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1.
Front Endocrinol (Lausanne) ; 15: 1399517, 2024.
Article in English | MEDLINE | ID: mdl-38982990

ABSTRACT

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.


Subject(s)
Non-alcoholic Fatty Liver Disease , Thyroid Gland , Humans , Non-alcoholic Fatty Liver Disease/blood , Thyroid Function Tests , Thyroid Gland/physiopathology , Thyroid Hormones/blood , Triiodothyronine/blood
2.
Sci Adv ; 10(18): eadn0172, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38691595

ABSTRACT

Collective cell dynamics is essential for tissue morphogenesis and various biological functions. However, it remains incompletely understood how mechanical forces and chemical signaling are integrated to direct collective cell behaviors underlying tissue morphogenesis. Here, we propose a three-dimensional (3D) mechanochemical theory accounting for biochemical reaction-diffusion and cellular mechanotransduction to investigate the dynamics of multicellular lumens. We show that the interplay between biochemical signaling and mechanics can trigger either pitchfork or Hopf bifurcation to induce diverse static mechanochemical patterns or generate oscillations with multiple modes both involving marked mechanical deformations in lumens. We uncover the crucial role of mechanochemical feedback in emerging morphodynamics and identify the evolution and morphogenetic functions of hierarchical topological defects including cell-level hexatic defects and tissue-level orientational defects. Our theory captures the common mechanochemical traits of collective dynamics observed in experiments and could provide a mechanistic context for understanding morphological symmetry breaking in 3D lumen-like tissues.


Subject(s)
Mechanotransduction, Cellular , Models, Biological , Morphogenesis , Biomechanical Phenomena , Animals
3.
Nat Commun ; 15(1): 3000, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589403

ABSTRACT

Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. However, during cell expansion under mechanical stress, actomyosin networks are strengthened and polarized to relax stress. Thus, cells face a conflicting situation between the enhanced actomyosin contractile properties and the expansion behaviour of the cell or tissue. To address this paradoxical situation, we study late Drosophila oogenesis and reveal an unusual epithelial expansion wave behaviour. Mechanistically, Rac1 and Rho1 integrate basal pulsatile actomyosin networks with ruffles and focal adhesions to increase and then stabilize basal area of epithelial cells allowing their flattening and elongation. This epithelial expansion behaviour bridges cell changes to oocyte growth and extension, while oocyte growth in turn deforms the epithelium to drive cell spreading. Basal pulsatile actomyosin networks exhibit non-contractile mechanics, non-linear structures and F-actin/Myosin-II spatiotemporal signal separation, implicating unreported expanding properties. Biophysical modelling incorporating these expanding properties well simulates epithelial cell expansion waves. Our work thus highlights actomyosin expanding properties as a key mechanism driving tissue morphogenesis.


Subject(s)
Actomyosin , Drosophila Proteins , Animals , Actomyosin/metabolism , Drosophila Proteins/metabolism , Epithelial Cells/metabolism , Actin Cytoskeleton/metabolism , Drosophila/metabolism , Epithelium/metabolism , Morphogenesis
4.
Clin Breast Cancer ; 24(5): e417-e427, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38555225

ABSTRACT

BACKGROUND: To explore whether the combination of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and nonmono-exponential (NME) model-based diffusion-weighted imaging (DWI) via deep neural network (DNN) can improve the prediction of breast cancer molecular subtypes compared to either imaging technique used alone. PATIENTS AND METHODS: This prospective study examined 480 breast cancers in 475 patients undergoing DCE-MRI and NME-DWI at 3.0 T. Breast cancers were classified as follows: human epidermal growth factor receptor 2 enriched (HER2-enriched), luminal A, luminal B (HER2-), luminal B (HER2+), and triple-negative subtypes. A total of 20% cases were withheld as an independent test dataset, and the remaining cases were used to train DNN with an 80% to 20% training-validation split and 5-fold cross-validation. The diagnostic accuracies of DNN in 5-way subtype classification between the DCE-MRI, NME-DWI, and their combined multiparametric-MRI datasets were compared using analysis of variance with least significant difference posthoc test. Areas under the receiver-operating characteristic curves were calculated to assess the performances of DNN in binary subtype classification between the 3 datasets. RESULTS: The 5-way classification accuracies of DNN on both DCE-MRI (0.71) and NME-DWI (0.64) were significantly lower (P < .05) than on multiparametric-MRI (0.76), while on DCE-MRI was significantly higher (P < .05) than on NME-DWI. The comparative results of binary classification between the 3 datasets were consistent with the 5-way classification. CONCLUSION: The combination of DCE-MRI and NME-DWI via DNN achieved a significant improvement in breast cancer molecular subtype prediction compared to either imaging technique used alone. Additionally, DCE-MRI outperformed NME-DWI in differentiating subtypes.


