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Abstract It is currently unclear whether there is a connection between Life’s Essential 8 (LE8) and cardiovascular disease (CVD), as well as mortality in people with nonalcoholic fatty liver disease (NAFLD). Our goal was to explore these relationships by examining data collected in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. We identified eligible participants with NAFLD based on NHANES 2005–2018 data. CVD status was acquired through self-reported information, and using the National Death Index, mortality data were prospectively matched. The diagnosis of NAFLD relied on noninvasive biomarkers. The research involved 9094 individuals who were identified as having NAFLD, with a mean age of 52.05 years. Each incremental LE8 score exhibited a significant association, leading to a 3%, 3%, 4%, 3%, 3%, 4%, and 4% reduction in the odds of experiencing CVD, ischemic heart disease, congestive heart failure, coronary heart disease, heart attack, angina, and stroke in individuals with NAFLD. A strong correlation was found between maintaining a superior level of Cardiovascular Health (CVH), as shown by a LE8 score ranging from 80 to 100, and a reduced occurrence of CVD and its various forms in NAFLD (all p for trend

Abstract Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Y2O3–Al2O3–ZrO2 composite ceramic powders are an important structural and functional material. The agglomeration problem in the ceramic powder drying process must be resolved to prepare high-quality ceramic powder, and choosing the right drying techniques can significantly lessen ceramic powder agglomeration. Y2O3–Al2O3–ZrO2 ceramic powder was dried using microwave drying. The drying kinetics of the powders were examined with their initial mass, moisture content, and microwave power. As microwave power, beginning moisture content, and initial mass rose, the average drying rate also increased, according to the experimental data. To better characterize the microwave drying process, the drying data were fitted and analyzed using four thin-layer drying kinetic models, namely Quadratic Model, Modified Page, Wang and Singh, and Two-term exponential. The outcomes demonstrate the good fitting effect of the Modified Page model and the compliance of the fitting parameters with the law. The samples before and after drying were characterized by Fourier transform infrared spectroscopy. Calculating the diffusion coefficient by Fick's second law shows that the effective diffusion coefficient of Y2O3–Al2O3–ZrO2 composite ceramic powder is 5.6 × 10−11 m2/s when the initial moisture content is 5%, the microwave heating power is 560 W, and the initial mass is 25 g. The activation energy for microwave drying of Y2O3–Al2O3–ZrO2 ceramic powders was calculated to be 22.83 W/g according to the Arrhenius formula. This paper aims to provide a theoretical basis and rich experimental data for the study of microwave drying of Y2O3–Al2O3–ZrO2 composite ceramic powder.

TiO2–Y2O3–ZrO2 composite ceramics exhibit excellent abrasion resistance, corrosion resistance, and high-temperature resistance, making them vital structural-functional materials in ceramics and refractories. The key to preparing high-quality TiO2–Y2O3–ZrO2 ceramic powders lies in controlling the agglomeration rate, which can be optimized by choosing an appropriate drying method. This study utilized microwave drying techniques to dehydrate TiO2–Y2O3–ZrO2 ceramic powders. It was found that the average drying rate is proportional to initial masses, initial moisture contents and microwave heating powers. To describe the drying process, four models—the Quadratic, Wang and Singh, Modified Page, and Page—were employed. The best model for the drying process was the Modified Page model. The specimens were analyzed to assess the alterations in the samples pre and post-drying by scanning electron microscopy and Fourier transform infrared spectroscopy. The findings revealed that microwaves can hasten the drying process of TiO2–Y2O3–ZrO2 and enhance its spread. Utilizing Fick's second law, the effective diffusion coefficient was ascertained, showing an inverse proportionality to the sample mass, and a proportionality to the microwave heating power and initial moisture content. Using the Arrhenius exponential model, it was ascertained that the microwave drying process's activation energy stands at 13.81834 W/g. This paper demonstrates that microwave drying effectively achieves efficient drying and lays the theoretical and experimental groundwork for the microwave heating and drying of other powdered materials.

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

Abstract Background Gastric cancer (GC) encompasses many different histological and molecular subtypes. It is a major driver of cancer mortality because of poor survival and limited treatment options. Personalised medicine in the form of patient-derived organoids (PDOs) represents a promising approach for improving therapeutic outcomes. The goal of this study was to overcome the limitations of current models by ameliorating organoid cultivation. Methods Organoids derived from cancer tissue were evaluated by haematoxylin and eosin staining, immunohistochemistry, mRNA, and whole-exome sequencing. Three representative chemotherapy drugs, 5-fluorouracil, docetaxel, and oxaliplatin, were compared for their efficacy against different subtypes of gastric organoids by ATP assay and apoptosis staining. In addition, drug sensitivity screening results from two publicly available databases, the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopaedia, were pooled and applied to organoid lines. Once key targeting genes were confirmed, chemotherapy was used in combination with poly (ADP ribose) polymerase (PARP)-targeted therapy. Results We successfully constructed GC PDOs surgically resected from GC patient tissue. PDOs closely reflected the histopathological and genomic features of the corresponding primary tumours. Whole-exosome sequencing and mRNA analysis revealed that changes to the original tumour genome were maintained during long-term culture. The drugs caused divergent responses in intestinal, poorly differentiated intestinal, and diffuse gastric cancer organoids, which were confirmed in organoid lines. Poorly differentiated intestinal GC patients benefited from a combination of 5-fluorouracil and veliparib. Conclusion The present study demonstrates that combining chemotherapy with PARP targeting may improve the treatment of chemotherapy-resistant tumours.

