Search

Abstract Background Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. Methods In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator’s overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. Discussion The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. Trial registration ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538

Background Body mass index (BMI) is associated with diabetic nephropathy (DN). However, the mediator factors in the BMI-DN effects remain unclear.Methods Univariate and multivariate Mendelian randomization (MR) analysis were performed to estimate the association between six lifestyles (moderate to vigorous physical activity levels, years of schooling, BMI, nap during day, number of treatments/medications taken and coffee intake) and DN. MR Egger, Weighted median, Simple mode, and Weighted mode was supplemental methods to Inverse variance weighted. Sensitivity analysis included heterogeneity test, horizontal pleiotropy test, and Leave-One-Out. Additionally, mediation MR was conducted to evaluate the mediating role of lifestyles between BMI and DN. Finally, functional enrichment analysis based on the mediation MR results was performed.Results univariate and multivariate Mendelian randomization (MR) analysis were performed to estimate the association between six lifestyles (moderate to vigorous physical activity levels, years of schooling, BMI, nap during day, number of treatments/medications taken and coffee intake) and DN. MR Egger, Weighted median, Simple mode, and Weighted mode was supplemental methods to Inverse variance weighted. Sensitivity analysis included heterogeneity test, horizontal pleiotropy test, and Leave-One-Out. Additionally, mediation MR was conducted to evaluate the mediating role of lifestyles between BMI and DN. Finally, functional enrichment analysis based on the mediation MR results was performed.Conclusion our results supported mediation role of vigorous physical activity level and number of treatments/medications in BMI-DN effects.

Abstract Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD‐L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD‐L1, and a lower proportion expressed PAX‐8 and TTF‐1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.

Brazil has a long history of using biological control and has the largest program in sugarcane agriculture to which a biocontrol program has been applied. This achievement is at least partly due to the utilization of the entomopathogenic fungus Metarhizium. This well-known fungal genus exhibits pathogenicity against a broad range of arthropod hosts and has been used globally as a biocontrol agent. This fungus is also a root symbiont, and in this capacity, it is a plant growth promoter. However, this feature (i.e., as a plant symbiont) has yet to be fully explored and implemented in Brazil, although the number of reports demonstrating Metarhizium’s utility as a plant bioinoculant is increasing. The Brazilian bioproduct industry targets agricultural pests, and is limited to two Metarhizium species represented by four fungal isolates as active ingredients. Entomopathogenic fungi have also been successful in controlling arthropods of public health concern, as shown in their control of mosquitoes, which are vectors of diseases. The isolation of new indigenous Metarhizium isolates from a variety of substrates such as soil, insects, and plants shows the wide genetic diversity within this fungal genus. In this review, we emphasize the significance of Metarhizium spp. for the biological control of insects in Brazil. We also suggest that the experience and success of biological control with fungi in Brazil is an important resource for developing integrated pest management and sustainable strategies for pest control worldwide. Moreover, the future implementation prospects of species of Metarhizium being used as bioinoculants and possible new advances in the utility of this fungus are discussed.

ObjectivesTo evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC).MethodsMeta-analysis was conducted to assess the caliber of the included literature by searching five databases for randomized controlled trials of DFMO chemoprevention in the high-risk population of CRC, with RevMan 5.4, Stata 15.0 and TSA 0.9.5.10 employed to statistically analyze the extracted data. Grade profiler 3.6 was employed for grading the evidence for the outcome indicators (disease progression and adenoma incidence).ResultsSix trials were finally included in this research, with the collective data indicating that the DFMO combination therapy was efficacious in lowering the incidence of recurrent adenomas in patients who had experienced advanced CRC [RR 0.34, 95% CI 0.14 - 0.83, P < 0.05]. Meta-analysis showed that DFMO combined therapy had no statistical difference in disease progression in patients with familial adenomatous polyposis[RR 0.52, 95% CI 0.14 - 1.86, P > 0.05]; Trial Sequential Analysis reveals that the combination therapy of DFMO effectively diminishes the occurrence of recurrent adenomas in patients with a history of advanced colorectal tumors, displaying a Risk Ratio (RR) of 0.33 with a 95% Confidence Interval (CI) of 0.12 - 0.90 and a significance level of P < 0.05. This combination exhibits a statistically significant difference. Subgroup analysis demonstrates that, depending on the drug treatment regimen (DFMO+ Aspirin/DFMO+ Sulindac), the combination of DFMO and aspirin exhibits an effect comparable to a placebo in diminishing the occurrence of new adenomas in patients with a history of advanced colorectal tumors. However, the combination of DFMO and sulindac significantly mitigates the incidence of recurrent adenomas in this patient population.ConclusionThis meta-analysis indicates that the existing randomized controlled trials are adequate to ascertain the efficacy of DFMO combination therapy in diminishing the incidence of recurrent adenomas in patients who have previously encountered advanced colorectal tumors. However, further clinical trials need to be conducted to evaluate the optimum dosage and treatment course of prophylactic implementation of DFMO combination therapy in high-risk populations.

Backgrounds: Spontaneous preterm birth (SPB) is a global problem. Early screening, identification, and prevention in asymptomatic pregnant women with risk factors for preterm birth can help reduce the incidence and mortality of preterm births. Therefore, this study systematically reviewed prediction models for spontaneous preterm birth, summarised the model characteristics, and appraised their quality to identify the best-performing prediction model for clinical decision-making. Methods: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP Database, and Wanfang Data were searched up to September 27, 2021. Prediction models for spontaneous preterm births in singleton asymptomatic pregnant women with risk factors were eligible for inclusion. Six independent reviewers selected the eligible studies and extracted data from the prediction models. The findings were summarised using descriptive statistics and visual plots. Results: Twelve studies with twelve developmental models were included. Discriminative performance was reported in 11 studies, with an Area Under the Curve (AUC) ranging from 0.75 to 0.95. The AUCs of the seven models were greater than 0.85. Cervical length (CL) is the most commonly used predictor of spontaneous preterm birth. A total of 91.7% of the studies had a high risk of bias in the analysis domain, mainly because of the small sample size and lack of adjustment for overfitting. Conclusion: The accuracy of the models for spontaneous preterm births in singleton asymptomatic women with risk factors was good. However, these models are not widely used in clinical practice because they lack replicability and transparency. Future studies should transparently report methodological details and consider more meaningful predictors with new progress in research on preterm birth.

