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The process of adenosine deaminase (ADAR)-catalyzed double-stranded RNA (dsRNA) Adenosine-to-Inosine (A-to-I) editing is essential for the correction of pathogenic mutagenesis, as well as the regulation of gene expression and protein function in mammals. The significance of dsRNA A-to-I editing in disease development and occurrence is explored using inferential statistics and cluster analyses to investigate the enzymes involved in dsRNA editing that can catalyze editing sites across multiple biomarkers. This editing process, which occurs in coding or non-coding regions, has the potential to activate abnormal signalling pathways that contributes to disease pathogenesis. Notably, the ADAR family enzymes play a crucial role in initiating the editing process. ADAR1 is upregulated in most diseases as an oncogene during tumorigenesis, whereas ADAR2 typically acts as a tumour suppressor. Furthermore, this review also provides an overview of small molecular inhibitors that disrupt the expression of ADAR enzymes. These inhibitors not only counteract tumorigenicity but also alleviate autoimmune disorders, neurological neurodegenerative symptoms, and metabolic diseases associated with aberrant dsRNA A-to-I editing processes. In summary, this comprehensive review offers detailed insights into the involvement of dsRNA A-to-I editing in disease pathogenesis and highlights the potential therapeutic roles for related small molecular inhibitors. These scientific findings will undoubtedly contribute to the advancement of personalized medicine based on dsRNA A-to-I editing.

Aims: This study is to investigate the effects of Cannabinoid type 2 receptor (CB2R) deficiency on microglia and cognitive function in both Aβ1–42-injected CB2R knockout mice and a transgenic mouse model of Alzheimer’s disease (AD) in brain. Methods: After hippocampal injection with Aβ1–42 oligomers in CB2R knockout mice with and without CB2R agonist treatment and in transgenic APP/PS1 mice with CB2R deletion, the novel object recognition (NOR) and Morris water maze (MWM) tests were performed to assess the animal behavior performance. Immunofluorescence staining was conducted to detect the microglial morphology and activation status. The expression of proinflammation and anti-inflammation cytokines were determined by qRT-PCR. Results: CB2R deficiency significantly aggravated cognitive impairment in both Aβ1–42-induced and transgenic APP/PS1 animal model in NOR. In Aβ-injected mice lacking CB2R and transgenic APP/PS1 mice with CB2R deletion, microglia in the prefrontal cortex exhibited enhanced immunoreactivity with altered morphology. Furthermore, transformation of activated microglial phenotype in the prefrontal cortex was reduced in Aβ1–42-injected CB2R knockout mice after CB2R agonist treatment. The CB2R deficiency significantly increased the expression of proinflammatory cytokines in the prefrontal cortex, while it was observed in the hippocampus in both Aβ1–42-injected and transgenic APP/PS1 AD mouse model. Furthermore, CB2R deficiency increased concentrations of soluble Aβ 40 in the prefrontal cortex, but did not affect plaques deposition. Conclusion: CB2R deletion led to enhanced neuroinflammatory responses via direct upregulating microglia activation in the prefrontal cortex during the early symptomatic phase of AD mice. CB2R modulates prefrontal cortical neuroinflammation, which is essential for regulating cognitive functions such as recognition memory at the early stage of AD.

The increasing interest in multilineage differentiating stress-enduring (Muse) cells within the field of regenerative medicine is attributed to their exceptional homing capabilities, prolonged viability in adverse conditions, and enhanced three-germ-layer differentiate ability, surpassing their parent mesenchymal stem cells. Given their abundant sources, non-invasive collection procedure, and periodic availability, human menstrual blood-derived endometrium stem cells (MenSCs) have been extensively investigated as a potential resource for stem cell-based therapies. However, there is no established modality to isolate Muse cells from MenSCs and disparity in gene expression profiles between Muse cells and MenSCs remain unknown. In this study, Muse cells were isolated from MenSCs by long-time trypsin incubation method. Muse cells expressed pluripotency markers and could realize multilineage differentiation in vitro. Compared with MenSCs, Muse cells showed enhanced homing ability and superior therapeutic efficacy in animal models of acute liver injury (ALI) and intracerebral hemorrhage (ICH). Furthermore, the RNA-seq analysis offers insights into the mechanism underlying the disparity in trypsin resistance and migration ability between Muse and MenSCs cells. This research offers a significant foundation for further exploration of cell-based therapies using MenSCs-derived Muse cells in the context of various human diseases, highlighting their promising application in the field of regenerative medicine.

Abstract The present study aims to explore group types of job stress in university teachers in China. Utilizing an indigenously developed university teachers’ job stress scale in China alongside other tools, a survey was conducted on 1988 teachers from 22 Chinese higher education institutions from a person-oriented perspective. Stratified cluster random sampling and K-means clustering techniques were employed to derive a classification model for job stress among university educators. According to job stress characteristics, Chinese university teachers were classified into six significantly heterogeneous groups: relatively high stress, task-related stress, relatively low stress, interpersonal-related stress, extremely low stress, and extremely high stress. The average job burnout and job satisfaction scores of the different groups exhibited varying features. In general, the extremely high stress group should be the most concerned, whereas university teachers with mid-level stress merit less attention. But the medium-stress group was further subdivided. University teachers under task-related stress have more stress-related consequences than those of university teachers under interpersonal-related stress. There are significant differences in the distribution of university teachers’ job stress group types across demographic groups defined by gender and university types. University administrators should focus on university teachers under task-related stress. This classification model offers direct references for the stress management and psychological aid of university teachers.

Abstract To investigate the erosive damage effect of the acidic solution on sandstone, experiments were conducted to examine the macro‐ and micro‐characteristics of sandstone samples under different acid etching times. Microscopic morphology changes, pore structure characteristics, mineral composition changes, and mechanical response characteristics were obtained before and after acid etching. Finally, a comprehensive evaluation index for acid etching damage was proposed. The results show that: (1) Acidic solution will erode the sandstone skeleton and cause the sandstone to collapse. The etched surface appears “flocculent” and yellow sediment is produced. (2) The pores in sandstone samples are mainly micro‐ and mesopores, and the total porosity increases exponentially with the duration of acid etching. The volume fraction of micropores can reach up to 81.5%. (3) The acid etching process of sandstone samples includes physical diffusion and chemical dissolution, which can be divided into four stages and three regions from the outside to the inside. After acid etching, the uniaxial compression failure mode of the sample changes from shear to mixed shear‐tensile failure. (4) The comprehensive evaluation index based on three failure modes generated during the loading process shows good consistency with the overall changes of characteristics parameters such as elastic modulus, peak stress, and peak strain. The research findings of this paper can provide theoretical support for the assessment of rock mass stability and disaster prevention in acidic environments.

