The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives.

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Multi-omics analysis reveals key regulatory defense pathways and genes involved in salt tolerance of rose plants.

Salinity stress causes serious damage to crops worldwide, limiting plant production. However, the metabolic and molecular mechanisms underlying the response to salt stress in rose (Rosa spp.) remain poorly studied. We therefore performed a multi-omics investigation of Rosa hybrida cv. Jardin de Granville (JDG) and Rosa damascena Mill. (DMS) under salt stress to determine the mechanisms underlying rose adaptability to salinity stress. Salt treatment of both JDG and DMS led to the buildup of reactive oxygen species (H2O2). Palisade tissue was more severely damaged in DMS than in JDG, while the relative electrolyte permeability was lower and the soluble protein content was higher in JDG than in DMS. Metabolome profiling revealed significant alterations in phenolic acid, lipids, and flavonoid metabolite levels in JDG and DMS under salt stress. Proteome analysis identified enrichment of flavone and flavonol pathways in JDG under salt stress. RNA sequencing showed that salt stress influenced primary metabolism in DMS, whereas it substantially affected secondary metabolism in JDG. Integrating these datasets revealed that the phenylpropane pathway, especially the flavonoid pathway, is strongly enhanced in rose under salt stress. Consistent with this, weighted gene coexpression network analysis (WGCNA) identified the key regulatory gene chalcone synthase 1 (CHS1), which is important in the phenylpropane pathway. Moreover, luciferase assays indicated that the bHLH74 transcription factor binds to the CHS1 promoter to block its transcription. These results clarify the role of the phenylpropane pathway, especially flavonoid and flavonol metabolism, in the response to salt stress in rose.

Effects of androgen suppression therapy on the incidence and prognosis of bladder cancer: An updated systematic review and meta-analysis.

INTRODUCTION: The influence of androgen suppression therapy (AST) on bladder cancer (BCa) remains controversial, as recent studies have not reached a consensus regarding the relationship between AST and the incidence or prognosis of BCa. MATERIALS AND METHODS: We perform an updated systematic review and meta-analysis utilizing the most recent evidence to investigate the potential influence of AST on the incidence and prognosis of BCa. A comprehensive literature search was performed on the PubMed, Medline, Embase, Web of Science, and the Cochrane Library databases to include potentially eligible studies. Hazard ratios (HR) and odds ratios (OR) were used to calculate the incidence and prognosis of BCa. RESULTS: This meta-analysis included 22 studies with 700,755 participants which investigated the impact of AST on the risk and prognosis of BCa. The pooled results revealed no significant relation between AST and a decreased incidence of BCa (OR: 0.92, 95%CI: 0.77-1.09, P = 0.342). Subgroup analysis reported that patients receiving 5-alpha reductase inhibitors (5-ARIs) exhibited a significantly lower risk of BCa (OR: 0.83, 95%CI: 0.75-0.91, P < 0.001), while androgen deprivation therapy did not show a significant reduction (OR: 1.00, 95%CI: 0.46-2.16, P = 0.995). AST may also significantly improve the recurrence-free survival of patients with BCa (HR: 0.69, 95%CI: 0.50-0.95, P = 0.023). We also detected a significant improvement in OS among BCa patients who received 5-ARIs compared to those without 5-ARIs (HR: 0.82, 95%CI: 0.68-0.99, P = 0.037). CONCLUSION: No significant correlation was found between AST and a decreased BCa incidence, while 5-ARIs have demonstrated efficacy in reducing BCa occurrence. Moreover, patients who received AST demonstrated improved prognosis.

Exercise-induced cardiac troponin elevations and cardiac ventricular dysfunction assessed by tissue Doppler echocardiography and speckle tracking among non-elite runners in Beijing marathon.

