PC71BM as Morphology Regulator for Highly Efficient Ternary Organic Solar Cells with Bulk Heterojunction or Layer-by-Layer Configuration.

The ternary strategy is one of the effective methods to regulate the morphology of the active layer in organic solar cells (OSCs). In this work, the ternary OSCs with bulk heterojunction (BHJ) or layer-by-layer (LbL) active layers are prepared by using the polymer donor PM6 and the non-fullerene acceptor L8-BO as the main system and the fullerene acceptor PC71BM as the third component. The power conversion efficiencies (PCEs) of BHJ OSCs and LbL OSCs are increased from 17.10% to 18.02% and from 17.20% to 18.20% by introducing PC71BM into the binary active layer, respectively. The in situ UV-vis absorption spectra indicate that the molecular aggregation and crystallization process can be prolonged by introducing PC71BM into the PM6:L8-BO or PM6/L8-BO active layer. The molecular orientation and molecular crystallinity in the active layer are optimized by introducing the PC71BM into the binary BHJ or LbL active layers, which can be confirmed by the experimental results of grazing incidence wide-angle X-ray scattering. This study demonstrates that the third component PC71BM can be used as a morphology regulator to regulate the morphology of BHJ or LbL active layers, thus effectively improving the performance of BHJ and LbL OSCs.

Highly Efficient Organic Solar Cells with the Highly Crystalline Third Component as a Morphology Regulator.

The morphology of the active layer is crucial for highly efficient organic solar cells (OSCs), which can be regulated by selecting a rational third component. In this work, the highly crystalline nonfullerene acceptor BTP-eC9 is selected as the morphology regulator in OSCs with PM6:BTP-BO-4Cl as the main system. The addition of BTP-eC9 can prolong the nucleation and crystallization progress of acceptor and donor molecules, thereby enhancing the order of molecular arrangement. Meanwhile, the nucleation and crystallization time of the donor is earlier than that of the acceptors after introducing BTP-eC9, which is beneficial for obtaining a better vertical structural phase separation. The exciton dissociation, charge transport, and charge collection are promoted effectively by the optimized morphology of the active layer, which improves the short-circuit current density and filling factor. After introducing BTP-eC9, the power conversion efficiencies (PCEs) of the ternary OSCs are improved from 17.31% to 18.15%. The PCE is further improved to 18.39% by introducing gold nanopyramid (Au NBPs) into the hole transport layer to improve photon utilization efficiency. This work indicates that the morphology can be optimized by selecting a highly crystalline third component to regulate the nucleation and crystallization progress of the acceptor and donor molecules.

Critical Residues Involved in the Coassembly of L1 and L2 Capsid Proteins of Human Papillomavirus 16.

Human papillomaviruses (HPV) are small DNA viruses associated with cervical cancer, warts, and other epithelial tumors. Structural studies have shown that the HPV capsid consists of 360 copies of the major capsid protein, L1, arranged as 72 pentamers in a T=7 icosahedral lattice, coassembling with substoichiometric amounts of the minor capsid protein, L2. However, the residues involved in the coassembly of L1 and L2 remain undefined due to the lack of structure information. Here, we investigated the solvent accessibility surfaces (SASs) of the central cavity residues of the HPV16 L1 pentamer in the crystal structure because those internal exposed residues might mediate the association with L2. Twenty residues in L1 protein were selected to be analyzed, with four residues in the lumen of the L1 pentamer identified as important: F256, R315, Q317, and T340. Mutations to these four residues reduced the PsV (pseudovirus) infection capacity in 293FT cells, and mutations to R315, Q317, and T340 substantially perturb L2 from coassembling into L1 capsid. Compared with wild-type (WT) PsVs, these mutant PsVs also have a reduced ability to become internalized into host cells. Finally, we identified a stretch of negatively charged residues on L2 (amino acids [aa] 337 to 340 [EEIE]), mutations to which completely abrogate L2 assembly into L1 capsid and subsequently impair the endocytosis and infectivity of HPV16 PsVs. These findings shed light on the elusive coassembly between HPV L1 and L2. IMPORTANCE Over 200 types of HPV have been isolated, with several high-risk types correlated with the occurrence of cervical cancer. The HPV major capsid protein, L1, assembles into a T=7 icosahedral viral shell, and associates with the minor capsid protein, L2, which plays a critical role in the HPV life cycle. Despite the important role of the L2 protein, its structure and coassembly with L1 remain elusive. In this study, we analyzed the amino acid residues at the proposed interface between L1 and L2. Certain mutations at these sites decreased the amount of L2 protein assembled into the capsid, which, in turn, led to a decrease in viral infectivity. Knowledge about these residues and the coassembly of L1 and L2 could help to expand our understanding of HPV biology and aid in the development of countermeasures against a wide range of HPV types by targeting the L2 protein.

