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Abstract Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a highly heterogeneous disease. According to large-scale RNA sequencing (RNA-seq) data, B-ALL patients can be divided into more than 10 subgroups. However, many genomic defects associated with resistance mechanisms have not yet been identified. As an individual clinical tool for molecular diagnostic risk classification, RNA-seq and gene expression pattern-based therapy could be potential upcoming strategies. In this study, we retrospectively analyzed the RNA-seq gene expression profiles of 45 children whose molecular diagnostic classifications were inconsistent with the response to chemotherapy. The relationship between the transcriptome and chemotherapy response was analyzed. Fusion gene identification was conducted for the included patients who did not have known high-risk associated fusion genes or gene mutations. The most frequently detected fusion gene pair in the high-risk group was the DHRSX duplication, which is a novel finding. Fusions involving ABL1, LMNB2, NFATC1, PAX5, and TTYH3 at onset were more frequently detected in the high-risk group, while fusions involving LFNG, TTYH3, and NFATC1 were frequently detected in the relapse group. According to the pathways involved, the underlying drug resistance mechanism is related to DNA methylation, autophagy, and protein metabolism. Overall, the implementation of an RNA-seq diagnostic system will identify activated markers associated with chemotherapy response, and guide future treatment adjustments.

Abstract Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis.

This study is to develop structures with the ability to convert a compression force into radial extension or shear force, to increase power output through piezo shear mode. In this work, a piezoceramic-spring system was developed with two types of force-spreading spring configurations, the Belleville disc springs and the crinkle washer. A force loading profile is applied to a piezoceramic element and structure causing the force to be distributed in different directions when compared to a conventional helical spring damping system or compression. The performances of these novel structures were studied using Multiphysics simulation and experiments. This work shows that both the Belleville disc and crinkle washer produce improved energy output between 15 and 22% compared to compression alone, whilst the Belleville disc spring outperformed a crinkle washer in both simulations and experiments. The results show that converting compression to shear force in energy harvesting could be a potential approach to increase the energy efficiency and energy density.

Summary: Background: Biliary atresia (BA) is a neonatal fibro-inflammatory cholangiopathy with ductular reaction as a key pathogenic feature predicting poor survival. Mucosal-associated invariant T (MAIT) cells are enriched in human liver and display multiple roles in liver diseases. We aimed to investigate the function of MAIT cells in BA. Methods: First, we analyzed correlations between liver MAIT cell and clinical parameters (survival, alanine transaminase, bilirubin, histological inflammation and fibrosis) in two public cohorts of patients with BA (US and China). Kaplan–Meier survival analysis and spearman correlation analysis were employed for survival data and other clinical parameters, respectively. Next, we obtained liver samples or peripheral blood from BA and control patients for bulk RNA sequencing, flow cytometry analysis, immunostaning and functional experiments of MAIT cells. Finally, we established two in vitro co-culture systems, one is the rhesus rotavirus (RRV) infected co-culture system to model immune dysfunction of human BA which was validated by single cell RNA sequencing and the other is a multicellular system composed of biliary organoids, LX-2 and MAIT cells to evaluate the role of MAIT cells on ductular reaction. Findings: Liver MAIT cells in BA were positively associated with low survival and ductular reaction. Moreover, liver MAIT cells were activated, exhibited a wound healing signature and highly expressed growth factor Amphiregulin (AREG) in a T cell receptor (TCR)-dependent manner. Antagonism of AREG abrogated the proliferative effect of BA MAIT cells on both cholangiocytes and biliary organoids. A RRV infected co-culture system, recapitulated immune dysfunction of human BA, disclosed that RRV-primed MAIT cells promoted cholangiocyte proliferation via AREG, and further induced inflammation and fibrosis in the multicellular system. Interpretation: MAIT cells exhibit a wound healing signature depending on TCR signaling and promote ductular reaction via AREG, which is associated with advanced fibrosis and predictive of low survival in BA. Funding: This work was funded by National Natural Science Foundation of China grant (82001589 and 92168108), National Key R&D Program of China (2023YFA1801600) and by Basic and Applied Basic Research Foundation of Guangdong (2020A1515110921).

Abstract Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanisms of ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, the gel gradually degrade, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increases during organoid differentiation, where inhibition of MMPs significantly suppresses the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs is found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.

Abstract Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

Abstract The global trade in live wildlife elevates the risk of biological invasions by increasing colonization pressure (the number of alien species introduced to an area). Yet, our understanding of species traded as aliens remains limited. We created a comprehensive global database on live terrestrial vertebrate trade and use it to investigate the number of traded alien species, and correlates of establishment richness for aliens. We identify 7,780 species involved in this trade globally. Approximately 85.7% of these species are traded as aliens, and 12.2% of aliens establish populations. Countries with greater trading power, higher incomes, and larger human populations import more alien species. These countries, along with island nations, emerge as hotspots for establishment richness of aliens. Colonization pressure and insularity consistently promote establishment richness across countries, while socio-economic factors impact specific taxa. Governments must prioritize policies to mitigate the release or escape of traded animals and protect global biosecurity.

Abstract Background Morinda officinalis How (MO) is a vine shrub distributed in tropical and subtropical regions, known as one of the “Four Southern Herbal Medicines” in China. The unclear responsive mechanism by which MO adapt to freezing stress limits progress in molecular breeding for MO freezing tolerance. Results In this study, morphological, physiological and microstructure changes in MO exposed to -2℃ for 0 h, 3 h, 8 h and 24 h were comprehensively characterized. The results showed that freezing stress caused seedling dehydration, palisade cell and spongy mesophyll destruction. A significant increase in the content of proline, soluble protein and soluble sugars, as well as the activity of superoxide dismutase and peroxidase was observed. Subsequently, we analyzed the transcriptomic changes of MO leaves at different times under freezing treatment by RNA-seq. A total of 24,498 unigenes were annotated and 3252 unigenes were identified as differentially expressed genes (DEGs). Most of these DEGs were annotated in starch and sucrose metabolism, plant hormone signal transduction and MAPK signaling pathways. Family Enrichment analysis showed that the glucosyl/glucuronosyl transferases, oxidoreductase, chlorophyll a/b binding protein and calcium binding protein families were significantly enriched. We also characterized 7 types of transcription factors responding to freezing stress, among which the most abundant family was the MYBs, followed by the AP2/ERFs and NACs. Furthermore, 10 DEGs were selected for qRT-PCR analysis, which validated the reliability and accuracy of RNA-seq data. Conclusions Our results provide an overall view of the dynamic changes in physiology and insight into the molecular regulation mechanisms of MO in response to freezing stress. This study will lay a foundation for freezing tolerance molecular breeding and improving the quality of MO.

