Deciphering the prognostic and therapeutic significance of BAG1 and BAG2 for predicting distinct survival outcome and effects on liposarcoma.

Liposarcoma (LPS) is the second most common kind of soft tissue sarcoma, and a heterogeneous malignant tumor derived from adipose tissue. Up to now, the prognostic value of BAG1 or BAG2 in LPS has not been defined yet. Expression profiling data of LPS patients were collected from TCGA and GEO database. Survival curves were plotted to verify the outcome differences of patients based on BAG1 or BAG2 expression. Univariate and multivariate Cox regression models were used to analyze the prognostic ability of BAG1 or BAG2. Chaperone's regulators BAG1 and BAG2 were identified as prognostic biomarkers for LPS patients, which exhibited distinct expression patterns and survival outcome prediction performances. Patients with high BAG2 expression and/or low BAG1 expression had worse prognosis. Enrichment analysis showed that BAG1 was involved in negative regulation of TGF-ß signaling. Low expression of BAG1 was associated with high abundance of regulatory T cells (Tregs). The 2-gene signature model further confirmed the improved risk assessment performance of BAG1 and BAG2: high risk patients displayed poor prognosis. BAG1 and BAG2 are supposed to be potential prognostic biomarkers for LPS and have impacts on liposarcomagenesis and immune infiltration in distinctive manners, which may function as potential therapy targets (BAG1 agonists/BAG2 inhibitors) for LPS.

Sarcopenic obesity is associated with cardiometabolic multimorbidity in Chinese middle-aged and older adults: a cross-sectional and longitudinal study.

OBJECTIVES: Sarcopenic obesity (SO) has been found to increase the risk of metabolic disorders, however, its relationship with cardiometabolic multimorbidity (CMM) remains unexplored. This study aims to investigate the potential association between SO and CMM in the middle-aged and older population. METHODS: Our study subjects were from CHARLS. SO was defined as the combination of impaired grip strength (grip strength <28 kg for men and <18 kg for women) and increased body mass index (BMI ≥25 kg/m2). CMM was defined as having two or more cardiometabolic diseases, including diabetes mellitus, stroke, and heart disease. The participants were divided into four groups according to their sarcopenia and obesity status, and logistic regression analysis was used to examine the association between SO and CMM. RESULTS: A total of 15,252 study subjects were included in the cross-sectional study, with an average age of 60.6 years and a male proportion of 47.4%. In the cross-sectional analysis conducted in 2015, the prevalence of CMM was highest in the SO group (9.1%), followed by the obesity (3.7%) and sarcopenia (3.5%) group. After adjustment for confounding factors, SO [OR (95%CI): 2.453 (1.742-3.455)], sarcopenia [OR (95% CI): 1.601 (1.157-2.217)], obesity [OR (95% CI): 1.446 (1.107-1.888)] were all observed to be associated with CMM, with the strongest association in the SO group. Furthermore, in the longitudinal analysis, only the SO group demonstrated a significant risk for developing CMM [OR (95% CI): 2.302 (1.239-4.228)]. CONCLUSIONS: SO was independently and positively associated with CMM in middle-aged and older population.

Two Stable Pillar-Layered Zn-LMOFs for Highly Fluorescence Sensing of Inorganic Pollutants and Nitro Aromatic Compounds in Water.

Luminescent metal-organic frameworks (LMOFs) are a potential class of functional materials for the photoluminescent detection of a wide range of analytes as well as for the detection of pollutants in wastewater. Herein, by using the pillar-layered strategy, two new luminescence Zn-LMOFs (JLU-MOF222 and JLU-MOF223) were successfully solvothermal synthesized. The 2D layers are both consisting of Zn2+ and TPHC [TPHC = (1,1':2',1″-terphenyl)-3,3″,4,4',4″,5'-hexacarboxylic acid] ligands and then pillared by the different N-donor ligands to form the 3D Zn-LMOFs with fsh topology. Benefiting from the uncoordinated carboxylate sites, uncoordinated N atom, or -NH2 group in the pillaring ligands and excellent stability in pH = 2-13 aqueous phase, JLU-MOF222 and JLU-MOF223 not only can sensitively detect trace amounts of inorganic pollutants (Fe3+, Cr2O72-) and nitro aromatic compounds TNP and 2,4-DNP (TNP = 2,4,6- trinitrophenol, 2,4-DNP = 2,4-dinitrophenol) through luminescence quenching but also exhibit high selectivity of other anti-interference competing analytes. The two new Zn-LMOFs can be used as potential luminescent sensors for pollutant detection in water due to their high KSV and low limit of detection (LOD).

