Morphology analysis of PEEK 450G using scanning electron microscopy directly on fast scanning calorimetry chips.

To explore the morphology of polyetheretherketone (PEEK), this study employed fast scanning calorimetry (FSC) and scanning electron microscopy (SEM). The objective was to observe the PEEK microstructure under various thermal profiles replicating the additive manufacturing material extrusion process. Samples were observed using SEM directly from the FSC chips, allowing high-accuracy evaluation of the microstructure relative to the thermal profiles. This approach allowed for the evaluation of the microstructure with high accuracy concerning the thermal profiles to which the samples were previously exposed. Each sample was coated with a 10 nm layer of gold-palladium (20-80% ratio), and no etching was necessary to observe the micro features of the microstructure. The approach enabled successful observation and quantification of PEEK microstructure, linking substrate temperature and temperature peaks to microstructural outcomes. Notably, temperature peaks during the process enhanced the formation of well-developed, thick lamellae due to increased chain mobility. Additionally, embryos formed post-remelting of the substrate structure were observed.

Combination therapy consisting of transarterial chemoembolization, lenvatinib, and programmed cell death protein 1 blockade for hepatocellular carcinoma with inferior vena cava tumor thrombus: a case series study and literature review.

INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava carcinoma tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors (TKIs) is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and one patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in one and three patients, respectively. Treatment-related adverse events of any grade occurred in of 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in one patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

Room-temperature synthesis of a Zr-UiO-66 metal-organic framework via mechanochemical pretreatment for the rapid removal of EDTA-chelated copper from water.

Treatment of heavy metal pollution in complexed states within water bodies presents significant challenges in the current water treatment field. Adsorption as a means for the removal of heavy metals is characterized by its simplicity of operation, stable effluent, and minimal equipment requirements. Metal-organic frameworks (MOFs) as adsorbents hold significant interest for applications in water treatment. In this study, we investigated a green synthesis approach for the ball-milling pretreated synthesis of UiO-66(Zr) at room temperature, abbreviated as UiO-66(Zr)-rm. Besides having the same thermal stability and crystal structure as the product from microwave-assisted synthesis (UiO-66(Zr)-mw), the resulting UiO-66(Zr)-rm features smaller particle size and superior mesoporous structure. The adsorption efficiency and mechanism for removing EDTA-chelated copper (EDTA-CuII), a complexed heavy metal in water, were extensively analyzed. UiO-66(Zr)-rm presented a maximum adsorption capacity over EDTA-CuII of 43 mg g-1 and a much higher adsorption rate (0.16 g (mg h)-1) than UiO-66(Zr)-mw (0.06 g (mg h)-1). Hierarchically mesostructured defects allow the sorbate to have more effective diffusion in a shorter time to achieve faster adsorption kinetics. Benefiting from the mild synthesis conditions and nontoxic solvents, UiO-66(Zr) has the potential to be produced at a scaled-up level, thereby exhibiting excellent adsorption performance for the removal of complexed heavy metals in the future.

EGR3 Inhibits Tumor Progression by Inducing Schwann Cell-Like Differentiation.

The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.

Central nervous system involvement in chronic lymphocytic leukemia: a case report and review of literature.

BACKGROUND: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. CASE PRESENTATION: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. CONCLUSION: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.

Hsa-miR-134-5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells.

This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa-miR-134-5p was found up-regulated in senescent EPCs where overexpression improved angiogenic activity. Hsa-miR-134-5p, which targeted transforming growth factor ß-activated kinase 1-binding protein 1 (TAB1) gene, down-regulated TAB1 protein, and inhibited phosphorylation of p38 mitogen-activated protein kinase (p38) in hsa-miR-134-5p-overexpressed senescent EPCs. Treatment with siRNA specific to TAB1 (TAB1si) down-regulated TAB1 protein and subsequently inhibited p38 activation in senescent EPCs. Treatment with TAB1si and p38 inhibitor, respectively, showed angiogenic improvement. In parallel, transforming growth factor Beta 1 (TGF-ß1) was down-regulated in hsa-miR-134-5p-overexpressed senescent EPCs and addition of TGF-ß1 suppressed the angiogenic improvement. Analysis of peripheral blood mononuclear cells (PBMCs) disclosed expression levels of hsa-miR-134-5p altered in adult life, reaching a peak before 65 years, and then falling in advanced age. Calculation of the Framingham risk score showed the score inversely correlates with the hsa-miR-134-5p expression level. In summary, hsa-miR-134-5p is involved in the regulation of senescence-related change of angiogenic activity via TAB1-p38 signalling and via TGF-ß1 reduction. Hsa-miR-134-5p has a potential cellular rejuvenation effect in human senescent EPCs. Detection of human PBMC-derived hsa-miR-134-5p predicts cardiovascular risk.

