Tumor-Specific Nano-Herb Delivery System with High L-Arginine Loading for Synergistic Chemo and Gas Therapy against Cervical Cancer.

Cancer metastasis poses significant challenges in current clinical therapy. Osthole (OST) has demonstrated efficacy in treating cervical cancer and inhibiting metastasis. Despite these positive results, its limited solubility, poor oral absorption, low bioavailability, and photosensitivity hinder its clinical application. To address this limitation, a glutathione (GSH)-responded nano-herb delivery system (HA/MOS@OST&L-Arg nanoparticles, HMOA NPs) is devised for the targeted delivery of OST with cascade-activatable nitric oxide (NO) release. The HMOA NPs system is engineered utilizing enhanced permeability and retention (EPR) effects and active targeting mediated by hyaluronic acid (HA) binding to glycoprotein CD44. The cargoes, including OST and L-Arginine (L-Arg), are released rapidly due to the degradation of GSH-responsive mesoporous organic silica (MOS). Then abundant reactive oxygen species (ROS) are produced from OST in the presence of high concentrations of NAD(P)H quinone oxidoreductase 1 (NQO1), resulting in the generation of NO and subsequently highly toxic peroxynitrite (ONOO-) by catalyzing guanidine groups of L-Arg. These ROS, NO, and ONOO- molecules have a direct impact on mitochondrial function by reducing mitochondrial membrane potential and inhibiting adenosine triphosphate (ATP) production, thereby promoting increased apoptosis and inhibiting metastasis. Overall, the results indicated that HMOA NPs has great potential as a promising alternative for the clinical treatment of cervical cancer.

Association of sleep duration with Visceral Adiposity Index: a cross-sectional study based on the NHANES 2007-2018.

OBJECTIVE: We aimed to assess the associations between sleep duration and Visceral Adiposity Index (VAI). DESIGN: Cross-sectional study. SETTING: The National Health and Nutrition Examination Survey (2007-2018). PARTICIPANTS: A total 11 252 eligible participants who have complete information for sleep duration and VAI. OUTCOME MEASURE: The VAI index, which is sex-specific and takes into consideration factors such as waist circumference, body mass index, high-density lipoprotein cholesterol and triglycerides, was calculated in accordance with prior research. Multiple linear regressions and subgroup analyses were employed to evaluate the connection between the duration of sleep and the VAI. RESULTS: The mean sleep duration and VAI of included participants were 7.05 hours/day and 2.03, respectively. After adjusting for the sociodemographic, lifestyle and other covariates, short sleep was significantly linked to increased VAI (ß=0.15, 95% CI 0.01 to 0.28) in relation to middle sleep duration, whereas no significant association was found between long sleep duration and VAI. An L-shaped relationship was observed between sleep duration and VAI. When sleep duration was less than 7.5 hours/day, a negative association between sleep duration and VAI was obvious. However, when sleep duration was >7.5 hours/day, VAI was increased with a longer sleep duration, although it was not significant. CONCLUSIONS: An L-shaped relationship was observed between sleep duration and VAI, with insufficient sleep, being independently linked to a higher VAI. This implies that sleep deprivation might be associated with visceral adipose distribution and disfunction.

Inactivation of Myostatin Delays Senescence via TREX1-SASP in Bovine Skeletal Muscle Cells.

The myostatin (MSTN) gene also regulates the developmental balance of skeletal muscle after birth, and has long been linked to age-related muscle wasting. Many rodent studies have shown a correlation between MSTN and age-related diseases. It is unclear how MSTN and age-associated muscle loss in other animals are related. In this study, we utilized MSTN gene-edited bovine skeletal muscle cells to investigate the mechanisms relating to MSTN and muscle cell senescence. The expression of MSTN was higher in older individuals than in younger individuals. We obtained consecutively passaged senescent cells and performed senescence index assays and transcriptome sequencing. We found that senescence hallmarks and the senescence-associated secretory phenotype (SASP) were decreased in long-term-cultured myostatin inactivated (MT-KO) bovine skeletal muscle cells (bSMCs). Using cell signaling profiling, MSTN was shown to regulate the SASP, predominantly through the cycle GMP-AMP synthase-stimulator of antiviral genes (cGAS-STING) pathway. An in-depth investigation by chromatin immunoprecipitation (ChIP) analysis revealed that MSTN influenced three prime repair exonuclease 1 (TREX1) expression through the SMAD2/3 complex. The downregulation of MSTN contributed to the activation of the MSTN-SMAD2/3-TREX1 signaling axis, influencing the secretion of SASP, and consequently delaying the senescence of bSMCs. This study provided valuable new insight into the role of MSTN in cell senescence in large animals.

