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Abstract Purpose Surgical site infection (SSI) is common after laparoscopic appendectomy, resulting in prolonged hospital stay and increased costs. This study examined the relationship between body composition parameters and risk of incisional SSI in patients with complicated appendicitis. Methods We included 411 patients who underwent laparoscopic surgery for complicated appendicitis at a single institution between March 2015 and October 2023. Body composition parameters were derived from preoperative computed tomography (CT). A nomogram was constructed based on the independent predictors of incisional SSI. Results Overall, 45 (10.9%) patients developed incisional SSI. Visceral fat area (VFA) was independently associated with risk of incisional SSI (hazard ratio 1.015, 95% confidence interval 1.010–1.020, P

Abstract The maintenance of hematopoietic stem cell (HSC) functional integrity is essential for effective hematopoietic regeneration when suffering from injuries. Studies have shown that the innate immune pathways play crucial roles in the stress response of HSCs, whereas how to precisely modulate these pathways is not well characterized. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 47 (Trim47) as a negative regulator of the mitochondrial antiviral-signaling protein (MAVS)-mediated innate immune pathway in HSCs. We find that Trim47 is predominantly enriched in HSCs, and its deficiency impairs the function and survival of HSCs after exposure to 5-flurouracil (5-FU) and irradiation (IR). Mechanistically, Trim47 impedes the excessive activation of the innate immune signaling and inflammatory response via K48-linked ubiquitination and degradation of MAVS. Collectively, our findings demonstrate a role of Trim47 in preventing stress-induced hematopoietic failure and thus provide a promising avenue for treatment of related diseases in the clinic.

Abstract With the widespread application of nuclear technology across various fields, ionizing radiation-induced injuries are becoming increasingly common. The bone marrow (BM) hematopoietic tissue is a primary target organ of radiation injury. Recent researches have confirmed that ionizing radiation-induced hematopoietic dysfunction mainly results from BM hematopoietic stem cells (HSCs) injury. Additionally, disrupting and reshaping BM microenvironment is a critical factor impacting both the injury and regeneration of HSCs post radiation. However, the regulatory mechanisms of ionizing radiation injury to BM HSCs and their microenvironment remain poorly understood, and prevention and treatment of radiation injury remain the focus and difficulty in radiation medicine research. In this review, we aim to summarize the effects and mechanisms of ionizing radiation-induced injury to BM HSCs and microenvironment, thereby enhancing our understanding of ionizing radiation-induced hematopoietic injury and providing insights for its prevention and treatment in the future.

Toppling deformation can be classified into deep toppling (DT) and shallow toppling (ST) based on deformation mechanisms and development depth of rock mass under different soft and hard rock conditions. Currently, the toppling zoning indicators and quantitative criteria are not uniform, and human factors have a significant influence on the toppling zoning indicators. Summerizing and analyzing the existing toppling cases and toppling zoning researches, this study selects rock layer toppled angle, maximum tension within layer, unit tension within layer, and longitudinal wave velocity as indicators for toppling zoning. Considering the differences in the characteristics of deep toppling (DT) and shallow toppling (ST), the quantitative criteria for the deep and shallow toppling zoning indicators are determined respectively. This study employs the Analytic Hierarchy Process (AHP) and fuzzy comprehensive evaluation method to establish toppling zoning evaluation models. The deep toppling dam site slope at Miaowei hydropower station and the shallow toppling bank slope of Xingguang Ⅲ formation at Xiluodu Hydropower Station were tested, respectively. These results are compared with toppling zoning of field surveys to verify the rationality and applicability of the models. This achievement holds significant reference value for the toppling zoning of rock masses in engineering slopes, especially in the construction, development, and engineering management of toppling slopes.

A few observational neuroimaging investigations have reported subcortical structural changes in the individuals who recovered from the coronavirus disease‐2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the causal relationships between COVID-19 and longitudinal changes of subcortical structures remain unclear. We performed two-sample Mendelian randomization (MR) analyses to estimate putative causal relationships between three COVID-19 phenotypes (susceptibility, hospitalization, and severity) and longitudinal volumetric changes of seven subcortical structures derived from MRI. Our findings demonstrated that genetic liability to SARS-CoV-2 infection had a great long-term impact on the volumetric reduction of subcortical structures, especially caudate. Our investigation may contribute in part to the understanding of the neural mechanisms underlying COVID-19-related neurological and neuropsychiatric sequelae.

Abstract Background Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. Methods A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. Results Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. Conclusions Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.

Abstract Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer’s disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.

The hematopoietic system is susceptible to ionizing radiation (IR), which can cause acute hematopoietic failure or long-term myelosuppression. As the most primitive cells of the hematopoietic hierarchy, hematopoietic stem cells (HSCs) maintain lifelong hematopoietic homeostasis and promote hematopoietic regeneration during stress. Numerous studies have shown that nuclear and mitochondrial genomes are the main targets of radiation injury in HSCs. More importantly, the damage of DNA may trigger a series of biological responses that largely determine HSC fate following IR exposure. Although some essential pathways and factors involved in DNA injury and damage in HSCs have been revealed, a comprehensive understanding of the biological effects of radiation on HSCs still needs to be improved. This review focuses on recent insights into the molecular mechanisms underlying DNA damage and repair in HSCs after IR. Then summarize corresponding regulatory measures, which may provide a reference for further research in this field.

Objective: This study aimed to evaluate the role of computed tomography (CT) imaging in the diagnosis and management of bone cancer during periods of limited access to histopathological testing. We aimed to determine the correlation between CT severity levels and subsequent patient management and care decisions, adhering to established oncological CT reporting guidelines. Methodology: A retrospective analysis was conducted on 60 symptomatic patients from January 2021 to January 2024. The cohort included patients aged between 50 and 86 years, with a mean age of 68 years, and 75 % were male. All patients had their bone cancer diagnosis confirmed through histopathological examination, and CT imaging was used as the reference method. The analysis involved assessing the correlation between CT severity scores and patient management, including ICU admissions. Results: The study found that CT imaging demonstrated a sensitivity of 92.6% in diagnosing bone cancer, with accuracy increasing to 97.6% in cases with high-probability CT characteristics. CT specificity also showed a consistent rise. Osteolytic lesions were the predominant finding, detected in 85.9% of cases. Among these, 88% exhibited engagement across multiple skeletal regions, 92.8% showed bilateral distribution, and 92.8% presented with peripheral involvement. In ICU patients, bone consolidation was observed in 81.5% of cases and was predominant in 66.7% of the ICU cohort. Additionally, ICU patients had significantly higher CT severity scores, with scores exceeding 14 being notably prevalent. Conclusions: During the management period of bone cancer at our hospital, characteristic features on CT imaging facilitated swift and sensitive investigation. Two distinct CT phenotypes, associated with the primary osteolytic phenotype and severity score, emerged as valuable indicators for assessing the severity of the disease, particularly during ICU care. These findings highlight the diverse manifestations and severity levels encountered in bone cancer patients and underscore the importance of CT imaging in their diagnosis and management.

