Hypoxia-inducible factor-targeting therapy augmented the sensitivity to programmed death ligand-1 blockade by enhancing interferon-γ-induced chemokines in tumor cells.

Immune checkpoint inhibitors (ICIs) targeting programmed death ligand-1 (PD-L1) provide clinical benefits for various advanced malignancies. However, the predictive factors that determine sensitivity to ICIs have not been fully elucidated. We focused on tumor-derived CXCL10/11 as a pivotal factor that determines the response to PD-L1 blockade by regulating T cell accumulation and tumor angiogenesis.

RNA G-quadruplexes and calcium ions synergistically induce Tau phase transition in vitro.

Tau aggregation is a defining feature of neurodegenerative tauopathies, including Alzheimer's disease, corticobasal degeneration, and frontotemporal dementia. This aggregation involves the liquid-liquid phase separation (LLPS) of Tau, followed by its sol-gel phase transition, representing a crucial step in aggregate formation both in vitro and in vivo. However, the precise cofactors influencing Tau phase transition and aggregation under physiological conditions (e.

Characterization of The Permeation Properties of Membrane Filters and Sorption Properties of Sorbents Used for Polar Organic Chemical Integrative Samplers.

Polar organic chemical integrative samplers (POCIS) are promising devices for measuring the time-weighted average concentrations of hydrophilic compounds in aquatic environments. However, the mechanisms underlying compound uptake by POCIS remain unclear. We investigated the permeation kinetics of polyethersulfone and polytetrafluoroethylene membrane filters, and the sorption kinetics of Oasis HLB (Waters), Envi-Carb (Supelco), and Oasis WAX (Waters) sorbents.

Development of Wrist Separated Exoskeleton Socket of Myoelectric Prosthesis Hand for Symbrachydactyly.

In recent years, the functionality of myoelectric prosthetic hands has improved as motors have become smaller and controls have become more advanced. Attempts have been made to reproduce the rotation and flexion of the wrist by adding degrees of freedom to the wrist joint. However, it is still difficult to fully reproduce the functionality of the wrist joint owing to the weight of the prosthesis and size limitations.

Granulocyte colony-stimulating factor has the potential to attenuate the therapeutic efficacy of chemo-immunotherapy for extensive-stage small-cell lung cancer.

Background: Granulocyte colony-stimulating factor (G-CSF) has the potential to attenuate the anti-tumor immune responses of T-cells by increasing immune suppressive neutrophils and myeloid-derived suppressor cells. However, the clinical impact of G-CSF on the efficacy of immunotherapy remains unknown. This multi-center retrospective analysis evaluated the impact of G-CSF in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemo-immunotherapy.

TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice.

In higher eukaryotes, tRNA methyltransferase 10A (TRMT10A) is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs. Pathogenic mutations in TRMT10A cause intellectual disability, microcephaly, diabetes, and short stature in humans, and generate cytotoxic tRNA fragments in cultured cells; however, it is not clear how TRMT10A supports codon translation or brain functions. Here, we generated Trmt10a null mice and showed that tRNAGln(CUG) and initiator methionine tRNA levels were universally decreased in various tissues; the same was true in a human cell line lacking TRMT10A.

Investigation of variability in the matrix effect on stable isotope-labeled internal standards in liquid chromatography-tandem mass spectrometry analysis of 25 pesticides in vegetables.

The matrix effects (ME) in simultaneous analysis of pesticide residue using liquid chromatography-tandem mass spectrometry (LC-MS/MS) were evaluated by comparing the slopes of matrix-matched and reagent-only calibrations of four types of vegetable samples. Both the sampling and measurement variances of the ME were also determined using one-way analysis of variance. Substantial ion suppression (ME<-20%) was observed in komatsuna, spinach, and tomato when a modified Japanese official method was implemented.

Lipoprotein Apheresis Alleviates Treatment-Resistant Peripheral Artery Disease Despite the Normal Range of Atherogenic Lipoproteins: The LETS-PAD Study.

Aim: Peripheral artery disease (PAD) severely impairs patient prognosis and quality of life (QOL). Although lipoprotein apheresis (LA) has been applied to patients with PAD and elevated serum atherogenic lipoproteins, we hypothesized that LA can be effective for treating PAD even in patients with controlled serum lipoproteins through pleiotropic anti-atherosclerotic effects beyond lipoprotein removal. This study aimed to evaluate the efficacy of LA in patients with treatment-resistant PAD and controlled serum lipoproteins focusing on QOL.

Structural polymorphism of the nucleic acids in pentanucleotide repeats associated with the neurological disorder CANVAS.

Short tandem repeats are inherently unstable during DNA replication depending on repeat length, and the expansion of the repeat length in the human genome is responsible for repeat expansion disorders. Pentanucleotide AAGGG and ACAGG repeat expansions in intron 2 of the gene encoding replication factor C subunit 1 (RFC1) cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and other phenotypes of late-onset cerebellar ataxia. Herein, we reveal the structural polymorphism of the RFC1 repeats associated with CANVAS in vitro.

