Long-term gridded land evapotranspiration reconstruction using Deep Forest with high generalizability.

Previous datasets have limitations in generalizing evapotranspiration (ET) across various land cover types due to the scarcity and spatial heterogeneity of observations, along with the incomplete understanding of underlying physical mechanisms as a deeper contributing factor. To fill in these gaps, here we developed a global Highly Generalized Land (HG-Land) ET dataset at 0.5° spatial resolution with monthly values covering the satellite era (1982-2018). Our approach leverages the power of a Deep Forest machine-learning algorithm, which ensures good generalizability and mitigates overfitting by minimizing hyper-parameterization. Model explanations are further provided to enhance model transparency and gain new insights into the ET process. Validation conducted at both the site and basin scales attests to the dataset's satisfactory accuracy, with a pronounced emphasis on the Northern Hemisphere. Furthermore, we find that the primary driver of ET predictions varies across different climatic regions. Overall, the HG-Land ET, underpinned by the interpretability of the machine-learning model, emerges as a validated and generalized resource catering to scientific research and various applications.

Five-year outcomes of immediate implant placement for mandibular molars with and without chronic apical periodontitis: A retrospective study.

BACKGROUND: Most physicians consider molars with chronic apical periodontitis (CAP) lesions as contraindications for immediate implant placement. At the patient's request, we perform immediate implant placement of the mandibular molars with CAP in clinical practice. AIM: To retrospectively analyze and compare the 5-year outcomes of immediate implant placement of the mandibular molars with CAP and those without obvious inflammation. METHODS: The clinical data of patients with immediate implant placement of the mandibular molars in the Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, from June 2015 to June 2017 were collected. The patients were divided into CAP (n = 52) and no-CAP (n = 45) groups. Changes in bone mineral density and bone mass around implants were analyzed 5 years after implant restoration. RESULTS: At 5 years after implantation, the peri-implant bone mineral density was 528.2 ± 78.8 Hounsfield unit (HU) in the CAP group and 562.6 ± 82.9 HU in the no-CAP group (P = 0.126). Marginal bone resorption around implants did not differ significantly between the two groups, including buccal (P = 0.268) or lingual (P = 0.526) resorption in the vertical direction or buccal (P = 0.428) or lingual (P = 0.560) resorption in the horizontal direction. Changes in the peri-implant jump space did not differ significantly between the two groups, including the buccal (P = 0.247) or lingual (P = 0.604) space in the vertical direction or buccal (P = 0.527) or lingual (P = 0.707) space in the horizontal direction. The gray value of cone-beam computed tomography measured using Image J software can reflect the bone mineral density. In the CAP area, the gray values of the bone tissue immediately and 5 years after implant placement differed significantly from those of the surrounding bone tissue (P < 0.01). CONCLUSION: The results of this study suggest that immediate implant placement of the mandibular molars with CAP can achieve satisfactory 5-year clinical results, without significant differences in the complications, survival rate, or bone tissue condition from the no-CAP mandibular molars.

Scutellarin Loaded on Ultradeformable Nanoliposome Scutellarin EDTMP (S-UNL-E) Promotes Osteogenesis in Osteoporotic Rats.

Scutellarin is known as a safe, effective, and low-cost traditional Chinese medicine and has a variety of biological activities. Studies reported that the scutellarin loaded on ultradeformable nanoliposome scutellarin EDTMP (S-UNL-E) could promote osteoblast differentiation and bone formation in vitro. However, its effect on promoting osteogenesis in vivo is still unclear. In this study, pharmacology network and transcriptome sequencing were used to screen the potential targets and pathways of scutellarin in treating osteoporosis. The female Sprague-Dawley (SD) rats were operated on with bilateral oophorectomy and femoral defect to establish an osteoporosis model and then treated separately with bone dust, single scutellarin, 40 mg/kg ultradeformable nanoliposome scutellarin (S-UNL), and the optimal concentration of 40 mg/kg S-UNL-E for a total of 56 d to detect the parameters of trabecular bones. And qRT-PCR and western blot were performed to determine the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), alkaline phosphatase (ALP), transcription factor 4 (TCF4), and ß-catenin. Results of microscopic computed tomography (Micro-CT) of trabecular bones showed that single scutellarin, S-UNL, and S-UNL-E all promoted the bone formation of osteoporotic rats, in which S-UNL-E manifested the most remarkable therapeutic effect. And it is found that 40 mg/kg of S-UNL-E increased the expression of PTGS2, ALP, TCF4, and ß-catenin, which indicated that S-UNL-E stimulated the secretion of ALP in bone defect areas to promote bone healing, and increased PTGS2 expression thereby enhancing the transcription and translation of key gene ß-catenin and TCF4 in the Wnt/ß-catenin signaling pathway to treat osteoporotic rats.

