Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

Expanded Field OCT Angiography Biomarkers for Predicting Clinically Significant Outcomes in Non-Proliferative Diabetic Retinopathy.

Purpose: To evaluate the utility of extended field swept-source Optical Coherence Tomography Angiography (SS-OCTA) imaging biomarkers in predicting the occurrence of clinically significant outcomes in eyes with Non-Proliferative Diabetic Retinopathy (NPDR).

Design: Retrospective clinical case-control study.

Methods: Single-center clinical study.

A multimodal generative AI copilot for human pathology.

Computational pathology has witnessed considerable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders. However, despite the explosive growth of generative artificial intelligence (AI), there have been few studies on building general-purpose multimodal AI assistants and copilots tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment Lamin A/C-Yes-associated protein axis in stem cells.

Background: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.

LncRNA MEG3: Targeting the Molecular Mechanisms and Pathogenic causes of Metabolic Diseases.

Background: Non-coding RNA is a type of RNA that does not encode proteins, distributed among rRNA, tRNA, snRNA, snoRNA, microRNA and other RNAs with identified functions, where the Long non-coding RNA (lncRNA) displays a nucleotide length over 200. LncRNAs enable multiple biological processes in the human body, including cancer cell invasion and metastasis, apoptosis, cell autophagy, inflammation, etc. Recently, a growing body of studies has demonstrated the association of lncRNAs with obesity and obesity-induced insulin resistance and NAFLD, where MEG3 is related to glucose metabolism, such as insulin resistance.

Association of obesity and mortality in sepsis patients: A meta-analysis from observational evidence.

The project aims to investigate the correlation between obesity, overweight, or low body weight and the risk of mortality in sepsis patients. We performed a rigorous and thorough search of major electronic databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, from the inception of these databases up to March 28, 2023. The data were analyzed with Stata software (version 16.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated.

First Report of Grey Spot on Tobacco caused by Alternaria alstroemeriae in China.

Tobacco (Nicotiana tabacum L.) is an important economic crop belonging to family Solanaceae and is widely cultivated in China (Basit 2021). From April to July in 2022, a foliar disease with symptoms similar to grey spot was extensively observed on tobacco in Guangxi Province (24°52' N, 111°23' E), China.

Enhanced photocatalytic toluene oxidation performance induced by two types of cooperative fluorine doping in polymeric carbon nitride with the first-principles calculations.

Fluorine atoms doping was reported in experiment to reduce the band gap, improve the oxidation potential of hole, and polarize the electron distribution of polymeric carbon nitride (PCN). However, the relationships between different types of F doping and the roles of F doping in electronic and optical properties remain elusive. In this work, we investigate several F doping types in PCN and analyze their different roles in electronic and optical properties with the first-principles calculations.

Ligand Fluorination to Mitigate the Raman Relaxation of Dy Single-Molecule Magnets: A Combined Terahertz, Far-IR and Vibronic Barrier Model Study.

The fast Raman relaxation process via a virtual energy level has become a puzzle for how to chemically engineer single-molecule magnets (SMMs) with better performance. Here, we use the trifluoromethyl group to systematically substitute the methyl groups in the axial position of the parent bis-butoxide pentapyridyl dysprosium(III) SMM. The resulting complexes-[Dy(OL ) py ][BPh ] (L =CH(CF ) 1, CH CF 2, CMe CF 3)-show progressively enhanced T (@100 Oe s ) from 17 K (for 3), 20 K (for 2) to 23 K (for 1).

Structural determinants of dual incretin receptor agonism by tirzepatide.

SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization.

Methionine and Arginine Supply Alters Abundance of Amino Acid, Insulin Signaling, and Glutathione Metabolism-Related Proteins in Bovine Subcutaneous Adipose Explants Challenged with -Acetyl-d-sphingosine.

The objective was to perform a proof-of-principle study to evaluate the effects of methionine (Met) and arginine (Arg) supply on protein abundance of amino acid, insulin signaling, and glutathione metabolism-related proteins in subcutaneous adipose tissue (SAT) explants under ceramide (Ce) challenge. SAT from four lactating Holstein cows was incubated with one of the following media: ideal profile of amino acid as the control (IPAA; Lys:Met 2.9:1, Lys:Arg 2:1), increased Met (incMet; Lys:Met 2.

Atrial Fibrillation in Patients with Chronic Kidney Disease.

There is a bidirectional relationship between atrial fibrillation (AF) and chronic kidney disease (CKD), with multiple shared risk factors. This article discusses an integrated care approach toward the management of patients with AF, including those with CKD. There is an increasing risk of both ischemic stroke and bleeding with progressive deterioration of renal function, complicating the decision of optimal stroke prevention strategies among patients with AF and CKD.

