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Abstract Background Although numerous endophytic bacteria have been isolated and characterized from cadmium (Cd) hyperaccumulators, the contribution and potential application of the core endophytic microbiomes on facilitating phytoremediation were still lack of intensive recognition. Therefore, a 2-year field sampling in different location were firstly conducted to identify the unique core microbiome in Cd hyperaccumulators, among which the representative cultivable bacteria of different genera were then selected to construct synthetic communities (SynComs). Finally, the effects and mechanisms of the optimized SynCom in regulating Cd accumulation in different ecotypes of Sedum alfredii were studied to declare the potential application of the bacterial agents based on core microbiome. Results Through an innovative network analysis workflow, 97 core bacterial taxa unique to hyperaccumulator Sedum was identified based on a 2-year field 16S rRNA sequencing data. A SynCom comprising 13 selected strains belonging to 6 different genera was then constructed. Under the combined selection pressure of the plant and Cd contamination, Alcaligenes sp. exhibited antagonistic relationships with other genera and plant Cd concentration. Five representative strains of the other five genera were further conducted genome resequencing and developed six SynComs, whose effects on Cd phytoremediation were compared with single strains by hydroponic experiments. The results showed that SynCom-NS comprising four strains (including Leifsonia shinshuensis, Novosphingobium lindaniclasticum, Ochrobactrum anthropi, and Pseudomonas izuensis) had the greatest potential to enhance Cd phytoremediation. After inoculation with SynCom-NS, genes related to Cd transport, antioxidative defense, and phytohormone signaling pathways were significantly upregulated in both ecotypes of S. alfredii, so as to promote plant growth, Cd uptake, and translocation. Conclusion In this study, we designed an innovative network analysis workflow to identify the core endophytic microbiome in hyperaccumulator. Based on the cultivable core bacteria, an optimized SynCom-NS was constructed and verified to have great potential in enhancing phytoremediation. This work not only provided a framework for identifying core microbiomes associated with specific features but also paved the way for the construction of functional synthetic communities derived from core microbiomes to develop high efficient agricultural agents. Video Abstract

Abstract Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

Abstract Gliomas are aggressive brain tumors associated with poor prognosis and limited treatment options due to their invasive nature and resistance to current therapeutic modalities. Research suggests that exosomal microRNAs have emerged as key players in intercellular communication within the tumor microenvironment, influencing tumor progression and therapeutic responses. Exosomal microRNAs (miRNAs), small non-coding RNAs, are crucial in glioma development, invasion, metastasis, angiogenesis, and immune evasion by binding to target genes. This comprehensive review examines the clinical relevance and implications of exosomal miRNAs in gliomas, highlighting their potential as diagnostic biomarkers, therapeutic targets and prognosis biomarker. Additionally, we also discuss the limitations of current exsomal miRNA treatments and address challenges and propose future directions for leveraging exosomal miRNAs in precision oncology for glioma management.

Abstract Background This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship . Methods A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation. Results During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = − 0.346, P

Abstract Prolonged disorder of consciousness (DoC) is a rising challenge. Pediatric data on diagnosis and prognosis of prolonged DoC were too limited and heterogeneous, making it difficult to define the natural course and evaluate the prognosis. The present study explored the emergence from the Minimally Conscious State (eMCS) incidence at different months postinjury drawing the natural course, and detected the predictors of the incidence in children with prolonged DoC. A hospital-based prospective cohort study was conducted. Kaplan–Meier curves, as well as univariate and multivariate COX regression analysis, were performed. The study enrolled 383 pediatric DoC individuals, including 220 males (57.4%), with an average age of 3.9 (1.9–7.3) years. The median duration between onset and rehabilitation is 30.0 (21.0–46.0) days. At enrollment, the ratio of vegetative state/unresponsive wakefulness syndrome (VS/WUS) to MCS is 78.9%–21.1%. Traumatic brain injury and infection are the major etiologies (36.8% and 37.1%, respectively), followed by hypoxia cerebral injury (12.3%). For children with prolonged DoC, the cumulative incidence of eMCS at months 3, 6, 12, and 24 was 0.510, 0.652, 0.731, 0.784 VS 0.290, 0.418, 0.539, 0.603 in the traumatic VS non-traumatic subgroup, respectively. For children in a persistent vegetative state (PVS), the cumulative incidence of emergence at months in 3, 6, 12, 24, 36 and 48 was testified as 0.439, 0.591, 0.683, 0.724, 0.743 and 0.743 in the traumatic subgroup, and 0.204, 0.349, 0.469, 0.534, 0.589 and 0.620 in the non-traumatic subgroup. Participants who exhibit any of the following four demographical and/or clinical characteristics—namely, older than 4 years at onset, accepted rehabilitation within 28 days of onset, remained MCS at enrollment, or with etiology of traumatic brain injuries—had a significantly positive outcome of consciousness recovery (eMCS). Moreover, both prolongation of the central somatosensory conductive time (CCT) (level 2) and absence of N20 (level 3) independently predict a negative outcome. In children with prolonged DoC, we found that 12 months postinjury was critical to eMCS, and a preferred timepoint to define chronic vegetative state (VS). The characteristics including age, etiology, time before rehabilitation, consciousness state, and SEP results were useful predictors of conscious recovery. Trial registration Registered 06/11/2018, the registration number is chiCTR1800019330 (chictr.org.cn). Registered prospectively.

Abstract Purpose To build an Mult-Task Learning (MTL) based Artificial Intelligence(AI) model that can simultaneously predict clinical stage, histology, grade and LNM for cervical cancer before surgery. Methods This retrospective and prospective cohort study was conducted from January 2001 to March 2014 for the training set and from January 2018 to November 2021 for the validation set at Beijing Chaoyang Hospital, Capital Medical University. Preoperative clinical information of cervical cancer patients was used. An Artificial Neural Network (ANN) algorithm was used to build the MTL-based AI model. Accuracy and weighted F1 scores were calculated as evaluation indicators. The performance of the MTL model was compared with Single-Task Learning (STL) models. Additionally, a Turing test was performed by 20 gynecologists and compared with this AI model. Results A total of 223 cervical cancer cases were retrospectively enrolled into the training set, and 58 cases were prospectively collected as independent validation set. The accuracy of this cervical cancer AI model constructed with ANN algorithm in predicting stage, histology, grade and LNM were 75%, 95%, 86% and 76%, respectively. And the corresponding weighted F1 score were 70%, 94%, 86%, and 76%, respectively. The average time consumption of AI simultaneously predicting stage, histology, grade and LNM for cervical cancer was 0.01s (95%CI: 0.01–0.01) per 20 patients. The mean time consumption doctor and doctor with AI were 581.1s (95%CI: 300.0-900.0) per 20 patients and 534.8s (95%CI: 255.0-720.0) per 20 patients, respectively. Except for LNM, both the accuracy and F-score of the AI model were significantly better than STL AI, doctors and AI-assisted doctors in predicting stage, grade and histology. (P

