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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Proteomic biomarkers for noninvasive left atrial appendage thrombus prediction in patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: The CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. METHODS: Deep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. RESULTS: The LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. CONCLUSIONS: Protein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.

RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway.

Background and Aims: Hepatic ischemia-reperfusion injury (HIRI) is a prevalent complication of liver transplantation, partial hepatectomy, and severe infection, necessitating the development of more effective clinical strategies. Receptor activity-modifying protein 1 (RAMP1), a member of the G protein-coupled receptor adapter family, has been implicated in numerous physiological and pathological processes. The study aimed to investigate the pathogenesis of RAMP1 in HIRI. Methods: We established a 70% liver ischemia-reperfusion model in RAMP1 knockout (KO) and wild-type mice. Liver and blood samples were collected after 0, 6, and 24 h of hypoxia/reperfusion. Liver histological and serological analyses were performed to evaluate liver damage. We also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 function. Results: Liver injury was exacerbated in RAMP1-KO mice compared with the sham group, as evidenced by increased cell death and elevated serum transaminase and inflammation levels. HIRI was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of proliferation. The absence of RAMP1 led to increased activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and yes-associated protein (YAP) phosphorylation, ultimately promoting apoptosis. SCH772984, an ERK/MAPK phosphorylation inhibitor, and PY-60, a YAP phosphorylation inhibitor, reduced apoptosis in in-vitro and in-vivo experiments. Conclusions: Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction, highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.

[Reversal Effect of NVP-BEZ235 on Doxorubicin-Resistance in Burkitt Lymphoma RAJI Cell Line].

OBJECTIVE: To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line. METHODS: The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin. The levels of Pgp, p-AKT, and p-mTOR in cells were detected by Western blot. Cell viability was detected by MTT assay. IC50 was computed by SPSS. RESULTS: The doxorubicin-resistant Burkitt lymphoma cell line, RAJI/DOX, was established successfully. The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line. NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line. NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line, and the effect was obvious when it was cooperated with doxorubicin. CONCLUSION: The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line. NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

[Expression of CD30 in Patients with Diffuse Large B-Cell Lymphoma and Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significance of CD30 in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on 124 cases of primary DLBCL diagnosed at Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2018 to July 2020. The expression of CD30 in patients with DLBCL was detected by immunohistochemical method, and the clinicopathological characteristics were analyzed and compared between CD30+ and CD30- groups. Kaplan-Meier analysis was used for survival analysis. The relationship between CD30 expression and clinical features and prognosis were analyzed. RESULTS: Among the 124 patients with DLBCL, 19 patients expressed CD30, and the positive rate is 15.32%. The clinico-pathological characteristics of CD30+ in patients with DLBCL were characterized by low age, more common in males, fewer extranodal lesions, lower international prognostic index (IPI), GCB type being more common in Hans subtype, and achieving better therapeutic effects (P < 0.05). However, there were no significant statistical differences in B-symptoms (P =0.323), Ann Arbor staging (P =0.197), Eastern Cooperative Oncology Group (ECOG) score (P =0.479), lactate dehydrogenase (LDH) (P =0.477), and the involvement of bone marrow (P =0.222). There were significant differences in OS and PFS between the CD30+ and CD30- groups (χ2=5.653, P =0.017; χ2＝4.109，P =0.043), the CD30+ group had a better prognosis than that of the CD30- group. The results of subgroup analysis showed that the CD30+ group in the IPI score=1-2, LDH elevated group had a better prognosis (P < 0.05). In the subgroups of Ann Arbor staging III-IV (P =0.055) and non GCB type (P =0.053), the CD30+ group had a good prognosis trend, but the difference was not statistically significant. The results of univariate analysis showed that the good prognosis of DLBCL patients was closely related to CD30+ expression, no B-symptoms, early Ann Arbor staging, low ECOG score, normal LDH, low IPI score, fewer extranodal involvement, and obtaining the best therapeutic effect as CR (all P <0.05). COX multivariate regression analysis showed that the presence of B-symptoms and achieving the best therapeutic effect as Non-CR were independent risk factors affecting the prognosis of DLBCL patients (P < 0.05). CONCLUSION: The CD30+ expression in DLBCL patients indicates a good prognosis and has certain diagnostic value in evaluating the prognosis of DLBCL patients.