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1.
Sci Rep ; 14(1): 12674, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830964

ABSTRACT

This longitudinal cohort study examined the long-term effect of statin therapy on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). A total of 1760 patients with stable coronary artery disease (CAD) were divided by receipt of statin therapy or not after index PCI. Baseline clinical characteristics, risk factors, angiographic findings, and medications after interventional procedure were assessed to compare long-term clinical outcomes between groups. Predictors for all-cause death and major adverse cardiovascular events (MACE), including myocardial infarction (MI), cardiovascular death, and repeated PCI procedures, were also analyzed. The statin therapy group had higher average serum cholesterol and more elevated low-density lipoprotein cholesterol (LDL-C) than the non-statin therapy group (189.0 ± 47.9 vs 169.3 ± 37.00 mg/dl, 117.2 ± 42.6 vs 98.7 ± 31.8 mg/dl, respectively, both P < 0.001). The non-statin group had higher rates of all-cause death and cardiovascular death compared to statin group (both P < 0.001). After adjustment for age, diabetes, and chronic kidney disease, Cox proportion hazard analysis revealed statin use significantly reduced all-cause death and repeated PCI procedure (hazard ratio: 0.53 and 0.69, respectively). Statin use seemed not reduce the hazard of cardiovascular death or MI in patients with stable CAD after PCI; however, statin therapy still was associated with reduced rates of all-cause death and repeat PCI procedure.


Subject(s)
Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Female , Middle Aged , Aged , Coronary Artery Disease/surgery , Coronary Artery Disease/mortality , Treatment Outcome , Longitudinal Studies , Risk Factors , Myocardial Infarction , Cholesterol, LDL/blood
2.
Sci Rep ; 14(1): 11584, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38773245

ABSTRACT

Climate change and disease threaten shrimp farming. Here, we studied the beneficial properties of a phytogenic formulation, Shrimp Best (SB), in whiteleg shrimp. Functional studies showed that SB dose-dependently increased shrimp body weight and decreased feed conversion ratio. We found that SB protected against Vibrio parahaemolyticus as evidenced by survival rate, bacterial load, and hepatopancreatic pathology in shrimp. Finally, we explored the likely mechanism by which SB affects growth performance and vibriosis in shrimp. The 16S rRNA sequencing data showed that SB increased 6 probiotic genera and decreased 6 genera of pathogenic bacteria in shrimp. Among these, SB increased the proportion of Lactobacillus johnsonii and decreased that of V. parahaemolyticus in shrimp guts. To dissect the relationship among SB, Lactobacillus and Vibrio, we investigated the in vitro regulation of Lactobacillus and Vibrio by SB. SB at ≥ 0.25 µg/mL promoted L. johnsonii growth. Additionally, L. johnsonii and its supernatant could inhibit V. parahaemolyticus. Furthermore, SB could up-regulate five anti-Vibrio metabolites of L. johnsonii, which caused bacterial membrane destruction. In parallel, we identified 3 fatty acids as active compounds from SB. Overall, this work demonstrated that SB improved growth performance and vibriosis protection in shrimp via the regulation of gut microbiota.


Subject(s)
Penaeidae , Vibrio parahaemolyticus , Animals , Penaeidae/microbiology , Penaeidae/growth & development , Vibrio parahaemolyticus/drug effects , Vibrio parahaemolyticus/growth & development , Vibrio parahaemolyticus/pathogenicity , Vibrio Infections/prevention & control , Vibrio Infections/veterinary , Vibrio Infections/microbiology , Lactobacillus/growth & development , RNA, Ribosomal, 16S/genetics , Vibrio/drug effects , Vibrio/pathogenicity , Probiotics
3.
Commun Biol ; 7(1): 549, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724689

ABSTRACT

Amphiphysin 2 (BIN1) is a membrane and actin remodeling protein mutated in congenital and adult centronuclear myopathies. Here, we report an unexpected function of this N-BAR domain protein BIN1 in filopodia formation. We demonstrated that BIN1 expression is necessary and sufficient to induce filopodia formation. BIN1 is present at the base of forming filopodia and all along filopodia, where it colocalizes with F-actin. We identify that BIN1-mediated filopodia formation requires IRSp53, which allows its localization at negatively-curved membrane topologies. Our results show that BIN1 bundles actin in vitro. Finally, we identify that BIN1 regulates the membrane-to-cortex architecture and functions as a molecular platform to recruit actin-binding proteins, dynamin and ezrin, to promote filopodia formation.


