Efficacy of Neuroendoscopy Surgery Combined With Postoperative Lokomat Rehabilitation Training in Patients With Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: To explore the effects of neuroendoscopy surgery combined with postoperative Lokomat rehabilitation training on patients with hypertensive cerebral hemorrhage. METHODS: A total of 88 patients with hypertensive cerebral hemorrhage who underwent surgical treatment in our hospital were retrospectively analyzed. They were divided into a study group and a conventional group with 44 patients in each group. The patients in the 2 groups were compared regarding operation-related conditions, hospital stay, preoperative and postoperative functional status scores, and postoperative complications. RESULTS: The operation time, intraoperative blood loss, hospital stays, and hematoma clearance rate of the study group were significantly better than those of the conventional group (P<0.001). Regarding scores of related functional status, there was no significant difference between the 2 groups before operation (P>0.05). The different scores of the study group were significantly better than those of the conventional group 1 month after the operation (P<0.05). Regarding complications, the study group also has significant advantages, with only one case of rebleeding. CONCLUSION: Compared to the traditional approach of small bone window craniotomy followed by postoperative Lokomat rehabilitation training, the combination of neuroendoscopy surgery and Lokomat training proves to be more efficient. This approach can effectively reduce the operating time and hospital stay of patients with hypertensive intracerebral hemorrhage, minimize intraoperative blood loss, improve the hematoma clearance rate, and lower the incidence of postoperative complications.

Global burden of stroke in adolescents and young adults (aged 15-39 years) from 1990 to 2019: a comprehensive trend analysis based on the global burden of disease study 2019.

INTRODUCTION: The incidence of stroke is rising among individuals aged 15-39. Insufficient research targeting this age group hampers the development of effective strategies. This study analyzes data from the Global Burden of Disease Study 2019 (GBD 2019) to examine trends from 1990 to 2019 and propose future interventions. METHODS: Data on ischemic strokes, intracerebral hemorrhage, and subarachnoid hemorrhage from 1990 to 2019 was collected from the Global Health Data Exchange (GHDx) platform. We used the Annual Average Percentage Change (AAPC) to assess global trends in incidence, prevalence, Disability-Adjusted Life Years (DALYs), and mortality rates across various stroke categories. Joinpoint models identified significant years of trend inflection. Trend analyses were segmented by age, gender, and Sociodemographic Index (SDI). FINDINGS: From 1990 to 2019, the global incidence of ischemic stroke within the adolescents and young adults (AYAs) cohort declined from 1990 to 1999, further decreased from 2000 to 2009, and then increased from 2010 to 2019. The overall AAPC p-value showed no significant difference. Mortality rates for ischemic strokes were consistently reduced during this period. The overall incidence rate of intracerebral hemorrhage has exhibited a downward trend. Meanwhile, the incidence rate of subarachnoid hemorrhage decreased from 1990 to 2009, yet saw a resurgence from 2010 to 2019. Male ischemic stroke incidence grew more than female incidence, but both absolute incidence and rates were higher for females. Differences in SDI levels were observed, with the fastest increase in incidence occurring in low-middle SDI regions, followed by high SDI regions, and the smallest increase in low SDI regions. Conversely, the most rapid decline was noted in high-middle SDI regions, with no significant change observed in middle SDI regions. CONCLUSION: A concerning trend of increasing ischemic stroke incidence, DALYs, and prevalence rates has emerged in the global 15-39 age group, especially among those aged 30-39. This increase is evident across regions with varying SDI classifications. To combat this alarming trend among adolescents and young adults, enhancing preventive efforts, promoting healthier lifestyles, strengthening the healthcare system's responsiveness, and maintaining vigilant epidemiological monitoring is essential.

Single-Molecule Assessment of DNA Hybridization Kinetics on Dye-Loaded DNA Nanostructures.

