E3 ubiquitin ligase DTX2 fosters ferroptosis resistance via suppressing NCOA4-mediated ferritinophagy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains the foremost contributor to cancer-related fatalities globally, with limited effective therapeutic modalities. Recent research has shed light on the role of ferroptosis in various types of cancers, offering a potential avenue for improving cancer therapy. Herein, we identified E3 ubiquitin ligase deltex 2 (DTX2) as a potential therapeutic target candidate implicated in promoting NSCLC cell growth by inhibiting ferroptosis. Our investigation revealed a significant upregulation of DTX2 in NSCLC cells and tissues, which was correlated with poor prognosis. Downregulation of DTX2 suppressed NSCLC cell growth both in vitro and in vivo, while its overexpression accelerated cell proliferation. Moreover, knockdown of DTX2 promoted ferroptosis in NSCLC cells, which was mitigated by DTX2 overexpression. Mechanistically, we uncovered that DTX2 binds to nuclear receptor coactivator 4 (NCOA4), facilitating its ubiquitination and degradation via the K48 chain, which subsequently dampens NCOA4-driven ferritinophagy and ferroptosis in NSCLC cells. Notably, DTX2 knockdown promotes cisplatin-induced ferroptosis and overcomes drug resistance of NSCLC cells. These findings underscore the critical role of DTX2 in regulating ferroptosis and NCOA4-mediated ferritinophagy, suggesting its potential as a novel therapeutic target for NSCLC.

The calcium signaling module CaM-IQM destabilizes IAA-ARF interaction to regulate callus and lateral root formation.

Induction of a pluripotent cell mass, called callus, from detached organs is an initial step in in vitro plant regeneration, during which phytohormone auxin-induced ectopic activation of a root developmental program has been shown to be required for subsequent de novo regeneration of shoots and roots. However, whether other signals are involved in governing callus formation, and thus plant regeneration capability, remains largely unclear. Here, we report that the Arabidopsis calcium (Ca2+) signaling module CALMODULIN IQ-MOTIF CONTAINING PROTEIN (CaM-IQM) interacts with auxin signaling to regulate callus and lateral root formation. We show that disruption of IQMs or CaMs retards auxin-induced callus and lateral root formation by dampening auxin responsiveness, and that CaM-IQM complexes physically interact with the auxin signaling repressors INDOLE-3-ACETIC ACID INDUCIBLE (IAA) proteins in a Ca2+-dependent manner. We further provide evidence that the physical interaction of CaM6 with IAA19 destabilizes the repressive interaction of IAA19 with AUXIN RESPONSE FACTOR 7 (ARF7), and thus regulates auxin-induced callus formation. These findings not only define a critical role of CaM-IQM-mediated Ca2+ signaling in callus and lateral root formation, but also provide insight into the interplay of Ca2+ signaling and auxin actions during plant regeneration and development.

The Complex Immune Cell Composition and Cellular Interaction in the Alveolar Compartment of Patients with Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by protein rich edema due to alveolar-capillary barrier dysfunction caused by inflammatory processes. Currently, our understanding of the inflammatory response in patients with ARDS is mainly based on assessment of the systemic compartment and preclinical studies. Investigations into the intricate network of immune cells and their critical functions in the alveolar compartment remain limited. However, with recent improvements in single cell analyses, our comprehensive understanding of the interactions between immune cells in the lungs has improved. In this review, we summarize the current knowledge about the cellular composition and interactions of different immune cell types within the alveolar space of patients with ARDS. Neutrophils and macrophages are the predominant immune cells in the alveolar space of ARDS patients. Yet, all immune cells present, including lymphocytes, participate in complex interactions, coordinate recruitment, modulate the lifespan and control apoptosis through various signaling pathways. Moreover, the cellular composition of alveolar immune cells is associated with clinical outcomes of ARDS patients. In conclusion, this synthesis advances our understanding of ARDS immunology, emphasizing the crucial role of immune cells within the alveolar space. Associations between cellular composition and clinical outcomes highlight the significance of exploring distinct alveolar immune cell subsets. Such exploration holds promise for uncovering novel therapeutic targets in ARDS pathophysiology, presenting avenues for enhancing clinical management and treatment strategies for ARDS patients. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Left Ventricular Dysfunction Associated With Brain Death: Results From the Donor Heart Study.

