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Abstract In this study, a chromosome-level genome of the tropical sea cucumber Stichopus monotuberculatus was generated by a combination of Nanopore long-read, Illumina short-read, and Hi-C sequencing technologies. The final assembly was 810.54 Mb in length, with contig N50 and scaffold N50 values of 10.15 Mb and 35.36 Mb, respectively. This assembly comprised 23 pseudo-chromosomes, covering 99.82% of the genome. Completeness analysis using BUSCO indicated that 97.8% of the metazoan conserved genes were presented in their entirety. A total of 29,596 protein-coding genes were predicted, with functional annotations available for 94.43% of these genes. The high-quality genome assembly produced in this study may provide an essential foundation for future researches on resource conservation and genetic breeding of S. monotuberculatus.

Abstract Despite the advances in antibody-guided cell typing and mass spectrometry-based proteomics, their integration is hindered by challenges for processing rare cells in the heterogeneous tissue context. Here, we introduce Spatial and Cell-type Proteomics (SCPro), which combines multiplexed imaging and flow cytometry with ion exchange-based protein aggregation capture technology to characterize spatial proteome heterogeneity with single-cell resolution. The SCPro is employed to explore the pancreatic tumor microenvironment and reveals the spatial alternations of over 5000 proteins by automatically dissecting up to 100 single cells guided by multi-color imaging of centimeter-scale formalin-fixed, paraffin-embedded tissue slide. To enhance cell-type resolution, we characterize the proteome of 14 different cell types by sorting up to 1000 cells from the same tumor, which allows us to deconvolute the spatial distribution of immune cell subtypes and leads to the discovery of subtypes of regulatory T cells. Together, the SCPro provides a multimodal spatial proteomics approach for profiling tissue proteome heterogeneity.

Abstract The mucosal immune response plays a crucial role in the prevention of respiratory viruses. Given the risk of recurrent SARS-CoV-2 infections in the population, the rapid development of next-generation intranasal COVID-19 vaccines with high safety and efficacy is paramount. In the current study, we developed a protein-based intranasal vaccine comprising the XBB.1.5 receptor binding domain (RBD)-derived trimeric recombinant protein (RBDXBB.1.5-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBDXBB.1.5-HR vaccine elicited robust and sustained humoral immune responses in mice and rats, resulting in high levels of neutralizing antibodies against XBB-lineage subvariants, with protection lasting for at least six months. The intranasal RBDXBB.1.5-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (TRM) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBDXBB.1.5-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBDXBB.1.5-HR vaccine as a heterologous booster shot showed more effective boosting effects after mRNA administration compared to homologous vaccination, as evidenced by the induction of superior systemic and extra mucosal immune response. Importantly, the intranasal RBDXBB.1.5-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBDXBB.1.5-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.

Abstract This paper introduces three different shapes of wireless charging containers (i.e. quadrangular prism, octagonal prism, and hexagonal prism) and presents optimal current flow designs for the coils to enhance the uniformity of magnetic flux distribution inside the containers. Additionally, the concept of folded coil design is introduced to further improve the even distribution of magnetic flux density within the containers. The performance of these designs is evaluated through simulations and practical experiments.

Abstract Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants. Three cRBDs were designed in our study. Compared with the BA.1 RBD protein, the cRBDs induced the production of higher levels of broader-spectrum neutralizing antibodies, suggesting stronger and broader protective efficacy. In viral challenge experiments, cRBDs were more effective than BA.1 RBD in attenuating lung pathologic injury. Among the three constructs, cRBD3 showed optimal broad-spectrum and protective effects and is a promising candidate for a broad-spectrum SARS-CoV-2 vaccine. In conclusion, immunization with cRBDs triggered immunity against a wide range of variants, including those that emerged after we had completed designing the cRBDs. This study preliminarily explores and validates the feasibility of incorporating hotspot mutations that contribute to immune evasion into the RBD to expand the activity spectrum of antigen-induced antibodies.

Introduction: Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells. Objectives: Introduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus. Methods: The AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging. Results: In vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone. Conclusions: The application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.

Camptothecin (CPT) exhibits potent antitumor activity; however, its clinical application is limited by significant gastrointestinal adverse effects (GAEs). Although the severity of GAEs associated with CPT derivatives has decreased, the incidence rate of these adverse effects has remained high. CPT multifunctional nanoparticles (PCRHNs) have the potential to increase the efficacy of CPT while reducing side effects in major target organs; however, the impact of PCRHNs on the GAEs from CPT remains uncertain. Here, we investigated the therapeutic effects of PCRHNs and different doses of CPT and examined their impacts on the intestinal barrier and the intestinal microbiota. We found that the therapeutic efficacy of PCRHNs + Laser treatment was superior to that of high-dose CPT, and PCRHNs + Laser treatment also provided greater benefits by helping maintain intestinal barrier integrity, intestinal microbiota diversity, and intestinal microbiota abundance. In summary, compared to high-dose CPT treatment, PCRHNs + Laser treatment can effectively balance therapeutic effects and GAEs. A high dose of CPT promotes the enrichment of the pathogenic bacteria Escherichia-Shigella, which may be attributed to diarrhea caused by CPT, thus leading to a reduction in microbial burden; additionally, Escherichia-Shigella rapidly grows and occupies niches previously occupied by other bacteria that are lost due to diarrhea. PCRHNs + Laser treatment increased the abundance of Lactobacillus (probiotics), possibly due to the photothermal effect of the PCRHNs. This effect increased catalase activity, thus facilitating the conversion of hydrogen peroxide into oxygen within tumors and increasing oxygen levels in the body, which is conducive to the growth of facultative anaerobic bacteria.

Abstract Toxoplasma gondii is a significant zoonotic pathogen of toxoplasmosis in humans and animals. Here a live attenuated Toxoplasma vaccine of WH3 Δrop18 was developed. The results showed that all mice vaccinated with WH3 Δrop18 were able to survive when challenge with various strains of Toxoplasma, including RH (type I), ME49 (type II), WH3 or WH6 (type Chinese 1). No cysts, if few, in the brain of the vaccinated animals were seen after challenge with cyst forming strains of ME49 or WH6. Vaccination with the WH3 Δrop18 triggered a strong immune response, including significantly increased level of the cytokines (IFN-γ, IL-12, TNF-α and IL-10) and the activation of CD4+ and CD8+ T-lymphocytes and long term of specific antibodies against Toxoplasma. Our results strongly indicate that vaccine of WH3 Δrop18 might provide effective immune protection against a wide range strains of Toxoplasma infections and be a promising live attenuated vaccine candidate.

