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Abstract Background Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. Methods In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. Results Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. Conclusions OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

Abstract Recent advancements in artificial intelligence (AI) have led to an increased use of large language models (LLMs) for language assessment tasks such as automated essay scoring (AES), automated listening tests, and automated oral proficiency assessments. The application of LLMs for AES in the context of non-native Japanese, however, remains limited. This study explores the potential of LLM-based AES by comparing the efficiency of different models, i.e. two conventional machine training technology-based methods (Jess and JWriter), two LLMs (GPT and BERT), and one Japanese local LLM (Open-Calm large model). To conduct the evaluation, a dataset consisting of 1400 story-writing scripts authored by learners with 12 different first languages was used. Statistical analysis revealed that GPT-4 outperforms Jess and JWriter, BERT, and the Japanese language-specific trained Open-Calm large model in terms of annotation accuracy and predicting learning levels. Furthermore, by comparing 18 different models that utilize various prompts, the study emphasized the significance of prompts in achieving accurate and reliable evaluations using LLMs.

Abstract Background This study aimed to analyze the relationship between physical activity and the risk of premenstrual syndrome among college students. Methods Eligible studies were searched from the PubMed, Web of Science, and Embase databases. The link between physical activity and the risk of premenstrual syndrome was evaluated using odds ratio (OR) and 95% confidence interval (CI). The heterogeneity of the included studies was tested and their sources were explored by subgroup analysis. A sensitivity analysis was performed to assess the effect of a single study on the pooled results. The included studies were evaluated for publication bias. Five moderate-quality studies were included in this meta-analysis. Results Physical activity levels were negatively associated with risk of premenstrual syndrome among college students (OR [95%CI] = 1.46 [1.09, 1.96], P = .011). The pooled results were not influenced after being stratified by the study region and whether multi-factor correction was performed or not. Publication bias was not observed in the included studies. Conclusion A high level of physical activity is dramatically associated with a reduced risk of premenstrual syndrome among female college students.

Abstract Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is highly expressed in both gastric cancer tissues and exosomes derived from plasma. Increased circATP8A1 was associated with advanced TNM stage and worse prognosis in patients with gastric cancer. We showed that the circATP8A1 knockdown significantly inhibited gastric cancer proliferation and invasion in vitro and in vivo. Functionally, exosome circATP8A1 induced the M2 polarization of macrophages through the STAT6 pathway instead of the STAT3 pathway. Mechanistically, circATP8A1 was shown to activate the STAT6 pathway through competitive binding to miR-1-3p, as confirmed by Fluorescence In Situ Hybridization (FISH), RNA immunoprecipitation, RNA pulldown, and Luciferase reporter assays. The reversal of circATP8A1-induced STAT6 pathway activation and macrophage polarization was observed upon blocking miR-1-3p. Macrophages treated with exosomes from gastric cancer cells overexpressing circATP8A1 were able to promote gastric cancer migration, while knockdown of circATP8A1 reversed these effects in vivo. In summary, exosome-derived circATP8A1 from gastric cancer cells induce macrophages M2 polarization via the circATP8A1/miR-1-3p/STAT6 axis, and tumor progression. Our results highlight circATP8A1 as a potential prognostic biomarker and therapeutic target in gastric cancer.

Abstract The development of highly active, reusable catalysts for aqueous‐phase reactions is challenging. Herein, metallic nickel is encapsulated in a nitrogen‐doped carbon–silica composite (SiO2@Ni@NC) as a catalyst for the selective hydrogenation of vanillin in aqueous media. The constructed catalyst achieved 99.8% vanillin conversion and 100% 4‐hydroxymethyl‐2‐methoxyphenol selectivity at room temperature. Based on combined scanning transmission electron microscopy, X‐ray photoelectron spectroscopy, and Raman analyses, the satisfactory catalytic performance is attributed to the composite structure consisting of an active metal, carbon, and silica. The hydrophilic silica core promoted dispersion of the catalyst in aqueous media. Moreover, the external hydrophobic NC layer has multiple functions, including preventing oxidation or leaching of the internal metal, acting as a reducing agent to reduce the internal metal, regulating the active‐site microenvironment by enriching the concentrations of H2 and organic reactants, and modifying the electronic structure of the active metal via metal–support interactions. Density functional theory calculations indicated that NC facilitates vanillin adsorption and hydrogen dissociation to promote aqueous‐phase hydrogenation. This study provides an efficient strategy for constructing encapsulated Ni‐based amphiphilic catalysts to upgrade biomass‐derived compounds.

Abstract Bacillus Calmette-Guèrin - vaccination induces not only protection in infants and young children against severe forms of tuberculosis, but also against non-tuberculosis related all-cause mortality. To delineate different factors influencing mycobacterial growth control, here we first investigate the effects of BCG-vaccination in healthy Dutch adults. About a quarter of individuals already control BCG-growth prior to vaccination, whereas a quarter of the vaccinees acquires the capacity to control BCG upon vaccination. This leaves half of the population incapable to control BCG-growth. Single cell RNA sequencing identifies multiple processes associated with mycobacterial growth control. These data suggest (i) that already controllers employ different mechanisms to control BCG-growth than acquired controllers, and (ii) that half of the individuals fail to develop measurable growth control irrespective of BCG-vaccination. These results shed important new light on the variable immune responses to mycobacteria in humans and may impact on improved vaccination against tuberculosis and other diseases.

Forward-looking imaging and target detection are highly desirable in many military and civilian fields, such as search and rescue, sea surface surveillance, airport surveillance, and guidance. However, during the processing procedure, imaging and target detection are usually regarded as two independent parts, which means that the imaging result will directly affect the detection performance. In this article, the LRSD-ADMM-net is proposed to achieve simultaneous super-resolution imaging and target detection for forward-looking scanning radar. First, low-rank and sparse constraints as regularization norms are incorporated to establish objective function, and the alternating direction multiplier method is used to solve simultaneous super-resolution and target detection problems. Then, the solving process is expanded into a neural network, where the weight parameters of each level are obtained through adaptive learning. At last, experiments are conducted to verify the effectiveness of the proposed method.

