A review of non-classical MAPK family member, MAPK4: A pivotal player in cancer development and therapeutic intervention.

Mitogen-Activated Protein Kinases (MAPKs) are serine/threonine protein kinases that play a crucial role in transmitting extracellular signals to the intracellular environment, influencing a wide range of cellular processes including proliferation, differentiation, apoptosis, metabolic activities, immune function and stress response. MAPK4, a non-classical MAPK, is frequently overexpressed in various malignancies, including prostate, breast, cervix, thyroid, and gliomas. It orchestrates cell proliferation, migration, and apoptosis via the AKT/mTOR and/or PDK1 signaling pathways, thus facilitating tumor cell growth. Furthermore, MAPK4 expression is closely associated with the effectiveness of specific inhibitors like PI3K and PARP1, and also correlate with the survival rates of cancer patients. Increasing evidence highlights MAPK4's involvement in the tumor microenvironment, modulating immune response and inflammation-related diseases. This review comprehensively explores the structure, function, and oncogenic role of MAPK4, providing a deeper understanding of its activation and mechanisms of action in tumorigenesis, which might be helpful for the development of innovative therapeutic strategies for cancer management.

Spatial distribution of benthic taxonomic and functional diversity in the Yellow River Basin: From ecological processes to associated determinant factors.

One of the fundamental objectives in ecology is to investigate the ecological processes and associated factors governing the abundance and spatial distribution patterns of biodiversity. However, the reaction of biological communities to environmental degradation remains relatively unknown, even for ecologically crucial communities like macroinvertebrates in aquatic ecosystems. Here, we sampled 117 locations to quantify relative contributions of geographical and environmental factors, including water quality, land use, climate, and hydrological factors, to determine the absolute and relative compositions of macroinvertebrate communities and their spatial distribution in the Yellow River Basin (YRB), the sixth-longest river system on Earth. We assessed relative roles of species sorting and dispersal in determining macroinvertebrate community structure along YRB. Our results demonstrated that alpha and beta diversity indices showed an increase from the up- to low-reaches of YRB. The middle and low-reaches exhibited elevated species diversity and both regions exhibited relatively stable community compositions. The biodiversity of macroinvertebrates was influenced by a combination of geographical factors and environmental variables, with environmental factors predominantly serving as the principal determinants. Results of multiple linear regression and variance decomposition showed that the effect of environmental factors was approximately three times greater than that of spatial factors. These findings provide support for the hypothesis that species sorting, driven by environmental gradients, plays a significant role in shaping the community structure of macroinvertebrates in running water ecosystems at the basin scales. Moreover, the factors contributing to substantial shifts in biodiversity across different segments of YRB indicate that distinct river sections have been influenced by varying stressors, with downstream areas being more susceptible to the impacts of water pollution and urbanization resulting from human activities.

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice.

Purpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown. Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen. Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation. Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.

Discovering the Order-Disorder Transition in Quinoline Intercalated Vanadium Oxide with Superior Calcium Storage via Polyhedral Distortion.

Calcium-ion batteries (CIBs) are considered as potential next-generation energy storage systems due to their abundant reserves and relatively low cost. However, irreversible structural changes and weak conductivity still hinder in current CIBs cathode materials. Herein, an organic molecular intercalation strategy is proposed, in which V2O5 regulated with quinoline, pyridine, and water molecules are studied as cathode material to provide fast ion diffusion channels, large storage host, and high conductivity for Ca ions. Among them, V2O5-quinoline (QVO) owns the largest interplanar spacing of 1.25 nm and the V-O chains are connected with organic molecular by hydrogen bond, which stabilizes the crystal structure. As a result, QVO exhibits a specific capacity of 168 mAh g-1 at 1 A g-1 and capacity retention of 80% after 500 cycles at 5 A g-1 than the other materials. Furthermore, X-Ray diffraction and X-ray absorption spectroscopy results reveal a reversible order-disorder transformation mechanism of Ca2+ for QVO, which can make full use of the abundant active sites for high capacity and simultaneously achieve fast reaction kinetics for excellent rate performance. These results demonstrate that QVO is a promising cathode material for CIBs, providing more choices for the development of high-performance CIBs.

