Palladium-Based Nanocomposites Remodel Osteoporotic Microenvironment by Bone-Targeted Hydrogen Enrichment and Zincum Repletion.

Osteoporosis presents a marked global public health challenge, characterized by deficient osteogenesis and a deteriorating immune microenvironment. Conventional clinical interventions primarily target osteoclast-mediated bone damage, yet lack a comprehensive therapeutic approach that balances bone formation and resorption. Herein, we introduce a bone-targeted nanocomposite, A-Z@Pd(H), designed to address these challenges by integrating diverse functional components.

Multiple topological states within a common bandgap of two non-trivial photonic crystals.

Topological photonic crystals (PCs) provide an effective method for controlling how light propagates and concentrates through their topological states. However, it remains unclear whether topological states can be obtained by combining two different two-dimensional (2D) PCs with topological non-trivial states. In this Letter, two types of 2D Penrose-square (P-S) PCs are proposed.

Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity.

Lipid nanoparticles (LNPs) can be designed to potentiate cancer immunotherapy by promoting their uptake by antigen-presenting cells, stimulating the maturation of these cells and modulating the activity of adjuvants. Here we report an LNP-screening method for the optimization of the type of helper lipid and of lipid-component ratios to enhance the delivery of tumour-antigen-encoding mRNA to dendritic cells and their immune-activation profile towards enhanced antitumour activity. The method involves screening for LNPs that enhance the maturation of bone-marrow-derived dendritic cells and antigen presentation in vitro, followed by assessing immune activation and tumour-growth suppression in a mouse model of melanoma after subcutaneous or intramuscular delivery of the LNPs.

Explainable prediction of daily hospitalizations for cerebrovascular disease using stacked ensemble learning.

Background: With the prevalence of cerebrovascular disease (CD) and the increasing strain on healthcare resources, forecasting the healthcare demands of cerebrovascular patients has significant implications for optimizing medical resources.

Methods: In this study, a stacking ensemble model comprised of four base learners (ridge regression, random forest, gradient boosting decision tree, and artificial neural network) and a meta learner (elastic net) was proposed for predicting the daily number of hospital admissions (HAs) for CD using the historical HAs data, air quality data, and meteorological data in Chengdu, China from 2015 to 2018. To solve the label imbalance problem, a re-weighting method based on label distribution smoothing was integrated into the meta learner.

An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues.

Complex 3D bioengineered tumour models provide the opportunity to better capture the heterogeneity of patient tumours. Patient-derived organoids are emerging as a useful tool to study tumour heterogeneity and variation in patient responses. Organoid cultures typically require a 3D microenvironment that can be manufactured easily to facilitate screening.

Real-time optical imaging of the hypoxic status in hemangioma endothelial cells during propranolol therapy.

Infantile hemangioma (IH) is the most common microvascular tumor of infancy involving the area of head and neck. One of the most important independent risk factors of IH is the hypoxia microenvironment. Fluorescent chemosensor provides a noninvasive intervention, high spatiotemporal resolution, ultrasensitive response, and real-time feedback approach to reveal the hypoxic status of cells.

The anti-tumor effect of proteasome inhibitor MG132 for human adenoid cystic carcinoma: correlate with the emerging role of Nrf2/Keap1 signaling pathway.

Background: Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. Moreover, the unique biological characteristics and complex structures of ACC contribute to its poor survival rates. Recently, proteasome inhibitors have been shown to elicit satisfactory therapeutic effects in the treatment of certain solid tumors, but few studies have been implemented to investigate the effects of proteasome inhibitor therapy for ACC.

Cognition and Social Behaviors Related to COVID-19 Among Students in Medical Colleges: A Cross-Sectional Study in Guangdong Province of China.

Background: The COVID-19 pandemic is a public health emergency of international concern. This study aimed to describe the cognition and social behaviors related to COVID-19 among medical college students in China and to explore the relevant factors that have affected individual social behaviors. The study could enrich practical research on the social behaviors of college students during the COVID-19 pandemic.

WTIP upregulates FOXO3a and induces apoptosis through PUMA in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive and heterogeneous clonal hematologic malignancy for which novel therapeutic targets and strategies are required. Emerging evidence suggests that WTIP is a candidate tumor suppressor. However, the molecular mechanisms of WTIP in leukemogenesis have not been explored.

Ultra-sensitive responsive near-infrared fluorescent nitroreductase probe with strong specificity for imaging tumor and detecting the invasiveness of tumor cells.

Hypoxia plays an important role in cancer progression, which is a characteristic feature of the tumor micro-environment and reflects the invasiveness of tumor cells. Nitroreductase (NTR) is overexpressed in hypoxic tumors, which making it an efficient target for detecting the hypoxic state in tumor. In this work, a new type of nitro-based fluorescent probe, named HNT-NTR, has been proposed, HNT-NTR could detect specifically and rapidly the NTR degree, which reflects the level of hypoxia in bidimensional (2D) tumor cells, three-dimensional (3D) tumor spheres and even the real tumors in vivo without biological toxicity.

18F-Choline PET Detected the Third Ventricle Craniopharyngioma.

Craniopharyngiomas are rare tumors of low histological malignancy (World Health Organization grade I) in the sellar and suprasellar region of the brain. We report a case of the third ventricular craniopharyngioma detected using 18F-choline PET/CT in a 43-year-old man. MRI of the brain revealed an intense gadolinium enhancement focus in the same area.

A microneedle platform for buccal macromolecule delivery.

