Trametinib and M17, a novel small molecule inhibitor of AKT, display a synergistic antitumor effect in triple negative breast cancer cells through the AKT/mTOR and MEK/ERK pathways.

Triple negative breast cancer (TNBC) is associated with a poor prognosis and limited response to traditional chemotherapy, necessitating the exploration of novel treatment approaches. Recent researches have highlighted the interconnected roles of the PI3K/AKT pathway and MAPK pathway in TNBC cells, contributing to the efficacy of treatments. Therefore, the concurrent inhibition of both pathways presents a potential new therapeutic strategy for TNBC patients.

Macrocycle-based self-assembled amphiphiles for co-delivery of therapeutic combinations to tumor.

For tumor treatment, the efficiency of single chemotherapeutic agent is generally limited and the traditional combination chemotherapies frequently result in the aggravation of side effects. Herein, an amphiphilic pillararene-based self-assembled nanoparticle (APSN) composed of hydrazide-pillar[5]arene (HP5A-6C) that achieve effective co-delivery of therapeutic combinations was reported. Through integrating multitudinous macrocyclic cavities into a single nanoparticle, the APSN could co-load two antitumor drugs, cisplatin (CP) and nitrogen mustard (NM) via host-guest interactions.

A giant macrocycle overcomes the post-treatment phototoxicity of photofrin through host-guest complexation.

Here we reported a supramolecular sequestration strategy to overcome the post-treatment phototoxicity of photofrin direct host-guest complexation. Efficient recognition potency of a giant pentaphen[3]arene derivative could favor suppressing sunlight-induced skin damage through weakening the ability of complexed photofrin to generate singlet oxygen.

Modifiable and non-modifiable risk factors of early-onset colorectal cancer: National Health Interview Survey analysis.

Background And Aims: Although the incidence of colorectal cancer (CRC) diagnosed in individuals younger than 50 years, early-onset CRC (EO-CRC), is rapidly increasing, the risk factors for EO-CRC are still being identified. This study aimed to confirm the modifiable and non-modifiable characteristics identified as risk factors for EO-CRC.

Methods: This cross-sectional study used 2004-2018 National Health Interview Survey (NHIS) data, which provides comprehensive health information gathered from national annual household interview surveys.

Macrocyclic Neutralizer to Polybrene Direct Host-Guest Complexation.

Hexadimethrine bromide (HB), a synthetic polycationic species, was introduced to clinical practice as a heparin antidote and recently used in gene therapy. However, HB causes various complications such as severe red blood cells (RBCs) aggregation and tissue damage. Herein, we have synthesized a water-soluble quaterphen[3]arene containing multiple sulfonate moieties (SQP3) as a novel macrocyclic neutralizer to reverse HB direct host-guest complexation.

Imidazolyl Lipids Enhanced LNP Endosomal Escape for Ferroptosis RNAi Treatment of Cancer.

Treatments for cancer that incorporate small interfering RNA (siRNA) to target iron-dependent ferroptosis are thought to be highly promising. However, creating a reliable and clinically feasible siRNA delivery system continues to be a major obstacle in the field of cancer treatment. Here, three imidazole-based ionizable lipid nanoparticles (LNPs) with pH-sensitive effects are rationally designed and synthesized for siRNA delivery.

Tumor Microenvironment-Responsive Polymer-Based RNA Delivery Systems for Cancer Treatment.

Ribonucleic acid (RNA) therapeutics offer a broad prospect in cancer treatment. However, their successful application requires overcoming various physiological barriers to effectively deliver RNAs to the target sites. Currently, a number of RNA delivery systems based on polymeric nanoparticles are developed to overcome these barriers in RNA delivery.

Real-world experience quantifying access to JAK inhibitor care for alopecia areata patients: a patient-centered survey study.

Background: Janus kinase inhibitor (JAKi) therapy has revolutionized the treatment landscape for alopecia areata (AA); however, access may be limited by a lack of insurance coverage and high out-of-pocket costs.

Objective: We aimed to evaluate real-world patient experiences regarding access to JAKi therapy.

Methods: We conducted an online patient-centered survey using the National Alopecia Areata Foundation listserv.

Opioid Prescribing and Outcomes in Patients With Sickle Cell Disease Post-2016 CDC Guideline.

Importance: Although the intention of the 2016 US Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain was not to limit pain treatment for patients with sickle cell disease (SCD), clinicians and patients have recognized the possibility that the guideline may have altered outcomes for this population. However, the outcomes of the 2016 guideline for this patient population are unknown.

Objective: To examine changes in opioid prescribing patterns and health outcomes among patients with SCD before and after the release of the 2016 CDC guideline.

A modified natural small molecule inhibits triple-negative breast cancer growth by interacting with Tubb3.

Background: Triple-negative breast cancer (TNBC) is a malignant tumor without specific therapeutic targets and a poor prognosis. Chemotherapy is currently the first-line therapeutic option for TNBC. However, due to the heterogeneity of TNBC, not all of TNBC patients are responsive to chemotherapeutic agents.

Platelet-Derived Growth Factor Nanocapsules with Tunable Controlled Release for Chronic Wound Healing.

Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds.

Changes in Cyclic Guanosine Monophosphate Channel of 661w Cells In vitro with Excessive Light Time.

Purpose: To determine the response time and protective mechanism of the cyclic guanosine monophosphate (cGMP) channel in 661w cells.

Methods: 661w cells were exposed to 4500Lux visible light for three and four days at the following exposure time periods per day: 20, 30, 60, 90, 120, and 180. Cells were incubated for the rest of the time without any other treatment.

