Exosomal miR-19a derived from melanoma cell promotes the vemurafenib resistance of malignant melanoma through directly targeting LRIG1 to reactivate AKT and MAPK pathway.

Exosomes derived from neighboring v-raf murine sarcoma viral oncogene homolog B1 inhibitor (BRAFi)-resistant melanoma cells mediate the formation of resistance in melanoma cells sensitive to BRAFi. The function and molecular mechanisms of exosomal miRNA in BRAFi resistance of melanoma have not been studied. We found that the expression of miR-19a in BRAFi resistant melanoma cells was significantly higher than that in sensitive cells, and miR-19a contributes to the resistance of melanoma cells to BRAFi by targeting immunoglobulin-like domains protein 1 (LRIG1). miR-19a was highly enriched in exosomes secreted from BRAFi resistant melanoma cells, and these exosomal miR-19a promote the spread of BRAFi resistant. The reactivation of Protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways is the main reason for the BRAFi resistant of melanoma cells. We demonstrated that exosomal miR-19a derived from melanoma cell promotes the formation and spread of BRAFi resistant in melanoma through targeting LRIG1 to reactivate AKT and MAPK pathway. Therefore, miR-19a may serve as a potential therapeutic target in melanoma patients with acquired drug resistance.

Silicon improves the drought tolerance in pepper plants through the induction of secondary metabolites, GA biosynthesis pathway, and suppression of chlorophyll degradation.

Drought stress caused by the global climate considerably disturbs plant yield and growth. Here, we explored the putative roles of silicon in repressing drought mechanisms in pepper and the prominent involvement of secondary metabolites, GA pathway, and photosystem II. Our research revealed that the transcript level of the flavonoid biosynthesis-associated genes, including the PAL, 4-CL, CHS, FLS-1, F3H and DFR, progressively induced in the pepper leaves treated with silicon during the drought stress duration. Moreover, the phenolic and flavonoid compounds extensively induced in the pepper plants. Furthermore, the pepper plants markedly inhibited chlorophyll catabolic-allied genes, senescence-related marker gene, and the Rbohs gene. Silicon application also sustained the membrane stability, supported via fewer electrolyte leakage processes and minor, O2- H2O2 and MDA levels during drought. Apart from this, the pepper plants significantly induced the expression level of the photosystem II-related genes, osmoprotectants pathway-associated genes, and antioxidant defense genes. Moreover, the GA biosynthesis genes were prompted, while the ABA signaling and biosynthesis genes were suppressed in the silicon-supplemented plants. These consequences infer that the role of Si supplementation on enhancing drought tolerance could be elucidated through the activation of secondary metabolites, flavonoid biosynthesis, osmoprotectants, GA pathway, the efficiency of PSII, and the suppression of chlorophyll degradation. Our research outcomes unveil new and remarkable characteristics of silicon supplementation and offer a series of candidate targets for improving the tolerance of pepper plants to drought stress.

Transcriptomic and proteomic investigations identify PI3K-akt pathway targets for hyperthyroidism management in rats via polar iridoids from radix Scrophularia.

High-polarity iridoids from Radix Scrophulariae (R. Scrophulariae) offer a range of benefits, including anti-inflammatory, antioxidant, antitumour, antibacterial, antiviral, and antiallergic effects. Although previous studies have indicated the potential of R. Scrophulariae for hyperthyroidism prevention and treatment, the specific active compounds involved and their mechanisms of action are not fully understood. This study explored the effects of high-polarity iridoid glycosides from R. Scrophulariae on hyperthyroidism induced in rats by levothyroxine sodium. The experimental design included a control group, a hyperthyroidism model group, and a group treated with iridoid glycosides. Serum triiodothyronine (T3) and thyroxine (T4) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Transcriptomic and proteomic analyses were applied to liver samples to identify differentially expressed genes and proteins. These analyses were complemented by trend analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The effectiveness of key factors was further examined through molecular biology techniques. ELISA results indicated a notable increase in T3 and T4 in the hyperthyroid rats, which was significantly mitigated by treatment with iridoid glycosides. Transcriptomic analysis revealed 6 upregulated and 6 downregulated genes in the model group, showing marked improvement following treatment. Proteomic analysis revealed changes in 30 upregulated and 50 downregulated proteins, with improvements observed upon treatment. The PI3K-Akt signalling pathway was investigated through KEGG enrichment analysis. Molecular biology methods verified the upregulation of Spp1, Thbs1, PI3K, and Akt in the model group, which was reversed in the treatment group. This study revealed that highly polar iridoids from R. Scrophulariae can modulate the Spp1 gene and Thbs1 protein via the PI3K-Akt signalling pathway, suggesting a therapeutic benefit for hyperthyroidism and providing a basis for drug development targeting this condition.

