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Nonlinear optical switches that reversibly convert between on/off states by thermal stimuli are promising for applications in the fields of photoelectronics and photonics. Currently one main drawback for practical application lies in the control of their switch temperature, especially for the temperature range near room temperature. By mixed melting treatment, here we describe an alloy-like nonlinear optical switch with tunable switch temperature via a dual solid solution approach within the coordination polymer system. We initially prepare a coordination polymer ( i -PrNHMe 2 )[Cd(SCN) 3 ], which functions as a high-contrast thermoresponsive nonlinear optical switch originating from a phase transition at around 328 K. Furthermore, by taking advantage of a synergistic dual solid solution effect, the melt mixing of it with its analogue (MeNHEt 2 )[Cd(SCN) 3 ], which features an unequal anionic chain templated by an isomeric ammonium, can afford coordination polymer solid solutions with switch temperatures that are tunable in a range of 273–328 K merely by varying the component ratio. Switching of nonlinear optical signals is attractive for photoelectronics and photonics, but development is hindered by a lack of control over the switch temperature. Here the authors report a coordination polymer system that serves as an alloy-like nonlinear optical switch with a tunable switch temperature.

Using a tight-binding approach, we systematically investigate the electronic properties of zigzag-edged β -graphyne nanoribbons subjected to mutually perpendicular magnetic and electric fields. Our results reveal the emergence of tilted Landau levels, which exhibit pronounced spatial distributions and quantized transport characteristics. By incorporating Zeeman splitting, we predict the existence of a quantum spin Hall phase in the system. Furthermore, we demonstrate that a topological phase transition can be induced by modulating either the Zeeman energy or the in-plane electric field strength. To quantify these effects, we calculate the spin and charge Hall conductivities within a four-terminal transport geometry.

Chronic nonspecific low back pain (CNLBP) is defined as pain or discomfort originating from the waist, which lasts for at least 12 weeks, but no radiculopathy or specific spinal diseases. CNLBP is a complicated medical problem and places a huge burden on healthcare systems. Clinical manifestation of CNLBP includes discogenic LBP, zygapophyseal joint pain, sacroiliac joint pain, and lumbar muscle strain. Further evaluation should be completed to confirm the diagnosis including auxiliary examination, functional assessment, and clinical assessment. The principle of the management is to relieve pain, restore function, and avoid recurrence. Treatment includes conservative treatment, minimally invasive treatment, and rehabilitation. Pharmacologic therapy is the first-line treatment of nonspecific LBP, and it is most widely used in clinical practice. Interventional therapy should be considered only after failure of medication and physical therapy. Multidisciplinary rehabilitation can improve physical function and alleviate short-term and long-term pain. The emphasis should be put on the prevention of NLBP and reducing relevant risk factors.

Abstract Context Radioiodine refractory differentiated thyroid cancer (RAIR-DTC) has been a global challenge due to its poor prognosis and limited treatment options. Objective We report here the long-term results of the phase II clinical trial of apatinib, an anti-angiogenic tyrosine kinase inhibitor, for RAIR-DTC. Methods This was an open-label, exploratory phase II clinical trial among progressive RAIR-DTC patients. Apatinib treatment was given once daily until disease progression, unmanageable toxicity, withdrawal, or death. The primary end points were objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS), overall survival (OS), duration of response, long-term safety, and the association between patients with different tumor genotype (BRAFV600E and TERT promotor mutation) and their PFS rates were also assessed. Results The ORR was 80%, and the DCR was 95%. The overall median PFS was 18.4 months (95% CI, 9.2-36.8 months) and the median OS was 51.6 months (95% CI, 29.2-not reached [NR]). Patients with BRAFV600E mutation (10 of 18 evaluated) had a longer median PFS compared with patients with BRAF wild-type (NR vs 9.2 months; P = 0.002). The most common adverse events included palmar-plantar erythrodysesthesia syndrome (19/20), proteinuria (18/20), and hypertension (16/20). Conclusion In this long-term evaluation, apatinib displayed sustainable efficacy and tolerable safety profile, warranting it as a promising treatment option for progressive RAIR-DTC.