Reservoir heterogeneity, water-oil mobility ratio, cementation degree, and strong injection and production significantly influence long-term waterflooding and polymer flooding processes in oil reservoir development, leading to the formation of low-resistance dominant seepage channels in the lower part of thick oil layers without internal laminations. Understanding the spatial distribution and evolution of dominant seepage channels in oil reservoirs during waterflooding and polymer flooding is crucial for improving reservoir development and recovery rates. It uses a streamlined numerical simulation method to quantitatively show the spatial and temporal distribution of dominant seepage channels in the oil reservoir. A model and chart were created to demonstrate the relationship between permeability and throat radius, capturing changes in reservoir permeabilities over time. The study developed a comprehensive mathematical model to identify dominant seepage channels, considering parameters such as inter-well flow ratio, injection efficiency, permeability change value, and water saturation. Research findings indicate a 14.8 % increase in reservoir permeability after polymer flooding, with slight changes in porosity and a 20.3 % decrease in clay content. The established mathematical model and identification criteria were used to comprehensively quantitatively evaluate flow channels, describing the distribution characteristics and evolution process of dominant seepage channels in the experimental area over four periods: pre-polymer flooding, low water-saturation period during polymer flooding, post-polymer injection, and subsequent 10 years of water flooding. Both polymer flooding and subsequent water flooding have significantly altered the distribution pattern of predominant fluid pathways: 254 well layers now demonstrate robust predominant fluid pathways (19 %); another 272 well layers feature moderately predominant fluid pathways (22 %); while an additional 440 well layers display weaker predominant fluid pathways (approximately 35 %). There has been a noticeable increase in both weak and moderate predominant fluid pathways, which are now more widespread in the area. However, localized occurrences of strong predominant fluid pathways persist with no significant change in their distribution characteristics. Analysis at four different time points shows a clear trend of increasing intensity as we move from polymer to subsequent water flooding in this decade. Additionally, examination along an axis from upper left to lower right reveals a linear progression that indicates clear connections among different categories of dominant seepage channel. The verification results show a strong correlation between the calculated dominant seepage channel distribution and actual water-injection profile test results, indicating that the method effectively identifies dominant seepage channels in oil reservoirs after polymer flooding and has the potential to enhance oil recovery further.

Abstract Background In facial plastic surgery, patients with nasal deformity are often treated by rib cartilage transplantation. In recent years, cartilage tissue engineering has developed as an alternative to complex surgery for patients with minor nasal defects via injection of nasal filler material. In this study, we prepared an injectable nasal filler material containing poly‐L‐lactic acid (PLLA) porous microspheres (PMs), hyaluronic acid (HA) and adipose‐derived mesenchymal stem cells (ADMSCs). Methods We seeded ADMSCs into as‐prepared PLLA PMs using our newly invented centrifugation perfusion technique. Then, HA was mixed with ADMSC‐incorporated PLLA PMs to form a hydrophilic and injectable cell delivery system (ADMSC‐incorporated PMH). Results We evaluated the biocompatibility of PMH in vitro and in vivo. PMH has good injectability and provides a favorable environment for the proliferation and chondrogenic differentiation of ADMSCs. In vivo experiments, we observed that PMH has good biocompatibility and cartilage regeneration ability. Conclusion In this study, a injectable cell delivery system was successfully constructed. We believe that PMH has potential application in cartilage tissue engineering, especially in nasal cartilage regeneration.

Abstract Internal insulation of high‐voltage power modules is facing interesting failure risks, including high temperature overheating, breakdown fault, material cracking etc., so it is imperative to urgently develop new dielectric materials with high thermal conductivity (λ), outstanding electrical insulation, and thermal stability properties. A method to construct controllable liquid crystalline cross‐linking networks based on the synthesis of biphenyl epoxy monomer and the change of curing agent structures and curing temperature is proposed. The uniform nematic rod‐like liquid crystalline domains were obtained by using 4,4‐diaminodiphenylmethane as a curing agent under a pre‐curing temperature of 105°C. The resulting film (abbreviated as TD‐105) exhibited λ up to 0.53 W m−1 K−1 and a dielectric breakdown strength of 57.69 kV mm−1, which showed a simultaneous enhancement of 178% and 16%, respectively, compared to traditional bisphenol A epoxy resin. Moreover, it also exhibited lower dielectric loss and magnitude of partial discharge while having higher glass‐transition temperature (190°C). A novel idea for the development of high‐performance epoxy insulating materials for the application of high‐voltage and large‐power electrical equipment is provided.

Abstract Purpose To conduct a head-to-head comparison between deep learning (DL) and radiomics models across institutions for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) and to investigate the model robustness and generalizability through rigorous internal and external validation. Methods This retrospective study included 2304 preoperative images of 576 HCC lesions from two centers, with MVI status determined by postoperative histopathology. We developed DL and radiomics models for predicting the presence of MVI using B-mode ultrasound, contrast-enhanced ultrasound (CEUS) at the arterial, portal, and delayed phases, and a combined modality (B + CEUS). For radiomics, we constructed models with enlarged vs. original regions of interest (ROIs). A cross-validation approach was performed by training models on one center’s dataset and validating the other, and vice versa. This allowed assessment of the validity of different ultrasound modalities and the cross-center robustness of the models. The optimal model combined with alpha-fetoprotein (AFP) was also validated. The head-to-head comparison was based on the area under the receiver operating characteristic curve (AUC). Results Thirteen DL models and 25 radiomics models using different ultrasound modalities were constructed and compared. B + CEUS was the optimal modality for both DL and radiomics models. The DL model achieved AUCs of 0.802–0.818 internally and 0.667–0.688 externally across the two centers, whereas radiomics achieved AUCs of 0.749–0.869 internally and 0.646–0.697 externally. The radiomics models showed overall improvement with enlarged ROIs (P 0.05 for all modalities, 1.6–2.1% differences in AUC for the optimal modality), whereas the radiomics models had relatively limited robustness across the two centers (12% drop-off in AUC for the optimal modality). Adding AFP improved the DL models (P 0.05). Conclusion Cross-institutional validation indicated that DL demonstrated better robustness than radiomics for preoperative MVI prediction in patients with HCC, representing a promising solution to non-standardized ultrasound examination procedures.

