Spatial evolution analysis of groundwater chemistry, quality, and fluoride health risk in southern Hebei Plain, China.

The present study investigated ion and fluoride concentrations in groundwater and their associated health risks to local populations in the southern Hebei Plain during 2018-2020. A total of 336 groundwater samples were collected from monitoring wells at 112 different locations. Statistical analysis, Gibbs diagram, principal ion ratio, and saturation index were carried out to clarify the chemical characteristics and control mechanism of groundwater. The results indicated that the groundwater types in the study area were mainly HCO3-Ca, Cl-Na, and SO4-Ca. The concentrations of cations and anions were Na+ > Ca2+ > Mg2+ > K+ and HCO3- > SO42- > Cl- > NO3- > F-, respectively. Based on the water chemical parameters, the pollution index of groundwater (PIG) was used to comprehensively evaluate the water quality. The results showed that during the study period, 60.41% of groundwater samples were suitable for drinking purposes, and 39.59% needed purification treatment to meet the requirements of drinking water standards. The groundwater quality in the western pre-hill plain areas was good, while the water quality in the northeastern and southeastern areas was poor and contaminated to varying degrees. Groundwater quality was mainly affected by the combined effect of total dissolved solids (TDS), Na+, Mg2+, Cl-, SO42- and HCO3- concentrations. Fluoride concentrations in the groundwater samples ranged from 0.07 to 8.51 mg/L, with 44% of the samples containing fluoride below the recommended limit of 0.5 mg/L, which would put the population at risk of dental caries. Also, 8% of the samples exceeded the permissible limit for fluoride in drinking water (1.5 mg/L), which would expose the local population to the risk of fluorosis. The human health risk evaluation of fluoride showed significant differences in non-carcinogenic effects between two different groups of children and adults. HIin values ranged from 0.08 to 10.19 for children and 0.03 to 4.65 for adults, with hazard indices greater than 1 at 29.16% and 10.11%, respectively. This indicates that children have a greater exposure risk than adults, and the entropy of higher risk is mainly distributed in the northeast of the study area. Based on the above analysis of the spatial evolution of groundwater chemistry, water quality, and fluoride health risks in the southern Hebei Plain region, corresponding protection and management measures were proposed, which also provided reference significance for the effective use of drinking water and health risk prevention in the region.

Evaluation of coal seam floor water bursting in multi-aquifer Gequan coal mine, China.

A water-bursting evaluation of the coal seam floor is critical to ensure safety of coal mine production. The vulnerability index method based on AHP is selected for this study's evaluation method. Water pressure, measured specific yield, equivalent thickness of effective aquiclude, brittle rock thickness under mining pressure damage zone, distribution of faults, distribution of collapse column, distribution of endpoints, and the intersection of fault are taken as the evaluation index based on the analysis of geological data in the study area. The authors assessed the threat posed by the two aquifers in the lower portion of the coal seam. Separate evaluations were conducted on the Benxi and Ordovician limestone aquifers. The results' veracity was confirmed by comparing the obtained results to the water bursting point and a few boreholes. The evaluation results provide recommendations for the safe operation of coal mines.

Revisiting bone morphogenetic protein-2 knuckle epitope and redesigning the epitope-derived peptides.

The bone morphogenetic protein-2 (BMP2) plays a crucial role in bone formation, growth and regeneration, which adopts a conformational wrist epitope and a linear knuckle epitope to interact with its type-I (BRI) and type-II (BRII) receptors, respectively. In this study, we systematically examine the BRII-recognition site of BMP2 at structural, energetic and dynamic levels and accurately locate hotspots of the recognition at BMP2-BRII complex interface. It is revealed that the traditional knuckle epitope (BMP2 residue range 73-92) do fully match the identified hotspots; the BMP2-recognition site includes the C-terminal region of traditional knuckle epitope as well as its flanked ß-strands. In addition, the protein context of full-length BMP2 is also responsible for the recognition by addressing conformational constraint on the native epitope segment. Therefore, we herein redefine the knuckle epitope to BMP2 residue range 84-102, which has a similar sequence length but is slid along the protein sequence by ~10 residues as compared to traditional knuckle epitope. The redefined one is also a linear epitope that is natively a double-stranded ß-sheet with two asymmetric arms as compared to the natively single ß-strand of the traditional version, although their sequences are partially overlapped to each other. It is revealed that the redefined epitope-derived peptide LN84-102 exhibits an improved affinity by >3-fold relative to the traditional epitope-derived peptide KL73-92 . Even so, the LN84-102 peptide still cannot fully represent the BMP2 recognition event by BRII that has been reported to have a nanomolar affinity. We further introduce a disulfide bond across the two arms of double-stranded ß-sheet to constrain the free LN84-102 peptide conformation, which mimics the conformational constraint addressed by protein context. Consequently, several cyclic peptides are redesigned, in which the LN84-102 (cyc89-101) is determined to exhibit a sub-micromolar affinity; this value is ~5-fold higher than its linear counterpart. Structural analysis also reveals that the cyclic peptide can interact with BRII in a similar binding mode with the redefined knuckle epitope region in full-length BMP2 protein.

