Self-Propagating Fabrication of a 3D Graphite@rGO Film Anode for High-performance Potassium-Ion Batteries.

Graphite, with abundant resources and low cost, is regarded as a promising anode material for potassium-ion batteries (PIBs). However, because of the large size of potassium ions, the intercalation/deintercalation of potassium between the interlayers of graphite results in its huge volume expansion, leading to poor cycling stability and rate performance. Herein, a self-propagating reduction strategy is adopted to fabricate a flexible, self-supporting 3D porous graphite@reduced graphene oxide (3D-G@rGO) composite film for PIBs. The 3D porous network can not only effectively mitigate the volume expansion in graphite but also provide numerous active sites for potassium storage as well as allow for electrolyte penetration and rapid ion migration. Therefore, compared to the pristine graphite anode, the flexible 3D-G@rGO film electrode exhibits greatly improved K-storage performance with a reversible capacity of 452.8 mAh g-1 at 0.1 C and a capacity retention rate of 80.4% after 100 cycles. It also presents excellent rate capability with a high specific capacity of 139.1 and 94.2 mAh g-1 maintained at 2 and 5 C, respectively. The proposed self-propagating reduction strategy to construct a three-dimensional self-supporting structure is a viable route to improve the structural stability and potassium storage performance of graphite anodes.

Integrative analysis of ferroptosis-related genes reveals that ABHD12 is a novel prognostic biomarker and facilitates hepatocellular carcinoma tumorigenesis.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, making the prognostic prediction challenging. Ferroptosis, an iron-dependent form of cell death, is a key regulator in the initiation, progression, and metastasis of HCC. However, the expression and function of ferroptosis-related genes (FRGs) in HCC remained largely unclear. In this study, we analyzed TCGA datasets and identified 58 survival-related deferentially expressed FRGs (DE-FRGs). Then, based on the results of LASSO analysis, we developed a novel prognostic model based on 12 survival-related DE-FRGs. Survival assays indicated a strong prognostic ability of this new model in predicting clinical prognosis of HCC patients. In addition, we conducted an exploration of molecular subtypes related to HCC and delved into the associated immune characteristics and gene expression patterns. Among the 12 survival-related DE-FRGs, our attention focused on ABHD12 (abhydrolase domain containing 12) which was highly expressed in HCC and associated with advanced clinical stages. Multivariate assays confirmed that ABHD12 was a significant prognostic factor for HCC patients. Immune analysis revealed that ABHD12 may play an important role in tumor microenvironment. Finally, we performed RT-PCR and confirmed that ABHD12 was highly expressed in HCC cells. Functional experiments revealed that ABHD12 knockdown may suppress the proliferation and migration of HCC cells. These findings emphasized the significance of ABHD12 as a potential prognostic marker for HCC and its crucial role in the field of tumor biology. Additionally, the study introduces a novel survival model that holds promise for enhancing prognostic predictions in HCC patients. Overall, this research provided valuable insights for a deeper comprehension of the complexity of HCC and the development of personalized treatment strategies.

Superfine Nanodomain Engineering Unleashing Ferroelectricity in Incipient Ferroelectrics.

Incipient ferroelectrics have emerged as an attractive class of functional materials owing to their potential to be engineered for exotic ferroelectric behavior, holding great promise for expanding the ferroelectric family. However, thus far, their artificially engineered ferroelectricity has fallen far short of rivaling classic ferroelectrics. In this study, we address this challenge by developing a superfine nanodomain engineering strategy. By applying this approach to representative incipient ferroelectric of SrTiO3-based films, we achieve unprecedentedly strong ferroelectricity, not only surpassing previous records for incipient ferroelectrics but also being comparable to classic ferroelectrics. The remanent polarization of the thin film reaches up to 17.0 µC cm-2 with an ultrahigh Curie temperature of 973 K. Atomic-scale investigations elucidate the origin of this robust ferroelectricity in the emergent high-density superfine nanodomains spanning merely 3-10 unit cells. Combining experimental results with theoretical assessments, we unveil the underlying mechanism, where the intentionally introduced diluted foreign Fe element creates a deeper Landau energy well and promotes a short-range ordering of polarization. Our developed strategy significantly streamlines the design of unconventional ferroelectrics, providing a versatile pathway for exploring new and superior ferroelectric materials.

