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Fusobacterium nucleatum (F. nucleatum), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of F. nucleatum are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral F. nucleatum in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of F. nucleatum strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with F. nucleatum facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen F. nucleatum and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.

E-commerce with the immersive scene of live streaming gives users a new interaction and consumption experience, extending a new path for traditional marketing. Live barrage, being the primary means of users’ social engagement in live e-commerce, encapsulates their inclination to purchase products, commonly referred to as consumption intention. The mining of live barrage enables the exploration of latent user behavior and consumption intention. The current methods employed for mining consumption intention in e-commerce live barrage encounter challenges including insufficient corpus, excessively brief text, and significant semantic deficiencies. Therefore, this study proposes a paradigm of consumption intention recognition by combining the text features of barrage: by constructing a dataset of Live barrage, cleaning the original dataset, and then using a fused BERT’s feature network model BERT-BiLSTM to identify the consumption intention in live e-commerce Live barrage. The experimental results demonstrate the efficacy of the proposed method for recognizing consumption intention. Finally, this study conducted text mining on live barrage containing consumption intent, including word cloud visualization, topic extraction, and co-occurrence analysis, further investigating consumers’ purchasing needs and intentions.

Abstract Background Many studies have confirmed that circular RNAs (circRNAs) mediate the malignant progression of various tumors including osteosarcoma (OS). Our study is to uncover novel molecular mechanisms by which circ_0000376 regulates OS progression. Methods The expression of circ_0000376, microRNA (miR)-577, hexokinase 2 (HK2) and lactate dehydrogenase-A (LDHA) was determined by quantitative real-time PCR. OS cell proliferation, apoptosis and invasion were measured using cell counting kit 8 assay, colony formation assay, EdU assay, flow cytometry and transwell assay. Besides, cell glycolysis was assessed by testing glucose consumption, lactate production, and ATP/ADP ratios. Protein expression was examined by western blot analysis. The interaction between miR-577 and circ_0000376 or HK2/LADA was verified by dual-luciferase reporter assay. The role of circ_0000376 on OS tumor growth was explored by constructing mice xenograft models. Results Circ_0000376 had been found to be upregulated in OS tissues and cells. Functional experiments revealed that circ_0000376 interference hindered OS cell growth, invasion and glycolysis. Circ_0000376 sponged miR-577 to reduce its expression. In rescue experiments, miR-577 inhibitor abolished the regulation of circ_0000376 knockdown on OS cell functions. MiR-577 could target HK2 and LDHA in OS cells. MiR-577 suppressed OS cell growth, invasion and glycolysis, and these effects were reversed by HK2 and LDHA overexpression. Also, HK2 and LDHA expression could be regulated by circ_0000376. In vivo experiments showed that circ_0000376 knockdown inhibited OS tumorigenesis. Conclusion Circ_0000376 contributed to OS growth, invasion and glycolysis depending on the regulation of miR-577/HK2/LDHA axis, providing a potential target for OS treatment. Graphical Abstract

We address mathematical modelling of respiratory mechanics and put forward a model based on double-exponential and fractional calculus for parameter estimation, model simulation, and evaluation based on actual data. Our model has been implemented on a publicly available executable code with adjustable parameters, making it suitable for different applications. Our analysis represents the first application of fractional calculus and double-exponential modelling to respiratory mechanics, and allows us to propose a hybrid model fitting experimental data in different ventilation modes. Furthermore, our model can be used to study the mechanical features of the respiratory system, improve the safety of ventilation techniques, reduce ventilation damages, and provide strong support for fast and adaptive determination of ventilation parameters.

