The m6A methyltransferase METTL3 drives neuroinflammation and neurotoxicity through stabilizing BATF mRNA in microglia.

Persistent neuroinflammation and progressive neuronal loss are defining features of acute brain injury including traumatic brain injury (TBI) and cerebral stroke. Microglia, the most abundant type of brain-resident immune cells, continuously surveil the environment and play a central role in shaping the inflammatory state of the central nervous system (CNS). In the study, we discovered that the protein expression of METTL3 (a m6A methyltransferase) was upregulated in inflammatory microglia independent of increased Mettl3 gene transcription following TBI in both human and mouse subjects. Subsequently, we identified TRIP12, a HECT-domain E3 ubiquitin ligase, as a negative regulator of METTL3 protein expression by facilitating METTL3 K48-linked polyubiquitination. Importantly, selective ablation of Mettl3 inhibited microglial pathogenic activities, diminished neutrophil infiltration, rescued neuronal loss and facilitated functional recovery post-TBI. Using MeRIP-seq and CUT&Tag sequencing, we identified that METTL3 promoted the expression of Basic Leucine Zipper Transcriptional Factor ATF-Like (BATF), which in turn directly bound to a cohort of characteristic inflammatory cytokines and chemokine genes. Enhanced activities of BATF in microglia elicited TNF-dependent neurotoxicity and can also promote neutrophil recruitment through releasing CXCL2. Pharmacological inhibition of METTL3 using a BBB-penetrating drug-loaded nano-system showed satisfactory therapeutic effects in both TBI and stroke mouse models. Collectively, our findings identified METTL3-m6A-BATF axis as a potential therapeutic target for terminating detrimental neuroinflammation and progressive neuronal loss following acute brain injury. METTL3 protein is significantly up-regulated in inflammatory microglia due to the decreased proteasomal degradation mediated by TRIP12 and ERK-USP5 pathways. METTL3 stabilized BATF mRNA stability and promoted BATF expression through the m6A-IGF2BP2-dependent mechanism. Elevated expression of BATF elicits a pro-inflammatory gene program in microglia, and aggravates neuroinflammatory response including local immune responses and peripheral immune cell infiltration. Genetic deletion or pharmaceutically targeting METTL3-BATF axis suppressed microglial pro-inflammatory activities and promoted neurological recovery following TBI and stroke.

Trends in injury-related mortality among residents of Jiangsu Province from 2012 to 2021: an age-period-cohort analysis.

Objective: We investigated the temporal trends and examined age-, period-, and cohort-specific effects of injury-related deaths among residents in Jiangsu to provide evidence for future injury prevention. Methods: This study included 406,936 injury deaths from the Jiangsu provincial population death registration system. The average annual percent change (AAPC) in age-standardized mortality rates (ASMRs) was analyzed using joinpoint regression. Age-period-cohort models were generated to explore the effects of age, period, and birth cohort effects on mortality risk. Results: ASMRs for all injuries (AAPC = -2.3%), road traffic accidents (AAPC = -5.3%), suicide (AAPC = -3.8%), and drowning (AAPC = -3.9%) showed a downward trend during 2012-2021(all p < 0.05), while unintentional falls showed an upward trend (AAPC = 5.1%, p < 0.05). From 2012 to 2021, the age-standardized mortality rates (ASMRs) for four primary types of injuries consistently exhibited higher among males compared to females, with rural regions displaying higher ASMRs than urban areas. Trends in ASMRs for road traffic accidents, drowning, and unintentional falls by sex and urban/rural areas were consistent with overall trends. Significant age, cohort, and period effects were identified in the trends of injury-related deaths for both sexes in Jiangsu. The age effect showed that the highest age effect for injury-related deaths was for the ages of 85 years and above, except for suicide, which was for the ages 80-84 years. Between 2012 and 2021, the period effect on road traffic accidents declined, while that on accidental falls increased. Initially, the period effect on suicide decreased but then rose, peaking in 2012 with a Relative Risk (RR) of 1.11 (95% CI: 1.04-1.19). Similarly, the period effect on drowning initially declined before rising, with the highest effect observed in 2013, at an RR of 1.12 (95% CI: 1.07-1.19). The highest cohort effects for road traffic accidents were observed in the 1957-1961 group, for accidental falls in the 1952-1956 group, and for both drowning and suicide in the 1927-1931 group. Conclusion: The mortality rate of unintentional falls has been increasing. Older adults are at high risk for the four leading injuries. The improvements in mortality rates can be attributed to advancements in education, urbanization, and the promulgation and implementation of laws and policies.

