Galactic Cosmic Ray Particle Exposure Does Not Increase Protein Levels of Inflammation or Oxidative Stress Markers in Rat Microglial Cells In Vitro.

Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk of neurodegenerative disease. As key regulators of inflammation and OS in the CNS, microglial cells may be involved in GCR-induced deficits, and therefore could be a target for neuroprotection. This study assessed the effects of exposure to helium (4He) and iron (56Fe) particles on inflammation and OS in microglia in vitro, to establish a model for testing countermeasure efficacy. Rat microglia were exposed to a single dose of 20 cGy (300 MeV/n) 4He or 2 Gy 56Fe (600 MeV/n), while the control cells were not exposed (0 cGy). Immediately following irradiation, fresh media was applied to the cells, and biomarkers of inflammation (cyclooxygenase-2 [COX-2], nitric oxide synthase [iNOS], phosphorylated IκB-α [pIκB-α], tumor necrosis factor-α [TNFα], and nitrite [NO2-]) and OS (NADPH oxidase [NOX2]) were assessed 24 h later using standard immunochemical techniques. Results showed that radiation did not increase levels of NO2- or protein levels of COX-2, iNOS, pIκB-α, TNFα, or NOX2 compared to non-irradiated control conditions in microglial cells (p > 0.05). Therefore, microglia in isolation may not be the primary cause of neuroinflammation and OS following exposures to helium or iron GCR particles.

Unicompartmental knee arthroplasty combined with posterior cruciate ligament reconstruction: a case report.

BACKGROUND: In this study, we present the unique case of a patient with knee osteoarthritis (OA) of the medial compartment and posterior cruciate ligament (PCL) deficiency who underwent simultaneous medial unicompartmental knee arthroplasty (UKA) and PCL reconstruction. CASE PRESENTATION: A 49-year-old male patient presented with a 1-year history of pain and instability in the left knee. The patient had previously experienced a trauma-related injury to the PCL of the left knee that was left untreated. Imaging and physical examination confirmed the presence of left medial knee OA along with PCL rupture. To address these issues, the patient underwent UKA combined with PCL reconstruction. The patient's Lysholm score was 47 before surgery and 81 three months after surgery, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 29 before surgery and 18 three months after surgery, and the International Knee Documentation Committee (IKDC) subjective score was 56.3 before surgery and 74.7 three months after surgery. Six months after surgery, the patient's gait returned to normal, and he was able to jog. CONCLUSION: This case report presents the first instance of UKA combined with PCL reconstruction and introduces a novel treatment approach for patients suffering from medial knee OA and ligament injury.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Surgical treatment for recurrent patellar dislocation with severe torsional deformities: Double-level derotational osteotomy may not have a clear advantage over single-level derotational osteotomy in improving clinical and radiological outcomes.

PURPOSE: The purpose of this study was to investigate whether double-level (femur + tibia) derotational osteotomy is superior to single-level femoral derotational osteotomy for recurrent patellar dislocation with severe femoral and tibial rotational deformities (femoral anteversion >30° and external tibial torsion >30°). METHODS: Between January 2015 and June 2020, a total of 115 knees with recurrent patellar dislocation treated with combined medial patellofemoral ligament reconstruction (MPFL-R) and derotational osteotomies were evaluated after a minimum follow-up of 2 years. Among these cases, 15 knees that underwent double-level derotational osteotomy were included in the double-level group, which was propensity-matched in a 1:2 ratio to a single-level group of patients who underwent single-level femoral derotational osteotomy (30 knees). The clinical and radiological outcomes were evaluated and compared between the groups. Furthermore, the foot progression angle was measured preoperatively and 2 years after surgery. RESULTS: The patient-specific variables did not differ significantly between the double- and the single-level groups after propensity score matching. The postoperative mean foot progression angle was significantly lower in the double-level group than in the single-level group (9° ± 8° vs. 15° ± 11°; p = 0.014); however, there were no statistically significant differences between the groups in terms of any other clinical and radiological assessments. CONCLUSION: For patients with severe femoral and tibial torsional deformities (femoral anteversion >30° and external tibial torsion >30°), the double-level derotational osteotomy is superior to single-level osteotomy in maintaining normal foot progression angle, but it does not show an advantage in terms of patient-reported outcomes, radiological results and redislocation rate at minimum 2 years of follow-up. Furthermore, concomitant excessive external tibial torsion (>30°) did not have an adverse effect on clinical outcomes in patients who underwent derotational distal femoral osteotomy with MPFL-R due to excessive femoral anteversion. LEVEL OF EVIDENCE: Level III.