Objective To investigate the efficacy and safety of a Compound Acid in improving seborrheic dermatitis of the scalp. Methods Fifty patients with seborrheic dermatitis who met the inclusion criteria were enrolled. The subjects underwent scalp brushing with Compound Acid for a total of four brushings, with the first acid brushing on the day of enrollment and subsequent brushings at one-week interval. Symptom scores were assessed before each acid brushing. A follow-up examination was conducted two weeks after the last acid brushing. Clinical signs and symptoms such as papules, greasiness, erythema, and dandruff were scored using skin microscopy. The status of Malassezia infection was detected using fungus fluorescent microscope. A questionnaire was used to evaluate subjects' scalp itching and pain. Results Forty-seven subjects completed this study. Following the use of the Compound Acid, subjects showed significant improvements in maculopapule scores (from 2.09±1.25 to 0.13±0.34), greasiness scores (from 3.19±0.77 to 0.87±0.65), erythema scores (from 3.23±0.63 to 0.43±0.68), and dandruff scores (from 3.26±0.94 to 0.55±0.65) (all P

Abstract Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.

IntroductionAdamantinomatous craniopharyngioma (ACP) is difficult to cure completely and prone to recurrence after surgery. Ferroptosis as an iron-dependent programmed cell death, may be a critical process in ACP. The study aimed to screen diagnostic markers related to ferroptosis in ACP to improve diagnostic accuracy.MethodsGene expression profiles of ACP were obtained from the gene expression omnibus (GEO) database. Limma package was used to analyze the differently expressed genes (DEGs). The intersection of DEGs and ferroptosis-related factors was obtained as differently expressed ferroptosis-related genes (DEFRGs). Enrichment analysis was processed, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), disease ontology (DO), gene set enrichment analysis (GSEA), and Gene Set Variation Analysis (GSVA) analysis. Machine learning algorithms were undertaken for screening diagnostic markers associated with ferroptosis in ACP. The levels of DEFRGs were verified in ACP patients. A nomogram was drawn to predict the relationship between key DEFRG expression and risk of disease. The disease groups were then clustered by consensus clustering analysis.ResultsDEGs were screened between ACP and normal samples. Ferroptosis-related factors were obtained from the FerrDb V2 and GeneCard databases. The correlation between DEFRGs and ferroptosis markers was also confirmed. A total of 6 overlapped DEFRGs were obtained. Based on the results of the nomogram, CASP8, KRT16, KRT19, and TP63 were the protective factors of the risk of disease, while GOT1 and TFAP2C were the risk factors. According to screened DEFRGs, the consensus clustering matrix was differentiated, and the number of clusters was stable. CASP8, KRT16, KRT19, and TP63, were upregulated in ACP patients, while GOT1 was downregulated. CASP8, KRT16, KRT19, TP63, CASP8, and GOT1 affect multiple ferroptosis marker genes. The combination of these genes might be the biomarker for ACP diagnosis via participating ferroptosis process.DiscussionFerroptosis-related genes, including CASP8, KRT16, KRT19, TP63, and GOT1 were the potential markers for ACP, which lays the theoretical foundation for ACP diagnosis.

Detection of ultralow magnetic field requires a magnetic sensor with high sensitivity and a low noise level. In this work, we used the Co20Fe60B20/Ti/Co20Fe60B20 magnetically coupled multilayer as the core structure of an anomalous Hall sensor. We adjusted the thickness of the Ti interlayer to modify its perpendicular magnetic anisotropy and interlayer magnetic coupling, thereby improving the sensitivity of the anomalous Hall sensor. Through the investigation of magnetic field response and noise properties of devices with different Ti thicknesses, the highest sensitivity of 34 803 Ω/T and the best magnetic field detectivity of 4.6 nT/Hz at 1 Hz were achieved with a Ti thickness of 2.0 nm at room temperature. This anomalous Hall sensor has both ultrahigh sensitivity and magnetic field detectivity, making it a good candidate for applications in detecting weak magnetic fields.

ABSTRACT Toxoplasma gondii, the causative parasite of toxoplasmosis, is an apicomplexan parasite that infects warm-blooded mammals. The ability of the calcium-binding proteins (CBPs) to transport large amounts of Ca2+ appears to be critical for the biological activity of T. gondii. However, the functions of some members of the CBP family have not yet been deciphered. Here, we characterized a putative CBP of T. gondii, TgpCaBP (TGME49_229480), which is composed of four EF-hand motifs with Ca2+-binding capability. TgpCaBP was localized in the cytosol and ER of T. gondii, and parasites lacking the TgpCaBP gene exhibited diminished abilities in cell invasion, intracellular growth, egress, and motility. These phenomena were due to the abnormalities in intracellular Ca2+ efflux and ER Ca2+ storage, and the reduction in motility was associated with a decrease in the discharge of secretory proteins. Therefore, we propose that TgpCaBP is a Ca2+ transporter and signaling molecule involved in Ca2+ regulation and parasitization in the hosts.IMPORTANCECa2+ signaling is essential in the development of T. gondii. In this study, we identified a calcium-binding protein in T. gondii, named TgpCaBP, which actively regulates intracellular Ca2+ levels in the parasite. Deletion of the gene coding for TgpCaBP caused serious deficits in the parasite’s ability to maintain a stable intracellular calcium environment, which also impaired the secretory protein discharged from the parasite, and its capacity of gliding motility, cell invasion, intracellular growth, and egress from host cells. In summary, we have identified a novel calcium-binding protein, TgpCaBP, in the zoonotic parasite T. gondii, which is a potential therapeutic target for toxoplasmosis.

Gastric cancer (GC) is a prevalent global malignancy, often diagnosed at advanced stage due to a lack of early symptoms and reliable markers. Previous research has identified gliomedin (GLDN) as a potential predictive marker for poor prognosis in cancer patients. However, the specific relationship between GLDN expression and GC prognosis has been unclear. Using the Tumor-Immune System Interaction Database (TISIDB), we examined GLDN expression in GC tissues and found a positive correlation with advanced clinical stages. Kaplan-Meier Plotter analysis further demonstrated that elevated GLDN levels were closely associated with poor prognosis in GC patients. To explore the functional significance of GLDN in GC, we conducted experiments involving GLDN overexpression and knockdown in GC cell lines, as well as subcutaneous tumor formation in nude mice. Our findings provided compelling evidence that GLDN promotes GC cell proliferation, viability, and migration, significantly enhancing tumor growth in vivo. Mechanistically, RNA-sequencing (RNA-seq) combined with bioinformatics analysis revealed that GLDN influences genes enriched in the p53 signaling pathway. Our data suggest that GLDN likely regulates cell proliferation through the p53-p21-CyclinD/CDK4 signaling axis. In conclusion, our study underscores GLDN's critical role in regulating GC cell proliferation and migration, and proposes its potential as a prognostic marker for GC patients.