BACKGROUND: Left ventricular dysfunction in potential donors meeting brain death criteria often results in nonuse of donor hearts for transplantation, yet little is known about its incidence or pathophysiology. Resolving these unknowns was a primary aim of the DHS (Donor Heart Study), a multisite prospective cohort study. METHODS: The DHS enrolled potential donors by neurologic determination of death (n=4333) at 8 organ procurement organizations across the United States between February 2015 and May 2020. Data included medications administered, serial diagnostic tests, and transthoracic echocardiograms (TTEs) performed: (1) within 48 hours after brain death was formally diagnosed; and (2) 24±6 hours later if left ventricular (LV) dysfunction was initially present. LV dysfunction was defined as an LV ejection fraction <50% and was considered reversible if LV ejection fraction was >50% on the second TTE. TTEs were also examined for presence of LV regional wall motion abnormalities and their reversibility. We assessed associations between LV dysfunction, donor heart acceptance for transplantation, and recipient 1-year survival. RESULTS: An initial TTE was interpreted for 3794 of the 4333 potential donors by neurologic determination of death. A total of 493 (13%) of these TTEs showed LV dysfunction. Among those donors with an initial TTE, LV dysfunction was associated with younger age, underweight, and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and troponin levels. A second TTE was performed within 24±6 hours for a subset of donors (n=224) with initial LV dysfunction; within this subset, 130 (58%) demonstrated reversibility. Sixty percent of donor hearts with normal LV function were accepted for transplant compared with 56% of hearts with reversible LV dysfunction and 24% of hearts with nonreversible LV dysfunction. Donor LV dysfunction, whether reversible or not, was not associated with recipient 1-year survival. CONCLUSIONS: LV dysfunction associated with brain death occurs in many potential heart donors and is sometimes reversible. These findings can inform decisions made during donor evaluation and help guide donor heart acceptance for transplantation.

The alveolar fibroproliferative response in moderate to severe COVID-19-related acute respiratory distress syndrome and 1-yr follow-up.

COVID-19-related acute respiratory distress syndrome (ARDS) can lead to long-term pulmonary fibrotic lesions. Alveolar fibroproliferative response (FPR) is a key factor in the development of pulmonary fibrosis. N-terminal peptide of procollagen III (NT-PCP-III) is a validated biomarker for activated FPR in ARDS. This study aimed to assess the association between dynamic changes in alveolar FPR and long-term outcomes, as well as mortality in COVID-19 ARDS patients. We conducted a prospective cohort study of 154 COVID-19 ARDS patients. We collected bronchoalveolar lavage (BAL) and blood samples for measurement of 17 pulmonary fibrosis biomarkers, including NT-PCP-III. We assessed pulmonary function and chest computed tomography (CT) at 3 and 12 mo after hospital discharge. We performed joint modeling to assess the association between longitudinal changes in biomarker levels and mortality at day 90 after starting mechanical ventilation. 154 patients with 284 BAL samples were analyzed. Of all patients, 40% survived to day 90, of whom 54 completed the follow-up procedure. A longitudinal increase in NT-PCP-III was associated with increased mortality (HR 2.89, 95% CI: 2.55-3.28; P < 0.001). Forced vital capacity and diffusion for carbon monoxide were impaired at 3 mo but improved significantly at one year after hospital discharge (P = 0.03 and P = 0.004, respectively). There was no strong evidence linking alveolar FPR during hospitalization and signs of pulmonary fibrosis in pulmonary function or chest CT images during 1-yr follow-up. In COVID-19 ARDS patients, alveolar FPR during hospitalization was associated with higher mortality but not with the presence of long-term fibrotic lung sequelae within survivors.NEW & NOTEWORTHY This is the first prospective study on the longitudinal alveolar fibroproliferative response in COVID-19 ARDS and its relationship with mortality and long-term follow-up. We used the largest cohort of COVID-19 ARDS patients who had consecutive bronchoalveolar lavages and measured 17 pulmonary fibroproliferative biomarkers. We found that a higher fibroproliferative response during admission was associated with increased mortality, but not correlated with long-term fibrotic lung sequelae in survivors.

R-loops' m6A modification and its roles in cancers.

R-loops are three-stranded nucleic acid structures composed of an RNA-DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.

Identification and functional analysis of GmPasL regulating pod color in vegetable soybean.

