Search

Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking.

Nasal chondromesenchymal hamartoma (NCMH) is a rare benign polypoid mesenchymal tumor arising in the nasal cavity and/or paranasal sinuses. Recognizing these sporadic, rare lesions is crucial, as surgical complete removal of the mass is the common treatment approach. This retrospective study analyzed the demographics, symptoms, and imaging data of 9 patients diagnosed with NCMH between January 2017 and June 2023, possibly representing the largest single-center adult case cohort to date. Diagnostic techniques included nasal endoscopy, CT/MRI scan, immunohistological studies, and morphologic comparisons. Pathologic specimens were subjected to Sanger sequencing of exons 24 and 25 of DICER1. The average age of 9 cases was 24.4 years, and the oldest was 55 years. Four of the patients were children, ranging from 1 year old to 11 years old, with an average of 4.5 years. Nasal congestion is the most common registered symptom. Endoscopic findings showed that most patients had smooth pink neoplasms or polypoid masses in the nasal meatus. Radiologic scanning revealed soft-tissue density masses that occupied the nasal cavity. Histologically, the characteristic structure of NCMHs is immature cellular cartilage nodules and mature cartilage nodules distributed in a loose mucoid matrix. Five of the 9 patients had somatic DICER1 missense mutations. Four of the patients with DICER1-mutated NCMH exhibited a p.E1813 missense hotspot mutation. We also report a case of a rare p.P1836H missense mutation. The detected DICER1 somatic mutations provide compelling evidence of an association with the DICER1 tumor family. We emphasize the importance of pathologic consultation and the need for pathologists to accumulate experience in NCMH diagnosis to avoid misdiagnosis.

Atopic dermatitis (AD), a recurrent inflammatory systemic skin disease, is difficult to cure. In the present study, several ethylenediamine-derived dehydrocostuslactone (DHCL) derivatives were prepared to assess their in vitroand in vivoanti-inflammatory activities. The results indicated that DHCL derivatives inhibited NO generation with low cytotoxicity. In particular, compound 5dexhibited the best anti-inflammatory activity. Subsequent experiments revealed that 5dnot only inhibited the LPS-induced inflammatory response in RAW264.7 cells viathe MAPK–NF-κB signaling pathway inhibition but also significantly decreased Th2-type cytokine levels and inhibited the NF-κB signaling pathway activation in mice with MC903-induced AD. Therefore, DHCL derivatives may be considered as new agents for the treatment of AD.

In this paper, fixed-time consensus tracking for multiagent systems (MASs) with dynamics in the form of strict feedback affine nonlinearity is addressed. A fixed-time antidisturbance consensus tracking protocol is proposed, which consists of a distributed fixed-time observer, a fixed-time disturbance observer, a nonsmooth antidisturbance backstepping controller, and the fixed-time stability analysis is conducted by using the Lyapunov theory correspondingly. This paper includes three main improvements. First, a distributed fixed-time observer is developed for each follower to obtain an estimate of the leader's output by utilizing the topology of the communication network. Second, a fixed-time disturbance observer is given to estimate the lumped disturbances for feedforward compensation. Finally, a nonsmooth antidisturbance backstepping tracking controller with feedforward compensation for lumped disturbances is designed. In order to mitigate the “explosion of complexity” in the traditional backstepping approach, we have implemented a modified nonsmooth command filter to enhance the performance of the closed-loop system. The simulation results show that the proposed method is effective.

Accurate prediction of thermoacoustic instability is a prerequisite for thermoacoustic control to avoid the damage of combustion chamber, however, this problem has not been completely solved yet. This paper proposes a data-driven method based on the Elman neural network (ENN) to predict the value of acoustic pressure of combustion instability. As a comparison, a model based on support vector machine (SVM) was built. It is proved that ENN has better prediction performance with a certain predicted time horizon compared to the SVM method. What is more, the prediction model based on ENN can adapt to time-varying characteristics of the transition scenario which is characterized by amplitude modulation, multiple frequencies, and irregular bursts. ENN model still maintains enough prediction accuracy for various input training sets, indicating that ENN can fully mine the features of data and has a strong feature extraction ability in combustion oscillation prediction. Hence, it is demonstrated that ENN is a promising prediction tool for thermoacoustic instability under various combustion conditions. These findings are of great significance for the accurate prediction and control of thermoacoustic instability.

