Employing unnatural promiscuity of sortase to construct peptide macrocycle libraries for ligand discovery.

With the increasing attention paid to macrocyclic scaffolds in peptide drug development, genetically encoded peptide macrocycle libraries have become invaluable sources for the discovery of high-affinity peptide ligands targeting disease-associated proteins. The traditional phage display technique of constructing disulfide-tethered macrocycles by cysteine oxidation has the inherent drawback of reduction instability of the disulfide bond. Chemical macrocyclization solves the problem of disulfide bond instability, but the involved highly electrophilic reagents are usually toxic to phages and may bring undesirable side reactions.

Umbilical cord blood-derived neutrophils possess higher viability than peripheral blood derived neutrophils.

Neutrophils, a primary type of immune cell, play critical roles in numerous biological processes. Both umbilical cord blood (UCB) and peripheral blood are rich in neutrophils. UCB is more abundant than peripheral blood, with cells generally at a more immature stage.

Molecular imaging reveals the heterogeneous progression of tumor cells and tumor stroma: a practice of FDG PET and FAPI PET in diagnosing PSMA-negative bone metastases of progressive prostate cancer.

Tumors are often with complex and heterogeneous biological processes, such as glycometabolism and fibrosis, which are the main biochemical pathways that determine therapeutic effects. Specifically, this study aims to assess the diagnosing performance of F-FDG and Ga-FAPI-04 PET for different stages of progressive bone metastases with PSMA-negative pathology. Bone metastatic mouse model of prostate cancer was constructed via intra-bone injection of PSMA-negative prostate cancer PC3 cells.

The critical roles of lnc-GLYATL2-2/PD-L1 axis in immune microenvironment and the clinical value of intracranial chordomas.

Intracranial chordomas (ICs) are associated with a poor prognosis due to low total resection rates and high recurrence rates. However, the role of immunotherapy in ICs remains unknown. RNA sequencing and immunohistochemical staining were performed on IC tissues and normal tissues, and the long noncoding RNA (lncRNA) lnc-GLYATL2-2 was identified.

Changes in transepithelial electrical resistance and intracellular ion concentration in TGF-β-induced epithelial-mesenchymal transition of retinal pigment epithelial cells.

Objective: This study aimed to investigate the changes in transepithelial electrical resistance (TEER) and ion concentrations, and their relationship in TGF-β-induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells.

Methods: RPE cell line ARPE-19 was employed and treated with 10 ng/ml TGF-β1 and TGF-β2 to establish the EMT model . The EMT markers fibronectin, N-cadherin, occludin, zona occludens 1(ZO-1) and claudin-19 were investigated by western blot and immunofluorescence.

A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling.

Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of clonal plasma cells. Based on the organic drug osalmid, the novel small molecule compound DCZ0858 was designed and synthesized for treating MM. DCZ0858 inhibited the proliferation and activity of MM cells and reduced colony formation.

Basic approaches, challenges and opportunities for the discovery of small molecule anti-tumor drugs.

Chemotherapy is one of the main treatments for cancer, especially for advanced cancer patients. In the past decade, significant progress has been made with the research into the molecular mechanisms of cancer cells and the precision medicine. The treatment on cancer patients has gradually changed from cytotoxic chemotherapy to precise treatment strategy.

Dual Size/Charge-Switchable Nanocatalytic Medicine for Deep Tumor Therapy.

Elevating intratumoral levels of highly toxic reactive oxygen species (ROS) by nanocatalytic medicine for tumor-specific therapy without using conventional toxic chemodrugs is recently of considerable interest, which, however, still suffers from less satisfactory therapeutic efficacy due to the relatively poor accumulation at the tumor site and largely blocked intratumoral infiltration of nanomedicines. Herein, an ultrasound (US)-triggered dual size/charge-switchable nanocatalytic medicine, designated as Cu-LDH/HMME@Lips, is constructed for deep solid tumor therapy via catalytic ROS generations. The negatively charged liposome outer-layer of the nanomedicine enables much-prolonged blood circulation for significantly enhanced tumoral accumulation, while the positively charged Fenton-like catalyst Cu-LDH released from the liposome under the US stimulation demonstrates much enhanced intratumoral penetration via transcytosis.