Abstract Introduction Emerging infectious diseases (EIDs) can disrupt the healthcare system, causing regulatory changes that affect the healthcare-seeking process and potentially increase patient-physician dissatisfaction. This study aimed to collect and analyze patients’ and physicians’ complaints during an EID outbreak to inform potential clues regarding medical quality and patient safety enhancement in future dealing with EIDs, employing text mining methodologies. Methods In this descriptive study, complaint records from January 2020 to February 2023 at West China Hospital, a national medical facility in China, were analyzed. Patient and physician complaints have been retrospectively retrieved from the record from the medical department, and then categorized into distinct groups based on reporting reasons, encompassing COVID-19-related policies, healthcare access, availability of medical resources, and financial concerns. Results During the COVID-19 pandemic, 541 COVID-19-related complaints were identified: 330 (61.00%) from patients and 211 (39.00%) from physicians. The monthly volume of complaints fluctuated, starting at 10 in 2020, peaking at 21 in 2022, and dropping to 14 in 2023. Most complaints from inpatients were expressed by older males aged 40 to 65 (38.82%, 210/541). The primary source of complaints was related to mandatory COVID-19 policies (79.30%, 429/541), followed by concerns regarding timely healthcare services (31.61%, 171/541). Few complaints were expressed regarding the insufficiency of medical resources (2.77%, 15/541) and the high costs (4.25%, 23/541). The frequency of complaints expressed by doctors and patients in the emergency department was higher compared with other departments (24.58%, 133/541). Conclusions Increased complaints may serve as a primitive and timely resource for investigating the potential hazards and drawbacks associated with policies pertaining to EIDs. Prompt collection and systematical analysis of patient and physician feedback could help us accurately evaluate the efficacy and repercussions of these policies. Implementing complaints-based assessment might improve care standards in forthcoming healthcare environments grappling with EIDs.

Abstract Despite widespread public interest in the health impact of exposure to microwave radiation, studies of the influence of microwave radiation on biological samples are often inconclusive or contradictory. Here we examine the influence of microwave radiation of frequencies 3.5 GHz, 20 GHz and 29 GHz on the growth of microtubules, which are biological nanotubes that perform diverse functions in eukaryotic cells. Since microtubules are highly polar and can extend several micrometres in length, they are predicted to be sensitive to non-ionizing radiation. Moreover, it has been speculated that tubulin dimers within microtubules might rapidly toggle between different conformations, potentially participating in computational or other cooperative processes. Our data show that exposure to microwave radiation yields a microtubule growth curve that is distorted relative to control studies utilizing a homogeneous temperature jump. However, this apparent effect of non-ionizing radiation is reproduced by control experiments using an infrared laser or hot air to heat the sample and thereby mimic the thermal history of samples exposed to microwaves. As such, no non-thermal effects of microwave radiation on microtubule growth can be assigned. Our results highlight the need for appropriate control experiments in biophysical studies that may impact on the sphere of public interest.

Abstract Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/− HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Abstract Light-emitting diodes (LEDs) based on perovskite semiconductor materials with tunable emission wavelength in visible light range as well as narrow linewidth are potential competitors among current light-emitting display technologies, but still suffer from severe instability driven by electric field. Here, we develop a stable, efficient and high-color purity hybrid LED with a tandem structure by combining the perovskite LED and the commercial organic LED technologies to accelerate the practical application of perovskites. Perovskite LED and organic LED with close photoluminescence peak are selected to maximize photon emission without photon reabsorption and to achieve the narrowed emission spectra. By designing an efficient interconnecting layer with p-type interface doping that provides good opto-electric coupling and reduces Joule heating, the resulting green emitting hybrid LED shows a narrow linewidth of around 30 nm, a peak luminance of over 176,000 cd m−2, a maximum external quantum efficiency of over 40%, and an operational half-lifetime of over 42,000 h.

It is of great importance to study the effects of transport corridors on ecological traits in highly cold grasslands in the context of climate change and increasing human activities. However, the patterns of ecological traits and the reasons of these patterns in these road areas were not yet well understood. Therefore, we examined three community properties and five leaf functional traits at three distances (0 m, 50 m and 100 m) from the edge of two roads on the Qinghai-Tibet Plateau and explored their relationships. The results showed that mean annual precipitation was the key factor shaping the patterns of ecological traits in the road areas. Roads exerted a positive influence on plant communities in desert steppes, as evidenced by increased vegetation height, vegetation coverage, leaf area, and leaf length. In contrast, roads had a negative effect in alpine meadows, resulting in thicker leaves. The study identified a mean annual precipitation threshold of 300 mm, above and below which the effects of distance on specific leaf area (or leaf thickness) exhibited opposite trends. This finding suggests that plants near roads pursued different strategies compared to those far from roads, with slower investment-return strategies in wet environments and faster investment-return strategies in dry environments. Significant relationships between productivity-related community properties and leaf traits were only observed in alpine steppes of the road areas. This study emphasizes the importance of water condition and grassland type on ecological traits in highly cold road areas.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Abstract Oncolytic viruses (OVs) have emerged as a powerful tool in cancer therapy. Characterized with the unique abilities to selectively target and lyse tumor cells, OVs can expedite the induction of cell death, thereby facilitating effective tumor eradication. Nanoengineering‐derived OVs overcome traditional OV therapy limitations by enhancing the stability of viral circulation, and tumor targeting, promising improved clinical safety and efficacy and so on. This review provides a comprehensive analysis of the multifaceted mechanisms through which engineered OVs can suppress tumor progression. It initiates with a concise delineation on the fundamental attributes of existing OVs, followed by the exploration of their mechanisms of the antitumor response. Amid rapid advancements in nanomedicine, this review presents an extensive overview of the latest developments in the synergy between nanomaterials, nanotechnologies, and OVs, highlighting the unique characteristics and properties of the nanomaterials employed and their potential to spur innovation in novel virus design. Additionally, it delves into the current challenges in this emerging field and proposes strategies to overcome these obstacles, aiming to spur innovation in the design and application of next‐generation OVs.