BACKGROUND: Vegetable soybean is rich in nutrients and has a unique flavor. It is highly preferred by people because of its pharmacological activities, including those that regulate the intestines and lower blood pressure. The pod color of vegetable soybeans is an important quality that indicates their freshness and has a significant impact on their commercialization. RESULTS: In this study, pod color was evaluated in 301 vegetable soybean accessions collected from various regions. Genome-wide association analysis was carried out using the Mixed linear model (MLM), a total of 18 quantitative trait loci including 117 SNPs were detected. Two significant QTLs located on chromosomes 6 (qGPCL4 /qGPCa1/qGPCb2) and 18 (qGPCL10/qGPCb3) were consistently detected across different variables. Based on gene functional annotation, 30 candidate genes were identified in these two candidate intervals. Combined with transcriptome analysis, Glyma.18g241700 has been identified as a candidate gene for regulating pod color in vegetable soybeans. Glyma.18g241700 encodes a chlorophyll photosystem I subunit XI. which localizes to the chloroplast named GmPsaL, qRT-PCR analysis showed that GmPsaL was specifically highly expressed in developing pods. Furthermore, overexpression of GmPsaL in transgenetic Arabidopsis plants produced dark green pods. CONCLUSIONS: These findings may be useful for clarifying the genetic basis of the pod color of vegetable soybeans. The identified candidate genes may be useful for the genetic improvement of the appearance quality of vegetable soybeans.

Insights into a functional model of key deubiquitinases UBP12/13 in plants.

Understanding the complexities of protein ubiquitination is crucial, as it plays a multifaceted role in controlling protein stability, activity, subcellular localization, and interaction, which are central to diverse biological processes. Deubiquitinases (DUBs) serve to reverse ubiquitination, but research progress in plant DUBs is noticeably limited. Among existing studies, UBIQUITIN-SPECIFIC PROTEASE 12 (UBP12) and UBP13 have garnered attention for their extensive role in diverse biological processes in plants. This review systematically summarizes the recent advancements in UBP12/13 studies, emphasizing their function, and their substrate specificity, their relationship with E3 ubiquitin ligases, and the similarities and differences with their mammalian orthologue, USP7. By unraveling the molecular mechanisms of UBP12/13, this review offers in-depth insights into the ubiquitin-proteasome system (UPS) in plants and aims to catalyze further explorations and comprehensive understanding in this field.

Plasma and serum metabolic analysis of healthy adults shows characteristic profiles by subjects' sex and age.

INTRODUCTION: Pre-analytical factors like sex, age, and blood processing methods introduce variability and bias, compromising data integrity, and thus deserve close attention. OBJECTIVES: This study aimed to explore the influence of participant characteristics (age and sex) and blood processing methods on the metabolic profile. METHOD: A Thermo UPLC-TSQ-Quantiva-QQQ Mass Spectrometer was used to analyze 175 metabolites across 9 classes in 208 paired serum and lithium heparin plasma samples from 51 females and 53 males. RESULTS: Comparing paired serum and plasma samples from the same cohort, out of the 13 metabolites that showed significant changes, 4 compounds related to amino acids and derivatives had lower levels in plasma, and 5 other compounds had higher levels in plasma. Sex-based analysis revealed 12 significantly different metabolites, among which most amino acids and derivatives and nitrogen-containing compounds were higher in males, and other compounds were elevated in females. Interestingly, the volcano plot also confirms the similar patterns of amino acids and derivatives higher in males. The age-based analysis suggested that metabolites may undergo substantial alterations during the 25-35-year age range, indicating a potential metabolic turning point associated with the age group. Moreover, a more distinct difference between the 25-35 and above 35 age groups compared to the below 25 and 25-35 age groups was observed, with the most significant compound decreased in the above 35 age groups. CONCLUSION: These findings may contribute to the development of comprehensive metabolomics analyses with confounding factor-based adjustment and enhance the reliability and interpretability of future large-scale investigations.

PEGylation renders carnosine resistant to hydrolysis by serum carnosinase and increases renal carnosine levels.