Abstract Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS‐C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue‐specific enrichment analysis indicate that the protective effect of PGS‐C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high‐cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS‐C.

This work offered a productive technique for resveratrol extraction from Polygonum Cuspidatum (P. Cuspidatum) using ionic liquids in synergy with ultrasound-enzyme-assisted extraction (UEAE). Firstly, ionic liquids with different carbon chains and anions were evaluated. Subsequently, a comprehensive investigation was carried out to evaluate the effect of seven crucial parameters on the resveratrol yield: pH value, enzyme concentration, extraction temperature, extraction time, ultrasonic power, concentration of ionic liquid (IL concentration) and the liquid–solid ratio. Employing the Plackett-Burman Design (PBD), the critical factors were effectively identified. Building upon this foundation, the process was further optimized through the application of Response Surface Methodology (RSM) and an Artificial Neural Network-Genetic Algorithm (ANN-GA). The following criteria were determined to be the ideal extraction conditions: an enzyme concentration of 2.18%, extraction temperature of 58 °C, a liquid–solid ratio of 29 mL/g, pH value of 5.5, extraction time of 30 min, ultrasonic power of 250 W, and extraction solvent of 0.5 mol/L 1-butyl-3-methylimidazolium bromide. Under these conditions, the resveratrol yield was determined to be 2.90 ± 0.15 mg/g. Comparative analysis revealed that the ANN-GA model provided a better fit to the experimental data of resveratrol yield than the RSM model, suggesting superior predictive capabilities of the ANN-GA approach. The introduction of a novel green solvent system in this experiment not only simplifies the extraction process but also enhances safety and feasibility. This research paves the way for innovative approaches to extracting resveratrol from botanical sources, showcasing its significant potential for a wide range of applications.

The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer’s disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.

For the widespread exposure of toppling deformation phenomena in anti-dip engineering slopes such as hydropower, transportation, and mining, especially deep-seated toppling, these large-scale deep-seated toppling deformations reaching depths of hundreds of meters have become significant geotechnical engineering problems that restrict large-scale engineering construction and require urgent solutions. There are significant differences in the failure characteristics and mechanisms of anti-dip rock slopes under different soft and hard rock conditions. This study, starting from the failure characteristics and mechanisms under different soft and hard conditions of rocks, summarizes two types of toppling deformation: ductile bending deep toppling (DBDT) and brittle fracture shallow toppling (BFST). The UDEC method is used to preliminarily explore the threshold of rock mechanical parameters for these two types of toppling, with 80 MPa (UCS, uniaxial compressive strength) mechanical parameters serving as the preliminary threshold. The results indicate that hard rock undergoes BFST, whereas soft rock undergoes DBDT. The rock mechanical parameters of 100 MPa (UCS) and 20 MPa (UCS) were selected to study the evolution process and mechanism of DBDT and BFST deformations, respectively. Numerical simulation results have innovatively revealed the mechanical behavior characteristics between rock layers during the process of toppling deformation. Because toppling deformation mainly originates from interlayer displacement deformation and intra-layer tensile deformation of rock layers, the interlayer mechanical characteristics are of great significance for understanding the mechanism of toppling deformation. This research can provide a theoretical basis for the stability assessment and development utilization of anti-dip rock slopes and toppled slopes.

Platelets, produced by megakaryocytes, play unique roles in physiological processes, such as hemostasis, coagulation, and immune regulation, while also contributing to various clinical diseases. During megakaryocyte differentiation, the morphology and function of cells undergo significant changes due to the programmed expression of a series of genes. Epigenetic changes modify gene expression without altering the DNA base sequence, effectively impacting the inner workings of the cell at different stages of growth, proliferation, differentiation, and apoptosis. These modifications also play an important role in megakaryocyte development and platelet biogenesis. However, the specific mechanisms underlying epigenetic processes or the vast epigenetic regulatory network formed by their interactions remain unclear. In this review, we systematically summarize the key roles played by epigenetics in megakaryocyte development and platelet formation, including DNA methylation, histone modification, and non-coding RNA regulation. We expect our review to provide a deeper understanding of the biological processes underlying megakaryocyte development and platelet formation and to inform the development of new clinical interventions aimed at addressing platelet-related diseases and improving patient prognoses.

Lycopene-rich guava (Psidium guajava L.) exhibits significant economic potential as a functional food ingredient, making it highly valuable for the pharmaceutical and agro-food industries. However, there is a need to enhance the extraction methods of lycopene to fully exploit its beneficial uses. In this study, we evaluated various ionic liquids to identify the most effective one for extracting lycopene from guava. Among thirteen ionic liquids with varying carbon chains or anions, 1-butyl-3-methylimidazolium chloride demonstrated the highest productivity. Subsequently, a single-factor experiment was employed to test the impact of several parameters on the efficiency of lycopene extraction using this selected ionic liquid. These parameters included extraction time, ultrasonic power, liquid-solid ratio, concentration of the ionic liquid, as well as material particle size. Moreover, models of artificial neural networks using genetic algorithms (ANN-GA) and response surface methodology (RSM) were employed to comprehensively assess the first four key parameters. The optimized conditions for ionic liquid ultrasound-assisted extraction (IL-UAE) were determined as follows: 33 min of extraction time, 225 W of ultrasonic power, 22 mL/g of liquid-solid ratio, 3.0 mol/L of IL concentration, and extraction cycles of three. Under these conditions, lycopene production reached an impressive yield of 9.35 ± 0.36 mg/g while offering advantages such as high efficiency, time savings, preservation benefits, and most importantly environmental friendliness.

Introduction and Objectives: Cholangiocarcinoma (CCA) is characterized by early distant invasion and metastasis, whereas the underlying mechanism is still obscure. Increasing evidence shows that collagen type Ι alpha 1 (COL1A1) is a gene associated with the progression of multiple diseases. Here, we attempted to investigate the role of COL1A1 in CCA. Materials and Methods: The expression of COL1A1 between tumor tissues and adjacent normal tissues obtained from CCA patients was detected by Western blot and immunofluorescence, followed by analysis of its clinical significance. Then, the biological effects of COL1A1 overexpression or knockdown on CCA cells were evaluated in vitro and in vivo. Finally, molecular mechanism of COL1A1 in regulating the invasion and metastasis of CCA cells was determined by a series of experiments. Results: COL1A1 expression was significantly higher in CCA pathological tissues than in corresponding adjacent normal tissues. Analysis of 83 CCA patients showed that higher expression of COL1A1 was correlated with poorer patient prognosis. Notably, overexpression or knockdown experiments revealed that COL1A1 contributed to the migration and invasion, as well as epithelial-to-mesenchymal transition (EMT), in CCA cells. Further investigations demonstrated that matrix metalloproteinase-2 (MMP2) promoted COL1A1 upregulation via the integrin alpha Ⅴ pathway, therefore affecting ECM remodelling and inducing EMT in CCA cells. Moreover, COL1A1 expression was positively related to PD-1 and PD-L1 in CCA, and COL1A1 increased PD-L1 expression by activating the NF-κB pathway. Conclusions: COL1A1 plays an important role in regulating CCA progression and may act as a promising biomarker and therapeutic target for CCA.