Value of fractional-order calculus (FROC) model diffusion-weighted imaging combined with simultaneous multi-slice (SMS) acceleration technology for evaluating benign and malignant breast lesions.

BACKGROUND: This study explores the diagnostic value of combining fractional-order calculus (FROC) diffusion-weighted model with simultaneous multi-slice (SMS) acceleration technology in distinguishing benign and malignant breast lesions. METHODS: 178 lesions (73 benign, 105 malignant) underwent magnetic resonance imaging with diffusion-weighted imaging using multiple b-values (14 b-values, highest 3000 s/mm2). Independent samples t-test or Mann-Whitney U test compared image quality scores, FROC model parameters (D,, ), and ADC values between two groups. Multivariate logistic regression analysis identified independent variables and constructed nomograms. Model discrimination ability was assessed with receiver operating characteristic (ROC) curve and calibration chart. Spearman correlation analysis and Bland-Altman plot evaluated parameter correlation and consistency. RESULTS: Malignant lesions exhibited lower D, and ADC values than benign lesions (P < 0.05), with higher values (P < 0.05). In SSEPI-DWI and SMS-SSEPI-DWI sequences, the AUC and diagnostic accuracy of D value are maximal, with D value demonstrating the highest diagnostic sensitivity, while value exhibits the highest specificity. The D and combined model had the highest AUC and accuracy. D and ADC values showed high correlation between sequences, and moderate. Bland-Altman plot demonstrated unbiased parameter values. CONCLUSION: SMS-SSEPI-DWI FROC model provides good image quality and lesion characteristic values within an acceptable time. It shows consistent diagnostic performance compared to SSEPI-DWI, particularly in D and values, and significantly reduces scanning time.

Physical properties and antioxidant activity of curcumin­zinc metal-organic frameworks.

Metal-organic frameworks (MOFs) offer diverse applications in the food industry, facilitating loading, protection, and controlled release of functional ingredients despite encountering loading capacity and functional activity limitations. This study focuses on curcumin­zinc MOFs, harnessing curcumin's renowned health benefits and zinc to enhance pharmacological properties. We evaluated their synthesis efficiency, stability under varying conditions (pH, salt concentration, temperature), loading and antioxidant capacity. The results showed that microwave synthesis yielded MOFs with a 23.2 ± 4.5% yield, stable within pH 4-10, gradually decomposing in PBS. DPPH, ABTS, and H2O2 assays revealed varying free radical scavenging abilities. MOFs disintegrate in either acidic environments or contain H2O2 (at a concentration threshold of 10 µM). Post-disintegration, these MOFs significantly inhibiting the secretion of TNF-α by RAW264.7 cells induced by LPS. These findings highlight the potential of novel curcumin­zinc MOF materials for nutrient delivery, addressing challenges in effectively delivering functional ingredients.

Lansoprazole (LPZ) reverses multidrug resistance (MDR) in cancer through impeding ATP-binding cassette (ABC) transporter-mediated chemotherapeutic drug efflux and lysosomal sequestration.