Abstract Metarhizium robertsii is an insect pathogen as well as an endophyte, and can antagonize the phytopathogen, Fusarium solani during bean colonization. However, plant immune responses to endophytic colonization by Metarhizium are largely unknown. We applied comprehensive plant hormone analysis, transcriptional expression and stomatal size analysis in order to examine plant immune responses to colonization by Metarhizium and/or Fusarium. The total amount of abscisic acid (ABA) and ABA metabolites decreased significantly in bean leaves by plant roots colonized by M. robertsii and increased significantly with F. solani compared to the un-inoculated control bean plant. Concomitantly, in comparison to the un-inoculated bean, root colonization by Metarhizium resulted in increased stomatal size in leaves and reduced stomatal size with Fusarium. Meanwhile, expression of plant immunity genes was repressed by Metarhizium and, alternately, triggered by Fusarium compared to the un-inoculated plant. Furthermore, exogenous application of ABA resulted in reduction of bean root colonization by Metarhizium but increased colonization by Fusarium compared to the control without ABA application. Our study suggested that ABA plays a central role in differential responses to endophytic colonization by Metarhizium and pathogenic colonization by Fusarium and, we also observed concomitant differences in stomatal size and expression of plant immunity genes.

Abstract. Introduction:. When initiating urate-lowering therapy, using anti-inflammatory prophylaxis therapy for at least 3 to 6 months is strongly recommended. Previous studies have found that zhengqing fengtongning sustained-release tablets (sinomenine) can improve inflammation in the acute phase of gout; however, the efficacy of urate-lowering therapy in reducing frequency of acute flares still needs to be investigated. The aim of the present study is to explore the efficacy and safety of sinomenine for prophylaxis of acute flares when initiating urate-lowering therapy. Methods and analysis:. This randomized, placebo-controlled, double-blinded trial will include a total of 210 gout patients who meet the study criteria. The patients will be randomized (1:1) to the test group and the control group. The intervention is planned to be performed for 12 weeks with a follow-up of 12 weeks. All patients would be administered febuxostat (40 mg/d) and concomitant anti-inflammatory prophylaxis therapy. Sinomenine and colchicine placebo are administered in the sinomenine group, sinomenine placebo and colchicine are administered in the colchicine group. The primary outcome is the rate of acute gout flares in subjects within 12 weeks of the treatment period. The secondary outcomes include the times of acute gout flares and the duration of each acute flares within 12 weeks; the compliance rate in patients whose UA levels ≤6.0 mg/dL (360 μmol/L) at the weekend of 2nd, 4th, 8th, and 12th week in each group; the proportion of patients with ≥1 and ≥2 gout flares within 12 weeks; average visual analogue scale/score pain score during gout flares; and the oral dose of etoricoxib will be used to control the onset of acute flares within 12 weeks. Ethics and dissemination:. The Institutional Medical Ethics Committee have approved the trial protocol. We plan to publish the results of this study in a peer-reviewed journal. Trial registration:. ChiCTR, ChiCTR2100045114, Registered 8 April 2021 http://www.chictr.org.cn/showproj.aspx?proj=124688

Abstract In locally convex Hausdorff topological vector spaces, the approximate Benson efficient solution is proposed for set-valued equilibrium problems and its relationship to the Benson efficient solution is discussed. Under the assumption of generalized convexity, by using a separation theorem for convex sets, Kuhn–Tucker-type and Lagrange-type optimality conditions for set-valued equilibrium problems are established, respectively.

Giant cell tumor (GCT) of the bone is a rare benign, locally aggressive tumor that occurs in the epiphysis of long bones, especially the lower femur and the upper tibia. GCT of the bone of cranial origin is very rare, accounting for 1% of all GCT of the bone. We report the diagnosis, treatment, and immunohistochemistry of a rare case of intracranial GCT of the bone. We also review and summarize the imaging features, diagnostic markers, and current major treatment options for GCT of the bone. Our case and literature review emphasizes the importance of considering the full picture when making a diagnosis, rather than relying on imaging alone to make the diagnosis.

New research has shown that the development of osteoarthritis (OA) is regulated by different mechanisms of cell death and types of cytokines. Therefore, elucidating the mechanism of action among various cytokines, cell death processes and OA is important towards better understanding the pathogenesis and progression of the disease. This paper reviews the pathogenesis of OA in relation to different types of cytokine-triggered cell death. We describe the cell morphological features and molecular mechanisms of pyroptosis, apoptosis, necroptosis, and ferroptosis, and summarize the current research findings defining the molecular mechanisms of action between different cell death types and OA.

Background and Aims. Diagnosing pediatric intussusception from ultrasound images can be a difficult task in many primary care hospitals that lack experienced radiologists. To address this challenge, this study developed an artificial intelligence- (AI-) based system for automatic detection of “concentric circles” signs on ultrasound images, thereby improving the efficiency and accuracy of pediatric intussusception diagnosis. Methods. A total of 440 cases (373 pediatric intussusception and 67 normal cases) were retrospectively collected from Children’s Hospital affiliated to Zhejiang University School of Medicine from January 2020 to December 2020. An improved Faster RCNN deep learning framework was used to detect “concentric circle” signs. Finally, independent validation set was used to evaluate the performance of the developed AI tool. Results. The data of pediatric intussusception were divided into a training set and validation set according to the ratio of 8 : 2, with training set (298 pediatric intussusception) and validation set (75 pediatric intussusception and 67 normal cases). In the “concentric circle” detection model, the detection rate, recall, specificity, and F1 score assessed by the validation set were 92.8%, 95.0%, 92.2%, and 86.4%, respectively. Pediatric intussusception was classified by “concentric circle” signs, and the accuracy, recall, specificity, and F1 score were 93.0%, 92.0%, 94.1%, and 93.2% on the validation set, respectively. Conclusion. The model established in this paper can realize the automatic detection of “concentric circle” signs in the ultrasound images of abdominal intussusception in children; the AI tool can improve the diagnosis speed of pediatric intussusception. It is necessary to further develop an artificial intelligence system for real-time detection of “concentric circles” in ultrasound images for the judgment of children with intussusception.

