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Thyroid cancer is a very common form of endocrine system malignancy. To date, the molecular mechanism underlying thyroid cancer remains poorly understood. Studies of oncocytic tumors have led to a hypothesis which proposes that defects in oxidative phosphorylation (OX- PHOS) may result in a compensatory increase in mitochondrial replication and gene expression. As a result, mitochondrial DNA (mtDNA) mutation analysis has become a useful tool to explore the molecular basis of this disease. Among these mutations, mitochondrial transfer RNAs (mttRNAs) are the hot spots for pathogenic mutations associated with thyroid cancer. However, due to its high mutation rate, the role of mt-tRNA variants in thyroid cancer is still controversial. To address this problem, in this study, we reassessed seven reported mt-tRNA variants: tRNAAsp G7521A, tRNAArg T10411C and T10463C, tRNALeu(CUN) A12308G, tRNAIle G4292C and C4312T, and tRNAAla T5655C, in clinical manifestations of thyroid cancer. We first performed the phylogenetic conservation analysis for these variants; moreover, we used a bioinformatic tool to compare the minimum free energy (G) of mt-tRNA with and without mutations. Most strikingly, none of these variants caused the significant change of the G between the wild-type and the mutant form, suggesting that they may not play an important roles in thyroid cancer. In addition, we screened the frequency of the “pathogenic” A12308G alternation in 300 patients with thyroid cancer and 200 healthy controls. We found that there were five patients and three control subjects carrying this variant. It seemed that the A12308G variant may be a common polymorphism in the human population. Taken together, our study indicated that variants in mt-tRNA genes may not play active roles in patients with thyroid cancer.

Importance: Immune checkpoint inhibitors (ICIs) are recognized as revolutionary cancer therapies but have raised concerns about immune-related adverse events, including the development of autoimmune diseases., Objective: To evaluate the psoriasis risk associated with the use of ICIs in patients with cancer., Design, Setting, and Participants: This nationwide cohort study with a target trial emulation design used data from the Taiwan National Health Insurance database and the Taiwan Cancer Registry. The participants included were patients who received antineoplastic medications for cancer at stages III and IV between January 1, 2019, and June 30, 2021. Data were analyzed from May 2023 to July 2024., Exposures: Patients treated with ICIs were classified as ICI users, while those who received chemotherapy or targeted therapies were categorized as non-ICI users., Main Outcome and Measures: The primary outcome was the incidence of psoriasis during the follow-up period. Stabilized inverse probability of treatment weighting (IPTW) was used to mitigate potential confounders. Cox and Fine-Gray hazard models were used to calculate hazard ratios (HRs) for psoriasis risk between groups., Results: Of 135 230 patients who received antineoplastic medications (mean [SD] age, 62.94 [13.01] years; 45.1% female), 3188 patients were eligible for the ICI user group, while 132 042 patients were eligible for the non-ICI user group. ICI users experienced a higher incidence of psoriasis at 5.76 cases per 1000 person-years, compared to 1.44 cases in the non-ICI group. After adjusting for demographics and comorbidities, ICI users were found to have a 2-fold increase in the risk of developing psoriasis (IPTW-adjusted HR, 3.31; IPTW-adjusted subdistribution HR, 2.43). Both as-started design and on-treatment design showed consistent findings, and the results were consistent and robust across all follow-up intervals and all sensitivity analyses., Conclusions and Relevance: In this cohort study, patients with cancer treated with ICIs faced an increased risk of psoriasis. Medical professionals should be aware of the potential adverse effects of immunotherapy to ensure optimal cancer care.

In layered Li-rich materials, over stoichiometric Li forms an ordered occupation of LiTM 6 in transition metal (TM) layer, showing a honeycomb superstructure along [001] direction. At the atomic scale, the instability of the superstructure at high voltage is the root cause of problems such as capacity/voltage decay of Li-rich materials. Here a Li-rich material with a high Li/Ni disorder is reported, these interlayer Ni atoms locate above the honeycomb superstructure and share adjacent O coordination with honeycomb TM. These Ni─O bonds act as cable-stayed bridge to the honeycomb plane, and improve the high-voltage stability. The cable-stayed honeycomb superstructure is confirmed by in situ X-ray diffraction to have a unique cell evolution mechanism that it can alleviate interlaminar lattice strain by promoting in-plane expansion along a-axis and inhibiting c-axis stretching. Electrochemical tests also demonstrate significantly improved long cycle performance after 500 cycles (86% for Li-rich/Li half cell and 82% for Li-rich/Si-C full cell) and reduced irreversible oxygen release. This work proves the feasibility of achieving outstanding stability of lithium-rich materials through superstructure regulation and provides new insights for the development of the next-generation high-energy-density cathodes., (© 2024 Wiley‐VCH GmbH.)