Molecular simulation screening and sensory evaluation unearth a novel kokumi compound with bitter-masking effect: N-lauroyl-L-tryptophan.

N-lauroyl-L-tryptophan (LT), which has the strongest potential flavor-presenting activity, was skillfully screened from numerous N-Lau-AAs docked to different taste receptors by molecular simulation techniques. Subsequently, LT was synthesized employing food-grade commercial enzymes and structurally characterized, the optimized yields of LT could reach 69.08%, 76.16%, and 50.40%, respectively. Sensory and E-tongue evaluations showed that LT at 1 mg/L significantly benefited the performance of different taste sensations and exhibited different bitter taste masking effects: L-Ile (68.42%), L-Trp (68.18%), D-salicylic acid (48.48%) and quinine (35.00%). The molecular docking results illustrated that LT had a high affinity for various taste receptors, dominated by hydrogen bonding and hydrophobic interactions. This work provided a rare systematic elucidation of the potential and mechanism of enzymatically synthesized LT in enhancing taste properties. It provides novel insights into the directions and strategies for the excavation and innovation of flavor enhancers and food flavors.

Causal association of circulating metabolites with diabetic retinopathy: a bidirectional Mendelian randomization analysis.

Introduction: The retina is a highly metabolically active tissue, and there is a lack of clarity about the relationship between metabolites and diabetic retinopathy (DR). This study used two-sample bidirectional Mendelian randomization (MR) analyses to identify causal relationships between metabolites and DR. Methods: Genetic variants were selected from the open-access Genome-Wide Association Studies (GWAS) summary database as proxies for the 1400 most recently published metabolites. MR analysis was performed to examine associations between these metabolite traits and DR. Single nucleotide polymorphism (SNP) data that were significantly associated with exposure were screened through association analysis. Validated instrumental variables (IVs) were obtained by removing SNPs with linkage disequilibrium (LD) and F-statistic values below 10. MR analyses were performed using the inverse variance weighted (IVW) method as the primary approach. The robustness of the results was verified by sensitivity analyses, including assessments of heterogeneity, horizontal pleiotropy, and the leave-one-out method. Results: In the IVW approach and in the primary analysis of several sensitivity analyses, genetically determined glycolithocholate sulfate levels, androstenediol (3 beta, 17 beta) monosulfate (1) levels, 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4) levels, 1-oleoyl-2-arachidonoyl-GPE (18:1/20:4) levels, 1-oleoyl-2-linoleoyl-GPE (18:1/18:2) levels, X-26109 levels, N6-methyllysine levels, (N6,N6-dimethyllysine levels), and (N2-acetyl,N6,N6-dimethyllysine levels) were negatively associated with the risk of DR. 5-hydroxymethyl-2-furoylcarnitine levels and the glutamate-to-alanine ratio were positively associated with the risk of DR. No reverse causal association was found between DR and metabolites. Discussion: This MR study suggests that nine metabolites may have a protective effect in DR, while two metabolites may be associated with an increased risk of DR. However, further research is needed to confirm these findings. Supplementation with beneficial metabolites may reduce DR risk and could potentially be a novel therapeutic approach to DR treatment.

Determinants and action paths of transboundary water pollution collaborative governance: A case study of the Yangtze River Basin, China.

With rapid economic growth, the issue of water pollution has become increasingly prominent, and there is a consensus that river basin management systems and cross-regional management coordination mechanisms need improving. In this study, 171 transboundary sections of the Yangtze River Basin were matched with the data of 57 cities to construct panel data from 2015 to 2021. Based on the four-dimensional framework of environment-determination-process-resources, the dynamic qualitative comparative analysis (QCA) method is used to identify the key influencing factors and action paths of water pollution collaborative governance effects. The results show that a single antecedent condition is not necessary to achieve efficient collaborative governance effects, and only the "number of collaborative governance" and "scale of collaboration" conditions played important roles. There are five paths that can achieve efficient collaborative governance effects: economy-oriented, ecology-oriented, technology-oriented, government-oriented, and all-oriented. Additionally, heterogeneous results show that the impact of the regional governance intention on efficient collaborative governance effect is limited in the middle and upstream sections of the Yangtze River Basin, while the downstream sections are more dependent on the basic condition of the basin. The results can help promote effective cross-regional collaboration in the Yangtze River Basin, provide scientific basis for regions to formulate targeted governance measures, and provide models for governance in other regions.

