Individual joints involvement pattern in psoriatic arthritis: A cross-sectional study in China.

Psoriatic arthritis (PsA) is characterized by multi-joint involvement, primarily affecting the small joints in the hands and feet. However, the specific pattern of joint involvement at an individual level remains uncertain. This study aimed to elucidate the pattern of joint involvement in a PsA cohort. Patients diagnosed with PsA were recruited for this cross-sectional study. Demographic, clinical, laboratory, personal and family history, and comorbidity data were collected. Descriptive statistical analysis was performed, and univariate and multivariate regression models were used to examine baseline factors influencing joint involvement. A total of 264 PsA patients (156 males) were included in the study. The results revealed a predominant involvement of peripheral facet joints. The second proximal interphalangeal joint (PIP) of the right hand exhibited the highest prevalence of swelling (18.9%), while the right knee joint had the highest prevalence of tenderness (24.2%). Older age and earlier onset of PsA were identified as independent factors associated with the swelling of the second PIP of the right hand. Older age, earlier onset of PsA, lower Psoriasis Area and Severity Index and higher Dermatology Life Quality Index scores were identified as independent factors associated with the tenderness of the right knee joint. In conclusion, the most commonly affected joints in PsA are the second PIP of the right hand and the right knee joint.

Organ-Specific Gene Expression Control Using DNA Origami-Based Nanodevices.

Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.

Emergency department visit frequency and health care costs following implementation of an integrated practice unit for frequent utilizers.

OBJECTIVES: The integrated practice unit (IPU) aims to improve care for patients with complex medical and social needs through care coordination, medication reconciliation, and connection to community resources. This study examined the effects of IPU enrollment on emergency department (ED) utilization and health care costs among frequent ED utilizers with complex needs. METHODS: We extracted electronic health records (EHR) data from patients in a large health care system who had at least four distinct ED visits within any 6-month period between March 1, 2018, and May 30, 2021. Interrupted time series (ITS) analyses were performed to evaluate the impact of IPU enrollment on monthly ED visits and health care costs. A control group was matched to IPU patients using a propensity score at a 3:1 ratio. RESULTS: We analyzed EHRs of 775 IPU patients with a control group of 2325 patients (mean [±SD] age 43.6 [±17]; 45.8% female; 50.9% White, 42.3% Black). In the single ITS analysis, IPU enrollment was associated with a decrease of 0.24 ED visits (p < 0.001) and a cost reduction of $466.37 (p = 0.040) in the first month, followed by decreases of 0.11 ED visits (p < 0.001) and $417.61 in costs (p < 0.001) each month over the subsequent year. Our main results showed that, compared to the matched control group, IPU patients experienced 0.20 more ED visits (p < 0.001) after their fourth ED visit within 6 months, offset by a reduction of 0.02 visits (p < 0.001) each month over the next year. No significant immediate or sustained increase in costs was observed for IPU-enrolled patients compared to the control group. CONCLUSIONS: This quasi-experimental study of frequent ED utilizers demonstrated an initial increase in ED visits following IPU enrollment, followed by a reduction in ED utilization over subsequent 12 months without increasing costs, supporting IPU's effectiveness in managing patients with complex needs and limited access to care.

Methyltransferase like-14 suppresses growth and metastasis of non-small-cell lung cancer by decreasing LINC02747.

