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Abstract Background The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. Methods Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and β-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. β-galactosidase (β-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice. Results Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P

ObjectiveThe current study aimed to assess the relationships between oxidative balance score (OBS) and OBS subclasses (dietary and lifestyle OBS) with risks of hyperuricemia (HUA) and gout among American adults.MethodsParticipants in the National Health and Nutrition Examination Survey from 2007 to 2018 were initially recruited and then the final sample was restricted to adults without missing values about serum uric acid, gout, OBS, and covariates. Rao-Scott adjusted chi-square test and analysis of variance were utilized to compare the baseline characteristics in adults of different quartiles of OBS, while the weighted stepped logistic regression models were used to explore the associations of overall, dietary, and lifestyle OBS with the risks of HUA and gout. Weighted restricted cubic spline analyses were conducted to explore the nonlinear dose-response associations.ResultsThe final sample consisted of 22,705 participants aged 20 years and older, which was representative of approximately 197.3 million non-institutionalized American adults. HUA and gout prevalence decreased with OBS quartiles. Compared with adults in the first quartile of OBS, those in the second (OR: 0.85, 95% CI: 0.72–0.99), third (OR: 0.71, 95% CI: 0.58–0.85), and fourth (OR: 0.48, 95% CI: 0.38–0.61) quartiles of OBS had reduced risks of hyperuricemia. Similarly, adults in the second (OR: 0.70, 95% CI: 0.51–0.97) quartile of OBS was associated with lower gout risk in comparison to adults in the lowest quartile. Regarding OBS subclasses, dietary and lifestyle OBS were both negatively correlated with the risk of HUA, and only higher lifestyle OBS was significantly associated with lower gout risk. Furthermore, the subgroup analyses and interaction effects also substantiated similar effects. Significant nonlinear dose-response relationships were observed between overall, dietary, and lifestyle OBS with HUA risk as well as that of lifestyle OBS with gout risk.ConclusionThis study strongly suggests the significant negative associations of OBS with HUA and gout in American adults and provides a dietary and lifestyle guideline to reduce the risks.

Objective: This study aimed to evaluate the efficacy of the Xianling Gubao (XLGB) capsule alone and its combination therapy in primary osteoporosis (POP). Methods: Databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and SinoMed were searched from their inception to January 16, 2024, for randomized controlled trials (RCTs) investigating the XLGB treatment for POP. A network meta-analysis (NMA) was performed to evaluate the efficacy and safety of multiple interventions in the treatment of POP. The Cochrane risk-of-bias tool was used to assess the quality of RCTs included in the meta-analysis. Software Stata (version 15.0) was used for statistical analysis. The surface under the cumulative ranking curve (SUCRA) method was used to present the findings from this NMA numerically and graphically by ranking multiple interventions. Results: A total of 107 RCTs were included in the meta-analysis, involving 10,032 participants and 21 interventions. Meta-analysis showed that XLGB + calcium (Ca) + calcitonin (99.9 %) was the most desirable treatment option for improving clinical efficacy. XLGB + Ca + bisphosphonate (BP) was most effective for improving bone mineral density (BMD) at the lumbar spine, femoral neck BMD, and serum bone Gla protein (BGP). SUCRA values for improving these three outcome measures by XLGB + Ca + BP were 87.4 %, 77.2 %, and 84.3 %, respectively. XLGB + calcitonin was the optimal option in terms of safety evaluation and improving visual analogue scale (VAS), with the SUCRA values being 89.6 % and 94.9 %, respectively. Conclusions: The XLGB combination therapy is a desirable option for treating POP as it can effectively improve the therapeutic effects, BMD, and serum BGP, as well as relieve pain in patients with POP.

