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Background Osteonecrosis of the femoral head (ONFH) is a common disabling disease in orthopedics. Blocking the progression of ONFH in the early stage is essential for avoiding total hip replacement. Purposes The purpose of this study is to evaluate the effect of invasive treatment on early-stage ONFH. Methods According to the PRISMA guidelines, relevant English databases were searched in August 2022 to collect published research. Extract result indicators and conduct network meta-analysis using R software. Results A total of 15 RCTs were included. All patients were diagnosed with early-stage ONFH. The surface under the cumulative ranking curve (SUCRA) showed that CD + BMMSC and CD + PRP were the most effective in improving HHS. The results of the league table showed that CD + BMMSC was superior to CD alone. Meanwhile, the SUCRA for FR showed that CD + BG + BMMSC was the most likely to be the most effective in reducing FR. The league table revealed that CD + BG, CD + BG + BMMSC, and CD + BMMSC were superior to CD alone, with statistically significant differences. Conclusion Considering the HHS and FR, CD + BMMSC may be the optimal treatment option to effectively delay the progression of ONFH and restore the postoperative function of patients. Registration Number : The study protocol has been registered on the PROSPERO platform (CRD42023380169).

Background Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%. Results Here we show that berberine, a natural plant product, is more effective than the frontline drug sulfasalazine in treating DSS (dextran sulfate sodium)-induced colitis in mice, and that berberine not only suppresses macrophage and granulocyte activation but also promotes epithelial restitution by activating Lgr5 + intestinal stem cells (ISCs). Mechanistically, berberine increases the expression of Wnt genes in resident mesenchymal stromal cells, an ISC niche, and inhibiting Wnt secretion diminishes the therapeutic effects of berberine. We further show that berberine controls the expression of many circadian rhythm genes in stromal cells, which in turn regulate the expression of Wnt molecules. Conclusions Our findings suggest that berberine acts on the resident stromal cells and ISCs to promote epithelial repair in experimental colitis and that Wnt-β-Catenin signaling may be a potential target for colitis treatment.

Against the backdrop of rapid urbanization, this study employs the Patch-based Land Use Simulation (PLUS) model to investigate land use dynamics in Guangzhou City over the last twenty years. The analysis reveals significant conversion of agricultural and forest lands into urban construction sites, driven by a complex interplay of natural and socio-economic factors. The PLUS model’s scenario simulations highlight the challenges of urban expansion on ecological spaces and sustainability. Findings suggest that Guangzhou City should adopt comprehensive land planning strategies that balance urban growth with ecological conservation. This involves implementing strict land use planning, optimizing urban layouts, and promoting ecologically friendly urban development methods. These recommendations aim to facilitate sustainable urban planning in Guangzhou, ensuring a harmonious coexistence between urban development and environmental preservation.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF‐EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment. This work identifies a natural peptide from a traditional Chinese medicine that activates gastric stem cells to regenerate gastric epithelia in experimental atrophic gastritis models and revitalizes the atrophic gastric organoids derived from patients. The peptide exerts its functions by stabilizing the EGF‐EGFR complex and specifically activating the downstream ERK and Stat1 signaling.

In the periphery of pancreatic ductal adenocarcinoma (PDAC), high accumulation of tumor-associated macrophages (TAMs), which exhibit M2 phenotype, has been shown to be correlated with extra-pancreatic invasion, lymph vessel invasion, lymph node involvement and shortened survival time. However, mechanisms by which tumor cells educate and reprogram TAMs remain largely unclear. The phenotype of TAMs in PDAC tissues was confirmed by immunofluoresence and confocal microscopy. Human CD14+ monocytes were incubated with recombinant human REG4 (rREG4) before being stimulated with LPS and IL-10 and IL-6 were measured with ELISA. A panel of M1 and M2 genes were measured by quantitative real-time PCR. Panc1, AsPC1 and BxPC3 cells were cultured in the conditioned medium (CM) and treated with REG4. The macrophages were infected with CREB shRNA or cultured by the CM of Panc1 cells infected with REG4 shRNA. The expression of CD163, CD206 and REG4 and the phosphorylation levels of epidermal growth factor receptor (EGFR), AKT and cAMP response element-binding protein (CREB) in cells were assessed with western blotting. Cell proliferation and invasiveness were also assessed. The rREG4 or the conditioned medium of Panc1 cells which secreted REG4 induced the polarization macrophages to M2 phenotype. Treatment of human macrophages with REG4 resulted in phosphorylation of EGFR, AKT and CREB. The latter was responsible for REG4-mediated macrophage polarization to M2. The conditioned medium of macrophages treated with rREG4 promoted the proliferation and invasion of pancreatic cancer cell lines. REG4, overexpressed in PDAC and secreted by cancer cells, promoted macrophage polarization to M2, through at least in part, activation of ERK1/2 and CREB and changed the microenvironment to facilitate cancer growth and metastasis.

