FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models.

Background: We developed the FORCE platform to overcome limitations of oligonucleotide delivery to muscle and enable their applicability to neuromuscular disorders. The platform consists of an antigen-binding fragment, highly specific for the human transferrin receptor 1 (TfR1), conjugated to an oligonucleotide via a cleavable valine-citrulline linker. Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by expanded CUG triplets in the DMPK RNA, which sequester splicing proteins in the nucleus, lead to spliceopathy, and drive disease progression.

Correlations between 14-gene RNA-level assay and clinical and molecular features in resectable non-squamous non-small cell lung cancer: a cross-sectional study.

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Accurate risk stratification is essential for optimizing treatment strategies. A 14-gene RNA-level assay of lung cancer, which involves quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of formalin-fixed paraffin-embedded (FFPE) tissue samples, offers a promising approach.

GbPP2C80 Interacts with GbWAKL14 to Negatively Co-Regulate Resistance to Fusarium and Verticillium wilt via MPK3 and ROS Signaling in Sea Island Cotton.

Fusarium wilt (FW) is widespread in global cotton production, but the mechanism underlying FW resistance in superior-fiber-quality Sea Island cotton is unclear. This study reveals that FW resistance has been the target of genetic improvement of Sea Island cotton in China since the 2010s. The key nonsynonymous single nucleotide polymorphism (SNP, T/C) of gene Gbar_D03G001670 encoding protein phosphatase 2C 80 (PP2C80) results in an amino acid shift (L/S), which is significantly associated with FW resistance of Sea Island cotton.

Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease.

Background: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood.

Chest wall pain after single-fraction thoracic stereotactic ablative Radiotherapy: Dosimetric analysis from the iSABR trial.

Background And Purpose: Concerns over chest wall toxicity has led to debates on treating tumors adjacent to the chest wall with single-fraction stereotactic ablative radiotherapy (SABR). We performed a secondary analysis of patients treated on the prospective iSABR trial to determine the incidence and grade of chest wall pain and modeled dose-response to guide radiation planning and estimate risk.

Materials And Methods: This analysis included 99 tumors in 92 patients that were treated with 25 Gy in one fraction on the iSABR trial which individualized dose by tumor size and location.

Rare-Earth Metalloligands for LowValent Cobalt Complexes: Fine Electronic Tuning Co→RE Dative Interactions.

Rare-earth metalloligand supported low-valent cobalt complexes were synthesized by utilizing a small-sized heptadentate phosphinomethylamine H and a large-sized arene-anchored hexadentate phosphinomethylamine H ligand precursors. The RE(III)-Co(-I)-N (RE = Sc, Lu, Y, Gd, La) complexes containing rare-earth metals including the smallest Sc and largest La were characterized by multinuclear NMR spectroscopy, X-ray diffraction analysis, electrochemistry, and computational studies. The Co(-I)→RE(III) dative interactions were all polarized with major contributions from the 3d orbital of the cobalt center, which was slightly affected by the identity of rare-earth metalloligands.

Integrative Single Cell Atlas Revealed Intratumoral Heterogeneity Generation from an Adaptive Epigenetic Cell State in Human Bladder Urothelial Carcinoma.

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1-positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis.

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up).

Deciphering the stereo-specific catalytic mechanisms of cis-epoxysuccinate hydrolases producing L(+)-tartaric acid.

Microbial epoxide hydrolases, cis-epoxysuccinate hydrolases (CESHs), have been utilized for commercial production of enantiomerically pure L(+)- and D(-)-tartaric acids for decades. However, the stereo-catalytic mechanism of CESH producing L(+)-tartaric acid (CESH[L]) remains unclear. Herein, the crystal structures of two CESH[L]s in ligand-free, product-complexed, and catalytic intermediate forms were determined.

In Vivo Analysis of Acromioclavicular Kinematics and Distance During Multiplanar Humeral Elevation.

Background: Knowledge of acromioclavicular (AC) joint kinematics and distance may provide insight into the biomechanical function and development of new treatment methods. However, accurate data on in vivo AC kinematics and distance between the clavicle and acromion remain unknown.

Purpose/hypothesis: The purpose of this study was to investigate 3-dimensional AC kinematics and distance during arm elevation in abduction, scaption, and forward flexion in a healthy population.

Zeolitic imidazolate framework-8/polyaniline nanocomposite-based electrochemical sensor for sensitive detection of imidaclothiz.

Imidaclothiz (IMZ) is a class of neonicotinoid insecticide which can pose potential threat to human health and be frequently detected in water and foods. Herein, a zeolitic imidazolate framework-8/polyaniline (ZIF-8/PANI) nanocomposite has been modified on the surface of glassy carbon electrode (GCE) for the electrochemical determination of IMZ, and the electrochemical detection performance of the modified electrode was investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV). With the large surface area of ZIF-8 and great electric conductivity of PANI, the ZIF-8/PANI-modified electrode showed a high catalytic performance towards IMZ reduction in PBS.

CIB2 Is a Novel Endogenous Repressor of Atrial Remodeling.

Background: Atrial fibrillation (AF) is a highly prevalent condition that can cause or exacerbate heart failure, is an important risk factor for stroke, and is associated with pronounced morbidity and death. Genes uniquely expressed in the atria are known to be essential for maintaining atrial structure and function. Atrial tissue remodeling contributes to arrhythmia recurrence and maintenance.

Gumarontinib in patients with non-small-cell lung cancer harbouring exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial.

Background: Approximately 3-4% of patients with non-small-cell lung cancer (NSCLC) have exon 14 (ex14) skipping mutations. We report primary results from the phase 2 stage of a phase 1b/2 study of gumarontinib, a selective, potent, oral MET inhibitor, in patients with ex14 skipping mutation-positive (ex14-positive) NSCLC.

