Preparation and epitope analysis of monoclonal antibodies against African swine fever virus DP96R protein.

BACKGROUND: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV. RESULTS: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined. CONCLUSION: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.

Preoperative prediction of perineural invasion of rectal cancer based on a magnetic resonance imaging radiomics model: A dual-center study.

BACKGROUND: Perineural invasion (PNI) has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer (RC). Preoperative prediction of PNI status is helpful for individualized treatment of RC. Recently, several radiomics studies have been used to predict the PNI status in RC, demonstrating a good predictive effect, but the results lacked generalizability. The preoperative prediction of PNI status is still challenging and needs further study. AIM: To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients. METHODS: This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers. The patients underwent pre-operative high-resolution magnetic resonance imaging (MRI) between May 2019 and August 2022. Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging (T2WI) and contrast-enhanced T1WI (T1CE) sequences. The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared (T2WI, T1CE and T2WI + T1CE fusion sequences). A clinical-radiomics (CR) model was established by combining the radiomics features and clinical risk factors. The internal and external validation groups were used to validate the proposed models. The area under the receiver operating characteristic curve (AUC), DeLong test, net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Among the radiomics models, the T2WI + T1CE fusion sequences model showed the best predictive performance, in the training and internal validation groups, the AUCs of the fusion sequence model were 0.839 [95% confidence interval (CI): 0.757-0.921] and 0.787 (95%CI: 0.650-0.923), which were higher than those of the T2WI and T1CE sequence models. The CR model constructed by combining clinical risk factors had the best predictive performance. In the training and internal and external validation groups, the AUCs of the CR model were 0.889 (95%CI: 0.824-0.954), 0.889 (95%CI: 0.803-0.976) and 0.894 (95%CI: 0.814-0.974). Delong test, NRI, and IDI showed that the CR model had significant differences from other models (P < 0.05). Calibration curves demonstrated good agreement, and DCA revealed significant benefits of the CR model. CONCLUSION: The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively, which facilitates individualized treatment of RC patients.

Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.

Viral myocarditis, an inflammatory disease of the myocardium, is a significant cause of sudden death in children and young adults. The current coronavirus disease 19 pandemic emphasizes the need to understand the pathogenesis mechanisms and potential treatment strategies for viral myocarditis. Here, we found that TRIM29 was highly induced by cardiotropic viruses and promoted protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses that promote viral replication in cardiomyocytes in vitro. TRIM29 deficiency protected mice from viral myocarditis by promoting cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive monocytic myeloid-derived suppressor cells (mMDSC) in vivo. Mechanistically, TRIM29 interacted with PERK to promote SUMOylation of PERK to maintain its stability, thereby promoting PERK-mediated signaling pathways. Finally, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK connection, thereby bolstering cardiac function, enhancing cardiac antiviral responses, and curbing inflammation and immunosuppressive mMDSC in vivo. Our findings offer insight into how cardiotropic viruses exploit TRIM29-regulated PERK signaling pathways to instigate viral myocarditis, suggesting that targeting the TRIM29-PERK axis could mitigate disease severity.

Linewidth compression of a single longitudinal mode ytterbium-doped fiber laser based on femtosecond laser fabricated fiber Bragg gratings.

We demonstrate a single longitudinal mode distributed Bragg reflection (DBR) fiber laser by directly fabricating fiber Bragg gratings (FBGs) on an ytterbium-doped fiber (YDF) using a femtosecond laser. A simple optical self-injection feedback method was used to effectively compress the linewidth and reduce relative intensity noise (RIN) of a single longitudinal mode DBR fiber laser. Further, we investigated the effect of self-injection feedback cavity length and reflectivity on linewidth compression and determined that the linewidth tends to decrease with the increase of the external cavity photon lifetime. By a self-injection feedback, the laser linewidth was compressed from 31.8 kHz to 1.4 kHz. Meanwhile, the relaxation oscillation peak from -103.2d B/H z at 1.51 MHz was suppressed to -122.3d B/H z at 0.16 MHz. This low-noise narrow linewidth single longitudinal mode fiber laser is expected to be a promising candidate for applications such as active detection of neutral atmosphere and distributed fiber sensing.

An Automated Deep Learning-Based Framework for Uptake Segmentation and Classification on PSMA PET/CT Imaging of Patients with Prostate Cancer.