Alternative means for drug delivery are needed to facilitate drug adherence and administration. Microneedles (MNs) have been previously investigated transdermally for drug delivery. To date, drug loading into MNs has been limited by drug solubility in the polymeric blend.

[Arctiin antagonizes triptolide-induced renal toxicity in rats via anti-inflammatory pathway].

Objective: To investigate the protective effect of arctiin with anti-inflammatory bioactivity against triptolide-induced nephrotoxicity in rats and explore the underlying mechanism.

Methods: Forty SD rats were divided into 4 groups for gastric lavage of normal saline, arctiin (500 mg/kg), triptolide (500 μg/kg), or both arctiin (500 mg/kg) and triptolide (500 μg/kg). Blood samples were collected for analysis of biochemical renal parameters, and the renal tissues were harvested for determining the kidney index and for pathological evaluation with HE staining.

Linalool inhibits the growth of human T cell acute lymphoblastic leukemia cells with involvement of the MAPK signaling pathway.

Linalool can inhibit the malignant proliferation of numerous human malignant solid tumors, including hepatocellular carcinoma, breast cancer, small cell carcinoma and malignant melanoma. However, the role of linalool in T cell acute lymphoblastic leukaemia (T-ALL) remains unclear. In the present study, human T-ALL cell lines (Jurkat, H9, Molt-4 and Raji cells) and peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with various concentrations of linalool (3.

A luminal unfolding microneedle injector for oral delivery of macromolecules.

Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort, show greater chemical stability at high temperatures, and do not generate biohazardous needle waste. An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract.

Homoharringtonine Combined with the Heat Shock Protein 90 Inhibitor IPI504 in the Treatment of FLT3-ITD Acute Myeloid Leukemia.

As a heterogeneous group of clonal disorders, acute myeloid leukemia with internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD) mutation usually shows an inferior prognosis. In the present study, we found that homoharringtonine (HHT), a protein translation inhibitor of plant alkaloid in China, exhibited potent cytotoxic effect against FLT3-ITD (+) cell lines and primary leukemia cells, and a remarkable synergistic anti-leukemia action was demonstrated in vitro and in vivo in xenograft mouse models when co-treated with the heat shock protein 90 inhibitor IPI504. Mechanistically, HHT combined with IPI504 synergistically inhibited the growth of leukemia cells by inducing apoptosis and G1 phase arrest.

Identification of the UBA2-WTIP fusion gene in acute myeloid leukemia.

Identifying and targeting oncogenic fusion genes have revolutionized the treatment of leukemia, such as PML-RARα fusion gene in acute promyelocytic leukemia. Here we identified an intrachromosomal fusion gene located on chromosome 19q.13 between UBA2 and WTIP gene in a case of acute myeloid leukemia.

Activation of CaMKIIγ potentiates T-cell acute lymphoblastic leukemia leukemogenesis via phosphorylating FOXO3a.

Ca/calmodulin-dependent protein kinase II γ (CaMKIIγ) can regulate the proliferation and differentiation of myeloid leukemia cells and accelerate chronic myeloid leukemia blast crisis, but the role of CaMKIIγ in T-cell acute lymphoblastic leukemia (T-ALL) leukemogenesis remains poorly understood. We observed that activated (autophosphorylated) CaMKIIγ was invariably present in T-ALL cell lines and in the majority of primary T-ALL samples. Overexpression of CaMKIIγ enhanced the proliferation, colony formation, tumorigenesis and increased DNA damage of T-ALL leukemia cells.

Identification of a novel RNA giant nuclear body in cancer cells.

Constitutive synthesis of oncogenic mRNAs is essential for maintaining the uncontrolled growth of cancer cells. However, little is known about how these mRNAs are exported from the nucleus to the cytoplasm. Here, we report the identification of a RNA giant nuclear body (RNA-GNB) that is abundant in cancer cells but rare in normal cells.

[Triptolide induces apoptosis of human acute T lymphocytic leukemia Jurkat cells via inhibiting transcription of human endogenous retrovirus HERV-K Np9 gene].

Objective: To investigate the molecular?mechanisms by which triptolide induces apoptosis of human acute T lymphocytic leukemia Jurkat cells.

Methods: MTT assay was employed to detect the proliferation inhibition of Jurkat cells by triptolide, and the IC50 was calculated by OriginPro8. Flow cytometry was used to analyze apoptosis of Jurkat cells.

Small-molecule induction of phospho-eIF4E sumoylation and degradation via targeting its phosphorylated serine 209 residue.

As phospho-eIF4E (p-eIF4E), unlike total eIF4E (t-eIF4E) essential for normal cells, is specifically required by cancer cells, it is an attractive, yet unrealized, target for anti-tumor intervention. Here we identify a small molecule, homoharringtonine (HHT), that antagonizes p-eIF4E function and eradicates acute myeloid leukemia (AML) expressing high level of p-eIF4E in vitro and in vivo. HHT selectively reduces p-eIF4E levels of leukemia cells without affecting t-eIF4E.

[The cloning expression, purification and activity of human angiostatin K (1-3) gene].

Objective: To clone the sequence of human Angiostatin cDNA and obtain the protein of recombinant angiostatin for further development.

Methods: Fresh human liver tissue was used for the extraction of total RNA and amplified the Angiostatin cDNA through RT-PCR method . After the recombinant plasmid pET30a-Angiostatin was constructed and confirmed, it was transduced into Rosetta (DE3).