Necessity of antiviral treatment for patients with chronic hepatitis B in the grey zone based on liver pathology analysis.

OBJECTIVE: 28-55% of chronic hepatitis B (CHB) patients belong to the grey zone (GZ). By analyzing the pathological characteristics of the liver of patients in the GZ, this study clarified whether the patients in the GZ need anti-hepatitis B virus treatment. METHOD: We reviewed 324 cases of liver pathology that underwent liver biopsy between 2011 and 2022. According to the total score of inflammation G, 0-6 points are classified as mild, 7-12 points are classified as moderate, and 13-18 points are classified as severe. According to the total score of fibrosis F, 0-2 is mild, 3-4 is moderate, and 5-6 is severe. Significant histological diseases (SHD) are defined as the presence of inflammation G ≥ 6 and/or fibrosis F ≥ 2 in liver biopsy specimens. RESULT: 324 GZ patients were scored using the Ishak method, with G7-18 accounting for 9%, F3-6 accounting for 19.2%, and SHD accounting for 37%. The inflammation, fibrosis, and SHD in the HBeAg (+) group were more pronounced than those in the HBeAg (-) group. Among the GZ-A ∼ GZ-D subgroups, the highest proportion of SHD in the GZ-B group was 58.35%. CONCLUSION: More than 1/3 of the patients in GZ need anti-hepatitis B virus treatment. More than half of GZ-B patients need anti-hepatitis B virus treatment. It is very necessary to carry out rescue anti-hepatitis B virus treatment for patients in GZ as soon as possible.

Artemether ameliorates acetaminophen-induced liver injury through Nrf2 pathway.

Acetaminophen (APAP) overdose is a prevalent cause of clinical pharmacological liver injury worldwide. Artemether (ART), a first-line antimalarial drug, has demonstrated hepatoprotective activity. However, its effect on APAP-induced acute liver injury (AILI) remains unclear. In this study, we investigated whether ART can protect against AILI and examined its underlying mechanisms. In vivo, ART mitigated APAP-induced liver histological changes, including mitochondrial damage, hepatocyte necrosis, hepatocyte apoptosis, and inflammatory infiltration. Additionally, ART reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in APAP-induced mice. ART also activated the Nrf2-HO-1/GPX4 signaling pathway, exerting antioxidant effects in both in vitro and in vivo models of AILI. To confirm Nrf2 as a target of ART in vivo, we pretreated C57BL/6 mice with the Nrf2 inhibitor, ML385. The results indicated that inhibiting Nrf2 diminishes the protective effect of ART against AILI. Overall, our findings suggest that ART's protective effect against AILI is mediated through the Nrf2-related antioxidant pathway.

53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).

Break-induced replication (BIR) is mutagenic, and thus its use requires tight regulation, yet the underlying mechanisms remain elusive. Here we uncover an important role of 53BP1 in suppressing BIR after end resection at double strand breaks (DSBs), distinct from its end protection activity, providing insight into the mechanisms governing BIR regulation and DSB repair pathway selection. We demonstrate that loss of 53BP1 induces BIR-like hyperrecombination, in a manner dependent on Polα-primase-mediated end fill-in DNA synthesis on single-stranded DNA (ssDNA) overhangs at DSBs, leading to PCNA ubiquitination and PIF1 recruitment to activate BIR. On broken replication forks, where BIR is required for repairing single-ended DSBs (seDSBs), SMARCAD1 displaces 53BP1 to facilitate the localization of ubiquitinated PCNA and PIF1 to DSBs for BIR activation. Hyper BIR associated with 53BP1 deficiency manifests template switching and large deletions, underscoring another aspect of 53BP1 in suppressing genome instability. The synthetic lethal interaction between the 53BP1 and BIR pathways provides opportunities for targeted cancer treatment.

The challenges and opportunities of offering and integrating training in clinical molecular genetics and clinical cytogenetics: A survey of LGG Fellowship Program Directors.

Purpose: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model. Methods: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education-accredited LGG fellowship programs at the time. The data were collected, and the responses were aggregated for each question. Results: All of the responding PDs had started training at least 1 LGG fellow. PDs noted challenges with funding, staff shortages, molecular/cytogenetics content integration, limited total training time, increased remote work, increased sendout testing, and a lack of prior cytogenetics knowledge among incoming fellows. Conclusion: This survey attempted to assess the challenges that LGG PDs have been facing in offering and integrating clinical molecular genetics and clinical cytogenetics fellowship training. Common challenges between programs were noted, and a set of 6 concluding comments are provided to facilitate future discussion.

