A porphyrin-modified CoMoO4 nanosensor array for the detection of crude baijiu.

The rapid classification of crude baijiu is pivotal for its industrialization and automated development. In this study, a colorimetric sensor array employing peroxidase nanase (Por-CoMoO4) was developed to detect reducing substances and crude baijiu. The peroxidase-like activity of CoMoO4 was significantly enhanced by porphyrin (Por), exhibiting a Km value of 0.044 mM and Vmax of 19.37 × 10-8 for TMB substrate. Peroxidase activity varies at different pH levels. Organic and crude baijiu scavenge free radicals, thereby inhibiting oxTMB formation and yielding distinctive fingerprint profiles. Using linear discriminant analysis, 14 types of small molecules and 16 varieties of Luzhou-flavor crude baijiu were identified within specific concentration ranges. The method achieved 100% accuracy in distinguishing baijiu samples sourced from different distilleries, offering a straightforward, rapid, and effective approach to differentiate crude baijiu during alcoholic beverage production.

Phloridzin prevents diabetic cardiomyopathy by reducing inflammation and oxidative stress.

Oxidative stress and inflammation significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Persistent inflammatory stimuli drive the progression of myocardial fibrosis and impaired cardiac function. Phloridzin (Phl), a natural compound, demonstrates both anti-inflammatory and antioxidant properties. Nevertheless, its therapeutic potential and underlying mechanisms in DCM remain unclear. This study aimed to elucidate the mechanisms through which Phl inhibited myocardial fibrosis and exerted its antioxidative effects. The impact of Phl on DCM was evaluated using a high-fat/high-sugar diet combined with streptozotocin to induce an animal model and an in vitro H9C2 cell model stimulated by high glucose (HG). Untargeted metabolomics identified potential mechanisms underlying myocardial fibrosis. Phl treatment significantly enhanced left ventricular ejection fraction (EF%) and shortening fraction (FS%), while reducing myocardial injury markers, such as lactate dehydrogenase and creatine phosphokinase-MB, and suppressing myocardial collagen fiber accumulation. Simultaneously, Phl attenuated myocardial inflammation via inhibition of MyD88/NF-κB signaling, modulated the Nrf2/GPX4 axis to counter oxidative stress, and mitigated ferroptosis. In vitro, Phl inhibited high glucose-induced myocardial hypertrophy and fibrosis in H9C2 cells, while also repressing NF-κB activation in cardiomyocytes. Metabolomic profiling revealed that Phl ameliorated DCM through modulation of glycerophospholipid metabolic pathways, linking these metabolic shifts to enhanced antioxidant capacity, thereby reflecting its ability to reduce oxidative stress in the myocardium. Collectively, Phl provides cardioprotective effects by alleviating inflammation and oxidative damage.

Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain.

While voltage-gated sodium channels Nav1.7 and Nav1.8 both contribute to electrogenesis in dorsal root ganglion (DRG) neurons, details of their interactions have remained unexplored. Here, we studied the functional contribution of Nav1.8 in DRG neurons using a dynamic clamp to express Nav1.7L848H, a gain-of-function Nav1.7 mutation that causes inherited erythromelalgia (IEM), a human genetic model of neuropathic pain, and demonstrate a profound functional interaction of Nav1.8 with Nav1.7 close to the threshold for AP generation. At the voltage threshold of -21.9 mV, we observed that Nav1.8 channel open-probability exceeded Nav1.7WT channel open-probability ninefold. Using a kinetic model of Nav1.8, we showed that a reduction of Nav1.8 current by even 25-50% increases rheobase and reduces firing probability in small DRG neurons expressing Nav1.7L848H. Nav1.8 subtraction also reduces the amplitudes of subthreshold membrane potential oscillations in these cells. Our results show that within DRG neurons that express peripheral sodium channel Nav1.7, the Nav1.8 channel amplifies excitability at a broad range of membrane voltages with a predominant effect close to the AP voltage threshold, while Nav1.7 plays a major role at voltages closer to resting membrane potential. Our data show that dynamic-clamp reduction of Nav1.8 conductance by 25-50% can reverse hyperexcitability of DRG neurons expressing a gain-of-function Nav1.7 mutation that causes pain in humans and suggests, more generally, that full inhibition of Nav1.8 may not be required for relief of pain due to DRG neuron hyperexcitability.

