IRTKS promotes osteogenic differentiation by inhibiting PTEN phosphorylation.

Insulin stimulates osteoblast proliferation and differentiation as an anabolic agent in bone. Insulin Receptor Tyrosine Kinase Substrate (IRTKS) is involved in insulin signaling as an adapter for insulin receptors (IR). Here, we showed that IRTKS levels were significantly decreased in bone marrow mesenchymal stem cells (BMSCs) derived from the bone marrow of patients with osteoporosis. Based on relevant experiments, we observed that IRTKS promoted the proliferation, migration, and osteoblast differentiation of BMSCs and MC3T3-E1 cells. In addition, we identified a Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN) as a potential active substrate of IRTKS. We demonstrated a direct interaction between IRTKS and PTEN using co-immunoprecipitation. Subsequently, we confirmed that the SH3 domain of IRTKS directly binds to the C-terminal tail of PTEN. Further experimental results demonstrated that PTEN attenuated the promoting effects of IRTKS on the proliferation, migration, and osteoblast differentiation of BMSCs and MC3T3-E1 cells. In conclusion, this study suggests that IRTKS contributes to osteogenic differentiation by inhibiting PTEN phosphorylation and provides a potential therapeutic target for osteoporosis patients.

Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-ß1 and CST3.

Microcystin-LR (MC-LR) is a toxic secondary metabolite produced by cyanobacteria that has been demonstrated to promote colorectal cancer (CRC). However, the mechanism by which MC-LR enhances CRC in the tumor microenvironment (TME) is poorly understood. To elucidate its role in TME, a co-culture system was established using CRC cells and M2 macrophages in a Transwell chamber. The study found that MC-LR promotes CRC cell migration by upregulating TGF-ß1 expression and secretion in M2 macrophages and downregulating CST3 in CRC cells. Neutralizing TGF-ß1 increased CST3 expression in CRC cells, while overexpressing CST3 in CRC cells suppressed TGF-ß1 expression in M2 macrophages, both of which weakened MC-LR-induced cellular motility in the co-culture system. In vivo, the mice in the MC-LR/AOM/DSS group had more tumor nodules, deeper tumor invasion, and higher M2 macrophage infiltration compared to the AOM/DSS group, and the expression of TGF-ß1 and CST3 in tumors was consistent with the cellular level. Overall, this study provides insights into the regulatory mechanism of MC-LR on TME, revealing that MC-LR upregulates the expression and secretion of TGF-ß1 in M2 macrophages, which in turn inhibits the expression of CST3 in CRC cells to promote migration.

Dynamic contribution and structural changes of carbon emissions in China's energy chemical industry with high-emission subsectors heterogeneity.

China's energy chemical industry accounts for about 12.01% of the national carbon emissions, while the heterogeneous carbon emission characteristics exhibited by the subsectors have not been reliably investigated. Based on the energy consumption data of the energy chemical industry subsectors in 30 Chinese provinces from 2006 to 2019, this study systematically identified the carbon emission contributions of high-emission subsectors, examined the evolutionary changes and correlation characteristics of carbon emissions from different perspectives, and further explored the carbon emission drivers. According to the survey, coal mining and washing (CMW) and petroleum processing, coking, and nuclear fuel processing (PCN) were high-emission sectors of the energy chemical industry, with annual emissions of more than 150 million tons, accounting for about 72.98% of the energy chemical industry. In addition, the number of high-emission areas in China's energy chemical industries has gradually increased, and the spatial disequilibrium of carbon emissions in industrial sectors has gradually deepened. The development of upstream industries had a strong correlation with carbon emissions, and the upstream industry sector still has not achieved carbon decoupling. The decomposition of the driving effects of carbon emissions showed that the economic output effect is the largest contributor to the growth of carbon emissions in the energy chemical industry, while energy restructuring and energy intensity reduction help reduce carbon emissions, but there is heterogeneity in the driving effects of subsectors.

Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis.

