Directly modulated deformed-square-FP coupled-cavity laser with intracavity-mode photon-photon resonance.

We propose and demonstrate a high-speed directly modulated laser based on a hybrid deformed-square-FP coupled cavity (DFC), aiming for a compact-size low-cost light source in next-generation optical communication systems. The deformed square microcavity is directly connected to the FP cavity and utilized as a wavelength-sensitive reflector with a comb-like and narrow-peak reflection spectrum for selecting the lasing mode, which can greatly improve the single-mode yield of the laser and the quality (Q) factor of the coupled mode. By optimizing the device design and operating condition, the modulation bandwidth of the DFC laser can be enhanced due to the intracavity-mode photon-photon resonance effect. Our experimental results show an enhancement of 3-dB modulation bandwidth from 19.3 GHz to 30 GHz and a clear eye diagram at a modulation rate of 25 Gbps.

Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Tryptophan deficiency induced by indoleamine 2,3-dioxygenase 1 results in glucose transporter 1-dependent promotion of aerobic glycolysis in pancreatic cancer.

Indoleamine 2,3-dioxygenase 1 (IDO1), the key enzyme in the catabolism of the essential amino acid tryptophan (Trp) through kynurenine pathway, induces immune tolerance and is considered as a critical immune checkpoint, but its impacts as a metabolism enzyme on glucose and lipid metabolism are overlooked. We aim to clarify the potential role of IDO1 in aerobic glycolysis in pancreatic cancer (PC). Analysis of database revealed the positive correlation in PC between the expressions of IDO1 and genes encoding important glycolytic enzyme hexokinase 2 (HK2), pyruvate kinase (PK), lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1). It was found that IDO1 could modulate glycolysis and glucose uptake in PC cells, Trp deficiency caused by IDO1 overexpression enhanced glucose uptake by stimulating GLUT1 translocation to the plasma membrane of PC cells. Besides, Trp deficiency caused by IDO1 overexpression suppressed the apoptosis of PC cells via promoting glycolysis, which reveals the presence of IDO1-glycolysis-apoptosis axis in PC. IDO1 inhibitors could inhibit glycolysis, promote apoptosis, and exhibit robust therapeutic efficacy when combined with GLUT1 inhibitor in PC mice. Our study reveals the function of IDO1 in the glucose metabolism of PC and provides new insights into the therapeutic strategy for PC.

Forging the Tetracyclic Core Framework of Rhodomolleins XIV and XLII: A Ring-Distortion Approach.

A ring distortion approach for the synthesis of an advanced intermediate en route to rhodomolleins XIV and XLII was described, which led to successful construction of the 5/8/5/5 tetracyclic core framework of the kalmane diterpenoids. Key steps of the strategy include an oxidative dearomatization-induced (ODI)-Diels-Alder cycloaddition, a Dowd-Beckwith rearrangement, and a bioinspired Wagner-Meerwein rearrangement.

Perception of Patients, Physicians, and Chaperones Regarding the Use of Chaperones During Patient Examinations for Plastic Surgery: A Systematic Review.

In this systematic review, we searched electronic databases for literature addressing physician use of chaperones during examinations of patients undergoing plastic surgery from the perspective of the patient, physician, and chaperone from inception of the database until April 2023. After screening 939 articles, we included seven studies in a systematic review. We conducted an inductive thematic analysis of four domains (physician perspective, patient perspective, chaperone perspective, and chaperone documentation). The results of the analysis showed that surgeons who are experienced, are men, or have received education related to using chaperones are more likely to provide chaperones during patient examinations for medicolegal protection and patient comfort. A small percentage of surgeons have faced accusations from patients of inappropriate behavior. Most of these incidents have occurred without a chaperone present. Patients who have long associations with a particular plastic surgery practice are less likely to want a chaperone. When physicians examine nonsensitive areas, most patients prefer having no chaperone. However, young patients and patients undergoing reconstructive procedures are more likely to request chaperones. Patients prefer having family members or friends serve as chaperones. Notably, despite the presence of a chaperone, we found that documentation of the presence of a chaperone was inadequate. Using a chaperone helps establish trust and ensure patient comfort. Further research, including qualitative studies and multinational approaches, is warranted to gain deeper insights and develop comprehensive guidelines for chaperone use that empowers both patients and health care providers.

