On the basis of the boron-masking strategy, new divalent cross-coupling modules have been designed for the efficient synthesis of boron-substituted oligoarenes. The modules, i.e., monoprotected o-, ...m-, and p-benzenediboronic acid derivatives, undergo highly selective Suzuki−Miyaura coupling with sp2 iodides, bromides, chlorides, and triflates, affording coupling products in which the protected boronyl groups are left intact.
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•The proposed structure for artemisidiyne A has been successfully synthesized.•Artemisidiyne A is a cytotoxic polyacetylene compound isolated from Artemisia lactiflora.•Sonogashira ...cross-coupling was employed as one of the key reactions.•The NMR data of synthetic artemisidiyne A did not agree with the reported data.•We concluded that the genuine artemisidiyne might be a trans-type diol rather than a cis-type.
Artemisidiyne A, a cytotoxic compound isolated from Artemisia lactiflora, exhibits an unprecedented structure consisting of the cis-4,5-dihydroxy-2-cyclopentenone core with 1,3-pentadiynyl and 4-hydroxybutyl side chains. Despite its unique structure and useful biological activity, to our knowledge, its synthesis has never been reported. Here, we report the synthesis of the proposed structure for artemisidiyne A and propose a structural revision of this naturally occurring compound.
Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely ...unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. Moreover, we identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection.
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•SARS-CoV-2 infectivity is enhanced by specific antibodies independent of the Fc receptor•The open RBD state is induced upon antibody binding to a specific site on the NTD•Divalent bridging of spikes is required to induce the RBD-up state•Infectivity-enhancing antibodies are detected in severe COVID-19 patients
A subset of antibodies detected in patients with severe COVID-19 target a specific region of the N-terminal domain of the spike protein and enhance binding of the virus to the ACE2 receptor.
Background: Pancreatic body and tail cancer easily invades retroperitoneal tissue, including the transverse mesocolon. It is difficult to ensure a dissected peripancreatic margin with standard distal ...pancreatectomy for advanced pancreatic body and tail cancer. Thus, we developed a novel surgical procedure to ensure dissection of the peripancreatic margin. This involved performing dissection deeper than the fusion fascia of Toldt and further extensive en bloc resection of the root of the transverse mesocolon. We performed distal pancreatectomy with transverse mesocolon resection (DP-TCR) using a mesenteric approach and achieved good outcomes. Methods: There are two main considerations for surgical procedures using a mesenteric approach: 1) dissection deeper than the fusion fascia of Toldt (securing the vertical margin) and 2) modular resection of the pancreatic body and tail, with the root of the transverse mesocolon and adjacent organs in a horizontal direction (ensuring the caudal margin). Results: From 2017 to 2019, we performed DP-TCR using a mesenteric approach for six patients with advanced pancreatic body and tail cancer. Histopathological radical surgery was possible in all patients who underwent DP-TCR. No Clavien-Dindo grade IIIa or worse perioperative complications were observed in any patient. Conclusions: We believe that DP-TCR is useful as a radical surgery for advanced pancreatic body and tail cancer with extrapancreatic invasion.
Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective ...antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864–882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2–specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.
Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates ...that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy remained unknown.
In this retrospective study we evaluated the effects of tocilizumab monotherapy on the clinical characteristics, serum biomediator levels, viral elimination, and specific IgG antibody induction in 13 severely to critically ill patients and compared with those of dexamethasone monotherapy and dexamethasone plus tocilizumab.
A single tocilizumab administration led to a rapid improvement in clinical characteristics, inflammatory findings, and oxygen supply in 7 of 11 patients with severe COVID-19, and could recover from mechanical ventilation management (MVM) in 2 patients with critically ill COVID-19. Four patients exhibited rapidly worsening even after tocilizumab administration and required MVM and additional methylprednisolone treatment. Tocilizumab did not delay viral elimination or inhibit IgG production specific for the virus, whereas dexamethasone inhibited IgG induction. A multiplex cytokine array system revealed a significant increase in the serum expression of 54 out of 80 biomediators in patients with COVID-19 compared with that in healthy controls. Compared with those who promptly recovered in response to tocilizumab, patients requiring MVM showed a significantly higher ratio of basal level of ferritin/CRP and a persistent increase in the levels of CRP and specific cytokines and chemokines including IL-6, IFN-γ, IP-10, and MCP-1. The basal high ratio of ferritin/CRP was also associated with clinical deterioration even in patients treated with dexamethasone and tocilizumab.
