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Osteocalcin (OCN), as a characteristic protein expressed at the mature stage of osteoblasts, plays an important role in crosstalk within the skeletal muscle system. Mature OCN is secreted out of the cell after carboxylation in the endoplasmic reticulum. According to the degree of carboxylation, it can be divided into carboxylated OCN (cOCN) and undercarboxylated OCN (ucOCN). The two forms of proteins exhibit different biological activities, which make their functions more complex than those currently recognized. Many literatures reported that more osteocalcin was expressed in the hypertrophic stage of chondrocytes, even as a marker protein of osteoarthritis (OA) chondrocytes. However, these studies paid few attention to the potential different roles of different carboxylated forms of OCN in chondrocytes. Here, we discovered that ucOCN played a significant protecting role in OA development. In OCN knockout (OCN-/-) mice, articular chondrocytes showed a hypertrophic tendency. But in mice OA model, OCN-/- mice didn’t develop more severe OA than WT mice. Meanwhile, OCN in chondrocytes increased significantly and ucOCN in synovial fluid decreased dramatically in WT mice. We hypothesized that intracellular OCN and extracellular ucOCN may play different roles in the development of OA. By manipulating the amount of ucOCN in the synovial fluid in wild type mice and a series of experiments in vitro, we confirmed the protective effect of ucOCN in OA. We further explored the downstream pathway of ucOCN in chondrocytes and verified that ucOCN activates HIF-1α pathway through G protein coupled receptor 6A (GPRC6A) to inhibit chondrocyte hypertrophy.

Four-and-a-half LIM domain protein 1 (FHL1) is a member of the FHL protein family that serves as a scaffold protein to maintain normal cellular structure and function. Its mutations have been implicated in multiple muscular diseases. These FHL1 related myopathies are characterized by symptoms such as progressive muscle loss, rigid or bent spine, even cardiac or respiratory failure in some patients, which implies pathological problems not only in muscles, but also in the nervous system. Moreover, decreased FHL1 protein level has been found in patients with FHL1 mutations, indicating the protein loss-of-function as a pathological cause of such diseases. These findings suggest the significance of understanding the systemic role of FHL1 in the homeostasis of nervous system and muscle. Here we reported that Fhl1 loss in C2C12 myotubes obscured acetylcholine receptor (AChR) clustering in addition to myotube fusion, which was associated with impaired MuSK phosphorylation. Mechanistically, myostatin-SMAD2/3 signaling was enhanced, whereas IGF-PI3K-AKT signaling was suppressed in Fhl1-/- C2C12 myotubes. Reversion of these molecular alterations rescued AChR clustering and differentiation deficits. These data outline a systemic regulation of AChR clustering and myotube fusion by FHL1, which may offer clues for mechanism study and development of therapeutic strategies to treat FHL1 related myopathies.

Forest regeneration plays an important role in the carbon (C) and nitrogen (N) budget after clear-cutting. Nonetheless, the effects of regeneration pattern on soilatmosphere exchange of greenhouse gases (GHG; CO 2 ,CH 4 and N O) remain poorly understood on the eastern Qinghai-Tibetan Plateau. This study reports measured field layer GHG fluxes from Picea asperata broadleaved mixed forest (MF, mixed forests with planted P. asperata and natural regeneration of broadleaved species), natural secondary forest (NF, natural without assisted regeneration), and P. asperata plantation forest (PF, artificial planting) to investigate the influence of regeneration patterns on soil GHG fluxes. The soils of the three forest types acted as CO 2 and N 2 O sources and CH sinks. The seasonal variation in GHG fluxes was related to soil temperature, rather than soil moisture. Forest types originating from different regeneration processes exhibited different gaseous C fluxes (CO 4 2 1 and CH ), but did not exhibit significant effect on N 2 O emissions. NF and MF had higher CO emissions than PF. The difference was related to soil C and N density, NH 4 + concentration, and soil ?-glucosidase activity, rather than the soil microbial community. NF had higher CH uptake than the other two forest types, which is possibly related to specific individual phospholipid fatty acids. Overall, forest types differing in regeneration patterns had a significant impact on the C balance from the perspective of soil-atmosphere exchange of gaseous C at our site. Therefore, the GHG fluxes should be considered when taking measures of forest management and regeneration practices in this region.