● This study clarified the critical processes and major factors that nitrogen transport from farm fields to surface water bodies.● Soil storage, exogenous inputs and meteorological hydrology were found to influence nitrogen loss from farmland.● Hydrology, biogeochemistry and nitrogen inputs were found to influence the transformation of nitrogen in the ditches and rivers. Agricultural non-point source pollution is increasingly an important issue affecting surface water quality. Currently, the majority of the studies on nitrogen loss have focused on the agricultural field scale, however, the response of surface water quality at the watershed scale into the nitrogen loss at the field scale is poorly understood. The present study systematically reviewed the critical processes and major factors that nitrogen transport from farm fields to surface water bodies. The critical processes of farmland nitrogen entering surface water bodies involve the processes of nitrogen transport from farmland to ditches and the transformation processes of nitrogen during migration in ditches/rivers. Nitrogen transport from farmland to ditches is one of the prerequisites and critical processes for farmland nitrogen transport to surface water bodies. The transformation of nitrogen forms in ditches/rivers is an intermediate process in the migration of nitrogen from farmland to surface water bodies. Nitrogen loss from farmland is related to soil storage and exogenous inputs. Therefore, nitrogen input management should not only consider the current input, but also the contribution of soil storage due to the historical surpluses. Ditches/rivers have a strong retention capacity for nitrogen, which will significantly affect the process of farmland nitrogen entering surface water bodies. The factors affecting nitrogen transformation in river/ditches can be placed in four categories: (1) factors affecting hydraulic retention time, (2) factors affecting contact area, (3) factors affecting biological activity, and (4) forms and amount of nitrogen loading to river/ditches. Ditch systems are more biologically (including plants and microbes) active than rivers with biological factors having a greater influence on nitrogen transformation. When developing pollution prevention and control strategies, ecological ditches can be constructed to increase biological activity and reduce the amount of surplus nitrogen entering the water body. The present research should be valuable for the evaluation of environment impacts of nitrogen loss and the non-point source pollution control.

ABSTRACTLong-term consumption of rapidly digestible starches is a major factor associated with diabetes and other metabolic diseases. In this study, cassava starch (CS) was used to investigate interactions between starch and different forms of glutenin protein and the effect of these interactions on in vitro digestibility. First, CS and natural glutenin (Glu), glutenin hydrolysate (GPH), or citric acid modified glutenin (CA-Glu) were heat treated. The physicochemical properties and digestibility of CS were then measured using differential scanning calorimetry, Raman spectroscopy, X-ray diffraction, and in vitro digestion methods. The results showed that Glu, GPH and CA-Glu increased starch gelatinization enthalpy. Glu, GPH, and CA-Glu also enhanced the ordered structure of starch and starch – protein interactions. Further, in vitro digestion studies showed that the addition of glutenin reduced CS digestibility, wherein CA-Glu had the largest impact. These results have implications for reducing effects of the human diet on disease and warrant further study.

Objective: Ameloblastoma (AM) is a prevalent benign odontogenic tumor affecting the jaw bone. Its potential for recurrence and malignant transformation is closely associated with the regulation of signaling pathways. The objective of this study was to examine the expression and clinical significance of Notch1 in AM, along with exploring the correlation between Notch1 expression and AM imaging patterns. Methods: The streptavidin-peroxidase (S-P) immunohistochemical technique was employed to detect the expression of Notch1 protein in the oral mucosa of 70 AM patients and 25 normal controls. Additionally, the preoperative cone-beam computed tomography (CBCT) images of the patients were classified, and the results were analyzed in relation to the expression of Notch1 protein in AM. Results: The positive expression rate of Notch1 in the 70 AM patients was 74.29% (52/70), while the Notch1 expression rate in 26 oral mucosa patients was 19.23% (5/26), indicating a statistically significant difference (P < 0.05). The expression rate of Notch1 was 58.06% in single-room AM and lower in multi-room AM (85.29%) and honeycomb AM (100%) (P < 0.01). However, there was no significant difference in the expression rate of Notch1 between multi-room AM and honeycomb AM (P > 0.05). Conclusion: Notch1 may serve as an important diagnostic indicator in AM, and the apoptosis inhibition ability and cell proliferation ability of single-room AM are lower compared to those of the room and honeycomb types

Summary: Familial Mediterranean fever (FMF) is a periodic fever syndrome caused by variation in MEFV. FMF is known for IL-1β dysregulation, but the innate immune landscape of this disease has not been comprehensively described. Therefore, we studied circulating inflammatory proteins, and the function of monocytes and (albeit less extensively) neutrophils in treated FMF patients in remission. We found that monocyte IL-1β and IL-6 production was enhanced upon stimulation, in concordance with alterations in the plasma inflammatory proteome. We did not observe changes in neutrophil functional assays. Subtle differences in chromatin accessibility and transcriptomics in our small patient cohort further argued for monocyte dysregulation. Together, these observations suggest that the MEFV-mutation-mediated primary immune dysregulation in monocytes leads to chronic inflammation that is subsequently associated with counterregulatory epigenetic/transcriptional changes reminiscent of tolerance. These data increase our understanding of the innate immune changes in FMF, aiding future management of chronic inflammation in these patients.

Summary: Septic cardiomyopathy is associated with high mortality in septic patients, characterized by reversible systolic and diastolic dysfunction. It is essential to monitor cardiac function and hemodynamic changes in septic animals. Here, we present a protocol to monitor cardiac function and hemodynamics in septic rodents. We describe steps for performing cecal ligation and puncture on rodents to induce sepsis, acquiring two-dimensional echocardiographic and M-mode ultrasonic images, and assessing mean arterial pressure in septic animals.For complete details on the use and execution of this protocol, please refer to Zhang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The improvement of nutrients in soil is essential for using deserts and decertified ecosystems and promoting sustainable agriculture. Grapevines are suitable crops for desert soils as they can adapt to harsh environments and effectively impact soil nutrients; however, the mechanisms underlying this remain unclear. This study explored the impact of the different duration(3, 6, and 10 years) of grape cultivation on soil organic carbon, physicochemical properties, enzyme activities, microbial communities, and carbon cycle pathways in both rhizosphere and bulk soils. Partial least squares path modeling was used to further reveal how these factors contributed to soil nutrient improvement. Our findings indicate that after long-term grape cultivation six years, soil organic carbon, total nitrogen, total phosphorus, microbial biomass carbon and nitrogen, and enzyme activities has significantly increased in both rhizosphere and bulk soils but microbial diversity decreased in bulk soil. According to the microbial community assembly analysis, we found that stochastic processes, particularly homogenizing dispersal, were dominant in both soils. Bacteria are more sensitive to environmental changes than fungi. In the bulk soil, long-term grape cultivation leads to a reduction in ecological niches and an increase in salinity, resulting in a decrease in soil microbial diversity. Soil enzymes play an important role in increasing soil organic matter in bulk soil by decomposing plant litters, while fungi play an important role in increasing soil organic matter in the rhizosphere, possibly by decomposing fine roots and producing mycelia. Our findings enhance understanding of the mechanisms of soil organic carbon improvement under long-term grape cultivation and suggest that grapes are suitable crops for restoring desert ecosystems.

It is essential to determine the occurrence of emerging organic contaminants (EOCs), such as pharmaceuticals and personal care products (PPCPs), in the ambient environment to address growing public concerns. However, such analysis is quite challenging due to the low trace level of such contaminants in water, which therefore requires several litres of water samples. In this study, a large volume solid phase extraction (LV-SPE) device was developed and evaluated for its performance in monitoring PPCPs as an example. Relatively good recoveries and reproducibility were obtained under specific operating conditions: a water sample volume of no more than 20 L, a flow rate not exceeding 120 mL/min, and a methanol elution volume of at least 30 mL. In addition, the results from the onsite enrichment approach using LV-SPE were compared with those from the conventional approach using a standard SPE device in the laboratory for real groundwater samples. Among the eight selected PPCPs (nalidixic acid, carbamazepine, bezafibrate, clofibric acid, sulfadiazine, sulfamethoxypyridazine, sulfamethazine and sulfamonomethoxine), LV-SPE approach detected more target compounds. While the detected concentrations were generally comparable, slightly higher concentrations were observed for carbamazepine, clofibric acid, sulfadiazine and sulfamethazine using the LV-SPE method. The developed LV-SPE device provides an alternative approach for trace analysis of PPCPs and may also be applicable for other emerging organic contaminants.

