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Abstract. Background:. In East Asia, Helicobacter pylori (H. pylori) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations. Methods:. We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori, and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies. Results:. We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40–62%) for metronidazole; 37% (95% CI: 20–53%) for clarithromycin; 19% (95% CI: 11–28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21–36%) and 10% (95% CI: 7–14%), highlighting the potential for diverse resistance patterns. Conclusions:. H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem. Registration:. PROSPERO, No. CRD42023402510.

Abstract Background The identification of spotted leaf 50 (spl50), a novel lesion mimic mutant (LMM) in rice, provides critical insights into the mechanisms underlying programmed cell death (PCD) and innate immunity in plants. Results Based on ethyl methane sulfonate (EMS)-induced mutagenesis, the spl50 mutant mimics hypersensitive responses in the absence of pathogen by displaying spontaneous necrotic lesions after the tillering phase. SPL50, an ARM repeat protein essential for controlling reactive oxygen species (ROS) metabolism and boosting resistance to blast disease, was identified by map-based cloning techniques. This work also demonstrates the detrimental effects of spl50 on photosynthetic efficiency and chloroplast development. The crucial significance of SPL50 in cellular signaling and stress response is shown by its localization to the cytoplasm and constitutive expression in various plant tissues. In light of growing concerns regarding global food security, this study highlights the pivotal role of SPL50 in regulating programmed cell death (PCD) and enhancing the immune response in plants, contributing to strategies for improving crop disease resistance. Conclusions The novel identification of the SPL50 gene in rice, encoding an ARM repeat protein, reveals its pivotal role in regulating PCD and innate immune responses independently of pathogen attack.

Abstract The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.

Abstract Background Life’s Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. Methods Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (

Abstract Monitoring and preventing coal-rock dynamic disasters are vital for safe mining. To investigate the time–frequency features of induced charge signals with coal damage and failure of roadways, the generation mechanism of free charge in loaded coal is analyzed and the induced charge monitoring test is conducted. According to the stress-induced charge-time curves, the time-domain features of charge signals at each loading stage are obtained. The wavelet threshold denoising approach and generalized Morse wavelet transform method are applied to denoise the raw signals and study the frequency-domain features. Further, the quantitative relationship between the de-noised induced charge signals and the degree of coal damage is established. The results show that the event number, amplitude and fluctuation degree of available induced charge signals are all at a low level in the compaction and elastic stages of the coal, which are mainly generated by the piezoelectric effect and predominantly represent discreteness. When entering the plastic and failure stages, the available signals are primarily produced by the crack propagation and triboelectric effects, with a significant increase in the event number, amplitude, and fluctuation degree. Then the induced charge signals gradually transit from discrete to continuous. Generally, the dominant frequency of the available induced charge signals during the coal damage process is concentrated at 0 ~ 11 Hz. The available induced charge is positively correlated with the degree of coal damage, which can perform the damage degree of coal mass, providing a new approach to evaluate the stability of roadway surrounding rocks.

Abstract Background It is always a challenging job to compare forest resources as there is not a standardized spatial unit with location information. Google Plus Code, the newest alphanumeric geocoding system, uses 20 specifically selected letters and numbers to assign a unique global ID to every cell at different levels of a hierarchical grid system which is established based on latitude and longitude. It can be used as a standardized, unique global geospatial unit to segment, locate, quantitate, evaluate, and compare natural resources with area, boundary, and location information embedded. Results For this proof-of-concept case study, forest inventory data from 1987, 2002, and 2019 for the Zijin Mountain National Forest Park in Jiangsu Province, China was analyzed based on Google Plus Code grid/cell. This enabled the quantification of carbon storage at each cell allowing for the comparison of estimated carbon storage at same or different locations over time. Conclusions This methodology is used to quantify the impacts of changing forest conditions and forest management activities on carbon storage with high spatial accuracy through the 32-year study period. Furthermore, this technique could be used for providing technical support and validation of carbon credit quantification and management.

Abstract Aims Rhythm control therapy has shown great benefits for patients with atrial fibrillation (AF) and heart failure (HF). However, few studies have evaluated the effects of rhythm control on left ventricular ejection fraction (LVEF) trajectory across the whole HF spectrum. Our study explored the prevalence and predictors of LVEF trajectory changes and their prognostic implications following rhythm control. Methods and results Depending on the treatment strategy, the cohort was classified into rhythm and rate control groups. Alterations in HF types and LVEF trajectory were recorded. The observational endpoints were all‐cause mortality and HF‐related admission. Predictors of LVEF trajectory improvement in the rhythm control group were evaluated. After matching, the two groups had similar age [mean age (years): rhythm/rate control: 63.96/65.13] and gender [male: rhythm/rate control: n = 228 (55.6%)/233 (56.8%)]. Based on baseline LVEF measurement, the post‐matched cohort had 490 HF with preserved ejection fraction (rhythm/rate control: n = 260/230; median LVEF: 58.00%/57.00%), 99 HF with mildly reduced ejection fraction (rhythm/rate control: n = 50/49; median LVEF: 45.00%/46.00%), and 231 HF with reduced ejection fraction (rhythm/rate control: n = 100/131; median LVEF: 32.50%/33.00%). Trajectory analysis found that the rhythm control group had a greater percentage of LVEF trajectory improvement than the rate control group [80 (53.3%) vs. 71 (39.4%), P = 0.012]. Cox regression analysis also showed that the rhythm control group was more likely to have improved LVEF trajectory compared with the rate control group {hazard ratio [HR] 1.671 [95% confidence interval (CI) 1.196–2.335], P = 0.003}. In the survival analysis, the rhythm control group experienced significant lower risks of all‐cause mortality [HR 0.600 (95% CI 0.366–0.983), P = 0.043] and HF‐related admission [HR 0.611 (95% CI 0.496–0.753), P

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance mutations. Therefore, finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system (UPS) has emerged as a focus. The UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological processes. In recent years, the study of UPS in hematological malignant tumors has resulted in effective treatments, such as bortezomib in the treatment of multiple myeloma and mantle cell lymphoma. In CML, the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL, interfering with CML-related signaling pathways, and negatively or positively affecting leukemia stem cells. Some of these molecules may help overcome TKI resistance and treat CML. In this review, the mechanism of TKI resistance is briefly described, the components of UPS are introduced, existing studies on UPS participating in TKI resistance are listed, and UPS as the therapeutic target and strategies are discussed.

