Integrated physiological, transcriptomic and metabolomic analyses reveal the mechanism of peanut kernel weight reduction under waterlogging stress.

Waterlogging stress (WS) hinders kernel development and directly reduces peanut yield; however, the mechanism of kernel filling in response to WS remains unknown. The waterlogging-sensitive variety Huayu 39 was subjected to WS for 3 days at 7 days after the gynophores touched the ground (DAG). We found that WS affected kernel filling at 14, 21, and 28 DAG. WS decreased the average filling rate and kernel dry weight, while transcriptome sequencing and widely targeted metabolomic analysis revealed that WS inhibited the gene expression in starch and sucrose metabolism, which reduced sucrose input and transformation ability. Additionally, genes related to ethylene and melatonin synthesis and the accumulation of tryptophan and methionine were upregulated in response to WS. WS upregulated the expression of the gene encoding tryptophan decarboxylase (AhTDC), and overexpression of AhTDC in Arabidopsis significantly reduced the seed length, width, and weight. Therefore, WS reduced the kernel-filling rate, leading to a reduction in the 100-kernel weight. This survey informs the development of measures that alleviate the negative impact of WS on peanut yield and quality and provides a basis for exploring high-yield and high-quality cultivation, molecular-assisted breeding, and waterlogging prevention in peanut farming.

Centralized and Federated Models for the Analysis of Clinical Data.

The progress of precision medicine research hinges on the gathering and analysis of extensive and diverse clinical datasets. With the continued expansion of modalities, scales, and sources of clinical datasets, it becomes imperative to devise methods for aggregating information from these varied sources to achieve a comprehensive understanding of diseases. In this review, we describe two important approaches for the analysis of diverse clinical datasets, namely the centralized model and federated model. We compare and contrast the strengths and weaknesses inherent in each model and present recent progress in methodologies and their associated challenges. Finally, we present an outlook on the opportunities that both models hold for the future analysis of clinical data.

Clinical phenotypes of adult-onset Behçet's syndrome: a comprehensive cross-sectional study in China.

Behçet's syndrome (BS) is a variant vasculitis that can involve multiple organs with inflammatory manifestations. This study aimed to provide a more comprehensive analysis of the clinical phenotypes and characteristics of BS patients. We enrolled 2792 BS patients referred from China nationwide to Huadong Hospital Affiliated to Fudan University from October 2012 to December 2022. Detailed assessments of demographic information, clinical manifestations, laboratory results, gastroscopy, and medical imaging were conducted. Cluster analysis was performed based on 13 variables to determine the clinical phenotypes, and each phenotype was characterized according to the features of BS patients. A total of 1834 BS patients were included, while 958 invalid patients were excluded. The median age at onset was 31 years (IQR, 24-40 years), and the median disease duration was 10 years (IQR, 5-15 years). Eight clusters were identified, including mucocutaneous (n = 655, 35.7%), gastrointestinal (n = 363, 19.8%), articular (n = 184, 10%), ocular (n = 223, 12.2%), cardiovascular (n = 119, 6.5%), neurological (n = 118, 6.4%), vascular (n = 114, 6.2%), and hematological phenotype (n = 58, 3.2%). Ocular (RR = 1.672 (95% CI, 1.327-2.106); P < 0.001), gastrointestinal (RR = = 1.194 (95% CI, 1.031-1.383); P = 0.018), cardiovascular (RR = = 2.582 (95% CI, 1.842-3.620); P < 0.001), and vascular (RR = = 2.288 (95% CI, 1.600-3.272); P < 0.001) involvement were more prevalent in male BS patients, while the hematological (RR = 0.528 (95% CI, 0.360-0.776); P = 0.001) involvement was more common among female patients. BS presents significant heterogeneity and gender differences. The eight phenotypes of BS patients we propose hold the potential to assist clinicians in devising more personalized treatment and follow-up strategies. Key Points • This cluster analysis divided adult-onset BS into eight clinical phenotypes. • BS demonstrates a high level of clinical heterogeneity and gender differences. • Hematologic phenotypes of BS present distinctive clinical characteristics.