Self-evolving persistent luminescence nanoprobes for autofluorescence-free ratiometric imaging and on-demand enhanced chemodynamic therapy of pulmonary metastatic tumors.

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.

Pyridostigmine attenuates hypertension by inhibiting activation of the renin-angiotensin system in the hypothalamic paraventricular nucleus.

Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension. Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension. 2K1C rats received pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated. Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression. Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.

Association of serum 25-hydroxyvitamin D levels, vitamin D-binding protein levels, and diabetes mellitus: Two-sample Mendelian randomization.

Studies have suggested that Vitamin D deficiency is associated with the occurrence of both type 1 and type 2 diabetes, and that vitamin D-binding proteins (VDBP) are necessary for metabolic stress in pancreatic α-cells. However, the causal relationship between serum 25-hydroxyvitamin D [25(OH)D] levels, VDBP, and the risk of diabetes mellitus (DM) remains unclear. Mendelian randomization (MR) was used to investigate the causal relationship between 25(OH)D, VDBP, and DM. Relevant recent data were downloaded from the NHGRI-EBI Catalog of published genome-wide association studies (GWAS) and filtered for single nucleotide polymorphisms (SNPs). We used multiple MR methods, including inverse variance weighting (IVW), and performed sensitivity analyses to detect whether pleiotropy or heterogeneity biased the results. There was a causal relationship between genetically predicted VDBP levels and serum 25(OH)D levels, and serum 25(OH)D levels increased with increasing VDBP levels (IVW: ß = 0.111, OR = 1.117, 95% CI:1.076-1.162, P = 1.41 × 10-8). There was no causal relationship between the genetically predicted VDBP levels, serum 25(OH)D levels, and DM (VDBP: IVW ß:0.001, OR:1.001, 95% CI:0.998-1.003, P > .05; 25(OH)D: IVW ß: -0.009, OR:0.991, 95% CI:0.982-1.001, P = .068). Sensitivity analysis indicated that horizontal pleiotropy was unlikely to bias causality in this study. MR analysis results demonstrated a positive causal relationship between VDBP levels and serum 25(OH)D levels in the European population. The 25(OH)D and VDBP levels were not causally related to an increased risk of diabetes.

Upconversion-based hydrogel kit with Python-assisted analysis platform for sample-to-result detection of organophosphorus pesticide.

On-site quantitative analysis of pesticide residues is crucial for monitoring environmental quality and ensuring food safety. Herein, we have developed a reliable hydrogel portable kit using NaYbF4@NaYF4: Yb, Tm upconversion nanoparticles (UCNPs) combined with MnO2 nanoflakes. This portable kit is integrated with a smartphone reader and Python-assisted analysis platform to enable sample-to-result analysis for chlorpyrifos. The novel UCNPs maximizes energy donation to MnO2 acceptor by employing 100 % of activator Yb3+ in the nucleus for NIR excitation energy collection and confining emitter Tm3+ to the surface layer to shorten energy transfer distance. Under NIR excitation, efficient quenching of upconversion blue-violet emission by MnO2 nanoflakes occurs, and the quenched emission is recovered with acetylcholinesterase-mediated reactions. This process allows for the determination of chlorpyrifos by inhibiting enzymatic activity. The UCNPs/MnO2 were embedded to fabricate a hydrogel portable kit, the blue-violet emission images captured by smartphone were converted into corresponding gray values by Python-assisted superiority chart algorithm which achieves a real-time rapid quantitative analysis of chlorpyrifos with a detection limit of 0.17 ng mL-1. At the same time, pseudo-color images were also added by Python in "one run" to distinguish images clearly. This sensor detection with Python-assisted analysis platform provides a new perspective on pesticide monitoring and broadens the application prospects in bioanalysis.

The interplay of soil physicochemical properties, methanogenic diversity, and abundance governs methane production potential in paddy soil subjected to multi-decadal straw incorporation.