Comparative Mitogenome of Phylogenetic Relationships and Divergence Time Analysis within Potamanthidae (Insecta: Ephemeroptera).

Potamanthidae belongs to the superfamily Ephemeroidea but has no complete mt genome released in the NCBI (except for two unchecked and one partial mt genome). Since the sister clade to Potamanthidae has always been controversial, we sequenced seven mt genomes of Potamanthidae (two species from Rhoenanthus and five species from Potamanthus) in order to rebuild the phylogenetic relationships of Potamanthidae in this study. The divergence time of Potamanthidae was also investigated by utilizing five fossil calibration points because of the indeterminate origin time. In addition, because Rhoenanthus coreanus and Potamanthus luteus are always in low-temperature environments, we aimed to explore whether these two species were under positive selection at the mt genome level. Amongst the 13 PCGs, CGA was used as the start codon in COX1, whereas other genes conformed to initiating with an ATN start codon. From this analysis, UUA (L), AUU (I), and UUU (F) had the highest usage. Furthermore, the DHU arm was absent in the secondary structure of S1 in all species. By combining the 13 PCGs and 2 rRNAs, we reconstructed the phylogenetic relationship of Potamanthidae within Ephemeroptera. The monophyly of Potamanthidae and the monophyly of Rhoenanthus and Potamanthus were supported in the results. The phylogenetic relationship of Potamanthidae + (Ephemeridae + Polymitarcyidae) was also recovered with a high prior probability. The divergence times of Potamanthidae were traced to be 90.44 Mya (95% HPD, 62.80-121.74 Mya), and the divergence times of Rhoenanthus and Potamanthus originated at approximately 64.77 Mya (95% HPD, 43.82-88.68 Mya), thus belonging to the late Pliocene Epoch or early Miocene Epoch. In addition, the data indicated that R. coreanus was under negative selection and that ATP8 and ND2 in Potamanthidae had a high evolutionary rate.

From cup to clock: exploring coffee's role in slowing down biological aging.

Background: Previous research has proposed that coffee consumption may have potential health benefits, yet the effect of coffee on one's biological age has not been determined to date. The purpose of this study is to investigate the influence of coffee drinking on biological aging. Methods: Participants were chosen from the National Health and Nutrition Examination Survey (NHANES) and had to meet the selection criteria. Coffee consumption was evaluated through two 24-hour dietary questionnaires. Biological age was measured using both the PhenoAge and KDM-BA algorithms. Multiple linear and logistic regression models were adopted to analyze the association of coffee consumption with biological aging. Results: A total of 13 384 participants with an average daily coffee consumption of 1.73 cups were included. Participants with higher coffee consumption tended to be older, male, non-Hispanic white; had a higher educational level beyond high school; were more likely to be married; had better financial status; and were less likely to smoke or engage in excessive drinking. These individuals with higher coffee consumption exhibited a younger biological age in relation to their chronological age, as indicated by lower mean advancements in PhenoAge and KDM-BA scores. Furthermore, coffee intake was found to be inversely related to PhenoAge and KDM-BA progressions, as well as to the chances of accelerated biological aging, both in unadjusted and adjusted models. These associations remained consistent across all age and gender groups. Additionally, some heterogeneity was also observed among body mass index and physical activity categories. Conclusions: Coffee drinking was inversely related to biological age advancements and the likelihood of accelerated biological aging. Moderate coffee consumption may offer substantial benefits in reducing biological aging.

