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Synthetic biology enables the design of gene networks to confer specific biological functions, yet it remains a challenge to rationally engineer a biological trait as complex as longevity. A naturally occurring toggle switch underlies fate decisions toward either nucleolar or mitochondrial decline during the aging of yeast cells. We rewired this endogenous toggle to engineer an autonomous genetic clock that generates sustained oscillations between the nucleolar and mitochondrial aging processes in individual cells. These oscillations increased cellular life span through the delay of the commitment to aging that resulted from either the loss of chromatin silencing or the depletion of heme. Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally designed gene circuits that slow aging.

Vagal responses and phrenic activation are commonly observed during pulsed field ablation (PFA). However, whether the vagal responses and phrenic activations are nerve damage or a neurological stress response due to electrical stimulation is unclear.The purpose of this study was to evaluate the effect of a PFA system for performing pulmonary vein isolation on the autonomic nervous system.Patients with paroxysmal atrial fibrillation (AF) who underwent PFA between August 2021 and November 2021 were included. Nerve injury biomarkers and heart rate variability were obtained preablation and postablation. Patients were scheduled to undergo magnetic resonance imaging and diffusion-weighted imaging to evaluate cerebral microembolus formation postablation.Acute electrical isolation was achieved in 100% of pulmonary veins (n = 72) in the 18 patients. Mean total procedural time was 64.1 ± 18.2 minutes, and mean fluoroscopy time was 12.3 ± 3.5 minutes. Serum nerve injury biomarkers did not show any changes preablation and immediately postablation and 24 hours after ablation (all P.05). Preablation and 30-day postablation heart rate variability did not differ (all P.05). Postablation diffusion-weighted imaging revealed no acute cerebral microembolus events. Moreover, there were no other procedure-related complications. The 8-month Kaplan-Meier estimate of freedom from arrhythmia was 83% ± 9%.PFA does not induce nerve injury during pulmonary vein isolation for paroxysmal AF.

This research developed a signal amplification strategy to construct a highly sensitive electrochemiluminescent (ECL) aptasensor by incorporating dysprosium metal-organic framework (Dy-MOF) as a co-reaction accelerator (CRA) in gadolinium (Gd) luminescent complex based ECL system. A new Gd(III) complex GdPc(acac) (Pc = phthalocyanine, acac = acetylacetonate) with semi-sandwich structure was rationally selected as ECL emitter, exhibiting excellent luminescence performance owing to the "antenna effect" from the conjugated macrocyclic ligand. For further improving the sensitivity of the ECL biosensor, Dy-MOF was introduced into the ECL system as CRA. The purposive design and configuration of the Dy-MOF structure accelerated the separation and transport of photogenerated charges, and the nanosheets formed by the composite material provided more active sites, which could not only greatly increased the luminophore loading, but also effectively shorten the transport distance of ions and co-reactants. The constructed biosensor showed superior performance to monitor kanamycin within 0.001 pg/mL-1000 ng/mL and a detection limit down to 0.3 fg/mL (S/N = 3). The current work opened up a skillful strategy to amplify ECL singnal, extending the application field of lanthanide complexes and providing valuable information for the future biosensor design.

The tail of imidazole regulated the assembly of fascinating 2D sql topology and 3D 2-fold interpenetrated lvt structure polyoxotungstate-based open frameworks with efficient visible-white-light-driven aerobic catalytic oxidation of sulfides.

The 5V spinel LiNi0.5Mn1.5O4 cathode materials with different morphology were prepared by a solid state calcination method and characterized by XRD, ICP, FE-SEM.

The unique flower-like 3D structure and dominant crystal endow the FeSe2 electrode with satisfactory sodium storage performance.

To evaluate and describe the clinical efficacy and safety of a modified unilateral biportal endoscopic lumbar discectomy.From February 2019 to February 2020, patients who met the inclusion criteria were treated using a modified unilateral biportal endoscopic lumbar discectomy. During the operation, the herniated disc was removed and the ligamentum flavum was preserved. Clinical efficacy was assessed via postoperative imaging and follow-up.A total of 70 patients were followed up for more than 2 years, including 51 males and 19 females, aged 49.4 ± 16.0 years. All operations were completed and no complications were noted. Postoperative lumbar magnetic resonance imaging showed that the decompression of the nerve root was sufficient and the ligamentum flavum was preserved in all patients. Postoperative lumbar CT showed that the caudal lamina and inferior articular process of the cephalad vertebral were partially removed. Lower back and leg pain were significantly relieved after surgery, and the Oswestry Disability Index was significantly improved compared to presurgery measurements (P ＜ 0.01). After 2 years of follow-up, the sensory and muscle strength of nerve roots were significantly recovered (P ＜ 0.01). According to the MacNab score of the patients, 40 cases were defined as "excellent," 26 cases were "good," 2 cases were "fair," and 2 cases were "poor."Modified unilateral biportal endoscopic lumbar discectomy can completely remove a lumbar herniated disc; relieve lower back and leg pain; improve lumbar function; reduce the risk of dural tearing, cerebrospinal fluid leakage, and epidural hematoma; and reduce the epidural adhesion and arachnoiditis caused by ligamentum flavum resection.