Promising clinical effect of arthroscopic autologous iliac bone grafting with suture anchor binding fixation for recurrent anterior shoulder instability.

Background: To evaluate the clinical efficacy of arthroscopic autologous iliac bone grafting with suture anchor binding fixation combined with a Bankart repair for recurrent anterior shoulder dislocation with a significant anterior glenoid defect. Methods: Patients with recurrent anterior shoulder dislocation with an anterior glenoid defect area greater than 20% admitted to our department from March 2019 to March 2022 were prospectively enrolled. Arthroscopic autologous iliac bone grafting with suture anchor binding fixation combined with a Bankart repair was performed. Computed tomography (CT) images were captured preoperatively, immediately after surgery, and at 3, 6, and 12 months postoperatively to evaluate the glenoid defect area, graft area, and graft healing. Shoulder function was assessed using the Instability Severity Index, Oxford Shoulder Instability, and Rowe scores recorded preoperatively and at the final follow-up. The shoulder range of motion, shoulder stability test, surgery-related complications, subluxation/dislocation, and revision surgery were also evaluated. Results: A total of 32 patients were included in the study, with an average follow-up time of 18.3 ± 6.3 months, when the graft healing rate was shown to be 100%. The area ratio of the graft to the glenoid was 37.6% ± 10.5% (range, 23.5%-44.1%) determined by an enface-view three-dimensional CT performed immediately after surgery, and 29.2 ± 8.2% (range, 19.6%-38.7%) at 12 months postoperatively. At the final follow-up, the glenoid defect had improved from 28.7 ± 6.4% (range, 20.5%-40.6%) before surgery to -10.2 ± 4.7% (range, -13.8% to 6.1%). The preoperative Rowe and Oxford scores were 56.4 ± 8.5 and 34.7 ± 7.1 respectively, which improved to 94.3 ± 6.7 and 15.3 ± 3.2 at the final follow-up (p < .001). All patients had no limited shoulder joint activity, no re-dislocation or revision surgery, and no neurovascular injury. Conclusions: For recurrent anterior shoulder dislocation with an anterior glenoid defect area greater than 20%, arthroscopic autologous iliac bone grafting with suture anchor fixation combined with a Bankart repair produced a promising clinical effect. A significant shoulder function score was achieved, as was a 100% bone healing rate and ideal glenoid reconstruction without major complications. Thus, this technique may be considered an alternative to the classic Latarjet approach to treat recurrent anterior shoulder dislocation with an anterior glenoid defect area greater than 20%. Level of Evidence: IV.

Engineering of a Multi-Modular DNA Nanodevice for Spatioselective Imaging and Evaluation of NK Cell-Mediated Cancer Immunotherapy.

Granzyme A (GzmA) secreted by natural killer (NK) cells has garnered considerable interest as a biomarker to evaluate the efficacy of cancer immunotherapy. However, current methodologies to selectively monitor the spatial distribution of GzmA in cancer cells during NK cell-targeted therapy are extremely challenging, primarily due to the existence of diverse cell populations, the low levels of GzmA expression, and the limited availability of GzmA probes. Herein we develop a multi-modular, structurally-ordered DNA nanodevice for evaluating NK cell-mediated cancer immunotherapy (MODERN), that permits spatioselective imaging of GzmA in cancer cells through GzmA-induced apurinic/apyrimidinic endonuclease 1 (APE1) inactivation. The MODERN incorporates multiple functional modules, including an APE1-gated recognition module, a photo-activated amplification module, an aptamer-mediated tumor-target module, and a polycatenane DNA module, enabling improved sensitivity and specificity towards intracellular GzmA. The MODERN was activated (on) in cancer cells due to the overexpression of APE1, whereas it remained silent (off) in the NK-treated cancer cells owing to the GzmA-induced APE1 inactivation. Furthermore, we demonstrated that GzmA-induced APE1 inactivation blocks the cellular repair of target cells, resulting in efficient cell death. This MODERN that relies on the specific inactivation of APE1 by GzmA should be beneficial for evaluating the efficacy of cancer immunotherapy.

