Bhlhe40 deficiency attenuates LPS-induced acute lung injury through preventing macrophage pyroptosis.

BACKGROUND: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. Recently, increasing evidence supports activated inflammation and gasdermin D (GSDMD)-mediated pyroptosis in macrophage are closely associated with ALI. Basic helix-loop-helix family member e40 (Bhlhe40) is a transcription factor that is comprehensively involved in inflammation. However, there is little experimental evidence connecting Bhlhe40 and GSDMD-driven pyroptosis. The study sought to verify the hypothesis that Bhlhe40 is required for GSDMD-mediated pyroptosis in lipopolysaccharide (LPS)-induced inflammatory injury. METHOD: We performed studies using Bhlhe40-knockout (Bhlhe40 -/-) mice, small interfering RNA (siRNA) targeting Bhlhe40 and pyroptosis inhibitor disulfiram to investigate the potential roles of Bhlhe40 on LPS-induced ALI and the underlying mechanisms. RESULTS: Bhlhe40 was highly expressed in total lung tissues and macrophages of LPS-induced mice. Bhlhe40-/- mice showed alleviative lung pathological injury and inflammatory response upon LPS stimulation. Meanwhile, we found that Bhlhe40 deficiency significantly suppressed GSDMD-mediated pyroptosis in macrophage in vivo and in vitro. By further mechanistic analysis, we demonstrated that Bhlhe40 deficiency inhibited GSDMD-mediated pyroptosis and subsequent ALI by repressing canonical (caspase-1-mediated) and non-canonical (caspase-11-mediated) signaling pathways in vivo and in vitro. CONCLUSION: These results indicate Bhlhe40 is required for LPS-induced ALI. Bhlhe40 deficiency can inhibit GSDMD-mediated pyroptosis and therefore alleviate ALI. Targeting Bhlhe40 may be a potential therapeutic strategy for LPS-induced ALI.

Associations of different combinations of moderate-vigorous physical activity and muscle-strengthening activity with mortality among US lung cancer survivors.

BACKGROUND: To investigate the associations of different combinations of moderate to vigorous physical activity (MVPA) and muscle strengthening activity (MSA) with all-cause and cancer mortality among lung cancer survivors. METHODS: This nationwide prospective cohort study used data from the US National Health Interview Survey 2009-2018. A total of 785 lung cancer survivors were included in the study. Participants were linked to the National Death Index through December 31, 2019. Self-reported MVPA and MSA frequency data were used to obtain 4 mutually exclusive exposure categories. Multivariate Cox proportional hazard models were applied to explore the association between exposure categories and outcomes. RESULTS: The mean (standard deviation [SD]) age of the study population was 69.1 (11.3) years and 429 (54.6%) were female. Among them, 641 (81.7%) were White and 102 (13.0%) were Black. The median follow-up time was 3 years (2526 person-years), and 349 (44.5%) all-cause deaths and 232 (29.6%) cancer deaths occurred. Compared to the MVPA < 60 min/week and MSA < 2 sessions/week group, individuals in the MVPA ≥ 60 min/week and MSA < 2 sessions/week group showed hazard ratios (HRs) of 0.50 (95% CI, 0.36-0.69) for all-cause mortality and 0.37 (95% CI, 0.20-0.67) for cancer mortality after the adjustment of covariates. Those in the MVPA ≥ 60 min/week and MSA ≥ 2 sessions/week group exhibited HRs of 0.52 (95% CI, 0.35-0.77) for all-cause mortality and 0.27 (95% CI, 0.12-0.62) for cancer mortality when compared to the MVPA < 60 min/week and MSA < 2 sessions/week group. We also identified distinct non-linear relationships between MVPA and outcomes risk among two MSA frequency subgroups. CONCLUSION: This cohort study demonstrated that higher levels of MVPA and MSA combined might be associated with optimal reductions of mortality risk in lung cancer survivors.

Physical and psychological status of emergency assistance personnel at major public health events: a qualitative descriptive study.

