Discovery and preclinical evaluations of TQB3616, a novel CDK4-biased inhibitor.

Among small-molecule CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) approved for metastatic breast cancers, abemaciclib has a more tolerable adverse effects in clinic. This is attributable to preferential inhibition of CDK4 over CDK6. In our search for a biased CDK4 inhibitor, we discovered a series of pyrimidine-indazole inhibitors.

Automatically optimized radiomics modeling system for small gastric submucosal tumor (<2 cm) discrimination based on EUS images.

Background And Aims: The clinical management of small gastric submucosal tumors (SMTs) (<2 cm) faces a non-negligible challenge because of the lack of guideline consensus and effective diagnostic tools. This article develops an automatically optimized radiomics modeling system (AORMS) based on EUS images to diagnose and evaluate SMTs.

Methods: A total of 205 patients with EUS images of small gastric SMTs (<2 cm) were retrospectively enrolled in the development phase of AORMS for the diagnosis and the risk stratification of GI stromal tumor (GIST).

Endoscopic full-thickness resection, indication, methods and perspectives.

Minimally invasive surgery has emerged as the dominant theme of modern surgery, in which endoscopic surgery plays a key role. The technique of endoscopic surgery has evolved continuously with extensive research, improving the treatment modalities as well as expanding the indications for its use. As an active perforation endoscopic technique, endoscopic full-thickness resection (EFTR) is mainly used in the treatment of submucosal tumors (SMTs) of the gastrointestinal tract.

Evaluation of skin-on goat meat processing on processing efficiency, carcass yield, meat quality, and sensory attributes.

The objective of this study was to evaluate the properties of skin-on and skin-off goat processing and carcasses for processing efficiency, fabrication time, biochemical factors, and sensory attributes for stewed goat meat. Thirty-one goats were harvested in 2 separate experiments, either skin-on (n = 16) or off (n = 15). The carcasses were fabricated into four primals and each primal was cut into cubes.

Heat Shock Protein Beta 1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most serious malignancies. The main features of HCC are vascular invasion and drug resistance. Ferroptosis is a novel cell program that is involved in several diseases, such as cancer.

Puerarin Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis in Mice by Inhibiting JAKs.

Intestinal mucositis resulting from 5-fluorouracil (5-FU)-based chemotherapy subjects patients to great pain and hampers cancer treatment progress. Puerarin, the major active ingredient in , exerts anti-inflammatory and antioxidative effects. However, whether puerarin has an effect on 5-FU-induced intestinal mucositis remains unknown.

Targeting JAK/STAT signaling pathways in treatment of inflammatory bowel disease.

Janus kinase/signal transduction and transcriptional activator (JAK/STAT) signaling pathway is a transport hub for cytokine secretion and exerts its effects. The activation of JAK/STAT signaling pathway is essential for the regulation of inflammatory responses. Inappropriate activation or deletion of JAK/STAT signaling pathway is the initiator of the inflammatory response.

Enhancing TNBC Chemo-immunotherapy via combination reprogramming tumor immune microenvironment with Immunogenic Cell Death.

Tumor-associated fibroblasts (TAFs) play an important role in tumor progression and therapeutic response, especially in the immunosuppressive tumor microenvironment (TME). To remodel immunosuppressive TME of 4T1 tumor, we developed a nano liposome to deliver silybin (SLN, an anti-liver fibrosis Chinese Traditional Medicine). Liposomal silybin (SLN/LIP) possessed a spherical shape with particle sizes of 75.

[Effects of the construction of fertile and cultivated upland soil layer on soil fertility and maize yield in black soil region in Northeast China.].

Organic amendment return could enhance soil fertility, improve soil structure, and increase crop yield. However, how construction of soil layers can affect soil fertility and crop yield are not fully understood. We examined the effects of constructions of fertile and cultivated soil layer on soil fertility and maize yield in the upland black soil region in Northeast China, to provide theoretical guidance in increasing soil fertility and sustainable development of agriculture.

Folate Modified Long Circulating Nano-Emulsion as a Promising Approach for Improving the Efficiency of Chemotherapy Drugs in Cancer Treatment.

Purpose: In order to improve the therapeutic efficiency of the chemotherapeutic drug paclitaxel in tumors, a folate-based Paclitaxel nanoemulsion (FNEs) was developed for tumor targeted treatment.

