Effects of vitrectomy combined with internal limiting membrane peeling in patients with diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME), a chronic microvascular complication of diabetes, is a leading cause of visual impairment and blindness. Pars plana vitrectomy (PPV) can restore the normal macular structure and reduce macular edema, whereas internal limiting membrane (ILM) peeling is used to treat tractional macular diseases. Despite the advantages, there is limited research on the combined effects of PPV with ILM peeling. AIM: To observe the effects of PPV combined with ILM peeling on postoperative central macular thickness (CMT), best-corrected visual acuity (BCVA), cystoid macular edema (CME) volume, and complications in patients with DME. METHODS: Eighty-one patients (92 eyes) diagnosed with DME at the Beijing Shanqu Liangxiang Hospital between January and December 2022 were randomly divided to undergo PPV alone (control group: 41 patients, 47 eyes) or PPV + ILM peeling (stripping group: 40 patients, 45 eyes); a single surgeon performed all surgeries. The two groups were compared preoperatively and 1 and 3 months postoperatively. RESULTS: Preoperatively, both groups had comparable values of CMT, BCVA, and CME volume (P > 0.05). After surgery (both 1 and 3 months), both groups showed significant reductions in CMT, BCVA, and CME volume compared to preoperative levels, with the stripping group showing more significant reductions compared to the control group (P < 0.05). Further repeated-measures ANOVA analysis for within-group differences revealed significant effects of group and time, and interaction effects for CMT, BCVA, and CME volume (P < 0.05). There were no significant differences in the incidence of complications between the groups (retinal detachment: control = 2, stripping = 1; endophthalmitis: Control = 4, stripping = 1; no cases of secondary glaucoma or macular holes; χ 2 = 0.296, P = 0.587). CONCLUSION: PPV with ILM peeling can significantly improve the visual acuity of patients with DME, reduce CMT, and improve CME with fewer complications.

Bibliometric analysis of phosphoglycerate kinase 1 expression in breast cancer and its distinct upregulation in triple-negative breast cancer.

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) has been identified as a possible biomarker for breast cancer (BC) and may play a role in the development and advancement of triple-negative BC (TNBC). AIM: To explore the PGK1 and BC research status and PGK1 expression and mechanism differences among TNBC, non-TNBC, and normal breast tissue. METHODS: PGK1 and BC related literature was downloaded from Web of Science Core Collection Core Collection. Publication counts, key-word frequency, cooperation networks, and theme trends were analyzed. Normal breast, TNBC, and non-TNBC mRNA data were gathered, and differentially expressed genes obtained. Area under the summary receiver operating characteristic curves, sensitivity and specificity of PGK1 expression were determined. Kaplan Meier revealed PGK1's prognostic implication. PGK1 co-expressed genes were explored, and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Disease Ontology applied. Protein-protein interaction networks were constructed. Hub genes identified. RESULTS: PGK1 and BC related publications have surged since 2020, with China leading the way. The most frequent keyword was "Expression". Collaborative networks were found among co-citations, countries, institutions, and authors. PGK1 expression and BC progression were research hotspots, and PGK1 expression and BC survival were research frontiers. In 16 TNBC vs non-cancerous breast and 15 TNBC vs non-TNBC datasets, PGK1 mRNA levels were higher in 1159 TNBC than 1205 non-cancerous breast cases [standardized mean differences (SMD): 0.85, 95% confidence interval (95%CI): 0.54-1.16, I² = 86%, P < 0.001]. PGK1 expression was higher in 1520 TNBC than 7072 non-TNBC cases (SMD: 0.25, 95%CI: 0.03-0.47, I² = 91%, P = 0.02). Recurrence free survival was lower in PGK1-high-expression than PGK1-low-expression group (hazard ratio: 1.282, P = 0.023). PGK1 co-expressed genes were concentrated in ATP metabolic process, HIF-1 signaling, and glycolysis/gluconeogenesis pathways. CONCLUSION: PGK1 expression is a research hotspot and frontier direction in the BC field. PGK1 may play a strong role in promoting cancer in TNBC by mediating metabolism and HIF-1 signaling pathways.

