Long-range mechanical force enables self-assembly of epithelial tubular patterns

Enabling long-range transport of molecules, tubules are critical for human body homeostasis. One fundamental question in tubule formation is how individual cells coordinate their positioning over long spatial scales, which can be as long as the sizes of tubular organs. Recent studies indicate that type I collagen (COL) is important in the development of epithelial tubules. Nevertheless, how cell–COL interactions contribute to the initiation or the maintenance of long-scale tubular patterns is unclear. Using a two-step process to quantitatively control cell–COL interaction, we show that epithelial cells developed various patterns in response to fine-tuned percentages of COL in ECM. In contrast with conventional thoughts, these patterns were initiated and maintained by traction forces created by cells but not diffusive factors secreted by cells. In particular, COL-dependent transmission of force in the ECM led to long-scale (up to 600 μm) interactions between cells. A mechanical feedback effect was encountered when cells used forces to modify cell positioning and COL distribution and orientations. Such feedback led to a bistability in the formation of linear, tubule-like patterns. Using micro-patterning technique, we further show that the stability of tubule-like patterns depended on the lengths of tubules. Our results suggest a mechanical mechanism that cells can use to initiate and maintain long-scale tubular patterns

Chiral topological metals with multiple types of quasiparticle fermions and large spin Hall effect in the SrGePt family materials

We present a prediction of chiral topological metals with several classes of unconventional quasiparticle fermions in a family of SrGePt-type materials in terms of first-principles calculations. In these materials, fourfold spin-3/2 Rarita-Schwinger-Weyl (RSW) fermion, sixfold excitation, and Weyl fermions coexist around the Fermi level as spin-orbit coupling is considered, and the Chern number for the first two kinds of fermions is the maximal value four. We found that large Fermi arcs from spin-3/2 RSW fermion emerge on the (010)-surface, spanning the whole surface Brillouin zone. Moreover, there exist Fermi arcs originating from Weyl points, which further overlap with trivial bulk bands. In addition, we revealed that the large spin Hall conductivity can be obtained, which attributed to the remarkable spin Berry curvature around the degenerate nodes and band-splitting induced by spin-orbit coupling. Our findings indicate that the SrGePt family of compounds provide an excellent platform for studying on topological electronic states and the intrinsic spin Hall effect.Comment: 10 pages and 7 figures in the main tex

Sex-specific prevalence and risk factors of metabolic-associated fatty liver disease among 75,570 individuals in eastern China

BackgroundMetabolic-associated fatty liver disease (MAFLD) is a newly proposed definition and there is limited data on MAFLD prevalence. We aimed to investigate the prevalence of MAFLD in an eastern Chinese population.MethodsThis cross-sectional study included participants from an eastern Chinese population who underwent regular health checkups. Based on current diagnostic criteria, MAFLD was diagnosed in individuals with both hepatic steatosis and metabolic disorders. The overall and stratified prevalence derived based on sex, age, body mass index (BMI), and various metabolic disorders were estimated. Multivariate logistic regression analysis was used to determine the risk factors for MAFLD.ResultsAmong the 75,570 participants, the overall prevalence of MAFLD was 37.32%, with higher rates in men (45.66%) than in women (23.91%). MAFLD prevalence was highest in men aged 40–49 years (52.21%) and women aged 70–79 years (44.77%). In all the BMI subgroups, the prevalence was higher in men than in women. In both sexes, the prevalence of MAFLD increased as BMI levels increased. Furthermore, MAFLD was associated with metabolic disorders, especially in the female participants with severe obesity (odds ratio 58.318; 95% confidence interval: 46.978–72.397).ConclusionMAFLD is prevalent in the general adult population in eastern China. Sex-specific differences in MAFLD prevalence were identified based on age, BMI, and metabolic disorders. MAFLD is associated with metabolic disorders, particularly obesity

Using Ipomoea aquatic as an environmental-friendly alternative to Elodea nuttallii for the aquaculture of Chinese mitten crab