Paving the way for small-molecule drug discovery.

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins, which have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. As commonly used medications, small-molecule drugs can be taken orally, which enter cells to act on intracellular targets.

Systematic analysis using a bioinformatics strategy identifies SFTA1P and LINC00519 as potential prognostic biomarkers for lung squamous cell carcinoma.

Lung cancer has high incidence and mortality rates, in which lung squamous cell carcinoma (LUSC) is a primary type of non-small cell lung carcinoma (NSCLC). The aim of our study was to discover long non-coding RNAs (lncRNAs) associated with diagnose and prognosis for LUSC. RNA sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database (TCGA).

Tumor microenvironment triggered biodegradation of inorganic nanoparticles for enhanced tumor theranostics.

Inorganic nanoparticles (NPs)-mediated tumor theranostics have attracted widespread attention due to their unique physicochemical properties, such as optical, electrical, magnetic, and thermal properties. In the past decade, great advancements have been made in inorganic NPs-associated drug delivery, multimodal tumor imaging, and tumor therapy. However, the potential toxicity of inorganic NPs due to their low biodegradability, background signals interference and treatment side effects limit their clinical application.

Auger Electrons Constructed Active Sites on Nanocatalysts for Catalytic Internal Radiotherapy.

Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (I) are used in situ to construct active sites in a nanocatalyst (TiO) and the application of this method is further extended to cancer catalytic internal radiotherapy (CIRT).

The mineralization, drug release and bone defect repair properties of calcium phosphates/PLA modified tantalum scaffolds.

Calcium phosphate based biomaterials have been widely studied in biomedical areas. Herein, amorphous calcium phosphate (ACP) nanospheres and hydroxyapatite (HA) nanorods were separately prepared and used for coating tantalum (Ta) scaffolds with a polymer of polylactide (PLA). We have found that different crystal phases of calcium phosphate coated on Ta scaffolds displayed different effects on the surface morphologies, mineralization and bovine serum albumin (BSA) release.

Neuropathic pain releasing calcitonin gene related peptide protects against stroke in rats.

Neuropathic pain (NPP) is deemed as a potential risk of stroke; however, recent pieces of evidence showed that calcitonin gene-related peptide is involving in pain progression as well as organ protection. The mechanisms underlying the neuroprotection of calcitonin gene-related peptide are yet poorly described with respect to stroke. The present study showed that the elevated level of calcitonin gene-related peptide-induced by NPP exerts a protective effect against stroke in rats, which was further confirmed in vivo and vitro via mitigation of inflammatory response, inhibition of neuronal cell apoptosis, and increase in regional cerebral blood flow.

Nanomedicine-Enabled Photonic Thermogaseous Cancer Therapy.

Local photothermal hyperthermia for tumor ablation and specific stimuliresponsive gas therapy feature the merits of remote operation, noninvasive intervention, and in situ tumor-specific activation in cancer-therapeutic biomedicine. Inspired by synergistic/sequential therapeutic modality, herein a novel therapeutic modality is reported based on the construction of two-dimensional (2D) core/shell-structured NbC-MSNs-SNO composite nanosheets for photonic thermogaseous therapy. A phototriggered thermogas-generating nanoreactor is designed via mesoporous silica layer coating on the surface of NbC MXene nanosheets, where the mesopores provide the reservoirs for NO donor (S-nitrosothiol (RSNO)), and the core of NbC produces heat shock upon second near-infrared biowindow (NIR-II) laser irradiation.

Light-Addressable Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Enhanced and Dynamic Magnetic Resonance Imaging of Arthritis.

Design of novel nanoplatforms with single imaging elements for dynamic and enhanced / -weighted magnetic resonance (MR) imaging of diseases still remains significantly challenging. Here, a facile strategy to synthesize light-addressable ultrasmall FeO nanoparticles (NPs) that can form nanoclusters (NCs) under laser irradiation for enhanced and dynamic / -weighted MR imaging of inflammatory arthritis is reported. Citric acid-stabilized ultrasmall FeO NPs synthesized via a solvothermal approach are linked with both the arthritis targeting ligand folic acid (FA) and light-addressable unit diazirine (DA) via polyethylene glycol (PEG) spacer.

