Valley edge states as bound states in the continuum.

Bound states in the continuum (BICs) are spatially localized states with energy embedded in the continuum spectrum of extended states. The combination of BICs physics and nontrivial band topology theory givs rise to topological BICs, which are robust against disorders and meanwhile, the merit of conventional BICs is attracting wide attention recently. Here, we report valley edge states as topological BICs, which appear at the domain wall between two distinct valley topological phases. The robustness of such BICs is demonstrated. The simulations and experiments show great agreement. Our findings of valley related topological BICs shed light on both BICs and valley physics, and may foster innovative applications of topological acoustic devices.

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Massive retroperitoneal hematoma caused by intercostal artery bleeding after blunt trauma: a case report.

BACKGROUND: The occurrence of massive retroperitoneal hematoma caused by intercostal artery bleeding is exceedingly uncommon. CASE PRESENTATION: A middle-aged male presented to the hospital after a fall. Computed tomography scan revealed a massive retroperitoneal hematoma without any evidence of organ or major vessel rupture. The angiogram revealed extravasation from a branch of the twelfth intercostal artery, and successful transcatheter arterial embolization was performed on this specific artery. CONCLUSIONS: The possibility of intercostal artery rupture should be considered in cases of retroperitoneal hematomas, and accurate diagnosis can be achieved through imaging studies. Transcatheter arterial embolization represents an effective treatment modality.

iso-BAI Guided Surface Recrystallization for Over 14% Tin Halide Perovskite Solar Cells.

Tin-based perovskite solar cells (PSCs) are promising environmentally friendly alternatives to their lead-based counterparts, yet they currently suffer from much lower device performance. Due to variations in the chemical properties of lead (II) and tin (II) ions, similar treatments may yield distinct effects resulting from differences in underlying mechanisms. In this work, a surface treatment on tin-based perovskite is conducted with a commonly employed ligand, iso-butylammonium iodide (iso-BAI). Unlike the passivation effects previously observed in lead-based perovskites, such treatment leads to the recrystallization of the surface, driven by the higher solubility of tin-based perovskite in common solvents. By carefully designing the solvent composition, the perovskite surface is effectively modified while preserving the integrity of the bulk. The treatment led to enhanced surface crystallinity, reduced surface strain and defects, and improved charge transport. Consequently, the best-performing power conversion efficiency of FASnI3 PSCs increases from 11.8% to 14.2%. This work not only distinguishes the mechanism of surface treatments in tin-based perovskites from that of lead-based counterparts, but also underscores the critical role in designing tailor-made strategies for fabricating efficient tin-based PSCs.

Enhancement of PRMT6 binding to a novel germline GATA1 mutation associated with congenital anemia.

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.Leu387Leufs*62) in a patient with congenital anemia and occasional thrombocytopenia. The C-terminal GATA1, a rarely studied mutational region, undergoes frameshifting translation as a consequence of this double-base deletion mutation. To investigate the specific function and pathogenic mechanism of this mutant, in vitro mutant models of stable re-expression cells were generated. The mutation was subsequently validated to cause diminished transcriptional activity of GATA1 and defective differentiation of erythroid and megakaryocytes. Using proximity labeling and mass spectrometry, we identified selective alterations in the proximal protein networks of the mutant, revealing decreased binding to a set of normal GATA1-interaction proteins, including the essential co-factor FOG1. Notably, our findings further demonstrated enhanced recruitment of the protein arginine methyltransferase PRMT6, which mediates histone modification at H3R2me2a and represses transcription activity. We also found an enhanced binding of this mutant GATA1/PRMT6 complex to the transcriptional regulatory elements of GATA1's target genes. Moreover, treatment of the PRMT6 inhibitor MS023 could partially rescue the inhibited transcriptional and impaired erythroid differentiation caused by the GATA1 mutation. Taken together, our results provide molecular insights into erythropoiesis in which mutation leads to partial loss of GATA1 function and the broader role of PRMT6 and its inhibitor MS023 in congenital anemia, highlighting PRMT6 binding as a negative factor of GATA1 transcriptional activity in aberrant hematopoiesis.

Observation of Higher-Order Nodal-Line Semimetal in Phononic Crystals.