Downregulated Long Non-Coding RNA MSC-AS1 Inhibits Osteosarcoma Progression and Increases Sensitivity to Cisplatin by Binding to MicroRNA-142.

BACKGROUND Osteosarcoma (OS) is the most prevalent malignant primary bone tumor, resulting from severe transformation of primitive mesenchymal cells, which induces osteogenesis. Long non-coding RNA (lncRNA) MSC-AS1 triggers osteogenic differentiation by sponging microRNA (miR)-140-5p. The present study assessed the mechanism of lncRNA MSC-AS1 in OS biological features and sensitivity to cisplatin (DDP) by binding to miR-142. MATERIAL AND METHODS Firstly, lncRNA MSC-AS1 expression in OS tissues and cells was analyzed. OS cells were transfected with silenced MSC-AS1 to determine its role in OS biological behaviors, and we also assessed the effect of MSC-AS1 on OS sensitivity to DDP. Then, website prediction and dual-luciferase reporter gene assay were utilized for verification of the binding site between MSC-AS1 and miR-142. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to determine the effect of MSC-AS1 on expression of miR-142, cyclin-dependent kinase 6 (CDK6), and the PI3K/AKT signaling pathway. Xenograft transplantation was also applied to confirm the in vitro experiments. RESULTS Overexpressed MSC-AS1 was associated with poor prognosis of OS patients. OS cell proliferation, invasion, and migration were reduced after silencing MSC-AS1, while cell apoptosis was enhanced. Moreover, silencing MSC-AS1 made OS cells more sensitive to DDP. Interestingly, MSC-AS1 knockdown induced miR-142 expression and reduced CDK6 levels, thereby decreasing the protein expression of p-PI3K/t-PI3K and p-AKT/t-AKT. Silencing MSC-AS1 repressed OS progression in vivo. CONCLUSIONS Our study demonstrated that silencing MSC-AS1 inhibited OS biological behaviors by enhancing miR-142 to decrease CDK6 and inactivating the PI3K/AKT axis. Our results may provide new insights for OS treatment.

Direct Observation of Landau Level Resonance and Mass Generation in Dirac Semimetal Cd3As2 Thin Films.

Three-dimensional topological Dirac semimetals have hitherto stimulated unprecedented research interests as a new class of quantum materials. Breaking certain types of symmetries has been proposed to enable the manipulation of Dirac fermions, and that was soon realized by external modulations such as magnetic fields. However, an intrinsic manipulation of Dirac states, which is more efficient and desirable, remains a significant challenge. Here, we report a systematic study of quasi-particle dynamics and band evolution in Cd3As2 thin films with controlled chromium (Cr) doping by both magneto-infrared spectroscopy and electrical transport. We observe the √B relation of inter-Landau-level resonance in Cd3As2, an important signature of ultrarelativistic massless state inaccessible in previous optical experiments. A crossover from quantum to quasi-classical behavior makes it possible to directly probe the mass of Dirac fermions. Importantly, Cr doping allows for a Dirac mass acquisition and topological phase transition enabling a desired dynamic control of Dirac fermions. Corroborating with the density-functional theory calculations, we show that the mass generation can be explained by the explicit C4 rotation symmetry breaking and the resultant Dirac gap engineering through Cr substitution for Cd atoms. The manipulation of the system symmetry and Dirac mass in Cd3As2 thin films provides a tuning knob to explore the exotic states stemming from the parent phase of Dirac semimetals.

