LncRNA DDX11-AS1 promotes cell growth, migration and invasion through regulating epithelial-mesenchymal transition in breast cancer.

This study aimed to investigate the expression of long non-coding ribonucleic acid (lncRNA) DDX11 antisense RNA 1 (DDX11-AS1) in breast cancer (BC) tissues and cells and investigate its biological function and potential molecular mechanism through in vitro experiments. Tissue specimens were obtained from 44 BC patients. TRIzol method was used to extract RNAs from the tissues. The relative expression of DDX11-AS1 in BC tissues and the expression of DDX11-AS1 in BC cells were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effect of DDX11-AS1 on the proliferation ability of BC cells was detected via cell counting kit-8 (CCK-8) assay. Flow cytometry was adopted to study the effect of DDX11-AS1 on the distribution of BC cell cycle. Transwell assays were performed to analyze the effects of DDX11-AS1 on the migration and invasion abilities of BC cells. Finally, after interfering with the expression of DDX11-AS1 in BC cells, changes in the expressions of molecular markers for epithelial-mesenchymal transition (EMT) were detected via Western blotting. According to the results of qRT-PCR, the expression of DDX11-AS1 was up-regulated in 38 out of 44 cases of BC tissues compared with that in the para-carcinoma tissues, and the expression of DDX11-AS1 in BC cells was up-regulated as well. After interference with the expression of DDX11-AS1 in BC cells, it was found via CCK-8 assay that the proliferation ability of BC cells was restrained, flow cytometry results showed that the BC cell cycle was arrested at G1/G0 phase, and the results of transwell assays revealed that the cell invasion and migration abilities were suppressed in experimental group compared with those in control group. According to the results of Western blotting, after interfering with the expression of DDX11-AS1 in BC cells, there were changes in the expressions of molecular markers for EMT. In BC, the expression of lncRNA DDX11-AS1 is up-regulated, which promotes the proliferation, migration and invasion of BC cells by regulating EMT.

Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer.

Differential activation of macrophages is associated with poor progression of breast cancer (BC). Many reports have elucidated the important involvement of exosomes produced by cancer cells in remodeling the macrophage activation phenotype to promote tumor expansion and invasion. However, the underlying mechanisms by which exosomes secreted by BC cells facilitate macrophage M2 polarization remain enigmatic and worth exploring. In this study, quantitative real-time PCR (RT-qPCR) was used to investigate miR-191-5p expression in BC tumor tissues and cells. Cell counting kit 8 (CCK-8), transwell, and flow cytometry were applied to assess the functional role of miR-191-5p in BC. Isolated nano-vesicles were identified using transmission electron microscopy and western blotting. We also observed that miR-191-5p was significantly elevated in BC clinical samples and that inhibition of miR-191-5p hindered the growth and metastasis of BC cells. Importantly, BC cells successfully accelerated macrophage M2-like polarization by directly transferring exosomes to macrophages, resulting in increased miR-191-5p levels in macrophages. Mechanistically, exosomal miR-191-5p directly inhibited the suppressors of cytokine signaling 3 (SOCS3) expression in macrophages and aggravated macrophage M2 polarization. Similarly, si-SOCS3 transfected macrophages boosted BC cell migration and invasion in a positive feedback manner. Overall, our results manifested a pro-growth and pro-metastatic role between the two cells by elucidating the crucial role of exosomal miR-191-5p in stimulating M2 macrophage polarization and mediating communication between BC cells and macrophages. These findings opened up new horizons for the development of BC therapeutic strategies.

Three-dimensional (3D) quantitative evaluation of the morphological changes of the upper anterior alveolar bone after retraction of a maxillary incisor.