DNA nanostructures offer a versatile platform for precise dye assembly, making them promising templates for creating photonic complexes with applications in photonics and bioimaging. However, despite these advancements, the effect of dye loading on the hybridization kinetics of single-stranded DNA protruding from DNA nanostructures remains unexplored. In this study, the DNA points accumulation for imaging in the nanoscale topography (DNA-PAINT) technique is employed to investigate the accessibility of functional binding sites on DNA-templated excitonic wires. The results indicate that positively charged dyes on DNA frameworks can accelerate the hybridization kinetics of protruded ssDNA through long-range electrostatic interactions. Furthermore, the impacts of various charged dyes and binding sites are explored on diverse DNA frameworks with varying cross-sizes. The research underscores the crucial role of electrostatic interactions in DNA hybridization kinetics within DNA-dye complexes, offering valuable insights for the functionalization and assembly of biomimetic photonic systems.

Deep learning-based magnetic resonance imaging analysis for chronic cerebral hypoperfusion risk.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a frequently encountered clinical condition that poses a diagnostic challenge due to its nonspecific symptoms. PURPOSE: To enhance the diagnosis of CCH and non-CCH through Magnetic Resonance Imaging (MRI), offering support in clinical decision-making and recommendations to ultimately elevate diagnostic accuracy and optimize patient treatment outcomes. METHODS: In the retrospective research, we collected 204 routine brain magnetic resonance imaging (MRI) from March 1 to September 10 2022, as training and testing cohorts. And a validation cohort with 108 samples was collected from November 14 2022 to August 4 2023. MRI sequences were processed to obtain T1-weighted (T1WI) and T2-weighted (T2WI) sequence images for each patient. We propose CCH-Network (CCHNet), an end-to-end deep learning model, integrating convolution and Transformer modules to capture local and global structural information. Our novel adversarial training method improves feature knowledge capture, enhancing both generalization ability and efficiency in predicting CCH risk. We assessed the classification performance of the proposed model CCHNet by comparing it with existing state-of-the-art deep learning algorithms, including ResNet34, DenseNet121, VGG16, Convnext, ViT, Coat, and TransFG. To better validate model performance, we compared the results of the proposed model with eight neurologists to evaluate their consistency. RESULTS: CCHNet achieved an AUC of 91.6% (95% CI: 86.8-99.1), with an accuracy (ACC) of 85.0% (95% CI: 75.6-95.2). It demonstrated a sensitivity (SE) of 80.0% (95% CI: 71.6-95.6) and a specificity (SP) of 90.0% (95% CI: 82.3-97.8) in the testing cohort. In the validation cohort, the model demonstrated an AUC of 86.0% (95% CI: 80.3-93.0), an ACC of 84.2% (95% CI: 70.2-93.6), a SE of 83.3% (95% CI: 68.3-95.5), and a SP of 84.7% (95% CI: 70.3-96.8). CONCLUSIONS: The model improved the diagnostic performance of MRI with high SE and SP, providing a promising method for the diagnosis of CCH.

Disruption of Zfh3 abolishes mulberry-specific monophagy in silkworm larvae.

Feeding behavior is critical for insect survival and fitness. Most researchers have explored the molecular basis of feeding behaviors by identifying and elucidating the function of olfactory receptors (ORs) and gustatory receptors (GRs). Other types of genes, such as transcription factors, have rarely been investigated, and little is known about their potential roles. The silkworm (Bombyx mori) is a well-studied monophagic insect which primarily feeds on mulberry leaves, but the genetic basis of its monophagy is still not understood. In this report, we focused on a transcription factor encoded by the Zfh3 gene, which is highly expressed in the silkworm central and peripheral nervous systems, including brain, antenna, and maxilla. To investigate its function, Zfh3 was abrogated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) mutagenesis. Since Zfh3 knockout homozygotes are not viable, we studied feeding behavior in heterozygotes, and found that disruption of Zfh3 affects both gustation and olfaction. Mutant larvae lose preference for mulberry leaves, acquire the ability to consume an expanded range of diets, and exhibit improved adaptation to the M0 artificial diet, which contains no mulberry leaves. These results provide the first demonstration that a transcription factor modulates feeding behaviors in an insect.

High-Voltage Na0.76Ni0.25-x/2Mgx/2Mn0.75O2-xFx Cathode Improved by One-Step In Situ MgF2 Doping with Superior Low-Temperature Performance and Extra-Stable Air Stability.