Effects of Anti-Seizure Medication on Neuregulin-1 Gene and Protein in Patients with First-Episode Focal Epilepsy.

Introduction: Neuregulin-1 (NRG-1) appears to play a role in the pathogenesis of several neuropsychiatric disorders, including epilepsy. We conducted a study to investigate the effect of anti-seizure medication on NRG-1 mRNA and NRG-1 protein levels in patients with first-episode focal epilepsy. Methods: The levels of NRG-1 mRNA isoforms (type I, II, III, and IV) in peripheral blood mononuclear cells (PBMCs) of 39 healthy controls, 39 first-episode focal epilepsy patients before anti-seizure medication (ASM) therapy and four weeks after administration of ASM were measured by RT-qPCR, and the levels of NRG-1 protein in the serum of samples of each group were determined using ELISA. In addition the relationship between efficacy, NRG-1 mRNA expression, and NRG-1 protein expression was analyzed. Results: The levels of NRG-1 mRNA progressively increased in patients with first-episode focal epilepsy treated with ASM and were distinctly different from those before medication, but remained lower than in healthy controls (all P < 0.001). Before and after drug administration, NRG-1 protein levels were substantially higher in epileptic patients than in healthy controls, and no significant changes were detected with prolonged follow-up (P < 0.001). Patients with epilepsy who utilized ASM were able to control seizures with an overall efficacy of 97.4%. There was a negative correlation between NRG-1 mRNA levels and efficacy: as NRG-1 mRNA levels increased, seizures reduced (all P < 0.05). Conclusion: Our research indicated that NRG-1 may play a role in the pathophysiology of epilepsy. NRG-1 mRNA may provide ideas for the discovery of novel epilepsy therapeutic markers and therapeutic targets for novel ASM.

Influencing Factors of Healthy Aging Risk Assessed Using Biomarkers: A Life Course Perspective.

Assessing individual risks of healthy aging using biomarkers and identifying associated factors have become important areas of research. In this study, we conducted a literature review of relevant publications between 2018 and 2023 in both Chinese and English databases. Previous studies have predominantly used single biomarkers, such as C-reactive protein, or focused on specific life course stages and factors such as socioeconomic status, mental health, educational levels, and unhealthy lifestyles. By summarizing the progress in this field, our study provides valuable insights and future directions for promoting healthy aging from a life course perspective.

Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia.

Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.

Mitochondrial-Targeted CS@KET/P780 Nanoplatform for Site-Specific Delivery and High-Efficiency Cancer Immunotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a form of malignancy with limited curative options available. To improve therapeutic outcomes, it is imperative to develop novel, potent therapeutic modalities. Ketoconazole (KET) has shown excellent therapeutic efficacy against HCC by eliciting apoptosis. However, its limited water solubility hampers its application in clinical treatment. Herein, a mitochondria-targeted chemo-photodynamic nanoplatform, CS@KET/P780 NPs, is designed using a nanoprecipitation strategy by integrating a newly synthesized mitochondria-targeted photosensitizer (P780) and chemotherapeutic agent KET coated with chondroitin sulfate (CS) to amplify HCC therapy. In this nanoplatform, CS confers tumor-targeted and subsequently pH-responsive drug delivery behavior by binding to glycoprotein CD44, leading to the release of P780 and KET. Mechanistically, following laser irradiation, P780 targets and destroys mitochondrial integrity, thus inducing apoptosis through the enhancement of reactive oxygen species (ROS) buildup. Meanwhile, KET-induced apoptosis synergistically enhances the anticancer effect of P780. In addition, tumor cells undergoing apoptosis can trigger immunogenic cell death (ICD) and a longer-term antitumor response by releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), which together contribute to improved therapeutic outcomes in HCC. Taken together, CS@KET/P780 NPs improve the bioavailability of KET and exhibit excellent therapeutic efficacy against HCC by exerting chemophototherapy and antitumor immunity.

