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Comprehensive Summary: The strategy of removable glycosylation modification was used to overcome the low‐efficiency problem encountered in the chemical synthesis of the mirror‐image D‐version of the immunoglobulin (Ig)‐like domain of tropomyosin receptor kinase A (DlgCTrkA), a protein molecule needed for mirror‐image screening of D‐peptide ligands targeting this cell membrane receptor. It was found that O‐linked‐β‐N‐acetyl‐D‐glucosamine (O‐GlcNAc) modification at DSer312, or DSer320 can significantly improve the efficiency of DlgCTrkA synthesis and folding, while O‐GlcNAc modification at DSer330 showed barely any improvement. This study provides a new example demonstrating the power of the removable glycosylation modification strategy in the chemical synthesis and folding of difficult‐to‐obtain proteins. It also presents evidence that removable glycosylation modification at different sites would significantly affect the efficiency of protein folding promoted by this strategy. [ABSTRACT FROM AUTHOR]

Background and Aims: The clinical effects of multivessel interventions in patients with unstable angina/non‐ST‐segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non‐culprit lession(s) among this cohort. Methods: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48‐month overall mortality between those undergoing multivessel PCI (MV‐PCI) through a single‐procedure or staged‐procedure approach and culprit vessel‐only PCI (CV‐PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast‐induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. Results: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV‐PCI had reduced all‐cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48–0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2) could not benefit from MV‐PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (Pinteraction < 0.01; HR = 0.95, 95% CI = 0.65–1.45). Although the staged‐procedure approach (N = 157) failed to bring additional survival benefits compared to single‐procedure MV‐PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV‐PCI and CV‐PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94–2.73). Conclusion: Among patients with UA/NSTEMI and non‐diabetic CKD and an eGFR > 30 mL/min/1.73 m2, MV‐PCI was associated with a reduced risk of long‐term death but did not increase the incidence of CIN during the management of MVD compared to CV‐PCI. And staged procedures might be a preferable option over single‐procedure MV‐PCI. [ABSTRACT FROM AUTHOR]

To improve the water solubility of anti‐human immunodeficiency virus (HIV) agent DB02, an excellent non‐nucleoside reverse‐transcriptase inhibitor (NNRTI) obtained in our previous efforts, we designed and synthesized four phosphate derivatives of DB02 based on the molecular model of DB02 with RT. Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound P‐2, which possessed a superior potency to the lead compound DB02 against wild‐type HIV‐1 and a variety of HIV‐resistant mutant viruses significantly. Furthermore, the water solubility of P‐2 was nearly 17 times higher than that of DB02, and the pharmacokinetic test in rats showed that P‐2 demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the C‐2 side chain of DB02 was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of S‐DACOs type of NNRTIs. [ABSTRACT FROM AUTHOR]

Chemical synthesis of insulin superfamily proteins (ISPs) has recently been widely studied to develop next‐generation drugs. Separate synthesis of multiple peptide fragments and tedious chain‐to‐chain folding are usually encountered in these studies, limiting accessibility to ISP derivatives. Here we report the finding that insulin superfamily proteins (e.g. H2 relaxin, insulin itself, and H3 relaxin) incorporating a pre‐made diaminodiacid bridge at A‐B chain terminal disulfide can be easily and rapidly synthesized by a single‐shot automated solid‐phase synthesis and expedient one‐step folding. Our new H2 relaxin analogues exhibit almost identical structures and activities when compared to their natural counterparts. This new synthetic strategy will expediate production of new ISP analogues for pharmaceutical studies. [ABSTRACT FROM AUTHOR]

