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Solid-state fluorescence was quenched by libration of a fluorophore in a dimethylfluorene-diyl bridged macrocage.

Inclusion crystals were formed from ketones with aromatic diimide-based macrocycles possessing adamantane units, where the oxygen atoms of guests interacted with the electron-deficient π-surfaces of the aromatic diimides through CO⋯π contacts.

Inclusion crystals containing several halocarbons were formed by three types of diimide-based macrocycles. Iodomethane was encapsulated within the cavity of the macrocycle through halogen-related interactions.

Adamantane-based macrocycles with pyrazine or tetrazine units afforded porous crystals with distinct surface properties of 1D pores, which captured multiple water molecules from the air or liquid water in a single-crystal-to-single-crystal fashion.

Second- and third-generation (2/3G) tyrosine kinase inhibitors (TKIs) possess excellent treatment effects on chronic myeloid leukemia (CML), and at least one 2/3G TKI is mostly incorporated into the first treatment of CML in all phases. However, the impact of 2/3G TKIs on subsequent allogeneic stem cell transplantation (allo-SCT) remains to be elucidated. We retrospectively evaluated how pretransplant therapy with TKIs affects the outcome of allo-SCT for CML using the clinical data of thirty-two patients with CML transplanted between 2001 and 2020 at our institution. Except for 11 patients who remained in the chronic phase (CP) until the time of allo-SCT, 10 patients were initially diagnosed with accelerated or blastic phase (AP/BP), and 11 patients progressed to AP/BP during the treatment for CP. With subsequent use of 2/3G TKI or imatinib (IM), 10 and 4 patients returned to the second CP at the time of allo-SCT, respectively. In univariate analysis, pretransplant use of 2/3 GTKI was significantly associated with higher 5-year overall survival (91.7%) and relapse-free survival (75.0%) than the use of IM (37.5% and 12.5%, respectively) in patients presenting with or progressing to AP/BP before allo-SCT. Our results suggest that pretransplant use of 2/3G TKI improves the outcome of allo-SCT in CML patients who present with AP/BP at diagnosis or progress to the advanced phase thereafter.

Neighboring group participation involving a 6-membered ring structure is rare, despite the privilege of 6-membered ring transition structures in organic chemistry. We examined the putative role of a 6-membered cyclic intermediate with neighboring group participation of nitrogen cation in

We studied the Z/E preference of N-phenylthioacetamide (thioacetanilide) derivatives in various solvents by means of 1H NMR spectroscopy, as well as molecular dynamics (MD) and other computational analyses. Our experimental results indicate that the Z/E isomer preference of secondary (NH)thioamides of N-phenylthioacetamides shows substantial solvent dependency, whereas the corresponding amides do not show solvent dependency of the Z/E isomer ratios. Detailed study of the solvent effects based on molecular dynamics simulations revealed that there are two main modes of hydrogen (H)-bond formation between solvent and (NH)thioacetamide, which influence the Z/E isomer preference of (NH)thioamides. DFT calculations of NH-thioamide in the presence of one or two explicit solvent molecules in the continuum solvent model can effectively mimic the solvation by multiple solvent molecules surrounding the thioamide in MD simulations and shed light on the precise nature of the interactions between thioamide and solvent. Orbital interaction analysis showed that, counterintuitively, the Z/E preference of NH-thioacetamides is mainly determined by steric repulsion, while that of sterically congested N-methylthioacetamides is mainly determined by thioamide conjugation.

From the leaves of Ardisia quinquegona, two alkylated tetronic acid derivatives, named ardisiatetrons A and B (1, 2), and four triterpenoids (3–6) were isolated together with one known compound (7) by a combination of various kinds of chromatography. The structure of new methyl migrated triterpene (3) was confirmed by X-ray crystallographic analysis. Compounds 2, 3, and 7 showed moderate anti-Leishmania activity and cytotoxicity towards A549 cells.

Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real-world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified.We performed a single-institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic HSCT recipients. Patients who underwent HSCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control.The cumulative incidence of clinically significant CMV infection (CS-CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs. 71.6%, p.05, at 100 days). In addition, the cumulative incidence of non-relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs. 19.8%, p.05). We then performed a risk factor analysis for developing CS-CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (Hazard ratio = 2.76, 95% confidence interval 1.14-6.68, p.05).Our study showed that letermovir prophylaxis significantly reduced the incidence of CS-CMVi and NRM in a real-world setting and that the CMV serostatus of the donor remained as a risk factor for CS-CMVi even under letermovir prophylaxis.

An adamantane-bearing macrocycle showed permanent intrinsic porosity and adsorption of small organic compounds in a single-crystal-to-single-crystal fashion. Guest uptake by the porous crystals gave rise to the structural transformation of the supramolecular organic framework, resulting in the change of shape and size of one-dimensional pores.