AIMS: Lansoprazole is one of the many proton pump inhibitors (PPIs) that acts more strongly with ABCB1 and ABCG2. The present study is to investigate the potential of lansoprazole on reversal of ABCB1/G2-mediated MDR in cancer, in vitro and in vivo. METHODS: Reversal studies and combination evaluation were conducted to determine the synergistic anti-MDR effects on lansoprazole. Lysosomal staining was used to determination of lansoprazole on ABCB1-mediated lysosomal sequestration. Substrate accumulation and efflux assays, ATPase activity, and molecular docking were conducted to evaluate lansoprazole on ABCB1/G2 functions. Western blot and immunofluorescence were used to detect lansoprazole on ABCB1/G2 expression and subcellular localization. MDR nude mice models were established to evaluate the effects of lansoprazole on MDR in vivo. RESULTS: Lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects with substrate drugs in MDR cells. In vivo experiments demonstrated that lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects that augmented the sensitivity of substrate anticancer drugs in ABCB1/G2-mediated settings without obvious toxicity. Lansoprazole impeded lysosomal sequestration mediated by ABCB1, leading to a substantial increase in intracellular accumulation of substrate drugs. The effects of lansoprazole were not attributable to downregulation or alterations in subcellular localization of ABCB1/G2. Lansoprazole promoted the ATPase activity of ABCB1/G2 and competitively bound to the substrate-binding region of ABCB1/G2. CONCLUSIONS: These findings present novel therapeutic avenues whereby the combination of lansoprazole and chemotherapeutic agents mitigates MDR mediated by ABCB1/G2 overexpression.

Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

Nanoscale Spatiotemporal Dynamics of Microbial Adhesion: Unveiling Stepwise Transitions with Plasmonic Imaging.

Understanding bacterial adhesion at the nanoscale is crucial for elucidating biofilm formation, enhancing biosensor performance, and designing advanced biomaterials. However, the dynamics of the critical transition from reversible to irreversible adhesion has remained elusive due to analytical constraints. Here, we probed this adhesion transition, unveiling nanoscale, step-like bacterial approaches to substrates using a plasmonic imaging technique. This method reveals the discontinuous nature of adhesion, emphasizing the complex interplay between bacterial extracellular polymeric substances (EPS) and substrates. Our findings not only deepen our understanding of bacterial adhesion but also have significant implications for the development of theoretical models for biofilm management. By elucidating these nanoscale step-like adhesion processes, our work provides avenues for the application of nanotechnology in biosensing, biofilm control, and the creation of biomimetic materials.

Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia.

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.

D-MAINS: A Deep-Learning Model for the Label-Free Detection of Mitosis, Apoptosis, Interphase, Necrosis, and Senescence in Cancer Cells.

BACKGROUND: Identifying cells engaged in fundamental cellular processes, such as proliferation or living/death statuses, is pivotal across numerous research fields. However, prevailing methods relying on molecular biomarkers are constrained by high costs, limited specificity, protracted sample preparation, and reliance on fluorescence imaging. METHODS: Based on cellular morphology in phase contrast images, we developed a deep-learning model named Detector of Mitosis, Apoptosis, Interphase, Necrosis, and Senescence (D-MAINS). RESULTS: D-MAINS utilizes machine learning and image processing techniques, enabling swift and label-free categorization of cell death, division, and senescence at a single-cell resolution. Impressively, D-MAINS achieved an accuracy of 96.4 ± 0.5% and was validated with established molecular biomarkers. D-MAINS underwent rigorous testing under varied conditions not initially present in the training dataset. It demonstrated proficiency across diverse scenarios, encompassing additional cell lines, drug treatments, and distinct microscopes with different objective lenses and magnifications, affirming the robustness and adaptability of D-MAINS across multiple experimental setups. CONCLUSIONS: D-MAINS is an example showcasing the feasibility of a low-cost, rapid, and label-free methodology for distinguishing various cellular states. Its versatility makes it a promising tool applicable across a broad spectrum of biomedical research contexts, particularly in cell death and oncology studies.

Functionality of arbuscular mycorrhizal fungi varies across different growth stages of maize under drought conditions.