Cardiac tumour necrosis factor receptor-associated factor 7 mediates the ubiquitination of apoptosis signal-regulating kinase 1 and aggravates cardiac hypertrophy.

AIMS: Cardiac remodelling is a common pathophysiological process in the development of various cardiovascular diseases, but there is still a lack of effective interventions. Tumour necrosis receptor-associated factor 7 (TRAF7) belongs to the tumour necrosis factor receptor-associated factor family and plays an important role in biological processes. Previous studies have shown that TRAF7 mutations lead to congenital defects and malformations of the heart. However, the molecular mechanisms of TRAF7 in the underlying pathogenesis of pathological cardiac hypertrophy remain unknown. We aim to study the molecular mechanisms and effects of TRAF7 in cardiac remodelling and whether it has the potential to become a therapeutic target for cardiac remodelling. METHODS AND RESULTS: The pressure overload-induced cardiac hypertrophy model in mice was established via transverse aortic constriction (TAC) surgery, and cardiomyocytes were treated with phenylephrine (PE) to induce hypertrophic phenotype. Levels of cardiac dysfunction and remodelling were measured with echocardiography and tissue or cell staining. RNA sequencing, western blot, qRT-PCR, co-immunoprecipitation, and in vivo ubiquitination assays were used to explore the molecular mechanisms. The results showed that the expression of TRAF7 increased gradually during the development of hypertrophy. Accordingly, TRAF7 significantly exacerbated the PE-induced enlargement of primary neonatal Sprague-Dawley rat cardiomyocytes, whereas TRAF7 knockdown alleviated the hypertrophic phenotype in primary cardiomyocytes. Cardiac-specific overexpression of TRAF7 accelerated hypertrophic phenotype in mice and cardiac-specific Traf7 conditional knockout mice improved hypertrophic phenotype induced by TAC. Mechanistically, TRAF7 directly interacted with apoptosis signal-regulating kinase-1 (ASK1) and promoted ASK1 phosphorylation by mediating the K63-linked ubiquitination of ASK1 in response to PE stimulation, which then promoted ASK1 activation and downstream signalling during cardiac hypertrophy. Notably, the pro-hypertrophic effect of TRAF7 was largely blocked by GS4997 in vitro and cardiac-specific Ask1 conditional knockout in vivo. CONCLUSION: In summary, we identified TRAF7 as an essential regulator during cardiac hypertrophy, and modulation of the regulatory axis between TRAF7 and ASK1 could be a novel therapeutic strategy to prevent this pathological process.

Microrna363-5p targets thrombospondin3 to regulate pathological cardiac remodeling.

Cardiac remodeling is an end-stage manifestation of multiple cardiovascular diseases, and microRNAs are involved in a variety of posttranscriptional regulatory processes. miR-363-5p targeting Thrombospondin3 (THBS3) has been shown to play an important regulatory role in vascular endothelial cells, but the roles of these two in cardiac remodeling are unknown. Firstly, we established an in vivo model of cardiac remodeling by transverse aortic narrow (TAC), and then we stimulated a human cardiomyocyte cell line (AC16) and a human cardiac fibroblast cell line (HCF) using 1 µmol/L angiotensin II (Ang II) to establish an in vitro model of cardiac hypertrophy and an in vitro model of myocardial fibrosis, respectively. In all three of the above models, we found a significant decreasing trend of miR-363-5p, suggesting that it plays a key regulatory role in the occurrence and development of cardiac remodeling. Subsequently, overexpression of miR-363-5p significantly attenuated myocardial hypertrophy and myocardial fibrosis in vitro as evidenced by reduced the area of AC16, the cell viability of HCFs, the relative expression of the protein of fetal genes (ANP, BNP, ß-MHC) and fibrosis marker (collagen I, collagen III, α-SMA), whereas inhibition of miR-363-5p expression showed the opposite trend. In addition, we also confirmed the targeted binding relationship between miR-363-5p and THBS3 by dual luciferase reporter gene assay, and the expression of THBS3 was directly inhibited by miR-363-5p. Moreover, overexpression of miR-363-5p with THBS3 simultaneously partially eliminated the delaying effect of miR-363-5p on myocardial hypertrophy and myocardial fibrosis in vitro. In conclusion, Overexpression of miR-363-5p attenuated the prohypertrophic and profibrotic effects of Ang II on AC16 and HCF by a mechanism related to the inhibition of THBS3 expression.