Gate-tunable negative longitudinal magnetoresistance in the predicted type-II Weyl semimetal WTe2.

The progress in exploiting new electronic materials has been a major driving force in solid-state physics. As a new state of matter, a Weyl semimetal (WSM), in particular a type-II WSM, hosts Weyl fermions as emergent quasiparticles and may harbour novel electrical transport properties. Nevertheless, such a type-II WSM material has not been experimentally observed. In this work, by performing systematic magneto-transport studies on thin films of a predicted material candidate WTe2, we observe notable negative longitudinal magnetoresistance, which can be attributed to the chiral anomaly in WSM. This phenomenon also exhibits strong planar orientation dependence with the absence along the tungsten chains, consistent with the distinctive feature of a type-II WSM. By applying a gate voltage, we demonstrate that the Fermi energy can be in-situ tuned through the Weyl points via the electric field effect. Our results may open opportunities for implementing new electronic applications, such as field-effect chiral devices.

Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.

BACKGROUND: This study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole. METHODS: One hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations. RESULTS: Patients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%). CONCLUSION: AI-associated bone loss can be prevented by concurrent zoledronic acid for postmenopausal breast cancer patients.

Effects of platelet-derived growth factor on chondrocyte proliferation, migration and apoptosis via regulation of GIT1 expression.

The formation of fibrocartilage, cartilaginous and bony calluses is vital for bone healing following a fracture. Fibroblasts, chondrocytes and osteoblasts are critical functional cells that are involved in these three processes, respectively. Platelet­derived growth factor (PDGF), a growth factor that is released from platelet particles and appears during the early stages at the site of fractures, is essential in bone healing via regulation of cell proliferation and differentiation. However, the effects of PDGF on the chondrocytes remain unclear. In the present study, PDGF promoted phosphorylation of Src and upregulated the expression level of G­protein­coupled receptor kinase interacting protein­1 (GIT1) according to the results of the cell culture of chondrocytes in vitro and western blotting. However, the effect of PDGF on the upregulation of GIT1 expression was mostly inhibited by the Src inhibitor, PP2. After knocking down GIT1 expression using siRNA, the phosphorylation of Src continued to be induced by PDGF, although the expression of GIT1 was inhibited. Furthermore, the results indicated that PDGF promoted chondrocyte proliferation and migration, however, the effect on cell apoptosis induction was suppressed after adding the Src inhibitor, PP2. Additionally, when knocking down GIT1 using siRNA, the expression level of GIT1 decreased, which is similar to the effect of the Src inhibitor, PP2. The current study demonstrates that PDGF may initially activate the phosphorylation of Src, and subsequently induce GIT1 expression to promote chondrocyte proliferation and migration, but suppress cell apoptosis.

Integrin-ß1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression.

Chondrocytes play a critical role in the repair process of osteoarthritis, which is also known as degenerative arthritis. Integrins, as the key family of cell surface receptors, are responsible for the regulation of chondrocyte proliferation, differentiation, survival and apoptosis through the recruitment and activation of downstream adaptor proteins. Moreover, G-protein-coupled receptor kinase interacting protein-1 (GIT1) exerts its effects on cell proliferation and migration through interaction with various cytokines. It has been previously suggested that GIT1 acts as a vital protein downstream of the integrin-mediated pathway. In the present study, we investigated the effects of integrin-ß1 on cell proliferation and apoptosis, as well as the underlying mechanisms in chondrocytes in vitro. Following transfection with a vector expressing integrin-ß1, our results revealed that the overexpression of integrin-ß1 enhanced GIT1 expression, whereas the knockdown of integrin-ß1 by siRNA suppressed GIT1 expression. However, no significant effect was observed on integrin-ß1 expression following the enforced overexpression of GIT1, which suggests that GIT1 is localized downstream of integrin-ß1. In other words, integrin-ß1 regulates the expression of GIT1. Furthermore, this study demonstrated that integrin-ß1 and GIT1 increased the expression levels of aggrecan and type II collagen, thus promoting chondrocyte proliferation; however, they inhibited chondrocyte apoptosis. Taken together, our data demonstrate that integrin-ß1 plays a vital role in chondrocyte proliferation, differentiation and apoptosis. GIT1 exerts effects similar to those of integrin-ß1 and is a downstream target of integrin-ß1.