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39 + Foxp3 + CD4 + regulatory T cells (CD39 + T-regs) and exhausted-like CD8 + T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39 + T-regs and CD39 + PD-1 + CD8 + T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease that is substantially associated with obesity-induced chronic inflammation. Macrophage activation and macrophage-medicated inflammation play crucial roles in the development and progression of NAFLD. Furthermore, fibroblast growth factor receptor 1 (FGFR1) has been shown to be essentially involved in macrophage activation. This study investigated the role of FGFR1 in the NAFLD pathogenesis and indicated that a high-fat diet (HFD) increased p-FGFR1 levels in the mouse liver, which is associated with increased macrophage infiltration. In addition, macrophage-specific FGFR1 knockout or administration of FGFR1 inhibitor markedly protected the liver from HFD-induced lipid accumulation, fibrosis, and inflammatory responses. The mechanistic study showed that macrophage-specific FGFR1 knockout alleviated HFD-induced liver inflammation by suppressing the activation of MAPKs and TNF signaling pathways and reduced fat deposition in hepatocytes, thereby inhibiting the activation of hepatic stellate cells. In conclusion, the results of this research revealed that FGFR1 could protect the liver of HFD-fed mice by inhibiting MAPKs/TNF-mediated inflammatory responses in macrophages. Therefore, FGFR1 can be employed as a target to prevent the development and progression of NAFLD., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC-apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA)., Methods: Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation., Results: The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators., Conclusion: PYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) is widely recognized as a globally prevalent malignancy. Immunotherapy is a promising therapy for HCC patients. Increasing evidence suggests that lncRNAs are involved in HCC progression and immunotherapy., Aim: The study reveals the mechanistic role of long non-coding RNA (lncRNA) FOXD1-AS1 in regulating migration, invasion, circulating tumor cells (CTCs), epithelial-mesenchymal transition (EMT), and immune escape in HCC in vitro., Methods: This study employed real-time PCR (RT-qPCR) to measure FOXD1-AS1, miR-615-3p, and programmed death-ligand 1 (PD-L1). The interactions of FOXD1-AS1, miR-615-3p, and PD-L1 were validated via dual-luciferase reporter gene and ribonucleoprotein immunoprecipitation (RIP) assay. In vivo experimentation involves BALB/c mice and BALB/c nude mice to investigate the impact of HCC metastasis., Results: The upregulation of lncRNA FOXD1-AS1 in malignant tissues significantly correlates with poor prognosis. The investigation was implemented on the impact of lncRNA FOXD1-AS1 on the migratory, invasive, and EMT of HCC cells. It has been observed that the lncRNA FOXD1-AS1 significantly influences the generation and metastasis of M CTC in vivo analysis. In mechanistic analysis, lncRNA FOXD1-AS1 enhanced immune escape in HCC via upregulation of PD-L1, which acted as a ceRNA by sequestering miR-615-3p. Additionally, lncRNA FOXD1-AS1 was found to modulate the EMT of CTCs through the activation of the PI3K/AKT pathway., Conclusion: This study presents compelling evidence supporting the role of lncRNA FOXD1-AS1 as a miRNA sponge that sequesters miR-655-3p and protects PD-L1 from suppression., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: To assess the overall effectiveness of non-pharmacological interventions on internet addiction (IA) in youth., Method: Randomized controlled trials (RCTs) published from their inception to April 1, 2023 were searched in Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese BioMedical Literature Database, and WanFang Data. Two reviewers independently extracted data and evaluated bias using the Cochrane Risk of Bias tool., Results: Sixty-six studies performed from 2007 to 2023, with a total of 4,385 participants, were identified. The NPIs included group counseling, cognitive behavioral therapy, sports intervention, combined interventions, eHealth, educational intervention, positive psychology intervention, sand play intervention, and electrotherapy. The results revealed that NPIs significantly reduced IA levels (standardized mean difference, SMD: -2.01, 95% confidence interval, CI: -2.29 to -1.73, I 2 = 93.0%), anxiety levels (SMD: -1.07, 95%CI: -1.41 to -0.73, I 2 = 72.4%), depression levels (SMD: -1.11, 95%CI: -1.52 to -0.7, I 2 = 84.3%), and SCL-90 (SMD: -0.75, 95%CI: -0.97 to -0.54, I 2 = 27.7%). Subgroup analysis stratified by intervention measure showed that cognitive behavioral therapy, group counseling, sports intervention, combined intervention, educational intervention, positive psychology intervention, sandplay intervention, and mobile health were all effective in relieving symptoms of IA except electrotherapy., Conclusion: NPIs appear to be effective in the treatment of IA in youth, which would act as an alternative treatment of IA. Further studies with larger sample sizes and robust designs are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Liu, Qin, Wang, He and Chen.)

In this study, platinum (Pt) and tungsten (W), two materials with dissimilar coefficients of thermal expansion (CTE) and work functions (WF), are used as the top electrode (TE) and the bottom electrode (BE) in metal/ferroelectric/metal (MFM) structures to explore the ferroelectricity of hafnium zirconium oxide (HZO) with a thickness less than 10 nm. The electrical measurements indicate that a higher CTE mismatch between HZO and TE/BE is beneficial for enhancing the ferroelectric properties of nanoscale HZO thin films. The different WFs of TE and BE generate a built-in electric field in the HZO layer, leading to shifts in the hysteresis loops and the capacitance-voltage characteristics. The structural characterizations reveal that the preferred formation of the orthorhombic phase in HZO is dominated by the W BE. The device in which W is used as the TE and BE (the W/HZO/W MFM structure) presents the optimal ferroelectric performance of a high remanent polarization (2 P r = 55.2 μ C cm -2 ). The presence of tungsten oxide (WO x ) at the W/HZO interfaces, as revealed by high-resolution transmission microscopy, is also responsible for the enhancement of ferroelectric properties. This study demonstrates the significant effects of different CTEs and WFs of TE and BE on the properties of ferroelectric HZO thin films., (© 2023 IOP Publishing Ltd.)

Atomic layer engineering is investigated to tailor the morphotropic phase boundary (MPB) between antiferroelectric, ferroelectric, and paraelectric phases. By increasing the HfO 2 seeding layer with only 2 monolayers, the overlying ZrO 2 layer experiences the dramatic phase transition across the MPB. Conspicuous ferroelectric properties including record-high remanent polarization (2P r ≈ 60 µC cm -2 ), wake-up-free operation, and high compatibility with advanced semiconductor technology nodes, are achieved in the sub-6 nm thin film. The prominent antiferroelectric to ferroelectric phase transformation is ascribed to the in-plane tensile stress introduced into ZrO 2 by the HfO 2 seeding layer. Based on the high-resolution and high-contrast images of surface grains extracted precisely by helium ion microscopy, the evolution of the MPB between tetragonal, orthorhombic, and monoclinic phases with grain size is demonstrated for the first time. The result indicates that a decrease in the average grain size drives the crystallization from the tetragonal to polar orthorhombic phases., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objective: This study aimed to examine the potential benefits of Thoracic Paravertebral Nerve Block (TPVB) coupled with Laryngeal Mask Airway (LMA) and the maintenance of spontaneous breathing anesthesia, in contrast to general anesthesia utilizing double-lumen endobronchial intubation, on promoting recovery following thoracoscopic surgery., Patients and Methods: A randomized controlled trial was carried out involving sixty patients set for Video-Assisted Thoracoscopic Surgery (VATS) at the Affiliated People's Hospital of Jiangsu University from February 2021 to January 2022. Patients were randomized to either the TPVB and LMA with spontaneous breathing anesthesia group (non-intubation group, NI group) or the general anesthesia with double-lumen endobronchial intubation group (Intubation group, I group). The primary outcome measured was the duration of hospitalization. Secondary outcomes included early postoperative rehabilitation indicators, postoperative complications, Visual Analogue Score (VAS), and inflammatory response markers., Results: Patients in the NI group experienced significantly shorter hospital stays than those in the I group (p < 0.05). Early postoperative recovery, assessed by metrics including the first exhaust time, food intake time, first ambulation time, and duration of chest-tube placement, was superior in the NI group (p < 0.05). Postoperative complications such as nausea and vomiting, pulmonary infection, atelectasis, sore throat, and hoarseness, along with cortisol and C-reactive protein (CRP) levels at the end of the operation and 24 h post-operation, and VAS values within the first 12 h post-operation, were significantly lower in the NI group (p < 0.05). However, blood loss, operation time, and VAS values at 24 h and 48 h post-surgery showed no significant differences between the two groups., Conclusions: Our findings suggest that TPVB, in conjunction with LMA and spontaneous breathing anesthesia, may expedite postoperative recovery in patients undergoing VATS.