Genome-wide association study and candidate gene identification for agronomic traits in 182 upward-growing fruits of C. frutescens and C. annuum.

Pepper agronomic traits serve as pivotal indicators for characterizing germplasm attributes and correlations. It is important to study differential genotypic variation through phenotypic differences of target traits. Whole genome resequencing was used to sequence the whole genome among different individuals of species with known reference genomes and annotations, and based on this, differential analyses of individuals or populations were carried out to identify SNPs for agronomic traits related to pepper. This study conducted a genome-wide association study encompassing 26 key agronomic traits in 182 upward-growing fruits of C. frutescens and C. annuum. The population structure (phylogenetics, population structure, population principal component analysis, genetic relationship) and linkage disequilibrium analysis were realized to ensure the accuracy and reliability of GWAS results, and the optimal statistical model was determined. A total of 929 SNPs significantly associated with 26 agronomic traits, were identified, alongside the detection of 519 candidate genes within 100 kb region adjacent to these SNPs. Additionally, through gene annotation and expression pattern scrutiny, genes such as GAUT1, COP10, and DDB1 correlated with fruit traits in Capsicum frutescens and Capsicum annuum were validated via qRT-PCR. In the CH20 (Capsicum annuum) and YB-4 (Capsicum frutescens) cultivars, GAUT1 and COP10 were cloned with cDNA lengths of 1065 bp and 561 bp, respectively, exhibiting only a small number of single nucleotide variations and nucleotide deletions. This validation provides a robust reference for molecular marker-assisted breeding of pepper agronomic traits, offering both genetic resources and theoretical foundations for future endeavors in molecular marker-assisted breeding for pepper.

Broadband nonlinear conversion and random quasi-phase-matching in transparent glass composite.

With the development of laser technology, nonlinear optics plays a crucial role in frequency conversion. However, the generation of second harmonics in nonlinear optical crystals is generally subject to rigorous phase-matching conditions that hinder the performance of broadband tunability. It is believed that introducing disorders in nonlinear optical materials is helpful to overcome this obstacle. In this work, we have prepared a nonlinear microcrystal-doped glass (NMG) composite material, allowing for tunable and polarization-independent nonlinear conversion from visible to near-infrared. The linear dependence of SHG intensity versus sample thickness indicated the facilitation of random quasi-phase matching by using the NMG. Our results provide a more stable and promising platform for disordered nonlinear photonic materials and suggest the possibility of more efficient nonlinear conversions using the NMG composite glass fibers in future.

Apoptosis-induced decline in hippocampal microglia mediates the development of depression-like behaviors in adult mice triggered by unpredictable stress during adolescence.