ObjectiveThis study aimed to translate and validate the reliability and validity of the Chinese version of the Philippines Sunlight Exposure Questionnaire.MethodsA total of 392 Chinese individuals aged at least 18 years, residing in various cities in Sichuan province for at least 1 year, were recruited. The reliability of the Chinese version of the questionnaire was measured through internal consistency, split-half reliability, and retest reliability, while validity was determined using the content validity index and the structure validity index.ResultsThe Chinese version of the Sunlight Exposure Questionnaire, which includes 19 items covering 5 factors, demonstrated McDonald’s omega coefficient of 0.788. The split-half reliability of the questionnaire was 0.823, and the retest reliability was 0.940. The content validity index (S-CVI) was 0.952. The five-factor structure, supported by eigenvalues, explained 66.2% of the total variance. Confirmatory factor analysis indicated favorable model fit.ResultsThe chi-square value degrees of freedom ratio (χ2/df) = 1.852, the goodness-of-fit index (GFI) = 0.938, the normed fit index (NFI) = 0.922, the incremental fit index (IFI) = 0.962, the comparative fit index (CFI) = 0.962, the Tucker–Lewis index (TLI) = 0.952, and root mean square error of approximation (RMSEA) = 0.047. The indicators of the fit of the model were within reasonable bounds.ConclusionThe Chinese version of the Sunlight Exposure Questionnaire shows validity and good reliability for assessing sun exposure among adults in a Chinese cultural context.

The work here involves designing a solar solution for safe cooking and low-power generation intended for application in rural communities. A system was developed that combines Concentrated Solar Power (CSP) and Thermoelectric Generator (TEG) technologies. The CSP provides heat for clean cooking, and the excess heat is harvested by the TEG and converted into electrical power. A storage tank was integrated into the system, storing excess energy and serving as the medium for indirect cooking and supplying the heat required by the TEG. The Parabolic Trough Collector, having a resulting average thermal efficiency value of 21%, provided the useful energy to store over 4.25kWh of heat in the tank during the initial testing of the system. The TEG developed has four Peltier modules and attained 23W - over 80% of their rated power and a maximum conversion efficiency of 4.14% at a temperature difference of 220°C between the cold and hot surfaces of the generator. During the experiment, the TEG operation was limited to only four hours before subjecting a no-load test to assess the total energy storable from the system. The initial results from the test carried out here show the potential of the hybrid system in storing energy in the tank for an extended period and simultaneous operation of the TEG. Excess energy stored can be utilised further in providing the heat required for cooking or further electrical power generation.

BackgroundLight influences the secretion of melatonin in the body and regulates circadian rhythms, which play an important role in sleep and mood. The light level of rooms in long-term care facilities is usually far below the threshold required to regulate the body’s circadian rhythm, and insufficient light can easily lead to sleep and mood disturbances among older residents in nursing homes. Therefore, the objective of this study was to investigate the effects of light therapy on sleep and circadian rhythm in older adults with type 2 diabetes residing in long-term care facilities.MethodsThis study was a prospective, single-blind, randomized controlled trial. Participants were randomly assigned to either the light therapy (LT) group or the control group and received the intervention for four weeks. Primary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and objective sleep parameters recorded by a sleep monitoring bracelet, Morningness-Eveningness Questionnaire (MEQ). The secondary outcome included glycated serum protein (GSP). Data was collected at three time points: at baseline (T0), immediate post-treatment (T1), and 4-week follow-up (T2). A linear mixed model analysis was used to analyzed the data.ResultsWe enrolled 45 long-term care residents. Compared with the control group, significant reductions in PSQI scores were observed at T1 and T2. At T2, the sleep score of objective sleep parameters was significantly higher in the LT group compared to the control group. Additionally, compared to the baseline T0, MEQ scores were significantly lower in the LT group at T1 and T2, with no significant difference in the control group. There was no significant difference between groups in glycated serum protein values at T1 and T2. However, compared to T0, glycated serum protein values decreased in the LT group while increased in the control group at T2.ConclusionLight therapy had a positive effect on subjective sleep quality and circadian rhythm time type in long-term care residents with type 2 diabetes, and had a possible delayed effect on objective sleep. However, no discernible alterations in blood glucose levels were detected in this study.

IntroductionMorinda officinalis How (MO) is a Rubiaceae plant, and its medicinal part is dried root, which is one of the “Four Southern Medicines” in China. At present, the plant MO breed seedlings mainly by cutting methods. Long-term asexual propagation makes pathogenic fungi accumulate in MO, leading to stem-base rot, which is caused by Fusarium oxysporum (Fon).MethodsIn this study, we used Trichoderma harzianum and Pestalotiopsis sp. as biocontrol fungi to investigate their antagonistic ability to Fon through in vitro antagonism and pot experiments, and combined with transcriptome sequencing to explore the mechanism of biocontrol.ResultsThe results showed that both Trichoderma harzianum and Pestalotiopsis sp. could inhibit the growth of Fon. In addition, Trichoderma harzianum and Pestalotiopsis sp. could also enhance the basic immunity to Fon by increasing the activities of defensive enzymes such as POD and SOD, chlorophyll content, soluble sugar content, and oligosaccharide content of MO. The mechanism of biological control of stem-base rot of MO was discussed by transcriptome technology. MO was treated with two treatments, root irrigation with biocontrol fungi or inoculation with Fon after root irrigation with biocontrol fungi. Transcriptome sequencing revealed that nearly 11,188 differentially expressed genes (DEGs) were involved in the process of inducing MO systemic resistance to Fon by biocontrol fungi. Meanwhile, Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as transcription factor (TFs) prediction showed that there were significant differences in the expression levels of MO roots under different treatments. Also, the genes of the “MAPK signaling pathway” and “plant hormone signaling pathway” were analyzed, in which the ERFs gene of the ethylene signal transduction pathway participated in the metabolism of glycosyl compounds. It is speculated that the ethylene signal may participate in the immune response of the sugar signal to the infection of Fon. After qRT-PCR verification of 10 DEGs related to the ethylene signal transduction pathway, the expression trend is consistent with the results of transcriptome sequencing, which proves the reliability of transcriptome sequencing.DiscussionIn conclusion, this study preliminarily identified the molecular mechanism of the biological control of MO stem-base rot and provided a scientific basis for further research on the prevention and control mechanism of MO stem-base rot.

Abstract Foamy macrophages containing prominent cytoplasmic lipid droplets (LDs) are found in a variety of infectious diseases. However, their role in Streptococcus uberis-induced mastitis is unknown. Herein, we report that S. uberis infection enhances the fatty acid synthesis pathway in macrophages, resulting in a sharp increase in LD levels, accompanied by a significantly enhanced inflammatory response. This process is mediated by the involvement of fatty acid binding protein 4 (FABP4), a subtype of the fatty acid-binding protein family that plays critical roles in metabolism and inflammation. In addition, FABP4 siRNA inhibitor cell models showed that the deposition of LDs decreased, and the mRNA expression of Tnf, Il1b and Il6 was significantly downregulated after gene silencing. As a result, the bacterial load in macrophages increased. Taken together, these data demonstrate that macrophage LD formation is a host-driven component of the immune response to S. uberis. FABP4 contributes to promoting inflammation via LDs, which should be considered a new target for drug development to treat infections.