Abstract As one of the main occupational hazards, welding fumes can cause oxidative damage and induce series of diseases, such as COPD or asthma. To clarify the effects of the metal fume ultrafine particulates (MF-UFPs) of welding fumes on oxidative damage, UFPs were collected by melt inert gas (MIG) and manual metal arc (MMA) welding, and the composition was confirmed. Human bronchial epithelial 16HBE cells were treated with 0–1000 µg/cm2 MF-UFPs to analyse the cytotoxicity, oxidative stress and cytokines. The protein and mRNA expression of Keap1-Nrf-2/antioxidant response elements (AREs) signalling pathway components were also analysed. After 4 h of treatment, the cell viability decreased 25% after 33.85 and 32.81 µg/cm2 MIG/MMA-UFPs treated. The intracellular ATP concentrations were also decreased significantly, while LDH leakage was increased. The decreased mitochondrial membrane potential and increased ROS suggested the occurrence of oxidative damage, and the results of proteome profiling arrays also showed a significant increase in IL-6 and IL-8. The expression of AREs which related to antioxidant and anti-inflammatory were also increased. These results indicate that the MF-UFPs can cause oxidative stress in 16HBE cells and activate the Nrf-2/ARE signalling pathway to against oxidative damage.

Abstract Hematological malignancies are a group of cancers that affect the blood, bone marrow, and lymphatic system. Cancer stem cells (CSCs) are believed to be responsible for the initiation, progression, and relapse of hematological malignancies. However, identifying and targeting CSCs presents many challenges. We aimed to develop a stemness index (HSCsi) to identify and guide the therapy targeting CSCs in hematological malignancies. We developed a novel one-class logistic regression (OCLR) algorithm to identify transcriptomic feature sets related to stemness in hematologic malignancies. We used the HSCsi to measure the stemness degree of leukemia stem cells (LSCs) and correlate it with clinical outcomes.We analyze the correlation of HSCsi with genes and pathways involved in drug resistance and immune microenvironment of acute myeloid leukemia (AML). HSCsi revealed stemness-related biological mechanisms in hematologic malignancies and effectively identify LSCs. The index also predicted survival and relapse rates of various hematologic malignancies. We also identified potential drugs and interventions targeting cancer stem cells (CSCs) of hematologic malignancies by the index. Moreover, we found a correlation between stemness and bone marrow immune microenvironment in AML. Our study provides a novel method and tool to assess the stemness degree of hematologic malignancies and its implications for clinical outcomes and therapeutic strategies. Our HSC stemness index can facilitate the precise stratification of hematologic malignancies, suggest possible targeted and immunotherapy options, and guide the selection of patients.

Abstract Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems.

Abstract Introduction In percutaneous endoscopic lumbar discectomy (PELD), pain occurs when the posterior longitudinal ligament (PLL) is exposed, removed, and decompressed. However, pain characteristics of the PLL stimulated in PELD have not been reported. Methods A total of 932 patients underwent PELD under local anesthesia. Pain distribution and intensity were recorded on a posterior body diagram during the operation. Pain intensity was assessed by the visual analog scale scores for the back (VAS-B). The PLL specimens were collected and observed using hematoxylin–eosin (HE) staining and immunohistochemistry. Results Patients with lumbar disc herniation (LDH) at L4/5 and L5/S1 had pain foci in different regions. The mean VAS-B scores between the ventral and dorsal sides of the PLL were 6.14 ± 0.97 and 4.80 ± 1.15, respectively (P

Abstract Multi-functional cysteine-targeting covalent warheads possess significant therapeutic potential in medicinal chemistry and chemical biology. Herein, we present novel unsaturated and asymmetric ketone (oxazolinosene) scaffolds that selectively conjugate cysteine residues of peptides and bovine serum albumin under normal physiological conditions. This unsaturated saccharide depletes GSH in NCI-H1299 cells, leading to anti-tumor effects in vitro. The acetyl group of the ketal moiety on the saccharide ring can be converted to other carboxylic acids in a one-pot synthesis. In this way, the loaded acid can be click-released during cysteine conjugation, making the oxazolinosene a potential multifunctional therapeutic agent. The reaction kinetic model for oxazolinosene conjugation to GSH is well established and was used to evaluate oxazolinosene reactivity. The aforementioned oxazolinosenes were stereoselectively synthesized via a one-step reaction of nitriles with saccharides and conveniently converted into a series of α, β-unsaturated ketone N-glycosides as prevalent synthetic building blocks. The reaction mechanisms of oxazolinosene synthesis were investigated through calculations and validated with control experiments. Overall, these oxazolinosenes can be easily synthesized and developed as cysteine-targeted covalent warheads carrying useful click-releasing groups.

Abstract Background Many studies have demonstrated the association between intestinal microbiota and joint diseases. The “gut-joint axis” also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. Results CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. Conclusion Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract

Abstract Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain–Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/β and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.