Objective: High‐risk papillary thyroid carcinoma (PTC) patients with BRAF mutation have lymph node and distant metastases and poor prognosis. Therefore, this study aims to develop a targeted ultrasound contrast agent for the BRAFV600E mutation to screen high‐risk PTC at early stage. Methods: The targeted lipid nanobubbles carrying BRAFV600E antibody were prepared using thin film hydration‐sonication and avidin‐biotin binding methods. The physicochemical properties and stability of the targeted nanobubbles were detected by transmission electron microscopy, atomic force microscopy, and confocal laser scanning microscopy. The target binding abilities of the targeted nanobubbles in the PTC cells (B‐CPAP) overexpressed mutant BRAFV600E were evaluated by immunofluorescence staining, quantitative real‐time polymerase chain reaction, western blot, and fluorescence microscopy. After PTC tumor models overexpressed mutant BRAFV600E were established, the enhanced images of targeted lipid nanobubbles and untargeted lipid nanobubbles on PTC tumors in nude mice were observed using contrast‐enhanced ultrasound imaging. Results: The targeted lipid nanobubbles revealed uniform, round morphology, and good stability with a nanoscale size. Besides, BRAFV600E monoclonal antibody was observed to be combined on the surface of lipid nanobubbles. Furthermore, the targeted nanobubbles had a good targeting diagnosis ability in PTC cells with BRAFV600E overexpression. Moreover, the targeted nanobubbles had better ultrasound enhancement and peak intensity of the time‐intensity curve (P <.001) in PTC tumors with BRAFV600E overexpression as compared to the untargeted lipid nanobubbles. Conclusion: The targeted lipid nanobubbles carrying BRAFV600E antibody could be regarded as a potential targeted ultrasound contrast agent for the diagnosis of high‐risk PTC. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Photocaged, activity‐based ubiquitin (Ub) probes (Ub‐ABPs) have been developed for the time‐resolved probing of deubiquitinating enzyme (DUB) activities, but many Ub‐ABPs are still challenging to photocage because their warheads (e.g. propargylamide (PA) or dehydroalanine (Dha)) are difficult to temporally block and activate. Here, we describe a new C‐terminal backbone modification strategy for the construction of photocaged Ub‐ABPs in which a light‐sensitive group is placed at the backbone amide bond of the Ub Gly75. This strategy enabled the facile generation of cell‐permeable photocaged Ub‐PA and Dha probes that could be activated to capture DUBs after photo‐irradiation, and were used to profile DUBs in cells under specially designed conditions (e.g. in cells experiencing oxidative stress) or DUBs with isopeptide linkage selectivity. This backbone modification strategy is anticipated to provide a general solution for the development of photocaged Ub ABPs bearing any warheads for DUB profiling. [ABSTRACT FROM AUTHOR]

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow‐growing, benign lesions occurring throughout the neuroaxis that are frequently misdiagnosed and overlooked by clinicians. Here, we report a case of a 56‐year‐old woman who presented with a history of recurrent headache for the previous six years. Magnetic resonance imaging (MRI) revealed a 2.3‐cm‐sized solid mass in the right frontal lobe that was surrounded by marked edematous areas. The lesion demonstrated dense calcification and avid enhancement. The lesion was initially diagnosed as oligodendroglioma, and then found to be CAPNON based on histopathology of a surgically resected tissue. Genetic analysis revealed a nonsense mutation in the CUL4B gene. The patient's condition appeared to reflect a reactive, rather than neoplastic, process. Clinicians should be prepared to detect such pseudotumors histopathologically in order to avoid unnecessary differential tests of neoplastic or infectious diseases, as well as potentially harmful therapies. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: The synthesis of an Asp lactam derivative of A‐183, a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity, is described. Our synthesis depends on the use of a removable backbone modification (RBM) strategy to prevent aspartimide formation, which thwarted all attempts to synthesize this target using direct solid‐phase peptide synthesis. Validation of the RBM strategy in the synthesis of a second Asp lactam derivative was also accomplished. The RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides. [ABSTRACT FROM AUTHOR]

