Assessment of intratumor heterogeneity for preoperatively predicting the invasiveness of pulmonary adenocarcinomas manifesting as pure ground-glass nodules.

Background: The increased use of low-dose computed tomography (CT) for lung cancer screening has improved the detection of ground-glass nodules. However, as the clinical utility of CT findings to predict the invasiveness of pure ground-glass nodules (pGGNs) is currently limited, differentiating pGGNs that indicate invasive adenocarcinoma (IAC) from those that represent other histological entities is challenging. We aimed to quantify intratumor heterogeneity of lung adenocarcinomas characterized by pGGNs on CT to assess its efficacy in predicting IACs before surgery.

Generating allogeneic CAR-NKT cells for off-the-shelf cancer immunotherapy with genetically engineered HSP cells and feeder-free differentiation culture.

The clinical potential of current chimeric antigen receptor-engineered T (CAR-T) cell therapy is hampered by its autologous nature that poses considerable challenges in manufacturing, costs and patient selection. This spurs demand for off-the-shelf therapies. Here we introduce an ex vivo feeder-free culture method to differentiate gene-engineered hematopoietic stem and progenitor (HSP) cells into allogeneic invariant natural killer T (NKT) cells and their CAR-armed derivatives (CAR-NKT cells).

Chirality Interplay of Peptide and Saccharide on Glycopeptide Self-Assembly.

Saccharides and peptides with markedly disparate stereochemical features serve as pivotal chiral molecular partners in living systems. The importance of glycosylation in influencing glycopeptide self-assembly has been recognized. However, how different chiral combinations of saccharides and peptides influence the macroscopic hydrogel mechanics, fiber nanomechanics, asymmetric molecular packing, and thermodynamic changes during glycopeptide self-assembly remains unknown.

Dual Ratiometric Fluorescence Sensors Based on Chiral Carbon Dots for the Sensitive and Specific Detection of Arginine.

Arginine (Arg) is involved in tissue metabolism and regulates the immune function; thereby, achieving the detection of Arg is crucial for early diagnosis and treatment of diseases. Herein, dual ratiometric fluorescence sensors were prepared with the blue emission of levorotatory/dextrorotatory carbon dots (CDs) and the red emission of porphyrin (L/D-CDs-PP) for the sensitive and portable detection of Arg. Interestingly, L-CDs-PP and D-CDs-PP displayed not only the dual emission peaks at 493 and 650 nm but also different response modes to Arg; thus, they could serve as dual ratiometric fluorescence sensors to achieve the accurate and reliable detection of Arg, with the detection limit of 23.

Validation Status of Electronic Sphygmomanometers in China: A National Survey.

Background: Although the information on the validation status of electronic sphygmomanometer (ES) devices in use in health care institutions and households is much more clinically relevant than that of ES models available on the market, it remains insufficient.

Methods: A national survey was conducted across all administrative regions of mainland China to assess the validation status of ESs. Fifty-eight cities were selected with stratification by municipality, provincial capital, and other cities, and health care institutions and households in each city were chosen by convenience to identify ES devices in use according to the study protocol.

Investigating the molecular mechanisms of Jiangu Decoction in treating type 2 diabetic osteoporosis.

Ethnopharmacological Relevance: Type 2 diabetic osteoporosis (T2DOP) is a metabolic bone disease characterized by impaired bone structure and decreased bone strength in diabetic patients. Jiangu Decoction (JGD), a traditional Chinese poly-herbal formulation, has shown efficacy in mitigating osteoporosis (OP) and fractures caused by osteoporosis in diabetic patients in clinical trials. In addition, JGD has been proven to promote the proliferation of osteoblasts.

Dipyridamole Attenuates Experimental Periodontitis by Regulating M1 Macrophage Polarization via PKA/PKG Pathways.