FNDC5 prevents oxidative stress and neuronal apoptosis after traumatic brain injury through SIRT3-dependent regulation of mitochondrial quality control.

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

Assessing the Impact of Charged Particle Radiation Therapy for Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis.

Purpose: Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential radiotherapy treatment for radioresistant malignancies. This study aims to conduct a meta-analysis to evaluate the impact of charged particle radiation therapy on HNACC. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, Web of Science, Embase, and Medline until December 31, 2022. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), while secondary outcomes included treatment-related toxicity. Version 17.0 of STATA was used for all analyses. Results: A total of 14 studies, involving 1297 patients, were included in the analysis. The pooled 5-year OS and PFS rates for primary HNACC were 78% (95% confidence interval [CI] = 66-91%) and 62% (95% CI = 47-77%), respectively. For all patients included, the pooled 2-year and 5-year OS, LC, and PFS rates were as follows: 86.1% (95% CI = 95-100%) and 77% (95% CI = 73-82%), 92% (95% CI = 84-100%) and 73% (95% CI = 61-85%), and 76% (95% CI = 68-84%) and 55% (95% CI = 48-62%), respectively. The rates of grade 3 and above acute toxicity were 22% (95% CI = 13-32%), while late toxicity rates were 8% (95% CI = 3-13%). Conclusions: Particle therapy has the potential to improve treatment outcomes and raise the quality of life for HNACC patients. However, further research and optimization are needed due to the limited availability and cost considerations associated with this treatment modality.

[Preliminarily study of arthrocentesis combined with liquid phase concentrated growth factor injection in the treatment of unilateral temporomandibular joint osteoarthritis].

OBJECTIVE: To observe the clinical effect of arthrocentesis combined with liquid phase concentrated growth factor (CGF) injection in the treatment of unilateral temporomandibular joint osteoarthritis (TMJOA), in order to provide a new treatment option for TMJOA patients. METHODS: In this non-randomized controlled study, patients diagnosed with unilateral TMJOA who visited the center for temporomandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects. The patients were divided into experimental group and control group, which were selected by patients themselves. The experimental group received arthrocentesis combined with liquid phase CGF injection and the control group received arthrocentesis combined with HA injection. Both groups were treated 3 times, once every two weeks. The clinical effect was evaluated by the maximum mouth opening, pain value and the degree of mandibular function limitation 6 months after treatment. The change of condylar bone was evaluated by cone beam CT (CBCT) image fusion technology before and after treatment. RESULTS: A total of 20 patients were included in the experimental group, including 3 males and 17 females, with an average age of (34.40±8.41) years. A total of 15 patients were included in the control group, including 1 male and 14 females, with an average age of (32.20±12.00) years. There was no statistical difference in general information between the two groups (P > 0.05). There were no statistical differences in the mouth opening, pain value and the degree of jaw function limitation between the two groups before treatment (P > 0.05), and all of them improved 6 months after treatment compared with before treatment (P < 0.05). However, the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment (P < 0.05), and the degree of jaw function limitation was significantly lower than that of control group (P < 0.05). CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment, and image fusion results showed that 10 patients (50.0%) in the experimental group and 5 patients (33.3%) in the control group had reparative remodeling area of condylar bone, and there was no statistical difference between them (P > 0.05). Except for one CGF patient, the other patients in both groups had some absorption areas of condylar bone. CONCLUSION: The arthrocentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term, and is better than HA in increasing mouth opening and improving jaw function. CBCT fusion images of both patient groups show some cases of condylar bone reparative remodeling and its relevance to treatment plans still requires further study.

Intelligent perceptual textiles based on ionic-conductive and strong silk fibers.

