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Increasing the proportion of bainite and martensite phases is one of the effective ways to enhance the toughness of medium-carbon low-alloy steel(42CrMo). In this paper, the surface heat treatment of 42CrMo steel is carried out by using a laser heat source to achieve complete austenitization, then with electromagnetic induction heating for several times to implement insulation, and eventually to promote bainite phase transformation. In conjunction with the temperature history curves, OM, SEM, and EBSD are used to characterize the bainite morphology and percentage of bainite via different parameters of the hybrid process. The results demonstrate that the hybrid process combined with twice electromagnetic induction heating can yield a considerable proportion of bainite phase in 42CrMo steel. The resulting duplex structure, consisting of bainite and a minor fraction of martensite, exhibits a significant increase (81.1%) in tensile strength, while maintaining similar impact toughness. The elongation after fracture only has a slight reduction of 5.5% compared to that of the substrate. This innovative process provides a practical alternative to traditional bainite isothermal treatment method which must perform in a heat treatment furnace. Therefore, it is presented as a promising solution for enhancing the mechanical properties of medium-carbon low-alloy high strength steels.

Abstract Background Oral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics. Methods A retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification. Results We found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs. Conclusion In this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

Abstract Layered bismuth (Bi) has been focused on two Peierls distortion derivatives, i.e., bulk stable β-phase (A7 phase), black phosphorus-like α-phase (A17 phase), and their mutated structures. Metastable structures beyond Peierls distortion system are yet rarely accessible. Here, Bi in square symmetry ( $${C}_{4v}$$ C 4 v ), called s-Bi, was grown via physical vapor deposition. The co-existence of three 120°-associated s-Bi crystal grains was analyzed using transmission electron microscopy. 120°-oriented one-dimensional (1D) nuclei indicate s-Bi heteroepitaxy on six-fold symmetric ( $${C}_{6v}$$ C 6 v ) mica (001). A subsequent nanorod-like nuclei coalescing could promote a morphology evolution, resulting in triangular or hexagonal nanosheets with the unique triple s-Bi structure suitable for later β-Bi growth. Lattice misfit and strain calculations suggest a supercell match between $$4\times 7$$ 4 × 7 s-Bi and $$3\times 3$$ 3 × 3 mica (001). This work demonstrates the metastable s-Bi structure via anisotropic heteroepitaxy of $${C}_{4v}$$ C 4 v s-Bi on $${C}_{6v}$$ C 6 v mica.

Abstract Background Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive oral cancer with a poor prognosis. Its polygenic risk is likely influenced by complex transcriptional disorders involving networks of co-expressed and functionally related genes, though such investigations are limited in OSCC. Methods We analyzed the GSE37991 dataset, comprising 40 OSCC and 40 normal oral tissue samples from the Gene Expression Omnibus. Tumor-specific modules were identified using weighted correlation network analysis (WGCNA), leading to the selection of hub mRNAs and lncRNAs. These lncRNAs were used to construct lncRNA–mRNA and competing endogenous RNA networks. We further examined the expression profiles and survival data of these genes from the Cancer Genome Atlas. Prognostic markers were identified and validated through 5-year survival analysis and Cox proportional hazards modeling. RT-qPCR was used to validate the expression levels in clinical OSCC tissues. Results We identified 1847 differentially expressed genes in OSCC tissues. WGCNA revealed four OSCC-specific modules, screening 120 hub mRNAs and five hub lncRNAs. Two prognostic markers (AQP5, IL-26) from hub mRNAs and three (FRMD5, INHBB, GUCY1A3) from the lncRNA–mRNA network were associated with survival. Validation showed lower expression of AQP5 and GUCY1A3, and higher expression of FRMD5 and INHBB in OSCC compared to normal tissues. Conclusion This study enhances our understanding of transcriptional dysregulation in OSCC and may highlights AQP5, IL-26, FRMD5, INHBB, and GUCY1A3 as promising prognostic biomarkers.

Abstract Arterial endothelial cells (AECs) are the founder cells for intraembryonic haematopoiesis. Here, we report a method for the efficient generation of human haemogenic DLL4+ AECs from pluripotent stem cells (PSC). Time-series single-cell RNA-sequencing reveals the dynamic evolution of haematopoiesis and lymphopoiesis, generating cell types with counterparts present in early human embryos, including stages marked by the pre-haematopoietic stem cell genes MECOM/EVI1, MLLT3 and SPINK2. DLL4+ AECs robustly support lymphoid differentiation, without the requirement for exogenous NOTCH ligands. Using this system, we find IL7 acts as a morphogenic factor determining the fate choice between the T and innate lymphoid lineages and also plays a role in regulating the relative expression level of RAG1. Moreover, we document a developmental pathway by which human RAG1+ lymphoid precursors give rise to the natural killer cell lineage. Our study describes an efficient method for producing lymphoid progenitors, providing insights into their endothelial and haematopoietic ontogeny, and establishing a platform to investigate the development of the human blood system.

Abstract Converting solar energy into fuels is pursued as an attractive route to reduce dependence on fossil fuel. In this context, photothermal catalysis is a very promising approach through converting photons into heat to drive catalytic reactions. There are mainly three key factors that govern the photothermal catalysis performance: maximized solar absorption, minimized thermal emission and excellent catalytic property of catalyst. However, the previous research has focused on improving solar absorption and catalytic performance of catalyst, largely neglected the optimization of thermal emission. Here, we demonstrate an optically selective catalyst based Ti3C2Tx Janus design, that enables minimized thermal emission, maximized solar absorption and good catalytic activity simultaneously, thereby achieving excellent photothermal catalytic performance. When applied to Sabatier reaction and reverse water-gas shift (RWGS) as demonstrations, we obtain an approximately 300% increase in catalytic yield through reducing the thermal emission of catalyst by ~70% under the same irradiation intensity. It is worth noting that the CO2 methanation yield reaches 3317.2 mmol gRu −1 h−1 at light power of 2 W cm−2, setting a performance record among catalysts without active supports. We expect that this design opens up a new pathway for the development of high-performance photothermal catalysts.

Abstract Background Obesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated. Methods In this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo. Results In hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3’UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling. Conclusions Our study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes. Graphical Abstract

Unique challenges have been elicited by climate change, demanding the utilisation of effective adaptation strategies that are both environmentally and economically sustainable. Regrettably, the agricultural sector has not been spared from the effects of climate change, but it is among the largest employers and the primary source of food security globally. The situation is worse in Pakistan, where poverty, hunger, and malnutrition are reported to be prevalent. The complexity of risks posed by climate change has called for climate-smart agriculture (CSA) technologies, which potentially could augment cost efficiency and yield in wheat production. Surprisingly, previous studies have largely overlooked this crucial aspect. Therefore, our research seeks to address two fundamental questions: What is the comparative cost efficiency between adopters and non-adopters of CSA practices in wheat production? And what are the yield effects associated with CSA adoption, particularly compared to non-adopters? To this end, a multi-stage sampling technique was employed to randomly select 400 farm households in a climate risk hotspot province in Pakistan, on which the stochastic frontier analysis (SFA) and endogenous switching regression (ESR) were applied. The results revealed that CSA adoption was associated with improved cost efficiency and yield. Interestingly, if non-adopters decided to adopt CSA, they would increase their wheat yield by about 20%. Given the importance of wheat for food security, this would contribute to poverty and hunger eradication. Therefore, our study conforms to the aspirations of the 2030 agenda by promoting rethinking food production through possible improvement in cost efficiency and yield in the face of a changing climate.