This study employed multiple MRI features to comprehensively evaluate the abnormalities in morphology, and functionality associated with Parkinson’s disease (PD) and distinguish them from normal physiological changes. For investigation purposes, three groups: 32 patients with PD, 42 age-matched healthy controls (HCg1), and 33 young and middle-aged controls (HCg2) were designed. The aim of the current study was to differentiate pathological cortical changes in PD from age-related physiological cortical volume changes. Integrating these findings with functional MRI changes to characterize the effects of PD on whole-brain networks. Cortical volumes in the bilateral temporal lobe, frontal lobe, and cerebellum were significantly reduced in HCg1 compared to HCg2. Although no significant differences in cortical volume were observed between PD patients and HCg1, the PD group exhibited pronounced abnormalities with significantly lower mean connectivity values compared to HCg1. Conversely, physiological functional changes in HCg1 showed markedly higher mean connectivity values than in HCg2. By integrating morphological and functional assessments, as well as network characterization of physiological aging, this study further delineates the distinct characteristics of pathological changes in PD.

Ring-array photoacoustic tomography (PAT) system has been widely used in noninvasive biomedical imaging. However, the reconstructed image usually suffers from spatially rotational blur and streak artifacts due to the non-ideal imaging conditions. To improve the reconstructed image towards higher quality, we propose a concept of spatially rotational convolution to formulate the image blur process, then we build a regularized restoration problem model accordingly and design an alternating minimization algorithm which is called blind spatially rotational deconvolution to achieve the restored image. Besides, we also present an image preprocessing method based on the proposed algorithm to remove the streak artifacts. We take experiments on phantoms and in vivo biological tissues for evaluation, the results show that our approach can significantly enhance the resolution of the image obtained from ring-array PAT system and remove the streak artifacts effectively.

IntroductionKlebsiella pneumoniae (K. pneumoniae) is the most common pathogen causing hospital respiratory tract infection and epidemic. Gold standard procedures of microscopic examination and biochemical identification are widely used in clinical diagnosis with disadvantages of low sensitivity, time-consuming and sophisticated equipment requiring. An efficient, nucleic acid amplification-based sensitive and specific on-site identification of K. pneumoniae in clinical is necessary to facilitate clinical medication and disease control.MethodsWe developed a closed dumbbell mediated isothermal amplification (CDA) assay for the rapid and sensitive detection of conserved rcsA gene in K. pneumoniae by real-time fluorescence monitoring and end-point colorimetric judgement. We designed and selected a pair of inner primers of CDA to detect K. pneumoniae. Then outer and loop primers were designed and verified to accelerate CDA reaction to achieve more efficient detection of K. pneumoniae.ResultsThe results showed the detection limit of CDA assay was 1.2 × 10−5 ng/μL (approximately 1 copy of the target gene) within 60 min, which was 100-fold more sensitive than real-time quantitative PCR (qPCR). Several pathogen genomic DNAs (Staphylococcus aureus, Shigella sonnei, Vibrio parahaemolyticus, Escherichia coli, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida albicans, Streptococcus agalactiae, Rickettsia, Listeria monocytogenes, Pseudomonas aeruginosa, Klebsiella oxytoca, and Klebsiella aerogenes) were used to evaluate the sensitivity and specificity of the established K. pneumoniae CDA assay. Total 224 batches of samples from other strains tested were negative and 296 batches of extracted K. pneumoniae DNA samples were positive by the developed CDA amplification approach, revealing high specificity and specificity of the diagnostic assay. In addition, the results of real-time fluorescence amplification of the K. pneumoniae CDA were in consistent with those of end-point colorimetric results.DiscussionThe established real-time fluorescence and visual CDA assays of K. pneumoniae with merits of rapid, sensitive and specificity could be helpful for on-site diagnosis and clinical screening in rural areas.

Objectives The blood urea nitrogen to creatinine (BUN/Cr) ratio is associated with early neurological deterioration in acute ischaemic stroke (AIS). However, the predictive value of the BUN/Cr ratio for the AIS prognosis remains unclear. Therefore, we evaluated the correlation between the BUN/Cr ratio and the 3-month outcome in patients with AIS, further testing their dose–response relationship.Design This retrospective cohort study enrolled patients with AIS who were admitted between 1 January 2013 and 31 May 2022. Poor clinical outcome was defined as 3-month Modified Rankin Scale (mRS) >2. Cox proportional HR was used to evaluate the correlation between the BUN/Cr ratio and 3-month outcome. Restricted cubic spline and robust locally weighted regression analyses were conducted to determine the dose–response relationship between the BUN/Cr ratio and the 3-month outcome.Results A total of 4952 eligible patients were included in the study. The patients were divided into three groups according to the tertiles of BUN/Cr ratio (T1, 0.093). After logistic regression adjustment for demographic and clinical characteristics, the BUN/Cr ratio was found to be independently associated with the 3-month outcome in patients with AIS. The restricted cubic spline and locally regression smoothing scatterplot graph showed a strong dose–response relationship between the BUN/Cr ratio and the 3-month outcome in patients with AIS.Conclusion A dose–response relationship was observed between the BUN/Cr ratio and the 3-month outcome in patients with AIS, suggesting that the BUN/Cr ratio could serve as a reliable predictor for the AIS prognosis.

BackgroundThe eradication regimen for Helicobacter pylori (H. pylori) infection can induce gut dysbiosis. In this open-label, prospective, and randomized clinical trial, we aimed to assess the effects of fucoidan supplementation on the eradication rate and gut microbial homeostasis in the context of quadruple therapy, as well as to investigate the combined effects of fucoidan and synbiotics supplementations.MethodsEighty patients with H. pylori infection were enrolled and randomly assigned to one of four treatment groups: the QT (a 2-week quadruple therapy alone), QF (quadruple therapy plus a 6-week fucoidan supplementation), QS (quadruple therapy plus a 6-week synbiotics supplementation), and QFS (quadruple therapy with a 6-week fucoidan and synbiotics supplementation), with 20 patients in each group. The QT regimen included rabeprazole, minocycline, amoxicillin, and bismuth potassium citrate. The synbiotics supplementation contained three strains of Bifidobacterium, three strains of Lactobacillus, along with three types of dietary fiber. All of the patients underwent 13C-urea breath test (13C-UBT) at baseline and at the end of the 6th week after the initiation of the interventions. Fresh fecal samples were collected at baseline and at the end of the 6th week for gut microbiota analysis via 16S rRNA gene sequencing.ResultsThe eradication rates among the four groups showed no significant difference. In the QT group, a significant reduction in α-diversity of gut microbiota diversity and a substantial shift in microbial composition were observed, particularly an increase in Escherichia-Shigella and a decrease in the abundance of genera from the Lachnospiraceae and Ruminococcaceae families. The Simpson index was significantly higher in the QF group than in the QT group. Neither the QS nor QFS groups exhibited significant changes in α-diversity or β-diversity. The QFS group was the only one that did not show a significant increase in the relative abundance of Escherichia-Shigella, and the relative abundance of Klebsiella significantly decreased in this group.ConclusionThe current study provided supporting evidence for the positive role of fucoidan and synbiotics supplementation in the gut microbiota. The combined use of fucoidan and synbioticss might be a promising adjuvant regimen to mitigate gut dysbiosis during H. pylori eradication therapy.