Physio-biochemical regulations governing crop growth period are pivotal for drought adaptation. Yet, the extent to which functionality of arbuscular mycorrhizal fungi (AM fungi) varies across different stages of maize growth under drought conditions remains uncertain. Therefore, periodic functionality of two different AM fungi i.e., Rhizophagus irregularis SUN16 and Glomus monosporum WUM11 were assessed at jointing, silking, and pre-harvest stages of maize subjected to different soil moisture gradients i.e., well-watered (80% SMC (soil moisture contents)), moderate drought (60% SMC), and severe drought (40% SMC). The study found that AM fungi significantly (p < 0.05) affected various morpho-physiological and biochemical parameters at different growth stages of maize under drought. As the plants matured, AM fungi enhanced root colonization, glomalin contents, and microbial biomass, leading to increased nutrient uptake and antioxidant activity. This boosted AM fungal activity ultimately improved photosynthetic efficiency, evident in increased photosynthetic pigments and photosynthesis. Notably, R. irregularis and G. monosporum improved water use efficiency and mycorrhizal dependency at critical growth stages like silking and pre-harvest, indicating their potential for drought resilience to stabilize yield. The principal component analysis highlighted distinct plant responses to drought across growth stages and AM fungi, emphasizing the importance of early-stage sensitivity. These findings underscore the potential of incorporating AM fungi into agricultural management practices to enhance physiological and biochemical responses, ultimately improving drought tolerance and yield in dryland maize cultivation.

Senescence induces miR-409 to down-regulate CCL5 and impairs angiogenesis in endothelial progenitor cells.

This study explores the impact of senescence on autocrine C-C motif chemokine ligand 5 (CCL5) in human endothelial progenitor cell (EPCs), addressing the poorly understood decline in number and function of EPCs during ageing. We examined the effects of replication-induced senescence on CCL5/CCL5 receptor (CCR5) signalling and angiogenic activity of EPCs in vitro and in vivo. We also explored microRNAs controlling CCL5 secretion in senescent EPCs, its impact on EPC angiogenic activity, and validated our findings in humans. CCL5 secretion and CCR5 levels in senescent EPCs were reduced, leading to attenuated angiogenic activity. CCL5 enhanced EPC proliferation via the CCR5/AKT/P70S6K axis and increased vascular endothelial growth factor (VEGF) secretion. Up-regulation of miR-409 in senescent EPCs resulted in decreased CCL5 secretion, inhibiting the angiogenic activity, though these negative effects were counteracted by the addition of CCL5 and VEGF. In a mouse hind limb ischemia model, CCL5 improved the angiogenic activity of senescent EPCs. Analysis involving 62 healthy donors revealed a negative association between CCL5 levels, age and Framingham Risk Score. These findings propose CCL5 as a potential biomarker for detection of EPC senescence and cardiovascular risk assessment, suggesting its therapeutic potential for age-related cardiovascular disorders.

Open Reduction and Internal Fixation for Supination-External Rotation Type IV Ankle Fractures by Means of Anterolateral and Posterolateral Approaches.

BACKGROUND: The present study aimed to analyze and compare the efficacy of the anterolateral and posterolateral approaches for surgical treatment of supination-external rotation type IV ankle fractures. METHODS: This retrospective study enrolled 60 patients (60 feet) with supination-external rotation type IV ankle fractures, including 30 patients (30 feet) treated by means of the anterolateral approach and 30 patients (30 feet) treated by means of the posterolateral approach. Postoperative clinical efficacy was compared between the groups based on operation time, intraoperative blood loss, postoperative complications, fracture healing time, visual analog scale scores, Short Form-36 Health Survey scores, and American Orthopedic Foot and Ankle Society scores. Comparisons between the two groups were performed using independent-samples t tests and analyses of variance. Intragroup differences were compared using paired t tests, and the χ2 test was used to compare categorical variables. RESULTS: All 60 included patients completed follow-up ranging from 12 to 18 months (mean duration, 14.8 ± 3.5 months). Although baseline characteristics were similar in the two groups, there were significant differences in operation time (86.73 ± 17.44 min versus 111.23 ± 10.05 min; P < .001) and intraoperative blood loss (112.60 ± 25.05 mL versus 149.47 ± 44.30 mL; P < .001). Although fracture healing time (10.90 ± 0.66 weeks versus 11.27 ± 0.94 weeks; P = .087) was shorter in the anterolateral group than in the posterolateral group, the difference was not significant. Postoperative complications occurred in one and three patients in the anterolateral and posterolateral approach groups, respectively. Visual analog scale scores were significantly lower in the anterolateral group than in the posterolateral group (1.43 ± 0.50 versus 1.83 ± 0.75; P = .019), although there was no significant difference in Short Form-36 Health Survey scores between the groups (73.63 ± 4.07 versus 72.70 ± 4.04; P = .377). However, American Orthopedic Foot and Ankle Society scores were higher in the anterolateral group than in the posterolateral group (80.43 ± 4.32 versus 75.43 ± 11.32; P = .030). CONCLUSIONS: Both the anterolateral and posterolateral approaches can achieve good results in the treatment of supination-external rotation type IV ankle fractures. Compared with the posterolateral approach, the anterolateral approach is advantageous for the treatment of supination-external rotation type IV ankle fractures given its safety and ability to reduce trauma, clear field of view revealed, and allow for exploration and repair of the inferior tibiofibular anterior syndesmosis within the same incision.