Endowing textiles with perceptual function, similar to human skin, is crucial for the development of next-generation smart wearables. To date, the creation of perceptual textiles capable of sensing potential dangers and accurately pinpointing finger touch remains elusive. In this study, we present the design and fabrication of intelligent perceptual textiles capable of electrically responding to external dangers and precisely detecting human touch, based on conductive silk fibroin-based ionic hydrogel (SIH) fibers. These fibers possess excellent fracture strength (55 MPa), extensibility (530%), stable and good conductivity (0.45 S·m-1) due to oriented structures and ionic incorporation. We fabricated SIH fiber-based protective textiles that can respond to fire, water, and sharp objects, protecting robots from potential injuries. Additionally, we designed perceptual textiles that can specifically pinpoint finger touch, serving as convenient human-machine interfaces. Our work sheds new light on the design of next-generation smart wearables and the reshaping of human-machine interfaces.

The Association of Serum Complement C1q with Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Coronary artery disease (CAD) is one of the leading causes of death in middle-aged and elderly people, and its incidence has been increasing in recent years. An in-depth understanding of the pathogenesis of CAD is important to ensure the health of CAD patients. Objective: To analyze the association of serum complement C1q with CAD," you could say something like "The objective of this meta-analysis is to investigate the relationship between serum complement C1q levels and the presence of CAD, aiming to provide insights for clinical diagnosis and treatment. Methods: Relevant studies on C1q and CAD were searched in PubMed, Web of Science and other literature databases. Two research team members independently cross-screened the literature according to the inclusion-exclusion criteria and assessed the literature quality. RevMan5.3 software was used for statistical analysis. Results: Three references were finally included, all of which had a Newcastle-Ottawa Scale (NOS) score ≥6, indicating high quality. A total of 2065 subjects were studied, including 1249 in the experimental group (CAD patients) and 816 in the control group (healthy population). Through the meta-analysis, it was found that the experimental group (CAD patients) had higher serum C1q than the control group (healthy controls) (P < .05). According to subgroup analysis, age, sex, sample size, diabetes mellitus (with/without), and serum complement C1q detection methods were not factors affecting the heterogeneity of the literature, and more data are needed for verification. Validation analysis with the fixed-effect model also showed higher C1q expression in the experimental group (P < .05). The graph of the funnel plot was basically symmetrical, suggesting low publication bias. Conclusions: Serum complement C1q is elevated in CAD patients, but its mechanism of action may have a dual effect, but further research is needed to understand its precise role and clinical implications.

Exosomal circ_0000735 contributes to non-small lung cancer malignant progression.

Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism in NSCLC progression need to be further explored. The expression levels of circ_0000735, miR-345-5p and A disintegrin and metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing and transwell assays were utilized to detect cell proliferation and metastasis. The protein levels of metastasis markers, exosome markers and ADAM19 were determined using western blot. Animal experiments were performed to confirm the role of circ_0000735 in NSCLC tumorigenesis. The exosomes from cells and serum were identified using transmission electron microscopy and nanoparticle tracking analysis. We found that circ_0000735 was upregulated in NSCLC, and its knockdown repressed NSCLC cell proliferation and metastasis. In terms of mechanism, circ_0000735 targeted miR-345-5p to regulate ADAM19. MiR-345-5p inhibitor reversed the suppressive effect of circ_0000735 knockdown on NSCLC progression, and ADAM19 overexpression abolished the inhibition effect of miR-345-5p on NSCLC progression. Also, animal experiments showed that silencing of circ_0000735 reduced NSCLC tumorigenesis. In addition, exosomes mediated the intercellular transmission of circ_0000735, and serum exosomal circ_0000735 might be an important indicator for the diagnosis of NSCLC. In conclusion, circ_0000735 facilitated NSCLC progression via miR-345-5p/ADAM19 pathway, and serum exosomal circ_0000735 might be a potential biomarker for NSCLC diagnosis.

Joint-GWAS, Linkage Mapping, and Transcriptome Analysis to Reveal the Genetic Basis of Plant Architecture-Related Traits in Maize.