SRSF2 plays a dual role, functioning both as a transcriptional regulator and a key player in alternative splicing. The absence of Srsf2 in MyoD + progenitors resulted in perinatal mortality in mice, accompanied by severe skeletal muscle defects. SRSF2 deficiency disrupts the directional migration of MyoD progenitors, causing them to disperse into both muscle and non-muscle regions. Single-cell RNA-sequencing analysis revealed significant alterations in Srsf2-deficient myoblasts, including a reduction in extracellular matrix components, diminished expression of genes involved in ameboid-type cell migration and cytoskeleton organization, mitosis irregularities, and premature differentiation. Notably, one of the targets regulated by Srsf2 is the serine/threonine kinase Aurka. Knockdown of Aurka led to reduced cell proliferation, disrupted cytoskeleton, and impaired differentiation, reflecting the effects seen with Srsf2 knockdown. Crucially, the introduction of exogenous Aurka in Srsf2-knockdown cells markedly alleviated the differentiation defects caused by Srsf2 knockdown. Furthermore, our research unveiled the role of Srsf2 in controlling alternative splicing within genes associated with human skeletal muscle diseases, such as BIN1, DMPK, FHL1, and LDB3. Specifically, the precise knockdown of the Bin1 exon17-containing variant, which is excluded following Srsf2 depletion, profoundly disrupted C2C12 cell differentiation. In summary, our study offers valuable insights into the role of SRSF2 in governing MyoD progenitors to specific muscle regions, thereby controlling their differentiation through the regulation of targeted genes and alternative splicing during skeletal muscle development.

Intercropping with hyperaccumulators can facilitate the safe utilization of cadmium-contaminated soil. However, the effectiveness of this approach is influenced by plant species and varieties, which necessitates research on optimal plant consortia. In this study, 8 tomato varieties (3 cherry tomatoes and 5 common large-fruit tomatoes) were intercropped with Sedum alfredii in a moderately Cd-contaminated vegetable field. The results showed that the Cd concentration in the fruits of common large-fruit tomato varieties under monoculture was 1.03–1.50 mg/kg, while that in the fruits of cherry tomato varieties was 0.67–0.71 mg/kg. After intercropping with S. alfredii, the fruit Cd concentrations of Hangza 501, Hangza 503, and Hangza 108 decreased by 16.42 %, 19.72 %, and 6.76 %, respectively, while those of the other varieties significantly increased, except for those of Hangza 8. In contrast, the shoot Cd concentration of cherry tomatoes was greater than that of large-fruit tomatoes under monoculture. Furthermore, a significant increase in the shoot Cd concentration was noted in the Hangza 501, Hangza 503 and Hangza 603 plants following intercropping. Additionally, intercropping with S. alfredii increased the concentration of soluble sugars in the fruits of Hangza 8, Hangza 501, Hangza 503 and Hangza 603 by 4.66 %, 17.91 %, 10.60 % and 17.88 %, respectively. Intercropping with tomatoes resulted in a decrease in both the biomass and Cd uptake of S. alfredii. Interestingly, the inhibitory effect on S. alfredii was less pronounced when intercropped with cherry tomatoes than when intercropped with large-fruit tomatoes. Among the intercropping treatments, S. alfredii exhibited the greatest total Cd accumulation (0.06 mg/plant) when intercropped with Hangza 503. In conclusion, the cherry tomato variety Hangza 503 was the most suitable for intercropping with S. alfredii and can be used safely for vegetable production and simultaneous phytoremediation of polluted soil. Our findings suggest that strategic selection of tomato varieties can optimize the effectiveness of “phytoextraction coupled with agro-safe production” technology for managing soil Cd concentrations.

Abstract Background Cancer-induced pre-metastatic niches (PMNs) play a decisive role in promoting metastasis by facilitating angiogenesis in distant sites. Evidence accumulates suggesting that microRNAs (miRNAs) exert significant influence on angiogenesis during PMN formation, yet their specific roles and regulatory mechanisms in gastric cancer (GC) remain underexplored. Methods miR-605-3p was identified through miRNA-seq and validated by qRT-PCR. Its correlation with the clinicopathological characteristics and prognosis was analyzed in GC. Functional assays were performed to examine angiogenesis both in vitro and in vivo. The related molecular mechanisms were elucidated using RNA-seq, immunofluorescence, transmission electron microscopy, nanoparticle tracking analysis, enzyme-linked immunosorbent assay, luciferase reporter assays and bioinformatics analysis. Results miR-605-3p was screened as a candidate miRNA that may regulate angiogenesis in GC. Low expression of miR-605-3p is associated with shorter overall survival and disease-free survival in GC. miR-605-3p-mediated GC-secreted exosomes regulate angiogenesis by regulating exosomal nitric oxide synthase 3 (NOS3) derived from GC cells. Mechanistically, miR-605-3p reduced the secretion of exosomes by inhibiting vesicle-associated membrane protein 3 (VAMP3) expression and affects the transport of multivesicular bodies to the GC cell membrane. At the same time, miR-605-3p reduces NOS3 levels in exosomes by inhibiting the expression of intracellular NOS3. Upon uptake of GC cell-derived exosomal NOS3, human umbilical vein endothelial cells exhibited increased nitric oxide levels, which induced angiogenesis, established liver PMN and ultimately promoted the occurrence of liver metastasis. Furthermore, a high level of plasma exosomal NOS3 was clinically associated with metastasis in GC patients. Conclusions miR-605-3p may play a pivotal role in regulating VAMP3-mediated secretion of exosomal NOS3, thereby affecting the formation of GC PMN and thus inhibiting GC metastasis.