Covalent Organic Framework-Based Theranostic Platforms for Restricting H1N1 Influenza Virus Infection.

Background: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection. Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe. Results: The multi-porosity COF core provided an excellent micro-environment and smooth delivery for T705. The ssDNA probe coating bound to the nucleic acids of H1N1 selectively, thus controlling drug release and allowing fluorescence imaging. The combination of COF and probe triggered the synergism, promoting drug further therapeutic outcomes. With the aid of T705@DATA-COF-Pro platforms, the H1N1-infected mouse models lightly achieved diagnosis and significantly prolonged survival. Conclusion: This research underscores the distinctive benefits and immense potential of COF materials in nano-preparations for virus infection, offering novel avenues for the detection and treatment of H1N1 virus infection.

Prevalence and Associated Factors of Type 2 Diabetes Mellitus Among Chinese Hakka Individuals Aged 35-65 Years: A Cross-Sectional Study.

Purpose: The prevalence of diabetes in China is increasing, influenced by economic and genetic factors, with varying rates across regions. The Hakka population in Ganzhou city has unique exposures compared to surrounding districts, while limited research reported the epidemiological characteristics of type 2 diabetes mellitus (T2DM) in this population. This study aims to investigate the prevalence and influencing factors of T2DM among the population, thereby establishing a robust foundation for disease prevention and control measures. Patients and Methods: In 2017, a multistage random sampling method selected 3028 individuals from Ganzhou City's permanent resident population. Physical examinations, blood tests, and questionnaire surveys were conducted for data collection, with binary logistic regression analysis used to examine factors affecting T2DM prevalence. Results: A total of 2978 valid samples were included in this study. The average age of the surveyed population was 52.83±7.88 years, comprising 966 males and 2012 females. The prevalence rates of T2DM were 11.8% and 12.9% in males and females, respectively, while the standardized prevalence rate was recorded as 9.1%. Logistic regression analysis revealed that age (Odds Ratio[OR]=1.05, 95% Confidence Interval [CI]:1.03-1.06), hypertension (OR=2.22, 95% CI:1.71-2.93), family history of diabetes (OR= 3.54, 95% CI: 2.58-4.85), overweight (OR=1.73, 95% CI: 1.20-2.48), high total cholesterol (OR=1.17, 95% CI:1.09-1.27), elevated low-density lipoprotein cholesterol (OR=1.19, 95% CI:1.00-1.40) and serum insulin (OR=1.05, 95% CI:1.03-1.06) were identified as significant risk factors for T2DM, Conversely, a higher level of high-density lipoprotein cholesterol (OR=0.55, 95% CI:0.36-0.84) was found to be inversely related to T2DM development. Conclusion: The prevalence of T2DM in Ganzhou city has significantly increased. The effective implementation of comprehensive management strategies aimed at addressing hypertension, overweight, dyslipidemia, and abnormal serum insulin level is essential for promoting overall well-being and efficiently controlling the prevalence of T2DM.

HGTMDA: A Hypergraph Learning Approach with Improved GCN-Transformer for miRNA-Disease Association Prediction.