Higher-order topological insulators and semimetals, which generalize the conventional bulk-boundary correspondence, have attracted extensive research interest. Among them, higher-order Weyl semimetals feature twofold linear crossing points in three-dimensional momentum space, 2D Fermi-arc surface states, and 1D hinge states. Higher-order nodal-point semimetals possessing Weyl points or Dirac points have been implemented. However, higher-order nodal-line or nodal-surface semimetals remain to be further explored in experiments in spite of many previous theoretical efforts. In this work, we realize a second-order nodal-line semimetal in 3D phononic crystals. The bulk nodal lines, 2D drumhead surface states guaranteed by Zak phases, and 1D flat hinge states attributed to k_{z}-dependent quadrupole moments are observed in simulations and experiments. Our findings of nondispersive surface and hinge states may promote applications in acoustic sensing and energy harvesting.

Developing a Prognostic Model for Primary Biliary Cholangitis Based on a Random Survival Forest Model.

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.

Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Whole mitochondrial genome analysis in highland Tibetans: further matrilineal genetic structure exploration.

Introduction: The Qinghai-Tibet Plateau is one of the last terrestrial environments conquered by modern humans. Tibetans are among the few high-altitude settlers in the world, and understanding the genetic profile of Tibetans plays a pivotal role in studies of anthropology, genetics, and archaeology. Methods: In this study, we investigated the maternal genetic landscape of Tibetans based on the whole mitochondrial genome collected from 145 unrelated native Lhasa Tibetans. Molecular diversity indices, haplotype diversity (HD), Tajima's D and Fu's Fs were calculated and the Bayesian Skyline Plot was obtained to determining the genetic profile and population fluctuation of Lhasa Tibetans. To further explore the genetic structure of Lhasa Tibetans, we collected 107 East Asian reference populations to perform principal component analysis (PCA), multidimensional scaling (MDS), calculated Fst values and constructed phylogenetic tree. Results: The maternal genetic landscape of Tibetans showed obvious East Asian characteristics, M9a (28.28%), R (11.03%), F1 (12.41%), D4 (9.66%), N (6.21%), and M62 (4.14%) were the dominant haplogroups. The results of PCA, MDS, Fst and phylogenetic tree were consistent: Lhasa Tibetans clustered with other highland Tibeto-Burman speakers, there was obvious genetic homogeneity of Tibetans in Xizang, and genetic similarity between Tibetans and northern Han people and geographically adjacent populations was found. In addition, specific maternal lineages of Tibetans also be determined in this study. Discussion: In general, this study further shed light on long-time matrilineal continuity on the Tibetan Plateau and the genetic connection between Tibetans and millet famers in the Yellow River Basin, and further revealed that multiple waves of population interaction and admixture during different historical periods between lowland and highland populations shaped the maternal genetic profile of Tibetans.

The transcription factor ELF4 alleviates inflammatory bowel disease by activating IL1RN transcription, suppressing inflammatory TH17 cell activity, and inducing macrophage M2 polarization.

Background: Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder affecting millions worldwide. Due to the complexity of its pathogenesis, the treatment options for IBD are limited. This study focuses on ELF4, a member of the ETS transcription factor family, as a target to elucidate its role in IBD and investigate its mechanism of action in alleviating IBD symptoms by activating IL1RN transcription to suppress the activity of inflammatory TH17 cells. Methods: Using the GEO database, this study examined LPS-induced intestinal inflammatory genes and their regulation mechanisms. We examined the colon length of LPS-treated mice and derived the Disease Activity Index (DAI). H&E staining, ELISA, and flow cytometry were used to detect mice colon tissue damage, inflammatory factor levels in mouse serum, mouse macrophage types and inflammatory TH17 cell activity. RT-qPCR and Western blot detected ELF4, IL1RN, M1, and M2 polarization markers. In Vitro, using dual-luciferase and ChIP assays, we tested mouse bone marrow-derived macrophages (BMDMs) and mouse intestinal epithelial cells for IL1RN promoter activity and ELF4 enrichment. Results: Bioinformatics showed that LPS-induced colitis animals have reduced ELF4 expression in their colon tissue. In vivo tests confirmed reduced ELF4 expression in mice with LPS-induced colitis. ELF4 overexpression reduced mouse intestinal inflammation. ELF4 activated IL1RN transcription in bioinformatics and in vitro tests. ELF4 promoted IL1RN transcription and macrophage M2 polarization to limit intestinal epithelial cell death and inflammation and reduce mouse intestinal inflammation in vitro. ELF4 also reduced the Th17/Treg ratio by increasing IL1RN transcription. Conclusion: ELF4 activates IL1RN transcription, suppresses inflammatory TH17 cells, and induces macrophage M2 polarization to treat IBD.