The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. Subsequently, miR-421-3p targeting KCNQ1OT1 was detected through a database search, and RNA fluorescent in situ hybridization, RNA immunoprecipitation, dual luciferase reporter assays all verified this relationship. Notably, KCNQ1OT1 stifled the miR-421-3p expression. The inhibition of proliferation, migration, and osteogenic differentiation caused by KCNQ1OT1 knock-down were reversed by an miR-421-3p inhibitor, further confirming the above findings. We verified that miR-421-3p specifically targeted the mammalian target of rapamycin (mTOR), and miR-421-3p inhibitor could reverse the negative effects of small interfering RNA of mTOR (si-mTOR) on MC3T3-E1 cells. Finally, osteoblasts isolated and cultured from OVX mice model and control mice also confirmed the observed trend. In combination, results mentioned above reveal that KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis.

[Assessment of soil quality under different land use types in the rocky mountain area of northern Hebei Province, China.] / 冀北土石山区不同土地利用类型土壤质量评价.

To assess the variations of soil quality among land use types and with altitude in the rocky mountain area of northern Hebei Province is critical for preventing further human-induced degradation of land and vegetation, and for formulating a strategic plan on vegetation restoration after the Beijing Winter Olympics. Taking Betula platyphylla natural forest, Larix gmelinii plantation, natural grassland and abandoned cropland as research objects, 13 soil physicochemical indices (e.g., soil bulk density, porosity and soil nutrient content) were measured to compare soil quality among land use types. The results showed that soil quality presented the trend as B. platyphylla natural forest > natural grassland > L. gmelinii plantation > abandoned cropland. B. platyphylla natural forest had the best soil quality due to high total nitrogen (3.24 ±1.42 g·kg-1) and phosphorus (0.59±0.10 g·kg-1) contents, suggesting that long-term soil nutrient accumulation played an important role in preventing soil degradation. Soil quality in natural grassland was lower than that in B. platyphylla natural forest, due to topographic factors and coarse soil fraction. Soil physical properties in L. gmelinii plantation had been substantially improved after 40 years restoration, as indicated by significant reductions in soil gravel fraction, while soil nutrient contents changed little. The low soil quality in abandoned cropland was attributable to low vegetation coverage and intense human activities in the low-altitude area. Driven by soil total nitrogen, soil quality under the four land use types increased with altitude, and peaked at about 1700 m. We suggested that enclosure and ecological restoration measures should be strengthened in ecologically-fragile, low-altitude areas, taking sustainable development into consideration for high-density stands and promoting plantations to adapt to environmental change.

Association between single-nucleotide polymorphism rs145497186 related to NDUFV2 and lumbar disc degeneration: a pilot case-control study.

OBJECTIVE: The association between the single-nucleotide polymorphisms (SNPs) rs28742109, rs12955018, rs987850, rs8093805, rs12965084 and rs145497186 related to gene named NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2) and lumbar disc degeneration (LDD) was preliminary investigated in a small sample size. METHODS: A total of 46 patients with LDD and 45 controls were recruited at Qilu Hospital of Shandong University, and each participant provided 5 mL peripheral venous blood. NA was extracted from the blood of each participant for further genotyping. The frequency of different genotypes in the case group and control group was determined, and analysis of the risk of LDD associated with different SNP genotypes was performed. The visual analogue scale (VAS) scores of the patients' degree of chronic low back pain were calculated, and the relationship between VAS scores and SNPs was analysed. RESULTS: After excluding the influence of sex, age, height, and weight on LDD, a significant association between SNP rs145497186 related to NDUFV2 and LDD persisted (P = 0.006). Simultaneously, rs145497186 was found to be associated with chronic low back pain in LDD populations. CONCLUSION: NDUFV2 rs145497186 SNP could be associated with susceptibility to LDD and the degree of chronic low back pain.

Long noncoding RNA KCNQ1OT1 inhibits osteoclast differentiation by regulating the miR-128-3p/NFAT5 axis.

