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The electric power industry is a high-risk industry with frequent accidents. To ensure the life safety of employees and reduce the probability of accidents, it is necessary to utilize certain technical means to identify the main causative factors in electric fatal accident reports. This research proposes an accident causation identification method that combines text categorization and catastrophe association analysis. First, an improved text feature extraction method (TF-IDF-GloVe-LDA) is proposed by fusing term frequency-inverse document frequency (TF-IDF), global vectors for word representation (GloVe), and latent dirichlet allocation (LDA) algorithms. Then, an SVM classifier was used to categorize the 473 accident report texts into five categories, ACCIDENT, PROCESS, CAUSE, PROBLEM, and RESPONSE, based on the extracted text feature vectors. Second, for the 461 CAUSEs categorized from the accident report texts, the TF-IDF algorithm is utilized to mine them to obtain 62 accident causative factors. Using the word cloud map and semantic network, a visualization analysis is performed to reveal the intrinsic connection between causative factors. The human factor analysis and classification system (HFACS) is combined to construct a framework and a Boolean dataset for electric power fatal accident causative factors. Finally, the catastrophe progression method is utilized to improve the FP-growth algorithm and propose a catastrophe association analysis method. It is utilized to mine the Boolean dataset to obtain 28 association rules and construct the accident causal network. The main causative factors were ultimately identified by analyzing the critical causal chains within the network and examining the frequency and sensitivity of each node. The findings of this study indicate that a lack of effective management, supervision, and training serves as the fundamental cause of fatal accidents in the electric power industry when compared to equipment and environmental factors. This paper offered a fresh perspective on identifying primary accident causative factors in non-standardized text and exploring their intricate mechanisms of interaction, which holds significant implications for the pre-control management of accidents in the power industry.

ABSTRACT: In this study, milk fat globule membrane (MFGM) ingredients enriched in polar lipids were prepared using membrane filtration, including microfiltration, diafiltration, and ultrafiltration from butter serum powder. Polar lipids (phospholipids, sterols, and gangliosides) in prepared MFGM ingredients were analyzed by 31P nuclear magnetic resonance spectroscopy, GC-MS, and ultra-performance liquid chromatography (UPLC)-MS/MS, respectively. The lipolysis degree and microstructure of MFGM ingredient and soybean lecithin (SL) emulsions during in vitro digestion were also analyzed. Microfiltration showed higher concentration efficiency than ultrafiltration, which increased by 2.16% and 2.73% in phospholipids, respectively. Moreover, diafiltration concentrated more polar lipids (6.39% of phospholipids) than microfiltration. Milk fat globule membrane ingredients had high levels of sphingomyelin (1.27%–1.36%) and ratio of GD3 to GM3 is 9.25- to 9.88-fold. The different lipolysis behaviors between MFGM ingredient emulsions and SL emulsions were correlated with their different polar lipid compositions. Phospholipids from both MFGM ingredients and SL could help maintain the initial structure during the gastric digestion. These results could provide a scientific basis for developing high-polar-lipids food, particularly infant formulas and special functional foods.

Under the dual regulation of government intervention and environmental constraints, user demand, low-carbon awareness, and the willingness of construction enterprise to reduce carbon emissions are crucial to the realization of low-carbon transportation infrastructure construction. Basing on prospect theory, this paper constructs an evolutionary game model for the government, construction enterprise, and user, explores the stabilization of the three-game players' strategy choices, and discusses the influence of key parameters on the behavior evolution of relevant players through simulation analysis. The results indicate that: the regulatory cost when the government adopts incentives or no incentives is an important factor affecting the strategy choice. The enhancement of incentives by the government can promote the construction of enterprise and the selection of low-carbon transportation infrastructure by user. However, when the benefit of government credibility outweighs the incremental cost of household subsidies, carbon subsidies, and regulation, the government changes its strategy and no longer adopts encouraging strategy. Improving benefits of build low-carbon transportation infrastructure reducing incremental costs, setting a ladder carbon tax rate, increasing carbon tax rate for traditional construction, and decreasing for low-carbon construction is an effective approach to stimulate enterprise to construct low-carbon transportation infrastructure. The user's choice of low-carbon transportation infrastructure strategy is positively correlated with the subsidy received and is less affected by environmental benefits. And the construction enterprise's strategy choice hasn't been influenced by user, which is related to the public service characteristics of transportation infrastructure.

Objective: Breast cancer poses a major health risk to millions of females globally. Asiaticoside (AC) is a naturally occurring compound derived from Centella asiatica, a widely used medicinal plant in the oriental countries and has potential antitumor properties. The primary aim of this study was to investigate the anti-cancer effects of synthesized AC at the cellular level and assess its ability to inhibit tumor growth and angiogenesis in breast cancer. Methods: The proliferative capacities of MCF-7 and MDA-MB-231 cells were determined using CCK-8 assay. To analyze invasion and migration, Transwell assays were conducted on the same cell lines. Additionally, apoptosis was analyzed in vitro using flow cytometry. Real-time RT-PCR was used to examine mRNA expression, and Western-blotting assay was employed to examine protein expression. Subcutaneous injection of MDA-MB-231 cells into female BALB/c nude mice was followed by treatment with AC to study its anti-tumor effects in vivo. Results: AC treatment reduced cell proliferation and triggered apoptosis in MCF-7 and MDA-MB-231 cells. The invasive and pro-angiogenesis ability were also impaired upon AC treatment. AC administration also impeded the tumor growth and tumor-associated angiogenesis of MDA-MB-231 cells in nude mice, which was accompanied by the decreased levels of YAP1 and VEGFA. Conclusion: Taken together, our results demonstrated the anti-cancer activity of AC in breast cancer. AC is able to suppress the malignancy of breast cancercells via YAP1/VEGFA signal pathway.

Study area: The headwater catchment of the Yellow River (HCYR) (95°90′–103°42′E, 32°16′–36°13′N) is located on the northeast of the Tibetan Plateau, a presentative high-cold region catchment, China. Study focus: HCYR serves as the primary water supply during the dry season in downstream of the Yellow River Basin. Herein, we applied linear regression and the Bernaola-Galvan heuristic segmentation algorithm to identify the baseflow trends and abrupt changes. Four baseflow signatures (baseflow index (BFI), seasonal ratio (SR), concave index (CI), and slope of baseflow duration curve (SBDC)) were used to investigate the characteristics of baseflow changes and the drivers quantitatively. New hydrological insights for the region: The main findings are: (1) the baseflow generally exhibited an increasing trend (R2 > 0.35, p < 0.1), (2) baseflow variation has an apparent spatiality, and it shows a more pronounced change in the middle part than the upper and lower parts, and (3) precipitation, sunshine hours, soil moisture and evapotranspiration were the controlling factors on the baseflow characteristics. These findings provide a deeper insight into baseflow behavior and drivers in high-cold regions, which are vital for ecosystem health, water resource safety and management in critical headwater catchments.

