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• Small molecules have been proposed as alternatives to regenerate bone tissue. • Small molecule drug dose can often be reduced while still achieving effective therapeutic. • The potential to improve bone repair by making it safer, easier, and more cost-effective with the use of a small molecule delivered in the short-term. Osteogenic small molecules have been adapted as one of the encouraging approaches to regenerate bone tissue. Small molecules used long term will usually result in adverse effects. A novel approach is short-term treatment with osteogenic small molecules. Demonstrating effectiveness for regenerating bone with a short-term treatment or a single-dose administration of osteogenic small molecules could enhance safety by reducing adverse effects. Over the past few years, many small molecules with the potential of regenerating bone tissue have been reported when used for short-term or single-dose administration. Here, I review the relevant literature, paying particular attention to prospects for small molecule-mediated bone regeneration with short-term exposure. [ABSTRACT FROM AUTHOR]

This paper develops a political perspective of just transition by linking the just transition concept with the concept of policy implementation, thereby drawing attention to the role of local policy implementers in the process and outcome of just transition. Focusing on the Chinese political context, it examines the degree of implementation flexibility in a broader context of authoritarian environmentalism. Implementation flexibility at the local level has been an enduring feature of Chinese environmental governance and can be considered as a key political process through which just transition can be achieved. However, recent studies suggest that the strengthening of top-down control over the environment means that the implementation process has become less flexible. Drawing on a case study of a logging town in the Greater Khingan Range transitioning under the National Forest Conservation Program, we found that while the strengthening of top-down control has resulted in an elevated level of compliance, flexibility remains an important dynamic in policy implementation. As such, local policy implementers still play an important role in just transition. This persistence of implementation flexibility is driven by a combination of local priorities, implementation difficulties, and top-down control. [ABSTRACT FROM AUTHOR]

There is no current standardized approach to anticoagulation in patients with Coronavirus Disease 2019 (COVID-19) while potential bleeding risks remain. Our study characterizes the patterns of anticoagulation use in COVID-19 patients and the risk of related bleeding. This is a single center retrospective analysis of 355 adult patients with confirmed diagnosis of COVID-19 from March 1 to May 31, 2020. Chi-square was used to analyze the relationship between degree of anticoagulant dose and bleeding events by site. Multivariable logistic regression was used to look at factors associated with inpatient death. 61% of patients were being treated with prophylactic doses of anticoagulation, while 7% and 29% were being treated with sub-therapeutic and therapeutic anticoagulation (TA) doses respectively. In 44% of patients, we found that the decision to escalate the dose of anticoagulation was based on laboratory values characterizing the severity of COVID-19 such as rising D-dimer levels. There were significantly higher rates of bleeding from non-CNS/non-GI sites (p = 0.039) and from any bleeding site overall (p = 0.019) with TA. TA was associated with significantly higher rates of inpatient death (41.6% vs 15.3% p < 0.0001) compared to those without. All patients who developed CNS hemorrhage died p = 0.011. After multivariable logistic regression, only age OR 1.04 95% CI (1.01 to 1.07) p = 0.008 and therapeutic anticoagulation was associated with inpatient mortality OR 6.16 95% CI (2.96 to 12.83) p ≤ 0.0001. The use of TA was significantly associated with increased risk of bleeding. Bleeding in turn exhibited trends towards higher inpatient death among patients with COVID-19. These findings should be interpreted with caution and larger more controlled studies are needed to verify the net effects of anticoagulation in patients with COVID-19. • Major bleeding is associated with use of therapeutic anticoagulation in COVID-19. • Therapeutic anticoagulation has shown higher mortality and major bleeding trends. • Risks and benefits of anticoagulation in COVID-19 should be weighed cautiously. [ABSTRACT FROM AUTHOR]

