Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation.

The synthesis of type I collagen, the main component of bone matrix, precedes the expression of Runx2, the earliest determinant of osteoblast differentiation. We hypothesized that the energetic needs of osteoblasts might explain this apparent paradox. We show here that glucose, the main nutrient of osteoblasts, is transported in these cells through Glut1, whose expression precedes that of Runx2. Glucose uptake favors osteoblast differentiation by suppressing the AMPK-dependent proteasomal degradation of Runx2 and promotes bone formation by inhibiting another function of AMPK. While RUNX2 cannot induce osteoblast differentiation when glucose uptake is compromised, raising blood glucose levels restores collagen synthesis in Runx2-null osteoblasts and initiates bone formation in Runx2-deficient embryos. Moreover, RUNX2 favors Glut1 expression, and this feedforward regulation between RUNX2 and Glut1 determines the onset of osteoblast differentiation during development and the extent of bone formation throughout life. These results reveal an unexpected intricacy between bone and glucose metabolism.

Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism.

The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism.

Enhanced removal organic compounds and particles from cooking fume using activated sludge scrubber filled loofah: From performance to the mechanism.

The catering industry's growth has resulted in cooking fume pollution becoming a major concern in people's lives. As a result, its removal has become a core research focus. Natural loofah is an ideal biofilm carrier, providing a conducive environment for microorganisms to grow. This study utilized natural loofah to fill domesticated activated sludge in a bioscrubber, forming biofilms that enhance the ability to purify cooking fume. This study found that the biomass of loofah biofilms per gram is 104.56 mg. The research also determined the removal efficiencies for oils, Non-methane total hydrocarbons (NMHC), PM2.5, and PM10 from cooking fumes, which were 91.53%, 67.53%, 75.25%, and 82.23%, respectively. The maximum elimination capacity for cooking fumes was found to be 20.7 g/(m3·h). Additionally, the study determined the kinetic parameters for the biodegradation of oils (Kc and Vmax) to be 4.69 mg L-1 and 0.026 h-1, respectively, while the enzyme activities of lipase and catalase stabilized at 75.50 U/mgprots and 67.95 U/mgprots. The microbial consortium identified in the biofilms belonged to the phylum Proteobacteria and consisted mainly of Sphingomonas, Mycobacterium, and Lactobacillus, among others.

Synthesis and Bioactivity of Guanidinium-Functionalized Pillar[5]arene as a Biofilm Disruptor.

Due to the inherent resistance of bacterial biofilms to antibiotics and their serious threat to global public health, novel therapeutic agents and strategies to tackle biofilms are urgently needed. To this end, we designed and synthesized a novel guanidinium-functionalized pillar[5]arene (GP5) that exhibited high antibacterial potency against Gram-negative E. coli (BH101) and Gram-positive S. aureus (ATCC25904) strains. More importantly, GP5 effectively disrupted preformed E. coli biofilms by efficient penetration through biofilm barriers and subsequent destruction of biofilm-enclosed bacteria. Furthermore, host-guest complexation between GP5 and cefazolin sodium, a conventional antibiotic that otherwise shows negligible activity against biofilms, exhibited much enhanced, synergistic disruption activity against E. coli biofilms, thus providing a novel supramolecular platform to effectively disrupt biofilms.

Supramolecular Polymerization-Induced Nanoassemblies for Self-Augmented Cascade Chemotherapy and Chemodynamic Therapy of Tumor.

The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H2 O2 level in tumor tissues. Herein, we developed a supramolecular nanoparticle via a simple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified ß-cyclodextrin-ferrocene conjugates as supramolecular monomers. The supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H2 O2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H2 O2 in the tumor tissue. Thus, the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapy via the self-augmented cascade radical generation and drug release. In addition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.

Novel Nonaqueous Liquid-Liquid Biphasic Solvent for Energy-Efficient Carbon Dioxide Capture with Low Corrosivity.

