-
1.
Decoding the gene regulatory network of endosperm differentiation in maize.
Yuan, Y, Huo, Q, Zhang, Z, Wang, Q, Wang, J, Chang, S, Cai, P, Song, KM, Galbraith, DW, Zhang, W, et al
Nature communications. 2024;(1):34
Abstract
The persistent cereal endosperm constitutes the majority of the grain volume. Dissecting the gene regulatory network underlying cereal endosperm development will facilitate yield and quality improvement of cereal crops. Here, we use single-cell transcriptomics to analyze the developing maize (Zea mays) endosperm during cell differentiation. After obtaining transcriptomic data from 17,022 single cells, we identify 12 cell clusters corresponding to five endosperm cell types and revealing complex transcriptional heterogeneity. We delineate the temporal gene-expression pattern from 6 to 7 days after pollination. We profile the genomic DNA-binding sites of 161 transcription factors differentially expressed between cell clusters and constructed a gene regulatory network by combining the single-cell transcriptomic data with the direct DNA-binding profiles, identifying 181 regulons containing genes encoding transcription factors along with their high-confidence targets, Furthermore, we map the regulons to endosperm cell clusters, identify cell-cluster-specific essential regulators, and experimentally validated three predicted key regulators. This study provides a framework for understanding cereal endosperm development and function at single-cell resolution.
-
2.
From bacteria to biomedicine: Developing therapies exploiting NAD+ metabolism.
Chen, Y, Ying, Y, Lalsiamthara, J, Zhao, Y, Imani, S, Li, X, Liu, S, Wang, Q
Bioorganic chemistry. 2024;:106974
Abstract
Nicotinamide adenine dinucleotide (NAD+) serves as a critical cofactor in cellular metabolism and redox reactions. Bacterial pathways rely on NAD+ participation, where its stability and concentration govern essential homeostasis and functions. This review delves into the role and metabolic regulation of NAD+ in bacteria, highlighting its influence on physiology and virulence. Notably, we explore enzymes linked to NAD+ metabolism as antibacterial drug targets and vaccine candidates. Moreover, we scrutinize NAD+'s medical potential, offering insights for its application in biomedicine. This comprehensive assessment informs future research directions in the dynamic realm of NAD+ and its biomedical significance.
-
3.
Ferroptosis in age-related vascular diseases: Molecular mechanisms and innovative therapeutic strategies.
Dai, Y, Wei, X, Jiang, T, Wang, Q, Li, Y, Ruan, N, Luo, P, Huang, J, Yang, Y, Yan, Q, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024;:116356
Abstract
Aging, an inevitable aspect of human existence, serves as one of the predominant risk factors for vascular diseases. Delving into the mystery of vascular disease's pathophysiology, the profound involvement of programmed cell death (PCD) has been extensively demonstrated. PCD is a fundamental biological process that plays a crucial role in both normal physiology and pathology, including a recently discovered form, ferroptosis. Ferroptosis is characterized by its reliance on iron and lipid peroxidation, and its significant involvement in vascular disease pathophysiology has been increasingly acknowledged. This phenomenon not only offers a promising therapeutic target but also deepens our understanding of the complex relationship between ferroptosis and age-related vascular diseases. Consequently, this article aims to thoroughly review the mechanisms that enable the effective control and inhibition of ferroptosis. It focuses on genetic and pharmacological interventions, with the goal of developing innovative therapeutic strategies to combat age-related vascular diseases.
-
4.
The efficacy and safety of modified ultraearly oral hydration for alleviating thirst in patients after thoracoscopic surgery: a prospective randomized controlled trial.