The escalating proliferation of cyanobacteria poses significant taste and odor (T/O) challenges, impacting freshwater ecosystems, public health, and water treatment costs. We examined monthly variations in four T/O compounds from September 2011 to August 2012 in Chaohu Lake’s eastern drinking water source (DECL). More importantly, we compared the reported T/O occurrence and the related factors in freshwater bodies worldwide. The assessment of T/O issues indicated a severe and widespread problem, with many cases surpassing odor threshold values. Remarkably, China reported the highest frequency and severity of odor-related problems. A temporal analysis revealed variations in odor occurrences within the same water body across different years, emphasizing the need to consider high values in all seasons for water safety. Globally, T/O issues were widespread, demanding attention to variations within the same water body and across different layers. Algae were crucial contributors to odor compounds, necessitating targeted interventions due to diverse odorant sources and properties. A correlation analysis alone lacked definitive answers, emphasizing the essential role of further validation, such as algae isolation. Nutrients are likely to have influenced the T/O, as GSM and MIB correlated positively with nitrate and ammonia nitrogen in DECL, resulting in proposed control recommendations. This study offers recommendations for freshwater ecosystem management and serves as a foundation for future research and management strategies to address T/O challenges.

Rubber concrete has been applied to a certain extent in fatigue-resistant structures due to its good durability. Based on a cohesive model of rubber composed of a five-phase material containing mortar, aggregate, rubber, aggregate-mortar interfacial transition zone (ITZ), and rubber-mortar ITZ, this paper studies the influence of the cohesive parameters in the rubber-mortar ITZ on the fatigue problem of rubber concrete on the mesoscopic scale. As the weak part of cement-based composite materials, the ITZ has a great influence on the mechanical properties and durability of concrete, but the performance of the ITZ is difficult to test in macro experiments, resulting in difficulties in determining its simulation parameters. Based on the cohesive model with a rubber content of 5%, this study uses Monofactor analysis and the Plackett-Burman test to quickly and effectively determine the primary and secondary influences of the cohesive model parameters in the rubber-mortar ITZ; further, the response surface method is used to optimize the cohesive parameters in the rubber-mortar ITZ, and the numerical simulation results after optimizing the cohesive parameters are compared and analyzed with the simulation results before optimization. The results show that, under the setting of the optimized parameters, the simulation results of each item of the optimal cohesive model parameters in the rubber-mortar ITZ are in line with the reality and closer to the experimental data, and they are also applicable to rubber concrete models with different rubber dosing.

It is crucial to simulate the physical processes of blood flow in functional medical materials in order to characterize their functional properties in different scenarios. In this paper, the microscopic obstruction model of blood coagulation by functional hemostatic materials with boundary growth factor is constructed by CFD for the first time. Moreover, the effects of different inlet pressures, temperatures and material shapes on the hemostatic properties of the materials were analyzed using blood flow rate and blockage time as metrics. The researches show that: as blood flows into the material, thrombus begins to form at the boundary and progresses toward the center; smaller inlet pressures promote thrombus growth; external temperature has little effect on thrombus growth; materials possessing smaller flow rates beneficial to thrombus growth; and the larger the cross-sectional area in the material’s flow channel, the faster blood coagulates. This study provides new ideas for characterizing the performance of functional hemostatic materials and the design of hemostatic materials in different application scenarios.

Abstract To date, genome‐wide association studies (GWASs) have discovered 35 susceptible loci of leprosy; however, the cumulative effects of these loci can only partially explain the overall risk of leprosy, and the causal variants and genes within these loci remain unknown. Here, we conducted out new GWASs in two independent cohorts of 5007 cases and 4579 controls and then a meta‐analysis in these newly generated and multiple previously published (2277 cases and 3159 controls) datasets were performed. Three novel and 15 previously reported risk loci were identified from these datasets, increasing the known leprosy risk loci of explained genetic heritability from 23.0 to 38.5%. A comprehensive fine‐mapping analysis was conducted, and 19 causal variants and 14 causal genes were identified. Specifically, manual checking of epigenomic information from the Epimap database revealed that the causal variants were mainly located within the immune‐relevant or immune‐specific regulatory elements. Furthermore, by using gene‐set, tissue, and cell‐type enrichment analyses, we highlighted the key roles of immune‐related tissues and cells and implicated the PD‐1 signaling pathways in the pathogenetic mechanism of leprosy. Collectively, our study identified candidate causal variants and elucidated the potential regulatory and coding mechanisms for genes associated with leprosy.

The most recent meta-analysis of gas cooking and respiratory outcomes in children was conducted by Lin et al. [93] in 2013. Since then, a number of epidemiology studies have been published on this topic. We conducted the first systematic review of this epidemiology literature that includes an in-depth evaluation of study heterogeneity and study quality, neither of which was systematically evaluated in earlier reviews. We reviewed a total of 66 relevant studies, including those in the Lin et al. [93] meta-analysis. Most of the studies are cross-sectional by design, precluding causal inference. Only a few are cohort studies that could establish temporality and they have largely reported null results. There is large variability across studies in terms of study region, age of children, gas cooking exposure definition, and asthma or wheeze outcome definition, precluding clear interpretations of meta-analysis estimates such as those reported in Lin et al. [93]. Further, our systematic study quality evaluation reveals that a large proportion of the studies to date are subject to multiple sources of bias and inaccuracy, primarily due to self-reported gas cooking exposure or respiratory outcomes, insufficient adjustment for key confounders (e.g., environmental tobacco smoke, family history of asthma or allergies, socioeconomic status or home environment), and unestablished temporality. We conclude that the epidemiology literature is limited by high heterogeneity and low study quality and, therefore, it does not provide sufficient evidence regarding causal relationships between gas cooking or indoor NO2 and asthma or wheeze. We caution against over-interpreting the quantitative evidence synthesis estimates from meta-analyses of these studies.

Nanocellulose has various outstanding properties and great potential for replacing petrochemical products. The utilization of lignocellulose to produce nanocellulose is of great significance to the sustainable development of the economy and society. However, the direct extraction of nanocellulose from lignocellulose by chemical method is challenged by toxic chemicals utilization, energy and time consumption, and waste water generation. Therefore, this paper addressed the conversion of lignocellulosic biomass into bacterial nanocellulose (BNC) by the biological method. Moreover, this article highlights the recent advances in potentials and challenges of lignocellulosic biomass for BNC production through the bioconversion process, including biomass pretreatment, enzymatic hydrolysis, glucose and xylose fermentation, GA accumulation, and inhibitor tolerant. The development in metabolic and evolutionary engineering to enhance the production capacity of BNC-producing strain is also discussed. It is expected to provide guidance on the effective bioproduction of nanocellulose from lignocellulosic biomass.