Subject(s)
Adaptor Proteins, Signal Transducing , Nerve Tissue Proteins , Nuclear Proteins , Pseudopodia , Tumor Suppressor Proteins , Humans , Animals , HeLa Cells , Cell Line , Actins/metabolism , Pseudopodia/metabolism , Nuclear Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Nerve Tissue Proteins/metabolism , Cell Membrane/metabolism
4.
Eur J Cell Biol ; 103(2): 151402, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38461706

ABSTRACT

At the cell surface, the actin cytoskeleton and the plasma membrane interact reciprocally in a variety of processes related to the remodeling of the cell surface. The actin cytoskeleton has been known to modulate membrane organization and reshape the membrane. To this end, actin-membrane linking molecules play a major role in regulating actin assembly and spatially direct the interaction between the actin cytoskeleton and the membrane. While studies in cells have provided a wealth of knowledge on the molecular composition and interactions of the actin-membrane interface, the complex molecular interactions make it challenging to elucidate the precise actions of the actin-membrane linkers at the interface. Synthetic reconstituted systems, consisting of model membranes and purified proteins, have been a powerful approach to elucidate how actin-membrane linkers direct actin assembly to drive membrane shape changes. In this review, we will focus only on several actin-membrane linkers that have been studied by using reconstitution systems. We will discuss the design principles of these reconstitution systems and how they have contributed to the understanding of the cellular functions of actin-membrane linkers. Finally, we will provide a perspective on future research directions in understanding the intricate actin-membrane interaction.


Subject(s)
Actins , Cell Membrane , Cell Membrane/metabolism , Actins/metabolism , Humans , Animals , Actin Cytoskeleton/metabolism
5.
Elife ; 122024 Mar 22.
Article in English | MEDLINE | ID: mdl-38517935

ABSTRACT

Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.


Subject(s)
Caveolin 1 , Endothelial Cells , Animals , Mice , Caveolae/metabolism , Caveolin 1/metabolism , Cell Membrane/metabolism , Endothelial Cells/metabolism , Exotoxins/metabolism
6.
J Formos Med Assoc ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38336509

ABSTRACT

BACKGROUND: Tracheostomized patients undergoing liberation from mechanical ventilation (MV) are exposed to the ambient environment through humidified air, potentially heightening aerosol particle dispersion. This study was designed to evaluate the patterns of aerosol dispersion during spontaneous breathing trials in such patients weaning from prolonged MV. METHODS: Particle Number Concentrations (PNC) at varying distances from tracheostomized patients in a specialized weaning unit were quantified using low-cost particle sensors, calibrated against a Condensation Particle Counter. Different oxygen delivery methods, including T-piece and collar mask both with the humidifier or with a small volume nebulizer (SVN), and simple collar mask, were employed. The PNC at various distances and across different oxygen devices were compared using the Kruskal-Wallis test. RESULTS: Of nine patients receiving prolonged MV, five underwent major surgery, and eight were successfully weaned from ventilation. PNCs at distances ranging from 30 cm to 300 cm showed no significant disparity (H(4) = 8.993, p = 0.061). However, significant differences in PNC were noted among oxygen delivery methods, with Bonferroni-adjusted pairwise comparisons highlighting differences between T-piece or collar mask with SVN and other devices. CONCLUSIONS: Aerosol dispersion within 300 cm of the patient was not significantly different, while the nebulization significantly enhances ambient aerosol dispersion in tracheostomized patients on prolonged MV.