Emerging biological functions of Twist1 in cell differentiation.

Twist1 is required for embryonic development and expresses after birth in mesenchymal stem cells derived from mesoderm, where it governs mesenchymal cell development. As a well-known regulator of epithelial-mesenchymal transition or embryonic organogenesis, Twist1 is important in a variety of developmental systems, including mesoderm formation, neurogenesis, myogenesis, cranial neural crest cell migration, and differentiation. In this review, we first highlight the physiological significance of Twist1 in cell differentiation, including osteogenic, chondrogenic, and myogenic differentiation, and then detail its probable molecular processes and signaling pathways. On this premise, we summarize the significance of Twist1 in distinct developmental disorders and diseases to provide a reference for studies on cell differentiation/development-related diseases.

Impact of COVID-19 pandemic on microplastic occurrence in aquatic environments: A three-year study in Taihu Lake Basin, China.

The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on microplastic (MP) occurrence in aquatic environments deserves an in-depth study. In this study, the occurrence of MPs and environmental flux of plastics before (2019) and during (2020 and 2021) the pandemic were comparatively investigated in various aquatic compartments in the Taihu Lake Basin in China. The field-based investigations from 2019 to 2021 for Taihu Lake have shown that, at the onset of the outbreak, the MP abundance declined at a rate of 62.3 %, but gradually recovered to the pre-pandemic level. However, the amount of plastics being released into aquatic environments showed a declining trend in 2020 and 2021 compared to those in 2019, with decrease rates of 13.7 % and 15.8 %, respectively. Characterization analysis of MP particles and source apportionment framework implied that while the contributions of tire abrasion and domestic waste to MP occurrence were depleted owing to the reduction in human activity during the pandemic, weathering and fragmentation of retained plastics contributed to the recovery of stored MPs. This study provides insights into the anthropogenic influences on MP occurrence, and supports policymakers in managing and controlling plastic contamination in large freshwater systems in the "new normal" phase.

Inflammatory damage caused by Echovirus 30 in the suckling mouse brain and HMC3 cells.

Echovirus 30 (E30), a member of the species B Enterovirus family, is a primary pathogen responsible for aseptic meningitis and encephalitis. E30 is associated with severe nervous system diseases and is a primary cause of child illness, disability, and even mortality. However, the mechanisms underlying E30-induced brain injury remain poorly understood. In this study, we used a neonatal mouse model of E30 to investigate the possible mechanisms of brain injury. E30 infection triggered the activation of microglia in the mouse brain and efficiently replicated within HMC3 cells. Subsequent transcriptomic analysis revealed inflammatory activation of microglia in response to E30 infection. We also detected a significant upregulation of polo-like kinase 1 (PLK1) and found that its inhibition could limit E30 infection in a sucking mouse model. Collectively, E30 infection led to brain injury in a neonatal mouse model, which may be related to excessive inflammatory responses. Our findings highlight the intricate interplay between E30 infection and neurological damage, providing crucial insights that could guide the development of interventions and strategies to address the severe clinical manifestations associated with this pathogen.

Clinical performance of the ASAS health index in chinese patients with ankylosing spondylitis and its influencing factors.

OBJECTIVE: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status. METHODS: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI. RESULTS: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status. CONCLUSION: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.

Association of Air Quality Improvement and Frailty Progression: A National Study across China.

Accumulating evidence strongly suggests that exposure to ambient air pollution is linked with increased frailty. However, little is known about the effect of improved air quality on frailty progression. We aimed to investigate whether improvements in air quality (PM1, PM2.5, PM10, NO2, and O3) can alleviate frailty progression, particularly in the aftermath of implementation of the "Clean Air Action" policy in China. The study involved 12,891 participants with geocoded environmental data from the nationwide China Health and Retirement Longitudinal Study (CHARLS) during the period from May 2011 to August 2015. Multivariate logistic regression models were used to analyze the association of air pollution improvements and frailty progression. The protective effects were noted for PM1, PM2.5, PM10, and NO2 indices, with an aOR (adjusted odds ratio) ranging from 0.72 to 0.79. Air quality improvement in PM1, PM2.5, PM10, and NO2 could alleviate the progression of frailty. The study is the first to examine the association between the improvement of air quality and the progression of frailty, setting a precedent for the importance of a nationwide clean air policy and its impact on healthy ageing.

Trigonometric Bundling Disulfide Unit Starship Synergizes More Effectively to Promote Cellular Uptake.