Abstract. Background:. Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure–response relationship of ANV among people living with HIV. Methods:. Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure–response analysis for virologic responses and safety responses. Results:. ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure–response model revealed no significant correlation between the virologic response (HIV-RNA

Abstract In recent years, the recognition of distinct lymphoma entities has expanded with advancements in molecular characterization. Large B‐cell Lymphoma with interferon regulatory factor‐4 (IRF4) rearrangement (LBCL‐IRF4‐R) is one such entity. We present a case of classic low‐grade follicular lymphoma with IRF4 rearrangement in a 50‐year‐old male, demonstrating an unusual immunophenotypic and genetic profile reminiscent of LBCL‐IRF4‐R. Molecular analysis revealed mutations in CREBBP, KMT2D, IRF4, and CARD11, with previously unreported variants identified in IRF4 and CREBBP. This case broadens the spectrum of B‐cell lymphomas associated with IRF4 rearrangement by demonstrating a small B‐cell lymphoma with this genetic feature.

Abstract The persistent infection of high-risk human papillomavirus (HPV) and the progression of cervical cancer necessitate the involvement of microenvironmental immunity. As cervical lesions advance, there is an observed increase in the infiltration of type 2 (M2) macrophages. However, the precise mechanism driving this increased infiltration of M2 macrophages remains unclear. In this study, we investigated the role of exosomes in polarising M2 macrophages in cervical lesions associated with HPV E6. Through the analysis of bioinformatics data and clinical specimens, we discovered a positive correlation between HPV E6/E7 mRNA copy number and the level of M2 macrophage infiltration. Exosomes derived from HPV E6 overexpressed (HPV E6+) cervical squamous cell carcinoma (CESC) cells were found to induce the polarisation of macrophages towards M2 type. Specifically, miR-204-5p, enriched in HPV E6 + CESC exosomes, was transported into macrophages and triggered M2 macrophage polarisation by inhibiting JAK2. The clinical relevance of exosomal miR-204-5p in the progression of cervical lesions was validated through serum samples from 35 cases. Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.

Abstract Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. Graphical abstract

Abstract Enhancers constitute a vital category of cis-regulatory elements with a Mediator complex within DNA sequences, orchestrating gene expression by activating promoters. In the development of T cells, some enhancers regulate the critical genes, which might also regulate T cell malignant lesions. This review is to comprehensively elucidate the contributions of enhancers in both normal T cell development and its malignant pathogenesis, proposing the idea that the precise subunits of the Mediator complex are the potential drug target for disrupting the specific gene enhancer for T cell malignant diseases.

Deterministically achieving on-chip photon storage and retrieval is a fundamental challenge for integrated photonics. Moreover, this requirement is increasingly urgent as photon storage and retrieval is crucial to realize truly scalable room-temperature quantum computing. However, most of existing quantum memories integrated on chips must either work at cryogenic temperature or else are strongly coupled with the environment, which hugely reduces the efficiency. Here, we propose an on-chip room-temperature quantum memory comprising three coupled microcavities, which presents an ideal dark state decoupled by a waveguide, thereby allowing on-demand photon storage and retrieval with high efficiency and high fidelity simultaneously. Furthermore, we demonstrate that the single-photon temporal duration can be increased or decreased by a factor of 103, thereby enabling many crucial quantum applications. Our error-robust approach highlights the potential for a solid-state photonic molecule for use as on-chip quantum memory and for optical quantum computing.

We propose an approach to learning sample embedding for analyzing multi-dimensional datasets. The basic idea is to extract rules from the given dataset and learn the embedding for each sample based on the rules it satisfies. The approach can filter out pattern-irrelevant attributes, leading to significant visual structures of samples satisfying the same rules in the projection. In addition, analysts can understand a visual structure based on the rules that the involved samples satisfy, which improves the projection’s pattern interpretability. Our research involves two methods for achieving and applying the approach. First, we give a method to learn rule-based embedding for each sample. Second, we integrate the method into a system to achieve an analytical workflow. Cases on real-world dataset and quantitative experiment results show the usability and effectiveness of our approach.

Wastewater surveillance (WWS) can leverage its wide coverage, population-based sampling, and high monitoring frequency to capture citywide pandemic trends independent of clinical surveillance. Here we conducted a nine months daily WWS for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 12 wastewater treatment plants (WWTPs), covering approximately 80% of the population, to monitor infection dynamics in Hong Kong, China. We found that the SARS-CoV-2 virus concentration in wastewater was correlated with the daily number of reported cases and reached two pandemic peaks three days earlier during the study period. In addition, two different methods were established to estimate the prevalence/incidence rates from wastewater measurements. The estimated results from wastewater were consistent with findings from two independent citywide clinical surveillance programmes (rapid antigen test (RAT) surveillance and serology surveillance), but higher than the cases number reported by the Centre for Health Protection (CHP) of Hong Kong, China. Moreover, the effective reproductive number (Rt) was estimated from wastewater measurements to reflect both citywide and regional transmission dynamics. Our findings demonstrate that large-scale intensive WWS from WWTPs provides cost-effective and timely public health information, especially when the clinical surveillance is inadequate and costly. This approach also provides insights into pandemic dynamics at higher spatiotemporal resolutions, facilitating the formulation of effective control policies and targeted resource allocation.

