Is Lobectomy Actually Worse Than Segmentectomy for All Stage I Non-Small Cell Lung Cancer?

INTRODUCTION: The recent results of the JCOG 0802 and CALGB 140503 studies suggest that segmentectomy should be considered instead of lobectomy for patients with peripheral <2 cm node-negative non-small cell lung cancer (NSCLC). This study aimed to test this hypothesis in a retrospective analysis of a larger dataset of patients with stage I NSCLC recorded in the Surveillance, Epidemiology, and End Results database. METHODS: Patients with all stage I NSCLC (≤4 cm in size) who underwent either segmentectomy or lobectomy from 2000 to 2017 were analyzed. The primary endpoints were overall survival and lung cancer-specific survival, while the secondary endpoints were the 30-day and 90-day mortality. RESULTS: Overall, 32,673 patients treated by lobectomy and 2166 patients treated by segmentectomy were included in the initial data collection. After 1:1 propensity score matching (PSM), 2016 patients in each group were enrolled in the final analysis with well-balanced baseline characteristics. After PSM, there was no difference between segmentectomy and lobectomy for all stage IA NSCLC (≤3 cm in size) in both overall survival and lung cancer-specific survival (hazard ratio: 0.87 [0.74-1.02], P value: 0.09 and hazard ratio: 0.81 [0.4-1.03], P value: 0.09, respectively). Furthermore, lobectomy had higher 30-day mortality than segmentectomy: 1.1% versus 2.1%, P value: 0.01. However, this difference was not significant for 90-day mortality, even after PSM (3.9% versus 3.0%, P value: 0.17). CONCLUSIONS: We found no evidence to support the use of lobectomy rather than segmentectomy in stage IA NSCLC in terms of either overall or lung cancer-specific long-term survival. The choice of lobectomy may also be detrimental to early postoperative recovery.

Prediagnosis recognition of acute ischemic stroke by artificial intelligence from facial images.

Stroke is a major threat to life and health in modern society, especially in the aging population. Stroke may cause sudden death or severe sequela-like hemiplegia. Although computed tomography (CT) and magnetic resonance imaging (MRI) are standard diagnosis methods, and artificial intelligence models have been built based on these images, shortage in medical resources and the time and cost of CT/MRI imaging hamper fast detection, thus increasing the severity of stroke. Here, we developed a convolutional neural network model by integrating four networks, Xception, ResNet50, VGG19, and EfficientNetb1, to recognize stroke based on 2D facial images with a cross-validation area under curve (AUC) of 0.91 within the training set of 185 acute ischemic stroke patients and 551 age- and sex-matched controls, and AUC of 0.82 in an independent data set regardless of age and sex. The model computed stroke probability was quantitatively associated with facial features, various clinical parameters of blood clotting indicators and leukocyte counts, and, more importantly, stroke incidence in the near future. Our real-time facial image artificial intelligence model can be used to rapidly screen and prediagnose stroke before CT scanning, thus meeting the urgent need in emergency clinics, potentially translatable to routine monitoring.

A novel function of claudin-5 in maintaining the structural integrity of the heart and its implications in cardiac pathology.

This study aims to investigate the role of claudin-5 (Cldn5) in cardiac structural integrity. Proteomic analysis was performed to screen the protein profiles in enlarged left atrium from atrial fibrillation (AF) patients. Cldn5 shRNA adeno-associated virus (AAV) or siRNA was injected into the mouse left ventricle or added into HL1 cells respectively to knockdown Cldn5 in cardiomyocytes to observe whether the change of Cldn5 influences cardiac morphology and function, and affects those protein expressions stem from the proteomic analysis. Mitochondrial density and membrane potential were also measured by Mitotracker staining and JC-1 staining under the confocal microscope in HL1 cells. Cldn5 was reduced in cardiomyocytes from the left atrial appendage of AF patients compared to non-AF donors. Proteomic analysis showed 83 proteins were less abundant and 102 proteins were more abundant in AF patients. KEGG pathway analysis showed less abundant CACNA2D2, CACNB2, MYL2 and MAP6 were highly associated with dilated cardiomyopathy. Cldn5 shRNA AAV injection caused severe cardiac atrophy, dilation and myocardial dysfunction in mice. The decreases in mitochondrial numbers and mitochondrial membrane potentials in HL1 cells were observed after Cldn5 knockdown. We demonstrated for the first time the mechanism of Cldn5 downregulation-induced myocyte atrophy and myocardial dysfunction might be associated with the downregulation of CACNA2D2, CACNB2, MYL2 and MAP6, and mitochondrial dysfunction in cardiomyocytes.

