Cross-Modality Reference and Feature Mutual-Projection for 3D Brain MRI Image Super-Resolution.

High-resolution (HR) magnetic resonance imaging (MRI) can reveal rich anatomical structures for clinical diagnoses. However, due to hardware and signal-to-noise ratio limitations, MRI images are often collected with low resolution (LR) which is not conducive to diagnosing and analyzing clinical diseases. Recently, deep learning super-resolution (SR) methods have demonstrated great potential in enhancing the resolution of MRI images; however, most of them did not take the cross-modality and internal priors of MR seriously, which hinders the SR performance. In this paper, we propose a cross-modality reference and feature mutual-projection (CRFM) method to enhance the spatial resolution of brain MRI images. Specifically, we feed the gradients of HR MRI images from referenced imaging modality into the SR network to transform true clear textures to LR feature maps. Meanwhile, we design a plug-in feature mutual-projection (FMP) method to capture the cross-scale dependency and cross-modality similarity details of MRI images. Finally, we fuse all feature maps with parallel attentions to produce and refine the HR features adaptively. Extensive experiments on MRI images in the image domain and k-space show that our CRFM method outperforms existing state-of-the-art MRI SR methods.

How to achieve high-quality development of SRDI enterprises-A study of the TOE framework-based configuration.

The high-quality development of SRDI enterprises is crucial for China to overcome critical technological bottlenecks and thereby achieve technological independence and strength. However, the factors driving the high-quality development of SRDI enterprises are not isolated elements, but rather a complex system of interconnected antecedents. This study employs the TOE framework and fuzzy set Qualitative Comparative Analysis (fsQCA) with 141 Chinese SRDI "little giant" listed companies as samples to explore how various factors contribute to their high-quality development. The findings indicate: (1) No single factor is necessary for SRDI enterprises' high-quality development. (2) It is the synergy of multiple factors, in various combinations, that drives their high-quality development. (3) Technological innovation plays a key role in these pathways; SRDI enterprises should leverage their resources and capabilities for a synergistic technology-organization-environment match, selecting the most suitable development path. The results of this study not only enrich our understanding of the factors influencing SRDI enterprises' high-quality development but also offer insights for both the enterprises and government policy-making.

Advances in PGD2/PTGDR2 signaling pathway in tumors: A review.

Studies have shown that the prostaglandin (PG) family acts as allergic inflammatory mediator in malignant diseases. Furthermore, prostaglandin E2 (PGE2) and its related receptors, as well as the prostaglandin D2 (PGD2)/PGD2 receptor (PTGDR2), play irreplaceable roles in tumorigenesis and anti-tumor therapy. Several experiments have demonstrated that PGD2 signaling through PTGDR2 not only directly inhibits cancer cell survival, proliferation, and migration but also reduces resistance towards conventional chemotherapeutic agents. Recent studies from our and other laboratories have shown that PGD2, its ligands, and related metabolites can significantly alter the tumor microenvironment (TME) by promoting the secretion of chemokines and cytokines, thereby inhibiting tumor progression. Additionally, reduced PGD2 expression has been associated with poor prognosis in patients with gastric, breast, lung, and pancreatic cancers, validating the preclinical findings and their clinical relevance. This review focuses on the current understanding of PGD2/PTGDR2 expression patterns and biological activity in cancer, proposing questions to guide the assessment of PGD2 and its receptors as potential targets for effective cancer therapies.

Effect of Adding Al on the Phase Structure and Gettering Performance of TiZrV Non-Evaporable Getter Materials.

Titanium zirconium vanadium (TiZrV) is a widely used non-evaporable getter (NEG) material with the characteristics of a low activation temperature and a large gas absorption capacity. At present, the research on TiZrV getters mainly focuses on the thin-film state, with little research on the bulk state. In this paper, a TiZrV getter was optimized by adding Al, and the phase structure, activation properties, and gettering performance were studied. With the addition of Al, the α-Zr phase and Ti2Zr phase changed into the Ti-Zr phase and Al-Zr, Al-Ti phase. The newly generated phase promoted the diffusion of hydrogen and oxygen atoms. The activation temperature decreased significantly, as shown in the in situ XPS results. The H2 and CO gettering performance of TiZrVAl samples was promoted to 2073 cm3·s-1 and 1912.8 cm3·s-1, increased by 40.7% and 40.3%. This paper provides valuable ideas for optimizing the properties of bulk TiZrV getters.