We report the feasibility of using gelatin hydrogel networks as the host for the in situ, environmentally friendly formation of well-dispersed zinc oxide nanoparticles (ZnONPs) and the evaluation of the antibacterial activity of the as-prepared composite hydrogels. The resulting composite hydrogels displayed remarkable biocompatibility and antibacterial activity as compared to those in previous studies, primarily attributed to the uniform distribution of the ZnONPs with sizes smaller than 15 nm within the hydrogel network. In addition, the composite hydrogels exhibited better thermal stability and mechanical properties as well as lower swelling ratios compared to the unloaded counterpart, which could be attributed to the non-covalent interactions between the in situ formed ZnONPs and polypeptide chains. The presence of ZnONPs contributed to the disruption of bacterial cell membranes, the alteration of DNA molecules, and the subsequent release of reactive oxygen species within the bacterial cells. This chain of events culminated in bacterial cell lysis and DNA fragmentation. This research underscores the potential benefits of incorporating antibacterial agents into hydrogels and highlights the significance of preparing antimicrobial agents within gel networks.

The 1,2-iminylalkylation of diazenes using alkyl iodides in combination with an O -benzoyl oxime is reported. In this transformation, O -benzoyl oxime acted as a radical precursor and XAT mediator. In addition to common alkyl iodides, other alkyl iodides such as iodomethane, iodomethane- d 3 , trifluoroiodomethane, ethyl difluoroiodoacetate, and iodoalkanes containing unprotected hydroxyl and amide groups can also serve as C-radical precursors in the 1,2-iminylalkylation with electrophilic diazenes as radical acceptors.

In this study, a metal-free difunctionalization strategy for diazenes was developed using a range of bifunctionalization reagents. This strategy involves a unique N(sp 3 )-N(sp 2 ) radical coupling between the hydrazine radical and the imine radical. More than 30 triazane core motifs were constructed by installing imines and various functional groups, including alkyl, phenyl, cyanoalkyl, and sulfonyl groups, on both ends of the nitrogen-nitrogen bond of diazenes in an efficient manner.

In this study, we developed a strategy using commercially available alkyl iodides and O -benzoyl oxime to efficiently introduce alkyl and iminyl groups via energy transfer and halogen-atom transfer processes. We performed three-component 1,2-carboimination of olefins and four-component 1,4-carboimination across olefins and alkynes, resulting in the synthesis of over 60 nitrogen-containing molecules. Moreover, this transformation enables the synthesis of molecules with sensitive groups that were previously difficult to achieve.

The effects of far infrared radiation drying (FID) on physical properties (drying kinetics, color, shrinkage ratio, rehydration ratio, and microstructural characterization) and volatile odor characteristics (volatile odor profile distinction and volatile compounds) of shiitake mushrooms were evaluated in this study. During the FID, the drying time decreased with the increase in drying temperature, and it had a less significant effect in the lower temperature range. The increase in drying temperature led to increasing shrinkage and collapse in the microstructure, resulting in a decreased rehydration rate and highlighting the influence of microstructure characteristics on macroscopic properties. Higher drying temperatures employed in the FID process were found to be associated with a decreasing L * value and an increasing Δ E value. The application of principal component analysis can effectively distinguish the significant effect of FID on the volatile odor profiles of shiitake mushrooms. Compared to raw shiitake mushrooms, FID treatment has endowed samples with a greater variety of volatile compounds. After processing with FID, there have been increases in volatile components such as sulfur compounds, acids, nitrogen compounds, and aldehydes, while volatile components like alcohols, ketones, and hydrocarbons have shown decreases.

Objective: To investigate the potential mechanism of treating varicocele-associated male infertility with Jujing pill using network pharmacology and molecular docking technology., Methods: The TCMSP and BATMAN databases were used to search for the Chinese medicine components of the Jujing pill and obtain the corresponding targets. The databases GeneCards, DISGENET, OMIM, and HPO were searched for 'varicocele' and 'male infertility' to identify the potential targets of varicocele-associated male infertility. Wayne diagrams were drawn using the jvenn tool to determine the intersection targets of the Chinese medicine targets and disease targets. The intersecting targets were further analyzed to identify the components and Chinese medicine corresponding to them. A Chinese medicine-active ingredient-target network map was constructed in Cytoscape 3.8.2. The protein-protein interaction (PPI) network of the intersecting targets was constructed using the STRING platform. The intersecting targets were imported into the DAVID database for GO enrichment analysis and KEGG-based pathway enrichment analysis. The KEGG database was used to select the most relevant pathway to the topic, and a KEGG pathway map was constructed using the mapper tool. The top 15 pathways with FDR values and their related targets and components were used to draw a core ingredient-target-pathway map. Finally, molecular docking was performed to verify the protein receptors and small molecule ligands of the core genes, and the results were visualized using AutoDock and PyMol software., Results: A total of 207 ingredients and 1103 predicted targets of Jujing pill were screened. Additionally, 285 targets of varicocele were also identified. By using a Venn diagram, 86 common targets were obtained. The analysis of Gene Ontology (GO) results revealed significant enrichment in various biological processes (BP) such as positive regulation of gene expression, positive regulation of transcription, positive and negative regulation of apoptotic processes, response to hypoxia, response to estradiol, and positive regulation of nitric oxide biosynthesis processes. Furthermore, significant enrichment in cellular components (CC) was observed in macromolecules, cytoplasm, nucleus, and phosphatidylinositol 3-kinase complex. In terms of molecular function (MF), enrichment was found in enzyme binding, identical protein binding, transcriptional co-activator binding, and others. KEGG analysis demonstrated enrichment in pathways related to cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, FoxO signaling pathway, and more. Molecular docking results indicated that the core ingredients exhibited a strong binding capacity with the key targets. Conclusion： The effective active ingredients of Jujing pill exert their therapeutic effects on varicocele-associated male infertility through multiple targets and pathways. These findings provide a theoretical basis for future cell and animal experiments to verify the mechanism of action of Jujing pill in treating varicocele-associated male infertility.

Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I 2  = 0%) were cured, and 82% (95% CI 70-90%, I 2  = 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I 2  = 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions., (© 2023. The Author(s).)

Background: The World Health Organization (WHO) has proposed healthy aging framework, supposing that intrinsic capacity (IC), environment and their interaction may have influence on functional ability (FA). It was still unclear how the IC level and age-friendly living environment impact on FA. This study aims to confirm the relationship between the IC level and age-friendly living environment with FA, especially in older adults with low IC., Methods: Four hundred eighty-five community-dwelling residents aged ≥ 60 years were enrolled. IC constructed by locomotion, cognition, psychological, vitality, and sensory domains was assessed using full assessment tools recommended by WHO. Age-friendly living environment was measured with 12 questions adapted from the spatial indicators framework of age-friendly cities. FA was assessed using activities of daily living (ADL) and one question about mobile payment ability. Multivariate logistic regression was used to explore the association between IC, environment and FA. The influence of the environment on electronic payment and ADL under the IC layer was assessed., Results: Of 485 respondents, 89 (18.4%) had ADL impairment, and 166 (34.2%) had mobile payment function impairment. Limited IC (odds ratio [OR] = 0.783, 95% confidence interval [CI] = 0.621-0.988) and poor environment (OR = 0.839, 95% CI = 0.733-0.960) were associated with mobile payment ability impairment. Our results suggested that a supportive age-friendly living environment influenced FA was more prominent in older adults with poor IC (OR = 0.650, 95% CI = 0.491-0.861)., Conclusions: Our results confirmed IC and the environment had an impact on mobile payment ability. The relationship between environment and FA showed differences according to IC level. These findings suggest that an age-friendly living environment is important to maintain and enhance elders' FA, especially in those with poor IC., (© 2023. The Author(s).)

