Modified Sistrunk Procedure in 391 Pediatric Thyroglossal Duct Cyst Cases: Clinical Analysis of Efficacy and Recurrence Risk.

Objectives: The study aims to retrospectively summarize the clinical features of pediatric thyroglossal duct cyst (TGDC), investigate the efficacy of the modified Sistrunk (mSis) procedure, and analyze the recurrence risks. Methods: The clinical data of 391 children with TGDC admitted to Beijing Children's Hospital affiliated Capital Medical University and Baoding Children's Hospital from March 2012 to December 2021 were retrospectively analyzed. All patients underwent cervical ultrasound for preoperative evaluation. Twenty cases had magnetic resonance imaging and 8 cases had computed tomography for further evaluation. All patients underwent the standard mSis procedure, and clinical manifestations information, surgical information, complications, and prognosis were analyzed. Results: Among the 391 TGDC cases, 118 (30.2%) had a history of recurrent neck infection and 36 (9.2%) had undergone previous neck cyst and fistula resection surgeries, initially diagnosed as neck cyst (22 cases), TGDC (12 cases), or branchial fistula (2 cases), with only 6 cases having undergone partial hyoid bone resection in the previous operation. During the 15 to 156 months of follow-up, 10 children experienced local wound infection, but no other complications were reported. The recurrence rate was 2.30%, and the recurrence time ranged from 0.5 to 34 (average, 7.2) months post surgery. In the Poisson regression model examining factors related to recurrence, the P values of the 3 factors were <.05: clearness of the lesion boundary, surgical history, and maximum diameter and the relative risk (RR) values corresponding to the 3 risk factors, such as Exp (B), were 27.918, 10.054, and 6.606, respectively. Conclusions: The mSis procedure demonstrated safety and efficacy with fewer complications and a low recurrence rate of 2.30% in the study. Furthermore, the indistinct lesion boundary, surgical history, and large lesion diameter (>2 cm) were independent risk factors for recurrence in pediatric TGDC.Level of Evidence: IV.

Natural selection shaped the protective effect of the mtDNA lineage against obesity in Han Chinese populations.

Mitochondria play a key role in lipid metabolism, and mitochondrial DNA (mtDNA) mutations are thus considered to affect obesity susceptibility by altering oxidative phosphorylation and mitochondrial function. In this study, we investigated mtDNA variants that may affect obesity risk in 2,877 Han Chinese individuals from three independent populations. The association analysis of 16 basal mtDNA haplogroups with body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) revealed that only haplogroup M7 was significantly negatively correlated with all three adiposity-related anthropometric traits in the overall cohort (P=0.003 for BMI, P=1×10-5 for WC, P=0.005 for WHR), which was verified by the analysis of a single population, i.e., the Zhengzhou population. Furthermore, subhaplogroup analysis suggested that M7b1a1 was the most likely haplogroup associated with a decreased obesity risk, and the variation T12811C (causing Y159H in ND5) harbored in M7b1a1 may be the most likely candidate for altering mitochondrial function. Specifically, we found that proportionally more nonsynonymous mutations accumulated in M7b1a1 carriers, indicating that M7b1a1 was either under positive selection or subject to a relaxation of selective constraints. We also found that nuclear variants, especially in DACT2 and PIEZO1, may functionally interact with M7b1a1.

Proangiogenic effect and underlying mechanism of holmium oxide nanoparticles: a new biomaterial for tissue engineering.

BACKGROUND: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue "tracking" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs. RESULTS: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced. CONCLUSION: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.

Fasudil alleviates alcohol-induced cognitive deficits and hippocampal morphology injury partly by altering the assembly of the actin cytoskeleton and microtubules.

Alcohol-Related Brain Damage (ARBD) manifests predominantly as cognitive impairment and brain atrophy with the hippocampus showing particular vulnerability. Fasudil, a Rho kinase (ROCK) inhibitor, has established neuroprotective properties; however, its impact on alcohol-induced cognitive dysfunction and hippocampal structural damage remains unelucidated. This study probes Fasudil's neuroprotective potential and identifies its mechanism of action in an in vivo context. Male C57BL/6 J mice were exposed to 30% (v/v, 6.0 g/kg) ethanol by intragastric administration for four weeks. Concurrently, these mice received a co-treatment with Fasudil through intraperitoneal injections at a dosage of 10 mg/kg/day. Fasudil was found to mitigate alcohol-induced spatial and recognition memory deficits, which were quantified using Y maze, Morris water maze, and novel object recognition tests. Concurrently, Fasudil attenuated hippocampal structural damage prompted by chronic alcohol exposure. Notably, Fasudil moderated alcohol-induced disassembly of the actin cytoskeleton and microtubules-mechanisms central to the maintenance of hippocampal synaptic integrity. Collectively, our findings indicate that Fasudil partially reverses alcohol-induced cognitive and morphological detriments by modulating cytoskeletal dynamics, offering insights into potential therapeutic strategies for ARBD.

