Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.

A standing Leidenfrost drop with Sufi whirling.

When a water drop is placed on a hot solid surface, it either undergoes explosive contact boiling or exhibits a stable state. In the latter case, the drop floats over an insulating layer of vapor generated by rapid vaporization of water at the surface/drop interface; this is known as the Leidenfrost state. Here, we discuss a previously unrecognized steady state in which a water drop "stands" on a hot smooth surface. In this state, the drop stabilizes itself with partial adhesion on the hot surface, leading to unique deformation and rotation behavior reminiscent of Sufi whirling-a form of spinning dance. Our analysis of this standing Leidenfrost state reveals the underlying mechanisms that drive the drop's stable partial adhesion and subsequent deformation with rotation. The heat-transfer efficiency of this standing state is up to 390% greater than that of the traditional floating Leidenfrost state.

IbNF-YA1 is a key factor in the storage root development of sweet potato.

As a major worldwide root crop, the mechanism underlying storage root yield formation has always been a hot topic in sweet potato [Ipomoea batatas (L.) Lam.]. Previously, we conducted the transcriptome database of differentially expressed genes between the cultivated sweet potato cultivar "Xushu18," its diploid wild relative Ipomoea triloba without storage root, and their interspecific somatic hybrid XT1 with medium-sized storage root. We selected one of these candidate genes, IbNF-YA1, for subsequent analysis. IbNF-YA1 encodes a nuclear transcription factor Y subunit alpha (NF-YA) gene, which is significantly induced by the natural auxin indole-3-acetic acid (IAA). The storage root yield of the IbNF-YA1 overexpression (OE) plant decreased by 29.15-40.22% compared with the wild type, while that of the RNAi plant increased by 10.16-21.58%. Additionally, IAA content increased significantly in OE plants. Conversely, the content of IAA decreased significantly in RNAi plants. Furthermore, real-time quantitative reverse transcription-PCR (qRT-PCR) analysis demonstrated that the expressions of the key genes IbYUCCA2, IbYUCCA4, and IbYUCCA8 in the IAA biosynthetic pathway were significantly changed in transgenic plants. The results indicated that IbNF-YA1 could directly target IbYUCCA4 and activate IbYUCCA4 transcription. The IAA content of IbYUCCA4 OE plants increased by 71.77-98.31%. Correspondingly, the storage root yield of the IbYUCCA4 OE plant decreased by 77.91-80.52%. These findings indicate that downregulating the IbNF-YA1 gene could improve the storage root yield in sweet potato.

Genome-wide identification, evolution, and role of SPL gene family in beet (Beta vulgaris L.) under cold stress.

BACKGROUND: SPL transcription factors play vital roles in regulating plant growth, development, and abiotic stress responses. Sugar beet (Beta vulgaris L.), one of the world's main sugar-producing crops, is a major source of edible and industrial sugars for humans. Although the SPL gene family has been extensively identified in other species, no reports on the SPL gene family in sugar beet are available. RESULTS: Eight BvSPL genes were identified at the whole-genome level and were renamed based on their positions on the chromosome. The gene structure, SBP domain sequences, and phylogenetic relationship with Arabidopsis were analyzed for the sugar beet SPL gene family. The eight BvSPL genes were divided into six groups (II, IV, V, VI, VII, and VIII). Of the BvSPL genes, no tandem duplication events were found, but one pair of segmental duplications was present. Multiple cis-regulatory elements related to growth and development were identified in the 2000-bp region upstream of the BvSPL gene start codon (ATG). Using quantitative real-time polymerase chain reaction (qRT-PCR), the expression profiles of the eight BvSPL genes were examined under eight types of abiotic stress and during the maturation stage. BvSPL transcription factors played a vital role in abiotic stress, with BvSPL3 and BvSPL6 being particularly noteworthy. CONCLUSION: Eight sugar beet SPL genes were identified at the whole-genome level. Phylogenetic trees, gene structures, gene duplication events, and expression profiles were investigated. The qRT-PCR analysis indicated that BvSPLs play a substantial role in the growth and development of sugar beet, potentially participating in the regulation of root expansion and sugar accumulation.