Unveiling the Role of Cationic Pyridine Sites in Covalent Triazine Framework for Boosting Zinc-Iodine Batteries Performance.

Rechargeable Zinc-iodine batteries (ZIBs) are gaining attention as energy storage devices due to their high energy density, low-cost, and inherent safety. However, the poor cycling performance of these batteries always arises from the severe leakage and shuttle effect of polyiodides (I3 - and I5 -). Herein, a novel cationic pyridine-rich covalent triazine framework (CCTF-TPMB) is developed to capture and confine iodine (I2) species via strong electrostatic interaction, making it an attractive host for I2 in ZIBs. The as-fabricated ZIBs with I2 loaded CCTF-TPMB (I2@CCTF-TPMB) cathode achieve a large specific capacity of 243 mAh g-1 at 0.2 A g-1 and an exceptionally stable cyclic performance, retaining 93.9% of its capacity over 30 000 cycles at 5 A g-1. The excellent electrochemical performance of the ZIBs can be attributed to the pyridine-rich cationic sites of CCTF-TPMB, which effectively suppress the leakage and shuttle of polyiodides, while also accelerating the conversion reaction of I2 species. Combined in situ Raman and UV-vis analysis, along with theoretical calculations, clearly reveal the critical role played by pyridine-rich cationic sites in boosting the ZIBs performances. This work opens up a promising pathway for designing advanced I2 cathode materials toward next-generation ZIBs and beyond.

Geranylgeranylacetone mitigates sepsis-associated intestinal injury through CHIP-dependent anti-inflammation and anti-oxidative effect.

Geranylgeranylacetone (GGA), an isoprenoid compound widely utilized as an antiulcer agent in Asia, confers protection against ischemia, anoxia, and oxidative stress by rapidly enhancing the expression of HSP70. Nevertheless, the impact of GGA on sepsis-associated intestinal injury remains unexplored. Thus, this study is crafted to elucidate the protective efficacy and underlying mechanisms of GGA against septic intestinal damage. Our findings revealed that GGA significantly extended the survival duration of septic mice, and mitigated lipopolysaccharide (LPS)-induced alterations in intestinal permeability and tissue damage. Furthermore, GGA effectively suppressed LPS-induced cytokine release, attenuated levels of reactive oxygen species (ROS) and malondialdehyde, and bolstered antioxidant-related parameters within the intestinal tissue of LPS-stimulated mice. Mechanistically, GGA significantly increased HSP70 expression and promoted E3 ubiquitin ligase CHIP to play the role in ubiquitination and degradation of karyopherin-α2 (KPNA2), resulting in inhibition of nuclear translocation of NF-κB and reduced NOX1, NOX2 and NOX4 expression. The inhibitory action of GGA on cytokine release and ROS generation was abolished by CHIP knockdown in IEC-6 cells treated with LPS. Simultaneously, the downregulation of CHIP reversed the suppressive role of GGA in the LPS-induced NF-κB activation and the expression of NOX1, NOX2 and NOX4 in IEC-6 cells. The effects of GGA on mitigating intestinal damage, inflammation and oxidative stress caused by LPS were eliminated in CHIP knockout mice. Our results demonstrate that the protective effect of GGA against LPS-caused intestinal injury of mice is dependent on CHIP activation, which promotes KPNA2 degradation and restrains translocation of NF-κB into nucleus, leading to suppressing LPS-induced inflammatory response and oxidative stress.

Tubulin alpha-1b chain was identified as a prognosis and immune biomarker in pan-cancer combing with experimental validation in breast cancer.

