The thermal condition over the Tibetan Plateau (TP) plays a vital role in the South Asian high (SAH) and the Asian summer monsoon (ASM); however, its prediction skill is still low. Here, two machine ...learning models are employed to address this problem. Expert knowledge and distance correlation are used to select the predictors from observational datasets. Both linear and nonlinear relationships are considered between the predictors and predictands. The predictors are utilized for training the machine learning models. The prediction skills of the machine learning models are higher than those of two state-of-the-art dynamic operational models and can explain 67% of the variance in the observations. Moreover, the SHapley Additive exPlanation method results indicate that the important predictors are mainly from the Southern Hemisphere, Eurasia, and western Pacific, and most show nonlinear relationships with the predictands. Our results can be applied to find potential climate teleconnections and improve the prediction of other climate signals.
With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid, the incidence of hyaluronic acid embolism has also increased ...commensurately. Hyaluronic acid embolism leads to serious complications, including blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for hyaluronic acid embolism by intraarterial thrombolysis therapy.
This study included 24 patients with a decrease in visual acuity and other complications induced by facial hyaluronic acid injection. Patients underwent emergency intraarterial thrombolysis therapy by injection of hyaluronidase (500 to 1500 units) alone or hyaluronidase (750 to 1500 units) combined with urokinase (100,000 to 250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy.
Ten (42 percent) of 24 patients ultimately had improvements to visual acuity, even when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases, patients' facial skin necrosis was restored to nearly normal appearance. In addition, the authors found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone.
The authors' results indicate that intraarterial thrombolysis therapy is beneficial to patients suffering from blindness induced by hyaluronic acid embolism. The therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision and was also beneficial in the recovery from other serious complications, including eye movement disorder, eye edema, headaches, and skin necrosis.
Therapeutic, IV.
Achieving C3-selective pyridine functionalization is a longstanding challenge in organic chemistry. The existing methods, including electrophilic aromatic substitution and C–H activation, often ...require harsh reaction conditions and excess pyridine and generate multiple regioisomers. Herein, we report a method for borane-catalyzed tandem reactions that result in exclusively C3-selective alkylation of pyridines. These tandem reactions consist of pyridine hydroboration, nucleophilic addition of the resulting dihydropyridine to an imine, an aldehyde, or a ketone, and subsequent oxidative aromatization. Because the pyridine is the limiting reactant and the reaction conditions are mild, this method constitutes a practical tool for late-stage functionalization of structurally complex pharmaceuticals bearing a pyridine moiety.
Cutaneous pseudolymphoma (CPL) encompasses various forms of benign lymphocytic proliferative dermatoses that mimic the clinical and/or pathological changes of lymphoma. The clinical manifestations of ...CPL vary due to differences in the pathogenesis, and accordingly, no specific treatment has been identified. Here, we report a case of CPL on the nose, which had a distinctive appearance and was treated successfully using a combination of intralesional interferon alpha‐1b and compound betamethasone (betamethasone sodium phosphate and betamethasone dipropionate). This combination may be a good option for localized CPLs at particular anatomical sites.
The chromatin modifier enhancer of zeste homolog 2 (EZH2) methylates lysine 27 of histone H3 (H3K27) and regulates T cell differentiation. However, the potential role of EZH2 in the pathogenesis of ...rheumatoid arthritis (RA) remains elusive. We analyzed EZH2 expression in PBMC, CD4+ T cells, CD19+ B cell, and CD14+ monocytes from active treatment-naïve RA patients and healthy controls (HC). We also suppressed EZH2 expression using EZH2 inhibitor GSK126 and measured CD4+ T cell differentiation, proliferation and apoptosis. We further examined TGFβ-SMAD and RUNX1 signaling pathways in EZH2-suppressed CD4+ T cells. Finally, we explored the regulation mechanism of EZH2 by RA synovial fluid and fibroblast-like synoviocyte (FLS) by neutralizing key proinflammatory cytokines. EZH2 expression is lower in PBMC and CD4+ T cells from RA patients than those from HC. EZH2 inhibition suppressed regulatory T cells (Tregs) differentiation and FOXP3 transcription, and downregulated RUNX1 and upregulated SMAD7 expression in CD4+ T cells. RA synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4+ T cells, which was partially neutralized by anti-IL17 antibody. Taken together, EZH2 in CD4+ T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4+ T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4+ T cells. Defective EZH2 in CD4+ T cells might contribute to Treg deficiency in RA.
•CD4+ T cells from RA patients expressed lower EZH2, which suppressed regulatory T cells (Tregs) differentiation in vitro.•EZH2 inhibition downregulated RUNX1 and upregulated SMAD7 expression, subsequently attenuating FOXP3 transcription.•RA-derived synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4+ T cells.