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson's disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson's disease. Forty-eight Parkinson's disease patients and 39 matched healthy controls underwent genotyping and 7T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson's disease diagnosis. We found that, in Parkinson's disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein (SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson's disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson's disease., Competing Interests: None

A new class of iminosulfonylation reagents were developed and extensively used in the 1,2-iminosulfonylation of various olefins. Olefins containing bioactive molecules, such as indomethacin, gemfibrozil, clofibrate, and fenbufen, afforded the desired iminosulfonylation products in synthetically useful yields. Furthermore, the first remote 1,6-iminosulfonylation of alkenes was realized by using oxime ester bifunctionalization reagents. Overall, more than 40 structurally diverse β-imine sulfones were obtained in moderate to excellent yields.

A vinyl radical-mediated 1,5-hydrogen atom transfer strategy for remote C(sp 3 )-H imination under visible-light-induced photochemical metal-free conditions afforded diverse γ-imino alkenes with excellent stereoselectivity. Oxime ester-based bifunctional reagents provided not only nucleophilic alkyl radicals for radical addition reactions with electron-deficient alkynes but also long-lived steady-state imine radicals for trapping alkyl radicals following the intramolecular 1,5-hydrogen migration of unstable olefin radicals.

To explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver. We also demonstrate the dependence receptor (DR) characteristics of ROBO1 in a follow-up mechanistic study. A neutralizing antibody targeting ROBO1 significantly attenuate liver metastasis of PDAC by preventing the coadaptation effect. Thus, we demonstrate that coadaptation is supported by the DR characteristics in the PMN and MMN., (© 2023. The Author(s).)

Constructing stable electrode/electrolyte interphase with fast interfacial kinetics is vital for fast-charging batteries. Herein, we investigate the interphase that forms between a high-voltage Na 3 V 2 (PO 4 ) 2 F 3 cathode and the electrolytes consisting of 3.0, 1.0, or 0.3 M NaClO 4 in an organic carbonate solvent (47.5 : 47.5 : 5 mixture of EC: PC: FEC) during charging up to 4.5 V at 55 °C. It is found that a higher anion/solvent ratio in electrolyte solvation structure induces anion-dominated interphase containing more inorganic species and more anion derivatives (C x ClO y ), which leads to a larger interfacial Na + transport resistance and more unfavorable gas evolution. In comparison, a low anion/solvent ratio derives stable anion-tuned interphase that enables better interfacial kinetics and cycle ability. Importantly, the performance of a failed cathode is restored by triggering the decomposition of C x ClO y species. This work elucidates the role of tuning interphase in fast-charging batteries., (© 2022 Wiley-VCH GmbH.)

The modular cyanoalkylamination of alkenes using bench-stable and easy-to-handle α-imino-oxy acid oxime esters as difunctional reagents creates new synthetic avenues. A metal-free photosensitization protocol for the installation of both amino and cyanoalkyl functionalities onto alkene feedstocks in a single step via two differently reactive nitrogen-centered radicals was developed via energy-transfer catalysis. Excellent functional group tolerance and mild reaction conditions also render this protocol suitable for the cyanoalkylamination of pharmaceutically relevant molecule-derived alkenes.

Cryptococcosis is a potentially lethal disease that is primarily caused by the fungus Cryptococcus neoformans, treatment options for cryptococcosis are limited. Here, we show glucuronoxylomannan, the major polysaccharide component of C. neoformans, induces the recruitment of neutrophilic myeloid-derived suppressor cells in mice and patients with cryptococcosis. Depletion of neutrophilic myeloid-derived suppressor cells enhances host defense against C. neoformans infection. We identify C-type lectin receptor-2d recognizes glucuronoxylomannan to potentiate the immunosuppressive activity of neutrophilic myeloid-derived suppressor cells by initiating p38-mediated production of the enzyme arginase-1, which inhibits T-cell mediated antifungal responses. Notably, pharmacological inhibition of arginase-1 expression by a specific inhibitor of p38, SB202190, or an orally available receptor tyrosine kinase inhibitor, vandetanib, significantly enhances T-cell mediated antifungal responses against cryptococcosis. These data reveal a crucial suppressive role of neutrophilic myeloid-derived suppressor cells during cryptococcosis and highlight a promising immunotherapeutic application by inhibiting arginase-1 production to combat infectious diseases., (© 2022. The Author(s).)

Owing to the lack of early diagnosis, pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal tumours. Because acinar-to-ductal metaplasia (ADM) is a critical process to pancreatic regeneration and PDAC initiation, we applied GSE65146, a dataset composed of transcripts at different time points in wild-type and Kras G12D mutant mice upon pancreatitis induction, to obtain regeneration- and tumour initiation-related genes. By overlapping with genes differentially expressed in human PDAC, we defined the initiation- and progression-related genes, and the most prognostic gene, SULF2, was selected for further verification. By using multiple PDAC genetically engineered murine models (GEMMs), we further verified that the expression of SULF2 was increased at the ADM and PDAC stages. Functionally, SULF2 was able to promote the dedifferentiation of acinar cells as well as the metastatic ability of PDAC. Additionally, our study revealed that SULF2 could enhance TGFβ-SMAD signalling via GDF15. More importantly, serum SULF2 was elevated in patients with PDAC, and in combination with CA19-9, it provided a better method for PDAC diagnosis. Herein, our study screened out key genes for the initiation and progression of PDAC, providing potential indicators for the diagnosis of the disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Poly(glycerol sebacate) (PGS), a soft, tough elastomer with excellent biocompatibility, has been exploited successfully in many tissue engineering applications. Although tunable to some extent, the rapid in vivo degradation kinetics of PGS is not compatible with the healing rate of some tissues. The incorporation of L-glutamic acid into a PGS network with an aim to retard the degradation rate of PGS through the formation of peptide bonds was conducted in this study. A series of poly(glycerol sebacate glutamate) (PGSE) containing various molar ratios of sebacic acid/L-glutamic acid were synthesized. Two kinds of amino-protected glutamic acids, Boc-L-glutamic acid and Z-L-glutamic acid were used to prepare controls that consist of no peptide bonds, denoted as PGSE-B and PGSE-Z, respectively. The prepolymers were characterized using 1 H-NMR spectroscopy. Cured elastomers were characterized using FT-IR, DSC, TGA, mechanical testing, and contact angle measurement. In vitro enzymatic degradation of PGSE over a period of 28 days was investigated. FT-IR spectroscopy confirmed the formation of peptide bonds. The glass transition temperature for the elastomer was found to increase as the ratio of sebacic acid/glutamic acid was increased to four. The decomposition temperature of the elastomer decreased as the amount of glutamic acid was increased. PGSE exhibited less stiffness and larger elongation at break as the ratio of sebacic acid/glutamic acid was decreased. Notably, PGSE-Z was stiffer and had smaller elongation at break than PGSE and PGSE-B at the same molar ratio of monomers. The results of in vitro enzymatic degradation demonstrated that PGSE has a lower degradation rate than does PGS, whereas PGSE-B and PGSE-Z degrade at a greater rate than does PGS. SEM images suggest that the degradation of these crosslinked elastomers is due to surface erosion. The cytocompatibility of PGSE was considered acceptable although slightly lower than that of PGS. The altered mechanical properties and retarded degradation kinetics for PGSE reflect the influence of peptide bonds formed by the introduction of L-glutamic acid. PGSE displaying a lower degradation rate compared to that for PGS can be used as a scaffold material for the repair or regeneration of tissues that are featured by a low healing rate.

