Discovery of Enantiopure ()-Methoprene Derivatives as Potent Biochemical Pesticide Candidates.

()-Methoprene has been widely applied as a powerful biochemical pesticide to control disease vectors and other pestiferous arthropods of economic importance. As a juvenile hormone analogue, many products based on ()-methoprene are developed and commercialized in the USA, Europe, and elsewhere. However, the agricultural use of ()-methoprene and its analogues remains underexplored.

Organocatalytic enantioselective construction of Si-stereocenters: recent advances and perspectives.

Silicon-stereogenic chiral organosilanes have found increasing applications in synthetic chemistry, medicinal chemistry, and materials science. In this context, various asymmetric catalytic methods have been established for the diverse synthesis of silicon-stereogenic silanes. In particular, asymmetric organocatalysis is emerging as an important and complementary synthetic tool for the enantioselective construction of silicon-stereocenters, along with the rapid development of chiral-metal catalyzed protocols.

Polyimide Films Based on β-Cyclodextrin Polyrotaxane with Low Dielectric and Excellent Comprehensive Performance.

In order to prepare polyimide (PI) films with a low dielectric constant and excellent comprehensive performance, a two-step method was employed in this study to integrate β-cyclodextrin into a semi-aromatic fluorine-containing polyimide ternary system. By introducing trifluoromethyl groups to reduce the dielectric constant, the dielectric constant was further reduced to 2.55 at 10 MHz.

Differential and substrate-specific inhibition of γ-secretase by the C-terminal region of ApoE2, ApoE3, and ApoE4.

Aberrant low γ-secretase activity is associated with most of the presenilin mutations that underlie familial Alzheimer's disease (fAD). However, the role of γ-secretase in the more prevalent sporadic AD (sAD) remains unaddressed. Here, we report that human apolipoprotein E (ApoE), the most important genetic risk factor of sAD, interacts with γ-secretase and inhibits it with substrate specificity in cell-autonomous manners through its conserved C-terminal region (CT).

Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells.

The essential role of store-operated Ca entry (SOCE) through Ca release-activated Ca (CRAC) channels in T cells is well established. In contrast, the contribution of individual Orai isoforms to SOCE and their downstream signaling functions in B cells are poorly understood. Here, we demonstrate changes in the expression of Orai isoforms in response to B cell activation.

Nickel-catalyzed regio- and enantio-selective Markovnikov hydromonofluoroalkylation of 1,3-dienes.

A highly enantio- and regio-selective Markovnikov hydromonofluoro(methyl)alkylation of 1,3-dienes was developed using redox-neutral nickel catalysis. It provided a facile strategy to construct diverse monofluoromethyl- or monofluoroalkyl-containing chiral allylic molecules. Notably, this represents the first catalytic asymmetric Markovnikov hydrofluoroalkylation of olefins.

The mitochondrial sodium/calcium exchanger NCLX (Slc8b1) in B lymphocytes.

Antigen receptor stimulation triggers cytosolic Ca signals, which activate transcriptional and metabolic programs critical for immune function. B-cell receptor (BCR) engagement causes rapid cytosolic Ca rise through the ubiquitous store-operated calcium entry (SOCE) pathway. Slc8b1, which encodes the mitochondrial Na/Ca exchanger (NCLX), extrudes Ca out of the mitochondria and maintains optimal SOCE activity.

The effect of the nucleotides immediately upstream of the AUG start codon on the efficiency of translation initiation in sperm cells.

It is widely known that an optimal nucleotide sequence context immediately upstream of the AUG start codon greatly improves the efficiency of translation initiation of mRNA in mammalian and plant somatic cells, which in turn increases protein levels. However, it is still unclear whether a similar regulatory mechanism is also present in highly differentiated cells. Here, we surveyed this issue in Arabidopsis thaliana sperm cells and found that the sequence context-mediated regulation of translation initiation in sperm cells is generally similar to that in somatic cells.

Curcumin and NCLX inhibitors share anti-tumoral mechanisms in microsatellite-instability-driven colorectal cancer.

Background And Aims: Recent evidences highlight a role of the mitochondria calcium homeostasis in the development of colorectal cancer (CRC). To overcome treatment resistance, we aimed to evaluate the role of the mitochondrial sodium-calcium-lithium exchanger (NCLX) and its targeting in CRC. We also identified curcumin as a new inhibitor of NCLX.

MicroRNA-221 promotes tumor progression by targeting HHIP in human glioblastoma.

Background: MicroRNAs are found to be aberrantly expressed in multiple cancers, including glioblastoma (GBM), and microRNA-221 (miR-221) has been verified as an oncogene in various human cancers. Nevertheless, the role of miR-221 in GBM is unclear. This study aimed to investigate the miR-221 expression level in GBM and to evaluate its function and underlying mechanisms.

STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma.

Airway remodeling and airway hyperresponsiveness are central drivers of asthma severity. Airway remodeling is a structural change involving the dedifferentiation of airway smooth muscle (ASM) cells from a quiescent to a proliferative and secretory phenotype. Here, we show up-regulation of the endoplasmic reticulum Ca sensor stromal-interacting molecule 1 (STIM1) in ASM of asthmatic mice.