Depression triggered by harmful stress during adolescence is a common problem that can affect mental health. To date, the mechanisms underlying this type of depression remain unclear. One mechanism for the promotion of depression by chronic stress in adulthood is the loss of hippocampal microglia. Since deleterious stress in adolescence also activates microglia, we investigated the dynamic changes of microglia in the hippocampus in mice exposed to chronic unpredictable stress (CUS) in adolescence. Our results showed that 12 days of CUS stimulation in adolescence induced typical depression-like behaviors in adult mice, which were accompanied by a significant decrease and dystrophy of microglia in the dentate gyrus of the hippocampus. Further analysis showed that this decrease in microglia was mediated by the initial response of microglia to unpredictable stress in the dentate gyrus of the hippocampus and their subsequent apoptosis. Blocking the initial response of microglia to unpredictable stress by pretreatment with minocycline was able to prevent apoptosis and microglial decline as well as the development of depression-like behaviors in adult mice induced by adolescent CUS. Moreover, administration of lipopolysaccharide (LPS) or macrophage-colony stimulatory factor (M-CSF), two drugs that reversed microglia decline in the dentate gyrus, ameliorated the depression-like behaviors induced by CUS stimulation in adolescence. These findings reveal a novel mechanism for the development of depression-like behaviors in animals triggered by deleterious stress in adolescence and suggest that reversing microglial decline in the hippocampus may be a hopeful strategy for the treatment of depression triggered by deleterious stress in adolescence.

Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Deep Augmented Metric Learning Network for Prostate Cancer Classification in Ultrasound Images.

Prostate cancer screening often relies on cost-intensive MRIs and invasive needle biopsies. Transrectal ultrasound imaging, as a more affordable and non-invasive alternative, faces the challenge of high inter-class similarity and intra-class variability between benign and malignant prostate cancers. This complexity requires more stringent differentiation of subtle features for accurate auxiliary diagnosis. In response, we introduce the novel Deep Augmented Metric Learning (DAML) network, specifically tailored for ultrasound-based prostate cancer classification. The DAML network represents a significant innovation in the metric learning space, introducing the Semantic Differences Mining Strategy (SDMS) to effectively discern and represent subtle differences in prostate ultrasound images, thereby enhancing tumor classification accuracy. Additionally, the DAML network strategically addresses class variability and limited sample sizes by combining the Linear Interpolation Augmentation Strategy (LIAS) and Permutation-Aided Reconstruction Loss (PARL). This approach enriches feature representation and introduces variability with straightforward structures, mirroring the efficacy of advanced sample generation techniques. We carried out comprehensive empirical assessments of the DAML model by testing its key components against a range of models, ensuring its effectiveness. Our results demonstrate the enhanced performance of the DAML model, achieving classification accuracies of 0.857 and 0.888 for benign and malignant cancers, respectively, underscoring its effectiveness in prostate cancer classification via medical imaging.

An integrated multi-omics approach reveals polymethoxylated flavonoid biosynthesis in Citrus reticulata cv. Chachiensis.

Citrus reticulata cv. Chachiensis (CRC) is an important medicinal plant, its dried mature peels named "Guangchenpi", has been used as a traditional Chinese medicine to treat cough, indigestion, and lung diseases for several hundred years. However, the biosynthesis of the crucial natural products polymethoxylated flavonoids (PMFs) in CRC remains unclear. Here, we report a chromosome-scale genome assembly of CRC with the size of 314.96 Mb and a contig N50 of 16.22 Mb. Using multi-omics resources, we discover a putative caffeic acid O-methyltransferase (CcOMT1) that can transfer a methyl group to the 3-hydroxyl of natsudaidain to form 3,5,6,7,8,3',4'-heptamethoxyflavone (HPMF). Based on transient overexpression and virus-induced gene silencing experiments, we propose that CcOMT1 is a candidate enzyme in HPMF biosynthesis. In addition, a potential gene regulatory network associated with PMF biosynthesis is identified. This study provides insights into PMF biosynthesis and may assist future research on mining genes for the biosynthesis of plant-based medicines.

Molecular and immune characterization of Chinese early-stage non-squamous non-small cell lung cancer: a multi-omics cohort study.

