The association between nutrition risk status assessment and hospital mortality in Chinese older inpatients: a retrospective study.

Purpose: The association between nutritional risk status assessment and hospital mortality in older patients remains controversial. The aim of this study was to assess the relationship between nutritional risk on admission and in-hospital mortality, and explore the best Nutritional Risk Status Screening 2002 (NRS2002) threshold for predicting in-hospital mortality of older inpatients in China.

Method: The elderly inpatients were recruited from a hospital in Hunan Province, China.

Radiomics of multimodal ultrasound for early prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer.

Rationale And Objectives: To construct and validate a clinical-radiomics model based on radiomics features extracted from two-stage multimodal ultrasound and clinicopathologic information for early predicting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients treated with NAC.

Materials And Methods: Consecutive women with biopsy-proven breast cancer undergoing multimodal US pretreatment and after two cycles of NAC and followed by surgery between January 2014 and November 2023 were retrospectively collected for clinical-radiomics model construction (n = 274) and retrospective test (n = 134). The predictive performance of it was further tested in a subsequent prospective internal test set recruited between January 2024 to July 2024 (n = 76).

Prevent and Reverse Metabolic Dysfunction-Associated Steatohepatitis and Hepatic Fibrosis via mRNA-Mediated Liver-Specific Antibody Therapy.

Chronic exposure of the liver to multiple insults culminates in the development of metabolic dysfunctionassociated steatohepatitis (MASH), a complicated metabolic syndrome characterized by hepatic steatosis and inflammation, typically accompanied by progressive fibrosis. Despite extensive clinical evaluation, there remain challenges in MASH drug development, which are primarily due to unsatisfactory efficacy and limited specificity. Strategies to address the unmet medical need for MASH with fibrosis before it reaches the irreversible stage of decompensated cirrhosis are critically needed.

circRNA18_46222157_46248185 inhibits melanogenesis by targeting miR-211/EP300 pathway in goat melanocytes.

Objective: This study investigated the effects of circRNA18_46222157_46248185 (named circRNA18) on goat melanogenesis, which differs significantly in goat skins isolated from white and brown coat-colored skins.

Methods: Expression patterns of circRNA18 in goat skin and melanocytes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. The circRNA18 interference vector was designed and synthesized to transfect melanocytes and detect the effect of circRNA18 interference on melanin production.

Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy.

Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative "LOOP" platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08 featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs.

mA-mediated HDAC9 upregulation promotes particulate matter-induced airway inflammation via epigenetic control of DUSP9-MAPK axis and acts as an inhaled nanotherapeutic target.

Exposure to particulate matter (PM) can cause airway inflammation and worsen various airway diseases. However, the underlying molecular mechanism by which PM triggers airway inflammation has not been completely elucidated, and effective interventions are lacking. Our study revealed that PM exposure increased the expression of histone deacetylase 9 (HDAC9) in human bronchial epithelial cells and mouse airway epithelium through the METTL3/mA methylation/IGF2BP3 pathway.

Injectable Gelled Multiple Emulsion for Glucose-Responsive Insulin Delivery.

A glucose-responsive insulin delivery system that sustains blood glucose equilibrium for an extended duration can address the low therapeutic window of insulin in diabetes treatment. Herein, insulin is loaded in a water-in-oil-in-water (W/O/W) gelled multiple emulsion using poly (4-vinylphenylboronic acid) (PVPBA) homopolymer as an effective emulsifier. The gelled multiple emulsion exhibits a high encapsulation efficiency (99%), enhanced stability and remarkable shear-thinning behavior, making it easy to inject.

Delivery of mRNA Encoding Interleukin-12 and a Stimulator of Interferon Genes Agonist Potentiates Antitumor Efficacy through Reversing T Cell Exhaustion.

T cell exhaustion has emerged as a major hurdle that impedes the clinical translation of stimulator of interferon genes (STING) agonists. It is crucial to explore innovative strategies to rejuvenate exhausted T cells and potentiate the antitumor efficacy. Here, we propose an approach utilizing MSA-2 as a STING agonist, along with nanoparticle-mediated delivery of mRNA encoding interleukin-12 (IL-12) to restore the function of T cells.

Red cell distribution width to total serum calcium ratio and in-hospital mortality risk in patients with acute ischemic stroke: A MIMIC-IV retrospective analysis.