3-Amide-ß-carbolines block the cell cycle by targeting CDK2 and DNA in tumor cells potentially as anti-mitotic agents.

ß-Carboline alkaloids are natural and synthetic products with outstanding antitumor activity. C3 substituted and dimerized ß-carbolines exert excellent antitumor activity. In the present research, 37 ß-carboline derivatives were synthesized and characterized. Their cytotoxicity, cell cycle, apoptosis, and CDK2- and DNA-binding affinity were evaluated. ß-Carboline monomer M3 and dimer D4 showed selective activity and higher cytotoxicity in tumor cells than in normal cells. Structure-activity relationships (SAR) indicated that the amide group at C3 enhanced the antitumor activity. M3 blocked the A549 (IC50 = 1.44 ± 1.10 µM) cell cycle in the S phase and inhibited A549 cell migration, while D4 blocked the HepG2 (IC50 = 2.84 ± 0.73 µM) cell cycle in the G0/G1 phase, both of which ultimately induced apoptosis. Furthermore, associations of M3 and D4 with CDK2 and DNA were proven by network pharmacology analysis, molecular docking, and western blotting. The expression level of CDK2 was downregulated in M3-treated A549 cells and D4-treated HepG2 cells. Moreover, M3 and D4 interact with DNA and CDK2 at sub-micromolar concentrations in endothermic interactions caused by entropy-driven adsorption processes, which means that the favorable entropy change (ΔS > 0) overcomes the unfavorable enthalpy change (ΔH > 0) and drives the spontaneous reaction (ΔG < 0). Overall, these results clarified the antitumor mechanisms of M3 and D4 through disrupting the cell cycle by binding DNA and CDK2, which demonstrated the potential of M3 and D4 as novel antiproliferative drugs targeting mitosis.

Maternal age-specific risks for adverse birth weights according to gestational weight gain: a prospective cohort in Chinese women older than 30.

BACKGROUND: It is unclear whether the effects of abnormal gestational weight gain (GWG) on birth outcomes are differently in women with different maternal ages. This study aimed to investigate maternal age-specific association between GWG and adverse birth weights in Chinese women older than 30. METHODS: 19,854 mother-child dyads were selected from a prospective cohort study in Southwest China between 2019 and 2022. Logistic regression model was used to assess the association between GWG, which defined by the 2009 Institute of Medicine guidelines, and adverse birth weights including large- and small-for-gestational-age (LGA and SGA), stratified by maternal age (31-34 years and ≥ 35 years). RESULTS: In both maternal age groups, excessive and insufficient GWG were associated with increased odds of LGA and SGA, respectively. After women were categorized by pre-pregnancy body mass index, the associations remained significant in women aged 31-34 years, whereas for women aged ≥ 35 years, the association between excessive GWG and the risk of LGA was only significant in normal weight and overweight/obese women, and the significant effect of insufficient GWG on the risk of SGA was only observed in underweight and overweight/obese women. Moreover, among overweight/obese women, the magnitude of the association between insufficient GWG and the risk of SGA was greater in those aged ≥ 35 years (31-34 years: OR 2.08, 95% CI 1.19-3.55; ≥35 years: OR 2.65, 95% CI 1.47-4.74), while the impact of excessive GWG on the risk of LGA was more pronounced in those aged 31-34 years (31-34 years: OR 2.18, 95% CI 1.68-2.88; ≥35 years: OR 1.71, 95% CI 1.30-2.25). CONCLUSIONS: The stronger associations between abnormal GWG and adverse birth weights were mainly observed in women aged 31-34 years, and more attention should be paid to this age group.

The association between outdoor light at night exposure and adult obesity in Northeastern China.

