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Abstract Background Mitochondrial calcium uniporter (MCU) plays pleiotropic roles in cellular physiology and pathology that contributes to a variety of diseases, but the role and potential mechanism of MCU in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) remain poorly understood. Methods and results Here, hepatic knockdown of MCU in C57BL/6J mice was achieved by tail vein injection of AAV8-mediated the CRISPR/Cas9. Mice were fed a Choline-deficient, L-amino acid-defined high-fat diet (CDAHFD) for 8 weeks to induce MASH and fibrosis. We find that expression of MCU enhanced in MASH livers of humans and mice. MCU knockdown robustly limits lipid droplet accumulation, steatosis, inflammation, and hepatocyte apoptotic death during MASH development both in vivo in mice and in vitro in cellular models. MCU-deficient mice strikingly mitigate MASH-related fibrosis. Moreover, the protective effects of MCU knockdown against MASH progression are accompanied by a reduced level of mitochondrial calcium, limiting hepatic oxidative stress, and attenuating mitochondrial dysfunction. Mechanically, RNA sequencing analysis and protein immunoblotting indicate that knockdown MCU inhibited the Hippo/YAP pathway activation and restored the AMP-activated protein kinase (AMPK) activity during MASH development both in vitro and in vivo. Conclusions MCU is up-regulated in MASH livers in humans and mice; and hepatic MCU knockdown protects against diet-induced MASH and fibrosis in mice. Thus, targeting MCU may represent a novel therapeutic strategy for MASH and fibrosis. Graphical Abstract

Abstract Magnetic skyrmions are potential candidates for high-density storage and logic devices because of their inherent topological stability and nanoscale size. Two-dimensional (2D) Janus transition metal chalcogenides (TMDs) are widely used to induce skyrmions due to the breaking of inversion symmetry. However, the experimental synthesis of Janus TMDs is rare, which indicates that the Janus configuration might not be the most stable MXY structure. Here, through machine-learning-assisted high-throughput first-principles calculations, we demonstrate that not all MXY compounds can be stabilized in Janus layered structure and a large proportion prefer to form other configurations with lower energy than the Janus configuration. Interestingly, these new configurations exhibit a strong Dzyaloshinskii–Moriya interaction (DMI), which can generate and stabilize skyrmions even under a strong magnetic field. This work provides not only an efficient method for obtaining ferromagnetic materials with strong DMI but also a theoretical guidance for the synthesis of TMDs via experiments.

Abstract The mechanism regulating cellular senescence of postmitotic muscle cells is still unknown. cGAS-STING innate immune signaling was found to mediate cellular senescence in various types of cells, including postmitotic neuron cells, which however has not been explored in postmitotic muscle cells. Here by studying the myofibers from Zmpste24−/− progeria aged mice [an established mice model for Hutchinson-Gilford progeria syndrome (HGPS)], we observed senescence-associated phenotypes in Zmpste24−/− myofibers, which is coupled with increased oxidative damage to mitochondrial DNA (mtDNA) and secretion of senescence-associated secretory phenotype (SASP) factors. Also, Zmpste24−/− myofibers feature increased release of mtDNA from damaged mitochondria, mitophagy dysfunction, and activation of cGAS-STING. Meanwhile, increased mtDNA release in Zmpste24−/− myofibers appeared to be related with increased VDAC1 oligomerization. Further, the inhibition of VDAC1 oligomerization in Zmpste24−/− myofibers with VBIT4 reduced mtDNA release, cGAS-STING activation, and the expression of SASP factors. Our results reveal a novel mechanism of innate immune activation-associated cellular senescence in postmitotic muscle cells in aged muscle, which may help identify novel sets of diagnostic markers and therapeutic targets for progeria aging and aging-associated muscle diseases.

First principles calculations in the framework of density functional theory (DFT) are performed to exploit replaceable perovskite oxides against the instability of traditional cubic SrTiO3 grown on silicon substrate. In this work, we consider more thermostable CaTiO3 and CaZrO3 with cubic and ground-state phase as the candidates to perform the gate dielectric. After the calibration of total energy and lattice transformation of ground-state perovskites to match with Si substrate, three categories of 2 × 2 heterostructures have been constructed and investigated through the geometrical change, atom displacement around interfacial layer, total energy and electronic structure change, under the variations on perovskite species, the concentration of interfacial layer and the thickness of perovskite film. And the results demonstrate that the category with half a monolayer of Ca/Sr atoms in interfacial layer and two unit-cell perovskite thicknesses show the type-I band alignment through their band alignment. Among this category, the heterostructure with Pnma CaZrO3 shows semiconductivity and excellent electrical property with larger band offset for the candidate of gate dielectric. This work provides a creative perspective to expand the perovskite diversity for the booming growth of integrated circuit technology.

Abstract Background and Aims Hepatocellular carcinoma (HCC) is a malignant tumour associated with high morbidity and mortality rates worldwide. Recently, TRPM8 was reported to play an important role in tumour progression. However, the precise role of TRPM8 in HCC remains unclear. In this study, we explored the expression levels, molecular functions and underlying mechanisms of TRPM8 in HCC. Methods Tissue samples were used to analyse the expression of TRPM8 to assess its diagnostic value for prognosis. Cell Counting Kit‐8, EdU and colony formation assays were performed to evaluate the effects of TRPM8 on cell proliferation, whereas the Transwell assay was used to assess cell migration and invasion. The role of TRPM8 in vivo was evaluated using a mouse subcutaneous xenograft tumour model. We performed PPI network analyses to understand the possible mechanisms of TRPM8 action. Results TRPM8 expression was decreased in HCC tissues and was correlated with histological grade and poor patient prognosis. Functionally, TRPM8 repressed the proliferation and metastasis of HCC cells both in vitro and in vivo by modulating the RTP3/STAT3 signalling pathway. Conclusion Our findings underscore the critical role of the TRPM8‐RTP3‐STAT3 axis in maintaining the malignant progression of HCC. Moreover, our study demonstrates that AD80 is involved in anti‐tumour processes by upregulating the expression of TRPM8.

The fermentation process was carried out with varied input variables, and all the models showed significant p-values for interaction of variance (

Abstract In the investigation of active ingredients from natural products, current technologies relying on drug–target affinity recognition analysis face significant challenges. This is primarily due to their limited specificity and inability to provide downstream pharmacodynamic information, such as agonistic or antagonistic activity. In this study, a two-point method was developed by immobilizing M3 acetylcholine receptor (M3R) through the combination of the conformation-specific peptide BJ-PRO-13a and the HaloTag trap system. We systematically assessed the specificity of the immobilized M3R using known M3R antagonists (pirenzepine and atropine) and agonists (cevimeline and pilocarpine). By frontal analysis and nonlinear chromatography, the performance of immobilized M3R was evaluated in terms of binding kinetics and thermodynamics of four drugs to the immobilized M3R. Additionally, we successfully identified two M3R antagonists within an extract from Daturae Flos (DF), specifically hyoscyamine and scopolamine. Our findings demonstrate that this immobilization method effectively captures receptor-ligand binding interactions and can discern receptor agonists from antagonists. This innovation enhances the efficiency of receptor chromatography to determine binding-affinity in the development of new drugs, offering promise for the screening and characterization of active compounds, particularly within complex natural products.