Accumulating scientific evidence highlights the pivotal role of miRNA-disease association research in elucidating disease pathogenesis and developing innovative diagnostics. Consequently, accurately identifying disease-associated miRNAs has emerged as a prominent research topic in bioinformatics. Advances in graph neural networks (GNNs) have catalyzed methodological breakthroughs in this field. However, existing methods are often plagued by data noise and struggle to effectively integrate local and global information, which hinders their predictive performance. To address this, we introduce HGTMDA, an innovative hypergraph learning framework that incorporates random walk with restart-based association masking and an enhanced GCN-Transformer model to infer miRNA-disease associations. HGTMDA starts by constructing multiple homogeneous similarity networks. A novel enhancement of our approach is the introduction of a restart-based random walk association masking strategy. By stochastically masking a subset of association data and integrating it with a GCN enhanced by an attention mechanism, this strategy enables better capture of key information, leading to improved information utilization and reduced impact of noisy data. Next, we build an miRNA-disease heterogeneous hypergraph and adopt an improved GCN-Transformer encoder to effectively solve the effective extraction of local and global information. Lastly, we utilize a combined Dice cross-entropy (DCE) loss function to guide the model training and optimize its performance. To evaluate the performance of HGTMDA, comprehensive comparisons were conducted with state-of-the-art methods. Additionally, in-depth case studies on lung cancer and colorectal cancer were performed. The results demonstrate HGTMDA's outstanding performance across various metrics and its exceptional effectiveness in real-world application scenarios, highlighting the advantages and value of this method.

A Senomorphlytic Three-Drug Combination Discovered in Salsola collina for Delaying Aging Phenotypes and Extending Healthspan.

The pursuit of pharmacological interventions in aging aims focuses on maximizing safety and efficacy, prompting an exploration of natural products endowed with inherent medicinal properties. Subsequently, this work establishes a unique library of plant extracts sourced from Yunnan Province, China. Screening of this herbal library herein revealed that Salsola collina (JM10001) notably enhances both lifespan and healthspan in C. elegans. Further analysis via network pharmacology indicates that the p53 signaling pathway plays a crucial role in mediating the anti-aging effects of JM10001. Additionally, this work identifies that a composition, designated as JM10101 and comprising three chemical constituents of JM10001, preserves the original lifespan-extending activity in C. elegans. Both JM10001 and JM10101 mitigate aging symptoms in senescence-accelerated mice treated with doxorubicin and in naturally aged mice. Notably, JM10101 exhibits a more sophisticated senomorphlytic role encompassing both senomorphic and senolytic functions than JM10001 in the modulation of senescent cells, offering a promising strategy for the discovery of combination drugs in the rational development of anti-aging therapies.

Effects of Different Soybean and Coconut Oil Additions on the Physicochemical and Sensory Properties of Soy Protein-Wheat Protein Mixture Subjected to High-Moisture Extrusion.

A protein mixture was prepared using a blend of soybean protein isolate, soybean protein concentrate, and wheat protein through high-moisture extrusion. This study investigated the effects of soybean oil/coconut oil additions (2%, 5%, and 8%) on the physiochemical properties of a soy protein-wheat protein mixture subjected to high-moisture extrusion. The protein extrudates underwent assessment for textural properties, fiber degree, sensory evaluation, microstructure, protein solubility, and protein secondary structure. The findings indicated that plant oils significantly reduced the hardness, springiness, and chewiness of the extrudates, and 5% plant oil significantly increased the fiber degree of the extrudates. In addition, the highest fiber degree and sensory evaluation score were achieved with 5% coconut oil. Observation of the macro- and microstructure indicated that the presence of unsaturated fatty acids in soybean oil did not benefit the improvement of the fibrous structure of protein extrudates during high-moisture extrusion processing. SDS-PAGE and FTIR results revealed that coconut oil, rich in saturated fatty acids, caused the clustering of medium- and low-molecular-weight subunits in texturized protein. Additionally, coconut oil elevated the ratio of 11S protein subunits containing sulfur-based amino acids and facilitated a shift from ß-turn to ß-sheet. The inclusion of plant oils increased the development of hydrogen and disulfide bonds, resulting in a denser, fibrous structure. DSC demonstrated that plant oils reduced the thermal stability of the texturized proteins but enhanced the order of protein structure.

Comparing Sediment Bacterial Communities of Volcanic Lakes and Surrounding Rivers in Inner Mongolia Autonomous Region, Northeastern China.