Abstract Background Early prediction of mortality in individuals with HIV (PWH) has perpetually posed a formidable challenge. With the widespread integration of machine learning into clinical practice, some researchers endeavor to formulate models predicting the mortality risk for PWH. Nevertheless, the diverse timeframes of mortality among PWH and the potential multitude of modeling variables have cast doubt on the efficacy of the current predictive model for HIV-related deaths. To address this, we undertook a systematic review and meta-analysis, aiming to comprehensively assess the utilization of machine learning in the early prediction of HIV-related deaths and furnish evidence-based support for the advancement of artificial intelligence in this domain. Methods We systematically combed through the PubMed, Cochrane, Embase, and Web of Science databases on November 25, 2023. To evaluate the bias risk in the original studies included, we employed the Predictive Model Bias Risk Assessment Tool (PROBAST). During the meta-analysis, we conducted subgroup analysis based on survival and non-survival models. Additionally, we utilized meta-regression to explore the influence of death time on the predictive value of the model for HIV-related deaths. Results After our comprehensive review, we analyzed a total of 24 pieces of literature, encompassing data from 401,389 individuals diagnosed with HIV. Within this dataset, 23 articles specifically delved into deaths during long-term follow-ups outside hospital settings. The machine learning models applied for predicting these deaths comprised survival models (COX regression) and other non-survival models. The outcomes of the meta-analysis unveiled that within the training set, the c-index for predicting deaths among people with HIV (PWH) using predictive models stands at 0.83 (95% CI: 0.75–0.91). In the validation set, the c-index is slightly lower at 0.81 (95% CI: 0.78–0.85). Notably, the meta-regression analysis demonstrated that neither follow-up time nor the occurrence of death events significantly impacted the performance of the machine learning models. Conclusions The study suggests that machine learning is a viable approach for developing non-time-based predictions regarding HIV deaths. Nevertheless, the limited inclusion of original studies necessitates additional multicenter studies for thorough validation.

Abstract Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress and dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known cell death mechanisms. This process involves the interaction of copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation and cell death. Recently, a growing number of studies have explored the link between cuproptosis and cancer development. This review comprehensively examines the systemic and cellular metabolism of copper, including tumor-related signaling pathways influenced by copper. It delves into the discovery and mechanisms of cuproptosis and its connection to various cancers. Additionally, the review suggests potential cancer treatments using copper ionophores that induce cuproptosis, in combination with small molecule drugs, for precision therapy in specific cancer types.

A novel design of micro-aluminum (μAl) powder coated with bi-/tri-component alloy layer, such as: Ni–P and Ni–P–Cu (namely, Al@Ni–P, Al@Ni–P–Cu, respectively), as combustion catalysts, were introduced to release its huge energy inside Al-core and promote rapid pyrolysis of ammonium perchlorate (AP) at a lower temperature in aluminized propellants. The microstructure of Al@Ni–P–Cu demonstrates that a three-layer Ni–P–Cu shell, with the thickness of ∼100 nm, is uniformly supported by μAl carrier (fuel unit), which has an amorphous surface with a thickness of ∼2.3 nm (catalytic unit). The peak temperature of AP with the addition of Al@Ni–P–Cu (3.5%) could significantly drop to 316.2 °C at high-temperature thermal decomposition, reduced by 124.3 °C, in comparison to that of pure AP with 440.5 °C. It illustrated that the introduction of Al@Ni–P–Cu could weaken or even eliminate the obstacle of AP pyrolysis due to its reduction of activation energy with 118.28 kJ/mol. The laser ignition results showed that the ignition delay time of Al@Ni–P–Cu/AP mixture with 78 ms in air is shorter than that of Al@Ni–P/AP (118 ms), decreased by 33.90%. Those astonishing breakthroughs were attributed to the synergistic effects of adequate active sites on amorphous surface and oxidation exothermic reactions (7597.7 J/g) of Al@Ni–P–Cu, resulting in accelerated mass and/or heat transfer rate to catalyze AP pyrolysis and combustion. Moreover, it is believed to provide an alternative Al-based combustion catalyst for propellant designer, to promote the development the propellants toward a higher energy.

Abstract Background The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored. Methods A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined. Results The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii. Conclusion The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies. Graphical Abstract

Objective To evaluate the efficacy of EECP in the prevention of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD).Methods A prospective trial was undertaken in the participants. A total of 280 patients with an estimated glomerular filtration rate (eGFR) of

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2− to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

ABSTRACTRe-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques (Macaca mulatta) that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.

Liver injury is closely related to poor outcomes in sepsis patients. Current studies indicate that sepsis is accompanied by metabolic disorders, especially those related to lipid metabolism. It is highly important to explore the mechanism of abnormal liver lipid metabolism during sepsis. As a key regulator of glucose and lipid metabolism, angiopoietin-like 8 (ANGPTL8) is involved in the regulation of multiple chronic metabolic diseases. In the present study, severe liver lipid deposition and lipid peroxidation were observed in the early stages of lipopolysaccharide (LPS) induced liver injury. LPS promotes the expression of ANGPTL8 both in vivo and in vitro. Knockout of Angptl8 reduced hepatic lipid accumulation and lipid peroxidation, improved fatty acid oxidation and liver function, and increased the survival rate of septic mice by activating the PGC1α/PPARα pathway. We also found that the expression of ANGPTL8 induced by LPS depends on TNF-α, and that inhibiting the TNF-α pathway reduces LPS-induced hepatic lipid deposition and lipid peroxidation. However, knocking out Angptl8 improved the survival rate of septic mice better than inhibiting the TNF-α pathway. Taken together, the results of our study suggest that ANGPTL8 functions as a novel cytokine in LPS-induced liver injury by suppressing the PGC1α/PPARα signaling pathway. Therefore, targeting ANGPTL8 to improve liver lipid metabolism represents an attractive strategy for the management of sepsis patients.

Deoxynivalenol (DON), commonly known as vomitoxin, is a mycotoxin produced by fungi and is frequently found as a contaminant in various cereal-based food worldwide. While the harmful effects of DON have been extensively studied in different tissues, its specific impact on the proliferation of skeletal muscle cells remains unclear. In this study, we utilized murine C2C12 myoblasts as a model to explore the influence of DON on their proliferation. Our observations indicated that DON exhibits dose-dependent toxicity, significantly inhibiting the proliferation of C2C12 cells. Through the application of RNA-seq analysis combined with gene set enrichment analysis, we identified a noteworthy downregulation of genes linked to the extracellular matrix (ECM) and condensed chromosome. Concurrently with the reduced expression of ECM genes, immunostaining analysis revealed notable changes in the distribution of fibronectin, a vital ECM component, condensing into clusters and punctate formations. Remarkably, the exposure to DON induced the formation of multipolar spindles, leading to the disruption of the normal cell cycle. This, in turn, activated the p53-p21 signaling pathway and ultimately resulted in apoptosis. These findings contribute significant insights into the mechanisms through which DON induces toxicity within skeletal muscle cells.