Abstract Background Metarhizium rileyi is an important entomopathogenic fungus which has a wide range of host pests. In this work, the virulence of M. rileyi EFNL-08 against 3rd instar larvae of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), was quantified. Additionally, the infection process and aspects of the host immunological response were described in the laboratory. Results Bioassay results proved that M. rileyi was highly virulent to 3rd instar S. frugiperda larvae with 98.33% mortality at 1 × 108 conidia/ml. Scanning electron microscopy was used to monitor morphological aspects of the infection process. When hyphal bodies (Hbs) of M. rileyi were injected into the hemocoel of host, they were not recognized by the host’s immune system as invaders. There were nonsignificant differences in the hemocytes and phenoloxidase activity between the infected and control larvae at the initial 30 h, indicating that fungus successfully avoids the attack from the immune system. However, it inhibited the enzyme activity at the latest stage when Hbs reached a high density. After infection with M. rileyi, the activity of glutathione-S-transferase (GST) of S. frugiperda larvae presented a significant upward trend, while the activity of acetylcholinesterase (AchE) initially increased, followed by a decrease, and eventually stabilized. However, the activity of both detoxification enzymes in the control group showed slight fluctuations in the initial stage, and then stabilized at a low level. Conclusion Obtained results provided new insights into the virulence and potential physiological responses of M. rileyi. This provides ideas for further development of novel and efficient entomopathogenic fungi (EPF) for pest control.

Abstract Aims We conducted a presentation on an 84‐year‐old male patient who has been diagnosed with TTRA81V (p. TTRA101V) hereditary transthyretin cardiac amyloidosis (hATTR‐CM). In order to establish its pathogenicity, we extensively investigated the biochemical and biophysical properties of the condition. Methods and results Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasingly acknowledged progressive infiltrative cardiomyopathy that leads to heart failure and potentially fatal arrhythmias. Gaining a comprehensive understanding of the biochemical and biophysical characteristics of genetically mutated TTR proteins serves as the fundamental cornerstone for delivering precise medical care to individuals affected by ATTR. Laboratory assessments indicated a brain natriuretic peptide of 200.12 ng/L (normal range: 0–100 ng/L) and high‐sensitivity cardiac troponin I of 0.189 μg/L (normal range: 0–0.1 μg/L). Echocardiography identified left atrial enlargement, symmetrical left ventricular hypertrophy (16 mm septal and 16 mm posterior wall), and a left ventricular ejection fraction of 56%. Cardiac‐enhanced magnetic resonance imaging revealed subendocardial late gadolinium enhancement. Tc‐99m‐PYP nuclear scintigraphy confirmed grade 3 myocardial uptake, showing an increased heart‐to‐contralateral ratio (H/CL = 2.33). Genetic testing revealed a heterozygous missense mutation in the TTR gene (c.302C>T), resulting in an alanine‐to‐valine residue change (p. Ala81Val, following the first 20 residues of signal sequence nomenclature). Biochemical analysis of this variant displayed compromised kinetic stability in both the TTRA81V:WT (wild‐type) heterozygote protein (half‐life, t1/2 = 21 h) and the TTRA81V homozygote protein (t1/2 = 17.5 h). The kinetic stability fell between that of the TTRWT (t1/2 = 42 h) and the early‐onset TTRL55P mutation (t1/2 = 4.4 h), indicating the patient's late‐onset condition. Kinetic stabilizers (Tafamidis, Diflunisal, and AG10) all exhibited the capacity to inhibit TTRA81V acid‐ and mechanical force‐induced fibril formation, albeit less effectively than with TTRWT. Chromatographic assessment of the patient's serum TTR tetramers indicated a slightly lower concentration (3.0 μM) before oral administration of Tafamidis compared with the normal range (3.6–7.2 μM). Conclusions We identified a patient with hATTR‐CM who possesses a rare TTRA81V mutation solely associated with cardiac complications. The slightly reduced kinetic stability of this mutation indicates its late‐onset nature and contributes to the gradual progression of the disease.

Beam shaping is of significance for applications in various fields, including laser fusion, laser processing, and optical manipulation. One conventional approach for beam shaping is using the superposition of eigenmodes, such as the Hermite-Gaussian (HG) modes. However, despite the generation of a flat-top beam by HG modes with identical coefficients, it is challenging to achieve other specific intensity distributions by this method. In this study, we validate the feasibility of the beam patterns modulation by optimizing the coefficients of the superimposed modes using an optimization algorithm. Beyond producing square flat-top spots with controllable size and intensity, this method can also achieve specialized intensity distributions including hollow square spots.

Abstract S-palmitoylases and S-depalmitoylases are differentially expressed in various cancers and several malignant tumors and show a strong prognostic ability. Notwithstanding, the potential clinical impact of S-palmitoylases and S-depalmitoylases, particularly in the prognosis and progression of lung adenocarcinoma (LUAD), has not been clarified. Expression levels of S-palmitoylases and S-depalmitoylases in LUAD were investigated using TCGA. GEPIA was used to evaluate the mRNA levels of S-palmitoylases and S-depalmitoylases at different pathological stages. Metascape was used to investigate the biological significance of S-palmitoylases and S-depalmitoylases. The Kaplan–Meier plotter was used to analyze the prognostic value of S-palmitoylases and S-depalmitoylases. CBioportal was used to analyze gene alterations in S-palmitoylases and S-depalmitoylases. UALCAN was used to examine DNA promoter methylation levels of S-palmitoylases and S-depalmitoylases. Finally, we investigated the relationship between S-palmitoylases, S-depalmitoylases, and tumor-infiltrating immune cells using TIMER. Correlations with immune checkpoint-related genes were determined using the R packages reshape2, ggpubr, ggplot2, and corrplot. PCR was also performed to assess the degree of ZDHHC4/12/18/24 and APT2 transcript expression in lung adenocarcinoma and adjacent normal lung tissues. HPA was utilized to investigate protein levels of S-palmitoylases and S-depalmitoylases in LUAD and normal lung tissue. Our study found that ZDHHC2/3/4/5/6/7/9/12/13/16/18/20/21/23/24, APT1/2, PPT1, LYPLAL1, ABHD4/10/11/12/13 and ABHD17C mRNA expression was significantly upregulated in LUAD, whereas ZDHHC1/8/11/11B/14/15/17/19/22, ABHD6/16A and ABHD17A mRNA expression was significantly downregulated. The functions of the differentially expressed S-palmitoylases and S-depalmitoylases were mainly associated with protein-cysteine S-palmitoyltransferase and protein-cysteine S-acyltransferase activities. Patients with high expression of ZDHHC4/12/18/24, APT2, ABHD4, ABHD11 and ABHD12 had a shorter overall survival. Infiltration of six immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) was closely associated with the expression of ZDHHC4/12/18/24 and APT2. ZDHHC4/12/18/24 and APT2 positively correlated with the immune checkpoint-related gene CD276. We assessed the mRNA levels of ZDHHC4/12/18/24 and APT2 using qRT-PCR and found increased expression of ZDHHC4/12/18/24 in LUAD compared with healty control lung tissues. ZDHHC4/12/18/24, and APT2 are potential prognostic biomarkers of LUAD. Their expression levels could be related to the tumor microenvironment in LUAD.

