Pairwise machine learning-based automatic diagnostic platform utilizing CT images and clinical information for predicting radiotherapy locoregional recurrence in elderly esophageal cancer patients.

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

Shenqi Fuzheng injection hinders non-small cell lung cancer cell growth by regulating the Bax/Bcl-2 signaling pathway.

INTRODUCTION: Lung cancer (LC) is the most common solid tumor and is currently considered the primary cause of cancer-related deaths worldwide. In clinical efficacy studies, it was not difficult to find that the combination of SFI and chemotherapy could improve the general condition of patients, reduce the side effects of chemotherapy drugs, and have a cooperative antitumor effect in NSCLC patients. However, whether SFI can be used as a novel antitumor drug is still unknown. METHODS: First, meta-analysis aimed to explore the efficacy of SFI in NSCLC patients, and SFI was identified by ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS). Cell proliferation, migration, and invasion were explored by Cell Counting Kit-8 (CCK-8), scratch healing, and Transwell assays, respectively. Cell cycle and apoptosis assays were performed by flow cytometry. Transcriptome sequencing analysis was performed in four NSCLC cell lines. Differential expression analysis was used to identify potential targets. Apoptosis-related protein levels were detected by Western blotting assays. The effects of SFI in NSCLC were further investigated by mouse xenografts. RESULTS: SFI could markedly improve the chemotherapy efficacy of NSCLC patients. The main active ingredients include flavonoids and terpenoids, which can effectively exert antitumor effects. SFI could not only inhibit tumor cell proliferation and cell migration/invasion but also regulate the cell cycle and promote tumor cell apoptosis. In NSCLC, SFI could enhance the transcription level of the CHOP gene, thereby upregulating the expression of the proapoptotic proteins Bax and caspase 3, and inhibiting the expression of the antiapoptotic protein Bcl-2. SFI hindered the growth of mouse NSCLC xenografts in vivo. CONCLUSIONS: SFI hindered tumor progression and might promote apoptosis by increasing the expression of Bax, caspase 3 and decreasing the level of Bcl-2 in NSCLC.

Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy.

BACKGROUND: A decreased autophagic capacity of bone marrow mesenchymal stromal cells (BMSCs) has been suggested to be an important cause of decreased osteogenic differentiation. A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis. AIM: To explore the effects of sinomenine (SIN) on the osteogenic differentiation of BMSCs and the underlying mechanisms. METHODS: For in vitro experiments, BMSCs were extracted from sham-treated mice and ovariectomized mice, and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concentrations of SIN and the autophagy inhibitor 3-methyladenine. In vivo, the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur. RESULTS: SIN reduced the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, inhibited mTOR activity, and increased autophagy ability of BMSCs, thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo. CONCLUSION: The Chinese medicine SIN has potential for the treatment of various types of osteoporosis, bone homeostasis disorders, and autophagy-related diseases.

Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination.

Approximately 40% of patients with lung adenocarcinoma (LUAD) often develop bone metastases during the course of their disease. However, scarcely any in vivo model of LUAD bone metastasis has been established, leading to a poor understanding of the mechanisms underlying LUAD bone metastasis. Here, we established a multiorgan metastasis model via the left ventricular injection of luciferase-labeled LUAD cells into nude mice and then screened out lung metastasis (LuM) and bone metastasis (BoM) cell subpopulations. BoM cells exhibited greater stemness and epithelial-mesenchymal transition (EMT) plasticity than LuM cells and initially colonized the bone and subsequently disseminated to distant organs after being reinjected into mice. Moreover, a CD74-ROS1 fusion mutation (C6; R34) was detected in BoM cells but not in LuM cells. Mechanistically, BoM cells bearing the CD74-ROS1 fusion highly secrete the C-C motif chemokine ligand 5 (CCL5) protein by activating STAT3 signaling, recruiting macrophages in tumor microenvironment and strongly inducing M2 polarization of macrophages. BoM cell-activated macrophages produce a high level of TGF-ß1, thereby facilitating EMT and invasion of LUAD cells via TGF-ß/SMAD2/3 signaling. Targeting the CD74-ROS1/CCL5 axis with Crizotinib (a ROS1 inhibitor) and Maraviroc (a CCL5 receptor inhibitor) in vivo strongly impeded bone metastasis and secondary metastasis of BoM cells. Our findings reveal the critical role of the CD74-ROS1/STAT3/CCL5 axis in the interaction between LUAD bone metastasis cells and macrophages for controlling LUAD cell dissemination, highlighting the significance of the bone microenvironment in LUAD bone metastasis and multiorgan secondary metastasis, and suggesting that targeting CD74-ROS1 and CCL5 is a promising therapeutic strategy for LUAD bone metastasis.