Abstract Detrital composition of sandstone is the most important data for siliciclastic studies including sandstone classification, provenance analysis, oil and gas exploration. A large amount of detrital composition data has accumulated over the past decades, however, they are scattered in publications without unified standards. Here we constructed a global dataset of detrital components of sandstones from 646 peer‐reviewed publications using Gazzi‐Dickinson method. A total of 19,861 samples from Precambrian to Quaternary are involved in this dataset. For each sample, we present details on reference information, geographic information, geological background, depositional age and the original data. It is a high‐quality dataset for the information on each sandstone sample from different studies which was standardized. The dataset can be used widely, such as for stratigraphic comparison, provenance analysis, exploring the general laws of the source‐to‐sink process and geological engineering.

The advent of online education has become indispensable for nursing students seeking to acquire knowledge. However, the efficacy of online education often falls short of initial expectations. Deep learning (DL) can assist learners tackle complex problems and make innovative decisions. Despite its potential, there has been limited exploration into the underlying mechanisms of DL among nursing students, both domestically and globally. This study examined the potential moderating effect of psychological capital (PC) on the association between academic self-concept (AS-c) and DL among nursing students from China enrolled in online courses. Conducted from October 2022 to January 2023, the survey involved 635 nursing students from four public universities in eastern China, utilizing convenience sampling. Data was collected using the AS-c scale, psychological capital scale, and DL scale in online courses. Correlation analyses, univariate analyses, multiple linear regression analyses, and the PROCESS macro were employed for a comprehensive examination. The results revealed a strong positive relationship between nursing students' DL and both their AS-c (r = 0.766, P

Background: Acupuncture stands out as a prominent complementary and alternative medicine therapy employed for functional dyspepsia (FD). We conducted a Bayesian meta-analysis to ascertain both the relative effectiveness and safety of various acupuncture methods in the treatment of functional dyspepsia. Methods: We systematically searched eight electronic databases, spanning from their inception to April 2023. The eligibility criteria included randomized controlled trials investigating acupuncture treatments for FD. Study appraisal was conducted using the Cochrane risk of bias tool. Pairwise and network meta-analyses were conducted using RevMan 5.3 and ADDIS V.1.16.6 software. Bayesian network meta-analysis was performed to compare and rank the efficacy of different acupuncture therapies for FD symptoms. Results: This study found that combining different acupuncture methods or using acupuncture in conjunction with Western medicine is more effective in improving symptoms of functional dyspepsia compared to using Western medicine alone. According to the comprehensive analysis results, notably, the combination of Western medicine and acupuncture exhibited superior efficacy in alleviating early satiation and postprandial fullness symptoms. For ameliorating epigastric pain, acupuncture combined with moxibustion proved to be the most effective treatment, while moxibustion emerged as the optimal choice for addressing burning sensations. Warming needle was identified as the preferred method for promoting motilin levels. Conclusion: The findings of this study demonstrate that acupuncture, both independently and in conjunction with other modalities, emerged as a secure and effective treatment option for patients with functional dyspepsia.

LncRNAs are vital regulators for lung squamous cell carcinoma (LUSC). However, the detailed role that LINC01133 plays in LUSC is unclear. This work sought to explore the potential function of LINC01133.Levels of LINC01133, miR-30d-5p, and MARCKS were separately tested in both tissues and cells using qRT-PCR. Proliferation was assessed through MTT experiment and apoptosis was detected upon flow cytometry. Transwell experiments were implemented to evaluate migratory and invasive abilities. The interaction between two genes was affirmed through luciferase reporter assay and RNA pull-down experiment. Western blotting measured the protein level of MARCKS. Animal models were established and tissues were taken for IHC analysis of MARCKS and Ki67.LINC01133 was elevated in LUSC and its downregulation could suppress proliferation, migration and invasion but induced apoptosis. LINC01133 interacted with and regulated the binding of miR-30d-5p to MARCKS. LINC01133/miR-30d-5p axis mediated proliferation, apoptosis, migration and invasion in LUSC cells, as well as modulated tumor growth in animal models. LINC01133 interacted with miR-30d-5p to modulate MARCKS expression, contributes to promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. These findings could provide possible therapeutic targets in view of LUSC treatment in the future.

The Chinese furniture market has a high demand for wood floors. Manual defect detection in wood floors is inefficient and lacks stability in accuracy. It is necessary to conduct research on automatic defect detection in wood floors. To improve the accuracy of detecting small defects in wood floors, this paper proposed a new network based on YOLOv7. The new network is called the cascade center of gravity YOLOv7 (CCG-YOLOv7). This paper designed cascade efficient layer aggregation networks (C-ELAN), streamlined the CBS, replaced the ELAN with the C-ELAN, introduced the rapid supervised attention module to connect the backbone and head layers, and simplified the head layer of the YOLOv7 network. These methods improved the detection accuracy and speed for detecting small defects on wood floor surfaces. The improved network can effectively detect small defects on the wooden board surfaces, including knots, scratches, and mildew. Compared to the original YOLOv7, CCG-YOLOv7 improves precision, recall, and mean average precision by 2.1%, 1.6%, and 1.2%, respectively.

The wall friction correlations of oscillatory natural circulation loops are highly loop-specific, making it difficult to perform 1-D system simulations before obtaining specific experimental data. To better predict the friction characteristics, the nonlinear dynamics of a toroidal single-phase natural circulation loop were numerically investigated, and the transition effect was considered. The k-kL-ω transitional turbulence and k-ω SST turbulence models were used to compute the flow characteristics of the loop under different heating powers varying from 0.48 to 1.0 W/cm2, and the results of both models were compared with previous experiments. The mass flow rates and friction factors predicted by the k-kL-ω model showed a better agreement with the experimental data than the results of the k-ω SST model. The oscillation frequencies calculated using both models agreed well with the experimental data. The k-kL-ω transitional turbulence model provided better friction-factor predictions in oscillatory natural circulation loops because it can reproduce the temporal and spatial variation of the wall shear stress more accurately by capturing the movement of laminar, transition turbulent zones inside unstable natural circulation loops. This study shows that transition effects are a possible explanation for the highly loop-specific friction correlations observed in various oscillatory natural circulation loops.

AimsWhite matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia.Main methodsWe employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups.Key findingsOur findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G *** GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7.SignificanceCaffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.