Selective Removal of Hemicellulose by Diluted Sulfuric Acid Assisted by Aluminum Sulfate.

Hemicellulose can be selectively removed by acid pretreatment. In this study, selective removal of hemicellulose was achieved using dilute sulfuric acid assisted by aluminum sulfate pretreatment. The optimal pretreatment conditions were 160 °C, 1.5 wt% aluminum sulfate, 0.7 wt% dilute sulfuric acid, and 40 min. A component analysis showed that the removal rate of hemicellulose and lignin reached 98.05% and 9.01%, respectively, which indicated that hemicellulose was removed with high selectivity by dilute sulfuric acid assisted by aluminum sulfate pretreatment. Structural characterizations (SEM, FTIR, BET, TGA, and XRD) showed that pretreatment changed the roughness, crystallinity, pore size, and functional groups of corn straw, which was beneficial to improve the efficiency of enzymatic hydrolysis. This study provides a new approach for the high-selectivity separation of hemicellulose, thereby offering novel insights for its subsequent high-value utilization.

Effects of the Charge Density of Nanopapers Based on Carboxymethylated Cellulose Nanofibrils Investigated by Complementary Techniques.

Cellulose nanofibrils (CNFs) with different charge densities were prepared and investigated by a combination of different complementary techniques sensitive to the structure and molecular dynamics of the system. The morphology of the materials was investigated by scanning electron microscopy (SEM) and X-ray scattering (SAXS/WAXS). The latter measurements were quantitatively analyzed yielding to molecular parameters in dependence of the charge density like the diameter of the fibrils, the distance between the fibrils, and the dimension of bundles of nanofibrils, including pores. The influence of water on the properties and the charge density is studied by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and broadband dielectric spectroscopy. The TGA measurements reveal two mass loss processes. The one at lower temperatures was related to the loss of water, and the second process at higher temperatures was related to the chemical decomposition. The resulting char yield could be correlated to the distance between the microfibrils. The DSC investigation for hydrated CNFs revealed three glass transitions due to the cellulose segments surrounded by water molecules in different states. In the second heating scan, only one broad glass transition is observed. The dielectric spectra reveal two relaxation processes. At low temperatures or higher frequencies, the ß-relaxation is observed, which is assigned to localized fluctuation of the glycosidic linkage. At higher temperatures and lower frequencies, the α-relaxation takes places. This relaxation is due to cooperative fluctuations in the cellulose segments. Both processes were quantitatively analyzed. The obtained parameters such as the relaxation rates were related to both the morphological data, the charge density, and the content of water for the first time.

Developing and validating machine learning-based prediction models for frailty occurrence in those with chronic obstructive pulmonary disease.

Background: Frailty is a medical syndrome caused by multiple factors, characterized by decreased strength, endurance, and diminished physiological function, resulting in increased susceptibility to dependence and/or death. Patients with chronic obstructive pulmonary disease (COPD) tend to be more vulnerable to frailty due to their physical and psychological burdens. Therefore, the aim of this study was to develop a reliable and accurate vulnerability risk prediction model for frailty in patients with COPD in order to improve the identification and prediction of patient frailty. The specific objectives of this study were to determine the prevalence of frailty in patients with COPD and develop a prediction model and evaluate its predictive power. Methods: Clinical information was analyzed using data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database, and 34 indicators, including behavioral factors, health status, mental health parameters, and various sociodemographic variables, were examined in the study. The adaptive synthetic sampling technique was used for unbalanced data. Three methods, ridge regressor, extreme gradient boosting (XGBoost) classifier, and random forest (RF) regressor, were used to filter predictors. Seven machine learning (ML) techniques including logistic regression (LR), support vector machines (SVM), multilayer perceptron, light gradient-boosting machine, XGBoost, RF, and K-nearest neighbors were used to analyze and determine the optimal model. For customized risk assessment, an online predictive risk modeling website was created, along with Shapley additive explanation (SHAP) interpretations. Results: Depression, smoking, gender, social activities, dyslipidemia, asthma, and residence type (urban vs. rural) were predictors for the development of frailty in patients with COPD. In the test set, the XGBoost model had an area under the curve of 0.942 (95% confidence interval: 0.925-0.959), an accuracy of 0.915, a sensitivity of 0.873, and a specificity of 0.911, indicating that it was the best model. Conclusions: The ML predictive model developed in this study is a useful and easy-to-use instrument for assessing the vulnerability risk of patients with COPD and may aid clinical physicians in screening high-risk patients.