Chemo-photothermal nanoplatform with diselenide as the key for ferroptosis in colorectal cancer.

Colorectal cancer (CRC) is a prevalent clinical malignancy of the gastrointestinal system, and its clinical drug resistance is the leading cause of poor prognosis. Mechanistically, CRC cells possess a specific oxidative stress defense mechanism composed of a significant number of endogenous antioxidants, such as glutathione, to combat the damage produced by drug-induced excessive reactive oxygen species (ROS). We report on a new anti-CRC nanoplatform, a multifunctional chemo-photothermal nanoplatform based on Camptothecin (CPT) and IR820, an indocyanine dye. The implementation of a GSH-triggered ferroptosis-integrated tumor chemo-photothermal nanoplatform successfully addressed the poor targeting ability of CPT and IR820 while exhibiting significant growth inhibitory effects on CRC cells. Mechanistically, to offset the oxidative stress created by the broken SeSe bonds, endogenous GSH was continuously depleted, which inactivated GPX4 to accumulate lipid peroxides and induce ferroptosis. Concurrently, exogenously administered linoleic acid was oxidized under photothermal conditions, resulting in an increase in LPO accumulation. With the breakdown of the oxidative stress defense system, chemotherapeutic efficacy could be effectively enhanced. In combination with photoacoustic imaging, the nanoplatform could eradicate solid tumors by means of ferroptosis-sensitized chemotherapy. This study indicates that chemotherapy involving a ferroptosis mechanism is a viable method for the treatment of CRC.

Efficacy, safety and genomic analysis of SCT200, an anti-EGFR monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type metastatic colorectal cancer: a phase â ¡ study.

BACKGROUND: Limited therapeutic options are available for metastatic colorectal cancer (mCRC) patients after failure of first- and second-line therapies, representing an unmet medical need for novel therapies. METHODS: This is an open-label, single arm, multicenter, phase Ⅱ study aiming to perform the efficacy, safety and genomic analysis of SCT200, a noval fully humanized IgG1 anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type mCRC. SCT200 (6 mg/kg) was given weekly for the first six weeks, followed by a higher dose of 8 mg/kg every two weeks until disease progression or unacceptable toxicity. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) and secondary endpoints included ORR in patients with left-sided tumor, disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. FINDINGS: From February 12, 2018 to December 1, 2019, a total of 110 patients aged between 26 and 77 years (median: 55; interquartile range [IQR]: 47-63) with fluorouracil, oxaliplatin, and irinotecan refractory RAS and BRAF wild-type mCRC were enrolled from 22 hospitals in China. As the data cut-off date on May 15, 2020, the IRC-assessed ORR and DCR was 31% (34/110, 95% confidence interval [CI] 22-40%) and 75% (82/110, 95% CI 65-82%), respectively. Thirty one percent (34/110) patients achieved confirmed partial response (PR). The median PFS and median OS were 5.1 months (95% CI 3.4-5.2) and 16.2 months (95% CI 11.1-not available [NA]), respectively. The most common ≥ grade 3 treatment-related adverse events (TRAEs) were hypomagnesemia (17%, 19/110) and acneiform dermatitis (11%, 12/110). No deaths occurred. Genomic analysis suggested positive association between MYC amplification and patients' response (P = 0.0058). RAS/RAF mutation and MET amplification were the most frequently detected resistance mechanisms. Patients with high circulating tumor DNA (ctDNA) at baseline or without ctDNA clearance at the 7th week after the first dose of SCT200 administration before receiving SCT200 had worse PFS and OS. INTERPRETATION: SCT200 exhibited promising clinical efficacy and manageable safety profiles in RAS and BRAF wild-type mCRC patients progressed on fluorouracil, irinotecan and oxaliplatin treatment. The baseline ctDNA and ctDNA clearance status at the 7th week after the first dose of SCT200 administration before receiving SCT200 could be a potential prognostic biomarker for RAS and BRAF wild-type mCRC patients with SCT200 therapy. FUNDING: This study was sponsored by Sinocelltech Ltd., Beijing, China and partly supported by the National Science and Technology Major Project for Key New Drug Development (2019ZX09732001-006, 2017ZX09304015).