An efficient Nd: A YAG single-frequency laser was demonstrated using a gradient-doped ceramic non-planar ring oscillator (NPRO). A thermal model of the gradient-doped ceramic NPRO was built to analyze the temperature field and thermal focal length. By employing a gradient-doped gain structure, the thermal distribution within the NPRO can be effectively smoothed to reduce thermal lensing effects. Up to 2.8 W of single-frequency output power at 1064 nm from the gradient-doped ceramic NPRO was obtained, with a slope efficiency of 38%.

Abstract Background The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1 + stromal cells, and epithelial cells are required for ISC proliferation and villus homeostasis. Intestinal stromal cells are heterogeneous and single-cell profiling has divided them into telocytes/subepithelial myofibroblasts, myocytes, pericytes, trophocytes, and Pdgfra low stromal cells. Yet, the niche function of these stromal populations remains incompletely understood. Results We show here that a Twist2 stromal lineage, which constitutes the Pdgfra low stromal cell and trophocyte subpopulations, maintains the crypt structure to provide an inflammation-restricting niche for regenerating ISCs. Ablating Twist2 lineage cells or deletion of one Wntless allele in these cells disturbs the crypt structure and impairs villus homeostasis. Upon radiation, Wntless haplo-deficiency caused decreased production of anti-microbial peptides and increased inflammation, leading to defective ISC proliferation and crypt regeneration, which were partially rescued by eradication of commensal bacteria. In addition, we show that Wnts secreted by Acta2 + subpopulations also play a role in crypt regeneration but not homeostasis. Conclusions These findings suggest that ISCs may require different niches for villus homeostasis and regeneration and that the Twist2 lineage cells may help to maintain a microbe-restricted environment to allow ISC-mediated crypt regeneration.

Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain, leading to neurodegeneration in Alzheimer's disease (AD). Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses, but is very challenging. Herein, an engineered macrophage-biomimetic versatile nanoantidote (OT-Lipo@M) is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression. Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain, but also efficiently reduce neurotoxin levels to prevent them from activating microglia. The loaded oxytocin (OT) can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4 (TLR4) on microglia, inhibiting TLR4-mediated pro-inflammatory signalling cascade. Benefiting from this two-pronged immunosuppressive strategy, OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits, inhibiting neuronal apoptosis, and enhancing synaptic plasticity in AD mice, accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging. This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.

Abstract Hyperhomocysteinemia (HHcy) is closely associated with thrombotic diseases such as myocardial infarction and stroke. Enhanced platelet activation was observed in animals and humans with HHcy. However, the influence of HHcy on thrombopoiesis remains largely unknown. Here, we reported increased platelet count (PLT) in mice and zebrafish with HHcy. In hypertensive patients (n = 11,189), higher serum level of total Hcy was observed in participants with PLT ≥ 291 × 109/L (full adjusted β, 0.59; 95% CI 0.14, 1.04). We used single-cell RNA sequencing (scRNA-seq) to characterize the impact of Hcy on transcriptome, cellular heterogeneity, and developmental trajectories of megakaryopoiesis from human umbilical cord blood (hUCB) CD34+ cells. Together with in vitro and in vivo analysis, we demonstrated that Hcy promoted megakaryocytes (MKs) differentiation via growth hormone (GH)-PI3K-Akt axis. Moreover, the effect of Hcy on thrombopoiesis is independent of thrombopoietin (TPO) because administration of Hcy also led to a significant increase of PLT in homozygous TPO receptor (Mpl) mutant mice and zebrafish. Administration of melatonin effectively reversed Hcy-induced thrombopoiesis in mice. ScRNA-seq showed that melatonin abolished Hcy-facilitated MK differentiation and maturation, inhibited the activation of GH-PI3K-Akt signaling. Our work reveals a previously unrecognized role of HHcy in thrombopoiesis and provides new insight into the mechanisms by which HHcy confers an increased thrombotic risk. Trial Registration clinicaltrials.gov Identifier: NCT00794885.

Despite breakthroughs in modern medical care, the incidence of cardiovascular disease (CVD) is even more prevalent globally. Increasing epidemiologic evidence indicates that emerging cardiovascular risk factors arising from the modern lifestyle, including psychosocial stress, sleep problems, unhealthy diet patterns, physical inactivity/sedentary behavior, alcohol consumption, and tobacco smoking, contribute significantly to this worldwide epidemic, while its underpinning mechanisms are enigmatic. Hematological and immune systems were recently demonstrated to play integrative roles in linking lifestyle to cardiovascular health. In particular, alterations in hematopoietic stem cell (HSC) homeostasis, which is usually characterized by proliferation, expansion, mobilization, megakaryocyte/myeloid-biased differentiation, and/or the pro-inflammatory priming of HSCs, have been shown to be involved in the persistent overproduction of pro-inflammatory myeloid leukocytes and platelets, the cellular protagonists of cardiovascular inflammation and thrombosis, respectively. Furthermore, certain lifestyle factors, such as a healthy diet pattern and physical exercise, have been documented to exert cardiovascular protective effects through promoting quiescence, bone marrow retention, balanced differentiation, and/or the anti-inflammatory priming of HSCs. Here, we review the current understanding of and progression in research on the mechanistic interrelationships among lifestyle, HSC homeostasis, and cardiovascular health. Given that adhering to a healthy lifestyle has become a mainstream primary preventative approach to lowering the cardiovascular burden, unmasking the causal links between lifestyle and cardiovascular health from the perspective of hematopoiesis would open new opportunities to prevent and treat CVD in the present age.

An accurate calculation of the indicator diagram of a pumping unit is the key factor in analyzing the performance of an oilfield production and operation and in preparing and optimizing an oilfield development plan. Aiming at the problems of the poor stability of the conventional load-displacement sensor method and the wave equation method, owing to the influence of an alternating load on the force sensor and the difficulty in measuring the crank angle using the electrical parameter method, a new soft sensing method employing the input electrical parameters of the motor and the beam inclination has been proposed to obtain the indicator diagram. At first, this method is established based on the beam angle of the pumping unit, which is easily measured using the suspension point displacement mathematics calculation model and the torque factor. Subsequently, the electric motor input parameters, the parameters of the four-bar linkage, and the relationship between the polished rod load have been established. Finally, the motor and the beam angle of the measured electrical parameters have been substituted into the calculation of the suspension point displacement and load value and pull in accordance with the guidelines to eliminate the singularity mutation values. After processing the measured data through a Butterworth filter, the indicator diagram is obtained. The results of the engineering experiment and application show that the average relative error of the method is less than 3.95%, and the maximum relative error remains within 2% for 6 months, which verifies the stability of the soft sensing method.