Silica nanoparticles induce liver lipid metabolism disorder via ACSL4-mediated ferroptosis.

The disease burden of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Emerging evidence has revealed that silica nanoparticles (SiNPs) could disorder the liver lipid metabolism and cause hepatotoxicity, but the underlying mechanism remains unknown. The purpose of this study is to elucidate the molecular mechanism of hepatic lipid metabolism disorder caused by SiNPs, and to reveal the role of ferroptosis in SiNPs-induced hepatotoxicity. To explore the phenotypic changes in liver, the wild-type C57BL/6J mice were exposed to different doses of SiNPs (5, 10, 20 mg/kg·bw) with or without melatonin (20 mg/kg·bw). SiNPs accelerated hepatic oxidative stress and promoted pathological injury and lipid accumulation, resulting in NAFLD development. Melatonin significantly inhibited the oxidative damage caused by SiNPs. Then, the hepatocytes were treated with SiNPs, the ferroptosis inducer and inhibitor, respectively. In vitro, SiNPs (25 µg/mL) generated mitochondrial and intracellular Fe2+ accumulation and lipid peroxidation repair ability impairment, decreased the activity of GPX4 through ACSL4/p38 MAPK signaling pathway, resulting in ferroptosis of hepatocytes. Notably, Erastin (the ferroptosis activator, 5 µM) increased the sensitivity of hepatocytes to ferroptosis. Ferrostatin-1 (Fer-1, the ferroptosis inhibitor, 5 µM) restored GPX4 activity and protected against deterioration of lipid hydroperoxides (LOOHs) to salvage SiNPs-induced cytotoxicity. Finally, the liver tissue conditional ACSL4 knockout (cKO) mice and ACSL4-KO hepatocytes were adopted to further identify the role of the ACSL4-mediated ferroptosis on SiNPs-induced NAFLD development. The results displayed ACSL4 knockout could down-regulate the lipid peroxidation and ferroptosis, ultimately rescuing the progression of NAFLD. In summary, our data indicated that ACSL4/p38 MAPK/GPX4-mediated ferroptosis was a novel and critical mechanism of SiNPs-induced NAFLD.

Association of triglyceride-glucose index and delirium in patients with sepsis: a retrospective study.

OBJECTIVE: It is well known that glucose and lipid metabolism disorders and insulin resistance are common in sepsis, which affect the occurrence and prognosis of multiple organ dysfunction in septic patients. Previous study reported the predictive value of triglyceride-glucose index (TyG), a clinical indicator for insulin resistance, in postoperative delirium patients. However, it remains unclear whether the TyG index is a novel predictive biomarker for sepsis-associated delirium. The aim of this study is to explore the relationship between TyG index and the risk of delirium in patients with sepsis. METHODS: Adult septic patients were identified from the MIMIC-IV database and divided into four groups based on the mean value of TyG. The primary outcome was the incidence of delirium. The association between TyG and the risk of developing delirium was evaluated by restricted cubic spline (RCS), multivariate logistic regression and subgroup analysis. Propensity Score Matching (PSM) method was used to balance the baseline data. RESULTS: A total of 3,331 septic patients were included in the analysis, and further divided into four groups: Q1 (TyG ≤ 8.67), Q2 (8.67 < TyG ≤ 9.08), Q3 (9.08 < TyG ≤ 9.61), and Q4 (TyG > 9.61). The RCS curves demonstrated a non-linear positive relationship between TyG index and the risk of developing delirium, and an optimal cut-of value 9.09 was recommended. After balancing the baseline information by PSM, patients in the TyG > 9.09 group had a significant higher incidence of delirium compared with those in the TyG ≤ 9.09 group. In logistic regression analysis, TyG > 9.09 was significantly associated with lower risk of developing delirium in both original cohort (OR 1.54-1.78, all P < 0.001) and the PSM cohort (OR 1.41-1.48, all P < 0.001). No association was found between the TyG index and mortality (all P > 0.05). In subgroup analysis, our findings were consistent (all OR > 1 in all subgroups). CONCLUSION: Our study demonstrated an independent association between TyG index and increased risk of delirium in septic patients, indicating that TyG index can serve as a biomarker for delirium in sepsis.

