Atroposelective synthesis of axially chiral molecules has attracted substantial attention from chemists because of the importance of such molecules. However, catalytic asymmetric synthesis of axially ...chiral styrenes or vinyl arenes is underdeveloped and challenging due to the low rotational barrier and weak configurational stability of such molecules. Therefore, the development of powerful strategies for the catalytic atroposelective synthesis of axially chiral styrenes or vinyl arenes is of great importance. In this work, we have accomplished the first atroposelective access to oxindole-based axially chiral styrenes by the strategy of catalytic kinetic resolution, and this strategy offered two kinds of oxindole-based axially chiral styrene derivatives in good diastereoselectivities (up to 94:6 dr) and excellent enantioselectivities (up to 98% ee) with high selectivity factors (S up to 106). This strategy not only provides easy access to oxindole-based axially chiral styrenes but also offers a robust method for synthesizing bisamide derivatives bearing both axial and central chirality. More importantly, this strategy has added a new class of members to the atropisomeric family, especially to the family of axially chiral styrenes.
Emerging cybersecurity vulnerabilities in supervisory control and data acquisition (SCADA) systems are becoming urgent engineering issues for modern substations. This paper proposes a novel intrusion ...detection system (IDS) tailored for cybersecurity of IEC 61850 based substations. The proposed IDS integrates physical knowledge, protocol specifications, and logical behaviors to provide a comprehensive and effective solution that is able to mitigate various cyberattacks. The proposed approach comprises access control detection, protocol whitelisting, model-based detection, and multiparameter-based detection. This SCADA-specific IDS is implemented and validated using a comprehensive and realistic cyber-physical test-bed and data from a real 500 kV smart substation.
Ferromagnetic/antiferromagnetic materials are of crucial importance in information storage and spintronics devices. Herein we present a comprehensive study of 2D Heisenberg-like antiferromagnetic ...material MnPS3 by optical contrast and Raman spectroscopy. We propose a criterion of 0.1 × (N – 1) < (ΔR/R)max < 0.1 × N (N ≤ 7) to quickly identify the layer number N by using maximum optical contrast (ΔR/R)max of few-layer MnPS3 on a SiO2/Si substrate (90 nm thick SiO2). The Raman modes are also identified by polarization Raman spectroscopy. Furthermore, by temperature-dependent Raman measurements, we obtain three phase transition temperatures of MnPS3. The transition temperature at around 80 K corresponds to the transition from the antiferromagnetic to paramagnetic phase; the one at around 120 K is related to its second magnetic phase transition temperature due to two-dimensional spin critical fluctuations; the one at around 55 K is associated with unbinding of spin vortices. Our studies provide more evidence to advance knowledge of the magnetic critical dynamics of 2D ferromagnetic/antiferromagnetic systems.
The effects of mesenchymal stem cells (MSC) on the growth and metastasis of human malignancies including hepatocellular carcinoma (HCC) are controversial, and the underlying mechanisms are not yet ...understood. The aim of this study was to explore the role of MSC in the progression of HCC. We investigated the effect of MSC on in vitro proliferation and invasion and in vivo tumor growth and pulmonary metastasis of MHCC97‐H HCC cells with a high metastatic potential. The mRNA and protein levels of transforming growth factor‐beta 1 (TGFβ1) and MMP, and their association with the effects of MSC on HCC cells were also evaluated. Co‐culture of MHCC97‐H cells with MSC conditioned medium significantly enhanced in vitro proliferation but inhibited invasiveness. Following MSC treatment of a nude mouse model bearing human HCC, the MSC were predominantly located in the HCC tissues. Compared with controls, MSC‐treated mice exhibited significantly larger tumors (3080.51 ± 1234.78 mm3vs 2223.75 ± 1000.60 mm3, P = 0.045), but decreased cellular numbers of lung metastases (49.75 ± 18.86 vs 227.22 ± 74.67, P = 0.046). Expression of TGFβ1 and MMP‐2 was significantly downregulated in the MSC‐treated HCC cells. TGFβ siRNA concurrently downregulated expression of TGFβ and MMP‐2 in HCC cells and blocked the MSC‐induced proliferation and invasiveness of MHCC97‐H cells. The MSC enhanced tumor growth but significantly inhibited the invasiveness and metastasis of HCC, possibly through downregulation of TGFβ1. These findings suggest that MSC could be useful in controlling metastatic recurrence of HCC. (Cancer Sci 2010; 101: 2546–2553)
Organic nitrates are broadly applied as pharmaceuticals (acting as efficient nitric oxide donor), energetic materials, building blocks in organic synthesis, etc. However, practical and direct methods ...to access organic nitrates efficiently are still rare, mainly due to the lack of powerful nitrooxylating reagents. Herein, we report bench‐stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagents, oxybis(aryl‐λ3‐iodanediyl) dinitrates (OAIDNs, 2), which are prepared just by using aryliodine diacetate and HNO3. The reagents are used to achieve a mild and operationally simple protocol to access diverse organic nitrates. By employing of 2, zinc‐catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers is realized efficiently to access the corresponding β‐nitrooxy ketones with high functional‐group tolerance. Moreover, a series of direct and catalyst‐free nitrooxylations of enolizable C−H bonds are carried out smoothly to afford the desired organic nitrates within minutes by just mixing the substrates with 2 in dichloromethane.