Unveiling the rheological and thermal behavior of a novel Salecan and whey protein isolate composite gel.

The burgeoning interest in the versatile hydrogel matrix, with its multifarious applications, has spurred extensive research in recent years. However, the implementation of chemically crosslinked gels on a large-scale has been hindered by their poor biosafety and excessive energy consumption. To address these challenges, this study focuses on harnessing physical methods to engineer novel composite hydrogels utilizing natural polysaccharides Salecan and whey protein isolate, obviating the need for structural modification or chemical crosslinking. The aim was to explore the rheological properties to understand their multiple behaviors. Various models, including Power-Law, Herschel-Bulkley, and Arrhenius, were also employed to compare and analyze rheological parameters. This study holds significance as it is the pioneering report on the hydrogels fabricated from Salecan/Whey protein isolate. These gels possess favorable attributes encompassing optimized elasticity, thermal-stability, enhanced injectability, and self-recovery, rendering them suitable for a multitude of applications in the realms of food and biomedicine.

Using three-dimensional model-based tumour volume change to predict the symptom improvement in patients with renal cell cancer.

In our recent study, we explored the efficacy of three-dimensional (3D) measurement of tumor volume in predicting the improvement of quality of life (QoL) in patients suffering from renal cell cancer (RCC), who were treated with axitinib and anti-PD-L1 antibodies. This study encompassed 18 RCC patients, including 10 men and 8 women, with an average age of 56.83 ± 9.94 years. By utilizing 3D Slicer software, we analyzed pre- and post-treatment CT scans to assess changes in tumor volume. Patients' QoL was evaluated through the FKSI-DRS questionnaire. Our findings revealed that 3D models for all patients were successfully created, and there was a moderate agreement between treatment response classifications based on RECIST 1.1 criteria and volumetric analysis (kappa = 0.556, p = 0.001). Notably, nine patients reported a clinically meaningful improvement in QoL following the treatment. Interestingly, the change in tumor volume as indicated by the 3D model showed a higher area under the curve in predicting QoL improvement compared to the change in diameter measured by CT, although this difference was not statistically significant (z = 0.593, p = 0.553). Furthermore, a multivariable analysis identified the change in tumor volume based on the 3D model as an independent predictor of QoL improvement (odds ratio = 1.073, 95% CI 1.002-1.149, p = 0.045).In conclusion, our study suggests that the change in tumor volume measured by a 3D model may be a more effective predictor of symptom improvement in RCC patients than traditional CT-based diameter measurements. This offers a novel approach for assessing treatment response and patient well-being, presenting a significant advancement in the field of RCC treatment.

Bioinspired Binickel Catalyst for Carbon Dioxide Reduction: The Importance of Metal-ligand Cooperation.