Purpose: Online integrated marketing is arousing extensive attention from industry and academia, whereas no uniform conclusion on the effectiveness of integrated versus single marketing has been reached thus far. Accordingly, the integrated marketing effectiveness of paid search advertising and social advertising, and the moderating role of product type in it are primarily investigated in this study. Design/methodology/approach: The interaction between paid search advertising and social advertising and purchase is elucidated. Moreover, the moderating effects of product type on the relationship are examined. The hypotheses are tested using an empirical model in accordance with the natural transaction data from Taobao. Findings/results: An empirical analysis confirms a complementary relationship between paid search and social advertising on enhancing purchase. Furthermore, this study suggests that paid search advertising is more probably employed for the purchase of hedonic products, and social advertising more markedly affects the sales of utilitarian products. Moreover, the above-described two advertisements jointly increase the sales of hedonic products. Practical implications: The results provide applicable guidance for sellers’ advertising strategies on online shopping platforms. Sellers should stimulate sales by strategically using integrated marketing tools, and they should adopt different marketing strategies in accordance with different product types. Originality/value: The findings reveal the complementary relationship between paid search and social advertising. Furthermore, this study expands the application of dual-process theory and analyses the information processing of utilitarian and hedonic products.

Osteocytes play an important role in the development and progression of tumour-associated bone disease. Here the authors report an interaction between malignant plasma cells and osteocytes in multiple myeloma and show that the osteocyte-expressed major histocompatibility complex class II transactivator (CIITA) contributes to myeloma-induced bone lesions.

Abstract Background Therapeutic resistance occurs in most patients with multiple myeloma (MM). One of the key mechanisms for MM drug resistance comes from the interaction between MM cells and adipocytes that inhibits drug-induced apoptosis in MM cells; MM cells reprogram adipocytes to morph into different characterizations, including exosomes, which are important for tumor-stroma cellular communication. However, the mechanism by which exosomes mediate the cellular machinery of the vicious cycle between MM cells and adipocytes remains unclear. Methods Adipocytes were either isolated from bone marrow aspirates of healthy donors or MM patients or derived from mesenchymal stem cells. Co-culturing normal adipocytes with MM cells was used to generate MM-associated adipocytes. Exosomes were collected from the culture medium of adipocytes. Annexin V-binding and TUNEL assays were performed to assess MM cell apoptosis. Methyltransferase activity assay and dot blotting were used to access the m6A methylation activity of methyltransferase like 7A (METTL7A). RIP, MeRIP-seq, and RNA–protein pull down for assessing the interaction between long non-cording RNAs (LncRNAs) and RNA binding proteins were performed. Adipocyte-specific enhancer of zeste homolog 2 (EZH2) knockout mice and MM-xenografted mice were used for evaluating MM therapeutic response in vivo. Results Exosomes collected from MM patient adipocytes protect MM cells from chemotherapy-induced apoptosis. Two LncRNAs in particular, LOC606724 and SNHG1, are significantly upregulated in MM cells after exposure to adipocyte exosomes. The raised LncRNA levels in MM cells are positively correlated to worse outcomes in patients, indicating their clinical relevancy in MM. The functional roles of adipocyte exosomal LOC606724 or SNHG1 in inhibition of MM cell apoptosis are determined by knockdown in adipocytes or overexpression in MM cells. We discovered the interactions between LncRNAs and RNA binding proteins and identified methyltransferase like 7A (METTL7A) as an RNA methyltransferase. MM cells promote LncRNA package into adipocyte exosomes through METTL7A-mediated LncRNA m6A methylation. Exposure of adipocytes to MM cells enhances METTL7A activity in m6A methylation through EZH2-mediated protein methylation. Conclusion This study elucidates an unexplored mechanism of how adipocyte-rich microenvironment exacerbates MM therapeutic resistance and indicates a potential strategy to improve therapeutic efficacy by blocking this vicious exosome-mediated cycle.

