Splicing factor YBX1 regulates bone marrow stromal cell fate during aging.

Senescence and altered differentiation potential of bone marrow stromal cells (BMSCs) lead to age-related bone loss. As an important posttranscriptional regulatory pathway, alternative splicing (AS) regulates the diversity of gene expression and has been linked to induction of cellular senescence. However, the role of splicing factors in BMSCs during aging remains poorly defined. Herein, we found that the expression of the splicing factor Y-box binding protein 1 (YBX1) in BMSCs decreased with aging in mice and humans. YBX1 deficiency resulted in mis-splicing in genes linked to BMSC osteogenic differentiation and senescence, such as Fn1, Nrp2, Sirt2, Sp7, and Spp1, thus contributing to BMSC senescence and differentiation shift during aging. Deletion of Ybx1 in BMSCs accelerated bone loss in mice, while its overexpression stimulated bone formation. Finally, we identified a small compound, sciadopitysin, which attenuated the degradation of YBX1 and bone loss in old mice. Our study demonstrated that YBX1 governs cell fate of BMSCs via fine control of RNA splicing and provides a potential therapeutic target for age-related osteoporosis.

131I Induced In Vivo Proteolysis by Photoswitchable azoPROTAC Reinforces Internal Radiotherapy.

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

Melatonin is a potential novel analgesic agent for osteoarthritis: Evidence from cohort studies in humans and preclinical research in rats.

Melatonin exhibits potential for pain relief and long-term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox-proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community-based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30-0.73) during the follow-up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation.

An interesting electrocardiogram caused by lead reversal.

BACKGROUND: During normal sinus rhythm, atrial depolarization is conducted from right atrium to left atrium through Bachmann's bundle, and a normal P wave axis which is measured on the frontal plane is between 0º and + 75º. The change of P wave polarity is helpful for the analysis of origin point. CASE PRESENTATION: We report a patient with negative P wave in lead I. The characteristics of QRS complex in leads V1 to V6 are helpful to preliminarily differential diagnosis. The 12-lead electrocardiogram (ECG) with correct limb leads (right arm-left arm) placement shows sinus rhythm with complete right bundle branch block (RBBB). CONCLUSIONS: The change of P wave polarity as well as characteristics of QRS complex can help identify limb-lead reversals.

From pollution to solutions: Insights into the sources, transport and management of plastic debris in pristine and urban rivers.

River systems are important recipients of environmental plastic pollution and have become key pathways for the transfer of mismanaged waste from the land to the ocean. Understanding the sources and fate of plastic debris, including plastic litter (>5 mm) and microplastics (MPs) (<5 mm), entering different riverine systems is essential to mitigate the ongoing environmental plastic pollution crisis. We comprehensively investigated the plastic pollution in the catchments of two rivers in the Yangtze River basin: an urban river, the Suzhou section of the Beijing-Hangzhou Grand Canal (SZ); and a pristine rural river, the Jingmen section of the Hanjiang River (JM). The abundance of plastic pollutants in SZ was significantly higher than in JM: 0.430 ± 0.450 items/m3 and 0.003 ± 0.003 items/m3 of plastic litter in the water; 23.47 ± 25.53 n/m3 and 2.78 ± 1.55 n/m3 MPs in the water; and 218.82 ± 77.40 items/kg and 5.30 ± 1.99 items/kg of MPs in the sediment, respectively. Plastic litter and MPs were closely correlated in abundance and polymer composition. Overall, the polymer type, shape and color of MPs were dominant by polypropylene (42.5%), fragment (60.4%) and transparent (40.0%), respectively. Source tracing analysis revealed that packaging, shipping, and wastewater were the primary sources of plastic pollutants. The mantel analysis indicated that socio-economic and geospatial factors play crucial roles in driving the hotspot formation of plastic pollution in river networks. The composition of the MP communities differed significantly between the sediments and the overlying water. The urban riverbed sediments had a more pronounced pollutant 'sink' effect compared with the pristine rivers. These findings suggested that the modification of natural streams during urbanization may influence the transport and fate of plastic pollutants in them. Our results offer pivotal insights into effective preventive measures.

Domain and range of the CIECAM16 forward transformation.