Enhancing the economic resilience of agriculture is essential for promoting sustainable and high-quality agricultural development. The emergence of digital technology has created new opportunities in this field. However, existing research predominantly focuses on traditional agricultural factors and technologies. Therefore, the impact of digital technology on agricultural economic resilience within the broader context of the “production–operation–industry” system in agriculture has not been comprehensively explored. To bridge this gap, this study analyzes panel data from 30 Chinese provinces from 2011 to 2020. It employs the static Van Dorn’s law and a dynamic spatial panel model to examine how digital technology empowers agricultural resilience. The findings indicate a continuous strengthening of digital technology development in China, albeit with significant polarization and spatial imbalances. Moreover, the resilience of the agricultural economy undergoes notable fluctuations, initially narrowing and subsequently displaying an upward trend. Digital technology clearly plays a pivotal role in empowering resilience through agricultural scale operation, industrial transformation, and technological progress. Its impact, particularly on the promotion of resilience in the eastern region and non-grain-producing areas and on high-level agricultural economies, also shows regional and technological variations.

Abstract Garnet oxide is one of the most promising solid electrolytes for solid-state lithium metal batteries. However, the traditional interface modification layers cannot completely block electron migrating from the current collector to the interior of the solid-state electrolyte, which promotes the penetration of lithium dendrites. In this work, a highly electron-blocking interlayer composed of potassium fluoride (KF) is deposited on garnet oxide Li6.4La3Zr1.4Ta0.6O12 (LLZTO). After reacting with melted lithium metal, KF in-situ transforms to KF/LiF interlayer, which can block the electron leakage and inhibit lithium dendrite growth. The Li symmetric cells using the interlayer show a long cycle life of ~3000 hours at 0.2 mA cm−2 and over 350 hours at 0.5 mA cm−2 respectively. Moreover, an ionic liquid of LiTFSI in C4mim-TFSI is screened to wet the LLZTO|LiNi0.8Co0.1Mn0.1O2 (NCM) positive electrode interfaces. The Li|KF-LLZTO | NCM cells present a specific capacity of 109.3 mAh g−1, long lifespan of 3500 cycles and capacity retention of 72.5% at 25 °C and 2 C (380 mA g−1) with an average coulombic efficiency of 99.99%. This work provides a simple and integrated strategy on high-performance quasi-solid-state lithium metal batteries.

DNA methylation is of crucial importance for biological genetic expression, such as biological cell differentiation and cellular tumours. The identification of DNA-6mA sites using traditional biological experimental methods requires more cumbersome steps and a large amount of time. The advent of neural network technology has facilitated the identification of 6 mA sites on cross-species DNA with enhanced efficacy. Nevertheless, the majority of contemporary neural network models for identifying 6 mA sites prioritize the design of the identification model, with comparatively limited research conducted on the statistically significant DNA sequence itself. Consequently, this paper will focus on the statistical strategy of DNA double-stranded features, utilising the multi-head self-attention mechanism in neural networks applied to DNA position probabilistic relationships. Furthermore, a new recognition model, PSATF-6 mA, will be constructed by continually adjusting the attentional tendency of feature fusion through an integrated learning framework. The experimental results, obtained through cross-validation with cross-species data, demonstrate that the PSATF-6 mA model outperforms the baseline model. The in-Matthews correlation coefficient (MCC) for the cross-species dataset of rice and m. musus genomes can reach a score of 0.982. The present model is expected to assist biologists in more accurately identifying 6 mA locus and in formulating new testable biological hypotheses.

PurposeHaemodynamic management is essential in sepsis management. Invasive blood pressure (IBP) monitoring is the gold standard for blood pressure (BP) assessment. Here, we identified the most advantageous time frame for IBP monitoring to mitigate adverse outcomes in patients with sepsis.MethodsWe included data on patients with sepsis from the Medical Information Mart for Intensive Care IV database. The primary endpoints comprised 28-and 90-day mortality rates, whereas secondary endpoints were acute kidney injury (AKI) rates and continuous renal replacement therapy (CRRT) requirement. To confirm our findings’ robustness, we performed multivariable Cox regression and logistic regression models, augmented by propensity score matching (PSM).ResultsOf 18,326 patients hospitalised for sepsis, 9,056 (49.42%) and 9,270 (50.58%) were included in the early and delayed IBP-monitoring groups, respectively. Our multivariable Cox regression models revealed 20 and 21% significant increases in 28-and 90-day mortality in the delayed IBP monitoring group, respectively [hazard ratios (95% confidence intervals) = 1.20 (1.11–1.31) and 1.21 (1.12–1.31), respectively; both p

Our skin serves as the primary barrier against external environmental insults, the latter of which can cause oxidative stress within cells, while various bioactive peptides sourced from natural resources hold promise in protecting cells against such oxidative stress. In this study, we investigate the efficacy of a low molecular weight extract from the sea cucumber Apostichopus japonicus, denoted as Sample-P, in facilitating cell migration and wound healing under oxidative stress conditions in skin cells. The naturally derived compound is a highly complex mix of peptides exhibiting antioxidative properties, as highlighted through liquid chromatography-mass spectrometry peptide screening and an in vitro antioxidant assay. Our results demonstrate that Sample-P is capable of promoting cell migration while preventing severe stress responses such as visible through mTOR expression. To further identify the molecular pathways underpinning the overall protective mechanism of Sample-P, we have utilised a proteomics approach. Our data reveal that Sample-P regulates protein expression associated with ribosomal pathways, glycolysis/gluconeogenesis and protein processing in the endoplasmic reticulum (ER), which help in preserving DNA integrity and safeguarding cellular organelles, such as mitochondria and the ER, under oxidative stress conditions in skin cells. In summary, in the presence of H2O2, Sample-P exhibits antioxidative properties at both molecular and cellular levels, rendering it a promising candidate for topical skin treatment to wound healing and to address age-related skin conditions.