BACKGROUND: Many personnel respond to natural disasters like earthquakes and tsunamis and frequent public health events like Ebola and COVID-19. However, research on emergency assistance personnel remains limited. This study aims to describe the perceived well-being among responders deployed in isolated or emergency international missions while providing practical references to intervene in developing similar missions. METHODS: For this qualitative phenomenological study, purposive sampling was used following the principle of maximum differentiation to select personnel deployed on an emergency mission for over a year. Data collection continued until data saturation. Phenomenologically semi-structured interviews helped explore the physical and psychological status of the participants with Colaizzi's method. RESULTS: Eleven personnel were interviewed after the mission, with four major themes being identified: 'perceived somatic change,' 'perceived emotional change,' 'behavioral change,' and 'coping with perceived change.' CONCLUSIONS: The mental health status of the emergency assistance personnel was affected by multiple factors from external and internal environments. The current study explored the physical and psychological feelings and emotions of emergency assistance personnel during an emergency mission. The study provided a practical reference for health management under similar missions. REGISTRATIONS: Not registered.

Identification and characterization of two SERPINC1 mutations causing congenital antithrombin deficiency.

BACKGROUND: Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. METHODS: Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. RESULTS: The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. CONCLUSIONS: The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

Design and test of a FBG acceleration sensor based on multi-stage flexible hinges.

High-precision and high-sensitivity vibration acceleration sensors have been a research hotspot in engineering technology, which play an important role in engineering structural health monitoring, earthquakes, tsunamis, and geological exploration. A novel, to the best of our knowledge, fiber Bragg grating (FBG) acceleration sensor incorporating a mass block and flexible hinge was proposed against the low sensitivity and poor transverse interference resistance of existing FBG acceleration sensors. The FBG accelerometer with the multi-stage flexible hinge was modeled and theoretically analyzed, the structural parameters of the sensor were optimized and actual sensors were developed, and a sensor performance test experiment was carried out in the end. The result suggested that the sensor's natural frequency was as high as 1400 Hz, and its response was flat in the frequency range of 50-800 Hz; its sensitivity was 18.4 pm/g, linearity R 2 was 0.9983, and transverse interference immunity was below 3.2%. The research findings offered a new way of thinking about high-precision and high-sensitivity vibration measurement in engineering technology.

Multicenter Study of Temporal Changes and Prognostic Value of a CT Visual Severity Score in Hospitalized Patients With Coronavirus Disease (COVID-19).

BACKGROUND. Chest CT findings have the potential to guide treatment of hospitalized patients with coronavirus disease (COVID-19). OBJECTIVE. The purpose of this study was to assess a CT visual severity score in hospitalized patients with COVID-19, with attention to temporal changes in the score and the role of the score in a model for predicting in-hospital complications. METHODS. This retrospective study included 161 inpatients with COVID-19 from three hospitals in China who underwent serial chest CT scans during hospitalization. CT examinations were evaluated using a visual severity scoring system. The temporal pattern of the CT visual severity score across serial CT examinations during hospitalization was characterized using a generalized spline regression model. A prognostic model to predict major complications, including in-hospital mortality, was created using the CT visual severity score and clinical variables. External model validation was evaluated by two independent radiologists in a cohort of 135 patients from a different hospital. RESULTS. The cohort included 91 survivors with nonsevere disease, 55 survivors with severe disease, and 15 patients who died during hospitalization. Median CT visual lung severity score in the first week of hospitalization was 2.0 in survivors with non-severe disease, 4.0 in survivors with severe disease, and 11.0 in nonsurvivors. CT visual severity score peaked approximately 9 and 12 days after symptom onset in survivors with nonsevere and severe disease, respectively, and progressively decreased in subsequent hospitalization weeks in both groups. In the prognostic model, in-hospital complications were independently associated with a severe CT score (odds ratio [OR], 31.28), moderate CT score (OR, 5.86), age (OR, 1.09 per 1-year increase), and lymphocyte count (OR, 0.03 per 1 × 109/L increase). In the validation cohort, the two readers achieved C-index values of 0.92-0.95, accuracy of 85.2-86.7%, sensitivity of 70.7-75.6%, and specificity of 91.4-91.5% for predicting in-hospital complications. CONCLUSION. A CT visual severity score is associated with clinical disease severity and evolves in a characteristic fashion during hospitalization for COVID-19. A prognostic model based on the CT visual severity score and clinical variables shows strong performance in predicting in-hospital complications. CLINICAL IMPACT. The prognostic model using the CT visual severity score may help identify patients at highest risk of poor outcomes and guide early intervention.

