A zebrafish NLRX1 isoform downregulates fish IFN responses by targeting the adaptor STING.

In mammals, NLRX1 is a unique member of the nucleotide-binding domain and leucine-rich repeat (NLR) family showing an ability to negatively regulate IFN antiviral immunity. Intron-containing genes, including NLRX1, have more than one transcript due to alternative splicing; however, little is known about the function of its splicing variants. Here, we identified a transcript variant of NLRX1 in zebrafish (Danio rerio), termed NLRX1-tv4, as a negative regulator of fish IFN response.

[Exploration of the diagnosis and treatment for benign prostatic hyperplasia with acupuncture based on theory].

Benign prostatic hyperplasia is caused by kidney deficiency and impaired transformation of the urinary bladder and is manifested by the stagnation of essence chamber. Based on (muscle region of meridian, sinew/fascia) theory and taking the visceral membrane as the principal, acupuncture is delivered at sinew/fascia to promote circulation, resolve stasis and open the orifice. Guided by CT, the needle is inserted at Zhongji (CV 3), the front- point of the urinary bladder, and then goes to the prostatic capsule, meaning "the disease of organ is treated by needling the front- point".

Idiopathic hypereosinophilic syndrome with hepatic sinusoidal obstruction syndrome: A case report and literature review.

Background: Hypereosinophilic syndrome (HES) is classified as primary, secondary or idiopathic. Idiopathic HES (IHES) has a variable clinical presentation and may involve multiple organs causing severe damage. Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by damage to the endothelial cells of the hepatic sinusoids of the hepatic venules, with occlusion of the hepatic venules, and hepatocyte necrosis.

Yellow catfish RIO kinases (RIOKs) negatively regulate fish interferon-mediated antiviral response.

In mammals, right open reading frame kinases (RIOKs) are initially reported to participate in cancer cell proliferation, apoptosis, migration and invasion, and recently they have been related to host immune response. Little is known about the homologs of RIOKs in fish. In the current study, we cloned three homologous genes of RIOK family in yellow catfish (Pelteobagrus fulvidraco), termed Pfriok1, Pfriok2 and Pfriok3.

Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development.

Building on our previous work on ibrutinib-based reversible covalent Bruton's tyrosine kinase (BTK) PROTACs, we explored a different irreversible BTK inhibitor poseltinib as the BTK binder for PROTAC development. Different from ibrutinib, converting the irreversible cysteine reacting acrylamide group of poseltinib to a reversible covalent cyano-acrylamide group dramatically decreases the binding affinity to BTK by over 700 folds. Interestingly, one of the reversible covalent BTK PROTACs based on poseltinib with a rigid linker, dubbed as PS-RC-1, is highly potent (IC = ~10 nM) in Mino cells but not in other mantle cell lymphoma (MCL) cell lines, such as Jeko-1 and Rec-R cells.

[Application characteristics of Qugu (CV 2) in ancient and modern literature].

To summarize and analyze the clinical application characteristics of Qugu (CV 2) in ancient and modern literature based on data mining technology. The (the 5th edition) was taken as the retrieval source of ancient literature, while the CNKI, Wanfang, and VIP databases were taken as the retrieval source of modern literature. The indications of Qugu (CV 2) used alone or with compatible acupoints, compatible acupoints, acupuncture-moxibustion manipulation, etc.

Zebrafish MARCH8 downregulates fish IFN response by targeting MITA and TBK1 for protein degradation.

Recent studies have related the membrane-associated RING-CH-type finger (MARCH) family proteins to host innate immune response. Zebrafish (Danio rerio) MARCH8 is reported to target SVCV glycoprotein for degradation; however, little is known about whether fish MARCH8 is involved in innate interferon (IFN) response. In this study, zebrafish march8 was significantly induced by SVCV infection.

Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response.

Interferon regulatory factors (IRFs) constitute a family of transcription factors that synchronize interferon (IFN) antiviral response through translocating to nucleus and binding to the promoters of IFN and IFN-stimulated genes (ISGs). Fish contain 11 IRF members; however, whether or how fish IRF family genes function in IFN response remains limited. Herein, we determine the regulatory roles of 11 zebrafish IRF family members in IFN response relevant to their subcellular localization and promoter binding.

Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry.

Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton's Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs.

[Effect of outer membrane vesicles derived from Escherichia coli on proliferation, apoptosis and migration of human neuroblastoma SK-N-SH cells in vitro].

Objective: To investigate the effect of outer membrane vesicles derived from Escherichia coli on proliferation, apoptosis and migration of human neuroblastoma SK-N-SH cells in vitro.

Methods: The outer membrane vesicles (OMVs) were obtained from wild-type Escherichia coli with ultracentrifugation method, and the morphology of the OMVs was observed by transmission electron microscopy and the vesicle diameter was determined using MALVERN ZEN3690. Human neuroblastoma SK-N-SH cells were treated with the OMVs at low (100 µg/mL), moderate (500 µg/mL) and high (1000 µg/mL) doses, and 24, 48 and 72 h later, the cell proliferation activity was detected with MTT assay.

Difluoromethylation of (hetero)aryl chlorides with chlorodifluoromethane catalyzed by nickel.

Relatively low reactivity hinders using chlorodifluoromethane (ClCFH) for general difluoromethylation with organic molecules, despite its availability as an inexpensive industrial chemical. To date, transformations of ClCFH are very limited and most of them involve difluorocarbene intermediate. Here, we describe a strategy for difluoromethylation of aromatics through nickel-catalyzed cross-coupling of ClCFH with readily accessible (hetero)aryl chlorides.

Intra-arterial ethanol embolization augments response to TACE for treatment of HCC with portal venous tumor thrombus.

Background: The prognosis of hepatocellular carcinoma with portal vein tumor thrombus remains extremely poor. This pilot study aimed to evaluate the technical feasibility, effectiveness and safety of transcatheter chemoembolization for tumors in the liver parenchyma plus intra-arterial ethanol embolization for portal vein tumor thrombus.

Methods: A pilot study was carried out on 31 patients in the treatment group (transcatheter chemoembolization plus intra-arterial ethanol embolization) and 57 patients in the control group (transcatheter chemoembolization alone).

A genetic variant in long non-coding RNA MALAT1 associated with survival outcome among patients with advanced lung adenocarcinoma: a survival cohort analysis.

Background: Recently studies have demonstrated that the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) may participate in the development and progression of lung cancer. In this study, we hypothesized that genetic variant of this lncRNA may affect the prognosis of lung cancer patients.

Methods: We conducted a follow-up study for 538 patients with non-small cell lung carcinoma (NSCLC), including 140 early-staged (stage I and II) and 398 advanced staged (stage III and IV) patients.

CT-guided I seed implantation for inoperable retroperitoneal sarcoma: A technique for delivery of local tumor brachytherapy.

Radical surgery is currently the first treatment of choice for retroperitoneal soft tissue sarcoma (RSTS). However, the prognosis of RSTS remains poor due to ineffective local control and a high incidence of metastasis after surgical resection. Brachytherapy has been shown to safely provide local radiotherapy for numerous types of cancer when used alone or in combination with surgical resection, but has not been well characterized in the management of RSTS.

CT-guided biopsy for Langerhans cell histiocytosis of the atlas: a case report and literature review.

Langerhans cell histiocytosis (LCH) is a rare disease, and involvement of the atlas is extremely uncommon. Biopsy of atlas lesions is difficult and risky. In this case report, we describe the performance of percutaneous computed tomography-guided biopsy of an atlantal LCH in a patient with no complication.

Mesenchymal stem cells generate pericytes to promote tumor recurrence via vasculogenesis after stereotactic body radiation therapy.

Background: Stereotactic body radiation therapy (SBRT) is postulated to enhance the recruitment of mesenchymal stem cells (MSCs) into the tumor microenvironment, which promote tumor recurrence. The aim of this study is to determine the molecular mechanisms behind SBRT stimulating MSC migration and differentiation.

Methods: In vitro, mediated factors and migrated MSCs (post-SBRT) were generated.