Improving Catalytic Efficiency of L-Arabinose Isomerase from Lactobacillus plantarum CY6 towards D-Galactose by Molecular Modification.

L-Arabinose isomerase (L-AI) has been commonly used as an efficient biocatalyst to produce D-tagatose via the isomerization of D-galactose. However, it remains a significant challenge to efficiently synthesize D-tagatose using the native (wild type) L-AI at an industrial scale. Hence, it is extremely urgent to redesign L-AI to improve its catalytic efficiency towards D-galactose, and herein a structure-based molecular modification of Lactobacillus plantarum CY6 L-AI (LpAI) was performed. Among the engineered LpAI, both F118M and F279I mutants showed an increased D-galactose isomerization activity. Particularly, the specific activity of double mutant F118M/F279I towards D-galactose was increased by 210.1% compared to that of the wild type LpAI (WT). Besides the catalytic activity, the substrate preference of F118M/F279I was also largely changed from L-arabinose to D-galactose. In the enzymatic production of D-tagatose, the yield and conversion ratio of F118M/F279I were increased by 81.2% and 79.6%, respectively, compared to that of WT. Furthermore, the D-tagatose production of whole cells expressing F118M/F279I displayed about 2-fold higher than that of WT cell. These results revealed that the designed site-directed mutagenesis is useful for improving the catalytic efficiency of LpAI towards D-galactose.

The bioaccumulation and ecotoxicity of co-exposure of per(poly)fluoroalkyl substances and polystyrene microplastics to Eichhornia crassipes.

Gen X and F-53B have been popularized as alternatives to PFOA and PFOS, respectively. These per(poly)fluoroalkyl substances pervasively coexist with microplastics (MPs) in aquatic environments. However, there are knowledge gaps regarding their potential eco-environmental risks. In this study, a typical free-floating macrophyte, Eichhornia crassipes (E. crassipes), was selected for hydroponic simulation of a single exposure to PFOA, PFOS, Gen X, and F-53B, and co-exposure with polystyrene (PS) microspheres. F-53B exhibited the highest bioaccumulation followed by Gen X, PFOA, and PFOS. In the presence of PS MPs, the bioavailabilities of the four PFASs shifted and the whole plant bioconcentration factors improved. All four PFASs induced severe lipid peroxidation, which was exacerbated by PS MPs. The highest integrated biomarker response (IBR) was observed for E. crassipes (IBR of shoot: 30.01, IBR of root: 22.79, and IBR of whole plant: 34.96) co-exposed to PS MPs and F-53B. The effect addition index (EAI) model revealed that PS MPs showed antagonistic toxicity with PFOA and PFOS (EAI < 0) and synergistic toxicity with Gen X and F-53B (EAI > 0). These results are helpful to compare the eco-environmental impacts of legacy and alternative PFASs for renewal process of PFAS consumption and provide toxicological, botanical, and ecoengineering insights under co-contamination with MPs.

NMR-based metabolomics approach to study the effect and related molecular mechanisms of Saffron essential oil against depression.

Depression currently ranks as the fourth leading cause of disability globally, affecting approximately 20% of the world's population. we established a chronic restraint stress (CRS) induced depression model in mice and employed fluoxetine as a reference drug. We assessed the therapeutic potential of saffron essential oil (SEO) and elucidated its underlying mechanisms through behavioral indices and NMR-based metabolomic analysis. The findings indicate that SEO ameliorates behavioral symptoms of depression, such as the number of entries into the central area, fecal count, latency to immobility, and duration of immobility in both the Tail Suspension Test (TST) and the Forced Swim Test (FST), along with correcting the dysregulation of 5-serotonin. Metabolomic investigations identified sixteen potential biomarkers across the liver, spleen, and kidneys. SEO notably modulated nine of these biomarkers: dimethylglycine, glycerol, adenosine, ß-glucose, α-glucose, uridine, mannose, sarcosine, and aspartate, with glycerol emerging as a common biomarker in both the liver and spleen. Pathway analysis suggests that these biomarkers participate in glycolysis, glycine serine threonine metabolism, and energy metabolism, potentially implicating a role in neural regulation. In summary, SEO effectively mitigates depressive-like behaviors in CRS mice, predominantly via modulation of glycolysis, amino acid metabolism, and energy metabolism, and potentially exerts antidepressant effects through neural regulation. Our study offers insights into small molecule metabolite alterations in CRS mice through a metabolomics lens, providing evidence for the antidepressant potential of plant essential oils and contributing to our understanding of the mechanisms of traditional Chinese medicine in treating depression.