Fish skin is a multipurpose tissue with important functions—protection, perception, and hormone metabolism—in the fish body. As a byproduct of fish processing, it can be used as a material for extracting collagen, making leather, and related pathological research. However, there have been few reports on the tissue structure of fish skin. This study aimed to analyze the structural characteristics of Thamnaconus septentrionalis fish skin in order to provide a reference for the utilization of its resources. Six T. septentrionalis samples were selected and their skins were observed using frozen sectioning, skeletal, hematoxylin & eosin (H & E), Periodic acid-Schiff (PAS), Masson, Van Gieson (VG) staining, and scanning electron microscopy. The images obtained by slice scanning were analyzed using SlideViewer (3DHISTECH), ImageJ, and Photoshop software. The SEM images were analyzed using ImageJ and Photoshop software. SPSS25.0 software was used to analyze the data of epidermal and squamous layers, conical bone bulge, basal layer, and dermis thicknesses. The results showed that the histological structure of the skin comprised four parts: epidermis, scale layer, dermis, and subcutaneous tissue. The thickness of the epidermal layer was (26.81±7.48) μm. This layer was mainly composed of epithelial and basal cells but also contained a large number of mucus cells. The scale layer consisted of the spine of conical bone and a substrate. The thickness of this layer was (22.49±5.19) μm, and there were two to four rows of the spine of conical bone with different diameters, different bending degrees at the top, and a height of (257.13±10.41) μm unevenly distributed on the base plate. The average thickness of the dermis was (176.97±21.11) μm, and the dermis thickness of the head was lower than that of the middle part of the body, but higher than that of the tail, mainly composed of collagen fiber. The subcutaneous tissue layer was mainly comprised of collagen fibers and non-fibrous stroma. In this study, the histological pattern of the skin of T. septentrionalis was mapped according to its characteristics, providing valuable information for fish skin resource usage.

Antibiotic resistant bacteria (ARB) with antibiotic resistance genes (ARGs) can reduce or eliminate the effectiveness of antibiotics and thus threaten human health. The United Nations Environment Programme considers antibiotic resistance the first of six emerging issues of concern. Advanced oxidation processes (AOPs) that combine ultraviolet (UV) irradiation and chemical oxidation (primarily chlorine, hydrogen peroxide, and persulfate) have attracted increasing interest as advanced water and wastewater treatment technologies. These integrated technologies have been reported to significantly elevate the efficiencies of ARB inactivation and ARG degradation compared with direct UV irradiation or chemical oxidation alone due to the generation of multiple reactive species. In this study, the performance and underlying mechanisms of UV/chlorine, UV/hydrogen peroxide, and UV/persulfate processes for controlling ARB and ARGs were reviewed based on recent studies. Factors affecting the process-specific efficiency in controlling ARB and ARGs were discussed, including biotic factors, oxidant dose, UV fluence, pH, and water matrix properties. In addition, the cost-effectiveness of the UV-based AOPs was evaluated using the concept of electrical energy per order. The UV/chlorine process exhibited a higher efficiency with lower energy consumption than other UV-based AOPs in the wastewater matrix, indicating its potential for ARB inactivation and ARG degradation in wastewater treatment. Further studies are required to address the trade-off between toxic byproduct formation and the energy efficiency of the UV/chlorine process in real wastewater to facilitate its optimization and application in the control of ARB and ARGs.

BackgroundNatural pyrethrins have long been widely used in the fields of environmental and household hygiene. Studies have reported that natural pyrethrins have potential liver toxicity, but their specific mechanisms are still unclear yet. ObjectiveTo explore the effect of natural pyrethrins on DNA damage in human liver cells. MethodsThis study used human liver cell QSG7701 as an in vitro testing model. After exposure to DMSO and a series of concentrations of natural pyrethrins (5, 10, 20, and 40 μg·mL−1) for 6 and 24 h, reactive oxygen species (ROS) was detected by fluorescence microscopy using a fluorescence probe, thiobarbituric acid reactive substance (TBARS) by colorimetric method using a microplate reader, DNA damage by comet assay through observing DNA fragment migration under microscope, and phospho H2AX (γH2AX) and 8-oxoguanine (8-oxoG) by immunofluorescence assay using a laser confocal microscope. ResultsAs the exposure concentration of natural pyrethrins increased, the fluorescence intensity of ROS significantly increased in a concentration-dependent manner. The differences in ROS between the 10 μg·mL−1 and above groups and the control group were statistically significant (P

Abstract Background Aging is a prominent risk factor for diverse diseases; therefore, an in-depth understanding of its physiological mechanisms is required. Nonhuman primates, which share the closest genetic relationship with humans, serve as an ideal model for exploring the complex aging process. However, the potential of the nonhuman primate animal model in the screening of human aging markers is still not fully exploited. Multiomics analysis of nonhuman primate peripheral blood offers a promising approach to evaluate new therapies and biomarkers. This study explores aging-related biomarker through multilayer omics, including transcriptomics (mRNA, lncRNA, and circRNA) and proteomics (serum and serum-derived exosomes) in rhesus monkeys (Macaca mulatta). Results Our findings reveal that, unlike mRNAs and circRNAs, highly expressed lncRNAs are abundant during the key aging period and are associated with cancer pathways. Comparative analysis highlighted exosomal proteins contain more types of proteins than serum proteins, indicating that serum-derived exosomes primarily regulate aging through metabolic pathways. Finally, eight candidate aging biomarkers were identified, which may serve as blood-based indicators for detecting age-related brain changes. Conclusions Our results provide a comprehensive understanding of nonhuman primate blood transcriptomes and proteomes, offering novel insights into the aging mechanisms for preventing or treating age-related diseases.

Abstract Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens, including prolonged circulation in the bloodstream, specific cell recognition and targeting capabilities, and potential for immunotherapy. Herein, we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM NPs. Comprising microporous Prussian blue nanoparticles (MPB NPs) serving as both a photothermal sensitizer and carrier for 3-bromopyruvate (3BP), these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory protein α (SIRPα) with enhanced affinity to CD47. As a result, MPB-3BP@CM NPs inherit the characteristics of the original cell membrane, exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer (CRC) cells. Notably, blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by macrophages. Additionally, 3BP, an inhibitor of hexokinase II (HK2), suppresses glycolysis, leading to a reduction in adenosine triphosphate (ATP) levels and lactate production. Besides, it promotes the polarization of tumor-associated macrophages (TAMs) towards an anti-tumor M1 phenotype. Furthermore, integration with MPB NPs-mediated photothermal therapy (PTT) enhances the therapeutic efficacy against tumors. These advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for CRC. Concurrently, it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.

