Thrombospondin-1 mimic peptide PKHB1 induced endoplasmic reticulum stress-mediated but CD47-independent apoptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies with high morbidity and mortality. PKHB1, a serum-stable Thrombospondin-1 (TSP-1) mimic peptide, has shown some effective ability in triggering cell death against several cancers. Here, we aimed to study the potential biological function of PKHB1 and its molecular mechanism in NSCLC. Our results revealed that PKHB1 significantly suppressed NSCLC cell proliferation, cell migration, and induced apoptosis in a dose-dependent manner. Additionally, we found that PKHB1 treatment resulted in mitochondrial transmembrane potential depolarization, Ca2+ overloading as well as the upregulation of proapoptotic proteins. Mechanistically, PKHB1 induced NSCLC cells apoptosis in a CD47-independent manner. Further study revealed that PKHB1 provoked endoplasmic reticulum (ER) stress principally through the activation of CHOP and JNK signaling, which could be alleviated in the presence of 4-PBA, an ER stress inhibitor. Furthermore, xenograft tumor models showed that PKHB1 treatment could notably inhibit NSCLC tumor growth in vivo. In conclusion, these findings suggested that PKHB1 exerted antitumor efficacy in NSCLC via triggering ER stress-mediated but CD47-independent apoptosis, potentially functioned as a promising peptide-based therapeutic agent for NSCLC.

A Modular Tubular Flow System with Replaceable Photocatalyst Membranes for Scalable Coupling and Hydrogenation.

Heterogeneous photocatalysis is effective for the selective synthesis of value-added chemicals at lab-scale, yet falls short of requirements for mass production (low cost and user friendliness). Here we report the design and fabrication of a modular tubular flow system embedded with replaceable photocatalyst membranes for scalable photocatalytic C-C, C-N homocoupling and hydrogenation reactions, which can be operated in either circular and continuous flow mode with high performance. The photocatalyst membranes almost fully occupy the volume of the reactor, thus enabling optimal absorption of the incident light. Additionally, the porous structured photocatalyst membranes facilitate the mass transfer of the reactants to efficiently use the active sites, resulting in 0th -order reaction kinetics and a high space-time yield compared to the batch reaction system at practical application levels and prolonged reaction times.

Heterogeneous Photocatalytic Recycling of FeX2 /FeX3 for Efficient Halogenation of C-H Bonds Using NaX.

Environmental-friendly halogenation of C-H bonds using abundant, non-toxic halogen salts is in high demand in various chemical industries, yet the efficiency and selectivity of laboratory available protocols are far behind the conventional photolytic halogenation process which uses hazardous halogen sources. Here we report an FeX2 (X=Br, Cl) coupled semiconductor system for efficient, selective, and continuous photocatalytic halogenation using NaX as halogen source under mild conditions. Herein, FeX2 catalyzes the reduction of molecular oxygen and the consumption of generated oxygen radicals, thus boosting the generation of halogen radicals and elemental halogen for direct halogenation and indirect halogenation via the formation of FeX3 . Recycling of FeX2 and FeX3 during the photocatalytic process enables the halogenation of a wide range of hydrocarbons in a continuous flow, rendering it a promising method for applications.

Dioscin elicits anti-tumour immunity by inhibiting macrophage M2 polarization via JNK and STAT3 pathways in lung cancer.

Tumour-associated macrophage (TAM) is an important component in tumour microenvironment. Generally, TAM exhibits the function of M2-like macrophage, which was closely related to angiogenesis and tumour progression. Dioscin, a natural steroidal saponin, has shown its powerful anti-tumour activity recently. However, the mechanism of dioscin involved in immune regulation is still obscure. Here, we observed dioscin induced macrophage M2-to-M1 phenotype transition in vitro and inhibited IL-10 secretion. Meanwhile, the phagocytosis of macrophages was enhanced. In subcutaneous lung tumour models, dioscin inhibited the augmentation of M2 macrophage populations. Furthermore, dioscin down-regulated STAT3 and JNK signalling pathways in macrophages in vitro. In BMDMs, activating JNK and inhibiting STAT3 induce macrophages to M1 polarization while inhibiting JNK and activating STAT3 to M2 polarization. Additionally, condition mediums from dioscin-pre-treated macrophages inhibited the migration of 3LL cells and the tube-formation capacity of HUVECs. What's more, dioscin-mediated macrophage polarization inhibited the in vivo metastasis of 3LL cells. In conclusion, dioscin may act as a new anti-tumour agent by inhibiting TAMs via JNK and STAT3 pathways in lung cancer.

Crucial Roles of RSAD2/viperin in Immunomodulation, Mitochondrial Metabolism and Autoimmune Diseases.

Autoimmune diseases are typically characterized by aberrant activation of immune system that leads to excessive inflammatory reactions and tissue damage. Nevertheless, precise targeted and efficient therapies are limited. Thus, studies into novel therapeutic targets for the management of autoimmune diseases are urgently needed. Radical S-adenosyl methionine domain-containing 2 (RSAD2) is an interferon-stimulated gene (ISG) renowned for the antiviral properties of the protein it encodes, named viperin. An increasing number of studies have underscored the new roles of RSAD2/viperin in immunomodulation and mitochondrial metabolism. Previous studies have shown that there is a complex interplay between RSAD2/vipeirn and mitochondria and that binding of the iron-sulfur (Fe-S) cluster is necessary for the involvement of viperin in mitochondrial metabolism. Viperin influences the proliferation and development of immune cells as well as inflammation via different signaling pathways. However, the function of RSAD2/viperin varies in different studies and a comprehensive overview of this emerging theme is lacking. This review will describe the characteristics of RSAD2/viperin, decipher its function in immunometabolic processes, and clarify the crosstalk between RSAD2/viperin and mitochondria. Furthermore, we emphasize the crucial roles of RSAD2 in autoimmune diseases and its potential application value.