IntroductionDelirium in patients with sepsis can be life-threatening. This study aims to investigate the impact of the use of beta-blockers on the occurrence of delirium in patients with sepsis in the ICU by utilizing a comprehensive dataset.MethodsThis is a cross-sectional study conducted using the data obtained from a single ICU in the USA. Patients diagnosed with sepsis and receiving beta-blockers were compared with those not receiving beta-blockers. Propensity score matching (PSM) and multiple regression analysis were employed to adjust for potential confounders.ResultsAmong the 19,660 patients hospitalized for sepsis, the beta-blocker and non-user groups comprised 13,119 (66.73%) and 6,541 (33.27%) patients, respectively. Multivariable logistic regression models revealed a significant reduction of 60% in 7-day delirium for beta-blocker users (OR = 0.40, 95% CI: 0.37–0.43, p

Background: Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver and is associated with poor prognosis. Despite the emerging role of glycine amidinotransferase (GATM) in cancer development, its function in CCA remains elusive. This study investigated the biological significance and molecular mechanisms of GATM in CCA. Method: GATM expression was measured using immunohistochemistry and western blotting. Cell proliferation, migration, and invasion were assessed through CCK-8, EdU, clone formation, wound healing, and Transwell assays. Rescue experiments were performed to determine whether the JNK/c-Jun pathway is involved in GATM-mediated CCA development. Immunoprecipitation and mass spectrometry were performed to screen for proteins that interact with GATM. The role of GATM in vivo was investigated according to the xenograft experiment. Result: GATM expression was downregulated in CCA tissues and cells (p

[Introduction] Fusion energy has the characteristics of large energy released through reactions, safe and reliable operation, abundant fuel sources, and low environmental pollution. Therefore, it is expected to become a commercial energy source that can be supplied in the market on a large scale, providing stable energy output and power supply in the future. To popularize the development path of magnetic confined fusion energy in China, the article reviews the discovery and realization path of fusion energy. [Method] The article provided an overview of the early research and development process of magnetic confined fusion energy in China by the method of literature review. The paper took the development of magnetic confined fusion energy as an example to provide a preliminary overview of the construction of typical research devices in China, such as tokamak, stellarator, spherical tokamak, reversed field pinch, magnetic mirror field, linear plasma, and dipole magnetic field devices. [Result] Based on the construction and researches of these devices, China has cultivated a group of scientific and technological talents in the field of magnetic confined fusion research, achieving significant progress. In addition, the article provides an overview of international cooperation in fusion energy research, as well as the International Thermonuclear Experimental Reactor (ITER) project that China is participating in construction. [Conclusion] Although the current research on fusion energy still needs to overcome significant challenges from various aspects, such as fusion plasma physics, fusion reactor materials, and tritium self-sustaining technology, it is believed that the magnetic confined fusion energy in China will turn from a blueprint into a reality in the future thanks to the urgent need for energy structure transformation and the strong support for fusion researches in China.

Abstract Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung cancer patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type EGFR tumors has been shown to be marginal. Methods that can sensitize EGFR-TKIs to EGFR wild-type NSCLC remain rare. Hence, we determined whether combination treatment can maximize the therapeutic efficacy of EGFR-TKIs. Methods We established a focused drug screening system to investigate candidates for overcoming the intrinsic resistance of wild-type EGFR NSCLC to EGFR-TKIs. Molecular docking assays and western blotting were used to identify the binding mode and blocking effect of the candidate compounds. Proliferation assays, analyses of drug interactions, colony formation assays, flow cytometry and nude mice xenograft models were used to determine the effects and investigate the molecular mechanism of the combination treatment. Results Betulinic acid (BA) is effective at targeting EGFR and synergizes with EGFR-TKIs (gefitinib and osimertinib) preferentially against wild-type EGFR. BA showed inhibitory activity due to its interaction with the ATP-binding pocket of EGFR and dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis. Mechanistic studies revealed that the combination strategy activated EGFR-induced autophagic cell death and that the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell cycle arrest. Activation of the mTOR pathway or blockade of autophagy by specific chemical agents markedly attenuated the effect of cell cycle arrest. In vivo administration of the combination treatment caused marked tumor regression in the A549 xenografts. Conclusions BA is a potential wild-type EGFR inhibitor that plays a critical role in sensitizing EGFR-TKI activity. BA combined with an EGFR-TKI effectively suppressed the proliferation and survival of intrinsically resistant lung cancer cells via the inhibition of EGFR as well as the induction of autophagy-related cell death, indicating that BA combined with an EGFR-TKI may be a potential therapeutic strategy for overcoming the primary resistance of wild-type EGFR-positive lung cancers. Graphical abstract

Abstract In the built heritage studies, the intricate web of social and selective processes that define heritage is evident. These processes are, in many cases, intertwined with the notion of scale, examplified through the production of heritage sites at the local, national, and transnational scales. While heritage and geography scholars have articulated the role played by scale in heritage-making and argue against a rigid, fixed, and hierarchical understanding of scale, they highlight the constant reproduction of scale. There is, so far, limited explanation of how the perception of scale gets reproduced and how crucial actors manipulate scalar power and resources for heritage making and the reproduction of scale. To fill this gap, this paper delves into mainland China’s heritage-making, using the southern Anhui historical villages as an example. Based on intensive 5-month field research, this paper has three findings: 1) The nomination process for a World Heritage Site is notably influenced by politics and selectivity; 2) Diverse stakeholders are pivotal in shaping heritage narratives; 3) Individual contributions to heritage creation directly interact with, and subsequently reshape, ‘scale’, an entity that is simultaneously discursive and tangible. By integrating the notion of ‘scale’ into heritage discussions, we illuminate two concurrent processes: creating hierarchies through rule assimilation by interpreting the UNESCO standard internally and evolving socio-spatial dynamics via the manifestation of individual agency with resource manipulation, scale jumping, and reproduction of scale. This approach aligns with the material orientation in human geography and repositions ‘scale’. Here, it’s not just an epistemological framework but also a tangible force that steers individual perceptions and actions and yields measurable material impacts.

Abstract Increasing people’s subjective well-being (SWB) remains a critical challenge for all countries. However, few studies have been dedicated to examining the influence of environmental governance programs on SWB, especially in developing and non-democratic societies. This paper aims to fill this void by taking the Rural Living Environment Improvement (RLEI) program in China—the largest rural living environment governance program in history, as an example to understand the role of environmental governance programs in SWB in the world’s biggest developing and non-democratic country. Based on 3747 individual samples from the China Labor-force Dynamics Survey database, we found that RLEI can significantly improve rural residents’ SWB. This effect remains significant after using the propensity score matching method and the instrumental variable approach to address potential selection bias and endogenous problems. The indirect analysis shows that RLEI can increase rural residents’ SWB mainly through improving their income, consumption expenditure, and health. Compared with rural sewage and livestock manure RLEI programs, rural waste RLEI program has a greater enhanced impact on rural residents’ SWB. The monetary value of RLEI based on the life satisfaction approach shows that the resulting improvement in rural residents’ SWB created by RLEI is almost equivalent to the effect of household income. While the monetary value of rural sewage, livestock manure, and rural waste RLEI program is equivalent to 1.2, 3.67, and 1.1 times the effect of household income. Heterogeneity analysis indicates that RLEI has a greater positive impact on SWB for junior and old-aged, low-educated, Midwestern and Northeastern, and working rural residents.

