Synthesis and Reactivity of an Alumanyl-Tin Species to Form an Al,N-Heteroallene Derivative.

The molecular chemistry of metal-metal bonds is crucial for understanding the bonding and reactivity of metal-containing molecules as well as solid metals and their alloys, especially with respect to their application as catalysts for organic transformations and industrial processes. Despite the high efficiency of the recently developed nucleophilic alumanyl anions in the synthesis of diverse Al-metal bonds, the bonding between main group metals in a low oxidation state and the Al atom remains largely unexplored. This paper describes the reaction of an alumanyl anion with a chlorostannylene precursor to afford a compound with an unprecedented covalent Al-Sn bond. The lability of the covalent Al-Sn bond renders it reactive toward the insertion of carbodiimide, N2O, and phenylacetylene. Remarkably, the reaction with benzonitrile furnished an unprecedented Al,N-heteroallene species that contains a linear Al═N═C linkage.

Base-Stabilized Gallium Sulfides and Selenides Supported by a Bis(oxazolinyl)(phenyl)methanide Ligand.

Gallylene supported by a bis(oxazolinyl)(phenyl)methanide (Boxm) ligand was synthesized and structurally characterized. The reaction of this gallylene with triphenylphosphine sulfide/selenide yielded dimeric gallium sulfide and selenide. These compounds could be converted to monomeric terminal sulfide and selenide by coordination of an external Lewis base such as an N-heterocyclic carbene (NHC or IMe4) and 4-dimethylaminopyridiene (DMAP). These doubly-base-stabilized gallium sulfide/selenide reacted with phenyl isocyanate to give the corresponding cycloadducts by releasing the Lewis base, indicating the formation of a single-base-stabilized gallium sulfide/selenide intermediate.

Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.

BACKGROUND: The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors. METHODS: Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies. RESULTS: Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling. CONCLUSIONS: This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.

We isolated Bacteroidota species from the feces of donors who were effectively cured of UC with fecal microbiota transplantation and proved the anti-inflammatory effects of Bacteroidota species, especially Alistipes putredinis, through cell experiments and in vivo experiments.

Alumanyl-Samarium(II): Synthesis, Characterization, and Reactivity Studies.

Metal-metal bonded species involving lanthanides are intriguing but rare. The recently reported salt metathesis reaction of an Al anion and SmI2(thf)2 yields novel heterometallic compound possessing two distinctive Al-Sm bonds. Although the Al-Sm bonds were considerably long [3.518(1) and 3.543(1) Å], DFT calculations indicated polar character of the Alδ--Smδ+ bonds. This is the first example of lanthanide species containing X-type Al ligands. Reactivity studies have demonstrated that the introduction of Sm(II) produces unique reactivity. The reaction with carbodiimide led to an insertion of carbodiimide into the Al-Sm bonds and reductive coupling of carbodiimide to create an oxalamidinate moiety, facilitated by Sm(II). Exposure of the Al-Sm-Al complex toward ethylene furnished a Sm(II) salt of anionic aluminacyclopropane that was spontaneously isomerized to a 1,4-dialuminacyclohexane derivative. The important role of Sm(II) to facilitate the ring expansion through an alkyl-relay mechanism was elucidated by DFT calculations.

Lung cancer progression alters lung and gut microbiomes and lipid metabolism.

Despite advances in medical technology, lung cancer still has one of the highest mortality rates among all malignancies. Therefore, efforts must be made to understand the precise mechanisms underlying lung cancer development. In this study, we conducted lung and gut microbiome analyses and a comprehensive lipid metabolome analysis of host tissues to assess their correlation. Alternations in the lung microbiome due to lung cancer, such as a significantly decreased abundance of Firmicutes and Deferribacterota, were observed compared to a mock group. However, mice with lung cancer had significantly lower relative abundances of Actinobacteria and Proteobacteria and higher relative abundances of Cyanobacteria and Patescibacteria in the gut microbiome. The activations of retinol, fatty acid metabolism, and linoleic acid metabolism metabolic pathways in the lung and gut microbiomes was inversely correlated. Additionally, changes occurred in lipid metabolites not only in the lungs but also in the blood, small intestine, and colon. Compared to the mock group, mice with lung cancer showed that the levels of adrenic, palmitic, stearic, and oleic (a ω-9 polyunsaturated fatty acid) acids increased in the lungs. Conversely, these metabolites consistently decreased in the blood (serum) and colon. Leukotriene B4 and prostaglandin E2 exacerbate lung cancer, and were upregulated in the lungs of the mice with lung cancer. However, isohumulone, a peroxisome proliferator-activated receptor gamma activator, and resolvin (an ω-3 polyunsaturated fatty acid) both have anti-cancer effects, and were upregulated in the small intestine and colon. Our multi-omics data revealed that shifts in the microbiome and metabolome occur during the development of lung cancer and are of possible clinical importance. These results reveal one of the gut-lung axis mechanisms related to lung cancer and provide insights into potential new targets for lung cancer treatment and prophylaxis.