A small molecule disulfide unit technology platform based on dynamic thiol exchange chemistry at the cell membrane has the potential for drug delivery. However, the alteration of the CSSC dihedral angle of the disulfide unit caused by diverse substituents directly affects the effectiveness of this technology platform as well as its own chemical stability. The highly stable open-loop relaxed type disulfide unit plays a limited role in drug delivery due to its low dihedral angle. Here, we have built a novel disulfide unit starship based on the 3,4,5-trihydroxyphenyl skeleton through trigonometric bundling. The intracellular delivery results showed that the trigonometric bundling of the disulfide unit starship effectively promoted cellular uptake without any toxicity, which is far more than 100 times more active than that of equipment with a single disulfide unit in particular. Then, the significant reduction in cell uptake capacity (73-93%) using thiol erasers proves that the trigonometric bundling of the disulfide starship is an endocytosis-independent internalization mechanism via a dynamic covalent disulfide exchange mediated by thiols on the cell surface. Furthermore, analysis of the molecular dynamics simulations demonstrated that trigonometric bundling of the disulfide starship can significantly change the membrane curvature while pushing lipid molecules in multiple directions, resulting in a significant distortion in the membrane structure and excellent membrane permeation performance. In conclusion, the starship system we built fully compensates for the inefficiency deficiencies induced by poor dihedral angles.

Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.

BACKGROUND: As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. METHODS: By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. RESULTS: A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. CONCLUSION: A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.

A dynamic attribute reduction algorithm based on relative neighborhood discernibility degree.

This paper addresses the current existence of attribute reduction algorithms for incomplete hybrid decision-making systems, including low attribute reduction efficiency, low classification accuracy and lack of consideration of unlabeled data types. To address these issues, this paper first redefines the weakly labeled relative neighborhood discernibility degree and develops a non-dynamic attribute reduction algorithm. In addition, this paper proposes an incremental update mechanism for weakly tagged relative neighborhood discernibility degree and introduces a new dynamic attribute reduction algorithm for increasing the set of objects based on it. Meanwhile, this paper also compares and analyses the improved algorithm proposed in this study with two existing attribute reduction algorithms using 8 data sets in the UCI database. The results show that the dynamic attribute reduction algorithm proposed in this paper achieves higher attribute reduction efficiency and classification accuracy, which further validates the effectiveness of the algorithm proposed in this paper.

Different Phenotypic, Photosynthetic, and Physiological Responses to Flooding between Q. nuttallii and Q. palustris.

Flooding stress is an increasingly serious problem in wetlands, often affecting large areas of crops and timber production areas. The current study aimed to explore the species differences in responses to flooding stress between Q. nuttallii and Q. palustris in an outdoor environment. All the tested plants survived after a 60-day flooding treatment that left 5 cm of water above the soil surface. This suggests that the two species are flood-tolerant, so they can be applied in the construction of riparian protection forests and wetland restoration. Compared with control conditions, flooding treatment significantly decreased seedling height and diameter and the Pn, Gs, Tr, Fv/Fm, ABS/CSm, TR0/CSm, ET0/CSm, RE0/CSm, IAA, and GA3 content and significantly increased the content of MDA, H2O2, soluble sugars, SOD, POD, ADH, ABA, and JA. Under control conditions, Q. nuttallii showed significantly greater growth and photosynthetic capability than Q. palustris. In contrast, Q. palustris exhibited less inhibition of growth and photosynthesis, oxidative stress levels, and antioxidant enzyme activities than Q. nuttallii under flooding conditions. The findings indicate that Q. palustris has better defense mechanisms against the damage caused by flooding stress than Q. nuttallii. Q. nuttallii was more sensitive and responsive to flooding than Q. palustris.

The synthesis and preliminary immunological evaluation of a dual-adjuvant SARS-CoV-2 RBD vaccine: Covalent integration of TLR7/8 and iNKT cell agonists.