P2-NaxMnO2 has garnered significant attention due to its favorable Na+ conductivity and structural stability for large-scale energy storage fields. However, achieving a balance between high energy density and extended cycling stability remains a challenge due to the Jahn-Teller distortion of Mn3+ and anionic activity above 4.1 V. Herein, we propose a one-step in situ MgF2 strategy to synthesize a P2-Na0.76Ni0.225Mg0.025Mn0.75O1.95F0.05 cathode with improved Na-storage performance and decent water/air stability. By partially substituting cost-effective Mg for Ni and incorporating extra F for O, the optimized material demonstrates both enhanced capacity and structure stability via promoting Ni2+/Ni4+ and oxygen redox activity. It delivers a high capacity of 132.9 mA h g-1 with an elevated working potential of ≈3.48 V and maintains ≈83.0% capacity retention after 150 cycles at 100 mA g-1 within 2-4.3 V, compared to the 114.9 mA h g-1 capacity and 3.32 V discharging potential of the undoped Na0.76Ni0.25Mn0.75O2. While increasing the charging voltage to 4.5 V, 133.1 mA h g-1 capacity and 3.55 V discharging potential (vs Na/Na+) were achieved with 72.8% capacity retention after 100 cycles, far beyond that of the pristine sample (123.7 mA h g-1, 3.45 V, and 43.8%@100 cycles). Moreover, exceptional low-temperature cycling stability is achieved, with 95.0% after 150 cycles. Finally, the Na-storage mechanism of samples employing various doping strategies was investigated using in situ EIS, in situ XRD, and ex situ XPS techniques.

Repression of YEATS2 induces cellular senescence in hepatocellular carcinoma and inhibits tumor growth.

Hepatocellular carcinoma (HCC) stands as the third leading cause of cancer-related fatalities globally. In this study, we observed a significant increase in the expression level of the YEATS2 gene in HCC patients, and it is negatively correlated with the patients' survival rate. While we have previously identified the association between YEATS2 and the survival of pancreatic cancer cells, the regulatory mechanisms and significance in HCC are still to be fully elucidated. Our study shows that knockdown (KD) of YEATS2 expression leads to DNA damage, which in turn results in an upregulation of γ-H2A.X expression and activation of the canonical senescence-related pathway p53/p21Cip1. Moreover, our transcriptomic analysis reveals that YEATS2 KD cells can enhance the expression of p21Cip1 via the c-Myc/miR-93-5p pathway, consequently fostering the senescence of HCC cells. The initiation of cellular senescence through dual-channel activation suggests that YEATS2 plays a pivotal regulatory role in the process of cell proliferation. Ultimately, our in vivo research utilizing a nude mouse tumor model revealed a notable decrease in both tumor volume and weight after the suppression of YEATS2 expression. This phenomenon is likely attributable to the attenuation of proliferative cell activity, coupled with a concurrent augmentation in the population of natural killer (NK) cells. In summary, our research results have supplemented the understanding of the regulatory mechanisms of HCC cell proliferation and indicated that targeting YEATS2 may potentially inhibit liver tumor growth.

The short-term outcome of intracranial stenosis with distal thrombosis treated with balloon-assisted tracking.

