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Chemical labeling of proteins with synthetic low-molecular-weight probes is an important technique in chemical biology. To achieve this, it is necessary to use chemical reactions that proceed rapidly under physiological conditions (i.e., aqueous solvent, pH, low concentration, and low temperature) so that protein denaturation does not occur. The radical reaction satisfies such demands of protein labeling, and protein labeling using the biomimetic radical reaction has recently attracted attention. The biomimetic radical reaction enables selective labeling of the C-terminus, tyrosine, and tryptophan, which is difficult to achieve with conventional electrophilic protein labeling. In addition, as the radical reaction proceeds selectively in close proximity to the catalyst, it can be applied to the analysis of protein–protein interactions. In this review, recent trends in protein labeling using biomimetic radical reactions are discussed.

Only few magnetoelectric materials, where magnetism and ferroelectricity are coupled, are known to exist at room temperature, and in most cases the magnetoelectric coupling is weak. The discovery of strong room-temperature magnetoelectric coupling in Sr 3 Co 2 Fe 24 O 41 at low magnetic fields is therefore a significant advance towards the practical application of multiferroics. The discoveries of gigantic ferroelectric polarization in BiFeO 3 (ref.  1 ) and ferroelectricity accompanied by a magnetic order in TbMnO 3 (ref.  2 ) have renewed interest in research on magnetoelectric multiferroics 3 , 4 , materials in which magnetic and ferroelectric orders coexist, from both fundamental and technological points of view 5 , 6 , 7 . Among several different types of magnetoelectric multiferroic 8 , 9 , magnetically induced ferroelectrics in which ferroelectricity is induced by complex magnetic orders, such as spiral orders, exhibit giant magnetoelectric effects, remarkable changes in electric polarization in response to a magnetic field. Many magnetically induced ferroelectrics showing the magnetoelectric effects have been found in the past several years 10 . From a practical point of view, however, their magnetoelectric effects are useless because they operate only far below room temperature (for example, 28 K in TbMnO 3 (ref.  2 ) and 230 K in CuO (ref.  11 )). Furthermore, in most of them, the operating magnetic field is an order of tesla that is too high for practical applications. Here we report materials, Z-type hexaferrites, overcoming these problems on magnetically induced ferroelectrics. The best magnetoelectric properties were obtained for Sr 3 Co 2 Fe 24 O 41 ceramics sintered in oxygen, which exhibit a low-field magnetoelectric effect at room temperature. Our result represents an important step towards practical device applications using the magnetoelectric effects.

Recently, boron neutron capture therapy (BNCT) has been attracting attention as a minimally invasive cancer treatment. In 2020, the accelerator-based BNCT with L-BPA (Borofalan) as its D-sorbitol complex (Steboronine®) for head and neck cancers was approved by Pharmaceutical and Medical Devices Agency for the first time in the world. As accelerator-based neutron generation techniques are being developed in various countries, the development of novel tumor-selective boron agents is becoming increasingly important and desired. The Japanese Society of Neutron Capture Therapy believes it is necessary to propose standard evaluation protocols at each stage in the development of boron agents for BNCT. This review summarizes recommended experimental protocols for in vitro and in vivo evaluation methods of boron agents for BNCT based on our experience with L-BPA approval.

Comparing newly obtained and previously known nucleotide and amino-acid sequences underpins modern biological research. BLAST is a well-established tool for such comparisons but is challenging to use on new data sets. We combined a user-centric design philosophy with sustainable software development approaches to create Sequenceserver, a tool for running BLAST and visually inspecting BLAST results for biological interpretation. Sequenceserver uses simple algorithms to prevent potential analysis errors and provides flexible text-based and visual outputs to support researcher productivity. Our software can be rapidly installed for use by individuals or on shared servers.

Allogeneic islet transplantation becomes a viable option for patients with unstable type 1 diabetes. However, considering the huge number of patients with type 1 diabetes, human donor shortage is a serious issue. To overcome the donor shortage issue, xenotransplantation is an attractive option. In fact, clinical islet xenotransplantation has been conducted since 1990s. The first clinical trial was performed using fetal pigs and demonstrated the porcine pancreatic tissue could survive in human body with immunosuppressive strategies. To scale up the islet production, Canadian group established a method for islet isolation from neonatal pigs. Their method has been used for clinical islet xenotransplantation in New Zealand, Russian, Mexico, Argentina, and China. Recently Korean group published a clinical protocol for islet xenotransplantation using adult pigs. For the next generation of islet xenotransplantation, gene-modified pigs were created. Especially “superislets” created by Belgian group demonstrated promising preclinical outcomes. With advanced donor pigs, islet xenotransplantation might become a suitable treatment for the majority of type 1 diabetic patients. Graphical Abstract Pig Pancreas from  Fetus  Neonatal  Adult  Gene modified

