Detoxifying bacterial genes for deoxynivalenol epimerization confer durable resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

Surface Crystallization Enhancement and Defect Passivation for Efficiency and Stability Enhancement of Inverted Wide-Bandgap Perovskite Solar Cells.

Wide-bandgap (WBG) inverted perovskite solar cells (PSCs) are used as the top cell for tandem solar cells, which is an effective way to outperform the Shockley-Queisser limit. However, the low efficiency and poor phase stability still seriously restrict the application of WBG inverted PSCs. Here, the surface of the WBG perovskite film was passivated by the synthesized 1,2,4-tris(3-thienyl)benzene (THB). The THB size well matches with the halogen ion vacancy on the perovskite surface, and the S atom in THB can strongly interact with Pb2+ on the surface of the WBG perovskite film to the greatest extent, which effectively passivates surface defects and suppresses the recombination of carriers caused by these defects. At the same time, the S atom in THB occupied the migration site of the halogen ions, which inhibits the migration of halogen ions. Due to the strong conjugation effect and stability of THB, it can be locked on the surface of perovskite to increase the lattice strength and inhibit the segregation of photoinduced halide, thus improving the performance and operational stability of PSCs. The THB-modified WBG (Eg = 1.71 eV) PSC achieves a maximum power conversion efficiency of 20.75%, and its 99.0% is retained after 1512 h at a relative humidity of 10-25%. Under the irradiation of 1000 lx LED light, the indoor power conversion efficiency of the THB-modified WBG PSC reaches 34.15%.

Mitochondria-Targeted Prodrug Nanoassemblies for Efficient Ferroptosis-Based Therapy via Devastating Ferroptosis Defense Systems.

Ferroptosis is a form of regulated cell death accompanied by lipid reactive oxygen species (ROS) accumulation in an iron-dependent manner. However, the efficiency of tumorous ferroptosis was seriously restricted by intracellular ferroptosis defense systems, the glutathione peroxidase 4 (GPX4) system, and the ubiquinol (CoQH2) system. Inspired by the crucial role of mitochondria in the ferroptosis process, we reported a prodrug nanoassembly capable of unleashing potent mitochondrial lipid peroxidation and ferroptotic cell death. Dihydroorotate dehydrogenase (DHODH) inhibitor (QA) was combined with triphenylphosphonium moiety through a disulfide-containing linker to engineer well-defined nanoassemblies (QSSP) within a single-molecular framework. After being trapped in cancer cells, the acidic condition provoked the structural disassembly of QSSP to liberate free prodrug molecules. The mitochondrial membrane-potential-driven accumulation of the lipophilic cation prodrug was delivered explicitly into the mitochondria. Afterward, the thiol-disulfide exchange would occur accompanied by downregulation of reduced glutathione levels, thus resulting in mitochondria-localized GPX4 inactivation for ferroptosis. Simultaneously, the released QA from the hydrolysis reaction of the adjacent ester bond could further devastate mitochondrial defense and evoke robust ferroptosis via the DHODH-CoQH2 system. This subcellular targeted nanoassembly provides a reference for designing ferroptosis-based strategy for efficient cancer therapy through interfering antiferroptosis systems.

Modulation of the RAC1/MAPK/ERK signalling pathway by farnesyl diphosphate synthase regulates granulosa cells proliferation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex gynaecological endocrine disease that occurs in women of childbearing age. The pathogenesis of PCOS is still unclear and further exploration is needed. Here, proteomic analysis indicated that the expression of farnesyl diphosphate synthase (FDPS) protein in ovarian tissue of PCOS mice was significantly decreased. The purpose of this study is to investigate the relationship between potential biomarkers of PCOS and granulosa cells (GCs) function. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 (Rac Family Small GTPase 1) activity and regulated MAPK/ERK signalling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the adeno-associated virus (AAV)-FDPS reverses the dehydroepiandrosterone (DHEA)-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK (mitogen-activated protein kinase/extracellular regulated protein kinases) pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.

Bifunctional ligand Co metal-organic framework derived heterostructured Co-based nanocomposites as oxygen electrocatalysts toward rechargeable zinc-air batteries.