Graphene-Based Nanomaterials for Dental Applications: Principles, Current Advances, and Future Outlook.

With the development of nanotechnology, nanomaterials have been used in dental fields over the past years. Among them, graphene and its derivatives have attracted great attentions, owing to their excellent physicochemical property, morphology, biocompatibility, multi-differentiation activity, and antimicrobial activity. In our review, we summarized the recent progress about their applications on the dentistry. The synthesis methods, structures, and properties of graphene-based materials are discussed. Then, the dental applications of graphene-based materials are emphatically collected and described. Finally, the challenges and outlooks of graphene-based nanomaterials on the dental applications are discussed in this paper, aiming at inspiring more excellent studies.

The role of NLRP3 inflammasome in the pathogenesis of rheumatic disease.

Inflammasome is a molecular platform that is formed in the cytosolic compartment to mediate host immune responses to infection and cellular damage. Inflammasome can activate caspase-1, leading to the maturation of two inflammatory cytokines interleukin 1ß (IL-1ß) and IL-18 and initiation of a proinflammatory form of cell death called pyroptosis. Among various inflammasome complexes, the NLRP3 inflammasome is by far the most studied inflammasome. NLRP3 inflammasome is a key factor in regulating host immune defense against infectious microbes and cellular damage. However, the dysregulated NLRP3 inflammasome activation also participates in the pathogenesis of many human disorders. NLRP3 inflammasome plays an important role in the pathogenesis of rheumatic disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Sjögren's syndrome (SS), dermatomyositis/polymyositis (DM/PM), gout, and systemic sclerosis (SSc). For example, NLRP3 inflammasome has been found highly activated in synovial tissues and peripheral blood mononuclear cells from RA patients. In this paper, we will discuss the role of NLRP3 inflammasome in the pathogenesis of rheumatic disease.

The Role of T Follicular Helper Cells and Interleukin-21 in the Pathogenesis of Inflammatory Bowel Disease.

T follicular helper (Tfh) cells represent a novel subset of CD4+ T cells which can provide critical help for germinal center (GC) formation and antibody production. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), programmed death 1 (PD-1), inducible costimulatory molecule (ICOS), B cell lymphoma 6 (BCL-6), and the secretion of interleukin-21 (IL-21). Given the important role of Tfh cells in B cell activation and high-affinity antibody production, Tfh cells are involved in the pathogenesis of many human diseases. Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases characterized by symptoms such as diarrhea, abdominal pain, and weight loss. Ulcerative colitis (UC) and Crohn's disease (CD) are the most studied types of IBD. Dysregulated mucosal immune response plays an important role in the pathogenesis of IBD. In recent years, many studies have identified the critical role of Tfh cells and IL-21 in the pathogenic process IBD. In this paper, we will discuss the role of Tfh cells and IL-21 in IBD pathogenesis.

Two-Tier Synergic Governance of Greenhouse Gas Emissions and Air Pollution in China's Megacity, Shenzhen: Impact Evaluation and Policy Implication.

Making a cost-effective governance of greenhouse gas (GHG) emissions and air pollution is of great importance for megacities to pursue a sustainable future. To achieve this, the present study advocates megacities to implement a two-tier synergic governance system consisting of both synergic governance between GHG and air pollutant emission reductions and between megacities and their surrounding regions. Based on the LEAP model and WRF-SMOKE-CMAQ simulation platform, this study found that climate governance of China's megacity, Shenzhen, could synergistically contribute to decreasing urban annual PM2.5 concentration by 5.6% in 2030. Using synergic governance with surrounding regions could further help cap and then quickly decrease the megacity's GHG emissions and lower its PM2.5 concentrations by an additional 11.8%. The results demonstrated the substantial effects of transdepartment and transregional synergic governance on Shenzhen's GHG emission reduction and air quality improvement. Furthermore, this study suggested road transportation and power generation and supply as the two priority fields for wide-ranging megacities to promote two-tier synergic governance, highlighting an integration of improved urban electrification with high-efficiency electricity use and a renewable-based power supply.

Removal of the root canal smear layer using Carisolv III and sodium hypochlorite.