The systematic role of pancreatic cancer exosomes: distant communication, liquid biopsy and future therapy.

Pancreatic cancer remains one of the most lethal diseases worldwide. Cancer-derived exosomes, benefiting from the protective role of the lipid membrane, exhibit remarkable stability in the circulatory system. These exosomes, released by tumor microenvironment, contain various biomolecules such as proteins, RNAs, and lipids that plays a pivotal role in mediating distant communication between the local pancreatic tumor and other organs or tissues. They facilitate the transfer of oncogenic factors to distant sites, contributing to the compromised body immune system, distant metastasis, diabetes, cachexia, and promoting a microenvironment conducive to tumor growth and metastasis in pancreatic cancer patients. Beyond their intrinsic roles, circulating exosomes in peripheral blood can be detected to facilitate accurate liquid biopsy. This approach offers a novel and promising method for the diagnosis and management of pancreatic cancer. Consequently, circulating exosomes are not only crucial mediators of systemic cell-cell communication during pancreatic cancer progression but also hold great potential as precise tools for pancreatic cancer management and treatment. Exosome-based liquid biopsy and therapy represent promising advancements in the diagnosis and treatment of pancreatic cancer. Exosomes can serve as drug delivery vehicles, enhancing the targeting and efficacy of anticancer treatments, modulating the immune system, and facilitating gene editing to suppress tumor growth. Ongoing research focuses on biomarker identification, drug delivery systems, and clinical trials to validate the safety and efficacy of exosome-based therapies, offering new possibilities for early diagnosis and precision treatment in pancreatic cancer. Leveraging the therapeutic potential of exosomes, including their ability to deliver targeted drugs and modulate immune responses, opens new avenues for innovative treatment strategies.

Recent Advancements in Biomaterials for Chimeric Antigen Receptor T Cell Immunotherapy.

Cellular immunotherapy is an innovative cancer treatment method that utilizes the patient's own immune system to combat tumor cells effectively. Currently, the mainstream therapeutic approaches include chimeric antigen receptor T cell (CAR-T) therapy, T cell receptor gene-modified T cell therapy and chimeric antigen receptor natural killer-cell therapy with CAR-T therapy mostly advanced. Nonetheless, the conventional manufacturing process of this therapy has shortcomings in each step that call for improvement. Marked efforts have been invested for its enhancement while notable progresses achieved in the realm of biomaterials application. With CAR-T therapy as a prime example, the aim of this review is to comprehensively discuss the various biomaterials used in cell immunotherapy, their roles in regulating immune cells, and their potential for breakthroughs in cancer treatment from gene transduction to efficacy enhancement. This article additionally addressed widely adopted animal models for efficacy evaluating.

Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

Comparative Analysis of Complete Mitochondrial Genomes of Five Chromodorididae Species (Nudibranchia:Doridina).

Mitochondrial genome is an important molecular marker for exploring the phylogenetic relationships of species and revealing molecular evolution. In the present study, 5 mitogenomes of Chromodorididae (Chromodoris lochi, Chromodoris colemani, Chromodoris elisabethina, Chromodoris annae and Hypselodoris whitei) were systemically investigated. The lengths of the mitogenomes sequences were 14248 bp, 14257 bp, 14252 bp, 14254 bp and 14856 bp, respectively. Most protein-coding genes (PCGs) were initiated with the common ATG codon and terminated with the TAA and TAG. We calculated Ka/Ks values for all 13 PCGs of Chromodorididae species, all ratios were less than 1, indicating selection by purification. Phylogenetic relationships were constructed by Bayesian inference (BI) and maximum likelihood (ML) methods based on all complete genomes of 50 species, primarily from the family Chromodorididae (Doridina) and 2 outgroups. This phylogenetic tree provided further additional references for the classification of the suborder Doridina. Gene rearrangement suggested a more conserved pattern of gene sequences in the superfamily Chromodoridoidea. These results and newly sequenced will contribute to a better understanding of Chromodorididae and provide reference for further phylogenetic studies.