Rational construction of efficient and robust bifunctional oxygen electrocatalysts is key but challenging for the widespread application of rechargeable zinc-air batteries (ZABs). Herein, bifunctional ligand Co metal-organic frameworks were first explored to fabricate a hybrid of heterostructured CoOx/Co nanoparticles anchored on a carbon substrate rich in CoNx sites (CoOx/Co@CoNC) via a one-step pyrolysis method. Such a unique heterostructure provides abundant CoNx and CoOx/Co active sites to drive oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), respectively. Besides, their positive synergies facilitate electron transfer and optimize charge/mass transportation. Consequently, the obtained CoOx/Co@CoNC exhibits a superior ORR activity with a higher half-wave potential of 0.88 V than Pt/C (0.83 V vs. RHE), and a comparable OER performance with an overpotential of 346 mV at 10 mA cm-2 to the commercial RuO2. The assembled ZAB using CoOx/Co@CoNC as a cathode catalyst displays a maximum power density of 168.4 mW cm-2, and excellent charge-discharge cyclability over 250 h at 5 mA cm-2. This work highlights the great potential of heterostructures in oxygen electrocatalysis and provides a new pathway for designing efficient bifunctional oxygen catalysts toward rechargeable ZABs.

High-Quality TiO2 Electron Transport Film Prepared via Vacuum Ultraviolet Illumination for MAPbI3 Perovskite Solar Cells.

The electron transport layer (ETL) plays an important role in determining the conversion efficiency and stability of perovskite solar cells (PSCs). Here, TiO2 thin film was prepared by irradiating diisopropoxy diacetylacetone titanium precursor thin film with 172 nm vacuum ultraviolet (VUV) at a low temperature. The prepared TiO2 thin film has higher electron mobility and conductivity. As it is used as an ETL for MAPbI3 PSCs, its band structure is better matched with the perovskite, and at the same time, due to the good interface contact, more uniform perovskite crystals are formed. Most importantly, a large number of hydroxyl radicals were formed during VUV irradiation of the precursor film, which made up for the oxygen defect present on the surface of the TiO2 thin film, and were adsorbed to the film surface. These hydroxyl groups form hydrogen bonds with methylammonium (MA) components on the MAPbI3 buried surface, thus promoting the transfer of photogenerated electrons at the MAPbI3/ETL interface. The power conversion efficiency of PSCs fabricated in air with the ETL prepared by VUV irradiation is 20.46%, which is higher than that of the contrast solar cell based on the sintered ETL (17.96%).

Association of tet methylcytosine dioxygenase 2 and 5-hydroxymethylcytosine in endometrioid adenocarcinoma and its clinical significance.

BACKGROUND: Aberrant DNA methylation is a vital molecular alteration commonly detected in type I endometrial cancers (EC), and tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine (5hmC) play significant roles in DNA demethylation. However, little is known about the function and correlation of TET2 and 5hmC co-expressed in EC. This study intended to investigate the clinical significance of TET2 and 5hmC in EC. METHODS: The levels of TET2 and 5hmC were detected in 326 endometrial tissues by immumohistochemistry, and the correlation of their level was detected by Pearson analysis. The association between the levels of TET2 and 5hmC and clinicopathologic characteristics was analyzed. Prognostic value of TET2 and 5hmC was explored by Kaplan-Meier analysis. The Cox proportional hazard regression model was used for univariate and multivariate analyses. RESULTS: Based on the analysis results, TET2 protein level was positively correlated with 5hmC level in EC tissues (r = 0.801, P < 0.001). TET2+5hmC+ (high TET2 and high 5hmC) association was significantly associated with well differentiation, myometrial invasion, negative lymph node metastasis, and tumor stage in EC. Association of TET2 and 5hmC was confirmed as a prognostic factor (HR = 2.843, 95%CI = 1.226-3.605, P = 0.007) for EC patients, and EC patients with TET2-5hmC- level had poor overall survival. CONCLUSIONS: In summary, the association of TET2 and 5hmC was downregulated in EC tissues, and may be a potential poor prognostic indicator for EC patients. Combined detection of TET2 and 5hmC may be valuable for the diagnosis and prognosis of EC.