Inhibition of the ERK1/2-ubiquitous calpains pathway attenuates experimental pulmonary fibrosis in vivo and in vitro.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with poor prognosis. Epithelial-mesenchymal transition (EMT) has been reported to play an important role in IPF. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) cascade, which regulates EMT and oncogenesis, has been implicated in the pathogenesis of IPF. Calpains, Ca2+-dependent cysteine proteinases that mediate controlled proteolysis of many specific substrates including epithelial cell marker E-cadherin, participate in organ fibrosis. Calpain-1 and calpain-2 of calpain family are ubiquitous calpains. ERK1/2 signaling stimulates the ubiquitous calpains activity in cancer development, but whether ERK1/2 signaling mediates the ubiquitous calpains activity in pulmonary fibrosis is unknown. Here we investigated whether inhibition of ERK1/2 signaling and the ubiquitous calpains attenuated experimental pulmonary fibrosis and examined the potential mechanism. Our results showed that inhibition of ERK1/2 signaling and the ubiquitous calpains both attenuated bleomycin (BLM)-induced lung fibrosis in mice. Inhibition of ERK1/2 signaling downregulated the expression of calpain-1 and calpain-2 in vivo and in vitro. We detected decreased E-cadherin expression and increased calpain-1 expression in IPF patients. Inhibition of ERK1/2 signaling and the ubiquitous calpains both suppressed the development of EMT in vivo and in vitro. Our study indicated that inhibition of the ERK1/2-ubiquitous calpains pathway protected pulmonary fibrosis from BLM, possibly via inhibition of EMT. Therefore, targeting ubiquitous calpains may be a potential strategy to attenuate IPF.

Functional analysis of a novel orthologous small heat shock protein (shsp) hsp21.8a and seven species-specific shsps in Tribolium castaneum.

Small heat shock proteins (sHSPs) are important modulators of insect survival. Previous research revealed that there is only one orthologous cluster of shsps in insects. Here, we identified another novel orthologous cluster of shsps in insects by comparative analysis. Multiple stress experiments and function investigation of Tchsp21.8a belonging to this orthologous cluster and seven species-specific shsps were performed in the stored-grain pest Tribolium castaneum. The results indicated that expression of Tchsp21.8a showed weak responses to different stresses. However, expressions of most species-specific shsps exhibited hyper-responses to heat stress, and expressions of all species-specific shsps displayed diverse responses during other stresses to protect beetles in a cooperative manner. Additionally, Tchsp21.8a and species-specific Tcshsp19.7 played important roles in the development of T. castaneum, and all Tcshsps had a certain impact on the fecundity. Our work created a comprehensive reliable scaffold of insect shsps that can further provide instructive insights to pest bio-control.

Design of a Low-Cost Small-Size Fluxgate Sensor.

Traditional fluxgate sensors used in geomagnetic field observations are large, costly, power-consuming and often limited in their use. Although the size of the micro-fluxgate sensors has been significantly reduced, their performance, including indicators such as accuracy and signal-to-noise, does not meet observational requirements. To address these problems, a new race-track type probe is designed based on a magnetic core made of a Co-based amorphous ribbon. The size of this single-component probe is only Φ10 mm × 30 mm. The signal processing circuit is also optimized. The whole size of the sensor integrated with probes and data acquisition module is Φ70 mm × 100 mm. Compared with traditional fluxgate and micro-fluxgate sensors, the designed sensor is compact and provides excellent performance equal to traditional fluxgate sensors with good linearity and RMS noise of less than 0.1 nT. From operational tests, the results are in good agreement with those from a standard fluxgate magnetometer. Being more suitable for modern dense deployment of geomagnetic observations, this small-size fluxgate sensor offers promising research applications at lower costs.