Noncoding RNAs play an important role in regulating osteoclast differentiation. We investigated whether and how potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a long noncoding RNA, regulates osteoclast differentiation. We found that the expression of KCNQ1OT1 was downregulated in osteoporotic bone tissue. Then transfection of KCNQ1OT1 overexpression vectors or small interfering RNAs showed that the proliferation, migration, and osteoclast differentiation of RAW 264.7 cells were inhibited by KCNQ1OT1 upregulation, while they were promoted by KCNQ1OT1 knockdown. Interestingly, we found and confirmed that miR-128-3p was a target of KCNQ1OT1 using online databases, dual luciferase reporter assays and quantitative real-time polymerase chain reaction, and that it inhibited the expression of miR-128-3p. Moreover, we confirmed that miR-128-3p directly targeted nuclear factor of activated T cell 5 (NFAT5), a protein that combines with osteoprotegerin and thus regulates osteoclastogenesis with the presence of the receptor activator of nuclear factor κB ligand. Furthermore, we demonstrated that both the knockdown of KCNQ1OT1 and the overexpression of miR-128-3p attenuate the expression of NFAT5, while upregulating the osteoclastogenesis markers c-Fos, NFATc1, and Ctsk. The results from overexpression of KCNQ1OT1 and the inhibition of miR-128-3p were contrary to the above. Finally, we found that the inhibition of osteoclast differentiation by KCNQ1OT1 overexpression could be rescued using a miR-128-3p mimic, while the enhancement of migration and osteoclast differentiation by si-NFAT5 could be reversed with a miR-128-3p inhibitor. These results suggested that KCNQ1OT1 regulates the osteoclast differentiation via the miR-128-3p/NFAT5 axis.

Carbon emissions' spatial-temporal heterogeneity and identification from rural energy consumption in China.

Carbon emissions from industry and cities have been the focus of global carbon emissions control, but the need to reduce carbon emissions from large agricultural countries cannot be ignored. This study measured rural carbon emissions based on the energy consumption of rural residents and agricultural production from 2000 to 2018 in China, and the spatial-temporal evolution and variation of rural carbon emissions were analyzed using the quadrant diagram method and Theil index, which also further identified the contribution elements of rural carbon emissions. The gradual growth of rural carbon emissions in China's provinces has been accompanied by a spatial clustering of high emissions, and the carbon emissions among the country's eight regions are characterized by large inter-regional and small intra-regional differences. By identifying the carbon emissions contributions of regions and the carbon sources, we found that the provinces in the central region produce the most emissions, with the top 3 of 11 provinces contributing up to 61.56% of the total national production. Furthermore, emissions from the dominant carbon source in rural China, raw coal, has decreased to 49.22%, and the low use of electricity and natural gas results in the structure of rural carbon sources being weakly decarbonized. The decomposition of carbon emissions indicated that rural economic development plays a prominent contributory role in carbon emissions, whereas energy consumption per unit output value has a significant inhibitory effect on carbon emissions. This study contributes to current carbon emission-related research by identifying the main contributors of rural carbon emissions from multiple perspectives.

Association of Single Nucleotide Polymorphism rs2228570 with Lumbar Disc Degeneration: A Case-Control Study and Meta-Analysis.

OBJECTIVE: To examine the association between single nucleotide polymorphisms (SNPs) rs2228570, rs731236, rs7975232, and rs1544410 and lumbar disc degeneration (LDD) predisposition. METHODS: A search strategy was carried out, and the data were extracted after being chosen by the inclusion and exclusion criteria. Pooled odds ratios and 95% confidence intervals were calculated to assess the association between the aforementioned SNPs and LDD under allelic, dominant, recessive, heterozygous, and homozygous genetic models. In addition, a case-control study involving 46 LDD cases and 45 controls was also performed in the analysis to verify the result. RESULTS: A total of 17 studies were included in this meta-analysis. The pooled results did not show any association between vitamin D receptor (VDR) gene polymorphisms and LDD. But, interestingly, in subgroup analysis, the rs2228570 polymorphism was associated with LDD under the allelic (OR = 0.70, 95% CI = 0.56-0.87, p = 0.002), recessive (OR = 0.60, 95% CI = 0.43-0.84, p = 0.003), and homozygous (OR = 0.47, 95% CI= 0.28-0.79, p = 0.004) genetic models in the Asian population. SNPs rs731236 and rs7975232 still did not show any obvious association. We obtained a similar result from the case-control study: rs2228570 had an obvious relationship with LDD under allelic and homozygous genetic models. At the same time, we found that rs2228570 was also associated with the degree of low back pain (visual analogue scale, VAS score) in LDD population. CONCLUSION: SNP rs2228570 was significantly associated with LDD predisposition and the degree of low back pain in the Asian population.

