Chemically engineered antibodies for autophagy-based receptor degradation.

Cell surface receptor-targeted protein degraders hold promise for drug discovery. However, their application is restricted because of the complexity of creating bifunctional degraders and the reliance on specific lysosome-shuttling receptors or E3 ubiquitin ligases. To address these limitations, we developed an autophagy-based plasma membrane protein degradation platform, which we term AUTABs (autophagy-inducing antibodies).

LNK/SH2B3 Loss Exacerbates the Development of Myeloproliferative Neoplasms in CBL-deficient Mice.

Genetic variations of signaling modulator protein LNK (also called SH2B3) are associated with relatively mild myeloproliferative phenotypes in patients with myeloproliferative neoplasms (MPN). However, these variations can induce more severe MPN disease and even leukemic transformation when co-existing with other driver mutations. In addition to the most prevalent driver mutation JAK2V617F, LNK mutations have been clinically identified in patients harboring CBL inactivation mutations, but its significance remains unclear.

Prenatal p25-activated Cdk5 induces pituitary tumorigenesis through MCM2 phosphorylation-mediated cell proliferation.

Aberrant expression of cyclin-dependent kinase 5 (Cdk5) has been reported in pituitary adenomas. However, the role of Cdk5 in the tumorigenesis remains unclear. We show that prenatal p25-activated Cdk5 phosphorylates minichromosome maintenance protein 2 (Mcm2), enhancing minichromosome maintenance (MCM) family proteins and driving intermediate lobe-located melanotrope-originated pituitary tumorigenesis.

Psoas attenuation is associated with early postoperative complications in geriatric patients undergoing multilevel lumbar fusion surgery for degenerative lumbar spinal stenosis.

Background: Morphometric analysis of the psoas major muscle has shown utility in predicting postoperative morbidity in various surgical fields, but its usefulness in predicting complications in elderly patients undergoing multilevel lumbar fusion surgery has not been studied. The study aimed to investigate if psoas major parameters are independent risk factors of early postoperative complication among elderly patients.

Methods: Patients who underwent multilevel lumbar fusion for degenerative lumbar spinal stenosis (DLSS) were included.

Prominent Intrinsic Proton Conduction in Two Robust Zr/Hf Metal-Organic Frameworks Assembled by Bithiophene Dicarboxylate.

To date, developing crystalline proton-conductive metal-organic frameworks (MOFs) with an inherent excellent proton-conducting ability and structural stability has been a critical priority in addressing the technologies required for sustainable development and energy storage. Bearing this in mind, a multifunctional organic ligand, 3,4-dimethylthiophene[2,3-]thiophene-2,5-dicarboxylic acid (HDTD), was employed to generate two exceptionally stable three-dimensional porous Zr/Hf MOFs, [ZrO(OH)(DTD)]·5DMF·HO () and [HfO(OH)(DTD)]·4DMF·HO ), using solvothermal means. The presence of Zr or Hf nodes, strong Zr/Hf-O bonds, the electrical influence of the methyl group, and the steric effect of the thiophene unit all contribute to their structural stability throughout a wide pH range as well as in water.

Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer.

Background: Cyclin-dependent kinase 12 (CDK12)-deficient prostate cancer defines a subtype of castration-resistant prostate cancer (CRPC) with a poor prognosis. Current therapy, including PARP inhibitors, shows minimal treatment efficacy for this subtype of CRPC, and the underlying mechanism remains elusive.

Methods: Based on bioinformatics analysis, we evaluated the relationship between CDK12 deficiency and prostate cancer patient's prognosis and treatment resistance.

Superprotonic conductivity of ketoenamine covalent-organic frameworks grafted by imidazole-based units.

The achievement of covalent organic frameworks (COFs) with high stability and exceptional proton conductivity is of tremendous practical importance and challenge. Given this, we hope to prepare the highly stable COFs carrying CN connectors and enhance their proton conductivity via a post-modification approach. Herein, one COF, TpTta, was successfully synthesized by employing 1,3,5-triformylphloroglucinol (Tp) and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)-trianiline (Tta) as starting materials, which has a β-ketoenamine structure bearing a large amount of -NH groups and intramolecular H-bonds.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs.