Volcanic lakes originate from a volcanic crater or caldera, and were a crucial component of aquatic ecosystems. Sediment bacteria play an important role in the nutrient cycling of aquatic ecosystems; however, their patterns distribution in volcanic lakes and the surrounding river habitats are unknown. In this study, we compare the sediment bacterial communities and their co-occurrence networks between these two habitats in the Inner Mongolia Autonomous Region, Northeastern China (the Arxan UNESCO Global Geopark), using 16S rRNA gene amplicon sequencing. The results revealed that there were significant variations in the physicochemical parameters of the sediment between these two habitats. The bacterial α-diversity, ß-diversity, and community composition of the sediment also significantly differed between these two habitats. Network analysis showed that the co-occurrence patterns and keystone taxa in the sediment differed between these two habitats. The sediment bacterial communities in the river habitats were more stable than those in the lake habitats in the face of environmental change. Canonical correspondence analysis demonstrated that both physical (pH and MC) and nutrition-related factors (TN, TP, LOI, and TOC) were the most important environmental factors shaping the variations of bacterial community composition (BCC) in the sediment between these two habitats. This work could greatly improve our understanding of the sediment BCC of the sediment from aquatic ecosystems in the UNESCO Global Geopark.

Potential of Marine Bacterial Metalloprotease A69 in the Preparation of Peanut Peptides with Angiotensin-Converting Enzyme (ACE)-Inhibitory and Antioxidant Properties.

Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g-1 and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC50 values of 1.50 mg mL-1 and 1.66 mg mL-1, respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC50 value of 0.71 mg mL-1. By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein.

Immunomodulatory Compounds from the Sea: From the Origins to a Modern Marine Pharmacopoeia.

From sea shores to the abysses of the deep ocean, marine ecosystems have provided humanity with valuable medicinal resources. The use of marine organisms is discussed in ancient pharmacopoeias of different times and geographic regions and is still deeply rooted in traditional medicine. Thanks to present-day, large-scale bioprospecting and rigorous screening for bioactive metabolites, the ocean is coming back as an untapped resource of natural compounds with therapeutic potential. This renewed interest in marine drugs is propelled by a burgeoning research field investigating the molecular mechanisms by which newly identified compounds intervene in the pathophysiology of human diseases. Of great clinical relevance are molecules endowed with anti-inflammatory and immunomodulatory properties with emerging applications in the management of chronic inflammatory disorders, autoimmune diseases, and cancer. Here, we review the historical development of marine pharmacology in the Eastern and Western worlds and describe the status of marine drug discovery. Finally, we discuss the importance of conducting sustainable exploitation of marine resources through biotechnology.

Prognostic Value of Serum Galectin-3 for Survival in Patients with Cardiac Light-Chain Amyloidosis.

BACKGROUND: Amyloid light-chain (AL) amyloidosis is a multisystem disorder, with cardiac amyloid infiltration being a prevalent manifestation. This study aimed to explore the prognostic value of galectin-3 (Gal-3), a soluble marker associated with fibrosis, inflammation, heart failure, and kidney injury, in patients with cardiac AL amyloidosis. METHODS: A total of 60 patients who were diagnosed with cardiac AL amyloidosis from January 2015 to May 2018 were enrolled. The prognostic value of Gal-3 was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of Gal-3. A Gal-3 cut-off value was identified to predict survival rates. RESULTS: The ROC curves demonstrated a moderate predictive accuracy of Gal-3 for 0.5- and 5-year survival, with area under the curve (AUC) values of 0.722 and 0.788, respectively. A Gal-3 cut-off value of 15.154 ng/mL was found to predict survival. Kaplan-Meier survival analysis revealed a significant difference in mean overall survival between patients with Gal-3 levels below and above the established cut-off (69.2 months versus 42.1 months, respectively; p = 0.036). Multivariate analysis confirmed that Gal-3 > 15.154 ng/mL remained an independent predictor of survival (HR 2.451, 95% CI 1.017-5.910, p = 0.046). CONCLUSIONS: This study suggests that Gal-3 holds independent prognostic value for survival in patients with cardiac AL amyloidosis. Gal-3 could potentially enhance the prognostic capabilities of the current soluble markers, thereby improving the management of cardiac AL amyloidosis. However, further validation in larger prospective studies is warranted.