Xue, Y, Wang, Q, Zhao, H, Pan, R, Xia, Y, Wang, H, Qin, X
BMC anesthesiology. 2024;(1):105
Abstract
OBJECTIVE Postoperative fasting following thoracoscopic surgery can cause intense thirst and oral discomfort. However, there is currently no research on ultraearly oral hydration (UEOH) in middle-aged or elderly patients after thoracoscopic surgery. The aim of this study was to investigate the effectiveness and safety of UEOH for improving oral discomfort after thoracoscopic surgery. METHODS This single-center prospective double-blind randomized controlled trial was conducted from April 2022 to November 2023. A total of 64 middle-aged and elderly patients who underwent the first thoracoscopic surgery on the day were enrolled at our institution. Postoperatively, in the Postanesthesia Care Unit (PACU), patients were randomly assigned at a 1:1 ratio to either the UEOH group or the standard care (SC) group. The primary outcome was the patient's thirst score at 6 h after surgery. Secondary outcomes included the incidence of postoperative oral discomfort; pain scores; the occurrence of adverse reactions such as nausea, vomiting, regurgitation and aspiration; anxiety scores on the first postoperative day; the time to first flatus; and recovery satisfaction scores. RESULTS The demographic and surgical characteristics were similar between the two groups. Patients in the UEOH group had lower thirst scores 6 h after surgery than did those in the SC group(16.1 ± 6.70 vs. 78.4 ± 8.42, P < 0.01). The incidence of postoperative oral discomfort (P < 0.01), anxiety scores on the first postoperative day (P<0.05), and time to first flatus (P<0.05) were better in the UEOH group. Additionally, the incidences of adverse reactions, such as postoperative nausea, vomiting, regurgitation and aspiration, were similar between the two groups (P>0.05). CONCLUSION For middle-aged and elderly patients undergoing thoracoscopic surgery, the use of a modified UEOH protocol postoperatively can improve thirst and promote gastrointestinal recovery without increasing complications. TRIAL REGISTRATION This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 07/12/2023 with the registration number ChiCTR2300078425.
-
5.
Sintilimab plus anlotinib as second or further-line therapy for extensive disease small cell lung cancer: a phase 2 investigator-initiated non-randomized controlled trial.
Ma, S, He, Z, Liu, Y, Wang, L, Yang, S, Wu, Y, Chen, H, Wu, Y, Wang, Q
EClinicalMedicine. 2024;:102543
Abstract
BACKGROUND Treatment options remain rather limited for extensive disease small cell lung cancer (ED-SCLC) patients in second or further-line setting. METHODS The phase 2 investigator-initiated non-randomized study enrolled patients who had disease progression on at least one line of platinum-based chemotherapy. Participants received intravenous sintilimab 200 mg on day one and oral daily anlotinib 12 mg on days 1-14 once every three weeks per cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov (NCT04055792). FINDINGS Forty-two patients were enrolled between August 29, 2019 and December 26, 2021 at Henan Cancer Hospital in China. 37 patients were evaluable for efficacy. The median follow-up was 24.8 months (IQR: 16.9-28.2). The median PFS was 6.1 months (95% CI: 5.0-7.3). The OS was 12.7 months (95% CI: 7.1-18.2). The ORR was 56.8% (21/37, 95% CI: 40.0-73.5) and the DCR was 89.2% (33/37, 95% CI: 78.7-99.7). Forty patients (40/42, 95%) had at least one treatment-related adverse event (TRAE). Immune-related adverse events (irAEs) were reported in 39 patients (39/42, 93%), while grade 3 or higher irAEs occurred in 11 patients (11/42, 26%). The most frequent irAEs were hypothyroidism (16/42, 38%), elevated gamma-glutamyl transpeptidase (15/42, 36%) and elevated creatine kinase MB (15/42, 36%). The most frequent grade 3 or higher irAEs were elevated gamma-glutamyl transpeptidase (5/42, 12%) and increased aspartate aminotransferase (3/42, 7%). INTERPRETATION Sintilimab plus anlotinib demonstrated promising antitumor activities as second or further-line therapy for ED-SCLC and had manageable toxicities. The findings support further randomized controlled trials of this combination regimen for ED-SCLC. FUNDING Henan Province Health and Youth Subject Leader Training Project, Henan Health Science and Technology Innovation Talents, ZHONGYUAN QIANREN JIHUA, Henan International Joint Laboratory of drug resistance and reversal of targeted therapy for lung cancer, Tumor Research Fund of Anti-Angiogenesis Targeted Therapy of China Anti-Cancer Association.
-
6.
Effectiveness of an intermittent fasting diet versus regular diet on fat loss in overweight and obese middle-aged and elderly people without metabolic disease: a systematic review and meta-analysis of randomized controlled trials.