To address the problems of the relatively high energy penalty and corrosivity of aqueous biphasic solvents, a novel nonaqueous biphasic solvent composed of 2-((2-aminoethyl)amino)ethanol (AEEA), dimethyl sulfoxide (DMSO), and N,N,N',N″,N″-pentamethyldiethylenetriamine (PMDETA) was proposed for CO2 capture. With optimization, this novel AEEA-DMSO-PMDETA (A-D-P) biphasic solvent could achieve a high CO2 loading of 1.75 mol·mol-1, of which 96.8% of the absorbed CO2 was enriched in the lower phase with only 49.6% of the total volume. 13C NMR analysis and quantum calculations revealed that A-D-P could absorb CO2 to form not only carbamate but also carbamic acid species, which were stabilized by DMSO via hydrogen-bonding interactions. Most products were highly polar and preferred to dissolve in polar DMSO rather than the less polar PMDETA, thus leading to the phase change. The thermodynamics results showed that the heat duty of A-D-P was only 1.66 GJ·ton-1 CO2 (393.15 K), which was significantly lower than that of the benchmark MEA (3.59 GJ·ton-1 CO2) and the reported aqueous biphasic solvents. Moreover, A-D-P presented a noncorrosive behavior to steel after CO2 saturation, clearly showing its superiority over MEA and the aqueous biphasic solvents. Therefore, with superior properties of energy savings and noncorrosiveness, the A-D-P biphasic solvent could be a promising candidate for CO2 capture.

An overview of the metabolic functions of osteocalcin.

A recent unexpected development of bone biology is that bone is an endocrine organ contributing to the regulation of a number of physiological processes. One of the functions regulated by bone through osteocalcin, an osteoblast specific hormone, is glucose homeostasis. In this overview, we explain the rationale why we hypothesized that there should be a coordinated endocrine regulation between bone mass and energy metabolism. We then review the experiments that identified the endocrine function of osteocalcin and the cell biology events that allow osteocalcin to become a hormone. We also demonstrate the importance of this regulation to understand whole-body glucose homeostasis in the physiological state and in pathological conditions. Lastly we discuss the epidemiological and genetic evidence demonstrating that this function of osteocalcin is conserved in humans.

An overview of the metabolic functions of osteocalcin.

A recent unexpected development of bone biology is that bone is an endocrine organ regulating a growing number of physiological processes. One of the functions regulated by bone through the hormone osteocalcin is glucose homeostasis. In this overview, we will explain why we hypothesized that bone mass and energy metabolism should be subjected to a coordinated endocrine regulation. We will then review the experiments that revealed the endocrine function of osteocalcin and the cell biology events that allow osteocalcin to become a hormone. We will also illustrate the importance of this regulation to understand whole-body glucose homeostasis in the physiological state and in pathological conditions. Lastly, we will mention epidemiological and genetic evidence demonstrating that this function of osteocalcin is conserved in humans.

Adsorption of high-temperature CO2 by Ca2+/Na+-doped lithium orthosilicate: characterization, kinetics, and recycle.

High-temperature solid adsorbent Li4SiO4 has received broad attention due to its high theoretical adsorption capacity, high regeneration capacity, and wide range of raw materials for preparation. In this paper, a Li4SiO4 adsorbent was prepared by MCM-48 as the silica precursor and modified by doping with metal ions (Ca2+ and Na+) for high-temperature capture of low-concentration CO2. The results showed that the surface of the Ca-doped (or Na-doped) Li4SiO4 adsorbent developed some particles that are primarily composed by Li2CaSiO4 (or Li3NaSiO4). Furthermore, the grains of the adsorbents became finer, effectively increasing the specific surface area and enhancing adsorption performance. Under 15 vol% CO2, the maximum CO2 adsorption was 25.63 wt% and 32.86 wt% when the Ca2+ doping amount was 0.06 and the Na+ doping amount was 0.12, respectively. These values were both higher than the adsorption capacity before the metal ion doping. After 10 adsorption/desorption cycles, the adsorption capacity of Na-doped Li4SiO4 increased by 9.68 wt%, while that of Ca-doped Li4SiO4 decreased by 7.98 wt%. This difference could be attributed to the easy sintering of the Ca-containing adsorbent. Furthermore, a biexponential model was used to fit the CO2 adsorption curve of the adsorbent in order to study the adsorption kinetics. Compared to the conventional Li4SiO4, the Ca/Na-doped adsorbent offers several advantages, such as a high CO2 adsorption capacity and stable cycling ability.

Targeted therapies of inflammatory diseases with intracellularly gelated macrophages in mice and rats.