The Mechanism of miR-155/miR-15b Axis Contributed to Apoptosis of CD34+ Cells by Upregulation of PD-L1 in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal diseases that are characterized by ineffective bone marrow hematopoiesis. Since studies have confirmed the significance of miRNAs in ineffective hematopoiesis in MDS, the current report elucidated the mechanism mediated by miR-155-5p. The bone marrow of MDS patients was collected to detect miR-155-5p and to analyze the correlation between miR-155-5p and clinicopathological variables. Isolated bone marrow CD34+ cells were transfected with lentiviral plasmids that interfere with miR-155-5p, followed by apoptosis analysis. Finally, miR-155-5p-targeted regulation of RAC1 expression was identified, as well as the interaction between RAC1 and CREB, the co-localization of RAC1 and CREB, and the binding of CREB to miR-15b. As measured, miR-155-5p was upregulated in the bone marrow of MDS patients. Further cell experiments validated that miR-155-5p promoted CD34+ cell apoptosis. miR-155-5p could reduce the transcriptional activity of miR-15b by inhibiting RAC1, dissociating the interaction between RAC1 and CREB, and inhibiting the activation of CREB. Upregulating RAC1, CREB, or miR-15b could reduce miR-155-5p-mediated apoptosis promotion on CD34+ cells. Additionally, miR-155-5p could force PD-L1 expression, and this effect was impaired by elevating RAC1, CREB, or miR-15b. In conclusion, miR-155-5p mediates PD-L1-mediated apoptosis of CD34+ cells in MDS by RAC1/CREB/miR-15b axis, thereby inhibiting bone marrow hematopoiesis.

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

Human-Like Artificial Intelligent System for Predicting Invasion Depth of Esophageal Squamous Cell Carcinoma Using Magnifying Narrow-Band Imaging Endoscopy: A Retrospective Multicenter Study.

INTRODUCTION: Endoscopic evaluation is crucial for predicting the invasion depth of esophagus squamous cell carcinoma (ESCC) and selecting appropriate treatment strategies. Our study aimed to develop and validate an interpretable artificial intelligence-based invasion depth prediction system (AI-IDPS) for ESCC. METHODS: We reviewed the PubMed for eligible studies and collected potential visual feature indices associated with invasion depth. Multicenter data comprising 5,119 narrow-band imaging magnifying endoscopy images from 581 patients with ESCC were collected from 4 hospitals between April 2016 and November 2021. Thirteen models for feature extraction and 1 model for feature fitting were developed for AI-IDPS. The efficiency of AI-IDPS was evaluated on 196 images and 33 consecutively collected videos and compared with a pure deep learning model and performance of endoscopists. A crossover study and a questionnaire survey were conducted to investigate the system's impact on endoscopists' understanding of the AI predictions. RESULTS: AI-IDPS demonstrated the sensitivity, specificity, and accuracy of 85.7%, 86.3%, and 86.2% in image validation and 87.5%, 84%, and 84.9% in consecutively collected videos, respectively, for differentiating SM2-3 lesions. The pure deep learning model showed significantly lower sensitivity, specificity, and accuracy (83.7%, 52.1% and 60.0%, respectively). The endoscopists had significantly improved accuracy (from 79.7% to 84.9% on average, P = 0.03) and comparable sensitivity (from 37.5% to 55.4% on average, P = 0.27) and specificity (from 93.1% to 94.3% on average, P = 0.75) after AI-IDPS assistance. DISCUSSION: Based on domain knowledge, we developed an interpretable system for predicting ESCC invasion depth. The anthropopathic approach demonstrates the potential to outperform deep learning architecture in practice.

Role of ferroptosis in colorectal cancer.

Colorectal cancer (CRC) is the second deadliest cancer and the third-most common malignancy in the world. Surgery, chemotherapy, and targeted therapy have been widely used to treat CRC, but some patients still develop resistance to these treatments. Ferroptosis is a novel non-apoptotic form of cell death. It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer drugs. This review summarizes recent advances in the prognostic role of ferroptosis in CRC and the mechanism of action in CRC.

