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Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Background: Anterior gradient 2 (AGR2) is highly enriched in several malignant tumors and can boost tumor metastasis. Whereas, AGR2 role in colorectal cancer (CRC) is not clear. Methods: AGR2 expression in the GEPIA database was studied, and the results were confirmed by Western blot in CRC cell lines (SW480, SW620, and HT-29). The impact of AGR2 on the multiplication, migration, invasion and EMT of CRC cells were studied by CCK-8 assay, as well as clone formation, wound healing and transwell assays. The protein concent related to the AKT/β-catenin signaling pathway were accessed via Western blot. Results: AGR2 concent in CRC tissues was notablely boosted versus normal colorectal tissues. Exogenous AGR2 boosted the multiplication of CRC cells. In addition, exogenous AGR2 induced EMT, which demonstrated that ZEB1, N-cadherin, Vimentin, Slug, Snail protein concent boosted and E-cadherin protein abated in CRC cells. In terms of mechanism, exogenous AGR2 upgulated p-AKT/AKT, p-GSK3β/GSK3β and β-catenin concent. Exogenous AGR2 combined with AKT agonist IGF- Ⅰ can further enhance the multiplication, migration and invasion of CRC cells. Conclusion: Exogenous AGR2 enhances the multiplication of CRC cells and induces EMT process, the mechanism of which is related to AKT/β-catenin signal pathway.

Geographical differences are conspicuous in lung cancer, and the distinct molecular features of lung tumor between Western patients and Asian patients have been demonstrated. However, the etiology of non-small-cell lung cancer (NSCLC) and the distribution of associated molecular aberrations in China have not been fully elucidated. The mutational profiles of 12 lung cancer-related genes were investigated in 85 patients from eastern China and 88 patients from southern China who had been histologically confirmed NSCLC. Overall, 93.6% (162/173) of tumor samples harbored at least one somatic alteration. The most frequently mutated genes were TP53 (56.1%), EGFR (50.3%), and KRAS (14.5%). We found that EGFR mutated much more frequently (60.0% vs 40.9%, P = 0.012) and TP53 mutations had significantly lower incidence (47.1% vs 64.8%, P = 0.019) in eastern cohort than that in southern cohort. Mutational signature analysis revealed a region-related mutagenesis mechanism characterized by a high prevalence of C to T transitions mainly occurring at CpG dinucleotides in southern patients. This study reveals the difference in the mutational features between NSCLC patients in eastern and southern China. The distinct patterns of gene mutation could provide clues for the mechanism of carcinogenesis of lung cancer, offering opportunities to stratify patients into optimal treatment plans based on genomic profiles.

Background: It is necessary to determine the diabetes knowledge level among non-endocrinology nurses in primary care hospitals to develop continuing education strategies. Method: A questionnaire survey was conducted among 6819 non-endocrinology nurses in 70 primary hospitals in the Guangxi Zhuang Autonomous Region to assess their diabetes knowledge level and training needs. Factors affecting knowledge level were analyzed using multiple linear regression models. Results: Diabetes knowledge was low, particularly for diabetes monitoring. Knowledge was higher in nurses who had in-service education and training in diabetes; most believed that training was necessary and hoped to improve their ability to care for diabetic patients. The most suitable training method was considered to be each nurse was taught by an assigned person after centralized specialized education and training. Conclusion: Non-endocrinology nurses in primary care hospitals lack knowledge of diabetes and have a strong need for training. Systematic training is required to ensure that patients receive high-quality and comprehensive care.

Polycationic vectors are a promising class of gene delivery systems. To improve delivery efficiency and reduce cytotoxicity, hydrophobic modification has been proposed as an effective way. Herein, we synthesized a class of terpolymer vectors with various hydrophobicities as well as multiple biodegradable disulfide bonds and cationic side chains. The chemical structure and hydrophobic modification ratio of polymers were characterized. The amphiphilic vectors were able to condense pDNA to form flexible and uniform nanoparticles with a size of 60–85 nm. The shielding effect of hydrophobic side chains led to a lower zeta potential and reduced cytotoxicity. The endocytosis efficiency of amphiphilic vectors was significantly increased and the endocytosis pathway shifted from mainly via the clathrin pathway to clathrin/caveolae/lipid raft co-mediated endocytosis. The amphiphilic vectors demonstrated significantly higher transfection efficiency. In addition, the hydrophobic structural domain of polymers could improve serum stability, alleviating the serum inhibition commonly seen in cationic polymers. Then, we tested the tumor-suppressor gene wtp53 delivered by the amphiphilic vectors in triple-negative breast cancer models both in vitro and in vivo. Tumor cell cycle arrest and apoptosis were triggered through the regulation of downstream cell cycle proteins and apoptosis proteins, inhibiting tumor growth with an excellent safety profile.