Mid-arm muscle circumference and triceps skinfold thickness associated with cardiometabolic disease in Chinese residents: A prospective cohort study.

BACKGROUND AND AIMS: The association of cardiometabolic disease (CMD) with body muscle and fat mass remains unclear. Mid-arm muscle circumference (MAMC) and triceps skinfold (TSF) thickness are easily obtained measuring methods for these two body compositions. This study aimed to investigate the association of CMD with MAMC and TSF thickness among Chinese residents. METHODS: A total of 9440 eligible participants from the China Health and Nutrition Survey were included in the analysis. Associations of CMD prevalence with MAMC and TSF thickness were estimated using logistic regression models. Multivariable COX proportional-hazards regression models were used to estimate the effect of baseline MAMC and TSF thickness on subsequent CMD. RESULTS: Positive associations of CMD prevalence with MAMC (odds ratio [OR] = 1.169, 95% confidence interval [CI] 1.110-1.232, P < 0.001) and TSF thickness (OR = 1.313, 95%CI 1.240-1.390, P < 0.001) were observed in the cross-sectional analysis. In the longitudinal study, a 1-SD increase in MAMC was associated with a 13.6% increased risk of CMD incidence (hazard ratio [HR] = 1.136, 95%CI 1.073-1.204, P < 0.001), and a 1-SD increase in TSF thickness had a 17.6% increased risk of CMD incidence (HR = 1.176, 95%CI 1.084-1.276, P < 0.001). For the CMD components, both MAMC and TSF thickness contributed to increased incidences of hypertension (HR = 1.163, 95%CI 1.097-1.233, P < 0.001 in MAMC; HR = 1.218, 95%CI 1.110-1.336, P < 0.001 in TSF thickness) and diabetes mellitus (HR = 1.166, 95%CI 1.028-1.323, P = 0.017 in MAMC; HR = 1.352, 95%CI 1.098-1.664, P = 0.004 in TSF thickness). CONCLUSIONS: Individuals with higher MAMC and TSF thickness had an increased incidence of CMD, mainly hypertension and diabetes mellitus. This study revealed a seemingly counterintuitive association between body muscle mass and metabolic homeostasis. Although the potential mechanisms require further exploration, the impact of body muscle mass on metabolic health cannot be ignored.

An Ellagic Acid Coordinated Copper-Based Nanoplatform for Efficiently Overcoming Cancer Chemoresistance by Cuproptosis and Synergistic Inhibition of Cancer Cell Stemness.

Drug resistance is one of the leading causes of treatment failure in current cancer chemotherapy. In addition to the classical drug efflux transporter-mediated chemoresistance, cancer cells with stemness features play a crucial role in escaping the maximum impact of chemotherapy. To sensitize cancer chemotherapy, in a novel approach, the hedgehog pathway inhibitor ellagic acid (EA) is coordinated with Cu2+ to develop nanoscale metal-organic frameworks (EA-Cu), which are then loaded with doxorubicin (DOX) and modified with targeted chondroitin sulfate (CS) to form the CS/E-C@DOX nanoplatform (CS/NPs). Notably, EA inhibits stemness maintenance by suppressing the hedgehog pathway, while Cu2+ further decreases stemness features of tumor cells by disrupting mitochondrial metabolism, effectively enhancing DOX-mediated chemotherapy. Meanwhile, EA can act synergistically with Cu2+ to cause mitochondrial dysfunction and cuproptosis, which effectively decreases ATP levels and subsequently suppresses the activity of P-glycoprotein (P-gp), thus reducing drug efflux and sensitizing DOX-mediated chemotherapy. Additionally, the attached CS endows CS/NPs with specific tumor targeting properties, whereas EA-Cu endows this nanoplatform with pH/glutathione (GSH) dual-responsive release behavior. Taken together, CS/NPs exhibited excellent antitumor effects by inducing cuproptosis and significantly inhibiting cancer cell stemness, which has great potential for overcoming cancer chemoresistance.