7.
Sci Rep ; 13(1): 8923, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37264037

ABSTRACT

Kt/V and URR (urea reduction ratio) measurements represent dialysis adequacy. Single-pool Kt/V is theoretically a superior method and is recommended by the Kidney Disease Outcomes Quality Initiative guidelines. However, the prognostic value of URR compared with Kt/V for all-cause mortality is unknown. The effect modifiers and cut-off values of the two parameters have not been compared. We investigated 2615 incident hemodialysis patients with URR of 72% and Kt/V (Daugirdas) of 1.6. The average patient age was 59 years, 50.7% were female, and 1113 (40.2%) died within 10 years. URR and Kt/V were both positively associated with nutrition factors and female sex and negatively associated with body weight and heart failure. In Cox regression mod-els for all-cause mortality, the hazard ratios (HRs) of high URR groups (65-70%, 70-75%, and > 75%) and the URR < 65% group were 0.748 (0.623-0.898), 0.693 (0.578-0.829), and 0.640 (0.519-0.788), respectively. The HRs of high Kt/V groups (Kt/V 1.2-1.4, 1.4-1.7, and > 1.7) and the Kt/V < 1.2 group were 0.711 (0.580-0.873), 0.656 (0.540-0.799), and 0.623 (0.498-0.779), respec-tively. In subgroup analysis, Kt/V was not associated with all-cause mortality in women. The prognostic value of URR for all-cause mortality is as great as that of Kt/V. URR > 70% and Kt/V > 1.4 were associated with a higher survival rate. Kt/V may have weaker prognostic value for women.


Subject(s)
Kidney Failure, Chronic , Renal Dialysis , Humans , Female , Middle Aged , Male , Prognosis , Follow-Up Studies , Taiwan/epidemiology , Renal Dialysis/methods , Urea
8.
Bioengineering (Basel) ; 10(6)2023 May 23.
Article in English | MEDLINE | ID: mdl-37370564

ABSTRACT

Over 70,000 people die of bacterial infections worldwide annually. Antibiotics have been liberally used to treat these diseases and, consequently, antibiotic resistance and drug ineffectiveness has been generated. In this environment, new anti-bacterial compounds are being urgently sought. Around 500 Artemisia species have been identified worldwide. Most species of this genus are aromatic and have multiple functions. Research into the Artemisia plants has expanded rapidly in recent years. Herein, we aim to update and summarize recent information about the phytochemistry, pharmacology and toxicology of the Artemisia plants. A literature search of articles published between 2003 to 2022 in PubMed, Google Scholar, Web of Science databases, and KNApSAcK metabolomics databases revealed that 20 Artemisia species and 75 compounds have been documented to possess anti-bacterial functions and multiple modes of action. We focus and discuss the progress in understanding the chemistry (structure and plant species source), anti-bacterial activities, and possible mechanisms of these phytochemicals. Mechanistic studies show that terpenoids, flavonoids, coumarins and others (miscellaneous group) were able to destroy cell walls and membranes in bacteria and interfere with DNA, proteins, enzymes and so on in bacteria. An overview of new anti-bacterial strategies using plant compounds and extracts is also provided.

9.
Front Nutr ; 10: 1136284, 2023.
Article in English | MEDLINE | ID: mdl-37255931

ABSTRACT

Non-insulin-based insulin resistance (IR) indices serve as the indicators of metabolic syndrome (MetS) but have limited value for predicting clinical outcomes. Whether the obesity paradox affects the predictive value of these indicators in patients with chronic kidney disease (CKD) remains unknown. We investigated whether MetS and non-insulin-based IR indices can predict all-cause mortality and renal outcomes in a prospective observational study with stage 1-4 CKD Asians (N = 2,457). These IR indices were associated with MetS. A Cox regression model including body mass index (BMI) revealed an association between MetS and renal outcomes. Among the IR indices, only high triglyceride-glucose (TyG) index was associated with adverse renal outcomes: the hazard ratio of Q4 quartile of the TyG index was 1.38 (1.12-1.70). All-cause mortality was marginally associated with MetS but not high IR indices. Low TyG and TyG-BMI indices as well as low BMI and triglyceride were paradoxically associated with increased risks of clinical outcomes. The triglyceride-to-high-density lipoprotein cholesterol ratio and metabolic score for IR indices were not associated with clinical outcomes. In conclusion, MetS and TyG index predict renal outcome and obesity paradox affects the prediction of IR indices in patients with stage 1-4 CKD.