N-acetylcysteine regulates oxalate induced injury of renal tubular epithelial cells through CDKN2B/TGF-ß/SMAD axis.

This study was aimed to investigate the preventive effects of N-acetyl-L-cysteine (NAC) against renal tubular cell injury induced by oxalate and stone formation and further explore the related mechanism. Transcriptome sequencing combined with bioinformatics analysis were performed to identify differentially expressed gene (DEG) and related pathways. HK-2 cells were pretreated with or without antioxidant NAC/with or silencing DEG before exposed to sodium oxalate. Then, the cell viability, oxidative biomarkers of superoxidase dismutase (SOD) and malondialdehyde (MDA), apoptosis and cell cycle were measured through CCK8, ELISA and flow cytometry assay, respectively. Male SD rats were separated into control group, hyperoxaluria (HOx) group, NAC intervention group, and TGF-ß/SMAD pathway inhibitor group. After treatment, the structure changes and oxidative stress and CaOx crystals deposition were evaluated in renal tissues by H&E staining, immunohistochemical and Pizzolato method. The expression of TGF-ß/SMAD pathway related proteins (TGF-ß1, SMAD3 and SMAD7) were determined by Western blot in vivo and in vitro. CDKN2B is a DEG screened by transcriptome sequencing combined with bioinformatics analysis, and verified by qRT-PCR. Sodium oxalate induced declined HK-2 cell viability, in parallel with inhibited cellular oxidative stress and apoptosis. The changes induced by oxalate in HK-2 cells were significantly reversed by NAC treatment or the silencing of CDKN2B. The cell structure damage and CaOx crystals deposition were observed in kidney tissues of HOx group. Meanwhile, the expression levels of SOD and 8-OHdG were detected in kidney tissues of HOx group. The changes induced by oxalate in kidney tissues were significantly reversed by NAC treatment. Besides, expression of SMAD7 was significantly down-regulated, while TGF-ß1 and SMAD3 were accumulated induced by oxalate in vitro and in vivo. The expression levels of TGF-ß/SMAD pathway related proteins induced by oxalate were reversed by NAC. In conclusion, we found that NAC could play an anti-calculus role by mediating CDKN2B/TGF-ß/SMAD axis.

Transceptor NRT1.1 and receptor-kinase QSK1 complex controls PM H+-ATPase activity under low nitrate.

NRT1.1, a nitrate transceptor, plays an important role in nitrate binding, sensing, and nitrate-dependent lateral root (LR) morphology. However, little is known about NRT1.1-mediated nitrate signaling transduction through plasma membrane (PM)-localized proteins. Through in-depth phosphoproteome profiling using membranes of Arabidopsis roots, we identified receptor kinase QSK1 and plasma membrane H+-ATPase AHA2 as potential downstream components of NRT1.1 signaling in a mild low-nitrate (LN)-dependent manner. QSK1, as a functional kinase and molecular link, physically interacts with NRT1.1 and AHA2 at LN and specifically phosphorylates AHA2 at S899. Importantly, we found that LN, not high nitrate (HN), induces formation of the NRT1.1-QSK1-AHA2 complex in order to repress the proton efflux into the apoplast by increased phosphorylation of AHA2 at S899. Loss of either NRT1.1 or QSK1 thus results in a higher T947/S899 phosphorylation ratio on AHA2, leading to enhanced pump activity and longer LRs under LN. Our results uncover a regulatory mechanism in which NRT1.1, under LN conditions, promotes coreceptor QSK1 phosphorylation and enhances the NRT1.1-QSK1 complex formation to transduce LN sensing to the PM H+-ATPase AHA2, controlling the phosphorylation ratio of activating and inhibitory phosphorylation sites on AHA2. This then results in altered proton pump activity, apoplast acidification, and regulation of NRT1.1-mediated LR growth.