Multiple epigenetic regulatory mechanisms exert critical roles in tumor development, and understanding the interactions and impact of diverse epigenetic modifications on gene expression in cancer is crucial for the development of precision medicine. We found that methyltransferase-like 14 (METTL14) was significantly downregulated in non-small-cell lung cancer (NSCLC) tissues. Functional experiments demonstrated that overexpression of METTL14 inhibited the proliferation and migration of NSCLC cells both in vivo and in vitro, and the colorimetric m6A quantification assay also showed that knockdown of METTL14 notably reduced global m6A modification levels in NSCLC cells. By using the methylated-RNA immunoprecipitation-qPCR and dual-luciferase reporter assays, we verified that long noncoding RNA LINC02747 was a target of METTL14 and was regulated by METTL14-mediated m6A modification, and silencing LINC02747 inhibited the malignant progression of NSCLC by modulating the PI3K/Akt and CDK4/Cyclin D1 signaling pathway. Further studies revealed that overexpression of METTL14 promoted m6A methylation and accelerated the decay of LINC02747 mRNA via increased recognition of the "GAACU" binding site by YTHDC2. Additionally, histone demethylase lysine-specific histone demethylase 5B (KDM5B) mediated the demethylation of histone H3 lysine 4 tri-methylation (H3K4me3) in the METTL14 promoter region and repressed its transcription. In summary, KDM5B downregulated METTL14 expression at the transcriptional level in a H3K4me3-dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer.

Demonstration of 4H-silicon carbide on an aluminum nitride integrated photonic platform.

The existing silicon-carbide-on-insulator photonic platform utilizes a thin layer of silicon dioxide under silicon carbide (SiC) to provide optical confinement and mode isolation. Here, we replace the underneath silicon dioxide layer with 1-µm-thick aluminum nitride and demonstrate a 4H-silicon-carbide-on-aluminum-nitride integrated photonic platform for the first time to our knowledge. Efficient grating couplers, low-loss waveguides, and compact microring resonators with intrinsic quality factors up to 210,000 are fabricated. In addition, by undercutting the aluminum nitride layer, the intrinsic quality factor of the silicon carbide microring is improved by nearly one order of magnitude (1.8 million). Finally, an optical pump-probe method is developed to measure the thermal conductivity of the aluminum nitride layer, which is estimated to be over 30 times of that of silicon dioxide.

A multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma.

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.

Bone morphogenetic protein 4 derived from the cerebrospinal fluid in patients with postherpetic neuralgia induces allodynia via the crosstalk between microglia and astrocyte.

INTRODUCTION: During postherpetic neuralgia (PHN), the cerebral spinal fluid (CSF) possesses the capability to trigger glial activation and inflammation, yet the specific changes in its composition remain unclear. Recent findings from our research indicate elevations of central bone morphogenetic protein 4 (BMP4) during neuropathic pain (NP), serving as an independent modulator of glial cells. Herein, the aim of the present study is to test the CSF-BMP4 expressions and its role in the glial modulation in the process of PHN. METHODS: CSF samples were collected from both PHN patients and non-painful individuals (Control) to assess BMP4 and its antagonist Noggin levels. Besides, intrathecal administration of both CSF types was conducted in normal rats to evaluate the impact on pain behavior, glial activity, and inflammation.; Additionally, both Noggin and STAT3 antagonist-Stattic were employed to treat the PHN-CSF or exogenous BMP4 challenged cultured astrocytes to explore downstream signals. Finally, microglial depletion was performed prior to the PHN-CSF intervention so as to elucidate the microglia-astrocyte crosstalk. RESULTS: BMP4 levels were significantly higher in PHN-CSF compared to Control-CSF (P < 0.001), with a positive correlation with pain duration (P < 0.05, r = 0.502). Comparing with the Control-CSF producing moderate paw withdrawal threshold (PWT) decline and microglial activation, PHN-CSF further exacerbated allodynia and triggered both microglial and astrocytic activation (P < 0.05). Moreover, PHN-CSF rather than Control-CSF evoked microglial proliferation and pro-inflammatory transformation, reinforced iron storage, and activated astrocytes possibly through both SMAD159 and STAT3 signaling, which were all mitigated by the Noggin application (P < 0.05). Next, both Noggin and Stattic effectively attenuated BMP4-induced GFAP and IL-6 upregulation, as well as SMAD159 and STAT3 phosphorylation in the cultured astrocytes (P < 0.05). Finally, microglial depletion diminished PHN-CSF induced astrogliosis, inflammation and endogenous BMP4 expression (P < 0.05). CONCLUSION: Our study highlights the role of CSF-BMP4 elevation in glial activation and allodynia during PHN, suggesting a potential therapeutic avenue for future exploration.