Low-Temperature Decomposition and Oxidation of the Nerve Agent Simulant on Mesoporous Nickel Oxide and Cu-Doped Nickel Oxide.

In an effort to develop the next frontier filtration material for chemical warfare agent (CWA) decomposition, we synthesized mesoporous NiO and CuxNi1-xO (x = 0.10 and 0.20) and studied the decomposition of CWA simulant diisopropyl fluorophosphate (DIFP) on their surfaces. Mesoporous NiO and CuxNi1-xO were fully characterized and found to be a solid solution with no phase separation up to 20% copper dopant. The synthesized materials were successfully templated producing ordered mesoporous metal oxides with high surface areas (67.89- 94.38 m2/g). Through Raman spectroscopy, we showed that pure NiO contained a high concentration of Ni2+ vacancies, while Cu2+ reduced these defects. Through in situ infrared spectroscopy, we determined the surface species formed, potential pathways, and driving factors for decomposition. Upon exposure of DIFP, all materials produced similar decomposition products CO, CO2, carbonyls, and carbonates. However, decomposition reactions were sustained longer on mesoporous NiO, facilitated by the higher Ni2+ vacancy concentration. NiO was further studied with DIFP, first at low dosing temperatures (-50 °C), which still resulted in the production of CO and carbonates, and then, second, with a higher pretreatment temperature, which showed the importance of terminal hydroxyls/water to fully oxidize decomposition products to CO2. Mesoporous NiO demonstrated high decomposition and oxidation capabilities at temperatures below room temperature, all without any external excitation or noble metals, making it a promising frontier filtration material for CWA decomposition.

Molecular simulation of CO production and adsorption in a coal-kaolinite composite gangue slit model.

To reveal the mechanism of CO gas generation and adsorption in coal gangue slits at the microscopic level, a new composite kaolinite-coal-kaolinite (KCK) slit model was constructed by combining the Hongqingliang (HQL) coal molecular model and the Bish kaolinite model to characterize the crack structure of the gangue. It is compared with the kaolinite model (TriK) commonly used in gangue research. Molecular dynamics was used to study the production of CO in different oxygen environments and variation in the adsorption amount, adsorption sites and diffusion coefficient in the temperature range from 293.15 K to 333.15 K. The results indicate that CO mainly comes from the decomposition of ether and phenol in organic structures, and the lower the oxygen concentration, the lesser the CO production time. The KCK model has a higher average adsorption capacity and weaker diffusion capacity mainly due to the additional adsorption sites provided by the carbon-containing structural layer, and CO is mainly adsorbed near the oxygen-containing functional groups. Although kaolinite exhibits bonding adsorption on the Al-O plane, its adsorption site is limited to the surface. The slit model with the carbon structure can better reflect the complex conditions of gas motion in the gangue, thus providing a reference to determine the spontaneous combustion conditions of the gangue hill via the index gas.

Emergence of phase clusters and coexisting states reveals the structure-function relationship.

The Brain Connectome Project has made significant strides in uncovering the structural connections within the brain on various levels. This has led to the question of how brain structure and function are related. Our research explores this relationship in an adaptive neural network in which synaptic conductance between neurons follows spike-time synaptic plasticity rules. By adjusting the plasticity boundary, the network exhibits diverse collective behaviors, including phase synchronization, phase locking, hierarchical synchronization (phase clusters), and coexisting states. Using graph theory, we found that hierarchical synchronization is related to the community structure, while coexisting states are related to the hierarchical self-organizing and core-periphery structure. The network evolves into several tightly connected modules, with sparsely intermodule connections resulting in the formation of phase clusters. In addition, the hierarchical self-organizing structure facilitates the emergence of coexisting states. The coexistence state promotes the evolution of the core-periphery structure. Our results point towards the equivalence between function and structure, with function emerging from structure, and structure being influenced by function in a complex dynamic process.

Structurally Regulated Design Strategy of Bi0.5Na0.5TiO3-Based Ceramics for High Energy-Storage Performance at a Low Electric Field.