The domain and range of the CIECAM16 forward transformation was numerically determined and visualized for CIE standard illuminants, using a linear programming approach that provides the gamuts and colour solids for optimum colours. The effect of the surround, adapting luminance, and luminance of the background on the range of the CIECAM16 forward transformation were individually analyzed, showing that their ranges increased when the surround changed from dark to dim or average, the adapting luminance increased, or the luminance of the background decreased. The proposed methodology for the determination and visualization of the domain and range of the CIECAM16 forward transformation can be used for any illuminant, as well as for CIECAM02, CAM16, CAM02-UCS and CAM16-UCS. The findings of this paper not only solve the long-term unresolved domain and range problems of the CIE colour appearance models, but also find applications in cross-media colour reproduction. Furthermore, it was also found that some non-CIE colours are inside the International Color Consortium Profile Connection Space (ICC PCS), and some CIE colours are not included in that space.

Barriers to compulsory waste sorting for a circular economy in China.

Household waste source separation substantially reduces the amount of rubbish sent to landfills and incinerators. It enables value recovery from useful waste for transitioning to a more resource efficient and circular economy. Confronted by the severe waste management problems, China recently implemented its most strict compulsory waste sorting program in big cities to date. Despite the failures of waste sorting projects in China in the past, it is unclear what the implementation barriers are, how they interact, and how they can be overcome. This study addresses this knowledge gap through a systematic barrier study involving all the relevant stakeholders in Shanghai and Beijing. It uncovers the complex interrelationships between barriers using the fuzzy decision-making trial and evaluation laboratory (Fuzzy DEMATEL) method. "Hasty and inappropriate planning" and "lack of policy support at the grassroots level", two new barriers that are not reported in the literature, are found to be the most influential barriers. Policy implications are discussed based on the study findings to inform the policy deliberations on the implementation of compulsory waste sorting.

Association of Metformin Use With Risk of Venous Thromboembolism in Adults With Type 2 Diabetes: A General-Population-Based Cohort Study.

Metformin is hypothesized to protect against the risk of venous thromboembolism (VTE); however, there is a paucity of data supporting this hypothesis. Among individuals aged 40-90 years with a diagnosis of type 2 diabetes in the Health Improvement Network database (2000-2019), we compared the risks of incident VTE, pulmonary embolism, and deep vein thrombosis among metformin initiators with those among sulfonylurea initiators. Individuals were followed from their first prescription refill to an incident VTE, drug discontinuation, switching or augmenting, plan disenrollment, or the end of the study, whichever occurred first. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox model, adjusting for confounders using inverse probability of treatment weighting. Among 117,472 initiators of metformin and 13,835 initiators of sulfonylureas, 555 (1.3/1,000 person-years) and 75 (2.1/1,000 person-years) VTE cases occurred in each group, respectively. The multivariable-adjusted HR was 0.65 (95% CI: 0.51, 0.84). The corresponding risks for pulmonary embolism (adjusted HR = 0.71, 95% CI: 0.50, 1.01) and deep vein thrombosis (adjusted HR = 0.64, 95% CI: 0.48, 0.87) were also lower in metformin initiators than in sulfonylurea initiators. Our study provided empirical evidence to support a lower risk of VTE after initiation of metformin as compared with sulfonylureas among patients with type 2 diabetes.

Interim connection space based on colorimetric values for spectral image compression and reproduction.

A new interim and connection space (ICS) and its reconstruction method are proposed. The proposed ICS,tD65A, consists of six colorimetric values or two sets of tristimulus values under CIE illuminant D65 and A respectively. In addition, a new spectral decomposition based on the tD65A ICS and the Wiener Estimation matrix MW was introduced for an improved spectral reconstruction. Accompanying the tD65A ICS, m important basis vectors for the metameric black space based on the new spectral decomposition, and a mapping matrix MP,k via a polynomial model of order k, were trained so that both the spectral and colorimetric accuracies for the reconstructed reflectance can be further enhanced. The proposed ICS and its reconstruction method can ensure exact colorimetric matches under two (real rather than synthetic) illuminants D65 and A, which is an advantage compared with other ICSs. The performance of the proposed method was tested and compared with five other ICSs using the NCS dataset and three spectral images respectively, using RMSE and GFC to measure the spectral accuracy, and using CIEDE2000 colour differences to measure the colorimetric accuracy under three types of illuminants (continuous, fluorescent, and LED). Performance test results showed the proposed methods outperform other ICSs in terms of both spectral accuracy and colorimetric measures (RMSE, GFC, and CIEDE2000 colour difference). Therefore, it is expected the proposed ICS and its reconstruction method can play an important role in spectral image compression and reproduction applications.

