Lamellar Hierarchical Porous Carbon Prepared from Coal Tar Pitch through a Lamellar Hard Template Combined with the Precarbonization and Activation Method for Supercapacitors

The lamellar porous carbon favors the diffusion and penetration of electrolyte ions and presents a fantastic advantage as an energy storage electrode material. In this work, the lamellar Mg5(OH)4(CO3)2·4H2O template is synthesized via a simple precipitation method in the low-temperature hydrothermal condition. Lamellar hierarchical porous carbon (LHPC) is successfully synthesized through the Mg5(OH)4(CO3)2·4H2O hard template and the KOH activation method using coal tar pitch (CTP) as the carbon source. The effects of activation temperature and activator dosage on the morphology, microstructure, and supercapacitor performance are researched at length. LHPCs-1–700 displays a good lamellar structure and an abundant mesoporous structure, so as to exhibit superior capacitive performance compared with other carbon electrodes. The specific capacitance for LHPCs-1–700 reaches 298 F g–1 at 1 A g–1 and still maintains 234 F g–1 at 50 A g–1 with a high capacitance retention of 78.5% in the three-electrode system. The kinetic behavior of the LHPCs-1–700 electrode was also analyzed according to the CV data obtained at different scan rates, and it was found that the fast kinetic capacitance contribution was up to 87% at 200 mV s–1. The assembled LHPCs-1–700 symmetric supercapacitor delivered an energy density of 16.73 W h kg–1 with a power density of 859.4 W kg–1 in 1 M Na2SO4 solution. Besides, the specific capacitance retention rate could still reach 95.8% after 8000 cycles

Discovery of Potent Benzocycloalkane Derived Diapophytoene Desaturase Inhibitors with an Enhanced Safety Profile for the Treatment of MRSA, VISA, and LRSA Infections

Blocking the biosynthesis process of staphyloxanthin has emerged as a promising antivirulence strategy. Our previous research revealed that diapophytoene desaturase was an attractive and druggable target against infections caused by pigmented <i>Staphylococcus aureus</i>. Benzocycloalkane-derived compounds were effective inhibitors of diapophytoene desaturase but limited by high hERG (human Ether-a-go-go Related Gene) inhibition activity. Here, we identified a new type of benzo-hepta-containing cycloalkane derivative as diapophytoene desaturase inhibitors. Among the fifty-eight analogues, <b>48</b> (hERG inhibition activity, half maximal inhibitory concentration, IC₅₀, of 16.1 μM) and <b>51</b> (hERG inhibition activity, IC₅₀ > 40 μM) were distinguished for effectively inhibiting the pigment production of <i>Staphylococcus aureus</i> Newman and three methicillin-resistant <i>Staphylococcus aureus</i> strains, and the four strains were highly sensitize to hydrogen peroxide killing without a bactericidal growth effect. In an <i>in vivo</i> assay, <b>48</b> and <b>51</b> displayed a comparable effect with linezolid and vancomycin in livers and hearts in mice against <i>Staphylococcus aureus</i> Newman and a more considerable effect against Mu50 and NRS271 with normal administration

Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity

CrtN has been identified as an attractive and druggable target for treating pigmented <i>Staphylococcus aureus</i> infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor <b>1</b>. Analogues <b>23a</b> and <b>23b</b> demonstrated a significant activity against pigmented <i>S. aureus</i> Newman and 13 MRSA strains (IC₅₀ = 0.02–10.5 nM), along with lower hERG inhibition (IC₅₀ > 30 μM, ∼10-fold decrease in comparison with <b>1</b>). Furthermore, <b>23a</b> and <b>23b</b> were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, <b>23a</b> could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that <b>23a</b> has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug

Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity

CrtN has been identified as an attractive and druggable target for treating pigmented <i>Staphylococcus aureus</i> infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor <b>1</b>. Analogues <b>23a</b> and <b>23b</b> demonstrated a significant activity against pigmented <i>S. aureus</i> Newman and 13 MRSA strains (IC₅₀ = 0.02–10.5 nM), along with lower hERG inhibition (IC₅₀ > 30 μM, ∼10-fold decrease in comparison with <b>1</b>). Furthermore, <b>23a</b> and <b>23b</b> were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, <b>23a</b> could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that <b>23a</b> has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug

DataSheet_1_Climatic responses and variability in bark anatomical traits of 23 Picea species.docx

In woody plants, bark is an important protective tissue which can participate in photosynthesis, manage water loss, and transport assimilates. Studying the bark anatomical traits can provide insight into plant environmental adaptation strategies. However, a systematic understanding of the variability in bark anatomical traits and their drivers is lacking in woody plants. In this study, the bark anatomical traits of 23 Picea species were determined in a common garden experiment. We analyzed interspecific differences and interpreted the patterns in bark anatomical traits in relation to phylogenetic relationships and climatic factors of each species according to its global distribution. The results showed that there were interspecific differences in bark anatomical traits of Picea species. Phloem thickness was positively correlated with parenchyma cell size, possibly related to the roles of parenchyma cells in the radial transport of assimilates. Sieve cell size was negatively correlated with the radial diameter of resin ducts, and differences in sieve cells were possibly related to the formation and expansion of resin ducts. There were no significant phylogenetic signals for any bark anatomical trait, except the tangential diameter of resin ducts. Phloem thickness and parenchyma cell size were affected by temperature-related factors of their native range, while sieve cell size was influenced by precipitation-related factors. Bark anatomical traits were not significantly different under wet and dry climates. This study makes an important contribution to our understanding of variability in bark anatomical traits among Picea species and their ecological adaptations.</p

Development of the First Generation of Disulfide-Based Subtype-Selective and Potent Covalent Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors

Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described bis­(4-morpholinyl thiocarbonyl)-disulfide (JX06, <b>16</b>) as the first covalent inhibitor of PDK1. Here, on the basis of the scaffold of <b>16</b>, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analogue, <b>3a</b>, effectively inhibits PDK1 both at the molecular (<i>k</i>_inact/<i>K</i>_i = 4.17 × 10³ M^–1 s^–1) and the cellular level (down to 0.1 μM). In contrast to <b>16</b>, <b>3a</b> is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2–4. <b>3a</b> also significantly alters glucose metabolic pathways in A549 cells by decreasing ECAR and increasing ROS. Moreover, in the xenograft models, <b>3a</b> shows significant antitumor activity with no negative effect to the mice weight. Collectively, these data demonstrate that <b>3a</b> may be an excellent lead compound for the treatment of cancer as a first-generation subtype-selective and covalent PDK1 inhibitor

Novel Staphyloxanthin Inhibitors with Improved Potency against Multidrug Resistant <i>Staphylococcus aureus</i>

Diapophytoene desaturase (CrtN) is a potential novel target for intervening in the biosynthesis of the virulence factor staphyloxanthin. In this study, 38 1,4-benzodioxan-derived CrtN inhibitors were designed and synthesized to overwhelm the defects of leading compound <b>4a</b>. Derivative <b>47</b> displayed superior pigment inhibitory activity, better hERG inhibitory properties and water solubility, and significantly sensitized MRSA strains to immune clearance in vitro. Notably, <b>47</b> displayed excellent efficacy against pigmented <i>S. aureus</i> Newman, Mu50 (vancomycin-intermediate MRSA, VISA), and NRS271 (linezolid-resistant MRSA, LRSA) comparable to that of linezolid and vancomycin in vivo

Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate <i>Staphylococcus aureus</i> Infections in Vivo

Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831−4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives <b>69</b> and <b>105</b> displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of <b>69</b> and <b>105</b> were displayed first with normal administration in the livers and hearts in mice against pigmented <i>S. aureus</i> Newman, Mu50 (vancomycin-intermediate <i>S. aureus</i>), and NRS271 (linezolid-resistant <i>S. aureus</i>), compared with linezolid and vancomycin. In summary, both <b>69</b> and <b>105</b> have the potential to be developed as good antibacterial candidates targeting virulence factors