Straw incorporation holds significant promise for enhancing soil fertility and mitigating air pollution stemming from straw burning. However, this practice concurrently elevates the production and emission of methane (CH4) from paddy ecosystems. Despite its environmental impact, the precise mechanisms behind the heightened CH4 production resulting from long-term straw incorporation remains elusive. In a 32-year field experiment featuring three fertilization treatments (CFS-chemical fertilizer with wheat straw, CF-chemical fertilizer, and CK-unamended), we investigated the impact of abiotic (soil physicochemical properties) and biotic (methanogenic abundance, diversity, and community composition) factors on CH4 production in paddy fields. Results revealed a significantly higher CH4 production potential under CFS treatment compared to CF and CK treatments. The partial least squares path model revealed that soil physicochemical properties (path coefficient = 0.61), methanogenic diversity (path coefficient = -0.43), and methanogenic abundance (path coefficient = 0.29) collectively determined CH4 production potential, explaining 77% of the variance. Enhanced soil organic carbon content and water content, resulting from straw incorporation, emerged as pivotal factors positively correlated with CH4 production potential. Under CFS treatment, lower Shannon index of methanogens, compared to CF and CK treatments, was attributed to increased Methanosarcina. Notably, the Shannon index and relative abundance of Methanosarcina exhibited negative and positive correlations with CH4 production potential, respectively. Methanogenic abundance, bolstered by straw incorporation, significantly amplified overall potential. This comprehensive analysis underscores the joint influence of abiotic and biotic factors in regulating CH4 production potential during multi-decadal straw incorporation.

Sleep restriction promotes brain oxidative stress and inflammation, and aggravates cognitive impairment in insulin-resistant mice.

Sleep deprivation and insulin resistance (IR) are two risk factors for Alzheimer's disease. As the population of people with IR increases and sleep restriction (SR) due to staying up late becomes the "new normal", it is necessary to investigate the effects and molecular pathogenesis of chronic SR on cognitive function in insulin resistance. In this study, 4-week-old mice were fed a high-fat diet (HFD) for 8 weeks to establish IR model, and then the mice were subjected to SR for 21 days, and related indicators were assessed, including cognitive capacity, apoptosis, oxidative stress, glial cell activation, inflammation, blood-brain barrier (BBB) permeability and adiponectin levels, for exploring the potential regulatory mechanisms. Compared with control group, IR mice showed impaired cognitive capacity, meanwhile, SR not only promoted Bax/Bcl2-induced hippocampal neuronal cell apoptosis and Nrf2/HO1- induced oxidative stress, but also increased microglia activation and inflammatory factor levels and BBB permeability, thus aggravating the cognitive impairment in IR mice. Consequently, changing bad living habits and ensuring sufficient sleep are important intervention strategies to moderate the aggravation of IR-induced cognitive impairment.

Persistent production of multiple active species with copper doped zinc gallate nanoparticles for light-independent photocatalytic degradation of organic pollutants.

Photocatalysis is considered as an environmentally friendly and sustainable method as it can produce active species to degrade pollutants. However, its applications are hindered by the turbidity of pollutants and the requirements for continuous or repeated in situ irradiation. To avoid the need for continuous in situ irradiation in the photocatalytic process, herein we report the doping of Cu(II) ions into zinc gallate (ZnGa2O4) as traps to capture photo-generated electrons. In this way, long lifetime charge release and separation were effectively achieved for the persistent degradation of organic dyes in wastewater. The Cu(II) doped ZnGa2O4 (ZGC) nanoparticles with a small size about 7.7 nm synthesized via a hydrothermal method exhibited a persistent photocatalytic activity with continuous production of reactive oxygen species for at least 96 h without in situ irradiation due to its unique electronic structure and carrier transport path, and enabled to degrade 82.2 % of rhodamine B in 1 h. Further investigation revealed that the doped Cu(II) ions occupied the octahedral sites of ZGC and highly increased the persistent production and availability of active species for the persistent degradation of organic dyes under pre-illuminated conditions.

An eco-friendly porous hydrogel adsorbent based on dextran/phosphate/amino for efficient removal of Be(II) from aqueous solution.

