MV-mimicking micelles loaded with PEG-serine-ACP nanoparticles to achieve biomimetic intra/extra fibrillar mineralization of collagen in vitro

Since their discovery, matrix vesicles (MVs) containing minerals have received considerable attention for their role in the mineralization of bone, dentin and calcified cartilage. Additionally, MVs' association with collagen fibrils, which serve as the scaffold for calcification in the organic matrix, has been repeatedly highlighted. The primary purpose of the present study was to establish a MVs–mimicking model (PEG-S-ACP/micelle) in vitro for studying the exact mechanism of MVs-mediated extra/intra fibrillar mineralization of collagen in vivo. In this study, high-concentration serine was used to stabilize the amorphous calcium phosphate (S-ACP), which was subsequently mixed with polyethylene glycol (PEG) to form PEG-S-ACP nanoparticles. The nanoparticles were loaded in the polysorbate 80 micelle through a micelle self-assembly process in an aqueous environment. This MVs–mimicking model is referred to as the PEG-S-ACP/micelle model. By adjusting the pH and surface tension of the PEG-S-ACP/micelle, two forms of minerals (crystalline mineral nodules and ACP nanoparticles) were released to achieve the extrafibrillar and intrafibrillar mineralization, respectively. This in vitro mineralization process reproduced the mineral nodules mediating in vivo extrafibrillar mineralization and provided key insights into a possible mechanism of biomineralization by which in vivo intrafibrillar mineralization could be induced by ACP nanoparticles released from MVs. Also, the PEG-S-ACP/micelle model provides a promising methodology to prepare mineralized collagen scaffolds for repairing bone defects in bone tissue engineering.     

Non‐pollinating cheater wasps benefit from seasonally poor performance of the mutualistic pollinating wasps at the northern limit of the range of Ficus microcarpa

1. Species interactions in tightly bound ecological mutualisms often feature highly specialised species' roles in which competitive exclusion may preclude multi‐species coexistence. Among the 800 fig (Ficus) species, it was originally considered that each was pollinated by their own wasp (Agaonidae). However, recent investigations show that this ‘one‐to‐one’ rule often breaks down, as fig species regularly host multiple agaonids but in ways suggesting that competitive processes still mediate biodiversity outcomes. 2. A phenological survey was conducted of the fig–fig wasp pair, Ficus microcarpa and its associated pollinating wasp, alongside its sister species, the cheating wasp, in Xishuangbanna, China. 3. Reproductive output underwent extreme seasonal variation. Seed and pollinator production fell markedly during cooler, drier months, although high levels of fig production continued. However, this resource was predominantly utilised by the cheater species, which offers no pollination services. Pollinators and cheaters rarely co‐occur, suggesting that temporal coexistence is constrained by competition for access to figs. 4. The overall findings indicate periodic rearrangements of mutualism dynamics, probably resulting from a strongly seasonal environment. Sympatric co‐occurrence may result from a window of opportunity for a functionally divergent agaonid, potentially due to constraints on the main pollinator in adapting to variable year‐round conditions that prevent competitive exclusion.     

Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

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Involvement of Kv1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity

Inflammatory responses mediated by activated microglia play a pivotal role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders. Studies on identification of specific targets to control microglia activation and resultant neurotoxic activity are imperative. Increasing evidence indicate that voltage-gated K⁺ (K_v) channels are involved in the regulation of microglia functionality. In this study, we investigated K_v1.3 channels in the regulation of neurotoxic activity mediated by HIV-1 glycoprotein 120 (gp120)-stimulated rat microglia. Our results showed treatment of microglia with gp120 increased the expression levels of K_v1.3 mRNA and protein. In parallel, whole-cell patch-clamp studies revealed that gp120 enhanced microglia K_v1.3 current, which was blocked by margatoxin, a K_v1.3 blocker. The association of gp120 enhancement of K_v1.3 current with microglia neurotoxicity was demonstrated by experimental results that blocking microglia K_v1.3 attenuated gp120-associated microglia production of neurotoxins and neurotoxicity. Knockdown of K_v1.3 gene by transfection of microglia with K_v1.3-siRNA abrogated gp120-associated microglia neurotoxic activity. Further investigation unraveled an involvement of p38 MAPK in gp120 enhancement of microglia K_v1.3 expression and resultant neurotoxic activity. These results suggest not only a role K_v1.3 may have in gp120-associated microglia neurotoxic activity, but also a potential target for the development of therapeutic strategies.     

Relationship of physical fitness, hormone replacement therapy, and hemostatic risk factors in postmenopausal women.

This cross-sectional study evaluated the relationship of physical fitness, hormone replacement therapy (HRT), and hemostatic profiles at rest and after an acute bout of maximal exercise in 48 healthy postmenopausal women. Subjects were categorized by fitness and HRT user status into four groups: unfit nonusers, fit nonusers, unfit users, and fit users. Fibrinolytic variables tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, and antigen and prothrombin fragment 1 + 2, a molecular marker of in vivo thrombin generation, were measured before and after maximal exercise. Fibrinogen was also measured at rest. Higher tPA and lower PAI-1 activities (P <0.05) were seen in HRT users and fit groups. tPA and PAI-1 antigens were lower in HRT and fit groups (P <0.05) but not after correction for body mass index. Prothrombin fragment 1 + 2 was lower in the fit groups regardless of HRT status (P <0.05). Fibrinogen was similar in all groups. Favorable hemostatic profiles were observed in physically fit compared with unfit women, especially in HRT nonusers. Thus fitness is more strongly related to these hemostatic risk factors compared with HRT since HRT did not affect these hemostatic variables in fit postmenopausal women.     

Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism

Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.Subject terms: Pharmacology, Molecular biology