Abstract Hydroxyl radical (•OH)‐sensitive carbon dots (CDs) with an excitation wavelength of 390 nm and emission wavelength of 525 nm were synthesized by microwave in one‐step. Using CDs as fluorescent probes, an •OH‐enhanced fluorescence quenching detection signal based on horseradish peroxidasecatalyzed H2O2 was introduced on the basis of enzyme‐linked immunoassay, and a •OH‐enhanced label‐free fluorescence quenching immunoassay (FQIA) was constructed for high‐sensitivity detection of six broad‐spectrum antibiotics. When used for nitrofuran Q2 metabolites (3‐amino‐1,3‐oxazolidin‐2‐one, 3‐amino‐5‐(morpholin‐4‐ylmethyl)‐1,3‐oxazolidin‐2‐one, 1‐aminohydantoin hydrochloride, semicarbazide hydrochloride), chloramphenicol (CAP) and florfenicol (FLR) detection, FQIAs achieved high sensitivity detection of 0.061, 0.0058, 0.064, 0.045, 0.015, and 0.01 ng/ml, respectively. Compared with ELISA, the detection sensitivity was improved by 2.03‐ to 7.8‐fold. On this basis, the sample pretreatment methods for six targets were optimized, and the simultaneous extraction and high‐sensitivity detection of six targets were achieved. The FQIA proposed in this work improved the detection sensitivity, reduced the sample consumption and pretreatment steps, shortened the extraction time, and improved the detection efficiency, which provided support for the development and application of new immunoassay products and the development of the rapid analysis industry.

Three new Ptychoptera Meigen, 1803 species from southern China, P. hekouensis sp. nov., P. longa sp. nov., and P. xiaohuangshana sp. nov., are described and illustrated. These new species are mainly distinguished from congeners by their body colors and male genitalia. The genus Ptychoptera is recorded from Guangdong, China for the first time. An updated key to all Chinese Ptychoptera species is provided.

There is growing appreciation that hematopoietic alterations underpin the ubiquitous detrimental effects of metabolic disorders. The susceptibility of bone marrow (BM) hematopoiesis to perturbations of cholesterol metabolism is well documented, while the underlying cellular and molecular mechanisms remain poorly understood. Here we reveal a distinct and heterogeneous cholesterol metabolic signature within BM hematopoietic stem cells (HSCs). We further show that cholesterol directly regulates maintenance and lineage differentiation of long-term HSCs (LT-HSCs), with high levels of intracellular cholesterol favoring maintenance and myeloid bias of LT-HSCs. During irradiation-induced myelosuppression, cholesterol also safeguards LT-HSC maintenance and myeloid regeneration. Mechanistically, we unravel that cholesterol directly and distinctively enhances ferroptosis resistance and boosts myeloid but dampens lymphoid lineage differentiation of LT-HSCs. Molecularly, we identify that SLC38A9–mTOR axis mediates cholesterol sensing and signal transduction to instruct lineage differentiation of LT-HSCs as well as to dictate ferroptosis sensitivity of LT-HSCs through orchestrating SLC7A11/GPX4 expression and ferritinophagy. Consequently, myeloid-biased HSCs are endowed with a survival advantage under both hypercholesterolemia and irradiation conditions. Importantly, a mTOR inhibitor rapamycin and a ferroptosis inducer imidazole ketone erastin prevent excess cholesterol-induced HSC expansion and myeloid bias. These findings unveil an unrecognized fundamental role of cholesterol metabolism in HSC survival and fate decisions with valuable clinical implications.

Abstract Background Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disease predominantly found in women of child-bearing age. Neurogenic pulmonary edema (NPE) is a recalcitrant complication that occurs after injury to the central nervous system and has an acute onset and rapid progression. Limbic encephalitis is an inflammatory encephalopathy caused by viruses, immune responses, or other factors involving the limbic system. NPE caused by SLE is rare. Case presentation Here, we report a case of a 21-year-old woman with SLE who experienced five episodes of generalized tonic–clonic seizure after headache and dyspnea. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 2 antibody was tested positive in the serum and cerebrospinal fluid. Electrocardiography (EEG) indicated paroxysmal or sporadic medium amplitude theta activity. In addition, chest computed tomography (CT) showed multiple diffuse consolidations and ground-glass opacities. We finally considered a diagnosis of NPE and AMPAR limbic encephalitis. The patient's symptoms improved obviously after methylprednisolone pulse therapy and antiepileptic treatment. Conclusions NPE can be a complication of neuropsychiatric lupus erythematosus (NPSLE). AMPAR2 antibodies may be produced in NPSLE patients, especially in those with high polyclonal IgG antibody titers. More basic and clinical studies are required to confirm these observations and elucidate the pathogenicity of encephalitis-related autoantibodies in SLE patients.

Introduction: Ablation therapy is a commonly used tool in the management of hepatocellular carcinoma (HCC). After ablation, dying cancer cells release a variety of substances that trigger subsequent immune responses. Immunogenic cell death (ICD) has been a trending topic in recent years and has been discussed many times along with oncologic chemotherapy. However, the subject of ablative therapy and ICDs has been little discussed. The purpose of this study was to investigate whether ablation treatment induces ICD in HCC cells and whether different types of ICDs arise because of different ablation temperatures.Methods: Four different HCC cell lines (H22, Hepa-16, HepG2 and SMMC7221) were cultured and treated under different temperatures (−80°C, −40°C, 0°C, 37°C, and 60°C). Cell Counting Kit-8 assay was performed to analyze the viability of different cell lines. Apoptosis was detected by flow cytometry assay, and a few ICD-related cytokines (calreticulin, ATP, high mobility group box 1, and CXCL10) were detected by immunofluorescence or enzyme-linked immunosorbent assay.Results: The apoptosis rate of all kinds of cells increased significantly in −80°C group (p < 0.01) and 60°C group (p < 0.01). The expression levels of ICD-related cytokines were mostly significantly different between the different groups. For calreticulin, Hepa1-6 cells and SMMC7221 cells showed significantly higher protein expression levels in 60°C group (p < 0.01) and significantly lower protein expression levels −80°C group (p < 0.01). The ATP, high mobility group box 1 and CXCL10 expression levels were significantly higher in 60°C, −80°C and −40°C group of all four cell lines (p < 0.01).Conclusion: Different ablative treatments could induce different types of ICDs in HCC cells, providing a promising track for the development of individualized cancer therapies.