Acoustic Higher-Order Weyl Semimetal with Bound Hinge States in the Continuum.

Higher-order topological phases have raised widespread interest in recent years with the occurrence of the topological boundary states of dimension two or more less than that of the system bulk. The higher-order topological states have been verified in gapped phases, in a wide variety of systems, such as photonic and acoustic systems, and recently also observed in gapless semimetal phase, such as Weyl and Dirac phases, in systems alike. The higher-order topology is signaled by the hinge states emerging in the common band gaps of the bulk states and the surface states. In this Letter, we report our first prediction and observation of a new type of hinge states, the bound hinge states in the continuum (BHICs) bulk band, in a higher-order Weyl semimetal implemented in phononic crystal. In contrast to the hinge state in gap, which is characterized by the bulk polarization, the BHIC is identified by the nontrivial surface polarization. The finding of the topological BHICs broadens our insight to the topological states, and may stimulate similar researches in other systems such as electronic, photonic, and cold atoms systems. Our Letter may pave the way toward high-Q acoustic devices in application.

Oxanorbornene-Fused Phenazine-Pyrene Scaffolds with Different Configurations.

New molecular scaffolds of C-, Z- and box-shaped configurations are constructed by fusing phenazine and pyrene units with oxanorbornene. As revealed by X-ray crystallography, the C-shaped molecules exhibit two interesting π-π stacking modes of phenazine depending on the substituting groups, and the box-shaped molecule accommodates two chloroform molecules in the cavity and forms H-bonds with another four molecules of chloroform. The C- and Z-shaped molecules as a pair of diastereomers exhibit almost the same charge transfer absorption and emission including positive solvatochromism, indicating that the intramolecular charge transfer between pyrene (π-donor) and phenazine (π-acceptor) is not dependent on the overall molecular geometry.

Tyrosine kinase SRC-induced YAP1-KLF5 module regulates cancer stemness and metastasis in triple-negative breast cancer.

SRC is the first identified oncogene, and its aberrant activation has been implicated as a driving event in tumor initiation and progression. However, its role in cancer stemness regulation and the underlying regulatory mechanism are still elusive. Here, we identified a YAP1 tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module, as the key downstream mediator of SRC kinase regulating cancer stemness and metastasis in triple-negative breast cancer (TNBC). SRC was overexpressed in TNBC patient tissues and its expression level was highly correlated with the tumor malignancy. SRC activation induced, while inhibition of SRC kinase reduced the cancer stemness, tumor cell growth and metastasis in vitro and in vivo. Transcriptomic and proteomic analysis revealed that SRC-mediated YAP1 tyrosine phosphorylation induced its interaction with Kruppel-like factor 5 (KLF5) to form a YAP1/TEAD-KLF5 complex in TNBC cells. YAP1-KLF5 association further promoted TEAD-mediated transcriptional program independently of canonical Hippo kinases, which eventually gave rise to the enhanced cancer stemness and metastasis. Disruption of YAP1-KLF5 module in TNBC cells dramatically attenuated the SRC-induced cancer stemness and metastasis in vitro and in vivo. Accordingly, co-upregulations of SRC and YAP1-KLF5 module in TNBC tissues were significantly positively correlated with the tumor malignance. Altogether, our work presents a novel tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module governing SRC-induced cancer stemness and metastasis in TNBC. Therefore, targeting YAP1/KLF5-mediated transcription may provide a promising strategy for TNBC treatment with SRC aberrantly activation.

SRC kinase-mediated signaling pathways and targeted therapies in breast cancer.

Breast cancer (BC) has been ranked the most common malignant tumor throughout the world and is also a leading cause of cancer-related deaths among women. SRC family kinases (SFKs) belong to the non-receptor tyrosine kinase (nRTK) family, which has eleven members sharing similar structure and function. Among them, SRC is the first identified proto-oncogene in mammalian cells. Oncogenic overexpression or activation of SRC has been revealed to play essential roles in multiple events of BC progression, including tumor initiation, growth, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of SRC kinase and SRC-relevant functions in various subtypes of BC and then systematically summarize SRC-mediated signaling transductions, with particular emphasis on SRC-mediated substrate phosphorylation in BC. Furthermore, we will discuss the progress of SRC-based targeted therapies in BC and the potential future direction.