Constructing artificial gap junctions to mediate intercellular signal and mass transport.

Natural gap junctions are a type of channel protein responsible for intercellular signalling and mass communication. However, the scope of applications for these proteins is limited as they cannot be prepared at a large scale and are unable to spontaneously insert into cell membranes in vitro. The construction of artificial gap junctions may provide an alternative strategy for preparing analogues of the natural proteins and bottom-up building blocks necessary for the synthesis of artificial cells. Here we show the construction of artificial gap junction channels from unimolecular tubular molecules consisting of alternately arranged positively and negatively charged pillar[5]arene motifs. These molecules feature a hydrophobic-hydrophilic-hydrophobic triblock structure that allows them to efficiently insert into two adjacent plasma membranes and stretch across the gap between the two membranes to form gap junctions. Similar to natural gap junction channels, the synthetic channels could mediate intercellular signal coupling and reactive oxygen species transmission, leading to cellular activity.

Physical activity, problematic smartphone use, and burnout among Chinese college students.

The aim of this study was to investigate the association between physical activity (PA), problematic smartphone use (PSU), and burnout, as well as to identify whether there is a mediating role for PSU. We recruited 823 college students (Mage = 18.55, SD = 0.83) from Wuhan, China, in December 2022, including 499 males and 324 females. Demographic information, the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Smartphone Addiction Scale-Short Version (SAS-SV), and the Maslach Burnout Inventory-Student Survey (MBI-SS) were used for assessments. Pearson correlation analysis showed that PA was significantly associated with PSU (r = -0.151, p < 0.001), PSU was significantly associated with burnout (r = 0.421, p < 0.001), and the association between PA and burnout was not statistically significant (r = -0.046, p > 0.05). The results of the mediation model test showed that PA could not predict burnout directly; it instead predicted burnout entirely indirectly through PSU. Furthermore, PSU mediated the predictive effect of PA on exhaustion and cynicism. In conclusion, there is no direct connection between PA levels and burnout. PA indirectly affects burnout through PSU, but does not fully apply to the three different dimensions of exhaustion, cynicism, and professional efficacy.

Enantioselective Synthesis of Inherently Chiral Calix[4]arenes via Palladium-Catalyzed Asymmetric Intramolecular C-H Arylations.

We report herein an efficient approach for the enantioselective synthesis of inherently chiral calix[4]arenes via palladium-catalyzed asymmetric intramolecular C-H arylations. Using a chiral bifunctional phosphine-carboxylate ligand, the inherent chirality on macrocyclic scaffolds was induced successfully, from which a wide range of calix[4]arenes with fluorenone motifs were obtained with good yields and excellent enantioselectivities (up to >99% ee). The synthetic utility of this method was demonstrated by diverse transformations of the products, thus substantially expanding the chemical space of chiral calix[4]arenes. Further investigations of photophysical and chiroptical properties revealed that calix[4]arenes bearing two fluorenone moieties displayed remarkable glum values (up to 0.019), highlighting the great potential of inherent chirality in the development of organic optoelectronic materials.

The relationship between exercise intention and behavior of Chinese college students: A moderated mediation model.

Inconsistency between intention and behavior is very common in daily life. This study explored the intention-behavior relationship in exercise, focusing on the mediating effect of action planning and the moderating effects of habit strength and gender. For the purpose of providing theoretical reference for the implementation of intervention strategies in the volitional phase, a total of 489 college students (M-age = 20.61, 57.46% female) from Hubei Province, China, were recruited to complete the questionnaire at two time points. The findings showed that exercise intention could positively predict exercise behavior via the mediating effect of action planning, with the mediating effect accounting for 48.52% of the total effect. The predictive effect of action planning × habit strength interaction on exercise behavior was statistically significant. As individuals' levels of habitual strength increased, so did the relationship between action plans and exercise behavior. The action planning-exercise behavior relationship was stronger in males than in females. In summary, action planning is a very important predictor of the post-intentional phase and has many advantages. For individuals whose exercise has become habitualized, forming a plan is not counterproductive and can still promote more exercise rather than in a mutually compensating manner.

Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake.