Four Lanthanide(III) Metal-Organic Frameworks Fabricated by Bithiophene Dicarboxylate for High Inherent Proton Conduction.

Currently, it is still a challenge to directly achieve highly stable metal-organic frameworks (MOFs) with superior proton conductivity solely through the exquisite design of ligands and the attentive selection of metal nodes. Inspired by this, we are intrigued by a multifunctional dicarboxylate ligand including dithiophene groups, 3,4-dimethylthieno[2,3-]thiophene-2,5-dicarboxylic acid (HDTD), and lanthanide ions with distinct coordination topologies. Successfully, four isostructural three-dimensional lanthanide(III)-based MOFs, [Ln(DTD)(DEF)]·DEF·6HO [Ln = Tb (), Eu (), Sm (), and Dy ()], were solvothermally prepared, in which the effective proton transport will be provided by the coordinated or free solvent molecules, the crystalline water molecules, and the framework components, as well as a large number of highly electronegative S and O atoms.

Ligand-Functionalized MIL-68-type Indium(III) Metal-Organic Frameworks with Prominent Intrinsic Proton Conductivity.

Indium-based metal-organic frameworks (In-MOFs) have now become an attractive class of porous solids in materials science and electrochemistry due to their diverse structures and promising applications. In the field of proton conduction, to find more crystalline MOFs with splendid proton-conductive properties, herein, five three-dimensional isostructural In-MOFs, or (X = NH, OH, Br, or NO) using terephthalic acid (HBDC) or functionalized terephthalic acids (HBDC-X) as multifunctional linkages were efficiently fabricated. First, the outstanding structural stability of the five MOFs, including thermal and water stability, was verified by thermal analysis and powder X-ray diffraction.

Predictors of achieving minimal clinically important difference in functional status for elderly patients with degenerative lumbar spinal stenosis undergoing lumbar decompression and fusion surgery.

Objective: To identify the predictors for the achievement of minimal clinically important difference (MCID) in functional status among elderly patients with degenerative lumbar spinal stenosis (DLSS) undergoing lumbar decompression and fusion surgery.

Methods: Patients who underwent lumbar surgery for DLSS and had a minimum of 1-year follow-up were included. The MCID achievement threshold for the Oswestry Disability Index (ODI) was set at 12.

Protective effect of chitosan-modified rice porous starch loaded catechin on HT-29 cells exposed to lead ion.

Unlabelled: To explore how chitosan-modified rice porous starch-loaded catechin (CT@RPS/CS) protects HT-29 cells exposed to lead ions.

Method: The HT-29 cells were treated differently based on their grouping. The effect of CT@RPS/CS on lead-induced toxicity was evaluated using cell proliferation, apoptosis, oxidative stress index, and cytokine tests.

Psoas muscle index and psoas muscle density are associated with functional status in patients with degenerative lumbar spinal stenosis.

Background: The factors affecting lumbar spinal function in patients with degenerative lumbar spinal stenosis (DLSS) are still unclear.

Objective: This study explored psoas major muscle morphology in patients with DLSS and its association with their functional status.

Methods: A retrospective study was conducted on 288 patients with DLSS and 260 control subjects.

YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated mA epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression.

Two R2R3-MYB transcription factors from Chinese cedar (Cryptomeria fortunei Hooibrenk) are involved in the regulation of secondary cell wall formation.

As the most abundant renewable energy source, wood comprises the secondary cell wall (SCW). SCW biosynthesis involves lignin and cellulose deposition. Increasing studies have illustrated that R2R3-MYB transcription factors (TFs) play pivotal roles in affecting lignin accumulation and SCW formation.

Topical Dihydroartemisinin Improves Wound Healing in Diabetic Mice.