BACKGROUND: The purpose of this study was to assess morphological changes of the upper anterior alveolus after retraction of a maxillary incisor by applying three-dimensional (3D) superimposition of pretreatment (T1) and posttreatment (T2) cone-beam computed tomography (CBCT) data. METHODS: The study group was comprised of 28 patients with skeletal Class II malocclusion who underwent incisor retraction. CBCT data were acquired before (T1) and after (T2) orthodontic treatment. Labial and palatal alveolar thickness were assessed at the crestal, midroot and apical levels of the retracted incisors. Following three-dimensional (3D) cranial base superimposition, we performed surface modeling and inner remodeling of the labial and palatal alveolar cortex of the maxillary incisors. Paired t-tests were used to compare T0 and T1 bone thickness and volume measurements. Comparisons between labial and palatal surface modeling, inner remodeling and outer surface modeling were performed with paired t-tests in SPSS 20.0 version. RESULTS: We observed controlled tipping retraction of the upper incisor. After treatment, the alveolar thickness on the labial sides increased and the palatal alveolar thickness decreased. The labial cortex showed a wider range of modeling area with a larger bending height and a smaller bending angle than the palatal side. The extent of inner remodeling was more prominent than the outer surface on both the labial and palatal sides. CONCLUSIONS: Adaptive alveolar surface modeling occurred in response to incisor tipping retraction on both the lingual and labial sides although these changes occurred in an uncoordinated manner. Tipping retraction of the maxillary incisors led to a reduction in alveolar volume.

Effect of fast-track surgery model on postoperative pain and hospital stay of patients undergoing thyroid surgery.

OBJECTIVE: To investigate the effect of fast-track surgery on emotions, pain, and length of hospital stay during the preoperative period for thyroid disease. STUDY DESIGN AND METHODS: From June 2020 to September 2020, 43 patients who received routine perioperative nursing for thyroid disease in Ganzhou People's Hospital were retrospectively included as a control group, and 51 patients who received nursing care on the basis of fast-track surgery strategy from June 2020 to September 2020 in Ganzhou People's Hospital were retrospectively included as an experimental group. Time spent out of bed, length of hospital stay, medical expenses, and time of indwelling catheter use were compared between the two groups. Visual analogue scale (VAS) was used to evaluate the variations in intensity of pain postoperatively. The incidence of adverse reactions was recorded and compared. The risk factors affecting complications in patients undergoing surgery for thyroid disease were evaluated. RESULTS: Patients in the experimental group had shorter time spent out of bed, shorter length of hospital stay, less medical expenses, and shorter time of indwelling catheter use than those in the control group (all P < 0.05). The experimental group exhibited lower VAS scores than control group at 3 to 5 days after surgery (both P < 0.05). The total incidence of adverse reactions in the experimental group was lower than that in the control group (P < 0.05). Univariate analysis showed that gender, reoperation, intraoperative blood loss, and the use of recurrent laryngeal nerve detector were single factors affecting perioperative complications, while Logistic regression analysis showed that reoperation, intraoperative blood loss and the use of recurrent laryngeal nerve detector were highly correlated with perioperative complications (all P < 0.05). CONCLUSION: Fast-track surgery can significantly accelerate the rehabilitation of patients, alleviate postoperative pain and adverse emotions, and reduce the incidence of adverse reactions in patients with thyroid disease, which has positive significance to improve the prognosis of patients, and thus it is recommended for clinical promotion.

Study on Hydro-Mechanical Coupling Failure and Permeability Enhancement Mechanisms for Sandstone with T-Shaped Fractures.

The rise in the connectivity of the fractures is a key task in oil/gas and geothermal exploitation systems. Natural fractures widely exist in underground reservoir sandstone, while the mechanical behavior of rock with fractures subjected to hydro-mechanical coupling loads is far from clear. This paper employed comprehensive experiments and numerical simulations to investigate the failure mechanism and permeability law for sandstone specimens with T-shaped faces subjected to hydro-mechanical coupling loads. The effects of crack closure stress, crack initiation stress, strength, and axial strain stiffness of the specimens under different fracture inclination angles are discussed, and the evolution processes of permeability are obtained. The results show that secondary fractures are created around the pre-existing T-shaped fractures through tensile, shear, or mixed modes. The fracture network causes an increase in the permeability of the specimen. T-shaped fractures have a more significant effect on the strength of the specimens than water. The peak strengths of T-shaped specimens decreased by 34.89%, 33.79%, 46.09%, 39.32%, 47.23%, 42.76%, and 36.02%, respectively, compared with intact specimen without water pressure. With the increase in deviatoric stress, the permeability of T-shaped sandstone specimens decreases first, then increases, reaching its maximum value when macroscopic fractures are formed, after which the stress suddenly decreases. When the prefabricated T-shaped fracture angle is 75°, the corresponding permeability of the sample at failure is maximum, with a value of 15.84 × 10-16 m2. The failure process of the rock is reproduced through numerical simulations, in which the influence of damage and macroscopic fractures on permeability is discussed.

Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/D2R heterodimers.

Growth hormone secretagogue receptor 1a (GHS-R1a) is an important G protein-coupled receptor (GPCR) that regulates a variety of functions by binding to ghrelin. It has been shown that the dimerization of GHS-R1a with other receptors also affects ingestion, energy metabolism, learning and memory. Dopamine type 2 receptor (D2R) is a GPCR mainly distributed in the ventral tegmental area (VTA), substantia nigra (SN), striatum and other brain regions. In this study we investigated the existence and function of GHS-R1a/D2R heterodimers in nigral dopaminergic neurons in Parkinson's disease (PD) models in vitro and in vivo. By conducting immunofluorescence staining, FRET and BRET analyses, we confirmed that GHS-R1a and D2R could form heterodimers in PC-12 cells and in the nigral dopaminergic neurons of wild-type mice. This process was inhibited by MPP+ or MPTP treatment. Application of QNP (10 µM) alone significantly increased the viability of MPP+-treated PC-12 cells, and administration of quinpirole (QNP, 1 mg/kg, i.p. once before and twice after MPTP injection) significantly alleviated motor deficits in MPTP-induced PD mice model; the beneficial effects of QNP were abolished by GHS-R1a knockdown. We revealed that the GHS-R1a/D2R heterodimers could increase the protein levels of tyrosine hydroxylase in the SN of MPTP-induced PD mice model through the cAMP response element binding protein (CREB) signaling pathway, ultimately promoting dopamine synthesis and release. These results demonstrate a protective role for GHS-R1a/D2R heterodimers in dopaminergic neurons, providing evidence for the involvement of GHS-R1a in PD pathogenesis independent of ghrelin.

Cellular communication network factor 1 interlinks autophagy and ERK signaling to promote osteogenesis of periodontal ligament stem cells.

OBJECTIVES: To investigate the effects of cellular communication network factor 1 (CCN1), a critical matricellular protein, on alveolar bone regeneration, and to elucidate the underlying molecular mechanism. BACKGROUND: In the process of orthodontic tooth movement, bone deposition on the tension side of human periodontal ligament stem cells (hPDLSCs) ensured high efficiency and long-term stability of the treatment. The matricellular protein CCN1 is responsive to mechanical stimulation, exhibiting important tasks in bone homoeostasis. However, the role and mechanism of CCN1 on alveolar bone remodeling of hPDLSCs remains unclear. METHODS: The expression and distribution of CCN1 in rat periodontal ligament were detected by immunofluorescence staining and immunohistochemical staining. ELISA verified the secretion of CCN1 triggered by stretch loading. To examine the mineralization ability of hPDLSCs induced by CCN1, Western blotting, qRT-PCR, ARS, and ALP staining were performed. CCK-8 and cell migration assay were performed to detect the cell proliferation rate and the wound healing. PI3K/Akt, MAPK, and autophagy activation were examined via Western blotting and immunofluorescence. RESULTS: Mechanical stimuli induced the release of CCN1 into extracellular environment by hPDLSCs. Knockdown of CCN1 attenuated the osteogenesis of hPDLSCs while rhCCN1 enhanced the expression of Runx2, Col 1, ALPL, and promoted the mineralization nodule formation. CCN1 activated PI3K/Akt and ERK signaling, and blockage of PI3K/Akt signaling reversed the accelerated cell migration triggered by CCN1. The enhanced osteogenesis induced by CCN1 was abolished by ERK signaling inhibitor PD98059 or autophagy inhibitor 3-MA. Further investigation demonstrated PD98059 abrogated the activation of autophagy. CONCLUSION: This study demonstrated that CCN1 promotes osteogenesis in hPDLSCs via autophagy and MAPK/ERK pathway.

Spatiotemporal evolution of online attention to vaccines since 2011: An empirical study in China.