We report the generation of parabolic pulses with broadband spectrum from a core-pumped Yb-doped fiber amplifier seeded by a dispersion managed fiber oscillator. The net cavity dispersion of Yb-doped oscillator was continuously changed from 0.074 to -0.170 ps2, which enabled us to achieve dissipative soliton, stretched pulse and soliton mode-locking operations. Spectral evolution processes in the core-pumped nonlinear fiber amplifier seeded by various input solitons were investigated experimentally and theoretically. Our finding indicates that cavity dispersion of oscillator can be used to engineer the input pulse parameter for amplifier, thus forming a pre-chirper free fiber amplification structure. In the experiment, we obtained 410-mW parabolic pulses with spectral bandwidth up to 56 nm. In combination with a passively synchronized frequency-doubled Er-doped fiber laser, we have demonstrated coherent anti-Stokes Raman imaging. The compact dual-color fiber laser source may facilitate practical applications of nonlinear biomedical imaging beyond the laboratory environment.

Background Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. Methods A murine TBI model was established by injuring C57BL/6 N mice with moderate-controlled cortical impact to evaluate the extent of brain damage and behavioral deficits. Ectoderm-derived FbMSCs were isolated from the frontal bone and their characteristics were assessed using multiple differentiation assays, flow cytometry and microarray analysis. Brain repairment and functional recovery were analyzed at different days post-injury with or without FbMSC application. Behavioral tests were performed to assess learning and memory improvements. RNA sequencing analysis, immunofluorescence staining, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to examine inflammation reaction and neural regeneration. In vitro co-culture analysis and quantification of glutamate transportation were carried out to explore the possible mechanism of neurogenesis and functional recovery promoted by FbMSCs. Results Ectoderm-derived FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs expressed the ectoderm-specific transcription factor Tfap2β. TBI mice showed impaired learning and memory deficits. Microglia and astrocyte activation, as well as neural damage, were significantly increased post-injury. FbMSC application ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. RNA sequencing analysis showed that signal pathways related to inflammation decreased, whereas those related to neural activation increased. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. Conclusions Ectoderm-derived FbMSC application significantly alleviated neuroinflammation, brain injury, and excitatory toxicity to neurons, improved cognition and behavioral deficits in TBI mice. Therefore, ectoderm-derived FbMSCs could be ideal therapeutic candidates for TBI which mostly affect cells from the same embryonic origins as FbMSCs.

This study investigates the asymmetric effects of government environmental subsidies (GES) and non-environmental subsidies (GNES) on corporate environmental responsibility (CER). Using a sample of Chinese listed companies over the period 2010 to 2020, we find that GES exhibits an inverted U-shaped impact on CER, while GNES shows a positive influence on CER, and these associations still exist after using the alternative measure of CER and addressing potential endogenous issues. In addition, we document that the effect of GES is not significant in companies operating in non-heavily polluting industries, and the effect of GNES is not significant in state-owned enterprises, firms with lower financing constraints and registered in regions with a lower degree of marketization. This study not only enriches the research on the influencing factors of CER but also provides theoretical guidance for the government to improve the efficiency of the use of different government subsidies and promote the greening process.

Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs highly expressed ectoderm-specific transcription factor Tfap2β and growth factor FGF1. FbMSC application significantly ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. Therefore, MSCs with characteristics of FbMSCs might be good candidates for TBI therapy.