Summary: During malaria infection, Plasmodium sporozoites, the fast-moving stage of the parasite, are injected by a mosquito into the skin of the mammalian host. In the skin, sporozoites need to migrate through the dermal tissue to enter the blood vessel. Sporozoite motility is critical for infection but not well understood. Here, we used collagen hydrogels with tunable fiber structures, as an in vitro model for the skin. After injecting sporozoites into the hydrogel, we analyzed their motility in three-dimension (3D). We found that sporozoites demonstrated chiral motility, in that they mostly follow right-handed helical trajectories. In high-concentration collagen gel, sporozoites have lower instantaneous speed, but exhibit straighter tracks compared to low-concentration collagen gel, which leads to longer net displacement and faster dissemination. Taken together, our study indicates an inner mechanism for sporozoites to adapt to the environment, which could help with their successful exit from the skin tissue.

Carbon fiber–reinforced epoxy composites are widely used in the marine and aviation sectors due to their superior mechanical properties. As research into these materials progresses, the demand for materials with even more complex and superior properties has increased. Traditional trial-and-error methods are limited to optimizing single factors and are plagued by heavy workloads and prohibitive costs when applied to multifactor composite designs. Addressing these problems, this study introduces a nonparametric multiobjective optimization process for composite materials. This approach employs a Gaussian process (GP) to establish a multiobjective regression model and uses nondominated sorting genetic algorithm II (NSGA II) to determine the Pareto front. Pareto solutions were ranked in accordance with their similarity to ideal solutions and on the basis of predetermined preference weights. The results demonstrate variations in optimal outcomes contingent on the weight values assigned. The differences between the optimized results and experimental validations reached 12.9%, with the minimum deviation being 0.6%. The effectiveness of the proposed method was demonstrated. The strategy combines GP and NSGA II to extend design methods for small samples and materials with multiple attributes. This method enables the simultaneous optimization of multiple conflicting objectives, offering greater efficiency than addressing them individually.

Immune cells are key players in acute tissue injury and inflammation, including acute kidney injury (AKI). Their development, differentiation, activation status, and functions are mediated by a variety of transcription factors, such as interferon regulatory factor 8 (IRF8) and IRF4. We speculated that IRF8 has a pathophysiologic impact on renal immune cells in AKI and found that IRF8 is highly expressed in blood type 1 conventional dendritic cells (cDC1s), monocytes, monocyte-derived dendritic cells (moDCs) and kidney biopsies from patients with AKI. In a mouse model of ischemia‒reperfusion injury (IRI)-induced AKI, Irf8−/− mice displayed increased tubular cell necrosis and worsened kidney dysfunction associated with the recruitment of a substantial amount of monocytes and neutrophils but defective renal infiltration of cDC1s and moDCs. Mechanistically, global Irf8 deficiency impaired moDC and cDC1 maturation and activation, as well as cDC1 proliferation, antigen uptake, and trafficking to lymphoid organs for T-cell priming in ischemic AKI. Moreover, compared with Irf8+/+ mice, Irf8−/− mice exhibited increased neutrophil recruitment and neutrophil extracellular trap (NET) formation following AKI. IRF8 primarily regulates cDC1 and indirectly neutrophil functions, and thereby protects mice from kidney injury and inflammation following IRI. Our results demonstrate that IRF8 plays a predominant immunoregulatory role in cDC1 function and therefore represents a potential therapeutic target in AKI.

Drug resistance presents a formidable challenge in the realm of breast cancer therapy. Accumulating evidence suggests that enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 (PRC2), may serve as a key regulator in controlling drug resistance. EZH2 overexpression has been observed in breast cancer and many other malignancies, showing a strong correlation with poor outcomes. This review aims to summarize the mechanisms by which EZH2 regulates drug resistance, with a specific focus on breast cancer, in order to provide a comprehensive understanding of the underlying molecular processes. Additionally, we will discuss the current strategies and outcomes of targeting EZH2 using both single agents and combination therapies, with the goal of offering improved guidance for the clinical treatment of breast cancer patients who have developed drug resistance.

Background and aims: Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. Methods: Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. Results: One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045–1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138–2.014, P = 0.004) were independent factors associated with advanced inflammation. Conclusions: High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

The deep earth, deep sea, and deep space are the main parts of the national “three deep” strategy, which is in the forefront of the strategic deployment clearly defined in China’s 14th Five-Year Plan (2021–2025) and the Long-Range Objectives Through the Year 2035. It is important to reveal the evolutionary process and mechanism of deep tectonics to understand the earth’s past, present and future. The academic connotation of Geology in Time has been given for the first time, which refers to the multi-field evolution response process of geological bodies at different time and spatial scales caused by geological processes inside and outside the Earth. Based on the deep in situ detection space and the unique geological environment of China Jinping Underground Laboratory, the scientific issue of the correlation mechanism and law between deep internal time-varying and shallow geological response is given attention. Innovative research and frontier exploration on deep underground in situ geo-information detection experiments for Geology in Time are designed to be carried out, which will have the potential to explore the driving force of Geology in Time, reveal essential laws of deep earth science, and explore innovative technologies in deep underground engineering.

This study aims to investigate the mechanical response and acoustic emission (AE) characteristic of pre-flawed sandstone under both monotonic and multilevel constant-amplitude cyclic loads. Specifically, we explored how coplanar flaw angle and load type impact the strength and deformation behavior and microscopic damage mechanism. Results indicated that being fluctuated before rising with increasing fissure angle under monotonic loading, the peak strength of the specimen first increased slowly and then steeply under cyclic loading. The effect of multilevel cyclic loading on the mechanical parameters was more significant. For a single fatigue stage, the specimen underwent greater deformation in early cycles, which subsequently stabilized. Similar variation pattern was also reflected by AE count/energy/b-value. Crack behaviors were dominated by the fissure angle and load type and medium-scale crack accounted for 74.83%–86.44% of total crack. Compared with monotonic loading, crack distribution of specimen under cyclic loading was more complicated. Meanwhile, a simple model was proposed to describe the damage evolution of sandstone under cyclic loading. Finally, SEM images revealed that the microstructures at the fracture were mainly composed of intergranular fracture, and percentage of transgranular fracture jumped under cyclic loading due to the rapid release of elastic energy caused by high loading rate.

Risk assessment is utilized to evaluate the risk level of the system and guide further operation and planning of utilities. However, to lower the cost of communication and storing, only a coarse resolution profile of load and PV can be collected and used to evaluate the risk level of the system, which may lead to inaccurate assessment. To this end, this paper investigates the impact of load-PV profile resolution on distribution system risk assessment. A super-resolution Generative Adversarial Network with pre- and post-processing processes is proposed to restore the high-frequency component of the load-PV profile. Then, with the generated high-resolution profile, a risk assessment model based on the exterior point method is proposed to evaluate the risk level of the distribution system. Case studies in a modified 33-bus system showed that the proposed super-resolution method could achieve the best performance to restore the peak values and high-frequency component of the load-PV profile compared to the other four methods. In addition, compared to super-resolution Generative Adversarial Networks without the post-processing process, the accuracy of risk assessment can be significantly improved using the proposed super-resolution method, which proves that the post-processing process is necessary.