Genome-Wide Identification and Expression Profile Analysis of the SnRK2 Gene Family in Nicotiana tabacum.

SnRK2 protein kinase family plays an important role in plant response to abiotic stress and has been identified in various plants. This study aimed to identify SnRK2 genes in tobacco and systematically analyze their expression under abscisic acid treatment and abiotic stress. We identified 22 NtSnRK2 members, which were divided into three groups and located on 13 chromosomes, mainly at both ends of the chromosomes; additionally, 11 duplicated NtSnRK2 gene pairs were observed. Phylogenetic analysis showed that these SnRK2 members were divided into three groups in tobacco. The motifs of NtSnRK2 proteins in the same group were highly similar. Subcellular localization indicated that NtSnRK2s in Group3 were present in the nucleus, cytomembrane, and cytoplasm. Gene expression pattern analysis revealed that NtSnRK2 genes played a role in the responses to several abiotic stresses (salt, drought, and low-temperature stress), indicating that they are widely involved in the adaptation of tobacco to adverse environmental conditions.

Screening and Demulsification Mechanism of Fluorinated Demulsifier Based on Molecular Dynamics Simulation.

In order to solve the problem of demulsification difficulties in Liaohe Oilfield, 24 kinds of demulsifiers were screened by using the interface generation energy (IFE) module in the molecular dynamics simulation software Materials Studio to determine the ability of demulsifier molecules to reduce the total energy of the oil-water interface after entering the oil-water interface. Neural network analysis (NNA) and genetic function approximation (GFA) were used as technical means to predict the demulsification effect of the Liaohe crude oil demulsifier. The simulation results show that the SDJ9927 demulsifier with ethylene oxide (EO) and propylene oxide (PO) values of 21 (EO) and 44 (PO) reduced the total energy and interfacial tension of the oil-water interface to the greatest extent, and the interfacial formation energy reached -640.48 Kcal/mol. NNA predicted that the water removal amount of the SDJ9927 demulsifier was 7.21 mL, with an overall error of less than 1.83. GFA predicted that the water removal amount of the SDJ9927 demulsifier was 7.41mL, with an overall error of less than 0.9. The predicted results are consistent with the experimental screening results. SDJ9927 had the highest water removal rate and the best demulsification effect. NNA and GFA had high correlation coefficients, and their R2s were 0.802 and 0.861, respectively. The higher R2 was, the more accurate the prediction accuracy was. Finally, the demulsification mechanism of the interfacial film breaking due to the collision of fluorinated polyether demulsifiers was studied. It was found that the carbon-fluorine chain had high surface activity and high stability, which could protect the carbon-carbon bond in the demulsifier molecules to ensure that there was no re-emulsion due to the stirring external force.

Drift in policy implementation: Incentives thwarted in a recycling programme.

An incentives-based residential recycling programme was designed and implemented for improving residential waste sorting in Shanghai city, but showed very limited success in its performance. To identify why, this study systematically analysed each step of implementation using key informant interviews and site observations. Results show that policy intentions were retained in the policy devolution processes from Municipality to District, and then to Street (ward) levels, but the incentives concepts were effectively nullified in the further devolution to community-level governance. The local implementers focused on formal key performance indicators (KPIs) in order to satisfy inspections. However, the KPIs, which had been devised to allow ease of measurement, were found to unintentionally cause divergence from the policy intention of incentivisation of residents. Furthermore, high scores for these KPIs masked the implementation failure. This identification of the effective derailing of a policy via conscientious implementation is worth highlighting for avoidance in other programmes, in recycling or elsewhere.

The role of autophagy in bone homeostasis.

Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.

Spectral Reconstruction Using an Iteratively Reweighted Regulated Model from Two Illumination Camera Responses.