Abstract Background Predicting invasiveness requires an understanding of the propensity of a given species to thrive in areas with novel ecological challenges. Evaluation of realized niche shift of an invasive species in its invasive range, detecting the main drivers of the realized niche shift, and predicting the potential distribution of the species can provide important information for the management of populations of invasive species and the conservation of biodiversity. The Australian redback spider, Latrodectus hasselti, is a widow spider that is native to Australia and established in Japan, New Zealand, and Southeast Asia. We used ecological niche models and ordinal comparisons in an integrative method to compare the realized niches of native and invasive populations of this spider species. We also assessed the impact of several climatic predictor variables and human activity on this niche shift. We hypothesized that human impact is important for successful establishment of this anthropophilic species, and that climatic predictor variables may determine suitable habitat and thus predict invasive ranges. Results Our models showed that L. hasselti distributions are positively influenced by human impact in both of the native and invasive ranges. Maximum temperature was the most important climatic variable in predictions of the distribution of native populations, while precipitation seasonality was the most important in predictions of invasive populations. The realized niche of L. hasselti in its invasive range differed from that in its native range, indicating possible realized niche shift. Conclusions We infer that a preference for human-disturbed environments may underlie invasion and establishment in this spider species, as anthropogenic habitat modifications could provide shelters from unsuitable climatic conditions and extreme climatic stresses to the spiders. Because Australia and the countries in which the species is invasive have differing climates, differences in the availability of certain climatic conditions could have played a role in the realized niche shift of L. hasselti.

Abstract Background Morinda officinalis How (MO) is a perennial herb distributed in tropical and subtropical regions, which known as one of the “Four Southern Herbal Medicines”. The extent of genetic variability and the population structure of MO are presently little understood. Here, nine morphological traits, six chemical components and Single nucleotide polymorphism (SNP) markers were used in integrative research of MO germplasm variation among 88 individuals collected from ten populations across four geographical provinces of China. Results Both phenotype and chemical composition have significant genetic variation, and there is a certain correlation between them such as root diameter and the nystose content, as well as geographical distribution. The principal component analysis (PCA) showed the leaf length, leaf width, nystose, 1F-furanosaccharide nystose, and the section color were the major contributors to diversity. The cluster analysis based on phenotypic and oligosaccharide data distinguished three significant groups, which was consistent with the result of a corresponding analysis with 228,615 SNP markers, and importantly, they all showed a significant correlation with geographical origin. However, there was little similarity between two cluster results. The Shannon’s information index (I) varied from 0.17 to 0.53 with a mean of 0.37, suggesting a high level of genetic diversity in MO populations, which mainly existed among individuals within populations, accounting for 99.66% of the total according to the analysis of molecular variance (AMOVA) results. Each population also maintains the connection because of certain gene communication, so that the genetic differentiation between populations was not very significant. The STRUCTURE software was used to analyse the population structure and the result showed that 88 accessions were clustered into three groups, and 67% of them were pure type, which was also confirmed through PCA. Conclusions The comprehensive study of phenotypic, chemical and molecular markers will provide valuable information for future breeding plans and understanding the phylogenetic relationship of MO population.

BackgroundMajor depressive disorder (MDD) with anxious distress is a relatively common condition that is often associated with a poor treatment response. In order to enhance the effectiveness of MDD treatment, 5-HT1A agonists like tandospirone are often prescribed in conjunction with antidepressants. While it is known that antidepressants can increase the risk of bleeding, whether tandospirone poses a similar risk remains uncertain.Case presentationWe presented the case of a 55-year-old Chinese woman diagnosed with MDD and anxious distress. After receiving various types of antidepressants, she experienced hematochezia following the administration of tandospirone, sertraline, and agomelatine. The occurrence of hematochezia ceased after tandospirone was discontinued. The patient was subsequently discharged with a treatment regime consisting of sertraline and agomelatine. During the 1-month follow-up, she reported no hematochezia.ConclusionTandospirone may potentially increase the risk of hematochezia in patients with MDD and anxious distress.

This review article provides a comprehensive analysis of the hydrogen landscape, outlining the imperative for enhanced hydrogen production, implementation, and utilisation. It places the question of how to accelerate hydrogen adoption within the broader context of sustainable energy transitions and international commitments to reduce carbon emissions. It discusses influencing factors and policies for best practices in hydrogen energy application. Through an in-depth exploration of key factors affecting hydrogen implementation, this study provides insights into the complex interplay of both technical and logistical factors. It also discusses the challenges of planning, constructing infrastructure, and overcoming geographical constraints in the transition to hydrogen-based energy systems. The drive to achieve net-zero carbon emissions is contingent on accelerating clean hydrogen development, with blue and green hydrogen poised to complement traditional fuels. Public–private partnerships are emerging as catalysts for the commercialisation of hydrogen and fuel-cell technologies, fostering hydrogen demonstration projects worldwide. The anticipated integration of clean hydrogen into various sectors in the coming years signifies its importance as a complementary energy source, although specific applications across industries remain undefined. The paper provides a good reference on the gradual integration of hydrogen into the energy landscape, marking a significant step forward toward a cleaner, greener future.

Summary: The rixosome and PRC1 silencing complexes are associated with deSUMOylating and deubiquitinating enzymes, SENP3 and USP7, respectively. How deSUMOylation and deubiquitylation contribute to rixosome- and Polycomb-mediated silencing is not fully understood. Here, we show that the enzymatic activities of SENP3 and USP7 are required for silencing of Polycomb target genes. SENP3 deSUMOylates several rixosome subunits, and this activity is required for association of the rixosome with PRC1. USP7 associates with canonical PRC1 (cPRC1) and deubiquitinates the chromodomain subunits CBX2 and CBX4, and inhibition of USP activity results in disassembly of cPRC1. Finally, both SENP3 and USP7 are required for Polycomb- and rixosome-dependent silencing at an ectopic reporter locus. These findings demonstrate that SUMOylation and ubiquitination regulate the assembly and activities of the rixosome and Polycomb complexes and raise the possibility that these modifications provide regulatory mechanisms that may be utilized during development or in response to environmental challenges.

Dendritic cells (DCs) are antigen-presenting cells that bridge innate and adaptive immune responses. Multiple cell types, including DCs, rely on cellular metabolism to determine their fate. DCs substantially alter cellular metabolic pathways during activation, such as oxidative phosphorylation, glycolysis, fatty acid and amino acid metabolism, which have crucial implications for their functionality. In this review, we summarize and discuss recent progress in DC metabolic studies, focusing on how metabolic reprogramming influences DC activation and functionality and the potential metabolic differences among DC subsets. Improving the understanding of the relationship between DC biology and metabolic regulation may provide promising therapeutic targets for immune-mediated inflammatory diseases.

Abstract Background The association of Apolipoprotein A‐I (APOAI) with T cell subsets and interferon‐ү (IFN‐γ) in patients with coronary artery disease (CAD) has been not reported. Thus, this study aimed to investigate the association of APOAI with T cell subsets and IFN‐γ in CAD. Methods This study included a total of 107 patients with CAD including acute coronary syndrome and chronic coronary syndrome. T cell subsets, and CD3‐CD56+ natural killer cells were quantified by flow cytometric analysis. The serum concentrations of IFN‐ү were measured by enzyme‐linked immunosorbent assay. Lipid profiles, C‐reactive protein (CRP), and fibrinogen were measured in the clinical laboratory. Clinical data was obtained duration hospitalization. Results The CD4+ T cells were higher in patients of the low‐APOAI group ( .05). The high‐density lipoprotein cholesterol (HDL‐C) was also inversely associated with CD4+ T cells (p .05). Conclusion The present study demonstrated the correlation of APOAI with T cell subsets and IFN‐γ in CAD. These results provided novel information for the regulatory action between APOAI and T cell subsets and inflammatory immunity in CAD.