Pulmo-protection of long-term swimming exercise via improving insulin sensitivity in monocrotaline-induced pulmonary hypertensive rats.

Exercise has been recognized as an effective intervention in the treatment of pulmonary arterial hypertension (PAH), supported by numerous studies. However, the precise effects of exercise on pulmonary function remain to be fully elucidated. In this study, using a rat model of swimming exercise training and monocrotaline-induced PAH, we aimed to explore its impact on pulmonary morphology and function. Our investigations revealed that MCT-treated rats exhibited augmented mean pulmonary arterial pressure (MPAP) and pulmonary vascular remodeling, which can be attenuated by 4 weeks of swimming exercise training (60 min/day, 5 days/week). Notably, MCT-treated rats showed impaired pulmonary function, as manifested by decreased tidal volume and dynamic compliance, which were reversed by exercise training. Assessment of pulmonary substrate in PAH rats indicated a prominent pro-inflammatory substrate, evidenced by macrophage accumulation through quantitative immunohistological analysis of macrophage-like cell expression (CD68), and extracellular matrix remodeling, evaluated by Masson staining. Importantly, both the pro-inflammatory substrate and extracellular matrix remodeling were ameliorated by swimming exercise training. Additionally, serum biochemical analysis demonstrated elevated levels of low-density lipoprotein cholesterol and Apolipoprotein B following MCT treatment, which were reduced with exercise intervention. Moreover, exercise enhanced systemic insulin sensitivity in both MCT-treated and untreated rats. Notably, MCT and exercise treatment both decreased fasting blood glucose (FBG) levels in rats, whereas exercise training reinstated FBG levels to normal in MCT-treated rats. In summary, our study suggests that swimming exercise confers a pulmonary protective effect in MCT-induced PAH rats, highlighting the potential importance of exercise-based rehabilitation in the management of PAH.

Direct Observation of Anionic Yields from the Liquid-Vapor Interface by Electron Irradiation.

Dissociative electron attachment (DEA) is widely believed to play a high-profile role in ionizing radiation damages of bioorganic molecules, and its fundamentals are mainly learned from the gas-phase studies. However, the DEA process in aqueous solution is still in debate. Here we provide experimental evidence about the DEA processes of liquid methanol by using electron-impact-time-delayed mass spectrometry. In contrast to the gas- and solid-phase DEAs, methoxide ion CH3O- is the predominant product from the liquid interface. Furthermore, this anion can be produced with both the primary low-energy electrons and the inelastically scattered and secondary low-energy electrons. On the contrary, the primary low-energy electrons in the liquid bulk are more likely to be solvated, rather than directly participating in the DEA process. Our study provides new insights into radiation chemistry, particularly of bioorganic relevance.

Taraxerone exerts antipulmonary fibrosis effect through Smad signaling pathway and antioxidant stress response in a Sirtuin1-dependent manner.

Idiopathic pulmonary fibrosis treatments are limited, often with severe side effects, highlighting the need for novel options. Taraxerone has diverse biomedical properties, but its mechanism remains unclear. This study investigates taraxerone's impact and the mechanisms involved in bleomycin-induced pulmonary fibrosis in mice. After establishing a pulmonary fibrosis mouse model, taraxerone was intraperitoneally injected continuously for 14-28 days. The in vivo antifibrotic and antioxidative stress effects of taraxerone were assessed. In vitro, the influence of taraxerone on transforming growth factor-ß1-induced myofibroblast transformation and oxidative stress was investigated. Subsequently, quantitative polymerase chain reaction screened the histone deacetylase and Sirtuin family, and taraxerone's effects on SIRT1 were assessed. After SIRT1 siRNA treatment, changes in myofibroblast transformation and antioxidant capacity in response to taraxerone were observed. Acetylation and phosphorylation levels of Smad3 were evaluated. We also examined the binding levels of SIRT1 with Pho-Smad3 and Smad3, as well as the nuclear localization of Smad2/3. EX527 confirmed SIRT1's in vivo action in response to taraxerone. In vitro experiments suggested that taraxerone inhibited myofibroblast differentiation by activating SIRT1 and reducing oxidative stress. We also observed a new interaction between SIRT1 and the Smad complex. Taraxerone activates SIRT1, enabling it to bind directly to Smad3. This leads to reduced Smad complex phosphorylation and limited nuclear translocation. As a result, the transcription of fibrotic factors is reduced. In vivo validation confirms taraxerone's SIRT1-mediated antifibrotic effectiveness. This suggests that targeting SIRT1-mediated inhibition of myofibroblast differentiation could be a key strategy in taraxerone-based therapy for pulmonary fibrosis.