The flowering of Amorphophallus bulbifer (A. bulbifer) plays an important role in its reproduction. The flowers and leaves of A. bulbifer cannot grow at the same time. However, the physiological and molecular mechanisms involved in flower bud and leaf bud formation are still unclear. In this study, the flower buds and leaf buds of A. bulbifer in the early stage of growth were used as research materials, transcriptome and metabolome analyses were carried out, and the soluble sugar and starch contents of A. bulbifer corms were determined. Transcriptome analysis revealed 5542 differentially expressed genes (DEGs) between flower buds and leaf buds, 3107 of which were upregulated and 2435 of which were downregulated. Enrichment analysis of the KEGG pathway showed that these differential genes were enriched mainly in the plant hormone signal transduction, DNA replication and fatty acid elongation pathways. A total of 5296 significant differentially abundant metabolites were screened out by nontargeted metabolomics analysis. The differentially abundant metabolites were functionally classified in the HMDB, and 118 were successfully matched, including 17 that were highly expressed in flower buds. The differentially abundant metabolites in the flower buds were mainly enriched in pathways such as amino acid metabolism, isoquinoline alkaloid biosynthesis and pyrimidine metabolism. Targeted metabolomics analysis revealed that the contents of ABA, ZT and iPA in flower buds were significantly greater than those in leaf buds, while the opposite trend was observed for IAA. The analysis of soluble sugar and starch contents showed that the starch and soluble sugar contents in flower buds were significantly greater than those in leaf buds. The results of this study showed that flower bud development in A. bulbifer was regulated by amino acids, starch, ABA, ZT, iPA, IAA and other hormones. These findings could lead to valuable genetic resources for further study of A. bulbifer flowering and provide a deeper understanding of the molecular basis of A. bulbifer flowering.

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disease which has risen to become the main cause of childhood disability, placing a heavy burden on families and society. To date, the treatment of patients with ASD remains a complicated problem, for which neuromodulation techniques are a promising solution. This study analyzed the global research situation of neuromodulation techniques in the treatment of ASD from 1992 to 2022, aiming to explore the global research status and frontier trends in this field. Methods The Web of Science (WoS) was searched for literature related to neuromodulation techniques for ASD from 1992 to October 2022. A knowledge atlas to analyze collaboration among countries, institutions, authors, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and burst keywords was constructed using Rstudio software, CiteSpace, and VOSviewer. Results In total, 392 publications related to the treatment of ASD using neuromodulation techniques were included. Despite some fluctuations, the number of publications in this field has shown a growing trend in recent years. The United States and Deakin University are the leading country and institution in this field, respectively. The greatest contributing authors are Peter G Enticott, Manuel F Casanova, and Paul B Fitzgerald et al. The most prolific and cited journal is Brain Stimulation and the most commonly co-cited journal is The Journal of Autism and Developmental Disorders. The most frequently cited article was that of Simone Rossi (Safety, ethical considerations, and application guidelines for the use of transverse magnetic stimulation in clinical practice and research, 2009). “Obsessive–compulsive disorder,” “transcranial direct current stimulation,” “working memory,” “double blind” and “adolescent” were identified as hotspots and frontier trends of neuromodulation techniques in the treatment of ASD. Conclusion The application of neuromodulation techniques for ASD has attracted the attention of researchers worldwide. Restoring the social ability and improving the comorbid symptoms in autistic children and adults have always been the focus of research. Neuromodulation techniques have demonstrated significant advantages and effects on these issues. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are new therapeutic methods introduced in recent years, and are also directions for further exploration.

Abstract Background Medication nonadherence is a significant public health problem as it contributes to poor clinical outcomes and increased healthcare costs. Older patients with multimorbidity and polypharmacy often have low medication adherence. These patients also have a high prevalence of potentially inappropriate medication (PIM) use. Aim To explore risk factors related to medication nonadherence in older patients with multimorbidity and polypharmacy and examine the association between medication nonadherence and PIM use. Method A multicenter cross-sectional study was conducted from May to December 2019 in 16 tertiary hospitals from 12 provinces and cities in China. Data were collected from outpatients 65 years or older with multimorbidity and polypharmacy. The PIMs were evaluated using the 2019 Beers Criteria. Self-reported medication adherence was assessed using the Visual Analog Scale (VAS). Results A total of 773 outpatients were recruited. The prevalence of medication nonadherence was 31.8%. In the univariate analysis, nonadherence was significantly associated with sex, cognitive impairment, stroke, visiting the same physicians, self-administration of medication, the percentage of drug costs ≥ 10% of the medical expenses, and PIMs for the alimentary tract and metabolism. In the multivariate analysis, the results almost paralleled those of the univariate associations. Notably, the use of PIM was significantly associated with medication adherence. Conclusion Several factors that influence medication adherence were identified. Targeted interventions can be implemented to improve medication adherence, such as encouraging self-administering medications and reducing medication expenses.

The isolation, purification and enzymatic properties of β-glucosidase from cassava roots were studied. The crude enzyme extract was obtained from cassava roots with buffer solution, and the activity of crude enzyme was 9.37 U/g cassava dry weight. Purified by acetone precipitation, ion exchange chromatography and gel filtration chromatography, β-glucosidase activity was 1.14 U/g cassava dry weight, purified β-glucosidase purity increased by 14.62 times, the total activity recovery was 12.14%, the molecular weight of β-glucosidase was about 70 kDa. The Km and Vmax of the enzyme were 3.60 mmol/L and 12.36 µmol/(min·mg protein) respectively. The optimum pH was 7.0, and it was stable when the pH was between 6.0 and 8.0. It had good stability within 40 ℃, and 81.78% enzyme activity remained after 30 days at 4 ℃. Mn2+ and K+ promoted the enzyme to a certain extent. Al3+, Cu2+, Mg2+, Zn2+, Ca2+, Ba2+, Na+, urea and SDS had no significant effect on the enzyme activity (P>0.05). Fe3+, Fe2+, Ag+ and EDTA all inhibited the enzyme activity to varying degrees, among which Ag+ had the strongest inhibitory effect. The results can provide theoretical basis for the application of β-glucosidase in cassava roots in the future.

A modern power system integrates more and more new energy and uses a large number of power electronic equipment, which makes it face more challenges in online optimization and real-time control. Deep reinforcement learning (DRL) has the ability of processing big data and high-dimensional features, as well as the ability of independently learning and optimizing decision-making in complex environments. This paper explores a DRL-based online combination optimization method of grid sections for a large complex power system. In order to improve the convergence speed of the model, it proposes to discretize the output action of the unit and simplify the action space. It also designs a reinforcement learning loss function with strong constraints to further improve the convergence speed of the model and facilitate the algorithm to obtain a stable solution. Moreover, to avoid the local optimal solution problem caused by the discretization of the output action, this paper proposes to use the annealing optimization algorithm to make the granularity of the unit output finer. The proposed method in this paper has been verified on an IEEE 118-bus system. The experimental results show that it has fast convergence speed and better performance and can obtain stable solutions.