Preparation of porous calcium phosphate microspheres with phosphate-containing molecules at room temperature for drug delivery and osteogenic differentiation.

Calcium phosphate (CaP) has similar chemical properties to those of the inorganic component of human bone tissue, for potential application in drug delivery for the chemotherapy of osteosarcoma. In this work, CaP with a porous microsphere structure has been synthesized using fructose-1,6-bisphosphate (FBP) as the phosphorus source by a simple wet-chemical strategy at room temperature. The CaP porous microspheres, as an organic-inorganic hybrid nano-platform, exhibit good doxorubicin (Dox) loading capacity, and Dox-loading CaP, enhancing the chemotherapy of osteosarcoma cells.

Tumor-suppressive microRNA-195-5p regulates cell growth and inhibits cell cycle by targeting cyclin dependent kinase 8 in colon cancer.

MicroRNAs (miRNAs) are key regulators in gene expression. Dysregulation of them in cancer development have been attracting increasing attention. The purpose of this study was to investigate the potential role of miR-195-5p in colon cancer (CC) biology.

Influences of continuous femoral nerve block on knee function and quality of life in patients following total knee arthroplasty.

Objective: Continuous femoral nerve block (CFNB), guided by ultrasound combined nerve stimulations, offers advantages for both sides and provides effective postoperative analgesia after total knee arthroplasty (TKA). The objective of this study was to evaluate the medium-term impact of continuous femoral nerve block on knee function and quality of life in patients following TKA.

Methods: This was a follow-up study.

The diagnosis value of acoustic radiation force impulse (ARFI) elastography for thyroid malignancy without highly suspicious features on conventional ultrasound.

Objective: The aim of this study was to evaluate the potential diagnostic performance of acoustic radiation force impulse (ARFI) elastography in identifying malignancy in nodules that do not appear highly suspicious on conventional ultrasound (US).

Methods: 330 pathologically confirmed thyroid nodules (40 malignant and 290 benign; mean size, 22.0±11.

Comparison of bupivacaine and parecoxib for postoperative pain relief after laparoscopic cholecystectomy: a randomized controlled trial.

Background: Pain is the most common complaint of patients on the first day after laparoscopic cholecystectomy (LC). The aim of this study was to compare the efficacy of local anesthesia with bupivacaine and intravenous parecoxib on postoperative abdominal pain relief up to 24 h after surgery.

Methods: One hundred and eighty patients who underwent LC were randomized to one of three groups with sixty patients each: Group A received 50 mg 0.

Clinical, pathological and sonographic characteristics of unexpected gallbladder carcinoma.

Objectives: To investigate the clinical, pathological, and sonographic characteristics of unexpected gallbladder carcinoma (UGC).

Methods: Of 5424 patients who had undergone cholecystectomy from December 2006 to October 2013, 54 patients with primary gallbladder carcinomas confirmed by pathological diagnosis were identified. The patients were divided into two groups: diagnosed before operation (n=34) and UGC groups (n=20), of whom the clinical, pathological, and sonographic characteristics were compared.

Acoustic radiation force impulse induced strain elastography and point shear wave elastography for evaluation of thyroid nodules.

The aim of the study was to evaluate the diagnostic performance of acoustic radiation force impulse (ARFI) induced strain elastography (SE), point shear wave elastography (p-SWE), and their combined use in differentiating thyroid nodules. This retrospective study included 155 thyroid nodules (94 benign and 61 malignant) in 136 patients. Ultrasound, ARFI-induced SE and p-SWE were performed on each nodule.

A novel two-dimensional quantitative shear wave elastography for differentiating malignant from benign breast lesions.

Objective: The purpose of this study was to evaluate the diagnostic performance of a novel quantitative shear wave elastography (SWE) of virtual touch tissue imaging quantification (VTIQ) in diagnosis of breast lesions.

Methods: The conventional ultrasound (US) and VTIQ images of 133 pathologically proven breast lesions in 98 patients were assessed. The breast lesions were classified by US breast imaging reporting and data system (BI-RADS) category.