Efficient fabrication of chitin-based films with high UV-blocking and fluorescence via Hantzsch reaction.

As the second most abundant polysaccharide on earth, chitin-based films are promising packaging and biomedical materials. However, the lack of special function (especially UV-blocking properties and fluorescence) usually restricts their further and high-value applications. Herein, high UV-blocking and fluorescence chitin-based films were fabricated via surface modification using acetoacetation and the Hantzsch reaction.

Day and Night Reversed Feeding Aggravates High-Fat Diet-Induced Abnormalities in Intestinal Flora and Lipid Metabolism in Adipose Tissue of Mice.

Background: The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic disorders. The intestinal microflora engages in regulating various physiological functions of the host through its metabolites.

Objectives: This study aimed to investigate the impact of reversed feeding schedules during the day and night on intestinal flora and lipid metabolism in high-fat diet-induced obese mice.

Ferroptosis-Related lncRNA to Predict the Clinical Outcomes and Molecular Characteristics of Kidney Renal Papillary Cell Carcinoma.

Kidney renal papillary cell carcinoma (KIRP) is a highly heterogeneous type of kidney cancer, resulting in limited effective prognostic targets for KIRP patients. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the regulation of ferroptosis and iron metabolism, making them potential targets for the treatment and prognosis of KIRP. In this study, we constructed a ferroptosis-related lncRNA risk score model (FRM) based on the TCGA-KIRP dataset, which represents a novel subtype of KIRP not previously reported.

knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis.

Disturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in double-knockout (DKO) and wild-type (WT) mice aged 4, 9, and 14 months.

Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and it is the major cause of kidney cancer death. Understanding tumor immune microenvironments (TMEs) is critical in cancer immunotherapies. Here, we studied the immune characterization at single-cell resolution by integrating public data of ccRCC across different tissue types, and comparing the transcriptome features and tumor TME differences in tumors, normal adjacent tissue, and peripheral blood.

Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice.

Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of Double knockout (DKO) reduced the reproductive capacity of elderly male mice. The sperm motility and spermatogenic capacity of male DKO mice were weak.

A programmable pAgo nuclease with RNA target preference from the psychrotolerant bacterium Mucilaginibacter paludis.

Argonaute (Ago) proteins are programmable nucleases found in eukaryotes and prokaryotes. Prokaryotic Agos (pAgos) share a high degree of structural homology with eukaryotic Agos (eAgos), and eAgos originate from pAgos. Although eAgos exclusively cleave RNA targets, most characterized pAgos cleave DNA targets.

Combination of ultrashort PCR and Argonaute for DNA detection.

A simple and user-friendly nucleic acid sensing platform with 10 aM sensitivity, named USPCRP (combines ultrashort PCR with Argonaute cleavage for nuleic acids detection) is reported. The product of this ultrashort PCR could be directly used as a DNA guide to mediate Ago cleavage of molecular beacons.

Growth arrest and DNA damage-inducible protein 34 (GADD34) contributes to cerebral ischemic injury and can be detected in plasma exosomes.

Growth arrest and DNA damage-inducible protein 34 (GADD34), one of the key effectors of negative feedback loops, is induced by stress and subsequently attempts to restore homeostasis. It plays a critical role in response to DNA damage and endoplasmic reticulum stress. GADD34 has opposing effects on different stimulus-induced cell apoptosis events in many nervous system diseases, but its role in ischemic stroke is unclear.

Pyrococcus furiosus Argonaute coupled with modified ligase chain reaction for detection of SARS-CoV-2 and HPV.

Infectious diseases caused by viruses such as SARS-CoV-2 and HPV have greatly endangered human health. The nucleic acid detection is essential for the early diagnosis of diseases. Here, we propose a method called PLCR (PfAgo coupled with modified Ligase Chain Reaction for nucleic acid detection) which utilizes PfAgo to only use DNA guides longer than 14-mer to specifically cleave DNA and LCR to precisely distinguish single-base mismatch.

A programmable omnipotent Argonaute nuclease from mesophilic bacteria Kurthia massiliensis.

Argonaute (Ago) proteins are conserved nucleic acid-guided proteins present in all domains of life. Eukaryotic Argonaute proteins (eAgos) are key players in RNA interference pathways and function as RNA-guided RNA endonucleases at physiological temperatures. Although eAgos are considered to evolve from prokaryotic Argonaute proteins (pAgos), previously studied pAgos were unable to catalyze RNA-guided RNA cleavage at physiological temperatures.

PfAgo-based detection of SARS-CoV-2.

In the present study, we upgraded Pyrococcus furiosus Argonaute (PfAgo) mediated nucleic acid detection method and established a highly sensitive and accurate molecular diagnosis platform for the large-scale screening of COVID-19 infection. Briefly, RT-PCR was performed with the viral RNA extracted from nasopharyngeal or oropharyngeal swabs as template to amplify conserved regions in the viral genome. Next, PfAgo, guide DNAs and molecular beacons in appropriate buffer were added to the PCR products, followed by incubating at 95 °C for 20-30 min.

Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic Signature in Kidney Renal Papillary Cell Carcinoma.