Abstract Diabetes mellitus (DM) is a well-documented risk factor of intervertebral disc degeneration (IVDD). The current study was aimed to clarify the effects and mechanisms of NADH: ubiquinone oxidoreductase subunit A3 (NDUFA3) in human nucleus pulposus cells (HNPCs) exposed to high glucose. NDUFA3 was overexpressed in HNPCs via lenti-virus transduction, which were co-treated with high glucose and rotenone (a mitochondrial complex I inhibitor) for 48 h. Cell activities were assessed for cell viability, cell apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) ratio, oxygen consumption rate (OCR) and mitochondrial complexes I activities. High glucose decreased cell viability, increased apoptotic cells, increased ROS production, decreased MMP levels and OCR values in HNPCs in a dose-dependent manner. Rotenone co-treatment augmented the high glucose-induced injuries on cell viability, apoptosis, ROS production and mitochondrial function. NDUFA3 overexpression counteracted the high glucose-induced injuries in HNPCs. HDAC/H3K27ac mechanism was involved in regulating NDUFA3 transcription. NDUFA3 knockdown decreased cell viability and increased apoptotic cells, which were reversed by ROS scavenger N-acetylcysteine. HDAC/H3K27ac-mediated transcription of NDUFA3 protects HNPCs against high glucose-induced injuries through suppressing cell apoptosis, eliminating ROS, improving mitochondrial function and oxidative phosphorylation. This study sheds light on candidate therapeutic targets and deepens the understanding of molecular mechanisms behind DM-induced IVDD.

Abstract Objective This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. Methods We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. Results Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. Conclusion Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation.

Benggang is a typical fragmented erosional landscape in southern and southeastern China, posing significant risk to the local residents and economic development. Therefore, an efficient and accurate fine-grained segmentation method is crucial for monitoring the Benggang areas. In this paper, we propose a deep learning-based automatic segmentation method for Benggang by integrating high-resolution Digital Orthophoto Map (DOM) and Digital Surface Model (DSM) data. The DSM data is used to extract slope maps, aiming to capture primary morphological features. The proposed method consists of a dual-stream convolutional encoder-decoder network in which multiple cascaded convolutional layers and a skip connection scheme are used to extract morphological and visual features of the Benggang areas. The rich discriminative information in the DOM and slope data is fused by a channel exchanging mechanism that dynamically exchanges the most discriminative features from either the DOM or DSM stream according to their importance at the channel level. Evaluation experiments were conducted on a challenging dataset collected from Guangdong Province, China, and the results show that the proposed channel exchanging network based deep fusion method achieves 84.62% IoU in Benggang segmentation, outperforming several existing unimodal or multimodal baselines. The proposed multimodal segmentation method greatly improves the efficiency of large-scale discovery of Benggang, and thus is important for the management and restoration of Benggang in southern and southeastern China, as well as the monitoring of other similar erosional landscapes.

The existing marine buoy communication mode is single, with low reliability, high packet loss rate, and poor real-time performance, which cannot meet the needs of large-scale marine data acquisition and cross-domain communication. In order to further strengthen the construction of marine global interconnection, a cross-domain communication buoy system with multi-source communication as the core was designed and manufactured. The system could complete the switching of multiple communication modes, multi-source information acquisition, and multi-link real-time cross-domain communication. An optimal communication link selection algorithm was designed for the system. According to the real-time signal quality of each communication module, the optimal communication link was selected to improve the reliability of communication. At the same time, the communication module with poor signal quality was closed to reduce the problem of large redundancy and power consumption of system communication that may occur when multiple communication methods are used at the same time. The experimental results show that the system realizes the cross-domain transmission of water surface and underwater data, and the multi-source communication design is feasible. The communication links are stable and reliable, and the comprehensive communication success rate is more than 99%. It provides a reference for the construction of a marine global observation network and communication network.

Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

Abstract Long-read sequencing holds great potential for characterizing complex microbial communities, yet taxonomic profiling tools designed specifically for long reads remain lacking. We introduce Melon, a novel marker-based taxonomic profiler that capitalizes on the unique attributes of long reads. Melon employs a two-stage classification scheme to reduce computational time and is equipped with an expectation-maximization-based post-correction module to handle ambiguous reads. Melon achieves superior performance compared to existing tools in both mock and simulated samples. Using wastewater metagenomic samples, we demonstrate the applicability of Melon by showing it provides reliable estimates of overall genome copies, and species-level taxonomic profiles.

Abstract Gas saturation is a critical parameter for the selection and development of coalbed methane, as well as a key indicator reflecting the challenges in coalbed methane development and productivity evaluation of coalbed methane wells. As one of the significant factors influencing gas saturation, gas content plays a vital role in comprehensively investigating coal pore properties to fully comprehend the process and conditions of methane adsorption and desorption. In this study, 3# and 15# coals from Qinshui Basin, China was selected as research subjects. The experimental evaluation encompassed an examination of composition, pore characteristics, permeability characteristics of coal, rock mechanical parameters while discussing the impact of temperature and pressure on coal's adsorption and desorption capacity. The mineral characteristics analysis revealed that vitrinite is the main component with varying percentages and reflectance values in both 3# and 15# coal seams. The gas content and methane concentration in the 15# coal seam are higher than those in the 3# coal seam. The relationship between gas content within a coal seam and burial depth depends on achieving a balance between positive pressure effects caused by overburden stress exertion on gases trapped within pores under high pressures during burial history versus negative temperature effects due to cooling during geological processes over time. Predictions were made regarding deep-coal gas content which holds significant implications for accurately understanding variations in desorption behavior along with optimizing fracturing engineering.

Highlights The types, working principles, advantages and limitations of pattern recognition methods based on chemiresistive gas sensor array are reviewed and discussed comprehensively. Outstanding and novel advancements in the application of machine learning methods for gas recognition in different important areas are compared, summarized and evaluated. The current challenges and future prospects of machine learning methods in artificial olfactory systems are discussed and justified.