The α-tubulin subtype, Tubulin α-1b chain (TUBA1B), has been shown to influence immune cell infiltration, cancer growth, and survival across various malignancies. However, a comprehensive study has not yet been undertaken examining the immunological and predictive effects of TUBA1B in a pan-carcinoma context. Using data from TCGA, GEO, and other databases, we analyzed TUBA1B expression across various carcinoma types using transcriptional profiling, prognostic implications, genetic and epigenetic alterations, methylation patterns, and immunological significance. To validate our findings, we conducted Western blot analysis to assess TUBA1B protein levels in matched breast cancer tissue samples and performed CCK-8 proliferation assay, flow cytometry, transwell invasion, and migration assays to comprehensively examine the functional impact of TUBA1B on breast cancer cells. Our pan-cancer analysis found TUBA1B upregulation across most tumor types, with varying expression patterns in distinct immune and molecular subtypes. High TUBA1B expression was an independent risk factor and associated with poor prognoses in several cancers, including BRCA, KICH, LGG, LUAD, and MESO. TUBA1B also demonstrates moderate to high diagnostic accuracy in most tumor types. Increased m6A methylation levels were observed in the TUBA1B gene, while its promoter region displayed low methylation levels. TUBA1B's expression impacted some cancers by elevating tumor mutation burden, microsatellite instability, neoantigen formation, immune cell infiltration, and the modulation of immune checkpoints. Functional enrichment analysis highlights TUBA1B's involvement in important cellular processes such as the cell cycle, p53 signaling, cell senescence, programmed cell death, and the regulation of immune-related pathways. Moreover, our study reveals higher TUBA1B protein expression in breast cancer tissues compared to adjacent tissues. In vitro experiments confirm that TUBA1B deletion reduces breast cancer cell proliferation, invasion, and migration while increasing apoptosis. In conclusion, our study suggests that TUBA1B could potentially serve as a diagnostic marker for predicting cancer immunological profiles and survival outcomes and shed light on the expression and role of TUBA1B in breast cancer, providing a solid foundation for considering it as a promising therapeutic target for breast cancer patient treatment.

ENDOGENOUS ß 3 -ADRENERGIC RECEPTOR ACTIVATION ALLEVIATES SEPSIS-INDUCED CARDIOMYOCYTE APOPTOSIS VIA PI3K/AKT SIGNALING PATHWAY.

ABSTRACT: ß 3 -adrenergic receptor (ß 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of ß 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of ß 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that ß 3 -AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of ß 3 -AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with ß 3 -AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8, and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-Akt Ser473 and p-eNOS Ser1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of ß 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous ß 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.

YL-109 attenuates sepsis-associated multiple organ injury through inhibiting the ERK/AP-1 axis and pyroptosis by upregulating CHIP.

Sepsis is a severe inflammatory disorder that can lead to life-threatening multiple organ injury. Lipopolysaccharide (LPS)-induced inflammation is the leading cause of multiple organ failure in sepsis. This study aimed to explore the effect of a novel agent, 2-(4-hydroxy-3-methoxyphenyl)-benzothiazole (YL-109), on LPS-induced multiple organ injury and the molecular mechanisms underlying these processes. The results showed that YL-109 protected against LPS-induced high mortality, cardiac dysfunction, pulmonary and intestinal injury through inhibiting the proinflammatory response, NLRP3 expression and pyroptosis-associated indicators in mouse tissues. YL-109 suppressed LPS-initiated cytokine release, pyroptosis and pyroptosis-related protein expression in HL-1, IEC-6 and MLE-12 cells, which was consistent with the results of the in vivo experiments. Mechanistically, YL-109 reduces phosphorylated ERK (extracellular signal-regulated kinase) levels and NF-κB activation, which are achieved through upregulating CHIP (carboxy terminus of Hsc70-interacting protein) expression, thereby inhibiting c-Jun and c-Fos activation as well as NLRP3 expression. As an E3 ligase, CHIP overexpression obviously promoted the degradation of phosphorylated ERK and inhibited the expression of NF-κB-mediated NLRP3 in cells stimulated with LPS. The protective effects of YL-109 against cardiac, pulmonary and intestinal damage, inflammation and pyroptosis caused by LPS were eliminated in CHIP knockout mice. Our results not only reveal the protective effect and molecular mechanism of YL-109 against LPS-mediated organs damage but also provide additional insights into the effect of CHIP on negatively regulating pyroptosis and inflammatory pathways.

Proteome, Lysine Acetylome, and Succinylome Identify Posttranslational Modification of STAT1 as a Novel Drug Target in Silicosis.