Background: As health-care institutions mobilize resources to address the coronavirus disease 2019 (COVID-19) pandemic, palliative care may potentially be underutilized. It is important to assess the use of palliative care in response to the COVID-19 pandemic.Methods: This is a retrospective single-center study of patients with COVID-19 diagnosed via reverse transcriptase-polymerase chain reaction assay admitted between March 1, 2020, and April 24, 2020. An analysis of the utilization of palliative care in accordance with patient comorbidities and other characteristics was performed while considering clinical outcomes. Chi-square test was used to determine associations between categorical variables while t-tests were used to compare continuous variables.Results: The overall mortality rate was 21.5% (n = 52), and in 48% (n = 25) of these patients, palliative care was not involved. Fifty-nine percent (n = 24) of those who had palliative consults eventually elected for comfort measures and transitioned to hospice care. Among those classified as having severe COVID-19, only 40% (n = 31) had palliative care involvement. Of these patients with severe COVID-19, 68% (n = 52) died. Patients who got palliative care consults were of older age, had higher rates of intubation, a need for vasopressors, and were dead.Conclusion: There was a low utilization rate of palliative care in patients with COVID-19. Conscious utilization of palliative care is needed at the time of COVID-19. [ABSTRACT FROM AUTHOR]

Voluntary resettlement, typically framed by the principle of free, prior, and informed consent (FPIC), has emerged as a preferred alternative to the heavily criticized forced resettlement approach, but there are growing concerns over whether those “voluntary” programs are genuinely voluntary. In China, the government maintains that its poverty alleviation resettlement (PAR) program is a successful example of voluntary resettlement. Under this national anti-poverty initiative, millions of people living in the poorest parts of the country have been resettled “voluntarily”. However, few studies have critically examined this claim. In this study, we collected empirical evidence through a survey of PAR resettlers. Drawing on a large and representative household survey (1723 resettlers from 30 different PAR projects) and 142 qualitative interviews, we report inconclusive and conflicting findings. On the one hand, the respondents strongly expressed that they willingly participated in resettlement. The perception of willingness was especially high among those who were younger, wealthier, and had off-farm employment. Furthermore, the consent to relocate was mostly free and driven by a desire to improve the quality of life. On the other hand, we observed that consent was not fully informed due to inadequate consultation. The villagers were not given detailed information about the resettlement or time to consider the implications. To ensure genuinely voluntary resettlement and to enhance the effectiveness of the program in poverty alleviation, the government needs to improve the consultation process, offer more targeted assistance to poor households, and provide better post-resettlement support. [ABSTRACT FROM AUTHOR]

Prostate cancer displays a wide spectrum of clinical behaviour from biological indolence to rapidly lethal disease, but we remain unable to accurately predict an individual tumor’s future clinical course at an early curable stage. Beyond basic dimensions and volume calculations, tumor morphometry is an area that has received little attention, as it requires the analysis of the prostate gland and tumor foci in three-dimensions. Previous efforts to generate three-dimensional prostate models have required specialised graphics units and focused on the spatial distribution of tumors for optimisation of biopsy strategies rather than to generate novel morphometric variables such as tumor surface area. Here, we aimed to develop a method of creating three-dimensional models of a prostate’s pathological state post radical prostatectomy that allowed the derivation of surface areas and volumes of both prostate and tumors, to assess the method’s accuracy to known clinical data, and to perform initial investigation into the utility of morphometric variables in prostate cancer prognostication. Serial histology slides from 21 prostatectomy specimens covering a range of tumor sizes and pathologies were digitised. Computer generated three-dimensional models of tumor and prostate space filling models were reconstructed from these scanned images using Rhinoceros 4.0 spatial reconstruction software. Analysis of three-dimensional modelled prostate volume correlated only moderately with weak concordance to that from the clinical data (r = 0.552, θ = 0.405), but tumor volume correlated well with strong concordance (r = 0.949, θ = 0.876). We divided the cohort of 21 patients into those with features of aggressive tumor versus those without and found that larger tumor surface area (32.7 vs 3.4cc, p = 0.008) and a lower tumor surface area to volume ratio (4.7 vs 15.4, p = 0.008) were associated with aggressive tumor biology. [ABSTRACT FROM AUTHOR]