PEG-PVP-Assisted Hydrothermal Synthesis and Electrochemical Performance of N-Doped MoS2/C Composites as Anode Material for Lithium-Ion Batteries.

Molybdenum disulfide shows promise as an anode material for lithium-ion batteries. However, its commercial potential has been constrained due to the poor conductivity and significant volume expansion during the charge/discharge cycles. To address these issues, in this study, N-doped MoS2/C composites (NMC) were prepared via an enhanced hydrothermal method, using ammonium molybdate and thiourea as molybdenum and sulfur sources, respectively. Polyethylene glycol 400 (PEG400) and polyvinylpyrrolidone (PVP) were added in the hydrothermal procedure as soft template surfactants and nitrogen/carbon sources. The crystal structure, morphology, elemental composition, and surface valence state of the N-doped MoS2/C composites were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), and X-ray photoelectron spectroscopy (XPS), respectively. The results indicate that the NMC prepared by this method are spherical particles with a nanoflower-like structure composed of MoS2 flakes, having an average particle size of about 500 nm. XPS analysis shows the existence of C and N elements in the samples as C-N, C-C, and pyrrolic N. As anodes for LIBs, the NMC without annealing deliver an initial discharge capacity of 548.2 mAh·g-1 at a current density of 500 mA·g-1. However, this capacity decays in the following cycles with a discharge capacity of 66.4 mAh·g-1 and a capacity retention rate of only 12% after 50 cycles. In contrast, the electrochemical properties of the counterparts are enhanced after annealing, which exhibits an initial discharge capacity of 575.9 mAh·g-1 and an ultimate discharge capacity of 669.2 mAh·g-1 after 70 cycles. The capacity retention rate decreases initially but later increases and elevated afterward to reach 116% at the 70th cycle, indicating an improvement in charge-discharge performance. The specimens after annealing have a smaller impedance, which indicates better charge transport and lithium-ion diffusion performance.

Changes of Mycobacterium tuberculosis specific antigen-stimulated CD27-CD38+IFN-γ+CD4+ T cells before and after anti-tuberculosis treatment.

BACKGROUND: The aim of the study was to investigate whether the expression of CD27-CD38+ in interferon (IFN)-γ+CD4+ T cells stimulated by the specific antigen early secreted antigenic target-6 (ESAT-6)/culture filter protein-10 (CFP-10) could be a potential new therapeutic evaluation indicator for anti-tuberculosis (TB) treatment. METHODS: Newly diagnosed active pulmonary TB patients, latent TB infection (LTBI) and healthy controls were enrolled from January 2021 to December 2021. PTB patients were treated by standard anti-TB regimen 2HREZ/4HR (2 months of isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (Z) followed by 4 months of isoniazid (H) and rifampin (R)). The difference of CD27-CD38+ expression in IFN-γ+CD4+ T cells before treatment, 2 months after treatment, and 6 months after treatment were compared. RESULTS: Total 45 PTB patients, 38 LTBI cases and 43 healthy controls were enrolled. The expression of CD27-CD38+ decreased significantly after anti-TB treatment and was comparable with that in LTBI and healthy controls when the 6-month anti-TB treatment course was completed. The decline rate of CD27-CD38+ between 6 months after treatment and baseline was positively correlated with erythrocyte sedimentation rate (r = 0.766, P < 0.0001), C-reactive protein (r = 0.560, P = 0.003) and chest computerized tomography severity score (r = 0.632, P = 0.0005). The area under receiver operator characteristic curve of CD27-CD38+ in distinguish pulmonary TB patients before and after treatment was 0.779. CONCLUSION: The expression of CD27-CD38+ in ESAT-6/CFP-10 stimulated IFN-γ+CD4+T cells can well reflect the changes of the disease before and after anti-TB treatment, which is expected to be a potential new therapeutic evaluation index. Clinical Registry number chiCTR1800019966.

Utilization of a novel soil-isolated strain Devosia insulae FS10-7 for deoxynivalenol degradation and biocontrol of Fusarium crown rot in wheat.

