miR-708-3p targetedly regulates LSD1 to promote osteoblast differentiation of hPDLSCs in periodontitis.

Periodontitis (PD) is a multifactorial inflammatory disease associated with periodontopathic bacteria. Lysine-specific demethylase 1 (LSD1), a type of histone demethylase, has been implicated in the modulation of the inflammatory response process in oral diseases by binding to miRNA targets. This study investigates the molecular mechanisms by which miRNA binds to LSD1 and its subsequent effect on osteogenic differentiation. First, human periodontal ligament stem cells (hPDLSCs) were isolated, cultured, and characterized. These cells were then subjected to lipopolysaccharide (LPS) treatment to induce inflammation, after which osteogenic differentiation was initiated. qPCR and western blot were employed to monitor changes in LSD1 expression. Subsequently, LSD1 was silenced in hPDLSCs to evaluate its impact on osteogenic differentiation. Through bioinformatics and dual luciferase reporter assay, miR-708-3p was predicted and confirmed as a target miRNA of LSD1. Subsequently, miR-708-3p expression was assessed, and its role in hPDLSCs in PD was evaluated through overexpression. Using chromatin immunoprecipitation (ChIP) and western blot assay, we explored the potential regulation of osterix (OSX) transcription by miR-708-3p and LSD1 via di-methylated H3K4 (H3K4me2). Finally, we investigated the role of OSX in hPDLSCs. Following LPS treatment of hPDLSCs, the expression of LSD1 increased, but this trend was reversed upon the induction of osteogenic differentiation. Silencing LSD1 strengthened the osteogenic differentiation of hPDLSCs. miR-708-3p was found to directly bind to and negatively regulate LSD1, leading to the repression of OSX transcription through demethylation of H3K4me2. Moreover, overexpression of miR-708-3p was found to promote hPDLSCs osteogenic differentiation in inflammatory microenvironment. However, the protective effect was partially attenuated by reduced expression of OSX. Our findings indicate that miR-708-3p targetedly regulates LSD1 to enhance OSX transcription via H3K4me2 methylation, ultimately promoting hPDLSCs osteogenic differentiation.

Stapler Strategies for Upcycling Mixed Plastics.

Mechanical recycling is one of the simplest and most economical strategies to address ever-increasing plastic pollution, but it cannot be applied to immiscible mixed plastics and suffers from property deterioration after each cycle. By combining the amphiphilic block copolymer strategy and reactive compatibilization strategy, we designed a series of stapler strategies for compatibilizing/upcycling mixed plastics. First, various functionalized graft copolymers were accessed via different synthetic routes. Subsequently, the addition of a very small amount of stapler molecules induced a synergistic effect with the graft copolymers that improved the compatibility and mechanical properties of mixed plastics. These strategies were highly effective for various binary/ternary plastic systems and can be directly applied to postconsumer waste plastics, which can increase the toughness of mixed postconsumer waste plastics by 162 times. Most importantly, it also effectively improved the impact resistance, adhesion performance, and three-dimensional (3D) printing performance of mixed plastics, and permitted the recycling of plastic blends 20 times with minimal degradation in their mechanical properties.

What Are the Functional, Radiographic, and Survivorship Outcomes of a Modified Cup-Cage Technique for Pelvic Discontinuity?