Yao, K, Su, H, Cui, K, Gao, Y, Xu, D, Wang, Q, Ha, Z, Zhang, T, Chen, S, Liu, T
The journal of nutrition, health & aging. 2024;(3):100165
Abstract
OBJECTIVE As the number of adults aged over 40 with obesity increases dramatically, intermittent fasting interventions (IF) may help them to lose fat and weight. This systematic review investigated the most recent research on the effects of intermittent fasting and a regular diet on body composition and lipids in adults aged over 40 with obesity without the metabolic disease. DATA SOURCES Randomized controlled trials (RCTs) on IF on adults aged over 40 with obesity were retrieved from PubMed, Web of Science, EBSCO, China Knowledge Network (CNKI), VIP database, Wanfang database with the experimental group using IF and the control group using a regular diet. Revman was used for meta-analysis. Effect sizes are expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). STUDY SELECTION A total of 9 articles of randomised controlled trials that met the requirements were screened for inclusion. Studies typically lasted 2-6 weeks. The experimental population was aged 42-66 years, with a BMI range of 25.7-35 kg/m2. SYNTHESIS A total of 9 RCTs were included. meta-analysis showed that body weight (MD: -2.05 kg; 95% CI (-3.84, -0.27); p = 0.02), BMI (MD: -0.73 kg/m2; 95% CI (-1.05, -0.41); p < 0.001), fat mass (MD: -2.14 kg; 95% CI (-3.81, 0.47); p = 0.01), and TG (MD = -0.32 mmol/L, 95% CI (-0.50, -0.15, p < 0.001) were significantly lower in the experimental group than in the control group. No significant reduction in lean body mass (MD: -0.31 kg; 95% CI (-0.96, 0.34); p = 0.35). CONCLUSION IF had a reduction in body weight, BMI, fat mass, and TG in adults aged over 40 with obesity without metabolic disease compared to RD, and IF did not cause a significant decrease in lean body mass, which suggests healthy and effective fat loss. However, more long-term and high-quality trials are needed to reach definitive conclusions.
-
7.
Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial.
Zhang, M, Zhang, G, Niu, Y, Zhang, G, Ji, Y, Yan, X, Zhang, X, Wang, Q, Jing, X, Wang, J, et al
Nature communications. 2024;(1):1512
Abstract
This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.
-
8.
The effect of exercise training intervention for patients with abdominal aortic aneurysm on cardiovascular and cardiorespiratory variables: an updated meta-analysis of randomized controlled trials.
Han, Q, Qiao, L, Yin, L, Sui, X, Shao, W, Wang, Q
BMC cardiovascular disorders. 2024;(1):80
Abstract
OBJECTIVE The purpose of this meta-analysis was to evaluate the effect of exercise training intervention in patients with abdominal aortic aneurysm (AAA). METHODS Eight randomized controlled trials (RCTs) that recruited 588 AAA patients were extracted using 4 databases (PubMed, Embase, Wanfang Data, and Cochrane Library). Physiological and biochemistry parameters that included in this study are high-sensitivity C-reactive protein (hs-CRP), respiratory peak oxygen uptake rate (VO2peak), triglyceride (TG), total cholesterol (TC), anaerobic threshold (AT), the diameter of AAA, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), and matrix metalloproteinase-9 (MMP-9). Standard mean difference (SMD) was used to assess the between group effect. RESULTS This meta-analysis was synthesized with findings from RCTs and found that hs-CRP (SMD, - 0.56 mg/dL; 95% CI: - 0.90 to 0.22; P = 0.001), VO2peak (SMD, 0.4 mL/kg/min; 95% CI, 0.21 to 0.60; P < 0.001), TG (SMD, - 0.39 mg/dL; 95% CI: - 0.02 to 0.77; P = 0.04), and AT (SMD, 0.75 mL/kg/min; 95% CI, 0.54 to 0.96; P < 0.001) were significantly improved in the exercise groups, while the size of AAA (SMD, - 0.15; 95% CI: - 0.36 to 0.06; P = 0.15), TC (SMD, 0.16 mg/dL; 95% CI: - 0.10 to 0.42; P = 0.23), HDL/LDL ratio (SMD, - 0.06; 95% CI: - 0.32 to 0.20; P = 0.64), HDL (SMD, - 0.09; 95% CI: - 0.39 to 0.20; P = 0.54), LDL (SMD, 0.08; 95% CI: - 0.21 to 0.38; P = 0.59), and MMP-9 (SMD, - 0.23 mg/dL; 95% CI: - 0.53 to 0.06; P = 0.12) did not differ in the exercise groups compared with the controls. CONCLUSION Exercise intervention improved some of the CVD risk factors but not all, hs-CRP, VO2peak and AT were significantly improved after exercise intervention, while, changes of MMP-9, the size of AAA, and the overall lipids profile were not. Exercise intervention provides an additional solution for improving cardiorespiratory capacity and health status among AAA patients, and might lead to a delay of AAA progression.
-
9.
Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies.