Deoxynivalenol (DON) is the most widespread mycotoxin contaminant hazardous to human and animal health globally. It acts as a crucial virulence factor to stimulate the spread of pathogenic Fusarium within wheat plants. Control of DON and Fusarium disease contributes enormously to food safety, which relies on chemical fungicides. Here, we report the biodegradation of DON using a novel soil bacterium, Devosia insulae FS10-7, and the biocontrol effect of that against Fusarium crown rot (FCR). We demonstrated that strain FS10-7 degraded DON to 3-epi-DON by forming a 3-keto-DON intermediate. Such degradation activity can be maintained at a wide range of pH (4-10) and temperature (16 to 42 °C) values under aerobic conditions. Notably, strain FS10-7 exhibited practical inhibitory effects on FCR disease caused by F. graminearum and F. pseudograminearum in the in vitro petri dish test under laboratory conditions and the pot experiment under greenhouse conditions. The mechanisms underlying the biocontrol ability of strain FS10-7 are preliminarily investigated to be associated with its high DON-degrading activity rather than direct antagonism. These results establish the foundation to develop further bioagents capable of biodegrading mycotoxins in cereals and derived products and, accordingly, biocontrol plant diseases caused by DON-producing pathogens.

Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.

PURPOSE: The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). EXPERIMENTAL DESIGN: A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. RESULTS: Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. CONCLUSION AND CLINICAL RELEVANCE: BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.

Microbial interventions in yak colibacillosis: Lactobacillus-mediated regulation of intestinal barrier.

Introduction: The etiology of Escherichia coli in yaks, along with its drug resistance, results in economic losses within the yak breeding industry. The utilization of lactic acid bacteria treatment has emerged as a viable alternative to antibiotics in managing colibacillosis. Methods: To elucidate the therapeutic mechanisms of Lactobacillus against Escherichia coli-induced intestinal barrier damage in yaks, we employed yak epithelial cells as the experimental model and established a monolayer epithelial barrier using Transwell. The study encompassed four groups: a control group, a model group (exposed to E. coli O78), a low-dose Lactobacillus group (E. coli O78 + 1 × 105CFU LAB), and a high-dose Lactobacillus group (E. coli O78 + 1 × 107CFU LAB). Various techniques, including transmembrane resistance measurement, CFU counting, RT-qPCR, and Western Blot, were employed to assess indicators related to cell barrier permeability and tight junction integrity. Results: In the Model group, Escherichia coli O78 significantly compromised the permeability and tight junction integrity of the yak epithelial barrier. It resulted in decreased transmembrane resistance, elevated FD4 flux, and bacterial translocation. Furthermore, it downregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while upregulating the mRNA expression and protein expression of FABP2 and Zonulin, thereby impairing intestinal barrier function. Contrastingly, Lactobacillus exhibited a remarkable protective effect. It substantially increased transmembrane resistance, mitigated FD4 flux, and reduced bacterial translocation. Moreover, it significantly upregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while downregulating the mRNA and protein expression of FABP2 and Zonulin. Notably, high-dose LAB demonstrated superior regulatory effects compared to the low-dose LAB group. Discussion: In conclusion, our findings suggest that Lactobacillus holds promise in treating yak colibacillosis by enhancing mucin and tight junction protein expression. Furthermore, we propose that Lactobacillus achieves these effects through the regulation of Zonulin.

Innovative Neuroimaging Biomarker Distinction of Major Depressive Disorder and Bipolar Disorder through Structural Connectome Analysis and Machine Learning Models.