Summary: This study investigates the efficacy of proteomic analysis of human remains to identify active infections in the past through the detection of pathogens and the host response to infection. We advance leprosy as a case study due to the sequestering of sufferers in leprosaria and the suggestive skeletal lesions that can result from the disease. Here we present a sequential enzyme extraction protocol, using trypsin followed by ProAlanase, to reduce the abundance of collagen peptides and in so doing increase the detection of non-collagenous proteins. Through our study of five individuals from an 11th to 18th century leprosarium, as well as four from a contemporaneous non-leprosy associated cemetery in Barcelona, we show that samples from 2 out of 5 leprosarium individuals extracted with the sequential digestion methodology contain numerous host immune proteins associated with modern leprosy. In contrast, individuals from the non-leprosy associated cemetery and all samples extracted with a trypsin-only protocol did not. Through this study, we advance a palaeoproteomic methodology to gain insights into the health of archaeological individuals and take a step toward a proteomics-based method to study immune responses in past populations.

Objective: Long-term alcohol consumption can cause organic damage to the brain, resulting in mental and nervous system abnormalities and intellectual impairment. Huanglian Jiedu decoction (HLJDD) is the classic representative of clearing heat and detoxifying. This study aimed to explore the effects and possible mechanisms of HLJDD on brain injury in chronic alcohol-exposed mice. Methods: The alcohol-exposed mice were treated with different doses of HLJDD to observe behavioral changes, hippocampal Aβ1-42 deposition, number and ultrastructural changes of neurons in the hippocampus and prefrontal cortex, and expressions of synaptic proteins. On this basis, transcriptome sequencing was used to analyze the differentially expressed genes in different treatment groups, and functional enrichment analysis was performed. Then, WB and RT-PCR were used to verify the expression of the pathway. Results: Chronic alcohol exposure reduced body weight in mice, led to motor cognitive impairment, increased Aβ1-42 in the hippocampus, decreased the number of neurons in the hippocampus and prefrontal cortex, and the expression of PSD95 and SYN in the hippocampus. HLJDD significantly improved the cognitive dysfunction of mice and alleviated the damage of the hippocampus and prefrontal cortex. Transcriptome sequencing results showed that the regulatory effects of HLJDD on chronic alcohol-exposed mice may be related to the RAS pathway. Further experiments confirmed that chronic alcohol exposure caused a significant increase in protein and gene expressions of the RAS-RAF-MEK-ERK pathway in mouse, and this activation was reversed by HLJDD. Conclusion: HLJDD may ameliorate brain damage caused by chronic alcohol exposure by regulating the RAS-RAF-MEK-ERK pathway.

Summary: Osteoporosis has gradually become a major public health problem. Further elucidation of the pathophysiological mechanisms that induce osteoporosis and identification of more effective therapeutic targets will have important clinical significance. Experiments in vitro on bone marrow stem cells (BMSCs) subjected to osteogenic and adipogenic differentiation and in vivo on surgical bilateral ovariectomy (OVX) mouse models revealed that exosomes of vascular endothelial cells (EC-EXOs) can promote osteogenic differentiation of BMSCs and inhibit BMSC adipogenic differentiation through miR-3p-975_4191. Both miR-3p-975_4191 and curcumin can target tumor necrosis factor (TNF) and act synergistically to regulate BMSCs fate differentiation and delay the progression of osteoporosis. Our findings suggest that EC-EXOs may exert a synergistic effect with curcumin in reversing the progression of osteoporosis by targeting TNF via miR-3p-975_4191. Our study may provide therapeutic options and potential therapeutic targets for osteoporosis and thus has important clinical implications.

Background: Diabetic cardiomyopathy is one common cardiovascular complication without effective treatments. Dihydromyricetin (DHY), a natural dihydroflavonol compound extracted from Ampelopsis grossedentata, possesses versatile pharmacologically important effects. In our current research, we planned to evaluate the impact and probable DHY mechanisms in high glucose (HG)-induced cardiomyocytes. Methods: Primary cardiomyocytes were pretreated with different concentrations of DHY (0, 20, 40, 80, 160, and 320 μM) for various time (0, 1, 2, 4, 12, and 24 h). They were then stimulated for 48 h with 5.5 mmol/L normal glucose (NG) and 33.3 mmol/L high glucose (HG). Cell viability, adenosine-triphosphate (ATP) levels, and lactate dehydrogenase (LDH) release of cardiomyocytes were detected. JC-1 staining was employed to measure the mitochondrial membrane potential. MitoSOX staining and dihydroethidium (DHE) staining were applied to evaluate the oxidative stress levels. TDT mediated dUTP nick end labeling (TUNEL) was used to measure apoptotic levels. Expressions of calcium/calmodulin-dependent protein kinase II (CaMKII), phospholamban (PLB), optic atrophy 1 (OPA1), dynamin-related protein 1 (DRP1), caspase 3, mixed kinase lineage domain like protein (MLKL), receptor interacting protein kinase 3 (RIPK3), and receptor interacting protein kinase 1 (RIPK1) were detected by immunofluorescence and/or Western blot. Results: DHY improved cell viability, enhanced ATP level, and decreased LDH content in HG-stimulated cardiomyocytes, suggesting DHY attenuating cell injury. DHY reduced number of TUNEL positive cells, inhibited RIPK3 and cleaved-caspase 3 expression, implying DHY alleviated necroptosis in HG-stimulated cardiomyocytes. DHY diminished JC-1 monomers, DHE and MitoSOX fluorescence intensity as well as DRP1 expression but increased JC-1 aggregates intensity and OPA1 expression, indicating that DHY attenuated oxidative stress in HG-stimulated cardiomyocytes. DHY also attenuated CaMKII activity by suppressed PLB phosphorylation and inhibited CaMKII oxidation in HG-stimulated cardiomyocytes. Conclusions: HG-induced cardiomyocytes injury was alleviated wherein DHY attenuated necroptosis, repressed ROS production, and inhibited CaMKII oxidation, suggesting that DHY may serve as potential agent to prevent and treat diabetic cardiomyopathy.

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway.

Nitrogen fertilizer supports agricultural intensification, but its manufacturing results in substantial contaminated sites. Ammonia nitrogen is the main specific pollutant in retired nitrogen fertilizer sites with potential human health and odor risks. However, few studies focus on ammonia nitrogen risk assessment at contaminated sites, particularly considering its solid-liquid partitioning process (Kd) and ammonium/ammonia equilibrium process (R) in the soil. This study took a closed nitrogen fertilizer factory site as an example and innovatively introduced Kd and R to scientifically assess the human health and odor risk of ammonia nitrogen. The risk control values (RCVs) of ammonia nitrogen based on human health and odor risk were also derived. The maximum concentration of ammonia nitrogen was 3380 mg/kg in the unsaturated soil, which was acceptable for human health because the health RCVs were 5589 ∼ 137,471 mg/kg in various scenarios. However, odor risk was unacceptable for RCVs were 296 ∼ 1111 mg/kg under excavation scenarios and 1118 ∼ 35,979 mg/kg under non-excavation scenarios. Of particular concern, introducing Kd and R in calculation increased the human health and odor RCVs by up to 27.92 times. Despite the advancements in ammonia risk assessment due to the introduction of Kd and R, odor risk during excavation remains a vital issue. These findings inform a more scientific assessment of soil ammonia risk at contaminated sites and provide valuable insights for the management and redevelopment of abandoned nitrogen fertilizer plant sites.

