Recent progress in copper-catalyzed difunctionalization of unactivated carboncarbon multiple bonds

AbstractCopper-catalyzed difunctionalization of unactivated carboncarbon multiple bonds involving a carboncarbon bond formation process is reviewed. Carboamination, carbooxygenation, carboboration, and other difunctionalization reactions of alkenes, alkynes, and allenes are described

A Pivotal Role for Interleukin-27 in CD8+ T Cell Functions and Generation of Cytotoxic T Lymphocytes

Cytotoxic T lymphocytes (CTLs) play a critical role in the control of various cancers and infections, and therefore the molecular mechanisms of CTL generation are a critical issue in designing antitumor immunotherapy and vaccines which augment the development of functional and long-lasting memory CTLs. Interleukin (IL)-27, a member of the IL-6/IL-12 heterodimeric cytokine family, acts on naive CD4+ T cells and plays pivotal roles as a proinflammatory cytokine to promote the early initiation of type-1 helper differentiation and also as an antiinflammatory cytokine to limit the T cell hyperactivity and production of pro-inflammatory cytokines. Recent studies revealed that IL-27 plays an important role in CD8+ T cells as well. Therefore, this article reviews current understanding of the role of IL-27 in CD8+ T cell functions and generation of CTLs

Machine learning-based prediction of relapse in rheumatoid arthritis patients using data on ultrasound examination and blood test

Recent effective therapies enable most rheumatoid arthritis (RA) patients to achieve remission; however, some patients experience relapse. We aimed to predict relapse in RA patients through machine learning (ML) using data on ultrasound (US) examination and blood test. Overall, 210 patients with RA in remission at baseline were dichotomized into remission (n = 150) and relapse (n = 60) based on the disease activity at 2-year follow-up. Three ML classifiers [Logistic Regression, Random Forest, and extreme gradient boosting (XGBoost)] and data on 73 features (14 US examination data, 54 blood test data, and five data on patient information) at baseline were used for predicting relapse. The best performance was obtained using the XGBoost classifier (area under the receiver operator characteristic curve (AUC) = 0.747), compared with Random Forest and Logistic Regression (AUC = 0.719 and 0.701, respectively). In the XGBoost classifier prediction, ten important features, including wrist/metatarsophalangeal superb microvascular imaging scores, were selected using the recursive feature elimination method. The performance was superior to that predicted by researcher-selected features, which are conventional prognostic markers. These results suggest that ML can provide an accurate prediction of relapse in RA patients, and the use of predictive algorithms may facilitate personalized treatment options

Local Anesthetic Systemic Toxicity Following General and Epidural Anesthesia in A patient with a History of Muscle Relaxant-induced Anaphylaxis

We here report that a 71-year-old Japanese woman with a history of anaphylaxis induced by muscle relaxants had local anesthetic systemic toxicity (LAST) following an abdominal surgery under general anesthesia with combined spinal-epidural anesthesia without muscle relaxants. The total dosages of local anesthetics reached 0.67 mg/kg of ropivacaine and 11.5 mg/kg of lidocaine over 12.5 h to obtain sufficient muscle relaxation for surgery. Regional anesthesia is useful in cases in which muscle relaxants are to be avoided during a surgery. However, especially for a patient with risk factors and prolonged surgery, precautions should be taken to prevent LAST

A guiding role of the Arabidopsis circadian clock in cell differentiation revealed by time-series single-cell RNA sequencing

Circadian rhythms and progression of cell differentiation are closely coupled in multicellular organisms. However, whether establishment of circadian rhythms regulates cell differentiation or vice versa has not been elucidated due to technical limitations. Here, we exploit high cell fate plasticity of plant cells to perform single-cell RNA sequencing during the entire process of cell differentiation. By analyzing reconstructed actual time series of the differentiation processes at single-cell resolution using a method we developed (PeakMatch), we find that the expression profile of clock genes is changed prior to cell differentiation, including induction of the clock gene LUX ARRYTHMO (LUX). ChIP sequencing analysis reveals that LUX induction in early differentiating cells directly targets genes involved in cell-cycle progression to regulate cell differentiation. Taken together, these results not only reveal a guiding role of the plant circadian clock in cell differentiation but also provide an approach for time-series analysis at single-cell resolution