HIV-1–associated nephropathy (HIVAN) is a severe complication of HIV-1 infection. To gain insight into the pathogenesis of kidney disease in the setting of HIV, a transgenic (Tg) mouse model [CD4C/HIV-negative regulator factor (Nef)] was used in which HIV-1 nefexpression is under control of regulatory sequences (CD4C) of the human CD4gene, thus allowing expression in target cells of the virus. These Tg mice develop a collapsing focal segmental glomerulosclerosis associated with microcystic dilatation, similar to human HIVAN. To identify kidney cells permissive to the CD4C promoter, CD4C reporter Tg lines were used. They showed preferential expression in glomeruli, mainly in mesangial cells. Breeding CD4C/HIV Tg mice on 10 different mouse backgrounds showed that HIVAN was modulated by host genetic factors. Studies of gene-deficient Tg mice revealed that the presence of B and T cells and that of several genes was dispensable for the development of HIVAN: those involved in apoptosis (Trp53, Tnfsf10, Tnf, Tnfrsf1b, and Bax), in immune cell recruitment (Ccl3, Ccl2, Ccr2, Ccr5, and Cx3cr1), in nitric oxide (NO) formation (Nos3and Nos2), or in cell signaling (Fyn, Lck, and Hck/Fgr). However, deletion of Srcpartially and that of Hck/Lynlargely abrogated its development. These data suggest that Nef expression in mesangial cells through hematopoietic cell kinase (Hck)/Lck/Yes novel tyrosine kinase (Lyn) represents important cellular and molecular events for the development of HIVAN in these Tg mice.

Exploring wild reservoirs of pathogenic viruses is critical for their long-term control and for predicting future pandemic scenarios. Here, a comparative in vitro infection analysis was first performed on 83 cell cultures derived from 55 mammalian species using pseudotyped viruses bearing S proteins from SARS-CoV-2, SARS-CoV, and MERS-CoV. Cell cultures from Thomas’s horseshoe bats, king horseshoe bats, green monkeys, and ferrets were found to be highly susceptible to SARS-CoV-2, SARS-CoV, and MERS-CoV pseudotyped viruses. Moreover, five variants (del69-70, D80Y, S98F, T572I, and Q675H), that beside spike receptor-binding domain can significantly alter the host tropism of SARS-CoV-2. An examination of phylogenetic signals of transduction rates revealed that closely related taxa generally have similar susceptibility to MERS-CoV but not to SARS-CoV and SARS-CoV-2 pseudotyped viruses. Additionally, we discovered that the expression of 95 genes, e.g., PZDK1and APOBEC3, were commonly associated with the transduction rates of SARS-CoV, MERS-CoV, and SARS-CoV-2 pseudotyped viruses. This study provides basic documentation of the susceptibility, variants, and molecules that underlie the cross-species transmission of these coronaviruses.

We carry out a series of experimental investigations in a model combustor to detect a precursor of thermoacoustic combustion oscillations based on permutation entropy, which can amplify the subtle changes effected in the time sequence to identify the anomaly. By changing the flame’s location or the fuel flow to a value, an abrupt switch from aperiodic small-amplitude oscillations to periodic large-amplitude oscillations would occur in pressure fluctuations. The characteristic frequency of combustion oscillation is obtained by spectral analysis, with which a modified algorithm of the permutation entropy is proposed. The impact evaluation on key parameters such as moving step sizes and window sizes reveals that the moving data permutation entropy has strong robustness, and can accurately detect the onset of thermoacoustic oscillations. Further nonlinear analysis exhibits peculiar dynamics of the combustion system, which result in specific patterns in the time series and provide a theoretical basis for anomaly detection. Our results suggest that the permutation entropy has a certain potential in early warning and detection of combustion oscillations.