BackgroundWith advances in medical technologies, more children with chronic diseases are now living on into adulthood. The development of proficient self-management skills is essential for adolescents and young adults to transition from pediatric to adult health care services. An innovative way to improve the current care model and foster self-management skills could be through eHealth or mHealth (mobile health) interventions, in particular, when considering the rising ownership of digital technology by adolescents and young adults. ObjectiveThis systematic review aimed to evaluate the features, acceptability, usability, engagement, and intervention efficacy of eHealth and mHealth interventions that support self-management and health care transition in adolescents and young adults with chronic disease. MethodsThis review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines (registration number CRD42023378355). We systematically searched the MEDLINE complete, Embase, Cochrane Library, CINAHL complete, and ProQuest Health & Medical complete. We considered only articles published in or since 2019, as we aimed to extend the data collected by 2 previous systematic reviews. ResultsA total of 16,752 studies were screened. After removing duplicates, 14,507 studies were excluded based on the title and abstract. Ultimately, 22 studies were included. The interventions ranged from simple text messages to complex interventions involving web-based games and engagement of health care providers, which were summarized into 6 themes: medication monitoring and reminders, symptom tracking and monitoring, management goal setting, knowledge education and self-management skills training, incentives and reinforcement, and communication. Most adolescents and young adults felt the eHealth and mHealth interventions were feasible, as they were convenient, easy to use, and accessible in the context of helping manage their health. However, user engagement was variable and presented a gradual decline in youth engagement with these apps over time. Barriers that prevent user engagement are diverse, such as time-consuming video uploads, noncontinuous access to a phone, reading literacy levels, language, and false impressions. Moreover, adolescents and young adults had different preferred styles of message delivery and functions, especially the engaging elements, disease-specific information, and opportunities to communicate with peers, health care providers, and app teams. ConclusionsThere remains limited data about the effectiveness of eHealth and mHealth interventions facilitating the self-management and health care transition of adolescents and young adults with chronic diseases. Based on the available evidence, they were receptive to and interested in receiving information and managing their health using mobile apps or websites. Considering adolescents and young adults had different preferred styles of message delivery and features, to improve user engagement and provide focused interventions, it would be better to involve them early in the design process to identify their specific needs, as well as collaborate with health care providers and app teams to obtain suggestions.

The pathogenesis of liver diseases is multifaceted and intricate, posing a persistent global public health challenge with limited therapeutic options. Therefore, further research into liver diseases is imperative for better comprehension and advancement in treatment strategies. Numerous studies have confirmed the endoplasmic reticulum (ER) and mitochondria as key organelles driving liver diseases. Notably, the mitochondrial-associated ER membranes (MAMs) establish a physical and functional connection between the ER and mitochondria, highlighting the importance of inter-organelle communication in maintaining their functional homeostasis. This review delves into the intricate architecture and regulative mechanism of the integrated MAM that facilitate the physiological transfer of signals and substances between organelles. Additionally, we also provide a detailed overview regarding the varied pathogenic roles of malfunctioning MAM in liver diseases, focusing on its involvement in the progression of ER stress and mitochondrial dysfunction, the regulation of mitochondrial dynamics and Ca2+ transfer, as well as the disruption of lipid and glucose homeostasis. Furthermore, the current challenges and prospects associated with MAM in liver disease research are thoroughly discussed. In conclusion, elucidating the specific structure and function of MAM in different liver diseases may pave the way for novel therapeutic strategies.

The functionalized polymer with scalable properties presents a promising option for flexible triboelectric nanogenerators designed for detecting human motion. In this study, a novel method to fabricate tribopositive composite film was proposed by incorporating high permittivity N-doped orange peel-based carbon dots (O-CDs) into the highly cross-linked polyvinyl alcohol (PVA). The O-CDs/PVA sensor showed elevated electrical output with the raised content of O-CDs until 1.5 wt. % with a peak voltage of 3.5 V. The response characteristics under various external force conditions were tested, and the maximum peak voltage and current reached 3.92 V and 28.6 A under the force of 50 N. Moreover, O-CDs/PVA sensors present superior high-output stability, durability, and accurate distinction to different movement states, even the vocal cord vibration. By introducing the support vector machine learning algorithm, intelligent gesture recognition was achieved. This work paves a facile, feasible, and scalable pathway to the self-powered human motion sensor device.

Abstract Understanding the impact of climate change on the geographical distribution of species is a fundamental requirement for biodiversity conservation and resource management. Quercus oxyphylla, an evergreen oak endemic to China, plays a crucial role in maintaining the ecological stability in subtropical regions and high economic value attributed to its dark and high‐density heartwood, but the existing resources are close to endangered. Currently, limited knowledge exists regarding its distribution and potential influences of climate change on suitable areas. This study utilized 63 occurrence records and Biomod2 platform, to predict changes in suitable areas for Q. oxyphylla under future climate change. The results revealed that (1) Q. oxyphylla showed a pattern of three disjunctive geographical centers in the eastern subregion of subtropical evergreen broad‐leaved forest region (IVA): Qinling‐Daba Mountains, Nanling Mountains and Wuyi Mountains center. Currently, the highly suitable areas concentrated in two zones divided by the Yangtze River, that is, the northern subtropical evergreen and deciduous broad‐leaved forest zone (IVAii) and the mid‐subtropical evergreen broad‐leaved forest zone (IVAi). (2) The temperature‐related variables, such as annual temperature range (Bio7), the mean diurnal range (Bio2), and annual mean temperature (Bio1), were identified as the key determinants of the distribution pattern. Because of its considerable climatic variations in temperature and water conditions, Q. oxyphylla's habitat displayed a wider climate niche and strong physiological tolerance to climate change. (3) Under future climate scenarios, the suitable area of the species was expected to overall expand with significant regional differences. The suitable area in IVAi was expected to expand significantly northward while that in IVAii was expected to gradually shrink. To address the impact of climate change, it is necessary to develop conservation plans focused around the three distribution centers, implement localized and regional conservation policies, and conduct educational outreach among local people.

