A UPR-Induced Soluble ER-Phagy Receptor Acts with VAPs to Confer ER Stress Resistance.

Autophagic degradation of the endoplasmic reticulum (ER-phagy) is triggered by ER stress in diverse organisms. However, molecular mechanisms governing ER stress-induced ER-phagy remain insufficiently understood. Here we report that ER stress-induced ER-phagy in the fission yeast Schizosaccharomyces pombe requires Epr1, a soluble Atg8-interacting ER-phagy receptor. Epr1 localizes to the ER through interacting with integral ER membrane proteins VAPs. Bridging an Atg8-VAP association is the main ER-phagy role of Epr1, as it can be bypassed by an artificial Atg8-VAP tether. VAPs contribute to ER-phagy not only by tethering Atg8 to the ER membrane, but also by maintaining the ER-plasma membrane contact. Epr1 is upregulated during ER stress by the unfolded protein response (UPR) regulator Ire1. Loss of Epr1 reduces survival against ER stress. Conversely, increasing Epr1 expression suppresses the ER-phagy defect and ER stress sensitivity of cells lacking Ire1. Our findings expand and deepen the molecular understanding of ER-phagy.

The ortholog of human REEP1-4 is required for autophagosomal enclosure of ER-phagy/nucleophagy cargos in fission yeast.

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, known as ER-phagy and nucleophagy, respectively, are processes whose mechanisms remain inadequately understood. Through an imaging-based screen, we find that in the fission yeast Schizosaccharomyces pombe, Yep1 (also known as Hva22 or Rop1), the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy but not for bulk autophagy. In the absence of Yep1, the initial phase of ER-phagy and nucleophagy proceeds normally, with the ER-phagy/nucleophagy receptor Epr1 coassembling with Atg8. However, ER-phagy/nucleophagy cargos fail to reach the vacuole. Instead, nucleus- and cortical-ER-derived membrane structures not enclosed within autophagosomes accumulate in the cytoplasm. Intriguingly, the outer membranes of nucleus-derived structures remain continuous with the nuclear envelope-ER network, suggesting a possible outer membrane fission defect during cargo separation from source compartments. We find that the ER-phagy role of Yep1 relies on its abilities to self-interact and shape membranes and requires its C-terminal amphipathic helices. Moreover, we show that human REEP1-4 and budding yeast Atg40 can functionally substitute for Yep1 in ER-phagy, and Atg40 is a divergent ortholog of Yep1 and REEP1-4. Our findings uncover an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos and shed new light on the functions and evolution of REEP family proteins.

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.

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.

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.

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.

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.

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.

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.

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.

Circ-ILF2 in oral squamous cell carcinoma promotes cisplatin resistance and induces M2 polarization of macrophages.

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP-resistant cell lines. The results showed that circ-ILF2 expression was higher in CDDP-resistant OSCC cell lines. The stability of circ-ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ-ILF2 contributes to CDDP resistance. Luciferase reporter-gene, RNA pull-down and quantitative real-time PCR (RT-qPCR) assays showed that circ-ILF2 functions as a microRNA sponge for miR-1252. Luciferase reporter assays, RNA pull-down, RT-qPCR and Western blotting showed that miR-1252 directly targeted and regulated the expression of KLF8. Circ-ILF2 plays an important role in CDDP resistance in OSCC. Circ-ILF2 exerts its function through the miR-1252/KLF8 pathway. In addition, tumour-associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ-ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ-ILF2 may represent a potential therapeutic target in CDDP-resistant OSCC.

SP2-induced circPUM1 modulates chemoresistance and nature killer cell toxicity in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR-770-5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR-770-5p and essential for circPUM1-mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR-770-5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC.

Amine-Imine Nickel Catalysts with Pendant O-Donor Groups for Ethylene (Co)Polymerization.