Summary: Background: Concurrent chemoradiotherapy is the standard nonoperative treatment for locally advanced esophageal squamous cell carcinoma. However, local recurrence is still the main failure pattern, accounting for more than half of all treatment failures, indicating that the sensitivity of radiotherapy still needs to be improved. This trial aimed at demonstrating whether PD-1 inhibitors followed by chemoradiotherapy could promote esophageal tumor vascular normalization, alleviate hypoxia, and thus enhance radiosensitivity and improve local control. Methods: We did a multicenter, single-arm, phase 2 trial in China. Patients with locally advanced esophageal cancer were enrolled in this study. In induction phase, patients received two cycles of sintilimab, paclitaxel and carboplatin once per 21 days. In concurrent phase, patients were treated with five cycles of carboplatin and paclitaxel once per week concurrent with radiotherapy of 50.4Gy delivered in 28 fractions. The primary endpoint was 2-year local control rate. Hypoxia and vessel normalization was assessed before and after induction phase using immunofluorescence and perfusion CT. This trial is registered with ClinicalTrials.gov (NCT03985046). Findings: Seventy-five patients with esophageal cancer were enrolled in this study between October 2019 and April 2021. The median follow-up of surviving patients was 33.6 months (IQR 29.3–35.7). The 2-year local control rate was 81.7% (95% confidence interval, 72.7%–90.7%), which was much higher than that in concurrent chemoradiation only (71.3%) in previous studies. Vascular normalization and hypoxia alleviation were observed in both biopsy specimens and perfusion CT. Interpretation: The addition of induction immunotherapy to standard concurrent chemoradiotherapy could improve radiosensitivity for locally advanced esophageal cancer as non-surgical treatment. New treatment combination led to higher local control rate through promoting vascular normalization and alleviating hypoxia. Our findings suggest that induction immunotherapy followed by concurrent chemoradiotherapy could be a potential option in future treatment. Funding: National Natural Science Foundation of China and Shanghai Rising-Star Program.

Background: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome (Barakat syndrome) is a rare autosomal dominant disorder caused by mutations in the gene encoding GATA3 on chromosome 10p14. Method: Informed consent was obtained from a 38-year-old female patient. 5 mL of venous blood was collected and sent for whole-exome sequencing. GATA3 constructs of both wild-type and mutant were transfected into HEK-293 T cells. Three-dimensional modeling, luciferase-reporter gene test, western blotting and cellular immunofluorescence were used to evaluate the effect of the mutation. Results: A novel frameshift mutation c. 677dup(p.Pro227AlafsTer77), named P227Afs, was found in GATA3. Three-dimensional modeling revealed that the mutation caused the loss of the dual zinc finger structures 1 and 2 (ZNF1 and ZNF2) of the synthesized protein. Expression of wild-type GATA3 produced a six-fold increase in luciferase activity when compared with pcDNA3.1 vector only (P

Background: Infants and children with feeding difficulties have swallowing dysfunction and high risk of aspiration, which could be silent without choking, resulting in recurrent pneumonia and long-term respiratory morbidity. Videofluoroscopic swallow study (VFSS) is a useful tool for real-time visualization of the swallowing process and airway aspiration. This study reported a single-institutional 10-year experience of VFSS in pediatric patients with feeding difficulties and the efficacy of swallowing therapy. Methods: From 2011 to 2020, 30 infants and children with feeding difficulties received VFSS examinations in a medical center at a median age of 19 months (range 7 days–8 years). The images of the swallowing process (oral phase, triggering of pharyngeal swallowing, and pharyngeal phase) under videofluoroscopy were analyzed by a radiologist and a speech-language pathologist. Aspiration severity was assessed from VFSS observations and rated by an eight-point Penetration-Aspiration-Scale (PAS), with higher scores indicating increased severity. Swallowing therapy was performed by experienced speech-language therapists, and follow-up of oral feeding tolerance and risk of aspiration pneumonia was done. Results: Of the 30 patients, 24 (80%) had neurological deficits. High PAS scores (6–8) were observed in 25 (83.4%) patients, and 22 had a PAS score of 8, indicating silent aspiration. Of the 25 patients with high PAS scores, 19 (76%) had neurological deficits, and 18 (72%) depended on tube feeding at a median age of 20 months. Swallowing problems occurred most frequently during the pharyngeal phase in the patients with high PAS scores. VFSS-based swallowing therapy improved oral feeding ability and reduced aspiration episodes. Conclusion: Infants and children with swallowing dysfunction and neurological deficits had high risk of severe aspiration. Swallowing problems in the pharyngeal phase were the most common VFSS findings in patients with severe aspiration. VFSS may help guide problem-oriented swallowing therapy to reduce the risk of recurrent aspiration.

Drought caused by climate change has significantly increased vegetation vulnerability in Afghanistan during the last decades. This paper investigates vegetation response to drought at multiple scales across the country based on historical data from 1980 to 2020. It explores the multiscale relationships between drought as indicated by the grid-based standardised precipitation evapotranspiration index (SPEI) and vegetation condition as represented by the satellite-derived vegetation anomaly index (VAI). It also examines the links of dominant land cover with drought and their implications for agriculture. We assess the spatiotemporal correlations by integrating TerraClimate grids with timeseries data sourced from NOAA AVHRR (National Oceanic and Atmospheric Administration Advanced Very High-Resolution Radiometer), MODIS (Moderate Resolution Imaging Spectroradiometer) images and ESA CCI (European Space Agency Climate Change Initiative) land cover maps. We evaluated the effect of cumulative drought on predominant land covers. Our results show years 2000–2001 and 2017–2018 as the driest in the last four decades, and vegetation substantially correlated to drought with spatial and temporal variations across Afghanistan. The most sensitive vegetation response months are June to July and the most significant cumulative drought impacts on vegetation are 6 to 8 months. The predominant land covers more prone to negative effects under severe drought are (in order) shrubland, rainfed cropland, grassland, trees, and irrigated cropland. These findings suggest the sensitivity of vegetation to drought that future national scale drought management should be focused on. This study also demonstrates the usefulness of open-access data to researchers and planners in data-poor countries.

Bisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.