Catalyst design for the efficient CO2 reduction reaction (CO2RR) remains a crucial challenge for the conversion of CO2 to fuels. Natural Ni-Fe carbon monoxide dehydrogenase (NiFe-CODH) achieves reversible conversion of CO2 and CO at nearly thermodynamic equilibrium potential, which provides a template for developing CO2RR catalysts. However, compared with the natural enzyme, most biomimetic synthetic Ni-Fe complexes exhibit negligible CO2RR catalytic activities, which emphasizes the significance of effective bimetallic cooperation for CO2 activation. Enlightened by bimetallic synergy, we herein report a dinickel complex, NiIINiII(bphpp)(AcO)2 (where NiNi(bphpp) is derived from H2bphpp = 2,9-bis(5-tert-butyl-2-hydroxy-3-pyridylphenyl)-1,10-phenanthroline) for electrocatalytic reduction of CO2 to CO, which exhibits a remarkable reactivity approximately 5 times higher than that of the mononuclear Ni catalyst. Electrochemical and computational studies have revealed that the redox-active phenanthroline moiety effectively modulates the electron injection and transfer akin to the [Fe3S4] cluster in NiFe-CODH, and the secondary Ni site facilitates the C-O bond activation and cleavage through electron mediation and Lewis acid characteristics. Our work underscores the significant role of bimetallic cooperation in CO2 reduction catalysis and provides valuable guidance for the rational design of CO2RR catalysts.

Establishment of novel anti-TIM-3 antibodies interfering with its binding to ligands.

The T cell immunoglobulin and mucin-domain containing-3 (TIM-3) receptor has gained significant attention as a promising target for cancer immunotherapy. The inhibitory effect of T cells by TIM-3 is mediated through the interaction between TIM-3 and its ligands. Ligand-blocking anti-TIM-3 antibodies possess the potential to reactivate antigen-specific T cells and augment anti-tumor immunity. However, the precise ligand-receptor interactions disrupted by the administration of TIM-3 blocking Abs have yet to be fully elucidated. In this study, we have developed a panel of monoclonal antibodies targeting human TIM-3, namely MsT001, MsT065, MsT229, and MsT286. They exhibited high sensitivities (10 pg/mL) and affinities (3.70 × 10-9 to 4.61 × 10-11 M) for TIM-3. The TIM-3 antibodies recognized distinct epitopes, including linear epitopes (MsT001 and MsT065), and a conformational epitope (MsT229 and MsT286). Additionally, the MsT229 and MsT286 displayed reactivity towards cynomolgus TIM-3. The interactions between TIM-3/Gal-9, TIM-3/HMGB-1, and TIM-3/CEACAM-1 disrupt the binding of MsT229 and MsT286, while leaving the binding of MsT001 and MsT065 unaffected. The inhibitory effect on the interaction between Gal-9 and TIM-3 was found to be dose-dependently in the presence of either MsT229 or MsT286. The findings suggested that the involvement of conformational epitopes in TIM-3 is crucial for its interaction with ligands, and we successfully generated novel anti-TIM-3 Abs that exhibit inhibitory potential. In conclusion, our finding offers valuable insights -on the comprehension and targeting of human TIM-3.

A Luciferase Imaging-Based Assay for Studying Temperature Compensation of the Circadian Clock.

The pace of circadian rhythms remains relatively unchanged across a physiologically relevant range of temperatures, a phenomenon known as temperature compensation. Temperature compensation is a defining characteristic of circadian rhythms, ensuring that clock-regulated processes occur at approximately the same time of day across a wide range of conditions. Despite the identification of several genes involved in the regulation of temperature compensation, the molecular mechanisms underlying this process are still not well understood. High-throughput assays of circadian period are essential for the investigation of temperature compensation. In this chapter, we present a luciferase imaging-based method that enables robust and accurate examination of temperature compensation in the plant circadian clock.

Sialylation of dietary mucin modulate its digestibility and the gut microbiota of elderly individuals.

Food-derived mucins are glycoproteins rich in sialic acid, but their digestive properties and potential health benefits for humans have been scarcely investigated. In this work, ovomucin (OVM, rich in N-acetylneuraminic acid, about 3 %), porcine small intestinal mucin (PSIM, rich in N-glycolylneuraminic acid, about 1 %), the desialylated OVM (AOVM) and the desialylated PSIM (APSIM) were selected to examine their digestion and their impact on the gut microbiota of elderly individuals. The results shown that, the proportion of low-molecular-weight proteins increased after simulated digestion of these four mucins, with concomitant comparable antioxidant activity observed. Desialylation markedly increased the degradation and digestion rate of mucins. In vitro fecal fermentation was conducted with these mucins using fecal samples from individuals of different age groups: young, low-age and high-age elderly. Fecal fermentation with mucin digestive solution stimulated the production of organic acids in the group with fecal sample of the elderly individuals. Among them, the OVM group demonstrated the most favorable outcomes. The OVM and APSIM groups elevated the relative abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, while diminishing the presence of pathogenic bacteria such as Klebsiella. Conversely, the probiotic effects of AOVM and PSIM were attenuated or even exhibited adverse effects. Hence, mucins originating from different sources and possessing distinct glycosylation patterns exhibit diverse biological functions. Our findings can offer valuable insights for developing a well-balanced and nutritious diet tailored to the elderly population.

