Precision-engineered PROTACs minimize off-tissue effects in cancer therapy.

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading to toxicity in healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated in tumor environments, and E3 ligase overexpression strategies.

One-Pot Time-Induced Proteome Integral Solubility Alteration Assay for Automated and Sensitive Drug-Target Identification.

The proteome integral solubility alteration (PISA) assay is widely used for identifying drug targets, but it is labor-intensive and time-consuming and requires a substantial amount of biological sample. Aiming at enabling automation and greatly reducing the sample amount, we developed one-pot time-induced (OPTI)-PISA. Here, we demonstrate OPTI-PISA performance on identifying targets of multiple drugs in cell lysate and scaling down the sample amount to sub-microgram levels, making the PISA method suitable for NanoProteomics.

MFP-YOLO: a multi-scale feature perception network for CT bone metastasis detection.

Bone metastasis is one of the most common forms of metastasis in the late stages of malignancy. The early detection of bone metastases can help clinicians develop appropriate treatment plans. CT images are essential for diagnosing and assessing bone metastases in clinical practice.

Study on the mechanism of 17-Hydroxy-jolkinolide B on anaplastic thyroid cancer cell.

Background: Anaplastic thyroid cancer (ATC) has a dismal prognosis, and the optimal treatment has not yet been confirmed. Euphorbia fischeriana Steud has been proven to exhibit pharmacological properties, including various antitumor effects, that can be used to treat numerous diseases and has been used to treat cancer. 17-Hydroxy-jolkinolide B (17-HJB) is one of the major diterpenoids produced from plants, but little research has investigated how it affects cancer.

Redox-Inducible Radiomimetic Photosensitizers Selectively Suppress Cancer Cell Proliferation by Damaging DNA through Radical Cation Chemistry.

Radiotherapy leverages ionizing radiation to kill cancer cells through direct and indirect effects, and direct effects are considered to play an equal or greater role. Several photosensitizers have been developed to mimic the direct effects of radiotherapy, generating radical cations in DNA models, but none has been applied in cellular studies. Here, we design a radiomimetic photosensitizer, producing DNA radical cations in cells for the first time.

Prognostic Value and Immune Landscapes of Four Types of RNA Modification Writer-Related LncRNAs Signature in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the predominant pathological subtype of non-small cell lung cancer (NSCLC). The four primary forms of RNA adenosine modifications, N6-methyladenosine (mA), N1-methyladenosine (mA), alternative polyadenylation (APA) and adenosine-to-inosine (A-to-I) RNA editing, play a critical role in tumor progression. However, the clinical significance of RNA modification writer-related long non-coding RNAs (lncRNAs) in LUAD remains unclear.

Targeting miR-31 represses tumourigenesis and dedifferentiation of BRAF-associated thyroid carcinoma.

Background: BRAF is the most common genetic mutation in differentiated thyroid cancer (DTC) occurring in 60% of patients and drives malignant tumour cell phenotypes including proliferation, metastasis and immune-escape. BRAF-mutated papillary thyroid cancer (PTC) also displays greatly reduced expression of thyroid differentiation markers, thus tendency to radioactive iodine (RAI) refractory and poor prognosis. Therefore, understanding the molecular mechanisms and main oncogenic events underlying BRAF will guide future therapy development.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively.

Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT and FT before and after treatment (FT-P/FT-A, FT-P/FT-A) on whether BTMs recovered.

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

Background: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample.

Adding Color to Mass Spectra of Biopolymers: Charge Determination Analysis (CHARDA) Assigns Charge State to Every Ion Peak.

Traditionally, mass spectrometry (MS) output is the ion abundance plotted versus the ionic mass-to-charge ratio /. While employing only commercially available equipment, Charge Determination Analysis (CHARDA) adds a third dimension to MS, estimating for individual peaks their charge states starting from = 1 and color coding in / spectra. CHARDA combines the analysis of ion signal decay rates in the time-domain data (transients) in Fourier transform (FT) MS with the interrogation of mass defects (fractional mass) of biopolymers.

Prognostic factors for postoperative papillary thyroid cancer with unexplained elevated Tg: A retrospective study.

Objective: This study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients.

Methods: From April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled.

Higher adjuvant radioactive iodine therapy dosage helps intermediate-risk papillary thyroid carcinoma patients achieve better therapeutic effect.

Objective: This retrospective study aims to evaluate the therapeutic effect of varying dosages of adjuvant radioactive iodine (RAI) therapy on intermediate-risk papillary thyroid carcinoma (PTC) patients.

Methods: This retrospective study involved a total of 427 intermediate-risk PTC patients, out of which 202 received a 3.7GBq dosage of RAI, and 225 received a 5.

Ultralight Ultrafast Enzymes.

Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it.

Macrocyclic-Albumin Conjugates for Precise Delivery of Radionuclides and Anticancer Drugs to Tumors.