The present study investigated the effectiveness of a Carisolv III + 0.5% sodium hypochlorite (NaOCl)-based root canal irrigant for smear layer removal.Forty maxillary incisors were randomly divided into 4 groups (n = 10 per group). The canals in group A (experimental) were prepared with 0.5% NaOCl, and Carisolv III and 0.5% NaOCl was used for the final washing; groups B and C (positive controls) used 2% and 5.25% NaOCl, respectively; and group D (negative control) used phosphate-buffered saline (PBS). Ethylenediaminetetraacetic acid (EDTA) was used for all of the groups. A 5-point scoring scale and scanning electron microscopy were used to evaluate the effectiveness of the irrigants. The canals were consistently cleaner in the coronal and middle thirds than in the apical thirds (P < .05).For cleaning the root canals, 5.25% NaOCl was more effective than 2% NaOCl, 0.5% NaOCl + Carisolv III, and phosphate-buffered saline , respectively (P < .05). The 2% NaOCl solution showed similar results to 0.5% NaOCl + Carisolv III (P > .05). The combination of 5.25% NaOCl and 17% EDTA remains the most effective irrigant for removal of the root canal smear layer.A combination of Carisolv III + 0.5% NaOCl (with 17% EDTA) showed a cleaning ability similar to that of 2% NaOCl (with 17% EDTA).

Influence of Simvastatin-Strontium-Hydroxyapatite Coated Implant Formed by Micro-Arc Oxidation and Immersion Method on Osteointegration in Osteoporotic Rabbits.

PURPOSE: Enhancing osteointegration of implants in osteoporosis patients is a necessity since implantations frequently fail in these patients. The aim of this work is to study how simvastatin-strontium-hydroxyapatite coated implants perform in rabbits with osteoporosis. MATERIALS AND METHODS: Crystalline HA and Sr-HA oxide film were prepared through micro-arc oxidation. Surface characterization including morphology, roughness, element composition, phase composition, hydrophilicity were then evaluated. Simvastatin loaded on porous films through immersion, and the effects of coatings on osteointegration in osteoporotic rabbits were investigated. All samples were obtained after 4, 8 and 12 weeks of healing. Some of them were subjected to biomechanical tests and others were subjected to histological and histomorphometric analysis. RESULTS: Coatings exhibited a microporous network structure with appropriate roughness and high hydrophilicity. Compared to control HA and machined surface implants, simvastatin-Sr-HA coated implants exhibited marked improvements in osteointegration, which is characterized by a quicker mineralization deposition rate, good bone formation mode (large amount of contact osteogenesis and a small amount of distance osteogenesis) and increased bone-to-implant contact and pull-out strength. CONCLUSION: These biological parameters demonstrate the excellent osteoconductivity of simvastatin-Sr-HA coatings in the osteoporotic state. Overall, this suggests that simvastatin-Sr-HA coatings would be applicable in poor-quality bones of patients experiencing osteoporosis.

Reduced Activity of HDAC3 and Increased Acetylation of Histones H3 in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis.

Aberrant histone acetylation and deacetylation are increasingly thought to play important roles in the pathogenesis of rheumatoid arthritis (RA). However, limited data from studies about the activity of histone deacetylases (HDACs) and histone acetyltransferase (HAT) in RA are controversial. Those conflicting results may be caused by sample size, medication, and age- and sex-matched controls. The aim of this study is to investigate the expression and activity of class I HDACs (1-3.8) and their effects on histone acetylation in peripheral blood mononuclear cells (PBMCs) from RA patients. The expression of class I HDACs in PBMCs from RA patients was decreased in both mRNA and protein levels in comparison with HCs. The nuclear HAT activities were dramatically increased. Further, we found HDAC3 activity to be the most significantly reduced in overall reduction of HDACs in the RA group. The extent of total histone H3, but not H4, acetylation in PBMCs from RA patients was increased compared to that in healthy controls (HCs) (p < 0.01). In RA PBMCs, the activity and expression of class I HDACs are decreased, which is accompanied with enhanced HAT activity. An altered balance between HDAC and HAT activity was found in RA PBMCs.

Scutellarin enhances osteoblast proliferation and function via NF-κB-mediated CXCR4 induction.