Subject(s)
Breast Neoplasms , Contrast Media , Diffusion Magnetic Resonance Imaging , Neural Networks, Computer , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Breast Neoplasms/classification , Middle Aged , Prospective Studies , Adult , Diffusion Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/methods , Aged , Receptor, ErbB-2/metabolism
5.
Nanomicro Lett ; 16(1): 112, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38334816

ABSTRACT

The undesirable dendrite growth induced by non-planar zinc (Zn) deposition and low Coulombic efficiency resulting from severe side reactions have been long-standing challenges for metallic Zn anodes and substantially impede the practical application of rechargeable aqueous Zn metal batteries (ZMBs). Herein, we present a strategy for achieving a high-rate and long-cycle-life Zn metal anode by patterning Zn foil surfaces and endowing a Zn-Indium (Zn-In) interface in the microchannels. The accumulation of electrons in the microchannel and the zincophilicity of the Zn-In interface promote preferential heteroepitaxial Zn deposition in the microchannel region and enhance the tolerance of the electrode at high current densities. Meanwhile, electron aggregation accelerates the dissolution of non-(002) plane Zn atoms on the array surface, thereby directing the subsequent homoepitaxial Zn deposition on the array surface. Consequently, the planar dendrite-free Zn deposition and long-term cycling stability are achieved (5,050 h at 10.0 mA cm-2 and 27,000 cycles at 20.0 mA cm-2). Furthermore, a Zn/I2 full cell assembled by pairing with such an anode can maintain good stability for 3,500 cycles at 5.0 C, demonstrating the application potential of the as-prepared ZnIn anode for high-performance aqueous ZMBs.

7.
Cell Biosci ; 14(1): 14, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38273376

ABSTRACT

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2-/- mice) and elucidate the underlying mechanisms. METHODS: Mdr2-/-mice (12-14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical analyses were used to assess fibrotic liver injury severity. Total RNAseq and pathway analyses were used to identify the potential signaling pathways modulated by BBR in the liver. The expression levels of key genes involved in regulating hepatic fibrosis, bile duct proliferation, inflammation, and bile acid metabolism were validated by qRT-PCR or Western blot analysis. The bile acid composition and levels in the serum, liver, small intestine, and feces and tissue distribution of BBR were measured by LC-MS/MS. Intestinal inflammation and injury were assessed by gene expression profiling and histological analysis. The impact on the gut microbiome was assessed using 16S rRNA gene sequencing. RESULTS: BBR treatment significantly ameliorated cholestatic liver injury, evidenced by decreased serum levels of AST, ALT, and ALP, and reduced bile duct proliferation and hepatic fibrosis, as shown by H&E, Picro-Sirius Red, and CK19 IHC staining. RNAseq and qRT-PCR analyses indicated a substantial inhibition of fibrotic and inflammatory gene expression. BBR also mitigated ER stress by downregulating Chop, Atf4 and Xbp-1 expression. In addition, BBR modulated bile acid metabolism by altering key gene expressions in the liver and small intestine, resulting in restored bile acid homeostasis characterized by reduced total bile acids in serum, liver, and small intestine and increased fecal excretion. Furthermore, BBR significantly improved intestinal barrier function and reduced bacterial translocation by modulating the gut microbiota. CONCLUSION: BBR effectively attenuates cholestatic liver injury, suggesting its potential as a therapeutic agent for PSC and other cholestatic liver diseases.