The steeply dipping coal seam is one of the main forms of coal storage in China. It is widely and regionally distributed. According to incomplete statistics, twenty-six provinces, autonomous regions and municipalities directly under the central government are involved in the mining of such coal seams, with abundant reserves, large production and high production concentration in the central and western regions. It shows diversity and complexity in terms of the conditions of existence, with different regions having different coal formation periods and different tectonic control processes, forming diverse and complex mining conditions and giving rise to different mining technology requirements. The mining of steeply dipping coal seam is technically difficult. The asymmetry of the movement and damage of the peripheral rock in the mining area affected by the inclination angle of the coal seam is obvious, and the difficulty of the stability control of the support system and equipment, the matching and coordination of the “three machines”, the layout and support of the mining roadway, and the safety guarantee of the “human-machine” environment at the working face has increased significantly, which seriously restricts the safe and efficient mining of the mine. This has seriously restricted the improvement of safe and efficient mining. The regional economic demand for the mining of steeply dipping coal seam is strong. This kind of coal seams and the production of more concentrated areas are mostly seen in the coal industry-based resource cities, the economic structure is relatively single, the safe and efficient development and utilization of coal resources for the regional energy supply, people’s livelihood, economic stability has the role of the bottom of the pocket, the demand is urgent. For a long time, mining technologies for the steeply dipping coal seam changes focus on solving the “difficult” and “need” contradiction. In the coal mining methods and techniques, strata control theory and technology, complete sets of equipment development and application of the three aspects of continuous improvement, innovation, development, to achieve the transformation from non-mechanized to fully-mechanized mining, the level of safety and production efficiency has increased dramatically, the personnel labor intensity has decreased dramatically, and the operating environment has improved significantly. In the mid-1990s, Lvshuidong Coal Mine of Sichuan Coal Industry Group Limited Liability Company successfully realized longwall fully-mechanized mining in steeply dipping coal seam with medium mining height for the first time, breaking through the "forbidden zone" in this filed. Under this demonstration, the three pioneering engineering practices of longwall fully-mechanical mining of steeply dipping coal seam with thick mining height, steeply dipping coal seam with large mining height, and longwall fully-mechanical mining of steeply dipping coal seam with thin mining height in pseudo-inclination have been successful successively, which innovated the non-linear limiting arrangement of the working face and the way of adjusting the slanting, established a multi-dimensional interactive control mode of the system stability of the “bracket-surrounding rock”, and researched and developed the “support and stability and heavy weight, high-strength and light-weight, safe and reliable, and matching synergistic” complete set of equipment of the working face, which has achieved good results, and the scope of application of the comprehensive mechanized mining technology has further been widened. At the same time, there are still many key scientific problems and technical bottlenecks that need to be broken through in the mining of steeply dipping coal seams, resulting in a large gap between the intelligence level and that of the flat/gently inclined coal seams. Research on the mining dynamics of coal and rock bodies in inclined bedded coal beds, revealing their control mechanisms on the disaster of the surrounding rocks in the mining field, and realizing quantitative characterization need to be further strengthened. It is necessary to further clarify the multi-dimensional dynamic process and law between the system of “rock-bearing structure - mining equipment group”, improve the theoretical and technological basis of “multi-dimensional dynamic multi-objective synergistic control of equipment and surrounding rock”, and realize the transformation and application of the technology. On the basis of breakthroughs in scientific issues, we will carry out systematic technological innovation and research and development of coal mining methods, mining techniques, rock formation control, and complete sets of equipment, so as to crack the bottleneck of the constraints on the double enhancement of “safety and efficiency” in the mining of steeply dipping coal seams, and make the upper limit of the inclination of the steeply dipping coal seams for comprehensive mechanized mining extend upward under the prerequisite of reliable technological safeguards, so as to lay the foundation for the realization of automated and intelligent mining.

With the rise of probiotics fermentation in food industry, fermented foods have attracted worldwide attention. In this study, protective effects of Rosa roxburghii & edible fungus fermentation broth (REFB) on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated. Results showed that REFB could improve the immune organ index, and promote the proliferation and differentiation of splenic T lymphocytes. In addition, it attenuated intestinal mucosal damage and improved intestinal cellular immunity. REFB administration also up-regulated the expression of IL-4, INF-γ, TNF-α, T-bet and GATA-3 mRNA in small intestine. Furthermore, administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus, such as Bacteroides. It also increased the production of fecal short-chain fatty acids. These indicate that REFB has the potential to improve immunity, alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

ABSTRACTPaediatric Mycoplasma pneumoniae pneumonia (MPP) is a heterogeneous disease with a diverse spectrum of clinical phenotypes. No studies have demonstrated the relationship between underlying endotypes and clinical phenotypes as well as prognosis about this disease. Thus, we conducted a multicentre prospective longitudinal study on children hospitalized for MPP between June 2021 and March 2023, with the end of follow-up in August 2023. Blood samples were collected and processed at multiple time points. Multiplex cytokine assay was performed to characterize serum cytokine profiles and their dynamic changes after admission. Cluster analysis based on different clinical phenotypes was conducted. Among the included 196 patients, the levels of serum IL-17A and IL-6 showed remarkable variabilities. Four cytokine clusters based on the two cytokines and four clinical groups were identified. Significant elevation of IL-17A mainly correlated with diffuse bronchiolitis and lobar lesion by airway mucus hypersecretions, while that of IL-6 was largely associated with lobar lesion which later developed into lung necrosis. Besides, glucocorticoid therapy failed to inhibit IL-17A, and markedly elevated IL-17A and IL-6 levels may correlate with lower airway obliterans. Our study provides critical relationship between molecular signatures (endotypes) and clustered clinical phenotypes in paediatric patients with MPP.

Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45 kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through in vitro and in vivo experiments. In vitro, our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. In vivo, we found that rhCOLIII could inhibit tumor growth and promote CD8+ T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.

BackgroundLittle is known about recovery from opioid use disorder (OUD) or outcomes of detoxification and drug-free treatment of chronic opioid therapy (COT). Harm reduction with medications for opioid use disorder (MOUD) is regarded as the only legitimate treatment.MethodsThe Institutional Review Board (IRB) approved reporting deidentified outcomes. Patients seen over a 10-year period whose records suggested recovery were called and interviewed.ResultsOverall, 69/86 (80%) confirmed that they had been sober for at least a year, including 41 patients with OUD (75%) and 28 COT patients (90%). 91% were drug-free, and 9% were on MOUD. 79% preferred a psychotherapy approach. 21% preferred MOUD. Coming for more treatment and abstinence from tobacco were significantly correlated with recovery.ConclusionThis is the first report that we are aware of regarding the frequency of recovery from OUD and COT. We have complicated the discussion about what is the best treatment for patients with OUD and patients on COT. Advising that maintenance is the only legitimate treatment for patients who suffer from OUD or who are on COT seems both premature and jeopardizes the ability of treaters to individualize treatment recommendations.