Background and purposes: Treating intracranial stenosis with distal thrombosis (IS&DT) using traditional mechanical thrombectomy (MT) techniques has proven challenging. This study aimed to summarize the experience of utilizing the balloon-assisted tracking (BAT) technique for IS&DT. Methods: Demographic and morphologic characteristics of patients with IS&DT were collected for this study. The BAT technique, involving a half-deflated balloon outside the intermediate catheter tip, was used in all patients to navigate through the proximal stenosis. Various parameters were recorded, including the sequence of vascular reperfusion, the puncture-to-reperfusion time (PRT), the residual stenosis rate, and the occurrence of re-occlusion. The thrombolysis in cerebral infarction (TICI) scale was used to assess the reperfusion of intracranial vessels, with a TICI score of ≥2b considered as successful perfusion. The clinical status of patients was evaluated at three time points: pre-procedure, post-procedure, and at discharge using the modified Rankin score (mRS). Results: In this study, a total of 10 patients were diagnosed with IS&DT, consisting of 9 male patients (90.0%) and 1 female patient (10.0%). The patients' mean age was 63.10 years (ranging from 29 to 79 years). The mean National Institute of Health Stroke Scale (NIHSS) score before treatment was 24.3 (ranging from 12 to 40), indicating the severity of their condition. Following the procedure, all patients achieved successful reperfusion with a thrombolysis in cerebral infarction (TICI) score of ≥2b. The average puncture-to-reperfusion time (PRT) was 51.8 min (ranging from 25 to 100 min), indicating the time taken for the procedure. During the perioperative period, three patients (30.0%) experienced complications. One patient had hemorrhage, while two patients had contrast extravasation. Among these cases, only the patient with hemorrhage (10%) suffered from a permanent neurological function deficit. At discharge, the patient's condition showed improvement. The mean NIHSS score decreased to 13.2 (ranging from 1 to 34), indicating a positive response to treatment. The mean mRS score at discharge was 3.2 (ranging from 1 to 5), showing some level of functional improvement. Conclusion: In conclusion, the use of the balloon-assisted tracking (BAT) technique for treating intracranial stenosis with distal thrombosis (IS&DT) showed promising results. However, a moderate rate of perioperative complications was observed, warranting further investigation and refinement of the procedure.

MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence.

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.

iTTCA-MVL: A multi-view learning model based on physicochemical information and sequence statistical information for tumor T cell antigens identification.

Immunotherapy is an emerging treatment method aimed at activating the human immune system and relying on its own immune function to kill cancer cells and tumor tissues. It has the advantages of wide applicability and minimal side effects. Effective identification of tumor T cell antigens (TTCAs) will help researchers understand their functions and mechanisms and carry out research on anti-tumor vaccine development. Considering that using biological experimental technology to identify TTCAs can be costly and time-consuming, it is necessary to develop a robust bioinformatics computing tool. At present, different machine learning models have been proposed for identifying TTCAs, but there is still room for further improvement in their performance. To establish a TTCA predictor with better prediction performance, we propose a prediction model called iTTCA-MVL in this paper. We extracted three sets of features from the views of physicochemical information and sequence statistics, namely the distribution descriptor of composition, transition, and distribution (CTDD), TF-IDF, and LSA topic. Then, we used least squares support vector machines (LSSVMs) as submodels and Hilbert‒Schmidt independence criteria (HSIC) as constraints to establish an independent and complementary multi-view learning model. The prediction accuracy of iTTCA-MVL on the independent test set is 0.873, and Matthew's correlation coefficient is 0.747, which is significantly better than those of existing methods. Therefore, iTTCA-MVL is an excellent prediction tool that researchers can use to accurately identify TTCAs.

Enabling High-Performance Layered Li-Rich Oxide Cathodes by Regulating the Formation of Integrated Cation-Disordered Domains.

Layered Li-rich oxide cathode materials are capable of offering high energy density due to their cumulative cationic and anionic redox mechanism during (de)lithiation process. However, the structural instability of the layered Li-rich oxide cathode materials, especially in the deeply delitiated state, results in severe capacity and voltage degradation. Considering the minimal isotropic structural evolution of disordered rock salt oxide cathode during cycling, cation-disordered nano-domains have been controllably introduced into layered Li-rich oxides by co-doping of d0-TM and alkali ions. Combining electrochemical and synchrotron-based advanced characterizations, the incorporation of the phase-compatible cation-disordered domains can not only hinder the oxygen framework collapse along the c axis of layered Li-rich cathode under high operation voltage but also promote the Mn and anionic activities as well as Li+ (de)intercalation kinetics, leading to remarkable improvement in rate capability and mitigation of capacity and voltage decay. With this unique layered/rocksalt intergrown structure, the intergrown cathode yields an ultrahigh capacity of 288.4 mAh g-1 at 0.1 C, and outstanding capacity retention of ≈90.0% with obviously suppressed voltage decay after 100 cycles at 0.5, 1, and 2 C rate. This work provides a new direction toward advanced cathode materials for next-generation Li-ion batteries.