Objective: To develop a model combining clinical and radiomics features from CT scans for a preoperative noninvasive evaluation of Huvos grading of neoadjuvant chemotherapy in patients with HOS. Methods: 183 patients from center A and 42 from center B were categorized into training and validation sets. Features derived from radiomics were obtained from unenhanced CT scans.Following dimensionality reduction, the most optimal features were selected and utilized in creating a radiomics model through logistic regression analysis. Integrating clinical features, a composite clinical radiomics model was developed, and a nomogram was constructed. Predictive performance of the model was evaluated using ROC curves and calibration curves. Additionally, decision curve analysis was conducted to assess practical utility of nomogram in clinical settings. Results: LASSO LR analysis was performed, and finally, three selected image omics features were obtained.Radiomics model yielded AUC values with a good diagnostic effect for both patient sets (AUCs: 0.69 and 0.68, respectively). Clinical models (including sex, age, pre-chemotherapy ALP and LDH levels, new lung metastases within 1 year after surgery, and incidence) performed well in terms of Huvos grade prediction, with an AUC of 0.74 for training set. The AUC for independent validation set stood at 0.70. Notably, the amalgamation of radiomics and clinical features exhibited commendable predictive prowess in training set, registering an AUC of 0.78. This robust performance was subsequently validated in the independent validation set, where the AUC remained high at 0.75. Calibration curves of nomogram showed that the predictions were in good agreement with actual observations. Conclusion: Combined model can be used for Huvos grading in patients with HOS after preoperative chemotherapy, which is helpful for adjuvant treatment decisions.

ObjectiveThe objective of this research is to investigate the relationship between dietary glycine consumption and the prevalence of hypertension, hyperlipidemia, and overweight or obesity in economically disadvantaged areas of northern China using a cross-sectional study design.MethodsA cross-sectional study involving 774 participants utilized a web-based dietary questionnaire (IDQC) and underwent physical measurements. Data analysis was conducted using IBM SPSS Statistics software (Version 21). Participants were stratified into four groups based on quartiles of their dietary glycine intake: Q1 (2.26). Continuous variables were reported as mean ± standard deviation and compared using ANOVA or the Kruskal-Wallis test, while categorical variables were presented as frequencies (%) and compared using the chi-square test. Finally, multivariable logistic regression with p-value of less than 0.05 was considered statistically significant.ResultsSignificant differences in dietary glycine intake were observed between the highest quartile group (Q4) and the lowest quartile group (Q1), with corresponding dominance ratios of 0.590 (95% CI, 0.360–0.966), 0.547 (95% CI, 0.327–0.913), and 0.547 (95% CI, 0.353–0.850) for the risk of hypertension, hyperlipidemia, and overweight/obesity, respectively. Furthermore, no significant correlation was found between dietary glycine intake and hypertension or hyperlipidemia within each sex and age subgroup.ConclusionThere exists a potential correlation between increased dietary glycine intake and reduced prevalence of hypertension, hyperlipidemia, and overweight/obesity. However, additional research is necessary to validate this finding through larger-scale studies conducted at a population level.

This study aims to explore the impact of metabolites from three vaginal bacteria on the expression of Syndecan 1 (SDC-1). Human cervical epithelial cells (HcerEpic) were separately incubated with the cell-free supernatants of Lactobacillus crispatus (LCS group), Gardnerella vaginalis (GVS group), and Atopobium vaginalis (AVS group). LCS showed a proliferative effect on HcerEpic, with the most significant effect observed at a concentration of 30 % (P 0.05). LCS promotes HcerEpic proliferation, without significant impact on SDC-1 expression and shedding. This provides molecular evidence for LCS as a protective factor against human papillomavirus infection in the cervix. Metabolites of GV and AV inhibit HcerEpic proliferation, induce cytokine secretion, suppress SDC-1 transcription and expression, and promote SDC-1 shedding.

During the last decade, the amount of research on the relationship between social networking sites (SNS) use and users’ subjective well-being (SWB) has increased, leading to discrepancies regarding the results. Our review of the literature generated 73 independent samples and indicated that considerable inconsistent results may be attributed to different measurements of SNS use, moderation effects, or media response states and their effects. In this study, meta-analytic procedures were used to assess the strength of the relationships between SNS use indicators, perceived social support (PSS), self-esteem and SWB. The results showed that PSS and self-esteem had stronger effects on SWB than SNS use indicators. Furthermore, a meta-analytic structural equation model was conducted to assess the strength of the relationships between SNS use indicators, PSS, self-esteem, and SWB. The results did not support the proposition SNS use is associated with SWB. Compared with SNS use indicators, media response states such as self-esteem and PSS, had more effects on SWB.

Abstract RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single‐nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre‐mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT.

Abstract Background The ephemeral flora of northern Xinjiang, China, plays an important role in the desert ecosystems. However, the evolutionary history of this flora remains unclear. To gain new insights into its origin and evolutionary dynamics, we comprehensively sampled ephemeral plants of Brassicaceae, one of the essential plant groups of the ephemeral flora. Results We reconstructed a phylogenetic tree using plastid genomes and estimated their divergence times. Our results indicate that ephemeral species began to colonize the arid areas in north Xinjiang during the Early Miocene and there was a greater dispersal of ephemeral species from the surrounding areas into the ephemeral community of north Xinjiang during the Middle and Late Miocene, in contrast to the Early Miocene or Pliocene periods. Conclusions Our findings, together with previous studies, suggest that the ephemeral flora originated in the Early Miocene, and species assembly became rapid from the Middle Miocene onwards, possibly attributable to global climate changes and regional geological events.

In an era of global population aging and a rising prevalence of obesity,the complex condition known as sarcopenic obesity(SO) has emerged as a subject of growing interest and concern.A relatively recent discovery,pyroptosis,a form of programmed cell death characterized by the activation of inflammasomes and the subsequent release of a multitude of inflammatory mediators,has garnered increasing attention.Emerging research suggests that pyroptosis plays a pivotal role in the intricate development and progression of SO.Understanding the intricate relationship between SO and pyroptosis holds the potential to shed light on the underlying mechanisms driving SO's pathogenesis.Such insights not only contribute to a deeper comprehension of SO but also offer valuable guidance for the development of targeted therapeutic interventions.