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Covalent Organic Framework with Donor1-Acceptor-Donor2 Motifs Regulating Local Charge of Intercalated Single Cobalt Sites for Photocatalytic CO2 Reduction to Syngas.

Covalent organic framework (COF) has attracted increasing interest in photocatalytic CO2 reduction, but it remains a challenge to achieve high conversion efficiency owing to the insufficient active site and fast charge recombination. Rationally optimizing the electronic structures of COF to regulate the local charge of active sites precisely is the key point to improving catalytic performance. Herein, intercalated single Co sites coordinated by imine-N motifs have been designed by using trinuclear copper-based imine-COFs with distinct electronic moieties via a molecular engineering strategy. It is confirmed that the charge delivery property and local charge distribution of these heterometallic frameworks can be profoundly influenced by electronic structures. Among these featured structures with mixed-state copper clusters, Co/Cu3-TPA-COF stands out for an exceptional photocatalytic CO2 reduction activity and tunable syngas (CO/H2) ratio by changing various bipyridines. Experimental and theoretical results indicate that interlayer Co-imine N motifs on the donor1-acceptor-donor2 structures facilitate the formation of a highly separated electron-hole state, which effectively induces the oriented electron transfer from dual electron donors to Co centers, achieving an enhanced CO2 activation and reduction. This work opens up an avenue for the design of high-performance COF-based catalysts for photocatalytic CO2 reduction.

Annual performance evaluation of a hybrid concentrated solar-micro gas turbine based on off-design simulation.

As the adoption of solar hybrid systems continues to rise due to their potential to compensate for the fluctuation of solar irradiation, it becomes imperative to accurately evaluate their performance, considering the variation of off-design conditions. This paper introduces a detailed analysis method for evaluating the annual performance of a solar-MGT system under transient boundary conditions for a whole-year operation range. A hybrid system of a micro gas turbine, recuperator, and solar dish is considered, and an off-design simulation model is developed and verified with available experimental results. Two different configurations for a recuperated cycle are considered, and simulations are conducted for a test case in Pretoria, SA. The results for Jun.21 and Dec.21 as low and high solar energy days are reported with more details to compare the configurations and demonstrate the effect of ambient temperature on the heat loss of the solar receiver and the overall performance of the system. The alternative configuration reduces heat loss with a lower temperature receiver but has higher fuel consumption compared to the conventional configuration. Operating strategies for different hours of operation from 1 h to 24 h per day are simulated for 365 days, based on real meteorological data, and compared with the operating in solar available hours. It is shown that the whole-year simulation of the system considering the variation of boundary conditions can change the estimation of fuel consumption by 25 %.

Electroacupuncture pre-treatment exerts a protective effect on LPS-induced cardiomyopathy in mice through the delivery of miR-381 via exosomes.

OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.

Evaluating site-of-care-related racial disparities in kidney graft failure using a novel federated learning framework.