Uptake segmentation and classification on PSMA PET/CT are important for automating whole-body tumor burden determinations. We developed and evaluated an automated deep learning (DL)-based framework that segments and classifies uptake on PSMA PET/CT. We identified 193 [18F] DCFPyL PET/CT scans of patients with biochemically recurrent prostate cancer from two institutions, including 137 [18F] DCFPyL PET/CT scans for training and internally testing, and 56 scans from another institution for external testing. Two radiologists segmented and labelled foci as suspicious or non-suspicious for malignancy. A DL-based segmentation was developed with two independent CNNs. An anatomical prior guidance was applied to make the DL framework focus on PSMA-avid lesions. Segmentation performance was evaluated by Dice, IoU, precision, and recall. Classification model was constructed with multi-modal decision fusion framework evaluated by accuracy, AUC, F1 score, precision, and recall. Automatic segmentation of suspicious lesions was improved under prior guidance, with mean Dice, IoU, precision, and recall of 0.700, 0.566, 0.809, and 0.660 on the internal test set and 0.680, 0.548, 0.749, and 0.740 on the external test set. Our multi-modal decision fusion framework outperformed single-modal and multi-modal CNNs with accuracy, AUC, F1 score, precision, and recall of 0.764, 0.863, 0.844, 0.841, and 0.847 in distinguishing suspicious and non-suspicious foci on the internal test set and 0.796, 0.851, 0.865, 0.814, and 0.923 on the external test set. DL-based lesion segmentation on PSMA PET is facilitated through our anatomical prior guidance strategy. Our classification framework differentiates suspicious foci from those not suspicious for cancer with good accuracy.

Quantification of Residual Water in Pharmaceutical Frozen Solutions Via 1H Solid-State NMR.

Freezing is essential for the stability of biological drug substances and products, particularly in frozen solution formulations and during the primary drying of lyophilized preparations. However, the unfrozen segment within the frozen matrix can alter solute concentration, ionic strength, and stabilizer crystallization, posing risks of increased biophysical instability and faster chemical degradation. While quantifying the unfrozen water content is important for designing stable biopharmaceuticals, there is a lack of analytical techniques for in situ quantitative measurements. In this study, we introduce a 1H magic angle spinning NMR technique to identify the freezing point (Tice) and quantify mobile water content in frozen biologics, applying this method to analyze the freezing of a commercial high-concentration drug product, Dupixent®. Our results demonstrate that water freezing is influenced by buffer salt properties and formulation composition, including the presence of sugar cryoprotectants and protein concentration. Additionally, the 1H chemical shift can probe pH in the unfrozen phase, potentially predicting the microenvironmental acidity in the frozen state. Our proposed methodology provides fresh insights into the analysis of freeze-concentrated solutions, enhancing our understanding of the stability of frozen and lyophilized biopharmaceuticals.

Cerebral tau deposition in co-morbid progressive supranuclear palsy and amyotrophic lateral sclerosis: an [18F]-flortaucipir and 7T MRI study.

Introduction Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes non-invasively for improved diagnosis. This study utilized tau-PET imaging and MRI techniques at 7 Tesla (7T) to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS). Method [18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson's syndrome; PSP-RS), and 15 healthy control volunteers. Standardized uptake value ratio (SUVR) in each brain region was compared between PSP participants and controls. Quantitative susceptibility mapping (QSM) and inflow-based vascular-space occupancy (iVASO) MRI at 7T were performed on the two PSP participants and on two age-matched healthy controls to evaluate for differences in regional brain iron content and arteriolar cerebral blood volume (CBVa), respectively. Results In the participant with PSP-ALS, the precentral gyrus demonstrated the highest [18F]-flortaucipir uptake of all brain regions relative to controls (z-score 1.94). In the participant with PSP-RS, [18F]-flortaucipir uptake relative to controls was highest in subcortical regions, including the pallidum, thalamus, hippocampus, and brainstem (z-scores 1.08, 1.41, 1.49, 1.32, respectively). Susceptibility values as a measure of brain iron content were higher in the globus pallidus and substantia nigra than in the midbrain and pons in each participant, regardless of group. CBVa values tended to be higher in the subcortical gray matter in PSP participants than in controls, although large measurement variability was noted in controls across multiple regions. Conclusion In vivo tau PET imaging of an individual with PSP-ALS overlap demonstrated increased tau burden in the motor cortex that was not observed in PSP-RS or control participants. Consistent with prior PET studies, tau burden in PSP-RS was mainly observed in subcortical regions, including the brainstem and basal ganglia. QSM data suggest that off-target binding to iron may account for some but not all of the increased [18F]-flortaucipir uptake in the basal ganglia in PSP-RS. These findings support existing evidence that tau PET imaging can distinguish among PSP subtypes by detecting distinct regional patterns of tau deposition in the brain. Larger studies are needed to determine whether CBVa is sensitive to changes in brain microvasculature in PSP.

Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity.

The discovery of toll-like receptors (TLRs) and the subsequent recognition that endogenous nucleic acids (NAs) could serve as TLR ligands have led to essential insights into mechanisms of healthy immune responses as well as pathogenic mechanisms relevant to systemic autoimmune and inflammatory diseases. In systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis, NA-containing immune complexes serve as TLR ligands, with distinct implications depending on the additional immune stimuli available. Plasmacytoid dendritic cells (pDCs), the robust producers of type I interferon (IFN-I), are providing critical insights relevant to TLR-mediated healthy immune responses and tissue repair, as well as generation of inflammation, autoimmunity and fibrosis, processes central to the pathogenesis of many autoimmune diseases. In this review, we describe recent data characterizing the role of platelets and NA-binding chemokines in modulation of TLR signaling in pDCs, as well as implications for how the IFN-I products of pDCs contribute to the generation of inflammation and wound healing responses by monocyte/macrophages. Chemokine modulators of TLR-mediated B cell tolerance mechanisms and interactions between TLR signaling and metabolic pathways are also considered. The modulators of TLR signaling and their contribution to the pathogenesis of systemic autoimmune diseases suggest new opportunities for identification of novel therapeutic targets.

An ATPase-Mimicking MXene nanozyme pharmacologically breaks the ironclad defense system for ferroptosis cancer therapy.

Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications.

2D Self-Assembly of Large-Sized Inorganic Nanosheets Leading to Enhanced Power Factors in Earth-Abundant Cu3SbSe4-Based Flexible Hybrid Films.

Fabrication of large-sized inorganic nanosheets is an efficient strategy to promote carrier transportation in flexible thermoelectric (TE) films. Herein, we report the self-assembly of large-sized Cu3SbSe4 nanosheets by using a Se nanowire template via wet chemical synthesis and then vacuum-assisted filter these plate-like microcrystals on nylon to prepare Cu3SbSe4 flexible thermoelectric (TE) hybrid films. SEM reveals that the as-synthesized Cu3SbSe4 powders by using Se nanowires as selenium sources presented 2D plate-like micron structures uniformly and tightly self-assembled by acute triangle-like nanoparticles. Furthermore, XPS evidences that extra Sb vacancies are generated in the unit cell of Cu3SbSe4 crystals synthesized by using the Se NW template, resulting in the shrinkage of the unit cell and the narrowing interplanar spacing, which are characterized by XRD and TEM. As a result, both carrier concentration and carrier mobility have been significantly improved. The high carrier concentration is proved to originate from the extra carriers induced by Sb vacancies, and the high carrier mobility of the film is mainly ascribed to its continuous grain boundaries in the plate-like microcrystal morphology. The large-sized nanosheet Cu3SbSe4/nylon hybrid film (CSS MPs) exhibits a high power factor (PF) of 235.45 µW m-1 K-2 at 400 K, which is 4.23 times higher than that of the Cu3SbSe4/nylon hybrid film (CSS NPs) where Cu3SbSe4 crystals are synthesized by using raw Se particles. This work reveals a novel approach to prepare plate-like Se-based semiconductors, which requires both high carrier concentration and high carrier mobility.

The effects of prophylactic use of esketamine on postoperative depression and quality of life: a meta-analysis.