Activity‐based E2 conjugating enzyme (E2)‐ubiquitin (Ub) probes have recently emerged as effective tools for studying the molecular mechanism of E3 ligase (E3)‐catalyzed ubiquitination. However, the preparation of existing activity‐based E2‐Ub probes depends on recombination technology and bioconjugation chemistry, limiting their structural diversity. Herein we describe an expedient total chemical synthesis of an E2 enzyme variant through a hydrazide‐based native chemical ligation, which enabled the construction of a structurally new activity‐based E2‐Ub probe to covalently capture the catalytic site of Cys‐dependent E3s. Chemical cross‐linking coupled with mass spectrometry (CXMS) demonstrated the utility of this new probe in structural analysis of the intermediates formed during Nedd4 and Parkin‐mediated transthiolation. This study exemplifies the utility of chemical protein synthesis for the development of protein probes for biological studies. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) derived from aberrant tumor metabolism could contribute to tumor invasion and metastasis. NAD(P)HX Epimerase (NAXE), an epimerase that allows the repair of damaged forms of antioxidant NADPH, is a potential cellular ROS scavenger and its role in tumor development is still elusive. Here, we found that NAXE is significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. NAXE downregulation is associated with poor clinicopathological characteristics and is an independent risk factor for overall and disease‐free survival of HCC patients after liver resection. In addition, low NAXE expression could identify worse prognosis of HCC patients before vascular invasion or in early stages of disease. In particularly, low NAXE expression in HCC is markedly associated with microvascular invasion (MVI) and its combination with MVI predicts poorer prognosis of HCC patients after liver resection. Furthermore, in vitro and in vivo experiments both showed that knockdown of NAXE expression in HCC cells promoted migration, invasion, and metastasis by inducing epithelial‐mesenchymal transition (EMT), whereas NAXE overexpression causes the opposite effects. Mechanistically, low NAXE expression reduced NADPH levels and further caused ROS level increase and hypoxia‐inducible factor‐1α (HIF‐1α) activation, thereby promoting invasion and metastasis of HCC by facilitating EMT. What is more, the tumor‐promoting effect of NAXE knockdown in HCC xenograft can be abolished by giving mice N‐acetyl‐l‐cysteine (NAC) in drinking water. Taken together, our findings uncovered a tumor suppressor role for NAXE in HCC by scavenging excessive ROS and inhibiting tumor‐promoting signaling pathways, suggesting a new strategy for HCC therapy by targeting redox signaling. [ABSTRACT FROM AUTHOR]

Triazole‐based deubiquitylase (DUB)‐resistant ubiquitin (Ub) probes have recently emerged as effective tools for the discovery of Ub chain‐specific interactors in proteomic studies, but their structural diversity is limited. A new family of DUB‐resistant Ub probes is reported based on isopeptide‐N‐ethylated dimeric or polymeric Ub chains, which can be efficiently prepared by a one‐pot, ubiquitin‐activating enzyme (E1)‐catalyzed condensation reaction of recombinant Ub precursors to give various homotypic and even branched Ub probes at multi‐milligram scale. Proteomic studies using label‐free quantitative (LFQ) MS indicated that the isopeptide‐N‐ethylated Ub probes may complement the triazole‐based probes in the study of Ub interactome. Our study highlights the utility of modern protein synthetic chemistry to develop structurally and new families of tool molecules needed for proteomic studies. [ABSTRACT FROM AUTHOR]

Advances are continually being made on shock initiation of heterogeneous explosives by single fragment impact. However, most research on shock initiation of heterogeneous explosives by multiple fragment impact is still in simulation stage owing to the limitations of testing conditions and methods, and experiments on it are rare. In this study, an experiment was conducted on shock initiation of the covered flake JH‐2 high explosive (HE) by simultaneous multiple fragment impact. The response level of the explosive under impact is determined by the damage degree of the cover plate and classified into detonation, explosion, deflagration and burn or no reaction. The u2d Held criterion was used to calculate the critical threshold Icr of each JH‐2 failure mode under the plate‐sandwich charging structure. Results indicated the JH‐2 HE deflagration occurs as Icr reaches 3570.91 m3/s2 by a single fragment impact, explosion occurs as Icr reaches 6267.69 m3/s2, and detonation Icr reaches 7232.41 m3/s2. Increasing the number of fragments reduces the Icr of JH‐2 HE each response level. The response level of multiple fragments impact is a multiple of single‐fragment. [ABSTRACT FROM AUTHOR]