Energy-Oriented Hybrid Cooperative Adaptive Cruise Control for Fuel Cell Electric Vehicle Platoons.

Given the complex powertrain of fuel cell electric vehicles (FCEVs) and diversified vehicle platooning synergy constraints, a control strategy that simultaneously considers inter-vehicle synergy control and energy economy is one of the key technologies to improve transportation efficiency and release the energy-saving potential of platooning vehicles. In this paper, an energy-oriented hybrid cooperative adaptive cruise control (eHCACC) strategy is proposed for an FCEV platoon, aiming to enhance energy-saving potential while ensuring stable car-following performance. The eHCACC employs a hybrid cooperative control architecture, consisting of a top-level centralized controller (TCC) and bottom-level distributed controllers (BDCs). The TCC integrates an eco-driving CACC (eCACC) strategy based on the minimum principle and random forest, which generates optimal reference velocity datasets by aligning the comprehensive control objectives of the platoon and addressing the car-following performance and economic efficiency of the platoon. Concurrently, to further unleash energy-saving potential, the BDCs utilize the equivalent consumption minimization strategy (ECMS) to determine optimal powertrain control inputs by combining the reference datasets with detailed optimization information and system states of the powertrain components. A series of simulation evaluations highlight the improved car-following stability and energy efficiency of the FCEV platoon.

Enhancing trabecular CT scans based on deep learning with multi-strategy fusion.

Trabecular bone analysis plays a crucial role in understanding bone health and disease, with applications like osteoporosis diagnosis. This paper presents a comprehensive study on 3D trabecular computed tomography (CT) image restoration, addressing significant challenges in this domain. The research introduces a backbone model, Cascade-SwinUNETR, for single-view 3D CT image restoration. This model leverages deep layer aggregation with supervision and capabilities of Swin-Transformer to excel in feature extraction. Additionally, this study also brings DVSR3D, a dual-view restoration model, achieving good performance through deep feature fusion with attention mechanisms and Autoencoders. Furthermore, an Unsupervised Domain Adaptation (UDA) method is introduced, allowing models to adapt to input data distributions without additional labels, holding significant potential for real-world medical applications, and eliminating the need for invasive data collection procedures. The study also includes the curation of a new dual-view dataset for CT image restoration, addressing the scarcity of real human bone data in Micro-CT. Finally, the dual-view approach is validated through downstream medical bone microstructure measurements. Our contributions open several paths for trabecular bone analysis, promising improved clinical outcomes in bone health assessment and diagnosis.

Lanternarene-Based Self-Sorting Double-Network Hydrogels for Flexible Strain Sensors.

Conductive flexible hydrogels have attracted immense attentions recently due to their wide applications in wearable sensors. However, the poor mechanical properties of most conductive polymer limit their utilizations. Herein, a double network hydrogel is fabricated via a self-sorting process with cationic polyacrylamide as the first flexible network and the lantern[33]arene-based hydrogen organic framework nanofibers as the second rigid network. This hydrogel is endowed with good conductivity (0.25 S m-1) and mechanical properties, such as large Young's modulus (31.9 MPa), fracture elongation (487%) and toughness (6.97 MJ m-3). The stretchability of this hydrogel is greatly improved after the kirigami cutting, which makes it can be used as flexible strain sensor for monitoring human motions, such as bending of fingers, wrist and elbows. This study not only provides a valuable strategy for the construction of double network hydrogels by lanternarene, but also expands the application of the macrocycle hydrogels to flexible electronics.

Investigation on the Epidemic Situation of Epidemic Hemorrhagic Fever in an Island Industrial Park in Zhoushan, China.