Wnt signaling is one of the key cascades regulating normal tissue development and has been tightly associated with cancer. The Wnt signaling can be subdivided into two categories: canonical & noncanonical. Noncanonical Wnt signaling pathways mainly include Wnt/PCP (planar cell polarity) signaling and Wnt-cGMP (cyclic guanosine monophosphate) /Ca2+ signaling. It has been well studied by previous researches that noncanonical Wnt signaling regulates multiple cell functions including proliferation, differentiation, adhesion, polarity, motility, and migration. The aberrant activation or inhibition of noncanonical Wnt signaling is crucial in cancer progression, exerting both oncogenic and tumor-suppressive effects. Recent studies show the involvement of noncanonical Wnt in regulating cancer cell invasion, metastasis, metabolism, and inflammation. Here, we review current insights into novel components of non-canonical signalings and describe their involvement in various cancer types. We also summarize recent biological and clinical discoveries that outline non-canonical Wnt signaling in tumorigenesis. Finally, we provide an overview of current strategies to target non-canonical Wnt signaling in cancer and challenges that are associated with such approaches.

Background: The Readiness for Hospital Discharge Scale (RHDS)−Parent Form shows satisfactory reliability and validity to assess the readiness of parents to take care of their children discharged from hospitals in Western countries. However, the reliability and validity of this instrument has not been evaluated in Chinese populations. Objectives: Evaluate the psychometric features of the RHDS−Parent Form among Chinese parents of preterm infants. Methods: The RHDS−Parent Form was translated into a Chinese version following an international instrument translation guideline. A total of 168 parents with preterm infants were recruited from the neonatal intensive care units of two tertiary-level hospitals in China. The internal consistency of this measure was assessed using the Cronbach's α coefficient; confirmatory factor analysis was conducted to evaluate the construct validity; and Pearson correlation coefficient was used to report the convergent validity. Results: The Chinese version of RHDS (C-RHDS)−Parent Form included 22 items with 4 subscales, accounting for 56.71% of the total variance. The C-RHDS−Parent Form and its subscales showed good reliability (Cronbach's α values 0.78–0.92). This measure and its subscales showed positive correlations with the score of Quality of Discharge Teaching Scale. Conclusion: The factor structure of C-RHDS−Parent Form is partially consistent with the original English version. Future studies are needed to explore the factors within this measure before it is widely used in Chinese clinical care settings.

Objective: The aim of this study was to assess the effect of flap design for impacted mandibular third molar extraction on the distal periodontal tissue of their neighbors clinically, immunologically, and microbiologically. Study design: This randomized controlled study comprised 100 patients who were allocated randomly to receive either a triangular flap or a modified triangular flap. The distal periodontal pocket depth, plaque index, bleeding on probing, the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, and the level of interleukin-1β, interleukin-8 and matrix metalloproteinase-8 of adjacent second molars were measured at baseline, and 1, 4 and 8 weeks after surgery. Results: After 1 and 4 weeks, distal periodontal conditions of adjacent second molars deteriorated, along with an increase in subgingival microbiota and inflammatory factors in both groups. And compared to the modified triangular flap group, the triangular flap group significantly increased (p

In this paper, the dynamic stress intensity factor (DSIF) at the crack tip of a PMMA beam containing an internal offset crack under impact loading was investigated by using a transmission digital caustic test system combined with high-speed camera. Firstly, the stress intensity factor, as well as velocity, of the mixed-mode crack tip under static and dynamic loading were derived based on the transmission caustic method; secondly, a drop hammer loading test was conducted on the different specimens with biased cracks in the beam using the transmission caustic test system to obtain the dynamic fracture mechanics parameters of internal crack initiation and expansion; then, the crack initiation angle and expansion path analysis of the impact-generated expansion cracks were performed based on the theoretical analysis and the differences between the fracture process and that of the specimens containing internal symmetric cracks were discussed. The results show that the different locations of the internal off-set cracks make the stress redistribution process inside the beam and the stress state at the crack tip during the crack extension process different, and the fracture process and fracture mechanics parameters are different from those of the specimens with internal symmetric cracks, the results of the caustic test are in good agreement with the numerical analysis. The research results can provide guidance for the study of the fracture process of brittle materials such as PMMA containing internal defects.

The Chinese Loess Plateau has been the cradle of Chinese civilization and the main human settlement in China for thousands of years, where anthropogenic activities are believed to have deeply eroded natural landscapes. After decades of minimal leopard sighting in forests of northern China, due to serious human interference, we recently discovered that the leopard population is recovering. This finding provides hope for successful biodiversity conservation in human-dominated ecosystems. To understand the mechanism of leopard return into such a highly fragmented landscape, we applied the concept of ecological networks (ENs) to identify key factors promoting leopard restoration and quantify the ecological links among habitats. We first determined the existence of a healthy leopard population in the study area based on the size of its home range and presence of breeding individuals. We then innovatively used the relationship between species richness and top predators to generate ENs, and found that the connectivity of ENs had a significant positive interaction with leopard survival. Our study validates the effectiveness of establishing ecologically connected habitats for leopard protection, and highlights the importance of applying ENs for conservation planning in highly fragmented ecosystems. This study provides a successful case for the protection of top predators in human-dominated landscapes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)