Latent profiles of multi-dimensional sleep characteristics and association with overweight/obesity in Chinese preschool children.

OBJECTIVES: To examine the association between latent profiles of multi-dimensional sleep characteristics and overweight/obesity (OWO) in Chinese preschool children. STUDY DESIGN: The cross-sectional analysis included 3204 preschool children recruited from 24 kindergartens in Shanghai. Parents reported children's demographics and sleep characteristics, including sleep duration, timing and disturbances. Latent profile analysis (LPA) was used to identify sleep subtypes. Logistic regression models were used to evaluate the associations between sleep characteristics/subtypes and OWO. RESULTS: Short sleep duration, late bedtime, long social jetlag and sleep disturbances were significantly associated with increased OWO. However, when considering the interplay of sleep duration and timing, there was no significant association between sleep duration and OWO for children sleeping later than 22:00. Three sleep subtypes were identified based on children's sleep duration, timing and disturbances: "Average Sleepers" (n = 2107, 65.8 %), "Good Sleepers" (n = 481, 15.0 %), and "Poor Sleepers" (n = 616, 19.2 %). "Good Sleepers" had reduced odds of being OWO (AOR, 0.72; 95 % CI, 0.56-0.93) compared to "Average Sleepers", while "Poor Sleepers" showed an increased risk of OWO (AOR, 1.36; 95 % CI, 1.11-1.67). CONCLUSIONS: These findings highlight that improving multiple sleep characteristics simultaneously is a promising option to prevent and intervene childhood obesity.

Interfacial interactions between colloidal polystyrene microplastics and Cu in aqueous solution and saturated porous media: Model fitting and mechanism analysis.

Microplastic (MP) and heavy metal pollution have received much attention. Few researches have been carried out on the influence of the interaction between MPs and heavy metals on their transport in saturated porous media, which concerns their fate. Therefore, the interaction mechanisms between colloidal polystyrene microplastics (PSMPs) and Cu were first carried out by applying batch adsorption experiments. Subsequently, the transport and retention of PSMPs and Cu in saturated porous media was explored through column experiments. The interaction process between PSMPs and Cu was further investigated using density functional theory (DFT) calculations. Findings demonstrated that PSMPs had strong adsorption capacity for Cu ((60.07 ± 2.57) mg g-1 at pH 7 and ionic strength 0 M) and the adsorption process was chemically dominated, non-uniform, and endothermic. The O-containing functional groups on PSMP surfaces showed essential roles in Cu adsorption, and the adsorption process mainly contained electrostatic and complexation interactions. In column experiments, Cu could inhibit PSMP transport by the cation bridging effect and changing the electrical properties of glass beads, while PSMPs may facilitate Cu transport through the carrying effect. These findings confirmed that interfacial interactions between MPs and Cu could influence their transport in saturated porous media directly, providing great environmental significance.

DcMYB62, a transcription factor from carrot, enhanced cadmium tolerance of Arabidopsis by inducing the accumulation of carotenoids and hydrogen sulfide.