Vanadium Alumanyl Complex: Synthesis, Characterization, Reactivity, and Application as a Catalyst for C-H Alumanylation of Alkenes.

A complex containing a V-Al bond is described. This species can be prepared by either transmetalation of a previously disclosed alumanylpotassium with Cp2VCl or photolytic oxidative alumination of Cp2V using the corresponding dialumane. Reaction of the resulting V-Al complex with H2 gave a Cp2V-dihydridoaluminate complex. These complexes were studied with X-ray crystallography, vanadium K-edge XANES spectroscopy, and DFT calculations. Finally, the reactivity of these molecules was studied opening the way to a catalytic C-H alumanylation of alkenes.

Mechanochemical Synthesis of Non-Solvated Dialkylalumanyl Anion and XPS Characterization of Al(I) and Al(II) Species.

A non-solvated alkyl-substituted Al(I) anion dimer was synthesized by a reduction of haloalumane precursor using a mechanochemical method. The crystallographic and theoretical analysis revealed its structure and electronic properties. Experimental XPS analysis of the Al(I) anions with reference compounds revealed the lower Al 2p binding energy corresponds to the lower oxidation state of Al species. It should be emphasized that the experimentally obtained XPS binding energies were reproduced by delta SCF calculations and were linearly correlated with NPA charges and 2p orbital energies.

A case of central adrenocortical insufficiency with alexithymia and alexisomia.

The patient was a 27-year-old woman. Following physical examination for unconscious hypoglycemia, the patient was diagnosed with central adrenocortical insufficiency. She also had alexithymia and alexisomia. Alexisomia is the inability to recognize or describe bodily sensations. Alexithymia is the difficulty of expressing one's feelings adequately. Alexisomia can be described as impaired interoceptive awareness. She had been maltreated and emotionally abused by her parents; thus, her upbringing may have influenced the development of alexithymia and alexisomia. In addition, her upbringing may have influenced the reduced hypothalamus-pituitary-adrenal axis activity. Her failure to perceive hypoglycemic symptoms as hypoglycemia was thought to have been influenced by her alexisomia. Interestingly, her alexisomia improved with steroid replacement therapy; however, the underlying mechanism remains unclear. However, exogenous steroids can also affect interoception. The patient was diagnosed with central adrenocortical insufficiency, an endocrine disorder, suggesting that psychosomatic factors may have been related to the patient's growth history.

Reactions of Tetra(o-tolyl)diborane(4) with Organic Azides: Formation of Fluorescent Boron-Fused Hexazenes.

The reaction of tetra(o-tolyl)diborane(4) with organic azides afforded three different compounds, diborylamines, diboryltriazenes, and B2 -hexazenes having a bicyclic B2 N6 ring system. The reaction with aryl azides gave diborylamines, while the reaction with 1 equiv. of alkyl azides furnished diboryltriazenes. In the case of the reaction with an excess amount of primary alkyl azide, a new heterocyclic B2 -hexazenes were obtained. The formation of the B2 N6 structure could be explained by one general reaction mechanism via the diboryltriazene intermediate according to the control experiments and DFT calculations. The B2 -hexazenes exhibited a strong fluorescence with a remarkably high fluorescent quantum yield of up to 96 %.

Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study.