Background: and Purpose: Fuzitang decoction (FZT), a classic prescription of traditional Chinese medicine (TCM), has excellent efficacy in treating gouty arthritis (GA). However, the underlying molecular mechanism remains obscure. In the present study, we aimed to explore the underlying mechanisms of FZT in treating GA by virtual screening combined with experimental verification. Methods: In this study, the active components of FZT and their corresponding targets were screened from the TCMSP database and TargetNet database. Then, the potential targets of FZT against GA were retrieved from multiple databases to generate a network. Protein-protein interaction, herbal-component-target, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were applied to identify potential targets and related signaling pathways. Furthermore, molecular docking simulation was applied to identify the interactions between the drug and targets. Finally, in vitro experiments were conducted to validate the potential targets and signaling pathways. Results: In the present study, several crucial components, including kaempferol, luteolin, catechin, deoxyandrographolide, and perlolyrine in FZT, were obtained through network pharmacology, and several potential targets to treat GA were developed, such as PPARG, CYP3A4, PTGS2 (known as COX2), VEGFA, and CYP1A1. Experimental validation suggested that deoxyandrographolide significantly suppressed the expression of IL-1β, COX2, NLRP3 and IL-6 in inflammatory monocyte cells. Conclusions: Our results identified a novel anti-inflammatory compound, deoxyandrographolide, which helps to explain the potential mechanism of FZT in treating GA and provides evidence to support FZT's clinical use.

Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, insulin resistance, and disorders of glucose and lipid metabolism cause vascular endothelial cell damage. Endothelial dysfunction is a key feature of diabetic vascular complications such as diabetic nephropathy, retinopathy, neuropathy, and atherosclerosis. Importantly, cell death is thought to be a key factor contributing to vascular endothelial injury. Morphologically, cell death can be divided into three forms: type I apoptosis, type II autophagy, and type III necrosis. According to the difference in function, cell death can be divided into accidental cell death (ACD) and regulated cell death (RCD). RCD is a controlled process involving numerous proteins and precise signaling cascades. Multiple subroutines covered by RCD may be involved in diabetic endothelial dysfunction, including apoptosis, autophagy, necroptosis, pyroptosis, entosis, ferroptosis, ferroautophagy, parthanatos, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, cuproptosis, and PANoptosis. This article briefly reviews the mechanism and significance of cell death associated with diabetic endothelial dysfunction, which will help deepen the understanding of diabetic endothelial cell death and provide new therapeutic ideas.

Background: Patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome have a worse prognosis compared to AIH or PBC alone and accurately predicting the severity and dynamically monitoring the progression of disease are therefore essential. We aimed to develop a nomogram-based model to predict advanced liver fibrosis in patients with AIH-PBC overlap syndrome. Methods: A total of 121 patients with AIH-PBC overlap syndrome were retrospectively included and randomly assigned to a development set and a validation set. Backward stepwise regression's best model with the lowest AIC was employed to create a nomogram. Diagnose accuracy was evaluated using the area under the receiver operator characteristic curve (AUROC), calibration analysis, and decision curve analysis (DCA) and was compared with aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors-4 (FIB-4) score. Results: The median age of patients was 53.0 years (IQR: 46.0–63.0), and female patients accounted for 95.0 %. Platelets, globulin, total bilirubin, and prothrombin time were associated with advanced fibrosis (≥S3) and used to construct an AIH-PBC overlap syndrome fibrosis (APOSF)-nomogram (available online at https://ndth-zzy.shinyapps.io/APOSF-nomogram/). The AUROCs of APOSF-nomogram were 0.845 (95 % CI: 0.754–0.936) and 0.843 (95 % CI: 0.705–0.982) in development set and validation set respectively, which was significantly better than APRI and FIB-4. Calibration revealed that the estimated risk fits well with biopsy-proven observation. DCA outperformed APRI and FIB4 in terms of net benefit, demonstrating clinical utility. Conclusion: This novel non-invasive web-based online APOSF-nomogram provided a convenient tool for identifying advanced fibrosis in patients with AIH-PBC overlap syndrome. Further prospective, multicenter studies with large sample size are necessary to validate the applicability of APOSF-nomogram.

Background/purpose: Periodical replacement of venous Hickman catheters is required for the nutritional care of patients with intestinal failure. The conventional de novo operation (DN-OP) involves inserting the catheter into a new venous tract in each replacement; however, this could result in fast consumption of functional central vessels in patients with intestinal failure. Recently, same-route operation (SR-OP) has been adopted as an alternative approach for retaining venous access. Methods: We conducted a retrospective study to compare the efficacy of Hickman catheters and the survival of venous vessels using two different operative strategies. Results: Overall, 181 catheters were inserted, 109 using DN-OP and 72 using SR-OP. The mean catheter duration was 11.9 ± 8.8 months in the DN-OP group and 10.5 ± 5.6 months in the SR-OP group; the infection rate was 0.74 in the DN-OP group and 0.44 in the SR-OP group. The vein accesses used in these insertions (n = 113) were classified: the DN-vein group for veins accessed only by DN-OP (n = 75) and the SR-vein group for veins accessed by an initial DN-OP and subsequent SR-OPs (n = 38). Mean working duration per vein access was 12.3 ± 10.1 months in the DN-vein group and 28.2 ± 14.8 months in the SR-vein group (p

Objective: This study aimed to examine the correlation between smoking, alcohol drinking, and the prognosis of Nasopharyngeal Carcinoma (NPC). Methods: Clinical data from 721 NPC cases treated at our hospital between January 2005 and December 2010 were collected. Information on smoking and drinking, including duration, daily quantity, and cumulative amount, was recorded and graded according to WHO standards. Statistical analysis was performed to assess the influence of smoking and alcohol drinking on NPC patient prognosis. After controlling for confounding factors, survival analysis compared the 5-year Progression-Free Survival rate (PFS) and Overall Survival rate (OS) among patients with varying degrees of smoking and drinking. The association between smoking, drinking, cumulative amount, and NPC patient prognosis was evaluated. Multivariate Cox regression analysis was then employed, considering patient demographic characteristics and clinical features, to comprehensively analyze prognostic influencing factors in NPC patients. Additionally, the multivariate Cox regression analysis was utilized to comprehensively examine the influencing factors of prognosis, taking into account the patients' basic demographic characteristics and clinical features. The findings revealed significant differences in the aforementioned rates. Results: (1) Analysis of PFS and OS differences in NPC patients considered smoking status, smoking duration, daily smoking quantity, and cumulative smoking amount. No significant influence of smoking on NPC patient PFS and OS within 5-years was observed (p > 0.05). (2) Non-drinkers with NPC exhibited higher 5-year PFS and OS rates compared to drinkers (p = 0.047, p = 0.026). Furthermore, non-drinkers and those with a drinking duration of less than 120 months or between 120–240 months showed higher 5-year PFS and OS rates than individuals with a drinking duration exceeding 240 months (p