Plant architecture is one of the key factors affecting maize yield formation and can be divided into secondary traits, such as plant height (PH), ear height (EH), and leaf number (LN). It is a viable approach for exploiting genetic resources to improve plant density. In this study, one natural panel of 226 inbred lines and 150 family lines derived from the offspring of T32 crossed with Qi319 were genotyped by using the MaizeSNP50 chip and the genotyping by sequence (GBS) method and phenotyped under three different environments. Based on the results, a genome-wide association study (GWAS) and linkage mapping were analyzed by using the MLM and ICIM models, respectively. The results showed that 120 QTNs (quantitative trait nucleotides) and 32 QTL (quantitative trait loci) related to plant architecture were identified, including four QTL and 40 QTNs of PH, eight QTL and 41 QTNs of EH, and 20 QTL and 39 QTNs of LN. One dominant QTL, qLN7-2, was identified in the Zhangye environment. Six QTNs were commonly identified to be related to PH, EH, and LN in different environments. The candidate gene analysis revealed that Zm00001d021574 was involved in regulating plant architecture traits through the autophagy pathway, and Zm00001d044730 was predicted to interact with the male sterility-related gene ms26. These results provide abundant genetic resources for improving maize plant architecture traits by using approaches to biological breeding.

Prioritized single vitrified blastocyst to be warmed between grades 3 or 4 blastocyst on day 5 transfer cycles.

PURPOSE: Selecting the optimal blastocyst to implant during cryopreservation and warming is critial for in vitro fertilization success. Therefore, the aim of this study was to explore which blastocyst should be prioritized to be thawed when facing a single vitrified blastocyst on day 5 transfer. METHODS: A retrospective study including 1,976 single vitrified-warmed blastocyst transfer cycles was conducted from January 2016 to December 2020. RESULTS: We found that grade 4 vitrified blastocyst had a higher clinical pregnancy (60.64% vs. 49.48%, P < 0.001) and live birth rates (50.12% vs 39.59%, P < 0.001) than the grade 3 vitrified blastocyst. However, no statistical difference was found between groups in miscarriage rate, birth weight, or gestational age. Besides, the grade 4 vitrified-thawed blastocyst had significant potential to develop into grade 6 blastocyst after further culturing for 16 h (73.68% vs. 48.60%, P < 0.001). The grade 6 transferred blastocyst was markedly higher in both clinical pregnancy rate (61.88% vs. 51.53%, P < 0.001) and live birth rate (50.91% vs. 40.46%, P < 0.001) compared to grade 5 transferred blastocyst. CONCLUSIONS: Grade 4 vitrified blastocyst is recommended when facing single vitrified blastocyst on day 5 transfer. More importantly, the "embryonic escape hypothesis" was firstly proposed to reveal the findings.

UV-A radiation increases biomass yield by enhancing energy flow and carbon assimilation in the edible cyanobacterium Nostoc sphaeroides.

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.

Omics Approaches Unveiling the Biology of Human Atherosclerotic Plaques.

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the buildup of plaques with the accumulation and transformation of lipids, immune cells, vascular smooth muscle cells, and necrotic cell debris. Plaques with collagen-poor thin fibrous caps infiltrated by macrophages and lymphocytes are considered unstable because they are at the greatest risk of rupture and clinical events. However, the current histologic definition of plaque types may not fully capture the complex molecular nature of atherosclerotic plaque biology and the underlying mechanisms contributing to plaque progression, rupture, and erosion. The advances in omics technologies have changed the understanding of atherosclerosis plaque biology, offering new possibilities to improve risk prediction and discover novel therapeutic targets. Genomic studies have shed light on the genetic predisposition to atherosclerosis, and integrative genomic analyses expedite the translation of genomic discoveries. Transcriptomic, proteomic, metabolomic, and lipidomic studies have refined the understanding of the molecular signature of atherosclerotic plaques, aiding in data-driven hypothesis generation for mechanistic studies and offering new prospects for biomarker discovery. Furthermore, advancements in single-cell technologies and emerging spatial analysis techniques have unveiled the heterogeneity and plasticity of plaque cells. This review discusses key omics-based discoveries that have advanced the understanding of human atherosclerotic plaque biology, focusing on insights derived from omics profiling of human atherosclerotic vascular specimens.

Hybrid Density Functional Valence Bond Method with Multistate Treatment.