Solid phase peptide synthesis (SPPS) strategy based on diaminodiacids had become an effective method for the synthesis of disulfide‐containing polypeptides. At present, it remains necessary to develop a diaminodiacid with more abundant chain structures to study the structure‐activity relationship. In this work, we developed a new type of diaminodiacids containing a six‐atom thioether (C−C‐S−C‐C−C, C−C‐C−S‐C−C) bridge. The key segment protected homo‐homocystine can be efficiently obtained by converting a side chain carboxyl group into a thiol group, which contribute to the facile and efficient synthesis of new diaminodiacid. With this diaminodiacid in hand, we successfully obtained tachyplesin containing new disulfide bond mimic by solid phase peptide synthesis. The tachyplesin analog not only has similar activity as natural counterpart, but also exhibits increased stability under reducing conditions. [ABSTRACT FROM AUTHOR]

The development of powerful and general methods to acquire ubiquitin (Ub) chains has prompted the deciphering of Ub‐mediated processes. Herein, the cysteine‐aminoethylation assisted chemical ubiquitination (CAACU) strategy is extended and improved to enable the efficient semi‐synthesis of atypical Ub chain analogues and Ub‐based probes. Combining the Cys aminoethylation and the auxiliary‐mediated protein ligation, several linkage‐ and length‐defined atypical Ub chains including di‐Ubs, K27C‐linked tri‐Ub, K11/K48C‐branched tri‐Ub, and even the SUMOlated Ub are successfully prepared from recombinantly expressed starting materials at about a 9–20 mg L−1 expression level. In addition, the utility of this strategy is demonstrated with the synthesis of a novel non‐hydrolyzable di‐Ub PA probe, which may provide a new useful tool for the mechanistic studies of deubiquitinase (DUB) recognition. [ABSTRACT FROM AUTHOR]

The Piezo channel is a versatile mechanosensitive cation channel that mediates tactile, vascular development, and proprioception. GsMTx4 is the only reported inhibitor specifically targeting Piezo channels. Although the sequence of GsMTx4 is reported, the crystal structure of GsMTx4 is still unknown. Here, we achieved the two‐segment synthesis of GsMTx4 and its enantiomer, enGsMTx4, through hydrazide based Native Chemical Ligation, and analyzed the crystal structure of GsMTx4 through the racemic crystallization technology. By analyzing the structure, we found that there is a hydrophobic patch surrounded by aromatic residues and charged residues. [ABSTRACT FROM AUTHOR]

Two unique dodecanuclear lanthanide clusters, [LnIII12Na3(µ3-OH)2(hmmp)6(piv)12(CO3)6(MeOH)6]OH ·5MeOH {Ln = Gd3+, Dy3+; hmmpH2 = 2-[(2-hydroxyethylimino)methyl]-6-methoxyphenol}, have been synthesized by treating the simple Schiff-base ligand hmmpH2 with the relevant lanthanide chloride and sodium pivalate (NaPiv). Single-crystal X-ray diffraction analysis revealed that the central cores of Gd12 and Dy12 are unprecedented and composed of a distorted four-layer triangular shelf-like molecular structure, which can be broken down into two types of four parallel triangular layers with an ABBA arrangement. Magnetic investigations revealed that the Gd12 cluster is a good candidate for magnetic refrigeration with a significant entropy change (-Δ Sm) of 30.99 J kg-1 K-1 for H = 7 T at 4 K, whereas the Dy12 cluster shows single-molecule magnet behavior. [ABSTRACT FROM AUTHOR]

Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one-pot native chemical ligation and metal-free desulfurization for chemical protein synthesis. This one-pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X-ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis coupled with a one-pot ligation-desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies. [ABSTRACT FROM AUTHOR]

We synthesized a lysine-linked auxiliary-derived building block, ϵ- N-2-mercapto-1-(2,4-dimethoxyphenyl)ethyl lysine, in 20 % isolated yield over a six-step route. The new building block is well compatible with Fmoc solid-phase peptide synthesis (SPPS) and hydrazide-based native chemical ligation (NCL). Furthermore, we successfully incorporated the new lysine-linked auxiliary handle into a protein segment and performed the chemical synthesis of K48-linked diubiquitin with stepwise NCL. [ABSTRACT FROM AUTHOR]