Study of Building Safety Monitoring by Using Cost-Effective MEMS Accelerometers for Rapid After-Earthquake Assessment with Missing Data.

Suffering from structural deterioration and natural disasters, the resilience of civil structures in the face of extreme loadings inevitably drops, which may lead to catastrophic structural failure and presents great threats to public safety. Earthquake-induced extreme loading is one of the major reasons behind the structural failure of buildings. However, many buildings in earthquake-prone areas of China lack safety monitoring, and prevalent structural health monitoring systems are generally very expensive and complicated for extensive applications. To facilitate cost-effective building-safety monitoring, this study investigates a method using cost-effective MEMS accelerometers for buildings' rapid after-earthquake assessment. First, a parameter analysis of a cost-effective MEMS sensor is conducted to confirm its suitability for building-safety monitoring. Second, different from the existing investigations that tend to use a simplified building model or small-scaled frame structure excited by strong motions in laboratories, this study selects an in-service public building located in a typical earthquake-prone area after an analysis of earthquake risk in China. The building is instrumented with the selected cost-effective MEMS accelerometers, characterized by a low noise level and the capability to capture low-frequency small-amplitude dynamic responses. Furthermore, a rapid after-earthquake assessment scheme is proposed, which systematically includes fast missing data reconstruction, displacement response estimation based on an acceleration response integral, and safety assessment based on the maximum displacement and maximum inter-story drift ratio. Finally, the proposed method is successfully applied to a building-safety assessment by using earthquake-induced building responses suffering from missing data. This study is conducive to the extensive engineering application of MEMS-based cost-effective building monitoring and rapid after-earthquake assessment.

Improved Resolution and Cost Performance of Low-Cost MEMS Seismic Sensor through Parallel Acquisition.

In earthquake monitoring, an important aspect of the operational effect of earthquake intensity rapid reporting and earthquake early warning networks depends on the density and performance of the deployed seismic sensors. To improve the resolution of seismic sensors as much as possible while keeping costs low, in this article the use of multiple low-cost and low-resolution digital MEMS accelerometers is proposed to increase the resolution through the correlation average method. In addition, a cost-effective MEMS seismic sensor is developed. With ARM and Linux embedded computer technology, this instrument can cyclically store the continuous collected data on a built-in large-capacity SD card for approximately 12 months. With its real-time seismic data processing algorithm, this instrument is able to automatically identify seismic events and calculate ground motion parameters. Moreover, the instrument is easy to install in a variety of ground or building conditions. The results show that the RMS noise of the instrument is reduced from 0.096 cm/s2 with a single MEMS accelerometer to 0.034 cm/s2 in a bandwidth of 0.1-20 Hz by using the correlation average method of eight low-cost MEMS accelerometers. The dynamic range reaches more than 90 dB, the amplitude-frequency response of its input and output within -3 dB is DC -80 Hz, and the linearity is better than 0.47%. In the records from our instrument, earthquakes with magnitudes between M2.2 and M5.1 and distances from the epicenter shorter than 200 km have a relatively high SNR, and are more visible than they were prior to the joint averaging.

The association between gaseous pollutants and non-accidental mortality: a time series study.

To evaluate the effects of gaseous pollutants (SO2, NO2) on non-accidental mortality of residents in Hefei city, we collected non-accidental deaths, air pollutants and meteorological data of Hefei city from 2014 to 2017. After controlling confounding factors with Poisson generalized additive model, we analyzed the relationship between air pollutants and non-accidental mortality and used subgroup analysis to identify susceptible groups. The number of non-accidental deaths during the study period was 42,116, with an average of 28.83 per day. The average concentrations of SO2 and NO2 were 16.08 µg/m3 and 39.10 µg/m3, respectively. In the single-pollutant model, every 10 µg/m3 increase in SO2 and NO2 concentrations was significantly associated with non-accidental mortality, and there was a significant lag effect. SO2 increased the risk of non-accidental death by 4.93% (95% CI: 1.94% ~ 8.00%) at lag0-3. In addition, male, the elderly, non-elderly and low-education people were more susceptible (P < 0.05). NO2 increased the risk of non-accidental death by 2.11% (95% CI: 1.18% ~ 3.05%) at lag0-1 and had an effect on all subgroups (P < 0.05). For every 10 µg/m3 increase in SO2 and NO2, the two-pollutant model showed that the risk of non-accidental death, respectively, increased by 3.34% (95% CI: 0.29% ~ 6.50%) and 1.82% (95% CI: 0.85% ~ 2.79%), suggesting that the effect was weakened. Our study suggested that SO2 and NO2 were associated with non-accidental mortality, and there were lag effects. Therefore, environmental management should be strengthened and health protection education should be carried out for different groups.