We investigated the relationship among red cell distribution width (RDW), to total serum calcium (TSC) ratio (RCR), and in-hospital mortality in patients with acute ischemic stroke (AIS). This study was a retrospective analysis. The data of 2700 AIS patients was retrospectively analyzed from the Medical Information Mart for Intensive Care database (version IV).

Targeted mRNA Nanoparticles Ameliorate Blood-Brain Barrier Disruption Postischemic Stroke by Modulating Microglia Polarization.

The ischemic stroke is a major global health concern, with high mortality and disability rates. Unfortunately, there is a dearth of effective clinical interventions for managing poststroke neuroinflammation and blood-brain barrier (BBB) disruption that are crucial for the brain injury evolving and neurological deficits. By leveraging the pathological progression of an ischemic stroke, we developed an M2 microglia-targeting lipid nanoparticle (termed MLNP) approach that can selectively deliver mRNA encoding phenotype-switching interleukin-10 (m) to the ischemic brain, creating a beneficial feedback loop that drives microglial polarization toward the protective M2 phenotypes and augments the homing of m-loaded MLNPs (m@MLNPs) to ischemic regions.

Prunolactones A-G, proangiogenic isocoumarin derivatives with an unusual 6/6/6/6/6 spiropentacyclic skeleton from the endophytic fungus Phomopsis prunorum.

Seven novel isocoumarins, prunolactones A-G (1-7), featuring an unusual 6/6/6/6/6 spiropentacyclic skeleton, together with two biosynthetic precursors phomopsilactone (8) and methyl 3-epi-shikimate (9), were isolated from the endophytic fungus Phomopsis prunorum guided by UPLC-QTOF-MS and H NMR spectroscopic analytical techniques. Their structures including absolute configurations of 1-7 were elucidated based on extensive spectroscopic data, X-ray diffraction analysis, and ECD calculations. Biogenetically, compounds 1-7 are proposed to be derived from polyketide and shikimate pathways via key intermolecular Diels - Alder reactions.

Modulating Plaque Inflammation Targeted mRNA Nanoparticles for the Treatment of Atherosclerosis.

Atherosclerosis is a common pathology present in many cardiovascular diseases. Although the current therapies (including statins and inhibitors of the serine protease PCSK9) can effectively reduce low-density lipoprotein (LDL) cholesterol levels to guideline-recommended levels, major adverse cardiovascular events still occur frequently. Indeed, the subendothelial retention of lipoproteins in the artery wall triggers multiple events of inflammation in macrophages and is a major contributor to the pathological progression of atherosclerosis.

Nanoparticle-Mediated RNA Therapy Attenuates Nonalcoholic Steatohepatitis and Related Fibrosis by Targeting Activated Hepatic Stellate Cells.

Chronic liver injury and inflammation triggered by metabolic abnormalities initiate the activation of hepatic stellate cells (HSCs), driving fibrosis and parenchymal dysfunction, culminating in disorders such as nonalcoholic steatohepatitis (NASH). Unfortunately, there are currently no approved drugs capable of effectively treating NASH due to the challenges in addressing fibrosis and restoring extracellular matrix (ECM) homeostasis. We discovered a significant up-regulation of interleukin-11 (IL-11) in fibrotic livers using two well-established murine models of NASH.

mRNA lipid nanoparticle-mediated pyroptosis sensitizes immunologically cold tumors to checkpoint immunotherapy.

Synergistically improving T-cell responsiveness is promising for favorable therapeutic outcomes in immunologically cold tumors, yet current treatments often fail to induce a cascade of cancer-immunity cycle for effective antitumor immunity. Gasdermin-mediated pyroptosis is a newly discovered mechanism in cancer immunotherapy; however, cleavage in the N terminus is required to activate pyroptosis. Here, we report a single-agent mRNA nanomedicine-based strategy that utilizes mRNA lipid nanoparticles (LNPs) encoding only the N-terminus of gasdermin to trigger pyroptosis, eliciting robust antitumor immunity.

Inhalable siRNA Nanoparticles for Enhanced Tumor-Targeting Treatment of -Mutant Non-Small-Cell Lung Cancer.

() is the most commonly mutated oncogene in lung cancers. Gene therapy is emerging as a promising cancer treatment modality; however, the systemic administration of gene therapy has been limited by inefficient delivery to the lungs and systemic toxicity. Herein, we report a noninvasive aerosol inhalation nanoparticle (NP) system, termed "si@GCLPP NPs," to treat -mutant non-small-cell lung cancer (NSCLC).

Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis.

Unlabelled: Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator.

The Relationship Between Mindfulness, Fatigue, and Perceived Symptoms Among Frontline Nurses Who Performed Nucleic Acid Sample Collection During the COVID-19 in China: A Cross-Sectional Study.

Objective: Given the immense stress faced by medical staff during the COVID-19 pandemic, this study aimed to evaluate the relationship between mindful attention awareness, fatigue, and perceived symptoms among frontline nurses who performed nucleic acid sample collection during the COVID-19 pandemic, to reduce their fatigue and help them cope with perceived uncomfortable symptoms.

Methods: A convenience sampling method was used to survey nurses who travelled to Hainan for nucleic acid sampling in August 2022 using an online (WeChat) questionnaire. A total of 514 frontline nurses who performed nucleic acid tests completed the questionnaire.

Alleviate Periodontitis and Its Comorbidity Hypertension using a Nanoparticle-Embedded Functional Hydrogel System.

Periodontitis and hypertension often occur as comorbidities, which need to be treated at the same time. To resolve this issue, a controlled-release composite hydrogel approach is proposed with dual antibacterial and anti-inflammatory activities as a resolution to achieve the goal of co-treatment of comorbidities. Specifically, chitosan (CS) with inherent antibacterial properties is cross-linked with antimicrobial peptide (AMP)-modified polyethylene glycol (PEG) to form a dual antibacterial hydrogel (CS-PA).

Discovery, total syntheses and potent anti-inflammatory activity of pyrrolinone-fused benzoazepine alkaloids Asperazepanones A and B from Aspergillus candidus.

Natural products are well established as an important resource and play an important role in drug discovery. Here, two pyrrolinone-fused benzoazepine alkaloids, (+)-asperazepanones A (1) and B (2) with a 6/7/5 ring system, together with the artifact (-)-asperazepanone A (1), were isolated from the coral-derived Aspergillus candidus fungus. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, single crystal X-ray diffraction, and ECD calculations.

Occurrence, transport and environmental risk assessment of pharmaceuticals and personal care products (PPCPs) at the mouth of Jiaozhou Bay, China based on stir bar sorptive extraction.

In recent years, research on pharmaceuticals and personal care products (PPCPs) in the marine environment has attracted increasing attention worldwide. However, more work is needed to improve PPCPs detection methods, specifically for seawater environments. An analytical method based on stir bar sorptive extraction (SBSE) had been developed and fully optimized for the pretreatment and detection of ten widely used PPCPs that are commonly found in seawater samples.

Lipid-Polymer Hybrid "Particle-in-Particle" Nanostructure Gene Delivery Platform Explored for Lyophilizable DNA and mRNA COVID-19 Vaccines.

SARS-CoV-2 has led to a worldwide pandemic, catastrophically impacting public health and the global economy. Herein, a new class of lipid-modified polymer poly (β-amino esters) (L-PBAEs) is developed via enzyme-catalyzed esterification and further formulation of the L-PBAEs with poly(d,l-lactide-coglycolide)--poly(ethylene glycol) (PLGA-PEG) leads to self-assembly into a "particle-in-particle" (PNP) nanostructure for gene delivery. Out of 24 PNP candidates, the top-performing PNP/C12-PBAE nanoparticles efficiently deliver both DNA and mRNA in vitro and in vivo, presenting enhanced transfection efficacy, sustained gene release behavior, and excellent stability for at least 12 months of storage at -20 °C after lyophilization without loss of transfection efficacy.

Inhaled siRNA nanoparticles targeting inhibit lung fibrosis and improve pulmonary function post-bleomycin challenge.

Interleukin-11 (IL-11) is a profibrotic cytokine essential for the differentiation of fibroblasts into collagen-secreting, actin alpha 2, smooth muscle-positive (ACTA2) myofibroblasts, driving processes underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF). Here, we developed an inhalable and mucus-penetrative nanoparticle (NP) system incorporating siRNA against (si@PPGC NPs) and investigated therapeutic potential for the treatment of IPF. NPs are formulated through self-assembly of a biodegradable PLGA-PEG diblock copolymer and a self-created cationic lipid-like molecule G0-C14 to enable efficient transmucosal delivery of si.