The driving ranges of electric vehicles (EVs) will decrease greatly with increased use of the vehicle heating system in a cold climate. Air conditioning heat pump (ACHP) systems, which convert energy stored in the ambient environment into heat, represent a promising approach for increasing the EV driving range. In this work, the performance of an ACHP system in an EV under extremely cold conditions is investigated experimentally. The requirements of an ACHP system for EVs at various ambient temperatures are determined using our capacity matching strategy. A prototype system designed based on these requirements is evaluated. Data collected from experiments performed at a full-scale facility under extreme temperature conditions are analyzed. The results show that the ACHP system proposed for EV applications can satisfy both the cooling and heating requirements for the passenger compartment. The system increased the driving range by 23% when compared with that of an EV using a positive-temperature-coefficient (PTC) heater at −10 °C.

BackgroundBladder cancer (BCa) is a commonly diagnosed malignancy worldwide that has poor survival depending on its intrinsic biologic aggressiveness and a peculiar radio- and chemoresistance features. Gaining a better understanding of tumorigenesis and developing new diagnosis and treatment strategies for BCa is important for improving BCa clinical outcome. SLC25 family member 21 (SLC25A21), a carrier transporting C5-C7 oxodicarboxylates, has been reported to contribute to oxoadipate acidemia. However, the potential role of SLC25A21 in cancer remains absolutely unknown.MethodsThe expression levels of SLC25A21 in BCa and normal tissues were examined by real-time PCR and immunohistochemistry. Gain-of- and loss-of-function experiments were performed to detect the biological functions of SLC25A21 in vitro and in vivo by CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models. The subcellular distribution of substrate mediated by SLC25A21, mitochondrial membrane potential and ROS production were assessed to explore the potential mechanism of SLC25A21 in BCa.ResultsWe found that the expression of SLC25A21 was downregulated in BCa tissues compared to normal tissues. A significant positive correlation between decreased SLC25A21 expression and poor prognosis was observed in BCa patients. Overexpression of SLC25A21 significantly inhibited cell proliferation, migration and invasion and induced apoptosis in vitro. Moreover, the enhanced SLC25A21 expression significantly suppressed tumor growth in a xenograft mouse model. Furthermore, we revealed that SLC25A21 suppressed BCa growth by inducing the efflux of mitochondrial α-KG to the cytosol, decreasing to against oxidative stress, and activating the ROS-mediated mitochondrion-dependent apoptosis pathway.ConclusionsOur findings provide the first link between SLC25A21 expression and BCa and demonstrate that SLC25A21 acts as a crucial suppressor in BCa progression, which may help to provide new targets for BCa intervention.

Abstract Background Systemic sclerosis is a disease that has significant clinical heterogeneity. This study aims to determine the causes and risk factors of death in a single center European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) cohort at the Peking Union Medical College Hospital (PUMCH) in China. Methods Patients clinically diagnosed with systemic sclerosis (SSc) between Feb 2009 and Dec 2015 were prospectively recruited from the EUSTAR database and Chinese Rheumatism Data Center (CRDC) of the PUMCH. Baseline and follow-up data were collected. Kaplan-Meier analysis was used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality. Results A total of 448 patients were included in the cohort, of whom 56.7% had limited cutaneous systemic sclerosis (lcSSc). The average age at diagnosis was 42.8 ± 12.1 years. The prevalence of interstitial lung disease (ILD) was 382/447 (85.5%). Among 402 patients, 348 of them took glucocorticoid during the disease course; 374 patients received immunosuppressors. Across 2167 patient-years, 40 patients died. Of these, 27 deaths were attributable to SSc, with pulmonary arterial hypertension (PAH) being the leading cause of death. The median survival time was 53 months. Survival rates from disease diagnosis were 97.0%, 94.6%, 91.1% and 87.8% at 1, 3, 5 and 10 years, respectively. Independent prognostic factors for mortality were PAH (HR 6.248, 95% CI 2.855, 13.674) and arrhythmia (HR 4.729, 95% CI 1.588, 14.082). Tripterygium wilfordii Hook F (TwHF) (log-rank test 7.851, p 0.005) and methotrexate (MTX) (log-rank test 7.925, p = 0.005) were found in survival analysis to be protective treatments against mortality. Patients who used cyclophosphamide (CTX) during the disease course had poorer prognosis (log-rank test 5.177, p = 0.023). Conclusions In china, although there is a high prevalence of ILD in patients with SSc (85.5%), most of them have reserved pulmonary function, which means that interstitial lung disease (ILD) is not the most important factor in the death of patients with SSc and also is not a risk factor for poor prognosis. Only ILD with pulmonary dysfunction is associated with poor outcome. The 10-year cumulative rate (87.8%) in patients with SSc in China is slightly lower than the Europe, and pulmonary arterial hypertension (PAH) and arrhythmia at baseline are independent prognostic factors, whereas PAH instead of ILD is the leading cause of death in patients with SSc. Interestingly, the Chinese traditional medicine TwHF, as a protective factor for survival deserves further study.

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

In the present study, the effect of Fumigaclavine C, a fungal metabolite, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of Fumigaclavine C dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco was also significantly reduced by Fumigaclavine C treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β and IL-17A, were markedly suppressed by Fumigaclavine C. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in Fumigaclavine C -treated mice which suggested that the NLRP3 inflammasome activation was suppressed. Furthermore, in the LPS plus ATP cell model, we found that Fumigaclavine C dose-dependent inhibited IL-1β release and caspase-1 activation. Taken together, our results demonstrate the ability of Fumigaclavine C to inhibit NLRP3 inflammasome activation and give some evidence for its potential use in the treatment of inflammatory bowel diseases.