ABSTRACT Streptococcus pneumoniae (Sp) frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and influenza vaccination improves protection against coinfection but does not always yield complete protection. Impaired innate and adaptive immune responses have been associated with attenuated bacterial clearance in influenza virus-infected hosts. In this study, we showed that preceding low-dose IAV infection caused persistent Sp infection and suppression of bacteria-specific T-helper type 17 (Th17) responses in mice. Prior Sp infection protected against subsequent IAV/Sp coinfection by improving bacterial clearance and rescuing bacteria-specific Th17 responses in the lungs. Furthermore, blockade of IL-17A by anti-IL-17A antibodies abrogated the protective effect of Sp preinfection. Importantly, memory Th17 responses induced by Sp preinfection overcame viral-driven Th17 inhibition and provided cross-protection against different Sp serotypes following coinfection with IAV. These results indicate that bacteria-specific Th17 memory cells play a key role in providing protection against IAV/Sp coinfection in a serotype-independent manner and suggest that a Th17-based vaccine would have excellent potential to mitigate disease caused by coinfection. IMPORTANCE Streptococcus pneumoniae (Sp) frequently causes secondary bacterial pneumonia after influenza A virus (IAV) infection, leading to increased morbidity and mortality worldwide. Current pneumococcal vaccines induce highly strain-specific antibody responses and provide limited protection against IAV/Sp coinfection. Th17 responses are broadly protective against Sp single infection, but whether the Th17 response, which is dramatically impaired by IAV infection in naïve mice, might be effective in immunization-induced protection against pneumonia caused by coinfection is not known. In this study, we have revealed that Sp-specific memory Th17 cells rescue IAV-driven inhibition and provide cross-protection against subsequent lethal coinfection with IAV and different Sp serotypes. These results indicate that a Th17-based vaccine would have excellent potential to mitigate disease caused by IAV/Sp coinfection.

Abstract The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage‐endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.

Abstract A finite element model is developed to study dynamics of atmospheric corrosion of carbon steel, focusing on the influence of thin electrolyte film thickness under varying corrosion product porosity. Calculations have been done to evaluate the impact of electrolyte film thickness and corrosion product porosity on oxygen diffusion path, and the hindrance effect of corrosion products on the metal surface activity. The time evolution of corrosion current density and controlling steps in the corrosion process are explored. When the corrosion products are loose, oxygen diffusion is the dominant controlling step, and the thicker the electrolyte film, the lower the corrosion rate. When they are dense, the corrosion process is controlled by the mixture of oxygen diffusion and the surface discharge. The oxygen diffusion path is determined only by the corrosion product porosity, and therefore the corrosion rate is not affected by the electrolyte film thickness.

Abstract Background Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. Methods VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0–7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. Results Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. Conclusions Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

Abstract Sézary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma (CTCL) with a poor prognosis. Intra-tumoral heterogeneity caused by different disease compartments (e.g., skin, blood) and poor understanding of the pathogenesis has created obstacles to the precise diagnosis and targeted treatment of the disease. Here we performed a comprehensive analysis by integrating single-cell transcriptomic data of 40,333 peripheral blood mononuclear cells (PBMCs) and 41,580 skin cells, as well as single-cell chromatin accessibility data of 11,058 PBMCs from an SS patient and matched healthy controls (HCs). Validation and functional investigation were carried out in an independent cohort consisting of SS patients, mycosis fungoides (MF) patients, psoriatic erythroderma patients, and HCs, as well as multiple cell lines. The analysis revealed that skin-derived Sézary cells (SCs) had a shifting trend to more advanced mature phenotypes compared to blood-derived SCs. A series of specific marker genes (TOX, DNM3, KLHL42, PGM2L1, and SESN3) shared in blood- and skin-derived SCs were identified, facilitating the diagnosis and prognosis of MF/SS. Moreover, luciferase reporter assays and gene knockdown assays were used to verify that KLHL42 was transcriptionally activated by GATA3 in SS. Functional assays indicated that KLHL42 silencing significantly inhibited aggressive CTCL cell proliferation and promoted its apoptosis. Therefore, targeting inhibition KLHL42 might serve as a promising therapeutic approach in CTCL.

Abstract Enhancer release and retargeting (ERR) events could activate disease-causing gene promoters for increasing the expression level of oncogenes. Meanwhile, class A orphan GPCRs (oGPCRs) are known as potential biomarkers or drug targets for various cancers, such as gastric cancer (GC). Hence, systemic investigation of ERR events for class A oGPCRs in GC could help to explore biomarkers for GC. In this study, ENCODE and GTEx eQTL data were utilized to define ERR events in GC. Only GPR35 was then detected that could be activated by ERR in GC based on these data and ChIP-seq. Then, activated GPR35 functional in GC cells were explored by flow cytometry, cell-based wound healing assay, Transwell migration assay, and M2 polarization of macrophages assay. Meanwhile, according to TCGA and GEO database, overall survival, immune-related gene expression, and immune cell infiltration level in different GPR35 expressions were calculated. Here, we found ERR event activate GPR35 results in GC cells proliferation and migration, and partly immune cells significance exhaustion (CD8 + T-cells and CD4 + memory T-cells) and/or infiltration (T-cells and macrophage). Meanwhile, high GRP35 level leads to a poor prognosis in GC patients, probably partly due to it promoting the immune infiltration level of macrophages and then inducing polarization of M2 macrophages. Notably, GPR35’s high expression in CTSB+ and CD68 + macrophage could be a genetic indicator for early warning of primary GC. Hence, our findings provide a novel activation approach for oGPCRs, and GPR35 could be determined as a new drugable receptor and early genetic indicator for GC.

The localisation of fluorophores is an important aspect of determining the biological function of cellular systems. Quantum correlation microscopy (QCM) is a promising technique for providing diffraction unlimited emitter localisation that can be used with either confocal or widefield modalities. However, so far, QCM has not been applied to three dimensional localisation problems. Here we show that QCM provides diffraction-unlimited three-dimensional localisation for two emitters within a single diffraction-limited spot. By introducing a two-stage maximum likelihood estimator, our modelling shows that the localisation precision scales as $1/\sqrt{t}$ where t is the total detection time. Diffraction unlimited localisation is achieved using both intensity and photon correlation from Hanbury Brown and Twiss measurements at as few as four measurement locations. We also compare the results of (MC) simulations with the Cramér–Rao lower bound.

