Achieving selective C−H activation at a single and strategic site in the presence of multiple C−H bonds can provide a powerful and generally useful retrosynthetic disconnection. In this context, a ...directing group serves as a compass to guide the transition metal to C−H bonds by using distance and geometry as powerful recognition parameters to distinguish between proximal and distal C−H bonds. However, the installation and removal of directing groups is a practical drawback. To improve the utility of this approach, one can seek solutions in three directions: 1) Simplifying the directing group, 2) using common functional groups or protecting groups as directing groups, and 3) attaching the directing group to substrates via a transient covalent bond to render the directing group catalytic. This Review describes the rational development of an extremely simple and yet broadly applicable directing group for PdII, RhIII, and RuII catalysts, namely the N‐methoxy amide (CONHOMe) moiety. Through collective efforts in the community, a wide range of C−H activation transformations using this type of simple directing group have been developed.
Clear directions: The simple N‐methoxy amide moiety is a versatile directing group for a wide range of C−H functionalization reactions using Pd, Rh, and Ru catalysis. Whereas it was initially used for Pd‐catalyzed C−H activation, it has also been employed in RhIII‐catalyzed variants and in combination with cheaper ruthenium catalysts.
Organic molecules are rich in carbon-hydrogen bonds; consequently, the transformation of C-H bonds to new functionalities (such as C-C, C-N, and C-O bonds) has garnered much attention by the ...synthetic chemistry community. The utility of C-H activation in organic synthesis, however, cannot be fully realized until chemists achieve stereocontrol in the modification of C-H bonds. This Review highlights recent efforts to enantioselectively functionalize C(sp
)-H bonds via transition metal catalysis, with an emphasis on key principles for both the development of chiral ligand scaffolds that can accelerate metalation of C(sp
)-H bonds and stereomodels for asymmetric metalation of prochiral C-H bonds by these catalysts.
The aging of the population is an inexorable change that challenges governments and societies in every developed country. Based on clinical and empirical data, social isolation is found to be ...prevalent among elderly people, and it has negative consequences on the elderly's psychological and physical health. Targeting social isolation has become a focus area for policy and practice. Evidence indicates that contemporary information and communication technologies (ICT) have the potential to prevent or reduce the social isolation of elderly people via various mechanisms.
This systematic review explored the effects of ICT interventions on reducing social isolation of the elderly.
Relevant electronic databases (PsycINFO, PubMed, MEDLINE, EBSCO, SSCI, Communication Studies: a SAGE Full-Text Collection, Communication & Mass Media Complete, Association for Computing Machinery (ACM) Digital Library, and IEEE Xplore) were systematically searched using a unified strategy to identify quantitative and qualitative studies on the effectiveness of ICT-mediated social isolation interventions for elderly people published in English between 2002 and 2015. Narrative synthesis was performed to interpret the results of the identified studies, and their quality was also appraised.
Twenty-five publications were included in the review. Four of them were evaluated as rigorous research. Most studies measured the effectiveness of ICT by measuring specific dimensions rather than social isolation in general. ICT use was consistently found to affect social support, social connectedness, and social isolation in general positively. The results for loneliness were inconclusive. Even though most were positive, some studies found a nonsignificant or negative impact. More importantly, the positive effect of ICT use on social connectedness and social support seemed to be short-term and did not last for more than six months after the intervention. The results for self-esteem and control over one's life were consistent but generally nonsignificant. ICT was found to alleviate the elderly's social isolation through four mechanisms: connecting to the outside world, gaining social support, engaging in activities of interests, and boosting self-confidence.