Dielectric ceramic capacitors are prospective energy-storage devices for pulsed-power systems owing to their ultrafast charge-discharge speed. However, low energy-storage density makes them difficult to commercialize for high-pulse-power technology applications. Herein, we presented a structurally regulated design strategy to disrupt a long-range ferroelectric order, refined grains, and eventually achieve excellent comprehensive energy-storage performance in (1 - x) (0.7Bi0.5Na0.5TiO3-0.3SrTiO3)-x Sm(Zn2/3Nb1/3)O3 eco-friendly ceramics. A large Wrec of ∼7.43 ± 0.05 J/cm3 and a high η of ∼85 ± 0.5% of 0.96 (0.7Bi0.5Na0.5TiO3-0.3SrTiO3)-0.04 Sm(Zn2/3Nb1/3)O3 were obtained at a low electric field of 290 kV cm-1 with good energy-storage temperature (25-120 °C), frequency (1-100 Hz) stability, and charge-discharge properties (PD ∼ 74 ± 1 MW/cm3 and τ0.9 ∼ 159 ± 2 ns). This strategy inspires rational structurally regulated designs and aims to promote the development of eco-friendly 0.7Bi0.5Na0.5TiO3-based ceramics with excellent energy-storage characteristics.

Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial.

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.

Multiscale characterizations of structural evolution in mesoporous CeO2.

In situ ultra-small-angle and wide-angle X-ray scattering enables simultaneous tracking of the structural parameters of mesoporous CeO2 from the atomic scale to the micron-size scale. This multiscale approach provides a path to better understand structure-property relationships in mesoporous polycrystalline materials under dynamic conditions such as high temperature cycling.

A Triboelectric-Electromagnetic Hybrid Generator for Harvesting River Energy and Wind Energy for River Ecosystem Monitoring.

Currently, monitoring the ecological conditions of watercourses is overly unitary and inefficient and is burdened by high costs. A cost-effective, efficient, self-powered sensor for incorporating the Internet of Things (IoT) into the surveillance of riverine ecosystems is lacking. This manuscript introduces a device designed for energy harvesting and sensing through a triboelectric-electromagnetic generator (CX-TEHG). The CX-TEHG is composed of a wind-driven electromagnetic generator (F-EMG), a river-driven electromagnetic generator (W-EMG), a triboelectric nanogenerator for measuring flow velocity (W-TENG), and another triboelectric nanogenerator for gauging the speed of floodwater level rise (F-TENG). It employs planetary gears to achieve a 6-fold increase in speed, facilitating efficient multienergy collection from wind and river currents. CX-TEHG achieves a peak power output of 183 mW and a power density of 373.5 W/m3 under environmental conditions featuring a wind speed of 4 m/s and a flow velocity of 0.5 m/s. This study developed a cost-efficient signal acquisition system and a mechanism for information transmission via a 5G module. Alerts are issued on both upper-level computers and mobile devices for river flow velocities exceeding 2.8 m/s and water levels reaching specified locations; thus, an innovative solution for applying the Internet of Things in riverine ecological monitoring is presented.

Academic visualization study of aesthetic medicine management and related legal research since 2000.

BACKGROUND: Aesthetics medicine, a controversial branch of clinical medicine known for its high degree of commercialization, faces numerous conflicts, particularly in some developing countries. The global aesthetics medicine industry requires enhancements of its legal and supervision framework and risk management systems. AIMS: This paper aimed to provide a comprehensive visual analysis of academic achievements related to regulatory and legal issues in the field of aesthetic medicine and to identify its development trends and research hotspots. METHODS: The Web of Science Core Collection was employed to retrieve relevant studies, resulting in a total of 602 research articles after selection. Utilizing bibliometric methods and CiteSpace, this study analyzed the primary countries, institutions, authors, journals, hotspots, frontiers, and trends in this domain. RESULTS: The findings indicated rapid increases in the number of published papers. The United States emerged as the leading contributor with 131 research papers and the highest intermediate centrality. Eleven keyword clusters were identified, with "adolescence" and "office-based surgery" being the most recent topics. We also analyzed the trends and frontiers of legal research in medical aesthetics. CONCLUSION: The importance of informed consent has been increasingly emphasized, and research in the field of medical aesthetics has been gradually expanding beyond individual cosmetic procedures. The management system has become more comprehensive, moreover, guidelines and medical laws have been continually published, with research shifting toward a holistic perspective that encompasses patients, medical aesthetic providers, and regulatory authorities in the study of medical aesthetics regulation and legislation. This paper also proposes some innovative directions for future research and applications.

