An intermediate open structure reveals the gating transition of the mechanically activated PIEZO1 channel.

PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation. However, its distinct structural states remain undefined. Here, we employed an open-prone PIEZO1-S2472E mutant to capture an intermediate open structure.

Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed.

Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions.

Adult brain activities are generally believed to be dominated by chemical and electrical transduction mechanisms. However, the importance of mechanotransduction mediated by mechano-gated ion channels in brain functions is less appreciated. Here, we show that the mechano-gated Piezo1 channel is expressed in the exploratory processes of astrocytes and utilizes its mechanosensitivity to mediate mechanically evoked Ca responses and ATP release, establishing Piezo1-mediated mechano-chemo transduction in astrocytes.

Epidemiology of Cardiopulmonary Arrest and Outcome of Resuscitation in PICU Across China: A Prospective Multicenter Cohort Study.

Objective: To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China.

Methods: A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017-October 2018).

Preparation of chitosan-cellulose-benzyl isothiocyanate nanocomposite film for food packaging applications.

To improve the mechanical and barrier properties of cellulose and chitosan (CS) and to allow the application of volatile antibacterial benzyl isothiocyanate (BITC) in active packaging, a double-layer nanocomposite film was prepared. Cellulose nanofibers (CNF) were crosslinked with CS via genipin to build the substrate. Quaternized cellulose nanocrystals (QCNC) were synthesized for carrying BITC as the coating material.

Tethering Piezo channels to the actin cytoskeleton for mechanogating via the cadherin-β-catenin mechanotransduction complex.

The mechanically activated Piezo channel plays a versatile role in conferring mechanosensitivity to various cell types. However, how it incorporates its intrinsic mechanosensitivity and cellular components to effectively sense long-range mechanical perturbation across a cell remains elusive. Here we show that Piezo channels are biochemically and functionally tethered to the actin cytoskeleton via the cadherin-β-catenin mechanotransduction complex, whose perturbation significantly impairs Piezo-mediated responses.

TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells.

TMEM120A, a member of the transmembrane protein 120 (TMEM120) family, has a pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells and have solved cryo-electron microscopy (cryo-EM) structures of human TMEM120A (TMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. TMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices.

Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels.

The evolutionarily conserved Piezo channel family, including Piezo1 and Piezo2 in mammals, serves as versatile mechanotransducers in various cell types and consequently governs fundamental pathophysiological processes ranging from vascular development to the sense of gentle touch and tactile pain. Piezo1/2 possess a unique 38-transmembrane (TM) helix topology and form a homotrimeric propeller-shaped structure comprising a central ion-conducting pore and three peripheral mechanosensing blades. The unusually curved TM region of the three blades shapes a signature nano-bowl configuration with potential to generate large in-plane membrane area expansion, which might confer exquisite mechanosensitivity to Piezo channels.

Antibacterial Activity and Potential Application in Food Packaging of Peptides Derived from Turbot Viscera Hydrolysate.

As a good choice for food preservation, antimicrobial peptides (AMPs) have received much attention in recent years. In this paper, peptides derived from the turbot viscera hydrolysate were identified by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), and the physicochemical properties and structural characteristics were analyzed by tools. Furthermore, three cationic peptides with potential hydrophobicity and amphipathy were synthesized; their cytotoxicity, hemolysis, and antibacterial activities were investigated.

Electrochemical strategy with zeolitic imidazolate framework-8 and ordered mesoporous carbon for detection of xanthine.

An accurate, safe, environmentally friendly, fast and sensitive electrochemical biosensors were developed to detect xanthine in serum. The metal-organic framework ZIF-8 was synthesised and elemental gold was supported on the surface of ZIF-8 by reduction method to synthesise Ag-ZIF-8. The mesoporous carbon material and the synthesised Ag-ZIF-8 were, respectively, applied to a glassy carbon electrode to construct biosensors.

Design of foveated contact lens display for augmented reality.

We present a design of a contact lens display, which features an array of collimated light-emitting diodes and a contact lens, for the augmented reality. By building the infrastructure directly on top of the eye, eye is allowed to move or rotate freely without the need of exit pupil expansion nor eye tracking. The resolution of light-emitting diodes is foveated to match with the density of cones on the retina.

Protein arginine methyltransferase-1 deficiency restrains depression-like behavior of mice by inhibiting inflammation and oxidative stress via Nrf-2.