Previous studies have linked exposure to light at night (LAN) with various health outcomes, but evidence is limited for the LAN-obesity association. Thestudy analysed data from 24,845 participants of the 33 Communities Chinese Health Study and obesity (BMI ≥28 kg/m2) was defined according to the Working Group on Obesity in China. The Global Radiance Calibrated Nighttime Lights data were used to estimate participants' LAN exposure. The mixed-effect regression models examined the LAN-BMI and LAN-obesity association. We found that higher LAN exposure was significantly associated with greater BMI and higher risk of obesity. Changes of BMI and the odds ratios (ORs) of obesity and 95% confidence intervals (CIs) for 2nd, 3rd, and 4th against the 1st quartile of LAN exposure were 0.363 (0.208, 0.519), 0.364 (0.211, 0.516) and 0.217 (0.051, 0.383); 1.228 (1.099, 1.371), 1.356 (1.196, 1.538) and 1.269 (1.124, 1.433), respectively. Age and regular exercise showed significant modification effects on the LAN-obesity association.

Diverse roles of MYB transcription factors in regulating secondary metabolite biosynthesis, shoot development, and stress responses in tea plants (Camellia sinensis).

Tea (Camellia sinensis) is concocted from tea plant shoot tips that produce catechins, caffeine, theanine, and terpenoids, which collectively determine the rich flavors and health benefits of the infusion. However, little is known about the integrated regulation of shoot tip development and characteristic secondary metabolite biosynthesis in tea plants. Here, we demonstrate that MYB transcription factors (TFs) play key and yet diverse roles in regulating leaf and stem development, secondary metabolite biosynthesis, and environmental stress responses in tea plants. By integrating transcriptomic and metabolic profiling data in different tissues at a series of developmental stages or under various stress conditions, alongside biochemical and genetic analyses, we predicted the MYB TFs involved in regulating shoot development (CsMYB2, 98, 107, and 221), epidermal cell initiation (CsMYB184, 41, 139, and 219), stomatal initiation (CsMYB113 and 153), and the biosynthesis of flavonoids (including catechins, anthocyanins, and flavonols; CsMYB8 and 99), caffeine (CsMYB85 and 86), theanine (CsMYB9 and 49), carotenoids (CsMYB110), mono-/sesquiterpenoid volatiles (CsMYB68, 147, 148, and 193), lignin (CsMYB164 and 192), and indolic compounds (CsMYB139, 162, and 198), as well as the MYB TFs that are likely involved in hormone signaling-mediated environmental stress and defense responses. We characterized the functions of some key MYBs in regulating flavonoid and carotenoid biosynthesis for tea quality and flavor. This study provides a cross-family analysis of MYBs in tea alongside new insights into the coordinated regulation of tea plant shoot development and secondary metabolism, paving the way towards understanding of tea quality trait formation and genetic improvement of quality tea plants.

Fluorescence Enhancement of Adamantane-Modified Dyes in Aqueous Solution via Supramolecular Interaction with Methyl-ß-cyclodextrin and Their Application in Cell Imaging.

The fluorescence of functional dyes was generally quenched in aqueous solution, which hindered their application in water-bearing detections. In this work, a novel strategy based on host-guest interaction was provided for the purpose of fluorescence enhancement in aqueous solution and cell imaging. Three adamantane-modified fluorescent dyes (Coum-Ad, NP-Ad, NR-Ad) with coumarin, 1,8-naphthalimide and Nile Red as fluorophores were initially designed and prepared. The ((adamantan-1-yl)methyl)amino group, as the auxochrome of those dyes, complexed with methylated ß-cyclodextrin (M-ß-CD) via supramolecular interaction, and then fluorescent supramolecular nanoparticles (FSNPs) were formed by self-assembly in water. The inclusion equilibrium constant (K) could be as high as 3.94×104  M-1 . With the addition of M-ß-CD, fluorescence quantum yields of these dyes were separately improved to 69.8 %, 32.9 % and 41.3 %. Inspired by the above satisfactory results, six adamantane-modified probes organelle-NPAds with organelle-targeting capability were further obtained. As the formation of hydrogen bonds between organelle-NPAd2 and M-ß-CD verified by theoretical calculation, K of organelle-NPAd2 (5.13×104  M-1 ~4.53×105  M-1 ) with M-ß-CD was higher than that of organelle-NPAd1 (1.15×104  M-1 ~3.66×104  M-1 ) and their fluorescence quantum yields increased to 32.8 %~83.6 % in aqueous solution. In addition, fluorescence enhancement was realized in cell imaging with the addition of M-ß-CD.

Shared Genetics and Comorbid Genes of Amyotrophic Lateral Sclerosis and Parkinson's Disease.