Aim: Periodontitis is a chronic inflammatory disease initiated by dysbiosis of the local microbial community. As a non-specific phosphodiesterase inhibitor, dipyridamole features anti-oxidant and anti-inflammatory properties. This study aimed to investigate the effects of dipyridamole in an experimental rat model of periodontitis.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Microbubble-Protected Oncolytic Virotherapy Targeted by Sonoporation Induces Tumor Necrosis and T-Lymphocyte Infiltration in Humanized Mice Bearing Triple-Negative Breast Cancer.

Oncolytic virotherapy has shown great promise in mediating targeted tumor destruction through tumor-selective replication and induction of anti-tumor immunity; however, obstacles remain for virus candidates to reach the clinic. These include avoiding neutralizing antibodies, preventing stimulation of the adaptive immune response during intravenous administration, and inducing sufficient apoptosis and immune activation so that the body's defense can work to eradicate systemic disease. We have developed a co-formulation of oncolytic viruses (OVs) with Imagent lipid-encapsulated, perfluorocarbon microbubbles (MBs) to protect the OVs from the innate and adaptive immune system.

Key enzymatic activities and metabolic pathway dynamics in acidogenic fermentation of food waste: Impact of pH and organic loading rate.

Acidogenic fermentation was an effective technology to recover volatile fatty acids (VFAs) ethanol and lactic acid from food wastes (FW) as bioresources. However, the impact of process controls on key functional enzymes and metabolic pathways has been inadequately understood. In this study, the metabolite distribution, key functional enzymes and metabolic pathways were completely elucidated using 16S rRNA gene high-throughput sequencing combined with PICRUSt2.

A bifunctional coumarin-based CD probe for chiral analysis of amino acids in aqueous solution.

Amino acids play important roles in human pathology and physiology and the qualitative and quantitative determination of chiral amino acids in humans and mammals also has important impacts on the life sciences. Therefore, the introduction of artificial probes to assess the concentrations and enantiomeric compositions [ee = ([D] - [L])/([D] + [L])] of amino acids in aqueous solution is necessary in understanding certain biological processes and diagnosing and treating diseases. Herein, a bifunctional achiral coumarin probe (Br-Coumarin) is reported to determine the absolute configuration, ee value, and concentration of 16 amino acids in THF/HO = 1/4 solution at micromolar concentrations.

Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

High-level nitrogen removal achieved by Feammox-based autotrophic nitrogen conversion.

Anaerobic ammonium oxidation coupled with Fe(III) reduction (Feammox) is an essential process in the geochemical iron and nitrogen cycling. This study explores Feammox-based nitrogen removal in a continuous laboratory up-flow bioreactor stimulated by intermittently adding 5 mM Fe(OH) at intervals of approximately two months. The feed was synthetic wastewater with a relatively low ammonium concentration (∼100 mg N/L), yet without organic carbon in order to test its autotrophic nitrogen removal performance.

Foam FeSO modified limestone sulfur concrete for non-stink and high-rate nitrogen and phosphorus removal from wastewater.

Aiming at disadvantages of conventional sulfur-limestone autotrophic denitrification system, such as producing stink (HS) and low-rate nitrogen and phosphorus removal from wastewater with low C/N, foam FeSO modified limestone sulfur concrete (FFLSC) was prepared. Experimental parameters of FFLSC biofilter, such as hydraulic retention time (HRT), influent NO-N, additional alkalinity and COD addition, were tested. For wastewater without COD, FFLSC biofilter could simultaneously remove TON (NO-N+NO-N) from 22.

Comparative Efficacy of Non-contrast vs. Contrast-enhanced CT Radiomics in Predicting Coronary Artery Plaques Among Patients with Low Agatston Scores.

Rationale And Objectives: Patients with a low Agatston score often present with clinical signs and symptoms suggestive of coronary artery disease, despite having minimal calcium deposits. This study aimed to compare the efficacy of low-dose non-contrast cardiac CT with coronary computed tomography angiography (CCTA) in pericoronary adipose tissue (PCAT) radiomics for predicting coronary artery plaques, using CCTA as the reference standard.