Seasonal human coronavirus NL63 epidemics in children in Guilin, China, reveal the emergence of a new subgenotype of HCoV-NL63.

Introduction: Seasonal human coronavirus NL63 (HCoV-NL63) is a frequently encountered virus linked to mild upper respiratory infections. However, its potential to cause more severe or widespread disease remains an area of concern. This study aimed to investigate a rare localized epidemic of HCoV-NL63-induced respiratory infections among pediatric patients in Guilin, China, and to understand the viral subtype distribution and genetic characteristics. Methods: In this study, 83 pediatric patients hospitalized with acute respiratory infections and positive for HCoV-NL63 were enrolled. Molecular analysis was conducted to identify the viral subgenotypes and to assess genetic variations in the receptor-binding domain of the spiking protein. Results: Among the 83 HCoV-NL63-positive children, three subgenotypes were identified: C4, C3, and B. Notably, 21 cases exhibited a previously unreported subtype, C4. Analysis of the C4 subtype revealed a unique amino acid mutation (I507L) in the receptor-binding domain of the spiking protein, which was also observed in the previously reported C3 genotype. This mutation may suggest potential increases in viral transmissibility and pathogenicity. Discussion: The findings of this study highlight the rapid mutation dynamics of HCoV-NL63 and its potential for increased virulence and epidemic transmission. The presence of a unique mutation in the C4 subtype, shared with the C3 genotype, raises concerns about the virus's evolving nature and its potential public health implications. This research contributes valuable insights into the understanding of HCoV-NL63's epidemiology and pathogenesis, which is crucial for effective disease prevention and control strategies. Future studies are needed to further investigate the biological significance of the observed mutation and its potential impact on the virus's transmissibility and pathogenicity.

The application of proteomics and phosphoproteomics to reveal the molecular mechanism of salidroside in ameliorating myocardial hypoxia.

Salidroside (SAL), belonging to a kind of the main active ingredient of Rhodiola rosea, is extensively utilized for anti-hypoxia and prevention of altitude sickness in the plateau region of China. However, the research on the systemic changes induced by SAL at intracellular protein level is still limited, especially at protein phosphorylation level. These limitations hinder a comprehensive understanding of the regulatory mechanisms of SAL. This study aimed to investigate the potential molecular mechanism of SAL in ameliorating the acute myocardial hypoxia induced by cobalt chloride using integrated proteomics and phosphoproteomics. We successfully identified 165 differentially expressed proteins and 266 differentially expressed phosphosites in H9c2 cells following SAL treatment under hypoxic conditions. Bioinformatics analysis and biological experiment validation revealed that SAL significantly antagonized CoCl2-mediated cell cycle arrest by downregulating CCND1 expression and upregulating AURKA, AURKAB, CCND3 and PLK1 expression. Additionally, SAL can stabilize the cytoskeleton through upregulating the Kinesin Family (KIF) members expression. Our study systematically revealed that SAL had the ability to protect myocardial cells against CoCl2-induced hypoxia through multiple biological pathways, including enhancing the spindle stability, maintaining the cell cycle, relieving DNA damage, and antagonizing cell apoptosis. This study supplies a comprehension perspective on the alterations at protein and protein phosphorylation levels induced by SAL treatment, thereby expanded our knowledge of the anti-hypoxic mechanisms of SAL. Moreover, this study provides a valuable resource for further investigating the effects of SAL.

Low serum apolipoprotein A1 impairs antitumor immunity of CD8+ T cells via the HIF-1α-glycolysis pathway.

An immunosuppressive microenvironment promotes the occurrence and development of tumors. Low apolipoprotein A1 (ApoA1) is closely related to tumor development, but the underlying mechanisms are unclear. This study investigated the association between serum ApoA1 levels and the immune microenvironment in endometrial, ovarian, and lung cancers. The serum ApoA1 level was decreased significantly in patients with endometrial and ovarian cancers compared with healthy controls. In endometrial cancer tissues, the low serum ApoA1 group showed increased CD163+ macrophage infiltration and decreased CD8+ T-cell infiltration compared with the normal serum ApoA1 group. Compromised tumor-infiltrating CD8+ T-cell functions and decreased CD8+ T-cell infiltration also were found in tumor-bearing ApoA1-knockout mice. CD8+ T-cell depletion experiments confirmed that ApoA1 exerted its antitumor activity in a CD8+ T cell-dependent manner. In vitro experiments showed that the ApoA1 mimetic peptide L-4F directly potentiated the antitumor activity of CD8+ T cells via a HIF-1α-mediated glycolysis pathway. Mechanistically, ApoA1 suppressed ubiquitin-mediated degradation of HIF-1α protein by downregulating HIF-1α subunit α inhibitor. This regulatory process maintained the stability of HIF-1α protein and activated the HIF-1α signaling pathway. Tumor-bearing ApoA1 transgenic mice showed an increased response to anti-PD-1 therapy, leading to reduced tumor growth along with increased infiltration of activated CD8+ T cells and enhanced tumor necrosis. The data reported herein demonstrate critical roles for ApoA1 in enhancing CD8+ T-cell immune functions via HIF-1α-mediated glycolysis and support clinical investigation of combining ApoA1 supplementation with anti-PD-1 therapy for treating cancer.