Abstract Background Ubiquitination is a critical post-translational modification which can be reversed with an enzyme family known as deubiquitinating enzymes (DUBs). It has been reported that dysregulation of deubiquitination leads to carcinogenesis. As a member of the DUBs family, proteasome 26 S subunit non-ATPase 7 (PSMD7) serves as an underlying tumour-promoting factor in multiple cancers. However, the clinical significance and biological functions of PSMD7 in pancreatic cancer (PC) remain unclear. Results In this study, we first reported frequent overexpression of PSMD7 in PC tissues, and high levels of PSMD7 were markedly linked to shorter survival and a malignant phenotype in PC patients. An array of in vitro and in vivo gain/loss-of-function tests revealed that PSMD7 facilitates the progression of PC cells. Additionally, we found that PSMD7 promotes PC cell progression by activating the Notch homolog 1 (Notch1) signalling. Interestingly, in PC cells, the inhibitory effect of PSMD7 knockdown on cellular processes was comparable to that observed upon Notch1 knockdown. Mechanistically, PSMD7 deubiquitinated and stabilised sex determining region Y (SRY)-box 2 (SOX2), a key mediator of Notch1 signalling. The stabilisation of SOX2, mediated by PSMD7, dramatically increased SOX2 protein levels, subsequently activating the Notch1 pathway. Finally, restoration of SOX2 expression abrogated the PSMD7-silenced antitumour effect. Conclusions Taken together, our work identifies and validates PSMD7 as a promoter of PC progression through augmentation of the Notch1 signalling pathway mediated by SOX2. This finding suggests that PSMD7 holds promise as a potential therapeutic target for the management of this refractory disease.

Qilou (arcade building) is a particular type of Chinese historical architecture combined with western and eastern building elements, which plays a significant role in the history of modern Chinese architecture. However, the recognition and classification of the qilou mainly rely on manual inspection, suppressing the cultural dissemination and protection of qilou relics. In this paper, we present a new framework that adopts multiple image processing algorithms and a deep learning network to automate qilou classification. First, image dataset of the qilou is enhanced based on the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm. Then, an improved Faster R-CNN with ResNet50 (Faster R-CNN-R) is deployed for qilou image recognition. A total of 760 images captured in Guangzhou were used for training, validation, and accuracy check of the proposed framework and several contrastive networks under the same conditions. Compared to other networks, the proposed framework works better than Faster R-CNN with VGG16 (Faster R-CNN-V) and FCOS. The accuracy of the proposed framework embedded with the Faster R-CNN-R, Faster R-CNN-V, and FCOS are 80.12%, 65.17%, and 66.35%, respectively. Based on digital images captured under different lighting conditions, the proposed framework can be used to classify nine different types of qilous, with high robustness.

Organ transplantation is the optimal treatment for patients with end-stage organ failure, but which faces the challenge of donor shortage. Two-dimensional cell culture and animal experiments are difficult to completely simulate the complex cellular microenvironment for drug testing. Three-dimensional (3D) bioprinting is an emerging manufacturing technology to fabricate artificial tissues and organs for transplantation and drug screening. This review first describes the bioprinting technologies used to fabricate constructs, including jetting-based, extrusion-based, vat photopolymerization-based methods and other emerging 3D bioprinting approaches. The various kinds of bioinks, cell sources, and the most recent applications of 3D bioprinting tissues and organs in transplantation and drug testing are subsequently summarized. Finally, we discuss the challenges and prospects of 3D bioprinting of tissues and organs. This review aims to facilitate the overcoming of the obstacles identified on the challenging journey towards the manufacturing and adoption of tissue and organs in transplantation and drug screening.

Background: Acute myeloid leukemia (AML) with t(8;21) manifests as a diverse hematological malignancy. Although it was categorized into a favorable subtype, 30–40% of patients experience relapse. The objective of this research was to devise a nomogram for the accurate anticipation of both overall survival (OS) and cancer-specific survival (CSS) in t(8;21) AML.Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, individuals diagnosed with t(8;21) AML from 2000 to 2018 were selected. Prognostic factors for t(8;21) AML were identified using Cox regression analysis and Akaike Information Criterion (AIC), forming the basis for constructing prognostic nomograms.Results: Key variables, including first primary tumor, age group, race, and chemotherapy, were identified and integrated into the nomogram. The C-index values for the nomograms predicting OS and CSS were 0.753 (validation: 0.765) and 0.764 (validation: 0.757), respectively. Ultimately, based on nomogram scores, patients were stratified into high-risk and low-risk groups, revealing significant disparities in both OS and CSS between these groups (P

AbstractIn contemporary times, the employment of vitrification freezing technology has led to the widespread adoption of frozen-thawed embryo transfer (FET) worldwide. Meanwhile, hormone replacement therapy (HRT) is a crucial protocol for priming the endometrium during FET cycles. Estrogen is required in HRT cycles for the induction of progesterone receptors and to promote endometrial thickness. However, there is no universal consensus on the treatment duration, dosage regimen, administration route, and target serum estrogen levels. Therefore, this study aimed to offer a comprehensive review of these topics. A shorter duration of estrogen exposure may elevate the risk of early miscarriage, while prolonged exposure to estrogen does not seem to confer advantages to general population and may be attempted in individuals with thin endometrium. Moreover, excessive estrogen levels on the day of progesterone administration may be associated with higher miscarriage rates and lower live birth rates (LBR). To offer more comprehensive guidance for clinical practice, extensive and prospective studies involving a large sample size are warranted to determine the optimal concentration and duration of estrogen exposure.

Property rights reform has been widely regarded as a powerful tool to narrow the urban-rural income gap (URIG). A recent nationwide property rights reform in China, namely, the rural collective property rights system reform (RCPRSR) was implemented in 2015, offering rural residents rights to rural collective assets, especially land assets. However, whether it can help to narrow URIG or not remains controversial. Based on 2,322 county-level big panel data in China from 2010 to 2019, this paper takes RCPRSR as a quasi-natural experiment and empirically evaluates its impact and mechanism on URIG by using a time-varying difference-in-differences (DID) model. The findings suggest that RCPRSR can decrease URIG by 4.2%, and this conclusion is still reliable after six robustness tests. Heterogeneity analysis shows that the positive effect of RCPRSR on narrowing URIG is significant in eastern and northeastern China, but not in central and western China. Mechanism analysis shows that RCPRSR can decrease URIG mainly through optimizing the industrial structure and improving the agricultural mechanization level. This study provides a reference on how to mitigate URIG through property rights reform in developing countries. JEL Classification: O20, D31, D63.

The oral and maxillofacial regions perform mastication, swallowing, speech, and expression; therefore, oral and maxillofacial tissue defects can seriously affect patient physical and mental health. Biomaterials can be used to repair maxillofacial defects. However, traditional biomaterials lack biocompatibility and cannot accurately match the shape of damaged tissues, leading to tissue immune rejection and chronic inflammation, thereby limiting their repair ability. Biomaterials can improve mesenchymal stem cell (MSC) survival by simulating the extracellular matrix (ECM). MSCs have excellent self-regenerative abilities and can differentiate into almost all cell types, making them valuable for tissue engineering. This review summarizes biomaterial-based, stem cell, and cell-free therapies and discusses their properties, advantages, disadvantages, and application mechanisms, with a particular focus on their use in oral and maxillofacial tissue defect repair and regeneration and the limitations of the current materials and strategies. This review provides insights into using biomaterials for oral and maxillofacial tissue defect repair and regeneration.