Membrane-camouflaged nanomedicines often suffer from reduced efficacy caused by membrane protein disintegration and spatial disorder caused by separation and reassembly of membrane fragments during the coating process. Here we show that intracellularly gelated macrophages (GMs) preserve cell membrane structures, including protein content, integration and fluidity, as well as the membrane lipid order. Consequently, in our testing GMs act as cellular sponges to efficiently neutralize various inflammatory cytokines via receptor-ligand interactions, and serve as immune cell-like carriers to selectively bind inflammatory cells in culture medium, even under a flow condition. In a rat model of collagen-induced arthritis, GMs alleviate the joint injury, and suppress the overall arthritis severity. Upon intravenous injection, GMs efficiently accumulate in the inflammatory lungs of acute pneumonia mice for anti-inflammatory therapy. Conveniently, GMs are amenable to lyophilization and can be stored at ambient temperatures for at least 1 month without loss of integrity and bio-activity. This intracellular gelation technology provides a universal platform for targeted inflammation neutralization treatment.

Priority index for critical Covid-19 identifies clinically actionable targets and drugs.

While genome-wide studies have identified genomic loci in hosts associated with life-threatening Covid-19 (critical Covid-19), the challenge of resolving these loci hinders further identification of clinically actionable targets and drugs. Building upon our previous success, we here present a priority index solution designed to address this challenge, generating the target and drug resource that consists of two indexes: the target index and the drug index. The primary purpose of the target index is to identify clinically actionable targets by prioritising genes associated with Covid-19. We illustrate the validity of the target index by demonstrating its ability to identify pre-existing Covid-19 phase-III drug targets, with the majority of these targets being found at the leading prioritisation (leading targets). These leading targets have their evolutionary origins in Amniota ('four-leg vertebrates') and are predominantly involved in cytokine-cytokine receptor interactions and JAK-STAT signaling. The drug index highlights opportunities for repurposing clinically approved JAK-STAT inhibitors, either individually or in combination. This proposed strategic focus on the JAK-STAT pathway is supported by the active pursuit of therapeutic agents targeting this pathway in ongoing phase-II/III clinical trials for Covid-19.

"Zombie" Macrophages for Targeted Drug Delivery to Treat Acute Pneumonia.

A cell-based drug delivery system has emerged as a promising drug delivery platform. Due to their innate inflammatory tropism, natural and engineered macrophages have exhibited targeted accumulation in inflammatory tissues, which has allowed targeted delivery of medicine for the treatment of a variety of inflammatory diseases. Nevertheless, live macrophages may take up the medicine and metabolize it during preparation, storage, and in vivo delivery, sometimes causing unsatisfactory therapeutic efficacy. In addition, live macrophage-based drug delivery systems are usually freshly prepared and injected, due to the poor stability that does not allow storage. "Off-the-shelf" products would be indeed conducive to the timely therapy of acute diseases. Herein, a cryo-shocked macrophage-based drug delivery system was developed via supramolecular conjugation of cyclodextrin (CD)-modified "zombie" macrophages and adamantane (ADA)-functionalized nanomedicine. "Zombie" macrophages exhibited a much better storage stability over time than their counterpart live macrophage drug carriers and maintained cell morphology, membrane integrity, and biological functions. In an acute pneumonia mouse model, "zombie" macrophages carried quercetin-loaded nanomedicine, hand-in-hand, to the inflammatory lung tissues and effectively alleviated the inflammation in mice.

Microalgae Microneedle Supplies Oxygen for Antiphotoaging Treatment.

UV exposure often triggers photoaging of the skin. Pharmacological treatment suffers from severe side effects as well as poor efficacy because of insufficient skin penetration. Dissolved oxygen has been previously shown to reverse photoaged skin; however, the treatment is often limited by the availability of equipment (e.g., high-pressure oxygen). Poor oxygen diffusion into the skin has also limited its therapeutic efficacy. Herein, we developed a microneedle patch to deliver living microalgae to the deeper layers of the skin for efficient oxygenation and reversal of photoaging. The continuous release of oxygen from microalgae in the skin through photosynthesis reversed the inflammatory microenvironment and reduced reactive oxygen species levels in the photodamaged skin, leading to collagen regeneration and reduced wrinkles. This study provides not only a means for highly efficient skin oxygenation and reversal of photoaging but also an important theoretical basis for the clinical treatment of photoaging.