Elodea nuttallii is widely used in Chinese mitten crab (CMC) rearing practice, but it is not a native aquatic plant and cannot endure high temperature. Thus, large E. nuttallii mortality and water deterioration events could occur during high-temperature seasons. The aim of this study was to identify the use of local macrophytes in CMC rearing practice, including Ipomoea aquatic and Oryza sativa. A completely randomized field experiment was conducted to investigate the crab yield, water quality, bacterioplankton community and functions in the three different systems (E. nuttallii, I. aquatic, and O. sativa). Average crab yields in the different macrophyte systems did not differ significantly. The I. aquatic and O. sativa systems significantly decreased the total nitrogen and nitrate-N quantities in the outflow waters during the rearing period compared to the E. nuttallii system, and the I. aquatic and O. sativa plants assimilated more nitrogen than the E. nuttallii plant. Moreover, the significant changes of bacterioplankton abundances and biodiversity in the three systems implied that cleanliness of rearing waters was concomitantly attributed to the differential microbial community and functions. In addition, principle component analysis successfully differentiated the bacterioplankton communities of the three macrophytes systems. Environmental factor fitting and the co-occurrence network analyses indicated that pH was the driver of bacterioplankton community structure. Functional predictions using PICRUSt (v.1.1.3) software based on evolutionary modeling indicated a higher potential for microbial denitrification in the I. aquatic and O. sativa systems. Notably, the O. sativa plants stopped growing in the middle of the rearing period. Thus, the I. aquatic system rather than the O. sativa system could be a feasible and environmental-friendly alternative to the E. nuttallii system in CMC rearing practice

targets and mechanisms of sulforaphane derivatives obtained from cruciferous plants with special focus on breast cancer contradictory effects and future perspectives

Abstract Breast cancer is the most common type of cancer among women. Therefore, discovery of new and effective drugs with fewer side effects is necessary to treat it. Sulforaphane (SFN) is an organosulfur compound obtained from cruciferous plants, such as broccoli and mustard, and it has the potential to treat breast cancer. Hence, it is vital to find out how SFN targets certain genes and cellular pathways in treating breast cancer. In this review, molecular targets and cellular pathways of SFN are described. Studies have shown SFN inhibits cell proliferation, causes apoptosis, stops cell cycle and has anti-oxidant activities. Increasing reactive oxygen species (ROS) produces oxidative stress, activates inflammatory transcription factors, and these result in inflammation leading to cancer. Increasing anti-oxidant potential of cells and discovering new targets to reduce ROS creation reduces oxidative stress and it eventually reduces cancer risks. In short, SFN effectively affects histone deacetylases involved in chromatin remodeling, gene expression, and Nrf2 anti-oxidant signaling. This review points to the potential of SFN to treat breast cancer as well as the importance of other new cruciferous compounds, derived from and isolated from mustard, to target Keap1 and Akt, two key regulators of cellular homeostasis

Identification of Genetic Mutations in Cancer: Challenge and Opportunity in the New Era of Targeted Therapy

The introduction of targeted therapy is the biggest success in the treatment of cancer in the past few decades. However, heterogeneous cancer is characterized by diverse molecular alterations as well as multiple clinical profiles. Specific genetic mutations in cancer therapy targets may increase drug sensitivity, or more frequently result in therapeutic resistance. In the past 3 years, several novel targeted therapies have been approved for cancer treatment, including drugs with new targets (i.e., anti-PD1/PDL1 therapies and CDK4/6 inhibitors), mutation targeting drugs (i.e., the EGFR T790M targeting osimertinib), drugs with multiple targets (i.e., the EGFR/HER2 dual inhibitor neratinib) and drug combinations (i.e., encorafenib/binimetinib and dabrafenib/trametinib). In this perspective, we focus on the most up-to-date knowledge of targeted therapy and describe how genetic mutations influence the sensitivity of targeted therapy, highlighting the challenges faced within this era of precision medicine. Moreover, the strategies that deal with mutation-driven resistance are further discussed. Advances in these areas would allow for more targeted and effective therapeutic options for cancer patients