Covalently linking an adjuvant to an antigenic protein enhances its immunogenicity by ensuring a synergistic delivery to the immune system, fostering a more robust and targeted immune response. Most adjuvant-protein conjugate vaccines incorporate only one adjuvant due to the difficulties in its synthesis. However, there is a growing interest in developing vaccines with multiple adjuvants designed to elicit a more robust and targeted immune response by engaging different aspects of the immune system for complex diseases where traditional vaccines fall short. Here, we pioneer the synthesis of a dual-adjuvants protein conjugate Vaccine 1 by assembling a toll-like receptor 7/8 (TLR7/8) agonist, an invariant natural killer T cell (iNKT) agonist with a clickable bicyclononyne (BCN). The BCN group can bio-orthogonally react with azide-modified severe acute respiratory syndrome coronavirus-2 receptor-binding domain (SARS-CoV-2 RBD) trimer antigen to give the three-component Vaccine 1. Notably, with a mere 3 µg antigen, it elicited a balanced subclass of IgG titers and 20-fold more IgG2a than control vaccines, highlighting its potential for enhancing antibody-dependent cellular cytotoxicity. This strategy provides a practicable way to synthesize covalently linked dual immunostimulants. It expands the fully synthetic self-adjuvant protein vaccine that uses a single adjuvant to include two different types of adjuvants.

Recyclable chitosan adsorbent: Facile functionalization strategy, excellent removal capacity of dyes and adsorption mechanism.

The development of chitosan-based adsorbents with facile preparation, high adsorption performance and reusability for the removal of contaminant dyes remains a persistent challenge. To overcome this challenge, herein, we have developed a novel and extremely facile one-step strategy by which a new high-performance chitosan/polyethyleneimine/polyethylene glycol diglycidyl ether adsorbent (named as CC/PEI/PGDE) has been successfully fabricated via direct functionalization of CC by PEI at ambient temperature followed by subsequent freeze-drying. The Box-Behnken Design was employed to optimize the concentrations of adsorbent components. Attractively, this adsorbent exhibit outstanding adsorption performances to congo red (RED), acid blue-25 (BLUE) and amino black-10B (BLACK) with 2901 mg g-1 (90.9 %), 3434 mg g-1 (90.9 %), and 1438 mg g-1 (90.1 %) of adsorption capacities (removal efficiencies), respectively, and maintains nearly the same adsorption behaviors to original adsorbent even after 6 cycles of adsorption-desorption processes. Meanwhile, three kinetic models, three isothermal models, and the Vant Hoff model are employed to further investigate the adsorption behaviors of RED, BLUE, and BLACK dyes by CC/PEI/PGDE. The results from SEM, EDS, BET, FT-IR, pHZPC and XPS confirm that hydrogen bond interactions and electrostatic attractions play crucial roles in facilitating dyes adsorption by CC/PEI/PGDE. It is expected that this work can bring forward a new perspective for the facile design of high-performance adsorbent for removing anionic dyes from wastewater.

Development of Novel ß-Carboline/Furylmalononitrile Hybrids as Type I/II Photosensitizers with Chemo-Photodynamic Therapy and Minimal Toxicity.

Chemo-photodynamic therapy is a treatment method that combines chemotherapy and photodynamic therapy and has demonstrated significant potential in cancer treatment. However, the development of chemo-photodynamic therapeutic agents with fewer side effects still poses a challenge. Herein, we designed and synthesized a novel series of ß-carboline/furylmalononitrile hybrids 10a-i and evaluated their chemo-photodynamic therapeutic effects. Most of the compounds were photodynamically active and exhibited cytotoxic effects in four cancer cells. In particular, 10f possessed type-I/II photodynamic characteristics, and its 1O2 quantum yield increased by 3-fold from pH 7.4 to 4.5. Most interestingly, 10f exhibited robust antiproliferative effects by tumor-selective cytotoxicities and hypoxic-overcoming phototoxicities. In addition, 10f generated intracellular ROS and induced hepatocellular apoptosis, mitochondrial damage, and autophagy. Finally, 10f demonstrated extremely low acute toxicity (LD50 = 1415 mg/kg) and a high tumor-inhibitory rate of 80.5% through chemo-photodynamic dual therapy. Our findings may provide a promising framework for the design of new photosensitizers for chemo-photodynamic therapy.

Unfolding Protein-Based Hapten Coupling via Thiol-Maleimide Click Chemistry: Enhanced Immunogenicity in Anti-Nicotine Vaccines Based on a Novel Conjugation Method and MPL/QS-21 Adjuvants.

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol-maleimide "click" chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine-BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

Harnessing the potential of de-sulfated heparin for targeted drug delivery: A three-component approach exemplified by conjugation with galactose and paclitaxel.