Ovarian carcinoma immune-related microRNA affects the heterogeneity of the endocrine microenvironment and anti-tumor immune pattern.

BACKGROUND: The eighth-leading cause of cancer-related mortality and the seventh-most prevalent malignancy in women globally is ovarian cancer (OV). However, 5-year survival expectancy after conventional treatment is not good. Therefore, there is an urgent need for novel signatures to guide the designation of therapeutic schemes for OV patients. METHODS: We used univariate Cox analysis to screen hormone secretion regulation axis-related microRNAs (miRNAs), least absolute shrinkage and selection operator analysis to select candidate miRNAs and multivariate Cox analysis to build the risk model. To evaluate possible route and functional differences, enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the differentially expressed genes (DEGs) across various risk groups. We compared Tumor Immune Dysfunction and Exclusion (TIDE) scores across risk categories by analyzing immune cell infiltration, immune checkpoint gene expression, immunological function and TIDE scores. In the end, we determined the half maximal inhibitory concentration (IC50 ) of chemotherapy and targeted medicines for individual patients. Cell assays were determined to test the migration of the miRNA-target genes and western blotting was used to test the correlation of the miRNA-target genes and the pathways. RESULTS: We finally identified hormone secretion regulation axis-related 13 microRNAs to build a risk model. The validation of observed and anticipated values revealed a fair level of agreement. To evaluate the molecular pathways between various groups in accordance with the GO and KEGG analyses, we then discovered 173 DEGs between distinct risk groups. The risk score was shown to be inversely related to the number of immune cells, including myeloid dendritic, granulocytes, M1 and M2 macrophages, B cells, t-lymphocytes, and CD4+ and CD8+ cells, suggesting that immune cells are more frequent in the low-risk group. Immune cell infiltration investigation yielded these results. Finally, we recognized 11 chemotherapeutic drugs and 30 novels targeted drugs on the basis of IC50 between the different risk groups. GJB5 was determined to be the mir-219 target gene and was identified as promoting the cell cycle process. In addition, hormone secretion regulation axis related miRNAs were reported to affects the heterogeneity of endocrine microenvironment and anti-tumor immune pattern. CONCLUSIONS: In conclusion, a 13-miRNA prognostic model was constructed to know the immune status, prognosis, immunotherapeutic response and anti-tumor drug sensitivity for OV, which provides theoretical guidance for the effective and individualized treatment of OV patients.

Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration.

OBJECTIVES: Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations. METHODS: Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies. RESULTS: We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype. CONCLUSIONS: Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.

Fast and high-precision tracking technology for image-based closed-loop cascaded control system with a Risley prism and fast steering mirror.

The Risley prism's compact structure, dynamic responsiveness, and high tracking accuracy make it ideal for photoelectric image tracking. To realize fast and high-precision tracking of the target, we propose an image-based closed-loop tracking cascade control (IBCLTCR-F) system using a single image detector that integrates the Risley prism and fast steering mirror (FSM). Firstly, We propose a cascade control input-decoupling method (CCIDM) for the IBCLTCR-F system to solve the complex problem of coarse-fine control input decoupling in traditional single detector cascaded control systems. Moreover, the CCIDM method ensures that the FSM deflection angle is small and does not exceed its range during the fine tracking process, by using the Risley prism to compensate for the FSM deflection angle. Next, we design the image-based closed-loop tracking controllers of the Risley prism system and FSM system and analyze the stability of the IBCLTCR-F system. Finally, we track static and moving targets through experiments. The experimental results verify the feasibility of the IBCLTCR-F system, the effectiveness of the decoupling method, and the fast and high-precision tracking of the targets.

The growth-promoting effects of protein hydrolysates and their derived peptides on probiotics: structure-activity relationships, mechanisms and future perspectives.