The pathogenesis of biliary atresia remains poorly understood. Here, the authors report that maternal butyrate treatment alters the gut microbiome and glutamine/hypoxanthine metabolites similar to human subjects, and suppresses biliary atresia in newborn mice.

The oral mucosa’s immune system is composed of tissue-resident and specifically recruited leukocytes that could effectively tolerate a wide range of microbial and mechanical assaults. Shortly after CD4+ helper T cells (TH17 cells) that produce interleukin 17 (IL-17) were identified, it was discovered that γδT cells could also induce substantial levels of this pro-inflammatory cytokine. In the past decades, it has become clear that due to a complicated thymic program of development, γδT cells frequently serve as the primary sources of IL-17 in numerous models of inflammatory diseases while also assisting in the maintenance of tissue homeostasis in the skin and intestine. But it wasn’t until recently that we took thorough insight into the complex features of γδT cells in the oral mucosa. Most gingival intraepithelial γδT cells reside in the junctional epithelium adjacent to the dental biofilm, suggesting their potential role in regulating oral microbiota. However, inconsistent results have been published in this regard. Similarly, recent findings showed contradictory data about the role of γδT lymphocytes in experimental periodontitis based on different models. In addition, conflicting findings were presented in terms of alveolar bone physiology and pathology underlying the oral mucosa. This review provided an overview of current knowledge and viewpoints regarding the complex roles played by oral-resident γδT cells in host-microbiota interactions, gingivitis and periodontitis, bone physiology and pathology.

ABSTRACT Klebsiella pneumoniae is an opportunistic pathogen that causes serious infections in humans and animals. However, the availability of epidemiological information on clinical mastitis due to K. pneumoniae is limited. To acquire new information regarding K. pneumoniae mastitis, data were mined about K. pneumoniae strains on dairy cattle farms (farms A to H) in 7 Chinese provinces in 2021. Hypermucoviscous strains of K. pneumoniae were obtained by the string test. MICs of antimicrobial agents were determined via the broth microdilution method. Ten antimicrobial resistance genes and virulence genes were identified by PCR. The prevalence of K. pneumoniae was 35.91% (65/181), and 100% of the bacteria were sensitive to enrofloxacin. Nine antimicrobial resistance genes and virulence genes were identified and compared among farms. The hypermucoviscous phenotype was present in 94.44% of isolates from farm B, which may be a function of the rmpA virulence gene. Based on these data, the multidrug-resistant strains SD-14 and HB-21 were chosen and sequenced. Genotypes were assayed for K. pneumoniae isolates from different countries and different hosts using multilocus sequence typing (MLST). Ninety-four sequence types (STs) were found, and 6 STs present a risk for spreading in specific regions. Interestingly, ST43 was observed in bovine isolates for the first time. Our study partially reveals the current distribution characteristics of bovine K. pneumoniae in China and may provide a theoretical basis for the prevention and treatment of bovine K. pneumoniae mastitis. IMPORTANCE K. pneumonia is ubiquitous in nature and infects a wide range of hosts, including animals, and humans. It is one of the leading inducements of clinical mastitis (CM) in dairy cows, a prevalent and costly disease that is predominantly associated with bacterial infection. In general, CM caused by Gram-negative bacteria is more difficult to cure than that associated with Gram-positive pathogens, with an average cost per case of 211.03 U.S. dollars (USD) for Gram-negative bacterial infections compared with 133.73 USD for Gram-positive bacterial CM cases. After Escherichia coli, K. pneumoniae is the second most common Gram-negative cause of bovine CM, but it is the most detrimental in terms of decreased milk yield, discarded milk, treatment costs, death, and culling. In view of the economic implications of K. pneumoniae infection in dairy farming, research into population structure and antibiotic resistance is particularly important.

Biliary atresia (BA) is a devastating cholangiopathy in neonate. Transcription factors (TFs), a type of master regulators in biological processes and diseases, have been implicated in pathogenesis of BA. However, a global view of TFs and how they link to clinical presentations remain explored. Here, we perform a joint transcriptional regulatory network and protein activity inference analysis in order to investigate transcription factor activity in BA. By integration of three independent human BA liver transcriptome datasets, we identify 22 common master regulators, with 14 activated- and 8 repressed TFs. Gene targets of activated TFs are enriched in biological processes of SMAD, NF-kappaB and TGF-beta, while those of repressed TFs are related to lipid metabolism. Mining the clinical association of TFs, we identify inflammation-, fibrosis- and survival associated TFs. In particular, ZNF14 is predictive of poor survival and advanced live fibrosis. Supporting this observation, ZNF14 is positively correlated with T helper cells, cholangiocytes and hepatic stellate cells. In sum, our analysis reveals key clinically associated master regulators for BA.

Long noncoding RNAs (lncRNAs) have been reported to play a key role in regulating tumor microenvironment and immunity. Cancer-associated fibroblasts (CAFs) are abundant in many tumors. However, the functional and clinical significance of lncRNAs specifically expressed in CAFs has not been fully elucidated. In this study, we identified a list of 95 CAF-specific lncRNAs (FibLnc), including HHLA3, TP53TG1, ST7-AS1, LINC00536, ZNF503-AS1, MIR22HG, and MAPT-AS1, based on immune cell transcriptome expression profiling data. Based on the Cancer Genome Atlas and Gene Expression Omnibus datasets, we found that the FibLnc score predicted differences in overall patient survival and performed well in multiple datasets. FibLnc score was associated with the clinical stage of patients with breast cancer but did not significantly correlate with the PAM50 classification. Functional analysis showed that FibLnc was positively correlated with signaling pathways associated with malignant tumor progression. In addition, FibLnc was positively correlated with tumor mutational load and could predict immunotherapy response in patients with breast cancer receiving anti-PD-1 or anti-CTLA4 therapy. Our proposed FibLnc score was able to reflect the status of the immune environment and immunotherapeutic response in breast cancer, which could help explore potential therapeutic decisions and regulatory mechanisms of CAF-specific lncRNAs.