BackgroundBilateral carotid body tumors with a concomitant skull-base paraganglioma are extremely rare, of which only one case has been reported in the literature to date.Case presentationWe present the case of a 35-year-old male with 1 year of hypertension and high levels of dopamine and 3-methoxytyramine. Magnetic resonance imaging (MRI) scans demonstrated three separate masses at the left middle cranial fossa floor and bilateral carotid bifurcation. Genetic testing showed succinate dehydrogenase complex subunit D mutation. The patient underwent the resection of the left skull base mass. Histopathology and immunohistochemistry confirmed the presence of a skull-base paraganglioma.ConclusionsSuccinate dehydrogenase complex subunit D mutation-associated bilateral carotid body tumors with a concomitant skull-base paraganglioma accompanied by abnormal dopamine and hypertension are extremely rare, which not only provides ideas for considering the association of gene mutations, biochemical abnormalities and clinical symptoms but also provides an expanded diagnostic spectrum for paraganglioma in atypical locations.

‘Shanghaiqing’ was sprayed with 1.0 mg/L EBR solution and stored at 20 ℃ and 2 ℃ respectively to study the effects of EBR on the quality, physiology and biochemistry of pakchoi after postharvest. The results showed that EBR treatment could inhibit the increase of L* and the decrease of hue angle H of pakchoi during storage at 2 ℃ and 20 ℃, and slow down the decrease of total chlorophyll, chlorophyll a and chlorophyll b content. At the end of storage, the total chlorophyll content of pakchoi was 5.57% and 46.25% higher than that of the control at 2 ℃ and 20 ℃ respectively. EBR treatment significantly inhibited the increase of chlorophyll degradation related enzymes (chlorophyllase, Mg-dechelatase and pheophytin pheophorbide hydrolase) of pakchoi during storage at 2 ℃ and 20 ℃, the activities of the three enzymes were more than 28% lower than those of the control at the end of storage. EBR treatment weakened the respiratory intensity of pakchoi, inhibited the decrease of the activities of antioxidant enzymes (superoxide dismutase, catalase and ascorbate peroxidase), decreased the activity of membrane lipid peroxidase (peroxidase and lipoxygenase), and inhibited the increase of superoxide anion, hydrogen peroxide and malondialdehyde content of pakchoi during storage at 2 ℃ and 20 ℃. At the end of storage, the malondialdehyde content of EBR treatment decreased by 8.91% and 19.18%, respectively, compared with the control. The results showed that pakchoi stored at 2 ℃ could maintain better quality and physiological and biochemical indexes than storage at 20 ℃. 1.0 mg/L EBR treatment could effectively delay the yellowing of pakchoi during storage at 2 ℃ and 20 ℃, and reduce the decline of quality and physiology, among them, the effect on the indexes of pakchoi stored at 20 ℃ was more obvious.

ABSTRACT Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of ulcerative colitis (UC). However, preliminary trials showed that only a subset of patients responded to FMT, and the heterogeneity in donor gut microbiota probably played important roles in patients’ responses, implying the significance of matching an appropriate donor to a specified patient. We developed a strategy to build a donor-recipient matching model to guide rational donor selection for UC in FMT. We collected and uniformly reanalyzed 656 fecal 16S rRNA gene sequencing samples (350 from UC patients and 306 from healthy subjects) from 9 studies. Significantly lower α-diversity indexes were observed in UC patients by random effects model. Thirty-four bacterial genera and 34 predicted pathways were identified with significant odds ratios and classification potentials for UC patients. Based on six bacterial indicators, including richness, overall distance, genera, and pathways (beneficial and harmful), the analytic hierarchy process-based donor-recipient matching model was set to rank and select appropriate donors for patients with UC. Finally, the model showed favorable classification powers (>70%) for FMT effectiveness in two previous clinical trials. This study revealed the dysbiosis of fecal bacterial diversity, composition, and predicted pathways of patients with UC by meta-analysis and hereby developed a donor-recipient matching strategy to guide donor selection for UC in FMT. This strategy can also be applied to other diseases associated with gut microbiota. IMPORTANCE Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient’s response to FMT may rely on the capability of the used donor’s microbiota to restore the specific gut disturbances of the patient. However, the biggest issues on the practical level are what should be considered in the selection process and how to set up such a donor-recipient matching model. In this study, we presented a bacterial profile-based donor-recipient matching strategy to guide donor selection for UC in FMT by first meta-analysis of 656 fecal 16S rRNA gene sequencing samples from 9 studies to identify significant indicators and then setting up the model by an analytic hierarchy process. The applicability and accuracy of this model were verified in the data sets from two previous FMT clinical studies. Our data indicate that the donor-recipient matching model built in this study enables researchers to rationally select donors for UC patients in FMT clinical practice, although it needs more samples and prospective trials for validation. The strategy adopted in this study to leverage existing data sets to build donor-recipient matching models for precision FMT is feasible for other diseases associated with gut microbiota.

Objective: Investigate the brain functional networks associated with motor impairment in people with Parkinson’s disease (PD). Background: PD is primarily characterized by motor dysfunction. Resting-state functional connectivity (RsFC) offers a unique opportunity to non-invasively characterize brain function. In this study, we hypothesized that the motor dysfunction observed in people with PD involves atypical connectivity not only in motor but also in higher-level attention networks. Understanding the interaction between motor and non-motor RsFC that are related to the motor signs could provide insights into PD pathophysiology. Methods: We used data from 88 people with PD (mean age: 68.2(SD:10), 55 M/33F) coming from 2 cohorts. Motor severity was assessed in practical OFF-medication state, using MDS‐UPDRS Part‐III motor scores (mean: 49 (SD:10)). RsFC was characterized using an atlas of 384 regions that were grouped into 13 functional networks. Associations between RsFC and motor severity were assessed independently for each RsFC using predictive modeling. Results: The top 5 % models that predicted the MDS-UPDRS-III motor scores with effect size >0.5 were the connectivity between (1) the somatomotor and Subcortical-Basal-ganglia, (2) somatomotor and Visual and (3) CinguloOpercular (CiO) and language/Ventral attention (Lan/VeA) network pairs. Discussion: Our findings suggest that, along with motor networks, visual- and attention-related cortical networks are also associated with the motor symptoms of PD. Non-motor networks may be involved indirectly in motor-coordination. When people with PD have deficits in motor networks, more attention may be needed to carry out formerly automatic motor functions, consistent with compensatory mechanisms in parkinsonian movement disorders.