BackgroundThe above studies indicate that the SCZ animal model has abnormal gamma oscillations and abnormal functional coupling ability of brain regions at the cortical level. However, few researchers have focused on the correlation between brain complexity and connectivity at the cortical level. In order to provide a more accurate representation of brain activity, we studied the complexity of electrocorticogram (ECoG) signals and the information interaction between brain regions in schizophrenic rats, and explored the correlation between brain complexity and connectivity.MethodsWe collected ECoG signal from SCZ rats. The frequency domain and time domain functional connectivity of SCZ rats were evaluated by magnitude square coherence and mutual information (MI). Permutation entropy (PE) and permutation Lempel-Ziv complexity (PLZC) were used to analyze the complexity of ECoG, and the relationship between them was evaluated. In addition, in order to further understand the causal structure of directional information flow among brain regions, we used phase transfer entropy (PTE) to analyze the effective connectivity of the brain.ResultsFirstly, in the high gamma band, the complexity of brain regions in SCZ rats is higher than that in normal rats, and the neuronal activity is irregularity. Secondly, the information integration ability of SCZ rats decreased and the communication of brain network information was hindered at the cortical level. Finally, compared with normal rats, the causal relationship between brain regions of SCZ rats was closer, but the information interaction center was not clear.ConclusionThe above findings suggest that at the cortical level, complexity and connectivity are valid biomarkers for identifying SCZ. This bridges the gap between peak potentials and EEG. This may help to understand the pathophysiological mechanisms at the cortical level in schizophrenics.

Abstract Helicobacter pylori (H. pylori) infection is the primary risk factor for the pathogenesis of gastric cancer (GC). N6‐methyladenosine (m6A) plays pivotal roles in mRNA metabolism and hnRNPA2B1 as an m6A reader is shown to exert m6A‐dependent mRNA stabilization in cancer. This study aims to explore the role of hnRNPA2B1 in H. pylori‐associated GC and its novel molecular mechanism. Multiple datasets and tissue microarray are utilized for assessing hnRNPA2B1 expression in response to H. pylori infection and its clinical prognosis in patients with GC. The roles of hnRNPA2B1 are investigated through a variety of techniques including glucose metabolism analysis, m6A‐epitranscriptomic microarray, Ribo‐seq, polysome profiling, RIP‐seq. In addition, hnRNPA2B1 interaction with poly(A) binding protein cytoplasmic 1 (PABPC1) is validated using mass spectrometry and co‐IP. These results show that hnRNPA2B1 is upregulated in GC and correlated with poor prognosis. H. pylori infection induces hnRNPA2B1 upregulation through recruiting NF‐κB to its promoter. Intriguingly, cytoplasm‐anchored hnRNPA2B1 coordinated PABPC1 to stabilize its relationship with cap‐binding eIF4F complex, which facilitated the translation of CIP2A, DLAT and GPX1 independent of m6A modification. In summary, hnRNPA2B1 facilitates the non‐m6A translation of epigenetic mRNAs in GC progression by interacting with PABPC1‐eIF4F complex and predicts poor prognosis for patients with GC.

IntroductionGastric cancer (GC) remains a major global health threat ranking as the fifth most prevalent cancer. Hypoxia, a characteristic feature of solid tumors, significantly contributes to the malignant progression of GC. Mitochondria are the major target of hypoxic injury that promotes mitochondrial dysfunction during the development of cancers including GC. However, the gene signature and prognostic model based on hypoxia- and mitochondrial dysfunction-related genes (HMDRGs) in the prediction of GC prognosis have not yet been established.MethodsThe gene expression profile datasets of stomach cancer patients were retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Prognostic genes were selected using Least Absolute Shrinkage and Selection Operator Cox (LASSO-Cox) regression analysis to construct a prognostic model. Immune infiltration was evaluated through ESTIMATE, CIBERSORT, and ssGSEA analyses. Tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were utilized to explore implications for immunotherapy. Furthermore, in vitro experiments were conducted to validate the functional roles of HMDRGs in GC cell malignancy.ResultsIn this study, five HMDRGs (ZFP36, SERPINE1, DUSP1, CAV1, and AKAP12) were identified for developing a prognostic model in GC. This model stratifies GC patients into high- and low-risk groups based on median risk scores. A nomogram predicting overall survival (OS) was constructed and showed consistent results with observed OS. Immune infiltration analysis indicated that individuals in the high-risk group tend to exhibit increased immune cell infiltration. Additionally, analysis of cancer immunotherapy responses revealed that high-risk group patients exhibit poorer responses to cancer immunotherapy compared to the low-risk group. Immunohistochemistry (IHC) staining indicated that the expression levels of HMDRGs were remarkably correlated with GC, of which, SERPINE1 displayed the most pronounced up-regulation, while ZFP36 exhibited the most notable down-regulation in GC patients. Furthermore, in vitro investigation validated that SERPINE1 and ZFP36 contribute to the malignant processes of GC cells correlated with mitochondrial dysfunction.ConclusionsThis study presents a novel and efficient approach to evaluate GC prognosis and immunotherapy efficacy, and also provides insights into understanding the pathogenesis of GC.

ObjectiveThis study aims to investigate the Knowledge, Attitude, and Practice (KAP) pertaining to constipation during pregnancy among pregnant women in Shanghai.MethodsDemographic data and KAP scores were collected using a questionnaire. Differences across groups were analyzed using either Wilcoxon-Mann–Whitney tests or Kruskal-Wallis analysis of variance. Spearman’s correlation analysis was utilized to evaluate the relationships between KAP scores. Multivariable logistic regression analyses were conducted to identify factors that influence KAP scores.ResultsEncompassing 241 individuals (46.6%) aged between 30 and 34 years, with 349 participants (67.5%) being nulliparous. The median scores for knowledge (possible range: 0–26), attitude (possible range: 7–35), and practice (possible range: 14–70) were 22 (18, 24), 26 (23, 29), and 51 (46, 56), respectively. Multivariate analysis indicated that being a medical professional (OR = 2.222, p = 0.043) and receiving education on constipation during pregnancy (OR = 0.432, p

The incidence of aortic dissection (AD) is steadily increasing, driven by the rising prevalence of chronic conditions such as hypertension and the global aging of the population. Oxidative stress emerges as a pivotal pathophysiological mechanism contributing to the progression of AD. Oxidative stress triggers apoptosis in vascular smooth muscle cells, reshapes the extracellular matrix (ECM), and governs ECM degradation and remodeling, subsequently impacting aortic compliance. Furthermore, oxidative stress not only facilitates the infiltration of macrophages and mononuclear lymphocytes but also disrupts the integral structure and functionality of endothelial cells, thereby inducing endothelial cell dysfunction and furthering the degeneration of the middle layer of the aortic wall. Investigating antioxidants holds promise as a therapeutic avenue for addressing AD.