Rural electrification is a crucial process of enhancing the modern energy access of rural communities which is an important global development goal. Electric cooperatives have played an important role as drivers of rural electrification worldwide, both historically and contemporaneously. The emerging role of cooperatives in rural electrification is yet to be examined in the context of East Africa, a region that experiences serious infrastructure deficits alongside widespread rural poverty. This study adopts a political economy perspective to explore the roles and challenges of cooperatives in rural electrification in Uganda. Through a high-level case study of two electric cooperatives, we show that while the cooperatives can deliver rural electrification, they face a series of political and economic challenges in fulfilling their mission. To enhance rural electrification through cooperatives, the challenges should be addressed by policy solutions: (1) providing more support to rural households that cannot afford electricity; (2) providing further support to cooperatives to avoid overburdening the community; (3) enhancing investment to upgrade the grid and extend its geographical coverage; and (4) exploring new financial and technological options for rural electrification. We expect the findings of this study to be useful to policymakers, implementers, cooperatives, and international donors currently working in rural electrification in Africa and beyond. [ABSTRACT FROM AUTHOR]

Environmental justice is a key concept for understanding the contested relationship between pastoralism and conservation. Our study adopted a political approach to examine conservation, pastoralism, and justice in the context of the grazing ban policy in China. Employing a qualitative, in-depth case study, we investigated the local political actors and processes that lead to environmental (in)justice. The evidence shows how injustice is perpetuated by both centralized and decentralized political processes and how herders use their knowledge and strategies in resistance to the injustice. In addition, the study contributed to a pluralistic understanding of justice by examining the different notions of justice held by the herders. We found that herders perceive injustices through different lenses, namely economic, ecological, and cultural aspects. Further, the similarities and differences between Han and Mongolian herders are discussed in terms of their notions of environmental justice and counteractions. [ABSTRACT FROM AUTHOR]

The microgrid is a new concept in China and may potentially play an important role in enhancing the resilience and sustainability of electricity generation and distribution. However, the development of microgrids faces many challenges. This study examines the barriers to microgrid development using a case study of a pilot zone in Qingdao. Drawing on the theories of multi-level perspective and multi-actor perspective, we presented new empirical evidence on how the pilot microgrid projects were rendered difficult by the resistance from the existing industrial regime and the challenging economic and socio-political environments. The monopoly of state-owned grid operators in electricity transmission and distribution is difficult to break at a local level. The findings deepen our understanding of the challenges encountered by innovators in China's microgrid development and hold implications for policymakers in making more targeted policy mixes to support energy transition activities. [ABSTRACT FROM AUTHOR]

Lithium is widely used as a treatment of bipolar disorder, a neuropsychiatric disorder associated with disrupted circadian rhythms. Lithium is known to lengthen period and increase amplitude of circadian rhythms. One possible pathway for these effects involves inhibition of glycogen synthase kinase-3β (GSK-3β), which regulates degradation of CRY2, a canonical clock protein determining circadian period. CRY1 is also known to play important roles in regulating circadian period and phase, although there is no evidence that it is similarly phosphorylated by GSK-3β. In this paper, we tested the hypothesis that lithium affects circadian rhythms through CRYs. We cultured fibroblasts and slices of the suprachiasmatic nucleus (SCN), the master circadian pacemaker of the brain, from Cry1 -/-, Cry2 -/-, or wild-type (WT) mice bearing the PER2:LUC circadian reporter. Lithium was applied in the culture medium, and circadian rhythms of PER2 expression were measured. In WT and Cry2-/- fibroblasts, 10 mM lithium increased PER2 expression and rhythm amplitude but not period, and 1 mM lithium did not affect either period or amplitude. In non-rhythmic Cry1 -/- fibroblasts, 10 mM lithium increased PER2 expression. In SCN slices, 1 mM lithium lengthened period ∼1 h in all genotypes, but did not affect amplitude except in Cry2-/- SCN. Thus, the amplitude-enhancing effect of lithium in WT fibroblasts was unaffected by Cry2 knockout and occurred in the absence of period-lengthening, whereas the period-lengthening effect of lithium in WT SCN was unaffected by Cry1 or Cry2 knockout and occurred in the absence of rhythm amplification, suggesting that these two effects of lithium on circadian rhythms are independent of CRYs and of each other. [ABSTRACT FROM AUTHOR]