BACKGROUND: Pelvic discontinuity (PD) presents a complex challenge in revision hip arthroplasty. The traditional cup-cage construct, which involves a screw-secured porous metal cup and an overlying antiprotrusio cage, has shown promising mid- to long-term results. However, there is limited information on the outcomes of modifications to the original technique. Our study aims to evaluate a modified technique in which the cup position is determined by the placement of the overlying cage, allowing for adjustments to achieve optimal orientation. QUESTIONS/PURPOSES: Among patients treated for PD with a cup-cage construct in which the cup position was dictated by the position of the cage: (1) What are Harris hip scores achieved at a minimum of 2 years of follow-up? (2) What is the Kaplan-Meier survivorship free from aseptic loosening or component migration? (3) What is the Kaplan-Meier survivorship free from revision for any reason? (4) What surgical complications are associated with the procedure? METHODS: Between October 2013 and January 2022, we performed 805 acetabular revisions. Among these, 33 patients with PD confirmed intraoperatively were considered potentially eligible for a cup-cage construct; no other method of surgical management was used. We performed 64% (21 of 33) of these procedures from October 2013 to January 2018, with 6% (2 of 33) of patients lost to follow-up before the minimum study follow-up of 2 years; these 19 patients were monitored over a period ranging from 70 to 115 months. A further 12 patients underwent this procedure from January 2018 to January 2022, with one lost to follow-up before the minimum study follow-up of 2 years; the other patients met the minimum 2-year follow-up requirement. The remaining 30 patients with data analyzed here (10 men, 20 women) had a mean ± SD age of 61 ± 12 years and a median BMI of 29 kg/m2 (range 20 to 33 kg/m2) at the time of revision surgery. Twenty-one patients underwent revision due to aseptic loosening, and nine due to periprosthetic joint infection (PJI). The causes of PD in our patients were as follows: cup aseptic loosening without significant osteolysis in 20% (6 of 30), where the loose cup caused erosion of the host bone, leading to PD; PJI in 30% (9 of 30); intraoperative iatrogenic PD in 3% (1 of 30); and osteolysis in 47% (14 of 30), which also resulted in aseptic loosening. The median follow-up time was 79 months (range 25 to 115 months). The Harris hip score was used to evaluate clinical outcomes, with preoperative values compared with the most recent follow-up. Radiographs were reviewed by two experienced surgeons at each follow-up visit to assess component loosening (defined as migration > 5 mm or the presence of circumferential radiolucent lines) or clear migration. PD was considered healed if bridging callus or trabecular bone was visible across the site of the discontinuity. Complications were assessed through a comprehensive review of electronic medical records. Kaplan-Meier analysis was used to estimate implant survivorship and radiographic loosening, with aseptic loosening or component migration as the endpoint, as well as survivorship free from any reoperation. RESULTS: The Harris hip score improved from a median of 39 (range 30 to 66) preoperatively to a median of 76 (range 30 to 90) postoperatively (median difference 33 [range 2 to 48]; p < 0.01). Within the limitations of two-dimensional (2D) radiographic imaging, successful bone graft integration and the healing of PD were noted in 83% (25 of 30) of patients. Kaplan-Meier survivorship free from radiographic signs of aseptic loosening or component migration was 100% (95% CI 100% to 100%) at 115 months. When any revision related to the acetabular component was considered the endpoint, survivorship free from acetabular component revision at 115 months after revision surgery was 100% (95% CI 100% to 100%). When the need for any reoperation was considered the endpoint, survivorship free from needing reoperation at 115 months after revision surgery was 85% for all patients (95% CI 73% to 100%). When including only patients with a follow-up time of > 4 years (20 of 30), survivorship free from needing reoperation at 115 months after revision surgery was 90% (95% CI 78% to 100%). Postoperative complications during the follow-up period included one early dislocation on the fifth day after surgery, treated with closed reduction and 6 weeks of abduction bracing. One femoral stem loosening occurred at 56 months postoperatively, although the acetabular component remained securely fixed; this patient declined revision surgery. One patient experienced a dislocation 5 months after surgery but refused treatment and opted for prolonged bed rest. Additionally, one patient underwent a debridement, antibiotics, and implant retention procedure 1 week after the revision surgery and subsequently showed no signs of infection at the latest follow-up, 38 months postoperatively. CONCLUSION: Our study highlights the effectiveness of a modified cup-cage technique in complex hip revisions, showing promising results in terms of construct survivorship and low complication rates. Surgeons could consider delaying screw fixation until after positioning the cage within the porous cup to allow for optimal adjustment and using metal augments for severe bone defects to achieve better alignment. Surgeon experience with the cup-cage technique is crucial for achieving optimal outcomes. Future studies should focus on long-term follow-up visits to assess the durability and effectiveness of these modifications and explore the comparative effectiveness versus other methods, such as custom triflange components and jumbo cups with distraction. LEVEL OF EVIDENCE: Level III, therapeutic study.

Improving Environmental Stress Cracking Resistance of High-Density Polyethylene Grades by Comonomer Addition and Nanocomposite Approach.