The impact of virtual reality on student engagement in the classroom-a critical review of the literature.

Objective: The purpose of this review is to identify the impact of virtual reality (VR) technology on student engagement, specifically cognitive engagement, behavioral engagement, and affective engagement. Methods: A comprehensive search of databases such as Google, Scopus, and Elsevier was conducted to identify English-language articles related to VR and classroom engagement for the period from 2014 to 2023. After systematic screening, 33 articles were finally reviewed. Results: The use of VR in the classroom is expected to improve student engagement and learning outcomes, and is particularly effective for students with learning disabilities. However, introducing VR into middle school education poses several challenges, including difficulties in the education system to keep up with VR developments, increased demands on students' digital literacy, and insufficient proficiency of teachers in using VR. Conclusion: To effectively utilize VR to increase student engagement, we advocate for educational policymakers to provide training and technical support to teachers to ensure that they can fully master and integrate VR to increase student engagement and instructional effectiveness.

Deep learning-accelerated T2WI: image quality, efficiency, and staging performance against BLADE T2WI for gastric cancer.

PURPOSE: The purpose of our study is to investigate image quality, efficiency, and diagnostic performance of a deep learning-accelerated single-shot breath-hold (DLSB) against BLADE for T2-weighted MR imaging (T2WI) for gastric cancer (GC). METHODS: 112 patients with GCs undergoing gastric MRI were prospectively enrolled between Aug 2022 and Dec 2022. Axial DLSB-T2WI and BLADE-T2WI of stomach were scanned with same spatial resolution. Three radiologists independently evaluated the image qualities using a 5-scale Likert scales (IQS) in terms of lesion delineation, gastric wall boundary conspicuity, and overall image quality. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated in measurable lesions. T staging was conducted based on the results of both sequences for GC patients with gastrectomy. Pairwise comparisons between DLSB-T2WI and BLADE-T2WI were performed using the Wilcoxon signed-rank test, paired t-test, and chi-squared test. Kendall's W, Fleiss' Kappa, and intraclass correlation coefficient values were used to determine inter-reader reliability. RESULTS: Against BLADE, DLSB reduced total acquisition time of T2WI from 495 min (mean 4:42 per patient) to 33.6 min (18 s per patient), with better overall image quality that produced 9.43-fold, 8.00-fold, and 18.31-fold IQS upgrading against BALDE, respectively, in three readers. In 69 measurable lesions, DLSB-T2WI had higher mean SNR and higher CNR than BLADE-T2WI. Among 71 patients with gastrectomy, DLSB-T2WI resulted in comparable accuracy to BLADE-T2WI in staging GCs (P > 0.05). CONCLUSIONS: DLSB-T2WI demonstrated shorter acquisition time, better image quality, and comparable staging accuracy, which could be an alternative to BLADE-T2WI for gastric cancer imaging.

Utility of Combined Use of Imaging Features From Abdominopelvic CT and CA 125 to Identify Presence of CT Occult Peritoneal Metastases in Advanced Gastric Cancer.

OBJECTIVE: The purpose of this study is to identify the presence of occult peritoneal metastasis (OPM) in patients with advanced gastric cancer (AGC) by using clinical characteristics and abdominopelvic computed tomography (CT) features. METHODS: This retrospective study included 66 patients with OPM and 111 patients without peritoneal metastasis (non-PM [NPM]) who underwent preoperative contrast-enhanced CT between January 2020 and December 2021. Occult PMs means PMs that are missed by CT but later diagnosed by laparoscopy or laparotomy. Patients with NPM means patients have neither PM nor other distant metastases, indicating there is no evidence of distant metastases in patients with AGC. Patients' clinical characteristics and CT features such as tumor marker, Borrmann IV, enhancement patterns, and pelvic ascites were observed by 2 experienced radiologists. Computed tomography features and clinical characteristics were combined to construct an indicator for identifying the presence of OPM in patients with AGC based on a logistic regression model. Receiver operating characteristic curves and the area under the receiver operating characteristic curve (AUC) were generated to assess the diagnostic performance of the combined indicator. RESULTS: Four independent predictors (Borrmann IV, pelvic ascites, carbohydrate antigen 125, and normalized arterial CT value) differed significantly between OPM and NPM and performed outstandingly in distinguishing patients with OPM from those without PM (AUC = 0.643-0.696). The combined indicator showed a higher AUC value than the independent risk factors (0.820 vs 0.643-0.696). CONCLUSIONS: The combined indicator based on abdominopelvic CT features and carbohydrate antigen 125 may assist clinicians in identifying the presence of CT OPMs in patients with AGC.