Protein fatty acylation regulates numerous cell signaling pathways. Polyunsaturated fatty acids (PUFAs) exert a plethora of physiological effects, including cell signaling regulation, with underlying mechanisms to be fully understood. Herein, we report that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) regulate PI3K-AKT signaling by modifying PDK1 and AKT2. DHA-administered mice exhibit altered phosphorylation of proteins in signaling pathways. Methylene bridge-containing DHA/EPA acylate δ1 carbon of tryptophan 448/543 in PDK1 and tryptophan 414 in AKT2 via free radical pathway, recruit both the proteins to the cytoplasmic membrane, and activate PI3K signaling and glucose uptake in a tryptophan acylation-dependent but insulin-independent manner in cultured cells and in mice. DHA/EPA deplete cytosolic PDK1 and AKT2 and induce insulin resistance. Akt2 knockout in mice abrogates DHA/EPA-induced PI3K-AKT signaling. Our results identify PUFA's methylene bridge tryptophan acylation, a protein fatty acylation that regulates cell signaling and may underlie multifaceted effects of methylene-bridge-containing PUFAs.

Adsorption-Based Detoxification of Endotoxins by Porous Flexible Organic Frameworks.

Bacterial lipopolysaccharides (LPS, endotoxins) cause sepsis that is responsible for a huge amount of mortality globally. However, their neutralization or detoxification remains an unmet medical need. We envisaged that cationic organic frameworks with persistent hydrophobic porosity may adsorb and thus neutralize LPS through a combination of cooperative ion-pairing electrostatic attraction and hydrophobicity. We here report the preparation of two water-soluble flexible organic frameworks (FOF-1 and FOF-2) from tetratopic and ditopic precursors through quantitative formation of hydrazone bonds at room temperature. The two FOFs are revealed to possess hydrodynamic diameters, which range from 20 to 120 nm, depending on the concentrations. Dynamic light scattering and isothermal titration calorimetric and chromogenic limulus amebocyte lysate experiments indicate that both frameworks are able to adsorb and thus reduce the concentration of free LPS molecules in aqueous solution, whereas cytokine inhibition experiments with RAW264.7 support that this adsorption can significantly decrease the toxicity of LPS. In vivo experiments with mice (five males per group) show that the injection of FOF-1 at a dose of 0.6 mg/kg realizes the survival of all of the mice administrated with LPS of the d-galactosamine (d-Gal)-sensitized absolute lethal dose (LD100, 0.05 mg/kg), whereas its maximum tolerated dose for mice is determined to be 10 mg/kg. These findings provide a new promising sequestration strategy for the development of porous agents for the neutralization of LPS.

Charged Tubular Supramolecule Boosting Multivalent Interactions for the Drastic Suppression of Aß Fibrillation.

Anti-Aß therapy has dominated clinical trials for the prevention and treatment of Alzheimer's disease (AD). However, suppressing Aß aggregation and disintegrating mature fibrils simultaneously remains a great challenge. In this work, we developed a new strategy using a charged tubular supramolecule (CTS) with pillar[5]arene as the backbone and modifying amino and carboxyl groups at the tubular terminals (noted as CTS-A, CTS-A/C, and CTS-C, respectively) to suppress Aß fibrillation for the first time. According to the spectroscopic and microscopic characterizations, Aß40 fibrillation can be efficiently suppressed by CTS-A in a very low inhibitor:peptide (I:P) molar ratio (1:10). A greatly alleviated cytotoxic effect of Aß peptides after the inhibition or disaggregation process is further disclosed. The well-organized supramolecular structure drives multivalent interaction and gains enhanced efficiency on amyloid fibrillar modulation. These results open a new path for the design of supramolecules in the application of AD treatment.

Voltage-Driven Flipping of Zwitterionic Artificial Channels in Lipid Bilayers to Rectify Ion Transport.

We developed a voltage-sensitive artificial transmembrane channel by mimicking the dipolar structure of natural alamethicin channel. The artificial channel featured a zwitterionic structure and could undergo voltage-driven flipping in the lipid bilayers. Importantly, this flipping of the channel could lead to their directional alignment in the bilayers and rectifying behavior for ion transport.

High time-resolved characterization of airborne microbial community during a typical haze pollution process.