Since the outbreak of Coronavirus Disease 2019 (COVID-19), the Chinese government has taken a number of measures to effectively control the pandemic. By the end of 2021, China achieved a full vaccination rate higher than 85%. The Chinese Plan provides an important model for the global fight against COVID-19. Internet search reflects the public's attention toward and potential demand for a particular thing. Research on the spatiotemporal characteristics of online attention to vaccines can determine the spatiotemporal distribution of vaccine demand in China and provides a basis for global public health policy making. This study analyzes the spatiotemporal characteristics of online attention to vaccines and their influencing factors in 31 provinces/municipalities in mainland China with Baidu Index as the data source by using geographic concentration index, coefficient of variation, GeoDetector, and other methods. The following findings are presented. First, online attention to vaccines showed an overall upward trend in China since 2011, especially after 2016. Significant seasonal differences and an unbalanced monthly distribution were observed. Second, there was an obvious geographical imbalance in online attention to vaccines among the provinces/municipalities, generally exhibiting a spatial pattern of "high in the east and low in the west." Low aggregation and obvious spatial dispersion among the provinces/municipalities were also observed. The geographic distribution of hot and cold spots of online attention to vaccines has clear boundaries. The hot spots are mainly distributed in the central-eastern provinces and the cold spots are in the western provinces. Third, the spatiotemporal differences in online attention to vaccines are the combined result of socioeconomic level, socio-demographic characteristics, and disease control level.

Condylar morphology and position changes after miniscrew-assisted rapid palatal expansion in skeletal Class III malocclusion adult patients with mandibular deviation and unilateral posterior crossbite.

BACKGROUND: To evaluate the morphological and positional changes of mandibular condyle after miniscrew-assisted rapid palatal expansion (MARPE) in skeletal Class III malocclusion adult patients with horizontal mandibular deviation (MD). METHODS: The sample consisted of 15 patients with MD (6 males and 9 females, mean age 21.58 ± 3.12 years). The CBCT scans were taken before and after MARPE immediately. The pre- and post-registered images of the cranial base and mandible were measured, respectively, by Mimics. RESULTS: After expansion, the distance between superior condylar point and the Frankfort horizontal plane on the deviated side and the non-deviated side increased by 0.96 ± 0.60 mm (P = 0.011) and 0.70 ± 0.65 mm (P = 0.046); coronal condylar angle of the deviated side increased by 0.39° ± 0.34 (P = 0.028) and 0.06° ± 0.49 (P = 0.917) on the non-deviated side. No statistically significant differences were found when comparing the condylar position on both sides before and after treatment. The degree of mandibular deviation decreased 0.43 mm (P = 0.270). CONCLUSIONS: This study suggested that for skeletal Class III malocclusion adult patients with horizontal MD, the condyle on the deviated side rotated toward the non-deviated side in the coronal direction; the condylar remodeling occurred mainly on the deviated side after MARPE in the vertical direction.

N-acetylcysteine promotes cyclic mechanical stress-induced osteogenic differentiation of periodontal ligament stem cells by down-regulating Nrf2 expression.

Background/purpose: Mechanical stress plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Cyclic mechanical stress may up-regulate reactive oxygen species (ROS) level. N-acetylcysteine (NAC) possesses powerful antioxidant capacity. However, it is undefined the impact of NAC on osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs. The aim of our research was to study the effect of NAC on PDLSCs during osteogenic differentiation under cyclic mechanical stress. Materials and methods: The expression levels of osteogenesis markers were used to examine the osteogenic differentiation of PDLSCs. ROS production were measured by flow cytometry. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were analyzed. We also examined the changes of alveolar bone and periodontal ligament (PDL) tissues in orthodontic rats by micro-computed tomography (micro-CT) system and immunohistochemistry (IHC) staining. The nuclear factor erythroid-2-related factor-2 (Nrf2) expression was examined. Results: NAC could enhance the osteogenic differentiation and up-regulate the GSH level as well as the ratio of GSH/GSSG, while down-regulate ROS generation and Nrf2 expression induced by cyclic mechanical stress in PDLSCs. NAC had beneficial effects on the microstructure of alveolar bone and enhanced the expression levels of osteogenesis markers, such as alkaline phosphatase (ALP) and collagen type 1 (COL1) in PDL in orthodontic rats at the tension side. Conclusion: NAC could improve the osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs and in orthodontic rats, suggesting a potential therapeutic approach for alveolar bone remodeling in orthodontics.