Recurrent patellar dislocation patients with high-grade J-sign have multiple structural bone abnormalities in the lower limbs.

PURPOSE: To explore the relationship between preoperative J-sign grading and structural bone abnormalities in patients with recurrent patellar dislocation (RPD). METHODS: A retrospective study was conducted on RPD patients over 5 years. Patients were categorised based on J-sign grade into low (J- and J1+), moderate (J2+) and high groups (J3+). Trochlear dysplasia (TD) and osseous structures (femoral anteversion angle [FAA], knee torsion, tibial tuberosity-trochlear groove [TT-TG] distance, Caton-Deschamps index) were assessed and grouped according to risk factor thresholds. The χ2 test was used to compare composition ratio differences of structural bone abnormalities among the groups. RESULTS: A total of 256 patients were included, with 206 (80.5%) females. The distribution of J-sign grade was as follows: 89 knees (34.8%) of low grade, 86 moderate (33.6%) and 81 high (31.6%). Among the five structural bone abnormalities, TD was the most common with a prevalence of 78.5%, followed by increased TT-TG at 47.4%. Excessive tibiofemoral rotation had the lowest occurrence at 28.9%. There were 173 (67.6%) patients who had two or more abnormalities, while 45 (17.6%) had four to five bony abnormalities. Among patients with any bony abnormality, the proportion of high-grade J-sign surpassed 40%. Patients with moderate and high-grade J-sign had more increased FAA and more pronounced patella alta (all p < 0.001). The proportion of excessive knee torsion and TD increased with increasing each J-sign grade, with the more notable tendency in knee torsion (high vs. moderate vs. low-grade: 61% vs. 22% vs 7%, p < 0.001). Furthermore, the higher J-sign grade was also associated with more combined bony abnormalities (p < 0.001). In the high-grade J-sign group, 90.2% of the knees had two or more bony risk factors and 40.7% had four or more, which were significantly higher than the moderate and low-grade J-sign groups (40.7% vs. 11.6% vs. 2.2%, p < 0.001). CONCLUSION: In patients with a high-grade J-sign, over 90% of the lower limbs had two or more structural bone risk factors, and more than 40% had four or more. These proportions were significantly higher compared to knees with low-grade and moderate J-sign. In clinical practice, when treating high-grade patellar mal-tracking, it is important to focus on and correct these strongly correlated abnormal bone structures. LEVEL OF EVIDENCE: Level III.

Identification and health risk evaluation of soil contaminated by polycyclic aromatic hydrocarbons at shale gas extraction sites based on positive matrix factorization.

The impact of shale gas extraction on surrounding environmental media remains unclear. In this study, the current state of contamination by polycyclic aromatic hydrocarbons (PAHs), which are high-frequency contaminants of shale gas, was investigated in the soil surrounding emerging shale gas development sites. The source analysis of PAHs was conducted in the soils of shale gas extraction sites using positive matrix factorization (PMF). The health risk assessment (HRA) was calculated for ingestion, dermal contact, and inhalation exposures, and the priority sources of PAHs in the soil were jointly identified by PMF and HRA to refine the contribution level of different individual PAHs to the carcinogenic risk. The results showed that both Sichuan and Chongqing mining site soils were contaminated to different degrees. Shale gas extraction has an impact on the surrounding soil, and the highest contributing source of PAHs in the mining site soil of Sichuan was anthropogenic activity, accounting for 31.6%, whereas that in the mining site soil of Chongqing was biomass combustion and mixed automobile combustion, accounting for 35.9%. At the two mining sites in Sichuan and Chongqing, none of the three exposure pathways (ingestion, dermal contact, and inhalation) posed a carcinogenic risk to children, whereas the dermal exposure pathway posed a carcinogenic risk to adults. Health risk assessments based on specific source assignments indicate that when managing soil pollution, the control of fossil fuel combustion and vehicular emissions should be prioritized.

The PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.

Cardiac computed tomography angiography-derived pulmonary vein volumetry as a predictor for atrial fibrillation recurrence after catheter ablation.