Background and purposeResection of radiation-induced ulcers often causes full-thickness defects of the chest wall. We retrospectively reviewed and evaluated 17 patients to explore a method of chest wall reconstruction.Materials and methodsA total of 17 breast cancer patients with radiation-induced ulcers were included. Various type of prostheses and flaps were used, results of clinic were evaluated.ResultsSixteen patients had full-thickness defects and one patient had only a soft tissue defect and underwent reconstruction with a pedicle latissimus dorsi (LD) myocutaneous flap. Among all 16 full-thickness defect cases, 15 patients underwent bony thoracic reconstruction using polymesh/3D-printed titanium plates or methyl methacrylate. For soft tissue reconstruction, 13 patients reconstruction using a free deep inferior epigastric perforator (DIEP) flap in combination with a contralateral transverse rectus abdominis myocutaneous (TRAM) flap, and 2 underwent pure free DIEP flap reconstruction. Among all the patients 15 healed with no complications, and 2 patients had delayed healing on the edges of the flaps.ConclusionsDistant pedicle or free flap can used for soft tissue defect coverage, for those severe patients with full-thickness defects and used prostheses, free deep inferior epigastric perforator flap in combination with a contralateral transverse rectus abdominis myocutaneous flap (TRAM + DIEP) would be an applicable choice.

Real-time condition monitoring of various types of machinery using sensor technology has gained significant importance in recent years. However, relying on batteries to power these sensors proves to be sub-optimal, as it necessitates regular charging or replacement. To address this, harvesting waste energy from ambient sources emerges as a more efficient alternative. Everyday applications like vehicle wheels, fans, and turbines present ambient sources of waste rotational energy. In this study, we propose a novel rotational energy harvester design that converts rotational energy into linear energy. This linear energy impacts a piezoelectric disk, generating an electric potential. Through simulations, the expected electric potential at varying frequencies was evaluated. Subsequently, experimental tests were conducted by connecting the harvester to a rectifier for AC-to-DC signal conversion and an oscilloscope for voltage measurement. A DC motor replicated the rotational motion at the frequencies from the simulation, and the power output was measured. Using the power transfer theorem, simulation and experimental power outputs were calculated, resulting in values of 188, 513, and 1293 μW and 88.89, 336, and 923 μW, respectively. These results reveal that the designed harvester is competitive with those of existing rotational energy harvester designs, demonstrating the promising potential of this novel harvester.

BackgroundSoluble lymphocyte activation gene 3 (sLAG3) may be used for diagnosis or prognosis in various diseases. However, the relationship between sLAG3 and coronary artery disease (CAD) are still unclear. This study aimed to investigate the levels of sLAG3 in patients with CAD, and its potential clinical association with the disease.MethodsA total of 66 subjects (49 patients with CAD and 17 control subjects without CAD) were enrolled. The sLAG3 level was measured using enzyme-linked immunosorbent assay (ELISA) kits. Clinical variables included demographics, biochemical markers, coronary angiography status, and ejection fraction of the heart (EF) were collected, and Gensini scores were calculated. LAG3 gene data was extracted from three datasets (GSE23561, GSE61144, GSE60993) in Gene Expression Omnibus (GEO) to compare differential expression between CAD and control subjects.ResultsThe sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060–0.746, P < 0.05]. Furthermore, the area under the curve (AUC) of sLAG3 level was significant (P < 0.05). The sLAG3 level in subjects with body mass index (BMI) ≥ 24 kg/m2 was lower compared to those with BMI < 24 kg/m2 (P < 0.05). The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05). Lastly, the LAG3 gene expression in peripheral whole blood of patients with CAD were down-regulated compared to healthy controls (P < 0.05).ConclusionThe sLAG3 level was negatively associated with the occurrence but not severity of CAD. Meanwhile, the sLAG3 was negatively associated with BMI and diabetes mellitus, suggesting the reduced sLAG3 might be a novel risk factor for developing CAD.

Conventional techniques (e.g., culture-based method) for bacterial detection typically require a central laboratory and well-trained technicians, which may take several hours or days. However, recent developments within various disciplines of science and engineering have led to a major paradigm shift in how microorganisms can be detected. The analytical sensors which are widely used for medical applications in the literature are being extended for rapid and on-site monitoring of the bacterial pathogens in food, water and the environment. Especially, within the low-resource settings such as low and middle-income countries, due to the advantages of low cost, rapidness and potential for field-testing, their use is indispensable for sustainable development of the regions. Within this context, this paper discusses analytical methods and biosensors which can be used to ensure food safety, water quality and environmental monitoring. In brief, most of our discussion is focused on various rapid sensors including biosensors and microfluidic chips. The analytical performances such as the sensitivity, specificity and usability of these sensors, as well as a brief comparison with the conventional techniques for bacteria detection, form the core part of the discussion. Furthermore, we provide a holistic viewpoint on how future research should focus on exploring the synergy of different sensing technologies by developing an integrated multiplexed, sensitive and accurate sensors that will enable rapid detection for food safety, water and environmental monitoring.

Wireless energy harvesting enables the conversion of ambient energy into electrical power for small wireless electronic devices. This technology offers numerous advantages, including availability, ease of implementation, wireless functionality, and cost-effectiveness. Radio frequency energy harvesting (RFEH) is a specific type of wireless energy harvesting that enables wireless power transfer by utilizing RF signals. RFEH holds immense potential for extending the lifespan of wireless sensors and wearable electronics that require low-power operation. However, despite significant advancements in RFEH technology for self-sustainable wearable devices, numerous challenges persist. This literature review focuses on three key areas: materials, antenna design, and power management, to delve into the research challenges of RFEH comprehensively. By providing an up-to-date review of research findings on RFEH, this review aims to shed light on the critical challenges, potential opportunities, and existing limitations. Moreover, it emphasizes the importance of further research and development in RFEH to advance its state-of-the-art and offer a vision for future trends in this technology.

Abstract Background Understanding the impacts of past and contemporary climate change on biodiversity is critical for effective conservation. Amphibians have weak dispersal abilities, putting them at risk of habitat fragmentation and loss. Both climate change and anthropogenic disturbances exacerbate these risks, increasing the likelihood of additional amphibian extinctions in the near future. The giant spiny frog (Quasipaa spinosa), an endemic species to East Asia, has faced a dramatic population decline over the last few decades. Using the giant spiny frog as an indicator to explore how past and future climate changes affect landscape connectivity, we characterized the shifts in the suitable habitat and habitat connectivity of the frog. Results We found a clear northward shift and a reduction in the extent of suitable habitat during the Last Glacial Maximum for giant spiny frogs; since that time, there has been an expansion of the available habitat. Our modelling showed that “overwarm” climatic conditions would most likely cause a decrease in the available habitat and an increase in the magnitude of population fragmentation in the future. We found that the habitat connectivity of the studied frogs will decrease by 50–75% under future climate change. Our results strengthen the notion that the mountains in southern China and the Sino-Vietnamese transboundary regions can act as critical refugia and priority areas of conservation planning going forward. Conclusions Given that amphibians are highly sensitive to environmental changes, our findings highlight that the responses of habitat suitability and connectivity to climate change can be critical considerations in future conservation measures for species with weak dispersal abilities and should not be neglected, as they all too often are.

It is still challenging to make accurate diagnosis of biliary atresia (BA) with sonographic gallbladder images particularly in rural areas without relevant expertise. Here, the authors develop a diagnostic deep learning model which favourable performance in comparison with human experts in multi-center external validation.