Urban expansion is a controversial process where territorial conflicts of differing interests and objectives become manifest. The existing interpretations of urban expansion pay insufficient attention to the strategies deployed by municipal governments to resolve the territorial conflicts arising out of urban expansion. This paper identifies two key bargaining arenas through which municipal governments mitigate the territorial complications of urban expansion. First, administrative annexation not only involves municipal governments to gain control over more territory, but also entails strategies adopted to reconcile conflicts created by administrative restructuration, such as offering preferential fiscal and job arrangements. Second, land acquisition is not only about livelihood restoration of landless farmers but is also about converting them into citizens constituting new urban communities and integrating them into the urban mode of production. These bargaining arenas are the sites where the benefits and concessions of urban expansion are negotiated, and they play a key role in ensuring the smooth operation of urban expansion by resolving potential conflicts among stakeholders. • Territorial conflicts are common in urban expansion projects. • Territorial conflicts arising from administrative annexation and land acquisition • Territorial conflicts can be resolved through bargaining and compromises. [ABSTRACT FROM AUTHOR]

Rumors are an important yet poorly understood dynamic in environmental politics, particularly regarding their role in environmental activism. Drawing on theories of rumors, environmental information governance, and environmental activism, we analyzed the eco-politics of rumors in a Chinese village that experienced rumor-fueled protests against the construction and operation of a limestone quarry. We make three arguments regarding the condition, control, and content of rumors. First, poor environmental information governance, driven by a development-first and prejudice-rich official narrative and the strategic behaviors of blame and accountability avoidance, provides an important condition for rumor formulation and circulation. Second, the generation and circulation of rumors can be understood as a collective sense-making process driven by the informal communication between external and internal sources of information. The ephemeral nature of communication and group sanctions on government supporters make it difficult for authorities to control rumors. Third, by conceptualizing rumors as information warfare against official narratives, we show that rumors can foster a sense of collective urgency, reframe a land-right protest into an environmental protest that is politically more likely to succeed, and undermine public trust in local authorities. The findings suggest that rumors are an important part of environmental politics in China because of their role in environmental activism. [ABSTRACT FROM AUTHOR]

State-owned forestry enterprises (SOFEs) in China, established during the Maoist era for forest exploitation, have undergone significant reorganization under the Natural Forest Conservation Program (NFCP). In this study, drawing on the perspectives of political ecology and a case study from a SOFE in the Greater Khingan Range in northeast China, we develop an eco-socialist perspective to understand this particular approach to forest conservation. The concept of eco-socialism is mobilized to describe how, as a form of all-encompassing social organization with overwhelming political, social, and economic power in the forestry regions, the eco-restructuring of SOFEs is key to the success of forest conservation. Four eco-restructuring processes have been identified: (1) declining timber sales and increasing central subsidies; (2) restructuring of work-units; (3) creating redundancies; and (4) developing new sustainable economic activities. Furthermore, these eco-restructuring processes, both mandated and supported by the central government, have a significant impact on state-society relationship. While the resources given by the central government allow SOFEs to maintain a stable relationship with some workers by providing them a relatively stable livelihood, the laid-off workers are the major victims of the process, as they suffer from loss of income, economic stability, and social self-esteem. This study enriches the literature by incorporating eco-socialist governmentality into the political ecology of forest conservation and illustrating how the political ecology perspective can be a powerful tool in the collective effort to craft sustainable and socially just futures in China. [ABSTRACT FROM AUTHOR]

Abstract: The Chinese government has promulgated a wide variety of low-carbon initiatives to control the rapid growth of energy consumption and carbon emissions in the cities. Past records, however, show that the central government's policies are often poorly implemented or distorted by local officials. Using a case study from the city of Changchun, this paper examines how and why the issue of poor implementation persists despite the establishment of the Energy Conservation Target Responsibility System (ECTRS). As a key institutional mechanism providing local officials with political incentives to implement low-carbon policies, the ECTRS has been constrained by a number of problems, including a poorly designed scoring system, weak targets, the use of energy intensity instead of absolute energy consumption as a policy objective, and the lack of reliable local energy statistics. [Copyright &y& Elsevier]