P4HA2 activates mTOR via hydroxylation and targeting P4HA2-mTOR inhibits lung adenocarcinoma cell growth.

Mammalian target of rapamycin (mTOR) kinase functions as a central regulator of cell growth and metabolism, and its complexes mTORC1 and mTORC2 phosphorylate distinct substrates. Dysregulation of mTOR signaling is commonly implicated in human diseases, including cancer. Despite three decades of active research in mTOR, much remains to be determined. Here, we demonstrate that prolyl 4-hydroxylase alpha-2 (P4HA2) binds directly to mTOR and hydroxylates one highly conserved proline 2341 (P2341) within a kinase domain of mTOR, thereby activating mTOR kinase and downstream effector proteins (e.g. S6K and AKT). Moreover, the hydroxylation of P2341 strengthens mTOR stability and allows mTOR to accurately recognize its substrates such as S6K and AKT. The growth of lung adenocarcinoma cells overexpressing mTORP2341A is significantly reduced when compared with that of cells overexpressing mTORWT. Interestingly, in vivo cell growth assays show that targeting P4HA2-mTOR significantly suppresses lung adenocarcinoma cell growth. In summary, our study reveals an undiscovered hydroxylation-regulatory mechanism by which P4HA2 directly activates mTOR kinase, providing insights for therapeutically targeting mTOR kinase-driven cancers.

Efficacy of radioactive 125I seed implantation in treating inoperable or refused operation head and neck cancers.

PURPOSE: This study aims to observe the curative effect of radioactive 125I seed implantation in treating inoperable or refused operation head and neck cancer. METHODS: Data from 132 patients with head and neck malignant tumors underwent computed tomography-guided radioactive 125I seed implantation from April 2004 to August 2020 were analyzed retrospectively. The Kaplan-Meier method was used to calculate the local control and survival rates. The logarithmic rank test and the Cox proportional risk model were used for univariate and multivariate analysis, respectively. RESULTS: A total of 132 patients were enrolled. All tumors were confirmed to be malignant through pathological analysis. Herein, we revealed that the seeds were implanted at the primary tumor site (23 cases, representing 17.4%), recurrent (9 cases, representing 6.8%), or metastatic lymph nodes (100 cases, representing 75.8%). Three months after the operation, 96 patients were evaluated as effective, whereas 36 patients were considered ineffective. The median local control time was 16 months; the local rates at 6, 12, 18, and 24 months were observed to be 75%, 47%, 35%, and 22%, respectively. The study reports a median survival period (OS) of 15 months. Additionally, the survival rates at 6, 12, 18, and 24 months were 61%, 42%, 31%, and 27%, respectively. Regarding side effects, skin or mucosal toxicity occurred in 14 patients. Grade I skin toxicity occurred in seven cases (5.3%), grade IV skin toxicity in one case (0.8%), grade I mucosal ulcer in four cases (3.0%), and grade I dry mouth in four cases (3.0%). The multivariate analysis showed that short-term efficacy and tumor site were independent prognostic factors (P < 0.001, 0.006, respectively). Additionally, the multivariate analysis showed that the independent OS influencing factors included D90, the longest tumor diameter, and short-term efficacy (P = 0.017, 0.001, <0.001). CONCLUSION: Radioactive 125I seed implantation is a safe and effective salvage therapy for patients with inoperable or refused operation head and neck cancer.

An adaptive detection model for IPv6 extension header threats based on deterministic decision automaton.