Background: Albeit considered with superior survival, around 30% of the early-stage non-squamous non-small cell lung cancer (Ns-NSCLC) patients relapse within 5 years, suggesting unique biology. However, the biological characteristics of early-stage Ns-NSCLC, especially in the Chinese population, are still unclear. Methods: Multi-omics interrogation of early-stage Ns-NSCLC (stage I-III), paired blood samples and normal lung tissues (n=76) by whole-exome sequencing (WES), RNA sequencing, and T-cell receptor (TCR) sequencing were conducted. Results: An average of 128 exonic mutations were identified, and the most frequently mutant gene was EGFR (55%), followed by TP53 (37%) and TTN (26%). Mutations in MUC17, ABCA2, PDE4DIP, and MYO18B predicted significantly unfavorable disease-free survival (DFS). Moreover, cytobands amplifications in 8q24.3, 14q13.1, 14q11.2, and deletion in 3p21.1 were highlighted in recurrent cases. Higher incidence of human leukocyte antigen loss of heterozygosity (HLA-LOH), higher tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were identified in ever-smokers than never-smokers. HLA-LOH also correlated with higher TMB, TNB, intratumoral heterogeneity (ITH), and whole chromosomal instability (wCIN) scores. Interestingly, higher ITH was an independent predictor of better DFS in early-stage Ns-NSCLC. Up-regulation of immune-related genes, including CRABP2, ULBP2, IL31RA, and IL1A, independently portended a dismal prognosis. Enhanced TCR diversity of peripheral blood mononuclear cells (PBMCs) predicted better prognosis, indicative of a noninvasive method for relapse surveillance. Eventually, seven machine-learning (ML) algorithms were employed to evaluate the predictive accuracy of clinical, genomic, transcriptomic, and TCR repertoire data on DFS, showing that clinical and RNA features combination in the random forest (RF) algorithm, with area under the curve (AUC) of 97.5% and 83.3% in the training and testing cohort, respectively, significantly outperformed other methods. Conclusions: This study comprehensively profiled the genomic, transcriptomic, and TCR repertoire spectrums of Chinese early-stage Ns-NSCLC, shedding light on biological underpinnings and candidate biomarkers for prognosis development.

Correlation between serum leptin level and sleep monitoring indexes in patients with obstructive sleep apnea hypopnea syndrome and its predictive value: a cross-sectional analysis.

Objective: To investigate the association between serum leptin (LP) level and polysomnography (PSG) parameters in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: A cross-sectional study was conducted. The data of subjects who underwent PSG at hospital between January 2021 and December 2022 were collected retrospectively, 220 participants were included. The subjects were categorized into simple snoring group (n = 45), mild OSAHS group (n = 63), moderate OSAHS group (n = 52), and severe OSAHS group (n = 60). The general characteristics, PSG indices, and serological indices were collected retrospectively. Pearson correlation analysis was used to observe the correlation between serum LP level and PSG parameters. The value of serum LP level in predicting OSAHS was analyzed by receiver operating characteristic curve. Results: The serum LP level was positively correlated with micro-arousal count, micro-arousal index (MAI), high apnea hypopnea index, times of blood oxygen decreased by≥3% and time in saturation lower 90%, and negatively correlated with lowest nocturnal oxygen saturation and mean oxygen saturation (p < 0.05). The area under the curve (AUC) of serum LP level in predicting the occurrence of OSAHS was 0.8276 (95% CI: 0.7713-0.8839), and when the Youden index was 0.587, the sensitivity was 72.00%, and the specificity was 86.67% (p < 0.0001). In the population with high MAI, the AUC of serum LP level in predicting the occurrence of OSAHS was 0.8825 (95% CI: 0.7833-0.9817), and when the Youden index was 0.690, the sensitivity was 79.00% and the specificity was 90.00% (p < 0.0001). Conclusion: Serum LP level is associated with the severity of OSAHS. Serum LP level demonstrates a strong predictive value for the occurrence of OSAHS, particularly in population with high MAI.

Spatiotemporal vortex strings.

Light carrying orbital angular momentum (OAM) holds unique properties and boosts myriad applications in diverse fields. However, the generation of an ultrafast wave packet carrying numerous vortices with various transverse OAM modes, i.e., vortex string, remains challenging, and the corresponding detection method is lacking. Here, we demonstrate that a vortex string with 28 spatiotemporal optical vortices (STOVs) with customizable topological charge (TC) arrangements can be generated in one wave packet. The diffraction rules of STOV strings are revealed theoretically and experimentally. Following these rules, the TC values and positions of all STOVs in a vortex string can be simultaneously recognized from the diffraction pattern. Such STOV strings facilitate STOV-based optical communication. As a proof-of-principle demonstration, the transmission of an image is realized with 16-STOV strings. This work provides guidance for revealing the underlying properties of the transverse OAM light and opens up opportunities for applications of the structured light in optical communication, quantum information processing, etc.