Background: There is an increasing evidence that pulmonary vein (PV) enlargement is associated with atrial fibrillation (AF); however, the predictive value of PV enlargement in AF recurrence remains unclear. This study sought to evaluate whether PV volume quantification derived from cardiac computed tomographic angiography (CCTA) could serve as a predictive indicator of the success of the catheter ablation (CA) procedure. Methods: The data of 160 patients diagnosed with AF who underwent both CCTA and CA treatments from January to June 2020 were retrospectively examined; the CCTA was conducted before the CA surgery. The study focused on documenting the PV structure, and the volume of the PV and left atrium (LA). The clinical, CCTA, and echocardiographic predictors of the recurrence and no-recurrence groups were compared. A multivariable logistic regression analysis was performed to adjust for confounders. Receiver operating characteristic (ROC) curves were analyzed to assess the predictive performance of the predictors of AF recurrence. Results: Of the 160 patients [55.6% male, 62.00 (55.25-68.00) years, 23.1% with persistent AF], 45 (28.1%) experienced AF recurrence within a one-year period. Notably, patients with AF recurrence had elevated CHADS2 scores (P=0.020) and increased LA and PV volumes (P<0.05). Patients with persistent AF (n=37) had significantly larger LA volume indexes (P<0.001) than those with paroxysmal AF, but there was no difference between the two groups in terms of the PV maximum volume index (P=0.200). Moreover, the PV maximum volume index [odds ratio (OR): 1.244, 95% confidence interval (CI): 1.008-1.536, P=0.042] and the LA minimum volume index (OR: 1.026, 95% CI: 1.001-1.052, P=0.038) were found to be significant predictors of AF recurrence. The ROC curves revealed that the PV maximum volume index threshold for predicting AF recurrence was 7.13 mL/m2, with a sensitivity of 84.4% and a specificity of 34.8% [area under the curve (AUC): 0.635, 95% CI: 0.540-0.730, P=0.008], and the LA minimum volume index threshold for predicting AF recurrence was 46.16 mL/m2, with a sensitivity of 88.9% and a specificity of 31.3% (AUC: 0.629, 95% CI: 0.534-0.723, P=0.012). A sub-analysis of patients with a lower left atrial dimension (LAD ≤38 mm in females, LAD ≤40 mm in males, n=120) demonstrated that the PV maximum volume index was a noteworthy indicator of AF recurrence (OR: 1.443: 95% CI: 1.145-1.820, P=0.002). Conversely, no significant correlation between AF recurrence and the LA volume index was found. The AUC value for the PV maximum volume index predictive of recurrent AF was 0.680 (95% CI: 0.577-0.781, P=0.003), with a sensitivity of 75.8%, specificity of 54%, and the cut-off value of the maximum AUC was 7.89 mL/m2. Conclusions: PV volume, derived from CCTA, may help to predict the recurrence of AF after CA, and is superior to the LA size in patients with less pronounced LA enlargement.

Derotational distal femoral osteotomy improves subjective function and patellar tracking after medial patellofemoral ligament reconstruction in recurrent patellar dislocation patients with increased femoral anteversion: A systematic review and meta-analysis.

PURPOSE: The purpose of this study is to systematically review and quantitatively analyse the clinical outcomes of combined derotational distal femoral osteotomy (D-DFO) and medial patellofemoral ligament reconstruction (MPFL-R) in the treatment of recurrent patellar dislocation (RPD) with increased femoral anteversion angle (FAA). METHODS: This study was performed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality Of Systematic Reviews) Guidelines. PubMed, Embase, Web of Science and Cochrane Library databases were searched to identify studies reporting clinical outcomes of combined D-DFO and MPFL-R in RPD patients with increased FAA. Data on patient-reported outcome measures, radiological parameters, patellar tracking as revealed by J-sign and complications were extracted based on the inclusion criteria. The Methodological Index for Non-Randomized Study score was used for quality assessment. Review Manager and R statistical software were used to perform the statistical analysis. RESULTS: Eleven studies with a total of 569 knees in 553 patients were included. Patients were predominantly female (79%). The weighted mean of FAA decreased from 33.6° to 13.0° (weighted mean difference = 20.59; p < 0.00001) after the combined procedure. Significant improvements (p < 0.00001) were identified in the Lysholm score (weighted mean: 55.5 vs. 80.4), International Knee Documentation Committee (IKDC) score (weighted mean: 52.8 vs. 78.6) and Kujala score (weighted mean: 54.5 vs. 80.6). The incidence of residual J-sign ranged from 14.3% to 38.3% with an overall pooled rate of 28.2% (95% confidence interval = 22.8%-33.6%). The overall redislocation rate was 1.1%. No patients experienced surgical site infection or bone nonunion. Two studies compared the clinical outcomes of MPFL-R with and without D-DFO. Compared with isolated MPFL-R, the combined procedure yielded a better Lysholm score (weighted mean: 84.9 vs. 79.3, p < 0.0001), IKDC score (weighted mean: 84.1 vs. 79.9, p = 0.001), Kujala score (weighted mean: 84.3 vs. 79.4, p < 0.0001) and a lower residual J-sign rate (26/97 [26.8%] vs. 44/105 [41.9%], p = 0.02), respectively. CONCLUSION: The combination of D-DFO and MPFL-R led to improved clinical outcomes and a low redislocation rate in patients with RPD and increased FAA. Additional D-DFO can achieve more favourable results in subjective function and patellar tracking than isolated MPFL-R in the setting of excessive FAA. LEVEL OF EVIDENCE: Level IV.