Puerarin mitigated LPS-ATP or HG-primed endothelial cells damage and diabetes-associated cardiovascular disease via ROS-NLRP3 signalling.

The occurrence and development of diabetic vascular diseases are closely linked to inflammation-induced endothelial dysfunction. Puerarin (Pue), the primary component of Pueraria lobata, possesses potent anti-inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against vascular damage induced by diabetes. In the study, Pue ameliorated lipopolysaccharide-adenosine triphosphate (LPS-ATP) or HG-primed cytotoxicity and apoptosis, while inhibited reactive oxygen species (ROS)-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced by significantly decreased ROS level, NOX4, Caspase-1 activity and expression of NLRP3, GSDMD, cleaved caspase-1, IL-1ß and IL-18. Meanwhile, ROS inducer CoCI2 efficiently weakened the effects of Pue against LPS-ATP-primed pyroptosis. In addition, NLRP3 knockdown notably enhanced Pue's ability to suppress pyroptosis in LPS-ATP-primed HUVECs, whereas overexpression of NLRP3 reversed the inhibitory effects of Pue. Furthermore, Pue inhibited the expression of ROS and NLRP3 inflammasome-associated proteins on the aorta in type 2 diabetes mellitus rats. Our findings indicated that Pue might ameliorate LPS-ATP or HG-primed damage in HUVECs by inactivating the ROS-NLRP3 signalling pathway.

Costunolide ameliorates MNNG-induced chronic atrophic gastritis through inhibiting oxidative stress and DNA damage via activation of Nrf2.

BACKGROUND: Chronic atrophic gastritis (CAG) is a chronic digestive disease. Modern research has revealed substantial evidence indicating that the progression of CAG is closely linked to the occurrence of oxidative stress-induced DNA damage and apoptosis in the gastric mucosa. Additionally, research has indicated that Costunolide (COS), the primary active compound found in Aucklandiae Radix, a traditional herb, exhibits antioxidant properties. Nevertheless, the therapeutic potential of COS in treating CAG and its molecular targets have not yet been determined. PURPOSE: The objective of this research was to explore the potential gastric mucosal protective effects and mechanisms of COS against N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG)-induced CAG. METHODS: Firstly, the MNNG-induced rat CAG model was established in vivo. Occurrence of CAG was detected through macroscopic examination of the stomachs and H&E staining. Additionally, we assessed oxidative stress, DNA damage, and apoptosis using biochemical detection, Western blot, immunohistochemistry and immunofluorescence. Then, an in vitro model was developed to induce MNNG-induced damage in GES-1 cells, and the occurrence of cell damage was determined by Hoechst 33,342 staining and flow cytometry. Finally, the key targets of COS for the treatment of CAG were identified through molecular docking, cellular thermal shift assay (CETSA), and inhibitor ML385. RESULTS: In vivo studies demonstrated that COS promotes the expression of Nrf2 in gastric tissues. This led to an increased expression of SOD, GSH, HO-1, while reducing the production of MDA. Furthermore, COS inhibited DNA damage and apoptosis by suppressing the expression of γH2AX and PARP1 in gastric tissues. In vitro studies showed that COS effectively reversed apoptosis induced by MNNG in GES-1 cells. Additionally, COS interacted with Nrf2 to promote its expression. Furthermore, the expression levels of SOD, GSH, and HO-1 were augmented, while the generation of ROS and MDA was diminished. CONCLUSIONS: Our results indicate that COS exhibits therapeutic effects on CAG through the promotion of Nrf2 expression and inhibition of oxidative stress and DNA damage. Therefore, COS has the potential to provide new drugs for the treatment of CAG.

Automatic Lenke classification of adolescent idiopathic scoliosis with deep learning.