Abstract Accurately measuring emission factors (Es) of biogenic volatile organic compounds (BVOCs) with consideration of intraspecific variability is vital but often overlooked. This study presents in‐situ measurements of BVOC emissions from 114 Eucalyptus urophylla individuals using the LI‐6800 portable photosynthesis system. We observed intraspecific variability exceeding an order of magnitude in BVOC Es. Despite this variability, our approach yielded statistically representative Es for E. urophylla, yet challenging the feasibility of extensive field measurements. By quickly screening net photosynthesis rate (Pn) across a broad set of individuals and selecting those within a specific Pn range, such as mean ± 0.1 × SD (standard deviation) of Pn for all screened individuals, for detailed BVOC emission measurements, we achieved comparable mean Es with approximately 10% of the original sampling effort. This offers a practical solution for efficient and accurate field measurement of representative BVOC Es, significantly reducing required sample size while effectively addressing intraspecific variability.

Summary: Social cooperation is fundamentally important for group animals but rarely studied in mice because of their natural aggressiveness. Here, we present a new water-reward assay to investigate mutualistic cooperative behavior in mice. We describe the construction of the apparatus and provide details of the procedures and analysis for investigators to characterize and quantify the mutualistic cooperative behavior. This protocol has been validated in mice and can be used for investigating mechanisms of cooperation.For complete details on the use and execution of this protocol, please refer to Zhang et al. and Wang et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundRecent studies have revealed changes in microbiota constitution and metabolites associated with tumor progression, however, no causal relation between microbiota or metabolites and diffuse large B-cell lymphoma (DLBCL) has yet been reported.MethodsWe download a microbiota dataset from the MiBioGen study, a metabolites dataset from the Canadian Longitudinal Study on Aging (CLSA) study, and a DLBCL dataset from Integrative Epidemiology Unit Open genome-wide association study (GWAS) project. Mendelian randomization (MR) analysis was conducted using the R packages, TwoSampleMR and MR-PRESSO. Five MR methods were used: MR-Egger, inverse variance weighting (IVW), weighted median, simple mode, and weighted mode. Reverse MR analyses were also conducted to explore the causal effects of DLBCL on the microbiome, metabolites, and metabolite ratios. Pleiotropy was evaluated by MR Egger regression and MR-PRESSO global analyses, heterogeneity was assessed by Cochran’s Q-test, and stability analyzed using the leave-one-out method.Results119 microorganisms, 1,091 plasma metabolite, and 309 metabolite ratios were analyzed. According to IVW analysis, five microorganisms were associated with risk of DLBCL. The genera Terrisporobacter (OR: 3.431, p = 0.049) andgenera Oscillibacter (OR: 2.406, p = 0.029) were associated with higher risk of DLBCL. Further, 27 plasma metabolites were identified as having a significant causal relationships with DLBCL, among which citrate levels had the most significant protective causal effect against DLBCL (p = 0.006), while glycosyl-N-tricosanoyl-sphingadienine levels was related to higher risk of DLBCL (p = 0.003). In addition, we identified 19 metabolite ratios with significant causal relationships to DLBCL, of which taurine/glutamate ratio had the most significant protective causal effect (p = 0.005), while the phosphoethanolamine/choline ratio was related to higher risk of DLBCL (p = 0.009). Reverse MR analysis did not reveal any significant causal influence of DLBCL on the above microbiota, metabolites, and metabolite ratios (p > 0.05). Sensitivity analyses revealed no significant heterogeneity or pleiotropy (p > 0.05).ConclusionWe present the first elucidation of the causal influence of microbiota and metabolites on DLBCL using MR methods, providing novel insights for potential targeting of specific microbiota or metabolites to prevent, assist in diagnosis, and treat DLBCL.

BackgroundCataracts, characterized by a decrease in vision due to the clouding of the lens, can progress to blindness in advanced stages. The rising incidence of cataract cases has led to a significant number of patients experiencing negative emotions associated with vision loss, thereby diminishing their quality of life. In clinical practice, it is imperative for healthcare professionals to consider the psychological well-being of cataract patients. Currently, there is a scarcity of research focusing on psychological evaluations, such as assessing feelings of meaninglessness among individuals with cataracts.ObjectiveThis study aims to investigate the factors influencing the anxiety of existential meaninglessness and to explore the relationships among existential anxiety, Herth hope index levels and fear of progression in the elderly cataract-affected population. Additionally, it evaluates the effectiveness of Orem’s nursing care strategies.MethodsUtilizing a sociodemographic questionnaire, the Existential Meaninglessness Anxiety Scale (EM-A), Herth Hope Index Level Scale, and the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), this research employed convenience sampling for a cross-sectional and intervention study. The retrospective study sample comprised 1,029 individuals, while the intervention study included 317. The intervention design assessed psychological changes in existential meaninglessness following Orem’s preoperative nursing interventions. Multiple linear regression analysis was employed to ascertain the determinants of EM-A within the population of elderly patients with senile cataracts. Pearson correlation analysis elucidated the relationship between EM-A, levels of hope, and the FoP-Q-SF among this demographic. Subsequent investigations, utilizing a t-test, evaluated the effects by comparing the data before and after the implementation of the interventions.ResultsThe correlation between EM-A, hope levels, and FoP-Q-SF was statistically significant (p

Abstract Anti‐virulence therapy that interferes with bacterial communication, known as “quorum sensing (QS)”, is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti‐virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in‐depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti‐virulence therapy. This review provides reference and inspiration for further research on the anti‐virulence application of nanomaterials.

Summary: Background: Adjunctive newer antiseizure medications (ASMs) are being used in patients with treatment-resistant focal-onset seizures (FOS). An updated network meta-analysis (NMA) was necessary to compile evidence in this critical area. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus from their inception until 17 January 2024, evaluating the efficacy, tolerability, and safety of rufinamide (RUF), brivaracetam (BRV), cenobamate (CNB), eslicarbazepine (ESL), lacosamide (LCM), retigabine (RTG), and perampanel (PER) as adjunctive treatments for FOS. Efficacy outcomes included seizure response and seizure freedom. Tolerability was assessed by discontinuation due to adverse events (AEs). Safety outcomes were evaluated based on the number of patients experiencing at least one AE and serious adverse events (SAEs). This review is registered with PROSPERO (CRD42023485130). Findings: A total of 29 studies involving 11,750 participants were included. For seizure response, all ASMs were significantly superior to placebo, with RTG ranking highest, followed by CNB. Considering dosage, CNB 400 mg/d was top-ranked, followed by RTG 1200 mg/d. For seizure freedom, BRV was highest-ranked, followed by CNB, with BRV 100 mg/d leading, followed by CNB 400 mg/d. Regarding tolerability, LCM 600 mg/d had the lowest ranking, followed by CNB 400 mg/d. For the safety outcome of AEs, ESL 1200 mg/d was ranked lowest, followed by CNB 400 mg/d. Regarding SAEs, LCM 400 mg/d was ranked lowest, followed by RTG 1200 mg/d. Interpretation: ASMs at different dosages have varying efficacy and tolerability profiles. We have provided hierarchical rankings of ASMs for efficacy and safety outcomes. Our findings offer the most comprehensive evidence available to inform patients, families, physicians, guideline developers, and policymakers about the choice of ASMs in patients with treatment-resistant FOS. Funding: None.