ITFG2, an immune-modulatory protein, targets ATP 5b to maintain mitochondrial function in myocardial infarction.

ITFG2, as an immune-modulatory intracellular protein that modulate the fate of B cells and negatively regulates mTORC1 signaling. ITFG2 is highly expressed in the heart, but its pathophysiological function in heart disease is unclear. In this study, we found that in MI mice, overexpression of ITFG2 via an AAV9 vector significantly reduced the infarct size and ameliorated cardiac function. Knockdown of endogenous ITFG2 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In cardiac-specific ITFG2 transgenic (TG) mice, myocardial infarction size was smaller, eject fraction (EF) and fractional shortening (FS) was higher compared to those in wild-type (WT) mice, suggesting ITFG2 reversed cardiac dysfunction induced by MI. In hypoxic neonatal cardiomyocytes (NMCMs), overexpression of ITFG2 maintained mitochondrial function by increasing intracellular ATP production, reducing ROS levels, and preserving the mitochondrial membrane potential (MMP). Overexpression of ITFG2 reversed the mitochondrial respiratory dysfunction in NMCMs induced by hypoxia. Knockdown of endogenous ITFG2 by siRNA did the opposite. Mechanism, ITFG2 formed a complex with NEDD4-2 and ATP 5b and inhibited the binding of NEDD4-2 with ATP 5b leading to the reduction ubiquitination of ATP 5b. Our findings reveal a previously unknown ability of ITFG2 to protect the heart against ischemic injury by interacting with ATP 5b and thereby regulating mitochondrial function. ITFG2 has promise as a novel strategy for the clinical management of MI.

A cell-free transcription-translation pipeline for recreating methylation patterns boosts DNA transformation in bacteria.

The bacterial world offers diverse strains for understanding medical and environmental processes and for engineering synthetic biological chassis. However, genetically manipulating these strains has faced a long-standing bottleneck: how to efficiently transform DNA. Here, we report imitating methylation patterns rapidly in TXTL (IMPRINT), a generalized, rapid, and scalable approach based on cell-free transcription-translation (TXTL) to overcome DNA restriction, a prominent barrier to transformation. IMPRINT utilizes TXTL to express DNA methyltransferases from a bacterium's restriction-modification systems. The expressed methyltransferases then methylate DNA in vitro to match the bacterium's DNA methylation pattern, circumventing restriction and enhancing transformation. With IMPRINT, we efficiently multiplex methylation by diverse DNA methyltransferases and enhance plasmid transformation in gram-negative and gram-positive bacteria. We also develop a high-throughput pipeline that identifies the most consequential methyltransferases, and we apply IMPRINT to screen a ribosome-binding site library in a hard-to-transform Bifidobacterium. Overall, IMPRINT can enhance DNA transformation, enabling the use of sophisticated genetic manipulation tools across the bacterial world.

lncRNA Gm20257 alleviates pathological cardiac hypertrophy by modulating the PGC-1α-mitochondrial complex IV axis.

Pathological cardiac hypertrophy, a major contributor to heart failure, is closely linked to mitochondrial function. The roles of long noncoding RNAs (lncRNAs), which regulate mitochondrial function, remain largely unexplored in this context. Herein, a previously unknown lncRNA, Gm20257, was identified. It markedly increased under hypertrophic stress in vivo and in vitro. The suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte hypertrophy. Conversely, the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensin II-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively, thus restoring cardiac function. Importantly, Gm20257 restored mitochondrial complex IV level and enhanced mitochondrial function. Bioinformatics prediction showed that Gm20257 had a high binding score with peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), which could increase mitochondrial complex IV. Subsequently, Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1α. Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1α was a direct downstream target of Gm20257. This interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial ATP. These findings suggest that Gm20257 improves mitochondrial function through the PGC-1α-mitochondrial complex IV axis, offering a novel approach for attenuating pathological cardiac hypertrophy.