Highlights: [•] Regenerative engineering has been recently proposed to regenerate complex tissue. [•] Therapeutic proteins have many limitations for their use in regenerating tissues. [•] Small-molecule-based therapeutics is emerging as an alternative strategy. [•] Small molecules may represent the next generation in musculoskeletal regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract: Renewable energy and energy efficiency (REEE) policies have far-reaching implications for energy security, climate change, economic competitiveness, pollution, and human livelihood. For these reasons, REEE has become a national priority for the Chinese government, particularly since 2005. This paper aims to critically review China's REEE policies in six sectors: electricity, industry, transportation, buildings, and local government. In addition to examining the progress China has made in the development and implementation of REEE policies, this review also identifies limitations and room for improvement. Finally, five policy recommendations are presented. [Copyright &y& Elsevier]

Abstract: The release of the Twelfth Five-Year Guideline for National Economic and Social Development in March 2011 marked the beginning of China’s Twelfth Five-Year Plan (12th FYP) period (2011–2015). Energy conservation continues to be a national priority. Since the release, new energy conservation policies and programs have been announced by many central ministries in accordance with the 12th FYP. Is this the beginning of a new paradigm or merely a continuation of the 11th FYP model? This paper describes and analyzes key changes in energy conservation since 2011, including a more conservative national energy conservation target, a more logical way of breaking down the target, new sectoral targets, the introduction of new programs, and the expansion of existing programs. However, one key problem of the 11th FYP period remains unresolved, namely the inability to shift the economy away from heavy industry. [Copyright &y& Elsevier]

Abstract: The emergence of gated communities for foreign residents in large Chinese cities is the result of economic globalisation, local institutional changes, social relations and cultural globalisation. Using a case study performed in Beijing, this paper seeks to analyse the complex dynamics of foreign gated communities through a critical examination of their key actors. The history of the gated community studied here is divided into two phases: development and localisation. During the development phase, the property developer not only attracted foreign residents through building an international community but also lured Hong Kong investors through the promise of soaring rental returns fuelled by strong demand. During the localisation phase, Chinese residents gradually replaced the developer as the project’s key actors. While the Chinese residents were attracted by the idea of international community, their arrival significantly transformed the community. This paper demonstrates how the survival, character and appearance of a foreign gated community was influenced by temporally and geographically dispersed actors who were subjected to a number of economic, social and cultural forces on a global and a local scale. [Copyright &y& Elsevier]

Abstract: Over the past several decades, recombinant human bone morphogenetic proteins (rhBMPs) have been the most extensively studied and widely used osteoinductive agents for clinical bone repair. Since rhBMP-2 and rhBMP-7 were cleared by the U.S. Food and Drug Administration for certain clinical uses, millions of patients worldwide have been treated with rhBMPs for various musculoskeletal disorders. Current clinical applications include treatment of long bone fracture non-unions, spinal surgeries, and oral maxillofacial surgeries. Considering the growing number of recent publications related to clincal research of rhBMPs, there exists enormous promise for these proteins to be used in bone regenerative medicine. The authors take this opportunity to review the rhBMP literature paying specific attention to the current applications of rhBMPs in bone repair and spine surgery. The prospective future of rhBMPs delivered in combination with tissue engineered scaffolds is also reviewed. [Copyright &y& Elsevier]

The cytoplasmic dynein 1 cargo binding domain is formed by five subunits including the intermediate chain and the DYNLT, DYNLL, and DYNLRB light chain families. Six isoforms of the intermediate chain and two isoforms of each of the light chain families have been identified in mammals. There is evidence that different subunit isoforms are involved in regulating dynein function, in particular linking dynein to different cargoes. However, it is unclear how the subunit isoforms are assembled or if there is any specificity to their interactions. Co-immunoprecipitation using DYNLT-specific antibodies reveals that dynein complexes with DYNLT light chains also contain the DYNLL and DYNLRB light chains. The DYNLT light chains, but not DYNLL light chains, associate exclusively with the dynein complex. Yeast two-hybrid and co-immunoprecipitation assays demonstrate that both members of the DYNLT family are capable of forming homodimers and heterodimers. In addition, both homodimers of the DYNLT family bind all six intermediate chain isoforms. However, DYNLT heterodimers do not bind to the intermediate chain. Thus, whereas all combinations of DYNLT light chain dimers can be made, not all of the possible combinations of the isoforms are utilized during the assembly of the dynein complex. [ABSTRACT FROM AUTHOR]