Lactic acid bacteria (LAB) are the main probiotics currently available in the markets and are essential for maintaining gut health. To guarantee probiotic function, it is imperative to boost the culture yield of probiotic organisms, ensure the sufficient viable cells in commercial products, or develop effective prebiotics. Recent studies have shown that protein hydrolysates and their derived peptides promote the proliferation of probiotic in vitro and the abundance of gut flora. This article comprehensively reviews different sources of protein hydrolysates and their derived peptides as growth-promoting factors for probiotics including Lactobacillus, Bifidobacterium, and Saccharomyces. We also provide a preliminary analysis of the characteristics of LAB proteolytic systems focusing on the correlation between their elements and growth-promoting activities. The structure-activity relationship and underlying mechanisms of growth-promoting peptides and their research perspectives are thoroughly discussed. Overall, this review provides valuable insights into growth-promoting protein hydrolysates and their derived peptides for proliferating probiotics in vivo or in vitro, which may inspire researchers to explore new options for industrial probiotics proliferation, dairy products fermentation, and novel prebiotics development in the future.

Hearing outcomes following cochlear implantation with anatomic or default frequency mapping in postlingual deafness adults.

PURPOSE: The aim of this study was to compare the outcomes of different mapping procedures based on anatomic or default frequency distribution in postlingual deafness adults who underwent cochlear implantation (CI). METHODS: Forty-eight adults with postlingual deafness who underwent CI (MED-EL) from January 2021 to May 2022 in our hospital were prospectively recruited. The participants were randomly assigned to two groups (the anatomic group and the default group). Postoperative computerized tomography (CT) scans were evaluated with Otoplan® to determine the angular insertion depth (AID) and the specific locations of the intracochlear electrodes. Anatomic maps were imported into MAESTRO 9.0 software (MED-EL) for anatomy-based fitting for anatomic group, while default mapping program was set up for the default group. Hearing thresholds, Speech Recognition Scores (SRS), and subjects' auditory and musical abilities were evaluated 1 year after using the CI. Differences were determined in two groups using Stata statistical software, with significance defined as p < 0.05. RESULTS: SRS under noisy conditions was significantly greater for anatomic group than the default group (p = 0.02). Under quiet conditions, however, mean hearing thresholds (0.5, 1, 2, and 4 kHz) and SRS did not differ significantly between the two groups (p = 0.07). Modified questionnaires showed that auditory (p = 0.02) and musical (p = 0.01) quality were significantly better following the anatomic mapping than the default procedure. CONCLUSION: CI program based on the anatomic distribution may bring better SRS under noise conditions as well as better auditory and musical qualities than based on the default frequency distribution.

Lumped Parameter Thermal Network Modeling and Thermal Optimization Design of an Aerial Camera.

The quality of aerial remote sensing imaging is heavily impacted by the thermal distortions in optical cameras caused by temperature fluctuations. This paper introduces a lumped parameter thermal network (LPTN) model for the optical system of aerial cameras, aiming to serve as a guideline for their thermal design. By optimizing the thermal resistances associated with convection and radiation while considering the camera's unique internal architecture, this model endeavors to improve the accuracy of temperature predictions. Additionally, the proposed LPTN framework enables the establishment of a heat leakage network, which offers a detailed examination of heat leakage paths and rates. This analysis offers valuable insights into the thermal performance of the camera, thereby guiding the refinement of heating zones and the development of effective active control strategies. Operating at a total power consumption of 26 W, the thermal system adheres to the low-power limit. Experimental data from thermal tests indicate that the temperatures within the optical system are maintained consistently between 19 °C and 22 °C throughout the flight, with temperature gradients remaining below 3 °C, satisfying the temperature requirements. The proposed LPTN model exhibits swiftness and efficacy in determining thermal characteristics, significantly facilitating the thermal design process and ensuring optimal power allocation for aerial cameras.

amer1 Regulates Zebrafish Craniofacial Development by Interacting with the Wnt/ß-Catenin Pathway.

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/ß-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/ß-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/ß-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/ß-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.

Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia.

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27-/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.

Distribution, sources, and risk assessment of polycyclic aromatic hydrocarbons in surface soils and plants from industrial and agricultural areas, Junggar Basin, Xinjiang.

