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Abstract Background Little is known about the changes in allergen sensitization in China secondary to the environmental variations over the past decade. We aimed at investigating the variations in sensitization among asthma and/or rhinitis patients in China between 2008 and 2018. Methods This study analyzed cross‐sectional data from national surveys conducted in China in 2008 and 2018. After finishing the questionnaire, participants underwent serum specific IgE measurements. A total of 2322 and 2798 patients were enrolled in 2008 and 2018, respectively. The significance of differences in sensitization rates among four regions of China were assessed. Correlation analysis was used to identify the associations of sensitization with climate change and planting of Artemisia desertorum between the two surveys. Results Compared with 2008, the general sensitization rate to mites significantly increased in 2018, which ranked highest among all tested allergens. Sensitization to pollens, especially Artemisia vulgaris, showed the greatest increase in the north. The annual mean temperature, rainfall and relative humidity in all four regions, and the Artemisia desertorum coverage in the northeastern area, increased significantly in 2018 as compared with 2008. From 2008 to 2018, an increase in Dermatophagoides pteronyssinus sensitization was significantly associated with an increase in relative humidity (r = 0.54, p = 0.037). The increase in A. vulgaris sensitization was significantly associated with the increase in the A. desertorum planting area (r = 0.67, p = 0.006) and with a decrease in rainfall (r = −0.59, p = 0.021). Conclusions House dust mites remain the most important allergen in Chinese individuals with asthma and/or rhinitis. Pollen sensitization dramatically increased in northern China. Increases in sensitization to dust mites and Artemisia were related to the increases in humidity and planting area of A. desertorum.

Phthalate esters (PAEs) are a ubiquitous kind of environmental endocrine that disrupt chemicals, causing environmental and health issues. EstJ6 is an effective phthalate-degrading hydrolase, and its mutant with a combination of three non-conservative distal mutations has an improved activity against PAEs with unknown molecular mechanisms. Herein, we attempt to fill the significant gap between distal mutations and the activity of this enzyme using computational approaches. We found that mutations resulted in a redistribution of the enzyme’s preexisting conformational states and dynamic changes of key functional regions, especially the lid over the active site. The outward motion of the lid upon the mutations made it easier for substrates or products to enter or exit. Additionally, a stronger substrate binding affinity and conformational rearrangements of catalytic reaction-associated residues in the mutant, accompanied by the strengthened communication within the protein, could synergistically contribute to the elevated catalytic efficiency. Finally, an attempt was made to improve the thermostability of EstJ6 upon introducing a distal disulfide bond between residues A23 and A29, and the simulation results were as expected. Together, our work explored the allosteric effects caused by distal mutations, which could provide insights into the rational design of esterases for industrial applications in the future.

The parathyroid hormone type 1 receptor (PTH1R) acts as a canonical class B G protein-coupled receptor, regulating crucial functions including calcium homeostasis and bone formation. The identification and development of PTH1R non-peptide allosteric modulators have obtained widespread attention. It has been found that a negative allosteric modulator (NAM) could inhibit the activation of PTH1R, but the implied mechanism remains unclear. Herein, extensive molecular dynamics simulations together with multiple analytical approaches are utilized to unravel the mechanism of PTH1R allosteric inhibition. The results suggest that the binding of NAM destabilizes the structure of the PTH1R–PTH–spep/qpep (the C terminus of Gs/Gq proteins) complexes. Moreover, the presence of NAM weakens the binding of PTH/peps (spep and qpep) and PTH1R. The intra- and inter-molecular couplings are also weakened in PTH1R upon NAM binding. Interestingly, compared with our previous study of the positive allosteric effects induced by extracellular Ca2+, the enhanced correlation between the PTH and G-protein binding sites is significantly reduced by the replacement of this negative allosteric regulator. Our findings might contribute to the development of new therapeutic agents for diseases caused by the abnormal activation of PTH1R.