Major depressive disorder (MDD) and bipolar disorder (BD) share clinical features, which complicates their differentiation in clinical settings. This study proposes an innovative approach that integrates structural connectome analysis with machine learning models to discern individuals with MDD from individuals with BD. High-resolution MRI images were obtained from individuals diagnosed with MDD or BD and from HCs. Structural connectomes were constructed to represent the complex interplay of brain regions using advanced graph theory techniques. Machine learning models were employed to discern unique connectivity patterns associated with MDD and BD. At the global level, both BD and MDD patients exhibited increased small-worldness compared to the HC group. At the nodal level, patients with BD and MDD showed common differences in nodal parameters primarily in the right amygdala and the right parahippocampal gyrus when compared with HCs. Distinctive differences were found mainly in prefrontal regions for BD, whereas MDD was characterized by abnormalities in the left thalamus and default mode network. Additionally, the BD group demonstrated altered nodal parameters predominantly in the fronto-limbic network when compared with the MDD group. Moreover, the application of machine learning models utilizing structural brain parameters demonstrated an impressive 90.3% accuracy in distinguishing individuals with BD from individuals with MDD. These findings demonstrate that combined structural connectome and machine learning enhance diagnostic accuracy and may contribute valuable insights to the understanding of the distinctive neurobiological signatures of these psychiatric disorders.

Text2NeRF: Text-Driven 3D Scene Generation with Neural Radiance Fields.

Text-driven 3D scene generation is widely applicable to video gaming, film industry, and metaverse applications that have a large demand for 3D scenes. However, existing text-to-3D generation methods are limited to producing 3D objects with simple geometries and dreamlike styles that lack realism. In this work, we present Text2NeRF, which is able to generate a wide range of 3D scenes with complicated geometric structures and high-fidelity textures purely from a text prompt. To this end, we adopt NeRF as the 3D representation and leverage a pre-trained text-to-image diffusion model to constrain the 3D reconstruction of the NeRF to reflect the scene description. Specifically, we employ the diffusion model to infer the text-related image as the content prior and use a monocular depth estimation method to offer the geometric prior. Both content and geometric priors are utilized to update the NeRF model. To guarantee textured and geometric consistency between different views, we introduce a progressive scene inpainting and updating strategy for novel view synthesis of the scene. Our method requires no additional training data but only a natural language description of the scene as the input. Extensive experiments demonstrate that our Text2NeRF outperforms existing methods in producing photo-realistic, multi-view consistent, and diverse 3D scenes from a variety of natural language prompts. Our code and model will be available upon acceptance.

Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment.

Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessment paradigms (CiPA and JiCSA), necessitating a 2D monolayer cardiac tissue, we integrated the TW system with a multi-electrode array. This gave rise to a hiPSC-derived closed-loop cardiac tissue (iCT), enabling spontaneous TW initiation and swift pacing of cardiomyocytes from various cell lines. The TW-paced cardiomyocytes demonstrated heightened sarcomeric and functional maturation, exhibiting enhanced response to isoproterenol. Moreover, these cells showcased diminished sensitivity to verapamil and maintained low arrhythmia rates with ranolazine-two drugs associated with a low risk of torsades de pointes (TdP). Notably, the TW group displayed increased arrhythmia rates with high and intermediate risk TdP drugs (quinidine and pimozide), underscoring the potential utility of this system in drug assessment applications.

Empagliflozin attenuates inflammation levels in autoimmune myocarditis through the STAT3 pathway and macrophage phenotype transformation.

OBJECTIVE: To investigate the anti-inflammatory actions and molecular mechanisms of the sodium/glucose cotransporter 2 (SGLT-2) inhibitor empagliflozin on autoimmune myocarditis. METHODS: The experimental autoimmune myocarditis (EAM) mouse model was constructed using peptides, and the therapeutic effects of empagliflozin on cardiac inflammation and fibrosis were observed using hematoxylin and eosin (HE), Sirius red staining, and Masson's trichome staining. Western blotting was used to identify the actions of empagliflozin on the surface marker expression levels of M2 macrophages and inflammatory factors. In vitro, experiments were completed using lentiviral overexpression of SGLT-2 in macrophages. Macrophage inflammation and anti-inflammatory models were constructed using lipopolysaccharide and interleukin-4, respectively. Enzyme-linked immunosorbent assay, immunofluorescence staining, and reverse-transcription polymerase chain reaction were applied to detect the effects of empagliflozin on the levels of inflammatory factors and macrophage surface markers. Western blotting was used to identify variability in SGLT-2 expression and the role of empagliflozin on the signal transducer and activator of the transcription 3 (STAT3) pathway. The Genomic Spatial Event 142564 dataset was studied in an EAM mouse model. We selected single-cell sequencing results from day 0 and day 21 of modeling to visualize differentially expressed genes. Immune cell infiltration correlation analysis was implemented to explore the expression of inflammatory factors and phenotypic markers. RESULTS: Empagliflozin increased the expression of the M2 macrophage surface marker CD206 and reduced the level of inflammatory factors in the EAM mouse model while reducing the levels of inflammation and fibrosis. In vitro experiments revealed that the phosphorylation of STAT3 pathway was enhanced after macrophages were polarized to M1 phenotype by LPS, the phosphorylation of STAT3 pathway was inhibited after empagliflozin intervention, and the levels of inflammatory factors were decreased. CONCLUSION: Empagliflozin can reduce the level of inflammation in autoimmune myocarditis through the STAT3 pathway and macrophage phenotype transformation. These results indicate the expression of SGLT-2 can be a target for autoimmune myocarditis therapy.