BRCA1 is one of the most frequently-mutated tumor suppressor genes in ovarian and breast cancers. Loss of BRCA1 triggers homologous recombination (HR) repair deficiency, consequently leading to genomic instability and PARP inhibitors (PARPi)-associated synthetic lethality. Although, the roles of BRCA1 in DNA repair and replication have been extensively investigated, its tumor suppressive functions beyond genome safeguard remain poorly understood. Here, we report that BRCA1 promotes ferroptosis susceptibility through catalyzing K6-linked polyubiquitination of GPX4 and subsequently accelerating GPX4 degradation. Depletion of BRCA1 induces ferroptosis resistance in ovarian cancer cells due to elevated GPX4 protein, and silence of GPX4 significantly suppresses the growth of BRCA1-deficient ovarian cancer xenografts. Importantly, we found that PARPi triggers ferroptosis in ovarian cancer cells, inhibition of GPX4 markedly increase PARPi-induced ferroptosis in BRCA1-deficient ovarian cancer cells. Combined treatment of GPX4 inhibitor and PARPi produces synergistic anti-tumor efficacy in BRCA1-deficient ovarian cancer cells, patient derived organoid (PDO) and xenografts. Thus, our study uncovers a novel mechanism via which BRCA1 exerts tumor suppressive function through regulating ferroptosis, and demonstrates the potential of GPX4 as a therapeutic target for BRCA1-mutant cancers.

Abstract Photoacoustic (PA) emitters are emerging ultrasound sources offering high spatial resolution and ease of miniaturization. Thus far, PA emitters rely on electronic transitions of absorbers embedded in an expansion matrix such as polydimethylsiloxane (PDMS). Here, it is shown that mid‐infrared vibrational excitation of C─H bonds in a transparent PDMS film can lead to efficient mid‐infrared photoacoustic conversion (MIPA). MIPA shows 37.5 times more efficient than the commonly used PA emitters based on carbon nanotubes embedded in PDMS. Successful neural stimulation through MIPA both in a wide field with a size up to a 100 µm radius and in single‐cell precision is achieved. Owing to the low heat conductivity of PDMS, less than a 0.5 °C temperature increase is found on the surface of a PDMS film during successful neural stimulation, suggesting a non‐thermal mechanism. MIPA emitters allow repetitive wide‐field neural stimulation, opening up opportunities for high‐throughput screening of mechano‐sensitive ion channels and regulators.

BackgroundMental health challenges are encountered by frail older adults as the population ages. The extant literature is scant regarding the correlation between depressive symptoms and social participation among frail older adults.MethodsThis study is based on an analysis of data from China Health and Retirement Longitudinal Study (CHARLS) participants aged 60 and older who are frail. A frailty index (FI) was developed for the purpose of assessing the frailty level of the participants. Additionally, latent class analysis (LCA) was employed to classify the participants’ social engagement patterns in 2015 and 2018. The study used ordered logistic regression to examine the relationship between social participation type and depressive symptoms. We also used Latent Transition Analysis (LTA) methods to explore the impact of changes in social activity types on depressive symptoms after three years of follow-up in 2018. In addition, the response surface analysis (RSM) investigation explored the relationship among FI, depression, and social participation.ResultsA total of 4,384 participants completed the baseline survey; three years later, 3,483 were included in the follow-up cohort. The baseline survey indicates that female older adults in rural areas who are single, have lower incomes, shorter sleep durations, and lighter weights exhibited more severe depressive symptoms. Social participation patterns were categorized into five subgroups by LCA. The findings indicate that individuals classified as “board game enthusiasts” (OR, 0.62; 95% CI, 0.47-0.82) and those as “extensive social interaction” (OR,0.67; 95% CI, 0.49-0.90) have a significantly lower likelihood of developing depressive symptoms compared to the “socially isolated” group. We also discovered that “socially isolated” baseline participants who transitioned to the “helpful individual” group after three years had significantly greater depressed symptoms (OR, 1.56; 95% CI, 1.00-2.44). More social activity types and less FI are linked to lower depression in our study.ConclusionThe results of the study emphasize the importance of social participation patterns and the number of social participation types in relation to the severity of depression among frail older adults individuals. This study’s findings may provide important insights for addressing depressive symptoms in frail older adults person.

Summary: Ferroptosis is a form of nonapoptotic cell death characterized by iron-dependent peroxidation of polyunsaturated phospholipids. However, much remains unknown about the regulators of ferroptosis. Here, using CRISPR-Cas9-mediated genetic screening, we identify protein arginine methyltransferase 1 (PRMT1) as a crucial promoter of ferroptosis. We find that PRMT1 decreases the expression of solute carrier family 7 member 11 (SLC7A11) to limit the abundance of intracellular glutathione (GSH). Moreover, we show that PRMT1 interacts with ferroptosis suppressor protein 1 (FSP1), a GSH-independent ferroptosis suppressor, to inhibit the membrane localization and enzymatic activity of FSP1 through arginine dimethylation at R316, thus reducing CoQ10H2 content and inducing ferroptosis sensitivity. Importantly, genetic depletion or pharmacological inhibition of PRMT1 in mice prevents ferroptotic events in the liver and improves the overall survival under concanavalin A (ConA) exposure. Hence, our findings suggest that PRMT1 is a key regulator of ferroptosis and a potential target for antiferroptosis therapeutics.

The millimeter-sized glass (SiO2) shells play key roles in inertial confinement fusion (ICF) experiments, especially for the so-called ''direct-drive'' configuration. The preparation of large diameter/thickness ratio glass shells and the exploration of transformation mechanisms for silicon-doped glow discharge polymer (Si-GDP) to SiO2 still face challenges. Here, we prepared large diameter/thickness ratio glass shells with the diameter of ∼1200 μm and shell thickness of ∼5 μm by increasing the Si contents in Si-GDP precursors. The influence of Si contents in Si-GDP shells on the compositions, morphologies and geometrical properties of glass shells were carefully investigated. The formability and uniformity of micro morphologies of the glass shells will improve with the increase of Si contents in precursors. The chemical composition of the prepared glass shells is SiO2 with some carbides adsorbed on their surfaces and the compositions present negligible relationship with the Si contents. The sphericity, thickness uniformity and surface quality will increase with the increase of Si contents in precursors. Besides, the oxidation mechanisms for Si-GDP to SiO2 were explored by the combination of an in situ high temperature infrared spectroscopy and a simultaneous thermal analyzer.

A dissociation set of a graph $ G $ refers to a set of vertices inducing a subgraph with maximum degree at most 1 and serves as a generalization of two fundamental concepts in graph theory: Independent sets and induced matchings. The enumeration of specific substructures in grid graphs has been a captivating area of research in graph theory. Over the past few decades, the enumeration problems related to various structures in grid graphs such as Hamiltonian cycles, Hamiltonian paths, independent sets, maximal independent sets, and dominating sets have been deeply studied. In this paper, we enumerated dissociation sets in grid graphs using the state matrix recursion algorithm.