Objective: In recent years, as the modern economy rapidly advances, and urbanization continues to flourish, Anhui Province has emerged as a significant hub for Wushu, boasting a rich historical tradition in this martial art form. However, despite this heritage, Wushu often remains associated with traditional sports, and the growth of the Wushu cultural industry has not been as robust as desired. This paper seeks to harness the potential of the Internet of Things (IoT) and capitalize on the burgeoning trends within the cultural industry to foster the development of Chinese Wushu. The primary objective of this study is to explore strategies for advancing the Wushu cultural industry in Anhui Province, leveraging IoT technology. To achieve this goal, we employ a novel approach, combining SWOT (Strength, Weakness, Opportunity, Threat) analysis with Analytic Hierarchy Process (AHP), providing a quantitative assessment of the region's Wushu cultural industry development. This approach minimizes subjective bias and offers a sound theoretical foundation for industrial progress. Our research yields promising results, as we effectively integrate Wushu, culture, and tourism. This not only facilitates the dissemination and popularization of Wushu culture but also enhances the appeal of local tourism resources. Notably, the fifth World Wushu Championship experienced sustained popularity, and in 2014, Anhui Province successfully hosted the sixth edition of the event in Jiuhuashan, yielding a significant income of 170 million yuan. The development of the Wushu cultural industry in Anhui Province has exhibited positive growth trends and garnered considerable attention. This study underscores the importance of embracing IoT technology and aligning with broader cultural industry trends to nurture the development of Chinese Wushu. The implications of our research extend to the realms of tourism, culture, and sports, offering valuable insights into leveraging technology for the advancement of traditional practices. This study represents a novel exploration of the intersection between Wushu and IoT technology, with the potential to inform and inspire further research in this evolving field.

Introduction and Objectives: Assessment of liver inflammation plays a vital role in the management of patients with autoimmune hepatitis (AIH). We aimed to establish and validate a nomogram to predict severe liver inflammation in AIH patients. Patients and Methods: AIH patients who underwent liver biopsy were included and randomly divided into a training set and a validation set. Independent predictors of severe liver inflammation were selected by the least absolute shrinkage and selection operator regression from the training set and used to conduct a nomogram. Receiver characteristic curves (ROC), calibration curves, and decision curve analysis (DCA) were adopted to evaluate the performance of nomogram. Results: Of the 213 patients, female patients accounted for 83.1% and the median age was 53.0 years. The albumin, gamma-glutamyl transpeptidase, total bilirubin, red cell distribution width, prothrombin time, and platelets were independent predictors of severe inflammation. An online AIHI-nomogram was established and was available at https://ndth-zzy.shinyapps.io/AIHI-nomogram/. The calibration curve revealed that the AIHI-nomogram had a good agreement with actual observation in the training and validation sets. The area under the ROCs of AIHI-nomogram were 0.795 in the training set and 0.759 in the validation set, showing significantly better performance than alanine aminotransferase and immunoglobulin G in the training and validation sets, as well in AIH patients with normal ALT in the training set. DCA indicated that the AIHI-nomogram was clinically useful. Conclusions: This novel AIHI-nomogram provided an excellent prediction of severe liver inflammation in AIH patients and could be used for the better management of AIH.

Ovarian aging is a significant challenge in gynecology, and there is currently no effective treatment for it. However, the medicinal agent Qingxin Zishen decoction (QZD) has shown potential in the treatment of ovarian dysfunction. The present study aimed to evaluate the mitochondrial apoptotic mechanism of delayed ovarian aging in QZD in aging rats. The healthy female Sprague-Dawley (SD) rats (n = 40, 350 ± 20 g) were randomly assigned to different dosage groups and 4-month-old SD rats (n = 10) were assigned to the control group. QZD groups were treated with QZD for four weeks, and ovarian tissues were extracted for mRNA and protein assays to examine the role of the apoptotic pathway in QZD. The results showed that QZD treatment for four weeks significantly increased the mRNA and protein expressions of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2) and Bcl-2/Bax ratio, as well as downregulated the pro-apoptotic genes Bax, caspase-3, and caspase-9. Moreover, QZD treatment effectively reduced the expression of cytochrome C (cyto-C) and apoptotic protease-activating factor 1 (Apaf-1), both of which are components of the intrinsic apoptotic pathway. These changes exhibited a dose-response manner. The findings suggest that QZD might have therapeutic potential in delaying ovarian mitochondrial function decline and in preventing and treating ovarian aging-related diseases by downregulating and upregulating the pro-apoptotic (Bax, caspase-3, caspase-9, cyto-C, Apaf-1) and anti-apoptotic (Bcl-2 and Bcl-2/Bax ratio) genes, respectively.

Purpose: In this study, we aimed to assess the geographic distribution and molecular characteristics of β-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia–Pacific region. Method: Isolates were investigated for extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing. Result: A total of 832 Enterobacterales isolates from 8 different countries with β-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC β-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC β-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %. Conclusion: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia–Pacific region.

Background: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. Methods: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0–18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. Results: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017–2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. Conclusions: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

In order to control the large deformation of tunnel surrounding rock, a new energy-absorbing bolt is developed. This bolt can be transformed into a rigid support when the deformation of the surrounding rock reaches the length of the sleeve tube, thus preventing the surrounding rock from continuing to deform. Moreover, this bolt has a simple structure and is easy to manufacture and assemble. Then the static tensile test is conducted on the bolt specimen to test its working performance. The test results show that when the cone angle of the cone block is small, the load–displacement curve of the bolt contains three stages; when the cone angle is large, the load–displacement curve contains only two stages. Meanwhile, both the average constant resistance and the maximum absorbed energy increase linearly with the increase of cone angle. On this basis, ignoring the influence of shear stress, and it is supposed that the thickness of the sleeve tube is constant, then the theoretical calculation formula of constant resistance for the new bolt is derived, and the rationality of the formula is verified using the static tensile test results. It is found that the error of the calculated result is less than 15% when the cone angle does not exceed 15°. At last, the numerical simulation method is used to analyze the performance of the new bolt. The simulation results indicate that the generation of shear stress and the change of tube thickness during the movement of the cone block are two important factors that cause theoretical errors.

In plants, a large number of anthocyanin biosynthetic genes encoding enzymes and regulatory genes encoding transcription factors are required for anthocyanin synthesis. Coleoptile purple lines are two purple lines on both sides of coleoptiles after seed germination. However, the molecular mechanism of coleoptile purple line is not clear in rice so far. In this study, two major dominant genes, coleoptile purple line 1 (OsCPL1, also known as OsC1) and coleoptile purple line 2 (OsCPL2), were isolated via map-based cloning, and both of them were required for anthocyanin biosynthesis of coleoptile purple line in rice. The knockout and complementation experiments confirmed that OsC1 was required for purple color in most organs, such as coleoptile line, sheath, auricle, stigma and apiculus, whereas OsCPL2 was just required for coleoptile purple line. OsC1 was predominantly expressed in coleoptiles, flag leaves, and green panicles, and highly expressed in young leaves, whereas OsCPL2 was predominantly expressed in coleoptiles, and extremely lowly expressed in the other tested organs. Loss-of-function of either OsC1 or OsCPL2 resulted in significant reduction of transcript levels of multiple anthocyanin biosynthesis genes in coleoptiles. Coleoptile purple line was further used as a marker trait in hybrid rice. Purity identification in hybrid rice seeds via coleoptile purple line just needed a little water, soil and a small plate and could be completed within 5 d. Molecular marker and field identification analyses indicated that coleoptile purple line was reliable for the hybrid seed purity identification. Our findings disclosed that coleoptile purple line in rice was regulated by two major dominant genes, OsC1 and OsCPL2, and can be used as a simple, rapid, accurate and economic marker trait for seed purity identification in hybrid rice.