Recently, a hybrid density functional valence bond (VB) method, λ-DFVB(U), has been proposed and shown to give accuracy that is comparable to that of CASPT2 in calculations of atomization energies, atomic excitation energies, and reaction barriers, while its computational cost is approximately the same as the valence bond self-consistent-field (VBSCF) method. However, the interaction between electronic states is not included in λ-DFVB(U) since the last step of λ-DFVB(U) is not a diagonalization of the Hamiltonian matrix on the electronic state basis. Therefore, λ-DFVB(U) gives the wrong topology of the potential energy surfaces (PESs) near the conical intersection region. In the present paper, we propose a novel hybrid density functional VB method with multistate treatment, named λ-DFVB(MS), in which an effective Hamiltonian matrix is constructed on the basis of the diabatic states obtained by the valence-bond-based compression approach for the diabatization scheme, and the interaction between electronic states can be included through the diagonalization of the effective Hamiltonian matrix. Test calculations show that λ-DFVB(MS) gives the correct topology of the PESs near the conical intersection region. We also show that the VBSCF wave function with selected VB structures can be applied as a reference in λ-DFVB(MS).

Cys-loop ligand-gated ion channel superfamily of Pardosa pseudoannulata: Implication for natural enemy safety.

Cys-loop ligand-gated channels mediate neurotransmission in insects and are receptors for many insecticides. Some insecticides acting on cysLGIC also have lethal effects on non-targeting organisms, but the mechanism of this negative effect is unclear due to information absence. The identification and analysis of cysLGIC family in Pardosa pseudoannulata, a pond wolf spider, can deepen the understanding of insecticides for natural enemy safety. Thirty-four cysLGIC genes were identified in P. pseudoannulata genome, including nicotinic acetylcholine receptors, γ-aminobutyric acid gated chloride channels, glutamate-gated chloride channels, histamine-gated chloride channels, and pH-sensitive chloride channels. The expansion of GABACls and HisCls accounts for the large number of cysLGICs in P. pseudoannulata, and the alternative splicing events in nAChR and RDL subunits enriched the diversity of the superfamily. Most cysLGIC genes show the highest expression in brain and lowest expression in the early-egg sac stage. Variable residues (R81, V83, R135, N137, F190, and W197) in P. pseudoannulata nAChR ß subunits and critical differences in α6 subunit TM4 region compared with insects would apply for the insensitivity to neonicotinoids and spinosyn. In contrast, avermectin and dieldrin may be lethal to P. pseudoannulata due to the similar drugs binding sites in GluCls compared with insects. These findings will provide a valuable clue for natural enemy protection and environmentally friendly insecticide development.

A dual-selective thermal emitter with enhanced subambient radiative cooling performance.

Radiative cooling is a zero-energy technology that enables subambient cooling by emitting heat into outer space (~3 K) through the atmospheric transparent windows. However, existing designs typically focus only on the main atmospheric transparent window (8-13 µm) and ignore another window (16-25 µm), under-exploiting their cooling potential. Here, we show a dual-selective radiative cooling design based on a scalable thermal emitter, which exhibits selective emission in both atmospheric transparent windows and reflection in the remaining mid-infrared and solar wavebands. As a result, the dual-selective thermal emitter exhibits an ultrahigh subambient cooling capacity (~9 °C) under strong sunlight, surpassing existing typical thermal emitters (≥3 °C cooler) and commercial counterparts (as building materials). Furthermore, the dual-selective sample also exhibits high weather resistance and color compatibility, indicating a high practicality. This work provides a scalable and practical radiative cooling design for sustainable thermal management.

Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair.

BACKGROUND: We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model. METHODS: In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups (n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. RESULTS: After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. CONCLUSIONS: MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.

Astrocyte-Derived Extracellular Vesicular miR-143-3p Dampens Autophagic Degradation of Endothelial Adhesion Molecules and Promotes Neutrophil Transendothelial Migration after Acute Brain Injury.