The introduction of a secondary interaction is an efficient strategy to modulate transition-metal-catalyzed ethylene (co)polymerization. In this contribution, O-donor groups were suspended on amine-imine ligands to synthesize a series of nickel complexes. By adjusting the interaction between the nickel metal center and the O-donor group on the ligands, these nickel complexes exhibited high activities for ethylene polymerization (up to 3.48 × 106 gPE·molNi-1·h-1) with high molecular weight up to 5.59 × 105 g·mol-1 and produced good polyethylene elastomers (strain recovery (SR) = 69-81%). In addition, these nickel complexes can catalyze the copolymerization of ethylene with vinyl acetic acid, 6-chloro-1-hexene, 10-undecylenic, 10-undecenoic acid, and 10-undecylenic alcohol to prepare the functionalized polyolefins.

Hepatitis C virus nonstructural protein 4B induces lipogenesis via the Hippo pathway.

Hepatitis C virus (HCV) infection causes abnormal lipid metabolism in hepatocytes, which leads to hepatic steatosis and even hepatocellular carcinoma. HCV nonstructural protein 4B (NS4B) has been reported to induce lipogenesis, but the underlying mechanism is unclear. In this study, western blots were performed to investigate the effect of NS4B protein levels on key effectors of the Hippo and AKT signaling pathways. Yes-associated protein (YAP) and moesin-ezrin-radixin-like protein (Merlin) are effectors of the Hippo pathway. NS4B downregulated Merlin and phosphorylated YAP (p-YAP) protein expression while increasing the expression of the key AKT pathway proteins p-AKT and NF-κB. By observing the levels of AKT pathway proteins when Merlin was overexpressed or silenced, it was determined that Merlin mediates the AKT pathway. We suggest that HCV NS4B may mediate the AKT signaling pathway by inhibiting the Hippo pathway. Lipid droplets were observed in Huh7.5 cells overexpressing NS4B, and they increased significantly in number when Merlin was silenced. Overexpression of NS4B and Merlin silencing enhanced the expression of sterol regulatory element binding proteins (SREBPs), which have been demonstrated to be key regulatory factors controlling fatty acid synthesis. NS4B and Merlin silencing also enhanced the in vitro proliferative capacity of hepatocellular carcinoma cells. In conclusion, NS4B induces lipogenesis via the effect of the Hippo-YAP pathway on the AKT signaling pathway and thereby plays a significant role in the pathogenesis of HCV-associated diseases.

More extreme duplication in FDA Adverse Event Reporting System detected by literature reference normalization and fuzzy string matching.

PURPOSE: Literature reports of adverse drug events can be replicated across multiple companies, resulting in extreme duplication (defined as a majority of reports being duplicates) in the FDA Adverse Event Reporting System (FAERS) database because they can escape legacy duplicate detection algorithms routinely deployed on that data source. Literature reference field, added to in 2014, could potentially be utilized to identify replicated reports. FAERS does not enforce adherence to the Vancouver referencing convention, thus the same article may be referenced differently leading to duplication. The objective of this analysis is to determine if variations of the same literature references observed in FAERS can be resolved with text normalization and fuzzy string matching. METHODS: We normalized the literature references recorded in the FAERS database through the first quarter of 2021 with a rule-based algorithm so that they better conform to the Vancouver convention. Levenshtein distance was then utilized to merge sufficiently similar normalized literature references together. RESULTS: Normalization of literature references increases the percentage that can be parsed into author, title, and journal from 61.74% to 93.93%. We observe that about 98% of pairs within groups do have a Levenshtein similarity of the title above the threshold. The extreme duplication ranged from 66% to 87% with a median of 72% of reports being duplicates and often involved addictovigilance scenarios. CONCLUSIONS: We have shown that these normalized references can be merged via fuzzy string matching to improve enumeration of all the individual case safety reports that refer to the same article. Inclusion of the PubMed ID and adherence to the Vancouver convention could facilitate identification of duplicates in the FAERS dataset. Awareness of this phenomenon may improve disproportionality analysis, especially in areas such as addictovigilance.

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models.

BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.

Effect of LSD1 on osteogenic differentiation of human periodontal ligament stem cells in periodontitis.