The cultural practices encompassing etiquette and customs, along with their associated spaces, play a crucial role in preserving traditional Chinese culture. However, these cultural elements are currently under significant and irreversible threats, necessitating the strengthening of relevant theories and case studies for their safeguarding. In light of this, following field investigations conducted in 47 traditional villages in Yuxian County, we selected Bubeibu Village as our case study to analyze its etiquette and custom cultural activities, spatial characteristics, and construction wisdom. We collected first-hand information through on-site investigations and conducted a comprehensive quantitative analysis from four perspectives (the overall structure of space, point space, linear space, and areal space) on three types of cultural activity spaces (festivals, ceremonies, and operas) within Bubeibu Village. In conclusion, we summarize the spatial characteristics of etiquette and custom cultural activities and highlight their construction wisdom. Our findings serve as foundational data for establishing digital databases related to Bubeibu Village, providing support for village planning and dynamic supervision. Insights into spatial characteristics and construction wisdom can also be valuable for reinvigorating Bubeibu Village and revitalizing local culture, contributing to the preservation of rural heritage worldwide.

● Gasification of cow dung was evaluated using Aspen Plus software.● Optimum reaction conditions were utilized to maximize hydrogen production.● Steam gasification can effectively increase hydrogen production.● Optimum hydrogen production was achieved at 800 °C and steam/biomass of 1.5 and 0.1 MPa. In this study, a biomass gasification model was developed and simulated based on Gibbs free energy minimization by using software Aspen Plus. Two reactors, RYIELD and RGIBBS, were moslty used. The biomass feedstock used was cow dung. The model was validated. The composition, H2/CO ratio and low heating value (LHV) of the resulting synthetic gas (also known as syngas) was estimated by changing the operating parameters of gasification temperatures, steam and biomass ratios and pressures. Simulation results showed that increased gasification temperature helped to elevate H2 and CO content and H2 peaked at 900 °C. When steam increased as the gasification agent, H2 production increased. However, the steam/biomass (S/B) ratio negatively affected CO and CH4, resulting in lower LHV. The optimal S/B ratio was 1.5. An increase in pressure lead to a decrease in H2 and CO content, so the optimal pressure for gasification was 0.1 MPa.

The use of polymer-coated urea (PCU) can improve nitrogen use efficiency (NUE), compared to the application of rapid-release urea (RU). However, the effect of PCU-based nitrogen management on grain yield and the NUE of rice and its underlying mechanism remain unclear. A japonica rice cultivar Jinxiangyu 1 was grown in the field with four treatments including N omission (0N), split application of RU (Control), one-time application of 100% PCU (T1), and one-time application of 70% PCU + 30% RU (T2). Results showed that, compared to the control, the grain yield was significantly increased in the T2 treatment, while it was comparable in the T1 treatment. This was mainly due to increased total spikelets in the T2 treatment. Root oxidation activity (ROA) and root zeatin (Z) + zeatin riboside (ZR) content during booting were the distinct advantages of the T2 treatment, compared to either the control or T1 treatment, exhibiting significant or highly significant correlations with leaf photosynthesis. This process contributed significantly to total spikelets and total N uptake. Additionally, the T2 treatment absorbed more N than the control without reducing the internal N use efficiency (IEN), primarily due to its unchanged harvest index (HI) driven by comparable non-structural carbohydrate remobilization. In conclusion, combining PCU with RU can enhance the coordination of root and shoot traits during booting while maintaining a competitive HI at maturity, thereby significantly improving grain yield and achieving a balance in N uptake and utilization.

Enhanced plasticity is obtained in a structurally rejuvenated Zr-based bulk metallic glass (BMG) that has been treated via cryogenic thermal cycling (CTC) for one hundred cycles. More than one primary shear band is activated due to the structural rejuvenation, which can inhibit the jerky and system-spanning propagation of shear bands to generate sluggish shear-dynamics. These are mapped to the slip statistics, including the decreased critical avalanche size, the much longer avalanche duration of large (system-spanning) slips, and a great number of small avalanches. Moreover, the universal scaling of slip avalanches for three applied stress ranges is addressed to predict the applied stress at which the failure avalanche appears most. These results indicate that slip statistics can be the fingerprints to show how much the BMG is rejuvenated, and the failure avalanche provides a good opportunity to intervene in the failure of BMGs in advance.

Abstract Background Cook Stage extubation is a tool developed by Cook Medical for patients with difficult airways. Multiple clinical studies demonstrated the effectiveness and safety of Cook Stage extubation Set (CSES). Currently, no systematic review evidence has been published in this field. Therefore, this study aimed to review the clinical success rate, safety, and tolerability of CSES in patients with difficult airways. Method The inclusion criteria were based on the population, intervention, comparator, outcomes, and study designs. An electronic search was conducted, and the following databases were used: PubMed, EMBASE, Cochrane Library, and Web of Science. Search keywords included difficult airway and CSES. The primary outcome was the CSES clinical success rate.The Joanna Briggs Institute Critical Appraisal tools for Case Series were used to assess the risk of bias in the included studies. R studio, version 4.2.2. was used to perform the statistical analysis. The Cochrane Q and I 2 statistics were used to test the heterogeneity among all studies. Details of the included case reports were summarized in the systematic review part. Results Five studies were eligible for meta-analysis, and 7 case reports were included for systematic review. The pooled overall CSES clinical success rate was 93% (95% CI: 85%, 97%). The CSES intolerable and complication incidence rates were 9% (95% CI: 5%, 18%) and 5% (95% CI: 2%, 12%), respectively. CSES clinical success rate was influenced by the study center and study design. The success rate of CSES was higher in multicenter and prospective design studies. Seven case reports have documented the successful operation of CSES intubation in obese, tall, oncologist, and pediatric patients. Discussion This meta-analysis suggested that CSES have achieved a high clinical success rate in adult and pediatric patients with different physical conditions and types of surgery. The results of all original studies and meta-analysis confirmed a remarkably high tolerance rate and low overall complication rate. However, regardless of the tools chosen, a personalized, safe intubation strategy and a highly qualified anesthesiologist should be considered as the fundamental guarantee of a high clinical success rate. Future studies should also focus on the success rate of reintubation using CSES in patients with airway difficulties.

BackgroundFibromyalgia has imposed substantial burdens on patients’ health and well-being, yet effective therapeutic options for this condition remain limited. Recently, vagus nerve stimulation (VNS) has emerged as a promising therapy for fibromyalgia. Nonetheless, despite the increasing number of randomized clinical trials (RCTs), current evidence remains inconclusive. Therefore, this protocol of a systematic review and meta-analysis aims to synthesize the existing evidence to clarify the efficacy and acceptability of VNS for treating fibromyalgia.MethodsA comprehensive search for eligible RCTs will be conducted across nine bibliographic databases, namely PubMed, Cochrane Library, Embase, AMED, PsycINFO, PEDro, Chinese BioMedical Literature Database, Chinese National Knowledge Infrastructure, and Wangfang database. Data obtained from the included studies will be synthesized quantitively using RevMan 5.4.1 for meta-analyses. The methodological soundness of included RCTs will be assessed via the Cochrane’s updated risk of bias tool (version 2.0). Additionally, sensitivity analyses, publication bias assessment, and subgroup analyses will be conducted as appropriate. Finally, we will utilize the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to evaluate the certainty for the body of evidence.ConclusionThe findings of our study are anticipated to ascertain the efficacy and acceptability of VNS as a promising treatment option for fibromyalgia. This will not only fill current research gap but also identify potential areas for future research. The findings will provide essential guidance for evidence-based treatment decisions for fibromyalgia, benefiting both patients and clinicians.