Heparin, an anticoagulant with a century-long history of use, has been investigated over the past decade as a potential drug delivery vehicle. Despite its safety and efficacy, its interactions with many proteins through specific sulfate patterns can complicate drug delivery by mediating diverse biological functions. Here, we present the synthesis of a three-component drug delivery system comprising de-sulfated heparin as the carrier, galactose as the targeting moiety, and paclitaxel as the therapeutic drug. Removal of sulfates eliminated most of its anticoagulant effects in all intermediates. Through coupling with galactose and paclitaxel, the system improved the solubility of the drug and achieved selective targeting and efficient drug delivery to HepG2 cells, a liver carcinoma cell line with high galactose receptor expression. While the three-component system exhibited a slightly higher IC50 value than native paclitaxel, demonstrating its efficacy as a drug carrier, the IC50 value for the normal human liver cell line QSG7701 was significantly higher, indicating its selectivity and safety. Our study introduces a novel approach utilizing desulfated heparin as a carrier, warranting further investigation to unlock its potential in targeted drug delivery strategies.

Deciphering adipose development: Function, differentiation and regulation.

The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming a major risk factor for human health, causing various relevant diseases (including hypertension, diabetes, osteoarthritis and cancers). Therefore, it is of significance to antagonize obesity to reduce the risk of obesity-related diseases. Excess lipid accumulation in adipose tissues is mediated by adipocyte hypertrophy (expansion of pre-existing adipocytes) or hyperplasia (increase of newly-formed adipocytes). It is necessary to prevent excessive accumulation of adipose tissues by controlling adipose development. Adipogenesis is exquisitely regulated by many factors in vivo and in vitro, including hormones, cytokines, gender and dietary components. The present review has concluded a comprehensive understanding of adipose development including its origin, classification, distribution, function, differentiation and molecular mechanisms underlying adipogenesis, which may provide potential therapeutic strategies for harnessing obesity without impairing adipose tissue function.

Macrophage depletion damages hematopoiesis partially through inhibition of cell homing and expansion after hematopoietic cell transplantation.

Bone marrow macrophages (Mφ) are essential components of the bone marrow niche that regulate the function of hematopoietic stem cells. Poor graft function and inhibition of hematopoietic production can result from abnormal macrophage function; however, the underlying mechanism is unclear. Clodronate liposomes (Clo-Lip) have been used widely to deplete macrophages and study their functions. Our previous results showed that Clod-Lip-mediated clearance of macrophages plays a vital role in regulating hematopoietic reconstruction after allogeneic hematopoietic cell transplantation (HCT). In this study, using an isogenic hematopoietic stem cell transplantation model, we found that Clod-Lip-mediated clearance of macrophages suppressed hematopoietic reconstruction by inhibiting the homing process of hematopoietic cells. We also demonstrated that macrophage depletion inhibited the direct supportive effect of macrophages on hematopoietic stem and progenitor cells and erythroid differentiation but promoted the production of megakaryocytic progenitors ex vivo. We showed that macrophages increase CD49e expression on hematopoietic stem and progenitor cells (HSPCs). However, CD49e inhibitors did not support the proliferative effect of macrophages on hematopoietic cells. In contrast, macrophage E-selectin/ intercellular cell adhesion molecule-1 (ICAM-1) may be involved in directly regulating HSPCs. In conclusion, macrophage depletion with Clo-Lip partially disrupts bone marrow hematopoiesis after HCT by impeding donor cell homing and macrophage-HSPCs interactions.

Metabolites, Healthy Lifestyle, and Polygenic Risk Score Associated with Upper Gastrointestinal Cancer: Findings from the UK Biobank Study.

Previous metabolomics studies have highlighted the predictive value of metabolites on upper gastrointestinal (UGI) cancer, while most of them ignored the potential effects of lifestyle and genetic risk on plasma metabolites. This study aimed to evaluate the role of lifestyle and genetic risk in the metabolic mechanism of UGI cancer. Differential metabolites of UGI cancer were identified using partial least-squares discriminant analysis and the Wilcoxon test. Then, we calculated the healthy lifestyle index (HLI) score and polygenic risk score (PRS) and divided them into three groups, respectively. A total of 15 metabolites were identified as UGI-cancer-related differential metabolites. The metabolite model (AUC = 0.699) exhibited superior discrimination ability compared to those of the HLI model (AUC = 0.615) and the PRS model (AUC = 0.593). Moreover, subgroup analysis revealed that the metabolite model showed higher discrimination ability for individuals with unhealthy lifestyles compared to that with healthy individuals (AUC = 0.783 vs 0.684). Furthermore, in the genetic risk subgroup analysis, individuals with a genetic predisposition to UGI cancer exhibited the best discriminative performance in the metabolite model (AUC = 0.770). These findings demonstrated the clinical significance of metabolic biomarkers in UGI cancer discrimination, especially in individuals with unhealthy lifestyles and a high genetic risk.