8.
Article in English | MEDLINE | ID: mdl-38197032

ABSTRACT

Purpose: The typical characteristic of COPD is airway remodeling, affected by environmental and genetic factors. However, genetic studies on COPD have been limited. Currently, the Abhd2 gene is found to play a critical role in maintaining alveolar architecture and stability. The research aims to investigate the predictive value of Abhd2 for airway remodeling in COPD and its effect on TGF-ß regulation. Methods: In humans, Abhd2 protein was obtained from peripheral blood monocytes. Peripheral blood TGF-ß, pulmonary surfactant proteins (SPs), metalloproteinases, inflammatory indicators (WBC, NEU, NLR, EOS, CRP, PCT, D-Dimer), chest CT (airway diameter and airway wall thickness), pulmonary function, and blood gas analysis were used to assess airway remodeling. In animals, Abhd2 deficient mice (Abhd2Gt/Gt) using gene trapping and C57BL6 mice were injected intraperitoneally with CSE to construct COPD models. HE staining, Masson staining and immunohistochemistry were used to observe the pathological changes of airway in mice, and RT-PCR, WB, ELISA and immunofluorescence were used to detect the expression of secreted proteins and EMT markers. Results: COPD patients with worse pulmonary function and higher airway remodeling-related inflammatory factors had lower Abhd2 protein expression. Moreover, indicators followed the same trend for COPD patients grouped by prognosis (Group A vs Group B). Serum TGF-ß was negatively correlated with Abhd2 protein expression, FEV1/FVC, FEV1, and FEV1% PRED. In mice, Abhd2 depletion promoted deposition of TGF-ß, leading to more pronounced emphysema, airway thickening, increased alveolar macrophage infiltration, decreased AECII number and SPs, and EMT phenomenon. Conclusion: Downregulation of Abhd2 can promote airway remodeling in COPD by modulating repair after injury and EMT via TGF-ß. This study suggests that Abhd2 may serve as a biomarker for assessing airway remodeling and guiding prognosis in COPD.


Subject(s)
Airway Remodeling , Hydrolases , Pulmonary Disease, Chronic Obstructive , Animals , Humans , Mice , Blood Gas Analysis , Down-Regulation , Mice, Inbred C57BL , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/genetics , Hydrolases/genetics
9.
J Magn Reson Imaging ; 59(4): 1425-1435, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37403945

ABSTRACT

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI commonly outperforms diffusion-weighted (DW) MRI in breast cancer discrimination. However, the side effects of contrast agents limit the use of DCE-MRI, particularly in patients with chronic kidney disease. PURPOSE: To develop a novel deep learning model to fully exploit the potential of overall b-value DW-MRI without the need for a contrast agent in predicting breast cancer molecular subtypes and to evaluate its performance in comparison with DCE-MRI. STUDY TYPE: Prospective. SUBJECTS: 486 female breast cancer patients (training/validation/test: 64%/16%/20%). FIELD STRENGTH/SEQUENCE: 3.0 T/DW-MRI (13 b-values) and DCE-MRI (one precontrast and five postcontrast phases). ASSESSMENT: The breast cancers were divided into four subtypes: luminal A, luminal B, HER2+, and triple negative. A channel-dimensional feature-reconstructed (CDFR) deep neural network (DNN) was proposed to predict these subtypes using pathological diagnosis as the reference standard. Additionally, a non-CDFR DNN (NCDFR-DNN) was built for comparative purposes. A mixture ensemble DNN (ME-DNN) integrating two CDFR-DNNs was constructed to identify subtypes on multiparametric MRI (MP-MRI) combing DW-MRI and DCE-MRI. STATISTICAL TESTS: Model performance was evaluated using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Model comparisons were performed using the one-way analysis of variance with least significant difference post hoc test and the DeLong test. P < 0.05 was considered significant. RESULTS: The CDFR-DNN (accuracies, 0.79 ~ 0.80; AUCs, 0.93 ~ 0.94) demonstrated significantly improved predictive performance than the NCDFR-DNN (accuracies, 0.76 ~ 0.78; AUCs, 0.92 ~ 0.93) on DW-MRI. Utilizing the CDFR-DNN, DW-MRI attained the predictive performance equal (P = 0.065 ~ 1.000) to DCE-MRI (accuracies, 0.79 ~ 0.80; AUCs, 0.93 ~ 0.95). The predictive performance of the ME-DNN on MP-MRI (accuracies, 0.85 ~ 0.87; AUCs, 0.96 ~ 0.97) was superior to those of both the CDFR-DNN and NCDFR-DNN on either DW-MRI or DCE-MRI. DATA CONCLUSION: The CDFR-DNN enabled overall b-value DW-MRI to achieve the predictive performance comparable to DCE-MRI. MP-MRI outperformed DW-MRI and DCE-MRI in subtype prediction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.