Phthalic acid esters (PAEs) are typical environmental endocrine disrupters, interfering with the endocrine system of organisms at very low concentrations. The plasma membrane is the first barrier for organic pollutants to enter the organism, so membrane permeability is a key factor affecting their biological toxicity. In this study, based on computational approaches, we investigated the permeation and intramembrane aggregation of typical PAEs (dimethyl phthalate, DMP; dibutyl phthalate, DBP; di-2-ethyl hexyl phthalate, DEHP), as well as their effects on membrane properties, and related molecular mechanisms were uncovered. Our results suggested that PAEs could enter the membrane spontaneously, preferring the headgroup-acyl chain interface of the bilayer, and the longer the side chain (DEHP > DBP > DMP), the deeper the insertion. Compared with the shortest DMP, DEHP apparently increased membrane thickness, order, and rigidity, which might be due to its stronger hydrophobicity. Potential of means force (PMF) analysis revealed the presence of an energy barrier located at the water-membrane interface, with a maximum value of 2.14 kcal mol−1 obtained in the DEHP-system. Therefore, the difficulty of membrane insertion is also positively correlated with the side-chain length or hydrophobicity of PAE molecules. These findings will inspire our understanding of structure-activity relationship between PAEs and their effects on membrane properties, and provide a scientific basis for the formulation of environmental pollution standards and the prevention and control of small molecule pollutants.

Epidermal growth factor receptor (EGFR) is an intensively focused target for anti-tumor compounds used in non-small cell lung cancer (NSCLC) therapy. Compared to the classical activating mutations, there are still many uncommon EGFR mutations associated with poorer responses to EGFR inhibitors. A detailed understanding of the molecular basis for multiple EGFR mutants exhibiting diverse responses to inhibitors is of critical importance for related drug development. Herein, we explored the molecular determinants contributing to the distinct responses of EGFR with a single rare mutation (G719S) or combined mutations (G719S/L858R and G719S/l861Q) to Gefitinib (IRE). Our results indicated that interactions, formed within the tetrad of residues S768 (in the αC-helix), D770 (in the αC-β4 loop), Y827 (in the αE-helix), and R831 (in the catalytic loop), play an important role in the stability of αC-helix and the maintenance of K745–E762 salt bridge in the absence of IRE, which are weakened in the EGFRG719S system and enhanced in the EGFRG719S/L858R system upon IRE binding. Besides, the introduced hydrogen bonds by the co-occurring mutation partner also contribute to the stability of αC-helix. The work done for inhibitor dissociation suggests that IRE exhibits a stronger binding affinity to EGFRG719S/L858R mutant. Together, these findings provide a deeper understanding of minor mutations, which is essential for drug development targeting EGFR with less common mutations.

In this study, coralline-activated materials were prepared using ball-milled coral powder as cementitious material and coral sand as fine aggregate. XRF (X-ray fluorescence) and chemical dissolution tests were carried out to determine the content and reactivity of various elements in coral powder. The compressive strength of the developed composites was evaluated at different ages, and the formation and transformation of mineral crystals in coralline-activated samples were further analyzed by XRD (X-ray diffractometer). The results show that the calcium content in coral powder was as high as 89.5% (loss on ignition). However, only 56% of the active calcium could participate in the polymerization reaction. The silicon and aluminum content was too low, and the slag addition could improve the deficiency of silicon and aluminum in coral powder. With the increase in slag content (from 0% to 50%), the compressive strength of the composites increases significantly. Nevertheless, the enhancement is not pronounced when the slag content exceeds 50%. The increase in slag amount can stimulate the transformation of calcium minerals, e.g., aragonite and calcite, into hydrated calcium silicate and calcium aluminosilicate gels, which significantly enhances the resulting compressive strength.

Successful intelligence theory suggests that creativity is necessary for personal achievement outside of intelligence. Unlike intelligence, creativity can develop in a supportive environment. People should consider the situation of disadvantaged groups, which are characterized by low personal achievement and a bad growth environment in creativity evaluation from a caring perspective. This study focuses on the effect of the creator’s situation on creative evaluation and the role of the rater’s empathy (i.e., cognitive empathy and affective empathy) and sympathy in creative evaluation. Four pairs of creator’s situations (by age, physical state, family situation, and economic state) were designed to represent people with disadvantages or advantages. A between-subject design was used with 590 undergraduate students randomly assigned to eight sub-conditions. The participants were asked to assess three products in eight situations. The rater’s empathy and sympathy in creativity evaluation were explored in the overall disadvantage (N = 300) and advantage (N = 290) conditions. The results showed that the participants only provided significantly higher ratings to the creative product made by a child. Cognitive empathy only predicted a creative rating under disadvantaged conditions, and affective empathy negatively moderated this effect. Affective empathy only predicted a creative rating under advantage conditions, and cognitive empathy positively moderated this effect. Affective empathy only predicted a creative rating under advantage conditions, and cognitive empathy positively moderated this effect. The possible mechanisms of the effect and implications for the establishment of a supportive environment for creativity and creativity teaching practice were discussed.