Abstract Olverembatinib (HQP1351) is a BCR‐ABL1 tyrosine kinase inhibitor with promising clinical activity. It is approved in China for the treatment of patients with chronic myeloid leukemia harboring drug‐resistant mutations, such as T315I. In vitro studies suggested that metabolism of olverembatinib is primarily mediated by cytochrome P450 (CYP3A4). The effects of CYP3A4 inhibition and induction on the pharmacokinetics of olverembatinib were evaluated in an open‐label, 2‐part, fixed‐sequence study in healthy volunteers. In Part 1 of this study, 16 participants received a single oral dose of olverembatinib (20 mg) and the oral CYP3A4 inhibitor itraconazole (200 mg). In Part 2, 16 participants received a single oral dose of olverembatinib (40 mg) and the oral CYP3A4 inducer rifampin (600 mg). To measure pharmacokinetic parameters, serial blood samples were collected after administration of olverembatinib alone and combined with itraconazole or rifampin. Coadministration of olverembatinib with itraconazole increased the peak plasma concentration of olverembatinib, its area under the time‐concentration curve (AUC)0‐last, and AUC0‐inf by 75.63%, 147.06%, and 158.66%, respectively. Coadministration with rifampin decreased these same variables by 61.27%, 74.21%, and 75.19%, respectively. These results confirm that olverembatinib is primarily metabolized by CYP3A4 in humans, suggesting that caution should be exercised with concurrent use of olverembatinib and strong CYP3A4 inhibitors or inducers.

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43 mg/L of the cured group and the 12.07 ± 2.68 mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138 mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537 mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138 mg/L) on day 5 after dosing.

The Forchheimer equation is one of the basic equations widely used in non-Darcy seepage. The determination of coefficients A and B in the equation has always been a hotspot and difficulty in the field of porous media seepage. Different studies have proposed various empirical formulas for the coefficients A and B from seepage experiments. However, there are few studies evaluating the applicability of each empirical formula under homogeneous condition and heterogeneous with mixed particle size. In this study, to provide basic information for selecting the empirical formula of the Forchheimer equation under different porous media conditions, the normalized objective function (NOF) and linear regression method are used to evaluate the applicability of the empirical formula of the Forchheimer equation, on the basis of the seepage resistance experiment. The results show that: for homogeneous porous media, Sidiropoulou’s formula has a good prediction effect on hydraulic gradient. For the porous media mixed two kinds of particle size, the mass ratio and size factors of the mixed particle size should be considered based on the average particle size. The prediction effect of the Macdonald formula is slightly affected by the mass ratio and the mixed particle size; while the predicted hydraulic gradient from the Kadlecan and Knight formula is relatively stable. As to the porous media mixed five kinds of particle size, the predictive effect of using d60 as the characteristic particle size is fine.The Kadlecan and Knight formula is suitable to predict coefficient A, and the Ergun formula is effective to predict coefficient B. This study can provide a basis for selecting the Forchheimer equation for seepage of homogeneous and heterogeneous loose sand and gravel porous media in engineering.

Abstract Background The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). Results Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. Conclusions Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

Abstract Background Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse outcomes in both mothers and their children. After delivery, women who experience GDM are also at higher risk of both subsequent GDM and type 2 diabetes mellitus (T2DM) than those who do not. Therefore, healthcare providers and public health practitioners need to develop targeted and effective interventions for GDM. In this study, we aimed to explore the perceptions regarding health behaviors and related factors during the inter-pregnancy period among Chinese women with a history of GDM through the lens of the theory of planned behavior (TPB). Methods Between December 2021 and September 2022, 16 pregnant Chinese women with a history of GDM were purposively recruited from a tertiary maternity hospital in Shanghai for face-to-face semi-structured interviews. They were asked questions regarding their health behaviors and related factors. The transcribed data were analyzed using a directed qualitative content analysis method based on the theory of TPB. Results The health-related behaviors of the women varied substantially. We identified five domains that influenced women’s behaviors according to TPB constructs and based on the data collected: behavioral attitude (perceived benefits of healthy behaviors and the relationship between experience and attitude towards the oral glucose tolerance testing); subjective norms (influences of significant others and traditional cultural beliefs); perceived behavior control (knowledge of the disease, multiple-role conflict, the impact of COVID-19, an unfriendly external environment and difficulty adhering to healthy diets), incentive mechanisms (self-reward and external incentives); preferences of professional and institutional support (making full use of social media platform and providing continuous health management). Conclusions The health-related behaviors of women with a history of GDM were found to be affected by multiple factors. Healthcare professionals are recommended to provide women with sufficient information regarding the disease and to take advantage of the power of the family and other social support networks to improve women’s subjective norms and to promote the adoption of a healthy lifestyle.

Abstract Purpose The aim of this study was to investigate the clinical efficacy of full endoscopic lumbar annulus fibrosus suture in the treatment of single-segment lumbar disc herniation (LDH). Methods The clinical data of patients with single-segment LDH who underwent full endoscopic lumbar discectomy from January 2017 to January 2019 in our hospital were retrospectively analysed. Patients with full endoscopic lumbar discectomy combined with annulus fibrosus suture were divided into group A, and those with simple full endoscopic lumbar discectomy were divided into group B. The general information, surgery-related data, visual analog scale (VAS), Oswestry disability index (ODI), modified MacNab score at the last follow-up, reoperation rate and recurrence were compared between the two groups. Results All patients were followed up for 12 to 24 months, and the surgical time was 133.6 ± 9.6 min in group A and 129.0 ± 11.7 min in group B. The difference was not statistically significant (p > 0.05). The blood loss of group A was higher than that of group B, and the difference was statistically significant when comparing the groups (p 0.05). The excellent rate of MacNab at the last follow-up in the two groups were 93.55% and 87.80%, respectively, with no statistically significant difference (p > 0.05). At the last follow-up, the recurrence rate of group A was significantly lower than that of group B, and the difference was statistically significant (p 0.05). Conclusions Full endoscopic lumbar discectomy combined with annulus fibrosus repair reduces the postoperative recurrence rate and achieves satisfactory clinical outcomes.