Tracking the Micro-Heterogeneity and Hydrogen-Bonding Interactions in Hydroxyl-Functionalized Ionic Liquid Solutions: A Combined Experimental and Computational Study.

Ionic liquids (ILs) are an important class of media that are usually used in combination with polar solvents to reduce costs and tune their physicochemical properties. In this regard, it is essential to understand the influence of adding solvents on the properties of ILs. In this work, the micro-heterogeneity and H-bonding interactions between a hydroxyl-functionalized IL, [HOEmim][TFSI], and acetonitrile (ACN) were investigated by attenuated total reflection Fourier transform infrared spectroscopy and molecular simulations.

Reactivation of the tumor suppressor PTEN by mRNA nanoparticles enhances antitumor immunity in preclinical models.

Increasing clinical evidence has demonstrated that the deletion or mutation of tumor suppressor genes such as the gene-encoding phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in cancer cells may correlate with an immunosuppressive tumor microenvironment (TME) and poor response or resistance to immune checkpoint blockade (ICB) therapy. It is largely unknown whether the restoration of functional PTEN may modulate the TME and improve the tumor's sensitivity to ICB therapy. Here, we demonstrate that mRNA delivery by polymeric nanoparticles can effectively induce expression of PTEN in -mutated melanoma cells and -null prostate cancer cells, which in turn induces autophagy and triggers cell death-associated immune activation via release of damage-associated molecular patterns.

Acceleration of Brain TOF-MRA with Compressed Sensitivity Encoding: A Multicenter Clinical Study.

Background And Purpose: The clinical practice of three-dimensional TOF-MRA, despite its capability in brain artery assessment, has been hampered by the relatively long scan time, while recent developments in fast imaging techniques with random undersampling has shed light on an improved balance between image quality and imaging speed. Our aim was to evaluate the effectiveness of TOF-MRA accelerated by compressed sensitivity encoding and to identify the optimal acceleration factors for routine clinical use.

Materials And Methods: One hundred subjects, enrolled at 5 centers, underwent 8 brain TOF-MRA sequences: 5 sequences using compressed sensitivity encoding with acceleration factors of 2, 4, 6, 8, and 10 (CS2, CS4, CS6, CS8, and CS10), 2 using sensitivity encoding with factors of 2 and 4 (SF2 and SF4), and 1 without acceleration as a reference sequence (RS).

Adaptively Learning Facial Expression Representation via C-F Labels and Distillation.

Facial expression recognition is of significant importance in criminal investigation and digital entertainment. Under unconstrained conditions, existing expression datasets are highly class-imbalanced, and the similarity between expressions is high. Previous methods tend to improve the performance of facial expression recognition through deeper or wider network structures, resulting in increased storage and computing costs.

Leukemic extracellular vesicles induce chimeric antigen receptor T cell dysfunction in chronic lymphocytic leukemia.

Chimeric antigen receptor (CAR) T cell therapy has yielded unprecedented outcomes in some patients with hematological malignancies; however, inhibition by the tumor microenvironment has prevented the broader success of CART cell therapy. We used chronic lymphocytic leukemia (CLL) as a model to investigate the interactions between the tumor microenvironment and CART cells. CLL is characterized by an immunosuppressive microenvironment, an abundance of systemic extracellular vesicles (EVs), and a relatively lower durable response rate to CART cell therapy.

Quantitative Handheld Swept-Source Optical Coherence Tomography Angiography in Awake Preterm and Full-Term Infants.

Purpose: To compare retinal vascular parameters acquired by handheld swept-source optical coherence tomography angiography (SS-OCTA) between nonsedated preterm and full-term infants.

Methods: Preterm and full-term infants at the University of Washington Medical Center were enrolled. Retinal angiograms (nominal size ∼7 × 7 mm) were obtained at each routine retinopathy of prematurity (ROP) screening session for preterms and once during the first 72 hours of life for full-terms.

Efficient sorptive removal of F-53B from water by layered double hydroxides: Performance and mechanisms.

Chlorinated polyfluoroalkyl ether sulfonates (trade name F-53B) has been detected in various environmental matrices, and reported to be equally or more toxic than perfluorooctane sulfonate. Efficient sorptive removal of F-53B from water by two types of layered double hydroxides (LDHs), NO-LDH and sodium dodecyl sulfate modified NO-LDH (SDS-LDH), was demonstrated in this study. Both LDHs removed F-53B in several minutes and had sorption capacities of over 860 mg/g.