SGSR: style-subnets-assisted generative latent bank for large-factor super-resolution with registered medical image dataset.

PURPOSE: We propose a large-factor super-resolution (SR) method for performing SR on registered medical image datasets. Conventional SR approaches use low-resolution (LR) and high-resolution (HR) image pairs to train a deep convolutional neural network (DCN). However, LR-HR images in medical imaging are commonly acquired from different imaging devices, and acquiring LR-HR image pairs needs registration. Registered LR-HR images have registration errors inevitably. Using LR-HR images with registration error for training an SR DCN causes collapsed SR results. To address these challenges, we introduce a novel SR approach designed specifically for registered LR-HR medical images. METHODS: We propose style-subnets-assisted generative latent bank for large-factor super-resolution (SGSR) trained with registered medical image datasets. Pre-trained generative models named generative latent bank (GLB), which stores rich image priors, can be applied in SR to generate realistic and faithful images. We improve GLB by newly introducing style-subnets-assisted GLB (S-GLB). We also propose a novel inter-uncertainty loss to boost our method's performance. Introducing more spatial information by inputting adjacent slices further improved the results. RESULTS: SGSR outperforms state-of-the-art (SOTA) supervised SR methods qualitatively and quantitatively on multiple datasets. SGSR achieved higher reconstruction accuracy than recently supervised baselines by increasing peak signal-to-noise ratio from 32.628 to 34.206 dB. CONCLUSION: SGSR performs large-factor SR while given a registered LR-HR medical image dataset with registration error for training. SGSR's results have both realistic textures and accurate anatomical structures due to favorable quantitative and qualitative results. Experiments on multiple datasets demonstrated SGSR's superiority over other SOTA methods. SR medical images generated by SGSR are expected to improve the accuracy of pre-surgery diagnosis and reduce patient burden.

The Posterosuperior Tetralogy Scoring System as a Practical Tool to Predict Shoulder Function After Posterosuperior Large-to-Massive Rotator Cuff Repairs.

Background: Fatty infiltration (FI) or atrophy alone has been found to be inaccurate in predicting shoulder function after repair of large-to-massive rotator cuff tears (L/MRCTs), especially when a diverse extent of FI and atrophy presents in multiple rotator cuff muscles. Purpose/Hypothesis: The Posterosuperior Tetralogy Scoring System (PS-Tetra Score), which integrates FI and atrophy, was proposed to predict shoulder function after surgery. It was hypothesized was that a PS-Tetra Score ≥3 would be a risk factor for poor shoulder function after repair of posterosuperior L/MRCTs and would possess greater diagnostic value than using isolated FI or atrophy of the supraspinatus (SSP) or infraspinatus (ISP). Study Design: Case-control study; Level of evidence, 3. Methods: A total of 187 arthroscopic repairs of posterosuperior L/MRCTs were reviewed. Magnetic resonance imaging evaluations were performed of FI and atrophy of the SSP and ISP, teres minor hypertrophy, tendon retraction, and acromiohumeral distance. A postoperative American Shoulder and Elbow Surgeons (ASES) score of 70 was used to subgroup patients according to shoulder function. Univariate and multivariate analyses were performed to determine the risk factors of poor shoulder function (ASES ≤70). The diagnostic values of different indicators for predicting shoulder function were evaluated. Results: In univariate analysis, female sex, higher Goutallier grade of the SSP and ISP, positive SSP tangent sign, and PS-Tetra Score ≥3 was significantly associated with ASES score ≤70, whereas in binary logistic regression analysis, a PS-Tetra Score ≥3 was the only significant risk factor for poor shoulder function. The occurrence rate of poor function in shoulders with a PS-Tetra Score of 0, 1, 2, 3, and 4 was 0% (0/52), 0% (0/52), 19.57% (9/46), 58.06% (18/31), and 83.33% (5/6), respectively. PS-Tetra Score ≥3 possessed higher crude agreement (87.70%), specificity (90.97%), positive predictive value (62.16%), and area under the receiver operating characteristic curve (0.814) than the other 3 indicators, with relatively high negative predictive value (94.00%) and moderate sensitivity (71.88%). Conclusion: PS-Tetra Score ≥3 was a risk factor of poor shoulder function after repair of posterosuperior L/MRCTs and possessed greater diagnostic value than using isolated FI or atrophy of SSP or ISP alone for predicting shoulder function.