Abstract Objective The early differentiation of adrenal lipid-poor adenomas from non-adenomas is a crucial step in reducing excessive examinations and treatments. This study seeks to construct an eXtreme Gradient Boosting (XGBoost) predictive model utilizing the minimum attenuation values (minAVs) from non-contrast CT (NCCT) scans to identify lipid-poor adenomas. Materials and methods Retrospective analysis encompassed clinical data, minAVs, CT histogram (CTh), mean attenuation values (meanAVs), and lesion diameter from patients with pathologically or clinically confirmed adrenal lipid-poor adenomas across two medical institutions, juxtaposed with non-adenomas. Variable selection transpired in Institution A (training set), with XGBoost models established based on minAVs and CTh separately. Institution B (validation set) corroborated the diagnostic efficacy of the two models. Receiver operator characteristic (ROC) curve analysis, calibration curves, and Brier scores assessed the diagnostic performance and calibration of the models, with the Delong test gauging differences in the area under the curve (AUC) between models. SHapley Additive exPlanations (SHAP) values elucidated and visualized the models. Results The training set comprised 136 adrenal lipid-poor adenomas and 126 non-adenomas, while the validation set included 46 and 40 instances, respectively. In the training set, there were substantial inter-group differences in minAVs, CTh, meanAVs, diameter, and body mass index (BMI) (p 0.05 for both). SHAP value analysis for the minAV model suggested that minAVs had the highest absolute weight (AW) and negative contribution. Conclusion The XGBoost predictive model based on minAVs demonstrates effective discrimination between adrenal lipid-poor adenomas and non-adenomas. The minAV variable is easily obtainable, and its diagnostic performance is comparable to that of the CTh model. This provides a basis for patient diagnosis and treatment plan selection.

Abstract Background Tuberculous meningitis (TBM) emerges as a grave complication of tuberculosis in people living with HIV (PLWH). The diagnosis and treatment of TBM pose significant challenges, leading to elevated mortality rates. To comprehensively grasp the epidemiological landscape of TBM in PLWH, a systematic review and meta-analysis were meticulously undertaken. Methods We performed a comprehensive search in PubMed, Embase, and Web of Science from database inception to September 19th, 2023, with no limitations on the publication type. The search terms were HIV/AIDS terms (AIDS OR HIV OR PLWH) and TBM-related terms (tuberculous meningitis OR TBM). Studies included in this meta-analysis evaluated the incidence of TBM among PLWH, or we were able to calculate the incidence of TBM among PLWH from the research. Results The analysis revealed that the prevalence of TBM among PLWH was 13.6% (95% CI: 6.6–25.9%), with an incidence rate of 1.5 cases per 1000 persons per year. The case fatality rate was found to be 38.1% (95% CI: 24.3–54.1%). No significant publication bias was observed. Meta-regression analysis identified the proportion of females and finance situation as factors influencing the outcomes. Conclusions Our study highlights TBM as a prevalent opportunistic infection that targets the central nervous system in PLWH. The elevated case fatality rate is especially prominent among PLWH in impoverished regions, underscores the pressing necessity for enhanced management strategies for PLWH suffering from TBM. Trial registration PROSPERO; No: CRD42022338586.

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in the liver and bone marrow, indicative of CAEBV. The liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores the diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management.

Abstract Although circular RNAs (circRNA) have been demonstrated to modulate tumor initiation and progression, their roles in the proliferation of hepatocellular carcinoma (HCC) are still poorly understood. Based on the analysis of GEO data (GSE12174), hsa-circRNA-0015004 (circ-0015004) was screened and validated in 80 sets of HCC specimens. Subcellular fractionation analysis was designed to determine the cellular location of circ-0015004. Colony formation and cell counting kit-8 were performed to investigate the role of circ-0015004 in HCC. Dual-luciferase reporter gene assays, RNA immunoprecipitation and chromatin immunoprecipitation were employed to verify the interaction among circ-0015004, miR-330-3p and regulator of chromatin condensation 2 (RCC2). The expression level of circ-0015004 was significantly upregulated in HCC cell lines and HCC tissues. HCC patients with higher circ-0015004 levels displayed shorter overall survival, and higher tumor size and TNM stage. Moreover, knockdown of circ-0015004 significantly reduced HCC cell proliferation in vitro and inhibited the growth of HCC in nude mice. Mechanistic studies revealed that circ-0015004 could upregulate the expression of RCC2 by sponging miR-330-3p, thereby promoting HCC cell proliferation. Furthermore, we identified that Ying Yang 1 (YY1) could function as an important regulator of circ-0015004 transcription. This study systematically demonstrated the novel regulatory signaling of circ-0015004/miR-330-3p/RCC2 axis in promoting HCC progression, providing insight into HCC diagnosis and treatment from bench to clinic.

Abstract Background Understanding the interactions and dynamics of microbiotas within biological wastewater treatment systems is essential for ensuring their stability and long-term sustainability. In this study, we developed a systematic framework employing multi-omics and Hi-C sequencing to extensively investigate prokaryotic and phage communities within a hybrid biofilm and activated sludge system. Results We uncovered distinct distribution patterns, metabolic capabilities, and activities of functional prokaryotes through the analysis of 454 reconstructed prokaryotic genomes. Additionally, we reconstructed a phage catalog comprising 18,645 viral operational taxonomic units (vOTUs) with high length and contiguity using hybrid assembly, and a distinct distribution of phages was depicted between activated sludge (AS) and biofilm. Importantly, 1340 host-phage pairs were established using Hi-C and conventional in silico methods, unveiling the host-determined phage prevalence. The majority of predicted hosts were found to be involved in various crucial metabolic processes, highlighting the potential vital roles of phages in influencing substance metabolism within this system. Moreover, auxiliary metabolic genes (AMGs) related to various categories (e.g., carbohydrate degradation, sulfur metabolism, transporter) were predicted. Subsequent activity analysis emphasized their potential ability to mediate host metabolism during infection. We also profiled the temporal dynamics of phages and their associated hosts using 13-month time-series metagenomic data, further demonstrating their tight interactions. Notably, we observed lineage-specific infection patterns, such as potentially host abundance- or phage/host ratio-driven phage population changes. Conclusions The insights gained from this research contribute to the growing body of knowledge surrounding interactions and dynamics of host-phage and pave the way for further exploration and potential applications in the field of microbial ecology. Video Abstract