The IPv6 extension header mechanism, a new feature of the IPv6 protocol, enhances flexibility and scalability but introduces numerous security threats like firewall evasion and covert channels. Existing threat detection methods face limitations in detection types, universality, and speed. Hence, an adaptive detection model for IPv6 extension header threats (ADM-DDA6) is proposed. Firstly, standard rule sets are designed for common IPv6 extension headers, successfully detecting 70 types of threats from THC-IPv6 and ExtHdr tools using only 20 rules. Secondly, by parsing IPv6 extension headers, matching rules, establishing transition relationships, and deciding packet threat status based on final states (Normal or Abnormal), complex threats like header disorder and header repetition can be detected. Finally, an adaptive rule matching method is introduced, which dynamically selects rule sets based on IPv6 extension header types, effectively reducing rule matching time. Experimental results show that under different threat magnitudes, ADM-DDA6 is 32% faster than Suricata v6.0.12 and 21.2% faster than Snort v3.1.61.0 in detection speed. Additionally, as the number of threats increases, on commodity hardware, ADM-DDA6 incurs only a 0.7% increase in CPU overhead with no significant memory consumption increase, maintains maximum throughput, and exhibits minor performance changes under low and moderate network load conditions.

Case report: Highly response to low-dose brachytherapy in recurrent retroperitoneal leiomyosarcoma with FANCD2 frameshift mutation: a unique case study.

We report a case of recurrent retroperitoneal leiomyosarcoma in a male who achieved a rapid and robust but transient clinical response to low-dose iodine-125 brachytherapy. A FANCD2 frameshift mutation was detected by gene sequencing in the cancerous tissue.

BIG enhances Arg/N-degron pathway-mediated protein degradation to regulate Arabidopsis hypoxia responses and suberin deposition.

BIG/DARK OVEREXPRESSION OF CAB1/TRANSPORT INHIBITOR RESPONSE3 is a 0.5-MDa protein associated with multiple functions in Arabidopsis (Arabidopsis thaliana) signalling and development. However, the biochemical functions of BIG are unknown. We investigated a role for BIG in the Arg/N-degron pathways, in which substrate protein fate is influenced by the N-terminal (Nt) residue. We crossed a big loss-of-function allele to two N-degron pathway E3 ligase mutants, proteolysis6 (prt6) and prt1, and examined the stability of protein substrates. Stability of model substrates was enhanced in prt6-1 big-2 and prt1-1 big-2 relative to the respective single mutants and the abundance of the PRT6 physiological substrates, HYPOXIA-RESPONSIVE ERF2 (HRE2) and VERNALIZATION2 (VRN2) was similarly increased in prt6 big double mutants. Hypoxia marker expression was enhanced in prt6 big double mutants; this constitutive response required arginyltransferase activity and RAP-type ERFVII transcription factors. Transcriptomic analysis of roots not only demonstrated increased expression of multiple hypoxia-responsive genes in the double mutant relative to prt6, but also revealed other roles for PRT6 and BIG, including regulation of suberin deposition through both ERFVII-dependent and independent mechanisms, respectively. Our results show that BIG acts together with PRT6 to regulate the hypoxia response and broader processes in Arabidopsis.

T-cell subsets and cytokines are indicative of neoadjuvant chemoimmunotherapy responses in NSCLC.