Objective: To investigate the epidemic factors of hemorrhagic fever with renal syndrome (HFRS) and compare the S and M gene sequences of hantavirus (HV) between rodents and the infected cases. Methods: Detailed epidemiological investigations were conducted on the cases' working and living areas. Captured rodents were classified by night trapping method, and their lungs and blood were collected for virus carriage detection after aseptic dissection. Viral S and M fragments of HV RNA were amplified and sequenced from positive samples of cases and mice, and their homology was analyzed. Results: After reconstruction, the geographic and living environment changed significantly, altering rodent behaviors. The industrial park, characterized by high population density, poor living conditions, and frequent contact of rodent (feces) and humans, had a high rodent density and HV virus infection ratio. Four workers infected with HV were positive for anti-HV immunoglobulin G (IgG) and IgM. Among the positive samples, HV RNA was detected in all two cases, and four Rattus norvegicus specimens were Seoul type HV S3 subtype. The virus had the closest relationship with Rod/2012/QHD/4/Gc (Hebei, China) and RuianRn180 (Zhejiang, China), with the 100% homology of M gene segment. The homology of viral S gene segment exhibited the closest relationship with the Jiangxi isolated JiangxiXinjianRn-09-2011, ranging from 99.6% to 99.8%. Conclusion: The HV sequencing showed a strong epidemiological relationship between the cases and host rodents. Improving living environmental health conditions, administering HFRS vaccine, and reducing rodent density and human-rodent contact can mitigate the risk of HFRS.

Short-chain fatty acids: bridges between diet, gut microbiota, and health.

In recent years, gut microbiota has become a hot topic in the fields of medicine and life sciences. Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota produced by microbial fermentation of dietary fiber, play a vital role in healthy and ill hosts. SCFAs regulate the process of metabolism, immune, and inflammation and have therapeutic effects on gastrointestinal and neurological disorders, as well as antitumor properties. This review summarized the production, distribution, and molecular mechanism of SCFAs, as well as their mechanisms of action in healthy and ill hosts. In addition, we also emphasized the negative effects of SCFAs, aiming to provide the public with a more comprehensive understanding of SCFAs.

RBS and ABS Coordinated Control Strategy Based on Explicit Model Predictive Control.

During the braking process of electric vehicles, both the regenerative braking system (RBS) and anti-lock braking system (ABS) modulate the hydraulic braking force, leading to control conflict that impacts the effectiveness and real-time capability of coordinated control. Aiming to enhance the coordinated control effectiveness of RBS and ABS within the electro-hydraulic composite braking system, this paper proposes a coordinated control strategy based on explicit model predictive control (eMPC-CCS). Initially, a comprehensive braking control framework is established, combining offline adaptive control law generation, online optimized control law application, and state compensation to effectively coordinate braking force through the electro-hydraulic system. During offline processing, eMPC generates a real-time-oriented state feedback control law based on real-world micro trip segments, improving the adaptiveness of the braking strategy across different driving conditions. In the online implementation, the developed three-dimensional eMPC control laws, corresponding to current driving conditions, are invoked, thereby enhancing the potential for real-time braking strategy implementation. Moreover, the state error compensator is integrated into eMPC-CCS, yielding a state gain matrix that optimizes the vehicle braking status and ensures robustness across diverse braking conditions. Lastly, simulation evaluation and hardware-in-the-loop (HIL) testing manifest that the proposed eMPC-CCS effectively coordinates the regenerative and hydraulic braking systems, outperforming other CCSs in terms of braking energy recovery and real-time capability.

Intelligent Vehicle Path Planning Based on Optimized A* Algorithm.

With the rapid development of the intelligent driving technology, achieving accurate path planning for unmanned vehicles has become increasingly crucial. However, path planning algorithms face challenges when dealing with complex and ever-changing road conditions. In this paper, aiming at improving the accuracy and robustness of the generated path, a global programming algorithm based on optimization is proposed, while maintaining the efficiency of the traditional A* algorithm. Firstly, turning penalty function and obstacle raster coefficient are integrated into the search cost function to increase the adaptability and directionality of the search path to the map. Secondly, an efficient search strategy is proposed to solve the problem that trajectories will pass through sparse obstacles while reducing spatial complexity. Thirdly, a redundant node elimination strategy based on discrete smoothing optimization effectively reduces the total length of control points and paths, and greatly reduces the difficulty of subsequent trajectory optimization. Finally, the simulation results, based on real map rasterization, highlight the advanced performance of the path planning and the comparison among the baselines and the proposed strategy showcases that the optimized A* algorithm significantly enhances the security and rationality of the planned path. Notably, it reduces the number of traversed nodes by 84%, the total turning angle by 39%, and shortens the overall path length to a certain extent.