We have developed a manufacturing process for micromirrors based on microelectromechanical systems (MEMS) technology. The process involves designing an electrostatic vertically comb-driven actuator and utilizing a self-alignment process to produce a height difference between the movable comb structure and the fixed comb structure of the micromirror. To improve the stability of the micromirror, we propose four instability models in micromirror operation with the quasi-static driving principle and structure of the micromirror considered, which can provide a basic guarantee for the performance of vertical comb actuators. This analysis pinpoints factors leading to instability, including the left and right gap of the movable comb, the torsion beams of the micromirror, and the comb-to-beams distance. Ultimately, the voltages at which device failure occurs can be determined. We successfully fabricated a one-dimensional micromirror featuring a 0.8 mm mirror diameter and a 30 μm device layer thickness. The height difference between the movable and fixed comb structures was 10 μm. The micromirror was able to achieve a static mechanical angle of 2.25° with 60 V@DC. Stable operation was observed at voltages below 60 V, in close agreement with the theoretical calculations and simulations. At the driving voltage of 80 V, we observed the longitudinal displacement movement of the comb fingers. Furthermore, at a voltage of 129 V, comb adhesion occurred, resulting in device failure. This failure voltage corresponds to the lateral torsional failure voltage.

Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment. Lactic acid (LA) has been identified as an influential factor in promoting immune escape and tumor progression. However, the mechanisms through which LA modulates TAMs in colorectal cancer (CRC) remain poorly understood. We used qRT-PCR to quantify the expression of LA-related genes (LDHA and LAMP2) in CRC tumor tissues and adjacent nontumor tissues (n = 64). The biological effects and mechanisms of LA on macrophages and tumors were evaluated via qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation assay in vitro, and allograft mouse tumor models in vivo. We found the expression of LDHA and LAMP2 was highly elevated in the tumor regions and positively associated with a poor clinical stage of CRC. A high concentration of LA was generated under hypoxia; it could promote tumor progression and metastasis with the involvement of macrophages. The inhibition of LA release impaired this protumor phenomenon. Mechanically, LA induced M2 macrophages through the AKT/ERK signaling pathway; subsequently, M2 macrophages secreted CCL8 and facilitated the proliferation and metastasis of CRC cells by activating the CCL8/CCR5/mTORC1 axis. This effect was inhibited by the antagonist or knockdown of CCR5. In conclusion, lactate-induced CCL8 in TAMs accelerated CRC proliferation and metastasis through the CCL8/CCR5/mTORC1 axis.

Background: Transcatheter edge-to-edge repair (TEER) of the mitral valve has emerged as an alternative treatment for mitral regurgitation (MR). However, the high radiation exposure during the process has been associated with multiple adverse effects for medical staff. In this study, we assessed the feasibility and safety of TEER performed solely under the echocardiographic (echo) guidance. Methods: Between April 2021 to August 2021, we retrospectively collected characteristics of 23 patients with MR who underwent TEER under echocardiographic guidance exclusively. Follow-up evaluations were performed at 1- , 3-months and 1-year post procedure. Results: All 23 patients (mean age, 66.1 ± 12.1 years; 65.2% males) successfully underwent echo-guided TEER, with 22 patients under transesophageal echo (TEE) guidance and 1 patient under transthoracic echo (TTE) guidance for severe esophageal stenosis. Of the patients, 60.9% received 1 implant and 39.1% received 2 implants. The median total procedural time was 130 (interquartile range, IQR: 90–150) min and the device procedure time was 73 (IQR: 58–100) min. The median length of stay was 6 (IQR: 5–9) days. At 3-months follow-up, 63.6% of patients had an MR ≤1+ and 90.9% had an MR ≤2+ (p < 0.001 vs. baseline). Improvement in functional status was observed, with 40.9% of patients classified as New York Heart Association (NYHA) functional class I and 45.5% as NYHA functional class II (p < 0.001 compared to baseline) at 3-months. At 1-year follow-up, 90.4% maintained MR reduction with MR ≤2+ (p < 0.001 vs. baseline). Single leaflet device attachment (SLDA) occurred in one patient (4.3%) 1-week post procedure. Conclusions: This retrospective, single-center, and pilot study demonstrates the feasibility, safety, and low complication rates of TEER guided solely by echocardiography. Our findings support the systematic use of echocardiography as the sole guidance modality for TEER, highlighting its potential as an alternative to fluoroscopy-guided procedures. Further multicenter and comparative studies are warranted to confirm these results and provide a more comprehensive evaluation of this approach.

Introduction: Gastric cancer (GC) is the fifth frequent malignancy and is responsible for the third leading cause of cancer-related deaths. Gastric cancer is an aging-related disease, with incidence and mortality rates increasing with aging. The development of GC is affected by lncRNAs, miRNAs, and mRNAs at the transcriptional and posttranscriptional levels. This study aimed to establish a prognostic panel for GC based on competing endogenous RNA (ceRNA) networks.Methods: RNA sequences were obtained from the TCGA database. Different expressions of RNAs were scrutinized with the EdgeR package. The ceRNA network was built using the starBase database and the Cytoscape. The prognostic panel was constituted with the LASSO algorithm. We developed a nomogram comprising clinical characteristic and risk score. The receiver operating characteristic (ROC) was used to evaluate the accuracy of the nomogram prediction. Hub RNAs expressions were detected by qPCR, immunohistochemistry and western blot respectively. Clinical relevance and survival analyses were analyzed. The relationship between RNAs and immune infiltrations, as well as immune checkpoints, was analyzed and evaluated using the CIBERSORT, TIMER and TISIDB databases.Results: Four DElncRNAs, 21 DEmiRNAs and 45 DEmRNAs were included in the ceRNA network. A 3-element panel (comprising lncRNA PVT1, hsa-miR-130a-3p and RECK) with poor overall survival (OS) was established and qPCR was applied to validate the expressions of hub RNAs. Hub RNAs were firmly associated with T, M, and N stage. The CIBERSORT database showed that the high lassoScore group exhibited a significantly high ratio of resting memory CD4+ T cells, M2 macrophages and a significantly low ratio of activated memory CD4+ T cells and M1 macrophages. According to the TIMER database, this panel was linked to immune infiltrations and immune cell gene markers. TISIDB database indicated that RECK was positively correlated with immune checkpoints (including CD160, CD244, PDCD1, and TGFBR1).Discussion: A novel triple prognostic panel of GC constructed based on the ceRNA network was associated with clinical prognostic, clinicopathological features, immune infiltrations, immune checkpoints and immune gene markers. This panel might provide potential therapeutic targets for GC and more experimental verification research is needed.

Summary: Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8+ T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1 to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.

Background: Dynactin (DCTN) can activate cytoplasmic dynein and drive intracellular organelle transport containing six family members (DCTN1 to DCTN6). The DCTN family has been studied as cancer-related genes or biomarkers in various cancers. Nevertheless, in hepatocellular carcinoma (HCC), the functions and prognostic roles of the DCTN family have been unexplored. Methods: We evaluated the diagnostic and survival effects of DCTN subunits in HCC through bioinformatics analysis and validated the results of bioinformatics by our data to address this problem. Results: The results of bioinformatics analysis found that DCTN2 was a significant prognostic factor in HCC, and high-level DCTN2 can predict poor patient survival in HCC. Cox regression analysis also suggested that DCTN2 (hazard ratio = 1.748, 95% confidence interval 1.190–2.568, P = 0.004) is an independent prognostic factor for patient survival. Western blot and quantitative reverse transcription-polymerase chain reaction assays confirmed that the protein and mRNA expression levels of DCTN2 were upregulated in HCC cell lines. The proliferation, invasion, and migration were decreased and cell apoptosis was enhanced after DCTN2 was knocked down in Huh7 and Hep3B cells. DCTN2 promoted the cell cycle progression through regulating the expression of cell cycle regulatory proteins cyclin-dependent kinase 4, Cyclin D1, and p21. Conclusions: We propose that DCTN2 can serve as a prognostic marker for HCC. DCTN2 acts as an oncogene and promotes the cell cycle progression through the G1/S phase-related signaling pathway.