BACKGROUND: Comorbidity exists between amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), but the role of genetic factors is unclear. OBJECTIVE: We aim to investigate genetic correlation, causal relationship, and comorbid genes between ALS and PD. METHODS: Leveraging the largest genome-wide association study data (ALS: 27,205 cases, 110,881 controls; PDG: 33,674 cases, 449,056 controls), we used linkage disequilibrium score regression and Mendelian randomization analysis for genetic correlation and causal inference. We performed genome-wide cross-trait analysis via Multi-Trait Analysis of Genome-Wide Association Studies and Cross-Phenotype Association to identify specific single-nucleotide polymorphisms, followed by functional mapping and annotation. Integrating expression quantitative trait loci data from 13 brain regions, we conducted a transcriptome-wide association study via functional summary-based imputation and joint-tissue imputation to explore comorbid genes, followed by pathway enrichment analysis. RESULTS: We found that PD positively correlates with ALS (rg = 0.144, P = 0.026) and confers a causal effect (odds ratio = 1.09, 95% confidence interval: 1.03-1.15, P = 3.00 × 10-3 ). We identified nine single-nucleotide polymorphisms (eight new), associating with three risk loci (chromosomes 4, 10, and 17) and seven genes (TMEM175, MAPT, NSF, LRRC37A2, ARHGAP27, GAK, and FGFRL1). In transcriptome-wide association study analysis, we showed six previously unreported pleiotropic genes (KANSL1, ARL17B, EFNA1, WNT3, ERCC8, and ADAM15), and we found these candidate genes are mainly enriched in negative regulation of neuron projection development (GO:0010977). CONCLUSIONS: Our work demonstrates shared genetic architecture between ALS and PD, reports new pleiotropic genes, and sheds light on the comorbid mechanism. © 2023 International Parkinson and Movement Disorder Society.

Hydrophobic Composite Foams with Asymmetric Gradient Sandwich Structure for Excellent Electromagnetic Interference Shielding and Photothermal Response.

The evolution of contemporary electronics urgently requires the use of versatile electromagnetic interference (EMI) shielding materials in complex environments. Interlayer polydimethylsiloxane (PDMS)/Fe3O4@multiwalled carbon nanotubes (MWCNTs) foams were prepared by a simple physical foaming method with excellent flexibility and electromagnetic wave absorption. The bottom nickel aramid paper (NiP) layer creates a dense conductive network by chemical plating technology, which ensures excellent EMI effectiveness. The upper carbon black (CB)/Fe3O4 layer further improves the absorption performance via conductive loss and magnetic loss. With the effective layout of the impedance matching layer, absorbing layer, and conductive shielding layer, the CB/Fe3O4-PDMS/Fe3O4@MWCNTs-NiP composite material achieves an EMI shielding effectiveness (EMI SE) of 61.7 dB and an absorption coefficient of 0.58 at X-band. In addition, the composite foam provides photothermal conversion and hydrophobicity due to the effective stacking of PDMS and CB/Fe3O4. Thus, the multifunctional composite foam presents a broad range of possible applications, benefiting EMI shielding as well as other specific areas.

Viscosity probes towards different organelles with red emission based on an identical hemicyanine structure.

A series of viscosity probes targeting different organelles were obtained using a single hemicyanine dye as the matrix structure. Specifically, probes 1a-d were obtained by introducing four amines (6-amino-2H-chromen-2-one, N-(2-aminoethyl)-4-methylbenzenesulfonamide, dodecan-1-amine and N,N diphenylbenzene-1,4-diamine) into the indole hemicyanine dye of the carboxylic acid with a D-π-A structure. Their maximum absorption wavelengths were in the range 570-586 nm and they had relatively large molar absorption coefficients, while their maximum emission wavelengths in the red light region were in the range 596-611 nm. Moreover, their fluorescence intensity in glycerol was 35-184 times higher than that in phosphate buffer solution (PBS). The lg(Fl) and lg η of probes 1a-d showed good linearity with high correlation coefficients according to the Förster-Hoffman equation. In addition, cell staining experiments demonstrated that 1a-c could target lysosomes, endoplasmic reticulum and mitochondria, respectively. They could also undergo viscosity-detectable changes in the corresponding organelles under the action of the corresponding ion carriers.

Conjugated structures based on quinazolinones and their application in fluorescent labeling.