Precise delivery of radionuclides and anticancer drugs to tumor tissue is crucial to ensuring drug synergism and optimal therapeutic effects in radionuclide-based combination radio-chemotherapy. However, current codelivery vectors often rely on physical embedment/adsorption to load anticancer drugs, which lacks precise mechanisms for drug loading and release, resulting in unpredictable combination effects. Herein, a macrocyclic-albumin conjugate (MAC) that enables precise loading and controlled release of anticancer drugs is presented.

Tandem Mass Spectrometry de novo Sequencing of the Skin Defense Peptides of the Central Slovenian Agile Frog .

Peptides released on frogs' skin in a stress situation represent their only weapon against micro-organisms and predators. Every species and even population of frog possesses its own peptidome being appropriate for their habitat. Skin peptides are considered potential pharmaceuticals, while the whole peptidome may be treated as a taxonomic characteristic of each particular population.

Experimental study on changes in metabolic mechanism of papillary thyroid carcinoma complicated with Hashimoto's thyroiditis.

Background: Whether the mechanism of thyroid papillary carcinoma (PTC) is the same in patients with a Hashimoto's thyroiditis (HT) background as compared with patients with a normal background remains a highly debated and controversial issue. In this study, we aimed to analyze the differences and similarities of the metabolic mechanism of PTC in normal and HT background, and to explore the relationship between HT and PTC.

Methods: The ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background).

EThcD Benefits for the Sequencing Inside Intramolecular Disulfide Cycles of Amphibian Intact Peptides.

Disulfide bonds formed by a pair of cysteine residues in the peptides' backbone represent a certain problem for their sequencing by means of mass spectrometry. As a rule, in proteomics, disulfide bonds should be cleaved before the analysis followed by some sort of chemical derivatization. That step is time-consuming and may lead to losses of minor peptides of the analyzed mixtures due to incomplete reaction, adsorption on the walls of the vials, etc.

Extrathyroidal extension or tumor size of primary lesion influences thyroid cancer outcomes.

Aims: Extrathyroidal extension (ETE) is a determined factor of T3 and T4 stage of differentiated thyroid cancer (DTC) in American Joint Committee on Cancer. We aimed to compare clinical outcomes between different extent of ETE according to tumor size.

Methods: Patients diagnosed with DTC were collected from the Surveillance, Epidemiology, and End Results database from 2004 to 2015.

Establishment and analytical performance of light-initiated chemiluminescence assay method for detecting thyrotropin receptor antibody.

To evaluate double-antibody competitive light-initiated chemiluminescence assay method for detecting the thyrotropin receptor antibody. The optimal working concentrations of competitive antibody and rTSHR were confirmed by checkerboard titration. Assay performance was assessed by precision, linearity, accuracy, limit of blank and clinical evaluation.

Hazard ratios of second primary malignancy after radioiodine for differentiated thyroid carcinoma: a large-cohort retrospective study.

Introduction: The objective of this study is to evaluate the benefits of radioactive iodine (RAI) treatment and the risk of second primary malignancy (SPM) in RAI-treated patients.

Material And Methods: The cohort for this analysis consisted of individuals diagnosed with a first primary differentiated thyroid carcinoma (DTC), reported by the Surveillance, Epidemiology, and End Results (SEER) database in 1988-2016. Overall survival (OS) difference was estimated by Kaplan-Meier curves and log-rank test, and hazard ratios (HR) were obtained by Cox proportional-hazards model to evaluate the association between RAI and SPM.

Establishment and validation of an AI-aid method in the diagnosis of myocardial perfusion imaging.

Background: This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease.

Methods: We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems.

Impacts of different reconstruction methods on the image quality of cadmium-zinc-telluride-based single photon emission computed tomography/computed tomography pulmonary perfusion imaging.

Objective: The objective was to evaluate the impacts of different reconstruction methods [filtered back projection (FBP) and ordered subset expectation maximization (OSEM)] and different filters (Butterworth filter and Gaussian filter) on the image quality in cadmium-zinc-telluride (CZT)-based single photon emission computed tomography (SPECT)/computed tomography (CT) pulmonary perfusion imaging.

Methods: A combinations including FBP with Butterworth filter, OSEM with Butterworth filter (OSEM + Butterworth filter ), and OSEM with Gaussian filter (OSEM + Gaussian filter) were used during SPECT image reconstruction. Visual and quantitative parameters [root mean square (RMS) noise, contrast and contrast-to-noise ratio (CNR)] were used to evaluate image quality.

Epidemiological and demographic drivers of lung cancer mortality from 1990 to 2019: results from the global burden of disease study 2019.

Background: Understanding the effects of demographic drivers on lung cancer mortality trends is critical for lung cancer control. We have examined the drivers of lung cancer mortality at the global, regional, and national levels.

Methods: Data on lung cancer death and mortality were extracted from the Global Burden of Disease (GBD) 2019.