We evaluated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on prostate cancer by evidence triangulation. Using Mendelian randomization, we found that genetically proxied SGLT2 inhibition reduced the risk of overall (odds ratio = 0.56, 95% confidence interval [CI] = 0.38 to 0.82; 79,148 prostate cancer cases and 61,106 controls), advanced, and early-onset prostate cancer. Using electronic healthcare data (nSGLT2i = 24,155; nDPP4i = 24,155), we found that the use of SGLT2 inhibitors was associated with a 23% reduced risk of prostate cancer (hazard ratio = 0.77, 95% CI = 0.61 to 0.99) in men with diabetes. Using data from two prospective cohorts (n4C = 57,779; nUK_Biobank = 165,430), we found little evidence to support the association of HbA1cwith prostate cancer, implying a non-glycemic effect of SGLT2 inhibition on prostate cancer. In summary, this study provides multiple layers of evidence to support the beneficial effect of SGLT2 inhibition on reducing prostate cancer risk. Future trials are warranted to investigate whether SGLT2 inhibitors can be recommended for prostate cancer prevention.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 μm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women’s mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

The interaction mechanism of internally-staged-swirling stratified flame is complex, and the pilot flame has a manifest influence on flame stability. To study this, a series of experimental investigations for the pilot flame has been carried out in a model swirl combustor by only supplying the pilot fuel. The CH*chemiluminescence images of the pilot flame are acquired by a high-speed camera with a CH*bandpass filter, whose dynamic characteristics are identified by image statistical analysis and proper orthogonal decomposition (POD) analysis. And the fast algorithm based on matrix theory proposed in this paper increases the operation efficiency and operability of POD. With the pilot equivalence ratio Φincrease, the pilot flame gradually shows an unstable state, whose POD energy distribution is significantly different. In the unstable state, the flame dynamics include three modes—spiral motion mode, flame shedding mode, and axial oscillation mode, whose formation reasons have also been further analyzed in combination with the experimental characteristics. And the fast Fourier transform (FFT) analysis of the time coefficients for the first four POD modes indicates all the dominant frequency is 280 Hz, which means the model combustor is in resonance. In addition, a sensitivity analysis based on the different image resolutions further reveals the robustness of the POD method and its optimization direction. These results emphasize the important influence of the pilot fuel flow rate on the stability of the pilot flame.

ABSTRACTLong non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) participates in the development of diverse cancers. Nevertheless, the impact of DANCR on cervical cancer (CC) remains largely unknown. This study aims to explore the effects of DANCR sponging microRNA-145-3p (miR-145-3p) on CC. Expression of KLF5, DANCR, miR-145-3p, and zinc finger E-box binding homeobox 1 (ZEB1) in CC and adjacent normal tissues was determined. Human CC cell lines were, respectively, treated with silenced DANCR or miR145-3p mimic/inhibitor. Then, the viability, migration, invasion, and apoptosis of CC cells were measured. The cell growth in vivowas observed as well. Chromatin immunoprecipitation assay was performed to analyze the binding of KLF5 and DANCR promoter. Interaction among DANCR, miR-145-3p, and ZEB1 was assessed. KLF5, DANCR, and ZEB1 were upregulated but miR-145-3p was downregulated in CC tissues. KLF5 activated DANCR expression and the high DANCR expression was related to tumor staging, infiltrating muscle depth and lymphatic metastasis of CC patients. Reduced DANCR or elevated miR-145-3p repressed malignant behaviors of CC cells. The tumor diameter and weight were also repressed by DANCR silencing or miR-145-3p elevation. The effect of DANCR knockdown on CC cells could be reversed by miR-145-3p inhibitor. MiR-145-3p was targeted by DANCR and ZEB1 was targeted by miR-145-3p. KLF5-induced overexpression of DANCR promotes CC progression via suppressing miR-145-3p to target ZEB1. This study may provide potential targets for CC treatment.