Recent evidence points out the role of the gut microbiota in the aging process. However, the specific changes and relevant interventions remain unclear. In this study, Senescence Accelerated Mouse-Prone 8 (SAMP8) mice were divided into four groups; young-FMT-group transplanted fecal microbiota from young donors (2–3°months old) and old-FMT-group transplanted from old donors (10–11°months old); additionally, other two groups either adult mice injected with saline solution or untreated mice served as the saline and blank control groups, respectively. All mice were intervened from their 7-months-old until 13-months-old. The open field test at 9 and 11°months of age showed that the mice transplanted with gut microbiota from young donors had significantly better locomotor and exploration ability than those of transplanted with old-donors gut microbiota and those of saline control while was comparable with the blank control. 16S rRNA gene sequencing showed that the gut microbiome of recipient mice of young donors was altered at 11°months of age, whereas the alternation of the gut microbiome of old-donor recipient mice was at 9°months. For comparison, the recipient mice in the blank and saline control groups exhibited changes in the gut microbiome at 10°months of age. The hallmark of aging-related gut microbiome change was an increase in the relative abundance of Akkermansia, which was significantly higher in the recipients transplanted with feces from older donors than younger donors at 9°months of age. This study shows that fecal microbiota transplantation from younger donors can delay aging-related declines in locomotor and exploration ability in mice by changing the gut microbiome.

Nowadays, the commercial potential of live e-commerce is being continuously explored, and machine vision algorithms are gradually attracting the attention of marketers and researchers. During live streaming, the visuals can be effectively captured by algorithms, thereby providing additional data support. This paper aims to consider the diversity of live streaming devices and proposes an extremely lightweight and high-precision model to meet different requirements in live streaming scenarios. Building upon yolov5s, we incorporate the MobileNetV3 module and the CA attention mechanism to optimize the model. Furthermore, we construct a multi-object dataset specific to live streaming scenarios, including anchor facial expressions and commodities. A series of experiments have demonstrated that our model realized a 0.4% improvement in accuracy compared to the original model, while reducing its weight to 10.52%.

Facial expressions, whether simple or complex, convey pheromones that can affect others. Plentiful sensory input delivered by marketing anchors' facial expressions to audiences can stimulate consumers' identification and influence decision-making, especially in live streaming media marketing. This paper proposes an efficient feature extraction network based on the YOLOv5 model for detecting anchors' facial expressions. First, a two-step cascade classifier and recycler is established to filter invalid video frames to generate a facial expression dataset of anchors. Second, GhostNet and coordinate attention are fused in YOLOv5 to eliminate latency and improve accuracy. YOLOv5 modified with the proposed efficient feature extraction structure outperforms the original YOLOv5 on our self-built dataset in both speed and accuracy.

Transcription factor Rme1 regulates meiosis and pseudohyphal growth in baker’s yeast, but its role in the meiosis-defective pathogen Candida albicans is unclear. Here, Hernández-Cervantes et al. show that Rme1 activates the expression of genes required for formation of asexual spores in Candida species.

Abstract Background Neuroinflammation is the major pathogenesis of cerebral ischemia. Microglia are activated and polarized to either the pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype, which act as a critical mediator of neuroinflammation. Sestrin2 has pro-survival properties against ischemic brain injury. However, whether sestrin2 has an anti-inflammatory function by shifting microglia polarization and its underlying mechanism is unknown. Methods Adult male C57BL/6 mice (N = 108) underwent transient middle cerebral artery occlusion (tMCAO) and were treated with exogenous sestrin2. Neurological deficit scores and infarct volume were determined. Cell apoptosis was examined by TUNEL staining and Western blotting. The expression of inflammatory mediators, M1/M2-specific markers, and signaling pathways were detected by reverse transcription-polymerase chain reaction, immunostaining, and Western blotting. To explore the underlying mechanism, primary neurons were subjected to oxygen-glucose deprivation (OGD) and then treated with oxygenated condition medium of BV2 cells incubated with different doses of sestrin2. Results Sestrin2 attenuated the neurological deficits, infarction volume, and cell apoptosis after tMCAO compared to those in the control (p < 0.05). Sestrin2 had an anti-inflammatory effect and could suppress M1 microglia polarization and promote M2 microglia polarization. Condition medium from BV2 cells cultured with sestrin2 reduced neuronal apoptosis after OGD in vitro. Furthermore, we demonstrated that sestrin2 drives microglia to the M2 phenotype by inhibiting the mammalian target of rapamycin (mTOR) signaling pathway and restoring autophagic flux. Conclusions Sestrin2 exhibited neuroprotection by shifting microglia polarization from the M1 to M2 phenotype in ischemic mouse brain, which may be due to suppression of the mTOR signaling pathway and the restoration of autophagic flux.