Abstract. Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target. In this review, we summarize the latest research in the field of diabetic cardiomyopathy, focusing on mitochondrial damage and adaptation, altered energy substrates, and potential therapeutic targets. A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

Abstract The incidence of acute kidney injury (AKI) due to ischemia–reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI.

Achieving efficient low-voltage actuation of microelectromechanical system (MEMS) resonators in high-temperature environments poses a difficult topic due to the thermal interference and the risk of high-temperature failure. In this work, the single-crystal diamond (SCD) resonators fabricated through the ion implantation-assisted lift-off (IAL) technique exhibit a SCD-on-SCD cantilever structure. We propose an electrical actuation system based on the electrostatic effect specifically designed for SCD MEMS resonators with a low radio-frequency amplitude of ∼ 100 mV. The SCD resonators demonstrate stable and efficient actuation across a wide temperature range, from room temperature to 500 °C. Importantly, the actuation voltage exhibits little impact on the resonance frequency and the Q factor of the resonator. The SCD resonator showcases exceptional thermal stability in resonance frequency, with a low temperature coefficient of frequency (TCF) below −12 ppm/°C up to 500 °C. The developed actuation scheme holds tremendous potential as a robust platform for realizing SCD MEMS devices, particularly in applications requiring high integration at high temperatures.

Abstract Neuromodulation is a powerful tool for fundamental studies in neuroscience and potential treatments of neurological disorders. Both photoacoustic (PA) and photothermal (PT) effects are harnessed for non‐genetic high‐precision neural stimulation. Using a fiber‐based device excitable by a nanosecond pulsed laser and a continuous wave laser for PA and PT stimulation, respectively, PA and PT neuromodulation is systematically investigated at the single neuron level. These results show that to achieve the same level of neuron activation recorded by Ca2+ imaging, the laser energy needed for PA stimulation is 1/40 of that needed for PT stimulation. The threshold energy for PA stimulation is found to be further reduced in neurons overexpressing mechano‐sensitive channels, indicating direct involvement of mechano‐sensitive channels in PA stimulation. Electrophysiology study of single neurons upon PA and PT stimulation is performed by patch clamp recordings. Electrophysiological features induced by PA are distinct from those by PT, confirming that PA and PT stimulation operate through different mechanisms. These insights offer a foundation for the rational design of more efficient and safer non‐genetic neural modulation approaches.

Abstract Ferroptosis is a predominant contributor to graft kidney ischemia‒reperfusion injury (IRI), resulting in delayed graft function (DGF). However, much less is known about the early predicting biomarkers and therapeutic targets of DGF, especially aiming at ferroptosis. Here, we propose a precise predicting model for DGF, relying on the Akirin1 level in extracellular vesicles (EVs) derived from recipient urine 48 h after kidney transplant. In addition, we decipher a new molecular mechanism whereby Akirin1 induces ferroptosis by strengthening TP53‐mediated suppression of SLC7A11 during the graft kidney IRI process, that is, Akirin1 activates the EGR1/TP53 axis and inhibits MDM2‐mediated TP53 ubiquitination, accordingly upregulating TP53 in two ways. Meanwhile, we present the first evidence that miR‐136‐5p enriched in EVs secreted by human umbilical cord mesenchymal stem cells (UM‐EVs) confers robust protection against ferroptosis and graft kidney IRI by targeted inhibition of Akirin1 but knockout of miR‐136‐5p in UM sharply mitigates the protection of UM‐EVs. The functional and mechanistic regulation of Akirin1 is further corroborated in an allograft kidney transplant model in wild‐type and Akirin1‐knockout mice. In summary, these findings suggest that Akirin1, which prominently induces ferroptosis, is a pivotal biomarker and target for early diagnosis and treatment of graft kidney IRI and DGF after kidney transplant.

Emerging evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating immunological functions and autoimmune responses. In the context of Crohn's disease (CD), an array of novel lncRNAs has been identified in the plasma and intestinal tissues of afflicted individuals, suggesting a dualistic influence on the disease progression, either exacerbating or mitigating its course. Current research has demonstrated the involvement of lncRNAs in competitive endogenous RNA, the inflammation process, epithelial barrier function, gut microbiota imbalance, and epigenetic regulation. This review aims to encapsulate the current knowledge on the lncRNA contribution to CD and underscore potential avenues for future research. LncRNAs are increasingly recognized as significant biomarkers and potential therapeutic targets, holding a key position in the pathogenesis of CD. Furthermore, the unique attributes of circulating lncRNAs, such as minimal side effects, combinational therapy potential, and personalized medicine, render them as promising therapeutic tools for individual health management in CD.

Aluminum/steel structures are widely proposed for weight reduction in aviation, aerospace, and automotive industries, whereas the applications of aluminum/steel structures are still limited due to the unreliable welding related to the intermetallic compounds. In this study, an amorphous layer was in-situ formed at the aluminum/steel interface, replacing the intermetallic compounds, and strengthening the welds. The effects of the plunge depth on the microstructure and mechanical properties of the Al/steel friction stir welds were further investigated. The amorphous phase was only formed when the welding tool was plunged to the interface precisely. Once the plunge depth was further increased, the amorphous layer would grow over the critical thickness of 18 nm and, subsequently, be replaced by the FeAl3 and FeAl. Different interfacial microstructure led to the different strength and fracture characteristics. The ultimate load of 6237 N was achieved with the in-situ formed amorphous layer, and it was improved by 45 %, as compared to the previous results.