Carnosine's protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH2). PEGylated carnosine (PEG-car) was used to study the hydrolysis of carnosine by human serum as well as to compare the pharmacokinetics of PEG-car and L-carnosine in mice after intravenous (IV) injection. While L-carnosine was rapidly hydrolyzed in human serum, PEG-car was highly resistant to hydrolysis. Addition of unconjugated PEG to carnosine or PEG-car did not influence hydrolysis of carnosine in serum. In mice PEG-car and L-carnosine exhibited similar pharmacokinetics in serum but differed in half-life time (t1/2) in kidney, with PEG-car showing a significantly higher t1/2 compared to L-carnosine. Hence, PEGylation of carnosine is an effective approach to prevent carnosine degradations and to achieve higher renal carnosine levels. However, further studies are warranted to test if the protective properties of carnosine are preserved after PEGylation.

Growth Modulation of High-Entropy Alloys for Electrocatalytic Methanol Oxidation Reaction.

High-entropy alloy (HEA) electrocatalysts have exhibited remarkable catalytic performance because of their synergistic interactions among multiple metals. However, the growth mechanism of HEAs remains elusive, primarily due to the constraints imposed by the current synthesis methodologies for HEAs. In this work, an innovative electrodeposition method was developed to fabricate Pt-based nanocomposites (Pt1Bi2Co1Cu1Ni1/CC), comprising HEA nanosheets and carbon cloths (CCs). The reaction system could be effectively monitored by taking samples out from the system during the reaction process, facilitating in-depth insight into the growth mechanism underlying the material formation. In particular, Pt1Bi2Co1Cu1Ni1/CC nanocomposites show superior methanol oxidation reaction (MOR) performance (mass activity up to 5.02 A mgPt-1). Upon structural analysis, the d-band center of Pt1Bi2Co1Cu1Ni1/CC is lower in comparison with that of Pt1Bi2/CC and Pt/CC, demonstrating the formation of a rich-electron structure. Both the uniformity of HEAs and the carbon-supported effect could provide additional active sites. These findings suggest that the strong electronic interaction within HEAs and additional active sites can effectively modulate the catalytic structure of Pt, which benefits the enhanced CO tolerance and MOR performance.

Precise Construction of the Triple-Phase Boundary and Its Antiphosphate Poisoning Effect in the Confined Region.

As a critical component for the oxygen reduction reaction (ORR), platinum (Pt) catalysts exhibit promising catalytic performance in High-temperature-proton exchange membrane fuel cells (HT-PEMFCs). Despite their success, HT-PEMFCs primarily utilize phosphoric acid-doped polybenzimidazole (PA-PBI) as the proton exchange membrane, and the phosphoric acid within the PBI matrix tends to leach onto the Pt-based layers, easily causing toxicity. Herein, we first propose UiO-66@Pt3Co1-T composites with precisely engineered interfacial structures. The UiO-66@Pt3Co1-T exhibits an octahedral porous framework with uniform structural dimensions and even distribution of surface nanoparticles, which demonstrate superior ORR performance compared to commercial Pt/C. The unique structure and morphology of the composites also exhibit a favorable half-wave potential in different concentrations of phosphoric acid electrolyte, regulated by the phosphoric acid adsorption site and intensity.This finding suggests that the incorporation of Co could effectively modulate the Pt d-band center, thereby enhancing the ORR performance. Furthermore, the selective adsorption of phosphoric acid by ZrO2 enables precise control over the phosphoric acid distribution. Notably, the retention of the octahedral framework post high-temperature treatment facilitates the establishment of dual transport pathways for gases and protons, leading to a stable and efficient triple-phase boundary.

Breath metabolomics for diagnosis of acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. AIM: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. METHODS: This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). RESULTS: A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. CONCLUSION: An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.

Cells in the liver microenvironment regulate the process of liver metastasis.

The research of liver metastasis is a developing field. The ability of tumor cells to invade the liver depends on the complicated interactions between metastatic cells and local subpopulations in the liver (including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells, and immune-related cells). These interactions are mainly mediated by intercellular adhesion and the release of cytokines. Cell populations in the liver microenvironment can play a dual role in the progression of liver metastasis through different mechanisms. At the same time, we can see the participation of liver parenchymal cells and nonparenchymal cells in the process of liver metastasis of different tumors. Therefore, the purpose of this article is to summarize the relationship between cellular components of liver microenvironment and metastasis and emphasize the importance of different cells in the occurrence or potential regression of liver metastasis.

Cracking the code of health security: unveiling the balanced indices through rank-ordered effect analysis.