Purpose: The Lenke classification system is widely utilized as the preoperative evaluation protocol for adolescent idiopathic scoliosis (AIS). However, manual measurement is susceptible to observer-induced variability, which consequently impacts the evaluation of progression. The goal of this investigation was to develop an automated Lenke classification system utilizing innovative deep learning algorithms. Methods: Using the database from the First Affiliated Hospital of Sun Yat-sen University, the whole spinal x-rays images were retrospectively collected. Specifically, images collection was divided into AIS and control group. The control group consisted of individuals who underwent routine health checks and did not have scoliosis. Afterwards, relative features of all images were annotated. Deep learning was implemented through the utilization of the key-point based detection method to realize the vertebral detection, and Cobb angle measurement and scoliosis classification were performed based on relevant standards. Besides, the segmentation method was employed to achieve the recognition of lumbar vertebral pedicle to determine the type of lumbar spine modifier. Finally, the model performance was further quantitatively analyzed. Results: In the study, a total of 2082 spinal x-ray images were collected from 407 AIS patients and 227 individuals in the control group. The model for vertebral detection achieved an F1-score of 0.809 for curve type evaluation and an F1-score of 0.901 for thoracic sagittal profile. The intraclass correlation efficient (ICC) of the Cobb angle measurement was 0.925. In the analysis of performance for vertebra pedicle segmentation model, the F1-score of lumbar modification profile was 0.942, the intersection over union (IOU) of the target pixels was 0.827, and the Hausdorff distance (HD) was 6.565 ± 2.583 mm. Specifically, the F1-score for ultimate Lenke type classifier was 0.885. Conclusions: This study has constructed an automated Lenke classification system by employing the deep learning networks to achieve the recognition pattern and feature extraction. Our models require further validation in additional cases in the future.

Entangled photon pair generation in an integrated SiC platform.

Entanglement plays a vital role in quantum information processing. Owing to its unique material properties, silicon carbide recently emerged as a promising candidate for the scalable implementation of advanced quantum information processing capabilities. To date, however, only entanglement of nuclear spins has been reported in silicon carbide, while an entangled photon source, whether it is based on bulk or chip-scale technologies, has remained elusive. Here, we report the demonstration of an entangled photon source in an integrated silicon carbide platform for the first time. Specifically, strongly correlated photon pairs are efficiently generated at the telecom C-band wavelength through implementing spontaneous four-wave mixing in a compact microring resonator in the 4H-silicon-carbide-on-insulator platform. The maximum coincidence-to-accidental ratio exceeds 600 at a pump power of 0.17 mW, corresponding to a pair generation rate of (9 ± 1) × 103 pairs/s. Energy-time entanglement is created and verified for such signal-idler photon pairs, with the two-photon interference fringes exhibiting a visibility larger than 99%. The heralded single-photon properties are also measured, with the heralded g(2)(0) on the order of 10-3, demonstrating the SiC platform as a prospective fully integrated, complementary metal-oxide-semiconductor compatible single-photon source for quantum applications.

Disparities in the prevalence of suicidal ideation according to oral contraceptive pill use among US women: A cross-sectional study.

Background and Aims: The relationship between oral contraceptive pill (OCP) and suicidal ideation remains unclear. This study aims to estimate the prevalence of suicidal ideation among US women and evaluate their associates overall and according to OCP use status. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2012 were used to calculate the prevalence and associates of suicidal ideation in women using OCP. Suicidal ideation was assessed using the Patient Health Questionnaire-9. Overall and OCP-specific weighted prevalence of suicidal ideation were estimated. Multivariable logistic regressions were used to investigate overall and OCP-specific associates. Results: The prevalence of suicidal ideation was 3.6% with no evident disparity between OCP groups, suggesting that OCP use is not associated with increased prevalence of suicidal ideation. Smoking was inversely associated with suicidal ideation in the former users of OCP. In the overall population, the prevalence of suicidal ideation was greater in those who were: Black or Hispanic, smoking, taking antidepressants, those with lower educational attainment, and women with low and middle income. Conclusion: Our findings suggest that OCP use was not associated with increased prevalence of suicidal ideation. Unique associates were identified among different OCP groups.