OBJECTIVES: We aimed to identify the major determinants of cardiac troponin changes response to exercise among non-elite runners participating in the Beijing 2022 marathon, with a particular focus on the associations with the cardiac function assessed by tissue Doppler echocardiography and speckle tracking. DESIGN: A prospective study. METHODS: A total of 33 non-elite participants in the 2022 Beijing Marathon were included in the study. Echocardiographic assessment and blood sample collection were conducted before, immediately after, and two weeks after the marathon. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Echocardiography included tissue Doppler and speckle tracking echocardiography. RESULTS: Following the marathon, significant increases were observed in cardiac biomarkers, with hs-cTnI elevating from 3.1 [2.3-6.7] to 49.6 [32.5-76.9] ng/L (P < 0.0001). Over 72 % of participants had post-race hs-TnI levels surpassing the 99th percentile upper reference limit. There was a notable correlation between pre-marathon hs-cTnI levels (ß coefficient, 0.56 [0.05, 1.07]; P = 0.042), weekly average training (ß coefficient, -1.15 [-1.95, -0.35]; P = 0.009), and hs-cTnI rise post-marathon. Echocardiography revealed significant post-race cardiac function changes, including decreased E/A ratio (P < 0.0001), GWI (P < 0.0001), and GCW (P < 0.0001), with LVEF (ß coefficients, 0.112 [0.01, 0.21]; P = 0.042) and RV GLS (ß coefficients, 0.124 [0.01, 0.23]; P = 0.035) changes significantly associated with hs-TnI alterations. All echocardiographic and laboratory indicators reverted to baseline levels within two weeks. CONCLUSIONS: Baseline hs-cTnI levels and weekly average training influence exercise-induced hs-cTnI elevation in non-elite runners. Echocardiography revealed post-race changes in cardiac function, with LVEF and RV GLS significantly associated with hs-TnI alterations. These findings contribute to understanding the cardiac response to exercise and could guide training and recovery strategies.

FTH1 overexpression using a dCasRx translation enhancement system protects the kidney from calcium oxalate crystal-induced injury.

The engineered clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system is currently widely applied in genetic editing and transcriptional regulation. The catalytically inactivated CasRx (dCasRx) has the ability to selectively focus on the mRNA coding region without disrupting transcription and translation, opening up new avenues for research on RNA modification and protein translation control. This research utilized dCasRx to create a translation-enhancement system for mammals called dCasRx-eIF4GI, which combined eukaryotic translation initiation factor 4G (eIF4GI) to boost translation levels of the target gene by recruiting ribosomes, without affecting mRNA levels, ultimately increasing translation levels of different endogenous proteins. Due to the small size of dCasRx, the dCasRx-eIF4GI translation enhancement system was integrated into a single viral vector, thus optimizing the delivery and transfection efficiency in subsequent applications. Previous studies reported that ferroptosis, mediated by calcium oxalate (CaOx) crystals, significantly promotes stone formation. In order to further validate its developmental potential, it was applied to a kidney stone model in vitro and in vivo. The manipulation of the ferroptosis regulatory gene FTH1 through single-guide RNA (sgRNA) resulted in a notable increase in FTH1 protein levels without affecting its mRNA levels. This ultimately prevented intracellular ferroptosis and protected against cell damage and renal impairment caused by CaOx crystals. Taken together, this study preliminarily validated the effectiveness and application prospects of the dCasRx-eIF4GI translation enhancement system in mammalian cell-based disease models, providing novel insights and a universal tool platform for protein translation research and future therapeutic approaches for nephrolithiasis.

Parallel Dual-Branch Fusion Network for Epileptic Seizure Prediction.

Epilepsy is a prevalent chronic disorder of the central nervous system. The timely and accurate seizure prediction using the scalp Electroencephalography (EEG) signal can make patients adopt reasonable preventive measures before seizures occur and thus reduce harm to patients. In recent years, deep learning-based methods have made significant progress in solving the problem of epileptic seizure prediction. However, most current methods mainly focus on modeling short- or long-term dependence in EEG, while neglecting to consider both. In this study, we propose a Parallel Dual-Branch Fusion Network (PDBFusNet) which aims to combine the complementary advantages of Convolutional Neural Network (CNN) and Transformer. Specifically, the features of the EEG signal are first extracted using Mel Frequency Cepstral Coefficients (MFCC). Then, the extracted features are delivered into the parallel dual-branches to simultaneously capture the short- and long-term dependencies of EEG signal. Further, regarding the Transformer branch, a novel feature fusion module is developed to enhance the ability of utilizing time, frequency, and channel information. To evaluate our proposal, we perform sufficient experiments on the public epileptic EEG dataset CHB-MIT, where the accuracy, sensitivity, specificity and precision are 95.76%, 95.81%, 95.71% and 95.71%, respectively. PDBFusNet shows superior performance compared to state-of-the-art competitors, which confirms the effectiveness of our proposal.

Inhibition of Lck/Fyn kinase activity promotes the differentiation of induced Treg cells through AKT/mTOR pathway.