Integrative analysis of the role of BOLA2B in human pan-cancer

Objective:BOLA2B is a recently discovered protein-coding gene. Here, pan-cancer analysis was conducted to determine the expression patterns of BOLA2B and its impact on immune response, gene mutation, and possible molecular biological mechanisms in different tumors, together with investigating its potential usefulness for cancer prognosis.Methods: Data on BOLA2B expression and mutations were downloaded from TCGA and GTEx databases. Clinical survival data from TCGA were used to analyze the prognostic value of BOLA2B. TIMER and ESTIMATE algorithms were used to assess correlations between BOLA2B and tumor-infiltrating immune cells, immune cytokines, and immune scores.Results: BOLA2B was found to be highly expressed at both mRNA and protein levels in multiple tumors, where it was associated with worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in all cancers apart from ovarian cancer. BOLA2B was also found to be positively correlated with copy number variation (CNV), and mutations in TP53, TTN, and MUC16 were found to influence BOLA2B expression. Post-transcriptional modifications, including m5C, m1A, and m6A, were observed to regulate BOLA2B expression in all cancers. Functional analysis showed that BOLA2B was enriched in pathways associated with iron–sulfur cluster formation, mTOR-mediated autophagy, and cell cycle inhibition. Decreased BOLA2B expression induced the proliferation of breast cancer cells and G2/M cell cycle arrest.Conclusion:BOLA2B was found to be highly expressed in malignant tumors and could be used as a biomarker of poor prognosis in multiple cancers. Further investigation into BOLA2B’s role and molecular functions in cancer would provide new insights for cancer diagnosis and treatment

Comparison of the therapeutic effects of mesenchymal stem cells derived from human dental pulp (DP), adipose tissue (AD), placental amniotic membrane (PM), and umbilical cord (UC) on postmenopausal osteoporosis

Background: Osteoporosis is a systemic bone disease characterized by bone loss and microstructural degeneration. Recent preclinical and clinical trials have further demonstrated that the transplantation of mesenchymal stem cells (MSCs) derived from human adipose tissue (AD), dental pulp (DP), placental amniotic membrane (AM), and umbilical cord (UC) tissues can serve as an effective form of cell therapy for osteoporosis. However, MSC-mediated osteoimmunology and the ability of these cells to regulate osteoclast-osteoblast differentiation varies markedly among different types of MSCs.Methods: In this study, we investigated whether transplanted allogeneic MSCs derived from AD, DP, AM, and UC tissues were able to prevent osteoporosis in an ovariectomy (OVX)-induced mouse model of osteoporosis. The homing and immunomodulatory ability of these cells as well as their effects on osteoblastogenesis and the maintenance of bone formation were compared for four types of MSCs to determine the ideal source of MSCs for the cell therapy-based treatment of OVX-induced osteoporosis. The bone formation and bone resorption ability of these four types of MSCs were analyzed using micro-computed tomography analyses and histological staining. In addition, cytokine array-based analyses of serological markers and bioluminescence imaging assays were employed to evaluate cell survival and homing efficiency. Immune regulation was determined by flow cytometer assay to reflect the mechanisms of osteoporosis treatment.Conclusion: These analyses demonstrated that MSCs isolated from different tissues have the capacity to treat osteoporosis when transplanted in vivo. Importantly, DP-MSCs infusion was able to maintain trabecular bone mass more efficiently with corresponding improvements in trabecular bone volume, mineral density, number, and separation. Among the tested MSC types, DP-MSCs were also found to exhibit greater immunoregulatory capabilities, regulating the Th17/Treg and M1/M2 ratios. These data thus suggest that DP-MSCs may represent an effective tool for the treatment of osteoporosis