Variations of bioaerosol characteristics during the process of haze pollution have rarely been explored. In this study, high time-resolved variations of the community structures of bacteria, fungi, and ammonia-oxidizing microorganisms (AOMs) were assessed during a typical haze pollution process. The impacts of meteorological factors, water-soluble inorganic ions (WSII), and organic dicarboxylic acids (DCA) on the airborne microbial community were systematically evaluated. The results showed that the bacterial community varied greatly during the formation stages of haze pollution, and tended to stabilize with the further development of haze pollution. Nevertheless, variations of the fungal community lasted throughout the whole haze pollution process. Furthermore, Nitrososphaera absolutely dominated the ammonia-oxidizing archaea (AOA) and declined as PM2.5 burst. Network analysis identified relatively weak interactions and co-occurrence patterns between dominant fungal genera. Importantly, dust source ions and PM2.5 acidity exerted the most significant impacts on bacterial and fungal communities. These results identify the high time-resolved variations of airborne microbial communities during the formation and development of haze pollution process, and provide valuable data to better understand the interaction between bioaerosols and haze pollution.

Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation.

Global histone acetylation varies with changes in the nutrient and cell cycle phases; however, the mechanisms connecting these variations are not fully understood. Herein, we report that nutrient-related and cell-cycle-regulated nuclear acetate regulates global histone acetylation. Histone deacetylation-generated acetate accumulates in the nucleus and induces histone hyperacetylation. The nuclear acetate levels were controlled by glycolytic enzyme triosephosphate isomerase 1 (TPI1). Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. CDK2 accumulates in the cytosol during the late G1/S phases. Inactivation or blockade of nuclear translocation of TPI1 abrogates nutrient-dependent and cell-cycle-dependent global histone acetylation, chromatin condensation, gene transcription and DNA replication. These results identify the mechanism of maintaining global histone acetylation by nutrient and cell cycle signals.

The source and transport of bioaerosols in the air: A review.

Recent pandemic outbreak of the corona-virus disease 2019 (COVID-19) has raised widespread concerns about the importance of the bioaerosols. They are atmospheric aerosol particles of biological origins, mainly including bacteria, fungi, viruses, pollen, and cell debris. Bioaerosols can exert a substantial impact on ecosystems, climate change, air quality, and public health. Here, we review several relevant topics on bioaerosols, including sampling and detection techniques, characterization, effects on health and air quality, and control methods. However, very few studies have focused on the source apportionment and transport of bioaerosols. The knowledge of the sources and transport pathways of bioaerosols is essential for a comprehensive understanding of the role microorganisms play in the atmosphere and control the spread of epidemic diseases associated with them. Therefore, this review comprehensively summarizes the up to date progress on the source characteristics, source identification, and diffusion and transport process of bioaerosols. We intercompare three types of diffusion and transport models, with a special emphasis on a widely used mathematical model. This review also highlights the main factors affecting the source emission and transport process, such as biogeographic regions, land-use types, and environmental factors. Finally, this review outlines future perspectives on bioaerosols.

Unimolecular artificial transmembrane channels showing reversible ligand-gating behavior.

A series of peptide-appended bisresorcinarenes were synthesized, which adopted tubular conformation induced by intramolecular hydrogen bonds. The derivatives formed unimolecular artificial transmembrane channels in lipid bilayers to enable selective transport of monovalent cations. Importantly, the channels exhibited reversible ligand-gating behavior in response to alkyl amine and Cu2+.

Gramicidin A-based unimolecular channel: cancer cell-targeting behavior and ion transport-induced apoptosis.

A series of glycoside-peptide conjugates were prepared by engineering at the N-terminus of the natural peptide gramicidin A. The conjugate containing galactose moiety formed a unimolecular transmembrane channel and mediated ion transport to induce apoptosis of cancer cells. More importantly, it exhibited liver cancer cell-targeting behavior due to the galactose-asialoglycoprotein receptor recognition.

Vertical variations in the concentration and community structure of airborne microbes in PM2.5.