Inhalation of crystalline silica dust induces incurable lung damage, silicosis, and pulmonary fibrosis. However, the mechanisms of the lung injury remain poorly understood, with limited therapeutic options aside from lung transplantation. Posttranslational modifications can regulate the function of proteins and play an important role in studying disease mechanisms. To investigate changes in posttranslational modifications of proteins in silicosis, combined quantitative proteome, acetylome, and succinylome analyses were performed with lung tissues from silica-injured and healthy mice using liquid chromatography-mass spectrometry. Combined analysis was applied to the three omics datasets to construct a protein landscape. The acetylation and succinylation of the key transcription factor STAT1 were found to play important roles in the silica-induced pathophysiological changes. Modulating the acetylation level of STAT1 with geranylgeranylacetone effectively inhibited the progression of silicosis. This report revealed a comprehensive landscape of posttranslational modifications in silica-injured mouse and presented a novel therapeutic strategy targeting the posttranslational level for silica-induced lung diseases.

Mechanic evaluation of Wu-Mei-Pill on colitis-associated colorectal cancer: An integrated transcriptomics, metabolomics, and experimental validation study.

BACKGROUND: Chronic intestinal inflammatory diseases play a crucial role in the onset of colorectal cancer (CRC). Effectively impeding the progression of colitis-associated colorectal cancer (CAC) can be instrumental in hindering CRC development. Wu-Mei-Pill (WMP), a formulation comprising various herbal extracts, is clinically employed for CAC treatment, yet the underlying mechanism of WMP's efficacy in CAC remains unclear. Our study firstly demonstrated the effects and mechanisms of WMP on transcriptional and metabolic levels based on integrated transcriptomics and untargeted metabolomics and relative experimental validations. MATERIALS AND METHODS: A CAC mouse model was established through a single injection of azoxymethane (AOM) followed by intermittent dextran sodium sulfate (DSS) intervention, with subsequent WMP administration. Initially, the therapeutic impact of WMP on the CAC model was assessed by observing survival rate, body weight change, colon length, tumor number, tumor load, and pathological changes in the colon tissue of CAC mice post-WMP intervention. Subsequently, differential genes and metabolites in the colorectal tissue of CAC mice following WMP intervention were identified through transcriptomics and non-targeted metabolomics. Finally, the influence of WMP on the peroxisome proliferator activated receptor (PPAR) pathway, Wnt pathway, and CC motif chemokine ligand 3 (CCL3)/ CC motif chemokine receptor 1 (CCR1) axis in CAC mice was verified through western blot, immunofluorescence, and ELISA based on the results of transcriptomics and non-targeted metabolomics. RESULTS: WMP intervention enhanced survival, alleviated body weight loss, shortened colon length, tumor occurrence, and pathological changes in the colorectal tissue of CAC mice, such as glandular damage, tumourigenesis, and inflammatory cell infiltration. Transcriptomic and non-targeted metabolomic results revealed that WMP intervention up-regulated the expression of key regulatory mechanisms of fatty acid oxidation PPAR pathway-related genes (Pparg, Ppara, Cpt1a, and Acadm) and metabolites (L-carnitine and L-palmitoylcarnitine). Additionally, it down-regulated Wnt pathway-related genes (Wnt3, Axin2, Tcf7, Mmp7, Lgr5, Wnt5a, Fzd6, Wnt7b, Lef1, and Fzd10 etc.) and pro-inflammatory related genes (Il1b, Il6, Il17a, Ccl3, and Ccr1 etc.). Experimental validation demonstrated that WMP up-regulated PPAR pathway-related proteins [PPARγ, PPARα, carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA dehydrogenase medium chain (ACADM)] in the colorectal tissue of CAC mice. It also down-regulated Wnt pathway-related proteins [ß-catenin, T-cell factor (TCF), lymphoid enhancer-binding factor (LEF), and matrix metallopeptidase 7 (MMP7)], inhibited the nuclear translocation of the key transcription factor ß-catenin in the Wnt pathway, and suppressed epithelial-to-mesenchymal transition (EMT) activation induced by the Wnt pathway (up-regulated E-cadherin and down-regulated Vimentin). Furthermore, WMP intervention reduced pro-inflammatory factors [interleukin (IL)-6, IL-1ß, and IL-17A] and decreased CCL3/CCR1 axis factors, including CCL3 protein levels and diminished F4/80+CCR1+ positive expressed cells. CONCLUSION: WMP significantly inhibits CAC tumorigenesis by up-regulating PPARα-mediated fatty acid oxidation, inhibiting the Wnt signaling pathway-mediated EMT, and suppressing CCL3/CCR1-mediated inflammatory responses.