Abstract Dendrite growth and other side‐reaction problems of zinc anodes in aqueous zinc‐ion batteries heavily affect their cycling lifespan and Coulombic efficiency, which can be effectively alleviated by the application of polymer‐based functional protection layer on the anode. However, the utilization rate of functional groups is difficult to improve without destroying the polymer chain. Here, a simple and well‐established strategy is proposed by controlling the orientation of functional groups (─SO3H) to assist the optimization of zinc anodes. Depending on the electrostatic effect, the surface‐enriched ─SO3H groups increase the ionic conductivity and homogenize the Zn2+ flux while inhibiting anionic permeation. This approach avoids the destruction of the polymer backbone by over‐sulfonation and amplifies the effect of functional groups. Therefore, the modified sulfonated polyether ether ketone (H‐SPEEK) coating‐optimized zinc anode is capable of longtime stable zinc plating/stripping, and moreover an enhanced cycling steadiness under high current densities is also detected in a series of Zn batteries with different cathode materials, which achieved by the inclusion of H‐SPEEK coating without causing any harmful effects on the electrolyte and cathode. This work provides an easy and efficient approach to further optimize the plating/stripping of cations on metal electrodes, and sheds lights on the scale‐up of high‐performance aqueous zinc‐ion battery technology.

BackgroundObesity and diabetes have been associated with depressive symptoms. The aim of this systematic review and meta-analysis was to evaluate the association between the triglyceride glucose index (TyG index) a novel indicator of insulin resistance (IR) and depression in the adult population.MethodsRelevant observational studies were acquired through comprehensive searches of the Medline, Web of Science, Embase, Wanfang, and China National Knowledge Internet databases. To account for heterogeneity, a random-effects model was employed to combine the findings. Additionally, multiple subgroup analyses were conducted to assess the impact of various study characteristics on the outcome.ResultsThe meta-analysis comprised eight datasets from six cross-sectional studies, encompassing a total of 28,973 adults. The pooled findings suggested that subjects with a high TyG index, compared to those with a low TyG index, were associated with a higher prevalence of depression (odds ratio [OR]: 1.41, 95% confidence interval (CI): 1.28–1.56, p0.05).ConclusionA high TyG index may be associated with a higher prevalence of depression in the adult population.

Maize is one of the major crops cultivated in northern Shandong Province and contributes significantly to China's maize production, and nitrogen (N) application to the soil can have a marked impact on maize yield and soil microbial productivity. The current environmental challenge, which needs urgently to be addressed, is to effectively utilize fertilizer nitrogen to improve crop production without causing environmental stress in sustainable agroecosystems. Soil fungi can improve plant health and crop performance through improved nutrient uptake and reducing plant stress levels. How soil N influences fungal diversity and maize yield at spatial patterns remains unclear. In this study, the influences of different soil N treatments on maize yields and fungal diversity were investigated in maize fields at five N rates (from 0 to 120 kg ha−1). High-throughput sequencing of the internal transcribed spacer (ITS) region revealed that α- and β-diversities of fungi significantly increased at 80 kg N ha−1 (N80) but decreased significantly in the control (N0) and other N treatments. Variations in the NC model predicted strong fungal distribution patterns (R2 = 0.60) among all the treatments. The highest proportion of operational taxonomic units (OTUs) (68.99 %) was observed at N80. The study also found that the complexity of the co-occurrence network significantly stabilized at N80, but a decrease in network complexity was observed at N120. The study showed that, relative to the control, the addition of N to the soil significantly increased the abundance of Ascomycota at the phylum level and Chaetomium, Fusarium, and Mortierella at the genus levels, with average abundances of 5.82 %, 1.67 %, and 19.58 %, respectively. Functional ecology analysis indicated that soil N upregulated the composition of ecological fungal communities by stochastic processes. The composition of major fungal sub-communities was positively correlated with nitrogen/carbon cycling at N80. Moreover, results also indicated that the yields (3.14 t ha−1) and other agronomic effects at N80 were significantly higher than those in the other treatments. This study demonstrates that optimal nitrogen application achieves increases in both fungal diversity and yield, contributing to improved crop production and sustainability at spatial scales.

Chemoresistance is a major therapeutic challenge in advanced gastric cancer (GC). N6-methyladenosine (m6A) RNA modification has been shown to play fundamental roles in cancer progression. However, the underlying mechanisms by which m6A modification of circRNAs contributes to GC and chemoresistance remain unknown. We found that hsa_circ_0030632 (circUGGT2) was a predominant m6A target of METTL14, and METTL14 knockdown (KD) reduced circUGGT2 m6A levels but increased its mRNA levels. The expression of circUGGT2 was markedly increased in cisplatin (DDP)-resistant GC cells. CircUGGT2 KD impaired cell growth, metastasis and DDP-resistance in vitro and in vivo, but circUGGT2 overexpression prompted these effects. Furthermore, circUGGT2 was validated to sponge miR-186–3p and upregulate MAP3K9 and could abolish METTL14-caused miR-186–3p upregulation and MAP3K9 downregulation in GC cells. circUGGT2 negatively correlated with miR-186–3p expression and harbored a poor prognosis in patients with GC. Our findings unveil that METTL14-dependent m6A modification of circUGGT2 inhibits GC progression and DDP resistance by regulating miR-186–3p/MAP3K9 axis.

Abstract Background Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. Methods In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. Results GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913–0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831–0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841–0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838–0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810–0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710–0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. Conclusion Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.

Abstract Background Allergic rhinitis is a common health concern that affects quality of life. This study aims to examine the online search trends of allergic rhinitis in China before and after the COVID-19 epidemic and to explore the association between the daily air quality and online search volumes of allergic rhinitis in Beijing. Methods We extracted the online search data of allergic rhinitis-related keywords from the Baidu index database from January 23, 2017 to June 23, 2022. We analyzed and compared the temporal distribution of online search behaviors across different themes of allergic rhinitis before and after the COVID-19 pandemic in mainland China, using the Baidu search index (BSI). We also obtained the air quality index (AQI) data in Beijing and assessed its correlation with daily BSIs of allergic rhinitis. Results The online search for allergic rhinitis in China showed significant seasonal variations, with two peaks each year in spring from March to May and autumn from August and October. The BSI of total allergic rhinitis-related searches increased gradually from 2017 to 2019, reaching a peak in April 2019, and declined after the COVID-19 pandemic, especially in the first half of 2020. The BSI for all allergic rhinitis themes was significantly lower after the COVID-19 pandemic than before (all p values