Objective The aim of the present study was to report a novel design of the chimeric deep inferior epigastric artery perforator flap (DIEP) to achieve dead space filling, Achilles tendon bridging, and skin resurfacing simultaneously with minimal donor‐site morbidity. Methods From September 2012 to May 2016, a retrospective study was carried out on six pediatric patients with composite soft tissue defects of the heel that were repaired with the chimeric DIEP flap. The chimeric flap design included a flap of the anterior sheath of the rectus, a block of rectus muscle, and a large skin paddle. All the parts were supplied by a common artery. After harvesting the flap, all element parts were inserted at the corresponding sites in a tension‐free manner. With one set of vessel anastomoses at the recipient site, accurate repair with tendon reconstruction, dead space elimination, and wound covering were accomplished. The donor site incisions were closed initially. Data on patient age, medical history, injury severity, defect size, flap dimensions, recipient vessels, donor site closure, complications, and follow‐up were collected and reviewed. Results Five of the six chimeric DIEP flaps survived without complications. The remaining one case experienced partial necrosis of the skin paddle caused by venous congestion, which healed after routine dressing changes. Primary donor site closure was accomplished in all cases. The mean follow‐up was 18.6 months (range, 10–36 months). Five patients had satisfactory aesthetic and functional outcomes; one patient needed a secondary debulking procedure. Compared to the unaffected side, the affected side showed no obvious difference for ankle movement, tiptoe function, and patient gait during the follow‐up period. Good ankle function was observed in all patients. There was no donor site breakdown, with only a slightly noticeable linear scar. Conclusion The chimeric DIEP flap reduced the operative time, solved the problem of deficiency of recipient vessels, and attained satisfactory functional and aesthetic outcomes with low donor site morbidity. Therefore, it is a promising option for three‐dimensional reconstruction of composite defects with dead space and Achilles tendon defects as well as skin loss in children.

Abstract Objectives The homeostasis of oral pathogenic bacteria and probiotics plays a crucial role in maintaining the well-being and healthy status of human host. Our previous study confirmed that imbalanced oral microbiota could impair mesenchymal stem cell (MSC) proliferation capacity and delay wound healing. However, the effects of balanced oral pathogenic bacteria and probiotics on MSCs and wound healing are far from clear. Here, the balance of pathogenic bacteria Porphyromonas gingivalis and probiotics Lactobacillus reuteri extracts was used to investigate whether balanced oral microbiota modulate the physiological functions of MSCs and promote wound healing. Methods The effects of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts on gingival MSCs (GMSCs) were tested using the migration, alkaline phosphatase activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts in the wound of mice, the wounds were established in the mucosa of palate and were inoculated with bacteria every 2 days. Results We found that the balance between pathogenic bacteria and probiotics enhanced the migration, osteogenic differentiation, and cell proliferation of MSCs. Additionally, local inoculation of the mixture of L. reuteri and P. gingivalis promoted the process of wound healing in mice. Mechanistically, we found that LPS in P. gingivalis could activate NLRP3 inflammasome and inhibit function of MSCs, thereby accelerating MSC dysfunction and delaying wound healing. Furthermore, we also found that reuterin was the effective ingredient in L. reuteri which maintained the balance of pathogenic bacteria and probiotics by neutralizing LPS in P. gingivalis, thus inhibiting inflammation and promoting wound healing. Conclusions This study revealed that the homeostasis of oral microbiomes played an indispensable role in maintaining oral heath, provided hopeful methods for the prevention and treatment of oral diseases, and had some referential value for other systemic diseases caused by dysfunction of microbiota and MSCs.

The CTC1-STN1-TEN1 (CST) complex plays a crucial role in telomere replication and genome stability. However, the detailed mechanisms of CST regulation in cancer remain largely unknown. Here, we perform a comprehensive analysis of CST across 33 cancer types using multi-omic data from The Cancer Genome Atlas. In the genomic landscape, we identify CTC1/STN1 deletion and mutation and TEN1 amplification as the dominant alteration events. Expressions of CTC1 and STN1 are decreased in tumors compared to those in adjacent normal tissues. Clustering analysis based on CST expression reveals three cancer clusters displaying differences in survival, telomerase activity, cell proliferation, and genome stability. Interestingly, we find that CTC1 and STN1, but not TEN1, are co-expressed and associated with better survival. CTC1-STN1 is positively correlated with CD8 T cells and B cells and predicts a better response to immune checkpoint blockade in external datasets of cancer immunotherapy. Pathway analysis shows that MYC targets are negatively correlated with CTC1-STN1. We experimentally validated that knockout of CTC1 increased the mRNA level of c-MYC. Furthermore, CTC1 and STN1 are repressed by miRNAs and lncRNAs. Finally, by mining the connective map database, we discover a number of potential drugs that may target CST. In sum, this study illustrates CTC1-STN1 as a protective factor and provides broad molecular signatures for further functional and therapeutic studies of CST in cancer.

The need to reduce energy consumption in greenhouse production has grown. Thermal heating demand alone accounts for 80% of conventional greenhouse energy consumption; this significantly reduces production profit. Since microclimate affects crop metabolic processes and output, it is essential to monitor and control it to achieve both quantity and quality production with minimum energy consumption for maximum profit. The Internet of Things (IoT) is an evolving technology for monitoring and controlling environments that have recently been adopted to boost greenhouse efficiency in many applications by integrating hardware and software solutions; therefore, its adoption is thus critical in enabling greenhouse energy consumption minimisation. The first objective of this study is to improve and validate a greenhouse dynamic air temperature model required to simulate or predict indoor temperature. To achieve the first objective, therefore, an existing model was enhanced and a closed loop test experimental data from the IoT cloud-based control system platform deployed in the prototype greenhouse built in Cranfield University was used to validate the model using an optimisation-based model fitting approach. The second goal is to control the greenhouse air temperature in simulation using relatively simple PI and on-off control strategies to maintain the grower’s desired setpoint irrespective of the inevitable disturbances and to verify the potential of the controllers in minimising the total energy input to the greenhouse. For the second objective, the simulation results showed that the two controllers maintained the desired setpoint; however, the on-off strategy retained a sustainable oscillation, and the tuned PI effectively maintained the desired temperature, although the average energy used by the controllers is the same.

This article presents a review to provide up-to-date research findings on concentrated photovoltaic (CPV) cooling, explore the key challenges and opportunities, and discuss the limitations. In addition, it provides a vision of a possible future trend and a glimpse of a promising novel approach to CPV cooling based on pulsating flow, in contrast to existing cooling methods. Non-concentrated photovoltaics (PV) have modest efficiency of up to around 20% because they utilise only a narrow spectrum of solar irradiation for electricity conversion. Therefore, recent advances employed multi-junction PV or CPV to widen the irradiation spectrum for conversion. CPV systems concentrate solar irradiation on the cell’s surface, producing high solar flux and temperature. The efficient cooling of CPV cells is critical to avoid thermal degradation and ensure optimal performance. Studies have shown that pulsating flow can enhance heat transfer in various engineering applications. The advantage of pulsating flow over steady flow is that it can create additional turbulence and mixing in the fluid, resulting in a higher heat transfer coefficient. Simulation results with experimental validation demonstrate the enhancement of this new cooling approach for future CPV systems. The use of pulsating flow in CPV cooling has shown promising results in improving heat transfer and reducing temperature gradients.