IntroductionEnhancer of zeste homolog 2 (Ezh2) is responsible for trimethylation of histone 3 at lysine 27 (H3K27me3), resulting in repression of gene expression. Here, we explore the role of Ezh2 in forebrain GABAergic interneuron development.MethodsWe removed Ezh2 in the MGE by generating Nkx2-1Cre;Ezh2 conditional knockout mice. We then characterized changes in MGE-derived interneuron fate and electrophysiological properties in juvenile mice, as well as alterations in gene expression, chromatin accessibility and histone modifications in the MGE.ResultsLoss of Ezh2 increases somatostatin-expressing (SST+) and decreases parvalbumin-expressing (PV+) interneurons in the forebrain. We observe fewer MGE-derived interneurons in the first postnatal week, indicating reduced interneuron production. Intrinsic electrophysiological properties in SST+ and PV+ interneurons are normal, but PV+ interneurons display increased axonal complexity in Ezh2 mutant mice. Single nuclei multiome analysis revealed differential gene expression patterns in the embryonic MGE that are predictive of these cell fate changes. Lastly, CUT&Tag analysis revealed that some genomic loci are particularly resistant or susceptible to shifts in H3K27me3 levels in the absence of Ezh2, indicating differential selectivity to epigenetic perturbation.DiscussionThus, loss of Ezh2 in the MGE alters interneuron fate, morphology, and gene expression and regulation. These findings have important implications for both normal development and potentially in disease etiologies.

Soil sampling and in situ measurements were conducted at 24 locations at three time points from May 2015 to April 2016. The statistical analysis showed that the variabilities of soil water content and soil penetration were moderate, while particle size and soil saturated hydraulic conductivity varied considerably. Rainfall before measurements contributed positively to the mean soil water content and negatively to particle size. This was mainly due to the soil aggregates and large soil particles being broken into smaller particles from rain splash. The detached small-sized soil particles could coalesce into larger-sized ones and even soil aggregates. Stressors in zones differ, resulting in variations between soil physical quality indices. The point-to-point comparisons indicated that the mean measured soil water content and soil saturated hydraulic conductivity were similar, if the measurements for these two indices were conducted under similar weather conditions during the same period between years. The investigation on the relationships among soil physical quality indices showed a negative relationship between the measured soil water content and soil saturated hydraulic conductivity. A positive correlation was also found between soil particle size and soil saturated hydraulic conductivity. Lower soil strength resulted in higher soil saturated hydraulic conductivity.

BackgroundDiabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus, which is the most common neuropathy worldwide. Owing to the inadequacies of existing treatment methods, managing DPN remains a significant challenge. Studies suggest that electroacupuncture (EA) could potentially serve as a beneficial alternative treatment for this condition. Nevertheless, there is still inadequate proof of its therapeutic effectiveness and safety. As a result, the goal of this protocol is to methodically compile the data pertaining to the effectiveness and security of EA in the management of DPN.MethodsTo find appropriate randomized controlled trials (RCTs), nine reliable databases in the English and Chinese languages will be examined. RevMan5.3 will be used to combine the retrieved data and perform meta-analyses. The methodological quality of the included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. The Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be utilized to evaluate the degree of strength and certainty of the evidence. We will also perform publication bias, sensitivity and subgroup analyses.DiscussionThis protocol describes the intended scope and approach for a forthcoming systematic review and meta-analysis that will inform therapeutic decision-making by offering current information on the efficacy and safety of EA in the treatment of DPN. The results of the study will help standardize strategies for EA in the treatment of DPN.

Ovarian mature teratoma represents a benign ovarian tumor, while ovarian yolk sac tumor (YST, endodermal sinus tumor) is a rare malignant tumor predominantly affecting young women, often associated with a grim prognosis post-metastasis. Both ovarian mature teratoma and ovarian YST are germ cell tumors. There are few studies on the correlation between ovarian YST and mature teratoma. Recurrence or malignant transformation may occur following the surgical intervention for ovarian mature teratoma. However, the occurrence of YST subsequent to such procedures is notably rare. In this investigation, we reported a case involving a 24-year-old unmarried woman with both mature ovarian teratoma and YST within a brief 1-year interval. Regular reexamination protocols facilitated the early-stage detection of YST. The patient underwent surgical treatment, chemotherapy, and measures to preserve ovarian function, resulting in a favorable prognosis. Our primary purpose is to distill clinical insights from the diagnostic and therapeutic journey of this patient. Our purpose is to enhance medical professionals’ awareness that YST may be secondary to mature teratoma. Additionally, we underscore the critical importance of routine postoperative surveillance for ovarian mature teratoma, emphasizing its pivotal role in early malignant tumor detection—a factor paramount to the prognosis of patients.

There is limited understanding of nanoparticle potential ecotoxicity, particularly regarding the influence of environmental factors that can be transferred through the food chain. Here, we assessed the transfer behavior and the ecotoxicity of commercially manufactured graphene oxide nano-materials (GO,

Background: Hypertension has become a part of the lives of many people worldwide. With the development, an increasing number of people have begun to control their hypertension through products of medicine food homology, such as Buyang Huanwu Decoction (BYHWD). However, there has been no objective review of the regulation of hypertension by BYHWD. Methods: As of 9 October 2023, this review made a detailed search of nine databases to look for random controlled trials (RCTs) focused on the use of BYHWD for treating hypertension. This was followed by network pharmacological analysis, and molecular docking assessment using AutoDockTools to explore the mode of action. Results: BYHWD was effective in reducing SBP (MD: 0.767; 95 % CI: 0.629, 0.905; p = 0.000), DBP (MD: 0.427; 95 % CI: 0.292, 0.561; p = 0.000), 24h SBP (MD: 0.665; 95 % CI: 0.368, 0.962; p = 0.000), 24h DBP (MD: 0.547; 95 % CI: 0.318, 0.777; p = 0.000), dSBP (MD: 0.625; 95 % CI: 0.395, 0.855; p = 0.000), dDBP (MD: 0.632; 95 % CI: 0.401, 0.862; p = 0.000), nSBP (MD: 0.859; 95 % CI: 0.340, 1.377; p = 0.001), nDBP (MD: 0.704; 95 % CI: 0.297, 1.112; p = 0.001), pv (MD: 1.311; 95 % CI: 0.363, 2.259; p = 0.007) and NIHSS (MD: 1.149; 95 % CI: 0.100, 2.199; p = 0.032), and elevating CER (OR = 2.848; 95 % CI: 1.388, 5.843; p = 0.004). However, BYHWD did not significantly reduce HCY, and there was no significant difference in the incidence of AE. In terms of the mechanism of action, the main active ingredient of BYHWD is quercetin, and the core targets are AKT1, MMP9, and others. Molecular docking also showed that quercetin mainly interacts with the amino acid residue CYS-28 of MMP2. Second, the KEGG analysis showed that BYHWD mainly act on HIF-1, Apelin, and cGMP-PKG signalling pathways, and GO analysis showed that it related to the apical part of the cell, circulatory system processes, and nuclear receptor activity. Conclusion: BYHWD can lowered blood pressure, reduced plasma viscosity, and restored neurological function with good tolerability, and had no significant effect on HCY levels. This study further demonstrated that quercetin is the main active ingredient of BYHWD that acts via the AKT1 and HIF-1 signalling pathways. These results provide new guidance for people's dietary choices by the general public.