Abstract Background Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). Methods In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. Results This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85–2.48) and stenosis (cOR, 1.47, 95% CI 1.26–1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24–1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P

Abstract Background Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction. Results Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score. Conclusions Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.

Abstract Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota dysbiosis and immune indicators remains unexplored. To address this gap in knowledge, we carried out 16 S rDNA sequencing, analyzed clinical fecal samples from children with sepsis (n = 30) and control children (n = 25), and obtained immune indicators, including T cell subtypes (CD3+, CD3+CD4+, CD3+CD8+, and CD4/CD8), NK cells, cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ), and immunoglobulin indices (IgA, IgE, IgM and IgG). In addition, we analyzed the correlation between gut microbiota dysbiosis and immune indicators, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. We found that children with sepsis exhibited gut bacterial dysbiosis and low alpha diversity. The Spearman’s rank correlation coefficient suggested that Rhodococcus erythropolis had a significantly positive correlation with IFN-γ and CD3 + T cells. Klebsiella pneumoniae and Streptococcus mitis were significantly correlated with NK cells. Bacteroides uniformis was significantly positively correlated with IgM and erythrocyte sedimentation rate, and Eubacterium eligens was significantly positively correlated with IL-4 and CD3+CD8+ T cells. The biomarkers discovered in this study had strong discriminatory power. These changes in the gut microbiome may be closely related to immunologic dysfunction and to the development or exacerbation of sepsis. However, a large sample size is required for verification.

Introduction: Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). However, it is unclear the interaction between dietary fiber and flavonoids in gut health. Objective: The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF + CF and CIDF + CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. Methods: 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. Results: Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. However, CSDF + CF showed weaker improvement than CF or SDF in most physical and biochemical signs. Furthermore, CSDF and CF decreased intestinal g_Escherichia-Shihella and g_Clostridium_sensu_stricto_1 induced by DSS administration. Interestingly, celery flavonoid promoted g_Akkermansia proliferation both in vivo and in vitro, and which can be inhibited by CSDF. Conclusions: This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect.

This study presents a comprehensive three-dimensional Computational Fluid Dynamics (CFD) analysis of the pre-cooling process of a Type B LNG tank using various refrigerants, including liquid nitrogen (LN), nitrogen gas (NG), liquefied natural gas (LNG), boil-off gas (BOG), and their combinations. The simulation model accounts for phase change (through the mixture multiphase model), convective heat transfer, and conjugate heat exchange between the fluid and the tank structure. The results indicate that liquid nitrogen is the most efficient refrigerant, achieving the highest cooling rate through both latent and sensible heat. LNG also demonstrated a relatively high cooling rate, 79% of that of liquid nitrogen. Gas-only pre-cooling schemes relying solely on sensible heat exhibited slower cooling rates, with BOG achieved 79.4% of the cooling rate of NG. Mixed refrigerants such as NG + LN and BOG + LNG can achieve comparable, while slightly slower, cooling than the pure liquid refrigerants, outperforming gas-only strategies. A further assessment of the heat transfer coefficient suggests the mixed cooling schemes have almost identical heat transfer coefficient on the inner tank surface to the liquid cooling scheme, over 5% higher than the gas refrigerants. The study also highlighted the uneven temperature distribution within the tank due to the bulkhead’s blockage effect, which can induce significant thermal stress and potentially compromise structural integrity. Mixed schemes exhibit thermal gradients higher than those of gas schemes but lower than those of liquid schemes, while achieving cooling speeds comparable to liquid schemes if the inlet velocity of the refrigerants is properly configured. These findings offer valuable insights for developing safer and more efficient pre-cooling procedures for Type B LNG tanks and similar cryogenic storage tanks.

This paper addresses the challenge of ranking the factors that affect the erosion resistance of lightweight alloys, with a specific focus on aluminum alloys. A three-factor, four-level orthogonal experimental design was employed to examine the influence of various sand particle sizes, erosion speeds, and sand concentrations on the abrasion qualities of these alloys. Parameters such as mass loss, depth, residual stresses, and failure mechanisms were assessed to determine erosion performance. Analysis of variance (ANOVA) and regression analysis of the three key factors were performed. Our findings resulted in an erosion rate formula: erosion rate = 0.679 sand particle size +0.067 sand concentration −0.002 erosion velocity +0.285. Our findings indicate that particle size is the most significant factor affecting erosion rate, with sand concentration and erosion velocity being secondary factors. The failure mechanism reveals that larger sand particles tend to produce deeper slides, and higher sand concentrations result in an increased number of slides. A lower concentration leads to the appearance of erosion pits. And the test conditions of high concentration and low velocity lead to more serious brittle fractures of the substrate, often accompanied by the appearance of cracks.

Rice (Oryza sativa L.), a fundamental global staple, nourishes over half of the world’s population. The identification of the ddt1 mutant in rice through EMS mutagenesis of the indica cultivar Shuhui527 revealed a dwarf phenotype, characterized by reduced plant height, smaller grain size, and decreased grain weight. Detailed phenotypic analysis and map-based cloning pinpointed the mutation to a single-base transversion in the LOC_Os03g04680 gene, encoding a cytochrome P450 enzyme, which results in a premature termination of the protein. Functional complementation tests confirmed LOC_Os03g04680 as the DDT1 gene responsible for the observed phenotype. We further demonstrated that the ddt1 mutation leads to significant alterations in gibberellic acid (GA) metabolism and signal transduction, evidenced by the differential expression of key GA-related genes such as OsGA20OX2, OsGA20OX3, and SLR1. The mutant also displayed enhanced drought tolerance, as indicated by higher survival rates, reduced water loss, and rapid stomatal closure under drought conditions. This increased drought resistance was linked to the mutant’s improved antioxidant capacity, with elevated activities of antioxidant enzymes and higher expression levels of related genes. Our findings suggest that DDT1 plays a crucial role in regulating both plant height and drought stress responses. The potential for using gene editing of DDT1 to mitigate the dwarf phenotype while retaining improved drought resistance offers promising avenues for rice improvement.