INTRODUCTION: The aim of this systemic review and meta-analysis was to assess the impact of prophylactic use of esketamine on postoperative depression and quality of life in patients. EVIDENCE ACQUISITION: We searched for all articles on esketamine in patients after surgury in electronic data bases, including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, up to the June 2023.The included studies compared the impact of using esketamine and placebo on postoperative depression and quality of life in patients through randomized controlled trials. The outcome measurements consist of postoperative depression and indicators that can reflect the impact on patients' post Cochrane Risk of Bias tool in Review Manager 5.4 tool was adopted to assess the risk of bias. EVIDENCE SYNTHESIS: The study included a total of 11 randomized controlled trials with 1447 participants. This meta-analysis demonstrated that the prophylactic use of esketamine alleviated postoperative depressive symptoms (standardized mean difference [SMD]: -0.61; 95% confidence interval [CI]: -0.96 to -0.25; P=0.0008) and incidence (relative risk [RR]:0.37;95% [CI]: 0.22 to 0.62; P=0.0001), reducing the occurrence of postoperative depression, anxiety, and chronic pain. Additionally, it improved postoperative sleep quality and enhanced the postoperative quality of life for patients. CONCLUSIONS: Prophylactic use of esketamine during the preoperative and anesthesia period has shown significant benefits in improving postoperative quality of life. It can effectively alleviate postoperative depression, anxiety, and chronic pain, as well as enhance sleep quality.

Dynamic contrast-enhanced magnetic resonance imaging assessment of residual tumor angiogenesis after insufficient microwave ablation and donafenib adjuvant therapy.

To analyze the correlation between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) permeability parameters and serum vascular endothelial growth factor (VEGF) levels in a rabbit VX2 liver cancer model with insufficient microwave ablation (MWA), to observe the dynamic changes in residual tumor angiogenesis in the short term after MWA, and to assess the effectiveness of donafenib as adjuvant therapy. Forty rabbits with VX2 liver tumors were randomly divided into three groups: an insufficient MWA group (n = 15), a combined treatment group (n = 15) and a control group (n = 10). The dynamic changes in VEGF expression after MWA and the effectiveness of donafenib as adjuvant therapy were evaluated by DCE-MRI and serum VEGF levels before surgery and 1, 3, 7, and 14 days after surgery. The correlation between the volume translate constant (Ktrans) of DCE-MRI parameters and serum VEGF levels fluctuated after ablation, but the coefficient was always positive (all p < 0.001). Repeated-measures ANOVA revealed significant changes in the serum VEGF concentration (F = 40.905, p < 0.001; partial η2 = 0.689), Ktrans (F = 13.388, p < 0.001; partial η2 = 0.420), and tumor diameter in each group (F = 34.065, p < 0.001; partial η2 = 0.648) at all five time points. Pairwise comparisons showed that the serum VEGF level, Ktrans value and tumor diameter in the insufficient MWA group and combined treatment group were significantly lower at 1 d than in the control group, but these values gradually increased over time (all p < 0.05). Ktrans and tumor diameter were significantly greater in the insufficient MWA group than in the control group at 14 days (all p < 0.05). The serum VEGF concentration, Ktrans, and tumor diameter were significantly lower in the combined treatment group than in the other two groups at 3, 7, and 14 days (all p < 0.05). Ktrans is positively correlated with the serum VEGF concentration. Ktrans and the serum VEGF concentration changed significantly after treatment with insufficient ablation or in combination with donafenib, and Ktrans may change faster. Insufficient MWA promotes the progression of residual tumors. Adjuvant treatment with donafenib is effective.

Deep Semisupervised Transfer Learning for Fully Automated Whole-Body Tumor Quantification and Prognosis of Cancer on PET/CT.