A simple dual-mode film with excellent utility is fabricated for personal thermal management.

Background It was recently suggested that the upregulation of podoplanin (PDPN) in cancer cells plays a significant role in tumor invasion and metastasis and that it is significantly associated with poor prognosis in oral, cutaneous, and esophageal squamous cell carcinoma. The aim of this study was to investigate the expression pattern of PDPN in sinonasal squamous cell carcinoma (SNSCC) and to evaluate its role as a prognostic factor for survival outcome.Patients and methods This study included 59 subjects with SNSCC. We retrospectively collected the clinical features of these patients from medical records and retrieved the associated formalin-fixed, paraffin-embedded tissues for PDPN immunohistochemical staining. Furthermore, PDPN expression was analyzed in relation to the patients’ clinicopathological features and prognosis.Results We observed positive staining for PDPN in both cancer cells and stromal cancer-associated fibroblasts (CAFs). Positive expression of PDPN in cancer cells of patients with SNSCC was significantly correlated with the primary tumor site (p = 0.009) and local recurrence (p = 0.024). In addition, patients with PDPN-positive cancer cells had significantly lower overall survival (OS) and disease-free survival (DFS) rates than did patients with PDPN-negative cancer cells (both p < 0.05). Multivariate analysis revealed that PDPN expression in cancer cells was an independent prognostic factor for both OS (p = 0.038) and DFS (p = 0.039).Conclusions Our findings demonstrated that PDPN overexpression may be both an independent prognostic biomarker and a therapeutic target in SNSCC.

A heavy-duty gas turbine, designed for natural gas, was used to burn the syngas with two different calorific values. This study was mainly to optimize the flow matching scheme for the gas turbine. Two models of gas turbine burning syngas with different calorific values were established and the calculation models of different flow matching schemes were provided. The optimum scheme was obtained by evaluating thermal efficiency and work output under different operating conditions. The results showed that the highest unit efficiency was achieved by, without significant drop in work output, increasing the throat area of the turbine nozzle and reducing the initial temperature of the gas. On the premise of ensuring the safety of the gas turbine unit, increasing the pressure ratio of the compressor could further improve the unit efficiency and the work output. Simply adjusting the angle of the inlet guide vane fails to match the flow of compressor and turbine. The measures such as reducing inlet temperature of turbine or air bleed still need to be adopted, but the thermal efficiency dropped significantly in this process.

The Co/N-doped carbon material, as an important electrocatalytic material, has been attracted intense interest in ORR and Zn–air battery. Here, we report an efficient Co@N-doped carbon catalyst (Co@N-C-1) obtained by pyrolysis of ZIF precursor with 2-aminobenzimidazole. The introduction of 2-aminobenzimidazole results in the formation of hierarchical meso/microporous structure of the as-prepared Co@N-C-1, effectively avoiding the aggregation of Co nanoparticles during pyrolysis and the higher N content, which contributes to enhance the ORR electrocatalytic activities. The obtained Co@N-C-1 exhibits remarkable ORR performance with a half-wave potential of 0.938 V vs RHE in alkaline media. As the air catalyst of zinc–air batteries, Co@N-C-1 displays 1.439 V of open-circuit voltage and 1413.3 Wh·kg–1of energy density.

Nanoporous Gd2O3powders (NGPs) with different specific surface areas were prepared by a non-aqueous sol-gel method and utilized to tune the exothermal decomposition of ammonium perchlorate (AP) for enhanced propellant efficiency and improved safety. It is found that with the increasing dosage of NGPs into AP, the two exothermal peaks of AP merge into one intense exothermal peak, indicating that an “energy stacking” has been achieved. Meanwhile, the unique delay of the first exothermal peak of AP is conducive to the safety of AP in application process. Furthermore, the dependence of decomposition heat of AP on dosage and calcination temperature is more evident than on the surface areas of NGPs, suggesting that the promotion effect of NGPs on the thermal decomposition of AP does not only rely on the surface interaction. Therefore, an electron transfer mechanism is proposed to illustrate the decomposition process of AP tuned by NGPs.