As an alkaloid, quinazolinone exhibits excellent biological properties; structurally, it also has the potential to construct fluorescent probes with conjugated structures. In this work, probes 5a-c and 6b were obtained by introducing quinazolone into aldehydes with different numbers of double bonds. Their absorption maxima were located at 420-540 nm and their emission maxima were at 500-600 nm in solvents of different polarities. In particular, probe 5c showed significant fluorescence enhancement with the increase in viscosity due to the limited intramolecular rotation, and its fluorescence intensity in glycerol was 37.8 times higher than that in water. Moreover, probes 5a-c and 6b containing the NH structure showed sensitive response to pH, and their fluorescence intensity in alkaline solution (pH 9-11) was suddenly enhanced, which was elucidated with the help of theoretical calculation. In addition, the cell experiments showed that probes 5a and 5b had the ability to target mitochondria and probes 5c and 6b targeted lysosomes in HeLa cells. Furthermore, the viscosity-sensitive probe 5c could be used for monitoring changes in lysosomal viscosity in HeLa cells, which had important guiding significance for designing multi-response fluorogenic probes and promoting the advancement of cancer diagnosis.

Inhibitor of nuclear factor kappa B kinase subunit epsilon regulates murine acetaminophen toxicity via RIPK1/JNK.

Drug-induced liver injury (DILI) still poses a major clinical challenge and is a leading cause of acute liver failure. Inhibitor of nuclear factor kappa B kinase subunit epsilon (IKBKE) is essential for inflammation and metabolic disorders. However, it is unclear how IKBKE regulates cellular damage in acetaminophen (APAP)-induced acute liver injury. Here, we found that the deficiency of IKBKE markedly aggravated APAP-induced acute liver injury by targeting RIPK1. We showed that APAP-treated IKBKE-deficient mice exhibited severer liver injury, worse mitochondrial integrity, and enhanced glutathione depletion than wild-type mice. IKBKE deficiency may directly upregulate the expression of total RIPK1 and the cleaved RIPK1, resulting in sustained JNK activation and increased translocation of RIPK1/JNK to mitochondria. Moreover, deficiency of IKBKE enhanced the expression of pro-inflammatory factors and inflammatory cell infiltration in the liver, especially neutrophils and monocytes. Inhibition of RIPK1 activity by necrostatin-1 significantly reduced APAP-induced liver damage. Thus, we have revealed a negative regulatory function of IKBKE, which acts as an RIPK1/JNK regulator to mediate APAP-induced hepatotoxicity. Targeting IKBKE/RIPK1 may serve as a potential therapeutic strategy for acute or chronic liver injury.

How ß-Cyclodextrin-Functionalized Biochar Enhanced Biodenitrification in Low C/N Conditions via Regulating Substrate Metabolism and Electron Utilization.

Biodenitrification plays a vital role in the remediation of nitrogen-contaminated water. However, influent with a low C/N ratio limits the efficiency of denitrification and causes the accumulation/emission of noxious intermediates. In this study, ß-cyclodextrin-functionalized biochar (BC@ß-CD) was synthesized and applied to promote the denitrification performance of Paracoccus denitrificans when the C/N was only 4, accompanied by increased nitrate reduction efficiency and lower nitrite accumulation and nitrous oxide emission. Transcriptomic and enzymatic activity analyses showed BC@ß-CD enhanced glucose degradation by promoting the activities of glycolysis (EMP), the pentose phosphate pathway (PPP), and the tricarboxylic acid (TCA) cycle. Notably, BC@ß-CD drove a great generation of electron donors by stimulating the TCA cycle, causing a greater supply of substrate metabolism to denitrification. Meanwhile, the promotional effect of BC@ß-CD on oxidative phosphorylation accelerates electron transfer and ATP synthesis. Moreover, the presence of BC@ß-CD increased the intracellular iron level, causing further improved electron utilization in denitrification. BC@ß-CD helped to remove metabolites and induced positive feedback on the metabolism of P. denitrificans. Collectively, these effects elevated the glucose utilization for supporting denitrification from 36.37% to 51.19%. This study reveals the great potential of BC@ß-CD for enhancing denitrification under low C/N conditions and illustrates a potential application approach for ß-CD in wastewater bioremediation.

Methylated Chromenoquinoline as a Novel Nucleus Fluorescent Probe for Nucleic Acid Imaging.