In the current study, we aimed to examine the function of scutellarin on human osteoblast proliferation and osteogenic function. The results indicated that scutellarin enhanced osteoblast proliferation over a seven day period. This increase in cell proliferation was associated with corresponding increases in osteoblast activity, as measured by alkaline phosphatase (ALP) secretion, intracellular calcium ion influx, and calcium deposition. These anabolic effects were associated with C-X-C chemokine receptor type 4 (CXCR4) mRNA levels and protein induction. Knockdown of CXCR4 reversed the scutellarin-induced increases in cell proliferation, ALP activity, and calcium deposition. Furthermore, scutellarin increased p65 phosphorylation in a dose-dependent manner, which resulted in the increased binding of phosphorylated p65 to the CXCR4 gene promoter region, to increase CXCR4 protein expression. p65 phosphorylation inhibition resulted in a decrease in CXCR4 protein expression. A p65 inhibitor blocked scutellarin-induced increases in osteoblast proliferation and function. Moreover, in a rat model of estrogen-deficient osteoporosis, scutellarin restored ovariectomy-induced bone loss in mice. Taken together, both cellular and animal models support the novel findings that scutellarin increased osteoblast proliferation and function through NF-κB/p65-mediated CXCR4 induction.

The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity.

AIM: The aim of this paper is to clarify the critical role of GPCR signaling in T cell immunity. METHODS: The G protein-coupled receptors (GPCRs) are the most common targets in current pharmaceutical industry, and represent the largest and most versatile family of cell surface communicating molecules. GPCRs can be activated by a diverse array of ligands including neurotransmitters, chemokines as well as sensory stimuli. Therefore, GPCRs are involved in many key cellular and physiological processes, such as sense of light, taste and smell, neurotransmission, metabolism, endocrine and exocrine secretion. In recent years, GPCRs have been found to play an important role in immune system. T cell is an important type of immune cell, which plays a central role in cell-mediated immunity. A variety of GPCRs and their signaling mediators (RGS proteins, GRKs and ß-arrestin) have been found to express in T cells and involved T cell-mediated immunity. We will summarize the role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function in this article. RESULTS: GPCR signaling plays an important role in T cell activation, homeostasis and function. CONCLUSION: GPCR signaling is critical in regulating T cell immunity.

Semiconductor laser irradiation improves root canal sealing during routine root canal therapy.

OBJECTIVE: To evaluate the effect of semiconductor laser irradiation on root canal sealing after routine root canal therapy (RCT). METHODS: Sixty freshly extracted single-rooted human teeth were randomly divided into six groups (n = 10). The anatomic crowns were sectioned at the cementoenamel junction and the remaining roots were prepared endodontically with conventional RCT methods. Groups A and B were irradiated with semiconductor laser at 1W for 20 seconds; Groups C and D were ultrasonically rinsed for 60 seconds as positive control groups; Groups E and F without treatment of root canal prior to RCT as negative control groups. Root canal sealing of Groups A, C and E were evaluated by measurements of apical microleakage. The teeth from Groups B, D and F were sectioned, and the micro-structures were examined with scanning electron microscopy (SEM). One way ANOVA and LSD-t test were used for statistical analysis (α = .05). RESULTS: The apical sealing of both the laser irradiated group and the ultrasonic irrigated group were significantly different from the control group (p<0.5). There was no significant difference between the laser irradiated group and the ultrasonic irrigated group (p>0.5). SEM observation showed that most of the dentinal tubules in the laser irradiation group melted, narrowed or closed, while most of the dentinal tubules in the ultrasonic irrigation group were filled with tooth paste. CONCLUSION: The application of semiconductor laser prior to root canal obturation increases the apical sealing of the roots treated.

Gαq Regulates the Development of Rheumatoid Arthritis by Modulating Th1 Differentiation.

The Gαq-containing G protein, an important member of Gq/11 class, is ubiquitously expressed in mammalian cells. Gαq has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how Gαq participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether Gαq controls RA via regulation of Th1 differentiation. We observed that the expression of Gαq was negatively correlated with the expression of signature Th1 cytokine (IFN-γ) in RA patients, which suggests a negative role of Gαq in differentiation of Th1 cells. By using Gαq knockout (Gnaq-/-) mice, we demonstrated that loss of Gαq led to enhanced Th1 cell differentiation. Gαq negative regulated the differentiation of Th1 cell by modulating the expression of T-bet and the activity of STAT4. Furthermore, we detected the increased ratio of Th1 cells in Gnaq-/- bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of Gαq promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA.

Expression of VSTM1-v2 Is Increased in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis and Is Correlated with Disease Activity.