In order to solve problems of the photo-generated charge recombination and low utilization efficiency of visible light in achieving green and sustainable development, a novel flower-like Z-type heterojunction CuS/Bi7O9I3composite catalyst was successfully prepared through a facile and mild process. The preparatory conditions of Bi7O9I3and CuS are low temperature and normal pressure with environment friendly reagents. The degradation performance of the catalyst was evaluated using ciprofloxacin (CIP) antibiotic. The results showed that degradation rate of the CuS/Bi7O9I3composite catalyst was 5 and 4 times that of the single CuS and Bi7O9I3catalysts, respectively. The actual performance of the catalyst was evaluated using simulated wastewater containing different ions and real water sources. Results showed that the new CuS/Bi7O9I3composite catalyst has excellent degradation and practical performances. At the same time, there is a synergistic effect between the photothermal and catalytic effects of the catalyst. The rapid temperature increase obviously inhibited the biological activity of bacteria, thereby affecting its metabolism and enhancing the destruction of the composite catalyst. Finally, using the free radical capture, VB-XPS and ESR measurements, photocatalytic mechanisms are proposed.

We take a fresh look at the interaction between crude oil prices and investor sentiment from the novel perspective of both the time and the frequency domains. By using principal component analysis, we first construct an investor sentiment indicator. Then, crude oil prices are decomposed into three oil price shocks through an SVAR model. Lastly, the dynamic relationship between investor sentiment and oil price shocks is comprehensively studied from both the time and the frequency domains via wavelet coherence analysis. Our results show the leading position of crude oil prices in the co-movement relationship with investor sentiment. Further, we distinguish the different effects of oil price shocks on investor sentiment at different times and frequencies. We also find that the patterns of the co-movement between oil prices (oil price shocks) and investor sentiment change not only with time but also with frequency.

ABSTRACTBackground: In Chinese women, breast and colorectal cancers are highly prevalent. In the early stage, the primary treatment for these cancers is surgical resection. However, many patients develop a metastatic recurrence. Thus, tools that help estimate the risk of recurrence are critical. Although synchronous breast and rectal cancer is uncommon, estimating recurrence risk is even more challenging in patients with two histologically distinct malignancies. Methods: Next generation sequencing (NGS) allows the comprehensive detection of simultaneous genome abnormalities. NGS-based circulating tumor DNA (ctDNA) profiling is a new molecular technique that has demonstrated great potential in the detection and differential diagnosis of cancer relapse. Results: We present a 43-year-old female patient with synchronous breast and rectal cancer that was surgically removed 2 years prior. During regular follow-up, elevated carcinoembryonic antigen (CEA) levels were detected. ctDNA profiling revealed multiple somatic mutations that were identical to those found in rectal cancer samples. Thus, we suspected relapse of rectal cancer. Positron emission tomography-computed tomography (PET-CT) and pathogenic analysis confirmed lung metastasis of rectal cancer. Conclusions: This case demonstrated the utility of ctDNA profiling in the detection and differential diagnosis of cancer relapse in a patient with synchronous breast and rectal cancer.

Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1–3. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia2, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+T cell responses against pathogens in treatment-naive mice bearing large tumors. Specifically, we identify CD45+erythroid progenitor cells (CD71+TER119+; EPCs) as robust immunosuppressors. CD45+EPCs, induced by tumor growth–associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45+EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45+EPC–mediated immunosuppression. Similarly, an immunosuppressive CD45+EPC population was detected in patients with cancer who have anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in patients with advanced cancer.