The psychopathology of patients with anorexia nervosa has been hypothesized to involve inappropriate self-referential processing, disturbed interoceptive awareness, and excessive cognitive control, including distorted self-concern, disregard of their own starvation state, and extreme weight-control behavior. We hypothesized that the resting-state brain networks, including the default mode, salience and frontal-parietal networks, might be altered in such patients, and that treatment might normalize neural functional connectivity, with improvement of inappropriate self-cognition. We measured resting-state functional magnetic resonance images from 18 patients with anorexia nervosa and 18 healthy subjects before and after integrated hospital treatment (nourishment and psychological therapy). The default mode, salience, and frontal-parietal networks were examined using independent component analysis. Body mass index and psychometric measurements significantly improved after treatment. Before treatment, default mode network functional connectivity in the retrosplenial cortex and salience network functional connectivity in the ventral anterior insula and rostral anterior cingulate cortex were decreased in anorexia nervosa patients compared with those in controls. Interpersonal distrust was negatively correlated with salience network functional connectivity in the rostral anterior cingulate cortex. Default mode network functional connectivity in the posterior insula and frontal-parietal network functional connectivity in the angular gyrus were increased in anorexia nervosa patients compared with those in controls. Comparison between pre- and post-treatment images from patients with anorexia nervosa exhibited significant increases in default mode network functional connectivity in the hippocampus and retrosplenial cortex, and salience network functional connectivity in the dorsal anterior insula following treatment. Frontal-parietal network functional connectivity in the angular cortex showed no significant changes. The findings revealed that treatment altered the functional connectivity in several parts of default mode and salience networks in patients with anorexia nervosa. These alterations of neural function might be associated with improvement of self-referential processing and coping with sensations of discomfort following treatment for anorexia nervosa.

Alkali Chloride Adducts of Acyclic Acylaluminum: Synthesis, Structure, and Reactivity Studies.

Two acyclic acylaluminums and one cyclic acylaluminum dimer were synthesized by reaction of the recently reported Al-anion with acyl chloride. The reaction of the acylaluminums with TMSOTf and DMAP gave a ring-expanded iminium-substituted aluminate and a 2-C-H cleaved product. In the reaction of acylaluminums toward C=O and C=N bonds, acyclic acylaluminums reacted as an acyl nucleophile, while the cycilc dimer showed no reactivity. Amide-bond forming ligation using acyclic acylaluminums and hydroxylamines was further demonstrated. Throughout the study, acyclic acylaluminums exhibited higher reactivity than that of the cyclic dimer.

Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis.

OBJECTIVES: Prevotella copri is considered to be a contributing factor in rheumatoid arthritis (RA). However, in some non-Westernised countries, healthy individuals also harbour an abundance of P. copri in the intestine. This study investigated the pathogenicity of RA patient-derived P. copri (P. copri RA) compared with healthy control-derived P. copri (P. copri HC). METHODS: We obtained 13 P. copri strains from the faeces of patients with RA and healthy controls. Following whole genome sequencing, the sequences of P. copri RA and P. copri HC were compared. To analyse the arthritis-inducing ability of P. copri, we examined two arthritis models (1) a collagen-induced arthritis model harbouring P. copri under specific-pathogen-free conditions and (2) an SKG mouse arthritis model under P. copri-monocolonised conditions. Finally, to evaluate the ability of P. copri to activate innate immune cells, we performed in vitro stimulation of bone marrow-derived dendritic cells (BMDCs) by P. copri RA and P. copri HC. RESULTS: Comparative genomic analysis revealed no apparent differences in the core gene contents between P. copri RA and P. copri HC, but pangenome analysis revealed the high genome plasticity of P. copri. We identified a P. copri RA-specific genomic region as a conjugative transposon. In both arthritis models, P. copri RA-induced more severe arthritis than P. copri HC. In vitro BMDC stimulation experiments revealed the upregulation of IL-17 and Th17-related cytokines (IL-6, IL-23) by P. copri RA. CONCLUSION: Our findings reveal the genetic diversity of P. copri, and the genomic signatures associated with strong arthritis-inducing ability of P. copri RA. Our study contributes towards elucidation of the complex pathogenesis of RA.

Base-Stabilized Neutral Oxoborane and Thioxoborane Supported by a Bis(oxazolinyl)(phenyl)methanide Ligand.