An improved spectral reflectance estimation method was developed to transform captured RGB images to spectral reflectance. The novelty of our method is an iteratively reweighted regulated model that combines polynomial expansion signals, which was developed for spectral reflectance estimation, and a cross-polarized imaging system, which is used to eliminate glare and specular highlights. Two RGB images are captured under two illumination conditions. The method was tested using ColorChecker charts. The results demonstrate that the proposed method could make a significant improvement of the accuracy in both spectral and colorimetric: it can achieve 23.8% improved accuracy in mean CIEDE2000 color difference, while it achieves 24.6% improved accuracy in RMS error compared with classic regularized least squares (RLS) method. The proposed method is sufficiently accurate in predicting the spectral properties and their performance within an acceptable range, i.e., typical customer tolerance of less than 3 DE units in the graphic arts industry.

A Stretchable Pillararene-Containing Supramolecular Polymeric Material with Self-Healing Property.

Constructing polymeric materials with stretchable and self-healing properties arise increasing interest in the field of tissue engineering, wearable electronics and soft actuators. Herein, a new type of supramolecular cross-linker was constructed through host-guest interaction between pillar[5]arene functionalized acrylate and pyridinium functionalized acrylate, which could form supramolecular polymeric material via photo-polymerization of n-butyl acrylate (BA). Such material exhibited excellent tensile properties, with maximum tensile strength of 3.4 MPa and strain of 3000%, respectively. Moreover, this material can effectively dissipate energy with the energy absorption efficiency of 93%, which could be applied in the field of energy absorbing materials. In addition, the material showed self-healing property after cut and responded to competitive guest.

Genome-wide identification and analysis of B-BOX gene family in grapevine reveal its potential functions in berry development.

BACKGROUND: The B-BOX (BBX) proteins are the class of zinc-finger transcription factors and can regulate plant growth, development, and endure stress response. In plants, the BBX gene family has been identified in Arabidopsis, rice, and tomato. However, no systematic analysis of BBX genes has been undertaken in grapevine. RESULTS: In this study, 24 grapevine BBX (VvBBX) genes were identified by comprehensive bioinformatics analysis. Subsequently, the chromosomal localizations, gene structure, conserved domains, phylogenetic relationship, gene duplication, and cis-acting elements were analyzed. Phylogenetic analysis divided VvBBX genes into five subgroups. Numerous cis-acting elements related to plant development, hormone and/or stress responses were identified in the promoter of the VvBBX genes. The tissue-specific expressional dynamics of VvBBX genes demonstrated that VvBBXs might play important role in plant growth and development. The transcript analysis from transcriptome data and qRT-PCR inferred that 11 VvBBX genes were down-regulated in different fruit developmental stages, while three VvBBX genes were up-regulated. It is also speculated that VvBBX genes might be involved in multiple hormone signaling (ABA, ethylene, GA3, and CPPU) as transcriptional regulators to modulate berry development and ripening. VvBBX22 seems to be responsive to multiple hormone signaling, including ABA, ethylene GA3, and CPPU. Some VvBBX genes were strongly induced by Cu, salt, waterlogging, and drought stress treatment. Furthermore, the expression of VvBBX22 proposed its involvement in multiple functions, including leaf senescence, abiotic stress responses, fruit development, and hormone response. CONCLUSIONS: Our results will provide the reference for functional studies of BBX gene family, and highlight its functions in grapevine berry development and ripening. The results will help us to better understand the complexity of the BBX gene family in abiotic stress tolerance and provide valuable information for future functional characterization of specific genes in grapevine.

Profiling the Vertical Transport of Microplastics in the West Pacific Ocean and the East Indian Ocean with a Novel in Situ Filtration Technique.

A new technique involving large-volume (10 m3) samples of seawater was used to determine the abundance of microplastics (MPs) in the water column in the West Pacific Ocean and the East Indian Ocean. Compared to the conventional sampling methods based on smaller volumes of water, the new data yielded abundance values for the deep-water column that were at least 1-2 orders of magnitude lower. The data suggested that limited bulk volumes currently used for surface sampling are insufficient to obtain accurate estimates of MP abundance in deep water. Size distribution data indicated that the lateral movement of MPs into the water column contributed to their movement from the surface to the bottom. This study provides a reliable dataset for the water column to enable a better understanding of the transport and fate of plastic contamination in the deep-ocean ecosystem.

Ras homolog family member A/Rho-associated protein kinase 1 signaling modulates lineage commitment of mesenchymal stem cells in asthmatic patients through lymphoid enhancer-binding factor 1.