Background: To ensure clinical efficacy and prolong patient survival, treatments such as surgery and microwave ablation (MWA) are used for early liver cancer. MWA is preferred because it effectively preserves the normal liver tissue and causes transient coagulation necrosis of local liver tumor cells. However, due to technical limitations, the cancerous liver tissue cannot be completely ablated; therefore, the probability of local tumor recurrence is high., Aim: To investigate the clinical efficacy and safety of ultrasound-guided percutaneous MWA in the treatment of small liver cancer., Methods: A total of 118 patients treated for small liver cancer in The Central Hospital of Yongzhou from January 2018 to April 2019 were selected. Sixty-six patients received ultrasound-guided percutaneous MWA (MWA group) and 52 received laparoscopic surgery (laparoscope group). The operation time, blood loss, hospital stay, and medical expenses of both groups were statistically analyzed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), alpha fetal protein (AFP), carcinoembryonic antigen (CEA), and peripheral blood regulatory T lymphocytes (Treg) levels were evaluated pre- and post-operatively. The cross-sectional area of tumors measured before and after ablation was analyzed statistically; the therapeutic effect was compared between both groups in terms of surgical complications, 2-year progression-free survival rate, and overall survival rate., Results: The operation time, blood loss, hospital stay, and medical expenses in the MWA group were lower than those of the laparoscope group, and the differences were significant ( P < 0.05); these parameters, and ALT, AST, TBIL, and ALB levels were compared preoperatively between both groups, and there was no significance ( P > 0.05). The operation time, blood loss, hospital stay, and medical expenses for 2 d and 1 wk after surgery, the ALT and AST of the MWA group were lower than those of the laparoscope group, and the difference was significant ( P < 0.05). The operation time, blood loss, hospital stay, and medical expenses, and serum AFP, CEA, and Treg levels were measured preoperatively and 4 and 8 wk postoperatively, and there were no significant differences between the two groups ( P > 0.05). Compared with preoperative levels, serum AFP, CEA, and Treg levels in both groups were decreased ( P < 0.05). The lesion in the MWA group had a maximum area of 4.86 ± 0.90 cm 2 , 1.24 ± 0.57 cm 2 , and 0.31 ± 0.11 cm 2 preoperatively, 1 and 3 mo postoperatively, respectively. Fifty-eight of them achieved complete response and eight achieved a partial response. After 2 years of follow-up, the progression-free and overall survival rates in the MWA group were 37.88% and 66.67%, respectively, compared with 44.23% and 76.92% in the laparoscope group, with no significant difference ( P > 0.05)., Conclusion: The effects of ultrasound-guided percutaneous MWA in the treatment of small liver cancer are similar to those of laparoscopic surgery. However, ablation causes less trauma and liver dysfunction., Competing Interests: Conflict-of-interest statement: The authors declared that there is no conflict of interest between them., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the risk factors for gestational diabetes mellitus (GDM) in elderly multipara women in the next pregnancy. Methods: A total of 219 elderly multipara women with 2 consecutive delivery records in Tianjin Binhai New Area Tanggu Obstetrics and Gynecology Hospital from January 2018 to May 2019 were included. Among them, 141 had normal glucose tolerance (NGT) and 78 of them had GDM. The clinical data of the previous and current pregnancy were collected to analyze the risk factors of GDM in elderly multipara women. Results: The average ages of 219 elderly women in previous pregnancy and this pregnancy were (31.9±2.2) and (36.7±1.5) years old, and the prevalence of GDM was 35.62% (78 cases). Compared to NGT group, GDM patients had higher fasting blood glucose(previous (5.51±1.43) vs (4.63±0.62) mmol/L; current (5.26±0.63) vs (4.59±0.30) mmol/L, 1 h blood glucose(previous (11.74±2.36) vs (9.50±1.82) mmol/L; current (11.03±2.03) vs (9.51±1.14) mmol/L) in 75 g oral glucose tolerance test (OGTT) in both previous and current pregnancy. The rates of cesarean section, in both previous and current pregnancy were higher in GDM group (previous 34.6% vs 4.3%; current 52.6% vs 22.0%). Furthermore, prenatal weight and body mass index (BMI) of the previous pregnancy, pre-pregnancy weight and BMI, and prenatal BMI of this pregnancy were also higher in GDM group, and the differences were all statistically significant (all P<0.05). Logistic multivariate regression analysis indicated cesarean section history ( OR =10.80, 95% CI : (4.09-28.54)), GDM history of previous pregnancy ( OR =10.64, 95% CI : (4.02-28.20)), 75 g OGTT fasting blood glucose≥ 4.86 mmol/L ( OR =2.70, 95% CI : (1.27-5.70)), 1 h blood glucose after glucose administration ≥ 8.45 mmol/L ( OR =1.78, 95% CI : (1.37-2.31)) were risk factors for GDM in elderly multipara women of this pregnancy. Conclusion: The risk of GDM in elderly multipara women with a history of cesarean section and GDM increases significantly. Results of OGTT in previous pregnancy also has predictive value.

Burkholderia pseudomallei is an important infectious disease pathogen that can cause melioidosis. Melioidosis is mainly prevalent in Thailand, northern Australia and southern China and has become a global public health problem. Early identification of B. pseudomallei is of great significance for the diagnosis and prognosis of melioidosis. In this study, a simple and visual device combined with lateral flow strip-based recombinase polymerase amplification (LF-RPA) was developed, and the utility of the LF-RPA assay for identifying B. pseudomallei was evaluated. In order to screen out the optimal primer probe, a total of 16 pairs of specific primers targeting the orf2 gene of B. pseudomallei type III secretion system (T3SS) cluster genes were designed for screening, and F1/R3 was selected as an optimal set of primers for the identification of B. pseudomallei , and parameters for LF-RPA were optimized. The LF-RPA can be amplified at 30-45°C and complete the entire reaction in 5-30 min. This reaction does not cross-amplify the DNA of other non- B. pseudomallei species. The limit of detection (LOD) of this assay for B. pseudomallei genomic DNA was as low as 30 femtograms (fg), which was comparable to the results of real-time PCR. Moreover, 21 clinical B. pseudomallei isolates identified by 16S rRNA gene sequencing were retrospectively confirmed by the newly developed LF-RPA system. Our results showed that the newly developed LF-RPA system has a simple and short time of operation and has good application prospect in the identification of B. pseudomallei., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhong, Shang, Li, Jiang, Zou, Ma, Huang and Lu.)