Microbiome in gynecologic malignancies: a bibliometric analysis from 2012 to 2022.

Microbiome and microbial dysbiosis have been proven to be involved in the carcinogenesis and treatment of gynecologic malignancies. However, there is a noticeable gap in the literature, as no comprehensive papers have covered general information, research status, and research frontiers in this field. This study addressed this gap by exploring the relationship between the gut and female reproductive tract (FRT) microbiome and gynecological cancers from a bibliometric perspective. Using VOSviewer 1.6.18, CiteSpace 6.1.R6, and HistCite Pro 2.1 software, we analyzed data retrieved from the Web of Science (WOS) Core Collection (WoSCC) database. Our dataset, consisting of 204 articles published from 2012 to 2022, revealed a consistent and upward publication trend. The United States and the United Kingdom were the primary driving forces, attributed to their prolificacy, high-quality output, and extensive cooperation. The University of Arizona Cancer Center, which is affiliated with the United States, ranked first among the top ten most prolific institutions. Frontiers in Cellular and Infection Microbiology emerged as the leading publisher. Herbst-Kralovetz MM led as the most productive author. Mitra A was the most influential author. Cervical cancer is notably associated with the microbiome, while endometrial and ovarian cancers are receiving increased attention in the last year. Intersections between the gut microbiome and estrogen are of growing importance. Current research focuses on identifying specific microbial species for etiological diagnosis, while frontiers mainly focus on the anticancer potential of microorganisms, such as regulating the effects of immune checkpoint inhibitors. In conclusion, this study sheds light on a novel and burgeoning direction of research, providing a one-stop overview of the microbiome in gynecologic malignancies. Its findings aim to help young researchers to identify research directions and future trends for ongoing investigations.

Emergence of novel hypervirulent Acinetobacter baumannii strain and herpes simplex type 1 virus in a case of community-acquired pneumonia in China.

BACKGROUND: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection. METHODS: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server. RESULTS: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3'')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1. CONCLUSIONS: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.

Clinical characteristics of patients with autoimmune nodopathy with anti-neurofascin155 antibodies.

Background: According to the latest guidelines on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), patients with CIDP with anti-neurofascin 155 (NF155) antibodies are referred to as autoimmune nodopathy (AN), an autoimmune disorder distinct from CIDP. We aimed to compare the clinical data of patients with AN with anti-NF155 antibodies with those of anti-NF155 antibodies-negative patients with CIDP, and to summarize the clinical characteristics of patients with AN with anti-NF155 antibodies. Methods: Nine patients with AN with anti-NF155 antibodies and 28 serologically negative patients with CIDP were included in this study. Diagnosis was made according to the diagnostic criteria in the European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines on CIDP published in 2021. Demographics, clinical manifestations, electrophysiological examination, cerebrospinal fluid (CSF) tests, and response to treatment were retrospectively analyzed. Results: Compared with serologically negative patients with CIDP, those patients with AN with anti-NF155 antibodies were younger (p=0.007), had a younger onset age (p=0.009), more frequent ataxia (p=0.019), higher CSF protein levels (p=0.001), and more frequent axon damage in electrophysiology (p=0.025). The main characteristics of patients with AN with anti-NF155 antibodies include younger age and onset age, limb weakness, sensory disturbance, ataxia, multiple motor-sensory peripheral neuropathies with demyelination and axonal damage on electrophysiological examination, markedly elevated CSF protein levels, and varying degrees of response to immunotherapy. Conclusions: Patients with AN with anti-NF155 antibodies differed from serologically negative patients with CIDP in terms of clinical characteristics. When AN is suspected, testing for antibodies associated with the nodes of Ranvier is essential for early diagnosis and to guide treatment.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma.

BACKGROUND: Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM: To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS: The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS: CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION: This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

Essential tremor is associated with reduced serum ceruloplasmin levels.