BACKGROUND: Health security is a critical issue which involves multiple dimensions. It has received increasing attention in recent years, especially in China. In order to improve the national health level, China has made many efforts, such as the "Healthy China 2030" plan proposed several years ago. However, due to the complexity of its national conditions and the difficulty of index design, the results of these efforts are not significant. Therefore, it is necessary to construct a new measurement index system. METHODS: Based on the questionnaire of "Health China 2030", we have collected a total of 3,000 participants from all 31 provinces, autonomous regions, and municipalities in China. We used statistical methods such as multiple correspondence analysis and rank-ordered effect analysis to process the data. The balance index is constructed by a series of actions such as weight division, order calculation and ranking. RESULTS: Through multiple correspondence analysis, we can find that there was a close relation in the correspondence space between the satisfaction degrees 1, 2, and 3, while a far distance from satisfaction degrees 4 and 5. There were four positive and four negative indices separately based on the average expected level and four clusters after ordinal rank cluster analysis. Generally speaking, there are no prominent discrepancies across gender and residential areas. CONCLUSIONS: We created and examined balanced indicators for health security in China based on the "Health China 2030" questionnaire. The findings of this study give insight into the overall situation of health security in China and indicate opportunities for improvement.

Associations between dietary patterns and renal impairment in individuals with diabetes: a cross-sectional study.

BACKGROUND: A variety of chronic diseases are affected by diet. To our knowledge, few studies have investigated the relationship between dietary patterns and renal impairment in individuals with diabetes within an Asian population. This study aimed to assess the relationship between renal impairment and dietary patterns in individuals with diabetes within a Chinese population. METHODS: In this cross-sectional survey, we analysed data on 1522 participants with diabetes aged 18 years or older who took part in the China National Diabetic Chronic Complications Study. We utilised the Chinese Diabetes Complications Questionnaire, including the semiquantitative food frequency questionnaire (SQFFQ). We identified three dietary patterns using factor analysis: Chinese traditional, healthy and plant-based dietary patterns, and these dietary patterns were used to classify participants into four groups based on the quartiles of their scores. A decrease in the estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m2 ) and an increase in the albumin-to-creatinine ratio (ACR; ≥3 mg/mmol) were used as indicators of renal impairment. Binary logistic regression models were used to estimate the odds ratio (OR) of the highest quartile (Q4: high intake levels of each dietary pattern) for renal impairment compared to the lowest quartile (Q1: low intake levels of each dietary pattern). RESULTS: Among the 1522 participants, there was a 5.5% prevalence of low eGFR, with prevalence rates of 5.2% in men and 5.9% in women, yet the prevalence of albuminuria was as high as 47.9%. After adjusting for confounders, participants in Q4 of the plant-based dietary pattern had a smaller OR for renal impairment than those in Q1. CONCLUSIONS: Our findings demonstrated that a plant-based dietary pattern is associated with a reduced risk of renal impairment in a population with diabetes.

Dynamic Cytoophidia during Late-Stage Drosophila Oogenesis.

CTP synthase (CTPS) catalyzes the final step of de novo synthesis of CTP. CTPS was first discovered to form filamentous structures termed cytoophidia in Drosophila ovarian cells. Subsequent studies have shown that cytoophidia are widely present in cells of three life domains. In the Drosophila ovary model, our previous studies mainly focused on the early and middle stages, with less involvement in the later stages. In this work, we focus on the later stages of female germline cells in Drosophila. We use live-cell imaging to capture the continuous dynamics of cytoophidia in Stages 10-12. We notice the heterogeneity of cytoophidia in the two types of germline cells (nurse cells and oocytes), manifested in significant differences in morphology, distribution, and dynamics. Surprisingly, we also find that neighboring nurse cells in the same egg chamber exhibit multiple dynamic patterns of cytoophidia over time. Although the described dynamics may be influenced by the in vitro incubation conditions, our observation provides an initial understanding of the dynamics of cytoophidia during late-stage Drosophila oogenesis.

Identification of a Branch Number Locus in Soybean Using BSA-Seq and GWAS Approaches.