Abstract Background Ophiocordyceps sinensis, which is only naturally found in the high-elevation extreme environment of the Tibetan Plateau, has been used in traditional Chinese medicine. Information concerning the evolutionary and geologic context of O. sinensis remains limited, however. Methods We constructed the high-quality genome of O. sinensis and provided insight into the evolution and ecology of O. sinensis using comparative genomics. Results We mapped the whole genome of the anamorph/asexual form Hirsutella of O. sinensis using Illumina and PacBio sequencing technologies and obtained a well assembled genome of 119.2 Mbp size. Long-read Single Molecule Real Time (SMRT) sequencing technology generated an assembly with more accurate representation of repeat sequence abundances and placement. Evolutionary analyses indicated that O. sinensis diverged from other fungi 65.9 Mya in the Upper Cretaceous, during the uplift of the Tibetan Plateau. Gene family expansions and contractions in addition to genome inflation via long terminal repeat (LTR) retrotransposon insertions were implicated as an important driver of O. sinensis divergence. The insertion rate of LTR sequences into the O. sinensis genome peaked ~ 30–40 Mya, when the Tibetan Plateau rose rapidly. Gene Ontology (GO) enrichment analysis suggested that O. sinensis contained more genes related to ice binding compared to other closely related fungi, which may aid in their adaptability to the cold Tibetan Plateau. Further, heavy metal resistance genes were in low abundance in the O. sinensis genome, which may help to explain previous observations that O. sinensis tissues contain high levels of heavy metals. Conclusions Our results reveal the evolutionary, geological, and ecological context for the evolution of the O. sinensis genome and the factors that have contributed to the environmental adaptability of this valuable fungus. These findings suggest that genome inflation via LTR retrotransposon insertions in O. sinensis coincided with the uplift of the Tibetan Plateau. LTRs and the specific genetic mechanisms of O. sinensis contributed to its adaptation to the environment on the plateau.

As a convenient and fraud-proof biometric, finger vein has received increasing attention from researchers. However, the deformation problem in finger vein images is still a challenge preventing the performance of finger vein recognition from prefect. In our opinion, the deformations are distinguishable between genuine and imposter fingers rather than performing as disturbing noises. It is because that the diversity between genuine images is mainly caused by different finger postures, and this difference can be characterized and utilized. While in the imposter matching, it is not the case. In this paper, we design a framework to ensemble the encoded deformation information with traditional texture-based method to improve the recognition performance. First, the pixel-level features are extracted to represent the finger vein images. Next, the best matching for each pixel is discovered by an optimized matching. Consequently, the displacement of each pixel is obtained, and the texture features of deformation is extracted from the displacement matrices. Furthermore, the results of direct and optimized matching for pixel-level features, together with the encoded deformations are fused using weights learned by the Support Vector Machine (SVM) model. Evaluated on the publicly available databases HKPU and SDU-MLA, extensive experiments demonstrate the superiority of the proposed method, with the Equal Error Rates (EERs) of 0.0040 and 0.0266 respectively on the two databases, which are much lower than recognition solely with deformation information. The proposed method is also applicable in high security scenarios, the False Reject Rate at zero False Accept Rate (FRR-at-0-FAR) can be reduced to 0.0363 on the HKPU database through adjusting the fusion parameters.