Background: The timing and incidence of recurrent bone metastasis (BM) after radical gastrectomy in patients with gastric cancer (GC) as well as the survival of these patients were not fully understood. The aim of this study was to analyze the data of an observational GC cohort and identify patients who underwent curative gastrectomy and had recurrent BM to describe and clarify the pattern and profile of BM evolution after surgery. Methods: Data were retrieved from a hospital-based GC cohort, and patients who underwent upfront radical gastrectomy were selected. The time points of specific organ metastatic events were recorded, and the person-year incidence rate of metastatic events was calculated. The latency period of BM events after gastrectomy was measured and compared with that of the other two most common metastatic events, liver metastasis (LM) and distant lymph node metastasis (LNM), using analysis of variance. Propensity score matching and subgroup analysis were used for sensitivity analysis. Results: A total of 1324 GC cases underwent radical gastrectomy between January 2011 and December 2021. Of these, 67 BM, 218 LM, and 248 LNM occurred before the last follow-up. The incidence of BM events was 1.7/100 person-years, which was approximately 3-fold lower than that of LM and distant LNM events (5.5 and 6.3 per 100 person-years, respectively). BM events had a significantly longer latency (median time, 16.5 months) than LM and LNM events (11.1 and 12.0 months, respectively). Recurrent BM led to a worse prognosis (median survival, 4.5 months) than those of LM and LNM events (median survival, 7.7 and 7.1 months, respectively). However, no difference in overall survival after gastrectomy was observed among the groups. Conclusions: Compared with other common metastatic events, BM in GC after gastrectomy is a late-onset event indicating poor survival. Trial registration: No. ChiCTR1800019978; http://www.chictr.org.cn/.

RFPA2D was used to simulate the crack propagation, failure mode, and fractal characteristics of composite strata with prefabricated cracks and holes under the uniaxial compression test. The crack propagation process was analyzed when the crack inclination angle and rock inclination angle changed. And it was concluded that: when the rock inclination angle is 0° and the crack inclination angle changes, the cracks are classified into X-type cracks and Y-type cracks. When the crack inclination angle is 0° and the rock inclination angle changes, the failure modes of the model specimens are divided into the through-cut failure mode of soft rock and the failure mode along the soft rock. The variation law of fractal dimension of cracks in the composite rock stratum with holes calculated by Matlab is the same as that of the compressive strength of the model specimen, and the fitting between fractal dimension and compressive strength has a significant linear relationship.

Emotion-Cause Pair Extraction (ECPE) aims to jointly extract emotion clauses and the corresponding cause clauses from a document, which is important for user evaluation or public opinion analysis. Existing research addresses the ECPE task through a two-step or an end-to-end approach. Although previous work shows promising performances, they suffer from two limitations: 1) they fail to take full advantage of emotion type information, which has advantages for modelling the dependencies between emotion and cause clauses from a semantic perspective; 2) they ignored the interaction between local and global information, which is important for ECPE. To address these issues, we propose an ECPE Pair Generator (ECPE-PG), with a Clause-Encoder layer, a Pre-Output layer and an Information Interaction-based Pair Generation (IIPG) Module embedded. This model first encodes clauses into vector representations through the Clause-Encoder layer and then preforms emotion clause extraction (EE), cause clause extraction (CE) and emotion type extraction (ETE), respectively, through the Pre-Output layer, on the basis of which the IIPG module analyzes the complex emotional logic of relationships between clauses and estimates the candidate pairs based on the interaction of global and local information. It should be noted that emotion type information is regarded as a crucial indication in the IIPG module to assist the identification of emotion-cause pairs. Experimental results show that our method outperforms the state-of-the-art methods on benchmark datasets.

Abstract Objective We investigated the impact of the long noncoding RNA LINC00958 on cellular activity and oxidative stress in osteoarthritis (OA). Methods We performed bioinformatics analysis via StarBase and luciferase reporter assays to predict and validate the interactions between LINC00958 and miR-214-3p and between miR-214-3p and FOXM1. The expression levels of LINC00958, miR-214-3p, and FOXM1 were measured by qRT-PCR and western blotting. To assess effects on CHON-001 cells, we performed MTT proliferation assays, evaluated cytotoxicity with a lactate dehydrogenase (LDH) assay, and examined apoptosis through flow cytometry. Additionally, we measured the levels of apoptosis-related proteins, including BAX and BCL2, using western blotting. The secretion of inflammatory cytokines (IL-6, IL-8, and TNF-α) was measured using ELISA. Results Our findings confirmed that LINC00958 is a direct target of miR-214-3p. LINC00958 expression was upregulated but miR-214-3p expression was downregulated in both OA cells and IL-1β-stimulated CHON-001 cells compared to the corresponding control cells. Remarkably, miR-214-3p expression was further reduced after miR-214-3p inhibitor treatment but increased following LINC00958-siRNA stimulation. Silencing LINC00958 significantly decreased its expression, and this effect was reversed by miR-214-3p inhibitor treatment. Notably, LINC00958-siRNA transfection alleviated the IL-1β-induced inflammatory response, as evidenced by the increased cell viability, reduced LDH release, suppression of apoptosis, downregulated BAX expression, and elevated BCL2 levels. Moreover, LINC00958 silencing led to reduced secretion of inflammatory factors from IL-1β-stimulated CHON-001 cells. The opposite results were observed in the miR-214-3p inhibitor-transfected groups. Furthermore, in CHON-001 cells, miR-214-3p directly targeted FOXM1 and negatively regulated its expression. Conclusion Our findings suggest that downregulating LINC00958 mitigates IL-1β-induced injury in CHON-001 cells through the miR-214-3p/FOXM1 axis. These results imply that LINC00958 plays a role in OA development and may be a valuable therapeutic target for OA.

Abstract Background Preeclampsia (PE), a pregnancy specific syndrome, is one kind of common gestational hypertension disease, which can cause maternal and perinatal mortality and morbidity. This study was conducted to identify key microRNAs (miRNAs), mRNAs and related signaling pathways in the pathogenesis of PE. Methods Whole transcriptome sequencing and small RNA sequencing of the peripheral blood from 3 PE patients and 3 normal pregnant women were performed. Differential expressed (DE) miRNAs were identified using the DEseq2 package. Target genes of the selected upregulated and downregulated DE miRNAs were predicted. Based on the hypergeometric distribution of DE miRNA target genes, we analyzed GO enrichment and KEGG pathway enrichment using R. Results Total 1291 and 1281 novel RNAs were obtained from the preeclampsia patients and healthy individuals. 70 miRNAs were screened out with significant levels with 51 significantly upregulated and 19 significantly downregulated. 44,306 genes were predicted as the targets of these miRNAs. Besides, KEGG pathway analysis revealed that the upregulated miRNAs were enriched in Glycosaminoglycan biosynthesis-chondroitin sulfate / dermatan sulfate, Base excision repair and the downregulated miRNAs were enriched in Tuberculosis, Phagosome. Conclusion We constructed regulatory networks of miRNAs and target genes, there were 2208 negative miRNA-mRNA interactions in total. The network and pathway information illustrate the potential functions of mRNAs and miRNAs in PE pathogenesis.