Minimalistic approach to left atrial appendage occlusion guided by cardiac computed tomography angiography.

OBJECTIVE: To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion (LAAO) guided by cardiac computed tomography angiography (CCTA). METHODS: Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched (1:2). Each step of the LAAO procedure in the computed tomography (CT) guidance group (CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using CCTA. RESULTS: A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years (P = 0.52), respectively. The procedure duration (45.6 ± 10.7 min vs. 58.8 ± 13.0 min, P < 0.001) and hospital stay (7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group (904.9 ± 348.0 mGy vs. 711.9 ± 211.2 mGy, P = 0.002). There were no significant differences in periprocedural pericardial effusion (3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events (13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months follow-up. CONCLUSIONS: CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.

Hydrogen Embrittlement as a Conspicuous Material Challenge─Comprehensive Review and Future Directions.

Hydrogen is considered a clean and efficient energy carrier crucial for shaping the net-zero future. Large-scale production, transportation, storage, and use of green hydrogen are expected to be undertaken in the coming decades. As the smallest element in the universe, however, hydrogen can adsorb on, diffuse into, and interact with many metallic materials, degrading their mechanical properties. This multifaceted phenomenon is generically categorized as hydrogen embrittlement (HE). HE is one of the most complex material problems that arises as an outcome of the intricate interplay across specific spatial and temporal scales between the mechanical driving force and the material resistance fingerprinted by the microstructures and subsequently weakened by the presence of hydrogen. Based on recent developments in the field as well as our collective understanding, this Review is devoted to treating HE as a whole and providing a constructive and systematic discussion on hydrogen entry, diffusion, trapping, hydrogen-microstructure interaction mechanisms, and consequences of HE in steels, nickel alloys, and aluminum alloys used for energy transport and storage. HE in emerging material systems, such as high entropy alloys and additively manufactured materials, is also discussed. Priority has been particularly given to these less understood aspects. Combining perspectives of materials chemistry, materials science, mechanics, and artificial intelligence, this Review aspires to present a comprehensive and impartial viewpoint on the existing knowledge and conclude with our forecasts of various paths forward meant to fuel the exploration of future research regarding hydrogen-induced material challenges.

Young patient with a giant gastric bronchogenic cyst: A case report and review of literature.

BACKGROUND: Gastric bronchogenic cysts (BCs) are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period. Gastric bronchial cysts are rare lesions that were first reported in 1956; as of 2023, only 33 cases are available in the PubMed online database. BCs usually have no clinical symptoms in the early stage, and imaging findings also lack specificity. Therefore, they are difficult to diagnose before histopathological examination. CASE SUMMARY: A 34-year-old woman with respiratory distress presented at our hospital. Endoscopic ultrasound revealed an anechoic mass between the spleen, left kidney and gastric fundus, with hyperechogenic and soft elastography textures and with a size of approximately 6.5 cm × 4.0 cm. Furthermore, a computed tomography scan demonstrated high density between the posterior stomach and the spleen and the left kidney, with uniform internal density and a small amount of calcification. The maximum cross section was approximately 10.1 cm × 6.1 cm, and the possibility of a cyst was high. Because the imaging findings did not suggest a malignancy and because the patient required complete resection, she underwent laparotomy surgery. Intraoperatively, this cystic lesion was found to be located in the posterior wall of the large curvature of the fundus and was approximately 8 cm × 6 cm in size. Finally, the pathologists verified that the cyst in the fundus was a gastric BC. The patient recovered well, her symptoms of chest tightness disappeared, and the abdominal drain was removed on postoperative day 6, after which she was discharged on day 7 for 6 months of follow-up. She had no tumor recurrence or postoperative complications during the follow-up. CONCLUSION: This is a valuable report as it describes an extremely rare case of gastric BC. Moreover, this was a very young patient with a large BC in the stomach.