Abstract Background The role of Serum uric acid (SUA) in acute myocardial infarction (AMI) was controversial, which might be influenced by the renal clearance function of the patients. The present study aimed to explore the association between serum uric acid to serum creatinine ratio (SUA/Scr), reflecting a net production of SUA, and the in-hospital outcomes of elderly patients with AMI. Methods In this retrospective study, a total of 330 elderly AMI patients (≥ 75 years) were enrolled. Data of SUA and Scr on admission were collected to calculate SUA/Scr ratio. Logistic regression analysis and receiver-operating curves were performed to assess the association between SUA/Scr ratio and in-hospital major adverse cardiovascular events (MACEs) and all-cause death. Results Among the 330 patients, 68 patients had MACEs and 44 patients died. Patients with MACEs or died had lower SUA/Scr values compared with those without MACEs or survival (P

The heavy oil is essentially comprised of asphaltene and nitrogen, sulphur, and oxygen-bearing (NSO) compounds, which records the alteration processes of aerobic biodegradation. In this study, six biodegraded oils were geochemically examined using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in negative-ion electrospray ionization (ESI(-)) mode to decipher the NSO heteroatom compounds molecular compositions. The results reveal that the NSO compounds, especially those strongly resistant to biodegradation, i.e., alcohol/phenols, carboxylic acids with various alkyl substitution, naphthenic acids with 2 to 5 naphthenic/aromatic rings, nitrogen- and sulphur-bearing carboxylic acids, and hydroxy acids (O3) and dibasic acids (O4) are enriched in biodegraded oils. The O1, N1O1, and O1S1 classes appear in trace amounts in severely to extremely biodegraded oils (PM > 7) but are abundant in moderately biodegraded oils (PM

Background: Partial bladder outlet obstruction (pBOO) causes deposition of extracellular matrix (ECM), promotes bladder fibrosis, and decreases bladder compliance. Methods: To investigate the effect of β-adrenoceptor (ADRB) on the ECM deposition of pBOO rat model and explore its underlying mechanism, human bladder smooth muscle cells (hBSMCs) were exposed to the pathological hydrostatic pressure (100 cm H2O) for 6 h, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were employed. Then the rats of sham operation and pBOO model were treated with vehicle or ADRB agonists for 3 weeks, and the alterations of the bladder were observed via Masson staining and immunohistochemical analysis. Results: 100 cm H2O hydrostatic pressure significantly upregulated the expression of collagen I (COL1), collagen III (COL3) and fibronectin (FN), and downregulated the expression of ADRB2 and ADRB3 of hBSMCs at 6 h. The agonists of ADRB2 and ADRB3, Formoterol and BRL 37344, decreased COL1 and FN expression of hBSMCs under 100 cm H2O for 6 h compared with the cells exposed to hydrostatic pressure only. As the classic downstream pathways of ADRB, the EPAC pathway inhibited COL1 and FN expression of hBSMCs via regulating SMAD3 and SMAD2 activities, respectively. In pBOO rats, Procaterol (ADRB2 agonist), and Mirabegron (ADRB3 agonist) inhibited the formation of collagen and decreased the expression of FN and COL1 in the bladders of pBOO rats. Conclusions: The bladder fibrosis of pBOO and deposition of hBSMCs ECM under hydrostatic pressure were regulated by ADRB2, and ADRB3 via EPAC/SMAD2/FN and EPAC/SMAD3/COL1 pathways, these findings pave an avenue for effective treatment of pBOO.

Our target USH reservoir in the D oilfield is characterized by “inverse rhythm” deposition with the noticeable features of “high porosity and low permeability”. The reservoir has been developed with waterflooding using horizontal wells. Due to the strong heterogeneity of the reservoir, water channeling is severe, and the water cut has reached 79%. Considering the high temperature and high salinity reservoir conditions, polymer microspheres (PMs) were selected to realize conformance control. In this study, characterization of the polymer microsphere suspension was achieved via morphology, size distribution, and viscosity measurement. Furthermore, a multi-scale visualization study of the reservoir development process, including waterflooding, polymer microsphere flooding, and subsequent waterflooding, was conducted using macro-scale coreflooding and calcite-etched micromodels. It was revealed that the polymer microspheres could swell in the high salinity brine (170,000 ppm) by 2.7 times if aged for 7 days, accompanied by a viscosity increase. This feature is beneficial for the injection at the wellbore while swelled to work as a profile control agent in the deep formation. The macro-scale coreflood with a 30 cm × 30 cm × 4.5 cm layer model with 108 electrodes installed enabled the oil distribution visualization from different perpendicular cross sections. In this way, the in situ conformance control ability of the polymer microsphere was revealed both qualitatively and quantitatively. Furthermore, building on the calcite-etched visible micro-model, the pore-scale variation of the residual oil when subjected to waterflooding, polymer microsphere waterflooding, and subsequent waterflooding was collected, which revealed the oil displacement efficiency increase by polymer microspheres directly. The pilot test in the field also proves the feasibility of conformance control by the polymer microspheres, i.e., more than 40,000 bbls of oil increase was observed in the produces, accompanied by an obvious water reduction.

Abstract Background A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. Methods Analysis of multi‐omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co‐immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual‐luciferase reporter, chromatin immunoprecipitation, western blotting and real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log‐rank test. Results c‐Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate‐aspartate shuttle (MAS) in NB cells. Mechanistically, c‐Myc directly promoted the expression of glutamyl‐prolyl‐tRNA synthetase (EPRS) and leucyl‐tRNA synthetase (LARS), resulting in translational up‐regulation of glutamic‐oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c‐Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre‐clinically, lobeline was discovered as a LMNA‐binding compound to facilitate its interaction with c‐Myc, which inhibited aminoacyl‐tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c‐Myc knock‐in mice. Low levels of LMNA or elevated expression of c‐Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. Conclusions These results suggest that targeting c‐Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

Introduction: Obesity, mainly caused by excessive accumulation of visceral fat, excessive fat metabolism will cause hormone secretion imbalance and inflammation and other diseases. is extremely detrimental to human health. Although many treatments are available for obesity, most treatments fail to exert a radical effect or are associated with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipid content and inflammation is considered effective. Based on previous studies, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were selected to prepare an innovative herbal formula. Methods: TCM was characterized by UHPLC-Q-Orbitrap-MS. The anti-inflammatory and lipid-lowering effects of the TCM formula prepared were evaluated in a high-fat diet-fed obese mouse model. The effects of the TCM formula on the intestinal flora were also investigated. Results: Weights and insulin resistance, as well as inflammation, decreased in the mice after treatment. At the same time, lipid metabolism increased after the mice were gavaged with the TCM formula for 2 weeks. The intestinal motility of the drug administration group was enhanced, with partial restoration of the intestinal flora. Conclusion: In summary, our innovative Chinese herbal formula significantly reduced weight, reduced intestinal inflammation, improved intestinal motility, and improved lipid metabolism in obese mice. Furthermore, the innovative formula effectively prevented relevant obesity-induced metastatic diseases in the mice.