Characterization of a novel adipose tissue located between abdominal lymph nodes and cervix/prostate in mice.

Perigonadal adipose tissue is a homogeneous white adipose tissue (WAT) in adult male mice, without any brown adipose tissue (BAT) present. However, there are congenital differences in the gonads between male and female mice. Whether heterogeneity existed in perigonadal ATs in female mice remains unknown. This study reported a perigonadal BAT located between abdominal lymph nodes and uterine cervix in female mice, termed lymph node-cervical adipose tissue (LNCAT). Its counterpart, lymph node-prostatic adipose tissue (LNPAT), exhibited white phenotype in adult virgin male mice. When exposed to cold, LNCAT/LNPAT increased UCP1 expression via activation of TH, in which abdominal lymph nodes were involved. Interestingly, the UCP1 expression in LNCAT/LNPAT varied under different reproductive stages. The UCP1 expression in LNCAT was upregulated at early pregnancy, declined at mid-late pregnancy, and reverted in weaning dams. Mating behavior stimulated LNPAT browning in male mice. We found that androgen but not estrogen or progesterone inhibited UCP1 expression in LNCAT. Androgen administration reversed the castration-induced LNPAT browning. Our results identified a perigonadal BAT in female mice and characterized its UCP1 expression patterns under various conditions.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption.

Introduction: Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR). Methods: Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes. Results: The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption. Conclusions: Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.

Human Biomonitoring of Environmental Chemicals among Elderly in Wuhan, China: Prioritizing Risks Using EPA's ToxCast Database.

In line with the "healthy aging" principle, we aim to assess the exposure map and health risks of environmental chemicals in the elderly. Blood samples from 918 elderly individuals in Wuhan, China, were analyzed using the combined gas/liquid-mass spectrometry technology to detect levels of 118 environmental chemicals. Cluster analysis identified exposure profiles, while risk indexes and bioanalytical equivalence percentages were calculated using EPA's ToxCast database. The detection rates for 87 compounds exceeded 70%. DEHP, DiBP, naphthalene, phenanthrene, DnBP, pyrene, anthracene, permethrin, fluoranthene, and PFOS showed the highest concentrations. Fat-soluble pollutants varied across lifestyles. In cluster 2, which was characterized by higher concentrations of fat-soluble substances, the proportion of smokers or drinkers was higher than that of nonsmokers or nondrinkers. Pesticides emerged as the most active environmental chemicals in peroxisome proliferator-activated receptor gamma antagonist, thyroid hormone receptor (TR) antagonist, TR agonist, and androgen receptor (AR) agonist activity assays. Additionally, PAEs and polycyclic aromatic hydrocarbons played significant roles as active contaminants for the corresponding targets of AR antagonists and estrogen receptor alpha. We proposed a list of priority pollutants linked to endocrine-disrupting toxic effects in the elderly, which may provide the groundwork for further research into environmental etiology.

Neoadjuvant Chemotherapy Is Effective in Those Infected With SARS-CoV-2: The Real-World Experience of a Large Chinese Breast Cancer Center.