Ultrasound-Base Radiomics for Discerning Lymph Node Metastasis in Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: Ultrasound is the imaging modality of choice for preoperative diagnosis of lymph node metastasis (LNM) in thyroid cancer (TC), yet its efficacy remains suboptimal. As radiomics gains traction in tumor diagnosis, its integration with ultrasound for LNM differentiation in TC has emerged, but its diagnostic merit is debated. This study assesses the accuracy of ultrasound-integrated radiomics in preoperatively diagnosing LNM in TC. METHODS: Literatures were searched in PubMed, Embase, Cochrane, and Web of Science until July 11, 2023. Quality of the studies was assessed by the radiomics quality score (RQS). A meta-analysis was executed using a bivariate mixed effects model, with a subgroup analysis based on modeling variables (clinical features, radiomics features, or their combination). RESULTS: Among 27 articles (16,410 TC patients, 6356 with LNM), the average RQS was 16.5 (SD:5.47). Sensitivity of the models based on clinical features, radiomics features, and radiomics features plus clinical features were 0.64, 0.76 and 0.69. Specificities were 0.77, 0.78 and 0.82. SROC values were 0.76, 0.84 and 0.81. CONCLUSION: Ultrasound-based radiomics effectively evaluates LNM in TC preoperatively. Adding clinical features does not notably enhance the model's performance. Some radiomics studies showed high bias, possibly due to the absence of standard application guidelines.

THE ACCURACY OF INTRAORAL SCAN IN OBTAINING DIGITAL IMPRESSIONS OF EDENTULOUS ARCHES: A SYSTEMATIC REVIEW.

OBJECTIVES: Accuracy is a crucial factor when assessing the quality of digital impressions. This systematic review aims to assess the accuracy of intraoral scan (IOS) in obtaining digital impressions of edentulous jaws. METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022382983). A thorough retrieval of 7 electronic databases was undertaken, encompassing MEDLINE (PubMed), Web of Science, EMBASE, Scopus, Cochrane Library, Virtual Health Library, and Open gray, through September 11, 2023. A snowball search was performed by tracing the reference lists of the included studies. The Population, Intervention, Comparison, and Outcome (PICO) question of this systematic review was: "What is the accuracy of intraoral scan in obtaining digital impressions of edentulous arches?" The Modified Methodological Index for Nonrandomized Studies (MINORS) was employed to assess the risk of bias. RESULTS: Among the studies retrieved from databases and manual search, a total of 25 studies were selected for inclusion in this systematic review, including 9 in vivo and 16 in vitro studies. Twenty-one of the included studies utilized the 3D deviation analysis method, while 4 studies employed the linear or angular deviation analysis method. The accuracy results of in vitro studies indicated a trueness range of 20-600 µm and a precision range of 2-700 µm. Results of in vivo studies indicated a trueness range of 40-1380 µm, while the precision results were not reported. CONCLUSION: According to the results of this study, direct digital impressions by IOS cannot replace the conventional impressions of completely edentulous arches in vivo. Edentulous digital impressions by IOS demonstrated poor accuracy in peripheral areas with mobile tissues, such as the soft palate, vestibular sulcus, and sublingual area.

Changes in the transformation of nitrogen and phosphorus under different microbial communities in sewage pipes.

Microbial communities living in different environments can affect the transformation of nitrogen and phosphorus in sewage pipes. Two different environments were simulated to investigate the differences in the transformation of nitrogen and phosphorus under different microbial communities in the pipe. Results showed that the concentration of nitrogen and phosphorus changed greatly in the first 25-33 days and the first 21 days, respectively, and then remained stable. The decrease in amino acid nitrogen (AAN) concentration and the increase in ammonia nitrogen (NH4 + -N) concentration in the sediments were evident in the contrast group. The concentrations of total phosphorus (TP), dissolved total phosphorus (DTP), and dissolved reactive phosphorus (DRP) in the overlying water and interstitial water decreased, and that of TP in the sediment increased. Some microorganisms in the sediments of both groups are related to the transformation of nitrogen and phosphorus, such as Clostridium_sensu_stricto_1, Sporacetigenium, Norank_f__Anaerolineaceae, Norank_f__norank_o__PeM15, and Caldisericum. The relative abundance of these microorganisms was remarkably differed between the two groups, which partly caused the difference in nitrogen and phosphorus transformation among overlying water, interstitial water, and sediment in the two environments. PRACTITIONER POINTS: The concentration of N and P changed greatly in the first 20-30 days. AAN and NH4 + -N in sediments had greater concentration variation in contrast group. In two groups, TP, DTP, and DRP of water decreased, and TP of sediment increased. Microbe related to the transformation of N and P differed between the two groups.