Many slabbing rock masses have emerged in hydropower slopes and underground engineering, with the construction of basic engineering and resource development projects along the zone of the Belt and Road. The anti-dip slabbing rock mass is prone to toppling and the degree of slabbing controls the development of toppling deformation. There are a few reports on the mechanical mechanism of rock mass toppling deformation after slabbing. Based on the analysis of the genetic conditions of rock mass slabbing, the influence of rock mass after slabbing on toppling deformation was explored by means of the mechanics method. The toppling bending deflection (TBD) and the toppling fracture depth (TFD) were selected as the analysis indexes, and the response regularity of slabbing on toppling rock mass was analyzed with examples. The results show that the width and thickness of the slabbing rock mass become narrower and thinner, the toppling bending deflection (TBD) increases, the toppling fracture depth (TFD) decreases, and the toppling deformation and failure intensify. The TBD is independent of the width of rock mass slabbing under self-weight, and the change of TBD is slow when the slab beam slabbing number (n) of thickness is

Abstract Background Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China. Results The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time. Conclusions DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.

Abstract Polydatin (PD), a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum, is widely used in inhibiting the inflammatory response and oxidative stress. PD has an anti‐inflammatory effect on colitis mice; however, information regulating the mechanism by which maintains the intestinal epithelium barrier is currently scarce. Here, we assessed the anti‐inflammatory and antioxidant of PD in lipopolysaccharide (LPS)‐induced macrophages in vitro, and explored its effects on inhibiting intestinal inflammation and maintaining the intestinal epithelium barrier in dextran sodium sulfate (DSS)‐induced colitis mice. Results showed that PD reduced the level of proinflammatory cytokines and enzymes, including tumor necrosis factor‐α, interleukin‐4 (IL‐4), IL‐6, cyclooxygenase‐2, and inducible nitric oxide synthase, in LPS‐induced macrophages, and improved the expression level of IL‐10. PD maintained the expression of tight junction proteins in medium (LPS‐induced macrophages medium)‐induced MCEC cells. Additionally, PD inhibited the phosphorylation of nuclear factor‐κB (NF‐κB), p65, extracellular signal‐regulated kinase‐1/2, c‐Jun N‐terminal kinase, and p38 signaling pathways in LPS‐induced macrophages and facilitated the phosphorylation of AKT and the nuclear translocation of Nrf2, improving the expression of HO‐1 and NQO1. Furthermore, PD ameliorated the intestinal inflammatory response and improved the dysfunction of the colon epithelium barrier in DSS‐induced colitis mice. Taken together, our results indicated that PD inhibited inflammation and oxidative stress, maintained the intestinal epithelium barrier, and the protective role of PD was associated with the NF‐κB p65, itogen‐activated protein kinases, and AKT/Nrf2/HO‐1/NQO1 signaling pathway.

Meat product is the main food and major source of daily protein intake. Polyphenols are always introduced into many meat products during processing. Some complex interactions may occur between polyphenol and meat protein during the processing, especially thermal processing, which may affect the digestion of protein. In this experiment, chicken protein and tea polyphenol were interacted in simulated systems to explore the effects of the interaction between meat protein and polyphenols on the digestion of meat protein. The mechanism of tea polyphenol inhibiting chicken protein digestion was studied by analyzing the changes of chicken protein in intrinsic fluorescence, surface plasmon resonance (SPR), reactive sulfhydryl group, and solubility in different solvents. The results showed that the chicken protein digestion had a negative correlation with tea polyphenol concentration and interaction temperature, and the meat protein has a higher affinity to EGCG than protease. The mechanism of tea polyphenol inhibiting chicken protein digestion was related to the changing spatial structure of chicken protein and the decreasing activity of proteases. In the simulation system, at low-concentration tea polyphenol, the inhibition of the tea polyphenol on the digestibility of chicken protein might be mainly caused by the changes in chicken protein structure, while at high concentration, the changes in protein structure and the inhibition of proteases activity played a role together. This experiment revealed the effect and the mechanism of polyphenols on the digestion performance of meat protein and provide more references for the further application of polyphenols in meat processing.

Alluvial fan deposits are identified as evidence of regional climatic variations and tectonic events; therefore, it is crucial to establish absolute time series by dating alluvial fan deposits. Limited exposure to light poses a challenge to accurately estimating the buried ages for alluvial deposits with optically stimulated luminescence (OSL). This challenge has been positively developed by controlling the number of grains on each disk to measure and choosing suitable statistical models for the equivalence dose (De) distribution to analyze. In this research, three modern alluvial samples and one modern loess-like sample were collected from the Dashuigou alluvial fan of Helan Mountain, China. The De distributions of these four samples were studied by the application of small aliquots (1-, 3-, and 5-mm aliquots) of quartz OSL with the average dose model, central age model, unlogged minimum age model (MAM), lowest 5%, internal/external consistency criterion minimum age model (IEU), and finite mixture model. It is concluded that an overestimation of De lower than 1 Gy can be obtained using quartz OSL dating of 1-mm aliquots (∼50 grains) with MAM and IEU for the alluvial sediments. The lowest 5% method may underestimate the De values of the 1-mm aliquots for young samples. This research makes the dose dependency of aliquot sizes and age models more definite and opens up the possibility of dating paleoalluvial deposits to establish a chronological framework to decipher the implications of paleoclimates and tectonics.

Across-season biomass assessment is crucial in the cultivar selection process to accurately evaluate the yield performance of lines under different growing conditions. However, it has been difficult to have an accurate, reliable, and repeated fresh biomass (FM) estimation of large populations of plants in the field without destructive harvesting, which incurs significant labor and operation costs. Sensor-based phenotyping platforms have advanced in the data collection of structural and vegetative information of plants, but the developed prediction models are still limited by low correlations at different growth stages and seasons. In this study, our objective was to develop and validate the global prediction models for across-season harvested fresh biomass (FM) yield based on the ground- and air-based sensor data including ground-based LiDAR, ground-based ultrasonic, and air-based multispectral camera to extract LiDAR plant volume (LV), LiDAR point density (LV_Den), height, and Normalized Difference Vegetative Index (NDVI). The study was conducted in a row-plot field trial with 480 rows (3 rows in a plot per cultivar) throughout the whole 2020 growing season up to the reproductive stage. We evaluated the performance of each plant parameter, their relationship, and the best subset prediction models using statistical stepwise selection at the row and plot levels through the seasonal and combined seasonal datasets. The best performing model: FM~LV∗LV_Den∗NDVI had a determination of coefficient R2 of at least 0.9 in vegetative stages and 0.8 in the reproductive stage. Similar results can be achieved in a simpler model with just two LiDAR variables—FM~LV∗LV_Den. In addition, LV and LV_Den showed a robust correlation with FM on their own over seasons and growth stages, while NDVI only performed well in some seasons. The simpler model based on only LiDAR data can be widely applied over season without the need of additional sensor data and may thus make the in-field across-season biomass assessment more feasible and practical for fast and cost-effective development of higher biomass yield cultivars.