Copper Cocatalyst Modulated Radical Generation for Selective Heterogeneous Photosynthesis of α-Haloketones.

The α-haloketones are important precursors for synthetic chemistry and pharmaceutical applications; however, their production relies heavily on traditional synthetic methods via halogenation of ketones that are toxic and environmentally risky. Here, we report a heterogeneous photosynthetic strategy of α-haloketone production from aromatic olefins using copper-modified graphitic carbon nitride (Cu-C3N4) under mild reaction conditions. By employing NiX2 (X = Cl, Br) as the halogen source, a series of α-haloketones can be synthesized using atmospheric air as the oxidant under visible-light irradiation. In comparison with pristine carbon nitride, the addition of Cu as a cocatalyst provides a moderate generation rate of halogen radicals and selective reduction of molecular oxygen into •OOH radicals, thus leading to a high selectivity to α-haloketones. The Cu-C3N4 also exhibits high stability and versatility, rendering it a promising candidate for solar-driven synthetic applications.

Th22 Cells/IL-22 Serves as a Protumor Regulator to Drive Poor Prognosis through the JAK-STAT3/MAPK/AKT Signaling Pathway in Non-Small-Cell Lung Cancer.

The interaction of immune cells and cytokines in the tumor microenvironment affects the development and prognosis of tumors with an unclear potential regulatory mechanism. Recent studies have elucidated the protumor role of Th22 cells and its lineage-specific cytokine IL-22 in different human cancers. The present study is aimed at investigating the biological effect of Th22 cells/IL-22 and its molecular mechanism in the pathogenesis process of non-small-cell lung cancer (NSCLC). It was initially found that Th22 cells were enriched in the peripheral blood of NSCLC patients. The level of Th22 cells in peripheral blood mononuclear cells (PBMCs) was positively correlated with the TNM stage, lymph node metastasis, and clinical tumor biomarkers. Furthermore, IL-22 not only antagonized the apoptosis inducing and cell cycle arresting effect by chemotherapy and molecular targeted drugs on NSCLC cell lines but also promoted tumor cell proliferation and tumor tissue growth. Moreover, IL-22 activated the JAK-STAT3/MAPK/AKT signaling pathway, both in vitro and in vivo. Conclusively, the present results confirm that Th22 cells/IL-22 may serve as a negative immune regulator in lung cancer.

Peripheral Lung Squamous Carcinoma With ROS1 Rearrangement Sensitive to Crizotinib: A Case Report.

ROS1 rearrangements have been identified as driver mutations, accounting for 1-2% of lung adenocarcinoma, but are extremely rare in case of lung squamous cell carcinoma. In this work, we report a lung squamous cell carcinoma in a patient with peripheral lung cancer radiological manifestation, harboring ROS1 rearrangement, with high sensitivity to crizotinib. Our findings suggest that clinicians should pay more attention toward the occurrence of ROS1 rearrangements and the application of crizotinib for lung squamous cell carcinoma treatment.

Possible environmental exposure-associated pulmonary cryptococcosis in a patient with rheumatoid arthritis: a case report and literature review.

Patients with rheumatoid arthritis (RA) taking long-term immunosuppressive drugs are more susceptible to opportunistic infections, such as cryptococcosis. A 65-year-old woman was transferred to our hospital for rapidly progressing pulmonary lesions identified by lung computed tomography. She had a 7-year history of RA and had been prescribed methotrexate and glucocorticoids for 10 months. Additionally, our patient had a history of environmental exposure to house renovation lasting approximately 1 week before onset. Her serological test results and histopathological examination confirmed the diagnosis of pulmonary cryptococcosis (PC). The patient recovered well after 6 months of fluconazole treatment. In addition, we summarized 28 reported cases of RA patients with PC and found that older age might be a risk factor for cryptococcal infection in RA patients. The most common location for pulmonary lesions was the lower lobe, and the most common radiologic manifestations were nodules. Detection of cryptococcal capsular polysaccharide antigen was important for diagnosis. Patients undergoing antirheumatic therapy should avoid exposure to Cryptococcus.

Dioscin facilitates ROS-induced apoptosis via the p38-MAPK/HSP27-mediated pathways in lung squamous cell carcinoma.

Lung squamous cell carcinoma (SCC) is one of the deadliest cancers both in China and worldwide. To date, the efficacy of lung SCC treatments is limited. Recent studies have elucidated the powerful anti-tumour role of dioscin in different human cancers. Here, our study aims to investigate the effect of dioscin on lung SCC and its underlying mechanism. First, we found that dioscin not only inhibited cell proliferation and cell migration and induced cell apoptosis in lung SCC cells but also suppressed tumour growth in tumour-bearing mice. Furthermore, we noted that the accumulation of intracellular reactive oxygen species (ROS) was triggered by dioscin in lung SCC cells, leading to the phosphorylation of HSP27 through p38-MAPK and consequent cell apoptosis. The activation of p38-MAPK/HSP27 induced by the p38-MAPK activator Anisomycin enhanced the apoptosis of lung SCC cells, while the ROS inhibitor N-acetyl-L-cysteine (NAC) and the p38-MAPK inhibitor SB203580 both attenuated dioscin-mediated cell apoptosis. Moreover, NAC suppressed the activation of p38-MAPK/HSP27 that induced by dioscin. In conclusion, these results confirm that dioscin facilitates ROS-induced apoptosis via the p38-MAPK/HSP27-mediated pathway in lung SCC.