Association of food insecurity with overall and disease-specific mortality among cancer survivors in the US.

PURPOSE: To investigate the association of food insecurity with overall and disease-specific mortality among US cancer survivors. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were used to examine the impact of food insecurity on mortality risks among cancer survivors in the US. Study participants aged ≥ 20 years who had a history of cancer and completed the Adult Food Security Survey Module were included. Mortality data [all-cause, cancer, and cardiovascular (CVD) specific] through December 31, 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazard regression, hazard ratios of mortality based on food security status were estimated. RESULTS: Among 5032 cancer survivors (mean age 62.5 years; 58.0% women; 86.2% non-Hispanic White), 596 (8.8%) reported food insecurity. Overall, 1913 deaths occurred (609 cancer deaths and 420 CVD deaths) during the median follow-up of 6.8 years. After adjusting for age, food insecurity was associated with a higher risk of overall (HR = 1.93; 95% CI = 1.56-2.39), CVD-specific (HR = 1.95; 95% CI = 1.24-3.05), and cancer-specific (HR = 1.70; 95% CI = 1.20-2.42) mortality (P < 0.001). However, after adjusting for socioeconomic characteristics and health-related factors (physical activity, diet quality measured by healthy eating index), the association between food insecurity and overall mortality was no longer statistically significant. CONCLUSIONS: Food insecurity was associated with a greater risk of overall mortality among cancer survivors. Further studies are needed to confirm these findings and evaluate whether the observed association represents a causal phenomenon and, if so, whether the effect is modifiable with food assistance programs.

The association of islet autoantibodies with the neural retinal thickness and microcirculation in type 1 diabetes mellitus with no clinical evidence of diabetic retinopathy.

OBJECTIVE: To examine the association between islet autoantibodies (IAbs) and the retinal neurovascular changes in type 1 diabetes mellitus (T1DM) with no diabetic retinopathy (NDR). METHODS: This cross-sectional study measured the neural retinal structure and microvascular density of 118 NDR eyes using spectral-domain optical coherence tomography angiography. Retinal structure parameters included retinal thickness (RT), inner retinal thickness (iRT), retina never fibral layer thickness (RNFL thickness), ganglion cell complex thickness (GCC thickness), and loss volume of GCC. Microvascular parameters included vessel density of superficial capillary plexus (sVD), vessel density of deep capillary plexus, and vessel density of choroid capillary plexus. Comparison and correlation analyses of these OCTA parameters were made with various IAbs, including glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase-related islet antigen 2 antibody (IA2A), and zinc transporter 8 antibody (ZnT8A). A general linear model was used to understand the association of IAbs with the retina parameters. RESULTS: The IAb positive (IAbs +) group, which included 85 patients, had thinner RT (235.20 ± 18.10 mm vs. 244.40 ± 19.90 mm at fovea, P = 0.021) and thinner iRT (120.10 ± 9.00 mm vs. 124.70 ± 6.90 mm at parafovea, P = 0.015), compared with the IAb negative (IAbs-) group comprising 33 patients. Furthermore, a more severe reduction of RT was demonstrated in the presence of multiple IAbs. Among the three IAbs, GADA was the most significant independent risk factor of all-round RT decrease (ß = -0.20 vs. -0.27 at fovea and parafovea, respectively, P < 0.05), while titers of IA2A negatively affect sVD in the parafovea (ß = -0.316, P = 0.003). CONCLUSIONS: IAbs are associated with neural retinal thinning and microcirculation reduction in T1DM patients before the clinical onset of diabetic retinopathy.

Analyst optimism, information disclosure, and stock price collapse risk: Empirical insights from China's A-share market.