Rhodium-Catalyzed ortho-Selective C-F Bond Borylation of Polyfluoroarenes with Bpin-Bpin.

An ortho-selective C-F bond borylation between N-heterocycle-substituted polyfluoroarenes and Bpin-Bpin with simple and commercially available [Rh(cod)2 ]BF4 as a catalyst is now reported. The reaction proceeds under mild reaction conditions with high efficiency and broad substrate scope, even toward monofluoroarene, thus providing a facile access to a wide range of borylated fluoroarenes that are useful for photoelectronic materials. Preliminary mechanistic studies reveal that a Rh(III/V) catalytic cycle via a key intermediate rhodium(III) hydride complex [(H)Rh(III) Ln (Bpin)] may be involved in the reaction.

Radiofrequency ablation versus percutaneous ethanol injection for hepatocellular carcinoma: a meta-analysis of randomized controlled trials.

Background: Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) are treatment methods for patients with early-stage hepatocellular carcinoma (HCC) who are not suitable for surgery. Although some reports indicate that RFA is better than PEI, results from previous reviews and analyses are inconsistent. Therefore, this meta-analysis was performed to more thoroughly evaluate the effects of these treatments in patients with HCC.

Targeting pyruvate kinase M2 contributes to radiosensitivity of non-small cell lung cancer cells in vitro and in vivo.

Aerobic glycolysis, a metabolic hallmark of cancer, is associated with radioresistance in non-small cell lung cancer (NSCLC). Pyruvate kinase M2 isoform (PKM2), a key regulator of glycolysis, is expressed exclusively in cancers. However, the impact of PKM2 silencing on the radiosensitivity of NSCLC has not been explored.

Nickel-catalyzed cross-coupling of functionalized difluoromethyl bromides and chlorides with aryl boronic acids: a general method for difluoroalkylated arenes.

Transition-metal-catalyzed difluoroalkylation of aromatics remains challenging despite the importance of difluoroalkylated arenes in medicinal chemistry. Herein, the first successful example of nickel-catalyzed difluoroalkylation of aryl boronic acids is described. The reaction allows access to a variety of functionalized difluoromethyl bromides and chlorides, and paves the way to highly cost-efficient synthesis of a wide range of difluoroalkylated arenes.

Highly selective gem-difluoroallylation of organoborons with bromodifluoromethylated alkenes catalyzed by palladium.

A first example of Pd-catalyzed gem-difluoroallylation of organoborons using 3-bromo-3,3-difluoropropene (BDFP) in high efficiency with high α/γ-substitution regioselectivity has been developed. The reaction can also be extended to substituted BDFPs and has advantages of low catalyst loading (0.8 to 0.

Rapid increase of serum neuron specific enolase level and tachyphylaxis of EGFR-tyrosine kinase inhibitor indicate small cell lung cancer transformation from EGFR positive lung adenocarcinoma?

We report the case of an 80-year-old male with relapsed EGFR exon 19 deletion lung adenocarcinoma treated with EGFR-tyrosine kinase inhibitor (TKI), but with poor response and rapid increase of serum neuron specific enolase (NSE). Repeat biopsy identified pathological transformation to small cell lung cancers (SCLC) retaining the same EGFR mutation. This case highlights routine serological testing of NSE may benefit for the lung adenocarcinoma patients resistant to TKIs.

Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: experimental and clinical evidence.

Purpose: This study aimed to examine the effect of the novel recombinant human endostatin (rh-Endo) protein on tumor vasculature, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT).

Methods: Tumor-perfusion parameters and hypoxia were monitored after rh-Endo treatment in 10 non-small cell lung-cancer (NSCLC) patients. Eight-week female C57BL/6J mice were randomized to receive rh-Endo or control (saline) once daily for 12 days when Lewis lung carcinoma (LLC) reached approximately 100-150 mm(3).

CT-guided percutaneous vertebroplasty of the upper cervical spine via a translateral approach.

Background: The clinical management of spinal hemangiomas and osteolytic metastases involving the upper cervical spine (C1-C3) is challenging. Symptoms vary from simple vertebral pain to progressive neurological deficits. Surgery and radiotherapy have been the treatment options for years.