Multi-functional adhesive hydrogel as bio-interface for wireless transient pacemaker.

Traditional temporary cardiac pacemakers (TCPs), which employ transcutaneous leads and external wired power systems are battery-dependent and generally non-absorbable with rigidity, thereby necessitating surgical retrieval after therapy and resulting in potentially severe complications. Wireless and bioresorbable transient pacemakers have, hence, emerged recently, though hitting a bottleneck of unfavorable tissue-device bonding interface subject to mismatched mechanical modulus, low adhesive strength, inferior electrical performances, and infection risks. Here, to address such crux, we develop a multifunctional interface hydrogel (MIH) with superior electrical performance to facilitate efficient electrical exchange, comparable mechanical strength to natural heart tissue, robust adhesion property to enable stable device-tissue fixation (tensile strength: ∼30 kPa, shear strength of ∼30 kPa, and peel-off strength: ∼85 kPa), and good bactericidal effect to suppress bacterial growth. Through delicate integration of this versatile MIH with a leadless, battery-free, wireless, and transient pacemaker, the entire system exhibits stable and conformal adhesion to the beating heart while enabling precise and constant electrical stimulation to modulate the cardiac rhythm. It is envisioned that this versatile MIH and the proposed integration framework will have immense potential in overcoming key limitations of traditional TCPs, and may inspire the design of novel bioelectronic-tissue interfaces for next-generation implantable medical devices.

Superstrong, sustainable, origami wood paper enabled by dual-phase nanostructure regulation in cell walls.

Constructing a crystalline-amorphous hybrid structure is an effective strategy to overcome the conflict between the strength and toughness of materials. However, achieving such a material structure often involves complex, energy-intensive processing. Here, we leverage the natural wood featuring coexisting crystalline and amorphous regions to achieve superstrong and ultratough wood paper (W-paper) via a dual-phase nanostructure regulation strategy. After partially removing amorphous hemicellulose and eliminating most lignin, the treated wood can self-densify through an energy-efficient air drying, resulting in a W-paper with high tensile strength, toughness, and folding endurance. Coarse-grained molecular dynamics simulations reveal the underlying deformation mechanism of the crystalline and amorphous regions inside cell walls and the failure mechanism of the W-paper under tension. Life cycle assessment reveals that W-paper shows a lower environmental impact than commercial paper and common plastics. This dual-phase nanostructure regulation based on natural wood may provide valuable insights for developing high-performance and sustainable film materials.

Clinical and pathological characteristics of gestational diabetes mellitus with different insulin resistance.

AIMS: To elucidate the clinical and pathological characteristics of gestational diabetes mellitus (GDM) with high and low insulin resistance. METHODS: In total, 1393 GDM and 1001 non-GDM singleton deliveries were included in this study. Insulin resistance subtypes were classified according to the HOMA2-IR value. Clinical data were analyzed using SPSS 26.0. Placenta samples were collected for pathological analysis. RESULTS: Maternal age and fasting glucose were identified as independent risk factors for GDM with high insulin resistance (p < 0.01), while fasting glucose was the sole risk factor for GDM with low insulin resistance (p < 0.001). Fetal distress was associated with both of GDM subtypes (both p < 0.01), while anemia, fetal growth restriction, large for gestational age and intrahepatic cholestasis in pregnancy were related to specific GDM insulin resistance subtype. In addition, GDM with high insulin resistance showed an increase of syncytial knots with down-regulation of PI3K/AKT signaling, while GDM with low insulin resistance showed normal syncytial knot counts and up-regulation of PI3K/AKT signaling. CONCLUSIONS: Our findings provide novel perspectives to the clinical and pathological comprehensions of GDM with high and low insulin resistance, which might facilitate the mechanism study of GDM and its precision pregnancy management.