OBJECTIVE: Periodontitis is a chronic inflammation of periodontal tissues. This study is expected to assess the effect of LSD1 on the osteogenic differentiation of hPDLSCs in periodontitis. METHODS: hPDLSCs were separated, cultivated, and identified, and then treated by LPS to induce inflammatory microenvironment and subjected to osteogenic differentiation. Subsequently, LSD1 expression was determined, and then silenced to assess its effect on hPDLSCs. Next, the binding relation between LSD1 and miR-590-3p was analyzed. miR-590-3p expression was detected and then overexpressed to evaluate its role in hPDLSCs in periodontitis. Afterward, the relation between LSD1 and OSX was analyzed. H3K4me2 level and OSX transcription were measured, and the role of H3K4me2 was determined. Additionally, the role of OSX in hPDLSCs was verified. RESULTS: LSD1 was poorly expressed after osteogenic differentiation of hPDLSCs while it was rescued upon LPS induction. The osteogenic differentiation of hPDLSC in periodontitis was strengthened upon LSD1 downregulation. Besides, miR-590-3p targeted LSD1 transcription, and LSD1 inhibited OSX transcription via H3K4me2 demethylation. miR-590-3p overexpression improved osteogenic differentiation of hPDLSCs in periodontitis. But this improvement was annulled by OSX inhibition. CONCLUSION: miR-590-3p targeted LSD1 transcription and upregulated H3K4me2 methylation to promote OSX transcription, thereby encouraging osteogenic differentiation of hPDLSCs in periodontitis.

Efficacy and safety of postoperative single-dose anticoagulant treatment in preventing venous thromboembolism after revision hip arthroplasty: a retrospective cohort study.

PURPOSE: The purpose of the study is to determine the efficacy and safety of postoperative single-dose anticoagulant treatment in preventing venous thromboembolism (VTE) after revision THA, in comparison with a multiple-dose chemoprophylaxis protocol. METHODS: We retrospectively compared 295 patients undergoing revision THA who received multiple-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once and oral rivaroxaban for 10 days) or single-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once) for VTE. The patients in both groups performed active lower limb exercises. Each group was further stratified into subgroups based on the aetiology of revision. The incidence of VTE, wound complications within three months, hidden blood loss (HBL), transfusion rate, and surgical drainage duration were recorded. RESULTS: The incidence rates of VTE (P = 0.870) did not differ between the two prophylaxis protocols. However, significant differences were observed in wound complications within three months (P = 0.002), HBL (P = 0.015), transfusion rate (P = 0.028). Surgical drainage duration was also shorter in the single-dose chemoprophylaxis group (P = 0.0023). In the subgroup analysis, the use of single-dose chemoprophylaxis protocol cannot significantly reduce HBL and transfusion rate after septic revision THA. The use of multiple-dose chemoprophylaxis protocol (OR = 2.89, P = 0.002) and high BMI (OR = 1.09, P = 0.037) were independent risk factors of wound complications. CONCLUSIONS: Single-dose chemoprophylaxis protocol effectively and safely prevented VTE after revision THA compared with multiple-dose chemoprophylaxis protocol. The effect in reducing HBL and postoperative transfusion rate was limited in septic revision.

Geometrical Bounds on Irreversibility in Squeezed Thermal Bath.

Irreversible entropy production (IEP) plays an important role in quantum thermodynamic processes. Here, we investigate the geometrical bounds of IEP in nonequilibrium thermodynamics by exemplifying a system coupled to a squeezed thermal bath subject to dissipation and dephasing, respectively. We find that the geometrical bounds of the IEP always shift in a contrary way under dissipation and dephasing, where the lower and upper bounds turning to be tighter occur in the situation of dephasing and dissipation, respectively. However, either under dissipation or under dephasing, we may reduce both the critical time of the IEP itself and the critical time of the bounds for reaching an equilibrium by harvesting the benefits of squeezing effects in which the values of the IEP, quantifying the degree of thermodynamic irreversibility, also become smaller. Therefore, due to the nonequilibrium nature of the squeezed thermal bath, the system-bath interaction energy has a prominent impact on the IEP, leading to tightness of its bounds. Our results are not contradictory with the second law of thermodynamics by involving squeezing of the bath as an available resource, which can improve the performance of quantum thermodynamic devices.