More well-designed studies that contain a minimum risk of research bias are needed to draw conclusions on the effectiveness of ICT interventions for elderly people in reducing their perceived social isolation as a multidimensional concept. The results of this review suggest that ICT could be an effective tool to tackle social isolation among the elderly. However, it is not suitable for every senior alike. Future research should identify who among elderly people can most benefit from ICT use in reducing social isolation. Research on other types of ICT (eg, mobile phone-based instant messaging apps) should be conducted to promote understanding and practice of ICT-based social-isolation interventions for elderly people.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Solid‐state white light‐emitting electrochemical cells (LECs) exhibit the following advantages: simple device structures, low operation voltage, and compatibility with inert metal electrodes. LECs ...have been studied extensively since the first demonstration of white LECs in 1997, due to their potential application in solid‐state lighting. This review provides an overview of recent developments in white LECs, specifically three major aspects thereof, namely, host–guest white LECs, nondoped white LECs, and device engineering of white LECs. Host–guest strategy is widely used in white LECs. Host materials are classified into ionic transition metal complexes, conjugated polymers, and small molecules. Nondoped white LECs are based on intra‐ or intermolecular interactions of emissive and multichromophore materials. New device engineering techniques, such as modifying carrier balance, color downconversion, optical filtering based on microcavity effect and localized surface plasmon resonance, light extraction enhancement, adjusting correlated color temperature of the output electroluminescence spectrum, tandem and/or hybrid devices combining LECs with organic light‐emitting diodes, and quantum‐dot light‐emitting diodes improve the device performance of white LECs by ways other than material‐oriented approaches. Considering the results of the reviewed studies, white LECs have a bright outlook.
Recent developments in white light‐emitting electrochemical cells (LECs) based on different functional materials including ionic transition metal complexes, conjugated polymers, and small molecules and device engineering of various new techniques, including tandem and/or hybrid devices combining LECs with organic light‐emitting diode (LEDs) and quantum dot LEDs to improve device efficiency, are reviewed.
The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic ...insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a result of decreased mitophagy activity and displayed functional, transcriptomic and epigenetic characteristics of terminally exhausted T cells. Mechanistically, reduced mitochondrial fitness in TILs was induced by the coordination of T cell receptor stimulation, microenvironmental stressors and PD-1 signaling. Enforced accumulation of depolarized mitochondria with pharmacological inhibitors induced epigenetic reprogramming toward terminal exhaustion, indicating that mitochondrial deregulation caused T cell exhaustion. Furthermore, supplementation with nicotinamide riboside enhanced T cell mitochondrial fitness and improved responsiveness to anti-PD-1 treatment. Together, our results reveal insights into how mitochondrial dynamics and quality orchestrate T cell antitumor responses and commitment to the exhaustion program.
Objective
T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Serum‐derived exosomes are increased in SLE patients and are correlated with disease severity. This ...study was undertaken to investigate whether T cell–derived exosomal proteins play a role in SLE pathogenesis.
Methods
We characterized proteins in T cell–derived exosomes from SLE patients and healthy controls by MACSPlex exosome analysis and proteomics. To study the potential pathogenic functions of the exosomal protein identified, we generated and characterized T cell–specific transgenic mice that overexpressed that protein in T cells.
Results
We identified eosinophil cationic protein (ECP, also called human RNase III) as overexpressed in SLE T cell–derived exosomes. T cell–specific ECP–transgenic mice (n = 5 per group) displayed early induction of serum interferon‐γ (IFNγ) levels (P = 0.062) and inflammation of multiple tissue types. Older T cell–specific ECP–transgenic mice (n = 3 per group) also displayed an increase in follicular helper T cell and plasma B cell numbers, and in autoantibody levels (P < 0.01). Single‐cell RNA sequencing showed the induction of IFNγ messenger RNA (P = 2.2 × 10‐13) and inflammatory pathways in ECP‐transgenic mouse T cells. Notably, adoptively transferred ECP‐containing exosomes stimulated serum autoantibody levels (P < 0.01) and tissue IFNγ levels in the recipient mice (n = 3 per group). The transferred exosomes infiltrated into multiple tissues of the recipient mice, resulting in hepatitis, nephritis, and arthritis.
Conclusion
Our findings indicate that ECP overexpression in T cells or T cell–derived exosomes may be a biomarker and pathogenic factor for nephritis, hepatitis, and arthritis associated with SLE.
Hepatitis B virus X protein (HBx) and hepatic stellate cells (HSCs) are critical for liver fibrosis development. Anti-fibrosis occurs via reversion to quiescent-type HSCs or clearance of HSCs via ...apoptosis or ferroptosis. We aimed to elucidate the role of chrysophanol in rat HSC-T6 cells expressing HBx and investigate whether chrysophanol (isolated from Rheum palmatum rhizomes) influences cell death via ferroptosis in vitro. Analysis of lipid reactive oxygen species (ROS), Bip, CHOP, p-IRE1α, GPX4, SLC7A11, α-SMA, and CTGF showed that chrysophanol attenuated HBx-repressed cell death. Chrysophanol can impair HBx-induced activation of HSCs via endoplasmic reticulum stress (ER stress) and ferroptosis-dependent and GPX4-independent pathways.