Zinc stearate (Znst) was physically blended with the sodium 4-[(4 chlorobenzoyl) amino] benzoate (SCAB) to obtain the SCAB-Znst composite nucleating agent. Znst was used to improve the dispersion property of SCAB and exert a lubricating effect on the PP matrix. The scanning electron microscopy and the fracture surface morphology of the PP/SCAB composite illustrated that the addition of Znst greatly reduced the aggregation phenomenon of SCAB in the PP matrix. The result of the rotary rheometer indicated that Znst exhibits internal lubrication in PP. The DSC result illustrated that the crystallization properties of PP were improved. Compared with pure PP, the Tc of the PP/SCAB composite increased by 1.44 °C (PP/Znst), 13.48 °C (PP/SCAB), and 14.96 °C (PP/SCAB-Znst), respectively. The flexural strength of pure PP, PP/SCAB, and PP/SCAB-Znst were 35.8 MPa, 38.8 MPa, and 40.6 MPa, respectively. The tensile strength of the PP/SCAB and PP/SCAB-Znst reached the values of 39.8 MPa and 42.9 MPa, respectively, compared with pure PP (34.1 MPa). The results demonstrated that Znst can promote the dispersion of SCAB in the PP matrix while exerting a lubricating effect, which enabled the enhancement of the crystalline and mechanical properties of PP.

IntroductionOat (Avena nuda L.) and common vetch (Vicia sativa L.) intercropping in the northern regions of China has resulted in substantial production capabilities. However, there is currently a dearth of comprehensive research on whether this intercropping system can enhance productivity through increased sowing densities and underlying interspecies interaction mechanisms.MethodsA two-year field experiment was conducted in 2022 and 2023 to investigate the yield, biological efficiency, economic efficiency, and competition indicators of oats and common vetch in a high-density intercropping system. Two cropping patterns (monocropping and intercropping) and five sowing densities (D1: 4.5×106 plants ha-1; D2:5.4×106 plants ha-1; D3:6.3×106 plants ha-1; D4: 7.2×106 plants ha-1; and D5: 8.1×106 plants ha-1) were arranged in a randomized block design.ResultsAt the same sowing density, the intercropped oats exhibited greater grain yield than the monocultures. Increasing the oat sowing density significantly enhanced oat yield, with the D3 level in intercropping showing the highest yield increase, ranging from 30.98% to 31.85%, compared with the monoculture. The common vetch intercropping grain yield was maximized in the D2 treatment. The land equivalent ratio was maximized at the D2 level in both years and was significantly higher than D1, with the land equivalent coefficient, system productivity index, and percentage yield difference suggesting that increasing oat sowing densities improved the productivity of the intercropping system, with the best performance observed at the D2 level. For both years, the proportionate actual yield loss of oat was the highest at the D3 level; significantly surpassing D1, proportionate actual yield loss of common vetch and actual yield loss were the highest at level D2, both significantly surpassing D1. These indicates that appropriate densification contributes to the realization of the advantages of intercropping. With an increased oat sowing density, the economic benefits of the intercropping system were maximized at the D2 and D3 levels. Regarding intercropping competition, oat was the dominant crop under different sowing densities (Aggressivity for oat (AO)>0, relative crowding coefficient for oat (KO)>1, competition ratio for oat (CRO)>1), whereas common vetch was the inferior crop. Compared with the D1 level, the D2 level harmonized the aggressivity, competitive ratio, and relative crowding coefficients of oat and common vetch, significantly increasing crowding coefficient for common vetch (KV) and competition ratio for common vetch by 19.76% to 21.94% and 4.80% to 7.51%, respectively, while reducing KO and CRO.DiscussionThis result suggests that in the intercropping of common vetch and oat in alpine regions, rational densification can harmonize interspecific competition and thus improve the biological efficiency and economic benefits of intercropping systems.

Objectives: Osteoarthritis (OA) is characterized by a high prevalence, poor prognosis, and a propensity to lead to disability. Despite the availability of standard therapies, they are associated with potential side effects and don't provide a complete cure for patients. Consequently, there is an urgent demand for the development of novel drugs. Method: The gene expression profiles (GSE64394, GSE178557 and GSE215039) of normal and OA chondrocytes samples were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by the ''LIMMA'' R package. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted using the R package clusterProfiler. A protein-protein (PPI) interaction network was performed to identify hub genes by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Small molecule compounds linked to OA were predicted through the NetworkAnalyst platform. Finally, molecular docking was conducted using AutoDock and Pymol software. Results: We identified 98 DEGs primarily implicated in endochondral ossification, extracellular matrix degradation, and Wnt signaling pathways. 23 DEGs were closely associated with OA, and 10 hub genes were found to be potential drug targets for OA. Two new targeted compounds, tetrachlorodibenzodioxin (TCDD) and valproic acid (VPA), were screened. And they both exhibited strong binding affinity to their respective targets. Conclusions: Reducing exposure to TCDD could be a crucial strategy in preventing OA, and VPA has gained recognition as a novel drug candidate for OA treatment.

High cadmium (Cd, 50 µM) caused transcriptional upregulation of Ca2+-dependent protein kinase 21 (CPK21) in roots and leaves of Populus euphratica. The promoter region (1803 bp) of PeCPK21 was engineered to fuse PeCPK21-pro::GUS and transformed in Arabidopsis. The activity of GUS significantly increased in roots, cotyledons, and hypocotyls under 100 μM CdCl2 treatment. The 1599 bp coding sequence of PeCPK21 was transferred into Arabidopsis, and overexpression of PeCPK21 increased Cd tolerance as evidenced by less reduction in root length and plant growth under CdCl2 stress conditions (100 µM, 7 d). PeCPK21-interacting proteins were enriched by HaloTag pull-down and corresponding expression profiles after Cd exposure indicate that PeCPK21 interacts with heavy metal stress-associated proteins (HMAPs) to mediate Cd tolerance in transgenic Arabidopsis. PeCPK21 interacted with the Cd-regulated cation/heavy metal transport proteins annexin, OPT3, COPT5, and PDF2.2 to limit Cd uptake and accumulation in transgenic plants. PeCPK21 may also interact with the V-type proton ATPase subunits, VHA-B1, VHA-C, and AVA-P2, which were transcriptionally upregulated by Cd to accelerate vacuolar Cd compartmentalization. Cd-triggered H2O2 production was limited in plants overexpressing PeCPK21, which was due to the activated antioxidant enzymes. The interaction of PeCPK21 with the antioxidant enzymes TAPX, APX1, APX2, TRXM4, GPX3, CDSP32, and PRXQ, which showed transcriptional upregulation by Cd, could enhance antioxidant defense in transgenic Arabidopsis. It is also possible that PeCPK21 interacts with plasma membrane intrinsic proteins, PIP1–1, PIP2A, and PIP2–7, which had an Cd-enhanced transcript, to improve water status in transgenic Arabidopsis. In summary, we hypothesize that the calcium sensor PeCPK21 can attenuate Cd toxicity by interacting with HMAPs to effectively limit Cd accumulation, increase ROS scavenging, and improve water status in transgenic Arabidopsis.