[Objectives] The paper was to explore the effects of different doses of water-retaining agent on the growth and development indicators, yield and quality of soybean plants subjected to drought stress. [Methods] The effects of drought stress (MDS) and drought stress with low (MDS-L), medium (MDS-M) and high doses (MDS-H) of the water-retaining agent on the growth and development indicators, root activity, MDA content, antioxidant enzyme activity, yield and quality of soybean were studied by field plot test, with the normal water supply serving as the control (CK). [Results] In response to drought stress, the plant height, stem diameter, and yield of soybean exhibited a notable decline. Additionally, the contents of protein, fat, linoleic acid, and linolenic acid in seeds demonstrated a significant reduction. Conversely, the root activity and antioxidant enzyme activity exhibited a noticeable decline, while the MDA content exhibited an increase. The application of varying doses of the water-retaining agent was found to significantly enhance soybean growth, stimulate root activity, and elevate antioxidant enzyme activity, while concurrently reducing MDA content. The observed effects were found to be dose-dependent, with the greatest effects observed at the highest dose. In comparison to MDS, the yields of soybean in the MDS-L, MDS-M, and MDS-H treatments exhibited a 18.38%, 25.58%, and 46.26% increase, respectively. Additionally, the content of protein, fat, linoleic acid, and linolenic acid in seeds demonstrated a notable enhancement. [Conclusions] The application of the water-retaining agent has been demonstrated to significantly promote the growth of soybean plants under conditions of drought strefs, resulting in an improvement in both the yield and the quality of the soybean crop. The recommended dosage of the water-retaining agent is 3.3 kg/(667 m². [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC). Methods: Meta-analysis was conducted to assess the caliber of the included literature by searching five databases for randomized controlled trials of DFMO chemoprevention in the high-risk population of CRC, with RevMan 5.4, Stata 15.0 and TSA 0.9.5.10 employed to statistically analyze the extracted data. Grade profiler 3.6 was employed for grading the evidence for the outcome indicators (disease progression and adenoma incidence). Results: Six trials were finally included in this research, with the collective data indicating that the DFMO combination therapy was efficacious in lowering the incidence of recurrent adenomas in patients who had experienced advanced CRC [RR 0.34, 95% CI 0.14 - 0.83, P < 0.05]. Meta-analysis showed that DFMO combined therapy had no statistical difference in disease progression in patients with familial adenomatous polyposis[RR 0.52, 95% CI 0.14 - 1.86, P > 0.05]; Trial Sequential Analysis reveals that the combination therapy of DFMO effectively diminishes the occurrence of recurrent adenomas in patients with a history of advanced colorectal tumors, displaying a Risk Ratio (RR) of 0.33 with a 95% Confidence Interval (CI) of 0.12 - 0.90 and a significance level of P < 0.05. This combination exhibits a statistically significant difference. Subgroup analysis demonstrates that, depending on the drug treatment regimen (DFMO+ Aspirin/DFMO+ Sulindac), the combination of DFMO and aspirin exhibits an effect comparable to a placebo in diminishing the occurrence of new adenomas in patients with a history of advanced colorectal tumors. However, the combination of DFMO and sulindac significantly mitigates the incidence of recurrent adenomas in this patient population. Conclusion: This meta-analysis indicates that the existing randomized controlled trials are adequate to ascertain the efficacy of DFMO combination therapy in diminishing the incidence of recurrent adenomas in patients who have previously encountered advanced colorectal tumors. However, further clinical trials need to be conducted to evaluate the optimum dosage and treatment course of prophylactic implementation of DFMO combination therapy in highrisk populations. [ABSTRACT FROM AUTHOR]

The advancement of high entropy alloys (HEAs) has stimulated the development of multicomponent L12 γ′ intermetallics, which exhibit both excellent strength and ductility. These intermetallics with long-range order are typically employed as coherent precipitates to enhance the high-temperature performance of HEAs. This study investigates the influence of multicomponent γ′ intermetallics on the irradiation response of the strengthened HEA γ phase, focusing on the role of the multicomponent γ/γ′ interface in defect production and evolution. Our results indicate that the chemical disorder within the multicomponent γ′ phase leads to a broad defect energy spectrum near the interface zone, diminishing its effectiveness as a defect sink. Based on these observations, we propose that, distinct from traditional superalloys, the γ/γ′ interface plays a minor role in the irradiation resilience of multicomponent γ′ intermetallics-strengthened HEAs. Instead, the inherent chemical disorder within the multicomponent γ′ intermetallics emerges as the key factor.

Abstract Background Hearing loss (HL) is the most common sensory birth deficit worldwide, with causative variants in more than 150 genes. However, the etiological contribution and clinical manifestations of X-linked inheritance in HL remain unclear within the Chinese HL population. In this study, we focused on X-linked hereditary HL and aimed to assess its contribution to hereditary HL and identify the genotype–phenotype relationship. Methods We performed a molecular epidemiological investigation of X-linked hereditary HL based on next-generation sequencing and third-generation sequencing in 3646 unrelated patients with HL. We also discussed the clinical features associated with X-linked non-syndromic HL-related genes based on a review of the literature. Results We obtained a diagnostic rate of 52.72% (1922/3646) among our patients; the aggregate contribution of HL caused by genes on the X chromosome in this cohort was ~ 1.14% (22/1922), and POU3F4 variants caused ~ 59% (13/22) of these cases. We found that X-linked HL was congenital or began during childhood in all cases, with representative audiological profiles or typical cochlear malformations in certain genes. Genotypic and phenotypic analyses showed that causative variants in PRPS1 and AIFM1 were mainly of the missense type, suggesting that phenotypic variability was correlated with the different effects that the replaced residues exert on structure and function. Variations in SMPX causing truncation of the protein product were associated with DFNX4, which resulted in typical audiological profiles before and after the age of 10 years, whereas nontruncated proteins typically led to distal myopathy. No phenotypic differences were identified in patients carrying POU3F4 or COL4A6 variants. Conclusions Our work constitutes a preliminary evaluation of the molecular contribution of X-linked genes in heritable HL (~ 1.14%). The 15 novel variants reported here expand the mutational spectrum of these genes. Analysis of the genotype–phenotype relationship is valuable for X-linked HL precise diagnostics and genetic counseling. Elucidation of the pathogenic mechanisms and audiological profiles of HL can also guide choices regarding treatment modalities.