Increased TT-TG distance caused by excessive tibiofemoral rotation predicts poor clinical outcomes after tibial tubercle osteotomy in recurrent patellar dislocation.

PURPOSE: To compare clinical outcome between recurrent patellar dislocation (RPD) with or without actual tibial tubercle lateralisation (TTL) after medial patellofemoral ligament reconstruction (MPFL-R) combined with tibial tubercle transfer. METHODS: From 2015 to 2018, a total of 172 knees with RPD and a tibial tubercle-trochlear groove (TT-TG) distance of > 20 mm were treated with MPFL-R combined with tibial tubercle transfer. Patients were divided into the lateralisation group (TT-PCL > 24 mm, n = 74) and the nonlateralisation group (TT-PCL ≤ 24 mm, n = 60) based on the presence or absence of actual TTL (TT-PCL > 24 mm). Clinical outcomes were assessed postoperatively at a minimum of 2 years. Second-look arthroscopic evaluations were available for 84 knees to assess cartilage damage. RESULTS: A total of 134 knees with a median follow-up time of 32 months were included. Tibiofemoral rotation (TFR) was significantly higher in the nonlateralisation group than in the lateralisation group (15.4° vs. 9.4°, P < 0.001). At the final follow-up, the nonlateralisation group had significantly lower Kujala (78.2 vs. 86.4, P = 0.001) and Lysholm (80.3 vs. 88.2, P = 0.003) scores than the lateralisation group. At the time of the second-look arthroscopic assessment, 38.9% of the patients in the nonlateralisation group showed cartilage worsening in the medial patellar facet that was significantly higher than that in the lateralisation group (38.9% vs. 12.5%, P = 0.015). CONCLUSION: Patients with RPD and an increased TT-TG distance of > 20 mm but without actual tibial tubercle lateralisation benefit less from tibial tubercle transfer than patients with actual tibial tubercle lateralisation, which may be related to the significantly higher tibiofemoral rotation angle of the former. LEVEL OF EVIDENCE: III.

Alternative polyadenylation reprogramming of MORC2 induced by NUDT21 loss promotes KIRC carcinogenesis.

Alternative polyadenylation (APA), a posttranscriptional mechanism of gene expression via determination of 3'UTR length, has an emerging role in carcinogenesis. Although abundant APA reprogramming is found in kidney renal clear cell carcinoma (KIRC), which is one of the major malignancies, whether APA functions in KIRC remains unknown. Herein, we found that chromatin modifier MORC2 gained oncogenic potential in KIRC among the genes with APA reprogramming, and moreover, its oncogenic potential was enhanced by 3'UTR shortening through stabilization of MORC2 mRNA. MORC2 was found to function in KIRC by downregulating tumor suppressor DAPK1 via DNA methylation. Mechanistically, MORC2 recruited DNMT3A to facilitate hypermethylation of the DAPK1 promoter, which was strengthened by 3'UTR shortening of MORC2. Furthermore, loss of APA regulator NUDT21, which was induced by DNMT3B-mediated promoter methylation, was identified as responsible for 3'UTR shortening of MORC2 in KIRC. Additionally, NUDT21 was confirmed to act as a tumor suppressor mainly depending on downregulation of MORC2. Finally, we designed an antisense oligonucleotide (ASO) to enhance NUDT21 expression and validated its antitumor effect in vivo and in vitro. This study uncovers the DNMT3B/NUDT21/APA/MORC2/DAPK1 regulatory axis in KIRC, disclosing the role of APA in KIRC and the crosstalk between DNA methylation and APA.

