Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure.

Acute liver failure (ALF) is a hepatology emergency with rapid hepatic destruction, multiple organ failures, and high mortality. Despite decades of research, established ALF has minimal therapeutic options. Here, we report that the small bioactive compound SCM-198 increases the survival of male ALF mice to 100%, even administered 24 hours after ALF establishment.

The chromatin-associated 53BP1 ortholog, HSR-9, regulates recombinational repair and X chromosome segregation in the Caenorhabditis elegans germ line.

53BP1 plays a crucial role in regulating DNA damage repair pathway choice and checkpoint signaling in somatic cells; however, its role in meiosis has remained enigmatic. In this study, we demonstrate that the Caenorhabditis elegans ortholog of 53BP1, HSR-9, associates with chromatin in both proliferating and meiotic germ cells. Notably, HSR-9 is enriched on the X chromosome pair in pachytene oogenic germ cells.

Application of dose-gradient function in reducing radiation induced lung injury in breast cancer radiotherapy.

Objective: Try to create a dose gradient function (DGF) and test its effectiveness in reducing radiation induced lung injury in breast cancer radiotherapy.

Materials And Methods: Radiotherapy plans of 30 patients after breast-conserving surgery were included in the study. The dose gradient function was defined as DGH=VDVp3, then the area under the DGF curve of each plan was calculated in rectangular coordinate system, and the minimum area was used as the trigger factor, and other plans were triggered to optimize for area reduction.

Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells.

The RNA-binding protein Musashi-1 (MSI1) regulates the proliferation and differentiation of adult stem cells. However, its role in embryonic stem cells (ESCs) and early embryonic development remains poorly understood. Here, we report the presence of short C-terminal MSI1 (MSI1-C) proteins in early mouse embryos and mouse ESCs, but not in human ESCs, under conventional culture conditions.

mutation enhances and embryonic lethality in .

In mice, mutation of results in embryonic lethality, which is partially suppressed by mutation. In contrast, mutation of the BRCA1 ortholog, or its binding partner, , lead to only mild embryonic lethality. We show that in , and embryonic lethality is enhanced when ortholog, , is also mutated.

Differential requirement for BRCA1-BARD1 E3 ubiquitin ligase activity in DNA damage repair and meiosis in the Caenorhabditis elegans germ line.

The tumor suppressor BRCA1-BARD1 complex regulates many cellular processes; of critical importance to its tumor suppressor function is its role in genome integrity. Although RING E3 ubiquitin ligase activity is the only known enzymatic activity of the complex, the in vivo requirement for BRCA1-BARD1 E3 ubiquitin ligase activity has been controversial. Here we probe the role of BRCA1-BARD1 E3 ubiquitin ligase activity in vivo using C.

Evi5 is required for limb and tail regeneration.

Amphibians such as salamanders and the African clawed frog are great models for regeneration studies because they can fully regenerate their lost organs. While axolotl can regenerate damaged organs throughout its lifetime, has a limited regeneration capacity after metamorphosis. The ecotropic viral integrative factor 5 (Evi5) is of great interest because its expression is highly upregulated in the limb blastema of axolotls, but remains unchanged in the fibroblastema of post-metamorphic frogs.

Inducible degradation of dosage compensation protein DPY-27 facilitates isolation of Caenorhabditis elegans males for molecular and biochemical analyses.

Biological sex affects numerous aspects of biology, yet how sex influences different biological processes have not been extensively studied at the molecular level. Caenorhabditis elegans, with both hermaphrodites (functionally females as adults) and males, is an excellent system to uncover how sex influences physiology. Here, we describe a method to isolate large quantities of C.

Glutathione-Activated NO-/ROS-Generation Nanoparticles to Modulate the Tumor Hypoxic Microenvironment for Enhancing the Effect of HIFU-Combined Chemotherapy.

The combination of high-intensity focused ultrasound (HIFU) and chemotherapy has promising potential in the synergistic treatment of various types of solid tumors. However, the clinical efficacy of HIFU in combination chemotherapy is often impeded by the pre-existing hypoxia tumor microenvironment-induced multidrug resistance (MDR). Therefore, it is imperative for HIFU combined with chemotherapy to overcome MDR by improving the tumor hypoxic microenvironment.

Meiotic Double-Strand Break Processing and Crossover Patterning Are Regulated in a Sex-Specific Manner by BRCA1-BARD1 in .