Background: Drug resistance is a major obstacle in the treatment of gastric cancers (GC). In recent years, the prognostic value of the mRNA expression-based stemness score (mRNAss) across cancers has been reported. We intended to search for the key genes associated with Cancer stem cells (CSCs) and drug resistance. Methods: All GC samples from The Cancer Genome Atlas (TCGA) were then divided into low- and high-mRNAss groups based on the median value of mRNAss. A weighted correlation network analysis (WCGNA) was used to identify co-expressed genes related to mRNAss groups. Differential gene expression analysis with Limma was performed in the GSE31811. The correlations between CYB5R1 and the immune cells and macrophage infiltration were analyzed by TIMER database. Spheroid formation assay was used to evaluate the stemness of gastric cancer cells, and transwell assay was used to detect the invasion and migration ability of gastric cancer cells. Results: GC patients with high mRNAss values had a worse prognosis than those with low mRNAss values. 584 genes were identified by WGCNA analysis. 668 differentially expressed genes (DEGs) (|logFC|>1) with 303 down-regulated and 365 up-regulated were established in drug-effective patients compared to controls. TCGA-STAD samples were divided into 3 subtypes based on 303 down-regulated genes. CYB5R1 was a potential biomarker that correlated with the response to drugs in GC (AUC=0.83). CYB5R1 participated in drug resistance and tumorigenesis through NFS1 in GC. Conclusions: Our study highlights the clinical importance of CYB5R1 in GC and the CYB5R1-NFS1 signaling-targeted therapy might be a feasible strategy for the treatment of GC.

In this study, a biomass gasification process model based on the Gibbs free energy minimization principle is established to determine the optimal parameters of biomass gasification. Without affecting the product composition, the impact of the use of high-temperature syngas to heat the biomass and gasification agent on the thermal load of the system was discussed, aiming to reduce the overall energy consumption of the system by optimizing the energy flow.The results show that when the gasification temperature is 750 °C, the mass flow ratio of gasification agent to biomass is 1/1, and the pressure is 1 atm, the product quality is the best. Under the above conditions, using high-temperature synthesis gas to heat the gasification agent (steam) is more conducive to reducing energy consumption than using high-temperature synthesis gas to heat biomass. When two regenerators are set to heat biomass and gasification agent at the same time, it is found that the effect of heating gasification agent after heating biomass is better than heating gasification agent first, and the system heat load is reduced by up to 32.47 %, that is, about 1.83 kW.

17β-Estradiol (E2) is a common environmental endocrine and excessive estrogen will disturb the endocrine balance of human body and lead to diseases because of its accumulation in human body. The main aim of this study is to determine the trace amount of E2 in various foods. Based on aptamer specific recognition, DNA walker molecular machine and Exonuclease III-assisted dual cycle signal amplification technology, a fluorescent aptamer sensor was constructed and applied to the detection of 17β-estradiol. Atomic force microscopy (AFM) and polyacrylamide gel electrophoresis (PAGE) were used to verify the feasibility of DNA walker participating in the reaction. Under the optimal conditions, 17β-estradiol concentration showed a good linear relationship with fluorescence in the range of 5.0 × 10−10–1.8 × 10−8 M, and the detection limit was 5.6 × 10−11 M. The fluorescent aptamer sensor established in this study has good selectivity, simple operation and good specificity, and the results of its application in the determination of milk samples are satisfactory. Research findings revealed that the E2 concentration in water and milk is less than the safe limits, indicating the foods in the market are safe and can be consumed. Though the foods are safe in present content, the health risk still exists because of continuous intake of trace E2.

Deep-water currents are geographically widespread and represent important tight-oil and -gas reservoirs. However, identifying deep-water traction current deposits is challenging work. The main objectives of this research were to identify a new type of reservoir deposited in deep-water traction currents. Based on high-quality 3D seismic data and drilling data (logging data and lithology), the sedimentary characteristics of the MKT Formation of the upper Carboniferous Moscow Stage, southeastern Pre-Caspian Basin, were determined. The MKT Formation of the upper Carboniferous Moscow Stage is mainly composed of mudstone and some thin-bedded siltstone. This formation contains a series of “reversal foresets” dipping west (early paleo–high provenance during the depositional stage). Based on the seismic data and drilling logging data, lithology, paleo-geographic position, seismic facies, and form and scale, deep-water traction current deposits were identified in the M block. The discovery of deep-water traction current deposits in the M block not only provides a precious example for research on Paleozoic deep-water traction current deposits, and enriches our knowledge of basin sedimentary types, but also proves that the M block had complex fluid features and unveils a new domain for petroleum exploration in the basin.

The droplet microfluidic device has become a widely used tool in fields such as physics, chemistry, and biology, but its complexity has limited its widespread application. This report introduces a modular and cost-effective droplet microfluidic device for the controlled production of complex emulsions, including oil and aqueous single emulsions, and double emulsions with varying numbers of encapsulated droplets. The droplet sizes can be precisely controlled by easily replacing flat needles and adjusting the needle position within an axially accelerated co-flow field. This modular device not only allows for easy repair and maintenance in case of device clogging or damage but can also be readily expanded to produce complex emulsions. The low-cost and user-friendly nature of the device greatly facilitates the widespread adoption and utilization of droplet microfluidics.

Along with reducing traffic congestion, electric car-sharing (ECS) can also solve travel demand, utilize idle resources, and enhance forms of transportation. Accordingly, university students are identified in Guangzhou, China as a promising customer group for ECS companies. Although university students in Guangzhou, China are unique in the context of ECS, few researchers have studied the factors that influence their willingness to use such services. Hence, this paper investigates the key determinants that affect university students’ behavioral intention (BI) to use ECS in Guangzhou, China. Based on an extension of the unified theory of acceptance and use of technology (UTAUT), this paper examines the effects of the constructs on BI to use ECS and the moderating role of trust in ECS. Based on results from a questionnaire of 486 university students in Guangzhou, China, conditional value (CV) was the most critical driver of BI, followed by personal attitude (PA) and sustainability (SUST). The moderating analysis showed that taking gender, education, and driving experience of university students as control variables, trust was found to have a significant positive moderating impact on the relationship between PA and BI to use ECS, and a significant negative moderating effect of trust on the relationship between CV and BI to use ECS. The implications of these findings are discussed.