Subject(s)
Breast Neoplasms , Deep Learning , Humans , Female , Diffusion Magnetic Resonance Imaging/methods , Breast Neoplasms/pathology , Prospective Studies , Magnetic Resonance Imaging/methods , Contrast Media , Retrospective Studies
10.
ACS Nano ; 17(24): 24668-24684, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38091551

ABSTRACT

The interfacial interactions between epithelia and cancer cells have profound relevance for tumor development and metastasis. Through monolayer confrontation of MCF10A (nontumorigenic human breast epithelial cells) and MDA-MB-231 (human epithelial breast cancer cells) cells, we investigate the epithelial-cancerous interfacial interactions at the tissue level. We show that the monolayer interaction leads to competitive interfacial morphodynamics and drives an intricate spatial organization of MCF10A cells into multicellular finger-like structures, which further branch into multiple subfinger-like structures. These hierarchical interfacial structures penetrate the cancer monolayer and can spontaneously segregate or even envelop cancer cell clusters, consistent with our theoretical prediction. By tracking the substrate displacements via embedded fluorescent nanobeads and implementing nanomechanical modeling that combines atomic force microscopy and finite element simulations, we computed mechanical force patterns, including traction forces and monolayer stresses, caused by the monolayer interaction. It is found that the heterogeneous mechanical forces accumulated in the monolayers are able to squeeze cancer cells, leading to three-dimensional interfacial bulges or cell extrusion, initiating the p53 apoptosis signaling pathways of cancer cells. We reveal that intercellular E-cadherin and P-cadherin of epithelial cells differentially regulate the interfacial organization including migration speed, directionality, spatial correlation, F-actin alignment, and subcellular protrusions of MCF10A cells; whereas E-cadherin governs interfacial geometry that is relevant to force localization and cancer cell extrusion, P-cadherin maintains interfacial integrity that enables long-range force transmission. Our findings suggest that the collaborative molecular and mechanical behaviors are crucial for preventing epithelial tissues from undergoing tumor invasion.


Subject(s)
Cadherins , Neoplasms , Humans , Cadherins/metabolism , Actins/metabolism , Epithelial Cells/metabolism , Cell Adhesion
11.
BMC Gastroenterol ; 23(1): 364, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37875811

ABSTRACT

BACKGROUND: Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations. METHODS: This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations. RESULTS: Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p < 0.001). Besides, men had greater CAP and LSM values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02-1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31-0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09-15.90; P = 0.037) in post-menopausal women were independently associated with liver steatosis grade. WC and visceral obesity were independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01-1.09, P = 0.013; OR, 3.92; 95% CI, 1.97-7.81; P < 0.001, respectively). CONCLUSIONS: Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women were independent correlates of more severe liver steatosis. In addition, increased WC and visceral obesity were independent correlates of worse liver fibrosis in men. These data support the sex- and reproductive status-specific management of NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Female , Humans , Male , Body Composition/physiology , Body Mass Index , Cross-Sectional Studies , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Obesity, Abdominal , Menopause , Sex Factors
12.
Acta Biomater ; 170: 519-531, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37659729

ABSTRACT

Understanding the principles underlying the self-organization of stem cells into tissues is fundamental for deciphering human embryo development. Here, we report that, without three-dimensional (3D) extracellular matrix (ECM) overlay, human pluripotent stem cells (hPSCs) cultured on two-dimensional soft elastic substrates can self-organize into 3D cysts resembling the human epiblast sac in a stiffness-dependent manner. Our theoretical modeling predicts that this cyst organization is facilitated and guided by the spontaneous nesting of the soft substrate, which results from the adhesion-dependent mechanical interaction between cells and substrate. Such substrate nesting is sufficient for the 3D assembly and polarization of hPSCs required for cyst organization, even without 3D ECM overlay. Furthermore, we identify that the reversible substrate nesting and cyst morphogenesis also require appropriate activation of ROCK-Myosin II pathway. This indicates a unique set of tissue morphomechanical signaling mechanisms that clearly differ from the canonical cystogenic mechanism previously reported in 3D ECM. Our findings highlight an unanticipated synergy between mechanical microenvironment and mechanotransduction in controlling tissue morphogenesis and suggest a mechanics-based strategy for generation of hPSCs-derived models for early human embryogenesis. STATEMENT OF SIGNIFICANCE: Soft substrates can induce the self-organization of human pluripotent stem cells (hPSCs) into cysts without three-dimensional (3D) extracellular matrix (ECM) overlay. However, the underlying mechanisms by which soft substrate guides cystogenesis are largely unknown. This study shows that substrate nesting, resulting from cell-substrate interaction, plays an important role in cyst organization, including 3D assembly and apical-basal polarization. Additionally, actomyosin contractility mediated by the ROCK-Myosin II pathway also contributes to the substrate deformation and cyst morphology. These findings demonstrate the interplay between the mechanical microenvironment and cells in tissue morphogenesis, suggesting a mechanics-based strategy in building hPSC-derived models for early human embryo development.