Methods: The single-arm, multicentre, open-label, phase 2 stage of the GLORY study was conducted at 42 centres across China and Japan.

Global Longitudinal Strain Is Associated with Mortality in Patients with Multiple Myeloma.

Patients with multiple myeloma (MM) are at a high risk for developing cardiovascular complications. Global longitudinal strain (GLS) can detect early functional impairment before structural abnormalities develop. It remains unknown if reduced GLS is associated with reduced survival in patients with MM.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

Bioremediation of phenanthrene in saline-alkali soil by biochar- immobilized moderately halophilic bacteria combined with Suaeda salsa L.

Polycyclic aromatic hydrocarbon (PAH) contaminated saline-alkali soil is commonly salinized and hardened, which leads to low self-purification efficiency, making it difficult to reuse and remediate. In this study, pot experiments were conducted to investigate remediation of PAH contaminated saline-alkali soil using biochar-immobilized Martelella sp. AD-3, and Suaeda salsa L (S.

Two Chiral Yb Enantiomeric Pairs with Distinct Enantiomerically Pure N-Donor Ligands Presenting Significant Differences in Photoluminescence, Circularly Polarized Luminescence, and Second-Harmonic Generation.

Using enantiomerically pure bidentate and tridentate N-donor ligands (L/L and L/L) to replace two coordinated HO molecules of Yb(tta)(HO), respectively, two eight- and nine-coordinated Yb enantiomeric pairs, namely, Yb(tta)L/Yb(tta)L (/) and [Yb(tta)L]·CHCN/[Yb(tta)L]·CHCN (/), were isolated, in which Htta = 2-thenoyltrifluoroacetone, L/L = (-)/(+)-4,5-pinene-2,2'-bipyridine, and L/L = (-)/(+)-2,6-bis(4',5'-pinene-2'-pyridyl)pyridine. Interestingly, they not only present distinct degrees of chirality but also show large differences in near-infrared (NIR) photoluminescence (PL), circularly polarized luminescence (CPL), and second-harmonic generation (SHG). Eight-coordinated with an asymmetric bidentate L ligand has a high NIR-PL quantum yield (1.

Structure-function analysis of CYP719As involved in methylenedioxy bridge-formation in the biosynthesis of benzylisoquinoline alkaloids and its de novo production.

Benzylisoquinoline alkaloids (BIAs) are a type of secondary metabolite with clinical application value. (S)-stylopine is a special BIA which contains methylenedioxy bridge structures. CYP719As could catalyze the methylenedioxy bridge-formation on the A or D rings of protoberberine alkaloids, while displaying significant substrate regiospecificity.

Two temperature-induced 1D Cu chain enantiomeric pairs showing different magnetic properties and nonlinear optical responses.

At different reaction temperatures, using Cu(NO)·3HO to react with enantiomerically pure N-donor ligands (L/L), respectively, two pairs of chiral one-dimensional (1D) Cu chain enantiomers formulated as [Cu(μ-NO)(NO)(L)]/[Cu(μ-NO)(NO)(L)] (S-1-Cu/R-1-Cu, formed at 40 °C with an NO group as a sole bridging ligand) and [Cu(μ-L)(NO)]/[Cu(μ-L)(NO)] (S-2-Cu/R-2-Cu, formed at 25 °C with L or L as a bridging ligand) were prepared, where L/L = (+)/(-)-4,5-pinenepyridyl-2-pyrazine. Interestingly, such a disparity in bridging ligands leads not only to their distinct structural features but also to their completely different magnetic couplings together with a large difference in their nonlinear optical responses. S-1-Cu with a 1D helical structure shows weak ferromagnetic coupling between Cu ions, while S-2-Cu with a 1D stairway-like structure presents weak antiferromagnetic coupling.

Genome-wide identification and expression analysis of two-component system genes in sweet potato ( L.).

Two-component system (TCS), which comprises histidine kinases (HKs), histidine phosphotransfer proteins (HPs), and response regulators (RRs), plays essential roles in regulating plant growth, development, and response to various environmental stimuli. TCS genes have been comprehensively identified in various plants, while studies on the genome-wide identification and analysis of TCS in sweet potato were still not reported. Therefore, in this study, a total of 90 TCS members consisting of 20 HK(L)s, 11 HPs, and 59 RRs were identified in the genome of .

S-Equol enhances osteoblastic bone formation and prevents bone loss through OPG/RANKL the PI3K/Akt pathway in streptozotocin-induced diabetic rats.

Background: This study aimed to explore whether S-Equol delays diabetes-induced osteoporosis and the molecular mechanisms underlying its therapeutic effects.

Materials And Methods: Thirty-five male Sprague-Dawley rats were randomized into five groups. The diabetic osteoporosis (DOP) group and three S-Equol treatment groups were intraperitoneally injected with streptozotocin (STZ) to develop a DOP model.

Modulating Two Pairs of Chiral Dy Enantiomers by Distinct β-Diketone Ligands to Show Giant Differences in Single-Ion Magnet Performance and Nonlinear Optical Response.

Using Dy(dbm)(HO) and Dy(btfa)(HO) to react with enantiopure -donors, (-)/(+)-4,5-pinenepyridyl-2-pyrazine (L/L), respectively, two pairs of chiral Dy enantiomers, Dy(dbm)L/Dy(dbm)L (/) and Dy(btfa)L/Dy(btfa)L (/) were obtained, wherein one of the benzene rings of dbm (dibenzoylmethanate) in / is displaced by the -CF group of btfa (4,4,4-trifluoro-1-phenyl-1,3-butanedionate) in /. Interestingly, this substitution results not only in giant differences in their single-ion magnetic (SIM) performances but also in their completely different nonlinear optical (NLO) responses. presents a large effective energy barrier ( = 265.