With the recent rapid development of urbanization, severe air pollution events frequently occur in China. Subsequently, variations of bioaerosols during air pollution events have attracted increasing attention in recent years. However, most published studies on bioaerosols mainly focus on the characteristics of airborne bacteria and fungi at a certain height near the ground surface. The vertical variations in microbial aerosols at different heights are not well understood. In this study, PM2.5 samples at three heights (1.5 m, 100 m and 229.5 m) were collected from September 2019 to January 2020 in Xi'an, China. The samples were then analyzed by a fluorescence staining and high-throughput sequencing to explore the vertical variations in the concentration and community structure of the airborne bacteria. The results show that the microbial concentration in PM2.5 decreased with increasing height on polluted days, while there was no significant difference at different heights on non-polluted days (p > 0.05). The bacterial community structures were similar at different heights on polluted days; however, on non-polluted days, the bacterial community structure at 229.5 m was significantly different from that at the other heights. Importantly, meteorological factors had more significant effects on the bacterial community at 229.5 m than at 1.5 m and 100 m. The present results can improve the understanding of vertical distribution of bioaerosols and their diffusion process.

Artificial Aquaporin That Restores Wound Healing of Impaired Cells.

Artificial aquaporins are synthetic molecules that mimic the structure and function of natural aquaporins (AQPs) in cell membranes. The development of artificial aquaporins would provide an alternative strategy for treatment of AQP-related diseases. In this report, an artificial aquaporin has been constructed from an amino-terminated tubular molecule, which operates in a unimolecular mechanism. The artificial channel can work in cell membranes with high water permeability and selectivity rivaling those of AQPs. Importantly, the channel can restore wound healing of the cells that contain function-lost AQPs.

Inhibiting MARSs reduces hyperhomocysteinemia-associated neural tube and congenital heart defects.

Hyperhomocysteinemia is a common metabolic disorder that imposes major adverse health consequences. Reducing homocysteine levels, however, is not always effective against hyperhomocysteinemia-associated pathologies. Herein, we report the potential roles of methionyl-tRNA synthetase (MARS)-generated homocysteine signals in neural tube defects (NTDs) and congenital heart defects (CHDs). Increased copy numbers of MARS and/or MARS2 were detected in NTD and CHD patients. MARSs sense homocysteine and transmit its signal by inducing protein lysine (N)-homocysteinylation. Here, we identified hundreds of novel N-homocysteinylated proteins. N-homocysteinylation of superoxide dismutases (SOD1/2) provided new mechanistic insights for homocysteine-induced oxidative stress, apoptosis and Wnt signalling deregulation. Elevated MARS expression in developing and proliferating cells sensitizes them to the effects of homocysteine. Targeting MARSs using the homocysteine analogue acetyl homocysteine thioether (AHT) reversed MARS efficacy. AHT lowered NTD and CHD onsets in retinoic acid-induced and hyperhomocysteinemia-induced animal models without affecting homocysteine levels. We provide genetic and biochemical evidence to show that MARSs are previously overlooked genetic determinants and key pathological factors of hyperhomocysteinemia, and suggest that MARS inhibition represents an important medicinal approach for controlling hyperhomocysteinemia-associated diseases.

Author Correction: Artificial water channels enable fast and selective water permeation through water-wire networks.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Artificial water channels enable fast and selective water permeation through water-wire networks.

Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic nanoarchitecture, peptide-appended hybrid[4]arene (PAH[4]), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH[4]s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for a rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAH[4]s can transport >109 water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~104, as illustrated by the water/NaCl permeability-selectivity trade-off curve. PAH[4]'s unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production and barrier applications.

Targeting the Cell Membrane by Charge-Reversal Amphiphilic Pillar[5]arene for the Selective Killing of Cancer Cells.

A charge-reversal amphiphilic pillar[5]arene, P5NH-DCA, bearing 10 charge-reversal headgroups is reported. It targets the cell membrane of cancer cells and selectively destroys the cancer cells by disrupting the membrane. In the acidic tumor microenvironment, the headgroup charge of P5NH-DCA reversed from negative to positive owing to hydrolysis of the acid-labile amide group. The hydrolyzed product bearing multiple positive charges can bind to the cell membrane and then disrupt the membrane of cancer cells with high efficiency. However, under the neutral microenvironment of healthy cells, the negatively charged P5NH-DCA remains stable and the cytotoxicity is considerably reduced. The strategy killing the cancer cells by membrane disruption may represent a new route of cancer chemotherapy.