M6[Cd2(CO3)2(B12O18)(OH)6] (M = K, Rb): Borate-Carbonates with Two CdCO3 Embedded in a Cyclic Oxoboron Anion.

Two metal borate-carbonates, M6[Cd2(CO3)2(B12O18)(OH)6] [M = K (1), Rb (2)], were obtained under surfactant-thermal conditions. In 1 and 2, each cyclic [(B12O18)(OH)6]6- anion captures two CdCO3 in two sides of the rings and finally forms the unusual (CdCO3)2@[(B12O18)(OH)6] cluster. Both 1 and 2 show moderate birefringence. Density functional theory calculations indicate that carbonate groups have a major contribution to electron-related optical transition.

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

The relationship of peripheral blood lncRNA-PVT1 and miR-146a levels with Th17/Treg cytokines in patients with Hashimoto's thyroiditis and their clinical significance.

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease. We investigated the relationship of peripheral blood long noncoding RNA-plasmacytoma variant translocation 1 (lncRNA-PVT1) and microRNA (miR)-146a levels with Th17/Treg-related cytokines in HT patients and their clinical significance. Correlations of lncRNA-PVT1 and miR-146a with Th17/Treg-related cytokines were analyzed, and its clinical value in diagnosing HT was assessed. Results showed reduced lncRNA-PVT1 and interleukin (IL)-10 levels and increased miR-146a and IL-17 levels in HT patients. lncRNA-PVT1 negatively interrelated with miR-146a, IL-17, IL-23 and IL-6, and positively interrelated with IL-10; miR-146a positively correlated with IL-17, IL-23 and IL-6, but negatively correlated with IL-10 in HT patients. The area under the curve (AUC) of lncRNA-PVT1 and miR-146a levels for diagnosing HT were 0.822 and 0.844, respectively (sensitivity 88.73% and 86.62%, specificity 67.02% and 69.15%, cut-off values 0.76 and 2.73), with their combined detections yielding a higher AUC. Patients with poorly expressed lncRNA-PVT1 and highly expressed miR-146a had elevated HT incidence. lncRNA-PVT1 and miR-146a levels were also found to be an independent influencing factor for HT occurrence. Our findings suggest that HT patients have low peripheral blood lncRNA-PVT1 expression and high miR-146a expression. lncRNA-PVT1 and miR-146a level changes were correlated with Th17/Treg cytokine imbalance and could be a potential diagnostic tool and independent influencing factor for HT.

Noncanonical WNT5A controls the activation of latent TGF-ß to drive fibroblast activation and tissue fibrosis.

Transforming growth factor ß (TGF-ß) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-ß remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-ß in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-ß. The activation of latent TGF-ß requires rapid JNK- and ROCK-dependent cytoskeletal rearrangements and integrin αV (ITGAV). Conditional ablation of WNT5A or its downstream targets prevented activation of latent TGF-ß, rebalanced TGF-ß signaling, and ameliorated experimental fibrosis. We thus uncovered what we believe to be a novel mechanism for the aberrant activation of latent TGF-ß in fibrotic diseases and provided evidence for targeting WNT5A/JNK/ROCK signaling in fibrotic diseases as a new therapeutic approach.