Regulatory T (Treg) cells are indispensable in maintaining the immune homeostasis and preventing autoimmune diseases. Regulatory T (Treg) cells include thymus derived Treg cells (tTregs) and peripherally induced Treg cells (iTreg), which are differentiated from antigen stimulated CD4+ naïve T cells in presence of TGFß. tTregs are quite stable, and more immune suppressive, while iTreg cells are less stable, and are prone to differentiate into inflammatory T cells. Therefore, identification of small molecules that could promote the differentiation of iTreg cells is an attractive strategy for autoimmune diseases. Inhibition of AKT/mTOR pathway promotes their differentiation. Whether inhibition of Lck/Fyn kinase activity (upstream of AKT/mTOR pathway) can be used to promote the differentiation of iTreg cells has not been determined. Here, we showed that Srci1, a small molecular inhibitor of Lck/Fyn, promoted the differentiation of FOXP3+ iTreg cells. Srci1 treatment resulted in inhibition of phosphorylation of key components of AKT/mTOR pathway, including mTOR, p70 S6K, 4EBP1, and promoted the expression of Foxp3 and its target genes, thereby promoted differentiation of in vitro iTreg cells. Srci1 treated iTreg cells showed more similar gene expression profile to that of tTreg cells. Our results thus suggest that inhibition of Lck/Fyn kinase activity can promote the differentiation of iTreg cells, and may have implication in autoimmune diseases.

Machine Learning-Assisted Study of RENxC6-x-Doped Graphene as Potential Electrocatalysts for Oxygen Electrode Reactions.

In the application of renewable energy, the oxidation-reduction reaction (ORR) and oxygen evolution reaction (OER) are two crucial reactions. Single-atom catalysts (SACs) based on metal-doped graphene have been widely employed due to their high activity and high atom utilization efficiency. However, the catalytic activity is significantly influenced by different metals and local coordination, making it challenging to efficiently screen through either experimental or density functional theory (DFT) calculations. To address this issue, this study employed a combination of DFT calculations and machine learning (DFT-ML) to investigate rare earth-modified carbon-based (RENxC6-x) electrocatalysts. Based on computational data from 75 catalysts, we trained two ML models to capture the underlying patterns of physical properties and overpotential. Subsequently, the candidate catalysts were screened, leading to the discovery of four ORR catalysts, nine OER catalysts, and five bifunctional electrocatalysts, all of which were thoroughly validated for their stability. Lastly, by integrating the ML models with the SHAP analysis framework, we revealed the influence of atomic radius, Pauling electronegativity, and other features on the catalytic activity. Additionally, we analyzed the physicochemical properties of potential catalysts through DFT calculations. The revolutionary DFT-ML approach provides a crucial driving force for the design and synthesis of potential catalysts in subsequent studies.

Corrigendum: Tpr deficiency disrupts erythroid maturation with impaired chromatin condensation in zebrafish embryogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.709923.].

Association between gut microbiota and spinal stenosis: a two-sample mendelian randomization study.

Introduction: Considerable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach. Materials and Methods: Data for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran's Q test to evaluate heterogeneity, and "leave-one-out" sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality. Results: The IVW results indicated that two gut microbial taxa, the genus Eubacterium fissicatena group and the genus Oxalobacter, have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, "leave-one-out" sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota. Conclusion: This analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.

The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

Efficient Fabrication of Quartz Glass Using Laser Coaxial Powder-Fed Additive Manufacturing Approach.

This article investigates a laser-directed energy deposition additive manufacturing (AM) method, based on coaxial powder feeding, for preparing quartz glass. Through synergistic optimization of line deposition and plane deposition experiments, key parameters of laser coaxial powder feeding AM were identified. The corresponding mechanical properties, thermal properties, and microstructure of the bulk parts were analyzed. The maximum mechanical strength of the obtained quartz glass element reached 72.36 ± 5.98 MPa, which is ca. 95% that of quartz glass prepared by traditional methods. The thermal properties of the obtained quartz glass element were also close to those prepared by traditional methods. The present research indicates that one can use laser AM technology that is based on coaxial powder feeding to form quartz glass with high density and good thermodynamic properties. Such quartz glass has substantial potential in, for example, optics and biomedicine.