Cadmium (Cd) is a significant heavy metal contaminant within the environment, carrying a notable level of toxicity that presents a substantial hazard to both plant and human. Carrot (Daucus carota), a significant root vegetable crop globally, have evolved multiple transcriptional regulatory mechanisms to cope with Cd stress, with a crucial involvement of the myeloblastosis (MYB) transcription factor. In this study, the DcMYB62 gene encoding 288 amino acids, localized in the nucleus and demonstrated transcription activation property, was isolated from carrot (cv. 'Kuroda'). There was a positive relationship observed between the levels of DcMYB62 expression and the accumulation patterns of carotenoids in two distinct carrot cultivars. Further investigation revealed that the expression of DcMYB62 improved Cd tolerance of Arabidopsis by increasing seed germination rate, root length, and overall survival rate. The levels of carotenoids in DcMYB62 transgenic Arabidopsis surpassed those in wild type, accompanied by elevated expression levels of 15-cis-phytoene desaturase, zeta-carotene desaturase, and carotenoid isomerase. Meanwhile, the heterologous expression of DcMYB62 promoted the biosynthesis of abscisic acid (ABA) and hydrogen sulfide (H2S), which in turn suppressed the formation of hydrogen peroxide and superoxide anion, while also stimulating stomatal closure. Furthermore, the heterologous expression of DcMYB62 increased the transcription of genes associated with heavy metal resistance in Arabidopsis, notably nicotianamine synthase. Overall, this study contributes to understanding how DcMYB62 promote Cd stress resistance of plants by regulating the biosynthesis pathways of carotenoids, ABA, and H2S, which offers valuable insights into the regulatory mechanism connecting DcMYBs with Cd stress response of carrot.

Cerium oxide mimetic enzyme based colorimetric detection of potential oesophageal cancer biomarkers.

Oesophageal cancer (OC) is a prevalent malignant tumor that poses a significant threat to individuals. Current mainstream detection method is endoscopy, which requires professional operators and expensive instruments. Therefore, it is crucial to develop a rapid, easy-to-operate, and low-cost detection method. In this study, an RNA colorimetric biosensor was successfully constructed using cerium oxide mimetic enzyme. The sensor is constructed on 96-well plates, which are immobilized with DNA-RNA-DNA complexes in microtiter wells when target RNA is present. This immobilization is based on the principle of base complementary pairing. The CeO2 immobilized has the unique advantage of catalyzing the bluing of 3,3',5,5'-tetramethylbenzidine (TMB) directly without the need any additional oxidant in microtiter wells. This property allows for the detection of RNA and enables the visualization of multiple sample assays. Furthermore, the RNA colorimetric sensor demonstrates good selectivity, immunity to interference, and high stability. Under optimal conditions, the sensor exhibited linearity in the range of 10-13 to 10-9 M with a detection limit of 33.26 fM. Therefore, this study presents a new detection method for oesophageal cancer screening.

Activation of Follicle-Stimulating Hormone Receptor in Adrenal Zona Fasciculata Cells Promotes Cortisol Secretion: Implications for the Development of Menopause-Associated Diseases.

OBJECTIVE: Changes in postmenopausal hormone levels are associated with a variety of disorders. This study elucidated the mechanism by which follicle-stimulating hormone (FSH) increases cortisol production involved in development of menopause-related diseases. METHODS: The expression of FSH receptors (FSHRs) in murine adrenal zona fasciculata (AZF) cells and ATC7 cells was verified by immunofluorescence, western blotting and RT-PCR. The function of FSHR in promoting cortisol production was analyzed by cell culture and molecular biological methods. FSHR signaling pathways in ATC7 cells were analyzed by ELISA, qRT-PCR, and western blotting. Further, a mouse model was established by ovariectomy. Ovariectomized mice were treated with GnRHa. Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH. Then serum FSH, luteinizing hormone (LH), estradiol, and cortisol, and bone mineral density (BMD), blood pressure (BP) and heart rate (HR) were determined. RESULTS: FSHRs were expressed in murine AZF cells and ATC7 cells. FSH accelerated cortisol production through activated protein kinase A (PKA), cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), protein kinase B (PKB/AKT) and 5' AMP-activated protein kinase (MAPK) signaling pathways by Gsα-coupled FSHRs in ATC7 cells. Serum FSH levels (P<0.001) were elevated in ovariectomized mice with concurrent increases in cortisol (P<0.01), areal BMD (aBMD) (P<0.05), volumetric BMD (vBMD) (P<0.05), systolic BP (SBP) (P<0.05), diastolic BP (DBP) (P<0.05), and HR (P<0.05). However, the administration of GnRHa suppressed the increase in FSH levels and the elevation of cortisol, aBMD, vBMD, SBP, DBP, and HR induced by ovariectomy, even in the presence of normal serum estradiol levels. CONCLUSION: The study findings indicate that elevated FSH levels stimulate cortisol secretion, through a mechanism related to FSHRs expression in AZF cells.