Role of upregulation of the KATP channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson's disease.

Accumulating evidence suggests that ATP-sensitive potassium (KATP ) channels play an important role in the selective degeneration of dopaminergic neurons in the substantia nigra (SN). Furthermore, the expression of the KATP channel subunit sulfonylurea receptor 1 (SUR1) is upregulated in the remaining nigral dopaminergic neurons in Parkinson's disease (PD). However, the mechanism underlying this selective upregulation of the SUR1 subunit and its subsequent roles in PD progression are largely unknown. In 3-, 6-, and 9-month-old A53T α-synuclein transgenic (α-SynA53T+/+ ) mice, only the SUR1 subunit and not SUR2B or Kir6.2 was upregulated, accompanied by neuronal damage. Moreover, the occurrence of burst firing in dopaminergic neurons was increased with the upregulation of the SUR1 subunit, whereas no changes in the firing rate were observed except in 9-month-old α-SynA53T+/+ mice. After interference with SUR1 expression by injection of lentivirus into the SN, the progression of dopaminergic neuron degeneration was delayed. Further studies showed that elevated expression of the transcription factors FOXA1 and FOXA2 could cause the upregulation of the SUR1 subunit in α-SynA53T+/+ mice. Our findings revealed the regulatory mechanism of the SUR1 subunit and the role of KATP channels in the progression of dopaminergic neuron degeneration, providing a new target for PD drug therapy.

Has COVID-19 Changed China's Digital Trade?-Implications for Health Economics.

Digital technologies have played a significant role in the defense against the COVID-19 pandemic. This development raises the question of whether digital technologies have helped Chinese exports recover quickly and even grow. To answer this question, we study monthly data on Chinese exports to 40 countries/regions from January 2019 to June 2020 and covering 97 product categories. The study takes the COVID-19 outbreak as a natural experiment and treats digital trade products as the treatment group. Using a generalized difference-in-differences (DID) approach, we empirically investigate how this major global public health crisis and digital trade have influenced Chinese exports. Our empirical analysis reveals that the COVID-19 pandemic has inhibited China's export trade overall, digital trade has significantly promoted trade, and the supply mechanism has played a significant role in promoting the recovery of exports. Heterogeneity tests on destination countries/regions reveal that digital trade has significantly promoted exports to countries/regions with different income levels, with a more significant effect on low-risk destinations than on high-risk destinations. The sector heterogeneity test demonstrates that digital trade has enhanced the export recovery of sectors dealing in necessities for pandemic prevention. Other robustness tests, including parallel trend and placebo tests, support the above conclusions. Finally, we extend the research conclusions and discuss their implication for health economics and the practice of fighting COVID-19.

Efficacy of Sequential Capecitabine on Adjuvant Chemotherapy of Triple-Negative Breast Cancer.

This paper aims to evaluate the efficacy of capecitabine as extended adjuvant treatment after anthracycline and paclitaxel combined adjuvant chemotherapy for women with early triple-negative breast cancer (TNBC). The patients with early TNBC were randomly assigned to capecitabine sequential treatment for 4 cycles and without any sequential treatment in the control group after anthracycline and paclitaxel combined adjuvant chemotherapy. The primary end point was disease-free survival (DFS). The secondary end point was overall survival (OS). One hundred patients were enrolled in this study between June 2013 and February 2015. Median age was 49 years ranging from 25 to 66 years and treatment was well tolerance. The median follow-up time after random allocation was 58 months (range: 11-62 months). There was no significant difference in DFS and OS between the two groups (hazard ratio (HR) of DFS was 0.50; 95% CI, 0.24-1.05; P=0.066). Our study shows that although the addition of four cycles capecitabine after anthracycline and paclitaxel combining adjuvant chemotherapy does not improve DFS and OS, but the trend of DFS is improved. The possible reason is that the four-cycle treatment of capecitabine is not enough, and another possible reason is that the number of cases is not enough.

Digital Technology, Knowledge Level, and Food Safety Governance: Implications for National Healthcare System.

