Multi-omics Techniques for Profiling Chromatin State Transitions in Low-input Primary Mouse Cholangiocytes.

Polycystic liver disease (PLD) is a hereditary disorder characterized by the formation of fluid-filled cysts derived from cholangiocytes, leading to progressive disease and a significant reduction in patients' quality of life. Current treatments for PLD are inadequate, emphasizing the need for novel therapeutic strategies. The role of epigenetic regulation in PLD progression, particularly chromatin accessibility and histone modifications, remains underexplored.

Somatostatin receptor 2 targeting peptide modifications for peptide-drug conjugate treatment of small cell lung cancer.

Peptide-drug conjugate (PDC) represents a special therapeutic strategy to enhance drug delivery by targeting tumor cell receptors while minimizing off-target effects. Comparing the antibody-drug conjugate (ADC), the targeting peptide constitutes the pivotal component of PDC, especially with easy optimization of peptides to promote their in vivo stability, and with the agonist stimulated GPCR internalization to facilitate drug distribution into tumor cell plasma. Herein, we have optimized a highly stable peptide molecule LanTC targeting somatostatin receptor 2 (SSTR2), through amino acid substitution and disulfide bond modification from an FDA proved peptide drug Lanreotide.

A large-dynamic-range high-time-resolved transmission grating spectrometer for the measurement of broadband x-ray spectrum.

The temporal measurement of broadband x-ray spectrum is important for the study of x-ray sources and their applications in high-energy-density plasmas. A spectrometer with a large dynamic range is required for these measurements. In this paper, a large-dynamic-range x-ray spectrometer has been designed, in which transmission grating is coupled to an x-ray streak camera with a novel varying-width slit photocathode.

Isolation and Culture of Primary Cholangiocytes from Mice with Polycystic Liver Disease Using a Two-step Digestion Method.

In this protocol, we optimized a two-step digestion method to isolate high-purity and high-viability primary cholangiocytes from wild-type mice and mice with polycystic liver disease (PLD). After anesthetizing the mice, the livers were perfused through the inferior vena cava with 50 mL of Solution A, followed by 30 mL of Solution B at 37 °C to enzymatically digest the liver tissue. Mechanical dissociation, shaking, and microdissection were performed to remove adherent parenchymal cells, leaving an intact biliary tree.

Photoactivatable base editors for spatiotemporally controlled genome editing in vivo.

CRISPR-based base editors (BEs) are powerful tools for precise nucleotide substitution in a wide range of organisms, but spatiotemporal control of base editing remains a daunting challenge. Herein, we develop a photoactivatable base editor (Mag-ABE) for spatiotemporally controlled genome editing in vivo for the first time. The base editing activity of Mag-ABE can be activated by blue light for spatiotemporal regulation of both EGFP reporter gene and various endogenous genes editing.

Multi-omics profiling of cholangiocytes reveals sex-specific chromatin state dynamics during hepatic cystogenesis in polycystic liver disease.

Background & Aims: Cholangiocytes transit from quiescence to hyperproliferation during cystogenesis in polycystic liver disease (PLD), the severity of which displays prominent sex differences. Epigenetic regulation plays important roles in cell state transition. We aimed to investigate the sex-specific epigenetic basis of hepatic cystogenesis and to develop therapeutic strategies targeting epigenetic modifications for PLD treatment.

Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues.

The endogenous cyclic tetradecapeptide SST14 was reported to stimulate all five somatostatin receptors (SSTR1-5) for hormone release, neurotransmission, cell growth arrest and cancer suppression. Two SST14-derived short cyclic SST analogues (lanreotide or octreotide) with improved stability and longer lifetime were developed as drugs to preferentially activate SSTR2 and treat acromegalia and neuroendocrine tumors. Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.

Probing Mechanical Properties of Brain in a Tuberous Sclerosis Model of Autism.

Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein.

A time-gated multi-channel x-ray crystal spectrometer on the Shenguang-III laser facility.

An eight-channel x-ray flat crystal spectrometer was developed for high energy density physics research at the Shenguang-III (SG-III) laser facility. The spectrometer uses trihydroxymethylaminomethane crystals (2 = 8.78 Å) to record Ti K-shell emission in the photon energy range of 4.

Adverse reactions analysis and prevention of antiseptic drug in the obstetrics and gynecology nursing.

Antimicrobial agents are widely used in gynecologic inflammation and surgical period, so as to cure some infectious diseases, reduce the chance of surgical incision infection, but at the same time, there are many adverse reactions. The use of nursing interventions in obstetrics and gynecology can significantly reduce the adverse drug reactions in the treatment. The results showed that the incidence of adverse reactions in the observation group was 8.

Characterizing viscoelastic mechanical properties of highly compliant polymers and biological tissues using impact indentation.

Unlabelled: Precise and accurate measurement of viscoelastic mechanical properties becomes increasingly challenging as sample stiffness decreases to elastic moduli <1 kPa, largely due to difficulties detecting initial contact with the compliant sample surface. This limitation is particularly relevant to characterization of biological soft tissues and compliant gels. Here, we employ impact indentation which, in contrast to shear rheology and conventional indentation, does not require contact detection a priori, and present a novel method to extract viscoelastic moduli and relaxation time constants directly from the impact response.

Characterizing Multiscale Mechanical Properties of Brain Tissue Using Atomic Force Microscopy, Impact Indentation, and Rheometry.

To design and engineer materials inspired by the properties of the brain, whether for mechanical simulants or for tissue regeneration studies, the brain tissue itself must be well characterized at various length and time scales. Like many biological tissues, brain tissue exhibits a complex, hierarchical structure. However, in contrast to most other tissues, brain is of very low mechanical stiffness, with Young's elastic moduli E on the order of 100s of Pa.

Layered and scrolled nanocomposites with aligned semi-infinite graphene inclusions at the platelet limit.

Two-dimensional (2D) materials can uniquely span the physical dimensions of a surrounding composite matrix in the limit of maximum reinforcement. However, the alignment and assembly of continuous 2D components at high volume fraction remain challenging. We use a stacking and folding method to generate aligned graphene/polycarbonate composites with as many as 320 parallel layers spanning 0.

Extreme ultraviolet spectrometer for the Shenguang III laser facility.

An extreme ultraviolet spectrometer has been developed for high-energy density physics experiments at the Shenguang-III (SG-III) laser facility. Alternative use of two different varied-line-spacing gratings covers a wavelength range of 10-260 Å. A newly developed x-ray framing camera with single wide strip line is designed to record time-gated spectra with ~70 ps temporal resolution and 20 lp/mm spatial resolution.

Calibration of a gated flat field spectrometer as a function of x-ray intensity.

We present an experimental determination of the response of a gated flat-field spectrometer at the Shenguang-II laser facility. X-rays were emitted from a target that was heated by laser beams and then were divided into different intensities with a step aluminum filter and collected by a spectrometer. The transmission of the filter was calibrated using the Beijing Synchrotron Radiation Facility.