Few-shot Class-incremental Learning for Retinal Disease Recognition.

Few-Shot Class-Incremental Learning (FSCIL) techniques are essential for developing Deep Learning (DL) models that can continuously learn new classes with limited samples while retaining existing knowledge. This capability is particularly crucial for DL-based retinal disease diagnosis system, where acquiring large annotated datasets is challenging, and disease phenotypes evolve over time. This paper introduces Re-FSCIL, a novel framework for Few-Shot Class-Incremental Retinal Disease Recognition (FSCIRDR). Re-FSCIL integrates the RETFound model with a fine-grained module, employing a forward-compatible training strategy to improve adaptability, supervised contrastive learning to enhance feature discrimination, and feature fusion for robust representation quality. We convert existing datasets into the FSCIL format and reproduce numerous representative FSCIL methods to create two new benchmarks, RFMiD38 and JSIEC39, specifically for FSCIRDR. Our experimental results demonstrate that Re-FSCIL achieves State-of-the-art (SOTA) performance, significantly surpassing existing FSCIL methods on these benchmarks.

NUCLEAR FACTOR-Y-POLYCOMB REPRESSIVE COMPLEX2 dynamically orchestrates starch and seed storage protein biosynthesis in wheat.

The endosperm in cereal grains is instrumental in determining grain yield and seed quality, as it controls starch and seed storage protein (SSP) production. In this study, we identified a specific nuclear factor-Y (NF-Y) trimeric complex in wheat (Triticum aestivum L.), consisting of TaNF-YA3-D, TaNF-YB7-B, and TaNF-YC6-B, and exhibiting robust expression within the endosperm during grain filling. Knockdown of either TaNF-YA3 or TaNF-YC6 led to reduced starch but increased gluten protein levels. TaNF-Y indirectly boosted starch biosynthesis genes by repressing TaNAC019, a repressor of cytosolic small ADP-glucose pyrophosphorylase 1a (TacAGPS1a), sucrose synthase 2 (TaSuS2), and other genes involved in starch biosynthesis. Conversely, TaNF-Y directly inhibited the expression of Gliadin-γ-700 (TaGli-γ-700) and low molecular weight-400 (TaLMW-400). Furthermore, TaNF-Y components interacted with SWINGER (TaSWN), the histone methyltransferase subunit of Polycomb repressive complex 2 (PRC2), to repress TaNAC019, TaGli-γ-700, and TaLMW-400 expression through trimethylation of histone H3 at lysine 27 (H3K27me3) modification. Notably, weak mutation of FERTILIZATION INDEPENDENT ENDOSPERM (TaFIE), a core PRC2 subunit, reduced starch but elevated gliadin and LMW-GS contents. Intriguingly, sequence variation within the TaNF-YB7-B coding region was linked to differences in starch and SSP content. Distinct TaNF-YB7-B haplotypes affect its interaction with TaSWN-B, influencing the repression of targets like TaNAC019 and TaGli-γ-700. Our findings illuminate the intricate molecular mechanisms governing TaNF-Y-PRC2-mediated epigenetic regulation for wheat endosperm development. Manipulating the TaNF-Y complex holds potential for optimizing grain yield and enhancing grain quality.

Buqi-Huoxue-Tongnao decoction drives gut microbiota-derived indole lactic acid to attenuate ischemic stroke via the gut-brain axis.