In this work, N-[2-(3-indolyl)ethyl]-cinnamamide (IA) synthesized from tryptamine (TA) and cinnamic acid was evaluated as green corrosion inhibitor for Q235 steel in 0.5 M HCl solution by weight loss tests, potentiodynamic polarization (PDP) curve and electrochemical impedance spectroscopy (EIS). Gravimetric measurements displayed the maximum inhibition efficiencies of TA and IA at 1.0 mM were up to 92.8% and 97.6%, respectively. PDP and EIS studies revealed they could hinder both hydrogen evolution and metal dissolution reactions and that the inhibiting effect was temperature and concentration dependent. The surface analysis of sample was presented through scanning electron microscope (SEM), energy dispersive spectroscopy (EDX) and atomic force microscope (AFM), which indicated the anti-corrosion ability of Q235 steel in hydrochloric acid was enhanced by the inhibitor. The adsorptive behavior of inhibitors including physisorption and chemisorption obeyed Langmuir isotherm. The inhibition mechanism was elucidated by determining the potential of zero charge (Epzc) at solid/liquid interface. Quantum chemistry calculation provided a theoretical estimate of the reactivities of TA and IA as corrosion inhibitors to ascertain the correlation between the inhibition efficiency and molecular structures. Results of molecular dynamics (MD) simulations confirm that IA shows better inhibitive performance due to higher interaction energy (– 79.1 kJ mol−1 for TA and – 144.16 kJ mol−1 for IA).

In this study, the Al–KBF4–K2TiF6–Y in situ reaction system was used to prepare rare earth (RE) element Y-modified TiB2 ceramic particles reinforced 7055 aluminum alloy welding consumables for inert gas shielded welding of spray-formed 7055 aluminum alloy. Compared with 0 Y- weld metal (WM), the grain size of the 0.1 Y-WM was refined from 30 μm to 25 μm. In the as-welded state, the tensile strength and elongation of 0 Y-7xxx and 0.1 Y-7xxx joints were 295 ± 6 MPa and 4.92 ± 0.24%, 327 ± 5 MPa and 6.45 ± 0.25%, respectively. The tensile strength and elongation of 0 Y-7xxx and 0.1 Y-7xxx joints after T6 heat treatment were 521 ± 5 MPa and 3.47 ± 0.24%, 557 ± 6 MPa and 4.84 ± 0.25%, respectively. The elongation of the 0.1Y-7xxx joint is 55.47% higher than that of the 0 Y-7xxx joint. The introduction of rare earth elements Y can improve the wettability of TiB2 particles and the substrate so that TiB2 particles are uniformly dispersed, and at the same time make TiB2 particles edge blunting, thereby improving the mechanical properties of welded joints.

Background: Asthma is the most prevalent chronic inflammatory ailment, which has major communal health implications for both adults and children worldwide. Flavokawain is a chalcones present in kawa plant extracts. They have anti-inflammatory, antioxidant, anti-cancer, antimicrobial, and other activities. Methods: In the present investigation, the potential of flavokawain on the IL-4-induced 16HBE cell line and the ovalbumin (OVA)-induced mouse model was analyzed. Results: The findings revealed that the IL-4-induced 16HBE cell line treated with flavokawain reduced cell apoptosis and increased cell proliferation. The NLRP3 inflammasome activity was suppressed by flavokawain. The level of immune cells was increased in the asthmatic mice, which was effectively reduced by the treatment with flavokawain. IgE, eotaxin, TNF-α and TXB levels were decreased by the flavokawain treatment in the asthmatic mice. Imbalances in Th1 and Th2 cytokines were effectively modulated by the flavokawain treatment in the asthmatic mice. The balance between the Th1 cytokines (IL-12 and IFN-γ) and the Th2 cytokines (IL-4, IL-5, IL-6, and IL-13) was maintained by flavokawain. The histopathology study of lungs revealed that the thickness of the airway membrane and inflammatory cell infiltration was reduced by the flavokawain, which indicates the decrease in inflammation. Conclusion: These findings recommend that flavokawain can be used as a potent candidate to treat asthma in the future.

Skin aging is a complex process involving intricate genetic and environmental factors. In this study, we performed a comprehensive analysis of the transcriptional regulatory landscape of skin aging in canines. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify aging-related gene modules. We subsequently validated the expression changes of these module genes in single-cell RNA sequencing (scRNA-seq) data of human aging skin. Notably, basal cell (BC), spinous cell (SC), mitotic cell (MC), and fibroblast (FB) were identified as the cell types with the most significant gene expression changes during aging. By integrating GENIE3 and RcisTarget, we constructed gene regulation networks (GRNs) for aging-related modules and identified core transcription factors (TFs) by intersecting significantly enriched TFs within the GRNs with hub TFs from WGCNA analysis, revealing key regulators of skin aging. Furthermore, we demonstrated the conserved role of CTCF and RAD21 in skin aging using an H2O2-stimulated cell aging model in HaCaT cells. Our findings provide new insights into the transcriptional regulatory landscape of skin aging and unveil potential targets for future intervention strategies against age-related skin disorders in both canines and humans.

Air quality prediction is a typical Spatiotemporal modeling problem, which always uses different components to handle spatial and temporal dependencies in complex systems separately. Previous models based on time series analysis and recurrent neural network (RNN) methods have only modeled time series while ignoring spatial information. Previous graph convolution neural networks (GCNs) based methods usually require providing spatial correlation graph structure of observation sites in advance. The correlations among these sites and their strengths are usually calculated using prior information. However, due to the limitations of human cognition, limited prior information cannot reflect the real station-related structure or bring more effective information for accurate prediction. To this end, we propose a novel Dynamic Graph Neural Network with Adaptive Edge Attributes (DGN-AEA) on the message passing network, which generates the adaptive bidirected dynamic graph by learning the edge attributes as model parameters. Unlike prior information to establish edges, our method can obtain adaptive edge information through end-to-end training without any prior information. Thus reducing the complexity of the problem. Besides, the hidden structural information between the stations can be obtained as model by-products, which can help make some subsequent decision-making analyses. Experimental results show that our model received state-of-the-art performance than other baselines.

Aminoacyl-tRNA synthetases (aaRSs) are indispensable players in translation. Usually, two or three genes encode cytoplasmic and mitochondrial threonyl-tRNA synthetases (ThrRSs) in eukaryotes. Here, we reported that Caenorhabditis elegans harbors only one tars-1, generating cytoplasmic and mitochondrial ThrRSs via translational reinitiation. Mitochondrial tars-1 knockdown decreased mitochondrial tRNAThr charging and translation and caused pleotropic phenotypes of delayed development, decreased motor ability and prolonged lifespan, which could be rescued by replenishing mitochondrial tars-1. Mitochondrial tars-1 deficiency leads to compromised mitochondrial functions including the decrease in oxygen consumption rate, complex Ⅰ activity and the activation of the mitochondrial unfolded protein response (UPRmt), which contributes to longevity. Furthermore, deficiency of other eight mitochondrial aaRSs in C. elegans and five in mammal also caused activation of the UPRmt. In summary, we deciphered the mechanism of one tars-1, generating two aaRSs, and elucidated the biochemical features and physiological function of C. elegans tars-1. We further uncovered a conserved connection between mitochondrial translation deficiency and UPRmt.