Exploring the intrinsic relationship between digital technology and the efficiency of food safety supervision contributes to a better understanding of the role of digital technology in food safety supervision and how to maximize its influence. This study employed sample data from 31 regions in China between 2015 and 2017 for an empirical analysis of the correlation between the two and to examine the moderating effects of the knowledge levels of food producers and consumers. The results show that the development of digital technology contributes to enhancing the efficiency of food safety supervision. In this process, the higher the knowledge level of consumers, the greater the positive promotional effect of digital technology. On the contrary, when the knowledge level of producers is higher, it is not conducive to enhancing the effect of digital technology on the efficiency of food safety supervision. The author holds the view that this is related to the fact that employees in the food production and manufacturing industry have insufficient moral and legal knowledge. This not only limits the effect of digital technology on enhancing the efficiency of food safety supervision, but also opens the door to illegal production for some unprincipled producers. The policy implications are that digital technology should be used to improve food safety supervision, the moral and legal knowledge of food producers should be improved, and consumers should be encouraged to use digital technology more in the pursuit of food safety. Implications for national healthcare system would be also discussed in our paper.

Threshold Effect of Foreign Direct Investment and Carbon Emissions Performance From the Perspective of Marketization Level: Implications for the Green Economy.

Exploring the path and mechanism of marketization level in the effect of foreign direct investment (FDI) on carbon emission performance will help to maximize the stimulation effect of foreign investment on green and low-carbon development. This study used the panel data of 11 provinces and cities in the Yangtze River Economic Belt from 2008 to 2016. A panel threshold model is constructed to explore the non-linear relationship between FDI and carbon emissions performance from the perspective of marketization level. The main conclusions are as follows: First, from the perspective of marketization level, a significant double threshold effect exists between foreign participation and carbon emission intensity, with threshold values of 4.4701 and 9.2516 respectively. Second, as the marketization level increases, the technology spillover effect of FDI increases, and the stimulation effect of foreign participation on carbon intensity decreases significantly, but it does not inhibit carbon intensity, indicating that the overall benefits brought by FDI technology spillovers are still insufficient to offset pollution caused by foreign investment. Third, the eastern region of the Yangtze River Economic Belt has crossed the second threshold. In the central and western regions, the marketization process is relatively slow except for Chongqing, and the regions are still firmly stuck between the first and second thresholds. In response to the conclusions of the empirical research, relevant policy suggestions are put forward from three dimensions, namely, the strategy of introducing foreign investment, construction of the marketization system, and environmental regulation, to achieve low-carbon and green development in the Yangtze River Economic Belt.

Silencing of circHIPK3 Sensitizes Paclitaxel-Resistant Breast Cancer Cells to Chemotherapy by Regulating HK2 Through Targeting miR-1286.

BACKGROUND: Resistance development to paclitaxel (PTX) has become a major obstacle in the successful treatment of breast cancer (BC). Circular RNAs (circRNAs) have been identified as essential regulators in PTX resistance of BC. Here, we explored the precise roles of circRNA homeodomain interacting protein kinase 3 (circHIPK3, circ_0000284) in PTX resistance of BC. METHODS: The expression levels of circHIPK3, microRNA (miR)-1286, and hexokinase 2 (HK2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Ribonuclease R (RNase R) assay was used to confirm the stability of circHIPK3. Cellular localization of circHIPK3 was assessed by subcellular localization assay. The half maximal inhibitory concentration (IC50) value for PTX was measured by Cell Counting Kit-8 (CCK-8) assay. Cell colony formation, cell cycle distribution, and apoptosis were gauged by colony formation assay and flow cytometry, respectively. Animal studies were performed to evaluate the role of circHIPK3 in vivo. The direct relationship between miR-1286 and circHIPK3 or HK2 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Our results showed that circHIPK3 was up-regulated in PTX-resistant BC tissues and cells compared with the sensitive counterparts. The silencing of circHIPK3 promoted PTX sensitivity of PTX-resistant BC cells in vitro and in vivo. CircHIPK3 directly targeted miR-1286, and miR-1286 acted as a downstream mediator of circHIPK3 function in vitro. HK2 was a direct target of miR-1286, and circHIPK3 modulated HK2 expression through miR-1286. The increased expression of miR-1286 sensitized PTX-resistant BC cells to PTX in vitro by down-regulating HK2. CONCLUSION: Our findings demonstrated that the silencing of circHIPK3 sensitized PTX-resistant BC cells to PTX therapy at least in part via the regulation of the miR-1286/HK2 axis.