Base-stabilized neutral oxoborane and thioxoborane supported by a bis(oxazolinyl)(phenyl)methanide ligand have been synthesized and structurally characterized. While previous synthetic attempts of oxoborane ligated by ß-diketiminate (NacNac) did not allow for its isolation in acid-free form, oxoborane supported by a bis(oxazolinyl)(phenyl)methanide ligand is isolable, due to the absence of imine ɑ-protons and steric protection of enamine carbon. Crystallographic analysis revealed the presence of a B-O double bond close to the shortest end of the reported lengths. Its reactivity has also been examined, and it was majorly governed by the nucleophilicity and basicity of the oxygen atom. The chemical inertness and synthetic convenience of the bis(oxazolinyl)(phenyl)methanide scaffold presented in this work suggest its utility as an innocent alternative to the NacNac scaffold.

Lipophilic N-Hydroxyimide Derivatives: Design, Synthesis, and Application to Aerobic Alkane Oxidation Under Neat Conditions.

This work reports the design and synthesis of a series of 5-membered and 6-membered N-hydroxyimides flanked by lipophilic alkyl groups adjacent to carbonyl groups, aiming to endow lipophilicity and tolerance toward ring opening degradation. Their solubility in cyclohexane was 5-20 times higher than those of unsubstituted N-hydroxyphthalimide (NHPI) and even 3-10 times higher than a formerly known lipophilic NHPI analog bearing a long alkyl ester. UV-Vis spectroscopy determined the rate constants of first-order decay of N-oxyls, which revealed enhanced stability of 3,5-di-tert-butyl-NHPI and N-hydroxyglutarimide flanked by spiro-cyclohexanes compared with that of NHPI. Their bond dissociation energies were assessed by EPR spectroscopy and DFT calculation, suggesting these lipophilic N-hydroxyimides catalyzed aerobic cyclohexane oxidation under neat conditions with up to 60 turnovers, which is the highest among hitherto reported reactions under neat conditions.

Clostridium butyricum-induced ω-3 fatty acid 18-HEPE elicits anti-influenza virus pneumonia effects through interferon-λ upregulation.

The precise mechanism by which butyrate-producing bacteria in the gut contribute to resistance to respiratory viral infections remains to be elucidated. Here, we describe a gut-lung axis mechanism and report that orally administered Clostridium butyricum (CB) enhances influenza virus infection resistance through upregulation of interferon (IFN)-λ in lung epithelial cells. Gut microbiome-induced ω-3 fatty acid 18-hydroxy eicosapentaenoic acid (18-HEPE) promotes IFN-λ production through the G protein-coupled receptor (GPR)120 and IFN regulatory factor (IRF)-1/-7 activations. CB promotes 18-HEPE production in the gut and enhances ω-3 fatty acid sensitivity in the lungs by promoting GPR120 expression. This study finds a gut-lung axis mechanism and provides insights into the treatments and prophylaxis for viral respiratory infections.

Al-Sc Bonded Complexes: Synthesis, Structure, and Reaction with Benzene in the Presence of Alkyl Halide.

An alumanyl anion possessing N,N'-bis(2,6-diisopropylphenyl)-1,3-propanediamine ligand was synthesized and characterized. Transmetalation of this Al anion with diaminoscandium chloride precursors afforded the corresponding Al-Sc complexes possessing an unprecedented Al-Sc bond. The Al-Sc[N(SiMe3)2] complex underwent intramolecular C-H cleavage to form a bridged dinuclear complex with µ-hydrido and µ-methylene ligands. The Al-Sc(NiPr2)2 complex reacted with benzene in the presence of alkyl bromide to furnish a 1,4-dialuminated cyclohexadiene product with a concomitant formation of the alkyl-alkyl coupled product. Although the latter product seems to form through the radical mechanism, DFT calculations revealed an ionic mechanism involving bimetallic reaction pathways to react with alkyl bromide and benzene, which provides new insight into the chemistry of metal-metal bonded compounds.

Cardiopulmonary exercise testing for patients with anorexia nervosa: a case-control study.