Spermatogenesis is a complex process intricately regulated by the hypothalamic-pituitary-testis (HPT) axis. However, research on the regulatory factors governing the HPT axis remains limited. This study addresses this gap by conducting a comprehensive analysis of transcriptomes from the pituitary and testis tissues across various developmental stages, encompassing embryonic day (E120), neonatal period (P0), pre-puberty (P90), and post-puberty day (P270). Utilizing edgeR and WGCNA, we identified stage-specific genes in both the pituitary and testis throughout the four developmental stages. Notably, 380, 242, 34, and 479 stage-specific genes were identified in the pituitary, while 886, 297, 201, and 3,678 genes were identified in the testis. Subsequent analyses unveiled associations between these stage-specific genes and crucial pathways such as the cAMP signaling pathway, GnRH secretion, and male gamete generation. Furthermore, leveraging single-cell data from the pituitary and testis, we identified some signaling pathways involving BMP, HGF, IGF, and TGF-β, highlighting mutual regulation between the pituitary and testis at different developmental stages. This study sheds light on the pivotal role of the pituitary-testis axis in the reproductive process of sheep across four distinct developmental stages. Additionally, it delves into the intricate regulatory networks governing reproduction, offering novel insights into the dynamics of the pituitary-testis axis within the reproductive system.

Epstein-Barr Virus (EBV) infection is closely associated with the development of lymphoma, as it plays a significant role in the malignant transformation of lymphocytes. The expression of programmed death-1 (PD-1), which binds to PD-L1 in tumor cells, can lead to immune evasion by lymphoma cells and promote tumor progression. In this study, immortalized B lymphoblastoid cell lines (B-LCLs) positive for EBV-specific proteins were established from human peripheral mononuclear cells (PBMCs) using EBV induction along with CpG-ODN 2006 and cyclosporin A. EBV-specific T cells (EBVST) were generated by multiple immunizations of CD3+ T lymphocytes using irradiated B-LCLs. Flow cytometry analysis confirmed the activation of EBVST through the detection of CD3+, CD4+, and CD8+ markers. Co-incubation of EBVST with EBV-positive B lymphocyte cell lines resulted in the secretion of perforin by EBVST, leading to granzyme B-mediated cell death and an increase in LDH levels. Silencing PD-1 in EBVST cells enhanced perforin production, increased granzyme B release, and upregulated cell death in co-incubated B lymphocytes. In a nude mice tumor transplantation model, silencing PD-1 in combination with EBV-specific killer T cells exhibited the maximum inhibition of B-lymphoblastoma. This treatment upregulated the expression of proteins associated with apoptosis and immune response, while inhibiting anti-apoptotic protein expression in tumor tissues. Silencing PD-1 also increased the infiltration of EBV-specific killer T cells in the tumor tissues. Overall, PD-1 silencing enhanced the tumor targeting effect of EBV-specific killer T cells on EBV-infected B lymphocytes and attenuated the immune escape effect mediated by the PD-1 pathway.

Based on the paraxial wave equation, this study extends the theory of small-scale self-focusing (SSSF) from coherent beams to spatially partially coherent beams (PCBs) and derives a general theoretical equation that reveals the underlying physics of the reduction in the B-integral of spatially PCBs. From the analysis of the simulations, the formula for the modulational instability (MI) gain coefficient of the SSSF of spatially PCBs is obtained by introducing a decrease factor into the formula of the MI gain coefficient of the SSSF of coherent beams. This decrease can be equated to a drop in the injected light intensity or an increase in the critical power. According to this formula, the reference value of the spatial coherence of spatially PCBs is given, offering guidance to overcome the output power limitation of the high-power laser driver due to SSSF.

To explore the washback of the HSK on students learning Chinese as a Second Language (CSL), the study surveyed 1,616 SCL students from 25 different mother tongue backgrounds and interviewed international students studying in China through questionnaire and interview. The following was found in this study: (a) The HSK influenced both the process and results of CSL learning, and the positive impact outweighed the negative impact. (b) Students’ motivation and perception of the HSK were the key factors that influenced the level of HSK washback. (c) The HSK had different intensities of washback on students at different HSK levels, with the strong effect on students at the lower level and a weak effect on students at the higher level. Based on the findings, some implications and suggestions for learners, teachers and test designers are provided.

Frequency modulation (FM)-to-amplitude modulation (AM) conversion is an important factor that affects the time–power curve of inertial confinement fusion (ICF) high-power laser facilities. This conversion can impact uniform compression and increase the risk of damage to optics. However, the dispersive grating used in the smoothing by spectral dispersion technology will introduce a temporal delay and can spatially smooth the target. The combined effect of the dispersive grating and the focusing lens is equivalent to a Gaussian low-pass filter, which is equivalent to 8 GHz bandwidth and can reduce the intensity modulation on the target to below 5% with 0.3 nm @ 3 GHz + 20 GHz spectrum phase modulation. The results play an important role in the testing and evaluating of the FM-to-AM on the final optics and the target, which is beneficial for comprehensively evaluating the load capacity of the facility and isentropic compression experiment for ICF.

In patients with Alzheimer’s disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer’s disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease (Aβ1–42–treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-β in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of β-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Abstract Polysaccharides are typically resistant to digestion in the gastrointestinal tract and are instead degraded by gut microbiota in the colon. As such, they are commonly employed as carriers for colon‐targeted drugs, with the potential to regulate gut microbiota. Pectin, carrageenan, guar gum, and xanthan gum are commonly used polysaccharide carriers, but their degradation in the gut microbiota under colitis conditions as well as their effects on gut microbiota remains unclear. In this study, we performed the in vitro fermentation of these four polysaccharides using colonic content microbiota from mice with colitis and evaluated the degree of polysaccharide degradation and the effects on pH, short‐chain fatty acids, and gut microbiota. Our findings indicate that pectin and guar gum had a greater degree of degradation and promoted the production of butyrate, inhibited the proliferation of harmful bacteria (e.g., Enterobacteriaceae), and increased beneficial bacteria (e.g., Bifidobacterium). In contrast, carrageenan and xanthan gum promote the proliferation of Enterobacteriaceae. These results provide theoretical guidance for the selection of drug delivery carriers for inflammatory bowel disease treatment and provide information on the relationship between polysaccharides and gut microbiota.

Abstract Background Treatment‐free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality‐of‐life (QoL) and mental health in CML patients with full‐dose TKI, low‐dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation. Methods We conducted a cross‐sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation. Results 1450 responses were included in the analysis. 44.3% of respondents reported a moderate‐to‐severe impact of TKI treatment on their QoL. 17% of respondents had moderate‐to‐severe anxiety. 24.4% of respondents had moderate‐to‐severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long‐term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full‐dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping. Conclusions TKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality‐of‐life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.