Intergenerational Educational Inequality and Its Transmission in China's Elite Universities.

China is experiencing high social inequality accompanying influential education reforms. The Independent Freshmen Admission (IFA) policy was one of the multiple strategies in higher education reforms in China against the social context of high social inequality and the expansion of higher education. By comparing students admitted through IFA with those admitted by the National College Entrance Examination (NCEE), we examined how family advantages contributed to higher education inequality in terms of educational opportunity, process, and results. Using data from an elite university in Beijing, we found that: (1) Family advantages improved a student's likelihood of being admitted through IFA, exhibiting opportunity inequality. (2) No significant difference in academic grades existed between the students admitted through IFA and NCEE. In comprehensive quality, however, those recruited through IFA performed significantly better than those admitted through NCEE. (3) Family social capital not only increased the likelihood of students being admitted through IFA but also, through direct and indirect effects, increased their comprehensive quality performance in terms of receiving student association and social practice awards.

What Do You Mean by Community Resilience? More Assets or Better Prepared?

OBJECTIVES: Understanding people's perception of community resilience to disaster is important. This study explores the correlations of household livelihood assets, the adopted household disaster preparedness activities, and individuals' assessment of community resilience. METHODS: The data was collected in 2018 by surveying a group of survivors affected by the 2008 Wenchuan earthquake in China. The CART (Community Advancing Resilience Toolkit) was used to measure individuals' perception of community resilience, while the livelihood assets included financial, physical, natural, human, and social capitals owned by the family, and the preparedness contained 13 activities. Ordinary least squares (OLS) regression models were used to test our hypotheses. RESULTS: Social capital is consistently and positively associated with the overall individuals' perceived community resilience, while the natural, human, and financial capitals' effects are not significant. The awareness and participation preparedness activities are positively correlated with the perceived community resilience, but the material preparedness activities are not. CONCLUSIONS: Social capital and disaster preparedness activities are critical in building community resilience. Community resilience can be achieved by making the community more connected and by providing disaster preparedness interventions.

Supramolecular erythrocytes-hitchhiking drug delivery system for specific therapy of acute pneumonia.

Acute pneumonia is an inflammatory syndrome often associated with severe multi-organ dysfunction and high mortality. The therapeutic efficacy of current anti-inflammatory medicines is greatly limited due to the short systemic circulation and poor specificity in the lungs. New drug delivery systems (DDS) are urgently needed to efficiently transport anti-inflammatory drugs to the lungs. Here, we report an inflammation-responsive supramolecular erythrocytes-hitchhiking DDS to extend systemic circulation of the nanomedicine via hitchhiking red blood cells (RBCs) and specifically "drop off" the payloads in the inflammatory lungs. ß-cyclodextrin (ß-CD) modified RBCs and ferrocene (Fc) modified liposomes (NP) were prepared and co-incubated to attach NP to RBCs via ß-CD/Fc host-guest interactions. RBCs extended the systemic circulation of the attached NP, meanwhile, the NP may get detached from RBCs due to the high ROS level in the inflammatory lungs. In acute pneumonia mice, this strategy delivered curcumin specifically to the lungs and effectively alleviated the inflammatory syndrome.

In vivo hitchhiking of immune cells by intracellular self-assembly of bacteria-mimetic nanomedicine for targeted therapy of melanoma.

Cell-based drug carriers are mostly prepared in vitro, which may negatively affect the physiological functions of cells, and induce possible immune rejections when applied to different individuals. In addition, the immunosuppressive tumor microenvironment limits immune cell-mediated delivery. Here, we report an in vivo strategy to construct cell-based nanomedicine carriers, where bacteria-mimetic gold nanoparticles (GNPs) are intravenously injected, selectively phagocytosed by phagocytic immune cells, and subsequently self-assemble into sizable intracellular aggregates via host-guest interactions. The intracellular aggregates minimize exocytosis of GNPs from immune cells and activate the photothermal property via plasmonic coupling effects. Phagocytic immune cells carry the intracellular GNP aggregates to melanoma tissue via inflammatory tropism. Moreover, an initial photothermal treatment (PTT) of the tumor induces tumor damage that subsequently provides positive feedback to recruit more immune cell-based carriers for enhanced targeting efficiency. The optimized secondary PTT notably improves antitumor immunotherapy, further strengthened by immune checkpoint blockade.