Immune-related cardiovascular toxicities of PD-1/PD-L1 inhibitors in solid tumors: an updated systematic review and meta-analysis.

Purpose: The objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors. Methods: A literature search was performed following the participants, interventions, comparisons, outcomes, and study design (PICOS) principles, and the study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analysis was conducted using Review Manager version 5.4. Results: This meta-analysis included 69 randomized controlled trials (RCTs) divided into five groups based on the treatment regimens: PD-1/PD-L1 + chemotherapy versus chemotherapy, PD-1/PD-L1 versus chemotherapy, PD-1/PD-L1 versus placebo, PD-1/PD-L1 + CTLA-4 versus PD-1/PD-L1 and PD-1/PD-L1 + CTLA-4 versus chemotherapy. Compared to chemotherapy treatment alone, PD-1/PD-L1 +chemotherapy significantly increased the risk of hypertension [all-grade (OR = 1.27, 95% CI [1.05, 1.53], p = 0.01); grade 3-5 (OR = 1.36, 95% CI [1.04, 1.79], p = 0.03)], hypotension [all-grade (OR = 2.03, 95% CI [1.19, 3.45], p = 0.009); grade 3-5 (OR = 3.60, 95% CI [1.22, 10.60], p = 0.02)], arrhythmia [all-grade (OR = 1.53, 95% CI [1.02, 2.30], p = 0.04); grade 3-5 (OR = 2.91, 95% CI [1.33, 6.39], p = 0.008)] and myocarditis [all-grade (OR = 2.42, 95% CI [1.06, 5.54], p = 0.04)]. The risk of all-grade hypotension (OR = 2.87, 95% CI [1.26, 6.55], p = 0.01) and all-grade arrhythmia (OR = 2.03, 95% CI [1.13, 3.64], p = 0.02) significantly increased when treated with PD-1/PD-L1 inhibitors compared to the placebo. The risks of cardiovascular toxicities are significantly higher with PD-1+CTLA-4 compared to PD-1 alone (OR = 2.02, 95% CI [1.12, 3.66], p = 0.02). Conclusion: PD-1/PD-L1 inhibitor leads to an increased risk of cardiovascular toxicities, especially hypertension, hypotension, arrhythmia, and myocarditis.

Integrative regulatory mechanisms of stomatal movements under changing climate.

Global climate change-caused drought stress, high temperatures and other extreme weather profoundly impact plant growth and development, restricting sustainable crop production. To cope with various environmental stimuli, plants can optimize the opening and closing of stomata to balance CO2 uptake for photosynthesis and water loss from leaves. Guard cells perceive and integrate various signals to adjust stomatal pores through turgor pressure regulation. Molecular mechanisms and signaling networks underlying the stomatal movements in response to environmental stresses have been extensively studied and elucidated. This review focuses on the molecular mechanisms of stomatal movements mediated by abscisic acid, light, CO2 , reactive oxygen species, pathogens, temperature, and other phytohormones. We discussed the significance of elucidating the integrative mechanisms that regulate stomatal movements in helping design smart crops with enhanced water use efficiency and resilience in a climate-changing world.