Meiosis is regulated in a sex-specific manner to produce two distinct gametes, sperm and oocytes, for sexual reproduction. To determine how meiotic recombination is regulated in spermatogenesis, we analyzed the meiotic phenotypes of mutants in the tumor suppressor E3 ubiquitin ligase BRC-1-BRD-1 complex in male meiosis. Unlike in mammals, this complex is not required for meiotic sex chromosome inactivation, the process whereby hemizygous sex chromosomes are transcriptionally silenced.

Ultrasound Combined with Core Cross-Linked Nanosystem for Enhancing Penetration of Doxorubicin Prodrug/Beta-Lapachone into Tumors.

Background: Nanosized drug delivery systems (NDDSs) have shown excellent prospects in tumor therapy. However, insufficient penetration of NDDSs has significantly impeded their development due to physiological instability and low passive penetration efficiency.

Methods: Herein, we prepared a core cross-linked pullulan-modified nanosized system, fabricated by visible-light-induced diselenide bond cross-linked method for transporting β-Lapachone and doxorubicin prodrug (boronate-DOX, BDOX), to improve the physiological stability of the NDDSs for efficient passive accumulation in tumor blood vessels (β-Lapachone/BDOX-CCS).

A redox-sensitive core-crosslinked nanosystem combined with ultrasound for enhanced deep penetration of nanodiamonds into tumors.

Nanodiamonds (NDs) as drug delivery vehicles are of great significance in anticancer therapy through enhancing drug retention. However, the major barrier to clinical application of NDs is insufficient tumor penetration owing to their strong aggregation and low passive penetration efficiency. Herein, the core-crosslinked pullulan carrier, assembled using the visible light-induced diselenide (Se-Se) bond crosslinking method for encapsulating nanodiamonds-doxorubicin (NDX), is proposed to improve monodispersity.

Enzyme-Catalytic Self-Triggered Release of Drugs from a Nanosystem for Efficient Delivery to Nuclei of Tumor Cells.

Stimulus-responsive drug delivery nanosystems (DDSs) are of great significance in improving cancer therapy for intelligent control over drug release. However, among them, many DDSs are unable to realize rapid and sufficient drug release because most internal stimulants might be consumed during the release process. To address the plight, an abundant supply of stimulants is highly desirable.

Spherical spindle shape promotes perpendicular cortical orientation by preventing isometric cortical pulling on both spindle poles during female meiosis.

Meiotic spindles are positioned perpendicular to the oocyte cortex to facilitate segregation of chromosomes into a large egg and a tiny polar body. In , spindles are initially ellipsoid and parallel to the cortex before shortening to a near-spherical shape with flattened poles and then rotating to the perpendicular orientation by dynein-driven cortical pulling. The mechanistic connection between spindle shape and rotation has remained elusive.

pH-sensitive pullulan-doxorubicin nanoparticles loaded with 1,1,2-trichlorotrifluoroethane as a novel synergist for high intensity focused ultrasound mediated tumor ablation.

Nanoemulsions as synergists of high intensity focused ultrasound (HIFU) have been widely investigated, since they possess huge potential for improving the efficiency to ablate tumor. However, their clinical applications are limited due to the unsatisfactory phase-transition effect of nanoemulsions during the process of generating nanobubbles. Herein, a novel synergist for HIFU therapy was designed by encapsulating 1,1,2-trichlorotrifluoroethane (CFC) into pH-sensitive pullulan-doxorubicin (Pu-DOX/CFC) nanoparticles.

LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining.

The Caenorhabditis elegans SUN domain protein, UNC-84, functions in nuclear migration and anchorage in the soma. We discovered a novel role for UNC-84 in DNA damage repair and meiotic recombination. Loss of UNC-84 leads to defects in the loading and disassembly of the recombinase RAD-51.

[Cloning and characterization of a thermostable urate oxidase from Microbacterium sp. strain ZZJ4-1].

In order to characterize a thermostable urate oxidase (Uox) from Microbacterium sp. strain ZZJ4-1, we cloned its gene (uox). The open reading frame of uox contained 894 base pairs and encoded a protein with 297 amino acids.

[Cloning, expression and characterization of a gamma-butyrobetaine hydroxylase gene bbh from Pseudomonas sp. L-1].

Objective: Gamma-butyrobetaine hydroxylase is an enzyme that catalyzes the last step in the biosynthesis of L-carnitine. We cloned, expressed and characterized a gamma-butyrobetaine hydroxylase gene bbh from Pseudomonas sp. L-1, to facilitate the production of L-carnitine using microorganisms.