The aim is to determine the effect of polymer density, correlated to the comonomer content, and nanosilica addition on the mechanical and Environmental Stress Cracking Resistance (ESCR) characteristics of high-density polyethylene (HDPE). In this regard, five HDPE samples with similar Melt Flow Index (MFI) and molar mass but various densities were acquired from a petrochemical plant. Two polymerization reactors work in series and differ only in the amount of 1-buene comonomer fed to the second reactor. To ascertain the microstructure of the studied samples, GPC and SSA (successive self-nucleation and annealing) analyses were accomplished. All samples resulted having similar characteristics but slightly various SCB/1000C=7.26-9.74 (SCB=Short Chain Branching). Consequently, meanwhile studied HDPEs reveal similar notched impact and stress at yield values, the tensile modulus, stress-at-break, and elongation-at-break tend to demonstrate different results with the SCB content. More significantly, ESCR characteristic varied considerably with SCB/1000C extent, so that higher amount of SCB acknowledged advanced ESCR. Notably, blending HDPE sample containing higher amount of SCB/1000C, with 3 wt.% of chemically modified nanosilica enhanced ESCR characteristic by 40%. DFT (Density Functional Theory) calculations unveiled the role of the comonomer, quantitatively by binding energies and qualitatively by Non Covalent Interaction (NCI) plots.

Reduced-Toxicity and Highly Luminescent Germanium-Lead Perovskites Enabled by Strain Reduction for Light-Emitting Diodes.

Germanium-lead (Ge-Pb) perovskites provide a promising solution for perovskite optoelectronic devices with reduced toxicity. However, Ge-Pb perovskite light-emitting diodes (PeLEDs) with >30 mol % Ge showed low emission efficiencies [Yang, D.; Zhang, G.; Lai, R.; Cheng, Y.; Lian, Y.; Rao, M.; Huo, D.; Lan, D.; Zhao, B.; Di, D. Germanium-Lead Perovskite Light-Emitting Diodes. Nat. Commun. 2021, 12 (1), 4295]. Here, we apply strain engineering to effectively improve the light emission efficiency and stability of Ge-Pb perovskite films and PeLEDs with 30 and 60 mol % Ge, through A-site modulation. The maximum external quantum efficiencies of the Ge-Pb PeLEDs with 30 and 60 mol % Ge are 8.5% and 3.0% at 3.32 mA cm-2 (∼922 cd m-2) and 0.53 mA cm-2 (∼60 cd m-2), respectively. Time-resolved transient absorption spectroscopy analysis of Ge-Pb perovskite films on different hole-transport layers shows that incorporating 30 mol % Ge into the perovskite with mixed A-site cations can effectively suppress trap-assisted recombination. Further analysis of their current density-voltage (J-V) curves reveals the efficiency loss mechanisms of Ge-Pb PeLEDs with high Ge fractions, indicating the possibility of further improvements.

Synthesis of Photoresponsive Fast Self-healing Polyolefin Composites by Nickel-Catalyzed Copolymerization of Ethylene and Lignin Cluster Monomers.

Polymers may suffer from sudden mechanical damages during long-term use under various harsh operating environments. Rapid and real-time self-healing will extend their service life, which is particularly attractive in the context of circular economy. In this work, a lignin cluster polymerization strategy (LCPS) was designed to prepare a series of lignin functionalized polyolefin composites with excellent mechanical properties through nickel catalyzed copolymerization of ethylene and lignin cluster monomers. These composites can achieve rapid self-healing within 30 seconds under a variety of extreme usage environments (underwater, seawater, extremely low temperatures as low as -60 °C, organic solvents, acid/alkali solvents, etc.), which is of great significance for real-time self-healing of sudden mechanical damage. More importantly, the dynamic cross-linking network within these composites enable great re-processability and amazing sealing performances.

3D Laser Writing of Low-Loss Cross-Section-Variable Type-I Optical Waveguide Passive/Active Integrated Devices in Single Crystals.

Optical waveguides fabricated in single crystals offer crucial passive/active optical components for photonic integrated circuits. Single crystals possess inherent advantages over their amorphous counterpart, such as lower optical losses in visible-to-mid-infrared band, larger peak emission cross-section, higher doping concentration. However, the writing of Type-I positive refractive index modified waveguides in single crystals using femtosecond laser technology presents significant challenges. Herein, this work introduces a novel femtosecond laser direct writing technique that combines slit-shaping with an immersion oil objective to fabricate low-loss Type-I waveguides in single crystals. This approach allows for precise control of waveguide shape, size, mode-field, and refractive index distribution, with a spatial resolution as high as 700 nm and a high positive refractive index variation on the order of 10-2, introducing new degrees of freedom to design and fabricate passive/active optical waveguide devices. As a proof-of-concept, this work successfully produces a 7 mm-long circular-shaped gain waveguide (≈10 µm in diameter) in an Er3+-doped YAG single crystal, exhibiting a propagation loss as low as 0.23 dB cm-1, a net gain of ≈3 dB and a polarization-insensitive character. The newly-developed technique is theoretically applicable to arbitrary single crystals, holding promising potential for various applications in integrated optics, optical communication, and photonic quantum circuits.

Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Metastatic clear cell sarcoma of the pancreas: A rare case report.

BACKGROUND: Clear cell sarcoma (CCS) is a rare soft-tissue sarcoma. The most common metastatic sites for CCS are the lungs, bones and brain. CCS is highly invasive and mainly metastasizes to the lung, followed by the bone and brain; however, pancreatic metastasis is relatively rare. CASE SUMMARY: We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man. The patient had a relevant medical history 3 years ago, with abdominal pain as the main clinical manifestation. No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography. Based on the medical history and postoperative pathology, the patient was diagnosed with CCS with pancreatic metastasis. The patient was successfully treated with surgical interventions, including distal pancreatectomy and splenectomy. CONCLUSION: This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.

Ba-Qi-Rougan formula alleviates hepatic fibrosis by suppressing hepatic stellate cell activation via the MSMP/CCR2/PI3K pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Ba-Qi-Rougan formula (BQRGF) is a traditional and effective compound prescription from Traditional Chinese Medicine (TCM) utilized in treating hepatic fibrosis (HF). AIM OF THE STUDY: We aimed to evaluate the therapeutic efficacy of BQRGF on HF and explore the underlying mechanisms of action. MATERIALS AND METHODS: UPLC-Q-TOF-MS technology was employed to identify the material basis of BQRGF. Mice with carbon tetrachloride (CCl4)-induced HF received BQRGF at three doses (3.87, 7.74, and 15.48 g/kg per day). We examined serum and liver biochemical indicators and liver histology to assess the therapeutic impact. Primary mouse cells were isolated and utilized for experimental analysis. MSMP expression levels were examined in vitro and in vivo experimental models, including human and mouse tissue. Furthermore, lentivirus and small interfering RNA (siRNA) transfections were employed to manipulate microseminoprotein (MSMP) expression in LO2 cells (human normal liver cells). These manipulated LO2 cells were then co-cultured with LX2 human hepatic stellate cells (HSCs). Through the modulation of MSMP expression in co-cultured cells, administering recombinant MSMP (rMSMP) with or without BQRGF-medicated serum, and using specific pathway inhibitors or agonists in LX2 cells, we elucidated the underlying mechanisms. RESULTS: A total of 48 compounds were identified from BQRGF, with 12 compounds being absorbed into the bloodstream and 9 compounds being absorbed into the liver. Four weeks of BQRGF treatment in the HF mouse model led to significant improvements in biochemical and molecular assays and histopathology, particularly in the medium and high-dose groups. These improvements included a reduction in the level of liver injury and fibrosis-related factors. MSMP levels were elevated in human and mouse fibrotic liver tissues, and this increase was mitigated in HF mice treated with BQRGF. Moreover, primary cells and co-culture studies revealed that BQRGF reduced MSMP expression, decreased the expression of the hepatic stellate cell (HSC) activation markers, and suppressed critical phosphorylated protein levels in the CCR2/PI3K/AKT pathway. These findings were further validated using CCR2/PI3K/AKT signaling inhibitors and agonists in MSMP-activated LX2 cells. CONCLUSIONS: Collectively, our results suggest that BQRGF combats HF by diminishing MSMP levels and inhibiting MSMP-induced HSC activation through the CCR2/PI3K/AKT pathway.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Pretreatment prostate-specific antigen density as a predictor of biochemical recurrence in patients with prostate cancer: a meta-analysis.