Aim: The aim of this study was to provide a comprehensive overview of floating hip injury and attempt to provide a management algorithm. Methods: PubMed was searched using the terms ‘Floating hip’ or ‘acetabular fracture’ and ‘Ipsilateral femoral fracture’ or ‘pelvic fracture’ and ‘Ipsilateral femoral fracture’. One author performed a preliminary review of the abstracts and references of the retrieved articles. Results: The mean injury severe score reported was higher than 20. Chest and abdominal injuries, as well as fractures at other sites, were the most common associated injuries. Despite the high disability rate, surgery remained the preferred option for managing these injuries. The surgical timing varied from a few hours to several days and was subjected to the principles of damage control orthopedics. Although, in most cases, fixation of femoral fractures took precedence over pelvic or acetabular fractures, there was still a need to consider the impact of damage control orthopedics, associated injuries, and surgeon's considerations and preferences. Posttraumatic arthritis, neurological deficits, heterotopic ossification, femoral head necrosis, femoral nonunion, and limb inequality were common complications of the floating hip injury. Conclusions: The severity of such injuries often exceeds that of an isolated injury and often requires specialized multidisciplinary treatment. In the management of these complex cases, the complexity and severity of the injury should be fully assessed, and an appropriate surgical plan should be developed to perform definitive surgery as early as possible, with attention to prevention of complications during the perioperative period.

Abstract Mesonephric-like adenocarcinoma is a new class of rare subtypes of the female reproductive system. Its clinical symptoms are similar to other types of ovarian tumors. The diagnosis is based on pathological and immunohistochemical methods. The main treatment option is surgery combined with chemotherapy. Few cases have been reported at home and abroad. We reported a case of a 45-year-old woman with a cystic solid mass in the left adnexa. The postoperative pathological diagnosis was mesonephric-like adenocarcinoma of the left ovary and mature cystic teratoma (partial infiltration of the small intestine). This case had no specific clinical symptoms. Immunohistochemical findings showed positive results of GATA3, TTF1, CD10, ER, and PR. Paclitaxel and carboplatin chemotherapy were given after the operation. Currently, no specific criteria are available for diagnosis and treatment of the disease. This article aims to improve the understanding of clinicians in this disease and create a basis for clinical diagnosis and treatment.

Characterization of the mechanical properties plays an essential role in the post-processing and evaluation of the functionality of the additively manufactured metallic parts. A number of studies have been focused on the tensile properties of additively manufactured metals. However, the quasi-static compression test of the additively manufactured 316L blocks with different heat-treatment conditions and scanning strategies seems to be overlooked in the literature. This paper aims to provide a comprehensive study of compressive mechanical response in plastic deformation of SS316L fabricated by selective laser melting (SLM). The mechanical response and microstructures in compressive deformation is analyzed for three printing strategies with 0°-, 90°- and 67.5°- scanning and three heat treatment conditions (450 °C for 3 h, 1100 °C for 1 h with furnace cool and 1100 °C for 1 h with water quenching) for selective laser melted (SLMed) stainless steel 316L in comparison with wrought stainless steel 316L in this work. Alteration of mechanical properties, microstructure evolution and compressive deformation mechanism is studied. Melt pool features are not significantly affected by low-temperature heat treatment (450 °C for 3 h) but fully dissolved through high-temperature heat treatment (1100 °C for 1 h). High-temperature heat treatment provides a higher resistance to compressive plastic deformation for SLMed 316L compared with the low-temperature heat-treated and as-built samples where more twinnings are observed. The compressive plastic deformation mechanism of 90°- and 67.5°-scanning samples is similar, which mainly results from twinning-induced plasticity. For 0°-scanning samples, the strong crystallographic texture is the main cause of anisotropic deformation. Modelling and simulation have been conducted to explain the anisotropic deformation mechanism of the 0°-scanning strategy. Simulation results suggest that the morphology difference of laser-scanning tracks and melt pools, which leads to material flow along the laser scanning direction, explains the anisotropic deformation mechanism.

Agarwood is a rare and valuable heartwood derived from Aquilaria sinensis in China. Compared with ordinary germplasm, Chi-Nan, a special germplasm of A. sinensis, has a better agarwood-producing capacity. However, the mechanisms underlying their different qualities remain poorly characterized. Here, a comparative transcriptome analysis of Chi-Nan and ordinary A. sinensis was carried out to investigate the wound responses of both germplasms. A total of 198.19 Gb of clean data were obtained with an average of 6.61 Gb of clean reads for each sample. By comparing with their control groups, more differentially expressed genes (DEGs) were observed in Chi-Nan germplasm. Kyoto Encyclopedia of Genes and Genomes (KEGG) and expression profile analysis suggested that Chi-Nan possesses a stronger ability to respond to wounding. Furthermore, the enrichment of biosynthetic pathways related to sesquiterpenes and 2-(2-phenylethyl) chromones (PECs) were more significant in Chi-Nan than in ordinary germplasm, and related genes showed significantly higher up-regulation in Chi-Nan after wounding. Sixteen candidate genes presumably involved in biosynthesis of agarwood components were identified and found to exhibit higher up-regulation in Chi-Nan than in ordinary germplasm in response to wounding. Overall, these results are helpful in explaining reasons for the higher agarwood-producing properties of Chi-Nan, and contribute to a further understanding of the mechanism of agarwood formation in A. sinensis.

Microsatellite DNA (SSR) is extensively used as molecular markers in diverse fields, including molecular ecology, conservation biology, and molecular breeding. Nevertheless, the efficient and easy acquisition of high-quality SSR molecular markers for economically cultured marine animals remains a challenge. Holothuria leucospilota is an economically and ecologically important tropical sea cucumber. Recently, artificial breeding and cultivation of this species have been reported. However, there is still a lack of highly polymorphic SSR molecular markers for geographical population differentiation and genetic breeding. This study aims to develop and utilize SSR markers from genomic data to assess the genetic variation and population structure of H. leucospilota in the South China Sea. A comprehensive pipeline was created, integrating microsatellite discovery, primer design, and assessment into a single platform. Through this, 15 highly polymorphic microsatellite loci were identified and validated. The results revealed high genetic diversity and low genetic differentiation among H. leucospilota populations. Larval dispersal and ocean currents in the South China Sea were identified as the primary factors influencing genetic connectivity between populations. In addition, the artificial culture and releasing of H. leucospilota have influenced the genetic structure of their wild populations in the South China Sea. This study provides a pipeline for identifying SSR markers within genome data, and applies it to assess the genetic diversity and structure of H. leucospilota. The outcomes of this research are expected to be beneficial and applicable to the future aquaculture of tropical sea cucumbers.

