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Abstract Background Gastric cancer presents a major health burden worldwide. Therefore, many molecular targeting agents have been evaluated for treatment of gastric cancer. Gefitinib has shown anticancer activity against gastric cancer which work through inhibiting epidermal growth factor receptor (EGFR). However, the effect of gefitinib is limited due to its resistance. Therefore, understanding the mechanisms of gefitinib resistance is desperately needed to formulate novel strategies against gastric cancer. Here, we analyzed resistance mechanism from the crosstalk between EGFR and integrin β4. Methods Integrin β4-expression vector or siRNA were used to analyze the functional effects of integrin β4 on chemoresistance of gastric cancer cells to gefitinib. EGFR and integrin β4 expression, proliferation and apoptosis of gastric cancer cells were assayed by indirect immunofluorescence, western blot, MTT and flow cytometry respectively. EGFR and integrin β4 expression were also assayed on patient samples. Results It was found that the integrin β4 expression was increased in gefitinib-resistant gastric cell line. The upregulated integrin β4 expression was identified to promote gefitinib resistance and proliferation, and inhibit apoptosis, while downregulation of integrin β4 was to inhibit gefitinib resistance and proliferation, and induce apoptosis. Moreover, the overexpression of integrin β4 in SGC7901 cells resulted in the down-regulation of p-EGFR protein levels while down-regulation of integrin β4, significantly resulted in overexpression of p-EGFR. The results of western blot from patients also showed there was obvious negative correlation between p-EGFR and integrin β4 in gastric cancer patients. Conclusion Considering the above results, it is concluded that the interaction of EGFR and integrin β4 may change the sensitivity of gefitinib treatment.

Precise time trajectories and detailed reaction pathways of the Diels-Alder reaction were directly observed using accurate single-molecule detection on an in situ label-free single-molecule electrical detection platform. This study demonstrates the well-accepted concerted mechanism and clarifies the role of charge transfer complexes with endo or exo configurations on the reaction path. An unprecedented stepwise pathway was verified at high temperatures in a high-voltage electric field. Experiments and theoretical results revealed an electric field-catalyzed mechanism that shows the presence of a zwitterionic intermediate with one bond formation and variation of concerted and stepwise reactions by the strength of the electric field, thus establishing a previously unidentified approach for mechanistic control by electric field catalysis.

With the increasing drilling depth of mines, the cross-complexity of fissures in the rock body, and the frequent occurrence of sudden water surges, polymer slurry, with its advantages of good permeability and strong water plugging, is increasingly used in mine grouting projects. Additional research is needed in order to further improve the grouting performance of polymer slurry, ensure the safety of mining operations, and reduce the grouting cost. In this paper, a polymer composite grouting material was prepared with diphenyl methyl diisocyanate, polyether polyol, and fly ash, as the main raw materials, with coupling agent and catalyst as auxiliary reagents. The performance of the composite grouting material in terms of mechanical properties, thermal stability, hydrophobicity, and bonding was explored. This study's findings indicated that incorporating fly ash led to notable enhancements in the thermal stability and water resistance of the polymer slurry. Furthermore, the introduction of fly ash notably raised the starting degradation temperature of the polymer, boosted the water contact angle of the composite material, and reduced the density and reaction temperature of the composite material. In addition, the catalyst and coupling agent as auxiliary reagents affected the polymers in terms of mechanical properties; in this paper, dibutyltin dilaurate was used as the catalyst, and organosilanes were used as the coupling agent. The catalyst successfully sped up the polymer's gel time, however, an excessive quantity of catalyst compromised the polymer's mechanical characteristics. The addition of organosilanes has a positive effect on the dynamic mechanical properties of the composites, fracture toughness, compression, bending, and bond strength. The research can offer a theoretical direction for creating polymer mixtures in mine grouting projects. [ABSTRACT FROM AUTHOR]

Single-molecule detection can reveal time trajectories and reaction pathways of individual intermediates/transition states in chemical reactions and biological processes, which is of fundamental importance to elucidate their intrinsic mechanisms. We present a reliable, label-free single-molecule approach that allows us to directly explore the dynamic process of basic chemical reactions at the single-event level by using stable graphene-molecule single-molecule junctions. These junctions are constructed by covalently connecting a single molecule with a 9-fluorenone center to nanogapped graphene electrodes. For the first time, real-time single-molecule electrical measurements unambiguously show reproducible large-amplitude two-level fluctuations that are highly dependent on solvent environments in a nucleophilic addition reaction of hydroxylamine to a carbonyl group. Both theoretical simulations and ensemble experiments prove that this observation originates from the reversible transition between the reactant and a new intermediate state within a time scale of a few microseconds. These investigations open up a new route that is able to be immediately applied to probe fast single-molecule physics or biophysics with high time resolution, making an important contribution to broad fields beyond reaction chemistry.