Microbial Inoculation during the Short-Term Composting Process Enhances the Nutritional and Functional Properties of Oyster Mushrooms (Pleurotus ostreatus).

In recent years, short-term composting techniques have been widely applied in oyster mushroom cultivation, but there is still a lack of systematic research on their impact on the nutritional and functional properties of fruiting bodies. In this study, the microbial inoculant Streptomyces thermoviolaceus BUA-FM01 (ST) was applied in the short-term composting process for oyster mushroom cultivation. The agronomic traits, nutritional composition, flavor compounds, and antioxidant activity of fruiting bodies from the first three flushes were evaluated. The results show that microbial inoculation significantly (p < 0.05) reduced the total carbon content and C/N ratio of the composted substrates and, furthermore, increased the total yield of the fruiting bodies. Moreover, microbial inoculation significantly (p < 0.05) increased the crude protein, crude polysaccharide, total amino acid, and essential amino acid contents of the fruiting bodies. The fruiting bodies of the first flush of ST treatment possessed the highest umami amino acid content and equivalent umami concentration value. Furthermore, microbial inoculation significantly (p < 0.05) enhanced the scavenging ability of crude polysaccharides toward free radicals. The results indicate that microbial inoculation has many benefits for the composting cultivating process of oyster mushrooms and good application prospects.

N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment.

The in-situ osmolarity is an important physicochemical factor that regulates cell fate of nucleus pulposus cells (NPCs). Our previous studies demonstrated that reduced N-cadherin (NCDH) expression in nucleus pulposus cells is associated with cellular damage under hyper-osmolarity microenvironment. This study was aimed at exploring the impacts of NCDH on senescence and apoptosis of NPCs, as well as the potential molecular mechanism. By comparing NPCs from patients with lumbar fractures and lumbar disc herniation, we identified a correlation between decreased NCDH expression and increased endoplasmic reticulum stress (ERS), resulting in undesirable cell fate (senescence and apoptosis). After blocking Reactive oxygen species (ROS) or ERS, it was indicated that hyper-osmolarity microenvironment induced ERS was ROS-dependent. Further results demonstrated the correlation in rat NPCs. Upregulation of NCDH expression reduced ROS-dependent ERS, thus limiting undesirable cell fates in vitro. This was further confirmed through the rat tail acupuncture injection model. NCDH overexpression successfully mitigated ERS, preserved extracellular matrix production and alleviating intervertebral disc degeneration in vivo. Together, NCDH can alleviate senescence and apoptosis of NPCs by suppressing ROS-dependent ERS via the ATF4-CHOP signaling axis in the hyper-osmolarity microenvironment, thus highlighting the therapeutic potential of NCDH in combating degenerative disc diseases.

Construction of Integral Decellularized Cartilage Using a Novel Hydrostatic Pressure Bioreactor.

