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Abstract Objective To analyze primary angle closure suspect (PACS) patients’ anatomical characteristics of anterior chamber configuration, and to establish artificial intelligence (AI)-aided diagnostic system for PACS screening. Methods A total of 1668 scans of 839 patients were included in this cross-sectional study. The subjects were divided into two groups: PACS group and normal group. With anterior segment optical coherence tomography scans, the anatomical diversity between two groups was compared, and anterior segment structure features of PACS were extracted. Then, AI-aided diagnostic system was constructed, which based different algorithms such as classification and regression tree (CART), random forest (RF), logistic regression (LR), VGG-16 and Alexnet. Then the diagnostic efficiencies of different algorithms were evaluated, and compared with junior physicians and experienced ophthalmologists. Results RF [sensitivity (Se) = 0.84; specificity (Sp) = 0.92; positive predict value (PPV) = 0.82; negative predict value (NPV) = 0.95; area under the curve (AUC) = 0.90] and CART (Se = 0.76, Sp = 0.93, PPV = 0.85, NPV = 0.92, AUC = 0.90) showed better performance than LR (Se = 0.68, Sp = 0.91, PPV = 0.79, NPV = 0.90, AUC = 0.86). In convolutional neural networks (CNN), Alexnet (Se = 0.83, Sp = 0.95, PPV = 0.92, NPV = 0.87, AUC = 0.85) was better than VGG-16 (Se = 0.84, Sp = 0.90, PPV = 0.85, NPV = 0.90, AUC = 0.79). The performance of 2 CNN algorithms was better than 5 junior physicians, and the mean value of diagnostic indicators of 2 CNN algorithm was similar to experienced ophthalmologists. Conclusion PACS patients have distinct anatomical characteristics compared with health controls. AI models for PACS screening are reliable and powerful, equivalent to experienced ophthalmologists.

Abstract The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability of an asymmetric polar cycloaddition of bicyclo[1.1.0]butane using a chiral Lewis acid catalyst and a bidentate chelating bicyclo[1.1.0]butane substrate, as exemplified by the current enantioselective formal (3 + 3) cycloaddition of bicyclo[1.1.0]butanes with nitrones. In addition to the diverse bicyclo[1.1.0]butanes incorporating an acyl imidazole group or an acyl pyrazole moiety, a wide array of nitrones are compatible with this Lewis acid catalysis, successfully assembling two congested quaternary carbon centers and a chiral aza-trisubstituted carbon center in the pharmaceutically important hetero-bicyclo[3.1.1]heptane product with up to 99% yield and >99% ee.

Abstract Backgrounds The study aimed to estimate bladder cancer burden and its attributable risk factors in China, Japan, South Korea, North Korea and Mongolia from 1990 to 2019, to discuss the potential causes of the disparities. Methods Data were obtained from the Global Burden of Disease Study 2019. The annual percent change (APC) and average annual percent change (AAPC) were calculated by Joinpoint analysis, and the independent age, period and cohort effects were estimated by age-period-cohort analysis. Results In 2019, the highest incidence (7.70 per 100,000) and prevalence (51.09 per 100,000) rates of bladder cancer were in Japan, while the highest mortality (2.31 per 100,000) and DALY rates (41.88 per 100,000) were in South Korea and China, respectively. From 1990 to 2019, the age-standardized incidence and prevalence rates increased in China, Japan and South Korea (AAPC > 0) and decreased in Mongolia (AAPC

Abstract Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak.

Abstract Background Atrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by β-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of β-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues . Methods We compared the difference of β-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of β-catenin in the development of AF was also explored in mice and primary cells. Results Firstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of β-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, β-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3β (GSK-3β) and Adenomatous Polyposis Coli (APC), which participated in the degradation of β-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting β-catenin expression in the AF model mice. Conclusions Based on human atrial pathological and molecular analyses, our findings provided evidence that β-catenin was associated with atrial fibrosis and AF progression.