The adoption of source-classified collection of municipal solid waste (MSW) systems has improved waste management and resource conservation in developing countries, including China. Here, we evaluated the effects of a new MSW source-classified collection system on the distribution and leaching of heavy metals in incineration residues as well as on the pozzolanic properties of residues used as additives in cement production. Cu, Cr, and Mn were found primarily in bottom ash, while the volatile metals Zn, Pb, and Cd became enriched primarily in fly ash during combustion. However, effective presorting of MSW prior to incineration reduced the heavy metal content of the MSW source material and increased the combustion efficiency and heat values of MSW. The system of source-classified collection of MSW resulted in decreased concentrations of heavy metals in bottom ash, as well as decreased leachate toxicity, which improved the viability of bottom ash for use as a non-hazardous raw material in cement production. The consistently high temperatures sustained during incineration of source-classified MSW increased the concentrations and leachate toxicity of Cd, Pb, Cu, Zn, and Cr in fly ash. Pozzolanic activity testing revealed that bottom ash may be used as a pozzolanic material in cement production, but that fly ash is not suitable. In contrast to bottom ash from the incineration of mixed MSW, bottom ash from the incineration of source-classified MSW fully satisfies China’s “Pozzolanic materials used for cement production” standards due to its low loss on ignition, high grindability, and the desired rupture strength, compressive strength, and stability that it adds to mortar mixtures.

Letter to the Editor

Polymeric micelles and polymersomes may have great potential as the drug delivery vehicles for solubilization of hydrophobic drugs.

An effect of the swirling flow on the combustion performance is studied by the computational fluid dynamics (CFD) in a micro-gas turbine with a centrifugal compressor, dump diffuser and forward-flow combustor. The distributions of air mass and the Temperature Pattern Factor (as: Overall Temperature Distribution Factor -OTDF) in outlet are investigated with two different swirling angles of compressed air as 0° and 15° in three combustors. The results show that the influences of swirling flow on the air distribution and OTDF cannot be neglected. Compared with no-swirling flow, the air through outer liner is more, and the air through the inner liner is less, and the pressure loss is bigger under the swirling condition in the same combustor. The Temperature Pattern Factor changes under the different swirling conditions.

Supplemental Digital Content is available in the text.One of the widely accepted hypotheses of Hirschsprung’s disease (HD) is that the absence of ganglion cells in the distal part of the intestine is caused by the death of enteric neural crest-derived cells following migration. Although a caspase-dependent pathway has not yet been detected in the HD bowel, it is unclear whether a caspase-independent pathway contributes toward aganglionosis. In the current study, we observed highly condensed marginal heterochromatin in nuclei only in the transitional segment using electron microscopy and a high proportion of TUNEL-positive cells were observed in the transitional segment. Activation of caspase was not observed in any segments of the HD bowel upon characterization of the apoptotic pathway. Rather, real-time PCR results showed that apoptosis-inducing factor (AIF) and calpain-1mRNAs were highly expressed in the transitional segment, whereas autophagy protein 5 (Atg5) was highly expressed in the narrow segment. Western blot results were consistent with mRNA levels, with increased AIF, calpain-1, and Atg5expressions in the transitional segment compared with the dilated segment. Furthermore, correlation analysis indicated an inverse correlation between calpain-1and Atg5mRNA levels in both the narrow segment and the transitional segment. These results indicated that apoptosis occurs in the HD bowel. The detection of related genes indicates that the AIF-mediated apoptotic pathway may be responsible for the absence of ganglion cells in HD and calpain-1 may act as the regulatory switch between autophagy and apoptosis.

Here we demonstrate the fabrication, electrochemical performance and application of an asymmetric supercapacitor (AS) device constructed with β–Ni(OH)2/MWCNTs as positive electrode and KOH activated honeycomb-like porous carbon (K-PC) derived from banana fibers as negative electrode. Initially, the electrochemical performance of hydrothermally synthesized β–Ni(OH)2/MWCNTs nanocomposite and K-PC was studied in a three-electrode system using 1M KOH. These materials exhibited a specific capacitance (Cs) of 1327F/g and 324F/g respectively at a scan rate of 10mV/s. Further, the AS device i.e., β–Ni(OH)2/MWCNTs// K-PC in 1M KOH solution, demonstrated a Cs of 156F/g at scan rate of 10mV/s in a broad cell voltage of 0–2.2V. The device demonstrated a good rate capability by maintaining a Cs of 59F/g even at high current density (25A/g). The device also offered high energy density of 63Wh/kg with maximum power density of 5.2kW/kg. The AS device exhibited excellent cycle life with 100% capacitance retention at 5000th cycle at a high current density of 25A/g. Two AS devices connected in series were employed for powering a pair of LEDs of different colors and also a mini fan.