Current evidence indicates that depression is accompanied by the activation of inflammatory response and oxidative stress. Protein arginine methyltransferase 1 (PRMT1) is a histone methyltransferase that methylates Arg3 on histone H4, playing crucial role in regulating various pathological processes. In the study, we attempted to explore the effects of PRMT1 on animal model with depression through a single administration of lipopolysaccharide (LPS).

Adiponectin Suppresses Human Pancreatic Cancer Growth through Attenuating the β-Catenin Signaling Pathway.

Adipokines are emerging as a link between obesity and obesity-related cancers, including pancreatic cancer. Adiponectin is an abundant adipokine with pleiotropic beneficial roles in metabolic disorders. Low adiponectin levels are commonly observed in human obesity and have been associated with increased pancreatic cancer risk in prospective epidemiologic studies.

Exposure to an enriched environment promotes the terminal maturation and proliferation of natural killer cells in mice.

The maturation of natural killer (NK) cells is critical for the acquisition of robust effector functions and the immune response to tumors. However, the influence of psychological stress on NK-cell maturation remains unknown. In this study, we investigated the alteration of NK-cell maturation in response to enriched environment (EE) exposure, which induced eustress, or positive stress, in mice.

Implantable sandwich PHBHHx film for burst-free controlled delivery of thymopentin peptide.

Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate--hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method.

Meta-analysis of SIRT1 expression as a prognostic marker for overall survival in gastrointestinal cancer.

Sirtuin 1 (SIRT1), a well-characterized NAD-dependent histone deacetylase, is generally up-regulated in gastrointestinal cancers. However, the prognostic value of SIRT1 in gastrointestinal cancer remains inconclusive. Therefore, we report a meta-analysis of the association of SIRT1 expression with overall survival (OS) in gastrointestinal cancer.

Simple strategy for sensitive detection of dopamine using CdTe QDs modified glassy carbon electrode.

Background: Cellular and brain metabolism of dopamine can be correlated with a number of neurodegenerative disorders, our study was to explore a simple and efficient method to detect dopamine in real samples.

Methods: A new quantum dots (CdTe QDs) could be prepared using the hydrothermal method, the electrochemical biosensor was established by dropping CdTe QDs on the surface of glassy carbon electrode (GCE).

Results: The CdTe QDs/GCE exhibited the excellent electrochemical catalytic activity toward dopamine (DA) with good stability and high sensitivity in presence of interfering substances.

A Label-Free Electrochemical Biosensor Based on a Reduced Graphene Oxide and Indole-5-Carboxylic Acid Nanocomposite for the Detection of .

A label-free DNA hybridization electrochemical sensor for the detection of Klebsiella pneumoniae was developed, which could be helpful in the diagnosis of bacterial infections. Indole-5-carboxylic acid (ICA) and graphene oxide (GO) were electrodeposited on a glassy carbon electrode, and the resulting reduced GO (rGO)-ICA hybrid film served as a platform for immobilizing oligonucleotides on a single-stranded DNA (ssDNA) sequence. The conditions were optimized, with excellent electrochemical performance.

Preparation of quantum dots CdTe decorated graphene composite for sensitive detection of uric acid and dopamine.

The assembly of quantum dots (QDs) in a simply method opens up opportunities to obtain access to the full potential of assembled QDs by virtue of the collective properties of the ensembles. In this study, quantum dots CdTe and graphene (Gr) nanocomposite was constructed for the simultaneous determination of uric acid (UA) and dopamine (DA). The CdTe QDs-Gr nanocomposite was prepared by ultrasonication and was characterized with microscopic techniques.

Upregulation of miR-125b by estrogen protects against non-alcoholic fatty liver in female mice.

Background & Aims: Due to the protective effect of estrogen against hepatic fat accumulation, the prevalence of non-alcoholic fatty liver disease (NAFLD) in premenopausal women is lower than that in men at the same age and in postmenopausal women. Our study was to further elucidate an underlying mechanism by which estrogen prevents NAFLD from miRNA perspective in female mice.

Methods: miRNA expression was evaluated by TaqMan miRNA assay.

Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety.

To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity.

Optimization of extraction and enrichment of steroidal alkaloids from bulbs of cultivated Fritillaria cirrhosa.

The bulbs of cultivated Fritillaria cirrhosa (BCFC) are used in China both for food and folk medicine due to its powerful biological activities. The aim of this study is to optimize the extraction and enrichment conditions of alkaloids from BCFC. Firstly, the orthogonal experimental design was used to optimize and evaluate four variables (ethanol concentration, solid-liquid ratio, extraction time, and temperature).