Annexin V-Modified Platelet-Biomimetic Nanomedicine for Targeted Therapy of Acute Ischemic Stroke.

Thromboembolic stroke is typically characterized by the activation of platelets, resulting in thrombus in the cerebral vascular system, leading to high morbidity and mortality globally. Intravenous thrombolysis by tissue plasminogen activator (tPA) administration within 4.5 h from the onset of symptoms is providing a standard therapeutic strategy for ischemic stroke, but this reagent simultaneously shows potential serious adverse effects, e.g., hemorrhagic transformation. Herein, a novel delivery platform based on Annexin V and platelet membrane is developed for tPA (APLT-PA) to enhance targeting efficiency, therapeutic effects, and reduce the risk of intracerebral hemorrhage in acute ischemic stroke. After preparation by extrusion of platelet membrane and subsequent insertion of Annexin V to liposomes, APLT-PA exhibits a high targeting efficiency to activated platelet in vitro and thrombosis site in vivo, due to the binding to phosphatidylserine (PS) and activated platelet membrane proteins. One dose of APLT-PA leads to obvious thrombolysis and significant improvement of neurological function within 7 days in mice with photochemically induced acute ischemic stroke. This study provides a novel, safe platelet-biomimetic nanomedicine for precise thrombolytic treatment of acute ischemic stroke, and offers new theories for the design and exploitation of cell-mimetic nanomedicine for diverse biomedical applications.

Hyaluronic acid-based supramolecular medicine with polyamines sequestration capability for cooperative anti-psoriasis.

Psoriasis seriously harms physical and mental health of patients. Hyaluronic acid (HA)-based topical formulation can increase drug concentration in psoriatic skin via CD44-assisted targeting. Herein, we developed a supramolecular medicine composed of curcumin-loaded HA-cucurbit[7]uril (HA-CB[7]@Cur), which could efficiently sequester polyamines (PAs) via host-guest interactions of CB[7] and PAs to suppress RNA-PAs immunocomplex formation. Meanwhile, anti-psoriasis drug Cur could be released from HA-CB[7]@Cur by PAs. With phenotypical disease evaluation, psoriasis area measurements and severity index scoring, and histological characterizations, we demonstrate topical administration of Carbopol gel formulation of HA-CB[7]@Cur on psoriasis-like skin in mice exhibited an enhanced anti-psoriasis activity, in comparison with gel of free Cur or HA-CB[7]. Cytokine expression analysis in psoriatic skin also supported the observed therapeutic outcomes. We provide a novel and effective supramolecular strategy to realize cooperative anti-psoriasis via controlled release of curcumin and PAs sequestration, which can be potentially expanded to treat other PA-involved skin inflammatory diseases.

Long-term effects of housing damage on survivors' health in rural China: Evidence from a survey 10 Years after the 2008 Wenchuan earthquake.

BACKGROUND: Disaster experiences have long-term health effects. However, less is known about the pathways of the association between disaster experiences and people's long-term health. We aimed to examine the long-term (10-year) effect of housing damage in the 2008 Wenchuan earthquake on survivors' health and to explore the pathways of the long-term effect. METHODS: We used data from a survey conducted in 2018 in rural areas affected by the 2008 Wenchuan earthquake. The survey collected information on housing damage caused by the earthquake from survivors aged 18 years old or above. Our primary outcome was dichotomous self-rated health in 2018. We considered decreased living standards and debt burden as mediators. To examine the long-term effect of housing damage on health, we performed multivariable binary logistic regression models. We also performed mediation analyses using the "KHB-method". RESULTS: Compared with no/slight damage, serious damage (odds ratio (OR): 1.50, 95% confidence interval (CI): 1.11,2.04) and collapse (OR: 1.57, 95% CI: 1.13,2.18) were associated with a higher risk of poor health. Decreased living standards and debt burden mediated 8.49% and 4.79%, respectively, of the association between serious damage and poor health and 10.64% and 6.10%, respectively, of the association between collapse and poor health. CONCLUSION: Housing damage in a natural disaster is a long-term risk for survivors' health. Long-term policies and interventions are necessary to protect and promote the health of survivors who experience housing damage. In addition to house reconstruction assistance, policies and interventions can be designed to promote living standards and financial situations to protect survivors' health.