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic β cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.

Liquid-chromatography-mass-spectrometry-based metabolomics is widely used in prospective case-control studies for disease prediction. Given the large amount of clinical and metabolomics data involved, data integration and analyses are crucial to provide an accurate understanding of the disease. We provide a comprehensive analysis approach to explore associations among clinical risk factors, metabolites, and disease. We describe steps for performing Spearman correlation, conditional logistic regression, casual mediation, and variance partitioning to investigate the potential effects of metabolites on disease.

Anti–PD-1/PD-L1 therapy, either by anti–PD-1 antibody or anti–PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8+T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8+T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200+cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200+T cells positively related to a favorable clinical outcome to anti–PD-1/PD-L1 therapy in three independent cohorts of patients with cancer. Using multiple mouse tumor models, we demonstrated that CD200+CTLs are essential for efficacious anti–PD-L1 therapy. Mechanistically, we observed a unique chromatin landscape in CD200+CTLs and found that these cells are enriched for tumor antigen–specific CTLs and have antitumor effector functions. Coinoculation of CD200+CTLs with tumor cells led to robust tumor regression in two transplanted mouse models. Clinically, we found that infiltration of CD200+CTLs into tumors could predict immunotherapy efficacy in six patient cohorts. Together, our findings reveal that CD200+CTLs in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy and could serve as a predictor of successful immunotherapy in the clinic.

Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum metabolites are modestly limited in the comprehensive catalog of risk factor–metabolite–diabetes associations. These findings reveal that systematic AAs and MRMs change profile before T2DM onset and support a potential role of metabolic alterations in the pathogenesis of diabetes.

Since antigen and adjuvant are rapid clearance in vivo, insufficient delivery to induce dendritic cells (DCs) maturation and cross-presentation, as well as limited migration efficiency of DCs to secondary lymph organs, greatly hinders the development of DCs-based immunotherapy. Herein, PCL-PEG-PCL polymersomes (PCEP-PS) as antigen and adjuvants delivery nanoplatforms (IMO-PS) were well-designed, which can electrostatically adsorb OVA antigen on the surface viaDOTAP lipid and effectively encapsulate OVA antigen into the inner hydrophilic cavity to achieve both initial antigen exposure as well as slow and sustained antigen release, incorporate MPLA within the lipid layer to ligate with extracellular TLR4 of DCs as well as encapsulate IMQ in the hydrophobic membrane to ligate with intracellular TLR7/8 of DCs for activating synergistic immune responses viadifferent signaling pathways. The IMO-PS significantly improved antigen uptake, promoted DCs maturation and cytokines production. DCs treated with IMO-PS could enhance migration into draining lymphoid nodes, and eventually induced antigen-specific CD8+and CD4+T cell responses and OVA-specific cytotoxic T lymphocyte (CTL) responses. Prophylactic vaccination of EG7-OVA tumor-bearing mice by IMO-PS + DCs significantly extended tumor-free time, effectively suppressed tumor growth, and greatly extended median survival time. The strategy may provide an effective nanoplatform for co-delivery antigen and dual-adjuvants in a spatio-temporally programmed manner for DC-based cancer immunotherapy.

Blockade of the T-type calcium channel (TCC), which is expressed in the renal efferent arterioles of the juxtamedullary nephron and vasa recta, has been shown to protect against renal injury. Studies were designed to determine the effects of a specific TCC blocker, R(−) efonidipine R(−)EFO, on the regulation of renal circulation.