Electromagnetic pollution seriously affects the human reproductive system, cardiovascular system, people's visual system, and so on. A novel versatile stretchable and biocompatible electromagnetic interference (EMI) shielding film has been developed, which could effectively attenuate electromagnetic radiation. The EMI shielding film was fabricated with a convenient solution casting and steam annealing with 2D MXene, iron oxide nanoparticles, and soluble polyurethane. The EMI shielding effectiveness is about 30.63 dB at 8.2 GHz, based on its discretized interfacial scattering and high energy conversion efficiency. Meanwhile, the excellent tensile elongation is 30.5%, because of the sliding migration and gradient structure of the nanomaterials doped in a polymer matrix. In addition, the film also demonstrated wonderful biocompatibility and did not cause erythema and discomfort even after being attached to the arm skin over 12 h, which shows the great potential for attenuation of electromagnetic irradiation and protection of human health.

The dynamic effects of forest regeneration pattern after clear-cutting primary forest on soil N mineralization (Nmin) have not been well investigated and whether the effects vary with season is unclear in eastern Tibetan Plateau. In this study, we compared soil net Nmin, i.e. net ammonification rate (net Ra) and net nitrification rate (net Rn) among Picea asperata-broadleaf mixed forest (natural regeneration after planting P. asperata, MF), natural secondary forest (natural without assisted regeneration, NF) and P. asperata plantation (reforestation after clear-cutting primary forest, PF) from June to November, and measured soil microbial community and enzyme activities. Forest regeneration pattern significantly altered net Ra as well as net Nmin in June and November. Net Ra of MF, NF and PF in June was −0.29, −0.52 and 0.04 mg kg−1 d-1, respectively. NF was likely to have higher net NH4+ consumption in June presumably by the greater microbial utilization (biomass and enzymes) directly drove by the larger initial NH4+ concentration. NF had higher net NH4+ production (0.30 mg kg−1 d-1) in November than MF (0.15 mg kg−1 d-1) and PF (0.03 mg kg−1 d-1). Net Rn was insignificantly different among the regenerated forests and ranged between −0.13 and 0.39 mg kg−1 d-1 with a unimodal seasonal pattern. Nitrate dominated the inorganic N pool in PF while it was similar to ammonium in MF and NF in the middle of growing season, possibly suggesting an alteration of N preferences among the regenerated forests. Independent edaphic factors (including soil organic matter and available N) had greater explanations of net Ra variability (19.0%), while net Rn variability was more determined by enzyme activities (21.8%) and microbial community (13.1%). Overall, our results highlighted that the variations in soil net Nmin among three regenerated forests were dependent on season. Ammonium concentration before the start of growing season might play an important role in soil N dynamics. NF exhibited a larger N demand with regard to net Ra, microbial induces and N-acquisition enzymes. These provided essential information for understanding soil N dynamics and for developing management practices of subalpine forests in eastern Tibetan Plateau.

A Yb-doped fiber laser mode locked by a nonlinear amplifying loop mirror (NALM) with a figure-9 configuration is experimentally realized. By coupling heterochromic 1580-nm optical pulses into the circular part of the Yb-doped laser oscillator, a new injection-induced Q-switched mode-locking (Q-ML) like transition state is found for the first time to the best of our knowledge. We have investigated the envelope interval and duration of this Q-switched envelope by changing the pump power, injection power, and cavity length detuning. Experimental results have shown the injected pulses serve as a complementary source for establishing mode-locking (ML). As a result, the self-starting ML threshold of the Yb-doped fiber laser is significantly reduced from 355 to 171 mW, which is only half that in the non-injection case. This optical pulse injection assisted ML process is observed with a real-time oscilloscope, revealing stable and consistent buildup dynamics. Our finding may provide a new approach for understanding the buildup dynamics and building mode-locked fiber lasers with low threshold and high consistency.