Cytoplasmic dynein is the motor protein responsible for the intracellular transport of various organelles and other cargoes toward microtubule minus ends. However, it remains to be determined how dynein is regulated to accomplish its varied roles. The dynein complex contains six subunits, including three classes of light chains. The two isoforms of the DYNLT (Tctex1) family of light chains, DYNLT1 and DYNLT3, have been proposed to link dynein to specific cargoes. However, no specific binding partner had been found for the DYNLT3 light chain. We find that DYNLT3 binds to Bub3, a spindle checkpoint protein. Bub3 binds exclusively to DYNLT3 and not to the other dynein light chains. Glutathione S-transferase pull-down and co-immunoprecipitation assays demonstrate that Bub3 interacts with the cytoplasmic dynein complex. DYNLT3 is present on kinetochores at prometaphase, but not later mitotic stages, demonstrating that this dynein light chain, like Bub3 and other checkpoint proteins, is depleted from the kinetochore during chromosome alignment. Knockdown of DYNLT3 with small interference RNA increases the mitotic index, in particular, the number of cells in prophase/prometaphase. These results demonstrate that dynein binds directly to a component of the spindle checkpoint complex through the DYNLT3 light chain. Thus, DYNLT3 contributes to dynein cargo binding specificity. These data also suggest that the subpopulation of dynein, containing the DYNLT3 light chain, may be important for chromosome congression, in addition to having a role in the transport of checkpoint proteins from the kinetochore to the spindle pole. [ABSTRACT FROM AUTHOR]

Cytoplasmic dynein is the multisubunit protein complex responsible for many microtubule-based intracellular movements. Its cargo binding domain consists of dimers of five subunits: the intermediate chains, the light intermediate chains, and the Tctex1, Roadblock, and LC8 light chains. The intermediate chains have a key role in the dynein complex. They bind the three light chains and the heavy chains, which contain the motor domains, but little is known about how the two intermediate chains interact. There are six intermediate chain isoforms, and it has been hypothesized that different isoforms may regulate specific dynein functions. However, there are little data on the potential combinations of the intermediate chain isoforms in the dynein complexes. We used co-immunoprecipitation analyses to demonstrate that all combinations of homo- and heterodimers of the six intermediate chains are possible. Therefore the formation of dynein complexes with different combinations of isoforms is not limited by interaction between the various intermediate chains. We further sought to identify the domain necessary for the dimerization of the intermediate chains. Analysis of a series of truncation and deletion mutants showed that a 61-amino-acid region is necessary for dimerization of the intermediate chain. This region does not include the N-terminal coiled-coil, the C-terminal WD repeat domain, or the three different binding sites for the Tctex1, LCS, and Roadblock light chains. Analytical gel filtration and covalent cross-linking of purified recombinant polypeptides further demonstrated that the intermediate chains can dimerize in vitro in the absence of the light chains. [ABSTRACT FROM AUTHOR]

The tumor suppressor protein p53 is known to undergo cytoplasmic dynein-dependent nuclear translocation in response to DNA damage. However, the molecular link between p53 and the minus end-directed microtubule motor dynein complex has not been described. We report here that the 8-kDa light chain (LC8) of dynein binds to p53-binding protein 1 (53BP1). The LC8-binding domain was mapped to a short peptide segment immediately N-terminal to the kinetochore localization region of 53BP1. The LC8-binding domain is completely separated from the p53-binding domain in 53BP1. Therefore, 53BP1 can potentially act as an adaptor to assemble p53 to the dynein complex. Unlike other known LC8-binding proteins, 53BP1 contains two distinct LC8-binding motifs that are arranged in tandem. We further showed that 53BP1 can directly associate with the dynein complex. Disruption of the interaction between LC8 and 53BP1 in vivo prevented DNA damage-induced nuclear accumulation of p53. These data illustrate that LC8 is able to function as a versatile accepter to link a wide spectrum of molecular cargoes to the dynein motor. [ABSTRACT FROM AUTHOR]