Mambalgins are a class of 57-residue polypeptide toxins isolated from the venom of the African mamba. They exhibit potent analgesic effects by inhibiting the acid-sensing ion channels. Classified as members of the family of three-finger toxins, mambalgins contain four pairs of disulfide bridges that help to stabilize the three-finger scaffold. Here, we report the chemical synthesis of functional mambalgin-1/2/3 by using one-step two-segment hydrazide-based native chemical ligation. The two-segment ligation approach reported here may enable efficient production of mambalgin toxins. These synthetic mambalgins are useful compounds for development of diagnostic or therapeutic reagents. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this study, we developed a general iron-catalyzed α-methylenation of ketones by using N,N-dimethylacetamide as the one-carbon source. Various ketones, including aryl and alkyl ketones, enones, and dicarbonyl compounds were well tolerated to yield the corresponding α,β-unsaturated carbonyl compounds in the presence of an iron catalyst, peroxides, and N,N-dimethylacetamide under aerobic conditions. [ABSTRACT FROM AUTHOR]

Sortase‐mediated hydrazinolysis of proteins with hydrazine or its derivatives was developed for the production of recombinant protein hydrazides. This process provides an alternative approach for protein semisynthesis through the use of recombinant protein hydrazides as thioester surrogates. It also provides an alternative method for C‐terminal modification of proteins with functional units as well as for the preparation of C‐to‐C fusion proteins. [ABSTRACT FROM AUTHOR]

The mechanisms whereby hepatic fibrosis develops in chronic liver diseases remain incompletely defined. Here, we sought to examine whether microRNA (miRNA) became dysregulated in dimethylnitrosamine-induced hepatic fibrosis in rats. Our microarray analysis revealed that the miR-34 family was upregulated along with other miRNAs in liver fibrotic tissues. Six miRNAs, such as rno-miR-878, were downregulated. The findings were confirmed by RT-PCR assays. Gene ontology analysis further showed that many of these dysregulated miRNAs were involved in lipid/fatty acid metabolism. The acyl-CoA synthetase long-chain family member 1 (ACSL1) gene contained specific binding sites for miR-34a/miR-34c. Additional enhanced green fluorescence protein reporter activity assays indicated that the miR-34 family targeted ACSL1. Our RT-PCR and immunoblotting assays further demonstrated that both the mRNA and protein levels of ACSL1 were markedly reduced in fibrotic liver tissues. Our findings suggest that miRNA becomes dysregulated during hepatic fibrosis, and that the miR-34 family may be involved in the process by targeting ACSL1. The mechanisms whereby chronic liver diseases develop hepatic fibrosis remain incompletely defined. In our study we found that microRNA became dysregulated in dimethylnitrosamine-induced hepatic fibrosis in rats. Gene ontology analysis further showed that many of these dysregulated miRNAs were involved in lipid/fatty acid metabolism. The upregulated miR-34 family may be involved in the hepatic fibrosis process by targeting ACSL1. [ABSTRACT FROM AUTHOR]