Magnetic iron-based nanoparticles biogeochemical behavior in soil-plant system: A critical review.

Increasing attention is being given to magnetic iron-based nanoparticles (MINPs) because of their potential environmental benefits. Owing to the earth abundance and high utilization of MINPs, as well as the significant functions of Fe in sustainable agriculture and environmental remediation, an understanding of the environmental fate of MINPs is indispensable. However, there are still knowledge gaps regarding the largely unknown environmental behaviors and fate of MINPs in soil-plant system. Thus, this review summarizes recent literature on the biogeochemical behavior (uptake, transportation, and transformation) of MINPs in soil and plants. The different possible uptake (e.g., foliar and root adsorption) and translocation (e.g., xylem, phloem, symplastic/apoplastic pathway, and endocytosis) pathways are discussed. Furthermore, drivers of MINPs uptake and transportation (e.g., soil characteristics, fertilizer treatments, copresence of inorganic and organic anions, meteorological conditions, and cell wall pores) in both soil and plant environments are summarized. This review also details the physical, chemical, and biological transformations of MINPs in soil-plant system. More importantly, a metadata analysis from the existing literature was employed to investigate the distinction between MINPs and other engineering nanoparticles biogeochemical behavior. In the future, more attention should be given to understanding the behavior of MINPs in soil-plant system and improving the capabilities of predictive models. This review thus highlights the main knowledge gaps regarding MINPs behavior and fate to provide guidance for their safe application in agrochemicals, crop production, and soil health.

Iron oxide nanoparticles in the soil environment: Adsorption, transformation, and environmental risk.

Iron oxide nanoparticles (IONPs) have great application potential due to their multifunctional excellence properties, leading to the possibility of their release into soil environments. IONPs exhibit different adsorption properties toward environmental pollutants (e.g., heavy metals and organic compounds), thus the adsorption performance for various contaminants and the molecular interactions at the IONPs-pollutants interface are discussed. After solute adsorption, the change in the environmental behavior of IONPs is an important transformation process in the natural environments. The aggregation, aging process, and chemical/biological transformation of IONPs can be altered by soil solution chemistry, as well as by the presence of dissolved organic matter and microorganisms. Upon exposure to soil environments, IONPs have both positive and negative impacts on soil organisms (e.g., bacteria, plants, nematodes, and earthworms). Moreover, we compared the toxicity of IONPs alone to combined toxicity with environmental pollutants and pristine IONPs to aged IONPs, and the mechanisms of IONPs toxicity at the cellular level are also reviewed. Given the unanswered questions, future research should include prediction and design of IONPs, new characterization technology for monitoring IONPs transformation in soil ecosystems, and further refinement the environmental risk assessment of IONPs. This review will greatly enhance our knowledge of the performance and impact of IONPs in soil systems.

Assessment of potential health risks from heavy metal pollution of surface water for drinking in a multi-industry area in Mali using a multi-indices approach.

The Niger River, Bamako's population's primary drinking water source, is threatened by human activities. This study examines the Niger River pollution trend using heavy metals pollution indexes and Bamako's population's non-carcinogenic and carcinogenic related health risks. Parameters were monitored at fifteen sampling locations in low and high flow seasons. pH (7.30-7.50) and fluoride (0.15-0.26 mg/L) were within the normal drinking water range. Among seven heavy metals (copper, zinc, cadmium, nickel, iron, manganese, and lead), the latter three were above the drinking water standard. The degree of contamination was negative, pointing to better water quality. However, the heavy metal evaluation index (HEI) was below the mean (5.88), between the mean and twice the mean, indicating a low and medium degree of pollution. Besides, heavy metal pollution indexes (HPI) were above the standard value (100), explaining a low-medium pollution level. High values of HPI could be explained by the industrial units' intensive activities coupled with the runoff effect. The hazard index (HI) indicated a low and medium non-carcinogenic health risk for adults and children. The probability of cancer risk (PCR) of nickel showed a cancer risk. Therefore, the river was polluted with trace elements and could not be used for drinking water without any treatment.

Effect of Bone Cement Thickness on the Risk of Scalded Skin in Joint Surgery.