Fibrosis-4 index is closely associated with clinical outcomes in acute cardioembolic stroke patients with nonvalvular atrial fibrillation.

Liver cirrhosis is a confirmed risk factor for poor prognosis of stroke; however, the contribution of clinically inapparent liver fibrosis to cardioembolic stroke (CES) and its outcomes are poorly understood. This study aimed to investigate the associations between liver fibrosis-measured by the Fibrosis-4 (FIB-4) score-and stroke severity and short-term clinical outcomes of patients with acute CES due to nonvalvular atrial fibrillation (NVAF). A total of 522 patients were followed for a median of 90 days. We calculated the FIB-4 score and defined liver fibrosis as follows: likely advanced fibrosis (FIB-4 > 3.25), indeterminate advanced fibrosis (FIB-4, 1.45-3.25), and unlikely advanced fibrosis (FIB-4 < 1.45). Logistic regression analysis and Cox regression analysis were used to investigate the relations between the FIB-4 score and stroke severity, major disability at discharge, and all-cause mortality. Among these 522 acute CES patients with NVAF, the mean FIB-4 score (2.28) on admission reflected intermediate fibrosis, whereas liver enzymes were largely normal. In multivariate regression analysis, patients with advanced liver fibrosis were more likely to have a higher risk of severe stroke (OR = 2.21, 95% CI 1.04-3.54), major disability at discharge (OR = 4.59, 95% CI 1.88-11.18), and all-cause mortality (HR = 1.25, 95% CI 1.10-1.56) than their counterparts. Regarding sex, these associations were stronger in males but not significant in females. In patients with acute CES due to NVAF, advanced liver fibrosis is associated with severe stroke, major disability, and all-cause death. Our findings indicate that early screening and management of liver fibrosis may decrease stroke severity and risk of death in patients with NVAF, especially for male patients. Consequently, FIB-4 > 3.25 of male patients should receive ultrasound elastography to further determine the degree of liver fibrosis.

Armchair Janus WSSe Nanotube Designed with Selenium Vacancy as a Promising Photocatalyst for CO2 Reduction.

Photocatalytic conversion of carbon dioxide into chemical fuels offers a promising way to not only settle growing environmental problems but also provide a renewable energy source. In this study, through first-principles calculation, we found that the Se vacancy introduction can lead to the transition of physical-to-chemical CO2 adsorption on Janus WSSe nanotube. Se vacancies work at the adsorption site, which significantly improves the amount of transferred electrons at the interface, resulting in the enhanced electron orbital hybridization between adsorbents and substrates, and promising the high activity and selectivity for carbon dioxide reduction reaction (CO2RR). Under the condition of illumination, due to the adequate driving forces of photoexcited holes and electrons, oxygen generation reaction (OER) and CO2RR can occur spontaneously on the S and Se sides of the defective WSSe nanotube, respectively. The CO2 could be reduced into CH4, meanwhile, the O2 is produced by the water oxidation, which also provides the hydrogen and electron source for the CO2RR. Our finding reveals a candidate photocatalyst for obtaining efficient photocatalytic CO2 conversion.

An EMS-induced allele of the brachytic2 gene can reduce plant height in maize.