Automatic detection and characterization of cancer are important clinical needs to optimize early treatment. We developed a deep, semisupervised transfer learning approach for fully automated, whole-body tumor segmentation and prognosis on PET/CT. Methods: This retrospective study consisted of 611 18F-FDG PET/CT scans of patients with lung cancer, melanoma, lymphoma, head and neck cancer, and breast cancer and 408 prostate-specific membrane antigen (PSMA) PET/CT scans of patients with prostate cancer. The approach had a nnU-net backbone and learned the segmentation task on 18F-FDG and PSMA PET/CT images using limited annotations and radiomics analysis. True-positive rate and Dice similarity coefficient were assessed to evaluate segmentation performance. Prognostic models were developed using imaging measures extracted from predicted segmentations to perform risk stratification of prostate cancer based on follow-up prostate-specific antigen levels, survival estimation of head and neck cancer by the Kaplan-Meier method and Cox regression analysis, and pathologic complete response prediction of breast cancer after neoadjuvant chemotherapy. Overall accuracy and area under the receiver-operating-characteristic (AUC) curve were assessed. Results: Our approach yielded median true-positive rates of 0.75, 0.85, 0.87, and 0.75 and median Dice similarity coefficients of 0.81, 0.76, 0.83, and 0.73 for patients with lung cancer, melanoma, lymphoma, and prostate cancer, respectively, on the tumor segmentation task. The risk model for prostate cancer yielded an overall accuracy of 0.83 and an AUC of 0.86. Patients classified as low- to intermediate- and high-risk had mean follow-up prostate-specific antigen levels of 18.61 and 727.46 ng/mL, respectively (P < 0.05). The risk score for head and neck cancer was significantly associated with overall survival by univariable and multivariable Cox regression analyses (P < 0.05). Predictive models for breast cancer predicted pathologic complete response using only pretherapy imaging measures and both pre- and posttherapy measures with accuracies of 0.72 and 0.84 and AUCs of 0.72 and 0.76, respectively. Conclusion: The proposed approach demonstrated accurate tumor segmentation and prognosis in patients across 6 cancer types on 18F-FDG and PSMA PET/CT scans.

Computed tomography-guided percutaneous cryoablation and microwave ablation in the treatment of perivascular hepatocellular carcinoma: A comparative study with propensity score matching.

OBJECTIVE: To evaluate the safety and efficacy of cryoablation (CYA) and microwave ablation (MWA) in the treatment of patients with perivascular hepatocellular carcinoma (HCC). METHODS: Patients with perivascular HCC who underwent computed tomography (CT)-guided percutaneous CYA or MVA treatment in our hospital from August 2009 to March 2019 were included. Propensity score matching (PSM) was performed to adjust for potential baseline differences in the two groups. The technical success rate (TS), complications, and visual analog scale (VAS) were analyzed. The overall survival (OS) was evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: After PSM, 32 patients from each group were selected. The technical success rate was 94 % for CYA and 91 % for MWA, and 13 patients developed recurrence (CYA, n = 5, 2 local, 3 distant; MWA, n = 8, 6 local, 2 distant). There were no significant differences in OS (36-months OS: CYA 53.1 % vs, MWA 40.6 %; P = 0.191). No intraoperative deaths or complication-related deaths were observed, and 19 patients (CYA, n = 8; MWA, n = 11) experienced complications (P = 0.435). The VAS in the MWA group (5.38 ± 1.21) was significantly higher than that in the CYA group (2.22 ± 0.87; P < 0.001). CONCLUSIONS: While CYA has equal safety and high primary efficacy as MWA in the treatment of perivascular HCC, it is associated with less periprocedural pain.

Effects of miR-214 on adenosine A2A receptor and carboxymethyl chitosan nanoparticles on the function of keloid fibroblasts and their mechanisms.

This work prepared and investigated the impact of carboxymethyl chitosan nanoparticles (MC-NPs) on the proliferative capability of keloid fibroblasts (KFBs) while analyzing the mechanistic roles of miR-214 and adenosine A2A receptor (A2AR) in fibroblasts within hypertrophic scars. MC-NPs were synthesized through ion cross-linking, were characterized using transmission electron microscopy (TEM) and laser particle size scattering. The influence of MC-NPs on the proliferation capacity of KFBs was assessed using the MTT method. Changes in the expression levels of miR-214 and A2AR in KFBs, normal skin fibroblasts (NFBs), hypertrophic scar tissue, and normal skin tissue were analyzed. KFBs were categorized into anti-miR-214, anti-miR-NC, miR-214 mimics, miR-NC, si-A2AR, si-con, anti-miR-214+ si-con, and anti-miR-214+ si-A2AR groups. Bioinformatics target prediction was conducted to explore the interaction between miR-214 and A2AR. Real-time quantitative PCR and immunoblotting (WB) were employed to detect the expression levels of miR-214, A2AR, apoptotic protein Bax, and TGF-ß in different cells. Cell counting kit-8 (CCK8) and flow cytometry were employed to assess cell proliferation activity and apoptosis. The results indicated that MC-NPs exhibited spherical particles with an average diameter of 236.47 ± 4.98 nm. The cell OD value in the MC-NPs group was lower than that in KFBs (P < 0.05). The mRNA levels of miR-214 in KFBs and hypertrophic scar tissue were lower than those in NFBs and normal tissue (P < 0.001), while the mRNA and protein levels of A2AR were significantly elevated (P < 0.05). Compared to the control group and anti-miR-NC, the anti-miR-214 group showed significantly increased cell OD values and Bcl-2 protein expression (P < 0.001), decreased levels of apoptotic gene Bax protein, TGF-ß gene mRNA, and protein expression (P < 0.001). Continuous complementary binding sites were identified between miR-214 and A2AR. Compared to the control group, the si-A2AR group exhibited a significant decrease in A2AR gene mRNA and protein expression levels (P < 0.001), reduced cell viability (P < 0.001), increased apoptosis rate (P < 0.001), and a significant elevation in TGF-ß protein expression (P < 0.001). miR-214 targetedly regulated the expression of A2AR, inducing changes in TGF-ß content, promoting the proliferation of keloid fibroblasts, and inhibiting cell apoptosis.