Dual-energy CT quantitative parameters to evaluate occult peritoneal metastasis in advanced gastric cancer preoperatively.

PURPOSE: To explore whether dual-energy CT (DECT) quantitative parameters could provide analytic value for the diagnosis of patients with occult peritoneal metastasis (OPM) in advanced gastric cancer preoperatively. MATERIALS AND METHODS: This retrospective study included 219 patients with advanced gastric cancer and DECT scans. The patient's clinical data and DECT related iodine concentration (IC) parameters and effective atomic number (Zeff) were collated and analyzed among noun-peritoneal metastasis (NPM), OPM and radiologically peritoneal metastasis (RPM) groups. The predictive performance of the DECT parameters was compared with that of the conventional CT features and clinical characteristics through evaluating area under curve of the precision-recall (AUC-PR), F1 score, balanced accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Borrmann IV type diagnosed on CT and serum tumor indicator CA125 index were statistically different between the NPM and OPM groups. DECT parameters included IC, normalized IC (NIC), and Zeff of PM group were lower than the NPM group. The DECT predictive nomogram combined three independent DECT parameters produced a better diagnostic performance than the conventional CT feature Borrmann IV type and serum CA125 index in AUC-PR with 0.884 vs 0.368 vs 0.189, but similar to the combined indicator which was based on the DECT parameters, the conventional CT feature, and serum CA125 index in AUC-PR with 0.884 vs 0.918. CONCLUSION: The lower quantitative NIC, IC ratio, and Zeff on DECT was associated with peritoneal metastasis in advanced gastric cancer and was promising to identify patients with OPM noninvasively.

Metaplastic regeneration in the mouse stomach requires a reactive oxygen species pathway.

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.

Multifunctional Polyoxometalates-Based Ionohydrogels toward Flexible Electronics.

Multifunctional flexible electronics present tremendous opportunities in the rapidly evolving digital age. One potential avenue to realize this goal is the integration of polyoxometalates (POMs) and ionic liquid-based gels (ILGs), but the challenge of macrophase separation due to poor compatibility, especially caused by repulsion between like-charged units, poses a significant hurdle. Herein, the possibilities of producing diverse and homogenous POMs-containing ionohydrogels by nanoconfining POMs and ionic liquids (ILs) within an elastomer-like polyzwitterionic hydrogel using a simple one-step random copolymerization method, are expanded vastly. The incorporation of polyzwitterions provides a nanoconfined microenvironment and effectively modulates excessive electrostatic interactions in POMs/ILs/H2O blending system, facilitating a phase transition from macrophase separation to a submillimeter scale worm-like microphase-separation system. Moreover, combining POMs-reinforced ionohydrogels with a developed integrated self-powered sensing system utilizing strain sensors and Zn-ion hybrid supercapacitors has enabled efficient energy storage and detection of external strain changes with high precision. This work not only provides guidelines for manipulating morphology within phase-separation gelation systems, but also paves the way for developing versatile POMs-based ionohydrogels for state-of-the-art smart flexible electronics.

Wavelength dependency and photosensitizer effects in UV-LED photodegradation of iohexol.