10.
J Formos Med Assoc ; 122(11): 1132-1140, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37169656

ABSTRACT

BACKGROUND: To analyze the predictability of an automatic tube compensation (ATC) screening test compared with the conventional direct liberation test performed before continuous oxygen support for MV liberation. METHODS: This retrospective study analyzed tracheostomized patients with prolonged MV in a weaning unit of a medical center in Taiwan. In March 2020, a four-day ATC test to screen patient eligibility for ventilator liberation was implemented, intended to replace the direct liberation test. We compared the predictive accuracy of these two screening methods on the relevant outcomes in the two years before and one year after the implementation of this policy. RESULTS: Of the 403 cases, 246 (61%) and 157 (39%) received direct liberation and ATC screening tests, respectively. These two groups had similar outcomes: successful weaning upon leaving the Respiratory Care Center (RCC), success on day 100 of MV, success at hospital discharge, and in-hospital survival. Receiver operating characteristic curve analysis showed that the ATC screening test had better predictive ability than the direct liberation test for RCC weaning, discharge weaning, 100-day weaning, and in-hospital survival. CONCLUSION: This closed-circuit ATC screening test before ventilator liberation is a feasible and valuable method for screening PMV patients undergoing ventilator liberation in the pandemic era. Its predictability for a comparison with the open-circuit oxygen test requires further investigation.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Respiration, Artificial , Retrospective Studies , Ventilator Weaning/methods , Oxygen
11.
Article in English | MEDLINE | ID: mdl-37114144

ABSTRACT

In this study, we set out to evaluate the antiobesity activities of our newly isolated Lacticaseibacillus paracasei LM-141 (LPLM141) using a high-fat diet (HFD)-fed rat model. Male Sprague-Dawley rats were fed with a HFD with or without low-dosage (2 × 107 CFU/day per rat) or high-dosage (2 × 109 CFU/day per rat) LPLM141 for 14 weeks. The results showed that administration of LPLM141 significantly decreased body weight gain, liver weight, adipose tissue weight, and epididymal white adipocyte size increased by HFD feeding. The abnormal serum lipid profile induced by HFD feeding was normalized by administration of LPLM141. The enhanced chronic low-grade inflammation in HFD-fed rats was reduced by LPLM141 supplementation, as reflected by decreased serum lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) levels, reduced macrophage infiltration in adipose tissue, and increased serum adiponectin concentration. In addition, the elevations of proinflammatory cytokine genes and suppression of PPAR-γ mRNA in adipose tissues of rats fed with a HFD were markedly reversed by LPLM141 administration. Oral administration of LPLM141 induced browning of epididymal white adipose tissue (eWAT) and activation of interscapular brown adipose tissue (iBAT) in rats fed with HFD. Consumption of LPLM141 exhibited a significant amelioration in insulin resistance, which were mechanistically caused by downregulation of the serum leptin level and upregulation of hepatic IRS-1 and p-Akt protein expressions, in HFD treated rats. LPLM141 consumption significantly decreased hepatic lipogenic gene expressions and preserved liver function stimulated by HFD treatment. Administration of LPLM141 obviously mitigated hepatic steatosis observed in HFD feeding rats. Our current findings shed light on LPLM141 supplementation that exhibited an antiobesity effect in HFD-fed rats by alleviating inflammation and insulin resistance, which further highlighted the potential of utilizing LPLM141 as a preventive/therapeutic probiotic agent for obesity.