Abstract Objective The mechanism by which mesenchymal stem cell (MSC) transplantation alleviates atherosclerosis in systemic lupus erythematosus (SLE) remains elusive. In this study, we aim to explore the efficacy and mechanism of MSC in ameliorating atherosclerosis in SLE. Methods ApoE−/− and Fas−/− mice on the B6 background were cross-bred to generate SLE mice with atherosclerosis. Myeloid-derived suppressor cells (MDSCs) were sorted and quantified. The apoE−/−Fas−/− mice were either treated with anti-Gr antibody or injected with MDSCs. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. Furthermore, the apoE−/−Fas−/− mice were transplanted with MSCs and lupus-like autoimmunity and atherosclerotic lesions were assessed. Results MDSCs in peripheral blood, spleen, draining lymph nodes increased in apoE−/−Fas−/− mice compared with B6 mice. Moreover, the adoptive transfer of MDSCs aggravated both atherosclerosis and SLE pathologies, whereas depleting MDSCs ameliorated those pathologies in apoE−/−Fas−/− mice. MSC transplantation in apoE−/−Fas−/− mice decreased the percentage of MDSCs, alleviated the typical atherosclerotic lesions, including atherosclerotic lesions in aortae and liver, and reduced serum cholesterol, triglyceride and low-density lipoprotein levels. MSC transplantation also reduced SLE pathologies, including splenomegaly, glomerular lesions, anti-dsDNA antibody in serum, urine protein and serum creatinine. Moreover, MSC transplantation regulated the generation and function of MDSCs through secreting prostaglandin E 2 (PGE2). Conclusion Taken together, these results indicated that the increased MDSCs contributed to atherosclerosis in SLE. MSC transplantation ameliorated the atherosclerosis and SLE through reducing MDSCs by secreting PGE2. Graphical Abstract

Background: Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD. Methods: Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed. Results: Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13–1.38) and 1.24 (95% CI, 1.11–1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9–28% and 9–27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well. Conclusion: The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.

Background Tumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling the tumor microenvironment and promoting tumor progression by secreting various cytokines.Methods Tissue microarray consisting of prostate cancer (PCa), normal prostate, and lymph node metastatic samples from patients with PCa were stained with Yin Yang 1 (YY1) and CD163. Transgenic mice overexpressing YY1 were constructed to observe PCa tumorigenesis. Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid–liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment.Results YY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. The proportion of tumor-infiltrated M2 macrophages increased in transgenic mice overexpressing YY1. In contrast, the proliferation and activity of anti-tumoral T lymphocytes were suppressed. Treatment targeting YY1 on M2 macrophages using an M2-targeting peptide-modified liposome carrier suppressed PCa cell lung metastasis and generated synergistic anti-tumoral effects with PD-1 blockade. IL-4/STAT6 pathway regulated YY1, and YY1 increased the macrophage-induced PCa progression by upregulating IL-6. Furthermore, by conducting H3K27ac-ChIP-seq in M2 macrophages and THP-1, we found that thousands of enhancers were gained during M2 macrophage polarization, and these M2-specific enhancers were enriched in YY1 ChIP-seq signals. In addition, an M2-specific IL-6 enhancer upregulated IL-6 expression through long-range chromatin interaction with IL-6 promoter in M2 macrophages. During M2 macrophage polarization, YY1 formed an LLPS, in which p300, p65, and CEBPB acted as transcriptional cofactors.Conclusions Phase separation of the YY1 complex in M2 macrophages upregulated IL-6 by promoting IL-6 enhancer–promoter interactions, thereby increasing PCa progression.

BackgroundGastric cancer (GC) is a serious threat to human health. The clinical GC characteristics in China may be impacted by changes in people’s lifestyles and the promotion of early GC (EGC) screening. The present study aims to evaluate the recent trends of GC characteristics in South China and search for hazardous factors limiting the survival time of GC patients.MethodsData on GC patients that were hospitalized in the Department of Digestive Center, the First Affiliated Hospital, Sun Yat-sen University, from 1994 to 2019 were collected and divided into two categories according to the time when the EGC screening began in China: the PRE group (previous 13 years, 1994–2006) and the PAS group (past 13 years, 2007–2019).ResultsWe found that, although the 5-year survival rate increased in the PAS group compared with the PRE group (P < 0.0001), patients with age ≥60 years or Borrmann type IV still had a worse prognosis. In the PAS group, the larger percentages of elderly patients and patients with Borrmann type IV in the lymphatic metastases (N1) group (41.0% vs. 51.1%, P = 0.0014) and stage IV subgroup (20.7% vs. 32.2%, P = 0.016), respectively, when compared with the PRE group, may have contributed to the poor outcome of GC. By comparing the odds ratio (OR) of 5-year overall survival (OS) in the two 13-year periods, female sex and T2 turned into risk factors because of a greater proportion of Borrmann type IV or elderly patients in the PAS group (OR = 0.983, 95% CI = 0.723–1.336 vs. OR = 1.277, 95% CI = 1.028–1.586 and OR = 1.545, 95% CI = 0.499–4.775 vs. OR = 2.227, 95% CI = 1.124–4.271, respectively).ConclusionsDespite the GC epidemiology changes, the overall prognosis of GC patients has improved in South China. However, old age and Borrmann type IV are still the major restrictions affecting the survival of GC patients, a situation which calls for additional attention.

BackgroundIn sepsis, brain dysfunction is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Our systematic review and meta-analysis aimed to explore the diagnostic and prognostic value of serum S100 calcium-binding protein B (S100B) in SAE patients.MethodsWe conducted a systematic search of the databases PubMed, Web of Science, Embase, Cochrane databases, CNKI, VIP, and WFSD from their inception dates until August 20, 2022. A Meta-analysis of the included studies was also performed using Review Manager version 5.4 and Stata16.0.ResultsThis meta-analysis included 28 studies with 1401 serum samples from SAE patients and 1591 serum samples from no-encephalopathy septic (NE) patients. The Meta-Analysis showed that individuals with SAE had higher serum S100B level than NE controls (MD, 0.49 [95% CI (0.37)-(0.60), Z =8.29, P < 0.00001]), and the baseline level of serum S100B in septic patients with burn was significantly higher than average (1.96 [95% CI (0.92)-(2.99), Z =3.71, P < 0.0002]) In addition, septic patients with favorable outcomes had lower serum S100B levels than those with unfavorable outcomes (MD, -0.35 [95% CI (-0.50)-(-0.20), Z =4.60, P < 0.00001]).ConclusionOur Meta-Analysis indicates that higher serum S100B level in septic patients are moderately associated with SAE and unfavorable outcomes (The outcomes here mainly refer to the mortality). The serum S100B level may be a useful diagnostic and prognostic biomarker of SAE.