Two chromenoquinoline-based fluorescent probes 1a-b have been synthesized and investigated. Photofading behaviors of compounds 1a-b showed that at least 89% absorption remained after 6 h irradiating, meanwhile, many of ions and amino acids had negligible impacts on their fluorescence intensity, which meant they had excellent photostability and selectivity. Probes 1a-b exhibited strong absorption and emission in organic solvents with large fluorescence quantum yields, even in water probe 1a still had a relatively large fluorescence quantum yield (20%). Combined with DFT calculation, the influence of alkylation on optical properties of 1b was elucidated. In addition, the fluorescence intensity of probe 1b with red emission enhanced by 5.4-fold and 5.3-fold after DNA and RNA added, and the fluorescence quantum yield increased from 3% to 17% and 14%, respectively, but the neutral molecule 1a had no response to nucleic acid. Furthermore, confocal microscopy imaging of probes 1a-b showed that 1a targeted lipid droplets while the methylated probe 1b to nucleus in living HeLa cells. The results indicated that the subcellular targeting zone could be changed by alkylation of nitrogen atom on chromenoquinoline-based conveniently, which provided a new idea for designing and synthesizing new subcellular labeled probes.

Prospective association of family members' sugar-sweetened beverages intake with children's sugar-sweetened beverages consumption in China.

PURPOSE: We aimed to investigate whether parental and siblings' sugar-sweetened beverage (SSB) intake had prospective impact on children's SSB consumption, and the potential sex difference in these associations. METHODS: This study included a total of 904 children and their parents enrolled from 2004 to 2011 China Health and Nutrition Survey (CHNS) cohort study. SSB consumption information was estimated using a short dietary questionnaire and total energy intake was assessed with three-day 24-h dietary assessments at recruitment and follow-up surveys. Multivariate logistic or linear regression analyses were used to assess the association for SSB consumption between parents, siblings and children after adjusting for age, body mass index (BMI) z-score, household income and parental educational level. RESULTS: In this study, a majority (87.6%) of children consumed SSB. Among them, the median consumption of SSB was 70.3 ml/day per capita and 205.4 ml/day per consumer. Parental SSB consumption was relevant to children's SSB consumption, and this association was more pronounced in boys than in girls. Meanwhile, fathers seemed to have a stronger impact on whether children consume SSB than mothers which was reflected by lower P and higher OR. Additionally, children's SSB intake was prospectively associated with their older siblings' SSB consumption (P for trend < 0.03). CONCLUSIONS: Parental and older siblings' SSB consumption was relevant to children's SSB intake. Particularly, boys were more susceptible to parental impact than girls, and fathers seemed to have a greater influence on children than mothers.

Mutations in DNA binding domain of p53 impede RSL1D1-p53 interaction to escape from degradation in human colorectal cancer cells.

Different from the nucleolus-specific localization in some types of cancer cells, ribosomal L1 domain-containing protein 1 (RSL1D1) distributes throughout the nucleus in human colorectal cancer (CRC) cells. RSL1D1 directly interacts with DNA binding domain (aa 93-292) of wild-type p53 (p53-WT) and thereby recruits p53 to HDM2. The ensuing formation of RSL1D1/HDM2/p53 complex enhances p53 ubiquitination and decreases the protein level of p53 in CRC cells. In this study, we investigated the interaction between RSL1D1 and mutant p53 proteins. We first corroborated that aa 93-224 of p53 is a more precise domain for RSL1D1 binding and mutation in either aa 93-224 or aa 225-292 domain of p53 affects RSL1D1-p53 interaction. R175H mutated p53 does not interact with RSL1D1, whereas R273H mutated p53 still can bind to RSL1D1 but showing a remarkably decreased affinity than p53-WT. Although p53-R273H retains a weakened binding affinity with RSL1D1, it can hardly be recruited to HDM2 by RSL1D1 in HCT116 CRC cells. Accordingly, RSL1D1 loses its capacity to negatively regulate either R175H or R273H p53 mutant via directly interaction in HCT116 cells, thereby facilitating p53 mutants to accumulate and gain oncogenic function. Our findings help explain why mutant p53 proteins are more stable than p53-WT in CRC cells.

Biofilm inhibition based on controlling the transmembrane transport and extracellular accumulation of quorum sensing signals.