The efficiency of the intersystem crossing process can be improved by reducing the energy gap between the singlet and triplet excited states (ΔEST), which offers the opportunity to improve the yield of the triplet excited state. Herein, we demonstrate that modulation of the excited states is also an effective strategy to regulate the singlet oxygen generation of photosensitizers. Based on our previous studies that photosensitizers with aggregation-induced emission characteristics (AIE) showed enhanced fluorescence and efficient singlet oxygen production in the aggregated state, a series of AIE fluorogens such as TPDC, TPPDC and PPDC were synthesized, which showed ΔEST values of 0.48, 0.35 and 0.27 eV, respectively. A detailed study revealed that PPDC exhibited the highest singlet oxygen efficiency (0.89) as nanoaggregates, while TPDC exhibited the lowest efficiency (0.28), inversely correlated with their ΔEST values. Due to their similar optical properties, TPDC and PPDC were further encapsulated into nanoparticles (NPs). Subsequent surface modification with cell penetrating peptide (TAT) yielded TAT-TPDC NPs and TAT-PPDC NPs. As a result of the stronger singlet oxygen generation, TAT-PPDC NPs showed enhanced cancer cell ablation as compared to TAT-TPDC NPs. Fine-tuning of the singlet-triplet energy gap is thus proven to be an effective new strategy to generate efficient photosensitizers for photodynamic therapy.

Acute pancreatitis (AP) is a common disease in the department of gastroenterology with variable severity, from being mild and self-limited to severe and fatal. The early diagnosis and accurate prediction of AP severity are of great importance. Our primary observation showed that fatty liver (FL) was frequently detected in patients with AP. In this retrospective study, we aimed to evaluate the relation between FL and the severity and outcomes of AP. The medical records of 2671 patients with AP were reviewed retrospectively, and characteristics of AP patients were recorded. FL was assessed by abdominal CT scan, and AP patients were categorized by the occurrence of FL for the analysis. The variation of mortality, clinical severity and the appearance of CT were analyzed between the non-FL group and FL groups. Compared with patients without FL, an obviously higher rate of death and higher frequency of severe AP (SAP) and necrotizing AP (ANP) were observed in patients with FL, as well as the incidence of local complications and systemic complications. Taking obesity into consideration, a higher rate of death and more severe AP were found in patients with FL, no matter whether they were obese or not. Alcoholic fatty liver (AFL) and non-alcoholic fatty liver (NAFL) were also separated for comparison in this study; the incidence of ANP and the clinical severity had no significant difference between the AFL and NAFL groups. In conclusion, FL could influence the severity and clinical outcome and may play a prognostic role in AP. This study is of clinical significance, because few reports have been previously issued on FL and AP.

In recent decades, polymer semiconductors, extensively employed as charge transport layers in devices like organic field‐effect transistors (OFETs), have undergone thorough investigation due to their capacity for large‐area solution processing, making them promising for mass production. Research efforts have been twofold: enhancing the charge mobilities of polymer semiconductors and augmenting their mechanical properties to meet the demands of flexible devices. Significant progress has been made in both realms, propelling the practical application of polymer semiconductors in flexible electronics. However, integrating excellent semiconducting and mechanical properties into a single polymer still remains a significant challenge. This review intends to introduce the design strategies and discuss the properties of high‐charge mobility stretchable conjugated polymers. In addition, another key challenge faced in this cutting‐edge field is maintaining stable semiconducting performance during long‐term mechanical deformations. Therefore, this review also discusses the development of healable polymer semiconductors as a promising avenue to improve the lifetime of stretchable device. In conclusion, challenges and outline future research perspectives in this interdisciplinary field are highlighted. [ABSTRACT FROM AUTHOR]

Since light propagation in water bodies is subject to absorption and scattering effects, underwater images using only conventional intensity cameras will suffer from low brightness, blurred images, and loss of details. In this paper, a deep fusion network is applied to underwater polarization images; that is, the underwater polarization images are fused with intensity images using the deep learning method. To construct a training dataset, we establish an experimental setup to obtain underwater polarization images and perform appropriate transformations to expand the dataset. Next, an end-to-end learning framework based on unsupervised learning and guided by an attention mechanism is constructed for fusing polarization and light intensity images. The loss function and weight parameters are elaborated. The produced dataset is used to train the network under different loss weight parameters, and the fused images are evaluated based on different image evaluation metrics. The results show that the fused underwater images are more detailed. Compared with light intensity images, the information entropy and standard deviation of the proposed method increase by 24.48% and 139%. The image processing results are better than other fusion-based methods. In addition, the improved U-net network structure is used to extract features for image segmentation. The results show that the target segmentation based on the proposed method is feasible under turbid water. The proposed method does not require manual adjustment of weight parameters, has faster operation speed, and has strong robustness and self-adaptability, which is important for research in vision fields, such as ocean detection and underwater target recognition. [ABSTRACT FROM AUTHOR]