13.
Medicine (Baltimore) ; 102(36): e35158, 2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37682149

ABSTRACT

To evaluate the clinical outcomes of the modified lateral approach combined with the medial percutaneous approach (MLACMPA) versus the triceps tongue-shaped flap approach (TTSFA) and the bilateral triceps brachii approach (BTBA) in the treatment of irreducible displaced supracondylar humeral fractures (SHFs) in children. Between March 2000 and July 2022, a total of 135 children who underwent open reduction and Kirschner wire cross internal fixation for irreducible displaced SHFs caused by trauma were retrospectively analyzed. According to the surgical approach, the patients were assigned to the TTSFA group (n = 36), the BTBA group (n = 40) and the MLACMPA group (n = 59). The duration of surgery, intraoperative blood loss, incision length, and elbow range of motion were compared. The 3 groups were similar in terms of mean age, sex distribution, and time from injury to operation. The duration of surgery, intraoperative blood loss, incision length and postoperative elbow range of motion in the MLACMPA group were significantly superior to those in the TTSFA group and BTBA group (P < .05). Compared the use of the TTSFA or the BTBA, using the MLACMPA for pin fixation in the treatment of irreducible displaced pediatric SHFs could significantly shorten the duration of surgery, reduce the operation trauma, facilitate earlier functional exercise of joints after operation and yield better elbow function.


Subject(s)
Elbow Joint , Humeral Fractures , Surgical Wound , Humans , Child , Blood Loss, Surgical , Retrospective Studies , Elbow Joint/surgery , Humeral Fractures/surgery
14.
iScience ; 26(10): 107864, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37766982

ABSTRACT

The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.

15.
Proc Natl Acad Sci U S A ; 120(36): e2306512120, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37639611

ABSTRACT

Cells migrate by adapting their leading-edge behaviors to heterogeneous extracellular microenvironments (ECMs) during cancer invasions and immune responses. Yet it remains poorly understood how such complicated dynamic behaviors emerge from millisecond-scale assembling activities of protein molecules, which are hard to probe experimentally. To address this gap, we establish a spatiotemporal "resistance-adaptive propulsion" theory based on the interactions between Arp2/3 complexes and polymerizing actin filaments and a multiscale dynamic modeling system spanning from molecular proteins to the cell. We quantitatively find that cells can accurately self-adapt propulsive forces to overcome heterogeneous ECMs via a resistance-triggered positive feedback mechanism, dominated by polymerization-induced actin filament bending and the bending-regulated actin-Arp2/3 binding. However, for high resistance regions, resistance triggers a negative feedback, hindering branched filament assembly, which adapts cellular morphologies to circumnavigate the obstacles. Strikingly, the synergy of the two opposite feedbacks not only empowers the cell with both powerful and flexible migratory capabilities to deal with complex ECMs but also enables efficient utilization of intracellular proteins by the cell. In addition, we identify that the nature of cell migration velocity depending on ECM history stems from the inherent temporal hysteresis of cytoskeleton remodeling. We also show that directional cell migration is dictated by the competition between the local stiffness of ECMs and the local polymerizing rate of actin network caused by chemotactic cues. Our results reveal that it is the polymerization force-regulated actin filament-Arp2/3 complex binding interaction that dominates self-adaptive cell migrations in complex ECMs, and we provide a predictive theory and a spatiotemporal multiscale modeling system at the protein level.


Subject(s)
Actin Cytoskeleton , Actins , Polymerization , Cell Movement , Cytoskeleton , Actin-Related Protein 2-3 Complex
16.
J Colloid Interface Sci ; 640: 510-520, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-36878069

ABSTRACT

Bacteria adapt the mechanical properties of their cell envelope, including cell wall stiffness, turgor, and cell wall tension and deformation, to grow and survive in harsh environments. However, it remains a technical challenge to simultaneously determine these mechanical properties at a single cell level. Here we combined theoretical modelling with an experimental approach to quantify the mechanical properties and turgor of Staphylococcus epidermidis. It was found that high osmolarity leads to a decrease in both cell wall stiffness and turgor. We also demonstrated that the turgor change is associated with a change in the viscosity of the bacterial cell. We predicted that the cell wall tension is much higher in deionized (DI) water and it decreases with an increase in osmolality. We also found that an external force increases the cell wall deformation to reinforce its adherence to a surface and this effect can be more significant in lower osmolarity. Overall, our work highlights how bacterial mechanics supports survival in harsh environments and uncovers the adaption of bacterial cell wall mechanical integrity and turgor to osmotic and mechanical challenges.