Supercritical Fluid-extracted Citrus aurantium L. var. amara Engl. Essential Oil Nanoemulsion: Preparation, Characterization, and Its Sleep-promoting Effect.

To overcome the defects of Citrus aurantium L. var. amara Engl. essential oil (CAEO), such as high volatility and poor stability, supercritical fluid-extracted CAEO nanoemulsion (SFE-CAEO-NE) was prepared by the microemulsification method. Emulsifiers comprising Tween 80, polyoxyethylenated castor oil (EL-40), and 1,2-hexanediol, and an oil phase containing SFE-CAEO were used for microemulsification. We examined the physicochemical properties of SFE-CAEO-NE and steam distillation-extracted CAEO nanoemulsion (SDE-CAEO-NE), which were prepared using different concentrations of the emulsifiers. The mean particle size and zeta potential were 21.52 nm and -9.82 mV, respectively, for SFE-CAEO-NE, and 30.58 nm and -6.28 mV, respectively, for SDE-CAEO-NE, at an emulsifier concentration of 15% (w/w). SFE-CAEO-NE displayed better physicochemical properties compared with SDE-CAEO-NE. Moreover, its physicochemical properties were generally stable at different temperatures (-20-60℃), pH (3-8), and ionic strengths (0-400 mM). No obvious variations in particle size, zeta potential, and Ke were observed after storing this nanoemulsion for 30 days at 4℃, 25℃, and 40℃, suggesting that it had good stability. The sleep-promoting effect of SFE-CAEO-NE was evaluated using a mouse model of insomnia. The results of behavioral tests indicated that SFE-CAEO-NE ameliorated insomnia-like behavior. Moreover, SFE-CAEO- NE administration increased the serum concentrations of neurotransmitters such as 5-hydroxytryptamine and γ-aminobutyric acid, and decreased that of noradrenaline in mice. It also exerted a reparative effect on the function of damaged neurons. Overall, SFE-CAEO-NE displayed a good sleep-promoting effect.

Quail GHRL and LEAP2 gene cloning, polymorphism detection, phylogenetic analysis, tissue expression profiling and its association analysis with feed intake.

The GHRL, LEAP2, and GHSR system have recently been identified as important regulators of feed intake in mammals and chickens. However, the complete cloning of the quail GHRL (qGHRL) and quail LEAP2 (qLEAP2) genes, as well as their association with feed intake, remains unclear. This study cloned the entire qGHRL and qLEAP2 cDNA sequence in Chinese yellow quail (Coturnix japonica), including the 5' and 3' untranslated regions. Sanger sequencing analysis revealed no missense mutations in the coding region of qGHRL and qLEAP2. Subsequently, phylogenetic analysis and protein homology alignment were conducted on the qGHRL and qLEAP2 in major poultry species. The findings of this research indicated that the qGHRL and qLEAP2 sequences exhibit a high degree of similarity with those of chicken and turkey. Specifically, the N-terminal 6 amino acids of GHRL mature peptides and all the mature peptide sequence of LEAP2 exhibited consistent patterns across all species examined. The analysis of tissue gene expression profiles indicated that qGHRL was primarily expressed in the proventriculus and brain tissue, whereas qLEAP2 exhibited higher expression levels in the intestinal tissue, kidney, and liver tissue, differing slightly from previous studies conducted on chicken. It is necessary to investigate the significance of elevated expression of qGHRL in brain and qLEAP2 in kidney in the future. Further research has shown that the expression of qLEAP2 can quickly respond to changes in different energy states, whereas qGHRL does not exhibit the same capability. Overall, this study successfully cloned the complete cDNA sequences of qGHRL and qLEAP2, and conducted a comprehensive examination of their tissue expression profiles and gene expression levels in the main expressing organs across different energy states. Our current findings suggested that qLEAP2 is highly expressed in the liver, intestine, and kidney, and its expression level is regulated by feed intake.

Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

Building adjustment capacity to cope with running water in cultured grass carp through flow stimulation conditions.