Abrocitinib-associated adverse events: a real-world pharmacovigilance study using the FAERS database.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Janus kinase (JAK) modulates cytokines involved in AD pathophysiology, and JAK inhibitors have emerged as effective pharmacotherapeutic remedies for AD. Abrocitinib, an oral selective inhibitor of JAK1, is indicated for the management of moderate-to-severe AD. The current study evaluated the adverse events (AEs) associated with abrocitinib in a real-world setting. METHODS: To quantify the signals of abrocitinib-associated AEs, we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study with two established pharmacovigilance methods. RESULTS: A total of 1071 AEs of abrocitinib were investigated as the primary suspected from the FAERS to detect and characterize relevant safety signals. The analysis revealed 85 signals for abrocitinib. The most common AE for abrocitinib was drug ineffective. The signal strength of eczema herpeticum was 515.87 (277.80-957.98) and 510.59 (5148.65) and exhibited the highest strength for abrocitinib. Rare AEs such as aggravated condition, pruritus, and hypersensitivity were not listed on the label, and attention to these AEs is required. CONCLUSION: The analysis of the AE signals may provide support for clinical monitoring and risk identification of abrocitinib.

Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of γδ T-cell function.

BACKGROUND: Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. METHODS: Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni-NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. RESULTS: In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αß T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. CONCLUSION: Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

3D hydrogel microfibers promote the differentiation of encapsulated neural stem cells and facilitate neuron protection and axon regrowth after complete transactional spinal cord injury.

Spinal cord injury (SCI) can cause permanent impairment to motor or sensory functions. Pre-cultured neural stem cell (NSC) hydrogel scaffolds have emerged as a promising approach to treat SCI by promoting anti-inflammatory effects, axon regrowth, and motor function restoration. Here, in this study, we performed a coaxial extrusion process to fabricate a core-shell hydrogel microfiber with high NSC density in the core portion. Oxidized hyaluronic acid, carboxymethyl chitosan, and matrigel blend were used as a matrix for NSC growth and to facilitate the fabrication process. During thein vitrodifferentiation culture, it was found that NSC microfibers could differentiate into neurons and astrocytes with higher efficiency compared to NSC cultured in petri dishes. Furthermore, duringin vivotransplantation, NSC microfibers were coated with polylactic acid nanosheets by electrospinning for reinforcement. The coated NSC nanofibers exhibited higher anti-inflammatory effect and lesion cavity filling rate compared with the control group. Meanwhile, more neuron- and oligodendrocyte-like cells were visualized at the lesion epicenter. Finally, axon regrowth across the whole lesion site was observed, demonstrating that the microfiber could guide renascent axon regrowth. Experiment results indicate that the NSC microfiber is a promising bioactive treatment for complete SCI treatment with superior outcomes.

The association between urbanization and depression in the elderly: A network analysis from the complexity science perspective.

IMPORTANCE: The global increase in urbanization has coincided with a rise in depression prevalence. However, the effect of urbanization on depression remains controversial, especially for the elderly. OBJECTIVE: To clarify how urbanization impacts depression in the elderly from a network perspective. DESIGN, SETTING, AND PARTICIPANTS: This sectional cohort study used data from China Health and Retirement Longitudinal Study (CHARLS). MAIN OUTCOMES AND MEASURES: The occurrence of depressive symptoms in urban and rural elderly residents. Network metrics of depressive symptoms. RESULTS: Of the 13,993 participants, lower incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 24.7 %-27.8 %) than in rural (40.4 %, 95 % CI, 39.5 %-41.3 %, P < 0.0001) residents. However, higher incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 25.2 %-28.4 %) than in rural (17.5 %, 95 % CI, 16.1 %-18.9 %, P < 0.0001) residents in a subset of 2898 pairs of participants after PSM. No difference in the network structure and metrics between urban and rural residents before (M = 0.071, p = 0.054, S = 0.037, p = 0.80) and after (M = 0.085, p = 0.133, S = 0.086, p = 0.47) PSM was detected. The networks structure revealed that negative affect was strongly connected to somatic symptoms and that the two anhedonic symptoms were also strongly connected. CONCLUSIONS: The current study indicated the homogeneity of the ultimate nature of depression between rural and urban residents from the network perspective, supporting the viewpoint that urbanization might not impose influence on depression. Further researches delving deeper into the complexity of the issue may provide new insights into our understanding of depression in an urban environment among the elderly.

Bioconcentration of Inorganic and Methyl Mercury by Algae Revealed Using Dual-Mass Single-Cell ICP-MS with Double Isotope Tracers.