Efficient monitoring and recognition of movement are crucial in enhancing athletic performance. Traditional methods have limitations in terms of high site requirements and power consumption, making them unsuitable for long-term tracking and monitoring. A potential solution to low-power monitoring of body area networks is triboelectric sensors. However, the current analysis method for badminton triboelectric sensing data is relatively simple, while flexible, triboelectric sensors based on 3D printing face issues such as discomfort when joints are bent or twisted in a large range. In light of this, a flexible arch-shaped triboelectric sensor based on 3D printing (FA-Sensor) is proposed. By combining neural network algorithms with the signal acquisition module and the master computer, an intelligent multi-sensor node system for badminton monitoring is established. The FA-Sensor exhibits high sensitivity to bending and twisting motions due to its elastic TPE shell and arched shape design. It minimizes interference with human motion during bending (10°–150°) or twisting (20°–100°) over a wide range. The peak output voltage of the FA-Sensor demonstrates a clear functional relationship with the bending angle, exhibiting piecewise sensitivities of 7.98 and 29.28 mV/°, respectively. For seven different parts of the human body, it can be quickly customized to different sizes, with stable and repeatable response outputs. In application, the badminton sports monitoring system enables real-time feedback and recognition of four typical technical movements, achieving a recognition accuracy rate of 97.2%. The system enables athletes to analyze and enhance badminton technology while also exhibiting promising potential for application in other intelligent sports domains.

Agarwood is a valuable traditional medicine and fragrance. The production process is a typical injury-induced defense response. Currently, there are approximately 22 known species in the genus Aquilaria Lam., all of which can produce agarwood, whereas there are only two legal species of traditional Chinese medicinal agarwood, Aquilaria sinensis (Lour.) Spreng. and Aquilaria agallocha (Lour.) Roxb. The Taiwan herbal Pharmacopoeia of China stipulates that the medicinal agarwood species are A. sinensis and its relatives in the same genus. Moreover, there are five species of agarwood available for clinical medicinal use in Japan, including A. agallocha and A. sinensis, which are often confused with each other or used in a mixed way in the trade process. Therefore, accurate identification of traditional Chinese medicinal agarwood species is important to ensure the authenticity of traditional medicines and to guide the safety of clinical medication. In this study, 59 specific single-nucleotide polymorphism loci were screened and obtained from the chloroplast genomes of 12 species of the genus Aquilaria Lam. We established an identification method for traditional Chinese medicinal agarwood using mini-barcoding combined with high-resolution melting (HRM) and designed and validated 10 pairs of primers from the psbM-trnD, psbA, rps16, petN, ndhE-psaC, rps4, atpE, ycf1, rps15-trnN, and matK regions. The amplification products were all less than 200 bp, with a high success rate of amplification. The method was applied to successfully identify traditional Chinese medicinal agarwood species from commercial agarwood samples. Overall, the sensitivity of this method was sufficient to detect 1% of adulterants in medicinal agarwood products, proving that mini-barcoding HRM is a powerful and flexible tool. This method can be used as a fast and effective high-throughput method for authenticity testing of traditional Chinese medicinal agarwood and its raw materials containing agarwood-containing proprietary Chinese medicines and is recommended for industrial applications.

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application has introduced new challenges, such as safety concerns, off-target toxicities, and significant costs. Natural killer (NK) cells are crucial components of the innate immune system, capable of eliminating tumor cells without prior exposure to specific antigens or pre-activation. This inherent advantage complements the limitations of T cells, making CAR-NK cell therapy a promising avenue for hematological tumor immunotherapy. In recent years, preclinical and clinical studies have yielded preliminary evidence supporting the safety and efficacy of CAR-NK cell therapy in hematological malignancies, paving the way for future advancements in immunotherapy. This review aims to succinctly discuss the characteristics, significant therapeutic progress, and potential challenges associated with CAR-NK cell therapy.

BackgroundImatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system.MethodsWe retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi’an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores.ResultsThe area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778–0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P

Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

Coix seed (CS) has high nutritional value, but the deep processing of CS is relatively limited. Sprouting can significantly improve nutritional value, laying the foundation for efficient consumption or further processing. The optimal conditions for the germination of CS are a soaking temperature of 36 °C for 10 h and a germination temperature of 29 °C for 24 h. Under these conditions, the final germination rate of CS reached 90%. Additionally, the content of γ-aminobutyric acid was 21.205 mg/100 g; soluble protein, free amino acids, γ-aminobutyric acid, and other essential substances increased in CS. Especially after germination, the γ-aminobutyric acid (GABA) content increased by 7.8 times compared with the GABA content of ungerminated CS. Therefore, the nutritional value and flavor of germinated CS are better than those of ungerminated ones, which establishs a solid foundation for its application in developing various products such as compound health drinks, coix yogurt, and others.

Abstract Liver cancer is a major malignant tumor, which seriously threatens human health and increases the economic burden on patients. At present, gene therapy has been comprehensively studied as an excellent therapeutic measure in liver cancer treatment. Oncolytic virus (OV) is a kind of virus that can specifically infect and kill tumor cells. After being modified by genetic engineering, the specificity of OV infection to tumor cells is increased, and its influence on normal cells is reduced. To date, OV has shown its effectiveness and safety in experimental and clinical studies on a variety of tumors. Thus, this review primarily introduces the current status of different genetically engineered OVs used in gene therapy for liver cancer, focuses on the application of OVs and different target genes for current liver cancer therapy, and identifies the problems encountered in OVs-based combination therapy and the corresponding solutions, which will provide new insights into the treatment of liver cancer.