This study explores the reasons (for and against) the adoption of AI in the hospitality industry among Pakistani customers. The hypothesis was tested using the sample obtained from Pakistani hospitality customers. The data is collected via an online survey and analyzed with the structural equation modeling and PROCESS macro. The study results indicate that cultural values positively associate reasons for, attitudes, and intentions to adopt. Moreover, the results prove that attitude mediates the relationship between reasons (for and against) and intention to adopt AI services in hospitality. Furthermore, the finding shows that customer emotional intelligence has no moderation effect on attitude and intention to adopt AI services. This study highlights technological complexity and safety concerns are the most significant barriers in the studied context. Further, addressing reason against (technological complexity and safety concerns) may allow policymakers to lessen the present customer attitude-intention gap by tackling the factors that cause customers to resist adopting AI services in hospitality. In this respect, marketers should develop a marketing campaign strategy focusing on the benefits of the adoption of AI services in comparison to employee service. This is the first empirical study examining cultural values, reasons (for and against) attitudes, their relationship with intentions, and moderating role of an attractive, important, yet ignored variable, customer emotional intelligence. This study confirms that the behavioral reasoning theory can better describe the customers' adoption behavior of AI services in the hospitality sector.

Study region: Major urban areas in Henan Province of central China. Study focus: data fusion technology is also a key and difficult point in the field of flood research. Remote sensing and text data have different modalities and scales, making fusion difficult. This study proposed a remote sensing and text bimodal data fusion model based on UFCLI, and we validated the spatiotemporal distribution of floods and the calculation results of disaster losses. The results show that through the coupling analysis of remote sensing and text bimodal data, rainstorm and flood events can be fully reproduced in space and time. The proposed UFCLI effectively improves the accuracy of remote sensing single-data inversion for urban flood disaster losses. The flood loss in Henan is 121.98 billion yuan, and the accuracy improvement result is R² increased by 0.08 and MAPE decreased by 0.88. New hydrological insights for the region: In the case of sudden urban storm flooding with complex spatial and temporal evolution, the traditional hydrological-hydraulic model has many pending parameters, which makes it difficult to accurately calculate large-scale disaster losses. By establishing a theoretical model of bimodal data fusion, we effectively use the complementary spatiotemporal information using remote sensing and text to solve the differences in spatiotemporal scales existing between remote sensing and text data. The timeliness and accuracy of urban flood damage estimation have further improved. Data Availability Statement: Not applicable.

Due to the brittle weld joints and worsening hot cracking tendency of spray-formed (SF) 7055 aluminum alloy, they are regarded as un-weldable. In this study, TiB2–Al3Ti/7055 (MA) aluminum matrix composites manufactured by the master alloy method were used to connect SF 7055 aluminum alloy. In the as-weld state, ceramic particles refine α-Al grains in weld metal (WM) and reduce the hot cracking tendency of weld joints. The tensile properties of weld joints increased from 240 ± 5 MPa, 1.4 ± 0.24% (7055) to 284 ± 5 MPa, 4.0 ± 0.35% (MA). In the heat treatment states (T6, T76, and RRA), the mechanical properties and corrosion resistance of MA-WM are superior to 7055-WM. The tensile strength of MA-T6 (485 ± 20 MPa, 3.10 ± 0.23%) is the best of the three heat treatment states, while the corrosion resistance of MA-T76 is the best. MA-RRA gains mechanical properties similar to MA-T6 and corrosion resistance close to MA-T76.

Many inflammatory and infectious entities can affect the peritoneum acutely, and patients with peritonitis often have painful expressions. Abdominal pain can be aggravated by coughing, breathing, and turning the body. Here we report the case of an 88-year-old patient with acute gastrointestinal perforation. The patient has been experiencing pain in the right lower abdomen, presenting persistent colic. The X-ray of abdomen and abdominal computed tomography showed perforation of digestive tract. In addition to the use of anti-infection and stomach protection agents, we use different analgesic injections, but the effect on reducing the pain was not obvious. After acupuncture treatment, the patient quickly relieved the pain of acute peritonitis in 1 minute. However, to our knowledge, there is few literature showing that acupuncture relieves preoperative opioid-induced hyperalgesia in patients with acute peritonitis. Based on this case, we suggest acupuncture as an option in the management of relieving the pain of acute peritonitis when opioid therapy is ineffective.

Summary: Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAFBhi microglia, as well as astrocytes and vascular cells with signatures of altered metabolism, oxidative stress, and interferon response. Furthermore, snRNA-seq provides insights into how brain cell types connect and interact, defining complex circuitries that impact demyelination and remyelination. As an explicative example, perturbation of microglia caused by TREM2 deficiency indirectly impairs the induction of DOLs. Altogether, this study provides a rich resource for future studies investigating mechanisms underlying demyelinating diseases.

Summary: Here, we present a protocol to efficiently direct human pluripotent stem cells (hPSCs) into hematopoietic stem and progenitor cells (HSPCs) under a chemically defined, albumin-free system. We describe the induction of aorta-gonad-mesonephros-like hematopoiesis from hPSCs into SOX17+ hemogenic endothelium and then into CD34+CD45+ HSPCs via application of Wnt activator and TGFβ inhibitor, respectively. The generated HSPCs, characterized by flow cytometry and colony-forming unit assay, express definitive hematopoiesis markers and exhibit multilineage differentiation potential and the capacity to expand.For complete details on the use and execution of this protocol, please refer to Chang et al. (2022a, 2022b).1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Glioblastoma (GBM) is the deadliest primary brain tumor and is generally resistant to immunotherapy because of severe dysfunction of T cells. Novel treatment options are critically needed to overcome the immunotherapy resistance of GBM. Here we demonstrate that Zika virus (ZIKV) treatment improves the efficacy of anti-PD ligand 1 (PD-L1) immunotherapy in GBM. We found that ZIKV induces a strong pro-inflammatory response and increases CD4+ and CD8+ T cell intratumoral infiltration and activation in GBM mouse models. ZIKV treatment of mice bearing GBM tumors inhibits tumor growth and prolongs survival. These therapeutic effects of ZIKV on GBM tumors are negated in mice depleted of T cells. Moreover, ZIKV dramatically promotes activation of the type I interferon signaling pathway in GBM cells. ZIKV treatment potently sensitizes GBM to PD-L1 blockade and provides significant and durable survival benefits. Our findings reveal that ZIKV overcomes the resistance of GBM to immune checkpoint blockade, which may lead to therapeutic applications of ZIKV in individuals with GBM receiving immunotherapy.