Assessing previous land-vegetation productivity relationships on mountainous areas hosting coming Winter Olympics Games in 2022.

In order to prevent land degradation in areas before hosting big events such as the Winter Olympic Games (WOG), developing strategic vegetation restoration plans is key. To evaluate four experimental areas with different degrees of human impacts located in the Chongli District, northern Hebei Province, China, where the coming WOG 2022 will take considering: i) the feedback mechanisms between vegetation and soil in the process of future vegetation restoration; ii) the vegetation productivity of land in different land-use types; iii) the management mode considering the sustainable development as the primary goal. To achieve these goals, we applied a minimum soil data set (MDS) to screen the most relevant indicators (soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), available phosphorus (AP), available potassium (AK), available nitrogen (AN), soil bulk density (BD), soil porosity (SP), pH, clay, silt, sand and gravel), and the nonlinear scoring method to establish a soil quality index (SQI). For this purpose, 400 soil samples (0-20 cm depth), the total biomass of one natural grassland (NG) and abandoned farmland (AF), and the growing stock of natural secondary forest (NF) and a larch plantation (LP). The results showed that the SQI can be established based on TN, silt, TP and gravel. Under LP and AF land-use type, vegetation showing a poor effect on the improvement of soil quality (SQIs were significantly lower than the NF and NG). It was also observed that above 1700 m, the growing stock of artificial vegetation exceeds the range of vegetation productivity (about 165 m3·h-1) that the land can carry under the LP. We concluded that the main reason is the excessive depletion of N and P after human impacts. On the other hand, the SQI of NF and NG were higher, which is due to the significant improvement of soil quality by the conservation of the vegetation, so that no longer limited by the spatial distribution law, also showing higher vegetation productivity of land at different altitudes. This demonstrates that it is key to develop effective restoration plans considering the soil-vegetation relationship status of the NF and NG land-use types in this area in the territories used by the activities of the WOG 2022.

Up-Regulation of Hsa_circ_0008792 Inhibits Osteosarcoma Cell Invasion and Migration and Promotes Apoptosis by Regulating Hsa-miR-711/ZFP1.

OBJECTIVE: Circular RNA is a newly discovered non-coding RNA. It plays an important role in regulating gene expression, and may take part in tumor progression. This study aimed to investigate the functions of hsa_circ_0008792 in osteosarcoma regulation. METHODS: We identified a circular RNA, hsa_circ_0008792, by using bioinformatics to analyze the GSE96962 dataset. The capacities of migration and invasion were assessed by wound-healing assay and transwell Matrigel assay. The ratios of G0/G1, S, and G2/M phases in cell cycle and apoptosis were measured using flow cytometry. RESULTS: Hsa_circ_0008792 is expressed at low levels in osteosarcoma cells, and up-regulation of hsa_circ_0008792 could suppress osteosarcoma cell migration and invasion and promote apoptosis. This regulation is mediated by hsa-miR-711/ZFP1. The expression level of hsa_circ_0008792 showed no influence on cell cycle of osteosarcoma cells. CONCLUSION: Osteosarcoma is suppressed by hsa_circ_0008792/hsa-miR-711/ZFP1 axis.

Hierarchical Porous Carbon Derived from Sichuan Pepper for High-Performance Symmetric Supercapacitor with Decent Rate Capability and Cycling Stability.