Hypoxia-inducible factor 1α from a high-altitude fish enhances cytoprotection and elevates nitric oxide production in hypoxic environment.

Hypoxia-inducible factors (HIFs) are master transcription factor regulating hypoxic responses in vertebrates. Species of Schizothoracine, a sub-family of cyprinidae, are highly endemic to the hypoxic Qinghai-Tibetan Plateau (QTP). What roles the HIFs play in hypoxic adaptation in the Schizothoracine fish is little known. In this study, the HIF-1α/B gene from Gymnocypris dobula (Gd) was characterized. The predicted protein for Gd-HIF-1α/B contains the main domains (bHLH, PAS, PAC, ODD, N-TAD, and C-TAD). Moreover, a specific mutation that the proline hydroxylation motif (LXXLAP) mutated into PxxLAP was observed in Gd-HIF-1α/B CODD domain, which may lead to changes in the function. To clarify whether HIF-1α/B of G. dobula possesses hypoxic adaptive features, Gd-HIF1α/B and Schizothorax prenanti-HIF1α/B (Sp-HIF1α/B) were cloned into an expression vector and transfected into 293T cells. Cell viability was found to be significantly higher in cells transfected with Gd-HIF-1α/B than those transfected with Sp-HIF-1α/B under hypoxic conditions. In addition, G. dobula HIF-1α/B showed stronger activity in transactivating the expression of nitric oxide (NO)-synthesizing enzyme, NOS2B under hypoxia stresses than the orthologous gene from S. prenanti, which were accompanied with upregulated expressions of NOS2B in heart of G. dobula, which may attribute to elevated NO levels detected in G. dobula than the lower land species. These results indicated that the HIF-1α plays an important role in mediating the iNOS signaling system in the process of evolutionary adaptation of the Schizothoracine to the highland environment.

Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF-κB signaling pathway in vivo and in vitro.

BACKGROUND AND OBJECTIVES: Sepsis that arises from uncontrolled pulmonary inflammation could induce acute lung injury (ALI), leading to the high death rate. Dachengqi decoction (DCQD) is a common traditional Chinese herbal medicine with strong anti-inflammatory effects. The current study aimed to explore the effect of DCQD on the inflammatory cytokines production, the aquaporin-1 (AQP-1) and AQP-5 protein expression in lipopolysaccharide (LPS)-induced ALI models, and the potential mechanisms underlying its effects. METHODS: Sprague-Dawley rats and HULEC-5a cells were used as study models in the research. To detect related molecules in the study, the real-time polymerase chain reaction analysis, cell counting kit-8 assay, Western blot analysis, and enzyme-linked immunosorbent assay were performed. RESULTS: DCQD could inhibit the expression of LPS-induced inflammatory cytokines, including interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α), in lung tissues and could reduce pulmonary edema by upregulating the expression of AQP-1 and AQP-5 in rats with LPS-induced ALI. Moreover, the results suggested that the toll-like receptor 4 (TLR4)/NF-κB signaling is indispensable for DCQD to increase the expression of AQP-1 and AQP-5 and inhibits the production of IL-6, IL-8, and TNF-α in LPS-induced HULEC-5a cells. CONCLUSION: The results of our study suggested that DCQD suppresses the TLR4/NF-κB signaling pathway, increases the protein expression of AQP-1 and AQP-5, and inhibits the production of inflammatory cytokines, by which it may alleviate the inflammatory reactions in ALI and benefit the treatments.