The contamination characteristics of Polycyclic Aromatic Hydrocarbons (PAHs) in different environmental functional areas are different. In this study, the contamination of PAHs in soils and common plants in typical mining and farmland areas in Xinjiang, China, was analyzed. The results showed that the contamination levels of PAHs in mining soils were significantly higher than those in farmland soils, and the mining soils were dominated by 4-5-ring PAHs and farmland soils by 3-4-ring PAHs. Analysis of their sources using a positive definite factor matrix model showed that PAHs in mining soils mainly originated from coal and natural gas combustion, and transportation processes; while farmland soils mainly came from biomass and coal combustion, and fossil fuel volatile spills. The cancer risk of PAHs in soils was evaluated using a combination of the Monte Carlo and the lifetime carcinogenic risk models, and the results showed that the overall level of cancer risk for mining soils was higher than that for farmland soils, and can put some people in high risk of cancer. For plant samples, except for individual crop samples, the contamination levels of mining plants and crops were similar, with 4-5-ring PAHs dominating in desert plants in mining areas and the highest proportion of 3-ring PAHs in crops in agricultural fields, and PAHs in both plants were mainly from biomass and coal combustion. The results of correlation analysis showed that 2-ring PAHs in crop roots were significantly positively correlated with it in corresponding soils, and some high-ring PAHs in crop leaves were significantly negatively correlated with it in corresponding soils. Therefore, there were significant differences in the pollution characteristics of PAHs in soils and common plants in mining and agricultural areas. Human health risks and ecological risks are mainly concentrated in mining areas, and appropriate intervention measures should be taken for pollution remediation.

Petersen's hernia after gastric cancer surgery: Unravelling clinical characteristics and optimal management approaches.

INTRODUCTION: Petersen's hernia is a rare and serious complication that can occur after radical gastrectomy and digestive tract reconstruction for gastric cancer. This article summarises the symptoms, diagnosis and treatment of Petersen's hernia after surgery for gastric cancer. PATIENTS AND METHODS: A retrospective analysis was conducted on 11 male patients who were diagnosed with Petersen's hernia and underwent surgical treatment at our hospital from January 2020 to December 2022. Their clinical manifestations, perioperative conditions and follow-up after treatment were collected. RESULTS: The median age was 58.5 years (range: 45-73), and the median time since gastrectomy was 24 months (range: 4-125). Open distal gastrectomy (45.5%) and open total gastrectomy (27.3%) were the most common procedures. Roux-en-Y (81.8%) was the predominant anastomosis method. All patients underwent emergency surgery within a median time of 30 h (range: 4-45). Intestine necrosis occurred in 36.4% of cases, with a perioperative death rate of 27.3%. CONCLUSION: Petersen's hernia after gastric cancer surgery can quickly lead to necrotising intestinal obstruction and poor prognosis. Enhanced abdominal computed tomography should be performed as soon as possible, and early exploratory laparotomy should be done to avoid intestinal necrosis. Routine closure of the mesenteric defect after gastric cancer resection can prevent the occurrence of Petersen's hernia. This article highlights the need for increased awareness and preventive measures to minimise the occurrence of Petersen's hernia in gastric cancer patients. It emphasises the importance of early detection and appropriate management strategies for improved patient outcomes.

Genome-wide identification, phylogenetic and expression pattern analysis of HSF family genes in the Rye (Secale cereale L.).