Background: Nurses in trauma centers encounter emergency patients and are exposed to occupational stressors under normalized pandemic control and prevention. Objective: The objective of this study was to examine the occupational stressors that nurses perceived during the COVID-19 pandemic in a level-1 trauma center in China. Methods: From December 2020 to May 2021, a qualitative study was conducted, employing conventional content analysis as the research methodology. A total of twelve nurses were purposefully selected from a trauma center at a major hospital in Beijing to participate in semi-structured interviews (40–50 min’ duration). The data collected in this study were analyzed using the conventional content analysis approach proposed by Graneheim and Lundman. Results: After analyzing the data, two themes emerged: 1) Critical conditions under normalized pandemic prevention and control; 2) Concerns about loved ones and colleagues, along with financial problems. Both these themes further revealed four categories: the complexity and uncertainty of epidemic prevention and health hazards in the former, and concerns for and from families and colleagues, and financial stress in the latter. Conclusions: The results of this study provide valuable insights into the practical implementation of epidemic prevention and control measures in Chinese trauma centers and shed light on the psychological stress faced by nurses. Improving the tripartite support system of hospital, family, and society, and providing emotional support may help reduce stress among nurses, thereby improving their health and care quality.

Abstract Background Post-traumatic massive hemorrhage demands immediately available first-aid supplies with reduced operation time and good surgical compliance. In-situ crosslinking gels that are flexibly adapting to the wound shape have a promising potential, but it is still hard to achieve fast gelation, on-demand adhesion, and wide feasibility at the same time. Methods A white-light crosslinkable natural milk-derived casein hydrogel bioadhesive is presented for the first time. Benefiting from abundant tyrosine residues, casein hydrogel bioadhesive was synthesized by forming di-tyrosine bonds under white light with a ruthenium-based catalyst. We firstly optimized the concentration of proteins and initiators to achieve faster gelation and higher mechanical strength. Then, we examined the degradation, cytotoxicity, tissue adhesion, hemostasis, and wound healing ability of the casein hydrogels to study their potential to be used as bioadhesives. Result Rapid gelation of casein hydrogel is initiated with an outdoor flashlight, a cellphone flashlight, or an endoscopy lamp, which facilitates its usage during first-aid and minimally invasive operations. The rapid gelation enables 3D printing of the casein hydrogel and excellent hemostasis even during liver hemorrhage due to section injury. The covalent binding between casein and tissue enables robust adhesion which can withstand more than 180 mmHg blood pressure. Moreover, the casein-based hydrogel can facilitate post-traumatic wound healing caused by trauma due to its biocompatibility. Conclusion Casein-based bioadhesives developed in this study pave a way for broad and practical application in emergency wound management.

Hearing impaired people use sign language for communication, which relies on the movement gestures of body parts and plays a vital role in human-computer interaction. Most wireless sensing-based gesture recognition studies have recognized simple gestures but overlooked the recognition of complex activities, such as sign language. In addition, cross-domain recognition often requires a large amount of data to train classifiers for each environment. Therefore, we propose RF-CSign, which aims to achieve high accuracy in sign language recognition and cross-domain recognition. First, we use Radio Frequency Identification (RFID) to collect signals and obtain denoised signals through data pre-processing, so that they can be processed in a neural network. Second, the RF-CSign network is proposed with the inclusion of large kernel convolution to reduce the complexity of the model and to make the model with long-range correlations, thereby enhancing recognition accuracy. Third, RF-CSign employs a pixel Normalization-based Attention Module (NAM) to enhance the stability of the model, thereby addressing the problem of model overfitting. Finally, RF-CSign achieves high accuracy in cross-domain environments through a migration learning approach. The experimental results showed that the average recognition accuracy of RF-CSign reached 99.17%, and the average recognition accuracy for new users and new environments recorded 96.67% and 97.50%, respectively.

Abstract Background MicroRNAs (miRNAs) are involved in the regulation of both the innate and adaptive immune response to Cryptosporidium parvum infection. We previously reported that C. parvum upregulated miR‑942‑5p expression in HCT‑8 cells via TLR2/TLR4‑NF‑κB signaling. In the present study, the role of miRNA-942-5p in the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated HCT-8 cell apoptosis induced by C. parvum was investigated. Methods Quantitative real-time polymerase chain reaction, western blotting, flow cytometry, and immunofluorescence were used for analysis. Results Forced expression of miRNA-942-5p resulted in decreased apoptosis and an increased C. parvum burden in HCT-8 cells. The opposite results were observed using the suppressed expression of miRNA-942-5p. The miRNA-942-5p led to the translational suppression of IFI27 gene through targeting the 3’-untranslated region of the IFI27 gene. Moreover, overexpression of the IFI27 gene produced a high apoptotic ratio and low C. parvum burden. In contrast, a low apoptotic ratio and a high C. parvum burden were observed following downregulation of the IFI27 gene. Both miR-942-5p and the IFI27 gene influenced TRAIL and caspase-8 expression induced by C. parvum in HCT-8 cells. Moreover, TRAIL promoted HCT-8 cell apoptosis in a concentration-dependent manner. Conclusions These data suggested that C. parvum induced the downregulation of IFI27 via relief of miR-942-5p-mediated translational suppression. IFI27 downregulation was affected the burden of C. parvum by regulating HCT-8 cell apoptosis through TRAIL-dependent pathways. Future studies should determine the mechanisms by which C. parvum infection increases miR-942-5p expression and the role of miR-942-5p in hosts' anti-C. parvum immunity in vivo. Graphical Abstract

The authors took a multimodal approach to characterize the differential transcriptome and epigenetic landscape between distinct regions of the embryonic mouse forebrain, revealing many unexplored presumptive promoter-enhancer interactions.

Small molecule drugs are the next-generation of immune checkpoint inhibitors (ICIs), but their in vivo therapeutic outcomes remain unsatisfactory for a long time. Herein, we proposed a combinatory regimen that delivered a small molecule ICI and an immunogenic cell death inducer in an in-situ formed hydrogel scaffold based on thermosensitive materials (Pluronic F127). This platform increased the tumor retention of administrated small molecules, creating more opportunities for the interaction between drugs and tumor cells. We found that atorvastatin (ATO) effectively downregulated the expression of programmed death ligand 1 (PD-L1) and reversed compensative PD-L1 upregulation after cyclophosphamide (CTX) chemotherapy on CT26 colon tumors. CTX not only killed tumor cells to reduce the tumor burden, but also release damage-associated molecular patterns (DAMPs) to stimulate T cell immunity, therefore amplifying statin-mediated immunotherapy. The platform reported in this study might be promising to overcome the limitation of small molecule ICIs with short retention time and potentiate tumor chemo-immunotherapy.