Emissions from mobile sources and stationary sources contribute to atmospheric pollution in China, and its components, which include ultrafine particles (UFPs), volatile organic compounds (VOCs), and other reactive gases, such as NH

Thermoelectric technology holds great promise as a green and sustainable energy solution, generating electric power directly from waste heat.

A series of bi- or mononuclear hexacoordinate iron(III) complexes, [Fe(L)][Fe(bpb)(CN)2]·CH3OH·0.5H2O (1), [Fe(L)] [Co(bpb)(CN)2]·CH3OH (2) [(Fe (L))2(4,4’-bipy)](BPh4)2 (3), [Fe(L)(py)](BPh4) (4) and [Fe(L)(dmap)](BPh4) (5) (bpb = 1,2-bis(pyridine-2-carboxamido)benzenate, L = N,N’-bis(2-hydroxybenzyliden)-1,7-diamino-4-azaheptane, dmap = 4-dimethylaminopyridine), have been prepared with the pentadentate Schiff base iron(III) compound as assemble precursor and characterized by element analysis, IR and X-ray diffraction. Single crystal structural determination revealed the neutral cyanide-bridged binuclear entity for complexes 1 and 2 and the cationic di- or mononuclear structure for complexes 3–5 with the positive charge(s) balanced by BPh4 – ion(s). The experimental study and theoretical simulation of the magnetic property discovered the ferromagnetic coupling between the Fe(III) ions bridged by cyanide group in complex 1 and the always high spin state of the Fe(III) ion coordinated to the Schiff base ligand in both complexes 1 and 2. The temperature dependent magnetic susceptibility investigation over complexes 3–5 showed the occurrence of the thermo-induced gradual complete spin crossover (SCO) property at about 115, 170 and 200 K, respectively.

Doxorubicin (DOX) is a chemotherapeutic drug for a variety of malignancies, while its application is restricted by the cardiovascular toxic effects characterized by oxidative stress. Ferroptosis is a novel iron-dependent regulated cell death driven by lipid peroxidation. Our study aimed to investigate the role of Elabela (ELA) in DOX-induced oxidative stress and ferroptosis. In cultured rat aortic adventitial fibroblasts (AFs), stimulation with DOX dramatically induced cytotoxicity with reduced cell viability and migration ability, and enhanced lactate dehydrogenase (LDH) activity. Importantly, ELA and ferrostatin-1 (Fer-1) mitigated DOX-mediated augmentation of reactive oxygen species (ROS) in rat aortic AFs, accompanied by upregulated levels of Nrf2, SLC7A11, GPX4, and GSH. In addition, ELA reversed DOX-induced dysregulation of apoptosis- and inflammation-related factors including Bax, Bcl2, interleukin (IL)-1β, IL6, IL-10, and CXCL1. Intriguingly, knockdown of Krüppel-like factor 15 (KLF15) by siRNA abolished ELA-mediated alleviation of ROS production and inflammatory responses. More importanly, KLF15 siRNA impeded the beneficial roles of ELA in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders.

Objective Cervical fractures with ankylosing spondylitis (CAS) are a specific type of spinal fracture with poor stability, low healing rate, and high disability rate. Its treatment is mainly surgical, predominantly through the anterior approach, posterior approach, and the anterior–posterior approach. Although many clinical studies have been conducted on various surgical approaches, controversy still exists concerning the choice of these surgical approaches by surgeons. The authors present here a systematic evaluation and meta-analysis exploring the utility of the anterior–posterior approach versus the anterior approach and the posterior approach. Methods After a comprehensive literature search of PubMed, Cochrane, Web of Science, and Embase databases, 12 clinical studies were included in the final qualitative analysis and 8 in the final quantitative analysis. Of these studies, 11 conducted a comparison between the anterior–posterior approach and the anterior approach and posterior approaches, while one examined only the anterior–posterior approach. Where appropriate, statistical advantage ratios and 95% confidence intervals were calculated. Results The present meta-analysis of postoperative neurological improvement showed no statistical difference in the overall neurological improvement rate between the anterior–posterior approach and anterior approach (OR 1.70, 95% CI 0.61 to 4.75; p = 0.31). However, the mean change in postoperative neurological function was lower in patients who received the anterior approach than in those who received the anterior–posterior approach (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). There was an identical trend between the anterior–posterior approach and posterior approach, with no statistically significant difference in the overall rate of neurological improvement (OR 1.37, 95% CI 0.70 to 2.56; p = 0.38). Nevertheless, the mean change in neurological function was smaller in patients receiving the anterior–posterior approach compared with the posterior approach, but there was no statistically significant difference between the two (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). Conclusions The results of this review and meta-analysis suggest that the benefits of the anterior–posterior approach are different from those of the anterior and posterior approaches in the treatment of ankylosing spondylitis-related cervical fractures. In a word, there is no significant difference between the cervical surgical approach and the neurological functional improvement. Therefore, surgeons should pay more attention to the type of cervical fracture, the displacement degree of cervical fracture, the spinal cord injury, the balance of cervical spine and other aspects to comprehensively consider the selection of appropriate surgical methods.