Abstract: In this paper, the global asymptotic stability of BAM neural networks with delays is investigated by utilizing Lyapunov functional method and the linear matrix inequality (LMI) technique. Distinct difference from other analytical approaches lies in “linearization” of the neural network model, by which the considered neural network model is transformed into a linear system. Then, a process, which is called parameterized first-order model transformation, is used to transform the linear system. Novel criteria for global asymptotic stability of the unique equilibrium point of BAM neural networks with delays are obtained. The results are related to the size of delays. The obtained results are less conservative and restrictive than those established in the earlier references. A numerical example is given to show the effectiveness of our proposed method. [Copyright &y& Elsevier]

Methylglyoxal, a metabolite of the glycolysis pathway, may play an important role in the development of diabetes and hypertension, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether methylglyoxal could directly induce insulin resistance and salt sensitivity in Sprague–Dawley rats.

The mouse mammary tumor virus (MMTV) provirus was found to target the Notch1gene, producing insertional mutations in mammary tumors of MMTV/neu transgenic (Tg) mice. In these mammary tumors, the Notch1gene is truncated upstream of the transmembrane domain, and the resulting Notch1 in-tracellular domain (Notch1intra), deleted of most extracellular sequences, is overexpressed. Although Notch1intratransforms mammary epithelial cells in vitro, its role in mammary gland tumor formation in vivowas not studied. Therefore, we generated MMTV/Notch1intraTg mice that overexpress murine Notch1intrain the mammary glands. We observed that MMTV/Notch1intraTg females were unable to feed their pups because of impaired ductal and lobulo-alveolar mammary gland development. This was associated with decreased proliferation of ductal and alveolar epithelial cells during rapid expansion at puberty and in early pregnancy, as well as decreased production of β-casein. Notch1intrarepressed expression of the β-casein gene promoter, as assessed in vitrowith a β-casein/luciferase reporter construct. The MMTV/Notch1intraTg females developed mammary gland tumors, confirming the oncogenic po-tential of Notch1intrain vivo. Furthermore, MMTV/Notch3intraTg mice exhibited a very similar pheno-type. Thus, these Tg mice represent novel models for studying the role of Notch1 or Notch3 in the development and transformation of the mammary gland.

ABSTRACTOne of the most important factors that limit the potency of CD8+cytotoxic T lymphocyte (CTL) responses is the tumor microenvironment (TME). Here, we provide evidence that miR-26a is a negative regulator of CTL function in the TME. Specifically, we identified miR-26a as a crucial suppressor gene in CTLs from the TME, as we found that, miR-26a expression was elevated in CTLs to respond to TME secretome stimulation. CTLs from miR-26a-transgenic mice showed impaired IFNγ and granzyme B production in response to their cognate antigen. Conversely, we found that miR-26a inhibition in CTLs could effectively increase the cytotoxicity and suppress tumor growth. Mechanically, we identified EZH2 as a direct target of miR-26a. miR-26a and EZH2 expression were found to be inversely correlated in CTLs, and the inhibition of EZH2 in CTLs impairs CTL function. These functional correlations were validated in a cohort of non-small cell lung cancer patients, indicating that the miR-26a-EZH2 axis is clinically relevant. Our findings suggested that miR-26a silencing as a novel strategy to improve the efficacy of CTL-based cancer immunotherapy.

Abstract: In this paper, the global exponential stability is investigated for the bi-directional associative memory networks with time delays. Several new sufficient conditions are presented to ensure global exponential stability of delayed bi-directional associative memory neural networks based on the Lyapunov functional method as well as linear matrix inequality technique. To the best of our knowledge, few reports about such “linearization” approach to exponential stability analysis for delayed neural network models have been presented in literature. The method, called parameterized first-order model transformation, is used to transform neural networks. The obtained conditions show to be less conservative and restrictive than that reported in the literature. Two numerical simulations are also given to illustrate the efficiency of our result. [Copyright &y& Elsevier]