Algae are an entry point for mercury (Hg) into the food web. Bioconcentration of Hg by algae is crucial for its biogeochemical cycling and environmental risk. Herein, considering the cell heterogeneity, we investigated the bioconcentration of coexisting isotope-labeled inorganic (199IHg) and methyl Hg (201MeHg) by six typical freshwater and marine algae using dual-mass single-cell inductively coupled plasma mass spectrometry (scICP-MS). First, a universal pretreatment procedure for the scICP-MS analysis of algae was developed. Using the proposed method, the intra- and interspecies heterogeneities and the kinetics of Hg bioconcentration by algae were revealed at the single-cell level. The heterogeneity in the cellular Hg contents is largely related to cell size. The bioconcentration process reached a dynamic equilibrium involving influx/adsorption and efflux/desorption within hours. Algal density is a key factor affecting the distribution of Hg between algae and ambient water. Cellular Hg contents were negatively correlated with algal density, whereas the volume concentration factors almost remained constant. Accordingly, we developed a model based on single-cell analysis that well describes the density-driven effects of Hg bioconcentration by algae. From a novel single-cell perspective, the findings improve our understanding of algal bioconcentration governed by various biological and environmental factors.

Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel.

Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.

Association Between Polymorphisms in DNA Damage Repair Pathway Genes and Female Breast Cancer Risk.

Breast cancer risk have been discussed to be associated with polymorphisms in genes as well as abnormal DNA damage repair function. This study aims to assess the relationship between genes single nucleotide polymorphisms (SNPs) related to DNA damage repair and female breast cancer risk in Chinese population. A case-control study containing 400 patients and 400 healthy controls was conducted. Genotype was identified using the sequence MassARRAY method and expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissues was analyzed by immunohistochemistry assay. The results revealed that ATR rs13091637 decreased breast cancer risk influenced by ER, PR (CT/TT vs. CC: adjusted odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.032; CT/TT vs. CC: adjusted OR = 1.63, 95%CI: 1.14-2.35, p = 0.008) expression. Stratified analysis revealed that PALB2 rs16940342 increased breast cancer risk in response to menstrual status (AG/GG vs. AA: adjusted OR = 1.72, 95%CI: 1.13-2.62, p = 0.011) and age of menarche (AG/GG vs. AA: adjusted OR = 1.54, 95%CI: 1.03-2.31, p = 0.037), whereas ATM rs611646 and Ku70 rs132793 were associated with reduced breast cancer risk influenced by menarche (GA/AA vs. GG: adjusted OR = 0.50, 95%CI: 0.30-0.95, p = 0.033). In a summary, PALB2 rs16940342, ATR rs13091637, ATM rs611646, and Ku70 rs132793 were associated with breast cancer risk.

Innovation of BiOBr/BiOI@Bi5O7I Ternary Heterojunction for Catalytic Degradation of Sodium P-Perfluorous Nonenoxybenzenesulfonate.

As an alternative for perfluorooctane sulfonic acid (PFOS), sodium p-perfluorononyloxybenzene sulfonate (OBS) has been widely used in petroleum, fire-fighting materials, and other industries. In order to efficiently and economically remove OBS contaminations from water bodies, in this study, a ternary heterojunction was constructed by coupling BiOBr and BiOI@Bi5O7I for improving the redox capacity and carrier separation ability of the material and investigating the effect of the doping ratios of BiOBr and BiOI@ Bi5O7I on the performance of the catalysts. Furthermore, the effects on the degradation of OBS were also explored by adjusting different catalyst doping ratios, OBS concentrations, catalyst amounts, and pH values. It was observed that when the concentration of OBS was 50 mg/L, the amount of catalyst used was 0.5 g/L, and the pH was not changed. The application of BiOBr/BiOI@ Bi5O7I consisting of 25% BiOBr and 75% BiOI@ Bi5O7I showed excellent stability and adsorption degradation performance for OBS, and almost all of the OBS in the aqueous solution could be removed. The removal rate of OBS by BiOBr/BiOI@ Bi5O7I was more than 20% higher than that of OBS by BiOI@Bi5O7I and BiOBr when the OBS concentration was 100 mg/L. In addition, the reaction rate constants of BiOBr/BiOI@ Bi5O7I were 2.4 and 10.8 times higher than those of BiOI@ Bi5O7I and BiOBr, respectively. Therefore, the BiOBr/BiOI@ Bi5O7I ternary heterojunction can be a novel type of heterojunction for the efficient degradation of OBS in water bodies.