Background The majority of lung cancer(LC) patients are diagnosed at advanced stage with a poor prognosis. However, there is still no ideal diagnostic and prognostic prediction model for lung cancer. Methods Data of CEA, CYFRA21-1 and NSE test of patients with LC and benign lung diseases (BLDs) or healthy people from Physical Examination Center was collected. Samples were divided into three data sets as needed. Reassign three kinds of tumor markers (TMs) according to their distribution characteristics in different populations. Diagnostic and prognostic models were thus established, and independent validation was conducted with other data sets. Results The diagnostic prediction model showed good discrimination ability: the area under the receiver operating characteristic curve (AUC) differentiated LC from healthy people and BLDs (diagnosed within 2 months), being 0.88 and 0.84 respectively. Meanwhile, the prognostic prediction model did great in prediction: AUC in training data set and test data set were 0.85 and 0.8 respectively. Conclusion Reassigned CEA, CYFRA21-1 and NSE can effectively predict the diagnosis and prognosis of LC. Compared with the same TMs that were considered individually, this diagnostic prediction model can identify high-risk population for LC screening more accurately. The prognostic prediction model could be helpful in making more scientific treatment and follow-up plans for patients.

Elevational variations in the growing environment and sex differences in individuals drive the diversification of photosynthetic capacity of plants. However, photosynthetic response of dioecious plants to elevation gradients and the mechanisms that cause these responses are poorly understood. We measured foliar gas exchange, chlorophyll fluorescence and nitrogen allocations of male and female Seabuckthorn (Hippophae rhamnoides L.) at the elevation of 1900–3700 m above sea level (a.s.l.) on the eastern Qinghai-Tibetan Plateau, China. Male and female plants showed increased leaf photosynthetic capacity at higher elevation generally with no sex-specific difference. Photosynthetic photon flux density-saturated photosynthesis (Asat) was limited mostly by diffusional components (77 ± 1%), whereas biochemical components contributed minor limitations (22 ± 1%). Mesophyll conductance (gm) played an essential role in Asat variation, accounting for 40 ± 2% of the total photosynthetic limitations and had a significant positive correlation with Asat. Leaf nitrogen allocations to Rubisco (PR) and bioenergetics (PB) in the photosynthetic apparatus were major drivers for variations in photosynthetic nitrogen-use efficiency. The increase of these resource uptake capacities enables H. rhamnoides to maintain a high level of carbon assimilation and function efficiently to cope with the harsh conditions and shorter growing season at higher elevation.

More and more studies have shown that microRNAs (miRNAs) play key roles in the treatment of heart failure. Studies have shown that miR-874 (miR-874) inhibitors can reduce H2O2-induced cardiomyocyte necrosis and may have a therapeutic effect on heart failure in terms of cardiomyocyte necrosis. Therefore, the purpose of this experiment is to study the other effects of miR-874 and miR-146a on the key pathways in cardiomyocytes and cardiac fibroblasts. In this study, the roles of miR-874 antagomiR and miR-146a in cardiomyocytes and cardiac fibroblasts were analyzed. we investigated the level of miR-874 expression in H9C2 cardiomyocytes after miR-874 antagomiR transfection and found that the miR-874 expression in the H9C2 cells transfected with miR-874 antagomiR group was significantly lower than that in the control group. The results showed that miR-874 was successfully knocked down by the transfection of miR-874 antagomiR. Our results demonstrated that miR-874 inhibition has no effect on the activity of Caspase-3/7 in cardiomyocytes. miR-874 antagomiR has no effect on the proliferation of cardiac fibroblasts, whereas it can inhibit the activity of caspase-8 in cardiac fibroblasts. In addition, the potential effect of miR-874 antagomiR on cardiac remodeling associated genes were examined. miR-874 antagomiR had no effect on SERCA2a mRNA level in H9C2 cells. In addition, miR-874 antagomiR were able to down-regulate the mRNA level of MMP9 and had no effect on MMP2 mRNA levels in H9C2 cells. Finally, The concentration of Ca2+ was measured using Fluo-4 NW Calcium Assay Kits following transfection of miRNAs or negative control in primary cardiomyocytes. miR-874 antagomiR was found to have no effect on Ca2+ concentration in cardiomyocytes. the concentration of Ca2+ in the cardiomyocytes transfected with miR-146a mimics was significantly lower than the mimic negative control group. In summary, miR-874 antagomiR and miR-146a may have a therapeutic effect on heart failure, but may also have side effects on heart failure treatment. Therefore, miR-874 antagomiR should be further studied to provide a basis for the development of drugs for heart failure.