The kidney renal papillary cell carcinoma (KIRP) is a relatively rare type of renal cell carcinoma (RCC). Currently, most kidney cancer studies primarily focus on RCC, and there has been no investigation to find a robust signature to predict the survival outcome of KIRP patients. In this study, we constructed a competing endogenous RNA (ceRNA) network, including 1,251 lncRNA-miRNA-mRNA interactions.

Application of ultrasound-guided epidural catheter indwelling in painless labour.

Objective: To study the application of ultrasound-guided indwelling epidural catheter in painless labour.

Methods: A total of 300 single-foetus cephalic position and full-term primipara who did not implement labour analgesia under the same conditions were randomly selected. According to the principle of random grouping, 150 pregnant women who requested and signed the informed consent for labour analgesia were selected as the analgesic group (group A).

Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis.

The pathogenesis of ischemic cerebrovascular disease has revealed that ischemia-reperfusion (I/R) injury often leads to aggravation of metabolic oxidative stress and blood-brain barrier (BBB) destruction, eventually causing secondary brain tissue damage. Accumulated reactive oxygen species (ROS) in focal ischemia activate mitochondria-mediated apoptosis and damage the BBB by degrading tight junction proteins (TJPs). Herein, we report macrophage-derived exosomes (Ex) loaded with curcumin (cur) as a multifunctional biomimetic delivery vehicle (Ex-cur) for targeting ischemic brain tissue and alleviating cerebral I/R injury by inhibiting ROS-mediated mitochondrial apoptosis in a transient cerebral ischemia rat model.

Brain Microvascular Endothelial Cell Derived Exosomes Potently Ameliorate Cognitive Dysfunction by Enhancing the Clearance of Aβ Through Up-Regulation of P-gp in Mouse Model of AD.

Accumulation of amyloid-β (Aβ) peptides in the brain is regarded as a major contributor to the pathogenesis and progression of Alzheimer's disease (AD). P-glycoprotein (P-gp) as a member of ABC transporter family situated in blood brain barrier (BBB) plays a role on cleaning of Aβ via its efflux transport effect in the treatment of AD. However, the expression of P-gp in pathological BBB was lower than that in normal BBB, thus impeding the clearance of Aβ.

Plasma exosomes protect against cerebral ischemia/reperfusion injury via exosomal HSP70 mediated suppression of ROS.

Aims: Ischemic stroke is the leading cause of severe disability and death worldwide. As the pathogenesis of stroke has not been clearly elucidated and the ability of current therapeutic drugs on crossing the blood-brain barrier (BBB) is extremely low, there is no effective strategy to treat stroke. We aim at investigating the specific advantages of using plasma exosomes (Pla-Exo) for targeting ischemic brain and exploring its underlying mechanism in neuroprotection.

Characterization of lncRNA-Associated ceRNA Network to Reveal Potential Prognostic Biomarkers in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most fatal malignant tumors harmful to human health. The complexity and behavior characteristics of long-non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in LUAD patients are still unclear. The purpose of this study was to elucidate the regulatory networks of dysregulated RNAs, view, and identify potential prognosis signatures involved in LUAD.

Pyrococcus furiosus Argonaute-mediated nucleic acid detection.

We demonstrate that short single-stranded DNA generated by Pyrococcus furiosus Argonaute (PfAgo) can initiate a second round of cleavage. Based on this principle, we established a molecular diagnostic method, termed PfAgo-mediated Nucleic acid Detection (PAND). This method could detect DNA at attomolar sensitivities, distinguish single-nucleotide mutants and accomplish multiplexed detection.

Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization.

Inflammation occurs throughout the progression of cerebral ischemia/reperfusion and mediates myriads of pathological events following an ischemic insult. After ischemic stroke, inflammation was significantly triggered and microglia were activated to phenotypes (M1) typically releasing pro-inflammatory mediators, thus inducing neuron apoptosis and exacerbating brain injury. Therefore, shifting the polarization of microglia from the detrimental pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype seems a promising therapeutic strategy in ischemic stroke.

Rapid and Error-Free Site-Directed Mutagenesis by a PCR-Free In Vitro CRISPR/Cas9-Mediated Mutagenic System.

The quality and efficiency of any PCR-based mutagenesis technique may not be optimal due to, among other things, amino acid bias, which means that the development of efficient PCR-free methods is desirable. Here, we present a highly efficient in vitro CRISPR/Cas9-mediated mutagenic (ICM) system that allows rapid construction of designed mutants in a PCR-free manner. First, it involves plasmid digestion by utilizing a complex of Cas9 with specific single guide RNA (sgRNA) followed by degradation with T5 exonuclease to generate a 15 nt homologous region.

Considerations for Clinical Review of Cellular Therapy Products: Perspectives of the China Food and Drug Administration Center for Drug Evaluation.

With increasing numbers of technical developments and clinical studies, pioneering cellular/gene therapies are now available that could cure life-threatening disease. Cellular/gene therapy products are broad-ranging and complicated, and thereby bring challenges for clinical review by regulatory agencies. This review discusses principles for the clinical review of cellular therapy products, including protection of clinical trial populations, pharmacodynamics, pharmacokinetics, dose evaluation, clinical efficacy, clinical safety, and risk-management plans.