PurposeThe current study aimed to explore the associations of diet quality assessed by healthy eating index-2015 (HEI-2015) with risks of osteoporosis and low bone mineral density (BMD) among American postmenopausal women aged 50 years and older.MethodsPostmenopausal women aged 50 years and older in the National Health and Nutrition Examination Survey from 2007 through 2018 were included in the final sample. Analysis of variance and Rao-Scott adjusted chi-square tests were used to compare the characteristics across tertiles of HEI-2015. Univariate and multivariate weighted logistic regression models were employed to explore the associations of HEI-2015 tertiles and continuous HEI-2015 with the risks of osteoporosis and low BMD. Nonlinear dose-response associations were evaluated using weighted restricted cubic spline analyses, and the contributions of various HEI-2015 components were assessed using weighted quantile sum regression models.ResultsThe final sample included 3,421 postmenopausal women aged 50 years and older representative for approximately 28.38 million non-institutionalized U.S. postmenopausal women. Osteoporosis prevalence decreased with HEI-2015 tertiles while the prevalence of low BMD showed no significant decrease. Compared with postmenopausal women in the first tertile of HEI-2015, those with the second (OR: 0.57, 95%CI: 0.38–0.84) and third (OR: 0.48, 95%CI: 0.29–0.78) HEI-2015 tertiles were associated with reduced osteoporosis risk after multivariate adjustments, but no significant association of HEI-2015 with the risk of BMD was identified. Furthermore, similar effects were confirmed in the sensitivity analyses and subgroup analyses and interaction effects. Moreover, significant nonlinear associations were observed between HEI-2015 with osteoporosis risk, and total vegetables, refined grains and greens and beans demonstrated the strongest protective effect among HEI-2015 components against osteoporosis.ConclusionsThis study strongly suggests the significant negative associations of HEI-2015 with osteoporosis risk in American postmenopausal women. These findings highlight the importance of adherence to the dietary guidelines for Americans in reducing the risk of osteoporosis.

Abstract Clinical studies have demonstrated an association between high myopia (HM) and neuropsychiatric disorders; however, the underlying mechanism of the association is not clear. We used whole exome sequencing (WES) in combination with the Genetic Variants Classification Criteria and Guidelines published by the American College of Medical Genetics (ACMG) and bioinformatics analysis to clarify the interrelationship between candidate genes. Causative genes for ocular diseases (45.38%) followed by neuropsychiatric disorders (22.69%) accounted for the highest proportion of genes that exhibited high pathogenicity in HM patients were found. Four pathogenic gene mutations were identified according to ACMG guidelines: c.164_165insACAGCA and c.C1760T in POLG, c.G1291A in COL5A1, and c.G10242T in ZNF469. Three causative genes for neuropsychiatric diseases, PTPRN2, PCDH15 and CDH23, were found to fall at the HM locus. The above results suggest that these genes may interact in high myopia and neuropsychiatric diseases.

The effect of β-sheet ratio and chain length on all-β proteins was investigated by MD simulations. Protein samples composed of different repeating units with various β-sheet ratios or a different number of repeating units were simulated under a broad temperature range. The simulation results show that the smaller radius of gyration was achieved by the protein with the higher proportion of β-sheet secondary structure, which had the lower nonbonded energy with more HBs within the protein. The root mean square deviation (RMSD) and the root mean square fluctuation (RMSF) both increased with temperature, especially in the case of a longer chain. The visible period was also shown according to the repeated secondary structure. Several minimum values of RMSF were located on the skeleton of Cα atoms participating in the β-sheet, indicating that it is a kind of stable secondary structure. We also concluded that proteins with a short chain or a lower ratio of β-sheet could easily transform their oriented and compact structures to other ones, such as random coils, turns, and even α-helices. These results clarified the relationship from the primary level to the 3D structure of proteins and potentially predicted protein folding.

ObjectiveThis study aimed to explore the association of the oxidative balance score (OBS) with total abdominal fat mass (TAFM) and visceral adipose tissue mass (VATM) percentages among young and middle-aged U.S. adults.MethodsYoung and middle-aged adults in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 were included. Analysis of variance and Rao-Scott adjusted chi-square tests were used to compare the characteristics across quartiles of OBS. Univariate and multivariate weighted logistic regression models were employed to explore the relationship between OBS and the risks of high TAFM or high VATM percentage in the general population and subgroups, while the interaction effects were tested with a likelihood test. Weighted restricted cubic spline analyses were utilized to assess the non-linear association of OBS with TAFM and VATM percentages.ResultsThe final sample included 8,734 young and middle-aged non-institutionalized U.S. adults representing 134.7 million adults. Compared with adults in the first quartile of OBS, those with higher OBS were less likely to have a high TAFM percentage; the ORs and 95% CI for adults in the second, third, and highest quartiles of OBS were 0.70 (0.53–0.94), 0.49 (0.36–0.60), and 0.25 (0.18–0.36), respectively. Similar trends were observed in the association between OBS and VATM percentages. Moreover, similar effects were confirmed in the sensitivity analyses and subgroup analyses according to demographic characteristics. Regarding the OBS subclass, higher dietary OBS and lifestyle OBS were also correlated with decreased ORs of high TAFM and VATM percentages.ConclusionThis study strongly suggests that higher OBS, as well as higher dietary OBS and lifestyle OBS, are significantly correlated with lower risks of abdominal obesity and visceral fat accumulation. The findings highlight the importance of an antioxidant-rich diet and maintaining a healthy lifestyle in reducing the risks.