PKC-ε regulates vesicle delivery and focal exocytosis for efficient IgG-mediated phagocytosis.

Protein kinase C (PKC)-ε is required for membrane addition during IgG-mediated phagocytosis, but its role in this process is ill defined. Here, we performed high-resolution imaging, which reveals that PKC-ε exits the Golgi and enters phagosomes on vesicles that then fuse. TNF and PKC-ε colocalize at the Golgi and on vesicles that enter the phagosome.

The Mitochondrial Ca uniporter is a central regulator of interorganellar Ca transfer and NFAT activation.

Mitochondrial Ca uptake tailors the strength of stimulation of plasma membrane phospholipase C-coupled receptors to that of cellular bioenergetics. However, how Ca uptake by the mitochondrial Ca uniporter (MCU) shapes receptor-evoked interorganellar Ca signaling is unknown. Here, we used CRISPR/Cas9 gene knockout, subcellular Ca imaging, and mathematical modeling to show that MCU is a universal regulator of intracellular Ca signaling across mammalian cell types.

Palladium/Zinc Co-Catalyzed Asymmetric Hydrogenation of γ-Keto Carboxylic Acids.

A palladium-catalyzed asymmetric hydrogenation of levulinic acid has been successful developed by using Zn(OTf) as co-catalyst. The present method not only has provided a strategy in the palladium-catalyzed asymmetric hydrogenation of ketone, but also allowed the preparation of a wide range of chiral γ-valerolactones in good yields with excellent enantioselectivities.

Singular perturbation-based saturated adaptive control for underactuated Euler-Lagrange systems.

This paper proposes a saturated smooth adaptive controller for regulating a certain type of underactuated Euler-Lagrange systems (UELSs) with modeling uncertainties and control saturations based on a singular perturbation approach. Compared with relevent literature, the advantages of the proposed controller include: (1) it renders the UELS semiglobally asymptotically track the desired position without the violation of control input constraints; (2) high-order derivatives of positions are not required in its implementation. The Hoppensteadt's Theorem is employed to show that the proposed saturated controller renders the UELS semiglobally asymptotically stable about the desired set point with the satisfaction of control input constraints.

[Preparation and application of mouse-derived monoclonal antibodies against mouse CD226].

Objective To prepare and preliminarily identify anti-mouse CD226 monoclonal antibodies (mAbs) using CD226 knockout (CD226 KO) mice as immunized animals. Methods Animals were immunized by recombinant mouse CD226 protein expressed by eukaryotic cells. Anti-mouse CD226 mAbs were prepared by conventional B-cell hybridoma technology.

Cobalt-catalyzed ring-opening addition of azabenzonorbornadienes via C(sp)-H bond activation of 8-methylquinoline.

The first ring-opening addition of a benzylic C(sp)-H bond to azabenzonorbornadienes is demonstrated. The reaction proceeded under the catalytic system of [Cp*CoI(CO)], AgSbF and Fe(OAc) in PhOMe. The methodology showed a good substrate scope with up to 96% yield.

Dichotomous role of the human mitochondrial Na/Ca2/Li exchanger NCLX in colorectal cancer growth and metastasis.

Despite the established role of mitochondria in cancer, the mechanisms by which mitochondrial Ca (mtCa) regulates tumorigenesis remain incompletely understood. The crucial role of mtCa in tumorigenesis is highlighted by altered expression of proteins mediating mtCa uptake and extrusion in cancer. Here, we demonstrate decreased expression of the mitochondrial Na/Ca/Li exchanger NCLX () in human colorectal tumors and its association with advanced-stage disease in patients.

Distinct pharmacological profiles of ORAI1, ORAI2, and ORAI3 channels.

The ubiquitous Ca release-activated Ca (CRAC) channel is crucial to many physiological functions. Both gain and loss of CRAC function is linked to disease. While ORAI1 is a crucial subunit of CRAC channels, recent evidence suggests that ORAI2 and ORAI3 heteromerize with ORAI1 to form native CRAC channels.

Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype.

Through its ability to evoke responses from cells in a paracrine fashion, the senescence-associated secretory phenotype (SASP) has been linked to numerous age-associated disease pathologies including tumor invasion, cardiovascular dysfunction, neuroinflammation, osteoarthritis, and renal disease. Strategies which limit the amplitude and duration of SASP serve to delay age-related degenerative decline. Here we demonstrate that the SASP regulation is linked to shifts in intracellular Ca homeostasis and strategies which rescue redox-dependent calcium entry including enzymatic HO scavenging, TRP modulation, or mTOR inhibition block SASP and TRPC6 gene expression.

L-type Ca channel blockers promote vascular remodeling through activation of STIM proteins.

Voltage-gated L-type Ca channel (Ca1.2) blockers (LCCBs) are major drugs for treating hypertension, the preeminent risk factor for heart failure. Vascular smooth muscle cell (VSMC) remodeling is a pathological hallmark of chronic hypertension.