Nrf2 activation is involved in osteogenic differentiation of periodontal ligament stem cells under cyclic mechanical stretch.

During orthodontic treatment, mechanical stretch serves a crucial function in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Up-regulated reactive oxygen species (ROS) level is a result of cyclic mechanical stretch in many cell types. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator in various antioxidants expression. However, it is not known whether cyclic mechanical stretch could induce the ROS generation in PDLSCs and whether Nrf2 participated in this process. The present study was aimed to investigate the role of Nrf2 in PDLSCs under cyclic mechanical stretch. Our results showed that cyclic mechanical stretch increased ROS level and the nuclear accumulation of Nrf2 during osteoblast differentiation. Knocking down Nrf2 by siRNA transfection increased ROS formation and suppressed osteogenic differentiation in PDLSCs. T-BHQ, a Nrf2 activator, promoted the osteogenic differentiation in PDLSCs under cyclic mechanical stretch, and improved the microstructure of alveolar bone during orthodontic tooth movement in rats by employing micro-CT system. Taken together, Nrf2 activation was involved in osteogenic differentiation under cyclic mechanical stretch in PDLSCs. T-BHQ could promote the osteogenic differentiation in vitro and in vivo, suggesting a promising option for the remodeling of the alveolar bone during orthodontic tooth movement.

Does the Price Support Policy Drive a Balanced Distribution of Profits in the Chinese Dairy Supply Chain? Implications for Supplier and Consumer Psychology.

Evaluating the price policy of raw milk is of great significance to the sustainable development of an industry supply chain. In this context, our study used the multi-period difference-in-difference method to systematically examine the impact of the policy implementation on product price and profit distribution in the supply chain. The results showed the following: (1) the price of raw milk in the implementation area of the price support policy is 13.54% higher than that of the unimplemented area; (2) the effect of price increase in the western region (15.5%) is higher than that in the eastern region (13%), and the central region (10.73%); (3) furthermore, the purchase price guidance policy of raw milk drives price increase or price suppression in the links of the supply chain to promote a balanced distribution of profits among the participants in the chain. These conclusions all have good stability and have reference significance for further improving and adjusting the price support policy of raw milk to realize the sustainable development of the Chinese dairy industry. This will enhance the production confidence of Chinese raw milk producers and improve Chinese consumers' expectations and consumer psychology regarding domestic dairy products.

Nrf2 Activation Is Involved in Cyclic Mechanical Stress-Stimulated Osteogenic Differentiation in Periodontal Ligament Stem Cells via PI3K/Akt Signaling and HO1-SOD2 Interaction.

Nuclear factor erythroid-2-related factor-2 (Nrf2), the major transcriptional regulator in antioxidant response and cellular defense, had the vital effect on regulating osteogenic differentiation. Our previous study revealed that Nrf2 activation was involved in cyclic mechanical stress-stimulated osteogenic differentiation in the human periodontal ligament stem cells (PDLSCs). However, the mechanisms of Nrf2 underlying this process remained unclear. The goal of the study was to explore the mechanisms of Nrf2 in PDLSCs during cyclic mechanical stress-stimulated osteogenic differentiation via the tandem mass tag (TMT)-based liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis. And we applied tert-Butylhydroquinone (t-BHQ), the Nrf2 activator, to the orthodontic rats and detected the expression levels of the osteogenesis markers by immunohistochemistry (IHC) staining. Our results showed that Nrf2 activation in PDLSCs was involved in cyclic mechanical stress-stimulated osteogenic differentiation via phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) pathway. The protein-protein interaction between Akt and Nrf2 was detected. And the protein-protein interaction between heme oxygenase 1 (HO1) and superoxide dismutase 2 (SOD2), the downstream antioxidants of Nrf2, was associated with cyclic mechanical stress-stimulated osteogenic differentiation. T-BHQ enhanced the expression levels of the osteogenesis markers in orthodontic rats. Nrf2 might possess the potential to be a feasible molecular target in orthodontics.