Protective effects of triptolide against oxidative stress in retinal pigment epithelium cells via the PI3K/AKT/Nrf2 pathway: a network pharmacological method and experimental validation.

PURPOSE: Among aging adults, age-related macular degeneration (AMD), is a prevalent cause of blindness. Nevertheless, its progression may be halted by antioxidation in retinal pigment epithelium (RPE). The primary effective constituent of Tripterygium wilfordii Hook. F., triptolide (TP), has demonstrated anti-inflammatory, antiproliferative, and antioxidant properties. The mechanics of the protective effect of triptolide against the oxidative damage in retinal pigment epithelial (RPE) were assessed in this study. METHODS: ARPE-19 cells were pretreated with TP, and then exposed to sodium iodate (SI). First, cell viability was assessed using CCK-8. Subsequently, we measured indicators for cell oxidation including reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Then, we used network pharmacological analysis and molecular docking to explore the signaling pathway of TP. Last, we used western blot, ELISA, and immunofluorescence assays to clarify the potential mechanistic pathways. RESULTS: The network pharmacology data suggested that TP may inhibit AMD by regulating the PI3K/Akt signaling pathway. Experimental results showed that the potential mechanism is that it regulates the PI3K/Akt pathway and promotes Nrf2 phosphorylation and activation, thereby raising the level of antioxidant factors (HO-1, NQO1) and reducing the generation of ROS, which inhibit oxidative damage. CONCLUSION: Our findings suggested that the effect of TP on SI-exposed RPE cells principally relies on the regulation of oxidative stress through the PI3K/Akt/Nrf2 signaling pathway.

Versatile dopamine-functionalized hyaluronic acid-recombinant human collagen hydrogel promoting diabetic wound healing via inflammation control and vascularization tissue regeneration.

The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing, delayed healing, susceptibility to infection, and elevated risk of reopening, highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels. Here, we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III (rhCol) by oxidative coupling of the catechol group using the H2O2/HRP catalytic system. The post-reactive hydrogel has a good porous structure, swelling rate, reasonable degradation, rheological and mechanical properties, and the catechol group and dopamine impart to the hydrogel tissue adhesiveness, antioxidant capacity, and excellent photothermal effects leading to superior in vitro antimicrobial activity. In addition, the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated. Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel. Wound closure, collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing. In summary, the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.

Outpatient Health Service Utilization Among Adults with Diabetes, Hypertension and Cardiovascular Disease During the COVID-19 Pandemic - Results of Population-Based Surveys in Germany from 2019 to 2021.