Right atrial thrombosis, which occurs alone, is rare in clinical practice. Its incidence and mechanism are unclear, but susceptibility factors are usually present at its occurrence: ischemic heart disease, heart failure, atrial fibrillation, and chronic kidney disease. Complete isolated right atrial thrombosis rarely occurs. We report here a 47-year-old male patient with a right atrial mass on cardiac ultrasound and chest computed tomography (CT) and a history of previous right heart surgery with type 2 diabetes mellitus and atrial fibrillation, complaining of “chest tightness and shortness of breath after activity for half a month.” The patient was admitted to the hospital and underwent right atrial mass resection, and the postoperative pathology showed “right atrial thrombus.” As right atrial thrombus is very rare and can be a serious threat to life when it occurs in the heart, the prevention and treatment of right atrial thrombus are very important. Based on the analysis of this case, we believe that for patients with special medical history such as “post right heart surgery and atrial fibrillation,” we need to be vigilant for atrial thrombosis.

Background: The association between the body surface and viscera remains obscure, but a better understanding of the body surface-viscera correlation will maximize its diagnostic and therapeutic values in clinical practice. Therefore, this study aimed to investigate the specificity of body surface-viscera correlation in the pathological state.Methods: The study subjects included 40 participants with chronic obstructive pulmonary disease (COPD) in the COPD group and 40 age-matched healthy participants in the healthy control group. Laser Doppler flowmetry, infrared thermography, and functional near-infrared spectroscopy were respectively adopted to measure 1) the perfusion unit (PU), 2) temperature, and 3) regional oxygen saturation (rSO2) of four specific sites distributed in the heart and lung meridians. These three outcome measures reflected the microcirculatory, thermal, and metabolic characteristics, respectively.Results: Regarding the microcirculatory and thermal characteristics of the body surface, the PU and temperature of specific sites on the body surface [i.e., Taiyuan (LU9) and Chize (LU5) in the lung meridian] in the COPD group were significantly increased compared with healthy controls (p < 0.05), whereas PU and temperature of other sites in the heart meridian [i.e., Shenmen (HT7) and Shaohai (HT3)] did not change significantly (p > 0.05). Regarding the metabolic characteristics, rSO2 of specific sites in the lung meridian [i.e., Taiyuan (LU9) and Chize (LU5)] and Shaohai (HT3) of the heart meridian in the COPD group was significantly decreased compared with healthy controls (p < 0.01), whereas rSO2 of Shenmen (HT7) in the heart meridian did not change significantly (p > 0.05).Conclusion: In the disease state of COPD, the microcirculatory, thermal, and metabolic characteristics of specific sites on the body surface in the lung meridian generally manifest more significant changes than those in the heart meridian, thereby supporting relative specificity for the body surface-viscera correlation in the pathological state.

Lung transplantation is the definitive end-stage treatment for many lung diseases, and postoperative pulmonary oedema severely affects survival after lung transplantation. Optimizing perioperative fluid management can reduce the incidence of postoperative pulmonary oedema and improve the prognosis of lung transplant patients by removing the influence of patient, donor’s lung and ECMO factors. Therefore, this article reviews seven aspects of lung transplant patients' pathophysiological characteristics, physiological characteristics of fluids, the influence of the donor lung on pulmonary oedema as well as current fluid rehydration concepts, advantages or disadvantages of intraoperative monitoring tools or types of fluids on postoperative pulmonary oedema, while showing the existing challenges in section 7. The aim is to show the specificity of perioperative fluid management in lung transplant patients and to provide new ideas for individualised fluid management in lung transplantation.

Summary: Efficient protocols to generate single-cell and single-nuclei suspensions are critical for the burgeoning field of single-cell/single-nuclei sequencing. Here we describe procedures to generate single-cell and single-nuclei suspensions from embryonic and adult mouse brains. This protocol can be modified for any brain region and/or neural cell type.For complete details on the use and execution of this protocol, please refer to Lee et al. (2022),1 Rhodes et al. (2022),2 Mahadevan et al. (2021),3 Ekins et al. (2020),4 and Wester et al. (2019).5 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Alopecia affects millions of individuals globally, with hair loss becoming more common among young people. Various traditional Chinese medicines (TCM) have been used clinically for treating alopecia, however, the effective compounds and underlying mechanism are less known. We sought to investigate the effect of Alpinetin (AP), a compound extracted from Fabaceae and Zingiberaceae herbs, in hair regeneration. Methods Animal model for hair regeneration was mimicked by depilation in C57BL/6J mice. The mice were then topically treated with 3 mg/ml AP, minoxidil as positive control (PC), or solvent ethanol as vehicle control (VC) on the dorsal skin. Skin color changes which reflected the hair growth stages were monitored and pictured, along with H&E staining and hair shaft length measurement. RNA-seq analysis combined with immunofluorescence staining and qPCR analysis were used for mechanism study. Meanwhile, Gli1CreERT2; R26RtdTomato and Lgr5EGFP−CreERT2; R26RtdTomato transgenic mice were used to monitor the activation and proliferation of Gli1+ and Lgr5+ HFSCs after treatment. Furthermore, the toxicity of AP was tested in keratinocytes and fibroblasts from both human and mouse skin to assess the safety. Results When compared to minoxidil-treated and vehicle-treated control mice, topical application of AP promoted anagen initiation and delayed catagen entry, resulting in a longer anagen phase and hair shaft length. Mechanistically, RNA-seq analysis combined with immunofluorescence staining of Lef1 suggested that Lgr5+ HFSCs in lower bulge were activated by AP via Wnt signaling. Other HFSCs, including K15+, Lef1+, and Gli1+ cells, were also promoted into proliferating upon AP treatment. In addition, AP inhibited cleaved caspase 3-dependent apoptosis at the late anagen stage to postpone regression of hair follicles. More importantly, AP showed no cytotoxicity in keratinocytes and fibroblasts from both human and mouse skin. Conclusion This study clarified the effect of AP in promoting hair regeneration by activating HFSCs via Wnt signaling. Our findings may contribute to the development of a new generation of pilatory that is more efficient and less cytotoxic for treating alopecia.