ObjectiveWe aimed to investigate the relationship of metal exposure and latent tuberculosis infection (LTBI) among US adults and adolescents.MethodsParticipants from the National Health and Nutrition Examination Surveys (NHANES 2011 ~ 2012) were included. Multiple logistic regression models were used to explore the associations between metal exposure and LTBI. A total of 5,248 adults and 1,860 adolescents were included in the present analysis.ResultsFor adults, we only found a positive association between total mercury and LTBI (OR: 1.411; 95% CI: 1.164 ~ 1.710) when used as a continuous variable. Compared with Q1, Q4 increased the prevalence of LTBI (2.303; 1.455 ~ 3.644) when used as a quartile. The OR of total mercury and LTBI was higher among females (1.517; 1.009 ~ 2.279), individuals aged 45 ~ 64 (1.457; 1.060 ~ 2.002), and non-Hispanic White individuals (1.773; 1.316 ~ 2.388). A relationship was observed among only participants with obesity (1.553; 1.040 ~ 2.319) or underweight (1.380; 1.076 ~ 1.771), with college or above (1.645; 1.184 ~ 2.286), with PIR > 3.0 (1.701; 1.217 ~ 2.376), reported smoking (1.535; 1.235 ~ 1.907) and drinking (1.464; 1.232 ~ 1.739). For adolescents, blood manganese was positively associated with LTBI. The OR and 95% CIs for each one-unit increase in the log-transformed level of blood manganese with LTBI were 9.954 (1.389 ~ 71.344).ConclusionSignificant associations were observed in girls, aged ≥12 years and in the non-Hispanic white population. In conclusion, total mercury is associated with an increased prevalence of LTBI among adults and positive association between blood manganese and LTBI was observed among adolescents. Further studies should be conducted to verify the results and explore potential biological mechanisms.

In order to uncover the growth and decline of microorganisms during the processing of frozen cooked crayfish and to determine the critical control points, the traditional microbial culture method combined with high-throughput sequencing was used to analyze the changes in the microbial community at different processing stages, namely, raw materials, sand spitting, washing, cooking and finished products. The results showed that the sand spitting process could significantly reduce the number of microbes in the gills by 98.9%, but did not change the number of microbes in the intestine. The total number of colonies in the gills and intestines of crayfish decreased by 4.22 and 4.64 (lg(CFU/g)), respectively during the cooking process. The microbial load in crayfish meat was below the detection limit. Besides, the coliform bacteria and Pseudomonas were killed completely. The high-throughput sequencing results showed that the species abundance and diversity in the gills and intestine of raw crayfish were lower than those in cooked crayfish meat. The microbial community in the crayfish gills was dominated by Proteobacteria, while that in the intestine was dominated by Firmicutes. The species abundance and diversity of crayfish were reduced during sand spitting, and the relative abundance of Proteobacteria in the crayfish intestine was decreased significantly. The relative abundance of Flavobacterium in the meat and gills of crayfish was more significantly decreased after cooking compared with washing. The key control points of microorganisms during the processing of frozen cooked crayfish were determined as sand spitting and cooking, which will provide a theoretical basis for improving the quality and safety of and preserving crayfish products.

Introduction: The Huitongshan skarn-type deposits, in which ore bodies primarily occur in the outer contact zone between K-feldspar granite and marble in the Beishan area, are evidently related to hydrothermal alteration of the surrounding rock. Key mineral alteration processes include serpentinization, epidotization, chloritization, carbonatization, jarosite, ferritization, and hematitization.Methods: WorldView-3 (WV-3), a satellite-recorded high-spatial resolution multispectral image, has been widely used in the exploration and prediction of different types of deposits around the world. In this study, WV-3 multispectral images were used to extract the spatial distribution data of the main altered minerals in the Huitongshan area. Dedicated radiometric calibration, atmospheric correction, and image fusion were used to pre-process the extracted spectral information related to hydrothermal alteration. In addition, directed principal component analysis (PCA) and a unique mineral index were designed based on the effective use of the WV-3 data band corresponding to the spectral absorption characteristics of altered minerals.Results: The findings of this study show that the PCA model and mineral index pro-posed herein are reliable both in theory and for practically obtaining extraction information. Additionally, the WV-3 data are well suited for identifying hydroxy-bearing alterations with rich short-wave infrared bands that distinguish Fe-OH–bearing alterations from Mg-OH–bearing alterations. The results obtained were applied to identify potential targets for skarn-type copper deposits and the implementation of prospecting practices.Discussion: This study provides a basis for the application of WV-3 data as an important and effective tool for alteration information extraction and determination of prospecting practice, thereby proving the validity of multispectral remote sensing images in mineral resource exploration.