OBJECTIVE: Bone cement releases a large amount of heat as it polymerizes. Skin burns caused by discarded bone cement are not well understood during arthroplasty. It is important to study the correlates and mechanisms of scalding and to accurately evaluate the severity of burns to guide treatment decisions. METHODS: Standardized burns were created in eight anesthetized rabbits using different thicknesses of bone cement. Bone cement was uniformly stirred to make thicknesses of 1 mm, 4 mm, 8 mm, 12 mm, 16 mm, and 20 mm and a 20 × 40 mm cuboid. Bone cement samples were then placed on the back of a rabbit, and the temperature changes were recorded with an industrial digital thermometer. One hour later, the appearance of scalded skin was observed, and the rabbits were euthanized. The scalded parts were cut to make pathological sections and stained with HE, and the differences in the depth of the scalded skin caused by different thicknesses of bone cement were observed under a light microscope. RESULTS: Damage caused by 1 mm-, 4 mm-, 8 mm-, 12 mm-, 16 mm-, and 20 mm-thick bone cement samples mainly involved the epidermis, the papillary dermis, the reticular dermis layer, and the full thickness of the skin and the subcutaneous tissue. The maximum temperature of 1 mm, 4 mm, 8 mm, and 12 mm bone cementation had a statistically significant difference (p < 0.001), while there was no significant difference between 12 mm, 16 mm, and 20 mm samples (p = 0.856). The time to severe scalding with bone cement at temperatures above 70°C was significantly different between different thicknesses (p < 0.001). CONCLUSION: The heat released by different thicknesses of bone cement leads to different maximum temperatures and the duration of severe burns, resulting in different degrees of skin burns. Attention should be paid to discarded bone cement to prevent this potential complication in knee arthroplasty.

[Clinical and radiologic outcomes after tendon insertion medialized repair of large-to-massive rotator cuff tears].

Objective: To evaluate the effectiveness of tendon insertion medialized repair in treatment of large-to-massive rotator cuff tears (L/MRCT). Methods: The clinical and imaging data of 46 L/MRCT patients who underwent arthroscopic insertion medialized repair between October 2015 and June 2019 were retrospectively analyzed. There were 26 males and 20 females with an average age of 57.7 years (range, 40-75 years). There were 20 cases of large rotator cuff tears and 26 cases of massive rotator cuff tears. Preoperative imaging evaluation included fatty infiltration (Goutallier grade), tendon retraction (modified Patte grade), supraspinatus tangent sign, acromiohumeral distance (AHD), and postoperative medializaiton length and tendon integrity. The clinical outcome was evaluated by visual analogue scale (VAS) score, American Society for Shoulder and Elbow Surgery (ASES) score, shoulder range of motion (including anteflexion and elevation, lateral external, and internal rotation) and anteflexion and elevation muscle strength before and after operation. The patients were divided into two groups (the intact tendon group and the re-teared group) according to the integrity of the tendon after operation. According to the medializaiton length, the patients were divided into group A (medialization length ≤10 mm) and group B (medialization length >10 mm). The clinical function and imaging indexes of the patients were compared. Results: All patients were followed up 24-56 months, with an average of 31.8 months. At 1 year after operation, MRI showed that the medializaiton length of supraspinatus tendon was 5-15 mm, with an average of 10.26 mm, 33 cases in group A and 13 cases in group B. Eleven cases (23.91%) had re-teared, including 5 cases (45.45%) of Sugaya type Ⅳ and 6 cases (54.55%) of Sugaya type Ⅴ. At last follow-up, the VAS score, ASES score, shoulder anteflexion and elevation range of motion, lateral external rotation range of motion, and anteflexion and elevation muscle strength significantly improved when compared with those before operation ( P<0.05); there was no significant difference in internal rotation range of motion between pre- and post-operation ( P>0.05). The Goutallier grade and modified Patte grade of supraspinatus muscle in the re-teared group were significantly higher than those in the intact tendon group, and the AHD was significantly lower than that in the intact tendon group ( P<0.05). There was no significant difference in other baseline data between the two groups ( P>0.05). Except that the ASES score of the intact tendon group was significantly higher than that of the re-teared group ( P<0.05), there was no significant difference in the other postoperative clinical functional indicators between the two groups ( P>0.05). There was no significant difference in the incidence of re-tear, VAS score, ASES score, range of motion of shoulder joint, and anteflexion and elevation muscle strength between group A and group B ( P>0.05). Conclusion: Tendon insertion medialized repair may be useful in cases with L/MRCT, and shows good postoperative shoulder function. Neither tendon integrity nor medialization length shows apparent correlations with postoperative shoulder function.