Abstract When managed bee colonies are brought to farms for crop pollination, they can be exposed to pesticide residues. Quantifying the risk posed by these exposures can indicate which pesticides are of the greatest concern and helps focus efforts to reduce the most harmful exposures. To estimate the risk from pesticides to bees while they are pollinating blueberry fields, we sampled blueberry flowers, foraging bees, pollen collected by returning honey bee and bumble bee foragers at colonies, and wax from honey bee hives in blooming blueberry farms in southwest Michigan. We screened the samples for 261 active ingredients using a modified QuEChERS method. The most abundant pesticides were those applied by blueberry growers during blueberry bloom (e.g., fenbuconazole and methoxyfenozide). However, we also detected highly toxic pesticides not used in this crop during bloom (or other times of the season) including the insecticides chlorpyrifos, clothianidin, avermectin, thiamethoxam, and imidacloprid. Using LD50 values for contact and oral exposure to honey bees and bumble bees, we calculated the Risk Quotient (RQ) for each individual pesticide and the average sample RQ for each farm. RQ values were considered in relation to the U.S. Environmental Protection Agency acute contact level of concern (LOC, 0.4), the European Food Safety Authority (EFSA) acute contact LOC (0.2) and the EFSA chronic oral LOC (0.03). Pollen samples were most likely to exceed LOC values, with the percent of samples above EFSA’s chronic oral LOC being 0% for flowers, 3.4% for whole honey bees, 0% for whole bumble bees, 72.4% for honey bee pollen in 2018, 45.4% of honey bee pollen in 2019, 46.7% of bumble bee pollen in 2019, and 3.5% of honey bee wax samples. Average pollen sample RQ values were above the EFSA chronic LOC in 92.9% of farms in 2018 and 42.9% of farms in 2019 for honey bee collected pollen, and 46.7% of farms for bumble bee collected pollen in 2019. Landscape analyses indicated that sample RQ was positively correlated with the abundance of apple and cherry orchards located within the flight range of the bees, though this varied between bee species and landscape scale. There was no correlation with abundance of blueberry production. Our results highlight the need to mitigate pesticide risk to bees across agricultural landscapes, in addition to focusing on the impact of applications on the farms where they are applied.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) is commonly used for the clinical treatment of major depressive disorder (MDD). The neuroimaging biomarkers and mechanisms of rTMS are still not completely understood. This study aimed to explore the functional neuroimaging changes induced by rTMS in adolescents with MDD. A total of ten sessions of rTMS were administrated to the L-DLPFC in thirteen adolescents with MDD once a day for two weeks. All of them were scanned using resting-state functional magnetic resonance imaging at baseline and after rTMS treatment. The regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and the subgenual anterior cingulate cortex (sgACC)-based functional connectivity (FC) were computed as neuroimaging indicators. The correlation between changes in the sgACC-based FC and the improvement in depressive symptoms was also analyzed. After rTMS treatment, ReHo and ALFF were significantly increased in the L-DLPFC, the left medial prefrontal cortex, bilateral medial orbital frontal cortex, and the left ACC. ReHo and ALFF decreased mainly in the left middle occipital gyrus, the right middle cingulate cortex (MCC), bilateral calcarine, the left cuneus, and the left superior occipital gyrus. Furthermore, the FCs between the left sgACC and the L-DLPFC, the right IFGoper, the left MCC, the left precuneus, bilateral post-central gyrus, the left supplementary motor area, and the left superior marginal gyrus were enhanced after rTMS treatment. Moreover, the changes in the left sgACC-left MCC FC were associated with an improvement in depressive symptoms in early improvers. This study showed that rTMS treatment in adolescents with MDD causes changes in brain activities and sgACC-based FC, which may provide basic neural biomarkers for rTMS clinical trials.

The dissolution of supercritical carbon dioxide (ScCO2) in water forms a ScCO2–H2O system, which exerts a transformative influence on the physicochemical characteristics of coal and significantly impacts the CO2-driven enhanced coalbed methane (CO2-ECBM) recovery process. Herein, the effect of ScCO2–H2O treatment on the physicochemical properties of coal was simulated in a high-pressure reactor. The migration of major elements, change in the pore structure, and change in the CH4 adsorption capacity of coal after the ScCO2–H2O treatment were detected using plasma emission spectroscopy, the low-temperature liquid nitrogen adsorption method, and the CH4 adsorption method, respectively. The results show that (1) the ScCO2–H2O treatment led to mineral reactions causing a significant migration of constant elements in the coal. The migration of Ca ions was the most significant, with an increase in their concentration in treated water from 0 to 16–970 mg·L−1, followed by Na, Mg, and K. Al migrated the least, from 0 to 0.004–2.555 mg·L−1. (2) The ScCO2–H2O treatment increased the pore volume and pore-specific surface area (SSA) of the coal via the dissolution and precipitation of minerals in the coal pores. The total pore volume increased from 0.000795–0.011543 to 0.001274–0.014644 cm3·g−1, and the total pore SSA increased from 0.084–3.332 to 0.400–6.061 m2·g−1. (3) Changes in the CH4 adsorption capacity were affected by the combined effects of a mineral reaction and pore structure change. The dissolved precipitates of the minerals in the coal pores after the ScCO2–H2O treatment caused elemental migration, which not only decreased the mineral content in the coal pores but also increased the total pore volume and total pore SSA, thus improving the CH4 adsorption capacity of the coal. This study provides theoretical support for CO2 sequestration and ECBM recovery.

Abstract Background Coal dust particles (CDP), an inevitable by-product of coal mining for the environment, mainly causes coal workers’ pneumoconiosis (CWP). Long-term exposure to coal dust leads to a complex alternation of biological processes during regeneration and repair in the healing lung. However, the cellular and complete molecular changes associated with pulmonary homeostasis caused by respiratory coal dust particles remain unclear. Methods This study mainly investigated the pulmonary toxicity of respirable-sized CDP in mice using unbiased single-cell RNA sequencing. CDP (< 5 μm) collected from the coal mine was analyzed by Scanning Electron Microscope (SEM) and Mass Spectrometer. In addition, western blotting, Elisa, QPCR was used to detect gene expression at mRNA or protein levels. Pathological analysis including HE staining, Masson staining, immunohistochemistry, and immunofluorescence staining were performed to characterize the structure and functional alternation in the pneumoconiosis mouse and verify the reliability of single-cell sequencing results. Results SEM image and Mass Spectrometer analysis showed that coal dust particles generated during coal mine production have been crushed and screened with a diameter of less than 5 µm and contained less than 10% silica. Alveolar structure and pulmonary microenvironment were destroyed, inflammatory and death (apoptosis, autophagy, and necrosis) pathways were activated, leading to pneumoconiosis in post 9 months coal dust stimulation. A distinct abnormally increased alveolar type 2 epithelial cell (AT2) were classified with a highly active state but reduced the antimicrobial-related protein expression of LYZ and Chia1 after CDP exposure. Beclin1, LC3B, LAMP2, TGF-ß, and MLPH were up-regulated induced by CDP, promoting autophagy and pulmonary fibrosis. A new subset of macrophages with M2-type polarization double expressed MLPH + /CD206 + was found in mice having pneumoconiosis but markedly decreased after the Vitamin D treatment. Activated MLPH + /CD206 + M2 macrophages secreted TGF-β1 and are sensitive to Vitamin D treatment. Conclusions This is the first study to reconstruct the pathologic progression and transcriptome pattern of coal pneumoconiosis in mice. Coal dust had obvious toxic effects on lung epithelial cells and macrophages and eventually induced pulmonary fibrosis. CDP-induced M2-type macrophages could be inhibited by VD, which may be related to the alleviation of the pulmonary fibrosis process.

On the basis of social information processing theory, this study proposes a model of the influence mechanism of self-serving leadership (SL) on employee innovative behavior (IB), with psychological entitlement as the mediating variable and moral identity as the moderating variable. The paired data of 82 leaders and 372 employees collected at three time points are analyzed by the hierarchical linear modeling. Results corroborate that SL impairs employee IB. Moreover, the relationship between SL and employee IB is mediated by psychological entitlement. Finally, moral identity has a negative moderating effect of SL on psychological entitlement and an indirect effect on employee IB through psychological entitlement.