BACKGROUND: Essential tremor (ET), a prevalent movement disorder, has an elusive pathogenesis. A reduction in ceruloplasmin (Cp) levels can be found in some patients with ET. In addition, some studies have suggested an association between ET and neurodegeneration. As a ferroxidase, Cp is critical for iron metabolism, protecting against oxidative stress and neurodegeneration. Iron metabolism dysregulation, linked to ferroptosis, has implications in neurodegenerative diseases. Yet, research on Cp and ET remains limited. OBJECTIVES: This study aims to elucidate the relationship between ET and serum Cp levels. METHODS: We collected demographic and clinical data from 62 patients with ET satisfying the diagnostic criteria and compared these to data from 100 healthy controls. RESULTS: The median Cp levels in ET patients were 21.5 (18.8, 23.9) mg/dL, significantly lower than those in controls (23.1 [(20.7, 25.7) mg/dL; P = 0.006]). A reduction in Cp levels emerged as a risk factor for ET incidence (odds ratio (OR) = 0.873, 95% confidence interval (CI), 0.795, 0.959; P = 0.005). The area under the receiver operating characteristic (ROC) curve for serum Cp levels to predict the onset of ET was 0.629 (95% CI, 0.537-0.720; P = 0.006), and the optimal cut-off value for Cp levels was 19.5 mg/dL with a sensitivity of 91% and a specificity of 33.9%. CONCLUSION: Our analysis suggests that reduced Cp levels are associated with ET. We speculate that reduced Cp levels may be involved in the pathogenesis of ET, which requires further studies.

The causality between CD8+NKT cells and CD16-CD56 on NK cells with hepatocellular carcinoma: a Mendelian randomization study.

BACKGROUND: Hepatocellular carcinoma (HCC), which is featured with high morbidity and mortality worldwide, is a primary malignant tumor of the liver. Recently, there is a wealth of supporting evidence revealing that NK cell-related immune traits are strongly associated with the development of HCC, but the causality between them has not been proven. METHODS: Two-sample Mendelian randomization (MR) study was performed to probe the causal correlation between NK cell-related immune traits and HCC. Genetic variations in NK cell-related immune traits were extracted from recent genome-wide association studies (GWAS) of individuals with European blood lineage. HCC data were derived from the UK Biobank Consortium's GWAS summary count data, including a total of 372,184 female and male subjects, with 168 cases and 372,016 controls, all of whom are of European ancestry. Sensitivity analysis was mainly used for heterogeneity and pleiotropy testing. RESULTS: Our research indicated the causality between NK cell-related immune traits and HCC. Importantly, CD8+NKT cells had protective causal effects on HCC (OR = 0.9996;95%CI,0.9993-0.9999; P = 0.0489). CD16-CD56 caused similar effects on NK cells (OR = 0.9997;95%CI,0.9996-0.9999; P = 0.0117) as CD8+NKT cells. Intercepts from Egger showed no pleiotropy and confounding factors. Furthermore, insufficient evidence was found to support the existence of heterogeneity by Cochran's Q test. CONCLUSION: MR analysis suggested that low CD8+NKT cells and CD16-CD56 expression on NK cells were linked with a higher risk of HCC.

A smartphone-based centrifugal mHealth platform implementing hollow daisy-shaped quick response chip for hematocrit measurement.

Due to the ever-increasing challenge of emerging and reemerging infections on global health, the development of POCT tools has been propelled. However, conventional point-of-care testing methods suffer from several limitations, including cumbersome operation, long detection times, and low accuracy, which hamper their widespread application. Compared to traditional disease diagnostic equipment, mobile health platforms offer several advantages, including portability, ease of operation, and automated analysis of detection results through recognition algorithms. Consequently, they hold great promise for the future. Here, we developed a smartphone-based centrifugal mHealth platform implementing daisy-shaped quick response chip for hematocrit measurement. The centrifugal microfluidic chip is combined with a smartphone through a back-clip-on mobile phone adapter whose control circuit is designed with low power consumption to enable the platform to operate without requiring a high-power source that is inconvenient to carry, thereby achieving the goal of portability. Concurrently, we designed a quick response chip featuring a unique hollow daisy structure that is in line with the properties of hematocrit detection. The distinctive configuration of the chip enables adequate centrifugal force to be supplied for hematocrit detection. Additionally, our customized quick response code recognition algorithm is able to recognize this chip, facilitating non-experts in performing hematocrit intelligent recognition with their smartphones.