Matrix mechanics regulate essential cell behaviors through mechanotransduction, and as one of its most important elements, substrate stiffness was reported to regulate cell functions such as ...viability, communication, migration, and differentiation. Neutrophils (Neus) predominate the early inflammatory response and initiate regeneration. The activation of Neus can be regulated by physical cues; however, the functional alterations of Neus by substrate stiffness remain unknown, which is critical in determining the outcomes of engineered tissue mimics. Herein, a three-dimensional (3D) culture system made of hydrogels was developed to explore the effects of varying stiffnesses (1.5, 2.6, and 5.7 kPa) on the states of Neus. Neus showed better cell integrity and viability in the 3D system. Moreover, it was shown that the stiffer matrix tended to induce Neus toward an anti-inflammatory phenotype (N2) with less adhesion molecule expression, less reactive oxygen species (ROS) production, and more anti-inflammatory cytokine secretion. Additionally, the aortic ring assay indicated that Neus cultured in a stiffer matrix significantly increased vascular sprouting. RNA sequencing showed that a stiffer matrix could significantly activate JAK1/STAT3 signaling in Neus and the inhibition of JAK1 ablated the stiffness-dependent increase in the expression of CD182 (an N2 marker). Taken together, these results demonstrate that a stiffer matrix promotes Neus to shift to the N2 phenotype, which was regulated by JAK1/STAT3 pathway. This study lays the groundwork for further research on fabricating engineered tissue mimics, which may provide more treatment options for ischemic diseases and bone defects.
•The 3D culture system was more suitable for neutrophils (Neus), providing an opportunity to mimic the in-vivo experiments.•Substrate stiffness could alter neutrophil phenotypes and stiffer substrate promoted Neus to shift to the N2 phenotype, which was regulated by modulating the JAK1/STAT3 pathway.•This work lays the foundation for the application of hydrogel-based biomaterials, which provides more treatment options for ischemic diseases and bone defects.
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The microfluidic chip-based nucleic acid detection method significantly improves the sensitivity since it precisely controls the microfluidic flow in microchannels. Nonetheless, significant ...challenges still exist in improving the detection efficiency to meet the demand for rapid detection of trace substances. This work provides a novel magnetic herringbone (M-HB) structure in a microfluidic chip, and its advantage in rapid and sensitive detection is verified by taking complementary DNA (cDNA) sequences of human immunodeficiency virus (HIV) detection as an example. The M-HB structure is designed based on controlling the magnetic field distribution in the micrometer scale and is formed by accumulation of magnetic microbeads (MMBs). Hence, M-HB is similar to a nanopore microstructure, which has a higher contact area and probe density. All of the above is conducive to improving sensitivity in microfluidic chips. The M-HB chip is stable and easy to form, which can linearly detect cDNA sequences of HIV quantitatively ranging from 1 to 20 nM with a detection limit of 0.073 nM. Compared to the traditional herringbone structure, this structure is easier to form and release by controlling the magnetic field, which is flexible and helps in further study. Results show that this chip can sensitively detect the cDNA sequences of HIV in blood samples, demonstrating that it is a powerful platform to rapidly and sensitively detect multiple nucleic acid-related viruses of infectious diseases.
Color‐tunable room temperature phosphorescence (RTP) luminescent materials with stimuli‐responsive properties are highly desirable for practical applications, but the fundamental design principles ...still need further exploitation. Herein, we report on the extended red‐shifted multicolor RTP afterglow from blue to orange, including white light, offered by a series of newly designed supramolecular polymers based on 1‐(2‐methylallyloxy)pyrene phosphor‐containing guest polymers and β‐cyclodextrin (β‐CD)/γ‐CD host molecules. RTP enhancement is efficiently realized, attributing to the strong restriction on the dimeric pyrene units by the host–guest inclusion complexation of CDs and the multiple interactions amongst polymer matrices and phosphorescent moieties. Interestingly, a more comprehensive blue‐shifted color tuning range is also enabled upon introducing pH‐sensitive fragments due to the self‐assembly of the ternary polymers aided by ionic bonding. Notably, optimized intelligent multicolor RTP systems induced by altered external stimuli, including concentration, irradiation, and pH, are established, showing great potential in developing stimuli‐responsive luminescent materials for practical applications. In addition, theoretical calculations are conducted to elucidate diverse emission mechanisms of pyrene units in different assembly states.
A new Ni coordination polymer Ni(MIP)(BMIOPE)n (1) was constructed (BMIOPE = 4,4′-bis(2-methylimidazol-1-yl)diphenyl ether, and H2MIP = 5-methylisophthalic acid), possessing two-dimensional (2D) ...twofold parallel interwoven net structure with a 44∙62 point symbol. Complex 1 has been successfully obtained based on mixed-ligand strategy. The fluorescence titration experiments revealed that complex 1 could act as multifunctional luminescent sensor to simultaneously detect UO22+, Cr2O72− and CrO42−, and NFT (nitrofurantoin). The limit of detection (LOD) values for complex 1 are 2.86 × 10−5, 4.09 × 10−5, 3.79 × 10−5 and 9.32 × 10−5 M for UO22+, Cr2O72−, CrO42− and NFT. The Ksv values are 6.18 × 103, 1.44 × 104, 1.27 × 104 and 1.51 × 104 M−1 for NFT, CrO42−, Cr2O72− and UO22+. Finally, the mechanism of its luminescence sensing is studied in detail. These results manifest that complex 1 is a multifunctional sensor for sensitive fluorescent UO22+, Cr2O72−, CrO42− and NFT detection.