The biology of Toxoplasma gondii, the causative pathogen of one of the most widespread parasitic diseases (toxoplasmosis), remains poorly understood. Lactate, which is derived from glucose metabolism, is not only an energy source in a variety of organisms, including T. gondii, but also a regulatory molecule that participates in gene activation and protein function. Lysine lactylation (Kla) is a type of post-translational modifications (PTMs) that has been recently associated with chromatin remodeling; however, Kla of histone and non-histone proteins has not yet been studied in T. gondii. To examine the prevalence and function of lactylation in T. gondii parasites, we mapped the lactylome of proliferating tachyzoite cells and identified 1964 Kla sites on 955 proteins in the T. gondii RH strain. Lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes, including mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, and many signaling pathways. We also performed a chromatin immunoprecipitation sequencing (ChIP-seq) analysis using a lactylation-specific antibody and found that the histones H4K12la and H3K14la were enriched in the promoter and exon regions of T. gondii associated with microtubule-based movement and cell invasion. We further confirmed the delactylase activity of histone deacetylases TgHDAC2–4, and found that treatment with anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced protein lactylation in T. gondii. This study offers the first dataset of the global lactylation proteome and provides a basis for further dissecting the functional biology of T. gondii.

Abstract To compensate for the influence of temperature on the efficiency of an ultrasonic motor (USM), this paper proposed a maximum efficiency point tracking control method for temperature drift by analysing the relationships between the maximum efficiency point and the voltage and frequency of the driving circuit. The method first calculates the frequency update step of the driving circuit by the polynomial surface fitting method, considers the influence of temperature rise on the voltage‐efficiency‐frequency characteristics, and then adjusts the frequency in real time to compensate for temperature effects. Simulation and experimental results show that our method can improve the USM performance at the maximum efficiency point under changing temperature. Maximum efficiency point tracking algorithm with temperature compensation algorithm achieves maximum efficiency in experiment.

AbstractContext Endometriosis (EMs) is a gynecological disorder. Ligustrazine has been reported to exert an anti-inflammatory effect on EMs. However, the underlying mechanisms are not completely understood.Objective To investigate the effects of ligustrazine on the progression of EMs and the underlying regulatory mechanisms.Materials and methods Human endometrial stromal cells (HESCs) were isolated from patients with EMs or control subjects. HESCs were treated with 25, 50, 100, or 200 μM ligustrazine for 1, 3, 6, or 12 h. Western blot and enzyme-linked immunosorbent assays were performed to determine the levels of proteins and inflammatory cytokines, respectively. The binding between STAT3 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by chromatin immunoprecipitation and dual-luciferase reporter assays. The relationship between IGF2BP1 and RELA was assessed by RNA immunoprecipitation and RNA pull-down assay.Results Phosphorylated STAT3, IGF2BP1, RELA, TNF-α, IL-6, and IL-1β were upregulated in EMs tissues compared with control tissues (by 1.79-, 2.55-, 1.58-, 3.01-, 2.55-, and 3.34-fold, respectively). Ligustrazine inhibited the expression of p-STAT3, IGF2BP1, RELA, IL-6, TNF-α, and IL-1β. Overexpression of STAT3 promoted RELA-mediated inflammatory responses, while ligustrazine (100 µM) notably reversed this phenomenon. Ligustrazine also alleviated RELA-induced inflammation via downregulating IGF2BP1. STAT3 bound to the promoter of IGF2BP1, and IGF2BP1 bound to the RELA mRNA.Discussion and conclusion Ligustrazine inhibited inflammation in EMs via regulating the STAT3/IGF2BP1/RELA axis. These findings propose a new agent against EMs and support the development of ligustrazine-based treatment strategies for EMs.

Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is associated with pronounced systemic inflammation, and neutrophil extracellular traps (NETs) are key components of this response. The primary objective of this study was to establish an NET-related scoring system for patients with HBV-ACLF. A prospective training cohort of 81 patients from the Beijing Ditan Hospital was included. The concentrations of NET markers (cell-free DNA, myeloperoxidase DNA [MPO-DNA], and citrullinated histone H3) in peripheral blood were quantified. Random survival forest, LASSO regression, and multivariate Cox regression analyses were used to identify prognostic factors associated with 90-day mortality in ACLF patients and develop a nomogram for visualization, which was followed by evaluation in a validation cohort (n = 40). NET-related marker levels were significantly higher in the non-survival group than in the survival group (p < 0.05). The NET score was constructed by combining MPO-DNA, neutrophil-to-lymphocyte ratio, and age data. The score’s diagnostic effectiveness, assessed by the area under the curve, yielded values of 0.83 and 0.77 in the training and validation sets, respectively, markedly surpassing those of other established models (p < 0.05). In both groups, the 90-day mortality rates were 88.8% and 75.0%, respectively, for patients categorized as high risk and 18.0% and 12.5%, respectively, for those classified as low risk.

BackgroundRice starch has high digestibility due to its large carbohydrate content. Synergistic modification of hot-melt extrusion (HME) and additives such as flavonoids, hydrocolloids, proteins, lipids, and other additives has the tendency to retard the rate of starch hydrolysis. Hence, the current investigation aimed to study the combined effect of the HME-assisted addition of nobiletin (NOB, 0, 2, 4, and 6%) on the multi-scale structures, interactions, thermal, and digestibility characteristics of rice starch.MethodsThe study employed density functional theory calculations and an infrared second derivative of an Fourier-transform infrared (FTIR) spectrometer to analyze the interactions between NOB and starch. The physicochemical properties of the starch extrudates were characterized by FTIR, 13C nuclear magnetic resonance, X-ray diffraction, and differential scanning calorimetry, while the digestibility was evaluated using an in vitro digestion model.ResultsHME was found to disrupt the crystalline structure, helix structure, short-ordered structure, and thermal properties of starch. The interaction between NOB and starch involved hydrophobic interactions and hydrogen bonds, effectively preventing the molecular chains of starch from interacting with each other and disrupting their double helix structure. The addition of NOB led to the formation of a highly single-helical V-type crystalline structure, along with the formation of ordered structural domains. Consequently, the combined treatment significantly enhanced the ordered structure and thermal stability of starch, thus effectively leading to an increase in resistant starch and slowly digestion starch.DiscussionThe study underscores that synergistic modification of HME and NOB holds promise for enhancing both the nutritional value and functional properties of rice starch. These findings offer valuable insights for developing high-quality rice starch products with broader applications.