Abstract Background Aspirin has been demonstrated to promote osteoblast-mediated bone formation and inhibit osteoclast (OC)-mediated bone resorption. However, it remains unclear whether aspirin influences other immune cells during bone resorption. Dendritic cells (DCs), the most potent antigen-presenting cells, can also transdifferentiate into active OCs in the presence of receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The effects of aspirin on DC-derived OCs (DDOCs) were investigated in the current study. Methods Flow cytometry and mixed lymphocyte reaction (MLR) assays were used for DC identification. The proliferative capacity of DCs was determined by BrdU assays. Apoptosis was examined by flow cytometry. The osteoclastic potential of DCs was tested using tartrate-resistant acid phosphatase (TRAP) staining, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). Western blotting was also used to examine signaling pathways. A mandibular bone defect model was established to assess the effect of aspirin on bone resorption. Results Aspirin had no influence on the surface phenotype, proliferation, or apoptosis of DCs, though aspirin significantly inhibited osteoclast differentiation in RANKL-stimulated DCs. DC osteoclast differentiation was modulated by aspirin via the nuclear factor kappa B (NF-κB)/nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) signaling pathway. Aspirin treatment also had favorable therapeutic effects on bone regeneration in the bone defect model, and the number of osteoclasts was decreased. Conclusions Aspirin inhibited RANKL-induced OC differentiation in DCs via the NF-κB pathway, downregulating expression of NFATc1. Aspirin treatment promoted bone regeneration by inhibiting DDOC activation in the early stages of inflammation in a rat mandibular bone defect model.

Abstract Background The balance of oral microbiomes is crucial to maintain oral health. Microecological imbalance can impair the function of mesenchymal stem cells (MSCs) and lead to delay wound healing. Probiotics is a promising prevention approach for the treatment of oral inflammatory diseases caused by a bacterial infection. However, the effect of probiotics on oral MSCs and wound healing is unclear. In the present study, we used one type of probiotics Lactobacillus reuteri extracts to determine whether bacterial extracts could regulate the functions of gingiva MSCs (GMSCs) and promote wound healing. Methods Lactobacillus reuteri was prepared with bacterial extracts using ultrasonic crushing apparatus. The effects of Lactobacillus reuteri extracts on GMSCs were tested using the cell scratch migration, alkaline phosphatase (ALP) activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of Lactobacillus reuteri extracts in the wound in mice, the wound position of bilateral mesial gingival of the maxillary first molar was established, the wound area with a size of 1 mm × 2 mm and the full thickness gingiva was removed. Mice with wound were randomly distributed to two groups: injection of 0.9% NaCl (NS group) or injection of 50 μg/ml bacterial extracts. Results We discovered that 50 μg/ml Lactobacillus reuteri extracts increased the capacities of migration, expression of stem cell markers, osteogenic differentiation, and proliferation of GMSCs. In addition, local injection of 50 μg/ml bacterial extracts could promote wound-healing process in mice models. Mechanistically, we found that Lactobacillus reuteri extracts accelerated the process of wound healing via PI3K/AKT/β-catenin/TGFβ1 pathway. Conclusions These data showed that Lactobacillus reuteri extracts could activate the potentials of GMSCs, thus promote wound healing. Our discovery provided the insight of the underlying mechanism activating functions of MSCs and identified Lactobacillus reuteri extracts as a potential therapeutic strategy for accelerating oral wound and potential application in the future dental clinic.

Abstract Background Cancer cells become immortalized through telomere maintenance mechanisms, such as telomerase reverse transcriptase (TERT) activation. In addition to maintaining telomere length, TERT activates manifold cell survival signaling pathways. However, telomerase-associated gene signatures in cancer remain elusive. Methods We performed a systematic analysis of TERT high (TERThigh) and low (TERTlow) cancers using multidimensional data from The Cancer Genome Atlas (TCGA). Multidimensional data were analyzed by propensity score matching weight algorithm. Coexpression networks were constructed by weight gene coexpression network analysis (WGCNA). Random forest classifiers were generated to identify cancer subtypes. Results The TERThigh-specific mRNA expression signature is associated with cell cycle-related coexpression modules across cancer types. Experimental screening of hub genes in the cell cycle module suggested TPX2 and EXO1 as potential regulators of telomerase activity and cell survival. MiRNA analysis revealed that the TERThigh-specific miR-17-92 cluster can target biological processes enriched in TERTlow cancer and that its expression is negatively correlated with the tumor/normal telomere length ratio. Intriguingly, TERThigh cancers tend to have mutations in extracellular matrix organization genes and amplify MAPK signaling. By mining the clinical actionable gene database, we uncovered a number of TERThigh-specific somatic mutations, amplifications and high expression genes containing therapeutic targets. Finally, a random forest classifier integrating telomerase-associated multi-omics signatures identifies two cancer subtypes showed profound differences in telomerase activity and patient survival. Conclusions In summary, our results depict a telomerase-associated molecular landscape in cancers and provide therapeutic opportunities for cancer treatment.

Background Sorafenib is mainly used to treat patients with hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage C, many of whom also have severe cirrhosis. However, hypersplenism and digestive tract hemorrhage are common complications of cirrhosis, which increase the risk and difficulty of treatment. Methods Nineteen patients with HCC BCLC stage C with hypersplenism were treated with sorafenib plus partial splenic embolism at Chongqing University Cancer Hospital, Chongqing, China, between January 2015 and June 2018. We analyzed the therapeutic effect and clinical safety of this treatment in these patients. Result Hypersplenism was rectified in all patients. The incidence rates of hemorrhage and myelosuppression were 0%, and the mean survival time was 11.2 months. Conclusion Sorafenib plus partial splenic embolism could relieve hypersplenism and prolong survival in patients with BCLC stage C HCC.

Streptococcus uberis (S. uberis) is an important pathogen causing mastitis, which causes continuous inflammation and dysfunction of mammary glands and leads to enormous economic losses. Most research on infection continues to be microbial metabolism-centric, and many overlook the fact that pathogens require energy from host. Mouse is a common animal model for studying bovine mastitis. In this perspective, we uncover metabolic reprogramming during host immune responses is associated with infection-driven inflammation, particularly when caused by intracellular bacteria. Taurine, a metabolic regulator, has been shown to effectively ameliorate metabolic diseases. We evaluated the role of taurine in the metabolic regulation of S. uberis-induced mastitis. Metabolic profiling indicates that S. uberis exposure triggers inflammation and metabolic dysfunction of mammary glands and mammary epithelial cells (the main functional cells in mammary glands). Challenge with S. uberis upregulates glycolysis and oxidative phosphorylation in MECs. Pretreatment with taurine restores metabolic homeostasis, reverses metabolic dysfunction by decrease of lipid, amino acid and especially energy disturbance in the infectious context, and alleviates excessive inflammatory responses. These outcomes depend on taurine-mediated activation of the AMPK–mTOR pathway, which inhibits the over activation of inflammatory responses and alleviates cellular damage. Thus, metabolic homeostasis is essential for reducing inflammation. Metabolic modulation can be used as a prophylactic strategy against mastitis.