PURPOSE: Patients with anorexia nervosa (AN) require appropriate nutrient therapy and physical activity management. Eating disorder treatment guidelines do not include safe, evidence-based intensity criteria for exercise. This study used cardiopulmonary exercise testing (CPX) to evaluate the exercise tolerance of patients with AN. METHODS: CPX was performed with 14 female patients with AN admitted to a specialized eating disorder unit between 2015 and 2019. Their anaerobic threshold (AT) was determined by assessing their exercise tolerance using CPX and compared with 14 healthy controls (HC). The metabolic equivalents (AT-METS) were compared when AT was reached. We examined factors related to AT (AN-AT) in the AN group, including age, body mass index (BMI), previous lowest weight, minimum BMI, past duration of BMI < 15, exercise history, and ΔHR (heart rate at the AT-resting heart rate). RESULTS: The AT of the AN group (BMI: 15.7 [Mean] ± 1.8 standard deviation [SD]) was significantly lower than that of the HC group (BMI: 19.7 ± 1.8) (AN: 10.0 ± 1.8 vs. HC: 15.2 ± 3.0 ml/kg/min, P < 0.001). AT-METS was also significantly lower in the AN group than in the HC group (AN: 2.9 ± 0.52 vs. HC: 4.4 ± 0.91, P < 0.001). AN-AT was highly influenced by ΔHR. CONCLUSIONS: This study showed that AT and AT-METS were lower in patients with AN than in HC. Patients with AN should be prescribed light-intensity aerobic exercise, and the current findings may help develop future physical management guidelines for patients with AN. LEVEL OF EVIDENCE: III: Evidence obtained from case-control analytic studies.

Rhodium-Catalyzed Acrylate Synthesis from Carbon Dioxide and Ethylene by using a Guanidine-Based Pincer Ligand: Perturbing Occupied d-Orbitals by pπ-dπ Repulsion Makes a Difference.

Rhodium-catalyzed acrylate synthesis from CO2 and ethylene was accomplished by using a guanidine-based NCN pincer ligand. The repulsion between pπ-electron of guanidine sidearms and occupied dπ orbital of rhodium center raised the level of d-electrons close to those of formerly known d8 -ruthenium catalyst, thereby promoting the metallalactone formation from carbon dioxide and ethylene. This work fills the absence of group-9 metal based catalyst for the acrylate synthesis and provides a designing approach for pincer-ligated d8 -metal catalysts to utilize pπ-dπ interaction for promoting desirable redox processes.

A Tetraorganyl-Alumaborane with An Al-B σ-Bond and Two Adjacent Lewis-Acidic Centers.

A tetraorganyl-alumaborane (3) that contains an Al-B bond and twisted Al and B planes was synthesized and structurally characterized. UV-vis absorption spectroscopy, electrochemical measurement, and DFT calculations were employed to reveal the electronic properties of 3. The reactivity of 3 toward DMSO and CO was studied to demonstrate its deoxygenating abilities. On the basis of the results of the DFT calculations, a detailed reaction mechanism was developed, which highlighted the important role of the distinct Lewis acidity of the group-13 elements Al and B in 3.

Potential impact of the COVID-19 pandemic on japanese patients with eating disorders -a cross-sectional study.

BACKGROUND: The COVID-19 pandemic and associated lockdown had a considerable impact on eating disorders (EDs). We evaluated the clinical features of Japanese ED patients before and after the first COVID-19 outbreak-related state of emergency (April 7, 2020). METHODS: We studied 148 patients who were divided into two groups based on when they arrived at our clinic: before (Before group: n = 86) or after (After group: n = 62) the start of the first state of emergency. All patients completed the Japanese versions of the Eating Disorder Inventory (EDI) and Parental Bonding Instrument (PBI). RESULTS: The After group was substantially younger than the Before group (p = .0187). Regardless of the ED type, patients who developed an ED during the first state of emergency tended to be significantly younger than those who developed one before. Differences in EDI characteristics were observed between the two groups. The PBI care subscale was notably higher (p = .0177) in the After group. The PBI maternal care subscale was the only statistically significant factor associated with age (ß = -0.35, p < .0001). CONCLUSIONS: Home confinement associated with the COVID-19 pandemic and the ensuing increase in parent-child closeness may have influenced the decreased age of ED patients at their initial consultation. Treatment interventions should consider the differences in the clinical features of EDs.