Chronic obstructive pulmonary disease in rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: The risk and prevalence of chronic obstructive pulmonary disease (COPD) in rheumatoid arthritis (RA) is still obscure. The current study was aimed to systematically review and meta-analyse the risk ratio (RR) and prevalence of COPD in RA. METHODS: A comprehensive systematic review was conducted based on PubMed, Web of Science and Cochrane Library from inception to April 30, 2018. The primary outcome of our study was the RR of COPD in RA patients compared with controls, and secondary was the prevalence of COPD in RA patients. Pooled effect sizes were calculated according to fixed effect model or random effects model depending on heterogeneity. RESULTS: Six and eight studies reported the RR and prevalence of COPD in RA respectively. Compared with controls, RA patients have significant increased risk of incident COPD with pooled RR 1.82 (95% CI = 1.55 to 2.10, P <  0.001). The pooled prevalence of COPD in RA patients was 6.2% (95% CI = 4.1 to 8.3%). Meta-regression identified that publication year was an independent covariate negatively associated with the RR of COPD, and smoker proportion of RA population was also positively associated with the prevalence of COPD significantly in RA patients. CONCLUSIONS: The present meta-analysis has demonstrated the significant increased risk and high prevalence of COPD in RA patients. Patients with RA had better cease tobacco use and rheumatologists should pay attention to the monitoring of COPD for the prevention and control of COPD.

Serum Sclerostin and Bone Morphogenetic Protein-2 Levels in Patients with Ankylosing Spondylitis: A Meta-Analysis.

Various studies have investigated the serum sclerostin and bone morphogenetic protein-2 (BMP-2) levels in patients with ankylosing spondylitis (AS), but the results were inconsistent. The aim of this meta-analysis was to synthetically assess the associations of serum levels of sclerostin and BMP-2 with AS. Multiple electronic databases were searched to locate relevant articles published before November 2018. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Totally, 21 studies were included. Meta-analysis results showed no significant difference between AS group and control group in serum sclerostin levels (SMD = 0.098, 95% CI - 0.395 to 0.591, p = 0.697). Nevertheless, serum BMP-2 levels in AS patients were higher than that in controls (SMD = 1.184, 95% CI 0.209 to 2.159, p = 0.017). Subgroup analysis demonstrated that European and South American AS patients had lower serum levels of sclerostin than controls. AS patients with age ≥ 40 years, erythrocyte sedimentation rate (ESR) ≤ 20 mm/h and Bath Ankylosing Spondylitis Functional Index (BASFI) < 4 had statistically significant lower serum sclerostin concentrations compared to controls. Chinese and Korean AS patients as well as patients with lower CRP had higher serum BMP-2 levels than controls, and country may be a source of heterogeneity across the studies. No publication bias existed and sensitivity analysis confirmed the stability of results. Serum BMP-2, but not sclerostin levels may be closely related to the development of AS.

Serum Levels of OPG, RANKL, and RANKL/OPG Ratio in Patients with Ankylosing Spondylitis: A Systematic Review and Meta-analysis.

Objectives: To investigate the role of osteoprotegerin (OPG), receptor activator of nuclear factor-kB ligand (RANKL), and RANKL/OPG ratio in the pathogenesis of ankylosing spondylitis (AS). Methods: Studies that compared serum levels of OPG, RANKL, and RANKL/OPG ratio between AS patients and healthy controls were gathered. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by the random-effects model. Results: Twenty studies containing 1592 AS patients and 1064 healthy controls were included in this meta-analysis. Serum levels of OPG, RANKL, and RANKL/OPG ratio in AS patients were significantly higher than that in normal controls (OPG: SMD = 0.401, 95%CI = 0.026-0.777, p = 0.036; RANKL: SMD = 1.116, 95%CI = 0.510-1.723, p < 0.001; RANKL/OPG ratio: SMD = 0.691, 95%CI = 0.084-1.299, p = 0.026, respectively). Subgroup analysis suggested that Asian AS patients and patients with elevated ESR (ESR >20 mm/h) had higher serum OPG levels compared to normal controls. Asian patients, CRP >10 mg/L, ESR >20 mm/h, duration of disease ≤8 years, and BASDAI score >4 points subgroups showed increased RANKL levels compared to controls. Conclusions: Serum levels of OPG, RANKL, and RANKL/OPG ratio may be used as potential susceptible biomarkers for AS, but they could be influenced by race, inflammatory factors, and disease activity of AS patients.