Streptococcus uberis infection can cause serious inflammation and damage to mammary epithelial cells and tissues that can be significantly alleviated by taurine. Autophagy plays an important role in regulating immunity and clearing invasive pathogens and may be regulated by taurine. However, the relationships between taurine, autophagy, and S. uberis infection remain unclear. Herein, we demonstrate that taurine augments PTEN activity and inhibits Akt/mTOR signaling, which decreases phosphorylation of ULK1 and ATG13 by mTOR and activates autophagy. Activating autophagy accelerates the degradation of intracellular S. uberis, reduces intracellular bacterial load, inhibits over-activation of the NF-κB pathway, and alleviates the inflammation and damage caused by S. uberis infection. This study increases our understanding of the mechanism through which taurine regulates autophagy and is the first to demonstrate the role of autophagy in S. uberis infected MAC-T cells. Our study also provides a theoretical basis for employing nutritional elements (taurine) to regulate innate immunity and control S. uberis infection. It also provides theoretical support for the development of prophylactic strategies for this important pathogen.

Summary: MED1 (mediator subunit 1) co-amplifies with HER2, but its role in HER2-driven mammary tumorigenesis is still unknown. Here, we generate MED1 mammary-specific overexpression mice and cross them with mouse mammary tumor virus (MMTV)-HER2 mice. We observe significantly promoted onset, growth, metastasis, and multiplicity of HER2 tumors by MED1 overexpression. Further studies reveal critical roles for MED1 in epithelial-mesenchymal transition, cancer stem cell formation, and response to anti-HER2 therapy. Mechanistically, RNA sequencing (RNA-seq) transcriptome analyses and clinical sample correlation studies identify Jab1, a component of the COP9 signalosome complex, as the key direct target gene of MED1 contributing to these processes. Further studies reveal that Jab1 can also reciprocally regulate the stability and transcriptional activity of MED1. Together, our findings support a functional cooperation between these co-amplified genes in HER2+ mammary tumorigenesis and their potential usage as therapeutic targets for the treatment of HER2+ breast cancers.

Candida parapsilosis is a major fungal pathogen that leads to sepsis. New and more effective antifungal agents are required due to the emergence of resistant fungal strains. MAF-1A is a cationic antifungal peptide isolated from Musca domestica that is effective against a variety of Candida species. However, the mechanism(s) of its antifungal activity remains undefined. Here, we used RNA-seq to identify differentially expressed genes (DEGs) in Candida parapsilosis following MAF-1A exposure. The early (6 h) response included 1,122 upregulated and 1,065 downregulated genes. Late (18 h) responses were associated with the increased expression of 101 genes and the decreased expression of 151 genes. Upon MAF-1A treatment for 18 h, 42 genes were upregulated and 25 genes were downregulated. KEGG enrichment showed that the DEGs in response to MAF-1A were mainly involved in amino acid synthesis and metabolism, oxidative phosphorylation, sterol synthesis, and apoptosis. These results indicate that MAF-1A exerts antifungal activity through interference with Candida parapsilosis cell membrane integrity and organelle function. This provides new insight into the interaction between Candida parapsilosis and this antimicrobial peptide and serves as a reference for future Candida parapsilosis therapies.

Heterozygous loss of chromosome 17p is a common genomic event in castration-resistant prostate cancers (CRPC). Here, the authors use CRISPR-based screen to identify RBX1 as a target gene for CRPC with 17p loss and targeting RBX1 sensitizes CRPC to the treatment of α-amanitin antibody conjugates.

Periodontitis is a common intraoral infection and is inextricably linked to systemic diseases. Recently, the regulation between host immunologic response and periodontal pathogens has become a hotspot to explain the mechanism of periodontitis and related systemic diseases. Since Porphyromonas gingivalis (P. gingivalis) was proved as critical periodontal pathogen above all, researches focusing on the mechanism of its virulence factors have received extensive attention. Studies have shown that in the development of periodontitis, in addition to the direct release of virulent factors by periodontal pathogens to destroy periodontal tissues, over-low or over-high intrinsic immune and inflammatory response mediated by Toll-like receptors (TLRs) can lead to more lasting destruction of periodontal tissues. It is very necessary to sort out how various cytopathic factors of P. gingivalis mediate inflammation and immune responses between the host through TLRs so as to help precisely prevent, diagnose, and treat periodontitis in clinic. This review summarizes the role of three most widely studied pathogenic factors produced by P. gingivalis (lipopolysaccharide, gingipains, pili) and their interactions with TLRs at the cellular and molecular level in the progress of periodontitis.

Heart rate monitoring is the predominant quantitative health indicator of a newborn in the delivery room. A rapid and accurate heart rate measurement is vital during the first minutes after birth. Clinical recommendations suggest that electrocardiogram (ECG) monitoring should be widely adopted in the neonatal intensive care unit to reduce infant mortality and improve long term health outcomes in births that require intervention. Novel non-contact electrocardiogram sensors can reduce the time from birth to heart rate reading as well as providing unobtrusive and continuous monitoring during intervention. In this work we report the design and development of a solution to provide high resolution, real time electrocardiogram data to the clinicians within the delivery room using non-contact electric potential sensors embedded in a neonatal intensive care unit mattress. A real-time high-resolution electrocardiogram acquisition solution based on a low power embedded system was developed and textile embedded electrodes were fabricated and characterised. Proof of concept tests were carried out on simulated and human cardiac signals, producing electrocardiograms suitable for the calculation of heart rate having an accuracy within ±1 beat per minute using a test ECG signal, ECG recordings from a human volunteer with a correlation coefficient of ~ 87% proved accurate beat to beat morphology reproduction of the waveform without morphological alterations and a time from application to heart rate display below 6 s. This provides evidence that flexible non-contact textile-based electrodes can be embedded in wearable devices for assisting births through heart rate monitoring and serves as a proof of concept for a complete neonate electrocardiogram monitoring system.

The ultra-short baseline underwater positioning is one of the most widely applied methods in underwater positioning and navigation due to its simplicity, efficiency, low cost, and accuracy. However, there exists environmental noise, which has negative impacts on the positioning accuracy during the ultra-short baseline (USBL) positioning process, which results in a large positioning error. The positioning result may lead to wrong decision-making in the latter processing. So, it is necessary to consider the error sources, and take effective measurements to minimize the negative impact of the noise. In our work, we propose a USBL positioning system with Kalman filtering to improve the positioning accuracy. In this system, we first explore a new kind of element array to accurately capture the acoustic signals from the object. We then organically combine the Kalman filters with the array elements to filter the acoustic signals, using the minimum mean-square error rule to obtain accurate acoustic signals. We got the high-precision phase difference information based on the non-equidistant quaternary original array and the phase difference acquisition mechanism. Finally, on account of the obtained accurate phase difference information and position calculation, we determined the coordinates of the underwater target. Comprehensive evaluation results demonstrate that our proposed USBL positioning method based on the Kalman filter algorithm can effectively enhance the positioning accuracy.