Effect of acupuncture on regulating IL-17, TNF-ɑ and AQPs in Sjögren's syndrome.

AIM: The aim of the study was to observe the effect of acupuncture on regulating interleukin (IL)-17, tumor necrosis factor (TNF)-ɑ, and aquaporins (AQPs) in Sjögren's syndrome (SS) on patients and on non-obese diabetic (NOD) models. METHODS: Levels of anti-AQP 1, 5, 8, and 9 antibodies, IL-17, and TNF-ɑ in the serum of SS patients were compared prior and following 20 acupuncture treatment visits during 8 weeks. While in murine model, five groups were divided to receive interventions for 4 weeks, including control, model, acupuncture, isoflurane, and hydroxychloroquine. The submaxillofacial gland index, histology, immunohistochemistry of AQP1, 5, salivary flow, together with IL-17, and TNF-ɑ expression in peripheral blood were compared among the groups. RESULTS: Acupuncture reduced IL-17, TNF-ɑ, and immunoglobin A levels, and numeric analog scale of dryness in 14 patients with SS (p < 0.05). The salivary flow was increased, and the water intake decreased in NOD mice receiving acupuncture treatments. IL-17 and TNF-ɑ levels in peripheral serum were down-regulated (p < 0.05) and AQP1, 5 expression in the submandibular glands up-regulated in mice. CONCLUSION: The effect on relieving xerostomia with acupuncture may be achieved by up-regulating the expression of AQP1. AQP5, down-regulating levels of IL-17 and TNF-ɑ, and a decrease in inflammation of glands.

Structural Optimization of Fibroblast Growth Factor Receptor Inhibitors for Treating Solid Tumors.

Small-molecule fibroblast growth factor receptor (FGFR) inhibitors have emerged as a promising antitumor therapy. Herein, by further optimizing the lead compound 1 under the guidance of molecular docking, we obtained a series of novel covalent FGFR inhibitors. After careful structure-activity relationship analysis, several compounds were identified to exhibit strong FGFR inhibitory activity and relatively better physicochemical and pharmacokinetic properties compared with those of 1. Among them, 2e potently and selectively inhibited the kinase activity of FGFR1-3 wildtype and high-incidence FGFR2-N549H/K-resistant mutant kinase. Furthermore, it suppressed cellular FGFR signaling, exhibiting considerable antiproliferative activity in FGFR-aberrant cancer cell lines. In addition, the oral administration of 2e in the FGFR1-amplified H1581, FGFR2-amplified NCI-H716, and SNU-16 tumor xenograft models demonstrated potent antitumor efficacy, inducing tumor stasis or even tumor regression.

Design, synthesis and evaluation of N3-substituted quinazolinone derivatives as potential Bloom's Syndrome protein (BLM) helicase inhibitor for sensitization treatment of colorectal cancer.

The homologous recombination repair (HRR) pathway is critical for repairing double-strand breaks (DSB). Inhibition of the HRR pathway is usually considered a promising strategy for anticancer therapy. The Bloom's Syndrome Protein (BLM), a DNA helicase, is essential for promoting the HRR pathway. Previously, we discovered quinazolinone derivative 9h as a potential BLM inhibitor, which suppressed the proliferation of colorectal cancer (CRC) cell HCT116. Herein, a new series of quinazolinone derivatives with N3-substitution was designed and synthesized to improve the anticancer activity and explore the structure-activity relationship (SAR). After evaluating their BLM inhibitory activity, the SAR was discussed, leading to identifying compound 21 as a promising BLM inhibitor. 21 exhibited the potent BLM-dependent cytotoxicity against the CRC cells but weak against normal cells. Further evaluation revealed that 21 could disrupt the HRR level while inhibiting BLM located on the DSB site and trigger DNA damage in the CRC cells. This compound effectively suppressed the proliferation and invasion of CRC cells, along with cell cycle arrest and apoptosis. Consequently, 21 might be a promising candidate for treating CRC, and the BLM might be a new potential therapeutic target for CRC.

Efficacy and Safety of Acupuncture on Symptomatic Improvement in Primary Sjögren's Syndrome: A Randomized Controlled Trial.