We reported a one-pot enantioselective three-component vinylogous Michael/aldol tandem reaction of prochiral 3-alkylidene oxindoles with methyleneindolinones and aldehydes using bifunctional organocatalysts. A variety of enantioenriched 3,3-disubstituted oxindoles 3 and spirolactones 4 were generated in moderate yields (up to 78%) with high stereoselectivities (up to >20:1 dr, >99% ee). Intriguingly, we observed that the aldol reaction with paraformaldehyde generates 3,3-disubstituted oxindoles 3 bearing a hydroxymethyl group, while the reaction with aliphatic aldehydes generates spirolactones 4 .

Neutrophil extracellular traps (NETs) are chromatin-based structures that are released from neutrophils during infections and prevent microbes from spreading in the body through efficient degradation of their composition. Based on this chromatin-driven strategy of capturing and killing bacteria, we designed NET-like structures using DNA and ZnO nanoparticles (NPs). DNA was first purified from kiwifruit and treated with HCl to increase hydroxyl groups in the opened-deoxylribose form. The carboxyl groups of citric acid were then thermally crosslinked with said hydroxyl and primary amine groups in DNA, forming DNA-HCl nanogels (NGs). ZnO NPs were then used as positively charged granule enzymes, adsorbed onto the DNA-HCl NG, obtaining ZnO/DNA-HCl NGs (with NET biomimicry). In an anti-inflammatory assay, ZnO/DNA-HCl NGs significantly inhibited TNF-α, IL-6, iNOS and COX-2 expression in LPS-stimulated Raw264.7 cells. Moreover, the ZnO/DNA-HCl NGs markedly alleviated clinical symptoms in LPS-induced mouse peritonitis. Finally, ZnO/DNA-HCl NGs suppressed E. coli from entering circulation in septic mice while prolonging their survival. Our results suggest that the ZnO/DNA-HCl NGs, which mimic NET-like structures in the blocking of bacteria-inducted inflammation, may be a potential therapeutic strategy for bacterial infections., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the influence of base materials on stress distribution in endodontically treated maxillary premolars restored with endocrowns using three-dimensional finite element analysis., Methods: A maxillary second premolar was scanned by Micro-CT and a three-dimensional finite element model of ceramic endocrown with 1 mm thickness of base was established. A model without base was also established as a negative control. Four kinds of conventional base materials with different elastic modulus were adopted: light cure glass ionomer(3M Vitrebond, 3 657 MPa), flowable composite resin(3M Filtek Z350XT Flowable Restorative, 7 300 MPa), high strength glass ionomer(GC Fuji Ⅸ, 13 130 MPa), and posterior composite resin(3M Filtek P60, 19 700 MPa). With a 200 N force loaded vertically and obliquely, the distribution and magnitude of stress in the tooth tissue and adhesive layer were investigated by three-dimensional finite element analysis., Results: The maximum von Mises stress values(vertical/oblique) in dentin and adhesive layer were measured as follows: (1) no base material: 19.39/70.49 MPa in dentin and 6.97/17.97 MPa in adhesive layer; (2) light cure glass ionomer: 19.00/69.75 MPa in dentin and 6.87/16.30 MPa in adhesive layer; (3) flowable composite resin: 18.78/69.33 MPa in dentin and 6.79/16.17 MPa in adhesive layer; (4) high strength glass ionomer: 18.71/69.20 MPa in dentin and 6.74/16.07 MPa in adhesive layer; (5) posterior composite resin: 18.61/69.03 MPa in dentin and 6.70/16.01 MPa in adhesive layer. Under the same loading condition, models with different elastic moduli of base materials had similar stress distribution patterns. The von Mises stress of tooth tissue was mainly concentrated in the tooth cervix. Under oblique load, the regions where von Mises stress concentrated in were similar to those under a vertical load, but the values increased. The stress concentration in the tooth cervix was alleviated in models with base materials compared with the model without base material. The maximum von Mises stress in the tooth tissue and adhesive layer decreased when the elastic modulus of base materials increased and got close to that of dentin., Conclusion: The posterior composite resin of which the elastic moduli is high and close to that of dentin is recommended as base material for premolar endocrowns to alleviate the concentration of stress in tooth cervix and adhesive layer.

Background: We aimed to evaluate the diagnostic yield of seven-tesla (7T) magnetic resonance imaging (MRI) with post-processing of three-dimensional (3D) T1-weighted (T1W) images by the morphometric analysis program (MAP) in epilepsy surgical candidates whose 3T MRI results were inconclusive or negative., Methods: We recruited 35 patients with pharmacoresistant focal epilepsy. A multidisciplinary team including an experienced neuroradiologist evaluated their seizure semiology, video-electroencephalography data, 3T MRI and post-processing results, and co-registered FDG-PET. Eleven patients had suspicious lesions on 3T MRI and the other 24 patients were strictly MRI-negative. 7T MRI evaluation was then performed to aid clinical decision. Among patients with pathologically proven focal cortical dysplasia (FCD) type II, signs of FCD were retrospectively evaluated in each MRI sequence (T1W, T2W, and FLAIR), and positive rates were analyzed in each MAP feature map (junction, extension, and thickness)., Results: 7T MRI evaluation confirmed the lesion in nine of the 11 (81.8%) patients with suspicious lesions on 3T MRI. It also revealed new lesions in four of the 24 (16.7%) strictly MRI-negative patients. Histopathology showed FCD type II in 11 of the 13 (84.6%) 7T MRI-positive cases. Unexpectedly, three of the four newly identified FCD lesions were located in the posterior quadrant. Blurred gray-white boundary was the most frequently observed sign of FCD, appearing on 7T T1W image in all cases and on T2W and FLAIR images in only about half cases. The 7T junction map successfully detected FCD (10/11) in more cases than the extension (1/11) and thickness (0/11) maps. The 3D T1W images at 7T exhibited superior cerebral gray-white matter contrast, more obviously blurred gray-white boundary of FCD, and larger and brighter positive zones in post-processing than 3T T1W images., Conclusion: 7T MRI with post-processing can enhance the detection of subtle epileptogenic lesions for MRI-negative epilepsy and may optimize surgical strategies for patients with focal epilepsy., Competing Interests: Conflict of interest statement: Dr. Y-C. Hsu is a senior research scientist in Siemens Healthcare, Shanghai, China. The other authors report no disclosures relevant to the manuscript., (© The Author(s), 2021.)