Abstract Developing high-performance multicomponent ceramics, which are promising in solving challenges posed by emerging technologies, shows grand difficulties because of the immense compositional space and complex local distortions. In this work, an accurate machine learning (ML) model built upon an ab initio database is developed to predict the mechanical properties and structural distortions of multicomponent transition metal carbides (MTMCs). The compositional space of MTMCs is thoroughly explored by the well-trained model. Combined with electronic and geometrical analysis, we show that the elemental adaptability to the rock-salt structure elegantly elucidates the mechanical characteristics of MTMCs, and such adaptability can be quantified by local lattice distortions. We further establish new design principles for high-strength MTMCs, and V–Nb–Ta-based MTMCs are recommended, which are validated by the present experiments. The proposed model and design philosophy pave a broad avenue for the rational design of MTMCs with exceptional properties.

Abstract Identifying genomic markers for phosphate-solubilizing bacteria (PSB) is vital for advancing agricultural sustainability. This study utilizes whole-genome sequencing and comprehensive bioinformatics analysis, examining the genomes of 76 PSB strains with the aid of specialized genomic databases and analytical tools. We have identified the pqq gene cluster, particularly the pqqC gene, as a key marker for (P) solubilization capabilities. The pqqC gene encodes an enzyme that catalyzes the conversion of precursors to 2-keto-d-gluconic acid, which significantly enhances P solubilization in soil. This gene’s importance lies not only in its biochemical function but also in its prevalence and effectiveness across various PSB strains, distinguishing it from other potential markers. Our study focuses on Burkholderia cepacia 51-Y1415, known for its potent solubilization activity, and demonstrates a direct correlation between the abundance of the pqqC gene, the quantitative release of P, and the production of 2-keto-d-gluconic acid over a standard 144-h cultivation period under standardized conditions. This research not only underscores the role of the pqqC gene as a universal marker for the rapid screening and functional annotation of PSB strains but also highlights its implications for enhancing soil fertility and crop yields, thereby contributing to more sustainable agricultural practices. Our findings provide a foundation for future research aimed at developing targeted strategies to optimize phosphate solubilization, suggesting areas for further investigation such as the integration of these genomic insights into practical agricultural applications to maximize the effectiveness of PSB strains in real-world soil environments.

Ordered L12 γ′ Ni3Al intermetallics are essential strengthening components to maintain the high strength of Ni-based superalloys and recently developed high entropy alloys at elevated temperatures. Under service conditions, structural disorder is usually encountered in these intermetallics, resulting in significant loss of their strengthening functionality. Thus, retaining the degree of order of the L12 intermetallics is vital for their long-term reliability and serviceability. In this study, atomistic simulations and rate equation analysis are employed to highlight a notable enhancement in the reordering ability of L12 intermetallics by incorporating multiple principal elements. Specifically, we examine the effects of Co and Ti addition on the irradiation-induced disordering and kinetic reordering process of L12 intermetallics. Our results reveal that the incorporation of Ti in the Al sublattice can maintain comparable disordering resistance as Ni3Al. Better yet, the introduction of Ti or Co fosters vacancy migration, which accelerates the kinetic reordering rate during the defect diffusion stage. A synergistic effect of Ti and Co in promoting kinetic reordering is also observed. Our work thus suggests a promising approach for designing irradiation-resistant multicomponent intermetallics, which can retain a high degree of structural order under irradiation with chemical disorder contributed by desirable compositions.

Tumor suppressor protein Adenomatous polyposis coli protein (APC) is an EB-binding and microtubule (MT) plus end-tracking protein; however, how exactly APC regulates MT dynamics remains elusive. Here, we show that in LLC-PK1 cells, APC and KIF2A, an MT depolymerase, form a complex clustering at the cell edge and destabilize MTs at the MT plus ends. Further biochemical characterization and mutational analysis reveal key residues for the APC-KIF2A interaction. In addition, APC counteracts the major MT-stabilizer CLASPs at MT plus ends and promotes directional cell migration via modulating cell adhesion force. Reconstitution experiments demonstrate that APC potentiates KIF2A-induced MT catastrophes and antagonizes the stabilizing effect of CLASP2 in vitro. In summary, APC functions as a positive regulator of MT-destabilizer and a negative regulator of MT-stabilizer to orchestrate MT dynamics.

Abstract Background Acute myocardial infarction (AMI) is a serious cardiovascular disease that adversely affects human health. Circular RNAs (circRNAs) are involved in the pathological and physiological processes of AMI, but the biological mechanism of their involvement and their clinical significance remain unknown. We aimed to identify circRNAs that are significantly associated with morbidity in the peripheral blood of patients with AMI and evaluate their diagnostic utility. Methods High-throughput sequencing was used to screen for differentially expressed circRNAs in peripheral blood samples obtained from five patients with AMI and five sex- and age-matched healthy controls. A series of bioinformatics tools and databases were used to determine the biological functional classification and pathway enrichment of the circRNAs based on data obtained from sequencing. A hypoxia model was established and used to evaluate the effect of hypoxia on circRNA expression in human cardiomyocytes. A cytoplasmic separation assay and enzyme resistance assay were employed to identify the biological characteristics of circRNA. Polymerase chain reaction validity testing and receiver operating characteristic (ROC) curve analysis were used to evaluate the utility of circRNA assessments in the diagnosis of AMI. Results A large number of circRNAs were found to be differentially expressed in the peripheral blood of patients with AMI, and significantly more of these circRNAs were highly expressed than lowly expressed. The genes encoding these circRNAs have a wide range of effects on various functions in the body. A hypoxic environment promoted the upregulation of circRNA expression in human cardiomyocytes, and hsa_circ_0116795 encoded by PPARA was highly expressed in the peripheral blood of the patients with AMI. In terms of biological characteristics, under physiological conditions, hsa_circ_0116795 (circ_PPARA) was mainly located in the cytoplasm of cardiomyocytes and found to be resistant to exonuclease. The ROC curve analysis showed that the expression levels of circ_PPARA in the peripheral blood of patients with AMI were significantly different from those in the peripheral blood of healthy controls. Conclusion A large number of abnormally expressed circRNAs are detectable in the peripheral blood of patients with AMI. In particular, circ_PPARA is highly expressed in human myocardial cells under hypoxic conditions, and its biological characteristics indicate that it could be employed as a biomarker for the early diagnosis of AMI.