Inhibition of TAF1B impairs ribosome biosynthesis and suppresses cell proliferation in stomach adenocarcinoma through promoting c-MYC mRNA degradation.

Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B, a major component of selectivity factor 1 (SL1), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B, in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.

Analysis of Effect of Minimally Invasive Fourth-ventricle Hematoma Removal for Patients with Intraventricular Hemorrhage Casting and Influence of Feedback Early Rehabilitation on Postoperative Neurological Function.

Purpose: To investigate the therapy effect of minimally invasive fourth-ventricle hematoma removal (MIFHR) for patients with intraventricular hemorrhage (IVH) casting and the influence of feedback early rehabilitation on post-operative neurological function. Methods: Eighty patients with IVH casting were enrolled from January 2019 to December 2020 in this retrospective study. Forty patients receiving MIFHR with feedback early rehabilitation were divided into the observational group, while the others receiving bilateral external ventricular drainage with traditional rehabilitation were divided into the control group. Glasgow Coma Scale (GCS) and neurological function before and after operation were compared between the two groups. In addition, hematoma clearance rate three days after surgery, drainage duration, hospitalization time, motor function and activity daily living (ADL) six months after surgery, and incidence of complications were also compared. Results: No significant differences were observed in GCS score and neurological function before surgery between the two groups (both P > .05). At the same time, there were significant differences GCS score and neurological function after surgery (both P < .05). Hematoma clearance rate three days after surgery, drainage duration, hospitalization time, and incidence of complications in the observational group were lower than those in the control group (all P < .05). In contrast, motor function and ADL six months after surgery were better in the observational group (both P < .05). Conclusion: MIFHR combined with feedback early rehabilitation is conducive to the recovery of neurological function, motor function, and ADL without increasing the incidence of complications.

Novel Low-Strain Layered/Rocksalt Intergrown Cathode for High-Energy Li-Ion Batteries.

Both layered- and rocksalt-type Li-rich cathode materials are drawing great attention due to their enormous capacity, while the individual phases have their own drawbacks, such as great volume change for the layered phase and low electronic and ionic conductivities for the rocksalt phase. Previously, we have reported the layered/rocksalt intergrown cathodes with nearly zero-strain operation, while the use of precious elements hinders their industrial applications. Herein, low-cost 3d Mn4+ ions are utilized to partially replace the expensive Ru5+ ions, to develop novel ternary Li-rich cathode material Li1+x[RuMnNi]1-xO2. The as-designed Li1.15Ru0.25Mn0.2Ni0.4O2 is revealed to have a layered/rock salt intergrown structure by neutron diffraction and transmission electron microscopy. The as-designed cathode exhibits ultrahigh lithium-ion reversibility, with 0.86 (231.1 mAh g-1) out of a total Li+ inventory of 1.15 (309.1 mAh g-1). The X-ray absorption spectroscopy and resonant inelastic X-ray scattering spectra further demonstrate that the high Li+ storage of the intergrown cathode is enabled by leveraging cationic and anionic redox activities in charge compensation. Surprisingly, in situ X-ray diffraction shows that the intergrown cathode undergoes extremely low-strain structural evolution during the charge-discharge process. Finally, the Mn content in the intergrown cathodes is found to be tunable, providing new insights into the design of advanced cathode materials for high-energy Li-ion batteries.

Self-adaption and texture generation: A hybrid loss function for low-dose CT denoising.

