In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem cells (BMSCs) for compensation of bone resorption by ...osteoclasts is a major reason for osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cell (ST)-derived exosomes (STExos) are found to remarkably enhance osteoblastic differentiation of BMSCs in vitro. However, intravenous injection of STExos is inefficient in ameliorating osteoporotic phenotypes in an ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which may be because STExos are predominantly accumulated in the liver and lungs, but not in bone. Hereby, the STExo surface is conjugated with a BMSC-specific aptamer, which delivers STExos into BMSCs within bone marrow. Intravenous injection of the STExo-Aptamer complex enhances bone mass in OVX mice and accelerates bone healing in a femur fracture mouse model. These results demonstrate the efficiency of BMSC-specific aptamer-functionalized STExos in targeting bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture.
Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short‐chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies ...mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs‐mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.
Short‐chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch that escape absorption in the small intestine, and serve as a major source of energy for colonocytes. SCFAs are microbial‐derived metabolites, which are readily absorbed and used as an energy source by colonocytes. Several mechanisms have been proposed to underlie the anticancerous mechanisms of SCFAs. SCFAs reduce epithelial inflammation and trigger cancer cell apoptosis via p21 activity, providing an important defensive capacity against colorectal carcinogenesis.
Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular ...calcification often occurs with osteoporosis, a contradictory association called "calcification paradox". Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.
Developing low‐cost and high‐activity pH‐universal hydrogen evolution reaction (HER) catalysts is very crucial to the industrialization of water electrolysis. However, the high price, low yield, and ...poor stability of current HER catalysts make them difficult to meet practical requirements. Herein, a plasma spraying technique is employed to prepare self‐supported Cu catalysts with tensile strain for the first time. The tensile strain upshifts the d‐band of Cu, improves the water dissociation and H* adsorption, eventually improves the intrinsic HER catalytic activity. As such, Cu electrode achieves overpotentials of 182 mV in 0.5 m H2SO4, 261 mV in 1 M PBS, and 121 mV in 1 M KOH at 10 mA cm–2. In addition, Cu electrode also performs well at high current densities, the overpotentials at 1 A cm–2 are much lower than those of Pt foil in acid, neutral, and alkaline solutions.
The Cu electrode prepared by plasma spraying exhibits an excellent pH‐universal HER catalytic activity, superb long‐term stability, and marvelous corrosion resistance. The superb HER activity is attributed to self‐supported porous structure, abundant active sites, tensile strain enhanced intrinsic catalytic activity, and small charge transfer resistance.
Premature ovarian failure (POF) is one of the common disorders found in women leading to 1% female infertility. Clinical features of POF are hypoestrogenism or estrogen deficiency, increased ...gonadotropin level, and, most importantly, amenorrhea. With the development of regenerative medicine, human mesenchymal stem cell (hMSC) therapy brings new prospects for POF. This study aimed to describe the types of MSCs currently available for POF therapy, their biological characteristics, and their mechanism of action. It reviewed the latest findings on POF to provide the theoretical basis for further investigation and clinical therapy.
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► Mainland China and adjacent areas harbor the world’s most diverse temperate flora. ► We review the phylogeographic literature on this flora for the first time. ► Studies generally ...reveal strong genetic imprints of Quaternary climate and environmental change. ► This challenges the oft-stated view of East Asia as a glacial sanctuary for temperate plants.
The Sino-Japanese Floristic Region (SJFR) of East Asia harbors the most diverse of the world’s temperate flora, and was the most important glacial refuge for its Tertiary representatives (‘relics’) throughout Quaternary ice-age cycles. A steadily increasing number of phylogeographic studies in the SJFR of mainland China and adjacent areas, including the Qinghai–Tibetan-Plateau (QTP) and Sino-Himalayan region, have documented the population histories of temperate plant species in these regions. Here we review this current literature that challenges the oft-stated view of the SJFR as a glacial sanctuary for temperate plants, instead revealing profound effects of Quaternary changes in climate, topography, and/or sea level on the current genetic structure of such organisms. There are three recurrent phylogeographic scenarios identified by different case studies that broadly agree with longstanding biogeographic or palaeo-ecological hypotheses: (i) postglacial re-colonization of the QTP from (south-)eastern glacial refugia; (ii) population isolation and endemic species formation in Southwest China due to tectonic shifts and river course dynamics; and (iii) long-term isolation and species survival in multiple localized refugia of (warm-)temperate deciduous forest habitats in subtropical (Central/East/South) China. However, in four additional instances, phylogeographic findings seem to conflict with a priori predictions raised by palaeo-data, suggesting instead: (iv) glacial in situ survival of some hardy alpine herbs and forest trees on the QTP platform itself; (v) long-term refugial isolation of (warm-)temperate evergreen taxa in subtropical China; (vi) ‘cryptic’ glacial survival of (cool-)temperate deciduous forest trees in North China; and (vii) unexpectedly deep (Late Tertiary/early-to-mid Pleistocene) allopatric-vicariant differentiation of disjunct lineages in the East China-Japan-Korea region due to past sea transgressions. We discuss these and other consequences of the main phylogeographic findings in light of palaeo-environmental evidence, emphasize notable gaps in our knowledge, and outline future research prospects for disentangling the evolution and biogeographic history of the region’s extremely diverse temperate flora.