Under the restriction of the national “double carbon” goal, how to realize the coordination between urbanization and low-carbon development in the Yellow River Basin is a problem worthy of attention. In this paper, a new urbanization and ecological carrying capacity evaluation index system is established to evaluate the new urbanization level and ecological carrying capacity of the Yellow River Basin. On this basis, the uncoordinated coupling level of new urbanization and ecological carrying capacity in the Yellow River Basin is measured by using the improved uncoordinated coupling model, and its temporal and spatial characteristics and internal impact mechanism are analyzed. The study shows that the new urbanization and ecological carrying capacity of the Yellow River Basin has a benign development trend as a whole. Shandong province belongs to the low-level uncoordinated coupling type; Gansu Province and Qinghai Province belong to the running-in uncoordinated type; and Shanxi Province, the Inner Mongolia Autonomous Region, Shaanxi Province, and the Ningxia Hui Autonomous Region belong to the antagonistic uncoordinated coupling type. The uncoordinated coupling degree between new urbanization and ecological carrying capacity in the Yellow River Basin has a spatial interaction effect. It presents a low-level cluster centered on Shaanxi Province and Shandong Province and a high-level cluster centered on Gansu Province, Qinghai Province, and the Ningxia Hui Autonomous Region. From the perspective of the internal main impact mechanism, water resources have a two-way impact on the development of the two systems of new urbanization and ecological carrying capacity; the number of permanent residents and the level of scientific and technological investment have a one-way impact on the process of new urbanization; and the green coverage rate of built-up areas has a one-way impact on the development of ecological carrying capacity. The main contributions of this paper are as follows. First, the evaluation index system of new urbanization and ecological carrying capacity has been improved in combination with the new development concept. The evaluation of new urbanization by this index system is more in line with the current national requirements for high-quality development. Second, the impact of potential resources and human regulation has been added to the traditional ecological carrying capacity evaluation index system, and the evaluation of ecological carrying capacity by this index system is more in line with reality. Thirdly, taking the time effect into account, an improved uncoordinated coupling method is proposed. Using this method to evaluate the relationship between systems is conducive to bringing the dynamic relationship within the system into the evaluation system, which is more in line with the reality of system changes. Fourth, from the perspective of problem diagnosis, research on the relationship between new urbanization and ecological carrying capacity will help to find the internal mechanism that affects the coordinated development of new urbanization and ecological carrying capacity in the Yellow River Basin. This method is universal for exploring the internal influence mechanism of the relationship between systems.

Compared R&D capital, the role of non-R&D intangible capital in TFP growth is under-researched. This study seeks to address this gap. The econometric analysis of industrial level data for 13 developed countries over the period of 1995–2010 shows that the growth of non-R&D intangible capital has a positive effect on TFP growth of a country. Further analysis finds that similar to R&D capital, non-R&D intangible capital also generates spillovers across industries and countries that drive TFP growth. It also shows that R&D and ICT intangible capital enhance the effect of non-R&D intangible capital. These findings extend the burgeoning literature on the role of non-R&D intangible capital in TFP growth and carry important policy implications.

Purpose The purpose of this paper is to examine how subnational institutions within a country explain the performance consequences of open innovation (OI) in emerging market enterprises (EMEs). Design/methodology/approach The paper conducts a regression analysis by using a novel panel data set comprising of 438 innovative Chinese firms over the period of 2008-2011. Findings The authors show that although on average openness to external actors improves innovation performance this effect is pronounced for EMEs that operate in subnational regions with a higher level of intellectual property rights (IPR) enforcement and of factor market development. The findings point to the context-dependent nature of OI strategy and the complementary effect of institutional parameters in emerging markets and help to reconcile the contrasting findings regarding the effect of OI in the prior literature. Originality/value This paper extends the literature on OI by suggesting that the analysis of the performance consequences of OI strategy should go beyond the nexus between OI and firm performance, and instead, focus on subnational-specific institutions, such as region-specific IPR enforcement, factor market development and intermediation market development, that may facilitate or constrain the effect of OI model.

NaCl induced PeJ3 (a DnaJ homolog) expression in Populus euphratica cell cultures. In contrast, salt treatment inhibited transcription of a J3-interacting protein kinase gene, PePKS5 (Salt Overly Sensitive 2-Like Protein Kinase 5). To clarify the mechanism by which PeJ3 conferred salinity tolerance, we isolated PeJ3 from P. euphratica and transformed it into Arabidopsis. PeJ3 overexpression inhibited AtPKS5 expression, but had no effect on AtJ3 transcripts. After 10-day exposures to 100 mM NaCl, PeJ3-transgenic lines showed prolonged survival (40–54.4%) and longer roots (43.8–51.1%) compared to wild-type (WT) and vector control (VC) plants. The observed differences in salt acclimation between transgenic and WT depended on their ability to exclude Na+ and maintain intracellular K+. PeJ3-transgenic Arabidopsis accumulated less Na+ in root cells, due at least in part, to the high Na+ efflux in roots. K+ flux recordings revealed that PeJ3-transgenic lines lost less K+ than WT and VC under salt stress. In vitro and in vivo activity assays revealed that PeJ3-overexpression upregulated plasma membrane H+-ATPase activity and enhanced H2O2 signaling in salt-stressed Arabidopsis. Consequently, PeJ3-transgenic plants retained high H+-pumping activity under NaCl salinity, which contributed to K+/Na+ homeostasis in roots. In conclusion, PeJ3 overexpression resulted in H+-ATPase activation through transcriptional AtPKS5 suppression and/or interactions with AtPKS5 kinase. Under salinity stress, upregulated H+-pumps (i) promoted Na+/H+ exchange across the Arabidopsis plasma membrane, (ii) reduced K+ efflux mediated by depolarization-activated plasma membrane channels, and (iii) stimulated H2O2 signaling, which increased cytosolic free Ca2+ and stimulated Na+ extrusion through Salt Overly Sensitive signaling in Arabidopsis.