A novel environmentally-friendly porous hydrogel adsorbent (GHPN) is firstly designed and prepared using dextran, phosphate, and calcium hydroxide for the adsorption of Be(II). GHPN shows good adsorption selectivity for Be(II) (Kd = 1.53 × 104 mL/g). According the adsorption kinetics and thermodynamics, the theoretical adsorption capacity of GHPN to Be(II) is 43.75 mg/g (35 °C, pH = 6.5), indicating a spontaneous exothermic reaction. After being reused for 5 cycles, the adsorption and desorption efficiencies of Be(II) with GHPN are obtained to be more than 80 %, showing acceptable recycling performance. Both of the characterizations and theoretical calculations indicate that the phosphate group, hydroxyl group, and amino group own the affinity to form stable complexes with Be(II). Benefiting from the introduction of phosphate and amino, the adsorption effect of the hydrogel adsorbent on Be(II) can be greatly improved, and surface precipitation, complexation, and ligand exchange are the dominant mechanisms of beryllium adsorption. The results suggest that GHPN has great potential to be utilized as an eco-friendly and useful adsorbent of Be(II) from aqueous solution.

Role of small nucleolar RNAs in alternative splicing of the doublesex gene in the silkworm, Bombyx mori.

More and more evidence shows that small noncoding RNAs (ncRNAs) play diverse roles in development, stress response and other cellular processes, but functional study of intermediate-size ncRNAs is still rare. Here, the expression profile of 16 intermediate-size ncRNAs in ovary and testis of silkworm Bombyx mori were analyzed. Twelve ncRNAs, including 5 small nucleolar RNAs (snoRNAs) and 7 unclassified ncRNAs, accumulated more in the testis than in the ovary of silkworm, especially Bm-163, Bm-51 and Bm-68. Four ncRNAs (including three orphan snoRNAs and one unclassified ncRNA) had higher expression level in the ovary than in the testis, especially Bm-86. Overexpression of the testis-enriched snoRNA Bm-68 in the female led to the accumulation of male-specific isoform of doublesex (BmdsxM) and increased the expression ratio of BmdsxM: BmdsxF. While overexpression of ovary-enriched snoRNA Bm-86 in the male decreased the expression ratio of BmdsxM: BmdsxF, indicating the roles of the two snoRNAs played in the alternative splicing of Bmdsx of silkworm, which will provide new clues for the functional study of snoRNAs in insects.

Nasal filter reveal exposure risks of inhalable particulates and heavy metals in urban women.

Urban populations, especially women, are vunerable to exposure to airborne pollution, particularly inhalable particulates (PM10). Thus, more accurate measurement of PM10 levels and evaluating their health effects is critical for guiding policy to improve human health. Previous studies obtained personal PM10 with time-weighted average by air filter-based sampling (AFS), which ignores individual differences and behavioral patterns. Here, we used nasal filters instead of AFS to obtain actual inhaled PM10 under short-term exposure for urban dwelling women during a severe haze event in Beijing in 2016. The levels of six heavy metals such as As, Cd, Ni, Cr, Pb, and Co in PM10 were investigated, and carcinogenic and non-carcinogenic risks evaluated based on an adjusted US EPA health risk assessment model. The health endpoints for urban dwelling women were further assessed through an exposure-reponse model. We found that the hourly inhaled dose of PM10 obtained through the nasal filter was about 2.5-17.6 times that obtained by AFS, which also resulted in 4.41-11.30 times more morbidity than estimated by AFS (p < 0.05). Proximity to traffic emissions resulted in greater exposure to particulate matter (>18.8 µg/kg·h) and heavy metals (>2.2 ng/kg·h), and these populations are therefore at greatest risk of developing non-cancer (HI = 4.16) and cancer (Rt = 7.8 × 10-3) related morbities.

Identification of co-expressed central genes and transcription factors in acute myocardial infarction and diabetic nephropathy.