KEY MESSAGE: D129 is an EMS-induced mutant with dwarf phenotype, which has important breeding potential to cultivate new varieties suitable for high-density planting in maize Plant height is one of the important agronomic traits that affecting maize planting density, identification of superior dwarf mutants can provide important genetic materials for breeding new varieties suitable for high-density planting. In this study, we identified a dwarf mutant, d129, from maize EMS-induced mutant population. Gene mapping indicated that a G-to-A transition in the second exon of the br2 gene was responsible for the dwarf phenotype of the d129 mutant using MutMap method, which was further validated through allelism testing. Compared with WT plants, the average plant height and ear height of d129 were reduced by 26.67% and 39.43%, respectively, mainly due to a decrease in internode length. Furthermore, the d129 mutant exhibited increased internode diameter, which is important for increasing planting density due to the lodging resistance may be enhanced. Endogenous hormone measurement demonstrated that the contents of IAA and GA3 in the internode of the mutant were significantly lower than that of WT plants. RNA-seq analysis indicated that at least fifteen auxin-responsive and signaling-related genes exhibited differential expression, and some genes involved in cell development and other types of hormone signaling pathways, were also identified from the differential expressed genes. These genes may be related to the reduced hormone contents and decreased elongation of internode cells of the d129 mutant. Our study provided a novel dwarf mutant which can be applied in maize breeding to cultivate new varieties suitable for high-density planting.

Argonaute-dependent ribosome-associated protein quality control.

Ribosome-associated protein quality control (RQC) is a protein surveillance mechanism that eliminates defective nascent polypeptides. The E3 ubiquitin ligase, Ltn1, is a key regulator of RQC that targets substrates for ubiquitination. Argonaute proteins (AGOs) are central players in miRNA-mediated gene silencing and have recently been shown to also regulate RQC by facilitating Ltn1. Therefore, AGOs directly coordinate post-transcriptional gene silencing and RQC, ensuring efficient gene silencing. We summarize the principles of RQC and the functions of AGOs in miRNA-mediated gene silencing, and discuss how AGOs associate with the endoplasmic reticulum (ER) to assist Ltn1 in controlling RQC. We highlight that RQC not only eliminates defective nascent polypeptides but also removes unwanted protein products when AGOs participate.

Predictive Value of Cardiac Magnetic Resonance for Left Ventricular Remodeling of Patients with Acute Anterior Myocardial Infarction.

Background: Heart failure is a serious complication resulting from left ventricular remodeling (LVR), especially in patients experiencing acute anterior myocardial infarction (AAMI). It is crucial to explore the predictive parameters for LVR following primary percutaneous coronary intervention (PPCI) in patients with AAMI. Methods: A total of 128 AAMI patients who were reperfused successfully by PPCI were enrolled sequentially from June 2018 to December 2019. Cardiovascular magnetic resonance (CMR) was performed at the early stage (<7 days) and after the 6-month follow-up. The patients were divided into LVR and non-LVR groups according to the increase of left ventricular end diastolic volume (LVEDV) measured by the second cardiac magnetic resonance examination ≥20% from baseline. (3) Results: The left ventricular ejection fraction (LVEF), the global longitudinal strain (GLS), the peak circumferential strain in infarcted segments, and the infarct size (IS) remained significantly different in the multivariate logistic regression analysis (all p < 0.05). The area under the receiver operating characteristic curve of Model 1, wherein the GLS was added to the LVEF, was 0.832 (95% CI 0.758−0.907, p < 0.001). The C-statistics for Model 2, which included the infarct-related regional parameters (IS and the peak circumferential strain in infarcted segments)was 0.917 (95% CI 0.870−0.965, p < 0.001). Model 2 was statistically superior to Model 1 in predicting LVR (IDI: 0.190, p = 0.002). (4) Conclusions: Both the global and regional CMR parameters were valuable in predicting LVR in patients with AAMI following the PPCI. The local parameters of the infarct zones were superior to those of the global ones.

A protocol for mimicking lipid-mediated phase separation on the membrane using giant unilamellar vesicles.

Here, we present a general protocol for mimicking lipid-mediated phase separation on the membrane using giant unilamellar vesicles (GUVs). In this protocol, we use GUVs to mimic Ago1 protein's phase separation behavior on the membrane through binding with phosphoinositides (PIPs). We provide procedures to prepare fluorescent-labeled Ago1 protein and PI(4,5)P2-containing GUVs, followed by steps to assess Ago1 protein's phase separation in 3D time-lapse images. This protocol can be applied to investigate a membrane-associated protein's behavior on the membrane. For complete details on the use and execution of this protocol, please refer to Gao et al. (2022).