Abstract Tumor immunotherapy, which targets immune checkpoints, presents a promising strategy for the treatment of various cancer types. However, current clinical data indicate challenges in its application to solid tumors. Recent studies have revealed a significant correlation between the degree of immune response in immunotherapy and the tumor microenvironment, particularly with regard to tumor-infiltrating immune cells. Among these immune cells, macrophages, a critical component, are playing an increasingly vital role in tumor immunotherapy. This review focuses on elucidating the role of macrophages within solid tumors and provides an overview of the progress in immunotherapy approaches centered around modulating macrophage responses through various immune factors. Video Abstract

In recent years, several small and rich lithologic oil and gas reservoirs have been discovered in the saline lacustrine beach bar sand in the Qaidam Basin. In order to expand the exploration scale of lithologic oil and gas reservoirs, find new exploration targets and zones, and increase storage and production of oilfields, based on coring, logging and seismic data, the controlling factors of oil and gas accumulation in lithologic reservoirs are defined, and some exploration succeeding fields of lithologic reservoirs are pointed out. The results show that: The southwestern Qaidam Basin has four favorable conditions for the formation of lithologic reservoirs. The first is the development of three stable ancient slopes, namely, the Qigequan-Hongliuquan, Shaxi-Yuejin, and Zahaquan-Wunan, which are inherited and conducive to the accumulation of oil and gas. The second is the proximity of two hydrocarbon generation centers, Hongshi and Zahaquan, with superior oil source conditions. The third is that the salt lake basin developed large braided river delta, widely distributed shoal-bar sand and algal hill-gray cloud flat deposits, forming two complementary types of reservoirs of clastic rock and carbonate rock. The fourth is the development of a variety of drainage systems, which can form several sets of oil-bearing strata vertically. Controlled by paleo-structural, sedimentary and diagenetic factors, there are four types of lithologic reservoirs in the southwestern Qaidam Basin: updip pinching out, sandstone lens, physical sealing and dolomitization trap. Lithologic reservoirs are controlled by three factors: paleo-structure, high-quality source rock and effective reservoir. Paleo-structure determines the type of lithologic traps and the direction of hydrocarbon migration. The high-quality source rock controls the distribution and scale of lithologic reservoirs and effective reservoir controls the accumulation of lithologic reservoirs. Comprehensive evaluation shows that the braided river delta front sand body is a favorable area for the exploration of lithologic reservoirs in the lower Ganchaigou Formation of the Lower Paleogene, mainly distributed in the basin dip end of Shaxi, Gasi, and Wunan. The dolomitization trap is a favorable area for exploration of lithologic reservoirs in the upper member of lower Ganchaigou Formation of Paleogene, mainly distributed around the Hongshi Sag. The widely distributed beach bar is a favorable area for lithologic oil exploration in the upper Ganchaigou Formation and lower Youshashan Formation of Neogene, mainly distributed in Yingxiongling, Gasi, Zhahaquan, Wunan, and other areas. This understanding supports a series of major breakthroughs in lithologic exploration, such as well Qietan 2 and the new series of Gasi, with important guiding significance for further exploration of lithologic reservoirs in the southwestern Qaidam Basin.

Abstract Retention time (RT) alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based proteomic and metabolomic experiments, especially for large cohort studies. The most popular alignment tools are based on warping function method and direct matching method. However, existing tools can hardly handle monotonic and non-monotonic RT shifts simultaneously. Here, we develop a deep learning-based RT alignment tool, DeepRTAlign, for large cohort LC-MS data analysis. DeepRTAlign has been demonstrated to have improved performances by benchmarking it against current state-of-the-art approaches on multiple real-world and simulated proteomic and metabolomic datasets. The results also show that DeepRTAlign can improve identification sensitivity without compromising quantitative accuracy. Furthermore, using the MS features aligned by DeepRTAlign, we trained and validated a robust classifier to predict the early recurrence of hepatocellular carcinoma. DeepRTAlign provides an advanced solution to RT alignment in large cohort LC-MS studies, which is currently a major bottleneck in proteomics and metabolomics research.

AbstractContext Fructus Ligustri Lucidi (FLL), a commonly used herb of traditional Chinese medicine (TCM), is the fruit of Ligustrum lucidum Ait. (Oleaceae). The ethanol extract of FLL is a potential candidate for preventing and treating postmenopausal osteoporosis (PMOP) by nourishing the liver and kidneys.Objective This study determines whether an ethanol extract of FLL has anti-osteoporotic effects in ovariectomized (OVX) mice and explores the underlying mechanism.Materials and methods The OVX model of eight-week-old C57BL/6J female mice was taken, and ovariectomy was used as PMOP. Mice were divided into five groups: sham-operated group (n = 10), OVX group (n = 10), OVX + E2 group (n = 10; 0.039 mg/kg), OVX + FLL group (n = 10; 2 g/kg) and OVX + FLL group (n = 10; 4 g/kg). Mice were treated by gavage with FLL or CMCNa once daily for 8 weeks. We harvested uteri, femur, and tibias from mice; bone mineral density (BMD) and bone microstructure were obtained by X-ray absorptiometry and micro-CT. Furthermore, the effect of FLL on the balance of osteoblast and adipocyte differentiation was investigated using bone marrow mesenchymal stem cells (BMMSCs).Results The results indicated that FLL did not affect OVX-induced estradiol reduction. Compared with OVX mice, FLL significantly increased BMD (63.54 vs. 61.96), Conn. D (86.46 vs. 57.00), and left tibial strength (13.91 vs. 11.27), decreased Tb. Sp (0.38 vs. 0.44) and body fat content (4.19% vs. 11.24%). FLL decreased osteoclast activity and enhanced RUNX2 expression; inhibited perilipin peroxisome proliferator-activated receptor gamma (PPARγ) expression and adipocyte differentiation from BMMSCs.Conclusions FLL prevented additional bone loss and improved bone microstructure in OVX mice by modulating bone and fat balance, suggesting that FLL might be a therapeutic agent for PMOP.

AbstractContext Da-Yuan-Yin is a Chinese traditional prescription.Objective This study explores the therapeutic effects of the Da-Yuan-Yin decoction polyphenol fraction (DYY-4) on acute lung injury (ALI) in mice induced by lipopolysaccharide (LPS).Materials and methods The mice (n = 10) were orally administrated with DYY-4 (15, 30, and 60 mg/kg) or DXM (5 mg/kg), half an hour after LPS (2 mg/kg) instilled intratracheally. The protein content and the levels of inflammatory factors, the levels of complements, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the level of myeloperoxidase (MPO) and superoxide dismutase (SOD), the expression of the IkB kinase (IKK) and nuclear factor-kappa B (NF-κB), the lung wet-to-dry weight (W/D) ratio and lung tissue were evaluated, 24 h after LPS challenge. Network pharmacology predicted potential targets.Results DYY-4 (30, 60 mg/kg, p