This study selects stock data of listed companies in China's A-share stock market from 2011 to 2020 as research samples. Using a fixed-effects model, it examines the impact of analyst optimism on stock price collapses and the moderating effect of information disclosure quality. Simultaneously, it conducts additional research to explore the potential transmission mechanisms involved. The main findings are as follows: Firstly, a positive correlation exists between analyst optimism and the risk of stock price collapse. Secondly, improving information disclosure quality of listed companies can enhance the positive impact of analyst optimism on the risk of stock price collapses and expedite the market's adjustment of overly optimistic valuations of listed companies. Additionally, analyst optimism can increase the risk of stock price collapses by affecting institutional ownership. These findings provide theoretical support for regulatory authorities to revise and improve the "information disclosure evaluation" system, regulate the analyst industry, guide analyst behavior, and encourage listed companies to enhance internal governance and improve information disclosure practices.

Drp1-dependent mitochondrial fragmentation mediates photoreceptor abnormalities in type 1 diabetic retina.

Recent studies have highlighted that retinal neurodegeneration precedes microvascular changes in diabetic retinopathy (DR), but the specific mechanisms remain unclear. Given the pivotal role of dysfunctional mitochondria and oxidative stress in early DR, our objective was to observe mitochondria-related alterations in the neural retina of type one diabetic mellitus mice with no evidence of DR (T1DM-NDR). We aimed to identify the key mitochondrial-related proteins contributing to mitochondrial injury. Our study revealed that T1DM-NDR mice exhibited outer retina thinning, including the ellipsoid zone, inner segment, and outer segment. Additionally, there was an impaired amplitude of the b-wave in electroretinogram (ERG) and a disorganized arrangement of the photoreceptor layer. In both the retina of DM mice and high glucose (HG)-treated 661w cells, mitochondria appeared swollen and fragmented, with disrupted cristae, disorganized or shortened branches in the mitochondrial network, and decreased mitochondrial membrane potential. Among the mitochondrial-related proteins, dynamin-related protein 1 (Drp1) was upregulated, and the ratio of phosphorylated Drp1 protein at serine 616 (S616) and serine 637 (S637) sites significantly increased in the retina of DM mice. The administration of Mdivi-1 ameliorated high-glucose-induced dysfunctional mitochondria, thereby protecting T1DM-NDR mice retina from morphological and functional injuries. Our findings suggest that hyperglycemia promotes Drp1-mediated mitochondrial dysfunction, which may be a significant factor in the development of DR. The inhibition of high-glucose-induced mitochondrial fission emerges as a potential and innovative intervention strategy for preventing DR.

An interpretable deep learning model for identifying the morphological characteristics of dMMR/MSI-H gastric cancer.

Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.

Efficient Raman Lasing and Raman-Kerr Interaction in an Integrated Silicon Carbide Platform.

Implementing stimulated Raman scattering in a low-loss microresonator could lead to Raman lasing. Here, we report the demonstration of an efficient Raman laser with >50% power efficiency in an integrated silicon carbide platform for the first time. By fine-tuning the free spectral range (FSR) of 43 µm-radius silicon carbide microresonators, the Stokes resonance corresponding to the dominant Raman shift of 777 cm-1 (23.3 THz) is aligned to the center of the Raman gain spectrum, resulting in a low power threshold of 2.5 mW. The peak Raman gain coefficient is estimated to be (0.75 ± 0.15) cm/GW in the 1550 nm band, with an approximate full width at half-maximum of (120 ± 30) GHz. In addition, the microresonator is designed to exhibit normal dispersion at the pump wavelength near 1550 nm while possessing anomalous dispersion at the first Stokes near 1760 nm. At high enough input powers, a Kerr microcomb is generated by the Stokes signal acting as the secondary pump, which then mixes with the pump laser through four-wave mixing to attain a wider spectral coverage. Furthermore, cascaded Raman lasing and the occurrence of multiple Raman shifts, including 204 cm-1 (6.1 THz) and 266 cm-1 (8.0 THz) transitions, are also observed. Finally, we show that the Stokes Raman could also help broaden the spectrum in a Kerr microcomb which has anomalous dispersion at the pump wavelength. Our example of a 100 GHz-FSR microcomb has a wavelength span from 1200 to 1900 nm with 300 mW on-chip power.

Machine learning for differentiating between pancreatobiliary-type and intestinal-type periampullary carcinomas based on CT imaging and clinical findings.