12.
Cell Mol Life Sci ; 80(4): 101, 2023 Mar 19.
Article in English | MEDLINE | ID: mdl-36935456

ABSTRACT

Pdia4 has been characterized as a key protein that positively regulates ß-cell failure and diabetes via ROS regulation. Here, we investigated the function and mechanism of PS1, a Pdia4 inhibitor, in ß-cells and diabetes. We found that PS1 had an IC50 of 4 µM for Pdia4. Furthermore, PS1 alone and in combination with metformin significantly reversed diabetes in db/db mice, 6 to 7 mice per group, as evidenced by blood glucose, glycosylated hemoglobin A1c (HbA1c), glucose tolerance test, diabetic incidence, survival and longevity (P < 0.05 or less). Accordingly, PS1 reduced cell death and dysfunction in the pancreatic ß-islets of db/db mice as exemplified by serum insulin, serum c-peptide, reactive oxygen species (ROS), islet atrophy, and homeostatic model assessment (HOMA) indices (P < 0.05 or less). Moreover, PS1 decreased cell death in the ß-islets of db/db mice. Mechanistic studies showed that PS1 significantly increased cell survival and insulin secretion in Min6 cells in response to high glucose (P < 0.05 or less). This increase could be attributed to a reduction in ROS production and the activity of electron transport chain complex 1 (ETC C1) and Nox in Min6 cells by PS1. Further, we found that PS1 inhibited the enzymatic activity of Pdia4 and mitigated the interaction between Pdia4 and Ndufs3 or p22 in Min6 cells (P < 0.01 or less). Taken together, this work demonstrates that PS1 negatively regulated ß-cell pathogenesis and diabetes via reduction of ROS production involving the Pdia4/Ndufs3 and Pdia4/p22 cascades.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin-Secreting Cells , Mice , Animals , Diabetes Mellitus, Type 2/metabolism , Reactive Oxygen Species/metabolism , Insulin/metabolism , Insulin-Secreting Cells/metabolism , Blood Glucose/metabolism , Mice, Inbred Strains , Mice, Inbred C57BL , Protein Disulfide-Isomerases/metabolism
14.
Diabetes Metab Res Rev ; 39(4): e3618, 2023 05.
Article in English | MEDLINE | ID: mdl-36731513

ABSTRACT

AIMS: To investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD). MATERIALS AND METHODS: We enroled 2500 patients with CKD stage 1-4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all-cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events. RESULTS: The MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non-DM subgroups was 1.56 (1.15-2.12) and 1.31 (1.02-1.70), respectively, while that for all-cause mortality was 1.00 (0.71-1.40) and 1.27 (0.92-1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non-DM/non-MetS group, the DM/MetS group (HR: 1.62 (1.31-2.02)) and the non-DM/MetS group (HR: 1.33 (1.05-1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all-cause mortality (HR: 1.43 (1.09-1.88)). CONCLUSIONS: MetS could predict renal outcome in patients with CKD stage 1-4 independent of DM.


Subject(s)
Diabetes Mellitus , Kidney Failure, Chronic , Metabolic Syndrome , Renal Insufficiency, Chronic , Humans , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Kidney/physiology , Diabetes Mellitus/epidemiology , Glomerular Filtration Rate , Risk Factors
15.
Acta Cardiol Sin ; 39(1): 109-115, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36685152

ABSTRACT

Background: Current guidelines recommend that all infected cardiac implantable electronic devices (CIEDs) should be removed. However, financial or anatomical concerns can lead to management of infection with simple debridement, as opposed to complete removal. In this observational study, we report the outcomes of our modified procedure for this real-world dilemma. Methods and Results: The Quarantine (RESQ) method is characterized as follows: the removal (R) of all non-essential foreign materials, including old sutures and leads; the excision (E) of all non-viable, chronically inflamed, granulation, or scar tissue; the sterilization (S) of the remaining generator; and the quarantine (Q) of a new pocket in the sub-muscular layer for reimplantation. From a review of electronic medical records, 30 patients were selected and divided into three groups according to the intervention used: RESQ (n = 9) in group A, simple debridement (n = 16) in group B, and guideline-recommended replacement (n = 5) in group C. Patient baseline characteristics were similar between the groups. After analyzing the proportion of patients that were free from infection one year following their respective interventions, we found that group A performed better than group B (100% and 31.2% infection-free, respectively, p = 0.001), and was comparable to group C (both 100% infection-free, p = not applicable). Conclusions: The RESQ method is a feasible and beneficial alternative for selected patients with CIED infections who are unable to receive a generator replacement according to the recommended guideline.