OBJECTIVES: Racial disparities in kidney transplant access and posttransplant outcomes exist between non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients in the United States, with the site of care being a key contributor. Using multi-site data to examine the effect of site of care on racial disparities, the key challenge is the dilemma in sharing patient-level data due to regulations for protecting patients' privacy. MATERIALS AND METHODS: We developed a federated learning framework, named dGEM-disparity (decentralized algorithm for Generalized linear mixed Effect Model for disparity quantification). Consisting of 2 modules, dGEM-disparity first provides accurately estimated common effects and calibrated hospital-specific effects by requiring only aggregated data from each center and then adopts a counterfactual modeling approach to assess whether the graft failure rates differ if NHB patients had been admitted at transplant centers in the same distribution as NHW patients were admitted. RESULTS: Utilizing United States Renal Data System data from 39 043 adult patients across 73 transplant centers over 10 years, we found that if NHB patients had followed the distribution of NHW patients in admissions, there would be 38 fewer deaths or graft failures per 10 000 NHB patients (95% CI, 35-40) within 1 year of receiving a kidney transplant on average. DISCUSSION: The proposed framework facilitates efficient collaborations in clinical research networks. Additionally, the framework, by using counterfactual modeling to calculate the event rate, allows us to investigate contributions to racial disparities that may occur at the level of site of care. CONCLUSIONS: Our framework is broadly applicable to other decentralized datasets and disparities research related to differential access to care. Ultimately, our proposed framework will advance equity in human health by identifying and addressing hospital-level racial disparities.

Investigation on acceptor-donor co-doped SnO2 nanoparticles enriched with oxygen vacancies: a capacitive humidity sensor for respiration detection.

In this work, we develop a novel capacitive humidity sensor based on Al-Si acceptor-donor co-doped SnO2 for real-time monitoring of ambient humidity and human respiration. XRD measurements reveal that all samples exhibit a tetragonal rutile phase and the crystallite size of SnO2 decreases with increasing Al-Si content. The high intensity of the Raman peak at 762 cm-1 confirms the presence of bridging mode oxygen vacancies in (Al + Si)0.02Sn0.98O2. The EPR results show that the amount of singly ionized oxygen vacancies increases after the introduction of Al-Si. Both types and amounts of oxygen vacancy defects are particularly sensitive to the adsorption of water molecules. Moreover, according to DFT calculations, the contribution of the Si 3s orbital and Al 3s orbital to the band edge verifies the formation of acceptor-donor complexes in Al-Si co-doped SnO2. The humidity sensing results reveal that the (Al + Si)0.02Sn0.98O2 humidity sensor shows high sensitivity (S = 839), low hysteresis (1.94%) and fast response/recovery times (25 s/5 s). The respiratory intervals during shallow, medium and deep breathing states of (Al + Si)0.02Sn0.98O2 were measured at 2.8 s, 3.8 s and 4.5 s, respectively. The chemical mechanism for the enhancement of humidity sensing performance corresponding to the oxygen vacancy defects induced by Al-Si interplay is proposed.

Bacillus subtilis: current and future modification strategies as a protein secreting factory.

Bacillus subtilis is regarded as a promising microbial expression system in bioengineering due to its high stress resistance, nontoxic, low codon preference and grow fast. The strain has a relatively efficient expression system, as it has at least three protein secretion pathways and abundant molecular chaperones, which guarantee its expression ability and compatibility. Currently, many proteins are expressed in Bacillus subtilis, and their application prospects are broad. Although Bacillus subtilis has great advantages compared with other prokaryotes related to protein expression and secretion, it still faces deficiencies, such as low wild-type expression, low product activity, and easy gene loss, which limit its large-scale application. Over the years, many researchers have achieved abundant results in the modification of Bacillus subtilis expression systems, especially the optimization of promoters, expression vectors, signal peptides, transport pathways and molecular chaperones. An optimal vector with a suitable promoter strength and other regulatory elements could increase protein synthesis and secretion, increasing industrial profits. This review highlights the research status of optimization strategies related to the expression system of Bacillus subtilis. Moreover, research progress on its application as a food-grade expression system is also presented, along with some future modification and application directions.

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice.

Purpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown. Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen. Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation. Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.