PURPOSE: Neoadjuvant PD-1 blockade combined with chemotherapy is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet the immunological mechanisms contributing to tumor regression and biomarkers corresponding to different pathological responses remain unclear. METHODS: Using dynamic and paired blood samples from NSCLC patients receiving neoadjuvant chemoimmunotherapy, we analyzed the frequencies of CD8 + T-cell and Treg subsets and their dynamic changes during neoadjuvant treatment through flow cytometry. Cytokine profiles and function-related gene expression of CD8 + T cells and Tregs were analyzed through flow cytometry and mRNA-seq. Infiltrating T-cell subsets in resected tissues from patients with different pathological responses were analyzed through multiplex immunofluorescence. RESULTS: Forty-two NSCLC patients receiving neoadjuvant chemoimmunotherapy were enrolled and then underwent surgical resection and pathological evaluation. Nineteen patients had pCR (45%), 7 patients had MPR (17%), and 16 patients had non-MPR (38%). In patients with pCR, the frequencies of CD137 + CD8 + T cells (P = 0.0475), PD-1 + Ki-67 + CD8 + T cells (P = 0.0261) and Tregs (P = 0.0317) were significantly different from those of non-pCR patients before treatment. pCR patients usually had low frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs, and their AUCs were higher than that of tissue PD-L1 expression. Neoadjuvant chemoimmunotherapy markedly improved CD8 + T-cell proliferation and activation, especially in pCR patients, as the frequencies of CD137 + CD8 + (P = 0.0136) and Ki-67 + CD8 + (P = 0.0391) T cells were significantly increased. The blood levels of cytokines such as IL-2 (P = 0.0391) and CXCL10 (P = 0.0195) were also significantly increased in the pCR group, which is consistent with the high density of activated cytotoxic T cells at the tumor site (P < 0.0001). CONCLUSION: Neoadjuvant chemoimmunotherapy drives CD8 + T cells toward a proliferative and active profile. The frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs at baseline might predict the response to neoadjuvant chemoimmunotherapy in NSCLC patients. The increase in IL-2 and CXCL10 might reflect the chemotaxis and enrichment of cytotoxic T cells at the tumor site and a better response to neoadjuvant chemoimmunotherapy.

Long-cycling and High-voltage Solid State Lithium Metal Batteries Enabled by Fluorinated and Crosslinked Polyether Electrolytes.

Solid-state lithium metal batteries (LMBs), constructed through the in situ fabrication of polymer electrolytes, are considered a critical strategy for the next-generation battery systems with high energy density and enhanced safety. However, the constrained oxidation stability of polymers, such as the extensively utilized polyethers, limits their applications in high-voltage batteries and further energy density improvements. Herein, an in situ fabricated fluorinated and crosslinked polyether-based gel polymer electrolyte, FGPE, is presented, exhibiting a high oxidation potential (5.1 V). The fluorinated polyether significantly improves compatibility with both lithium metal and high-voltage cathode, attributed to the electron-withdrawing -CF3 group and the generated LiF-rich electrolyte/electrode interphase. Consequently, the solid-state Li||LiNi0.6Co0.2Mn0.2O2 batteries employing FGPE demonstrate exceptional cycling performances of 1000 cycles with 78 % retention, representing one of the best results ever reported for polymer electrolytes. Moreover, FGPE enables batteries to operate at 4.7 V, realizing the highest operating voltage of polyether-based batteries to date. Notably, our designed in situ FGPE provides the solid-state batteries with exceptional cycling stability even at practical conditions, including high cathode loading (21 mg cm-2) and industry-level 18650-type cylindrical cells (1.3 Ah, 500 cycles). This work provides critical insights into the development of oxidation-stable polymer electrolytes and the advancement of practical high-voltage LMBs.

Solid-State Emissive meso-Aryl/Alkyl-Substituted and Heteroatom-Mixed BOPPY Dyes: Syntheses, Structures, Physicochemical, Redox Properties, and Computational Analysis.

A series of solid-state emissive meso-aryl/alkyl-substituted and heteroatom-mixed bisBF2-anchoring fluorophore incorporating pyrrolyl-pyridylhydrazone (BOPPY) dyes have been developed by a one-pot condensation of ketonized or formylated pyrroles and 2-heterocyclohydrazine as well as the subsequent borylation coordination. Interestingly, the BOPPY dyes with meso-alkyl-substituted groups or oxygen-substituted pyridine moieties exhibit high fluorescence quantum yields (QYs) of up to 79%, the highest solid QY of 74%, and long lifetimes independent of polarity in the available BOPPYs. On the other hand, the BOPPYs with meso-aryl or N-substituted moieties display a high solution QY of up to 93% and slight emission wavelength maxima. However, the S-substituted BOPPY dye exhibited weak fluorescence in all studied solvents, which was attributed to the structural flexibility of the N-C-S bond and different from those BOPPYs with O or N substitution, indicated by quantum calculations. And the significant excited-state structural rearrangement in a polar solvent is further confirmed by femtosecond time-resolved transient absorption spectroscopy. More importantly, those novel and barely fluorescent BOPPYs in acetonitrile show advantageous aggregation-induced enhanced emission and viscosity-dependent activities. These advancements in the photophysical and electrochemical properties of BOPPY dyes offer valuable insights into their further development and potential applications.