Introduction: Current assays based on the 0-hour/1-hour (0-/1-h) algorithm using high-sensitivity cardiac troponin (hs-cTn) are limited to only Abbott Architect hs-cTnI, Siemens Vista hs-cTnI, and Roche Elecsys hs-cTnT. Objective: This study aimed to evaluate this new hs-cTnI assay, LumipulsePresto hs Troponin I, for diagnosis of acute myocardial infarction (AMI) on admission and on 0-/1-h algorithm to stratify AMI patients precisely. Methods: This prospective cohort study included 442 patients with suspected non-ST-elevation myocardial infarction in three hospitals in Japan and Taiwan from June 2016 to January 2019. We enrolled patients presenting to the emergency department with symptoms suggestive of AMI and collected blood samples on admission and 1 hour later. Two independent cardiologists centrally adjudicated final diagnoses; all clinical information was reviewed twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis) and Lumipulse Presto Lumipulse Presto, second, using the Lumipulse Presto hs-cTnI measurements. At first, we compared diagnostic accuracy quantified using receiver operating characteristic (ROC) curves for AMI. Then, we evaluated major adverse cardiovascular events (cardiac death, AMI) in the rule-out group according to a 0-hour/1-hour algorithm at the 30-day follow-up. Results: Diagnostic accuracy at presentation by the ROC curve for AMI was very high and similar for the LumipulsePresto hs-cTnI and hs-cTnT,(area under the curve [AUC]: LumipulsePresto hs-cTnI, 0.89, 95% confidence interval [CI] 0.86–0.93; hs-cTnT, 0.89, 95% CI 0.85–0.93; p = 0.82). In early presenters, the LumipulsePresto hs-cTnI appeared to maintain the diagnostic performance of hs-cTn for patients with p = 0.81). The algorithm using the LumipulsePresto hs-cTnI ruled out AMI in 200 patients with negative predictive value and sensitivity of 100% (95% CI 97.3%–100%) and 100% (95% CI 92.7%–100%), respectively, in the rule-out group. Conclusion: Diagnostic accuracy and clinical utility of the novel LumipulsePresto hs-cTnI assay are high and comparable with the established hs-cTn assays.

A 61-year-old woman underwent laparoscopy-assisted distal gastrectomy (LADG) with extragastric lymph node dissection (D2). Two months later, she was readmitted to hospital to be treated for chylous ascites. Oral intake was discontinued and total parenteral nutrition started, but increasing body weight and decreasing serum albumin concentration was not controllable. Percutaneous transabdominal thoracic duct embolization (PTTDE) was performed on the 8th day after the readmission. Five days after PTTDE, oral intake was resumed. Seventeen days after PTTDE, the patient was discharged without recurrence of ascites. She has remained asymptomatic. We describe here the first patient with chylous ascites two months after LADG with D2 dissection for early gastric cancer who was successfully treated by PTTDE.

Halogen⋯halogen contacts are considerably important intermolecular interactions. An adamantane-based macrocycle with pyridazine moieties (1) was synthesized from 3,6-dichloropyridazine and disubstituted adamantane possessing chlorophenol moieties in 57% yield as a new host molecule. The crystallization of 1 in various solvents afforded six inclusion crystals. The macrocyclic framework had a nearly hexagonal structure with a cavity, and was assembled into various network structures composed of layer architectures bearing channels. In crystals containing cyclic ethers, halogen⋯halogen interactions between all chlorine atoms of 1 were observed. Meanwhile, in crystals containing halomethanes and aromatic compounds, CH⋯Cl interactions alternately and partially appeared.

A methylene- and adamantane-bridged macrocycle with four biphenyl units (1) was synthesized as a host molecule. The vapor diffusion of n-hexane into a chloroform solution of 1 afforded a co-inclusion crystal (1a) containing both guests, which was confirmed by X-ray crystallographic analysis. In the case of the other four hexane isomers, a crystal (1b) containing only one chloroform molecule was obtained, indicating the selective inclusion of n-hexane from among the five hexane isomers. When n-heptane or n-pentane instead of n-hexane was employed as an alkane guest, crystal 1b or guest-free crystal 1c was formed, showing that the macrocycle recognizes the length of the alkyl chain. Furthermore, when dichloromethane was used instead of chloroform, crystal 1d with only a dichloromethane guest was generated, showing that chloroform is essential for the accommodation of n-hexane into the crystals.

The crystalline sponge (CS) method was developed as an X-ray crystallographic molecular structure analysis method that can be performed without the need for crystallization of the analyte. CS has strong molecular-recognition properties and a highly flexible framework. The amount of analyte can be reduced to a sub-milligram level. These features of the crystalline nano-space allow for determining the absolute structure of a trace analyte. In this review, we focus on the discovery of the CS method and its applications to biosynthetic products in combination with NMR spectroscopy. We also describe some examples of the CS method that are used mainly in combination with mass spectrometry (MS). Both approaches demonstrate the potential of microanalysis to determine the molecular structure of an unknown sample. Finally, we mention the use of a crystalline "nano-surface" rather than a crystalline nano-space in MS, which can detect small metabolites as well as post-translation biomolecules.