Abstract Background In our previous investigation, we revealed a significant increase in the expression of microRNA-6881-3p (miR-6881-3p) in follicular fluid granulosa cells (GCs) from women with diminished ovarian reserve (DOR) compared to those with normal ovarian reserve (NOR). However, the role of miR-6881-3p in the development of DOR remains poorly understood. Objective This study aimed to elucidate the involvement of miR-6881-3p in the regulation of granulosa cells (GCs) function and the pathogenesis of DOR. Materials and methods Initially, we assessed the expression levels of miR-6881-3p in GCs obtained from human follicular fluid in both NOR and DOR cases and explored the correlation between miR-6881-3p expression and clinical outcomes in assisted reproduction technology (ART). Bioinformatic predictions and dual-luciferase reporter assays were employed to identify the target gene of miR-6881-3p. Manipulation of miR-6881-3p expression was achieved through the transfection of KGN cells with miR-6881-3p mimics, inhibitor, and miRNA negative control (NC). Following transfection, we assessed granulosa cell apoptosis and cell cycle progression via flow cytometry and quantified target gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Finally, we examined the correlation between target gene expression levels in GCs from NOR and DOR patients and their association with ART outcomes. Results Our findings revealed elevated miR-6881-3p levels in GCs from DOR patients, which negatively correlated with ovarian reserve function and ART outcomes. We identified a direct binding interaction between miR-6881-3p and the 3’-untranslated region of the SMAD4. Transfection with miR-6881-3p mimics induced apoptosis in KGN cell. Furthermore, miR-6881-3p expression negatively correlated with both mRNA and protein levels of the SMAD4. The mRNA and protein levels of SMAD4 were notably reduced in GCs from DOR patients, and SMAD4 mRNA expression positively correlated with ART outcomes. In addition, the mRNA levels of FSHR, CYP11A1 were notably reduced after transfection with miR-6881-3p mimics in KGN cell, while LHCGR notably increased. The mRNA and protein levels of FSHR, CYP11A1 were notably reduced in GCs from DOR patients, while LHCGR notably increased. Conclusion This study underscores the role of miR-6881-3p in directly targeting SMAD4 mRNA, subsequently diminishing granulosa cell viability and promoting apoptosis, and may affect steroid hormone regulation and gonadotropin signal reception in GCs. These findings contribute to our understanding of the pathogenesis of DOR.

Visual feedback gain is a crucial factor influencing the performance of precision grasping tasks, involving multiple brain regions of the visual motor system during task execution. However, the dynamic changes in brain network during this process remain unclear. The aim of this study is to investigate the impact of changes in visual feedback gain during precision grasping on brain network dynamics. Sixteen participants performed precision grip tasks at 15% of MVC under low (0.1°), medium (1°), and high (3°) visual feedback gain conditions, with simultaneous recording of EEG and right-hand precision grip data during the tasks. Utilizing electroencephalogram (EEG) microstate analysis, multiple parameters (Duration, Occurrence, Coverage, Transition probability(TP)) were extracted to assess changes in brain network dynamics. Precision grip accuracy and stability were evaluated using root mean square error(RMSE) and coefficient of variation(CV) of grip force. Compared to low visual feedback gain, under medium/high gain, the Duration, Occurrence, and Coverage of microstates B and D increase, while those of microstates A and C decrease. The Transition probability from microstates A, C, and D to B all increase. Additionally, RMSE and CV of grip force decrease. Occurrence and Coverage of microstates B and C are negatively correlated with RMSE and CV. These findings suggest that visual feedback gain affects the brain network dynamics during precision grasping; moderate increase in visual feedback gain can enhance the accuracy and stability of grip force, whereby the increased Occurrence and Coverage of microstates B and C contribute to improved performance in precision grasping. Our results play a crucial role in better understanding the impact of visual feedback gain on the motor control of precision grasping.

Abstract Background Studies have investigated how adults with severe depressive symptoms are more likely to attempt suicide, and these adults often have traumatic experiences and chaotic sleep/wake rhythms. Thus, this study using Latent class analysis aimed to investigate the relationship between childhood trauma class, chronotype, and suicide attempts among emerging adults with severe depressive symptoms. Methods This study was conducted among emerging adults with severe depressive symptoms covering 63 Universities in Jilin Province, China. A total of 1,225 emerging adults (mean age = 19.6 ± 1.78) constructed the final sample. In addition to measuring socio-demographic characteristics, the Childhood Trauma Questionnaire-Short Form, the Single-Item Chronotyping, and a single item for suicide attempts were used to evaluate childhood trauma, chronotype, and suicide attempts, respectively. Latent class analysis was applied to identify the classes of childhood trauma within emerging adults who had severe depressive symptoms. Hierarchical logistic regression models were run to investigate the effects of socio-demographic characteristics, chronotype, and childhood trauma class on suicide attempts. Results Three latent classes were identified: the Low-risk for childhood trauma class, the Neglect class, and the High-risk for childhood abuse class. Those who suffered sexual, emotional, and physical abuse at the same time were divided into the High-risk for childhood abuse class, and were significantly more likely to experience suicide attempts than those in the Neglect class (OR = 1.97, 95%CI = 1.34–2.89, p < 0.001) and the Low-risk for childhood trauma class (OR = 2.28, 95% CI = 1.50-3.46, p

Motor imagery electroencephalogram (MI-EEG) classification is essential in brain-computer interface (BCI), and many classification methods have been proposed recently. However, the MI-EEG classification accuracy of the public dataset still has room for improvement, and designing a suitable model to extract and fuse the multi-modality features efficiently is crucial. In this study, we proposed a Multi-scale Space-time Frequency fusion Network (MSFNet) to improve the MI-EEG classification accuracy. The MSFNet comprises data acquisition and preprocessing, multi-scale time-conv fusion unit, multi-scale frequency-conv fusion unit, feature fusion, and classification. Multi-scale time-conv fusion unit can extract multi-scale spatiotemporal features, and multi-scale frequency-conv fusion unit can extract five frequency sub-band features. These two features were concatenated to complete the multi-modality features fusion, and MI-EEG was classified. Average accuracy, kappa value, and F1 score were adopted as the evaluation metric, and BCI Competition 2008 IV 2a and High Gamma datasets were employed to demonstrate the effectiveness of the MSFNet. The superiority of this proposed model was demonstrated by comparison against the state-of-the-art methods, and the classification result is the highest. Overall, we achieved an average accuracy of 80.47%, kappa value of 0.783, and F1 score of 0.743 in the BCI Competition 2008 IV 2a dataset, and we achieved an average accuracy of 93.56%, kappa value of 0.933, and F1 score of 0.915 in High Gamma dataset. This model realized the extraction and efficient fusion of spatiotemporal and frequency domain features and the high-precision MI-EEG classification, which has an important application value.

ABSTRACT The incidence of pancreatitis in children has increased over the past two decades. With advances in molecular biological techniques and clinical research, genetic variations have emerged as a pivotal etiological factor in pediatric pancreatitis. This review aims to summarize recent clinical research advancements in understanding pediatric pancreatitis caused by various gene mutations. As of the year 2020, researchers had identified 12 genes implicated in the pathogenesis of pancreatitis. These genes primarily contributed to the development of pancreatitis through three mechanisms. Pancreatitis resulting from these gene mutations exhibits several distinct characteristics, including early onset, a heightened risk of developing pancreatic duct stones, rapid disease progression, and a significantly increased risk of pancreatic endocrine and exocrine dysfunction, as well as pancreatic cancer in the future. Genetic sequencing is recommended for children with pancreatitis based on six indications. The sequencing not only assists in the clinical diagnosis but also enhances our understanding of the pathophysiology of pancreatitis.