Background Osteoporosis is a disease associated with bone resorption, characterized primarily by the excessive activation of osteoclasts. Ginkgetin is a compound purified from natural ginkgo leaves which has various biological properties, including anti-inflammation, antioxidant, and anti-tumor effects. This study investigated the bone-protective effects of ginkgetin in ovariectomized (OVX) mice and explored their potential signaling pathway in inhibiting osteoclastogenesis in a mouse model of osteoporosis. Methods Biochemical assays were performed to assess the levels of Ca, ALP, and P in the blood. Micro CT scanning was used to evaluate the impact of ginkgetin on bone loss in mice. RT-PCR was employed to detect the expression of osteoclast-related genes (ctsk, c-fos, trap) in their femoral tissue. Hematoxylin and eosin (H&E) staining was utilized to assess the histopathological changes in femoral tissue due to ginkgetin. The TRAP staining was used to evaluate the impact of ginkgetin osteoclast generation in vivo. Western blot analysis was conducted to investigate the effect of ginkgetin on the expression of p-NF-κB p65 and IκBα proteins in mice. Results Our findings indicate that ginkgetin may increase the serum levels of ALP and P, while decreasing the serum level of Ca in OVX mice. H&E staining and micro CT scanning results suggest that ginkgetin can inhibit bone loss in OVX mice. The TRAP staining results showed ginkgetin suppresses the generation of osteoclasts in OVX mice. RT-PCR results demonstrate that ginkgetin downregulate the expression of osteoclast-related genes (ctsk, c-fos, trap) in the femoral tissue of mice, and this effect is dose-dependent. Western blot analysis results reveal that ginkgetin can inhibit the expression of p-NF-κB p65 and IκBα proteins in mice. Conclusion Ginkgetin can impact osteoclast formation and activation in OVX mice by inhibiting the NF-κB/IκBα signaling pathway, thereby attenuating bone loss in mice.

Deltamethrin (DM) is a highly effective and widely used pyrethroid pesticide. It is an environmental factor affecting public and occupational health and exerts direct toxic effects on the central nervous system. As the major target organs for neurotoxicity of DM, the hippocampus and the cerebellum are critical to the learning and motor function. Pregnant Wistar rats were randomly divided into four groups and gavaged at doses of 0, 1, 4or 10 mg/kg/d DM from gestational day (GD) 0 to postnatal day (PN) 21. The PC12 cells were selected to further verify the regulatory mechanisms of DM on the neurodevelopmental injury. We found that maternal exposure to DM caused learning, memory and motor dysfunction in male offspring. Maternal exposure to DM induced the decrease in the density of hippocampal dendritic spines in male offspring through the reduced expression of M1 mAchRs, which in turn reduced the mediated AKT/mTOR signaling pathway, contributing to the inhibition of dynamic changes of GluA1. Meanwhile, DM exposure inhibited the BDNF/TrkB signaling pathway, thereby reducing phosphorylation of stathmin and impairing cerebellar purkinje cell dendrite growth and development. Taken together, maternal exposure to DM during pregnancy and lactation could impair neurodevelopment of male offspring.

Salt caverns produced by solution mining in Southern Ontario provide ideal spaces for gas storage due to their low permeability. Underground hydrogen storage (UHS) is an important part of the future renewable energy market in Ontario in order to achieve global carbon neutrality and to fill the gap left by retiring nuclear power plants. However, large-scale hydrogen storage is still restricted by limited storage space on the ground’s surface. In this study, hydrogen’s physical and chemical properties are first introduced and characterized by low molecular weight, high diffusivity, low solubility, and low density. Then, the geological conditions of the underground reservoirs are analyzed, especially salt caverns. Salt caverns, with their inert cavity environments and stable physical properties, offer the most promising options for future hydrogen storage. The scales, heights, and thicknesses of the roof and floor salt layers and the internal temperatures and pressures conditions of salt caverns can affect stabilities and storage capacities. Finally, several potential problems that may affect the safe storage of hydrogen in salt caverns are discussed. Through the comprehensive analysis of the influencing factors of hydrogen storage in salt caverns, this study puts forward the most appropriate development strategy for salt caverns, which provides theoretical guidance for UHS in the future and helps to reduce the risk of large-scale storage design.

Deep shales refer to the shales with buried depth greater than 3500 m. Yields of shale gases depend on the form of their occurrence at the depth, but the major controlling factors on shale gas occurrence state in deep high-over mature shales are poorly understood. Using the Longmaxi Formation as an example, the shale gas occurrence characteristics of deep high-over mature shales were quantitatively characterized, and the effects of temperature, pressure, pore structure, and organic matter abundance on the occurrence characteristics of shale gas were studied by using the control variable method. The results show that the Longmaxi shale is mainly organic-rich argillaceous shale, with an average porosity of 7.54%. The pore volumes are mainly contributed by mesopores, whereas the total specific surface areas are primarily by micropores. The Longmaxi shale has high gas contents, with total gas contents of 3.82∼7.89 m3/t rock, in which the proportion of free gas varies from 71% to 83%, with an average of 77%. The high proportion of free gas depends on the particular geological conditions in the Longmaxi Formation. High temperature is not conducive to shale gas storage, and its negative effect on adsorbed gas is greater than that on free gas. High pressure is beneficial to shale gas storage, and its positive influence on free gas is greater than that on adsorbed gas. The large pore volume dominated by mesopores provides sufficient storage place for free gas. High organic matter content is beneficial for shale gas enrichment but reduce the proportion of free gas. In conclusion, high pressure and large pore volume are the major factors for the high proportion of free gas.