Abstract Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

Abstract The central lymph node metastasis (CLNM) status in the cervical region serves as a pivotal determinant for the extent of surgical intervention and prognosis in papillary thyroid carcinoma (PTC). This paper seeks to devise and validate a predictive model based on clinical parameters for the early anticipation of high-volume CLNM (hv-CLNM, > 5 nodes) in high-risk patients. A retrospective analysis of the pathological and clinical data of patients with PTC who underwent surgical treatment at Medical Centers A and B was conducted. The data from Center A was randomly divided into training and validation sets in an 8:2 ratio, with those from Center B serving as the test set. Multifactor logistic regression was harnessed in the training set to select variables and construct a predictive model. The generalization ability of the model was assessed in the validation and test sets. The model was evaluated through the receiver operating characteristic area under the curve (AUC) to predict the efficiency of hv-CLNM. The goodness of fit of the model was examined via the Brier verification technique. The incidence of hv-CLNM in 5897 PTC patients attained 4.8%. The occurrence rates in males and females were 9.4% (128/1365) and 3.4% (156/4532), respectively. Multifactor logistic regression unraveled male gender (OR = 2.17, p 10 mm) as 0.803 (0.757–0.85) and 0.747 (0.709–0.785), age groups (≤ 31 years and > 31 years) as 0.778 (0.720–0.881) and 0.837 (0.806–0.867), multifocal and solitary cases as 0.803 (0.767–0.838) and 0.809 (0.769–0.849), and Hashimoto’s thyroiditis (HT) and non-HT cases as 0.845 (0.793–0.897) and 0.845 (0.819–0.871). Male gender, multifocality, and larger lesion size are risk factors for hv-CLNM in PTC patients, whereas age serves as a protective factor. The clinical predictive model developed in this research facilitates the early identification of high-risk patients for hv-CLNM, thereby assisting physicians in more efficacious risk stratification management for PTC patients.

The spider genus Argiope Audouin, 1826, comprises 88 species worldwide, including 23 species occurring in China. Two Argiope species were collected by the spider survey on Yarlung Zangbo Grand Canyon National Nature Reserve, Xizang, southwest China, conducted in 2023.Two species of the orb-weaver spider genus Argiope from Xizang, China are described, including a new species, A. beibeng Mi & Wang, sp. nov. (♂♀) and a known species, A. caesarea Thorell, 1897 (♂♀). The unknown male of A. caesarea is described for the first time.

Abstract The application of terahertz time-domain spectroscopy (THz-TDS) in the quantitative analysis of major minerals in Bayan Obo magnetite ore was explored. The positive correlation between the optical parameters of the original ore and its iron content is confirmed. The detections of three main iron containing minerals, including magnetite, pyrite, and hematite, were simulated using corresponding reagents. The random forest algorithm is used for quantitative analysis, and FeS2 is detected with precision of R2 = 0.7686 and MAE = 0.6307% in ternary mixtures. The experimental results demonstrate that THz-TDS can distinguish specific iron containing minerals and reveal the potential application value of this testing method in exploration and mineral processing fields.

Abstract Background Despite rapid advances in genomic-resolved metagenomics and remarkable explosion of metagenome-assembled genomes (MAGs), the function of uncultivated anaerobic lineages and their interactions in carbon mineralization remain largely uncertain, which has profound implications in biotechnology and biogeochemistry. Results In this study, we combined long-read sequencing and metatranscriptomics-guided metabolic reconstruction to provide a genome-wide perspective of carbon mineralization flow from polymers to methane in an anaerobic bioreactor. Our results showed that incorporating long reads resulted in a substantial improvement in the quality of metagenomic assemblies, enabling the effective recovery of 132 high-quality genomes meeting stringent criteria of minimum information about a metagenome-assembled genome (MIMAG). In addition, hybrid assembly obtained 51% more prokaryotic genes in comparison to the short-read-only assembly. Metatranscriptomics-guided metabolic reconstruction unveiled the remarkable metabolic flexibility of several novel Bacteroidales-affiliated bacteria and populations from Mesotoga sp. in scavenging amino acids and sugars. In addition to recovering two circular genomes of previously known but fragmented syntrophic bacteria, two newly identified bacteria within Syntrophales were found to be highly engaged in fatty acid oxidation through syntrophic relationships with dominant methanogens Methanoregulaceae bin.74 and Methanothrix sp. bin.206. The activity of bin.206 preferring acetate as substrate exceeded that of bin.74 with increasing loading, reinforcing the substrate determinantal role. Conclusion Overall, our study uncovered some key active anaerobic lineages and their metabolic functions in this complex anaerobic ecosystem, offering a framework for understanding carbon transformations in anaerobic digestion. These findings advance the understanding of metabolic activities and trophic interactions between anaerobic guilds, providing foundational insights into carbon flux within both engineered and natural ecosystems. Video Abstract

Allium mongolicum is a wild vegetable with high nutritional value and is famous for its taste and aroma. This study used headspace solid-phase microextraction-mass spectrometry coupled with gas chromatography–mass spectrometry techniques to study the metabolic profile of A. mongolicum in different ecological environments. A total of 624 volatile organic compounds (VOCs) were identified. Ester compounds, heterocyclic compounds and terpenoids are the key metabolites that determine flavor differences. KEGG analysis showed that monoterpenoid biosynthesis, zein biosynthesis, α-linolenic acid metabolism and secondary metabolite biosynthesis were the most important metabolic pathways. Compared with Minqin A. mongolicum and Tengger A. mongolicum, Alxa A. mongolicum flavor substance notes sensory flavor has more green, fruity, sweet, floral, spicy, metallic, rose, almond, apple, grassy, tropical, citrus, fresh, herbal and other flavor combinations. Overall, this study reveals the main reason for the unique flavor of Alxa A. mongolicum through metabolomic evidence.

Summary: Lysosomal biothiols play critical roles in numerous cellular processes and diseases. Researching an effective method for real-time labeling biothiols in lysosomes is of great significance and urgency, as it could provide essential information for the diagnosis of relevant diseases. In this study, we developed a lysosome-targeted fluorescent probe (LY-DCM-P) with a large Stokes shift of 150 nm for the sensitive and selective detection of biothiols in vivo and in vitro. Additionally, LY-DCM-P showed low cytotoxicity and excellent lysosome-targeted ability. The probe was successfully employed to monitor fluctuations in lysosomal biothiols in various living systems, enabling enormous potential to accurately monitor the occurrence and progress of biothiol-related diseases.