Aberrant expression of LGALS3BP drives an unfavorable prognosis and more aggressive in HCC via regulating PI3K/AKT signaling.

Lectin galactoside-binding soluble 3-binding protein (LGALS3BP) is associated with cancer metastasis and is a promising prognostic marker in neoplasms. In hepatocellular carcinoma (HCC), the prognostic impact and pro-metastatic function of LGALS3BP remain unclear. This study evaluated the endogenous LGALS3BP expression in HCC tissue and its association with prognosis. LGALS3BP protein levels were significantly elevated in clinical HCC tissues and cell lines. Increased LGALS3BP expression was closely associated with disease progression in HCC patients, and they also exhibited an unfavorable prognosis. Furthermore, the knockdown of LGALS3BP inhibited the growth, migration, and invasion of HCC cells in vitro. In mice xenografts, silencing LGALS3BP significantly inhibited tumor cell growth in vivo. Mechanically, upon LGALS3BP depletion, the tumor-suppressive function was dependent on inactivating Phosphatidylinositol 3-kinase (PI3K)/V-akt murine thymoma viral oncogene homolog (AKT) signaling pathway. Collectively, these findings suggest that LGALS3BP employs a pro-tumorigenic function in HCC and may be a promising HCC prognostic marker.

Unconventional hcp/fcc Nickel Heteronanocrystal with Asymmetric Convex Sites Boosts Hydrogen Oxidation.

Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H2O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mgNi-1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites.

Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation, causing structural damage and lung failure. Stem cell therapy and mesenchymal stem cells-extracellular vesicles (MSC-EVs) offer new hope for PF treatment. AIM: To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis, oxidative stress, and immune inflammation in A549 cells and bleomycin (BLM)-induced mouse model. METHODS: The effect of MSC-EVs on A549 cells was assessed by fibrosis markers [collagen I and α-smooth muscle actin (α-SMA), oxidative stress regulators [nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and inflammatory regulators [nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-1ß, and IL-2]. Similarly, they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection. MSC-EVs ion PF mice were detected by pathological staining and western blot. Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice. RESULTS: Transforming growth factor (TGF)-ß1 enhanced fibrosis in A549 cells, significantly increasing collagen I and α-SMA levels. Notably, treatment with MSC-EVs demonstrated a remarkable alleviation of these effects. Similarly, the expression of oxidative stress regulators, such as Nrf2 and HO-1, along with inflammatory regulators, including NF-κB p65 and IL-1ß, were mitigated by MSC-EV treatment. Furthermore, in a parallel manner, MSC-EVs exhibited a downregulatory impact on collagen deposition, oxidative stress injuries, and inflammatory-related cytokines in the lungs of mice with PF. Additionally, the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response. The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes, oxidative stress, and inflammatory responses associated with PF. CONCLUSION: MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition, oxidative stress, and immune-inflammatory responses.

Multiple forms of perceived job discrimination and hypertension risk among employed women: Findings from the Sister Study.

BACKGROUND: Hypertension has been linked to socially patterned stressors, including discrimination. Few studies have quantified the risk of hypertension associated with exposure to perceived job discrimination. METHODS: We used prospective cohort data from the Sister Study (enrollment from 2003-2009) to estimate self-reported incident hypertension associated with perceived job discrimination based on race, gender, age, sexual orientation, or health status. Job discrimination in the prior 5 years was assessed in 2008-2012, and incident doctor-diagnosed hypertension was ascertained in previously hypertension-free participants. RESULTS: Among the 16,770 eligible participants aged 37-78 years at the start of follow-up, 10.5% reported job discrimination in the past 5 years, and 19.2% (n = 3226) reported incident hypertension during a median follow-up of 9.7 years (interquartile range 8.2-11.0 years). Self-reported poor health or inclusion in minoritized groups based on race/ethnicity or sexual orientation were more frequent among those reporting job discrimination. In a Cox proportional hazards model adjusting for covariates, report of at least one type of job discrimination (compared to none) was associated with a 14% (hazard ratio = 1.14 [95% confidence: 1.02-1.27]) higher hypertension risk. Results from sensitivity analyses reinforced the findings. CONCLUSIONS: Results suggest that interventions addressing job discrimination could have workplace equity and health benefits.