Changes in the free zinc(II) concentration are closely related to cell proliferation and apoptosis, especially during the early apoptotic process. In the present paper, we demonstrated that zinc(II) probe FluoZin-3AM owns sensitive properties to distinguish different stages of apoptotic cell (induced by an anticancer agent, etoposide) according to trace intracellular zinc(II) fluorescence flux. When apoptosis in HeLa or K562 cells was artificially induced, FluoZin-3AM selectively and strongly stained apoptotic cells only at early and middle stages, which was attributed to significantly increased free zinc(II) flux during these stages. This conclusion was further verified by comparing it with the conventional apoptosis detector probe Annexin-V-FITC and PI. Furthermore, FluoZin-3AM was found cell permeable to detect the intracellular zinc(II) fluorescence enhancement to threefolds within 120 s with low cytotoxicity when zinc(II) was incorporated into the cell by zinc(II) ionophore pyrithione. All the above implied that monitoring intracellular zinc fluorescence flux was an effective method to distinguish cell apoptosis from necrosis, and FluoZin-3AM was found to be a suitable probe acting alone to fulfill the work. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The strategy of removable glycosylation modification was used to overcome the low‐efficiency problem encountered in the chemical synthesis of the mirror‐image D‐version of the immunoglobulin (Ig)‐like domain of tropomyosin receptor kinase A (DlgCTrkA), a protein molecule needed for mirror‐image screening of D‐peptide ligands targeting this cell membrane receptor. It was found that O‐linked‐β‐N‐acetyl‐D‐glucosamine (O‐GlcNAc) modification at DSer312, or DSer320 can significantly improve the efficiency of DlgCTrkA synthesis and folding, while O‐GlcNAc modification at DSer330 showed barely any improvement. This study provides a new example demonstrating the power of the removable glycosylation modification strategy in the chemical synthesis and folding of difficult‐to‐obtain proteins. It also presents evidence that removable glycosylation modification at different sites would significantly affect the efficiency of protein folding promoted by this strategy. [ABSTRACT FROM AUTHOR]

Background: Mean corpuscular volume (MCV) is the average volume of red blood cells (RBC). Larger MCV reduces the amount of RBC reaching the brain, while smaller MCV was associated with iron‐deficiency anemia and the subsequent cognitive impairment. Few studies have relating MCV levels to cognitive impairment and their findings were inconsistent. This study aimed to explore this association in community‐dwelling older adults. Method: This study is part of an ongoing cohort study Taiwan Initiatives for Geriatric Epidemiological Research (TIGER, 2011‐ present). A total of 605 non‐demented older adults (age 65+) were recruited at baseline (2011‐2013). After exclusion of participants with dementia at baseline, history of stroke, brain tumor, loss of consciousness, missing data of MCV, 319 elderly were included for analysis. Global and domain‐specific cognition (logical memory, attention, verbal fluency, and executive function) were assessed for each participant at baseline, 2‐year, 4‐year, and 6‐year follow‐ups. MCV was assessed at baseline and then tertitled; high MCV indicates the highest tertile (≥92.7 fL); low MCV indicates the lower tertiles (<92.6 fL). The generalized linear mixed models (GLMM) were used to estimate the association between MCV and cognitive impairment adjusted for important covariates. Result: At baseline, the mean age of the study participants was 71.6 years old and the mean MCV at baseline was 90.7 fL. For the multivariable analyses, the effect of baseline MCV on global cognition (assessed by Montreal Cognitive Assessment–Taiwanese version, MoCA‐T) increased as age increased [MCV×age interaction: β= ‐0.07, 90% confidence interval (CI)= ‐0.14 to ‐0.004, p‐value= 0.04], which became more evident in women (β= ‐0.15, 95% CI= ‐0.23 to ‐0.06). After stratification by age groups, the increase of baseline MCV was associated with poor global cognition in the older group (age ≥75: β= ‐0.90, 95% CI= ‐1.65 to ‐0.15). No significant findings were observed in cognitive domains or other strata. Conclusion: High baseline MCV was associated with an increased risk of cognitive impairment as age increased. MCV may be used an early marker for dementia in the community‐dwelling older adults. [ABSTRACT FROM AUTHOR]

The title process features a broad substrate scope and tolerates a wide variety of functional groups. [ABSTRACT FROM AUTHOR]

A practical, new Pd-catalyzed selective C-H borylation of acetanilides under acidic conditions is developed, which shows a good functional group tolerance. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: The synthesis of an Asp lactam derivative of A‐183, a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity, is described. Our synthesis depends on the use of a removable backbone modification (RBM) strategy to prevent aspartimide formation, which thwarted all attempts to synthesize this target using direct solid‐phase peptide synthesis. Validation of the RBM strategy in the synthesis of a second Asp lactam derivative was also accomplished. The RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides. [ABSTRACT FROM AUTHOR]