Purpose: Fear of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and lockdown measures may have an impact on health care utilization particularly for people with chronic diseases. We investigated changes in outpatient utilization behavior in pandemic phases among people with selected chronic diseases in Germany. Methods: The nationwide population-based telephone surveys German Health Update (GEDA) 2019/2020 (April 2019 to September 2020) and GEDA 2021 (July to December 2021) covered 4 out of 7 pandemic phases from the pre-pandemic to the 4th pandemic wave. Data on hypertension, diabetes and major cardiovascular diseases (CVD) in the past 12 months and visiting a general practitioner (GP) or a specialist (excluding dentist) in the past 4 weeks was collected using a standardized questionnaire. Proportions and odds ratios were derived from logistic regression models adjusted for age, sex, education and federal states. Results: Among 27,967 participants aged ≥16 years, 8,449, 2,497 and 1,136 individuals had hypertension, diabetes and major CVD. Participants with these chronic diseases visited a GP or specialist significantly more often than the overall study population, irrespective of pandemic phases. Compared to the pre-pandemic phase, a significant reduction in specialist-visiting was found in the first pandemic wave among people with hypertension (34.3% vs 24.1%), diabetes (39.5% vs 25.5%) and major CVD (41.9% vs 25.6%). GP-visiting was lower only among people with hypertension (53.0% vs 46.0%). No difference in GP or specialist visiting was found in the 4th pandemic wave compared to the pre-pandemic phase. Conclusion: The observed decrease particularly in specialist utilization among people with the selected chronic diseases at the beginning of the pandemic was not observed for the second half of 2021 despite the ongoing pandemic. Further studies are required to examine whether the temporary changes in the utilization of ambulatory health care have affected the disease management of people with chronic diseases.

Intersectional analysis of social disparities in type 2 diabetes risk among adults in Germany: results from a nationwide population-based survey.

BACKGROUND: Differences in type 2 diabetes risk have been reported for several sociodemographic determinants including sex/gender or socioeconomic status. From an intersectional perspective, it is important to not only consider the role of social dimensions individually, but also their intersections. This allows for a deeper understanding of diabetes risk and preventive needs among diverse population groups. METHODS: As an intersectionality-informed approach, multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was used in a population-based sample of adults without known diabetes in Germany from the cross-sectional survey "Disease knowledge and information needs- Diabetes mellitus (2017)". Diabetes risk was assessed by the German Diabetes Risk Score (GDRS, range 0-122 points), estimating the individual risk of developing type 2 diabetes within the next 5 years based on established self-reported risk factors. Nesting individuals in 12 intersectional strata defined by combining sex/gender, educational level, and history of migration, we calculated measures to quantify the extent to which individual differences in diabetes risk were explained at strata level, and how much this was due to additive or multiplicative intersectional effects of social determinants. RESULTS: Drawing on data of 2,253 participants, we found good discriminatory accuracy of intersectional strata (variance partition coefficient = 14.00% in the simple intersectional model). Model-predicted GDRS means varied between 29.97 (corresponding to a "low risk" of < 2%) in women with high educational level and a history of migration, and 52.73 ("still low risk" of 2-5%) in men with low educational level without a history of migration. Variance in GDRS between strata was mainly explained by additive effects of social determinants (proportional change in variance to intersectional interaction model = 77.95%) with being male and having low educational level being associated with higher GDRS. There was no evidence of multiplicative effects in individual strata. CONCLUSIONS: Type 2 diabetes risk differed between intersectional strata and can to some extent be explained at strata level. The role of intersectional effects was minor and needs to be further investigated. Findings suggest a need for specific preventive measures targeted at large groups with increased diabetes risk, such as men and persons with low educational level.

Sulfur dioxide-free wine with polyphenols promotes lipid metabolism via the Nrf2 pathway and gut microbiota modulation.

Moderate wine consumption is often associated with preventing obesity, yet concerns arise due to the health risks linked to its constituent antioxidant, SO2. Recent focus has turned to polyphenols as a potential substitute for SO2. This investigation explores the impact and mechanisms of sulfur dioxide-free wine enriched with polyphenols on lipid regulation. Through a comprehensive analysis involving oxidative stress, lipid metabolism, and gut microorganisms in high-fat-diet mouse models, this study reveals that sulfur dioxide-free wine containing the polyphenol resveratrol exhibits a heightened ability to regulate lipids. It modulates oxidative stress by influencing NF-E2-related factor 2, a crucial factor, while enhancing lipid metabolism and fatty acid ß-oxidation through key genes such as carnitine palmitoyltransferase I and peroxisome proliferator-activated receptor alpha. Furthermore, oral administration of sulfur dioxide-free wine supplemented with resveratrol demonstrates an increase in the relative abundance of beneficial intestinal microflora, such as Turicibacter, Allobaculum, Bacteroides, and Macellibacteroides, while decreasing the Firmicutes/Bacteroidetes ratio.