The determination of the soybean branch number plays a pivotal role in plant morphogenesis and yield components. This polygenic trait is subject to environmental influences, and despite its significance, the genetic mechanisms governing the soybean branching number remain incompletely understood. To unravel these mechanisms, we conducted a comprehensive investigation employing a genome-wide association study (GWAS) and bulked sample analysis (BSA). The GWAS revealed 18 SNPs associated with the soybean branch number, among which qGBN3 on chromosome 2 emerged as a consistently detected locus across two years, utilizing different models. In parallel, a BSA was executed using an F2 population derived from contrasting cultivars, Wandou35 (low branching number) and Ruidou1 (high branching number). The BSA results pinpointed a significant quantitative trait locus (QTL), designated as qBBN1, located on chromosome 2 by four distinct methods. Importantly, both the GWAS and BSA methods concurred in co-locating qGBN3 and qBBN1. In the co-located region, 15 candidate genes were identified. Through gene annotation and RT-qPCR analysis, we predicted that Glyma.02G125200 and Glyma.02G125600 are candidate genes regulating the soybean branch number. These findings significantly enhance our comprehension of the genetic intricacies regulating the branch number in soybeans, offering promising candidate genes and materials for subsequent investigations aimed at augmenting the soybean yield. This research represents a crucial step toward unlocking the full potential of soybean cultivation through targeted genetic interventions.

The XCL1-Mediated DNA Vaccine Targeting Type 1 Conventional Dendritic Cells Combined with Gemcitabine and Anti-PD1 Antibody Induces Potent Antitumor Immunity in a Mouse Lung Cancer Model.

With the advent of cancer immunotherapy, there is a growing interest in vaccine development as a means to activate the cellular immune system against cancer. Despite the promise of DNA vaccines in this regard, their effectiveness is hindered by poor immunogenicity, leading to modest therapeutic outcomes across various cancers. The role of Type 1 conventional dendritic cells (cDC1), capable of cross-presenting vaccine antigens to activate CD8+T cells, emerges as crucial for the antitumor function of DNA vaccines. To address the limitations of DNA vaccines, a promising approach involves targeting antigens to cDC1 through the fusion of XCL1, a ligand specific to the receptor XCR1 on the surface of cDC1. Here, female C57BL/6 mice were selected for tumor inoculation and immunotherapy. Additionally, recognizing the complexity of cancer, this study explored the use of combination therapies, particularly the combination of cDC1-targeted DNA vaccine with the chemotherapy drug Gemcitabine (Gem) and the anti-PD1 antibody in a mouse lung cancer model. The study's findings indicate that fusion antigens with XCL1 effectively enhance both the immunogenicity and antitumor effects of DNA vaccines. Moreover, the combination of the cDC1-targeted DNA vaccine with Gemcitabine and anti-PD1 antibody in the mouse lung cancer model demonstrates an improved antitumor effect, leading to the prolonged survival of mice. In conclusion, this research provides important support for the clinical investigation of cDC1-targeting DNA vaccines in combination with other therapies.

Fully sp2 Carbon-Conjugated Covalent Organic Frameworks with Multiple Active Sites for Advanced Lithium-Ion Battery Cathodes.

Covalent organic frameworks (COFs) hold great promise for rechargeable batteries. However, the synthesis of COFs with abundant active sites, excellent stability, and increased conductivity remains a challenge. Here, chemically stable fully sp2 carbon-conjugated COFs (sp2c-COFs) with multiple active sites are designed by the polymerization of benzo[1,2-b:3,4-b':5,6-b'']trithiophene-2,5,8-tricarbaldehyde) (BTT) and s-indacene-1,3,5,7(2H,6H)-tetrone (ICTO) (denoted as BTT-ICTO). The morphology and structure of the COF are precisely regulated from "butterfly-shaped" to "cable-like" through an in situ controllable growth strategy, significantly promoting the exposure and utilization of active sites. When the unique "cable-like" BTT-ICTO@CNT is employed as lithium-ion batteries (LIBs) cathode, it exhibits exceptional capacity (396 mAh g-1 at 0.1 A g-1 with 97.9 % active sites utilization rate), superb rate capacity (227 mAh g-1 at 5.0 A g-1), and excellent cycling performance (184 mAh g-1 over 8000 cycles at 2.0 A g-1 with 0.00365 % decay rate per cycle). The lithium storage mechanism of BTT-ICTO is exhaustively revealed by in situ Fourier transform infrared, in situ Raman, and density functional theory calculations. This work provides in-depth insights into fully sp2c-COFs with multiple active sites for high-performance LIBs.