Objective: This study aimed to assess the efficacy and safety of traditional Chinese medicine decoction as an adjunctive treatment for diabetic nephropathy in systematic evaluations.Methods: A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering the period from January 2013 to July 2023. The search was restricted to randomized controlled trials (RCTs) conducted within the past decade that investigated the use of TCM decoction as an adjunctive treatment for diabetic nephropathy. The control group received western medicine treatment, while the intervention group received TCM decoction in addition to the conventional treatment. Endnote and Excel were employed for literature management and data organization, and Revman 5.3 and Stata 16 software were used for the analyses.Results: 66 RCTs involving 6,951 participants were included in this study. The clinical efficacy of TCM decoction as an adjunctive treatment for diabetic nephropathy was found to be significantly higher than that of the control group (OR = 3.12, 95% CI [2.70, 3.60], I2 = 0%, p < 0.00001). The incidence of adverse events did not differ significantly between the intervention group and the control group (OR = 0.94, 95% CI [0.60, 1.48], I2 = 0%, p = 0.94). According to the secondary outcomes of renal function and blood glucose indicators, the intervention group showed better therapeutic efficacy compared to the control group. The most frequently used TCM categories were tonifying medicine, blood-activating medicine, astringent medicine, diuretic medicine, heat-clearing medicine, and laxative medicine. Among them, the top five frequently used Chinese medicine were Astragalus mongholicus Bunge [Fabaceae; Astragali mongholici radix](58 times), Salvia miltiorrhiza Bunge [Lamiaceae; Radix et rhizoma salviae miltiorrhizae] (42 times), Dioscorea oppositifolia L. [Dioscoreaceae; Dioscoreae rhizoma] (38 times), Poria cocos (Schw.) Wolf [Polyporaceae; Poria] (38 times), and Cornus officinalis Siebold & Zucc. [Cornaceae; Corni fructus] (35 times).Conclusion: The combined use of TCM decoction with western medicine in the treatment of diabetic nephropathy can enhance clinical effectiveness and 2 This is a provisional file, not the final typeset article achieve superior therapeutic effects in comparison to western medicine alone, without significant risks.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier [CRD42022529144].

Small and imbalanced fault samples have a profound impact on the diagnostic performance of a model in the process of locating and quantifying the rolling bearing damage of aeroengines in practice. Therefore, a Siamese Convolutional Neural Network-Bidirectional Long Short-Term Memory (CNN-BiLSTM) model was proposed in this paper. Random selection and cross combination methods were used to augment and balance sample sizes at first. Then, two weight-sharing CNN-BiLSTM models were used for adaptive extraction and distance measurement of weak fault features. Finally, the fault classification was performed based on feature distance. Model performance was verified using simulated fault test data of rolling bearings. The results showed that the Siamese CNN-BiLSTM model could achieve an accuracy of up to 96.0% for quantitative diagnosis and 98.0% for location diagnosis. This model was also capable of solving the imbalanced classification of samples and made it possible to transfer between different rotating speeds and working conditions.

Introduction Transcatheter aortic valve replacement (TAVR) has become an important treatment in patients with aortic valve disease with the continuous advancement of technology and the improvement of outcomes. However, TAVR-related complications still increase patient morbidity and mortality. Remote ischaemic preconditioning (RIPC) is a simple procedure that provides perioperative protection for many vital organs. However, the efficiency of RIPC on TAVR remains unclear based on inconsistent conclusions from different clinical studies. Therefore, we will perform a protocol for a systematic review and meta-analysis to identify the efficiency of RIPC on TAVR.Methods and analysis English databases (PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library), Chinese electronic databases (Wanfang Database, VIP Database and China National Knowledge Infrastructure) and trial registry databases will be searched from inception to December 2023 to identify randomised controlled trials of RIPC on TAVR. We will calculate mean differences or standardised mean differences with 95% CIs for continuous data, and the risk ratio (RR) with 95% CIs for dichotomous data by Review Manager version 5.4. Fixed-effects model or random-effects model will be used according to the degree of statistical heterogeneity assessed by the I-square test. We will evaluate the risk of bias using the Cochrane risk-of-bias tool 2 and assess the evidence quality of each outcome by the Grading of Recommendations Assessment, Development and Evaluation. The robustness of outcomes will be evaluated by trial sequential analysis. In addition, we will evaluate the publication bias of outcomes by Funnel plots and Egger’s regression test.Ethics and dissemination Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications.PROSPERO registration number CRD42023462926

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) recently caused a global pandemic, resulting in more than 702 million people being infected and over 6.9 million deaths. Patients with coronavirus disease (COVID‐19) may suffer from diarrhea, sleep disorders, depression, and even cognitive impairment, which is associated with long COVID during recovery. However, there remains no consensus on effective treatment methods. Studies have found that patients with COVID‐19 have alterations in microbiota and their metabolites, particularly in the gut, which may be involved in the regulation of immune responses. Consumption of probiotics may alleviate the discomfort caused by inflammation and oxidative stress. However, the pathophysiological process underlying the alleviation of COVID‐19‐related symptoms and complications by targeting the microbiota remains unclear. In the current study, we summarize the latest research and evidence on the COVID‐19 pandemic, together with symptoms of SARS‐CoV‐2 and vaccine use, with a focus on the relationship between microbiota alterations and COVID‐19‐related symptoms and vaccine use. This work provides evidence that probiotic‐based interventions may improve COVID‐19 symptoms by regulating gut microbiota and systemic immunity. Probiotics may also be used as adjuvants to improve vaccine efficacy.