BACKGROUND: Ischemic stroke belongs to "apoplexy" and its pathogenesis is characterized by qi deficiency and blood stasis combining with phlegm-damp clouding orifices. Buqi-Huoxue-Tongnao decoction (BHTD) is a traditional Chinese medicine formula for qi deficiency, blood stasis and phlegm obstruction syndrome. However, its efficacy and potential mechanism on ischemic stroke are still unclear. This study aims to investigate the protective effect and potential mechanism of BHTD against ischemic stroke. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) surgery was carried out to establish an ischemic stroke model in rats. Subsequently, the rats were gavaged with different doses of BHTD (2.59, 5.175, 10.35 g/kg) for 14 days. The protective effects of BHTD on the brain and gut were evaluated by neurological function scores, cerebral infarction area, levels of brain injury markers (S-100B, NGB), indicators of gut permeability (FD-4) and bacterial translocation (DAO, LPS, D-lactate), and tight junction proteins (Occludin, Claudin-1, ZO-1) in brain and colon. 16S rRNA gene sequencing and metabolomic analysis were utilized to analyze the effects on gut microecology and screen for marker metabolites to explore potential mechanisms of BHTD protection against ischemic stroke. RESULTS: BHTD could effectively mitigate brain impairment, including reducing neurological damage, decreasing cerebral infarction and repairing the blood-brain barrier, and BHTD showed the best effect at the dose of 10.35 g/kg. Moreover, BHTD reversed gut injury induced by ischemic stroke, as evidenced by decreased intestinal permeability, reduced intestinal bacterial translocation, and enhanced intestinal barrier integrity. In addition, BHTD rescued gut microbiota dysbiosis by increasing the abundance of beneficial bacteria, including Turicibacter and Faecalibaculum. Transplantation of the gut microbiota remodeled by BHTD into ischemic stroke rats recapitulated the protective effects of BHTD. Especially, BHTD upregulated tryptophan metabolism, which promoted gut microbiota to produce more indole lactic acid (ILA). Notably, supplementation with ILA by gavage could alleviate stroke injury, which suggested that driving the production of ILA in the gut might be a novel treatment for ischemic stroke. CONCLUSION: BHTD could increase gut microbiota-derived indole lactic acid to attenuate ischemic stroke via the gut-brain axis. Our current finding provides evidence that traditional Chinese medicine can ameliorate central diseases through regulating the gut microbiology.

Microsphere-Composite Hydrogel for Recruiting Stem Cells and Promoting Osteogenic Differentiation.

By recruiting stem cells into scaffolds and differentiating them into osteoblasts, stem cells can be mobilized to directly repair bone defects, which avoids a series of disadvantages of exogenous stem cell implantation. In this study, a microsphere-composite hydrogel for the recruitment and osteogenic differentiation of stem cells was constructed. Methacrylic anhydride modified gelatin (GelMA) and heparin (HepMA), as well as nanohydroxyapatite (nHAP), were used to prepare microspheres followed by adsorbing platelet-derived growth factor BB (PDGF-BB) whose loading efficiency was 53.7 ± 2.2%. Then the microspheres were compounded to the GelMA hydrogel encapsulated with simvastatin (SIM) to obtain microsphere-composite hydrogel GHnH-P@GS. GHnH-P@GS hydrogel could slowly release SIM and PDGF-BB, and the extents of release within 7 days were 44.1 ± 2.0% and 32.8 ± 1.1%. The synergistic effect of small molecule drugs and growth factors not only induced the recruitment of rabbit bone marrow-derived mesenchymal stem cells, but also promoted the osteogenic differentiation of stem cells, which was confirmed by experiments of cell migration, alkaline phosphatase, and alizarin red staining. Collectively, the microsphere-composite hydrogel GHnH-P@GS has a certain reference significance for the design of scaffolds for alveolar bone repair and regeneration.

Eco-friendly α,ß-C(sp3)-H difunctionalization of tertiary amines via sequential [1,5]-hydride transfer and hetero-Diels-Alder cyclization.

An unprecedented eco-friendly multi-component domino reaction for the synthesis of novel N,O-acetals is reported. The protocol involves sequential coupling, [1,5]-hydride transfer and hetero-Diels-Alder cyclization. This new strategy enables direct α,ß-difunctionalization of cyclic amines utilizing enamines generated in situ. The methodology features high atom and step economy, excellent regioselectivity, a simple work-up procedure and molecular diversity.