DNM3OS/miR-127-5p/CDH11, activates Wnt3a/ß-catenin/LEF-1 pathway to form a positive feedback and aggravate spine facet joint osteoarthritis.

Spinal facet joint osteoarthritis (FJOA) is an OA disease with pathogenesis and progression uncovered. Our present study was performed to elucidate the role of DNM3OS on spinal FJOA. In this study, spine facet joint tissue of patients were collected. In vitro and in vivo models were constructed with SW1353 cells and rats. Hematoxylin and eosin (HE) staining, Safranin O-fast Green, Alcian blue staining, and Tolueine blue O (TBO) staining were employed for histology analyses. Quantitative PCR, western blotting, and Immunofluorescence were performed to evaluate the expression of genes. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay analysis. Cell Counting Kit-8 and flow cytometry were used for cell activity and apoptosis evaluation. The targeting sites between microRNA (miR)-127-5p and cadherin 11 (CDH11) were predicted TargetScan and miRbase database and confirmed by Dual-luciferase reporter assays. CHIP and EMS assay were employed to confirm the binding of LEF1and DNM3OS promoter. Our results showed that DNM3OS was found to upregulated, while miR-127-5p was downregulated in severe FJOA patients and inflammation-induced chondrosarcoma SW1353 cells. DNM3OS reduced cell activity, induced cell apoptosis and extracellular matrix (ECM) degradation by sponging miR-127-5p in vitro. miR-127-5p targeted CDH11 and inhibited wnt3a/ß-catenin pathway to regulate OA in vitro. LEF1 promoted DNM3OS transcription to form a positively feedback in activated wnt3a/ß-catenin pathway. In vivo rat model also confirmed that DNM3OS aggravated FJOA. In summary, DNM3OS/miR-127-5p/CDH11 enhanced Wnt3a/ß-Catenin/LEF-1 pathway to form a positive feedback and aggravate spinal FJOA.

Effects of exercise therapy on anxiety and depression in patients with COVID-19: a systematic review and meta-analysis.

Objective: With increasing rates of anxiety and depression during COVID-19, exercise treatment has drawn attention for its effects on COVID-19 patients with anxiety and depression. This study set out to assess the impact of exercise therapy on COVID-19 patients' anxiety and depression. Methods: PubMed, EMBASE, Web of Science and Cochrane Library were used to search articles about exercise therapy as a means of treating anxiety and depression in COVID-19 patients from inception to April 30, 2023. The risk of bias was assessed by the Cochrane Collaboration bias risk tool. Data were pooled with the random effects model. RevMan version 5.4 was used for the statistical analyses. This work was registered in the PROSPERO database (registration number: CRD42023406439). Selection criteria: Randomized clinical trials (RCTs) of COVID-19 patients with anxiety and depression were included to assess the impact of physical exercise on COVID-19 patients with anxiety and depression. Results: 6 studies including a total of 461 COVID-19 patients were analyzed in this meta-analysis. Overall, the meta-analysis showed that compared with the control group, exercise could significantly improve anxiety (SMD = -0.76; 95%CI: -0.96, -0.55; p < 0.00001), depression level (SMD = -0.39; 95%CI: -0.70, -0.09; p = 0.01), the PHQ-9 score (MD = -1.82; 95%CI: -2.93, -0.71; p = 0.001) and the sleep quality (SMD = -0.73; 95%CI: -1.32, -0.14; p = 0.01) in COVID-19 patients. Conclusion: The research provided evidence that exercise therapy is able to help COVID-19 patients experience less anxiety and depression and have better-quality sleep. Systematic review registration: CRD42023406439.