Objective: This network meta-analysis aimed to explore the effect of different drugs on mortality and neurological improvement in patients with traumatic brain injury (TBI), and to clarify which drug might be used as a more promising intervention for treating such patients by ranking.Methods: We conducted a comprehensive search from PubMed, Medline, Embase, and Cochrane Library databases from the establishment of the database to 31 January 2022. Data were extracted from the included studies, and the quality was assessed using the Cochrane risk-of-bias tool. The primary outcome measure was mortality in patients with TBI. The secondary outcome measures were the proportion of favorable outcomes and the occurrence of drug treatment–related side effects in patients with TBI in each drug treatment group. Statistical analyses were performed using Stata v16.0 and RevMan v5.3.0.Results: We included 30 randomized controlled trials that included 13 interventions (TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, simvastatin, and placebo). The analysis revealed that these drugs significantly reduced mortality in patients with TBI and increased the proportion of patients with favorable outcomes after TBI compared with placebo. In terms of mortality after drug treatment, the order from the lowest to the highest was progesterone + vitamin D, beta-blocker therapy, EPO, simvastatin, Enoxaparin, Bradycor, Tracoprodi, selenium, atorvastatin, TXA, progesterone, dexanabinol, and placebo. In terms of the proportion of patients with favorable outcomes after drug treatment, the order from the highest to the lowest was as follows: Enoxaparin, progesterone + vitamin D, atorvastatin, simvastatin, Bradycor, EPO, beta-blocker therapy, progesterone, Tracoprodi, TXA, selenium, dexanabinol, and placebo. In addition, based on the classification of Glasgow Outcome Scale (GOS) scores after each drug treatment, this study also analyzed the three aspects of good recovery, moderate disability, and severe disability. It involved 10 interventions and revealed that compared with placebo treatment, a higher proportion of patients had a good recovery and moderate disability after treatment with progesterone + vitamin D, Bradycor, EPO, and progesterone. Meanwhile, the proportion of patients with a severe disability after treatment with progesterone + vitamin D and Bradycor was also low.Conclusion: The analysis of this study revealed that in patients with TBI, TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, and simvastatin all reduced mortality and increased the proportion of patients with favorable outcomes in such patients compared with placebo. Among these, the progesterone + vitamin D had not only a higher proportion of patients with good recovery and moderate disability but also a lower proportion of patients with severe disability and mortality. However, whether this intervention can be used for clinical promotion still needs further exploration.

Increasingly studies have shown that the formation mechanism of many human diseases is very complex, which is determined by environmental factors and genetic factors rather than fully following Mendel’s genetic law of inheritance. Long non-coding RNA (lncRNA) is a class of endogenous non-protein coding RNA with a length greater than 200 nt, which has attracted much attention in recent years. Studies have shown that lncRNAs have a wide range of biological functions, such as roles in gene imprinting, cell cycle progression, apoptosis, senescence, cell differentiation, and stress responses, and that they regulate the life processes of mammals at various levels, such as epigenetic transcription, processing, modification, transport, translation and degradation. Analyzing the characteristics of lncRNAs and revealing their internal roles can not only deepen our understanding of human physiological and pathological processes, but also provide new ideas and solutions for the diagnosis, prevention and treatment of some diseases. This article mainly reviews the biological characteristics of lncRNAs and their relationship with some diseases, so as to provide references for the related research of lncRNAs.

Background: Sleep is critical to human beings in a surprisingly diverse set of ways, and there is, thus, continual investigation into the mechanisms of sleep. Although current studies have confirmed that multiple brain regions are involved in the regulation of both sleep and wakefulness, the association between certain important brain regions such as the insula and sleep is still unclear. Objective: The purpose of this study was to systematically review studies on the insula and sleep and to discuss the relationship between the insula and sleep. Methods: We searched the PubMed and Web of Science Core Collection (WoSCC) for articles on sleep and the insula. The time span was from inception to June 30, 2022. The search results were then narratively summarized. Results: A total of 939 studies were identified in the PubMed and WoSCC of which 115 studies were finally included in the narrative synthesis. These 115 studies can be roughly divided into 41 studies on insomnia, 39 on sleep deprivation, 33 on sleep-related experiments examining the insula, and 2 studies using basic experiments. Conclusion: The combined findings of many sleep-related studies have confirmed a close link between the insula and sleep loss, including insomnia, sleep deprivation, sleep-related disorders, and more. Although these results do not directly confirm that the insula is involved in sleep, a overall analysis of the results indicates that the insula may be a potential key brain region involved in sleep.

Metal materials will produce fatigue cracks under long-term cyclic loading. It is difficult to fully image the topography of defects with the current mainstream ultrasound imaging technology. The Reverse time migration (RTM), which has extensive application in geophysical exploration, can image complex geological structures. This research introduces the RTM into the field of ultrasonic non-destructive testing. Through numerical simulation, it is concluded that the RTM based on no absorbing boundary can make the defect contour clearer, but the RTM based on the absorbing boundary can make the image contrast metric higher. In order to obtain the RTM results with high contrast metric and clear defect contours, the solution given in this study is to increase the migration aperture. Then this research discusses the influence of different cross-correlation imaging condition on the imaging quality. And compared with the prevailing total focusing methods (TFM), it shows the superiority of the RTM to the bottom opening crack (BOC) imaging. Finally, the RTM was used to complete the imaging of the curved and bifurcated cracks with complex structures. And after reducing the number of ultrasonic transducers, there are still good imaging results, which can reduce the waste of resources and energy.

Abstract Septic shock with acute kidney injury (AKI) is common in critically ill patients. Our aim was to evaluate the association between albumin infusion and outcomes in patients with septic shock and AKI. Medical Information Mart for Intensive Care (MIMIC)-III was used to identify patients with septic shock and AKI. Propensity score matching (PSM) was employed to balance the baseline differences. Cox proportional hazards model, Wilcoxon rank-sum test, and logistic regression were utilized to determine the associations of albumin infusion with mortality, length of stay, and recovery of kidney function, respectively. A total of 2861 septic shock patients with AKI were studied, including 891 with albumin infusion, and 1970 without albumin infusion. After PSM, 749 pairs of patients were matched. Albumin infusion was associated with improved 28-day survival (HR 0.72; 95% CI 0.59–0.86; P = 0.002), but it was not difference in 90-day mortality between groups (HR 0.94; 95% CI 0.79–1.12; P = 0.474). Albumin infusion was not associated with the renal function recovery (HR 0.91; 95% CI 0.73–1.13; P = 0.393) in either population. Nevertheless, subgroup analysis showed that albumin infusion was distinctly associated with reduced 28-day mortality in patients with age > 60 years. The results need to be validated in more randomized controlled trials.