16.
Sci Adv ; 8(41): eabp8677, 2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36240267

ABSTRACT

Filopodia are actin-rich membrane protrusions essential for cell morphogenesis, motility, and cancer invasion. How cells control filopodium initiation on the plasma membrane remains elusive. We performed experiments in cellulo, in vitro, and in silico to unravel the mechanism of filopodium initiation driven by the membrane curvature sensor IRSp53 (insulin receptor substrate protein of 53 kDa). We showed that full-length IRSp53 self-assembles into clusters on membranes depending on PIP2. Using well-controlled in vitro reconstitution systems, we demonstrated that IRSp53 clusters recruit the actin polymerase VASP (vasodilator-stimulated phosphoprotein) to assemble actin filaments locally on membranes, leading to the generation of actin-filled membrane protrusions reminiscent of filopodia. By pulling membrane nanotubes from live cells, we observed that IRSp53 can only be enriched and trigger actin assembly in nanotubes at highly dynamic membrane regions. Our work supports a regulation mechanism of IRSp53 in its attributes of curvature sensation and partner recruitment to ensure a precise spatial-temporal control of filopodium initiation.

17.
Front Nutr ; 9: 982519, 2022.
Article in English | MEDLINE | ID: mdl-36185692

ABSTRACT

Patients with chronic kidney disease (CKD) demonstrate a survival benefit with a high body mass index (BMI); this is the obesity paradox. Central obesity has a higher prognostic value than BMI, even in those with normal weight. Whether total body fat percentage (TBF%) provides more information than BMI and waist circumference (WC) remains unknown. We included 3,262 Asian patients with stage 3-5 CKD and divided these patients by TBF% and waist-to-height ratio (WHtR) quartiles (Q1-Q4). TBF% was associated with BMI, WC, nutritional markers, and C-reactive protein. In all patients, BMI but not TBF% or WHtR demonstrated a survival paradox. In patients with BMI <25 kg/m2, but not in those with BMI ≥ 25 kg/m2, TBF% Q4 and WHtR Q4 were associated with all-cause mortality, with hazard ratios [HRs; 95% confidence intervals (CIs)] of 2.35 (1.31-4.22) and 1.38 (1.06-1.80), respectively. The HRs of TBF% Q4 for all-cause mortality were 2.90 (1.50-5.58) in patients with a normal WC and 3.81 (1.93-7.50) in patients with normal weight and normal WC (All P for interaction < 0.05). In conclusion, TBF% can predict all-cause mortality in patients with advanced CKD and a normal weight, normal WC, or both.

18.
J Cell Biol ; 221(11)2022 11 07.
Article in English | MEDLINE | ID: mdl-36169638

ABSTRACT

Intracellular trafficking is mediated by transport carriers that originate by membrane remodeling from donor organelles. Tubular carriers contribute to the flux of membrane lipids and proteins to acceptor organelles, but how lipids and proteins impose a tubular geometry on the carriers is incompletely understood. Using imaging approaches on cells and in vitro membrane systems, we show that phosphatidylinositol-4-phosphate (PI4P) and biogenesis of lysosome-related organelles complex 1 (BLOC-1) govern the formation, stability, and functions of recycling endosomal tubules. In vitro, BLOC-1 binds and tubulates negatively charged membranes, including those containing PI4P. In cells, endosomal PI4P production by type II PI4-kinases is needed to form and stabilize BLOC-1-dependent recycling endosomal tubules. Decreased PI4KIIs expression impairs the recycling of endosomal cargoes and the life cycles of intracellular pathogens such as Chlamydia bacteria and influenza virus that exploit the membrane dynamics of recycling endosomes. This study demonstrates how a phospholipid and a protein complex coordinate the remodeling of cellular membranes into functional tubules.