BACKGROUND: Heat shock factor (HSF), a typical class of transcription factors in plants, has played an essential role in plant growth and developmental stages, signal transduction, and response to biotic and abiotic stresses. The HSF genes families has been identified and characterized in many species through leveraging whole genome sequencing (WGS). However, the identification and systematic analysis of HSF family genes in Rye is limited. RESULTS: In this study, 31 HSF genes were identified in Rye, which were unevenly distributed on seven chromosomes. Based on the homology of A. thaliana, we analyzed the number of conserved domains and gene structures of ScHSF genes that were classified into seven subfamilies. To better understand the developmental mechanisms of ScHSF family during evolution, we selected one monocotyledon (Arabidopsis thaliana) and five (Triticum aestivum L., Hordeum vulgare L., Oryza sativa L., Zea mays L., and Aegilops tauschii Coss.) specific representative dicotyledons associated with Rye for comparative homology mapping. The results showed that fragment replication events modulated the expansion of the ScHSF genes family. In addition, interactions between ScHSF proteins and promoters containing hormone- and stress-responsive cis-acting elements suggest that the regulation of ScHSF expression was complex. A total of 15 representative genes were targeted from seven subfamilies to characterize their gene expression responses in different tissues, fruit developmental stages, three hormones, and six different abiotic stresses. CONCLUSIONS: This study demonstrated that ScHSF genes, especially ScHSF1 and ScHSF3, played a key role in Rye development and its response to various hormones and abiotic stresses. These results provided new insights into the evolution of HSF genes in Rye, which could help the success of molecular breeding in Rye.

Mendelian randomization under the omnigenic architecture.

Mendelian randomization (MR) is a common analytic tool for exploring the causal relationship among complex traits. Existing MR methods require selecting a small set of single nucleotide polymorphisms (SNPs) to serve as instrument variables. However, selecting a small set of SNPs may not be ideal, as most complex traits have a polygenic or omnigenic architecture and are each influenced by thousands of SNPs. Here, motivated by the recent omnigenic hypothesis, we present an MR method that uses all genome-wide SNPs for causal inference. Our method uses summary statistics from genome-wide association studies as input, accommodates the commonly encountered horizontal pleiotropy effects and relies on a composite likelihood framework for scalable computation. We refer to our method as the omnigenic Mendelian randomization, or OMR. We examine the power and robustness of OMR through extensive simulations including those under various modeling misspecifications. We apply OMR to several real data applications, where we identify multiple complex traits that potentially causally influence coronary artery disease (CAD) and asthma. The identified new associations reveal important roles of blood lipids, blood pressure and immunity underlying CAD as well as important roles of immunity and obesity underlying asthma.

Oral-microbiome-derived signatures enable non-invasive diagnosis of laryngeal cancers.

BACKGROUND: Recent studies have uncovered that the microbiota in patients with head and neck cancers is significantly altered and may drive cancer development. However, there is limited data to explore the unique microbiota of laryngeal squamous cell carcinoma (LSCC), and little is known regarding whether the oral microbiota can be utilized as an early diagnostic biomarker. METHODS: Using 16S rRNA gene sequencing, we characterized the microbiome of oral rinse and tissue samples from 77 patients with LSCC and 76 control patients with vocal polyps, and then performed bioinformatic analyses to identify taxonomic groups associated with clinicopathologic features. RESULTS: Multiple bacterial genera exhibited significant differences in relative abundance when stratifying by histologic and tissue type. By exploiting the distinct microbial abundance and identifying the tumor-associated microbiota taxa between patients of LSCC and vocal polyps, we developed a predictive classifier by using rinse microbiota as key features for the diagnosis of LSCC with 85.7% accuracy. CONCLUSION: This is the first evidence of taxonomical features based on the oral rinse microbiome that could diagnose LSCC. Our results revealed the oral rinse microbiome is an understudied source of clinical variation and represents a potential non-evasive biomarker of LSCC.

Data-independent acquisition mass spectrometry reveals comprehensive plasma protein profiles in the natural history of patients with hereditary transthyretin amyloidosis (ATTRv).