In this study, the accurate effectiveness of CaO in mitigating Cd bioavailability in paddy soil-rice system was investigated and moreover, the potential for reversibility of CaO liming process was provided. Increasing soil pH to ≥6.5 by CaO was determined to be the minimal threshold for minimizing Cd transfer into rice in historically contaminated soils across light to severe Cd levels, while an elevated CaO ratio was needed for soil with recent input of Cd. In CaO remediation treatment, a reduced pool of bioavailable Cd in rhizosphere soil coupled with an increased Cd retention by Fe plaque and an inhibited planta Cd transfer was determined consistently and proposed to be largely responsible for the significant reduction in brown rice Cd. Under continuous simulated acid precipitation test, a negligible level of Cd in eluate with ∼1 unit higher pH than control was recorded with CaO. Significant acidification, however, increased Cd solubilization in the limed soil than in unlimited control, notably at pH 5.5–6.5. As indicated by Visual MINTEQ, a higher Cd-carbonate solubility and much decreased Cd complexation on Fe-(hydr)-oxides across this pH range occurred as a result of elevated Ca input. This suggests that a high soil pH (≥6.5) needs to be permanently maintained once liming has been performed to minimize Cd mobilization. Therefore, amending Cd-contaminated soils with CaO is a cost-effective remedial measure for reducing Cd bioavailability to paddy rice, while a high soil pH need to be permanently maintained to sustain this beneficial effect.

Ambient air pollution ranks high among the risk factors that increase the global burden of disease. Previous studies focused on assessing mortality risk and were sparsely performed in populous developing countries with deteriorating environments. We conducted a time-series study to evaluate the air pollution-associated years of life lost (YLL) and mortality risk and to identify potential modifiers relating to the season and demographic characteristics. Using linear (for YLL) and Poisson (for mortality) regression models and controlling for time-varying factors, we found that an interquartile range (IQR) increase in a three-day average cumulative (lag 0–2 day) concentrations of PM 2.5 , PM 10 , NO 2 and SO 2 corresponded to increases in YLL of 12.09 (95% confidence interval [CI]: 2.98–21.20), 13.69 (95% CI: 3.32–24.07), 26.95 (95% CI: 13.99–39.91) and 24.39 (95% CI: 8.62–40.15) years, respectively, and to percent increases in mortality of 1.34% (95% CI: 0.67–2.01%), 1.56% (95% CI: 0.80–2.33%), 3.36% (95% CI: 2.39–4.33%) and 2.39% (95% CI: 1.24–3.55%), respectively. Among the specific causes of death, cardiovascular and respiratory diseases were positively associated with gaseous pollutants (NO 2 and SO 2 ), and diabetes was positively correlated with NO 2 (in terms of the mortality risk). The effects of air pollutants were more pronounced in the cool season than in the warm season. The elderly (>65 years) and females were more vulnerable to air pollution. Studying effect estimates and their modifications by using YLL to detect premature death should support implementing health risk assessments, identifying susceptible groups and guiding policy-making and resource allocation according to specific local conditions.

We have implemented a coincidence-pumping frequency upconversion system with a nonlinear conversion efficiency up to 80%, which enabled to demonstrate high-performance midinfrared photon detection and photon-number-resolving capability at 3.1 pm.