Methods: In this study, we designed a folate-targeted nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) based on the traditional nanoemulsion using the principle of long-circulation targeting receptor mediated. The nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) was fabricated using high-pressure homogenization with a microfluidizer.

Tumor Microenvironment Stimuli-Responsive Nanoparticles for Programmed Anticancer Drug Delivery.

It is well-known that large size nanoparticles stay for a long time in the circulation system, but show poor tissue penetration and low cellular uptake. In order to reconcile the conflicting needs for extended circulation time, extensive tumor tissue penetration, and enhanced cellular uptake for nanodrug delivery systems, we designed DOX-containing hypersensitive nanoparticles that responded to the tumor microenvironment for programmed DOX delivery. A supersensitive polymer material, poly(2-ethyl-2-oxazoline)-poly(methacryloyl sulfadimethoxine), was synthesized (PEOz--PSD, p = 6.

An Effective Cationic Human Serum Albumin-Based Gene-Delivery Carrier Containing the Nuclear Localization Signal.

Considerable effort has been devoted to the development of gene carriers over the years. However, toxicity, immunogenicity, and low transfection efficiency are still major barriers. How to overcome these obstacles has become a burning question in gene delivery.

A novel disulfide bond-mediated cleavable RGD-modified PAMAM nanocomplex containing nuclear localization signal HMGB1 for enhancing gene transfection efficiency.

Background: Polyamidoamine (PAMAM) dendrimers modified by polyethylene glycol (PEG) have frequently been investigated as a delivery carrier for gene therapy. However, modification of PAMAM with PEG using covalent linkage significantly reduces the cellular uptake rate and the transfection efficiency. How to conquer these barriers becomes a burning question in gene delivery.

Adenovirus‑mediated knockdown of activin A receptor type 2A attenuates immune‑induced hepatic fibrosis in mice and inhibits interleukin‑17‑induced activation of primary hepatic stellate cells.

Fibrosis induces a progressive loss of liver function, thus leading to organ failure. Activins are secreted proteins that belong to the transforming growth factor (TGF)‑β superfamily, which initiate signaling by binding to their two type II receptors: Activin A receptor type 2A (ACVR2A) and activin A receptor type 2B. Previous studies that have explored the mechanisms underlying immune‑induced hepatic fibrosis have mainly focused on TGF‑β signaling, not activin signaling.

Chemically modified heparin inhibits in vitro L-selectin-mediated human ovarian carcinoma cell adhesion.

Accumulating evidence indicates that hematogenous metastasis is facilitated by tumor cell-leukocyte emboli formation, and L-selectin plays a major role in the process. Several independent studies have indicated that tumor metastasis can be inhibited by chemically modified heparin with low anticoagulant activity in the different tumor models. In the present study, we demonstrated that chemically modified nonanticoagulation heparin derivate (periodate-oxidized, borohydride-reduced heparin [RO-heparin]) can inhibit the binding of L-selectin to HO-8910 cells, block the adhering of HO-8910 to Chinese hamster ovary cells expressing a transfected human L-selectin complementary DNA, and affect the interactions of neutrophils with HO-8910 cells.

[Prophylactic immunization of dangguibuxue decoction against Cryptosporidium infection in immune suppressed mice].

Objective: To explore the prophylaxis of dangguibuxue decoction, a traditional Chinese medicine made from Angelica sinensis and Radix astragalus, on immunosuppressed mice infected by Cryptosporidium parvum.

Methods: 48 BALB/c mice were randomly divided into 4 groups: normal control (A), immunosuppressed control (B), high dose (C), and low dose (D). Mice in groups B, C and D were intragastrically administered with dexamethasone (DXM) for 8 days, and in the same time mice in groups C and D were given high dose (2 g/kg) and low dose (1 g/kg) dangguibuxue decoction respectively.

[Effect of yupingfengsan on the growth of tumor and immunological function in tumor-bearing mice].

Aim: To explore the effect of yupingfengsan on the growth of tumor and immunological function in tumor-bearing mice.

Methods: The models of tumor-bearing mice were established by inoculating the healthy mice with S180 tumor carneus cells cultured in vitro. Then the ratio of tumor restriction was calculated.