PurposeWe prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application.MethodsA total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy.ResultsAll patients were followed up for 33–52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P

Abstract Detrusor underactivity (DUA) is a common and thorny problem in urology, which severely impairs patients’ bladder function and quality of life. However, its underlying pathophysiological mechanism remains unclear. Hence, we sequenced 69,973 cells from five controls and nine patients with bladder dysfunction using single‐cell RNA sequencing. Twelve distinct cell types were identified and they showed high cellular and functional heterogeneity among each group. Among them, fibroblasts, macrophages, and epithelial cells had the most intercellular communications. Their aberrant gene expressions and altered intercellular interactions were mainly involved in extracellular matrix organization, inflammation/immune regulation, and cellular injury. Further re‐cluster analysis revealed an accumulation of the RBFOX1+ fibroblasts and RIPOR2+ macrophages in dysfunctional bladder wall, which mediated bladder remodeling through dysfunctional extracellular matrix organization and inflammation/immune reaction. Besides, the subtype of the epithelial cells was significantly altered. They underwent an intricate process including inflammation, damage, and repair during bladder remodeling. Overall, this work constructed the first single‐cell atlas for obstruction‐induced DUA, which could provide a valuable resource for deciphering the cellular heterogeneity and function changes in DUA, as well as potential strategies for bladder function improvement.

Backgrounds: Short-term exposure to air pollutants increases the risk of migraine, but the long-term impacts of exposure to multiple pollutants on migraine have not been established. The aim of this large prospective cohort study was to explore these links. Methods: A total of 458,664 participants who were free of migraine at baseline from the UK Biobank were studied. Cox proportional hazards models were used to estimate the risk of new-onset migraine from combined long-term exposure to four pollutants, quantified as an air pollution score using principal component analysis. Results: During a median (IQR) follow-up of 12.5 (11.8, 13.2) years, a total of 5417 new-onset migraine cases were documented. Long-term exposure to multiple air pollutants was associated with an increased risk of new-onset migraine, as indicated by an increased in the SDs of PM2.5 (hazard ratio (HR): 1.04, 95% CI: 1.01–1.06, P = 0.009), PM10 (HR: 1.07, 95% CI: 1.04–1.10, P < 0.001), NO2 (HR: 1.10, 95% CI: 1.07–1.13, P < 0.001) and NOx (HR: 1.04, 95% CI: 1.01–1.07, P = 0.005) in the main model. The air pollution score showed a doseresponse association with an increased risk of new-onset migraine. Similarly, compared with those of the lowest tertile, the HRs (95% CI) of new-onset migraine were 1.11 (95% CI: 1.04–1.19, P = 0.002) and 1.17 (95% CI: 1.09–1.26, P < 0.001) in tertiles 2 and 3, respectively, according to the main model (P trend < 0.001). Conclusion: Long-term individual and joint exposure to multiple air pollutants is associated with an increased risk of new-onset migraine.

Abstract Autophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome marker GFP-LC3 in the cytoplasm of cells, as well as the downregulation of its nuclear pool indicative of autophagic flux. In this respect, 3,4-DC showed a broader autophagy-inducing activity than another chalcone (4,4- dimethoxychalcone), spermidine and triethylene tetramine. Thus, we characterized the potential antiatherogenic activity of 3,4-DC in two different mouse models, namely, (i) neointima formation with smooth muscle expansion of vein segments grafted to the carotid artery and (ii) genetically predisposed ApoE −/− mice fed an atherogenic diet. In the vein graft model, local application of 3,4-DC was able to maintain the lumen of vessels and to reduce neointima lesions. In the diet-induced model, intraperitoneal injections of 3,4-DC significantly reduced the number of atherosclerotic lesions in the aorta. In conclusion, 3,4-DC stands out as an autophagy inducer with potent antiatherogenic activity.

Abstract Background Recent evidence reveals the emerging functions of circular RNA (circRNA) and protein glycosylation in cancer progression. However, the roles of circRNA in regulating glycosyltransferase expression in gastric cancer remain to be determined. Methods Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by chromatin immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its partners on the glycosylation, growth, invasion, and metastasis of gastric cancer cells. Results Circ-hnRNPU, an exonic circRNA derived from heterogenous nuclear ribonuclear protein U (hnRNPU), was identified to exert tumor suppressive roles in protein glycosylation and progression of gastric cancer. Mechanistically, circ-hnRNPU physically interacted with non-POU domain containing octamer binding (NONO) protein to induce its cytoplasmic retention, resulting in down-regulation of glycosyltransferases (GALNT2, GALNT6, MGAT1) and parental gene hnRNPU via repression of nuclear NONO-mediated c-Myc transactivation or cytoplasmic NONO-facilitated mRNA stability. Rescue studies indicated that circ-hnRNPU inhibited the N- and O-glycosylation, growth, invasion, and metastasis of gastric cancer cells via interacting with NONO protein. Pre-clinically, administration of lentivirus carrying circ-hnRNPU suppressed the protein glycosylation, tumorigenesis, and aggressiveness of gastric cancer xenografts. In clinical cases, low circ-hnRNPU levels and high NONO or c-Myc expression were associated with poor survival outcome of gastric cancer patients. Conclusions These findings indicate that circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