Chitin is the most abundant biopolymer after cellulose but it has not been fully utilized yet. Because of biologically fixed nitrogen, effective conversion of chitin or its derivatives to value‐added ...organonitrogen compounds is a promising strategy to valorize chitin biomass, which has attracted increasing attention. Recently, a novel concept of shell biorefinery has been proposed on account of the huge potentials of chitin valorization. Until now, a number of valuable organonitrogen chemicals, including amino sugars, amino alcohols, amino acids, and heterocyclic compounds, have been produced from chitin biomass. In this Minireview, the focus is on the recent advances in the synthesis of organonitrogen chemicals employing chitin biomass as starting material via different catalytic processes. An outlook on the challenges and opportunities for more effective valorization of chitin will be given.
Shelling it: The selective catalytic conversion of chitin biomass to value‐added organonitrogen chemicals is of great significance for effective utilization of bio‐fixed nitrogen in shell waste. Herein, an introduction into recent advances in the production of nitrogen‐containing compounds (typically, amino sugars, amino alcohols, amino acids, and heterocyclic chemicals) and the strategies proposed for green conversion of chitin biomass are presented.
Abstract
Thirty years ago, Coullet et al. proposed that a special optical field exists in laser cavities bearing some analogy with the superfluid vortex. Since then, optical vortices have been widely ...studied, inspired by the hydrodynamics sharing similar mathematics. Akin to a fluid vortex with a central flow singularity, an optical vortex beam has a phase singularity with a certain topological charge, giving rise to a hollow intensity distribution. Such a beam with helical phase fronts and orbital angular momentum reveals a subtle connection between macroscopic physical optics and microscopic quantum optics. These amazing properties provide a new understanding of a wide range of optical and physical phenomena, including twisting photons, spin–orbital interactions, Bose–Einstein condensates, etc., while the associated technologies for manipulating optical vortices have become increasingly tunable and flexible. Hitherto, owing to these salient properties and optical manipulation technologies, tunable vortex beams have engendered tremendous advanced applications such as optical tweezers, high-order quantum entanglement, and nonlinear optics. This article reviews the recent progress in tunable vortex technologies along with their advanced applications.
Drought stress is a major threat to crop production, but effective methods to mitigate the adverse effects of drought are not available. Here, we report that adding fluorine atoms in the benzyl ring ...of the abscisic acid (ABA) receptor agonist AM1 optimizes its binding to ABA receptors by increasing the number of hydrogen bonds between the compound and the surrounding amino acid residues in the receptor ligand-binding pocket. The new chemicals, known as AMFs, have long-lasting effects in promoting stomatal closure and inducing the expression of stress-responsive genes. Application of AMFs or transgenic overexpression of the receptor PYL2 in Arabidopsis and soybean plants confers increased drought resistance. The greatest increase in drought resistance is achieved when AMFs are applied to the PYL2-overexpression transgenic plants. Our results demonstrate that the combining of potent chemicals with transgenic overexpression of an ABA receptor is very effective in helping plants combat drought stress.
The conventional strategy for cancer gene therapy offers limited control of specificity and efficacy. A possible way to overcome these limitations is to construct logic circuits. Here we present ...modular AND gate circuits based on CRISPR-Cas9 system. The circuits integrate cellular information from two promoters as inputs and activate the output gene only when both inputs are active in the tested cell lines. Using the luciferase reporter as the output gene, we show that the circuit specifically detects bladder cancer cells and significantly enhances luciferase expression in comparison to the human telomerase reverse transcriptase-renilla luciferase construct. We also test the modularity of the design by replacing the output with other cellular functional genes including hBAX, p21 and E-cadherin. The circuits effectively inhibit bladder cancer cell growth, induce apoptosis and decrease cell motility by regulating the corresponding gene. This approach provides a synthetic biology platform for targeting and controlling bladder cancer cells in vitro.
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