PURPOSE: During the major shift in China's policies on coronavirus disease 2019 (COVID-19), many residents will be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over a short period, including a few patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Moreover, it is unknown whether this comorbidity affects the efficacy of NAC for breast cancer and the patient's psychological state and quality of life (QOL). This study aims to answer these questions. METHODS: The clinical data of 2,793 patients with breast cancer who received NAC at The Affiliated Hospital of Qingdao University were retrospectively collected. The infected and non-infected groups were divided according to whether they were infected with COVID-19 during NAC. Propensity score matching was used to reduce patient selection bias. The effectiveness, psychological well-being, and QOL of the two groups were compared. RESULTS: No discernible differences were observed in the pathological complete response rates (p = 0.307) and major histological responses rate (p = 0.398) between the infected and non-infected groups. Following the full course of NAC, the Functional Assessment of Cancer Treatment General (p < 0.001) and Functional Assessment of Cancer Therapy for Breast Cancer (p < 0.001) were lower in the infected group than the non-infected group, the Hospital Anxiety and Depression Scale (HADS) anxiety scale (p < 0.001) and HADS depression scale (p < 0.001) were considerably higher in the infected group than the non-infected group. CONCLUSION: With timely treatment and effective medical management, SARS-CoV-2 does not appear to affect the efficacy of NAC; however, it can significantly affect the QOL of patients and increase their psychological distress. Therefore, in addition to a timely assessment of the efficacy of NAC, it is necessary to dynamically understand the patient's psychological state and QOL.

Two 2D Metal-Organic Frameworks Based on Purine Carboxylic Acid Ligands for Photocatalytic Oxidation of Sulfides and CO2 Chemical Fixation.

Two two-dimensional (2D) layered metal-organic frameworks (MOFs), namely, {[Yb(L)(H2O)2NO3]·2H2O}n (Yb-MOF) and [Er(L)(H2O)3Cl]n (Er-MOF) (H2L = 5-((6H-purin-6-yl)amino)isophthalic acid), were constructed by a solvothermal method and characterized. The catalytic performance study showed that the Yb-MOF could efficiently catalyze the oxidation of sulfides to sulfoxides under 15 W light-emitting diode (LED) blue light irradiation. Electron paramagnetic resonance spectroscopy and free-radical trapping experiments demonstrated that the photocatalytic reaction process involved •O2-, and the corresponding mechanism was proposed. Moreover, Er-MOF exhibited good catalytic efficiency and excellent substrate tolerance in the cycloaddition reaction of CO2, and the reaction conditions were mild. After 5 cycles, the catalytic activities of two MOFs did not significantly decrease, and the framework structures remained unchanged. Therefore, the Yb-MOF and Er-MOF were considered efficient and stable heterogeneous catalysts.

Poly(3,4-Ethylenedioxythiophene)/Functional Gold Nanoparticle films for Improving the Electrode-Neural Interface.

Implantable neural electrodes are indispensable tools for recording neuron activity, playing a crucial role in neuroscience research. However, traditional neural electrodes suffer from limited electrochemical performance, compromised biocompatibility, and tentative stability, posing great challenges for reliable long-term studies in free-moving animals. In this study, a novel approach employing a hybrid film composed of poly(3,4-ethylenedioxythiophene)/functional gold nanoparticles (PEDOT/3-MPA-Au) to improve the electrode-neural interface is presented. The deposited PEDOT/3-MPA-Au demonstrates superior cathodal charge storage capacity, reduced electrochemical impedance, and remarkable electrochemical and mechanical stability. Upon implantation into the cortex of mice for a duration of 12 weeks, the modified electrodes exhibit notably decreased levels of glial fibrillary acidic protein and increased neuronal nuclei immunostaining compared to counterparts utilizing poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate). Additionally, the PEDOT/3-MPA-Au modified electrodes consistently capture high-quality, stable long-term electrophysiological signals in vivo, enabling continuous recording of target neurons for up to 16 weeks. This innovative modification strategy offers a promising solution for fabricating low-impedance, tissue-friendly, and long-term stable neural interfaces, thereby addressing the shortcomings of conventional neural electrodes. These findings mark a significant advancement toward the development of more reliable and efficacious neural interfaces, with broad implications for both research and clinical applications.

[Effect and mechanism of free total rhubarb anthraquinones on pyroptosis of J774A.1 macrophages].

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.

Extracellular Matrix-Mimetic Intrinsic Versatile Coating Derived from Marine Adhesive Protein Promotes Diabetic Wound Healing through Regulating the Microenvironment.