BACKGROUND: Numbers of mesenchymal stem cells (MSCs) are increased in the airways after allergen challenge. Ras homolog family member A (RhoA)/Rho-associated protein kinase 1 (ROCK) signaling is critical in determining the lineage fate of MSCs in tissue repair/remodeling. OBJECTIVES: We sought to investigate the role of RhoA/ROCK signaling in lineage commitment of MSCs during allergen-induced airway remodeling and delineate the underlying mechanisms. METHODS: Active RhoA expression in lung tissues of asthmatic patients and its role in cockroach allergen-induced airway inflammation and remodeling were investigated. RhoA/ROCK signaling-mediated MSC lineage commitment was assessed in an asthma mouse model by using MSC lineage tracing mice (nestin-Cre; ROSA26-EYFP). The role of RhoA/ROCK in MSC lineage commitment was also examined by using MSCs expressing constitutively active RhoA (RhoA-L63) or dominant negative RhoA (RhoA-N19). Downstream RhoA-regulated genes were identified by using the Stem Cell Signaling Array. RESULTS: Lung tissues from asthmatic mice showed increased expression of active RhoA when compared with those from control mice. Inhibition of RhoA/ROCK signaling with fasudil, a RhoA/ROCK inhibitor, reversed established cockroach allergen-induced airway inflammation and remodeling, as assessed based on greater collagen deposition/fibrosis. Furthermore, fasudil inhibited MSC differentiation into fibroblasts/myofibroblasts but promoted MSC differentiation into epithelial cells in asthmatic nestin-Cre; ROSA26-EYFP mice. Consistently, expression of RhoA-L63 facilitated differentiation of MSCs into fibroblasts/myofibroblasts, whereas expression of RhoA-19 switched the differentiation toward epithelial cells. The gene array identified the Wnt signaling effector lymphoid enhancer-binding factor 1 (Lef1) as the most upregulated gene in RhoA-L63-transfected MSCs. Knockdown of Lef1 induced MSC differentiation away from fibroblasts/myofibroblasts but toward epithelial cells. CONCLUSIONS: These findings uncover a previously unrecognized role of RhoA/ROCK signaling in MSC-involved airway repair/remodeling in the setting of asthma.

Spectra estimation from raw camera responses based on adaptive local-weighted linear regression.

An improved spectral reflectance estimation method is developed to transform raw camera RGB responses to spectral reflectance. The novelty of our method is to apply a local weighted linear regression model for spectral reflectance estimation and construct the weighting matrix using a Gaussian function in CIELAB uniform color space. The proposed method was tested using both a standard color chart and a set of textile samples, with a digital RGB camera and by ten times ten-fold cross-validation. The results demonstrate that our method gives the best accuracy in estimating both the spectral reflectance and the colorimetric values in comparison with existing methods.

The association between CD31hiEmcnhi endothelial cells and bone mineral density in Chinese women.

Osteoporosis is the most common bone disease in humans. During bone remodeling, specialized blood vessels influenced by the endothelial cells (CD31hiEmcnhi, also called type H cells) are formatted to supply nutrients. Reductions in vascular supply are associated with bone loss resulting in osteoporosis. Therefore, the objective of the present study was to explore the association between the CD31hiEmcnhi endothelial cells and bone mineral density (BMD). In this prospective study, 134 Chinese women were enrolled and examined. BMD was measured by DEXA method while the percentage of CD31hiEmcnhi endothelial cells in the intertrochanteric part was measured by flow cytometry. The percentage of CD31hiEmcnhi endothelial cells in postmenopausal subjects was significantly lower compared with premenopausal women (8.7 ± 4.0% vs 13.2 ± 5.6%, P < 0.01). Meanwhile, the CD31hiEmcnhi endothelial cell levels in osteopenia and osteoporosis were significantly lower compared with subjects with normal BMD (9.84 ± 4.2% in osteopenia and 7.11 ± 3.2% in osteoporosis vs 12.7 ± 5.6% in subjects with normal T score, P < 0.01). Multiple regression analyses showed that the CD31hiEmcnhi endothelial cells level was positively associated with femur neck and total hip BMD, but not with lumbar BMD. Our study suggests a significantly positive association between CD31hiEmcnhi endothelial cells and local BMD in Chinese women. The proportion of CD31hiEmcnhi endothelial cells is a marker of bone quality and represents a potential target for treatment of bone loss.