An Analytical Geometry Optimization Model for Current-Mode Cross-Like Hall Plates.

This paper presents a new analytical geometry optimization model to depict the optimal current sensitivity and signal-to-noise ratio (SNR) for the current-mode Hall devices. The conformal mapping calculation is performed to study the influence of device geometry on the current sensitivity and SNR of the current-mode cross-like Hall plates. The analytical model indicates that a current-mode cross-like Hall plate can achieve optimal current sensitivity and SNR in the device length-to-width ratio (L/W) range of 0.4-0.5 when the thermal noise is taken into account. Three-dimensional (3D) technology computer aided design (TCAD) simulation validates the accuracy of the analytical model. The proposed analytical model provides a geometry design rule to achieve optimal sensitivity and SNR at the same time for the current-mode cross-like Hall plates.

miRNA-152 targets GATA1 to regulate erythropoiesis in Chionodraco hamatus.

Chionodraco hamatus is a teleost within the suborder Notothenioidei, the members of which are known to lack functional erythrocytes with modified hematopoiesis. Hematopoiesis is an essential process during the development of animals, where it is tightly regulated by many different transcription factors, signaling proteins, chromatin modifications, and microRNAs (miRNAs). The miRNAs are known to regulate the expression of their target genes at the post-transcriptional level. However, little is known about the miRNA-mediated regulation of hematopoiesis. In this study, we confirmed that miR-152 plays a crucial role in hematopoiesis during the development of C. hamatus. The overexpression of miR-152 reduced hematopoiesis according to the decreased expression of GATA1 and reduced o-dianisidine staining of hemoglobin. Mechanistically, reduced hematopoiesis was regulated by the miR-152-mediated down-regulated expression of GATA1. Bioinformatics analysis was used to predict the target gene of miR-152. Western blotting as well as dual luciferase and EGFP reporter assays were employed to investigate the expression of GATA1 mediated by miR-152. Finally, verification experiments in the zebrafish autologous model strongly supported the effect of miR-152 on hematopoiesis. In conclusion, we suggest that miR-152 is a novel molecular factor that regulates hematopoiesis during the development of C. hamatus by down-regulating the expression of GATA1.

Associations of Estrogen Receptor Alpha Gene Polymorphisms with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Systematic Review and Meta-Analysis.

The associations between PvuII (T>C) and XbaI (A>G) polymorphisms of estrogen receptor alpha (ESR1) gene with type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) are reported in many studies, but the results are inconsistent. This present work aims to assess the associations by performing a comprehensive meta-analysis. Relevant studies were searched through several databases. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of PvuII and XbaI polymorphisms with the risk of T2DM and MetS by using the STATA 14.0 software. Eight studies for T2DM and three articles about MetS were included in this meta-analysis. The overall results indicated that PvuII, rather than XbaI polymorphism, was associated with T2DM (regressive model: OR=0.673, 95% CI=0.550 to 0.823, praw<0.001, pFDR<0.003). The subgroup analysis based on race revealed an association of PvuII polymorphism with the decreased T2DM risk in Chinese population and a relationship between XbaI polymorphism and the reduced T2DM susceptibility in Caucasians. The difference of country may be one source of the heterogeneity for PvuII polymorphism and T2DM. However, neither PvuII nor XbaI polymorphism was related to the risk of MetS. The C allele of PvuII polymorphism presents a protective role in T2DM risk, especially in Chinese people. The G allele of XbaI polymorphism is related to a reduced risk for T2DM in Caucasian population. Nevertheless, neither of PvuII nor XbaI polymorphism is associated with MetS risk.