Thermal treatment of lipids rich in fatty acids contributes to the formation of lipid oxidation products (LOPs), which have potentially harmful effects on human health. This study included soybean oil (SO), palm oil (PO), olive oil (OO), and lard oil (LO) as the research objects, with an aim to investigate the impact of heating temperature and fatty acid type on the generation of LOPs (α-dicarbonyl compounds, malondialdehyde (MDA), α,β-unsaturated aldehydes, and 16 volatile aldehydes). Results showed that LOPs increased significantly (p < 0.05) with the increase in temperature (100 ~ 200°C). Furthermore, the amount of 2,3-butanedione (159.53 μg/g), MDA (3.15 μg/g), 4-hydroxy-hexenal (3.03 μg/g), 2-butenal (292.18%), 2-pentenal (102.26%), hexanal (898.72%), and 2,4-heptadienal (E, E) (2182.05%) were more at 200°C in SO rich in polyunsaturated fatty acids (PUFAs) than other oils. Results from heat map analysis indicated that the 2, 4-heptadienal, and glyoxal related to the myristic acid of oil. Moreover, the MDA was in close association with PUFAs. Based on the effect of temperature and fatty acid type on the generation of LOPs, this study could serve as a control method to reduce harmful LOPs.

Background and objective Acute cerebral infarction is a form of Trousseau syndrome (TS), but is relatively rare and often overlooked by clinicians. The aim of this study was to investigate the clinical, laboratory and imaging features of acute cerebral infarction in non-small cell lung cancer (NSCLC) patients with TS. Methods Clinical data, laboratory examination and imaging data of 25 NSCLC patients with TS presented with acute cerebral infarction were collected retrospectively for analysis. Results Of the 25 patients, 18 males and 7 females, aged 39-78 years old, including 22 cases of adenocarcinoma, 2 cases of squamous cell carcinoma, and 1 case of large cell carcinoma; all patients had clinical symptoms and signs of acute cerebral infarction; plasma D-dimer was significantly increased, and prothrombin time and activated partial thromboplastin time were shortened to varying degrees; all patients showed acute multiple cerebral infarction foci involving multiple intracranial arterial blood supply areas on plain head magnetic resonance imaging (MRI) [diffusion-weighted imaging (DWI) sequence], the blood supply vessel lumen corresponding to the infarction foci did not show moderate to severe stenosis on the head MR angiography (MRA). Conclusion NSCLC with multiple acute cerebral infarctions is a rare manifestation of TS, which is characterized by multiple acute cerebral infarctions involving multiple arterial blood supply areas with significant hypercoagulability. Improving the early understanding of this disease can provide some help for clinical diagnosis and treatment.

Schizophrenia (SCZ) is an idiopathic psychiatric disorder with a heritable component and a substantial public health impact. Although abnormalities in total brain volumetric measures (TBVMs) have been found in patients with SCZ, it is still unknown whether these abnormalities have a causal effect on the risk of SCZ. Here, we performed a Mendelian randomization (MR) study to investigate the possible causal associations between each TBVM and SCZ risk. Specifically, genome-wide association study (GWAS) summary statistics of total gray matter volume, total white matter volume, total cerebrospinal fluid volume, and total brain volume were obtained from the United Kingdom Biobank database (33,224 individuals), and SCZ GWAS summary statistics were provided by the Psychiatric Genomics Consortium (150,064 individuals). The main MR analysis was conducted using the inverse variance weighted method, and other MR methods, including MR-Egger, weighted median, simple mode, and weighted mode methods, were performed to assess the robustness of our findings. For pleiotropy analysis, we employed three approaches: MR-Egger intercept, MR-PRESSO, and heterogeneity tests. No TBVM was causally associated with SCZ risk according to the MR results, and no significant pleiotropy or heterogeneity was found for instrumental variables. Taken together, this study suggested that alterations in TBVMs were not causally associated with the risk of SCZ.

Abstract Background Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated. Results The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation increased the proportions of G2/M phase and Caveolin-1 content in 4T1 breast cancer cells, contributing to an endocytic enhancement of PINPs@PM. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. Conclusion The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.

Hematopoietic system is one of the main target organs of irradiation injury. Exposure to radiation can cause acute myelosuppression and long-term hematopoietic injury due to the direct and indirect damage of hematopoietic stem cells (HSCs) that can self-renew and differentiate into all types of blood cells. So far, many factors in the modulation of HSC biology at steady status have been revealed, while how to orchestrate HSCs in the context of radiation has not been well established. Recently, an increasing number of studies focus on the underlying mechanisms involved in regulating HSC fate after radiation exposure by affecting DNA damage response (DDR), including DNA-damage repair, cell-cycle arrest, apoptosis and senescence, or bone marrow (BM) microenvironment. In this review, we summarize recent findings on intrinsic and extrinsic factors in the regulation of HSC fate after radiation exposure, which may further deepen our understanding of the radioprotection of HSCs.

Studies have shown the indicative role of handgrip strength in health. However, there is limited evidence revealing its potential effect on death events among middle-aged and older adults in China. We aimed to prospectively evaluate if lower handgrip strength is associated with the event of death. Among 17,167 middle-aged and older adults between age 45 to 96, handgrip strength was collected by a handheld dynamometer in a Chinese longitudinal study of aging trend (CHARLS) 2011–2018. Using Cox proportional hazard models with exposures, we assessed the association between handgrip strength and death events. Elevated handgrip strength values were independently associated with the decreased death risk. These results illustrate that lower handgrip strength is an independent indicator of death risks among middle-aged and older Chinese, which highlights the significance of related intercessions. The median values of five levels of handgrip strength in the entire cohort were 16.5,23,28,33,42kg at baseline. A linear association existed between the handgrip strength values and the risk of all-cause death within 34.2kg. Handgrip strength can serve as an independent indicator for death risks.

Autism spectrum disorders (ASDs) are a group of heterogeneous neurodevelopmental disorders that are highly heritable and are associated with impaired dynamic functional connectivity (DFC). However, the molecular mechanisms behind DFC alterations remain largely unknown. Eighty-eight patients with ASDs and 87 demographically matched typical controls (TCs) from the Autism Brain Imaging Data Exchange II database were included in this study. A seed-based sliding window approach was then performed to investigate the DFC changes in each of the 29 seeds in 10 classic resting-state functional networks and the whole brain. Subsequently, the relationships between DFC alterations in patients with ASDs and their symptom severity were assessed. Finally, transcription-neuroimaging association analyses were conducted to explore the molecular mechanisms of DFC disruptions in patients with ASDs. Compared with TCs, patients with ASDs showed significantly increased DFC between the right dorsolateral prefrontal cortex (DLPFC) and left fusiform/lingual gyrus, between the DLPFC and the superior temporal gyrus, between the right frontal eye field (FEF) and left middle frontal gyrus, between the FEF and the right angular gyrus, and between the left intraparietal sulcus and the right middle temporal gyrus. Moreover, significant relationships between DFC alterations and symptom severity were observed. Furthermore, the genes associated with DFC changes in ASDs were identified by performing gene-wise across-sample spatial correlation analysis between gene expression extracted from six donors’ brain of the Allen Human Brain Atlas and case-control DFC difference. In enrichment analysis, these genes were enriched for processes associated with synaptic signaling and voltage-gated ion channels and calcium pathways; also, these genes were highly expressed in autistic disorder, chronic alcoholic intoxication and several disorders related to depression. These results not only demonstrated higher DFC in patients with ASDs but also provided novel insight into the molecular mechanisms underlying these alterations.