Gut microbiota dysbiosis is closely associated with ulcerative colitis (UC). Prebiotic therapy is a potential approach for UC management especially remission maintaining. Xylo-oligosaccharide (XOS) is an efficient prebiotic with proven health benefits and few side effects. However, the effects of XOS on the gut microbiota of patients with UC have not been investigated previously. The aim of this study was to evaluate the prebiotic effects of XOS on the fecal microbiota of patients with UC in clinical remission using an in vitro fermentation model. Five patients with UC in clinical remission and five healthy volunteers were enrolled in this study. Fresh fecal samples of UC patients were diluted and inoculated in yeast extract, casitone and fatty acid (YCFA) medium alone or with XOS. After fermentation for 48 h, samples were collected for 16S rDNA sequencing to investigate the gut microbiota composition. Differences in the gut microbiota between healthy volunteers and UC patients in clinical remission were detected using original fecal samples. Subsequently, the differences between the YCFA medium alone or with XOS samples were analyzed to illustrate the effects of XOS on the gut microbiota of UC patients. In both principal coordinate analysis (PCoA) and principal component analysis (PCA), the fecal samples of UC patients differed from those of healthy volunteers. Linear discriminant analysis effect size (LEfSe) analysis revealed that the relative abundances of g_Roseburia and g_Lachnospiraceae_ND3007_group were higher in healthy volunteers than in UC patients, while o_Lactobacillales abundance showed the opposite trend (P < 0.05). Wilcoxon rank-sum test bar plot showed that the abundances of g_Eubacterium_halli_group and g_Lachnospiraceae_ND3007_group were higher in the healthy volunteers than in the UC patients (P < 0.05). In addition, in UC patients, the Wilcoxon rank-sum test showed that XOS fermentation promoted the growth of bacterial groups including g_Roseburia, g_Bifidobacterium, and g_Lactobacillus, which is beneficial for recovery of intestinal diseases. These results suggest that XOS can relieve dysbiosis in the feces of UC patients in clinical remission and thus represent a potential prebiotic material for maintaining remission.

Osteolytic destruction is a hallmark of multiple myeloma and impairs myeloma patients’ quality of life. However, the molecular mechanism underlying the pathogenesis of myeloma-associated bone disease remains unclear. In this study, we demonstrate the role of myeloma cell-expressed integrin α6 in bone. Integrin α6 binds to laminin 8 and epidermal growth factor receptor on mesenchymal stem cells (MSCs) to form a trimer complex and upregulates the secretion of osteolytic cytokines from both myeloma cells and MSCs, leading to enhanced bone resorption and reduced bone formation. Thus, this study elucidates an important mechanism for myeloma-induced bone lesions and implicates that targeting integrin α6 may be a viable approach for bone healing in myeloma patients.

As an important tool for loading, unloading, and distributing palletized goods, forklifts are widely used in different links of industrial production process. However, due to the rapid increase in the types and quantities of goods, item statistics have become a major bottleneck in production. Based on machine vision, the paper proposes a method to count the amount of goods loaded and unloaded within the working time limit to analyze the efficiency of the forklift. The proposed method includes the data preprocessing section and the object detection section. In the data preprocessing section, through operations such as framing and clustering the collected video data and using the improved image hash algorithm to remove similar images, a new dataset of forklift goods was built. In the object detection section, the attention mechanism and the replacement network layer were used to improve the performance of YOLOv5. The experimented results showed that, compared with the original YOLOv5 model, the improved model is lighter in size and faster in detection speed without loss of detection precision, which could also meet the requirements for real-time statistics on the operation efficiency of forklifts.