BACKGROUND: Deep learning has been successfully applied to low-dose CT (LDCT) denoising. But the training of the model is very dependent on an appropriate loss function. Existing denoising models often use per-pixel loss, including mean abs error (MAE) and mean square error (MSE). This ignores the difference in denoising difficulty between different regions of the CT images and leads to the loss of large texture information in the generated image. PURPOSE: In this paper, we propose a new hybrid loss function that adapts to the noise in different regions of CT images to balance the denoising difficulty and preserve texture details, thus acquiring CT images with high-quality diagnostic value using LDCT images, providing strong support for condition diagnosis. METHODS: We propose a hybrid loss function consisting of weighted patch loss (WPLoss) and high-frequency information loss (HFLoss). To enhance the model's denoising ability of the local areas which are difficult to denoise, we improve the MAE to obtain WPLoss. After the generated image and the target image are divided into several patches, the loss weight of each patch is adaptively and dynamically adjusted according to its loss ratio. In addition, considering that texture details are contained in the high-frequency information of the image, we use HFLoss to calculate the difference between CT images in the high-frequency information part. RESULTS: Our hybrid loss function improves the denoising performance of several models in the experiment, and obtains a higher peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). Moreover, through visual inspection of the generated results of the comparison experiment, the proposed hybrid function can effectively suppress noise and retain image details. CONCLUSIONS: We propose a hybrid loss function for LDCT image denoising, which has good interpretation properties and can improve the denoising performance of existing models. And the validation results of multiple models using different datasets show that it has good generalization ability. By using this loss function, high-quality CT images with low radiation are achieved, which can avoid the hazards caused by radiation and ensure the disease diagnosis for patients.

TAF1B depletion leads to apoptotic cell death by inducing nucleolar stress and activating p53-miR-101 circuit in hepatocellular carcinoma.

Background: TAF1B (TATA Box Binding Protein (TBP)-Associated Factor) is an RNA polymerase regulating rDNA activity, stress response, and cell cycle. However, the function of TAF1B in the progression of hepatocellular carcinoma (HCC) is unknown. Objective: In this study, we intended to characterize the crucial role and molecular mechanisms of TAF1B in modulating nucleolar stress in HCC. Methods: We analyzed the differential expression and prognostic value of TAF1B in hepatocellular carcinoma based on The Cancer Genome Atlas (TCGA) database, tumor and paraneoplastic tissue samples from clinical hepatocellular carcinoma patients, and typical hepatocellular carcinoma. We detected cell proliferation and apoptosis by lentiviral knockdown of TAF1B expression levels in HepG2 and SMMC-7721 cells using clone formation, apoptosis, and Western blotting (WB) detection of apoptosis marker proteins. Simultaneously, we investigated the influence of TAF1B knockdown on the function of the pre-initiation complex (PIC) by WB, and co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays verified the interaction between the complexes and the effect on rDNA activity. Immunofluorescence assays measured the expression of marker proteins of nucleolus stress, fluorescence in situ hybridization (FISH) assays checked the rDNA activity, and qRT-PCR assays tested the pre-rRNA levels. Regarding molecular mechanisms, we investigated the role of p53 and miR-101 in modulating nucleolar stress and apoptosis. Finally, the impact of TAF1B knockdown on tumor growth, apoptosis, and p53 expression was observed in xenograft tumors. Result: We identified that TAF1B was highly expressed in hepatocellular carcinoma and associated with poor prognosis in HCC patients. TAF1B depletion modulated nucleolar stress and apoptosis in hepatocellular carcinoma cells through positive and negative feedback from p53-miR-101. RNA polymerase I transcription repression triggered post-transcriptional activation of miR-101 in a p53-dependent manner. In turn, miR-101 negatively feeds back through direct inhibition of the p53-mediated PARP pathway. Conclusion: These findings broaden our comprehension of the function of TAF1B-mediated nucleolar stress in hepatocellular carcinoma and may offer new biomarkers for exploring prospective therapeutic targets in HCC.

Towards an Optimized Distributed Message Queue System for AIoT Edge Computing: A Reinforcement Learning Approach.

The convergence of artificial intelligence and the Internet of Things (IoT) has made remarkable strides in the realm of industry. In the context of AIoT edge computing, where IoT devices collect data from diverse sources and send them for real-time processing at edge servers, existing message queue systems face challenges in adapting to changing system conditions, such as fluctuations in the number of devices, message size, and frequency. This necessitates the development of an approach that can effectively decouple message processing and handle workload variations in the AIoT computing environment. This study presents a distributed message system for AIoT edge computing, specifically designed to address the challenges associated with message ordering in such environments. The system incorporates a novel partition selection algorithm (PSA) to ensure message order, balance the load among broker clusters, and enhance the availability of subscribable messages from AIoT edge devices. Furthermore, this study proposes the distributed message system configuration optimization algorithm (DMSCO), based on DDPG, to optimize the performance of the distributed message system. Experimental evaluations demonstrate that, compared to the genetic algorithm and random searching, the DMSCO algorithm can provide a significant improvement in system throughput to meet the specific demands of high-concurrency AIoT edge computing applications.

Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Self-supervised contrastive learning using CT images for PD-1/PD-L1 expression prediction in hepatocellular carcinoma.

Background and purpose: Programmed cell death protein-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) expression status, determined by immunohistochemistry (IHC) of specimens, can discriminate patients with hepatocellular carcinoma (HCC) who can derive the most benefits from immune checkpoint inhibitor (ICI) therapy. A non-invasive method of measuring PD-1/PD-L1 expression is urgently needed for clinical decision support. Materials and methods: We included a cohort of 87 patients with HCC from the West China Hospital and analyzed 3094 CT images to develop and validate our prediction model. We propose a novel deep learning-based predictor, Contrastive Learning Network (CLNet), which is trained with self-supervised contrastive learning to better extract deep representations of computed tomography (CT) images for the prediction of PD-1 and PD-L1 expression. Results: Our results show that CLNet exhibited an AUC of 86.56% for PD-1 expression and an AUC of 83.93% for PD-L1 expression, outperforming other deep learning and machine learning models. Conclusions: We demonstrated that a non-invasive deep learning-based model trained with self-supervised contrastive learning could accurately predict the PD-1 and PD-L1 expression status, and might assist the precision treatment of patients withHCC, in particular the use of immune checkpoint inhibitors.

The use of modified TI-RADS using contrast-enhanced ultrasound features for classification purposes in the differential diagnosis of benign and malignant thyroid nodules: A prospective and multi-center study.

Objectives: To evaluate the diagnostic efficacy of a modified thyroid imaging reporting and data system (TI-RADS) in combination with contrast-enhanced ultrasound (CEUS) for differentiating between benign and malignant thyroid nodules and to assess inter-observer concordance between different observers. Methods: This study included 3353 patients who underwent thyroid ultrasound (US) and CEUS in ten multi-centers between September 2018 and March 2020. Based on a modified TI-RADS classification using the CEUS enhancement pattern of thyroid lesions, ten radiologists analyzed all US and CEUS examinations independently and assigned a TI-RADS category to each thyroid nodule. Pathology was the reference standard for determining the diagnostic performance (accuracy (ACC), sensitivity (SEN), specificity (SPN), positive predictive value (PPV), and negative predictive value (NPV)) of the modified TI-RADS for predicting malignant thyroid nodules. The risk of malignancy was stratified for each TI-RADS category-based on the total number of benign and malignant lesions in that category. ROC curve was used to determine the cut-off value and the area under the curve (AUC). Cohen's Kappa statistic was applied to assess the inter-observer agreement of each sonological feature and TI-RADS category for thyroid nodules. Results: The calculated malignancy risk in the modified TI-RADS categories 5, 4b, 4a, 3 and 2 nodules was 95.4%, 86.0%, 12.0%, 4.1% and 0%, respectively. The malignancy risk for the five categories was in agreement with the suggested malignancy risk. The ROC curve showed that the AUC under the ROC curve was 0.936, and the cutoff value of the modified TI-RADS classification was >TI-RADS 4a, whose SEN, ACC, PPV, NPV and SPN were 93.6%, 91.9%, 90.4%, 93.7% and 88.5% respectively. The Kappa value for taller than wide, microcalcification, marked hypoechoic, solid composition, irregular margins and enhancement pattern of CEUS was 0.94, 0.93, 0.75, 0.89, 0.86 and 0.81, respectively. There was also good agreement between the observers with regards to the modified TI-RADS classification, the Kappa value was 0.80. Conclusions: The actual risk of malignancy according to the modified TI-RADS concurred with the suggested risk of malignancy. Inter-observer agreement for the modified TI-RADS category was good, thus suggesting that this classification was very suitable for clinical application.