Biochemical and microstructural determinants of the development of serous retinal detachment secondary to retinal vein occlusion.

Purpose: To study the alteration of cytokine factors in aqueous humor and retinal microstructure in the formation of serous retinal detachment (SRD) secondary to retinal vein occlusion.

Methods: The subjects were 39 patients with RVO, of whom 31 patients had SRD (RVO-SRD). Spectral Domain Optical Coherence Tomography (SD-OCT) was used to measure the completeness of photoreceptor inner segment/outer segment (IS/OS) and the external limiting membrane (ELM) as well as the structure of RVO-SRD, including the height and shape of SRD.

Case Report: Primary low-grade dedifferentiated liposarcoma of the urinary bladder with molecular confirmation.

Liposarcomas originating in the urinary bladder are extremely rare. Only six cases of bladder liposarcoma have been reported, and all have been described as myxoid liposarcomas. Notably, none of the patients underwent molecular testing.

Research Advances in the High-Value Utilization of Peanut Meal Resources and Its Hydrolysates: A Review.

Peanut meal (PM) is a by-product of extracting oil from peanut kernels. Although peanut meal contains protein, carbohydrates, minerals, vitamins, and small amounts of polyphenols and fiber, it has long been used as a feed in the poultry and livestock industries due to its coarse texture and unpleasant taste. It is less commonly utilized in the food processing industry.

Selective Fluorescent Sensing for Iron in Aqueous Solution by A Novel Functionalized Pillar[5]arene.

Iron ion is one of the most physiologically important elements in metabolic processes, indispensable for all living systems. Since its excess can lead to severe diseases, new approaches for its monitoring in water samples are urgently needed to meet requirements. Here, we firstly report a novel and universal route for the synthesis of a series of pillar[n]arene derivates containing one benzoquinone unit by photocatalysis.

Host-Guest Formulation of Carboxylatopillar[6]arene with Ergothioneine as a New Antidote for Combinational Detoxification of Paraquat.

Paraquat (PQ) is exceptionally toxic to the human body. PQ ingestion can cause severe organ damage with a mortality rate of 50-80%, resulting from the absence of effective antidotes and detoxification solutions. Herein, a host-guest formulation is proposed, in which ergothioneine (EGT), an antioxidant drug, was encapsulated by carboxylatopillar[6]arene (CP6A) to achieve a combinational therapy for PQ poisoning.

Assessment of Vigilance Level during Work: Fitting a Hidden Markov Model to Heart Rate Variability.

This study aimed to enhance the real-time performance and accuracy of vigilance assessment by developing a hidden Markov model (HMM). Electrocardiogram (ECG) signals were collected and processed to remove noise and baseline drift. A group of 20 volunteers participated in the study.

Synthesis of Cationic Biphen[4, 5]arenes as Biofilm Disruptors.

Since bacteria in biofilms are inherently resistant to antibiotics and biofilm-associated infections pose a serious threat to global public health, new therapeutic agents and schemes are urgently needed to meet clinical requirements. Here two quaternary ammonium-functionalized biphen[n]arenes (WBPn, n=4, 5) were designed and synthesized with excellent anti-biofilm potency. Not only could they inhibit the assembly of biofilms, but also eradicate intractable mature biofilms formed by Gram-positive S.

-associated soft tissue tumors with bone metaplasia: Clinicopathologic and genetic analysis and the identification of novel fusion partners.

Introduction: Among those tumors with consistent USP6 rearrangement, some arise from soft tissue and show bone metaplasia, including myositis ossificans (MO), fibro-osseous pseudotumor of digits (FOPD), soft tissue aneurysmal bone cyst (ST-ABC) and fasciitis ossificans (FO). These lesions are easily confused with malignancies because they show a rapid growth rate and brisk mitoses. Here, we aim to clarify the clinicopathologic and genetic characteristics of this entity and analyze the correlations among the different subtypes in one of the largest cohorts.

A Biocompatible Liquid Pillar[n]arene-Based Drug Reservoir for Topical Drug Delivery.

Advanced external preparations that possess a sustained-release effect and integrate few irritant elements are urgently needed to satisfy the special requirements of topical administration in the clinic. Here, a series of liquid pillar[n]arene-bearing varying-length oligoethylene oxide chains (OEPns) were designed and synthesized. Following rheological property and biocompatibility investigations, pillar[6]arene with triethylene oxide substituents (TEP6) with satisfactory cavity size were screened as optimal candidate compounds.

Patient-Defined Goals and Preferences Among Adults With Advanced Neuroendocrine Tumors.

Background: Patient preferences (quantity vs quality of life; present vs future health) have not been investigated in patients with neuroendocrine tumors (NETs). The goal of this cross-sectional study was to evaluate patient values toward treatment goals and competing health outcomes among adults with NETs.

Patients And Methods: Patients with well-differentiated, grade 1 or 2, advanced NETs starting a new systemic therapy completed 4 tools: (1) Health Outcomes Tool, which ranks the importance of 4 outcomes (survival, function/independence, freedom from pain, freedom from symptoms); (2) Attitude Scale, which identifies the extent to which patients agree with statements related to health outcomes; (3) Now versus Later Tool, which ranks the relative importance of quality of life (QoL) now versus 1 and 5 years from now; and (4) Prognosis and Treatment Perceptions Questionnaire, which identifies the amount of information the patient prefers to receive about their disease and treatment, the patient's treatment goal, the patient's perception of the physician's treatment goal, and self-reported health status.