New matrix metalloproteinase 1 (MMP-1) inhibitors were predicted using the structure–activity relationship (SAR) transfer method based on a series of analogues of kinesin-like protein 11 (KIF11) inhibitors. Compounds 5 – 7 predicted to be highly potent against MMP-1 were synthesized and tested for MMP-1 inhibitory activity. Among these, compound 6 having a Cl substituent at the R 1 site was found to possess ca. 3.5 times higher inhibitory activity against MMP-1 than the previously reported compound 4 . The observed potency was consistent with the presence of an SAR transfer event between analogous MMP-1 and KIF11 inhibitors. Pharmacophore fitting revealed that the higher inhibitory activity of compound 6 compared to compound 4 against MMP-1 might be due to a halogen bond interaction between the Cl substituent of compound 6 and residue ARG214 of MMP-1.

Lung cancer frequently co-exists with idiopathic interstitial pneumonia (IIP), which can be subdivided into idiopathic pulmonary fibrosis (IPF) and IIP other than IPF (other IIP). Although chemotherapy in small cell lung cancer (SCLC) patients with IIP may result in the exacerbation of IIP, these patients commonly receive chemotherapy. This study aimed to assess the risks and benefits of chemotherapy in SCLC patients with IIP. We retrospectively analyzed the medical records of 122 patients with SCLC who received chemotherapy. Patients with secondary interstitial lung disease (ILD) of known etiology were excluded. Eligible patients were divided into two groups: SCLC with and without IIP. The former group was subdivided into those with IPF and other IIP. Of the 47 (39.2%) SCLC patients with IIP, 20 had IPF and 27 had other IIP. The frequency of chemotherapy-induced ILD development or IIP exacerbation was higher in patients with IPF (40.0%) than in those with other IIP (3.7%) and non-IIP (1.4%). Logistic regression analysis demonstrated that ILD development or IIP exacerbation was independently associated with IPF (P = 0.007). Time to treatment failure (P < 0.001) and overall survival (P = 0.001) were different among the groups., Cox proportional hazard model revealed that IPF was independently associated with time to treatment failure (P = 0,017) and overall survival (P = 0.006). Other IIP had no impact on time to treatment failure or overall survival. Development of ILD or exacerbation of IIP independently reduced time to treatment failure and overall survival. Comorbid IPF can be an independent, negative prognostic indicator and at high risk of ILD development or IIP exacerbation in SCLC patients. Early diagnosis and intervention for chemotherapy-induced IIP exacerbation will be beneficial for SCLC patients with IPF, who need close monitoring for its onset.

Epstein–Barr virus (EBV) is involved in the pathogenesis of various lymphomas and carcinomas, whereas Kaposi’s sarcoma-associated herpesvirus (KSHV) participates in the pathogenesis of endothelial sarcoma and lymphomas. EBV and KSHV are responsible for 120,000 and 44,000 annual new cases of cancer, respectively. Despite this clinical importance, no chemotherapies or vaccines have been developed for virus-specific treatment and prevention of these viruses. Humans are the only natural host for both EBV and KSHV, and only a limited species of laboratory animals are susceptible to their experimental infection; this strict host tropism has hampered the development of their animal models and thereby impeded the study of therapeutic and prophylactic strategies. To overcome this difficulty, three main approaches have been used to develop animal models for human gammaherpesvirus infections. The first is experimental infection of laboratory animals with EBV or KSHV. New-world non-human primates (NHPs) and rabbits have been mainly used in this approach. The second is experimental infection of laboratory animals with their own inherent gammaherpesviruses. NHPs and mice have been mainly used here. The third, a recent trend, employs experimental infection of EBV or KSHV or both to immunodeficient mice reconstituted with human immune system components (humanized mice). This review will discuss how these three approaches have been used to reproduce human clinical conditions associated with gammaherpesviruses and to analyze the mechanisms of their pathogenesis.

The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg-Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk's lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg-Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI.

Feglymycin is a naturally occurring, anti-HIV and antimicrobial 13-mer peptide that includes highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Here we describe the total synthesis of feglymycin based on a linear/convergent hybrid approach. Our originally developed micro-flow amide bond formation enabled highly racemizable peptide chain elongation based on a linear approach that was previously considered impossible. Our developed approach will enable the practical preparation of biologically active oligopeptides that contain highly racemizable amino acids, which are attractive drug candidates. Feglymycin is a biologically active peptide but a challenging synthetic target due to the highly racemizable nature of the 3,5-dihydroxyphenylglycine groups. Here the authors report the synthesis of feglymycin using a microflow system, allowing amide bond formation without severe racemization.