Rheumatoid arthritis (RA) is a chronic, systematic autoimmune disease that mainly affects joints and bones. Although the precise etiology is still unknown, Th17 cell is being recognized as an important mediator in pathogenesis of RA. VSTM1-v2 is a novel cytokine which has recently been reported to promote the differentiation of Th17 cells. This study is performed to study whether VSTM1-v2 can be recognized as a biomarker of RA, and is correlated to IL-17 expression. We obtained peripheral blood mononuclear cells (PBMCs) from 40 patients with RA and 40 age- and sex-matched healthy controls by standard Ficoll-Paque Plus density centrifugation. The mRNA expression levels of VSTM1-v2 and IL-17A in PBMCs were detected by real time-PCR. Disease activity parameters of RA were measured by routine methods. Our results showed that VSTM1-v2 mRNA expression in PBMCs from RA patients was significantly increased in comparison of that in healthy individuals. The VSTM1-v2 mRNA expression level was positively correlated with IL-17A mRNA expression level, DAS28, CRP and ESR, but was not correlated to RF, Anti-CCP or ANA. VSTM1-v2 might be a biomarker of RA and a novel factor in the pathogenesis of RA.

Gαq controls rheumatoid arthritis via regulation of Th17 differentiation.

Gαq, the α-subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gαq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gαq negatively controls the disease activity of RA. However, how Gαq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gαq in control of Th17 differentiation. We investigated the relationship between Gαq and Th17 in RA patients. We then investigated the mechanism of how Gαq regulated Th17 differentiation by using Gnaq(-/-) mice. We observed that the expression of Gαq was negatively associated with interleukin-17A expression in RA patients, indicating that Gαq negatively controlled the differentiation of Th17 cells. By using Gnaq(-/-) mice, we demonstrated that Gαq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal-regulated kinase-1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and RORα (RAR-related orphan receptor-α). These data suggest the possibility of targeting Gαq to develop a novel therapeutic regimen for autoimmune disease.

Progress of biological agents on psoriatic arthritis.

Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by mild arthralgia to severe joint deformities. Long term management of these diseases with nonsteroidal anti-inflammatory drugs (NSAIDs) and diseasemodifying antirheumatic drugs (DMARDs) is limited due to lack of efficacy and potential organ toxicity. Recently, the approval of injectable biologics, such as T cell inhibitors and TNF-α antagonist, has changed the treatment of moderateto- severe psoriasis and PsA. Unlike NSAIDs and DMARDs, TNF-α antagonists not only provide unambiguous benefits for the skin and joints, but also prevent the progression of structural damage in peripheral joints. Biological agents in the treatment of PsA have broad prospects. More and more biological agents are being developed for the treatment of PsA. In the current review, we will discuss the progress of biological agents on PsA.

The use of biologic therapies in the treatment of rheumatoid arthritis.

The use of biologic agents has revolutionized the management of rheumatoid arthritis (RA) in the past two decades. These biologic agents directly target molecules and cells involved in the pathogenesis of RA. Biologic agents indeed lead to a better prognosis and clinical remission in patients with RA, especially in patients who are not well-controlled with traditional disease-modifying anti-rheumatic drugs (DMARDs). Currently, five TNF inhibitors (infliximab, etanercept, adalimumab, golimumab and certolizumab pegol), an IL-6 receptor antagonist (tocilizumab), an IL-1 receptor antagonist (anakinra), a B cell depleting agent (rituximab) and a T cell co-stimulation inhibitor (abatacept) have been approved for the treatment of RA. With the increased understanding of the pathogenic mechanisms of RA and advantages in manufacturing biotechnology of pharmaceutical companies, a series of novel biologic therapeutic approaches are being developed. In the present paper, we will summarize the biologic agents currently available to treat RA, and the prospective biologic therapies that might be used in the management of RA in future.

The deficiency of Gαq leads to enhanced T-cell survival.

We have previously reported that Gαq, the α subunit of the Gq protein, had important roles in dendritic cell migration, B-cell survival and autoimmunity. In this study, we showed that the deficiency of Gαq led to enhanced T-cell survival. Cultured Gnaq(-/-) T cells exhibited survival advantages both in medium alone and in the presence of anti-CD3 stimulation. Gnaq(-/-) T cells still exhibited a survival advantage when they were cultured in the presence of interleukin (IL)-2 or IL-7. Gnaq(-/-) T cells were more resistant to activation-induced cell death (AICD) in vitro. The survival advantage of Gnaq(-/-) T cells was further confirmed by transferring T cells into syngeneic hosts in vivo. Gαq deficiency might promote T-cell survival by upregulated Bcl-xL expression and downregulated Fas and FasL expressions. Furthermore, upon T-cell receptor (TCR) ligation, Akt activity was increased in Gnaq(-/-) T cells in comparison with wild-type (WT) T cells. The survival advantage of Gnaq(-/-) T cells was significantly attenuated after adding Akt inhibitor. Taken together, our data demonstrated a negative role of Gαq in regulating T-cell survival.