A Phase I Dose-Finding Design Incorporating Intra-Patient Dose Escalation.

Conventional Phase I trial designs assign a single dose to each patient, necessitating a minimum number of patients per dose to reliably identify the maximum tolerated dose (MTD). However, in many clinical trials, such as those involving pediatric patients or patients with rare cancers, recruiting an adequate number of patients can pose challenges, limiting the applicability of standard trial designs. To address this challenge, we propose a new Phase I dose-finding design, denoted as IP-CRM, that integrates intra-patient dose escalation with the continual reassessment method (CRM).

Injectable hyaluronate-L- cysteine gel potentiates photothermal therapy in osteosarcoma via vorinostat-copper cell death.

The prognosis for osteosarcoma patients, a devastating malignancy affecting young individuals, remains grim despite multimodal therapeutic advances. Recently, the advent of cuproptosis, a novel programmed cell death, offers hope in fighting osteosarcoma. In this study, we introduce SAHA@{[Cu(HA-Cys)]Cl}, an injectable hyaluronate-L-cysteine hydrogel that integrates both copper ions (Cu) and vorinostat (SAHA) for the possible therapeutic effect.

Evaluating the spatiotemporal land ecological changes in the Yangtze-to-Huaihe Water Diversion Project area.

As a fundamental component of human existence, land is inextricably linked to human development, and its ecological functions are closely associated with multiple sustainable development goals. This paper presents a framework for constructing and optimizing ecological function space, with the Yangtze-to-Huaihe Water Diversion Project area serving as a case study. A comprehensive land ecological index system is established, encompassing natural foundation, land degradation, land production, ecological structure, and ecological protection.

Treatment Comparisons in Adaptive Platform Trials Adjusting for Temporal Drift.

An adaptive platform trial (APT) is a multi-arm trial in the context of a single disease where treatment arms are allowed to enter or leave the trial based on some decision rule. If a treatment enters the trial later than the control arm, there exist non-concurrent controls who were not randomized between the two arms under comparison. As APTs typically take long periods of time to conduct, temporal drift may occur, which requires the treatment comparisons to be adjusted for this temporal change.

The application effect of the optimized scheduling model of virtual power plant participation in the new electric power system.

To build a comprehensive framework for virtual power plant (VPP) development aligned with market dynamics and to devise effective strategies to foster its growth, this study undertakes several key steps. Firstly, it constructs a VPP development framework based on market conditions, to drive the evolution of new power systems and facilitating energy transformation. Secondly, through a blend of theoretical analysis and model construction, the fundamental principles of VPP are systematically elucidated, and a decision model for the VPP development framework, focusing on price demand response, is formulated.

Eml1 promotes axonal growth by enhancing αTAT1-mediated microtubule acetylation.

Microtubule stabilization is critical for axonal growth and regeneration, and many microtubule-associated proteins are involved in this process. In this study, we found that the knockdown of echinoderm microtubule-associated protein-like 1 (EML1) hindered axonal growth in cultured cortical and dorsal root ganglion neurons. We further revealed that EML1 facilitated the acetylation of microtubules and that the impairment of axonal growth due to EML1 inhibition could be restored by treatment with deacetylase inhibitors, suggesting that EML1 affected tubulin acetylation.

Polymersomal Poly(I:C) Self-Magnifies Antitumor Immunity by Inducing Immunogenic Cell Death and Systemic Immune Activation.

Immunotherapy has emerged as a powerful weapon against lung cancer, yet only a fraction of patients respond to the treatment. Poly(I:C) (PIC) effectively triggers both innate and adaptive immunity. It can also induce immunogenic cell death (ICD) in tumor cells.

GIP attenuates neuronal oxidative stress by regulating glucose uptake in spinal cord injury of rat.

Aim: Glucose-dependent insulinotropic polypeptide (GIP) is a ligand of glucose-dependent insulinotropic polypeptide receptor (GIPR) that plays an important role in the digestive system. In recent years, GIP has been regarded as a hormone-like peptide to regulate the local metabolic environment. In this study, we investigated the antioxidant role of GIP on the neuron and explored the possible mechanism.

Carbon dots-based dual-emission ratiometric fluorescent sensors for fluorescence and visual detection of hypochlorite and Cu.

Carbon dots (CDs) with blue emission were synthesized by solvothermal method using hydroquinone and 5-aminoisphthalic acid as precursors. The strong oxidation of ClO caused the fluorescence quenching of CDs at 405 nm, and synchronously generated a new emission peak at 500 nm. Furthermore, upon the addition of Cu to CDs-ClO system, the green fluorescence at 500 nm was quenched, while the blue emission at 405 nm remained unchanged, due to the complexation between Cu and the amino group on the CDs surface.

Enhanced Apc adenoma formation after epithelial CUL4B deletion by recruitment of myeloid-derived suppressor cells.

Colorectal cancer (CRC) stands as a prevalent malignancy globally. A pivotal event in CRC pathogenesis involves the loss-of-function mutation in the APC gene, leading to the formation of benign polyps. Despite the well-established role of APC, the contribution of CUL4B to CRC initiation in the pre-tumorous stage remains poorly understood.

The Substitution of Fishmeal with Yeast Culture in the Yellow Catfish () Diet: Growth, Serum Biochemical Indices, and Intestinal and Hepatopancreatic Histology.

Yeast culture is a complex fermentation product consisting of fermentation substrate, yeast cells and their metabolites. This study investigated the potential of yeast culture in replacing fishmeal in the diet of yellow catfish (). First, a basal diet was formulated to contain 160 g/kg fishmeal (CON), and then the dietary fishmeal was decreased to 120, 80, 40 and 0 g/kg via yeast culture inclusion, respectively, to form another four isonitrogenous and isolipidic diets (YC-12, YC-8, YC-4 and YC-0).