Iodinated X-ray contrast media (ICM) are ubiquitously present in water sources and challenging to eliminate using conventional processes, posing a significant risk to aquatic ecosystems. Ultraviolet light-emitting diodes (UV-LED) emerge as a promising technology for transforming micropollutants in water, boasting advantages such as diverse wavelengths, elimination of chemical additives, and no induction of microorganisms' resistance to disinfectants. The research reveals that iohexol (IOX) degradation escalates as UV wavelength decreases, attributed to enhanced photon utilization efficiency. Pseudo-first-order rate constants (kobs) were determined as 3.70, 2.60, 1.31 and 0.65 cm2 J-1 at UV-LED wavelengths of 255, 265, 275 and 285 nm, respectively. The optical properties of dissolved organic matter (DOM) and anions undeniably influence the UV-LED photolysis process through photon competition and the generation of reactive substances. The influence of Cl- on IOX degradation was insignificant at UV-LED 255, but it promoted IOX degradation at 265, 275 and 285 nm. IOX degradation was accelerated by ClO2-, NO3-and HA due to the formation of various reactive species. In the presence of NO3-, the kobs of IOX followed the order: 265 > 255 > 275 > 285 nm. Photosensitizers altered the spectral dependence of IOX, and the intermediate photoactivity products were detected using electron spin resonance. The transformation pathways of IOX were determined through density functional theory calculations and experiments. Disinfection by-products (DBPs) yields of IOX during UV-LED irradiation decreased as the wavelength increased: 255 > 265 > 275 > 285 nm. The cytotoxicity index value decreased as the UV-LED wavelength increased from 255 to 285 nm. These findings are crucial for selecting the most efficient wavelength for UV-LED degradation of ICM and will benefit future water purification design.

ISR inhibition reverses pancreatic ß-cell failure in Wolfram syndrome models.

Pancreatic ß-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of ß cell specific Wfs1 knockout were applied to model ß-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS ß-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted ß-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to ß-cell failure. Notably, further investigation of the stress trajectory identified activated integrated stress response (ISR) as a crucial mechanism underlying WS ß-cell failure, characterized by aberrant eIF2 signaling in WFS1-deficient SC-islets, along with elevated expression of genes in regulating stress granule formation. Significantly, we demonstrated that ISRIB, an ISR inhibitor, efficiently reversed ß-cell failure in WFS1-deficient SC-islets. We further validated therapeutic efficacy in vivo with ß-cell specific Wfs1 knockout mice. Altogether, our study provides novel insights into WS pathogenesis and offers a strategy targeting ISR to treat WS diabetes.

Gastric intestinal metaplasia: progress and remaining challenges.

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.

Re-evaluating the impact and mechanism of digital economy on regional pollution intensity from the perspective of spatial spillover.

Based on the panel data of 259 cities across China from 2011 to 2019, the study investigates the long-run impact of digital economy on regional pollution intensity by employing multiple models. The estimation results reveal that (1) the relatively heavily polluted areas are concentrated in the north, especially in the northeast of China; the overall pollution intensity is decreasing year by year at the national level; (2) the development of digital economy can significantly contribute to the reduction of regional pollution intensity and it has a statistically significant negative spatial spillover effect on the pollution intensity of neighboring cities; (3) mechanism analysis shows that the development of digital economy not only has a direct effect on the reduction of pollution intensity but also promotes the reduction through the channel of industrial structure upgrading and green technology progress; (4) the results of threshold model suggest that as the level of development of the digital economy increases, its marginal inhibitory effect of promoting the decrease in pollution intensity will diminish; (5) heterogeneity analysis shows that the development of digital economy makes the strongest marginal contribution to pollution intensity reduction in the northeast region. Finally, the conclusions remain valid after controlling for exogenous shocks such as "smart city" policy, various robustness, and endogeneity tests.

MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription.

BACKGROUND: The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. METHODS: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. RESULTS: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. CONCLUSION: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.

Enhanced 2-MIB degradation by UV-LED/chlorine process: reaction kinetics, wavelength dependence, influencing factors and degradation pathways.

The efficient removal of 2-Methylisoborneol (2-MIB), a typical odour component, in water treatment plants (WTPs), poses a great challenge to conventional water treatment technology due to its chemical stability. In this study, the combination of ultraviolet light-emitting diode (UV-LED) and chlorine (UV-LED/chlorine) was exploited for 2-MIB removal, and the role of ultraviolet (UV) wavelength was investigated systematically. The results showed that UV or chlorination alone did not degrade 2-MIB effectively, and the UV/chlorine process could degrade 2-MIB efficiently, following the pseudo-first-order kinetic model. The 275 nm UV exhibited higher 2-MIB degradation efficiency in this UV-LED/chlorine system than 254 nm UV, 265 nm UV and 285 nm UV due to the highest mole adsorption coefficient and quantum yield of chlorine in 275 nm UV. ·OH and ·Cl produced in the 275 nm UV/chlorine system played major roles in 2-MIB degradation. HCO3- and Natural organic matter (NOM), prevalent in water, consumed ·OH and ·Cl, thus inhibiting the 2-MIB degradation by UV-LED/chlorine. In addition, NOM and 2-MIB could form a photonic competition effect. The degradation of 2-MIB by UV-LED/chlorine was done mainly through dehydration and demethylation, and odorous intermediates, such as camphor, were produced. 2-MIB was degraded through the α bond fracture and six-membered ring opening to form saturated or unsaturated hydrocarbons and aldehydes. Four DBPs, chloroform (CF), trichloroacetaldehyde (TCE), trichloroacetone (TCP) and dichloroacetone (DCP), were mainly generated, and CF was the most significant by-product.