Abstract Haemoglobin (Hb) G‐Makassar is a rare Hb variant. It presents a diagnostic challenge as it imitates sickle Hb (Hb S) in standard electrophoresis and high‐performance liquid chromatography assays requiring DNA analysis to confirm diagnosis. Both have point mutations in codon 6, exon 1 in the β‐globin (HBB) gene with different pathogenicities. This study describes the clinical phenotype, haematology and genotype of Hb G‐Makassar. Clinical and laboratory data of 38 cases of Hb G‐Makassar over 8 years were analysed. Hb G‐Makassar was confirmed by a direct sequencing of HBB gene and co‐inheritance of α‐thalassaemia determined through multiplex gap‐PCR and multiplex Amplification Refractory Mutation System polymerase chain reaction. All cases were Malays, predominantly from Terengganu (n = 20, 52.6%). There were 14 (36.8%) males and 24 (63.2%) females with median age of 25 years. Majority (n = 33, 86.8%) had features of thalassaemia trait with mean ± SD for Hb, mean cell volume (MCV) and mean cell haemoglobin (MCH) as 13.21 g/dL ± 1.69, 73.06 ± 4.48 fL and 24.71 ± 1.82 pg, respectively. None had evidence of haemolysis or thromboembolic complications. Six genotypes were identified; ßG‐Makassar/ß,αα/αα (n = 19, 50.0%), ßG‐Makassar/ßE,αα/αα (n = 4, 10.5%), ßG‐Makassar/ßNewYork,αα/αα (n = 1, 2.6%), ßG‐Makassar/ß,αα/‐α (n = 11, 28.9%), ßG‐Makassar/ß,αα/αAdanaα (n = 2, 5.3%) and ßG‐Makassar/ß,αα/–SEA (n = 1, 2.6%). The ßG‐Makassar/ß,αα/αα showed that features of thalassaemia trait with mean ± SD for Hb, MCV and MCH were 13.74 g/dL ± 2.40, 76.18 ± 6.02 fL and 25.79 ± 2.41 pg, respectively. This is the largest study reporting a significant number of Hb G‐Makassar in Malaysia. Although the mutation is similar to Hb S, the phenotype is benign.

Zirconia composite ceramic materials are popular for their many excellent properties. In this study, nTi-3Y–ZrO2 composite ceramics were produced by the mechanical alloying-microwave sintering method with different Ti-doping amounts and microwave sintering temperatures. The sample's phase composition, stability rate, lattice parameters, micromorphology, relative density, and grain size are characterized. The results showed that when the sintering temperature is 1200 °C, the samples with different doping amounts are mainly mixed crystalline structures with tetragonal and cubic phases, and the stability rate remains above 90 %. As TiO2 doping increases, the lattice parameters a(Å) and b(Å)first increase and then decrease, while the lattice parameter c (Å) shows an overall increasing trend. Raman data demonstrated that the increase in Ti content promoted the generation of tetragonal phase zirconia. The average grain size is 61.33 nm, 76.23 nm, 58.77 nm, 63.35 nm, and 68.99 nm, respectively. The increase in doping is also accompanied by a narrowing of the grain size distribution, which increases the sintering activity of the sample. In addition, the relative densities of the samples were 67.85 %, 73.94 %, 84.25 %, 84.87 %, and 77.54 %, respectively, showing a gradual increasing trend overall. When the microwave sintering temperature is 1200 °C, and the doping amount is 5Ti–3Y–92Zr, the performance of the sample is superior to other groups. The preparation of nTi-3Y–ZrO2 composite ceramics can provide certain ideas for preparing ceramic materials with excellent performance in various aspects.

This paper analyzes the current research status of digital platforms for underground coal mine drilling in China from three aspects: digitization of measurement while drilling, digitization of drilling site environment monitoring, and digitization of drilling rig monitoring. Combined with the actual needs of intelligent drilling in coal mines, the overall architecture of the digital platform for directional drilling in coal mines was designed, and the connotation and path of key technologies such as multi-sensor data fusion and remote interaction were analyzed. The engineering practice of related technologies was carried out in Tianrong Coal Mine of Wuhai Mining Area, and the comprehensive management and control capability of the digital platform for drilling was verified through the trial operation system. Finally, it points out the digital development trend of directional drilling in coal mines.

Abstract The swift advancement of technology has led to the widespread utilization of artificial intelligence (AI) in the diagnosis of diseases and prediction of prognoses, particularly in the field of intensive care unit (ICU) and Anesthesia. Numerous evidential data have demonstrated the extensive potential of AI in monitoring and predicting patient outcomes in these fields. Using bibliometric analysis, this study provides an overview of the current state of knowledge regarding the application of AI in ICU and Anesthesia and investigates prospective avenues for future research. Web of Science Core Collection was queried on May 6, 2023, to select articles and reviews regarding AI in ICU and Anesthesia. Subsequently, various analytical tools including Microsoft Excel 2022, VOSviewer (version 1.6.16), Citespace (version 6.2.R2), and an online bibliometric platform were employed to examine the publication year, citations, authors, countries, institutions, journals, and keywords associated with this subject area. This study selected 2196 articles from the literature. focusing on AI-related research within the fields of ICU and Anesthesia, which has increased exponentially over the past decade. Among them, the USA ranked first with 634 publications and had close international cooperation. Harvard Medical School was the most productive institution. In terms of publications, Scientific Reports (impact factor (IF) 4.996) had the most, while Critical Care Medicine (IF 9.296) had the most citations. According to numerous references, researchers may focus on the following research hotspots: “Early Warning Scores”, “Covid-19″, “Sepsis” and “Neural Networks”. “Procalcitonin” and “Convolutional Neural Networks” were the hottest burst keywords. The potential applications of AI in the fields of ICU and Anesthesia have garnered significant attention from scholars, prompting an increase in research endeavors. In addition, it is imperative for various countries and institutions to enhance their collaborative efforts in this area. The research focus in the upcoming years will center on sepsis and coronavirus, as well as the development of predictive models utilizing neural network algorithms to improve well-being and quality of life in surviving patients. Graphical Abstract

Abstract Mitochondrial mass and quality are tightly regulated by two essential and opposing mechanisms, mitochondrial biogenesis (mitobiogenesis) and mitophagy, in response to cellular energy needs and other cellular and environmental cues. Great strides have been made to uncover key regulators of these complex processes. Emerging evidence has shown that there exists a tight coordination between mitophagy and mitobiogenesis, and their defects may cause many human diseases. In this review, we will first summarize the recent advances made in the discovery of molecular regulations of mitobiogenesis and mitophagy and then focus on the mechanism and signaling pathways involved in the simultaneous regulation of mitobiogenesis and mitophagy in the response of tissue or cultured cells to energy needs, stress, or pathophysiological conditions. Further studies of the crosstalk of these two opposing processes at the molecular level will provide a better understanding of how the cell maintains optimal cellular fitness and function under physiological and pathophysiological conditions, which holds promise for fighting aging and aging-related diseases.