Impact of sarcopenia on variceal rebleeding in patients after endoscopic therapy: a multicenter retrospective cohort study based on propensity score matching.

BACKGROUND: Sarcopenia is a common complication of liver cirrhosis and can be used for predicting dismal prognostic outcomes. This study aimed to evaluate the role of sarcopenia in rebleeding and mortality of liver cirrhosis patients after endoscopic therapy. METHODS: The liver cirrhosis patients who received endoscopic treatment were enrolled. Propensity score matching (PSM) was used to overcome selection bias. Two-year rebleeding episodes and mortality after endoscopic therapy were recorded. RESULTS: A total of 109 (32.4%) sarcopenia patients were reported. Before PSM, the frequency of rebleeding was significantly higher in the sarcopenia group relative to the non-sarcopenia group (41.3% vs. 15.9%, p < 0.001). Moreover, the multivariable analysis revealed that sarcopenia (p < 0.001, HR:2.596, 95% CI 1.591-4.237) was independently associated with a 2-year rebleeding episode. After PSM, the sarcopenia group exhibited an increased rebleeding rate as compared with non-sarcopenia group (44.4% vs. 15.3%, p < 0.001). According to multivariable analysis, sarcopenia (p < 0.001, HR:3.490, 95% CI 1.756-6.938) was identified as a significant predictor for 2-year rebleeding. CONCLUSION: Sarcopenia was significantly associated with a high 2-year rebleeding rate in liver cirrhosis patients after endoscopic treatment. Therefore, the precise evaluation of a patient's nutritional status, including sarcopenia becomes mandatory before endoscopic treatment.

Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in quadrivalent influenza vaccine vaccinated mice.

There are considerable avenues through which currently licensed influenza vaccines could be optimized. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus-derived defective interfering (SDI) RNA, a RIG-I agonist; and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), a TLR7/8 agonist. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating direct delivery of SDI RNA to the cytosol, where RIG-I sensing induces inflammatory and type I interferon responses. We previously tested SDI RNA and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here, we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The LNPs were incorporated with SDI RNA to determine its potential as a combination adjuvant with IMDQ-PEG-Chol by evaluating the host immune response to vaccination and infection in immunized BALB/c mice. Adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated with quadrivalent inactivated influenza vaccine (QIV), showing robust induction of antibody titers and T-cell responses. Depending on the adjuvant combination and LNP formulation, humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with the protective responses to viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was tested by challenging mice with a vaccine-matched strain of influenza A virus A/Singapore/gp1908/2015 IVR-180 (H1N1). Groups that received either LNP formulated with SDI or IMDQ-PEG-Chol, or both, showed very low levels of viral replication in their lungs at 5 days post-infection (DPI). These studies provide evidence that the combination of vaccines with LNPs and/or adjuvants promote antigen-specific cellular responses that can contribute to protection upon infection. Interestingly, we observed differences in humoral and cellular responses to vaccination between different groups receiving K-Ac7-Dsa or S-Ac7-Dog lipids in LNP formulations. The differences were also reflected in inflammatory responses in lungs of vaccinated animals to infection, depending on LNP formulations. Therefore, this study suggests that the composition of the LNPs, particularly the ionizable lipid, plays an important role in inducing inflammatory responses in vivo, which is important for vaccine safety and to prevent adverse effects upon viral exposure.

Correlation Between Li-Fe Anti-Site and Memory Effect of LiFePO4 in Li-Ion Batteries.