Background: Accumulating evidence has demonstrated that bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) can be used effectively to transfer drugs and biomolecules to target lesions. Meanwhile, BMSCs have been reported to be beneficial in the treatment of rheumatoid arthritis (RA). In this study, we employ gain- and loss-of-function experiments to determine how BMSCs-derived EVs alleviate RA in vitro and in vivo. Methods: We isolated EVs from BMSCs and characterized them by transmission electron microscopy and western blot analysis. The regulatory relationship between miR-21 and TET1 was predicted by bioinformatics analysis and validated by dual luciferase assay. Next, we utilized bisulfite sequencing PCR to decipher how TET1 promoted KLF4 transcription. Then, we established an RA mouse model and determined the role of miR-21 in RA progression. Functional assays were used to validate the role the miR-21-TET1-KLF4 regulatory axis in controlling mouse fibroblast-like synoviocytes (mFLS) cell proliferation and inflammatory cytokines secretion in vitro. Results: RT-qPCR results revealed that miR-21 was highly expressed in BMSCs-derived EVs, and confirmed that BMSCs-derived EVs transferred miR-21 into mFLS cells. Bioinformatic analysis predicted that TET1 was the directly downstream target of miR-21, which was further validated by dual luciferase assay. TET1 promoted KLF4 promoter methylation to increase its expression. Collectively, BMSCs-derived EVs relieved RA by delivering miR-21, while the exosomal miR-21 alleviated RA through targeting the TET1/KLF4 regulatory axis. Conclusion: miR-21 from BMSCs-derived EVs suppresses KLF4 to relive RA by targeting TET1.

Nanoscale flows appear widely in nanofiber fabrication especially in electrospinning, where nanoscale jets are multi-phase fluid including solvents and additives. This paper shows the fiber morphology can be effectively controlled by adjusting the density of the multi-phase jet. TiO2 is used as an additive in this paper to produce PAN nanofibers by electrospinning, the results elucidate that uniform nanofiber can be obtained, and this phenomenon is explained theoretically.

Vasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear. This study aimed to confirm that EphA2 is one of the potential targets of COE, and to explore the effect of EphA2 in VM formation in hypoxia context in HCC. TCM Systems Pharmacology database and proteomics analysis were used to explore the key targets of COE in HCC treatment. CD31-PAS double staining and VE-CAD staining were used to indicate vasculogenic mimicry. The localization of EphA2 and VE-CAD was examined through fluorescent microscopy. CCK8 assay, cell invasion assay, and tube formation assay were used to indicate the formation of VM under hypoxic conditions. The regulatory relationship of EphA2 upstream and downstream molecules were evaluated through COIP and Western Blot. The nude mouse xenograft tumor models were used to observe the VM formation after knocking down or overexpressing EphA2. EphA2 is identified to the target of COE, and the driving gene of HCC. In HCC surgical specimens, EphA2 expression is closely associated with the VM formation of HCC. COE-regulated EphA2 is involved in hypoxia-induced VM formation in HCC cells in vitro. EphA2 is regulated by HIF directly or indirectly by C-MYC. Overexpression of EphA2 can promote the VM formation of HCC in nude mice, while knocking down EphA2 can inhibit the VM formation. EphA2, as a target of COE, plays a crucial regulatory role in the formation of vasculogenic mimicry in HCC, involving upstream HIF/MYC transcriptional promotion and downstream PI3K/FAK/VE-CAD expression regulation.

Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor.

Isoflavonoids represent a privileged scaffold among various bioactive natural products, rendering their structural diversification through green synthesis and subsequent biological evaluations a compelling research area. In this study, an NHC organocatalytic radical acylalkylation of 1,3‐enynes using salicylaldehydes is presented, followed by a cascade intramolecular annulation, yielding a series of fluorinated isoflavone derivatives with substantial yields under environmental‐friendly conditions. This approach, distinguished by its excellent modularity and high functional group tolerance, represents an unprecedented organocatalytic 1,3,4‐trifunctionalization of 1,3‐enynes designed for the green synthesis of bioactive isoflavones in a single step. Furthermore, it is demonstrated that these synthesized fluorinated isoflavonoids effectively suppress proliferation in breast cancer cells, with the most potent compound 8 also inhibiting migration in MDA‐MB‐231 cells. An NHC‐catalyzed transformation is successfully developed to modularly synthesize novel fluorinated isoflavone derivatives under environmental‐friendly conditions. This approach represents an unprecedented organocatalytic 1,3,4‐trifunctionalization of 1,3‐enynes designed for the green synthesis of bioactive isoflavones in a single step. Additionally, we demonstrated that these synthesized fluorinated isoflavonoids effectively suppress proliferation in breast cancer cells, with the most potent compound 8 also inhibiting migration in MDA‐MB‐231 cells.