Impaired skin wound healing is a common complication of diabetes mellitus. Angiogenesis is a critical step in wound healing because it allows oxygen and nutrients to reach the injured area, thereby promoting wound cell proliferation, re-epithelialisation, and collagen regeneration. However, the neovascularisation ability of patients with diabetes often decreases.

Physiological and gene expression changes of Hooibrenk families under heat stress.

Heat stress is one of the major abiotic stresses affecting plant growth and productivity. (Chinese cedar) is an excellent timber and landscaping tree species in southern China thanks to its beautiful appearance, straight texture and ability to purify the air and improve the environment. In this study, we first screened 8 excellent families (#12, #21, #37, #38, #45, #46, #48, #54) in a second generation seed orchard.

Correlation of psoas major muscle morphology with function and clinical symptoms in patients with symptomatic multilevel lumbar spinal stenosis.

Objective: This study was performed to quantify the morphological characteristics of the psoas major muscle in patients with symptomatic multilevel degenerative lumbar spinal stenosis (SMLSS) and assess the correlations of these morphological characteristics with function and clinical symptoms.

Methods: One hundred fourteen patients diagnosed with SMLSS (≥ 3 segments) were included. The patients' presenting symptoms were assessed with the Oswestry Disability Index (ODI), and visual analogue scale (VAS) scores were recorded.

Synthesis and Full Characterization of One Organometallic Polyoxometalate-Based Copper(I)-Alkene Complex.

An alkene-bridged thioether ligand (L) was designed and used for its first study within a polyoxometalate (POM) hybrid system, and a POM-based copper(I)-alkene compound [(CuL)(PMoO)]·(CuL) () was isolated and characterized by X-ray crystallography. A unique alkene-coordinating N(η-C═C)N mode of L is observed, and the Cu centers are captured by σ,π-L in a pocket fashion, giving birth to discrete [CuL] cations and [(CuL)(PMo)] anions. The ionic crystal exhibits solubility in aprotic polar solvents, and the electrospray ionization mass spectrometry is used to explore the nature of species present in the solution.

A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through mA reader YTHDC1.

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (mA) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC).

Overexpression of from Enhances Cold, Drought and Salt Stress in Poplar.

, a regulator of the cold-inducible transcriptome and freezing tolerance, is currently widely believed to be involved in plant resistance to cold stress. In this study, from was transformed into poplar. Physiological indicators of transgenic, empty vector and wild-type poplar after abiotic stress (cold, drought and salt) were determined.

Androgen Metabolism and Response in Prostate Cancer Anti-Androgen Therapy Resistance.

All aspects of prostate cancer evolution are closely related to androgen levels and the status of the androgen receptor (AR). Almost all treatments target androgen metabolism pathways and AR, from castration-sensitive prostate cancer (CSPC) to castration-resistant prostate cancer (CRPC). Alterations in androgen metabolism and its response are one of the main reasons for prostate cancer drug resistance.

Characteristics of catechin loading rice porous starch/chitosan functional microsphere and its adsorption towards Pb.

In this paper, we explore the adsorption potential of catechin (CT) loaded composite microspheres and provide a new micron scale carrier of functional factor. Chitosan (CS) modified rice porous starch (RPS/CS) was used as a CT adsorption carrier to prepare bioactive CT-loaded composite microspheres (CT@RPS/CS). The adsorption kinetics, storage characteristics, and biological activity maintenance of CT@RPS/CS were studied in an aqueous solution, and the sustained-release characteristics of CT@RPS/CS were studied during simulated gastrointestinal digestion.

Transcriptome and Metabolome Analyses Reveal Differences in Terpenoid and Flavonoid Biosynthesis in Needles Across Different Seasons.

(Chinese cedar) has outstanding medicinal value due to its abundant flavonoid and terpenoid contents. The metabolite contents of needles differ across different seasons. However, the biosynthetic mechanism of these differentially synthesized metabolites (DSMs) is poorly understood.