The management of diabetic wound healing remains a severe clinical challenge due to the complicated wound microenvironments, including abnormal immune regulation, excessive reactive oxygen species (ROS), and repeated bacterial infections. Herein, we report an extracellular matrix (ECM)-mimetic coating derived from scallop byssal protein (Sbp9Δ), which can be assembled in situ within 30 min under the trigger of Ca2+ driven by strong coordination interaction. The biocompatible Sbp9Δ coating and genetically programmable LL37-fused coating exhibit outstanding antioxidant, antibacterial, and immune regulatory properties in vitro. Proof-of-concept applications demonstrate that the coating can reliably promote wound healing in animal models, including diabetic mice and rabbits, ex vivo human skins, and Staphylococcus aureus-infected diabetic mice. In-depth mechanism investigation indicates that improved wound microenvironments accelerated wound repair, including alleviated bacterial infection, lessened inflammation, appearance of abundant M2-type macrophages, removal of ROS, promoted angiogenesis, and re-epithelialization. Collectively, our investigation provides an in situ, convenient, and effective approach for diabetic wound repair.

Impact of acute glycemic variability on short-term outcomes in patients with ST-segment elevation myocardial infarction: a multicenter population-based study.

BACKGROUND: Given the increasing attention to glycemic variability (GV) and its potential implications for cardiovascular outcomes. This study aimed to explore the impact of acute GV on short-term outcomes in Chinese patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This study enrolled 7510 consecutive patients diagnosed with acute STEMI from 274 centers in China. GV was assessed using the coefficient of variation of blood glucose levels. Patients were categorized into three groups according to GV tertiles (GV1, GV2, and GV3). The primary outcome was 30-day all-cause death, and the secondary outcome was major adverse cardiovascular events (MACEs). Cox regression analyses were conducted to determine the independent correlation between GV and the outcomes. RESULTS: A total of 7136 patients with STEMI were included. During 30-days follow-up, there was a significant increase in the incidence of all-cause death and MACEs with higher GV tertiles. The 30-days mortality rates were 7.4% for GV1, 8.7% for GV2 and 9.4% for GV3 (p = 0.004), while the MACEs incidence rates was 11.3%, 13.8% and 15.8% for the GV1, GV2 and GV3 groups respectively (p < 0.001). High GV levels during hospitalization were significantly associated with an increased risk of 30-day all-cause mortality and MACEs. When analyzed as a continuous variable, GV was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.679, 95% confidence Interval [CI] 1.005-2.804) and MACEs (HR 2.064, 95% CI 1.386-3.074). Additionally, when analyzed as categorical variables, the GV3 group was found to predict an increased risk of MACEs, irrespective of the presence of diabetes mellitus (DM). CONCLUSION: Our study findings indicate that a high GV during hospitalization was significantly associated with an increased risk of 30-day all-cause mortality and MACE in Chinese patients with STEMI. Moreover, acute GV emerged as an independent predictor of increased MACEs risk, regardless of DM status.

Treg-Derived Extracellular Vesicles: Roles in Diseases and Theranostics.

Regulatory T cells (Tregs), a subset of CD4+ T cells, are indispensable in maintaining immune self-tolerance and have been utilized in various diseases. Treg-derived extracellular vesicles (Treg-EVs) have been discovered to play an important role in the mechanism of Treg functions. As cell-derived membranous particles, EVs carry multiple bioactive substances that possess tremendous potential for theranostics. Treg-EVs are involved in numerous physiological and pathological processes, carrying proteins and miRNAs inherited from the parental cells. To comprehensively understand the function of Treg-EVs, here we reviewed the classification of Treg-EVs, the active molecules in Treg-EVs, their various applications in diseases, and the existing challenges for Treg-EVs based theranostics. This Review aims to clarify the feasibility and potential of Treg-EVs in diseases and theranostics, facilitating further research and application of Treg-EVs.

DockingGA: enhancing targeted molecule generation using transformer neural network and genetic algorithm with docking simulation.

Generative molecular models generate novel molecules with desired properties by searching chemical space. Traditional combinatorial optimization methods, such as genetic algorithms, have demonstrated superior performance in various molecular optimization tasks. However, these methods do not utilize docking simulation to inform the design process, and heavy dependence on the quality and quantity of available data, as well as require additional structural optimization to become candidate drugs. To address this limitation, we propose a novel model named DockingGA that combines Transformer neural networks and genetic algorithms to generate molecules with better binding affinity for specific targets. In order to generate high quality molecules, we chose the Self-referencing Chemical Structure Strings to represent the molecule and optimize the binding affinity of the molecules to different targets. Compared to other baseline models, DockingGA proves to be the optimal model in all docking results for the top 1, 10 and 100 molecules, while maintaining 100% novelty. Furthermore, the distribution of physicochemical properties demonstrates the ability of DockingGA to generate molecules with favorable and appropriate properties. This innovation creates new opportunities for the application of generative models in practical drug discovery.