An Evaluation of the Safety and Feasibility of Adenosine-assisted Clipping Surgery for Unruptured Cerebral Aneurysms: Study Protocol

The effectiveness of adenosine-induced flow arrest in surgical clipping for the cerebral aneurysms with difficulties in temporary clip placement to the proximal main trunk has been reported. This is the first clinical trial to evaluate the safety and feasibility of adenosine-assisted clipping surgery for unruptured cerebral aneurysms (UCAs) in Japan. The inclusion criteria are as follows: patients over 20 years old, patients who agree to be enrolled in this study after providing informed consent, patients who undergo clipping surgery for UCA in our institute, and patients in whom the surgeons (T.H. or I.D.) judge that decompression of the aneurysm is effective. The primary endpoint is a modified Rankin Scale (mRS) score 30 days after surgery. We plan to enroll 10 patients in this study. The original protocol of adenosine administration was established in this trial. Herein, we present the study protocol

SPARC Endogenous Level, rather than Fibroblast-Produced SPARC or Stroma Reorganization Induced by SPARC, Is Responsible for Melanoma Cell Growth

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that changes in the level of SPARC produced by malignant cells and neighboring stromal cells have on melanoma growth. Melanoma cell growth in monolayer was only slightly affected by changes in SPARC levels. However, melanoma growth in spheroids was strongly inhibited upon SPARC hyperexpression and conversely enhanced when SPARC expression was downregulated. Interestingly, SPARC overexpression in neighboring fibroblasts had no effect on spheroid growth irrespective of SPARC levels expressed by the melanoma cells, themselves. Downregulation of SPARC expression in melanoma cells induced their rejection in vivo through a mechanism mediated exclusively by host polymorphonuclear cells. On the other hand, SPARC hyperexpression enhanced vascular density, collagen deposition, and fibroblast recruitment in the surrounding stroma without affecting melanoma growth. In agreement with the in vitro data, overexpression of SPARC in co-injected fibroblasts did not affect melanoma growth in vivo. All the data indicate that melanoma growth is not subject to regulation by exogenous SPARC, nor by stromal organization, but only by SPARC levels produced by the malignant cells themselves

Boron-Catalyzed alpha-Functionalizations of Carboxylic Acids

Catalytic, chemoselective, and asymmetric alpha-functionalizations of carboxylic acids promise up-grading simple feedstock materials to value-added functional molecules, as well as late-stage structural diversifications of multifunctional molecules, such as drugs and their leads. In this personal account, we describe boron-catalyzed alpha-functionalizations of carboxylic acids developed in our group (five reaction types). The reversible boron carboxylate formation is key to the acidification of the alpha-protons and enolization using mild organic bases, allowing for chemoselective and asymmetric bond formations of carboxylic acids. The ligand effects on reactivity and stereoselectivity, substrate scopes, and mechanistic insights are summarized

Photoperiod sensitivity of the Arabidopsis circadian clock is tissue-specific.

Tissue-specific functions of the circadian clock in Arabidopsis have recently been revealed. The vasculature clock shows distinctive gene expression profiles compared to the clock in other tissues under light-dark cycles. However, it has not yet been established whether the vasculature clock also shows unique gene expression patterns that correlate with temperature cycles, another important environmental cue. Here, we detected diel phase of TIMING OF CAB EXPRESSION 1 (TOC1) expression in the vasculature and whole leaf under long-day light-dark cycles and temperature cycles. We found that the vasculature clock had advanced TOC1 phase under light-dark cycles but not under temperature cycles, suggesting that the vasculature clock has lower sensitivity against temperature signals. Furthermore, the phase advancement of TOC1 was seen only under long-day condition but not under short-day condition. These results support our previous conclusion that the circadian clock in vasculature preferentially senses photoperiodic signals