Complete mitochondrial genome assembly of Juglans regia unveiled its molecular characteristics, genome evolution, and phylogenetic implications.

BACKGROUND: The Persian walnut (Juglans regia), an economically vital species within the Juglandaceae family, has seen its mitochondrial genome sequenced and assembled in the current study using advanced Illumina and Nanopore sequencing technology. RESULTS: The 1,007,576 bp mitogenome of J. regia consisted of three circular chromosomes with a 44.52% GC content encoding 39 PCGs, 47 tRNA, and five rRNA genes. Extensive repetitive sequences, including 320 SSRs, 512 interspersed, and 83 tandem repeats, were identified, contributing to genomic complexity. The protein-coding sequences (PCGs) favored A/T-ending codons, and the codon usage bias was primarily shaped by selective pressure. Intracellular gene transfer occurred among the mitogenome, chloroplast, and nuclear genomes. Comparative genomic analysis unveiled abundant structure and sequence variation among J. regia and related species. The results of selective pressure analysis indicated that most PCGs underwent purifying selection, whereas the atp4 and ccmB genes had experienced positive selection between many species pairs. In addition, the phylogenetic examination, grounded in mitochondrial genome data, precisely delineated the evolutionary and taxonomic relationships of J. regia and its relatives. We identified a total of 539 RNA editing sites, among which 288 were corroborated by transcriptome sequencing data. Furthermore, expression profiling under temperature stress highlighted the complex regulation pattern of 28 differently expressed PCGs, wherein NADH dehydrogenase and ATP synthase genes might be critical in the mitochondria response to cold stress. CONCLUSIONS: Our results provided valuable molecular resources for understanding the genetic characteristics of J. regia and offered novel perspectives for population genetics and evolutionary studies in Juglans and related woody species.

African swine fever virus MGF360-4L protein attenuates type I interferon response by suppressing the phosphorylation of IRF3.

African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host's innate immune responses. However, whether ASFV MGF360-4L could inhibit type I interferon (IFN-I) signaling pathway and the underlying molecular mechanisms remain unknown. Our study, indicated that ASFV MGF360-4L could negatively regulates the cGAS-STING mediated IFN-I signaling pathway. Overexpressing ASFV MGF360-4L could inhibit the cGAS/STING signaling pathway by inhibiting the interferon-ß promoter activity, which was induced by cGAS/STING, TBK1, and IRF3-5D, and further reduced the transcriptional levels of ISG15, ISG54, ISG56, STAT1, STAT2, and TYK2. Confocal microscopy and immunoprecipitation revealed that MGF360-4L co-localized and interacted with IRF3, and WB revealed that ASFV MGF360-4L suppressed the phosphorylation of IRF3. 4L-F2 (75-162 aa) and 4L-F3 (146-387 aa) were the crucial immunosuppressive domains and sites. Altogether, our study reveals ASFV MGF360-4L inhibited cGAS-STING mediated IFN-I signaling pathways, which provides insights into an evasion strategy of ASFV involving in host's innate immune responses.

Coronary artery calcification and cardiovascular outcome as assessed by intravascular OCT and artificial intelligence.

Coronary artery calcification (CAC) is a marker of atherosclerosis and is thought to be associated with worse clinical outcomes. However, evidence from large-scale high-resolution imaging data is lacking. We proposed a novel deep learning method that can automatically identify and quantify CAC in massive intravascular OCT data trained using efficiently generated sparse labels. 1,106,291 OCT images from 1,048 patients were collected and utilized to train and evaluate the method. The Dice similarity coefficient for CAC segmentation and the accuracy for CAC classification are 0.693 and 0.932, respectively, close to human-level performance. Applying the method to 1259 ST-segment elevated myocardial infarction patients imaged with OCT, we found that patients with a greater extent and more severe calcification in the culprit vessels were significantly more likely to have major adverse cardiovascular and cerebrovascular events (MACCE) (p < 0.05), while the CAC in non-culprit vessels did not differ significantly between MACCE and non-MACCE groups.