Intestinal fungi are critical for modulating host immune homeostasis and underlying mechanisms remain unclear. We show that dendritic cell (DC)-specific deficiency of casitas B-lineage lymphoma (c-Cbl) renders mice susceptible to dextran sodium sulfate (DSS)-induced colitis. Mechanistically, we identify that c-Cbl functions downstream of Dectin-2 and Dectin-3 to mediate the ubiquitination and degradation of noncanonical nuclear factor κB subunit RelB. Thus, c-Cbl deficiency in DCs promotes α-mannan-induced activation of RelB, which suppresses p65-mediated transcription of an anti-inflammatory cytokine gene, il10 , thereby aggravating DSS-induced colitis. Moreover, suppressing fungal growth with fluconazole or inhibition of RelB activation in vivo attenuates colitis in mice with DC-specific deletion of c-Cbl. We also demonstrate an interaction between c-Cbl and c-Abl tyrosine kinase and find that treatment with DPH, a c-Abl agonist, synergistically increases fungi-induced c-Cbl activation to restrict colitis. Together, these findings unravel a previously unidentified fungi-induced c-Cbl/RelB axis that sustains intestinal homeostasis and protects against intestinal inflammation., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

This study aimed to explore whether APOC1 expression has a function in the biological behavior of clear cell renal cell carcinoma (ccRCC) cells and its possible mechanism. Bioinformatics analysis of data TCGA and OnComine was conducted to explore the expression pattern and prognostic value of APOC1, as well as the relationship between APOC1 expression and clinical indicators. Loss- and gain- of APOC1 function assays were carried out to assess the biological functions of APOC1. Western blotting was applied to detect protein expression. We revealed that APOC1 was upregulated in ccRCC tissues. APOC1 expression was related to gender, grade, pathologic-T, pathologic-stage, and pathologic-M in patients with ccRCC. Meanwhile, Kaplan-Meier analysis evidenced that the high APOC1 expression indicated unfavorable outcomes of ccRCC. Functional experiments in vitro revealed that upregulation of APOC1 in UT33A cells promoted cell proliferation, invasion, and migration, while downregulation of APOC1 in 786-O cells had the opposite effect. Furthermore, epithelial mesenchymal transition (EMT) was activated in cells with upregulated APOC1 but inhibited in cells with down-regulated APOC1. Collectively, our data suggested that APOC1 was overexpressed in ccRCC cells and promoted the malignant biological behaviors and EMT of ccRCC cells., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objective: To describe the clinical manifestations, neuroimaging, cerebrospinal fluid(CSF) cytology and prognosis of Leptomeningeal metastases(LM). Methods: The clinical manifestations, imaging features and CSF cytology of LM patients admitted to Henan Provincial People's Hospital from May 1, 2015 to May 31, 2020 were retrospectively analyzed. The overall survival (OS) was evaluated by the time from the diagnosis of LM to death. Results: A total of 88 patients with LM were enrolled in the study, and the median age was 59 years (range:28-78 years). There were 42 males (47.7%) and 46 females (52.3%). According to the pathological classification, it was lung cancer in 58 cases (65.9%), gastric cancer in 13 cases (14.8%), breast cancer in 7 cases (8.0%), melanoma in 1 case, esophageal cancer in 1 case, gallbladder cancer in 1 case, renal cell carcinoma in 1 case, double source cancer in 2 cases, and unknown source in 4 cases. The median Karnofsky Performance Scale (KPS) score was 50. LM was the initial manifestation of cancer in 34 patients. All patients had LM-related clinical symptoms, including headache in 73 cases (83.0%), nausea and vomiting in 63 cases (71.6%), abnormal physical and mental behaviors in 37 cases (42.0%), seizure in 41 cases (46.6%). Cranial nerve involvement was observed in 23 patients (39.0%) and spinal nerve involvement in 20(33.9%). There were 61 patients (83.6%) who showed neuroimaging features of LM. Tumor cells or atypical cells were found in 90.8% of patients for the first time, and activated monocytes in 47 cases (54.7%). The median OS was 13.0 weeks (95% CI :2.9-23.1) with the 1-year survival rate of 19.1%. Univariate analysis of survival indicated that lung cancer, lower KPS score, tyrosine kinase inhibitors (TKIs) and whole brain radiotherapy were favorable predictors of survival ( P <0.05). Conclusions: The overall prognosis of LM is poor. Good physical condition, TKIs treatment and whole brain radiotherapy might improve clinical outcomes of LM patients.

Objective: To examine the early and mid-term results of coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) in the treatment of diffuse coronary artery stenosis. Methods: The clinical data and follow-up results of 248 patients who underwent CE+CABG surgery from January 2010 to January 2019 at Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University was analyzed retrospectively. There were 201 males and 47 females, aged (65.6±8.5) years (range: 43 to 79 years). The on-pump group included 156 patients and the off-pump group included 92 patients. CABG was performed after CE. CE was performed on 248 patients who represented 269 target coronary lesions, of which 108 were located on the left anterior descending artery and sub-branches, 140 were located on the right coronary artery and sub-branches, and 21 were located on the left circumflex artery and obtuse marginal artery. A total of 872 bypass grafts were performed, including 248 left internal thoracic arteries, 48 radial arteries, and 576 great saphenous veins, with (3.5±0.8) grafts (range:2 to 6 grafts) per patient.The grafts had satisfactory bridge blood flow after CE, with the graft flow rates of (26±8) ml/min (range: 13 to 59 ml/min) and the pulsatility index value of 3.1±0.8 (range: 2.0 to 6.7). The t test and χ 2 test was used to compare the surgical results and graft patency rate between patients in on-pump and off-pump group, respectively. Results: The number of graft vessels of on-pump group and off-pump group was 3.6±0.9 and 3.2±0.7, respectively( t =1.637, P =0.085). There were 3 deaths during the perioperative period, with a mortality rate of 1.2%. Two people died of renal failure, and one case was due to postoperative refractory low cardiac output. Perioperative myocardial infarction occurred in 9 cases. The follow-up time was (41.8±21.4) months (range:1 to 68 months). The all graft patency rate was 78.4%(812/232) in 1 year and 69.8%(162/232) in 3 years postoperatively. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate(1-year: 87.4% vs. 73.1%, χ²=6.533, P =0.011, 3-year: 78.2% vs. 64.8%, χ²=4.588, P =0.032). There was no significant difference in graft patency rates between the on-pump group and off-pump group (1-year: 80.0% vs. 76.9%, χ²=0.277, P =0.599, 3-year:71.5% vs. 67.9%, χ²=0.300, P =0.584). Conclusions: CE+CABG is a safe and feasible technique for patients with diffuse coronary artery disease to get more satisfied complete revascularization, with good early and medium-term results and graft patency rates. The outcomes of on-pump or off-pump CE+CABG are similar.