Materials And Methods: This retrospective study analyzed 459 patients with suspected coronary artery disease and a coronary artery calcium score < 100 Agatston units, who were treated between June 2021 and December 2023 at a tertiary hospital.

Single-cell data-driven design of armed oncolytic virus to boost cooperative innate-adaptive immunity against cancer.

Oncolytic viruses have been considered promising cancer immunotherapies. However, oncovirotherapy agents impart durable responses in only a subset of cancer patients. Thus, exploring the cellular and molecular mechanisms underlying the heterogeneous responses in patients can provide guidance to develop more effective oncolytic virus therapies.

Growth Hormone-Releasing Peptide 2 May Be Associated With Decreased M1 Macrophage Production and Increased Histologic and Biomechanical Tendon-Bone Healing Properties in a Rat Rotator Cuff Tear Model.

Purpose: To explore the potential of growth hormone-releasing peptide 2 (GHRP-2) for tendon-bone healing in a rat rotator cuff tear (RCT) model.

Methods: The impact of GHRP-2 on M1 macrophage polarization in vitro was determined using real-time polymerase chain reaction, Western blot, and immunofluorescence staining. GHRP-2 was then applied in a rat RCT model, and the healing of the tendon-bone interface was systemically evaluated by histologic staining, radiologic assessments, gait analysis, and biomechanical tests.

Start-up of Anammox-HAP in IC reactors: Revelation of sludge characteristics and microbial community structure.

The scarcity of seed sludge poses a significant barrier to the advancement of anaerobic ammonia oxidation (anammox) process. In this investigation, two alternative sludge (anaerobic granular sludge (AGS) and activated flocculent sludge (AFS)) were employed to start up the anammox process in internal circulation (IC) reactors with the hydroxyapatite (HAP) strategy. Both reactors achieved rapid start-up on days 83 and 53, respectively.

Improved Catalytic Performance of Lipase Within Hydrogel Microspheres Incorporating L/D-CoO Nanoparticles.

Lipases have drawn significant attention due to their crucial roles across various industries, including oil processing, food, medicine, and daily chemicals. Nevertheless, their catalytic efficiency is susceptible to fluctuations in external environmental conditions, which remains a major barrier to their broader application. In this research, chiral hydrogel microspheres (HMSs) are developed by incorporating L/D-CoO nanoparticles (NPs) into the synthetic process of HMSs, which are discovered to enhance the catalytic performance of lipases.

GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders.

Background: Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported.

Methods: GSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3β and GSK3α).

Metal Ion-Mediated Supramolecular Nanotube Catalyst for Enantioselective Reactions.

Rational control over the morphologies of supramolecular assemblies for asymmetric catalysis with enhanced enantioselectivity represents a pivotal challenge in the realm of synthetic chemistry and material technology. Herein, Cu(II) ion-mediated supramolecular nanostructures assembled from chiral amino acid-based amphiphiles (l/d-AlaC) are fabricated as chiral catalysts for Diels-Alder cycloaddition between aza-chalcone and cyclopentadiene. In particular, compared with the supramolecular nanosheet formed by l/d-AlaC without Cu(II) ions, we found that the l/d-alanine chiral amphiphile can form supramolecular nanotubes with a multilayer structure and with the thickness of the tubular wall about 15 nm through the transition from a nanoribbon to tubular structure in the presence of Cu(II) ions.

Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.

Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.

Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies.

Research Progress on Membrane Separation Technology for Oily Wastewater Treatment.

This paper presents the research progress and future prospects of membrane separation technology for treating oily wastewater. It discusses various treatment methods tailored to different sources and characteristics of oily wastewater, summarizing the features of different membrane separation technologies and the latest advancements in their application. The paper concludes by emphasizing the need for future research to focus on developing environmentally friendly and efficient coupled membrane treatment technologies, optimizing membrane material design and enhancing the environmental benefits of oily wastewater treatment.