BACKGROUND: A consensus has not been reached on the value of prostate-specific antigen density (PSAD) as a predictor of biochemical recurrence of prostate cancer. This meta-analysis aimed to evaluate the association between PSAD and biochemical recurrence of prostate cancer after primary treatment. METHODS: Two authors systematically searched PubMed, Web of Science, and Embase databases (up to August September 10, 2023) to identify studies that assessed the value of pretreatment PSAD in predicting biochemical recurrence after primary treatment (radical prostatectomy or radiotherapy) of prostate cancer. A random effect model was used to pool adjusted hazard ratios (HR) with 95% confidence intervals (CI) for biochemical recurrence. RESULTS: Nine studies with 4963 patients were eligible for the meta-analysis. The reported prevalence of biochemical recurrence ranged from 4 to 55.1%. For patients with higher PSAD compared to those with low PSAD, the pooled HR of biochemical recurrence was 1.59 (95% CI 1.21-2.10). Subgroup analysis showed that the pooled HR of biochemical recurrence was 1.80 (95% CI 1.34-2.42) for patients who received radical prostatectomy, and 0.98 (95% CI 0.66-1.45) for patients who received radiotherapy. CONCLUSIONS: Elevated pretreatment PSAD may be an independent predictor for biochemical recurrence of prostate cancer after radical prostatectomy. Determining PSAD could potentially improve the prediction of biochemical recurrence in patients with prostate cancer.

Association Between Pretreatment Blood 25-Hydroxyvitamin D Level and Survival Outcomes in Patients With Clinically Localized Prostate Cancer: An Updated Meta-Analysis.

Studies on the prognostic value of the blood 25-hydroxyvitamin D level have yielded controversial results in prostate cancer (PCa) patients. This updated meta-analysis aimed to evaluate the association between pretreatment 25-hydroxyvitamin D level with survival outcomes among patients with clinically localized PCa. PubMed, Web of Science, and Embase databases were searched to identify studies evaluating the association of pretreatment 25-hydroxyvitamin D level with PCSM and all-cause mortality among clinically localized PCa patients. Ten cohort studies with 10,394 patients were identified. The meta-analysis revealed that PCa patients with the lowest 25-hydroxyvitamin D levels had an increased risk of PCSM (adjusted hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.26-1.83; p < 0.001) and all-cause mortality (adjusted HR 1.31; 95% CI 1.00-1.90; p = 0.047) compared to those with higher reference 25-hydroxyvitamin D level. Subgroup analyses based on different sample sizes, follow-up duration, and adjusted times of blood draw also exhibited a significant association of vitamin D deficiency with the risk of PCSM. Lower pretreatment level of 25-hydroxyvitamin D may be an independent predictor of reduced survival in patients with clinically localized PCa. Measuring the pretreatment blood 25-hydroxyvitamin D level can provide valuable information for risk stratification of survival outcomes in these patients.

Suppression of wavelength-dependent polarization fading using hybrid-polarization scheme in OFDR.

What we believe to be a new hybrid-polarization diversity scheme which can eliminate the polarization state variation caused by wavelength tuning of laser in optical frequency domain reflectometry is proposed in the paper. In the scheme, a 45° polarizer is used to maintain the polarization of signals. It decreases the polarization angle fluctuation to 2.81° and realizes a -145 dB test sensitivity with a 32 dB Rayleigh scattering signal-to-noise ratio in a 10 m fiber single test. The polarization fading suppression is achieved for tests with a large wavelength tuning range from 1480 nm to 1640 nm. Meanwhile, a 6 µm spatial resolution is also achieved. The proposed scheme can be applied to the structure measurement of high-precision optical fiber devices with high spatial resolution and sensitivity.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma.

The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour-associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage-related clusters. We developed a M2 macrophage-related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single-cell sequencing data (GSE139324). We identified three distinct M2 macrophage-related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage-related genes significantly impact the development and progression of HNSC. The M2 macrophage-related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.

Bright and Stable Red Perovskite LEDs under High Current Densities.

Perovskite LEDs (PeLEDs) have emerged as a next-generation light-emitting technology. Recent breakthroughs were made in achieving highly stable near-infrared and green PeLEDs. However, the operational lifetimes (T50) of visible PeLEDs under high current densities (>10 mA cm-2) remain unsatisfactory (normally <100 h), limiting the possibilities in solid-state lighting and AR/VR applications. This problem becomes more pronounced for mixed-halide (e.g., red and blue) perovskite emitters in which critical challenges such as halide segregation and spectral instability are present. Here, we demonstrate bright and stable red PeLEDs based on mixed-halide perovskites, showing measured T50 lifetimes of up to ∼357 h at currents of ≥25 mA cm-2, a record for the operational stability of visible PeLEDs under high current densities. The devices produce intense and stable emission with a maximum luminance of 28,870 cd m-2 (radiance: 1584 W sr-1 m-2), which is record-high for red PeLEDs. Key to this demonstration is the introduction of sulfonamide, a dipolar molecular stabilizer that effectively interacts with the ionic species in the perovskite emitters. It suppresses halide segregation and migration into the charge-transport layers, resulting in enhanced stability and brightness of the mixed-halide PeLEDs. These results represent a substantial step toward bright and stable PeLEDs for emerging applications.