Pivotal roles of extracellular vesicles (EVs) in the pathogenesis of central nervous system (CNS) disorders including acute brain injury are increasingly acknowledged. Through the analysis of EVs packaged miRNAs in plasma samples from patients with intracerebral hemorrhage (ICH), it is discovered that the level of EVs packaged miR-143-3p (EVs-miR-143-3p) correlates closely with perihematomal edema and neurological outcomes. Further study reveals that, upon ICH, EVs-miR-143-3p is robustly secreted by astrocytes and can shuttle into brain microvascular endothelial cells (BMECs). Heightened levels of miR-143-3p in BMECs induce the up-regulated expression of cell adhesion molecules (CAMs) that bind to circulating neutrophils and facilitate their transendothelial cell migration (TEM) into brain. Mechanism-wise, miR-143-3p directly targets ATP6V1A, resulting in impaired lysosomal hydrolysis ability and reduced autophagic degradation of CAMs. Importantly, a VCAM-1-targeting EVs system to selectively deliver miR-143-3p inhibitor to pathological BMECs is created, which shows satisfactory therapeutic effects in both ICH and traumatic brain injury (TBI) mouse models. In conclusion, the study highlights the causal role of EVs-miR-143-3p in BMECs' dysfunction in acute brain injury and demonstrates a proof of concept that engineered EVs can be devised as a potentially applicable nucleotide drug delivery system for the treatment of CNS disorders.

Stretchable, Programmable and Magnet-Insensitive Protonic Display Based on Integrated Ionic Circuit.

As a new approach to "More than Moore", integrated ionic circuits serve as a possible alternative to traditional electronic circuits, yet the integrated ionic circuit composed of functional ionic elements and ionic connections is still challenging. Herein, a stretchable and transparent ionic display module of the integrated ionic circuit has been successfully prepared and demonstrated by pixelating a proton-responsive hydrogel. It is programmed to excite the hydrogel color change by a Faraday process occurring at the electrode at the specific pixel points, which enables the display of digital information and even color information. Importantly, the display module exhibits stable performance under strong magnetic field conditions (1.7 T). The transparent and stretchable nature of such ionic modules also allows them to be utilized in a broad range of scenarios, which paves the way for integrated ionic circuits.

Ultraviolet sensing based on an in-fiber ZnO microwire constructed Mach-Zehnder interferometer.

We propose a Mach-Zehnder interferometer based on an in-fiber ZnO microwire structure for ultraviolet sensing. The device undergoes femtosecond laser micromachining and chemical etching on a single-mode optical fiber initially, creating a microgroove that extends to half of the core's depth, into which a single ZnO microwire is transferred. The ZnO microwire and the remaining core are used as the sensing arm and the reference arm, respectively, forming a Mach-Zehnder interferometer. To enhance the stability and the sensitivity, ZnO nanoparticles are filled into the microgroove after the ZnO microwire is transferred. The fabricated device exhibits a sensitivity of 0.86 nm/(W·cm-2) for ultraviolet sensing, along with a response time of 115 ns (rise time) and 133 µs (decay time), respectively. The proposed sensor exhibits good ultraviolet sensitivity, offering a novel approach for ultraviolet sensing technology.

Sustainable Biochar Nanosheets Derived from Sweet Sorghum Residues via Superbase Pretreatment.

Two-dimensional (2D) sheet-like biochar as promising alternatives to graphene nanosheets has gained significant attention in materials science while being highly restricted by its complicated synthetic steps. In this study, the dimethyl sulfoxide/potassium hydroxide (DMSO/KOH) superbase system was first used to pretreat sweet sorghum residues (SS) and then carbonized to prepare sheet-like biochar. Ascribing to the strong nucleophilicity of DMSO/KOH, a synergistic effect was achieved by partially removing non-cellulosic components in SS and swelling the amorphous region of cellulose, leaving more layered cellulose behind (∼46.5 wt %), which was favorable for the formation of 2D biochar nanosheets with high graphitization degrees (∼93.1%). This strategy was also suitable for other biomass fibers (e.g., straw, wood powders, and nuclear shells) to obtain sheet-like biochar. The resulting sheet-like biochar could be compounded with cellulose nanofibers to achieve the structural design of composites and solve the molding problem of biochar, which was beneficial for dyeing wastewater treatment. Thus, this work provides insight into a simple strategy for developing 2D ultrathin sheet-like biochar from sustainable biomass wastes.