In Li-ion batteries, the origin of memory effect in Al-doped Li4Ti5O12 has been revealed as the reversible Al-ion switching between 8a and 16c sites in the spinel structure, but it is still not clear about that for olivine LiFePO4, which is one of the most important cathode materials. In this work, a series of Na-doped and Ti-doped LiFePO4 are prepared in a high-temperature solid-state method, electrochemically investigated in Li-ion batteries and characterized by X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Magic-Angle-Spinning Nuclear Magnetic Resonance (MAS NMR). Compared with non-doped LiFePO4, the Ti doping can simultaneously suppress the memory effect and the Li-Fe anti-site, while they are simultaneously enhanced by the Na doping. Meanwhile, the Ti doping improves the electrochemical performance of LiFePO4, opposite to the Na doping. Accordingly, a schematic diagram of phase transition is proposed to interpret the memory effect of LiFePO4, in which the memory effect is attributed to the defect of Li-Fe anti-site.

Interfacial Heterojunction Enables High Efficient PbS Quantum Dot Solar Cells.

Colloidal quantum dots (CQDs) are promising optoelectronic materials for solution-processed thin film optoelectronic devices. However, the large surface area with abundant surface defects of CQDs and trap-assisted non-radiative recombination losses at the interface between CQDs and charge-transport layer limit their optoelectronic performance. To address this issue, an interface heterojunction strategy is proposed to protect the CQDs interface by incorporating a thin layer of polyethyleneimine (PEIE) to suppress trap-assisted non-radiative recombination losses. This thin layer not only acts as a protective barrier but also modulates carrier recombination and extraction dynamics by forming heterojunctions at the buried interface between CQDs and charge-transport layer, thereby enhancing the interface charge extraction efficiency. This enhancement is demonstrated by the shortened lifetime of carrier extraction from 0.72 to 0.46 ps. As a result, the resultant PbS CQD solar cells achieve a power-conversion-efficiency (PCE) of 13.4% compared to 12.2% without the heterojunction.

Pioglitazone reduces serum ketone bodies in sodium-glucose cotransporter-2 inhibitor-treated non-obese type 2 diabetes: A single-centre, randomized, crossover trial.

AIM: To examine the effects of the thiazolidinedione (TZD) pioglitazone on reducing ketone bodies in non-obese patients with T2DM treated with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin. METHODS: Crossover trials with two periods, each treatment period lasting 4 weeks, with a 4-week washout period, were conducted. Participants were randomly assigned in a 1:1 ratio to receive pioglitazone combined with canagliflozin (PIOG + CANA group) versus canagliflozin monotherapy (CANA group). The primary outcome was change (Δ) in ß-hydroxybutyric acid (ß-HBA) before and after the CANA or PIOG + CANA treatments. The secondary outcomes were Δchanges in serum acetoacetate and acetone, the rate of conversion into urinary ketones, and Δchanges in factors related to SGLT2 inhibitor-induced ketone body production including non-esterified fatty acids (NEFAs), glucagon, glucagon to insulin ratio, and noradrenaline (NA). Analyses were performed in accordance with the intention-to-treat principle. RESULTS: Twenty-five patients with a mean age of 49 ± 7.97 years and a body mass index of 25.35 ± 2.22 kg/m2 were included. One patient discontinued the study during the washout period. Analyses revealed a significant increase in the levels of serum ketone bodies and an elevation in the rate of conversion into urinary ketones after both interventions. However, differernces in levels of ketone bodies (except for acetoacetate) in the PIOG + CANA group were significantly smaller than in the CANA group (219.84 ± 80.21 µmol/L vs. 317.69 ± 83.07 µmol/L, p < 0.001 in ß-HBA; 8.98 ± 4.17 µmol/L vs. 12.29 ± 5.27 µmol/L, p = 0.018 in acetone). NEFA, glucagon, glucagon to insulin ratio, and NA were also significantly increased after both CANA and PIOG + CANA treatments; while only NEFAs demonstrated a significant difference between the two groups. Correlation analyses revealed a significant association between the difference in Δchanges in serum NEFA levels with the differences in Δchanges in ketones of ß-HBA and acetoacetate. CONCLUSION: Supplementation of pioglitazone could alleviate canagliflozin-induced ketone bodies. This benefit may be closely associated with decreased substrate NEFAs rather than other factors including glucagon, fasting insulin and NA.

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.