Summary: Montmorillonite was used as raw clay to prepare the Al-pillared interlayer clay (Al-PILC) as support by impregnation methods. Co and Fe were loaded in series on Al-PILC to prepare the bimetal catalysts (Fe-Co/Al-PILC). The SCR-CH4 was evaluated in a fixed bed reactor and the results indicated that 0.27Fe-Co/Al-PILC exhibited 100% N2 selectivity and above 63% NO conversion in the presence of 10% H2O, and the introduction of Fe significantly improved the Co/Al-PILC catalyst’s resistance to H2O and SO2. Characterization showed that Lewis and Brønsted acids co-existed on the catalyst surface, and the Lewis acid was the dominant active acid site and enhanced the activation of methane over the 0.27Fe-Co/Al-PILC. Fe promoted the formation of isolated Co2+ and CoO species, and the isolated Fe3+ particles improved CH4-SCR performance. The reaction route was proposed based on in situ DRIFTS tests and the active intermediates were mainly various nitrates and nitromethane (CH3NO2).

Introduction: A new method is introduced to test the tensile strength of concrete: the cylinder transverse splitting test. Compared with the cylinder splitting (or Brazilian) test, the cylinder transverse splitting test involves different load positions and offers the advantages of doubling the data volume with the same number of specimens and improving the detection accuracy.Methods: Finite element analysis software was used to simulate the concrete cylinder transverse splitting test and the stress distribution on the failure surface was determined.Results and Discussion: The results show that the fracture of a cylinder is mainly determined by tensile stress. The splitting strength of normal concrete and crumb rubber concrete, a new environmentally friendly concrete material that has gathered considerable attention in recent years, was obtained by cylinder transverse and cube splitting tests. The cylinder transverse splitting test data show a stable correlation with the cube splitting test data and well characterize the concrete strength. The relationship between the cylinder nominal transverse splitting strength (f2) and cube splitting strength (f1) was established on the basis of linear analysis of the test data: f1 = 0.51f2. The calculated cube splitting strength is in good agreement with the test values.

Abstract Gas-bearing property evaluation and main controlling factor analysis have remained a concern in shale gas research. The application of principal component analysis, an important mathematical statistical method, in gas-bearing property evaluation and main controlling factor analysis of the Longmaxi shale in the Weirong area, Sichuan Basin, was examined. The Longmaxi shale exhibits high heterogeneity, manifested in the organic matter abundance, mineral composition, and pore structure. Seven geological factors, including the temperature, pressure, TOC content, clay content, brittle mineral content, pore volume, and specific surface area (SSA), were selected in principal component analysis. Four principal components with geological significance, such as mineral composition, formation condition, pore structure, and organic matter abundance, were extracted through principal component analysis, and further constituted a comprehensive factor. Shale gas-bearing properties were evaluated according to the score of the comprehensive factor. The Longmaxi shale could be identified as exhibiting good, medium, and poor gas-bearing properties based on the comprehensive factor scores of these samples. According to each geological factor’s contribution to the comprehensive factor, combined with geological analysis, it could be considered that gas-bearing properties are primarily controlled by pore volume, SSA, and clay content, followed by TOC content, brittle mineral content, temperature and pressure.

Abstract Background The mitochondrial 12S rRNA A1555G mutation is the most prevalent deafness-causing mitochondrial DNA (mtDNA) mutation and is inherited maternally. Studies have suggested that A1555G mutations have multiple origins, although there is no direct evidence of this. Here, we identified a family with a de novo A1555G mutation. Method Based on detailed mtDNA analyses of the family members using next-generation sequencing with 1% sensitivity to mutated mtDNA, the level of heteroplasmy in terms of the A1555G mutation in blood DNA samples was quantified. Results An individual harbored a heterogeneous A1555G mutation, at 28.68% heteroplasmy. The individual’s son was also a heterogeneous carrier, with 7.25% heteroplasmy. The individual’s brother and mother did not carry the A1555G mutation, and both had less than 1% mitochondrial 12S rRNA A1555G heteroplasmy. Conclusion The A1555G mutation arose de novo in this family. This is the first report of a family with a de novo A1555G mutation, providing direct evidence of its multipoint origin. This is important for both diagnostic investigations and genetic counselling.

Abstract Background Mutations in the MYO15A gene are a widely recognized cause of autosomal recessive non-syndromic sensorineural hearing loss (NSHL) globally. Here, we examined the role and the genotype–phenotype correlation of MYO15A variants in a cohort of Chinese NSHL cases. Methods Eighty-one cases with evidenced MYO15A variants from the 2263 Chinese NSHL cases, who underwent next-generation sequencing (NGS), were enrolled in the study. We investigated the association of MYO15A variants with the severity, progression and age of onset of hearing loss, as well as compared it to the previous reports in different nationalities. The cases were divided into groups according to the number of truncating variants: 2 truncating, 1 truncating and 1 non-truncating, 2 non-truncating variants, and compared the severity of HL among the groups. Results MYO15A accounted for 3.58% (81/2263) of all NSHL cases. We analyzed 81 MYO15A-related NSHL cases, 73 of whom were with congenital bilateral, symmetric or severe-to-profound hearing loss (HL), however, 2 of them had a postlingual, asymmetric, mild or moderate HL. There were 102 variants identified in all MYO15A structural domains, 76.47% (78/102) of whom were novel. The most common types of detected variants were missense (44/102, 43.14%), followed by frameshift (27/102, 26.47%), nonsense (14/102, 13.72%), splice site (10/102, 9.80%), in frame (4/102, 3.92%), non-coding (2/102, 1.96%) and synonymous (1/102, 0.98%). The most recurrent variant c.10245_10247delCTC was detected in 12 cases. We observed that the MYO15A variants, located in its N-terminal, motor and FERM domains, led to partial deafness with better residual hearing at low frequencies. There were 34 cases with biallelic truncating variants, 37 cases with monoallelic truncating variants, and 13 cases with biallelic non-truncating variants. The biallelic non-truncating variants group had the least number of cases (12/81), and most of them (10/12) were with profound NSHL. Conclusions MYO15A is a major gene responsible for NSHL in China. Cases with MYO15A variants mostly showed early-onset, symmetric, severe-to-profound hearing loss. This study is by far the largest focused on the evaluation of the genotype–phenotype correlations among the variants in the MYO15A gene and its implication in the outcome of NSHL. The biallelic non-truncating MYO15A variants commonly caused profound HL, and the cases with one or two truncating MYO15A variants tended to increase the risk of HL. Nevertheless, further investigations are needed to clarify the causes for the variable severities and progression rates of hearing loss and the detected MYO15A variants in these cases.