Submucosal dissection to close wide cleft palate with folded mucoperiosteum for bilateral cleft lip and palate with popliteal pterygium syndrome.

Characteristic features of popliteal pterygium syndrome (PPS) associated with the craniofacial region include cleft palate, syngnathia, and difficulty with reconstruction. We developed a new procedure of submucosal dissection with periosteotomy to close the folded mucosa in bilateral cleft lip and palate patients with PPS. This technique could be applicable for patients with wide cleft palate.

A multicenter, open-label, phase II trial of pemetrexed plus bevacizumab in elderly patients with previously untreated advanced or recurrent nonsquamous non-small cell lung cancer.

Background: Although the incidence of lung cancer in elderly individuals has been increasing in recent years, the number of clinical trials designed specifically for elderly patients with advanced non-small cell lung cancer (NSCLC) is still limited. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of pemetrexed (PEM) plus bevacizumab (Bev) combination chemotherapy in elderly patients with nonsquamous NSCLC.

Methods: A total of 29 elderly patients (≥75 years old) with nonsquamous NSCLC were enrolled in this multicenter, open-label, phase II study, and 27 patients were finally analyzed.

A cyclic pyrrole-imidazole polyamide reduces pathogenic RNA in CAG/CTG triplet repeat neurological disease models.

Expansion of CAG and CTG (CWG) triplet repeats causes several inherited neurological diseases. The CWG repeat diseases are thought to involve complex pathogenic mechanisms through expanded CWG repeat-derived RNAs in a noncoding region and polypeptides in a coding region, respectively. However, an effective therapeutic approach has not been established for the CWG repeat diseases.

Enhancement of photodegradation of polyethylene with adsorbed polycyclic aromatic hydrocarbons under artificial sunlight irradiation.

The photodegradation of plastic waste produces microplastics (MPs) in marine environments. Plastics can adsorb hydrophobic organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) and can be transported over long distances. However, the impact of adsorbed pollutants on the photodegradation remains unknown.

FoundationOne CDx detected an uncovered variant of exon 19 deletion by Oncomine Dx target test in a patient with lung adenocarcinoma.

A non-smoker woman with advanced lung adenocarcinoma was referred to us. The Oncomine Dx target test (ODxTT), a next-generation sequencing (NGS)-based hot spots panel test, did not detect any driver mutations, so we treated her with chemo-immunotherapy. After second-line chemotherapy, we performed FoundationOne CDx, a NGS-based comprehensive genomic profiling (CGP) test, and identified a rare variant of exon 19 deletion that had not been covered by ODxTT.

RNA G-quadruplex organizes stress granule assembly through DNAPTP6 in neurons.

Consecutive guanine RNA sequences can adopt quadruple-stranded structures, termed RNA G-quadruplexes (rG4s). Although rG4-forming sequences are abundant in transcriptomes, the physiological roles of rG4s in the central nervous system remain poorly understood. In the present study, proteomics analysis of the mouse forebrain identified DNAPTP6 as an RNA binding protein with high affinity and selectivity for rG4s.

Improvement of Precision Grasping Performance by Interaction Between Soft Finger Pulp and Hard Nail.

In this study, we investigated the effect of the presence or absence of fingernails on precision grasping using artificial anthropomimetic fingers. We hypothesized that fingernails improve precision grasping performance by increasing the friction coefficient while suppressing fingertip deformation. To test our hypothesis, we developed artificial fingertips, each composed of bone, nail, skin, and soft tissue, and fabricated three types of artificial fingers with different skin softness grades and artificial fingers without nails as the control condition.

α-Synuclein decoy peptide protects mice against α-synuclein-induced memory loss.

Aims: We previously found that a decoy peptide derived from the C-terminal sequence of α-Synuclein (αSyn) prevents cytotoxic αSyn aggregation caused by fatty acid-binding protein 3 (FABP3) in vitro. In this study, we continued to utilize αSyn-derived peptides to further validate their effects on αSyn neurotoxicity and behavioral impairments in αSyn preformed fibrils (PFFs)-injected mouse model of Parkinson's disease (PD).

Methods: Mice were injected with αSyn PFFs in the bilateral olfactory bulb (OB) and then were subjected to behavioral analysis at 2-week intervals post-injection.

Two lateral parametria in radical hysterectomy: History and outcome.

Aim: Some anatomic concepts for 20th century radical hysterectomy (RH) did not conform to progress in surgical technique. The purpose of this article was to put forward a new practical anatomy and application to surgical procedures.

Methods: Following a historical review the author reexamined his surgical procedures from 1980 to 2005 on 131 patients with cervical cancer.

[The neuropathological mechanism on guanine-rich repeat expansion diseases].

Repeat expansion diseases are caused by the aberrant repeat expansions within specific genes. RNAs derived from aberrant repeat sequences form non-canonical secondary structures, contributing to induce cell toxicity. In particular, RNA G-quadruplexes (G4RNAs) formed in guanine-rich repeat expanded RNAs trigger neurodegeneration.