The decellularized extracellular matrix (ECM) of cartilage is a widely used natural bioscaffold for constructing tissue-engineered cartilage due to its good biocompatibility and regeneration properties. However, current decellularization methods for accessing decellularized cartilaginous tissues require multiple steps and a relatively long duration to produce decellularized cartilage. In addition, most decellularization strategies lead to damage of the microstructure and loss of functional components of the cartilaginous matrix. In this study, a novel decellularization strategy based on a hydrostatic pressure (HP) bioreactor was introduced, which aimed to improve the efficiency of producing integral decellularized cartilage pieces by combining physical and chemical decellularization methods in a perfusing manner. Two types of cartilaginous tissues, auricular cartilage (AC) and nucleus pulposus (NP) fibrocartilage, were selected for comparison of the effects of ordinary, positive, and negative HP-based decellularization according to the cell clearance ratio, microstructural changes, ECM components, and mechanical properties. The results indicated that applying positive HP improved the efficiency of producing decellularized AC, but no significant differences in decellularization efficiency were found between the ordinary and negative HP-treated groups. However, compared with the ordinary HP treatment, the application of the positive or negative HP did not affect the efficiency of decellularized NP productions. Moreover, neither positive nor negative HP influenced the preservation of the microstructure and components of the AC matrix. However, applying negative HP disarranged the fibril distribution of the NP matrix and reduced glycosaminoglycans and collagen type II contents, two essential ECM components. In addition, the positive HP was beneficial for maintaining the mechanical properties of decellularized cartilage. The recellularization experiments also verified the good biocompatibility of the decellularized cartilage produced by the present bioreactor-based decellularization method under positive HP. Overall, applying positive HP-based decellularization resulted in a superior effect on the production of close-to-natural scaffolds for cartilage tissue engineering. Impact statement In this study, we successfully constructed a novel hydrostatic pressure (HP) bioreactor and used this equipment to produce decellularized cartilage by combining physical and chemical decellularization methods in a perfusing manner. We found that positive HP-based decellularization could improve the production efficiency of integral decellularized cartilage pieces and promote the maintenance of matrix components and mechanical properties. This new decellularization strategy exhibited a superior effect in the production of close-to-natural scaffolds and positively impacts cartilage tissue engineering.

Localized Oxidation Embellishing Strategy Enables High-Performance Perovskite Solar Cells.

Perovskite solar cell (pero-SC) has attracted extensive studies as a promising photovoltaic technology, wherein the electron extraction and transfer exhibit pivotal effect to the device performance. The planar SnO2 electron transport layer (ETL) has contributed the recent record power conversion efficiency (PCE) of the pero-SCs, yet still suffers from surface defects of SnO2 nanoparticles which brings energy loss and phase instability. Herein, we report a localized oxidation embellishing (LOE) strategy by applying (NH4 )2 CrO4 on the SnO2 ETL. The LOE strategy builds up plentiful nano-heterojunctions of p-Cr2 O3 /n-SnO2 and the nano-heterojunctions compensate the surface defects and realize benign energy alignment, which reduces surface non-radiative recombination and voltage loss of the pero-SCs. Meanwhile, the decrease of lattice mismatch released the lattice distortion and eliminated tensile stress, contributing to better stability of the devices. The pero-SCs based on α-FAPbI3 with the SnO2 ETL treated by the LOE strategy realized a PCE of 25.72 % (certified as 25.41 %), along with eminent stability performance of T90 >700 h. This work provides a brand-new view for defect modification of SnO2 electron transport layer.

Entecavir versus tenofovir for prevention of hepatitis B virus-associated hepatocellular carcinoma after curative resection: study protocol for a randomized, open-label trial.

BACKGROUND: Entecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection. METHODS: This study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery. DISCUSSION: This study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02650271. Registered on January 7, 2016.

Dexmedetomidine post-treatment exacerbates metabolic disturbances in septic cardiomyopathy via α2A-adrenoceptor.

Cardiomyopathy is a common complication and significantly increases the risk of death in septic patients. Our previous study demonstrated that post-treatment with dexmedetomidine (DEX) aggravates septic cardiomyopathy. However, the mechanisms for the side effect of DEX post-treatment on septic cardiomyopathy are not well-defined. Here we employed a cecal ligation and puncture (CLP) model and α2A-adrenoceptor deficient (Adra2a-/-) mice to observe the effects of DEX post-treatment on myocardial metabolic disturbances in sepsis. CLP mice displayed significant cardiac dysfunction, altered mitochondrial dynamics, reduced cardiac lipid and glucose uptake, impaired fatty acid and glucose oxidation, enhanced glycolysis and decreased ATP production in the myocardium, almost all of which were dramatically enhanced by DEX post-treatment in septic mice. In Adra2a-/- mice, DEX post-treatment did not affect cardiac dysfunction and metabolic disruptions in CLP-induced sepsis. Additionally, Adra2a-/- mice exhibited impaired cardiac function, damaged myocardial mitochondrial structures, and disturbed fatty acid metabolism and glucose oxidation. In sum, DEX post-treatment exacerbates metabolic disturbances in septic cardiomyopathy in a α2A-adrenoceptor dependent manner.