Association between Charlson comorbidity index and survival outcomes in patients with prostate cancer: A meta-analysis.

Objective: This meta-analysis aimed to assess the influence of comorbidity, as assessed by the Charlson comorbidity index (CCI), on survival outcomes in patients with prostate cancer (PCa). Methods: We conducted a comprehensive search of the PubMed, Web of Science, and Embase databases to identify studies that examined the association between CCI-defined comorbidity and survival outcomes in PCa patients. We employed a random effect model to merge adjusted hazard ratios (HR) with 95 % confidence intervals (CI) for survival outcomes. Results: Sixteen studies reporting on 17 articles, which collectively included 457,256 patients. For the presence (CCI score ≥1) versus absence (CCI score of 0) of comorbidity, the pooled HR was 1.59 (95 % CI 1.43-1.77) for all-cause mortality, 0.98 (95 % CI 0.90-1.08) for PCa-specific mortality, and 1.88 (95 % CI 1.61-2.21) for other-cause mortality. When compared to a CCI score of 0, the pooled HR of all-cause mortality was 1.30 (95 % CI 1.18-1.44) for a CCI score of 1, 1.65 (95 % CI 1.37-2.00) for a CCI score ≥2, and 1.75 (95 % CI 1.57-1.95) for a CCI score ≥3. Additionally, the pooled HR of other cause mortality was 1.53 (95 % CI 1.41-1.67) for a CCI score of 1, 1.93 (95 % CI 1.74-2.75) for a CCI score ≥2, and 3.95 (95 % CI 2.13-7.34) for a CCI score ≥3. Conclusions: Increased comorbidity, as assessed by the CCI, significantly predicts all-cause and other-cause mortality in patients with PCa, but not PCa-specific mortality. The risk of all-cause and other-cause mortality increases with the burden of comorbidity.

REEPing the harvest of reticulophagy and nucleophagy.

Under stress conditions, the endoplasmic reticulum and nucleus undergo turnover through selective macroautophagy/autophagy processes termed reticulophagy and nucleophagy, respectively. Our recent study has identified the protein Hva22/Rop1/Yep1, a member of the REEP1-REEP4 subfamily of the REEP protein family, as an essential factor for both processes in the fission yeast Schizosaccharomyces pombe. In the absence of Hva22/Yep1, reticulophagy and nucleophagy cargos without surrounding autophagic membranes accumulate in the cytoplasm. Interestingly, human proteins in the REEP1-REEP4 subfamily can functionally substitute for Hva22/Yep1 to facilitate reticulophagy. Phylogenetic and synteny analyses further reveal that the budding yeast reticulophagy receptor Atg40 is also a REEP1-REEP4 subfamily member. Similar to human REEP1-REEP4 subfamily proteins, Atg40 can functionally replace Hva22/Yep1. Based on our findings, we propose that promoting reticulophagy is a conserved function of REEP1-REEP4 subfamily proteins.

In-situ photo-crosslinkable elastomer based on polyalphaolefin/halloysite nanohybrid.

In this research, new injectable and in situ photocurable elastomeric nanohybrids have been fabricated from polyalphaolefin (PAO) resins and halloysite nanofiller. In this regard, the co-oligomerization of long α-olefin monomers (C6, C8 and C10) with alkenol counterparts was carried out via a simple cationic route to provide OH-functionalized PAOs. The newly formed PAO type copolymer resins as well as halloysite nanoclay were then equipped with photocurable CC bonds containing an acrylate moiety. After the characterization of the final chemical substances and also of the intermediate structures, experimentally and computationally by means of Density Functional Theory (DFT) calculations, the neat treated PAO and PAO/halloysite nanohybrids were subjected to a curing process by visible light irradiation (λ âˆ¼ 475 nm, blue light). The crosslinking efficiency of the neat resins and the formed nanohybrid was evaluated using shrinkage strain-time curves and equilibrium swelling method. The suggested nanohybrid is not only biocompatible (96 % in the MTT assay), and hydrophilic (with a water contact angle of 61°), but also exhibits an easy, fast and robust curing process with great potential for coating and sealing technologies for medical devices.