Drug resistance from BCR-ABL tyrosine kinase inhibitors (TKIs) and other chemotherapeutics results in treatment failure and disease progression in chronic myeloid leukemia (CML). However, the mechanism is still uncertain. In this study, we investigated the role of angiopoietin-1 (ANG-1) as a potential prognostic factor for drug resistance in CML. Both intracellular and secretory ANG-1 (iANG-1 and sANG-1) were overexpressed in multidrug-resistant CML samples. The IC

With rare genetic variations having been increasingly recognized at a preclinical stage, a variety of early-phase clinical trials have been launched. Due to the low incidence rate of these variations, although the sample size of trials are small, it still needs a large number of patients for screening. With the advent of next-generation sequencing (NGS), multiple genetic variations can be detected simultaneously. Multiple biomarkers and agents can be evaluated using umbrella clinical trials, which rapidly and effectively screen and enroll patients for parallel sub-studies using NGS.We designed an open-label, multi-center, phase II clinical trial CTONG1702. This is an adaptive umbrella trial that will evaluate the efficacy and safety of several biomarker-driven agents, including tyrosine kinase inhibitors (TKIs) and a PD-1 inhibitor, in stage IIIB to IV patients (eighth AJCC) with non-small-cell lung cancer (NSCLC) patients. Patients will be enrolled in parallel sub-studies based on the results of NGS and PD-L1 IHC analysis. Patients who are not eligible for CTONG1702 will be enrolled in the observational real-world study CTONG1705. This study aims to develop a large-scale genomic database and explore the relationship between genetic variations in NSCLC patients and clinical outcomes.The adaptive umbrella trial will evaluate multi-targets and multi-drugs in advanced NSCLC patients (CTONG1702). In addition, the simultaneously initiated real-world study will provide additional data for clinical practice (CTONG1705).

Hypertension is one of the leading causes of chronic kidney disease characterized with renal fibrosis. This study aimed to investigate roles and mechanisms of sirtuin 7 (SIRT7) in hypertensive renal injury. Mini-pumps were implanted to male C57BL/6 mice to deliver angiotensin (Ang) Ⅱ (1.5 mg/kg/d) or saline for 2 weeks. Ang Ⅱ infusion resulted in marked increases in systolic blood pressure levels, renal ferroptosis and interstitial fibrosis in hypertensive mice, concomitantly with downregulated SIRT7 and Krüppel-like factor 15 (KLF15) levels. Notably, administration of recombinant adeno-associated virus-SIRT7 or ferroptosis inhibitor ferrostatin-1 effectively mitigated Ang Ⅱ-triggered renal ferroptosis, epithelial-mesenchymal transition (EMT), interstitial fibrosis, renal functional and structural injury in hypertensive mice by blunting the KIM-1/NOX4 signaling and enforcing the KLF15/Nrf2 and xCT/GPX4 signaling, respectively. In primary cultured mouse renal tubular epithelial cells (TECs), Ang Ⅱ pretreatment led to repressed SIRT7 expression and augmented ferroptosis as well as partial EMT, which were substantially antagonized by rhSIRT7 or ferrostatin-1 administration. Additionally, both Nrf2 inhibitor ML385 and KLF15 siRNA strikingly abolished the rhSIRT7-mediated beneficial roles in mouse renal TECs in response to Ang Ⅱ with reduced expression of Nrf2, xCT and GPX4. More importantly, ML385 administration remarkably amplified Ang Ⅱ-mediated ROS generation, lipid peroxidation and ferroptosis in renal TECs, which were significantly reversed by ferrostatin-1. In conclusion, SIRT7 alleviates renal ferroptosis, lipid peroxidation, and partial EMT under hypertensive status by facilitating the KLF15/Nrf2 signaling, thereby mitigating renal fibrosis, injury and dysfunction. Targeting SIRT7 signaling serves as a promising strategy for hypertension and hypertensive renal injury.