PURPOSE: To develop a diagnostic model for distinguishing pancreatobiliary-type and intestinal-type periampullary adenocarcinomas using preoperative contrast-enhanced computed tomography (CT) findings combined with clinical characteristics. METHODS: This retrospective study included 140 patients with periampullary adenocarcinoma who underwent preoperative enhanced CT, including pancreaticobiliary (N = 100) and intestinal (N = 40) types. They were randomly assigned to the training or internal validation set in an 8:2 ratio. Additionally, an independent external cohort of 28 patients was enrolled. Various CT features of the periampullary region were evaluated and data from clinical and laboratory tests were collected. Five machine learning classifiers were developed to identify the histologic type of periampullary adenocarcinoma, including logistic regression, random forest, multi-layer perceptron, light gradient boosting, and eXtreme gradient boosting (XGBoost). RESULTS: All machine learning classifiers except multi-layer perceptron used achieved good performance in distinguishing pancreatobiliary-type and intestinal-type adenocarcinomas, with the area under the curve (AUC) ranging from 0.75 to 0.98. The AUC values of the XGBoost classifier in the training set, internal validation set and external validation set are 0.98, 0.89 and 0.84 respectively. The enhancement degree of tumor, the growth pattern of tumor, and carbohydrate antigen 19-9 were the most important factors in the model. CONCLUSION: Machine learning models combining CT with clinical features can serve as a noninvasive tool to differentiate the histological subtypes of periampullary adenocarcinoma, in particular using the XGBoost classifier.

Triptolide attenuates cardiac remodeling by inhibiting pyroptosis and EndMT via modulating USP14/Keap1/Nrf2 pathway.

Background: Cardiac remodeling is a common pathological feature in many cardiac diseases, characterized by cardiac hypertrophy and fibrosis. Triptolide (TP) is a natural compound derived from Tripterygium wilfordii Hook F. However, the related mechanism of it in cardiac remodeling has not been fully understood. Methods and results: Transverse aortic constriction (TAC)-induced cardiac hypertrophic mouse model and angiotensin II (Ang II)-induced cardiomyocytes hypertrophic model were performed. Firstly, the results indicate that TP can improve cardiac function, decreased cardiomyocyte surface area and fibrosis area, as well as lowered the protein expressions of brain natriuretic peptide (BNP), ß-major histocompatibility complex (ß-MHC), type I and III collagen (Col I and III). Secondly, TP suppressed cardiac pyroptosis, and decreased the levels of Interleukin-1ß (IL-1ß), Interleukin-18 (IL-18) by Enzyme-linked immunosorbent assay (ELISA), and pyroptosis-associated proteins. Furthermore, TP enhanced the expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase 1 (HO-1). Interestingly, when Nrf2 was silenced by siRNA, TP lost its properties of reducing pyroptosis and cardiac hypertrophy. In addition, in the Transforming Growth Factor ß1 (TGF-ß1)-induced primary human coronary artery endothelial cells (HCAEC) model, TP was found to inhibit the process of endothelial-to-mesenchymal transition (EndMT), characterized by the loss of endothelial-specific markers and the gain of mesenchymal markers. This was accompanied by a suppression of Slug, Snail, and Twist expression. Meanwhile, the inhibitory effect of TP on EndMT was weakened when Nrf2 was silenced by siRNA. Lastly, potential targets of TP were identified through network pharmacology analysis, and found that Ubiquitin-Specific Protease 14 (USP14) was one of them. Simultaneously, the data indicated that decrease the upregulation of USP14 and Kelch-like ECH-Associated Protein 1 (Keap1) caused by cardiac remodeling. However, Keap1 was decreased and Nrf2 was increased when USP14 was silenced. Furthermore, CoIP analysis showed that USP14 directly interacts with Keap1. Conclusion: TP can observably reduce pyroptosis and EndMT by targeting the USP14/Keap1/Nrf2 pathway, thereby significantly attenuating cardiac remodeling.