ABSTRACT This study investigated the effect of Ca ascorbate on the biocontrol efficacy of Pichia kudriavzevii and the possible mechanisms. The results indicated that the biocontrol activity of P. kudriavzevii was significantly enhanced by 0.15 g L−1 of Ca ascorbate, with higher growth rates of yeast cells in vitro and in vivo. The antioxidant enzyme activity in P. kudriavzevii, including catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), were improved by Ca ascorbate and reached the maximum at 96 h, 96 h, and 72 h, respectively. The expression of the antioxidant enzyme-related genes CAT1 (8.55-fold) and SOD2 (7.26-fold) peaked at 96 h, while PRXIID (2.8-fold) peaked at 48 h, which were similar to the trends of enzyme activities. Compared with the control, 0.15 g L−1 of Ca ascorbate and CaCl2 increased the activity of succinate dehydrogenase in P. kudriavzevii, thereby enhancing the utilization of nutrients by yeast cells, and calcium ascorbate had the strongest effect. The expressions of HXT5, ADH6, PET100p, and Pga62 were significantly higher in the Ca ascorbate treatment than the other groups, and the CaCl2 treatment was also significantly higher than the control. These results indicated that Ca ascorbate can effectively improve the energy metabolism and cell wall synthesis and slow down the senescence of yeast cells. In general, Ca ascorbate can improve the environmental adaptability of P. kudriavzevii and thus improve the biocontrol effect, which is associated with inducing antioxidant enzymes in yeast cells and enhancing energy metabolism and nutrient utilization efficiency to increase nutrient competition with pathogens. IMPORTANCE Antagonistic yeast is a promising way to control postharvest fruit decay because of its safety and broad-spectrum resistance. However, the biocontrol efficacy of yeast is limited by environmental stress, such as oxidative stress. Therefore, the improvement of antioxidant capacity has become a research hot spot in improving the biocontrol efficacy of yeast. The induction of Ca ascorbate on the antioxidant capacity and physiological activity of yeast was studied. The results showed better induction of antioxidant enzyme and physiological activity in yeast by Ca ascorbate for better antioxidant capacity, and Ca2+ also played a synergistic promotion effect, which improved the biocontrol efficacy. These results provide an approach for the research and application of improving the environmental adaptability and biocontrol effectiveness of yeast.

An increase in the number of infections caused by resistant bacteria worldwide necessitates the development of alternatives to antibiotics. Human defensin (HD) 5 is an innate immune peptide with broad-spectrum antibacterial activity, but its complicated structure makes its preparation difficult. Herein, we truncated the HD5 structure by extracting the highly conserved γ-core motif. A structure-activity study showed that this motif was ineffective in killing bacteria in the absence of specific spatial conformation. Notably, after the introduction of two intramolecular disulfide bonds, its antibacterial activity was markedly improved. Glu and Ser residues were then replaced with Arg to create the derivative RC18, which exhibited stronger potency than HD5, particularly against methicillin-resistant S. aureus (MRSA). Mechanistically, RC18 bound to lipid A and lipoteichoic acid at higher affinities than HD5. Furthermore, RC18 was more efficient than HD5 in penetrating the bacterial membranes. Molecular dynamics simulation revealed that five Arg residues, Arg1, Arg7, Arg9, Arg15, and Arg18, mediated most of the polar interactions of RC18 with the phospholipid head groups during membrane penetration. In vivo experiments indicated that RC18 decreased MRSA colonization and dramatically improved the survival of infected mice, thus demonstrating that RC18 is a promising drug candidate to treat MRSA infections.

Additives and antibiotic abuse during food production and processing are among the key factors affecting food safety. The efficient and rapid detection of hazardous substances in food is of crucial relevance to ensure food safety. In this study, a water-soluble quantum dot with glutathione as a ligand was synthesized as a fluorescent probe by hydrothermal method to achieve the detection and analysis of H2O2. The detection limits were 0.61 μM in water and 68 μM in milk. Meanwhile, it was used as a fluorescent donor probe and manganese dioxide nanosheets were used as a fluorescent acceptor probe in combination with an immunoassay platform to achieve the rapid detection and analysis of enrofloxacin (ENR) in a variety of foods with detection limits of 0.05–0.25 ng/mL in foods. The proposed systems provided new ideas for the construction of fluorescence sensors with high sensitivity.

The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

Abstract Background The roles played by cholesterol in cancer development and progression represent a popular field in the cancer community. High cholesterol levels are positively correlated with the risk of various types of cancer. APOA-I binding protein (AIBP) promotes the reverse cholesterol transport pathway (RCT) in cooperation with Apolipoprotein A-I (APOA-I) or high-density lipoprotein cholesterol. However, the combined effect of AIBP and APOA-I on intestinal tumor cells is still unclear. Methods Immunohistochemistry, western blot and qPCR were performed to investigate the expression of AIBP and APOA-I in intestinal tumor tissues and cell lines. The anti-tumor activity of AIBP and APOA-I was evaluated by overexpression or recombinant protein treatment. Cholesterol efflux and localization of lipid raft-related proteins were analyzed by a cholesterol efflux assay and lipid raft fraction assay, respectively. Results Here, we reported that both AIBP expression and APOA-I expression were associated with the degree of malignancy in intestinal tumors. Co-overexpression of AIBP and APOA-I more potently inhibited colon cancer cell-mediated tumor growth and metastasis compared to overexpression of each protein individually. Additionally, the recombinant fusion proteins of AIBP and APOA-I exhibited a significant therapeutic effect on tumor growth in Apcmin/+ mice as an inherited intestinal tumor model. The synergistic effect of the two proteins inhibited colon cancer cell migration, invasion and tumor-induced angiogenesis by promoting cholesterol efflux, reducing the membrane raft content, and eventually disrupting the proper localization of migration- and invasion-related proteins on the membrane raft. Moreover, cyclosporine A, a cholesterol efflux inhibitor, rescued the inhibitory effect induced by the combination of AIBP and APOA-I. Conclusions These results indicate that the combination of APOA-I and AIBP has an obvious anticancer effect on colorectal cancer by promoting cholesterol efflux.