Liu, D, Wang, S, Liu, S, Wang, Q, Che, X, Wu, G
Molecular aspects of medicine. 2024;:101270
Abstract
The onset of sarcopenia is intimately linked with aging, posing significant implications not only for individual patient quality of life but also for the broader societal healthcare framework. Early and accurate identification of sarcopenia and a comprehensive understanding of its mechanistic underpinnings and therapeutic targets paramount to addressing this condition effectively. This review endeavors to present a cohesive overview of recent advancements in sarcopenia research and diagnosis. We initially delve into the contemporary diagnostic criteria, specifically referencing the European Working Group on Sarcopenia in Older People (EWGSOP) 2 and Asian Working Group on Sarcopenia (AWGS) 2019 benchmarks. Additionally, we elucidate comprehensive assessment techniques for muscle strength, quantity, and physical performance, highlighting tools such as grip strength, chair stand test, dual-energy X-ray Absorptiometry (DEXA), bioelectrical impedance analysis (BIA), gait speed, and short physical performance battery (SPPB), while also discussing their inherent advantages and limitations. Such diagnostic advancements pave the way for early identification and unequivocal diagnosis of sarcopenia. Proceeding further, we provide a deep-dive into sarcopenia's pathogenesis, offering a thorough examination of associated signaling pathways like the Myostatin, AMP-activated protein kinase (AMPK), insulin/IGF-1 Signaling (IIS), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Each pathway's role in sarcopenia mediation is detailed, underscoring potential therapeutic target avenues. From a mechanistic perspective, the review also underscores the pivotal role of mitochondrial dysfunction in sarcopenia, emphasizing elements such as mitochondrial oxidative overload, mitochondrial biogenesis, and mitophagy, and highlighting their therapeutic significance. At last, we capture recent strides made in sarcopenia treatment, ranging from nutritional and exercise interventions to potential pharmacological and supplementation strategies. In sum, this review meticulously synthesizes the latest scientific developments in sarcopenia, aiming to enhance diagnostic precision in clinical practice and provide comprehensive insights into refined mechanistic targets and innovative therapeutic interventions, ultimately contributing to optimized patient care and advancements in the field.
-
10.
Inhibiting acid-sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis.
Shi, X, Liu, R, Wang, Y, Yu, T, Zhang, K, Zhang, C, Gu, Y, Zhang, L, Wu, J, Wang, Q, et al
CNS neuroscience & therapeutics. 2024;(2):e14596
-
-
Free full text
-
Abstract
BACKGROUND Epilepsy is a chronic neurological disease characterized by repeated and unprovoked epileptic seizures. Developing disease-modifying therapies (DMTs) has become important in epilepsy studies. Notably, focusing on iron metabolism and ferroptosis might be a strategy of DMTs for epilepsy. Blocking the acid-sensing ion channel 1a (ASIC1a) has been reported to protect the brain from ischemic injury by reducing the toxicity of [Ca2+ ]i . However, whether inhibiting ASIC1a could exert neuroprotective effects and become a novel target for DMTs, such as rescuing the ferroptosis following epilepsy, remains unknown. METHODS In our study, we explored the changes in ferroptosis-related indices, including glutathione peroxidase (GPx) enzyme activity and levels of glutathione (GSH), iron accumulation, lipid degradation products-malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) by collecting peripheral blood samples from adult patients with epilepsy. Meanwhile, we observed alterations in ASIC1a protein expression and mitochondrial microstructure in the epileptogenic foci of patients with drug-resistant epilepsy. Next, we accessed the expression and function changes of ASIC1a and measured the ferroptosis-related indices in the in vitro 0-Mg2+ model of epilepsy with primary cultured neurons. Subsequently, we examined whether blocking ASIC1a could play a neuroprotective role by inhibiting ferroptosis in epileptic neurons. RESULTS Our study first reported significant changes in ferroptosis-related indices, including reduced GPx enzyme activity, decreased levels of GSH, iron accumulation, elevated MDA and 4-HNE, and representative mitochondrial crinkling in adult patients with epilepsy, especially in epileptogenic foci. Furthermore, we found that inhibiting ASIC1a could produce an inhibitory effect similar to ferroptosis inhibitor Fer-1, alleviate oxidative stress response, and decrease [Ca2+ ]i overload by inhibiting the overexpressed ASIC1a in the in vitro epilepsy model induced by 0-Mg2+ . CONCLUSION Inhibiting ASIC1a has potent neuroprotective effects via alleviating [Ca2+ ]i overload and regulating ferroptosis on the models of epilepsy and may act as a promising intervention in DMTs.