Integrative analysis indicates the potential values of ANKRD53 in stomach adenocarcinoma.

BACKGROUND: Ankyrin repeat domain 53 (ANKRD53) plays an important role in maintaining chromosome integrity and stability, and chromosome instability is associated with cancer. Through integrative analysis, this study investigates the potential value of ANKRD53 in stomach adenocarcinoma (STAD). METHODS: RNA-seq and scRNA-seq data were used for integrative analysis based on online databases. Expression of ANKRD53 was confirmed by RT-PCR after bioinformatic analysis. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of ANKRD53 in STAD. Gene set enrichment analysis (GSEA) was performed to evaluate ANKRD53-related signaling pathways. In addition, the interaction of ANKRD53 with immunity was also investigated. RESULTS: RT-PCR in STAD cell lines confirmed that ANKRD53 was downregulated in STAD samples compared to normal samples in the online databases. As an independent predictive biomarker, ANKRD53 was combined with other clinicopathological parameters to create a prognostic nomogram. Using GSEA, ANKRD53 was found to be involved in five pathways, including the TGF-ß signaling pathway. Further investigation revealed that ANKRD53 was associated with immune checkpoint molecules, immunological pathways, and immunotherapy, in addition to MSI, TMB and neoantigens. In addition, scRNA-seq data revealed that ANKRD53 is mainly expressed in CD8+ T and dendritic cells. CONCLUSIONS: ANKRD53 is an important biomarker for STAD that deserves further attention.

Mechanistic insights into the role of cyclodextrin in the regioselective radical CH trifluoromethylation of aromatic compounds.

The regioselective radical CH trifluoromethylation of aromatic compounds have been shown to proceed in good yield and high regioselectivity when cyclodextrin (CD) is present. Yet, the reaction mechanism and the role of CD during the reaction have remained obscure. To this end, here we performed density functional theory (DFT) calculations to the conformations obtained by semiempirical quantum mechanical molecular dynamics calculations to reveal the reaction mechanism and the role of CD in controlling regioselectivity. The results show that metal salt increases the yield but do not affect the regioselectivity, which we further confirmed by an experiment. In contrast, multiple CD-substrate complex conformations and reaction pathways were obtained, and CD was shown to contribute to improving the regioselectivity by stabilizing the intermediate state via encapsulation. The present study indicates that CDs can increase the regioselectivity by stabilizing the intermediate and product states while only marginally affecting the transition state.

Peri-device leakage and delayed endothelialization of the Watchman device: a computed tomography study.

OBJECTIVES: This study aimed to explore the endothelialization process and assess the potential association between endothelialization and peri-device leak (PDL) following Watchman implantation via a quantitative method. METHODS: This is a single-center retrospective study of consecutive patients undergoing LAAO between December 2015 and November 2021. Device endothelialization, compared between PDL and non-PDL group, were quantitatively analyzed based on hypoattenuated thickening in cardiac computed tomography angiography (CCTA). Advancement in endothelialization over time were explored using the Cochran-Armitage test and generalized estimating equation approach. Potential risk factors of delayed endothelialization were analyzed using the Cox proportional-hazards model. RESULTS: A total of 172 patients (mean age, 68 years ± 10 [standard deviation], 114 men) were finally included. The average endothelialization ratio of the study population was 89.8 ± 7.2 percent. In the follow-up period of postprocedural 3 months to more than 12 months, an incremental trend of endothelialization over time was observed with the ratio of 85.8 ± 8.0, 89.6 ± 7.6, 92.2 ± 4.5, 94.3 ± 2.9 percent, respectively (p < 0.0001). Notably, patients without PDL exhibited a swifter advancement in endothelialization compared to those with PDL, irrespective of device size. The multivariable Cox regression model showed that PDL (HR = 2.113, 95%CI: 1.300-3.435, p = 0.003), DSP (HR = 1.717, 95%CI: 1.113-2.647, p = 0.014) were independent risk factors of delayed endothelialization. CONCLUSION: CCTA holds promise as an effective means of quantitatively assessing device endothelialization. Endothelialization advanced gradually over time, with PDL potentially impeding device endothelialization. CLINICAL RELEVANCE STATEMENT: A comprehensive understanding of the correlation between endothelialization ratio, time, and residual shunt can establish a more dependable foundation for determining the appropriate anticoagulation treatment following left atrial appendage closure. KEY POINTS: Current recommendations for postleft atrial appendage occlusion anti-platelet and anticoagulation therapy are based on animal studies. Cardiac computed tomography angiography (CCTA) combined with the UNet neural network model enables the quantitative assessment of device endothelialization. This technique will allow for additional studies to better understand device endothelialization to optimize treatments in this population.