A Novel Combination Strategy of Ultrasound-Guided Percutaneous Radiofrequency Ablation and Corticosteroid Injection for Treating Recalcitrant Plantar Fasciitis: A Retrospective Comparison Study.

INTRODUCTION: The best treatment yielding clinical benefits was still equivocal and controversial for the treatment of recalcitrant plantar fasciitis (PF). This study aimed to propose a novel combination strategy of ultrasound-guided percutaneous radiofrequency ablation (RFA) and corticosteroid injection (CI) for recalcitrant PF, and to compare its therapeutic effects with CI alone and continued conservative management. METHODS: We retrospectively reviewed consecutive patients with recalcitrant PF who underwent combined strategy (RFA + CI), CI alone, and continue conservative treatment at our institution between October 2021 and February 2023. The technical pearls were described elaborately. A comparison of demographic data and clinical outcomes, including visual analog scale (VAS), Ankle-Hindfoot Scale (AOFAS-AHS), and plantar fascia thickness, were conducted among the three groups. RESULTS: Seventy-one eligible patients were enrolled in this study, with 17 in the combined strategy group, 25 in the CI group, and 29 in the continued conservative treatment group. Both the combined strategy group and the CI group showed significant improvements in VAS scores, AOFAS-AHS scores, and significant reductions in plantar fascia thickness during the 12-month follow-up period compared to those preoperatively (P < 0.05). The combined strategy group achieved comparable immediate pain relief to the CI group after the intervention ([25.7 ± 15.7] vs. [20.6 ± 17.6], P = 0.850). However, the combined strategy group demonstrated superior improvement in symptom and function compared to the CI group at the 3-month (VAS: [21.9 ± 13.5] vs. [39.6 ± 20.4]; AOFAS-AHS: [77.9 ± 12.4] vs. [60.5 ± 17.4], P < 0.05) and 12-month follow-up (VAS: [15.7 ± 12.0] vs. [56.8 ± 17.5]; AOFAS-AHS: [84.5 ± 10.7] vs. [53.8 ± 12.4], P < 0.05). Obvious adverse effects or complications were not identified in either group, while two cases (11.8%) in the combined strategy group and five cases (20.0%) in the CI group experienced unsatisfactory symptom remission. CONCLUSIONS: We introduced and detailed a novel combination strategy involving ultrasound-guided percutaneous RFA and CI for treating recalcitrant PF. The strategy is both effective and safe in alleviating pain and enhancing function throughout the entire treatment course.

A molecular module connects abscisic acid with auxin signals to facilitate seasonal wood formation in Populus.

Perennial trees have a recurring annual cycle of wood formation in response to environmental fluctuations. However, the precise molecular mechanisms that regulate the seasonal formation of wood remain poorly understood. Our prior study indicates that VCM1 and VCM2 play a vital role in regulating the activity of the vascular cambium by controlling the auxin homoeostasis of the cambium zone in Populus. This study indicates that abscisic acid (ABA) affects the expression of VCM1 and VCM2, which display seasonal fluctuations in relation to photoperiod changes. ABA-responsive transcription factors AREB4 and AREB13, which are predominantly expressed in stem secondary vascular tissue, bind to VCM1 and VCM2 promoters to induce their expression. Seasonal changes in the photoperiod affect the ABA amount, which is linked to auxin-regulated cambium activity via the functions of VCM1 and VCM2. Thus, the study reveals that AREB4/AREB13-VCM1/VCM2-PIN5b acts as a molecular module connecting ABA and auxin signals to control vascular cambium activity in seasonal wood formation.