Rationale Primary biliary non-Hodgkin's lymphoma (PBNHL) is a rare disease with only 41 cases reported since 1982. The incidence of PBNHL in patients with malignant cholangiocarcinoma was 0.6%, and PBNHL accounted for 0.4% of extranodal non-Hodgkin's lymphoma, and only 0.016% of all non-Hodgkin's lymphoma cases. Patient concerns We present a rare case of PBNHL in a 59-year-old female who had jaundice for 3 days with weight loss and Epstein-Barr virus infection. Initial computed tomography and magnetic resonance imaging showed diffuse thickening wall of bile ducts with corresponding lumen stenosis, blurred fat space around the portal vein, lymphadenopathy, and a normal spleen. These manifestations and images were similar to hilar cholangiocarcinoma. So, the diagnosis of hilar cholangiocarcinoma was initially considered. Diagnoses Postoperative pathology confirmed the final diagnosis was PBNHL. Interventions The patient and her family requested to clarify the histologic diagnosis by laparotomy biopsy. Because the biopsy result could not be defined during operation, then right hemihepatectomy and choledochojejunostomy were performed. She did not receive any antitumor treatment. Outcomes One month after the patient's first examination, both computed tomography and magnetic resonance images showed diminished stenosis of common bile duct and left hepatic duct, but a new mass in segment IV of liver was observed. Unfortunately, the patient died due to disease progression. Lessons This case reminds us that although PBNHL is rare, making accurate diagnosis difficult preoperatively, PBNHL should be considered when encountering a case with Epstein-Barr virus infection and those typical imaging findings.

Reduction-oxidation-sensitive green fluorescent proteins (roGFPs) have been demonstrated to be valuable tools in sensing cellular redox changes in mammalian cells and model plants, yet have not been applied in crops such as maize. Here we report the characteristics of roGFP1 in transiently transformed maize mesophyll protoplasts in response to environmental stimuli and knocked-down expression of ROS-scavenging genes. We demonstrated that roGFP1 in maize cells ratiometrically responds to cellular redox changes caused by H2O2 and DTT, as it does in mammalian cells and model plants. Moreover, we found that roGFP1 is sensitive enough to cellular redox changes caused by genetic perturbation of single ROS genes, as exemplified by knocked-down expression of individual ZmAPXs, in maize protoplasts under controlled culture conditions and under stress conditions imposed by H2O2 addition. These data provide evidence that roGFP1 functions in maize cells as a biosensor for cellular redox changes triggered by genetic lesion of single ROS genes even under stress conditions, and suggest a potential application of roGFP1 in large-scale screening for maize mutants of ROS signaling involved in development and stress resistance.

A greenhouse experiment was conducted to assay the bioaccumulation and tolerance characteristics of Rhus chinensis Mill. to lead (Pb). The effects of exposing R. chinensis Mill seedlings to increasing Pb concentrations (0, 250, 500, 100mgkg-1) in the soil were assessed by measuring Pb accumulation, subcellular distribution, ultrastructure, photosynthetic characteristics, antioxidative enzyme activity, malondialdehyde content, and phytochelatin content. The majority of Pb taken up by R. chinensis Mill was associated with the cell wall fraction in the roots, where the absorption of Ca increased to maintain cell wall stability, and Pb deposits were found in the intercellular space or in the cell wall structures. In leaves, Pb was primarily stored in the cell wall, while it was compartmentalized into the vacuolar structures in the stem. Pb concentrations adversely affected the morphology of Rhus chinensis Mill cellular substructures. Furthermore, increased Peroxidase (POD) and catalase (CAT) activity was observed in plants grown in Pb-amended soil, and this may have led to reduced ROS to maintain the function of the membrane. Changes in phytochelatin levels (PCs) that were observed in Pb treated plants suggest that PCs formed complexes with Pb in the cytoplasm to reduce Pb2+ toxicity in the metabolically active cellular compartment. This mechanism may allow for the plant to accumulate higher concentrations of toxic Pb and survive for a longer period of time. Our study provides a better understanding of how Rhus chinensis Mill detoxifies Pb.