BACKGROUND: Acute myocardial infarction (AMI) and diabetic nephropathy (DN) are common clinical co-morbidities, but they are challenging to manage and have poor prognoses. There is no research on the bioinformatics mechanisms of comorbidity, and this study aims to investigate such mechanisms. METHODS: We downloaded the AMI data (GSE66360) and DN datasets (GSE30528 and GSE30529) from the Gene Expression Omnibus (GEO) platform. The GSE66360 dataset was divided into two parts: the training set and the validation set, and GSE30529 was used as the training set and GSE30528 as the validation set. After identifying the common differentially expressed genes (DEGs) in AMI and DN in the training set, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and protein-protein interaction (PPI) network construction were performed. A sub-network graph was constructed by MCODE, and 15 hub genes were screened by the Cytohubba plugin. The screened hub genes were validated, and the 15 screened hub genes were subjected to GO, KEGG, Gene MANIA analysis, and transcription factor (TF) prediction. Finally, we performed TF differential analysis, enrichment analysis, and TF and gene regulatory network construction. RESULTS: A total of 46 genes (43 up-regulated and 3 down-regulated) were identified for subsequent analysis. GO functional analysis emphasized the presence of genes mainly in the vesicle membrane and secretory granule membrane involved in antigen processing and presentation, lipopeptide binding, NAD + nucleosidase activity, and Toll-like receptor binding. The KEGG pathways analyzed were mainly in the phagosome, neutrophil extracellular trap formation, natural killer cell-mediated cytotoxicity, apoptosis, Fc gamma R-mediated phagocytosis, and Toll-like receptor signaling pathways. Eight co-expressed hub genes were identified and validated, namely TLR2, FCER1G, CD163, CTSS, CLEC4A, IGSF6, NCF2, and MS4A6A. Three transcription factors were identified and validated in AMI, namely NFKB1, HIF1A, and SPI1. CONCLUSIONS: Our study reveals the common pathogenesis of AMI and DN. These common pathways and hub genes may provide new ideas for further mechanistic studies.

Robot-assisted surgery for dental implant placement: A narrative review.

OBJECTIVE: To determine the current status and accuracy of robotic computer-assisted implant surgery (CAIS) applications by examining the associated clinical and experimental outcomes. DATA AND SOURCES: PubMed, Medline, and Cochrane Library databases were searched for relevant studies published between January 2000 and November 2023, and focusing on robotic CAIS in dental implant surgery. All search results were then manually reviewed to identify only the pertinent articles. Only in vitro and clinical studies were included in this narrative review, with implant placement accuracy considered the main outcome. RESULT: Based on our inclusion and exclusion criteria, we included 21 studies (with 1085 implant sites); of them, 8 were clinical studies, 12 were in vitro studies, and 1 included both an in vitro study and a case series. The ranges of the mean implant shoulder, apical, and angular deviations were respectively 0.43-1.04 mm, 0.53-1.06 mm, and 0.77°-3.77° in the clinical studies and 0.23-1.04 mm, 0.24-2.13 mm, and 0.43°-3.78° in the in vitro studies, respectively. CONCLUSION: The accuracy of robotic CAIS in dental implant procedures appears to be within the clinically acceptable ranges. However, further relevant clinical trials validating the existing evidence are needed. CLINICAL SIGNIFICANCE: Robotic CAIS can achieve clinically acceptable implant placement accuracy. This innovative technology may improve the precision and success rates of dental implant procedures, with benefit for surgeons and patients.

Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway.

OBJECTIVE AND DESIGN: To elucidate Sirt1's role in gouty arthritis inflammation and its potential mechanisms. MATERIAL: Constructed murine models of gouty arthritis and conducted THP-1 cell experiments. TREATMENT: 1 mg of MSU crystals injected into mice ankle joints for a 72-h intervention. After a 3-h pre-treatment with Sirt1-specific inhibitor (EX527) and agonist (SRT2104), inflammation was induced for 21 h using lipopolysaccharide (LPS) plus MSU crystals. METHODS: We assessed gouty arthritis severity through joint inflammation index, swelling, and hematoxylin and eosin (H&E) staining, and measured CD68 mononuclear macrophages and Sirt1 expression in synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, and Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK/NF-κB/AP-1 and Nrf2/HO-1 pathways proteins. RESULTS: Significant joint swelling, synovial tissue edema, and inflammatory cell infiltration were observed. CD68 mononuclear macrophages and Sirt1 expression were elevated in synovium. Sirt1 activation decreased inflammatory factors, M1 polarization, and ROS generation. Sirt1 activation reduced p38/JNK phosphorylation, thereby inhibiting downstream NF-κB p65/AP-1 and enhancing Nrf2/HO-1, thus suppressing inflammation. CONCLUSIONS: Sirt1 alleviates M1 macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Thus, activating Sirt1 may provide a new therapeutic target for gouty arthritis.