ABSTRACTRemodeling the erythrocyte membrane and skeleton by the malarial parasite Plasmodium falciparum is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic α-spectrin, but not β-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of P. falciparum, from the ring to the schizont stage. We further observed an upregulated expression of P. falciparum phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased α-spectrin ubiquitination and degradation during P. falciparum development. We further revealed that inhibition of the activity of PfPI3K impaired P. falciparum development in vitro and Plasmodium berghei infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of α-spectrin during the intraerythrocytic development of Plasmodium species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria.IMPORTANCEPlasmodium falciparum is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after P. falciparum invasion, while β-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by P. falciparum phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in P. falciparum-infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18–75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265–0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

Abstract Telomere and telomerase are crucial factors in cell division and chromosome stability. Telomerase activity in most cells depends on the transcription control by the telomerase reverse transcriptase (TERT). The introduction of an exogenous human TERT (hTERT) in cultured cells could enhance telomerase activity and elongate the lifespan of various cells. Telomere elongation mechanisms vary between insects and are complex and unusual. Whether the use of exogenous hTERT can immortalize primary insect cells remains to be investigated. In this study, we used a recombinant virus expressing hTERT to infect primary cultured cells of Periplaneta americana and evaluated its effects on insect cell immortalization. We found that hTERT was successfully expressed and promoted the growth of P. americana cells, shortening their doubling time. This was due to the ability of hTERT to increase the activity of telomerase in P. americana cells, thus prolonging the telomeres. Our study lays the foundation for understanding the mechanisms of telomere elongation in P. americana, and suggests that the introduction of hTERT into insect cells could be an efficient way to establish certain insect cell lines.

Abstract Background Extravillous trophoblasts (EVTs) are essential cells during the formation of the placenta, with the major function of invading the maternal decidua, anchoring the developing placenta to the uterus, remodeling uterine arteries, and regulating immune responses to prevent rejection. During early pregnancy, the decidua undergoes a hypoxic and acidic microenvironment, which has been shown to participate in tumor cell migration, invasion, growth, and angiogenesis. Nevertheless, the mechanisms by which EVTs sense and respond to the acidic microenvironment, thereby executing their functions, remain poorly understood. Methods The effects of G protein-coupled receptor 65 (GPR65) on cell adhesion and other cellular functions were tested using JAR spheroids, mouse blastocysts, and HTR-8/SVneo cells. Specifically, we employed HTR-8/SVneo cells for gene overexpression and silencing to investigate the underlying mechanism of GPR65's impact on trophoblast cell function under acidic conditions. Additionally, villus tissue samples obtained from early pregnancy loss patients were utilized to explore the potential association between GPR65 and its related signaling pathway molecules with the disease. Results This study identified GPR65 expression widely in trophoblasts, with the highest level in EVTs. Importantly, optimal GPR65 levels are required for maintaining normal adhesion, migration, and invasion, whereas overexpression of GPR65 inhibits these functions by activating the cAMP-ERK signaling pathway, upregulating myosin light chain kinase (MYLK) and MYLK3 expression, and subsequently downregulating fibronectin. Consistently, elevated expression of GPR65, MYLK, and MYLK3 is observed in patients suffering from early pregnancy loss. Conclusions This work offers insights into the suppressive effects of GPR65 on EVT function under acidic conditions and highlights a putative target for therapeutic intervention in early pregnancy complications. Video Abstract

Abstract Background Galla chinensis is a traditional Chinese medicine (TCM) produced due to the interaction between the Fordinae aphids and the Rhus plant species. Horned galls with high tannin content are the most widely cultivated gall type, and Wufeng county of Hubei province in China is the center of cultivation. However, long-term artificial cultivation and domestication of horned galls to meet the increasing production demand have led to quality degradation. Understanding the reasons underlying quality degradation is urgent for horned gall production and application. The present study used a combination of metabolic, genetic, and ecological analyses to investigate the quality and genetic differentiation of the horned galls under long-term domestication as well as the potential relationships between them. Results Analysis of gallic acid content and other three phenotypic traits (fresh weight, gall size, and wall thickness) revealed quality differentiation of horned galls collected from five locations in Wufeng, in which the cultivated samples from Wang Jiaping (WJP) showed the highest degradation. Genetic differentiation between the cultivated and wild Rhus chinensis trees in WJP, and between WJP and the other populations was detected based on SSR molecular markers, however, no significant difference in genetic structure was seen for the aphid populations. Among the various ecological factors examined, temperature was identified as the primary one affecting the quality of horned galls. Conclusions Both genetic and ecological factors caused quality differentiation of horned galls. The collection of diverse germplasm of host trees and aphids will help reduce the quality degradation of horned galls in Wufeng.

High-density polyethylene (HDPE) pipelines in nuclear power plants (NPPs) have to meet high requirements for seismic performance. HDPE pipes have been proved to have good seismic performance, but joints are the weak links in the pipelines, and pipeline failures usually initiate from the defects inside the joints. Limited data are available on the seismic performance of butt-fusion joints of HDPE pipelines in NPPs, especially in terms of defects changes inside the joints after earthquakes. In this paper, full-scale shaking table tests were performed on a test section of suspended HDPE pipelines in an NPP, which included straight pipes, elbows, and 10 butt-fusion joints. During the tests, the seismic load-induced strain of the joints was analyzed by strain gauges, and it was much smaller than the internal pressure and self-weight-induced strain. Before and after the shaking table tests, phased array ultrasonic testing (PA-UT) was conducted to detect defects inside the joints. The locations, numbers, and dimensions of the defects were analyzed. It was found that defects were more likely to occur in elbows joints. No new defect was observed after the shaking table tests, and the defects showed no significant growth, indicating the satisfactory seismic performance of the butt-fusion joints.

Overt hepatic encephalopathy (OHE), a serious complication of liver cirrhosis, is associated with alterations in lipid and lipoprotein metabolism. We evaluated the correlation between high-density lipoprotein cholesterol (HDL-C) levels and transplant-free (TF) mortality in patients with OHE. Patients with OHE admitted to Beijing Ditan Hospital between January 2010 and August 2016 (n = 821) and between September 2016 and December 2020 (n = 480) were included in the training and validation sets, respectively. Independent predictors were explored by a multivariate Cox regression analysis, and the area under the receiver operating characteristic curve (AUC) was used to assess the prognostic value of these factors. The prognostic value of HDL-C was good (AUC at 1 year: 0.745) and was equivalent to that of the Model for End-Stage Liver Disease (MELD) score (AUC at 1 year: 0.788). The optimal threshold values for HDL-C and MELD were 0.5 mmol/L and 17, respectively. The 1-year TF mortality rates in the low-risk (HDL-C ≥ 0.5 mmol/L and MELD < 17) and high-risk (HDL-C < 0.5 mmol/L and MELD ≥ 17) groups were 7.5% and 51.5% in the training set and 10.1% and 48.2% in the validation set, respectively. HDL-C level < 0.5 mmol/L and MELD score > 17 can facilitate the identification of high-risk patients and provide a basis for timely treatment.