Subject(s)
Endosomes , Intracellular Membranes , Intracellular Signaling Peptides and Proteins , Phosphatidylinositol Phosphates , Cell Membrane/metabolism , Endosomes/metabolism , Intracellular Membranes/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Lysosomes/metabolism , Phosphatidylinositol Phosphates/metabolism , Protein Transport
19.
Polymers (Basel) ; 14(16)2022 Aug 10.
Article in English | MEDLINE | ID: mdl-36015508

ABSTRACT

Polymers reinforced with conducting fibers to achieve electrical conductivity have attracted remarkable attention in several engineering applications, and injection molding provides a cost-effective way for mass production. However, the electrical performance usually varies with the molding conditions. Moreover, high added content of conducting fibers usually results in molding difficulties. In this study, we propose using microcellular (MuCell) injection molding for polypropylene (PP)/carbon fiber (CF, 20, and 30 wt%) composites and hope that the MuCell injection molding process can improve both electrical and mechanical performance as compared with conventional injection molded (CIM) parts under the same CF content. Both molding techniques were also employed with and without gas counter pressure (GCP), and the overall fiber orientation, through-plane electrical conductivity (TPEC), and tensile strength (TS) of the composites were characterized. Based on the various processing technologies, the results can be described in four aspects: (1) Compared with CIM, microcellular foaming significantly influenced the fiber orientation, and the TPECs of the samples with 20 and 30 wt% CF were 18-78 and 5-8 times higher than those of the corresponding samples molded by CIM, respectively; (2) when GCP was employed in the CIM process, the TPEC of the samples with 20 and 30 wt% CF increased by 3 and 2 times, respectively. Similar results were obtained in the case of microcellular injection molding-the TPEC of the 20 and 30 wt% composites increased by 7-74 and 18-32 times, respectively; (3) although microcellular injection molding alone (i.e., without GCP) showed the greatest influence on the randomness of the fiber orientation and the TPEC, the TS of the samples was the lowest due to the uncontrollable foaming cell size and cell size uniformity; (4) in contrast, when GCP was employed in the microcellular foaming process, high TS was obtained, and the TPEC was significantly enhanced. The high foaming quality owing to the GCP implementation improved the randomness of fiber orientation, as well as the electrical and mechanical properties of the composites. Generally speaking, microcellular injection combined with gas counter pressure does provide a promising way to achieve high electrical and mechanical performance for carbon-fiber-added polypropylene composites.

20.
Nat Commun ; 13(1): 5070, 2022 08 29.
Article in English | MEDLINE | ID: mdl-36038550

ABSTRACT

Cells remodel their cytoplasm with force-generating cytoskeletal motors. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic and germ cells. These forces are transmitted inside the nucleus, yet their consequences on liquid-like biomolecular condensates residing in the nucleus remain unexplored. Here, we probe experimentally and computationally diverse nuclear condensates, that include nuclear speckles, Cajal bodies, and nucleoli, during cytoplasmic remodeling of female germ cells named oocytes. We discover that growing mammalian oocytes deploy cytoplasmic forces to timely impose multiscale reorganization of nuclear condensates for the success of meiotic divisions. These cytoplasmic forces accelerate nuclear condensate collision-coalescence and molecular kinetics within condensates. Disrupting the forces decelerates nuclear condensate reorganization on both scales, which correlates with compromised condensate-associated mRNA processing and hindered oocyte divisions that drive female fertility. We establish that cytoplasmic forces can reorganize nuclear condensates in an evolutionary conserved fashion in insects. Our work implies that cells evolved a mechanism, based on cytoplasmic force tuning, to functionally regulate a broad range of nuclear condensates across scales. This finding opens new perspectives when studying condensate-associated pathologies like cancer, neurodegeneration and viral infections.


Subject(s)
Cell Nucleolus , Cell Nucleus , Animals , Coiled Bodies , Cytoplasm , Female , Mammals , Oocytes
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