Overall, this study demonstrates gut microbiome ecological processes in Langya layers at various stocking densities and finds possible connections between stocking density, microbiome and production performance. Our study will contribute to new insights associating suitable density patterns and production performance in laying hens by harnessing such a relative microbiome. [ABSTRACT FROM AUTHOR]