The regulation of bacterial quorum sensing (QS) has been used to inhibit biofouling in wastewater treatment plants and the formation of biofilms. In contrast to traditional QS regulation strategies, this study aimed to obstruct the transmembrane transport process of QS signals to decrease their extracellular accumulation. Three phytochemicals, astragaloside IV, eugenol, and baicalin were selected, their effects on biofilm formation by Pseudomonas aeruginosa PA14 were studied, and the mechanisms determined. The inhibition efficiency of biofilm formation by 50 mg/L astragaloside IV, 1 mg/L eugenol, and 1 mg/L baicalin were 37%, 26%, and 26%, respectively. Confocal laser scanning microscopy and analysis of extracellular polymeric substances indicated that the three inhibitors affected the structure and composition of the biofilms. Furthermore, bacterial motility and a variety of QS-related virulence factors were suppressed by the inhibitor treatment due to changes in bacterial QS. Notably, the three inhibitors all decreased the extracellular concentration of the QS signaling molecule 3-oxo-C12-homoseine lactone by affecting the function of efflux pump MexAB-OprM. This indirectly interfered with the bacterial QS system and thus inhibited biofilm formation. In conclusion, this study revealed the inhibitory effects and inhibition mechanism of three phytochemicals on efflux pump and QS of P. aeruginosa and realized the inhibition on biofilm formation. We update the efflux pump inhibitor library and provide a new way for biofilm contamination control.

Association between long-term ambient ozone exposure and attention-deficit/hyperactivity disorder symptoms among Chinese children.

BACKGROUND: Although ozone exposure has neurological toxicity, it remains unclear whether it was associated with an increased risk of attention-deficit/hyperactivity disorders (ADHD) among childhood. METHODS: We matched the four-year average ozone concentration with questionnaire data for 35,103 children aged 3-12 years from seven cities in Liaoning, China, 2012-2013. Using mixed-effect logistic regression models, we assessed the association of ozone concentration with multiple ADHD indicators using the Conners Abbreviated Symptom Questionnaire (C-ASQ), including explicit attention-deficit/hyperactivity symptoms (ADHD; score ≥15), attention-deficit/hyperactivity disorder tendencies (ADHD-T; 11 ≤ score ≤14), and attention-deficit/hyperactivity problems (ADHP; score ≥11). Results were also stratified by sociodemongraphics. RESULTS: After adjusting for covariates, we found that each interquartile range (IQR) increase in ozone concentration was associated with an increased risk of ADHD, ADHD-T, and ADHP (P < 0.001) with an odds ratio of 1.12 (95% confidence interval, 1.04-1.21), 1.08 (1.03-1.13), and 1.09 (1.05-1.14), respectively. Additionally, we found greater effect estimates in children who reported longer exercise time (vs those with limited exercise time) with odds ratio of 1.18 (1.07-1.31) vs 1.06 (0.96-1.17) for ADHD, 1.13 (1.06-1.21) vs 1.03 (0.96-1.10) for ADHD-T, and 1.15 (1.08-1.21) vs 1.04 (0.98-1.10) for ADHP. Non-breastfed children were also shown to be more vulnerable to ADHD with an odds ratio of 1.22 (1.09-1.36) compared with 1.06 (0.96-1.16) among the rest. CONCLUSIONS: Long-term ozone exposure may be associated with increased ADHD among children. Additional studies are needed to validate our findings and support policies and interventions to address this growing public health concern.

A prospective analysis of optimal total weight gain ranges and trimester-specific weight gain rates for Chinese pregnant women.

BACKGROUND: Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. METHODS: Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized Additive Models were performed to determine the associations of GWG with the risk of aggregated adverse outcomes (gestational diabetes mellitus, preeclampsia, cesarean delivery, stillbirth, preterm birth, macrosomia, large for gestational age, and small for gestational age). The range that did not exceed a 2.5% increase from the lowest risk of aggregated adverse outcomes was defined as the optimal GWG range. RESULTS: Among all participants, U-shaped prospective association was found between GWG and the risk of aggregated adverse pregnancy outcomes. The optimal GWG range of 8.2-13.0 kg was proposed for underweight, 7.3-12.5 kg for normal weight, and 2.0-9.4 kg for overweight/obese women. Meanwhile, a higher GWG rate in the first two trimesters than that in the last trimester was suggested, except for overweight/obese women. After stratified by maternal age, mothers ≥35 years were suggested to gain less weight compared to younger mothers. CONCLUSIONS: To keep a balance between maternal health and neonatal growth, optimal GWG ranges based on Asia-specific BMI categories was suggested for Chinese women with different pre-gravid BMIs and maternal ages.