Study region: The Nujiang Fault Zone near Baoshan in western Yunnan. Study focus: Major hydrochemical elements and stable isotopes of 15 hot spring water samples are analyzed to reveal hydrogeochemical evolution processes, recharge sources, geothermal conditions, and structural control genesis of the hot springs. New hydrological insight for the region: Baoshan is experiencing a wave of clean energy development, specifically geothermal energy. The Nujiang Fault Zone, which separates the Tengchong Block from the Baoshan Block, constitutes a low- to medium-temperature geothermal system characterized by numerous hot springs. The hot springs under investigation are located near Baoshan along the Nujiang Fault. Four hydrochemical types have been identified, with HCO3-Ca⋅Mg being the predominant type. The primary components of spring waters originate from the weathering or dissolution of carbonate and silicate minerals, as well as the reverse cation exchange. Stable isotopes indicate that these hot springs are predominantly formed by the atmospheric precipitation during the summer monsoon. The recharge areas are located in the mountainous regions around the Nujiang River, at elevations ranging from 1606 to 2504 m and temperatures between 3°C and 8°C. The estimated temperature of the geothermal reservoir ranges from 73°C to 192°C. During the ascent process, the mixing ratio of cold water is between 60 % and 79 %, and the circulation depth ranges from 1928 to 4221 m. The positive correlation between Li and Cl indicates that hot springs originate from the same parent geothermal fluid controlled by the Nujiang Fault or by two secondary faults intersecting at depths. The hot springs with shallower circulation depths are mainly composed of HCO3-Ca⋅Mg type, while the deeper circulating spring waters consist primarily of HCO3-Na type. The height difference between the discharge location of the hot springs and the surface of the Nujiang River correlates positively with the geothermal reservoir temperature. This paper emphasizes the hydrogeochemical characterization of hot springs within regional fault zones, which holds significant implications for the development and exploration of geothermal systems in similar structural control areas.

Epilepsy affects ∼ 65 million people worldwide. In this study, peripheral blood mononuclear cells were isolated from a young patient patient bearing a Nitrogen Perntease Regulator Like 3 Protein (NPRL3) mutation and suffering from Epilepsy verified by clinical and genetic diagnosis. Induced pluripotent stem cells (iPSCs) were established by a non-integrative method, using plasmids carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSCs presented typical pluripotent cells morphology, normal karyotype, and potential to differentiate into three germ layers. Our approach offers a useful model to explore pathogenesis and therapy of Epilepsy.

Frozen soil is a vital component of the cryosphere and is sensitive to climate changes, accelerating thaw when the anthropogenic climate warms. Identifying the state of soil freeze/thaw is crucial for effective water resource management, cold region engineering construction, agriculture development, etc. In this study, we used Landsat remote sensing images data to identify the freeze/thaw state of frozen soil, focusing on the eastern Tibetan Plateau (ETP) as a case study. We compared the target detection models of two architectures and the semantic segmentation model framework of four models with different encoders. We used Mean Pixel Accuracy (MAP), Mean Intersection over Union (MIoU), Taylor diagrams, and surface borehole data as metrics to analyze the model’s accuracy. Our results showed that the YOLOv8-Large target detection model performed better than other detection models, with the MAP50 of 0.53. The ResNet34 encoder in the semantic segmentation model demonstrated the highest accuracy of 86.92%, effectively resisting interference, and could identify freeze–thaw with higher accuracy in noisy images. Our study provides a high-resolution pathway to identify freeze/thaw state of frozen soils, which can benefit studies in cryosphere science, hydrology, ecology and climate change.

ABSTRACT: Skeletal muscle development is a complex, regulated physiological process that involves myoblast proliferation and differentiation and the fusion of myotubes. In this study, phenotypic differences in the breast and leg muscles of 180-day-old Jingyuan chickens were investigated. Differentially methylated genes (DMG) that regulate muscle development were identified through differential expression analysis and weighted gene co-expression network analysis. Moreover, myoblasts were used as test material and treated with cycloleucine to investigate the effect of N6-methyladenosine (m6A) modification on their proliferation and differentiation. The results revealed that the myofiber diameter and cross-sectional area in the breast muscle of Jingyuan chickens were significantly smaller than those in the leg muscle, while myofiber density in the breast muscle was significantly higher. A total of 484 DMG were identified in both muscle types. Module gene association analysis with DMGs revealed multiple DMG associated with muscle development. In vitro cell model analysis revealed that cycloleucine treatment significantly downregulated the m6A modification level of myoblasts and inhibited their proliferation and differentiation. Additionally, stage-specific differences in LDHA, LDHB, and GAPDH expressions were observed during myoblast differentiation. Cycloleucine treatment significantly inhibited LDHA, LDHB, and GAPDH expression. These findings indicate that m6A methylation modifications play significant regulatory roles in muscle development, with LDHA, LDHB, and GAPDH being potential candidate genes for regulating muscle development. This study provides an essential theoretical basis for further study on the functional mechanisms of m6A modifications involved in muscle development.

Background This study aimed to evaluate the efficiency of noninvasive prenatal screening (NIPS) technology in screening for microdeletions in the 7q11.23 region.Methods 19,607 pregnant women underwent NIPS in our hospital. Maternal peripheral cell-free foetal DNA (cffDNA) was routinely screened for aneuploidy by cffDNA enrichment and simultaneously analyzed for pathogenic copy number variants (CNVs). The Williams syndrome (WS) 7q11.23 region was targeted in this study. Chromosomal microarray analysis (CMA) was used to verify the screen-positive samples.Results The mean concentration of cffDNA before and after enrichment increased from 9.44% to 19.32%, with a statistically significant difference. Two out of 19,607 samples tested for CNVs were found to have a heterozygous deletion at the 7q11.23 region, indicating a high risk for WS. CMA results confirmed the 1.5 megabase (Mb) deletions at the 7q11.23 region in amniotic fluid samples. One of the two WS foetuses had a small left ventricle by ultrasound screening, and the other did not have a significant cardiovascular abnormality phenotype.Conclusions NIPS screening for Williams syndrome can be achieved by enriching cell-free foetal DNA and improving bioinformatic analysis algorithms.