Abstract Background Hearing loss (HL) is the most frequent sensory deficit in humans, HL has strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counseling for the patient’s family. Methods We undertook pedigree analysis in 92 Chinese non-syndromic HL patients by targeted next-generation sequencing and Sanger sequencing. Results Among the 92 HL patients, 18 were assigned a molecular diagnosis with 33 different variants in 14 deafness genes. Eighteen of the variants in 12 deafness genes were novel. Variants in TMC1, CDH23, LOXHD1 and USH2A were each detected in two probands, and variants in POU3F4, OTOA, GPR98, GJB6, TRIOBP, SLC26A4, MYO15A, TNC, STRC and TMPRSS3 were each detected in one proband. Conclusion Our findings expand the spectrum of deafness gene variation, which will inform genetic diagnosis of deafness and add to the theoretical basis for the prevention of deafness.

Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Multi-principal element alloys (MPEAs), including high entropy alloys, show exceptional mechanical properties and corrosion resistance. These unusual properties are mostly attributed to their particular diffusion behaviors, such as sluggish diffusion. However, this phenomenon is still controversial. Although state-of-the-art simulations report that the percolation effect plays a crucial role in triggering sluggish diffusion in binary alloys, whether this correlation could be generalized to a broad class of MPEAs is unknown. In this work, we combine machine learning (ML) with kinetic Monte Carlo (kMC) to accurately determine the diffusion coefficients in ternary CoCrNi MPEAs. Special care is taken to understand the effects of percolation on diffusion. We find that percolation does not always lead to sluggish diffusion. Instead, the diffusion properties are exclusively governed by the potential energy landscape (PEL) that the diffusing objects experience. By comparing the reduced systems of CoNi and FeNi, we reveal that the percolation effect on triggering the sluggish diffusion strongly depends on the diffusion properties of the slow-diffuser in these systems. These results shed light on the understanding of the complex diffusion behaviors in MPEAs, highlighting the importance of tunning species-dependent PEL in order to tailor their diffusion properties.

Mutations of SOX10 result in Waardenburg syndrome characterized by sensorineural hearing loss and pigmentary abnormalities, which can be found in association with a defect of migrating neural crest cells. The role of SINE-VNTR-Alu (SVA) retrotransposon insertions in disorders has only been minimally explored and there have been no reports of WS cases related to SVA retrotransposons. Here, we report the successful establishment and characterization of an iPSC line from a patient diagnosed with Waardenburg syndrome carrying an insertion of SVA in intron 2 of SOX10.

Atmospheric PAHs (polycyclic aromatic hydrocarbons) and their derivatives are a global concern that influences environments and threatens human health. Concentrations of 52 PAHs and the main derivatives in six Chinese megacities were measured in the winter of 2019. The concentrations of ∑PAHs (sum of 52 PAHs) ranged from 19.42 ± 7.68 to 65.40 ± 29.84 ng m−3, with significantly higher levels in northern cities (Harbin [HB], Beijing [BJ], and Xi’an [XA]) than southern ones (Wuhan [WH], Chengdu [CD] and Guangzhou [GZ]). Source apportionment of ∑PAHs was conducted by the PMF model and results showed coal combustion and traffic emissions were the two dominant sources, which dominated ∑PAHs in northern and southern cities, respectively. Biomass burning was also characterized as a crucial source of ∑PAHs and showed extremely high contributions in XA (42.5%). Assisted by the individual PAH source apportionment results, the source-depend TEQ (total BaP equivalent) and incremental lifetime cancer risk (ILCR) were firstly reported in these cities. The results highlighted the contributions of coal combustion and biomass burning to both TEQ and ILCR, which were underestimated by ∑PAHs source apportionment. Secondary organic aerosol-derived PAHs were demonstrated to increase the TEQ compared with the fresh PAHs and three parameters, namely temperature, relative humidity, and O3 concentrations were characterized by multiple linear regression as the principal factors influencing secondary reactions of PAHs in winter. This study provides accurate human health-orientated results and potential control measures to mitigate the toxicity of secondary formed PAHs, and significantly decrease the uncertainty level of traditional methods. The results also revealed great progress in air pollution control by the Chinese government in the past 20 years, but still a long way to go to formulate strict emission control strategies from both environmental and human health-protective perspectives.

In the current article, the effect of Si/Al ratio on the NOx adsorption and storage capacity over Pd/Beta with 1 wt% Pd loading was investigated. The XRD, 27Al NMR and 29Si NMR measurements were used to determine the structure of Pd/Beta zeolites. XAFS, XPS, CO-DRIFT, TEM and H2-TPR were used to identify the Pd species. The results showed that the NOx adsorption and storage capacity on Pd/Beta zeolites gradually decreased with the increase of Si/Al ratio. Pd/Beta-Si (Si-rich, Si/Al~260) rarely has NOx adsorption and storage capacity, while Pd/Beta-Al (Al-rich, Si/Al~6) and Pd/Beta-C (Common, Si/Al~25) exhibit excellent NOx adsorption and storage capacity and suitable desorption temperature. Pd/Beta-C has slightly lower desorption temperature compared to Pd/Beta-Al. The NOx adsorption and storage capacity increased for Pd/Beta-Al and Pd/Beta-C by hydrothermal aging treatment, while the NOx adsorption and storage capacity on Pd/Beta-Si had no change.