Aerobic glycolysis, also known as the Warburg effect, is emerged as a hallmark of most cancer cells. Increased aerobic glycolysis is closely associated with tumor aggressiveness and predicts a poor prognosis. Pancreatic ductal adenocarcinoma (PDAC) is characterized by prominent genomic aberrations and increased glycolytic phenotype. However, the detailed molecular events implicated in aerobic glycolysis of PDAC are not well understood. In this study, we performed a comprehensive molecular characterization using multidimensional ''omic'' data from The Cancer Genome Atlas (TCGA). Detailed analysis of 89 informative PDAC tumors identified substantial copy number variations ( MYC , GATA6 , FGFR1 , IDO1, and SMAD4 ) and mutations ( KRAS , SMAD4 , and RNF43 ) related to aerobic glycolysis. Moreover, integrated analysis of transcriptional profiles revealed many differentially expressed long non-coding RNAs involved in PDAC aerobic glycolysis. Loss-of-function studies showed that LINC01559 and UNC5B-AS1 knockdown significantly inhibited the glycolytic capacity of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate. Moreover, genetic silencing of LINC01559 and UNC5B-AS1 suppressed tumor growth and resulted in alterations in several signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, and transcriptional misregulation in cancer. Notably, high expression of LINC01559 and UNC5B-AS1 predicted poor patient prognosis and correlated with the maximum standard uptakevalue (SUVmax) in PDAC patients who received preoperative 18 F-FDG PET/CT. Taken together, our results decipher the glycolysis-associated copy number variations, mutations, and lncRNA landscapes in PDAC. These findings improve our knowledge of the molecular mechanism of PDAC aerobic glycolysis and may have practical implications for precision cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Sluggish kinetics and limited reversible capacity present two major challenges for layered titanates to achieve satisfactory sodium-ion storage performance at subzero-temperatures (subzero-T). To facilitate sodiation dynamics and improve reversible capacity, we proposed an additive-free anode with Sn(II) located between layers. Sn-5s in interlayer-confining Sn(II), which has a larger negative charge, will hybridize with O-2p to trigger charge redistribution, thereby enhancing electronic conductivity. H-titanates with an open framework are designed to stabilize Sn(II) and restrain subsequent volume expansion, which could potentially surpass the capacity limitation of titanate-based materials via a joint alloying-intercalation reaction with high reversibility. Moreover, the generation of conductive Na 14 Sn 4 and the expansion of interlayer spacing resulting from the interlayered alloying reaction are beneficial for charge transfer. These effects synergistically endow the modified sample with a considerably lower activation energy and a 3-fold increase in diffusion. Consequently, the designed anode delivers excellent subzero-T adaptability when compared to the unmodified sample, maintaining capacity retention of 91% after 1200 cycles at -20 °C and 90% after 850 cycles at -30 °C.

Cancer metastasis is a central oncology concern that worsens patient conditions and increases mortality in a short period of time. During metastatic events, mitochondria undergo specific physiological alterations that have emerged as notable therapeutic targets to counter cancer progression. In this study, we use drug-free, cationic peptide fibrillar assemblies (PFAs) formed by poly(L-Lysine)- block -poly(L-Threonine) (Lys- b -Thr) to target mitochondria. These PFAs interact with cellular and mitochondrial membranes via electrostatic interactions, resulting in membranolysis. Charge repulsion and hydrogen-bonding interactions exerted by Lys and Thr segments dictate the packing of the peptides and enable the PFAs to display enhanced membranolytic activity toward cancer cells. Cytochrome c (cyt c ), endonuclease G, and apoptosis-inducing factor were released from mitochondria after treatment of lung cancer cells, subsequently inducing caspase-dependent and caspase-independent apoptotic pathways. A metastatic xenograft mouse model was used to show how the PFAs significantly suppressed lung metastasis and inhibited tumor growth, while avoiding significant body weight loss and mortality. Antimetastatic activities of PFAs are also demonstrated by in vitro inhibition of lung cancer cell migration and clonogenesis. Our results imply that the cationic PFAs achieved the intended and targeted mitochondrial damage, providing an efficient antimetastatic therapy.

Background: To evaluate the role of high-resolution computed tomography (HRCT) in the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia and to provide experience in the early detection and diagnosis of 2019-nCoV pneumonia., Methods: Seventy-two patients confirmed to be infected with 2019-nCoV from multiple medical centers in western China were retrospectively analyzed, including epidemiologic characteristics, clinical manifestations, laboratory findings and HRCT chest features., Results: All patients had lung parenchymal abnormalities on HRCT scans, which were mostly multifocal in both lungs and asymmetric in all patients, and were mostly in the peripheral or subpleural lung regions in 52 patients (72.22%), in the central lung regions in 16 patients (22.22%), and in both lungs with "white lung" manifestations in 4 patients (5.56%). Subpleural multifocal consolidation was a predominant abnormality in 38 patients (52.78%). Ground-glass opacity was seen in 34 patients (47.22%). Interlobular septal thickening was found in 18 patients, 8 of whom had only generally mild thickening with no zonal predominance. Reticulation was seen in 8 patients (11.11%), and was mild and randomly distributed. In addition, both lungs of 28 patients had 2 or 3 CT imaging features. Out of these 72 patients, 36 were diagnosed as early stage, 32 patients as progressive stage, and 4 patient as severe stage pneumonia. Moreover, the diagnostic accuracy of HRCT features combined with epidemiological history was not significantly different from the detection of viral nucleic acid (all P >0.05)., Conclusions: The HRCT features of 2019-nCoV pneumonia are characteristic to a certain degree, which when combined with epidemiological history yield high clinical value in the early detection and diagnosis of 2019-nCoV pneumonia., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5731). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

We report an efficient growth factor delivering system based on polypeptide/heparin composite hydrogels for wound healing application. Linear and star-shaped poly(l-lysine) (l-PLL and s-PLL) were chosen due to not only their cationic characteristics, facilitating the efficient complexation of negatively charged heparin, but also the ease to tune the physical and mechanical properties of as-prepared hydrogels simply by varying polypeptide topology and chain length. The results showed that polymer topology can be an additional parameter to tune hydrogel properties. Our experimental data showed that these composite hydrogels exhibited low hemolytic activity and good cell compatibility as well as excellent antibacterial activity, making them ideal as wound dressing materials. Unlike other heparin-based hydrogels, these composite hydrogels with heparin densely deposited on the surface can increase the stabilization and concentration of growth factor, which can facilitate the healing process as confirmed by our in vivo animal model. We believe that these PLL/heparin composite hydrogels are promising wound dressing materials and may have potential applications in other biomedical fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8 + T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8 + T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8 + T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8 + T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion-triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8 + T-cell infiltration and a reduced Th1/Th2 ratio. SIGNIFICANCE: These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion., (©2020 American Association for Cancer Research.)