A BIGRU-Based Stacked Attention Network for Biomedical Named Entity Recognition with Chinese EMRs.

Biomedical named entity recognition (BNER) is an effective method to structure the medical text data. It is an important basic task for building the medical application services such as the medical knowledge graphs and the intelligent auxiliary diagnosis systems. Existing medical named entity recognition methods generally leverage the word embedding model to construct text representation, and then integrate multiple semantic understanding models to enhance the semantic understanding ability of the model to achieve high-performance entity recognition. However, in the medical field, there are many professional terms that rarely appear in the general field, which cannot be represented well by the general domain word embedding model. Second, existing approaches typically only focus on the extraction of global semantic features, which generate a loss of local semantic features between characters. Moreover, as the word embedding dimension becomes much higher, the standard single-layer structure fails to fully and deeply extract the global semantic features. We put forward the BIGRU-based Stacked Attention Network (BSAN) model for biomedical named entity recognition. Firstly, we use the large-scale real-world medical electronic medical record (EMR) data to fine-tune BERT to build the proprietary embedding representations of the medical terms. Second, we use the Convolutional Neural Network model to extract semantic features. Finally, a stacked BIGRU is constructed using a multi-layer structure and a novel stacking method. It not only enables comprehensive and in-depth extraction of global semantic features, but also requires less time. Experimentally validated on the real-world datasets in Chinese EMRs, the proposed BSAN model achieves 90.9% performance on F1-values, which is stronger than the BNER performance of other state-of-the-art models.

Unveiling human origins of replication using deep learning: accurate prediction and comprehensive analysis.

Accurate identification of replication origins (ORIs) is crucial for a comprehensive investigation into the progression of human cell growth and cancer therapy. Here, we proposed a computational approach Ori-FinderH, which can efficiently and precisely predict the human ORIs of various lengths by combining the Z-curve method with deep learning approach. Compared with existing methods, Ori-FinderH exhibits superior performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.9616 for K562 cell line in 10-fold cross-validation. In addition, we also established a cross-cell-line predictive model, which yielded a further improved AUC of 0.9706. The model was subsequently employed as a fitness function to support genetic algorithm for generating artificial ORIs. Sequence analysis through iORI-Euk revealed that a vast majority of the created sequences, specifically 98% or more, incorporate at least one ORI for three cell lines (Hela, MCF7 and K562). This innovative approach could provide more efficient, accurate and comprehensive information for experimental investigation, thereby further advancing the development of this field.

The Protective Effect of IDO1 Inhibition in Aß-Treated Neurons and APP/PS1 Mice.

Alzheimer's disease (AD) is an inflammatory associated disease, in which dysregulated kynurenine pathway (KP) plays a key role. Through KP, L-tryptophan is catabolized into neurotoxic and neuroprotective metabolites. The overactivation of indolamine 2,3-dioxygenase1 (IDO1), the first rate-limiting enzyme of KP, and the abnormal accumulation of KP metabolites have been noted in AD, and blocking IDO1 has been suggested as a therapeutic strategy. However, the expression patterns of KP enzymes in AD, and whether these enzymes are related to AD pathogenesis, have not been fully studied. Herein, we examined the expression patterns of inflammatory cytokines, neurotrophic factors and KP enzymes, and the activity of IDO1 and IDO1 effector pathway AhR (aryl hydrocarbon receptor) in AD mice. We studied the effects of IDO1 inhibitors on Aß-related neuroinflammation in rat primary neurons, mouse hippocampal neuronal cells, and APP/PS1 mice. The results further demonstrated the importance of IDO1-catalyzed KP in neuroinflammation in Alzheimer's disease.