Abstract Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C 2v and C 4v symmetry denoted as C 2v - OC-4 and C 4v - OC-4, respectively. Heating induces the efficient stepwise conversion of C 2v - to C 4v - OC-4 via a C s -symmetric intermediate (C s -OC-4). It differs from the typical transition state-mediated processes of simple C–C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C 2v - and C s -OC-4 from C 4v - OC-4. In contrast to C 2v - OC-4, C 4v - OC-4 can bind linear guests to form pseudo-rotaxans, or bind C60 or C70 efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations.

Abstract Background To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. Methods We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. Results A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two‐field lymph node dissection including the para‐recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. Conclusions Currently, in China, minimally invasive surgery‐oriented multimodality treatment, including complete two‐field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Abstract Background This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). Methods LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. Results LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. Conclusions Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Abstract This study aimed to investigate the effects of tea green leafhopper damage on the sensory quality and metabolite composition of Oriental Beauty by using tea leaves from different varieties of tea plants and processing factories. The results indicated that tea green leafhopper damage could reduce bitterness and increase the level of fruity aroma, which was related to the content changes of catechin components and alcohol substances. Furthermore, the tea green leafhopper salivary treatment experiment revealed that the decrease of catechin content and increase of theaflavin content were mainly influenced by the action of saliva and mechanical injury, and changes in volatile components such as linalool oxidation were responsible for the alteration in aroma. These findings provide a theoretical reference for the aroma formation and quality improvement of Oriental Beauty.

Gaining insight into the underlying mechanisms driving nanoindentation-induced behavior in tungsten is essential for comprehending its mechanical properties. Although the plasticity of conventional pure tungsten under nanocontact conditions is well understood, these theoretical constructs may become inadequate when applied to irradiated tungsten due to the interplay between helium bubbles and dislocations. Here, we employed an integrated approach, combining crystal defect theories, molecular dynamics simulations, and machine learning, to explore the initiation and progression of dislocations in tungsten containing helium bubbles during nanoindentation, focusing on elucidating the impact of helium bubbles. In contrast to the typical dislocation nucleation in pure tungsten, the presence of helium bubbles mitigates local shear strain, thereby hindering dislocation nucleation and propagation, leading to a reduction of indentation force. Additionally, we conducted a comparative analysis between samples with and without helium bubbles, examining factors such as atomic displacement, strain localization parameters, dislocation line length, and stress component distribution. More importantly, a significant outcome of our study is the establishment of a relationship between the consistent alteration in the shape of helium bubbles and their size during micro-scale nanoindentation, achieved through machine learning techniques. Our findings reveal that the area occupied by helium bubbles post-nanoindentation is inversely correlated with indentation depth and directly linked to helium bubble size. These discoveries represent a notable advancement in understanding the effects of irradiation to a certain degree.

The interaction between irradiation defects and dislocations could lead to macroscopic hardening and embrittlement. In this study, molecular dynamics (MD) and machine learning were conducted to study three-dimensional void- and Cu-cluster-induced kinetics models under interaction with dislocations in body-centered cubic Fe-based alloys. MD Results show that dislocation climb and shear are two types of interaction mechanism based on the defect size. Combined MD results and machine learning, it was found that the dislocation length increased linearly with an increase in the size of the defects after the interaction. In addition, the number of atoms in the Cu-rich cluster and the reduced number of vacancies in the voids had a square relationship with the defect size where 0.85D2 is for Cu-rich cluster and 0.50D2 is for void. Furthermore, atomic-scale three-dimensional irradiation-induced defect kinetics models were developed and incorporated into the crystal plasticity finite element model (CPFEM). We also analyzed the contributions of various defects to the increase in the yield stress during CPFEM simulation. Compared with DBH model, the prediction of MD data-driven CPFEM matches better with the experimental data. Cluster contributed the most to hardening with low obstacle strength due to the higher number density compared with dislocation loops and voids. The loops also contributed to hardening; however, their contribution was smaller than that of the clusters. Although the number density and size of voids were minimized, they may have contributed because of the high obstacle strengths. This work can indeed deepen the understanding of irradiation effect in Fe-based alloys.