Hierarchical micro-mesoporous carbon (denoted as HPC-2 in this study) was synthesized by pre-carbonization of biomass Sichuan pepper followed by KOH activation. It possessed well-developed porosity with the specific surface area of 1823.1 m² g-1 and pore volume of 0.906 cm³ g-1, and exhibited impressive supercapacitive behaviors. For example, the largest specific capacitance of HPC-2 was tested to be ca. 171 F g-1 in a three-electrode setup with outstanding rate capability and stable electrochemical property, whose capacitance retention was near 100% after cycling at rather a high current density of 40 A g-1 for up to 10,000 cycles. Furthermore, a two-electrode symmetric supercapacitor cell of HPC-2//HPC-2 was constructed, which delivered the maximum specific capacitance and energy density of ca. 30 F g-1 and 4.2 Wh kg-1, respectively, had prominent rate performance and cycling stability with negligible capacitance decay after repetitive charge/discharge at a high current density of 10 A g-1 for over 10,000 cycles. Such electrochemical properties of HPC-2 in both three- and two-electrode systems are superior or comparable to those of a great number of porous biomass carbon reported previously, hence making it a promising candidate for the development of high-performance energy storage devices.

The diagnostic value of circulating microRNAs as a biomarker for gastric cancer: A meta­analysis.

Recently, cancer research microRNA studies have drawn great attention. However, the results of these studies have been inconsistent and variable regarding the availability of circulating miRNAs in gastric cancer (GC) diagnosis. Thus, results should be interpreted cautiously. The purpose of the present study was to assess the diagnostic performance of circulating miRNAs in GC diagnosis. We conducted a systematic and comprehensive approach for the inclusion of studies. The sensitivity, specificity, and diagnostic odds ratio were pooled with random effects models, and a summary of receiver operator characteristic (SROC) curves were plotted. The potential heterogeneity was assessed with Q test and I2 statistics. Subgroup analyses and meta­regressions further investigated the sources of heterogeneity. A total of 77 studies from 48 articles were eligible for the meta­analysis. The results revealed a sensitivity of 0.76, a specificity of 0.81, and an AUC of 0.86 for gastric cancer diagnosis with circulating miRNAs. In addition, subgroup analyses indicated that multiple miRNAs assays, non­microarray screening approaches, and serum­based miRNA assays exhibited good diagnostic performance in contrast to a single miRNA assay, microarray expression profiling screening, and plasma­based miRNA group analysis. The diagnostic ability of miRNAs in early stage I­II groups and the high expression group were approximately similar to that in the stage I­IV groups and the low expression group. For the circulating miRNAs, our meta­analysis identified a combination of multiple miRNAs, non­microarray chip screening, and serum­based miRNA assays were associated with the most effective GC diagnostic performance. However, many unclear molecular mechanisms limited the accuracy of the diagnostic results, and should be interpreted with caution. Further large­scale prospective studies are required for validating the diagnostic applicability of circulating miRNAs in gastric cancer patients.

Effects of amiloride on physiological activity of stem cells of human lung cancer and possible mechanism.

Lung cancer is a common malignant tumor, the cancer stem cells (CSCs) were regarded responsible for the development of cancer tissue. The effects of amiloride on lung cancer stem cells and the possible mechanism were not much investigated. In this study, human NCI-H1975 lung CSCs were selected by flow cytometry, and the effects of amiloride at different concentrations (0, 12.5, 25, 50, and 100 µmol/L) were evaluated on proliferation, migration, invasion and apoptosis of CSCs using cell counting kit-8 and Transwell migration assays as well as flow cytometry. Wstern blot analysis was performed to investigate the effect of amiloride on the level of proteins in uPA system, NF-kB pathway, and PI3K-AKT-mTOR pathway in CSCs. As a result, we found that amiloride inhibited proliferation, migration and invasion of lung CSCs, and promoted apoptosis. Further, we found that amiloride decreased levels of target proteins in the uPA system, as well as the NF-kB and PI3K-AKT-mTOR pathways. These results indicated that amiloride could inhibit proliferation, migration and invasion of lung CSCs, and promotes apoptosis, these effects may be related to decreased levels of proteins in the uPA system, the NF-kB pathway, and the PI3K-AKT-mTOR pathway.