In recent times, the diagnosis and treatment of superficial laryngopharyngeal cancers has been receiving a lot of attention. Here, we present a case of superficial hypopharyngeal cancer and superficial esophageal cancer for which endoscopic laryngo-pharyngeal surgery (ELPS) and endoscopic submucosal dissection (ESD) were performed simultaneously. The patient was a 67-year-old male. During his follow-up for distal gastrectomy performed earlier for stomach cancer, an upper gastrointestinal endoscopy revealed three primary cancers: superficial hypopharyngeal cancer, superficial esophageal cancer, and esophagogastric junction cancer. Total resection of the remnant stomach was performed followed by hypopharyngeal ELPS combined with esophageal ESD. He developed aspiration pneumonia after the surgery; however, he recovered and was discharged on the 16th day. Thus, safe and effective endoscopic therapy can be performed even for double superficial cancers of the laryngopharynx and esophagus.

This work reports that cyclophanes and their [2]catenanes were synthesized by the SN Ar reactions of disubstituted adamantanes bearing halophenol units and 3,6-dichlorotetrazine in moderate yields. In the crystalline state, the cyclophanes had hexagonal structures with a cavity. The [2]catenanes were composed of two macrocycles that were singly interlocked and orthogonally arranged, indicating the construction from eight component molecules through eight C-O bonds in a one-step reaction in up to 33 % yield. The cyclophanes were assembled to afford a supramolecular organic framework in the solid state, which exhibited permanent intrinsic porosity and adsorption of leaf alcohol or aldehyde in a single-crystal to single-crystal fashion. The molecular structures of the liquid guests were determined by single-crystal X-ray analysis. The formation of catenanes and the use of cyclophane-based porous crystals in the crystalline sponge method may be largely ascribed to the solvophobic effects and the van der Waals interactions that originate in the aliphatic and bulky nature of the adamantane units.

Cholesterol, a necessary component of animal cell membranes, is also needed by the lethal human malaria parasite Plasmodium falciparum. Because P. falciparum lacks a cholesterol synthesis pathway and malaria patients have low blood cholesterol, we speculated that it scavenges cholesterol from them in some way. We used time-lapse holotomographic microscopy to observe cholesterol transport in live P. falciparum parasites and structurally investigate erythrocyte membranes, both during and after P. falciparum invasion of human erythrocytes. After P. falciparum initially acquired free cholesterol or inner erythrocytic membrane-derived cholesterol, we observed budding lipid membranes elongating into the cytosol and/or membrane segments migrating there and eventually fusing with the parasite membranes, presumably at the parasitophorous vacuole membrane (PVM). Finally, the cholesterol-containing segments were seen to surround the parasite nucleus. Our imaging data suggest that a novel membrane transport system operates in the cytosol of P. falciparum-infected erythrocytes as a cholesterol import system, likely between the PVM and the erythrocyte membrane, and that this transportation process occurs during the live erythrocyte stages of P. falciparum.

Lymphoma comprises a group of diseases characterized by neoplastic proliferation of mature B, T, and NK cells. This disease entity is widely recognized to be clinically, pathologically, molecularly, and genetically heterogeneous. The classification of lymphomas was classically based on morphology and immunology, but recent dramatic advances in next-generation sequencing technology have revealed various genetic alterations in lymphomas, which influenced the revision of the WHO classification in 2017. Accumulating evidence on genetic alterations has enabled the development of more accurate diagnostic strategies and prognostic markers. Moreover, these findings provide opportunities to exploit new therapeutics that target genetic alterations, which would facilitate the use of precision medicine in lymphomas. Here, we briefly review the fundamental methods of genetic analysis using next-generation sequencing technology and describe the entire scenario of genetic alterations, focusing on the recent major studies that have revealed various genetic alterations in each lymphoma subtype and present a detailed discussion of the results and methods.

A novel molecular gyrotop with a furan-2,5-diyl was synthesized. The furan-diyl rotor showed rotation inside the cage in a solution. However, no furan-rotor dynamics was observed in a crystalline s...

Construction of hydrogen-bonded networks among hydroxyl groups has often been utilized to synthesize specific structures on the basis of supramolecular chemistry. In this study, resorcyltriptycene ...

Disubstituted adamantanes having pyrogallol derivatives as V-shaped host molecules were synthesized to prepare complexes with carboranes, which are representative spherical guest molecules for macrocyclic compounds, including calixarenes and cyclotriveratrylenes. The crystallization of o-carborane (a) and 1,3-bis(3,4,5-trimethoxyphenyl)adamantane (1) in toluene resulted in the formation of inclusion crystals (1a) in a 1 : 1 ratio. X-ray crystallographic analysis revealed that two oxygen atoms in 1 interact with two hydrogen atoms of a through CH⋯O interactions to afford the complexes. In the case of 1,3-bis(3,4,5-triethoxyphenyl)adamantane (2), no inclusion crystal was obtained due to steric hindrance of the ethyl groups. Furthermore, the crystallization of 1 and a benzoquinone derivative (b) provided reddish crystals (1b) with a 1 : 2 host : guest complexation stoichiometry, where lone pair⋯π interactions in the complexes were observed in addition to donor–acceptor interactions.