Impact of exogenous melatonin foliar application on physiology and fruit quality of wine grapes (Vitis vinifera) under salt stress.

Soil salinisation is an important abiotic stress faced in grape cultivating, leading to weakened plant vigour and reduced fruit quality. Melatonin as a novel hormone has shown positive exogenous application value. Therefore, this study used wine grape (Vitis vinifera ) 'Pinot Noir' as a test material to investigate the changes of foliar spraying with different concentrations of melatonin on the physiology and fruit quality of wine grapes in a field under simulated salt stress (200mmolL-1 NaCl). The results showed that foliar spraying of melatonin significantly increased the intercellular CO2 concentration, maximum photochemical quantum yield of PSII, relative chlorophyll and ascorbic acid content of the leaves, as well as the single spike weight, 100-grain weight, transverse and longitudinal diameters, malic acid, α-amino nitrogen and ammonia content of fruits, and decreased the initial fluorescence value of leaves, ascorbate peroxidase activity, glutathione content, fruit transverse to longitudinal ratio and tartaric acid content of plants under salt stress. Results of the comprehensive evaluation of the affiliation function indicated that 100µmolL-1 melatonin treatment had the best effect on reducing salt stress in grapes. In summary, melatonin application could enhance the salt tolerance of grapes by improving the photosynthetic capacity of grape plants under salt stress and promoting fruit development and quality formation, and these results provide new insights into the involvement of melatonin in the improvement of salt tolerance in crop, as well as some theoretical basis for the development and industrialisation of stress-resistant cultivation techniques for wine grapes.

Surface Oxygen Defect Engineering of A2B2O7 Pyrochlore Semiconductors Boosts the Electrocatalytic Reduction of CO2-to-HCOOH.

The electrocatalytic conversion of inert CO2 to value-added chemical fuels powered by renewable energy is one of the benchmark approaches to address excessive carbon emissions and achieve carbon-neutral energy restructuring. However, the adsorption/activation of supersymmetric CO2 is facing insurmountable challenges that constrain its industrial-scale applications. Here, this theory-guided study confronts these challenges by leveraging the synergies of bimetallic sites and defect engineering, where pyrochlore-type semiconductor A2B2O7 is employed as research platform and the conversion of CO2-to-HCOOH as the model reaction. Specifically, defect engineering intensified greatly the chemisorption-induced CO2 polarization via the bimetallic coordination, thermodynamically beneficial to the HCOOH production via the *HCO2 intermediate. The optimal V-BSO-430 electrocatalyst with abundant surface oxygen vacancies achieved a superior HCOOH yield of 116.7 mmol h-1 cm-2 at -1.2 VRHE, rivalling the incumbent similar reaction systems. Furthermore, the unique catalytic unit featured with a Bi1-Sn-Bi2 triangular structure, which is reconstructed by defect engineering, and altered the pathway of CO2 adsorption and activation to allow the preferential affinity of the suspended O atom in *HCO2 to H. As a result, V-BSO-430 gave an impressive FEHCOOH of 93% at -1.0 VRHE. This study held promises for inspiring the exploration of bimetallic materials from the massive semiconductor database.