Tocilizumab as monotherapy has substantial beneficial effects in some patients with severe COVID-19, who showed a relatively low level of the ratio of ferritin/CRP and prompt reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1. The high ratio of ferritin/CRP is associated with rapid worsening of pneumonia. Further evaluation is warranted to clarify whether tocilizumab monotherapy or its combination with corticosteroid is preferred for severely to critically ill patients with COVID-19.
Background: Pancreatic body and tail cancer easily invades retroperitoneal tissue, including the transverse mesocolon. It is difficult to ensure a dissected peripancreatic margin with standard distal ...pancreatectomy for advanced pancreatic body and tail cancer. Thus, we developed a novel surgical procedure to ensure dissection of the peripancreatic margin. This involved performing dissection deeper than the fusion fascia of Toldt and further extensive en bloc resection of the root of the transverse mesocolon. We performed distal pancreatectomy with transverse mesocolon resection (DP-TCR) using a mesenteric approach and achieved good outcomes. Methods: There are two main considerations for surgical procedures using a mesenteric approach: 1) dissection deeper than the fusion fascia of Toldt (securing the vertical margin) and 2) modular resection of the pancreatic body and tail, with the root of the transverse mesocolon and adjacent organs in a horizontal direction (ensuring the caudal margin). Results: From 2017 to 2019, we performed DP-TCR using a mesenteric approach for six patients with advanced pancreatic body and tail cancer. Histopathological radical surgery was possible in all patients who underwent DP-TCR. No Clavien-Dindo grade IIIa or worse perioperative complications were observed in any patient. Conclusions: We believe that DP-TCR is useful as a radical surgery for advanced pancreatic body and tail cancer with extrapancreatic invasion.
Fabrication of abrupt InGaP on GaAs (InGaP/GaAs) and GaAs on InGaP (GaAs/InGaP) hetero-interfaces has been difficult using metal organic vapor phase epitaxy (MOVPE) due to the exchange of P and As ...during the fabrication steps. Indium (In) surface segregation during InGaP growth also degrades the abruptness. Here, the MOVPE gas-switching sequence to fabricate atomically abrupt hetero-interfaces was optimized and the effects of this optimization on the hetero-interface abruptness were quantitatively evaluated using the Z-contrast method with scanning transmission electron microscopy (STEM). Results revealed that (a) in the fabrication of InGaP/GaAs hetero-interface, the GaAs top layer should be stabilized using As-source gas supply, and the excess As layer on GaAs should be terminated using an additional supply of Ga species, and (b) in the fabrication of GaAs/InGaP interface, the InGaP layer should be grown using the flow modulation method to suppress In surface segregation. In conclusion, the abruptness of hetero-interfaces of InGaP/GaAs and GaAs/InGaP was improved by using these optimized gas-switching sequences.
► We fabricated abrupt InGaP/GaAs and GaAs/InGaP hetero-interfaces using MOVPE. ► Improvement of hetero-interface was realized by optimized gas-switching sequence. ► Abruptnesses of hetero-interfaces were quantitatively evaluated by STEM.
BackgroundPancreatic body and tail cancer easily invades the retroperitoneal tissue, including the transverse mesocolon. It is difficult to ensure a dissected peripancreatic margin using standard ...distal pancreatectomy for advanced pancreatic body and tail cancer.Thus, we developed a novel surgical procedure to ensure dissection of the peripancreatic margin. This involved performing dissection deeper than the fusion fascia of Toldt and further extensive en bloc resection of the root of the transverse mesocolon. We performed distal pancreatectomy with transverse mesocolon resection (DP-TCR) using the mesenteric approach and achieved good outcomes.MethodsThere are two main considerations regarding the surgical procedure using the mesenteric approach: 1) dissection deeper than the fusion fascia of Toldt (securing the vertical margin) and 2) modular resection of the pancreatic body and tail, with the root of the transverse mesocolon and adjacent organs in a horizontal direction (ensuring the caudal margin).ResultsFrom 2017 to 2019, we performed DP-TCR using the mesenteric approach for six patients with advanced pancreatic body and tail cancer. Histopathological radical surgery was possible in all patients who underwent DP-TCR. No perioperative complications of grade IIIa or above in the Clavien–Dindo classification were observed in any patients.ConclusionsWe believe that DP-TCR is useful as a radical surgery for advanced pancreatic body and tail cancer with extrapancreatic invasions.
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