Effect of Sleep Position on Sleep-Disordered Breathing in Young Children With Unrepaired Incomplete Cleft Palates.

Children with cleft lip/palate are usually faced with upper airway problems after surgical repair. The severity of upper airway obstruction is more likely associated with the age and preoperative diagnosis of obstructive sleep apnea (OSA). This study aimed to investigate the severity of OSA in toddlers before palatoplasty from the perspective of polysomnography. In this retrospective cohort study, 97 children with unrepaired cleft palate and habitual prone sleeping were identified with a mean age of 1.6 years (SD 0.6) and divided into 2 age groups (1.5 year or younger and older than 1.5 year). Detailed information was collected including demographics, sleep parameters, and respiratory disturbances. Polysomnography results showed these children were at high risks of OSA with averagely moderate severity at night during their early childhood [apnea-hypopnea index 7.2±3.2 events/hour; obstructive apnea index (OAI) 6.5±2.8 events/hour]. Positional OAI was greatly lower in prone than that in laterals or in supine. Far more sleep time was spent in prone than in supine (42.9%±42.2% versus 8.5%±15.7%), which were consistent with parental reporting of prone sleeping habits. There were no significant differences found between the 2 age groups in respiratory disturbances such as apnea-hypopnea index, OAI, mean oxygen saturation, and nadir oxygen saturation ( P =0.097-0.988). Thus, prone sleeping with a history of snoring might be indicators for early screening for OSA in the cleft population. Adequate attention should be paid to their upper airway and, if available, overnight polysomnography should be performed to ascertain their potential respiratory problems before repair surgery.

Blueberry treatment administered before and/or after lipopolysaccharide stimulation attenuates inflammation and oxidative stress in rat microglial cells.

ABSTRACTMicroglia are key regulators of inflammation and oxidative stress (OS) in the CNS. Microglia activation can lead to chronic inflammation, OS, and neurodegeneration. Blueberries (BB) reduce inflammation and OS when administered to microglia before stressors such as lipopolysaccharide (LPS), but the therapeutic value of BBs administered after activation by stressors has not been examined. Therefore, this study investigated the differential effects of pre-, post-, and pre-/post-BB on inflammation and OS in LPS-activated microglia. Rat microglia were pretreated with BB (0.5 mg/mL) or control media (C) for 24 hours, incubated overnight with LPS (0 or 200 ng/mL), and post-treated with BB or C for 24 hours. Biomarkers of inflammation (e.g. nitrite [NO2-], tumor necrosis factor-ɑ [TNFɑ], inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2], phosphorylated IκB-α [pIκB-ɑ]) and OS (e.g. NADPH oxidase [NOX2]) were assessed. LPS increased NO2-, TNFɑ, COX-2, iNOS, pIκB-ɑ, and NOX2 compared to non-stressed conditions (P < 0.05), however BB before and/or after LPS significantly reduced these markers compared to no BB (P < 0.05). Pre-BB was more effective than post-BB at reducing LPS-induced NO2-, TNFɑ, and COX-2 (P < 0.05). Pre-BB was also more effective than pre-/post-BB at attenuating LPS-induced NO2- and TNFɑ (P < 0.05). All BB treatments were equally effective in reducing LPS-induced iNOS, pIκB-ɑ, and NOX2. Results suggest that BBs can target the downstream events of LPS-induced microglial activation and prevent stressor-induced neuroinflammation and OS. Furthermore, BBs may not need to be present prior to microglial activation for beneficial effects, suggesting that dietary interventions may be effective even after initiation of disease processes.Graphical Abstract. Cascade of inflammatory and OS-inducing events associated with self-propelling microglial activation by LPS and the effects of blueberry (0.5 mg/mL) administered before and/or after LPS on these processes (blue arrows). BB, blueberry; COX2, cyclooxygenase-2; IκB-ɑ, inhibitor kappa-B-ɑ; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; NF-κB, nuclear factor kappa-B; NO, nitric oxide; NOX2, NADPH oxidase; OS, oxidative stress; ROS, reactive oxygen species; TNFɑ, tumor necrosis factor-ɑ.