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Pentoses and hexoses contain more than three oxygen-bearing stereocentres and are ideal starting materials for the synthesis of multiply oxygenated natural products such as sagittamide D, maitotoxin and hikizimycin. Here we demonstrate new radical–radical homocoupling reactions of sugar derivatives with minimal perturbation of their chiral centres. The radical exchange procedure using Et 3 B/O 2 converted sugar-derived α-alkoxyacyl tellurides into α-alkoxy radicals via decarbonylation and rapidly dimerized the monomeric radicals. The robustness of this process was demonstrated by a single-step preparation of 12 stereochemically diverse dimers with 6–10 secondary hydroxy groups, including the C5–C10 stereohexad of sagittamide D and the enantiomer of the C51–C60 stereodecad of maitotoxin. Furthermore, the optimally convergent radical–radical cross-coupling reaction achieved a one-step assembly of the protected C1–C11 oxygenated carbon chain of the anthelmintic hikizimycin. These exceptionally efficient homo- and heterocoupling methods together provide a powerful strategy for the expedited total synthesis of contiguously hydroxylated natural products. Pentoses and hexoses represent important structural motifs in bioactive secondary metabolites, though their synthesis often requires several elongation steps. Now, a method for radical–radical coupling reactions of sugar derivatives enables the single-step preparation of the oxygenated carbon chains of several natural products, including sagittamide D, maitotoxin and hikizimycin.

A three-component coupling reaction of structurally simple 6–8 was successfully applied for expeditious synthesis of the 6/5/9-membered tricyclic structure 3 of cladieunicellin D (1) and klysimplexin U (2). Upon treatment with the Et3B/O2 reagent system, α-alkoxyacyl telluride 6, six-membered enone 7, and (Z)-4-hexenal (8) were linked in one pot to provide the densely functionalized 5 via sequential decarbonylative radical generation, radical addition, boron enolate formation, and intermolecular aldol reaction. Subsequent Lewis acid-promoted reductive etherification and SiO2-induced C10-epimerization gave rise to the cis-fused five-membered ether of 4. Finally, cyclization of the nine-membered ring was achieved by the ring-closing metathesis reaction, giving rise to 3. Compound 3 possesses the six stereocenters of 1 and 2, and would thus serve as an advanced intermediate for their total syntheses.

The reactive hyperemia index (RHI) is a marker of peripheral microvascular function influenced by both endothelium‐dependent and independent mechanisms. Myocardial bridging (MB) may impact coronary microvascular function, but its effect on the relationship between RHI and coronary microvascular function remains unclear. In this cross‐sectional study, 38 patients underwent noninvasive RHI assessment alongside invasive coronary microvascular function testing. MB was identified via coronary angiography, while endothelium‐dependent and independent coronary microvascular function were evaluated using coronary flow reserve in response to intracoronary administration of acetylcholine and microvascular resistance reserve in response to intravenous administration of adenosine, respectively. Among 38 patients (mean age: 59 years, 34% male), 14 had MB. RHI correlated with an index of endothelium‐independent coronary microvascular function (r = 0.34, p = 0.04), whereas it did not correlate with that of endothelium‐dependent function. This correlation persisted in patients without MB (r = 0.54, p = 0.01) but was lost in those with MB (p = 0.83). RHI is associated with endothelium‐independent coronary microvascular function, but MB disrupts this relationship, suggesting a local impact on coronary microvascular physiology.

An 86‐year‐old woman suffering from repeated methicillin‐resistant Staphylococcus aureus (MRSA) bacteremia underwent percutaneous lead extraction using an excimer laser. Since negative blood cultures were confirmed three times after lead extraction under intravenous infusion of anti‐MRSA drugs, a Micra transcatheter pacing system (Micra TPS) was implanted 7 days after the lead extraction. Although infusion of anti‐MRSA drugs was continued for 5 weeks, MRSA was isolated in four separate samples of blood cultures 3 weeks after the discontinuation of the anti‐MRSA therapy. The micra TPS was successfully retrieved using a steerable sheath and snare at 8 weeks after implantation.

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of unknown etiology with few treatment options. Although tetraspanins are involved in various diseases, their roles in fibrosis have not been determined. To investigate the role of tetraspanin CD151 in pulmonary fibrosis. CD151 knockout (KO) mice were studied by histological, biochemical, and physiological analyses and compared with wild-type mice and CD9 KO mice. Further mechanistic analyses were performed in vitro, in vivo, and on samples from patients with IPF. A microarray study identified an enrichment of genes involved in connective tissue disorders in the lungs of CD151 KO mice, but not in CD9 KO mice. Consistent with this, CD151 KO mice spontaneously exhibited age-related pulmonary fibrosis. Deletion of CD151 did not affect pulmonary fibroblast functions but instead degraded epithelial integrity via attenuated adhesion strength on the basement membrane; CD151-deleted alveolar epithelial cells exhibited increased α-SMA expression with activation of p-Smad2, leading to fibrotic changes in the lungs. This loss of epithelial integrity in CD151 KO lungs was further exacerbated by intratracheal bleomycin exposure, resulting in severe fibrosis with increased mortality. We also observed decreased numbers of CD151-positive alveolar epithelial cells in patients with IPF. CD151 is essential for normal function of alveolar epithelial cells; loss of CD151 causes pulmonary fibrosis as a result of epithelial disintegrity. Given that CD151 may protect against fibrosis, this protein represents a novel target for the treatment of fibrotic diseases.

Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2–3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis. We identified disease-specific autoantibodies and enriched KEGG pathways unique to each disease, and demonstrated that IPF and INSIP are serologically distinct. Furthermore, we discovered a new INSIP-specific autoantibody, anti–myxovirus resistance-1 (MX1) autoantibody. Patients positive for anti-MX1 autoantibody constituted 17.5% of all cases of chronic fibrosing IIPs. Notably, patients rarely simultaneously carried the anti-MX1 autoantibody and the anti–aminoacyl-transfer RNA synthetase autoantibody, which is common in chronic fibrosing IIPs. Because MX1 is one of the most important interferon-inducible anti-viral genes, we have not only identified a new diagnostic autoantibody of INSIP but also obtained new insight into the pathology of INSIP, which may be associated with viral infection and autoimmunity.

Cardiac perforation by a transvenous lead is an uncommon but serious complication. We herein present a case of very late perforation of a Riata implantable cardioverter‐defibrillator lead, which occurred 8 years after implantation. The patient was successfully treated with percutaneous lead extraction using an excimer laser. Lead perforation should be considered, even after years from implantation.