Idiopathic mesenteric phlebosclerosis occurring in a patient with liver cirrhosis: A case report.

Background: Idiopathic mesenteric phlebosclerosis (IMP) is a rare gastrointestinal disease with unclear etiology and pathogenesis. IMP occurring in a patient with liver cirrhosis is more scarcely reported than independent IMP. In this study, we reported a case of IMP occurring in a patient with liver cirrhosis, so as to provide a reference for understanding liver cirrhosis with IMP.

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure.

Background: The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis.

Methods: Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice.

Adaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies.

Targeted agents and immunotherapies have revolutionized cancer treatment, offering promising options for various cancer types. Unlike traditional therapies the principle of "more is better" is not always applicable to these new therapies due to their unique biomedical mechanisms. As a result, various phase I-II clinical trial designs have been proposed to identify the optimal biological dose that maximizes the therapeutic effect of targeted therapies and immunotherapies by jointly monitoring both efficacy and toxicity outcomes.

Assessment of urban blue-green space cooling effect linking maximum and accumulative perspectives in the Yangtze River Delta, China.

The development of urban blue-green spaces is highly recommended as a nature-based solution for mitigating the urban heat island phenomenon, improving urban sustainability, and enhancing resident well-being. However, limited attention has been given to the accumulative impact of the cooling effect and the comparison of different types of landscapes. Based on the maximum and accumulative perspectives, this study selected 375 green spaces, water bodies, and urban parks in 25 cities of the Yangtze River Delta (YRD) region in China to quantify their cooling effect.

Technical note: Preprocessing of portal images to improve image quality of VMAT-CT.

Background: The concept of volumetric modulated arc therapy-computed tomography (VMAT-CT) was proposed more than a decade ago. However, its application has been very limited mainly due to the poor image quality. More specifically, the blurred areas in electronic portal imaging device (EPID) images collected during VMAT heavily degrade the image quality of VMAT-CT.

Integrin-targeting disulfide-crosslinked micellar docetaxel eradicates lung and prostate cancer patient-derived xenografts.

Actively targeted nanomedicines though conceptually attractive for tumor therapy are extremely hard to realize due to problems of premature drug leakage, excessive liver accretion, inadequate tumor uptake, and/or retarded drug release inside tumor cells. Here, we systemically studied the influence of disulfide crosslinking on the in vitro and in vivo performance of integrin-targeting micellar docetaxel (t-MDTX). Of note, t-M5DTX with a high disulfide content was clearly advantageous in terms of stability, intracellular drug release, anti-tumor activity toward αβ-overexpressing A549 cells, blood circulation and therapeutic efficacy in orthotopic A549-luc lung tumor-bearing mice.

Transcriptomics unveils immune metabolic disruption and a novel biomarker of mortality in patients with HBV-related acute-on-chronic liver failure.

Background & Aims: HBV-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome associated with high short-term mortality. This study aims to reveal the molecular basis and identify novel HBV-ACLF biomarkers.

Methods: Seventy patients with HBV-ACLF and different short-term (28 days) outcomes underwent transcriptome sequencing using peripheral blood mononuclear cells.

Effects of nitrification and urease inhibitors on ammonia-oxidizing microorganisms, denitrifying bacteria, and greenhouse gas emissions in greenhouse vegetable fields.

Soil microorganisms and N cycling are important components of biogeochemical cycling processes. In addition, the study of the effects of nitrification and urease inhibitors on N and microorganisms in greenhouse vegetable fields is essential to reducing N loss and greenhouse gas emissions. The effects of nitrification inhibitors [2-chloro-6-(trichloromethyl) pyridine (CP), dicyandiamide (DCD)], and urease inhibitor [N-(n-butyl) thiophosphoric triamide (NBPT)] on soil inorganic N (NH-N, NO-N and NO-N) concentrations and the production rates of greenhouse gases (NO, CH, and CO) in greenhouse vegetable fields were investigated via indoor incubation experiments.

RGD-directed 24 nm micellar docetaxel enables elevated tumor-liver ratio, deep tumor penetration and potent suppression of solid tumors.

Nanomedicines while showing a great potential in improving the performance of chemotherapeutics like docetaxel (DTX) are distressed by a high liver deposition and poor tumor penetration, which might not only cause liver toxicity but also moderate therapeutic effect. Herein, we report that cRGD-directed 24 nm disulfide-crosslinked micellar docetaxel (cRGD-MDTX) presents low liver accumulation, high tumor uptake, and deep tumor penetration, leading to the potent suppression of different solid tumors. cRGD-MDTX was optimized with a cRGD density of 4% and DTX loading of 10 wt%.

Biomarker-based precision dose finding for immunotherapy combined with radiotherapy.

Recent success of sequential administration of immunotherapy following radiotherapy (RT), often referred to as immunoRT, has sparked the urgent need for novel clinical trial designs to accommodate the unique features of immunoRT. For this purpose, we propose a Bayesian phase I/II design for immunotherapy administered after standard-dose RT to identify the optimal dose that is personalized for each patient according to his/her measurements of PD-L1 expression at baseline and post-RT. We model the immune response, toxicity, and efficacy as functions of dose and patient's baseline and post-RT PD-L1 expression profile.

Allergen Sensitization in Children in Weifang, China: Differences Between Monosensitization and Polysensitization.

Background: Children are the age group with the highest prevalence of allergy diseases. There is currently a lack of knowledge regarding monosensitization and polysensitization characteristics in children. In this study, we investigated the characteristics and differences between monosensitization and polysensitization in children in Weifang, eastern China.