The combination of nano sizes, large pore sizes and green synthesis is recognized as one of the most crucial and challenging problems in constructing metal-organic frameworks (MOFs). Herein, a water-based strategy is proposed for the synthesis of nanoscale hierarchical MOFs (NH-MOFs) with high crystallinity and excellent stability. This approach allows the morphology and porosity of MOFs to be fine tuned, thereby enabling the nanoscale crystal generation and a well-defined hierarchical system. The aqueous solution facilitates rapid nucleation kinetics, and the introduced modulator acts as a deprotonation agent to accelerate the deprotonation of the organic ligand as well as a structure-directing agent (SDA) to guide the formation of hierarchical networks. The as-synthesized NH-MOFs (NH-ZIF-67) were assessed as efficient adsorbents and heterogeneous catalysts to facilitate the diffusion of guest molecules, outperforming the parent microZIF-67. This study focuses on understanding the NH-MOF growth rules, which could allow tailor-designing NH-MOFs for various functions.

Abstract Inflammation‐responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)‐responsive injectable hydrogel is constructed by integrating an MMP‐cleavable peptide (pp) into a covalent tetra‐armed poly‐(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro‐regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG‐pp‐PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG‐pp‐PS to transform macrophages into the anti‐inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell‐free strategy on simultaneous immunoregulation and osteoinduction in bone engineering.

Sepsis-induced myocardial dysfunction (SIMD) is associated with poor prognosis and increased mortality in patients with sepsis. Cytokines are important regulators of both the initiation and progression of sepsis. Interleukin-15 (IL-15), a pro-inflammatory cytokine, has been linked to protective effects against myocardial infarction and myocarditis. However, the role of IL-15 in SIMD remains unclear. We established a mouse model of SIMD via cecal ligation puncture (CLP) surgery and a cell model of myocardial injury via lipopolysaccharide (LPS) stimulation. IL-15 expression was prominently upregulated in septic hearts as well as cardiomyocytes challenged with LPS. IL-15 pretreatment attenuated cardiac inflammation and cell apoptosis and improved cardiac function in the CLP model. Similar cardioprotective effects of IL-15 pretreatment were observed in vitro. As expected, IL-15 knockdown had the opposite effect on LPS-stimulated cardiomyocytes. Mechanistically, we found that IL-15 pretreatment reduced the expression of the pro-apoptotic proteins cleaved caspase-3 and Bax and upregulated the anti-apoptotic protein Bcl-2. RNA sequencing and Western blotting further confirmed that IL-15 pretreatment suppressed the activation of nuclear factor kappa B (NF-κB) signaling in mice with sepsis. Besides, the addition of NF-κB inhibitor can significantly attenuate cardiomyocyte apoptosis compared to the control findings. Our results suggest that IL-15 pretreatment attenuated the cardiac inflammatory responses and reduced cardiomyocyte apoptosis by partially inhibiting NF-κB signaling in vivo and in vitro, thereby improving cardiac function in mice with sepsis. These findings highlight a promising therapeutic strategy for SIMD.

Mitochondria plays an essential role in regulating cellular metabolic homeostasis, proliferation/differentiation, and cell death. Mitochondrial dysfunction is implicated in many age-related pathologies. Evidence supports that the dysfunction of mitochondria and the decline of mitochondrial DNA copy number negatively affect ovarian aging. However, the mechanism of ovarian aging is still unclear. Treatment methods, including antioxidant applications, mitochondrial transplantation, emerging biomaterials, and advanced technologies, are being used to improve mitochondrial function and restore oocyte quality. This article reviews key evidence and research updates on mitochondrial damage in the pathogenesis of ovarian aging, emphasizing that mitochondrial damage may accelerate and lead to cellular senescence and ovarian aging, as well as exploring potential methods for using mitochondrial mechanisms to slow down aging and improve oocyte quality.

IntroductionAcute pulmonary embolism (APE) is a life-threatening medical condition that is frequently encountered and associated with significant incidence and mortality rates, posing a substantial threat to patients’ well-being and quality of life. Sepsis is prominent independent risk factor for the development of APE. Despite recent investigations indicating a reduced APE risk through statin therapy, its impact on patients with sepsis and APE remains unresolved.MethodsThe Medical Information Mart for Intensive Care (MIMIC)-IV database was utilized to identify patients diagnosed with sepsis and APE, irrespective of statin treatment status, as part of this study. The primary study aim was to assess the risk of APE, which was analyzed using multivariate logistic regression models.ResultsThe study encompassed a total of 16,633 participants, with an average age of 64.8 ± 16.2 years. Multivariate logistic regression revealed that septic patients receiving statin therapy in the intensive care unit (ICU) exhibited a 33% reduction in the risk of developing APE (OR = 0.67, 95% CI: 0.52–0.86, p

Abstract Agricultural intensification affects natural and crop ecosystems, and increases the risk of agricultural pests in agroecosystems. Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is an important pest that damages a wide range of crops. However, the effect of agricultural intensification on the genetic diversity of this pest is still unclear. In this study, we investigated the effects of the composition and configuration of the landscape on the genetic diversity of the agricultural pest H. armigera based on cytochrome oxidase subunit I (COI) analyses. In total, 10 haplotypes were found in 2016 and 15 haplotypes in 2021 based on COI genes. The haplotype diversity and nucleotide diversity were the highest in the Anqiu (AQ) region during 2016 and in the Bincheng (BC) region during 2021. Haplotype 2 and haplotype 3 (Hap2 and Hap3) were the dominant haplotypes in the H. armigera population. Agricultural intensification had no effect on the genetic diversity of H. armigera between 2016 and 2021. Our study highlights the effect of agricultural intensification on the genetic diversity of H. armigera. Understanding the genetic consequences of agricultural intensification is essential for the green control of agricultural pests and the sustainable development of agriculture.

K+ channels regulate morphogens to scale adult fins, but little is known about what regulates the channels and how they control morphogen expression. Using the zebrafish pectoral fin bud as a model for early vertebrate fin/limb development, we found that K+ channels also scale this anatomical structure, and we determined how one K+-leak channel, Kcnk5b, integrates into its developmental program. From FLIM measurements of a Förster Resonance Energy Transfer (FRET)-based K+ sensor, we observed coordinated decreases in intracellular K+ levels during bud growth, and overexpression of K+-leak channels in vivo coordinately increased bud proportions. Retinoic acid, which can enhance fin/limb bud growth, decreased K+ in bud tissues and up-regulated regulator of calcineurin (rcan2). rcan2 overexpression increased bud growth and decreased K+, while CRISPR-Cas9 targeting of rcan2 decreased growth and increased K+. We observed similar results in the adult caudal fins. Moreover, CRISPR targeting of Kcnk5b revealed that Rcan2-mediated growth was dependent on the Kcnk5b. We also found that Kcnk5b enhanced depolarization in fin bud cells via Na+ channels and that this enhanced depolarization was required for Kcnk5b-enhanced growth. Lastly, Kcnk5b-induced shha transcription and bud growth required IP3R-mediated Ca2+ release and CaMKK activity. Thus, we provide a mechanism for how retinoic acid via rcan2 can regulate K+-channel activity to scale a vertebrate appendage via intercellular Ca2+ signaling.