The 8-kDa light chain of dynein (DLC8) is ubiquitously expressed in various cell types. Other than serving as a light chain of the dynein complexes, this highly conserved protein has been shown to bind a larger number of proteins with diverse biological functions. DLC8 forms a homodimer via three-dimensional domain swapping of an internal β-strand (the β2-strand) at neutral pH. The protein undergoes non-reversible dimer-tomonomer dissociation when the pH value of the protein solution decreases. The three-dimensional structure of the DLC8 monomer determined by NMR spectroscopy at pH 3.0 showed that the protein is well folded. The major conformational change accompanied by dimer dissociation is in the β2-strand of the protein, which undergoes transition from a β-strand to a nascent α-helix. The monomer form of DLC8 is not capable of binding to target proteins. Insertion of two flexible amino acid residues in the tight β1/β2-1oop dramatically stabilized the monoruer conformation of the protein. NMR studies showed that the mutation altered the conformation as well as the three-dimensional domain swapping-mediated assembly of the DLC8 dimer. The mutant DLC8 was unable to bind to its targets even at physiological pH. The threedimensional structure of the mutant protein in its monomeric form provides the structural basis of the mutation-induced stabilization of the monomer conformation. Based on the experimental data, we conclude that the formation of the β2-strand swapping-mediated dimer is mandatory for the structure and function of DLC8. We further note that the DLC8 dimer represents a novel mode of three-dimensional domain swapping. [ABSTRACT FROM AUTHOR]

The rapid decline of solar PV costs and the urgency to develop effective post-Fukushima climate/energy plans in recent years have led to an upsurge of policy interest in deploying solar in international megacities including New York, Tokyo and Singapore. Nonetheless, overcoming barriers to large-scale uptake of urban solar PV remains under-explored. This study conducted 57 face-to-face interviews with potential solar PV adopters from the residential, institutional, and commercial sectors in Hong Kong, to understand perceived barriers and policy preferences. We found that firstly, most interviewees perceived high upfront costs and long payback period as primary barriers. Secondly, a reduced payback period is effective in improving their attitude towards installing solar. A majority of the residential interviewees shifted away from the "low level of interest" group to higher levels of interest if payback periods could be reduced from 35 years (business-as-usual scenario) to 8 years. Thirdly, potential PV adopters had different policy preferences. While residential interviewees indicated a strong preference for subsidies, institutional interviewees leaned towards regulatory measures, and commercial interviewees preferred feed-in-tariffs. Our findings suggest that the Hong Kong government needs to adopt the enabling framework developed in this study to effectively steer, nurture, and regulate PV deployment. [ABSTRACT FROM AUTHOR]

Repair and regeneration of human tissues and organs using biomaterials, cells, and/or growth factors is a great challenge for tissue engineers and surgeons. The convergence of advanced materials science, nanotechnology, stem cell science, and developmental biology, which we define as Regenerative Engineering, represents the next multidisciplinary paradigm to engineer complex tissues. One of the grand challenges in this field is to mimic closely the hierarchical architecture and properties of the extracellular matrices (ECM) of the native tissues. A bio-inspired approach to creating biomaterials with nanoscale topographical features, micro- and macroscale gradient structures, and biological domains to interact with target growth factors and cells is key to overcoming this challenge for successful tissue regeneration. Furthermore, the healing and repair of diseased musculoskeletal tissues rely on many signaling pathways, involving numerous growth factors and their receptors. Thus, pharmacological manipulation of the signaling pathways with bioactive molecules is an important component of tissue regeneration. This review summarizes current strategies to develop advanced nanofibrous polymer-based scaffolds via electrospinning, their applications in regenerating human musculoskeletal tissues, and the use of polymer nanofibers to deliver growth factors or small molecules for regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract: In a remote part of Northeast China, thousands of villages have disappeared from the map. Their inhabitants, more than 600,000 farmers, have been instructed by the government to relocate to nearby towns and commute to their farms to work. By concentrating the dispersed rural population in a small number of urban cores, the government hopes to improve housing conditions and accessibility to services, stimulate economic development, and free up more land for farming. This paper analyzes this kind of urbanization, which is distinct from the much-studied city-centered urbanization and in situ urbanization in coastal China. In addition to the resettlement program, this urbanization process is driven by agricultural modernization and economic liberalization. Urbanization has produced a rural–urban hybrid settlement system where urban construction coexists with a mostly agrarian economy. Urbanization has also improved the livelihood of many rural households, but there are significant social, economic, and environmental challenges. [Copyright &y& Elsevier]