Subject(s)
Bacteria , Cell Wall , Microscopy, Atomic Force , Cell Wall/metabolism , Cell Membrane , Osmotic Pressure
17.
Phys Rev E ; 107(2-1): 024405, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36932565

ABSTRACT

The morphology and motion behavior of a cell are highly influenced by its external biological, chemical, and physical stimuli, and geometric confinement. In this paper, it is revealed that the mean curvature of the substrate significantly influences the adhesion of vesicles. By employing the variational method and investigating the Helfrich free energy, the configuration of axisymmetric vesicles adhered to curved spherical substrates is obtained theoretically. Moreover, numerical simulations based on the finite element method are also carried out to investigate the adhesion of vesicles on curved substrates with complex shapes. It is found that for a fixed area of a vesicle, its total free energy depends mainly on the mean curvature of the adhesion region but is insensitive to the specific shape of the substrate, and the total free energy monotonically decreases with the increase in the mean curvature. In addition, possible biological significances of the curvature-dependent adhesion, such as the shape of the cell and antibiofouling, are discussed. This study may deepen our understanding of the underlying mechanisms of adhesion in cellular activities.

18.
Front Immunol ; 14: 1166711, 2023.
Article in English | MEDLINE | ID: mdl-36895561

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2022.1089469.].

19.
Neuroimage ; 269: 119934, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36754123

ABSTRACT

Human brain experiences vibration of certain magnitude and frequency during various physical activities such as vehicle transportation and machine operation, which may cause traumatic brain injury or other brain diseases. However, the mechanisms of brain pathogenesis due to vibration are not fully elucidated due to the lack of techniques to study brain functions while applying vibration to the brain at a specific magnitude and frequency. Here, this study reported a custom-built head-worn electromagnetic actuator that applied vibration to the brain in vivo at an accurate frequency inside a magnetic resonance imaging scanner while cerebral blood flow (CBF) was acquired. Using this technique, CBF values from 45 healthy volunteers were quantitatively measured immediately following vibration at 20, 30, 40 Hz, respectively. Results showed increasingly reduced CBF with increasing frequency at multiple regions of the brain, while the size of the regions expanded. Importantly, the vibration-induced CBF reduction regions largely fell inside the brain's default mode network (DMN), with about 58 or 46% overlap at 30 or 40 Hz, respectively. These findings demonstrate that vibration as a mechanical stimulus can change strain conditions, which may induce CBF reduction in the brain with regional differences in a frequency-dependent manner. Furthermore, the overlap between vibration-induced CBF reduction regions and DMN suggested a potential relationship between external mechanical stimuli and cognitive functions.


Subject(s)
Brain , Vibration , Humans , Magnetic Resonance Imaging , Cognition , Cerebrovascular Circulation/physiology
20.
Soft Matter ; 19(4): 708-722, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36602136

ABSTRACT

The growth of biological tissues, which is regulated by a variety of factors, can induce stresses that may, in turn, destabilize the tissues into diverse patterns. In most previous studies, however, tissue growth was usually assumed as a prescribed parameter independent of stresses, limiting our understanding of the mechanobiological morphogenesis of real tissues. In this paper, we propose a theoretical model to investigate the mechanobiological response of soft tissues undergoing stress-modulated growth. Linear stability analysis is first performed to elucidate the surface instability mechanism induced by stress-modulated volumetric growth. We further conduct finite element simulations to validate the theoretical prediction and, particularly, to capture the post-buckling pattern evolution. Our results show that the non-uniform stresses, which evolve with the tissue growth and morphogenesis, exert mechanical feedback on the growth itself, producing up-down asymmetric surface morphologies as observed in, for example, the gyrification of human brains and brain organoids. It is also revealed that large residual stresses are unnecessary to cause mechanobiological instability and subsequent asymmetric patterning, which has long been believed to be driven by sufficiently high stresses. The present work could help us to understand the morphological changes of biological tissues under physiological and pathological conditions.


Subject(s)
Models, Biological , Models, Theoretical , Humans , Morphogenesis , Stress, Mechanical , Finite Element Analysis
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