OBJECTIVES: Hereditary transthyretin amyloidosis (ATTRv) is a rare, fatal, autosomal dominant disease with more than 140 mutations discovered. Three phenotypes of amyloid infiltration are neuropathy (ATTRv-PN), cardiopathy (ATTRv-CM), and neuropathy + cardiopathy (ATTRv-MIX). The lack of ATTR-specific biomarkers, difficulties in biopsy evidence, and limited known pathogenic mechanisms have made diagnosis difficult. Newly emerging noninvasive measures for monitoring progression and disease-modifying therapies have improved early diagnosis and patient management. METHODS: Our research applies the latest technology, Data-Independent Acquisition-Based Quantitative Proteomics (DIA), to reveal comprehensive plasma protein profiles in the natural history of Chinese patients with hereditary transthyretin amyloidosis (ATTRv). We analyzed differentially expressed proteins (DEPs) in three phenotypes (ATTRv-PN, ATTRv-CM, and ATTRv-MIX). RESULTS: Serum samples were collected from a total of 18 patients (6 ATTRv-PN, 5 ATTRv-CM, and 7 ATTRv-MIX patients) and 20 healthy participants as a control group. Combined with the results of the proteomic and bioinformatic analyses, we found 30 DEPs and protein interaction networks clustered in KRT family proteins and DSC3 between ATTRv-PN and the control, which were rich in the estrogen signaling pathway and the cell adhesion molecule (CAM) pathway. CONCLUSION: This study demonstrates a global and significant proteomic profile in different stages of ATTRv.

Identification of gut microbiota dysbiosis in bullous pemphigoid under different disease activity.

Bullous pemphigoid (BP) is a severe autoimmune blistering disease affecting patients' quality of life. Gut microbiota (GM) dysbiosis have been investigated to be associated with multiple autoimmune diseases. However, the relationship between GM and BP onset and remission remains to be established by a systematic study. We conducted a study that enrolled 24 patients with BP onset (BP group), 24 patients under remission stage (BP-R group) and 24 healthy controls (HC group). We applied 16S rRNA sequencing on faecal samples and revealed a separation of the microbiota structure. At the family level, Lachnospiraceae, Prevotellaceae and Veillonellaceae were more abundant in the HC and BP-R groups, while Bacteroidaceae, Ruminococcaceae and Enterobacteriaceae were more abundant in the BP group. Bugbase analysis revealed the potentially pathogenic bacteria had an increasing trend in the BP group compared with the HC group and this variation vanished in the BP-R group. At the amplicon sequence variants (ASV) level, Bacteroides ovatus (ASV40) and Veillonella dispar (ASV140) significantly decreased, while Prevotella copri (ASV54) increased in the BP group compared to the HC and BP-R groups. The HC group and BP-R group shared similar abundance. Furthermore, by correlation analysis, we investigated key ASVs correlated with clinical parameters and found some discriminate biomarkers between the BP and BP-R groups. Our study established a dynamic GM profile in BP patients under different disease activity, providing a new direction to understand the role of GM in BP pathogenesis and therapeutic effects.

Effect of dietary intervention on the prevalence of asymptomatic malaria among 6-18-month-old children in rural Malawi.

BACKGROUND: The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. This study tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6-18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them. METHODS: A total of 840 6-month-old children were enrolled in a randomized trial. The participants received 12-month supplementation with three different daily dietary supplementations: CSB, soy-LNS, or milk-LNS, and one control group without supplementation. The prevalence rate of asymptomatic Plasmodium falciparum was determined by real-time PCR from the participant's dried blood spots (DBS) collected at the baseline and every 3 months. The global null hypothesis was tested using modified Poisson regression to estimate the prevalence ratio (PR) between the control group and three intervention groups at all ages combined. All the models were adjusted for malaria at baseline, season of DBS sample collection, site of enrolment, and household asset Z-score. RESULTS: All children combined, the prevalence of P. falciparum was 14.1% at enrollment, 8.7% at 9 months, 11.2% at 12 months, 13.0% at 15 months and 22.4% at 18 months of age. Among all samples that were taken after enrolment, the prevalence was 12.1% in control group, 12.2% in milk-LNS, 14.0% in soy-LNS, and 17.2% in CSB group. Compared to children in the control group the prevalence ratio of positive malaria tests was 1.19 (95% CI 0.81-1.74; P = 0.372) in the milk-LNS group, 1.32 (95% CI 0.88-1.96; P = 0.177) in the soy-LNS group and 1.72 (95% CI 1.19-2.49; P = 0.004) in the CSB group. CONCLUSION: The study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children. In contrast, there was a signal of a possible increase in malaria prevalence among children supplemented with CSB.