A large outbreak of monkeypox occurred in 2022, and most people lack immunity to orthopoxvirus. Smallpox vaccination is essential for preventing further smallpox outbreaks. This study evaluated the effectiveness, protection, safety, and cross-immunogenicity of smallpox vaccine in preventing monkeypox infection. PubMed, Embase, Scopus, and Web of Science were searched from database inception to 10 March 2024. We included studies involving “monkeypox virus” and “vaccinations”, and excluded reviews, animal studies, and articles with missing or duplicate data. A total of 37 studies with 57,693 participants were included in the final analysis. The effectiveness data showed that monkeypox infection rates were lower in the smallpox-vaccinated group than in the unvaccinated group (risk ratio [RR]: 0.46; 95% confidence interval [CI]: 0.31–0.68). The protection data showed that smallpox vaccination effectively reduced the risk of severe monkeypox infection (RR: 0.61; 95% CI: 0.42–0.87). Third-generation vaccines showed greater efficacy (RR: 0.36, 95% CI: 0.22–0.56) than first-generation vaccines. The number of doses of smallpox vaccine has no significant effect on monkeypox. Safety data showed that adverse reactions after smallpox vaccination were mainly mild and included local erythema, swelling, induration, itching, and pain. Meanwhile, we found that smallpox vaccination could induce the production of neutralizing antibodies against monkeypox. Our findings offer compelling evidence supporting the clinical application of the smallpox vaccine for preventing monkeypox and advocate that high-risk groups should be prioritized for receiving one dose of the smallpox vaccine if the vaccine stockpile is low.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at −21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.

AbstractPlatelets are terminally differentiated anucleated cells, but they still have cell-like functions and can even produce progeny platelets. However, the mechanism of platelet sprouting has not been elucidated so far. Here, we show that when platelet-rich plasma(PRP) was cultured at 37°C, platelets showed a spore phenomenon. The number of platelets increased when given a specific shear force. It is found that AMP-related signaling pathways, such as PKA and AMPK are activated in platelets in the spore state. Meanwhile, the mRNA expression levels of genes, such as CNN3, CAPZB, DBNL, KRT19, and ESPN related to PLS1 skeleton proteins also changed. Moreover, when we use the AMPK activator AICAR(AI) to treat washed platelets, cultured platelets can still appear spore phenomenon. We further demonstrate that washed platelets treated with Forskolin, an activator of PKA, not only platelet sprouting after culture but also the AMPK is activated. Taken together, these data demonstrate that AMPK plays a key role in the process of platelet budding and proliferation, suggesting a novel strategy to solve the problem of clinical platelet shortage.

ABSTRACTUrban rail transit (URT) systems play an evident role in shaping city spatial structures; however, the principles and mechanisms behind this influence are not fully understood. This paper reviews research progress on the coupling relationship between URT and urban space, focusing on big data analysis methods and the timeliness and sequence of coupling effects. It highlights the importance of the temporal dimension in coupling analysis. By thoroughly exploiting data value and extracting key elements, big data technology imparts temporal attributes to these elements, exploring their interaction and influence mechanisms over different time sequences. The paper also discusses the potential application of big data to urban planning to support sustainable urban development. Finally, the paper outlines future research directions, including the deepened application of big data to urban spatial analysis and the role of new data sources in understanding and shaping the coupling relationship between URT and urban space. This analysis offers new perspectives and methodologies for urban development and transportation planning.

BackgroundThis study aims to improve the solubility and the toxicity of Bufonis venenum, and finally enhance the therapeutic outcomes of hepatocellular carcinoma (HCC).MethodsThe cholesterol-free liposomes simultaneously encapsulate bufadienolides and indolealkylamines (Non-Cholesterol-Bufonis Venenum Extract-Liposome, Non-Chol-BVE-LP) was prepared by the thin-film evaporation technique. In vitro, the cytotoxicity, cell apoptosis study, cellular uptake and hemolysis studies were evaluated in HepG2 cells. In vivo, the biodistribution and anti-tumor activity studies were conducted in BALB/C mice with HepG2 cells.ResultsThe liposomes showed good size distribution, encapsulation efficiency drug loading capacity and slower drug release. Non-Chol-BVE-LP had higher cytotoxicity on HepG2 cells and induced more apoptosis on HepG2 Cells compared with BVE. In addition, the liposomes could accumulate in tumor by passive targeting, thus facilitating the anti-tumor effects. In vivo, Non-Chol-BVE-LP showed equivalent anti-tumor efficacy to the first-line anti-HCC drug sorafenib.ConclusionThe study provided new ideas for the development and clinical application of Bufonis venenum related formulation and offered new drug for the treatment of HCC.

BackgroundWith a growing global population affected by Chronic Obstructive Pulmonary Disease (COPD), the traditional Chinese herbal formula Houpo Mahuang Decoction (HPMHD) has been used for centuries to address respiratory ailments. While studies have demonstrated the therapeutic benefits of HPMHD in COPD, the effective active ingredients, potential targets, and molecular mechanisms underlying its effectiveness remained unclear.MethodsThe mechanisms of action of certain HPMHD components, targets, and pathways for the treatment of COPD were predicted using a network pharmacology method. We induced a COPD mouse model using porcine pancreatic elastase and evaluated the pathological changes and healing processes through HE and Masson staining. Immunofluorescence was used to assess the levels of IL-6 and TNF-ɑ. RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) in the lungs of normal, control, and treated mice, revealing the biological pathways enriched by HPMHD in COPD treatment. Finally, the expression of DEGs was verified using Western blotting and RT-qPCR.ResultsHPMHD effectively alleviated pathological symptoms and improved COPD in mice by modulating the IL-17 signaling pathway. Treatment with HPMHD improved lung morphology and structure, reduced inflammatory cell infiltration, and inhibited IL-6 and TNF-ɑ levels. Network pharmacology and transcriptomics further revealed the mechanism, indicating that the IL-17 signaling pathway might been instrumental in the inhibitory effect of HPMHD on mouse model of COPD. Subsequent experiments, including protein blotting and RT-qPCR analysis, confirmed the activation of the IL-17 signaling pathway by HPMHD in the COPD mouse model, further supporting the initial findings.ConclusionHPMHD was shown to alleviate COPD and reduce lung inflammation in mice, potentially through the activation of the IL-17 signaling pathway. This study provides a novel direction for the development of COPD drugs.