In this study, 69 lactobacilli isolated from Tibetan Qula, a raw yak milk cheese, were screened for their potential use as probiotics. The isolates were tested in terms of: Their ability to survive at pH 2.0, pH 3.0, and in the presence of 0.3% bile salts; tolerance of simulated gastric and intestinal juices; antimicrobial activity; sensitivity against 11 specific antibiotics; and their cell surface hydrophobicity. The results show that out of the 69 strains, 29 strains (42%) had survival rates above 90% after 2 h of incubation at pH values of 2.0 or 3.0. Of these 29 strains, 21 strains showed a tolerance for 0.3% bile salt. Incubation of these 21 isolates in simulated gastrointestinal fluid for 3 h revealed survival rates above 90%; the survival rate for 20 of these isolates remained above 90% after 4 h of incubation in simulated intestinal fluid. The viable counts of bacteria after incubation in simulated gastric fluid for 3 h and simulated intestinal fluid for 4 h were both significantly different compared with the counts at 0 h (p

Myosin light chain kinase is a key enzyme in smooth muscle cell contraction. However, whether myosin light chain kinase plays a role in the occurrence or development of intracranial aneurysms is not clear. The present study explored the function of myosin light chain kinase in human intracranial aneurysm tissues. Five aneurysm samples and five control samples were collected, and smooth muscle cells (SMCs) were dissociated and cultured. A label-free proteomic analysis was performed to screen the differentially expressed proteins between aneurysm and control samples. The expression and function of myosin light chain kinase in aneurysms were examined. We found that 180 proteins were differentially expressed between the aneurysm and control samples, among which 88 were increased and 92 (including myosin light chain kinase) were decreased in aneurysms compared to control tissues. In a model of the inflammatory environment, contractility was weakened and apoptosis was increased in aneurysm SMCs compared to human brain SMCs (p < 0.05). The knock down of myosin light chain kinase in human brain SMCs caused effects similar to those observed in aneurysm SMCs. These results indicated that myosin light chain kinase plays an important role in maintaining smooth muscle contractility, cell survival and inflammation tolerance.

Millet bran contains an abundance of phytochemicals, among which polyphenols exhibit a wide range of pharmacological and medicinal properties. Polyphenols in millet bran are found in the free as well as bound forms and exist mainly in the bound form. Bound polyphenols in millet bran exhibit higher biological activities, including antioxidant, antitumour, immunomodulation, antifungal and anti-hyperglycaemia effects, while the underlying mechanisms of antitumour effects towards human colorectal cancer HCT-116 cells are not investigated. In this study, bound polyphenols of inner shell (BPIS) were isolated from foxtail millet bran that could inhibit the growth and induce apoptosis in human colorectal cancer HCT-116 cell and in HCT-116-bearing nude mice. Furthermore, the data implicated that the anti-colon cancer effects of BPIS were realized by promoting reactive oxygen species (ROS) generation in HCT-116 cell. Mechanistically, its pro-apoptotic activity was mainly attributed to the activation of mitochondria-mediated intrinsic pathways and the blockage of NF-κB signalling pathway of the downstream of ROS. The results indicated that millet bran-derived BPIS displayed anti-colon cancer functions though its pro-oxidant activity. It suggests that the millet bran-derived BPIS can act as a natural therapeutic agent against colon cancer.

Foxtail millet (Setaria italica) is one of the most important food crops in Northern China. The millet-derived antioxidant components play important roles in disease prevention. Here, we reported a peroxidase from foxtail millet bran, named FMBP, could display anti-migration effects on human colon cancer cells of DLD1. Notably, it had no effects on the normal colon epithelial cells of FHC. The anti-migration effects of FMBP were mainly realized by virtue of antagonizing epithelial–mesenchymal transition (EMT). Mechanistically, FMBP treatment decreased the phosphorylation of JAK1 and its downstream signaling molecular STAT3, followed by the reduced expression of c-Myc and Snail1, both of them are critical regulators of EMT. Consistently, STAT3 overexpression could partially reverse the migration inhibition caused by FMBP. It demonstrated that FMBP hampered colon cancer cell migration by targeting the STAT3 pathway. Therefore, the millet bran-derived peroxidase may be exploited as a natural therapeutic agent against colon cancer metastasis.