Aim: We sought to evaluate the efficacy of acupuncture in treating the main symptoms of primary Sjögren's syndrome, specifically dryness, pain, and fatigue. Methods: A total of 120 patients with primary Sjögren's syndrome were randomized in a parallel-group, controlled trial. Participants received acupuncture or sham acupuncture for the first 8 weeks, then were followed for 16 weeks thereafter. The primary outcome was the proportion of participants with a ≥ 30% reduction in ≥ 2 of 3 numeric analog scale scores for dryness, pain, and fatigue. The secondary outcomes included the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient-reported Index (ESSPRI); the EULAR Sjögren's Syndrome Disease Activity Index; the Schirmer test score; unstimulated saliva flow; serum immunoglobulin G, A, and M concentrations; the Medical Outcome Study Short Form 36 score; salivary gland ultrasound imaging; and the Hospital Anxiety and Depression Scale score. Results: The proportions of patients meeting the primary endpoint were 28.33% (17/60) in the acupuncture group and 31.66% (19/60) in the sham group, without a statistically significant difference (P = 0.705). The IgG concentration at week 16 and the homogeneity in ultrasonography of the salivary glands at week 8 showed significant differences between the 2 groups (P = 0.0490 and P = 0.0334, respectively). No other differences were observed between the 2 groups. ESSPRI and unstimulated saliva flow were improved in both groups compared to baseline, albeit with a significant difference between them. Conclusion: In patients with primary Sjögren's syndrome, acupuncture did not satisfactorily improve symptoms compared to placebo. However, interesting discoveries and possible underlying reasons were demonstrated and discussed, which may be useful to studies in the future. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02691377].

Engineering Bismuth-Tin Interface in Bimetallic Aerogel with a 3D Porous Structure for Highly Selective Electrocatalytic CO2 Reduction to HCOOH.

Electrochemical reduction of CO2 (CO2 RR) into valuable hydrocarbons is appealing in alleviating the excessive CO2 level. We present the very first utilization of metallic bismuth-tin (Bi-Sn) aerogel for CO2 RR with selective HCOOH production. A non-precious bimetallic aerogel of Bi-Sn is readily prepared at ambient temperature, which exhibits 3D morphology with interconnected channels, abundant interfaces and a hydrophilic surface. Superior to Bi and Sn, the Bi-Sn aerogel exposes more active sites and it has favorable mass transfer properties, which endow it with a high FEHCOOH of 93.9 %. Moreover, the Bi-Sn aerogel achieves a FEHCOOH of ca. 90 % that was maintained for 10 h in a flow battery. In situ ATR-FTIR measurements confirmed that the formation of *HCOO is the rate-determining step toward formic acid generation. DFT demonstrated the coexistence of Bi and Sn optimized the energy barrier for the production of HCOOH, thereby improving the catalytic activity.

Correction: Recent development of two-dimensional metal-organic framework derived electrocatalysts for hydrogen and oxygen electrocatalysis.

Correction for 'Recent development of two-dimensional metal-organic framework derived electrocatalysts for hydrogen and oxygen electrocatalysis' by Hengbo Wu et al., Nanoscale, 2020, 12, 18497-18522 DOI: 10.1039/D0NR04458J.

Recent development of two-dimensional metal-organic framework derived electrocatalysts for hydrogen and oxygen electrocatalysis.

Developing efficient and low-cost electrocatalysts with unique nanostructures is of great significance for improved electrocatalytic reactions, including the hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR). Two-dimensional (2D) metal-organic frameworks (MOFs) have attracted recent attention because of their unique dimension-related properties, such as ultrathin thickness, large specific surface area, and abundant accessible active sites that can act as good precursors for the derivation of a variety of nanocomposites as active materials in electrocatalysis and energy-related devices. In this review, we present recent developments in 2D MOF-derived nanomaterials for hydrogen and oxygen reactions in overall water-splitting and rechargeable Zn-air batteries. The advantages of various synthetic strategies are summarized and discussed in detail. Finally, we discuss the main challenges and future perspectives of the development of 2D MOF-derived electrocatalysts.

MOF-derived two-dimensional N-doped carbon nanosheets coupled with Co-Fe-P-Se as efficient bifunctional OER/ORR catalysts.

Developing highly efficient, low-cost and bifunctional electrocatalysts for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) plays a pivotal role in the scalable applications of zinc-air (Zn-air) batteries. Herein, Co-Fe-P-Se nanoparticles supported on two-dimensional nitrogen-doped carbon (Co-Fe-P-Se/NC) to construct a three-dimensional nanostructure were obtained under the assistance of metal-organic frameworks (MOFs). The two-dimensional nanosheet facilitated the electron transfer rate and exposed abundant active sites. The three-dimensional morphology composed of nanosheets was favorable for electrolyte transport and provided abundant channels for gas diffusion during the catalytic process. Moreover, the coexistence of Co and Fe had important effects on promoting the catalytic performances. Lastly, the catalytic performances for OER and ORR could be promoted effectively after the introduction of selenium and phosphorous in the designed electrocatalyst. Benefiting from the above merits, the prepared Co-Fe-P-Se/NC exhibited excellent catalytic performances for OER (overpotential of 0.27 V at 10 mA cm-2), ORR (half-wave potential of 0.76 V) and rechargeable batteries (a low voltage gap of 0.719 V, high power density of 104 mW cm-2 at 200 mA cm-2 and high energy density of 805 W h KgZn-1). Moreover, the prepared electrocatalyst possessed more stable long-term stability in all the conducted experiments. This work provides a novel approach to develop and construct high-performance bifunctional nanocatalysts for metal-air batteries.