Bacteremia and associated bacterial sepsis are potentially fatal and occur when the host response to microbial invasion is impaired or compromised. This motivated us to develop carbonized polymer ...dots (CPDs
Man/AA
) from a mixture of mannose (Man) and positively charged amino acids AAs; lysine, arginine (Arg), or histidine through a one-step mild pyrolysis procedure, which effectively inhibited drug-resistant bacterial strains isolated from septic patients. The as-prepared CPDs
Man/AA
showed broad-spectrum antibacterial activity, including multidrug-resistant bacteria, even in human plasma. The minimal inhibitory concentration of CPDs
Man/Arg
is
ca.
1.0 μg mL
−1
, which is comparable to or lower than those of other tested antibiotics (
e.g.
, ampicillin, gentamicin, and vancomycin). In addition to directly disrupting bacterial membranes, the CPDs
Man/Arg
feature a structure similar to aminoglycoside antibiotics that could bind to 16S rRNA, thereby blocking bacterial protein synthesis
. In vitro
cytotoxic and hemolytic assays demonstrated the high biocompatibility of the CPDs
Man/AA
. In addition,
in vivo
studies on methicillin-resistant
Staphylococcus aureus
-infected mice treated with the CPDs
Man/Arg
showed a significant decrease in mortality-even better than that of antibiotics. Overall, the synthesis of the CPDs
Man/AA
is cost-efficient, straightforward, and effective for treating bacteremia. The polymeric features of the CPDs
Man/Arg
, including cationic charges and specific groups, can be recognized as a safe and broad-spectrum biocide to lessen our reliance on antibiotics to treat systemic bacterial infections in the future.
Aminoglycoside-mimicking carbonized polymer dots (CPDs) for bacteremia treatment by blocking the synthesis of bacterial proteins and disrupting bacterial membranes.
The catalyst‐controlled diversity‐oriented synthesis of spirohydroquinoline‐indandiones and 3‐methylenehydroquinoline‐indandiones from ortho‐sulfonamidophenyl‐substituted para‐quinone methides and ...allylidene‐indandiones is reported. The strategies utilized an organobase such as DMAP or TMG to control the reaction pathway chemoselectively, furnishing the corresponding products in 40–99% yields with excellent diastereoselectivities. The mechanistic studies revealed that spirohydroquinoline‐indandione was the kinetic product to afford 3‐methylenehydroquinoline‐indandione in the presence of TMG, which probably involved an unusual base‐initiated 1,3‐nitrogen rearrangement process.
Autotrophic plants have evolved distinctive mechanisms for maintaining a range of homeostatic states for sugars. The on/off switch of reversible gene expression by sugar starvation/provision ...represents one of the major mechanisms by which sugar levels are maintained, but the details remain unclear. α-Amylase (αAmy) is the key enzyme for hydrolyzing starch into sugars for plant growth, and it is induced by sugar starvation and repressed by sugar provision. αAmy can also be induced by various other stresses, but the physiological significance is unclear. Here, we reveal that the on/off switch of αAmy expression is regulated by 2 MYB transcription factors competing for the same promoter element. MYBS1 promotes αAmy expression under sugar starvation, whereas MYBS2 represses it. Sugar starvation promotes nuclear import of MYBS1 and nuclear export of MYBS2, whereas sugar provision has the opposite effects. Phosphorylation of MYBS2 at distinct serine residues plays important roles in regulating its sugar-dependent nucleocytoplasmic shuttling and maintenance in cytoplasm by 14-3-3 proteins. Moreover, dehydration, heat, and osmotic stress repress MYBS2 expression, thereby inducing αAmy3. Importantly, activation of αAmy3 and suppression of MYBS2 enhances plant growth, stress tolerance, and total grain weight per plant in rice. Our findings reveal insights into a unique regulatory mechanism for an on/off switch of reversible gene expression in maintaining sugar homeostatic states, which tightly regulates plant growth and development, and also highlight MYBS2 and αAmy3 as potential targets for crop improvement.
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