Penicillium capsulatum is a rare Penicillium species used in paper manufacturing, but recently it has been reported to cause invasive infection. To research the pathogenicity of the clinical Penicillium strain, we sequenced the genomes and transcriptome of the clinical and environmental strains of P. capsulatum. Comparative analyses of these two P. capsulatum strains and close related strains belonging to Eurotiales were performed. The assembled genome sizes of P. capsulatum are approximately 34.4 Mbp in length and encode 11,080 predicted genes. The different isolates of P. capsulatum are highly similar, with the exception of several unique genes, INDELs or SNP in the genes coding for glycosyl hydrolases, amino acid transporters and circumsporozoite protein. A phylogenomic analysis was performed based on the whole genome data of 38 strains belonging to Eurotiales. By comparing the whole genome sequences and the virulence-related genes from 20 important related species, including fungal pathogens and non-human pathogens belonging to Eurotiales, we found meaningful pathogenicity characteristics between P. capsulatum and its closely related species. Our research indicated that P. capsulatum may be a neglected opportunistic pathogen. This study is beneficial for mycologists, geneticists and epidemiologists to achieve a deeper understanding of the genetic basis of the role of P. capsulatum as a newly reported fungal pathogen.

Abstract Aims Left ventricular hypertrophy (LVH) is frequently detected via echocardiography in individuals with Fabry disease (FD), sometimes leading to confusion with hypertrophic cardiomyopathy (HCM) of other aetiologies. Considering this diagnosis challenge, FD should be included in the list of differential diagnosis for patients presenting with LVH. To address this concern, we conducted a prospective screening study in China, using dried blood spot (DBS) testing, to evaluate patients with unexplained LVH. Methods Our study was designed as a nationwide, multicentre prospective investigation. A total of 1015 patients from 55 different centres who were diagnosed with LVH by echocardiography were screened in the study from September 2022 to December 2023. Demographic information, biochemistry data, echocardiography parameters and clinical observations were meticulously collected from all participants. The DBS method was used to assess α‐galactosidase A (α‐Gal A) activity in males and both α‐Gal A and globotriaosylsphingosine (lyso‐Gb3) levels in females. Results The final screening population included 906 patients (589 males, 65%) with LVH, characterized by a mean maximal myocardial thickness of 14.8 ± 4.6 mm and an average age of 56.9 ± 17.2 years. In total, 43 patients (38 males, 5 females) exhibited low α‐Gal A activity measurement (1.1 ng/mL). Among these patients, eight individuals (7 males and 1 female) were genetically confirmed to harbour pathogenic GLA mutations, resulting in a total prevalence of 0.88%. Compared with patients without FD, patients with FD tended to have proteinuria (75% vs. 21.2%, P = 0.001), family history of HCM (37.5% vs. 2.3%, P T) and c.547+3A>G, were deemed potentially pathogenic. Subsequent familial validation post‐diagnosis identified an additional 14 confirmed cases. Conclusions This pioneering screening study for FD among Chinese patients with unexplained LVH using DBS measurement, revealed an FD detection rate of 0.88%. Our findings confirmed that the combined measurement of lyso‐Gb3 and α‐Gal A activity is beneficial for primary screening of FD in patients with LVH. Given the availability of efficacious therapies and the value of cascade screening in extended families, early detection of FD in LVH patients is clinically important.

Abstract Aims Limited literature shows the existence of sex differences in the long‐term prognosis of heart failure (HF) patients with frailty. In this study, whether sex differences exist in the impact of frailty on death from cardiovascular causes in patients with HF was investigated by conducting a retrospective cohort study. Methods and results Data from the National Health and Nutrition Examination Survey (NHANES) study (2009–2018) were used to conduct a retrospective cohort study of 958 participants with HF. Patients were grouped based on sex and frailty index (FI). The relationship between death from cardiovascular causes and baseline frailty was assessed by Cox proportional hazard analysis and the Kaplan–Meier (K‐M) plot. The study population had an age of 67.3 ± 12.3. Among them, around 54.5% were male. A median follow‐up of 3.6 years was performed. After that, females who died from cardiovascular causes exhibited higher baseline FI values, while males did not show this trend (P