The adaptability of cultured fish to complex flow conditions is crucial for their survival after being released into the wild. Running water in natural environments poses significant challenges for the proliferation and release of cultured fish. This study aimed to investigate the effects of flow stimulation on the adjustment capacity of cultured fish to cope with running water. The target fish were cultured grass carp. An annular flume was used to conduct tests on training and control groups. The results demonstrated an enhancement in the adjustment capacity of cultured fish following appropriate flow stimulation training. (1) The trained fish exhibited a heightened preference for low-velocity areas. (2) The trained fish displayed the ability to select a route characterized by low energy consumption, predominantly following the periphery of the low-velocity area. This suggested that an appropriate flow velocity could improve the sensitivity of training fish to water flow information, and their adjustment capacity to cope with running water improved to a certain extent. A higher adjustment capacity allowed them to process flow rate information rapidly and identify a migration strategy with lower energy consumption. This study provides a useful reference for enhancing the survival rate of grass carp through stock enhancement initiatives and contributes to the sustainability of freshwater ecosystems.

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms.

Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a "mucosal mask". The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.

GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway.

The orphan G protein-coupled receptor (GPCR) GPR161 plays a central role in development by suppressing Hedgehog signaling. The fundamental basis of how GPR161 is activated remains unclear. Here, we determined a cryogenic-electron microscopy structure of active human GPR161 bound to heterotrimeric Gs. This structure revealed an extracellular loop 2 that occupies the canonical GPCR orthosteric ligand pocket. Furthermore, a sterol that binds adjacent to transmembrane helices 6 and 7 stabilizes a GPR161 conformation required for Gs coupling. Mutations that prevent sterol binding to GPR161 suppress Gs-mediated signaling. These mutants retain the ability to suppress GLI2 transcription factor accumulation in primary cilia, a key function of ciliary GPR161. By contrast, a protein kinase A-binding site in the GPR161 C terminus is critical in suppressing GLI2 ciliary accumulation. Our work highlights how structural features of GPR161 interface with the Hedgehog pathway and sets a foundation to understand the role of GPR161 function in other signaling pathways.

MLFLHMDA: predicting human microbe-disease association based on multi-view latent feature learning.

Introduction: A growing body of research indicates that microorganisms play a crucial role in human health. Imbalances in microbial communities are closely linked to human diseases, and identifying potential relationships between microbes and diseases can help elucidate the pathogenesis of diseases. However, traditional methods based on biological or clinical experiments are costly, so the use of computational models to predict potential microbe-disease associations is of great importance. Methods: In this paper, we present a novel computational model called MLFLHMDA, which is based on a Multi-View Latent Feature Learning approach to predict Human potential Microbe-Disease Associations. Specifically, we compute Gaussian interaction profile kernel similarity between diseases and microbes based on the known microbe-disease associations from the Human Microbe-Disease Association Database and perform a preprocessing step on the resulting microbe-disease association matrix, namely, weighting K nearest known neighbors (WKNKN) to reduce the sparsity of the microbe-disease association matrix. To obtain unobserved associations in the microbe and disease views, we extract different latent features based on the geometrical structure of microbes and diseases, and project multi-modal latent features into a common subspace. Next, we introduce graph regularization to preserve the local manifold structure of Gaussian interaction profile kernel similarity and add Lp,q-norms to the projection matrix to ensure the interpretability and sparsity of the model. Results: The AUC values for global leave-one-out cross-validation and 5-fold cross validation implemented by MLFLHMDA are 0.9165 and 0.8942+/-0.0041, respectively, which perform better than other existing methods. In addition, case studies of different diseases have demonstrated the superiority of the predictive power of MLFLHMDA. The source code of our model and the data are available on https://github.com/LiangzheZhang/MLFLHMDA_master.

Colonic microflora and plasma metabolite-based comparative analysis of unilateral ureteral obstruction-induced chronic kidney disease after treatment with the Chinese medicine FuZhengHuaYuJiangZhuTongLuo and AST-120.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

[Pathogenesis and Targeted Treatment Progress of Splenomegaly in Primary Myelofibrosis--Review].

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm with splenomegaly as the major clinical manifestation, which is commonly considered to be linked to splenic extramedullary hematopoiesis. Alteration of CXCL12/CXCR4 pathway can lead to the migration of hematopoietic stem cells and hematopoietic progenitor cells from bone marrow to spleen which results in splenic extramedullary hematopoiesis. In addition, low GATA1 expression and the abnormal secretion of cytokines were found to be significantly associated with splenomegaly. With the application of JAK1/2 inhibitors in clinical, the symptoms of splenomegaly have been significantly improved in PMF patients. This article will review the pathogenesis and targeted treatment progress of splenomegaly in PMF.