A bench‐stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagent is prepared from aryliodine diacetate and HNO3. This reagent facilitates the zinc‐catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers with broad scope, and also can be used in the nitrooxylation of various enolizable C−H bonds.
Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. ...Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.
To assess the effects of cetuximab plus chemotherapy as first-line treatment for unresectable colorectal liver metastases (CLMs).
After resection of their primary tumors, patients with KRAS wild-type ...synchronous nonresectable liver-limited metastases from colorectal cancer were randomly assigned to receive chemotherapy (FOLFIRI fluorouracil, leucovorin, and irinotecan or mFOLFOX6 modified fluorouracil, leucovorin, and oxaliplatin) plus cetuximab (arm A) or chemotherapy alone (arm B). The primary end point was the rate of patients converted to resection for liver metastases. Secondary end points included tumor response and survival.
The intent-to-treat population comprised 138 patients; 70 patients were randomly assigned to arm A and 68 to arm B. After a median of 25.0 months of follow-up, the 3-year overall survival (OS) rate and median survival time (MST) for all patients were 30% and 24.4 months, respectively. The R0 resection rates for liver metastases were 25.7% (18 of 70 patients) in arm A and 7.4% (five of 68 patients) in arm B, which were significantly different (P < .01). Patients in arm A had improved objective response rates (57.1% v 29.4%; P < .01), increased 3-year OS rate (41% v 18%; P = .013) and prolonged MST (30.9 v 21.0 months; P = .013) compared with those in arm B. In addition, in arm A, patients who had resection of liver metastases had a significantly improved MST (46.4 v 25.7 months; P < .01) compared with those who did not undergo surgery.
For patients with initially unresectable KRAS wild-type CLMs, cetuximab combined with chemotherapy improved the resectability of liver metastases and improved response rates and survival compared with chemotherapy alone.
Plant immunity often penalizes growth and yield. The transcription factor Ideal Plant Architecture 1 (IPA1) reduces unproductive tillers and increases grains per panicle, which results in improved ...rice yield. Here we report that higher IPA1 levels enhance immunity. Mechanistically, phosphorylation of IPA1 at amino acid Ser
within its DNA binding domain occurs in response to infection by the fungus
and alters the DNA binding specificity of IPA1. Phosphorylated IPA1 binds to the promoter of the pathogen defense gene
and activates its expression, leading to enhanced disease resistance. IPA1 returns to a nonphosphorylated state within 48 hours after infection, resuming support of the growth needed for high yield. Thus, IPA1 promotes both yield and disease resistance by sustaining a balance between growth and immunity.
A 16‐year‐old male was admitted to the hospital for weakness of both lower extremities. Magnetic resonance imaging revealed an intraspinal extramedullary subdural mass at the thoracic 9 level. ...Microscopically, the tumor cells were small to medium sized and round to ovoid in shape. They were distributed in diffuse sheets or showed nodular appearance. The nucleus of the tumor had mild‐to‐moderate atypia, with vesicular chromatin and prominent nucleoli. A smaller proportion of tumor cells demonstrated rhabdoid morphology. Focal myxoid stromal change was present, in which tumor cells exhibited spindle shapes. Approximately two mitoses were counted per 10 high‐power fields. No necrosis was observed. The tumor cells were focal positive for CD99; multifocal positive for WT1; diffuse positive for nestin, synaptophysin, and D2‐40; partial positive for GFAP; focal positive for desmin and SSTR2; and scattered positive for S‐100 protein. The Ki‐67 labeling index was approximately 20%. Genetic testing revealed CIC‐LEUTX gene fusion. Considering the patient's history, clinical data, pathological findings and genetic findings, we rendered a rare tumor named CIC‐rearranged sarcoma with CIC‐LEUTX gene fusion.
A Lewis acid‐catalyzed (3+2) cycloaddition of 2‐indolylmethanols with β,γ‐unsaturated α‐ketoesters was established, which afforded a series of cyclopentabindoles in overall high yields (up to 98 %) ...with excellent diastereoselectivities (up to >95 : 5 dr). This reaction not only represents the first C3‐nucleophilic (3+2) cycloaddition of 2‐indolylmethanols, but also provides a good example for (2+n) cycloaddition of β,γ‐unsaturated α‐ketoesters, which will add new contents to the chemistry of 2‐indolylmethanols. In addition, this approach provides an atom‐economic and useful method for the construction of biologically important cyclopentabindole scaffold.
A Lewis acid‐catalyzed (3+2) cycloaddition of 2‐indolylmethanols with β,γ‐unsaturated α‐ketoesters was established. Various cyclopentabindoles were obtained in overall high yields with excellent diastereoselectivities. This reaction not only represents the first C3‐nucleophilic (3+2) cycloaddition of 2‐indolylmethanols, but also provides a good example for (2+n) cycloaddition of β,γ‐unsaturated α‐ketoesters.
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