The cross-sectional study reveals an inverted-U relationship between housing prices and migrant integration. Migrant integration initially increases with housing price appreciation but starts to decrease as rising house prices pass a turning point. Various robustness and variation tests have been conducted to show that the inverted-U relationship is reliable. • We found an inverted-U relationship between house prices and migrant integration. • Migrant integration initially increases and then decreases with rising house prices. • This relationship is highly robust. [ABSTRACT FROM AUTHOR]

The secretome is defined as the set of molecules and biological factors that are secreted by cells into the extracellular space. In the past decade, secretome-based therapies have emerged as a promising approach to overcome the limitations associated with cell-based therapies for tissue and organ regeneration. Considering the growing number of recent publications related to secretome-based therapies, this review takes a step-by-step engineering approach to evaluate the role of the stem cell secretome in regenerative engineering. We discuss the functional benefits of the secretome, the techniques used to engineer the secretome and tailor its therapeutic effects, and the delivery systems and strategies that have been developed to use the secretome for tissue regeneration. The stem cell secretome has emerged as a promising cell-free alternative to cell-based therapies. Secretome-based therapies have many of the therapeutic benefits of cell-based therapies, while obviating many of the safety and logistical concerns associated with directly using stem cells. The secretome is highly dynamic and its therapeutic effects can be engineered and customized according to its intended application. Delivery systems and strategies have been developed to harness the therapeutic benefits of the secretome for the repair and regeneration of various tissues and organs. [ABSTRACT FROM AUTHOR]

Bone scientists are actively investigating a range of methods to promote skeletal tissue regeneration. A review of recent literature has revealed that several ions are uniquely capable of inducing stem cell differentiation down desired lineages. There exists enormous promise for these ions to be used in bone regenerative medicine. Given that these ions can be released from biodegradable polymeric materials, their long-term delivery can be achieved through a variety of controlled-release strategies compared with the relatively few options available for expensive and fragile polypeptide-based growth factors. In this review, we highlight the developments in using ions in conjunction with biomaterials for bone regeneration. [ABSTRACT FROM AUTHOR]

Delivering drugs specifically to bone tissue is very challenging due to the architecture and structure of bone tissue. Poly(lactic- co -glycolic acid) (PLGA)-based nanoparticles (NPs) hold great promise for the delivery of therapeutics to bone tissue. The goal of the present research was to formulate a PLGA-based NP drug delivery system for bone tissue exclusively. Since poly-aspartic acids (poly-Asp) peptide sequence has been shown to bind to hydroxyapatite (HA), and has been suggested as a molecular tool for bone-targeting applications, we fabricated PLGA-based NPs linked with poly-Asp peptide sequence. Nanoparticles made of methoxy – poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged poly-Asp peptide was conjugated to the surface of the nanoparticles via the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the C C double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged poly-Asp peptide to PLGA NPs was confirmed by NMR analysis and fluorescent microscopy. The developed nanoparticle system is highly aqueous dispersible with an average particle size of ∼80 nm. In vitro binding analyses demonstrated that FITC-poly-Asp NPs were able to bind to HA gel as well as to mineralized matrices produced by human mesenchymal stem cells and mouse bone marrow stromal cells. Using a confocal microscopy technique, an ex vivo binding study of mouse major organ ground sections revealed that the FITC-poly-Asp NPs were able to bind specifically to the bone tissue. In addition, proliferation studies indicated that our FITC-poly-Asp NPs did not induce cytotoxicity to human osteoblast-like MG63 cell lines. Altogether, these promising results indicated that this nanoscale targeting system was able to bind to bone tissue specifically and might have a great potential for bone disease therapy in clinical applications. [ABSTRACT FROM AUTHOR]

Highlights: [•] Regenerative engineering has been recently proposed to regenerate skeletal tissue. [•] Regenerative small molecules play a vital role in bone regenerative engineering. [•] Numerous small molecules have been recently discovered for bone regeneration. [•] Polymeric scaffolds play an important role to delivery small molecules in vivo. [Copyright &y& Elsevier]