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Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The T cell receptor (TCR) and B cell receptor (BCR) are the receptors on the surface of T or B cell, which are crucial for recognizing tumor antigens. It is profound to establish a practical TCR/BCR-related gene signature prognostic model for the further diagnosis and treatment among HCC patients., Methods: In this study, we categorized gene expression data of HCC patients from The Cancer Genome Altas and identified TCR related genes by the Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analysis. Both the CIBERSORT algorithm and the TB tools were used to analyze the features and heterogeneity of the tumor microenvironment., Results: Finally, an 8-gene prognostic model was successfully established and achieved the validation in both the International Cancer Genome Consortium and Nanfang Hospital cohorts. Patients were divided into high-risk and low-risk groups based on the median of the risk scores. We observed that tumor differentiation was worse while the fibrinogen concentration was higher in the high-risk group of patients. Both the number of unique TCR and BCR clonotypes and the expanded clones were higher in the low-risk group than in the high-risk group., Conclusions: Together, our study screened a TCR/BCR-related signature prognostic model, which might turn into a beneficial and practical tool to solve the perplexities of the treatment, prognosis prediction and management for HCC patients., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Institutional Ethics Committee of Nanfang Hospital, approval number NFEC-201208-K3. All patients provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This study aimed to analyze and compare the proportion of patients with different types of inflammatory arthritis and investigate the clinical characteristics, including symptoms and signs, medication choices, and disease activity, in the daily clinical practice of China., Methods: Patients with inflammatory arthritis were recruited from 16 Grade-A tertiary hospitals between August 2021 and April 2022. The medical profiles, encompassing sociodemographic characteristics, clinical and laboratory date, were collected., Results: This study included 2,693 patients with arthritis, with rheumatoid arthritis (RA) accounting for the highest proportion (50.50%). Significant differences were observed in terms of age, gender, body mass index (BMI), disease duration, smoking and family history among patients with different types of inflammatory arthritis. Physical activity and cold exposure were identified as the main predisposing factors for RA, psoriatic arthritis (PsA), osteoarthritis (OA), and ankylosing spondylitis (AS), while alcohol consumption was the most common inducing factor for gout. Hypertension and hyperlipidemia were the primary concomitant diseases in RA, OA, and AS, whereas hyperuricemia and hypertension were mainly associated with gout, psoriasis and diabetes were the most common comorbidities in PsA. Peripheral joints were predominantly affected in PsA, RA, OA, and gout, while axial joints were mainly affected in AS. Methotrexate and leflunomide were the main therapeutic drugs for RA, while biologics were commonly prescribed for PsA and AS. OA and gout patients mainly utilized nonsteroidal anti-inflammatory drugs (NSAIDs)., Conclusion: Patients with different types of inflammatory arthritis exhibited varying predisposing factors, joint inflammation, concomitant diseases, and medication choices, highlighting the importance of individualized approaches in the clinic. Key Points • 2,693 patients classified and diagnosed with inflammatory arthritis were recruited in this study from 16 Grade-A tertiary hospitals in China between August 2021 and April 2022. • This study analyzed and compared the proportion of patients with different types of arthritis in routine clinical practice in China. • Joint inflammation, comorbidities, and medication choices were assessed among patients with the most common types of arthritis in this study. • This study also provided some epidemiologically relevant information about inflammatory arthritis patients in China., Competing Interests: Compliance with ethical standards. Ethics and consent to participate: The study was approved by the Research Ethics Committee at Peking University People’s Hospital, Beijing, China (approval No.2020PHB021-01). All patients provided written informed consent. Generative AI and AI-assisted technologies in the writing process: During the preparation of this work, the authors did not use any AI tools. Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Purpose: To investigate the efficacy of ultrasound fusion imaging-assisted microwave ablation (MWA) for patients with colorectal liver metastases (CRLM) based on stratified analysis of tumor size and location., Methods: Patients with CRLM who underwent ultrasound fusion imaging-assisted MWA in our hospital between February 2020 and February 2023 were enrolled into this retrospective study. Ultrasound fusion imaging was used for detection, guidance, monitoring and immediate evaluation throughout the MWA procedures. Technical success, technique efficacy, local tumor progression (LTP), intrahepatic progression and overall survival (OS) were recorded and analyzed. The subgroup analysis of intrahepatic progression of MWA for CRLM was performed according to tumor size and location., Results: A total of 51 patients with 122 nodules were enrolled. Both technical success and technique efficacy were acquired in all nodules. In a median follow-up period of 19 months, 2.5% of the nodules (3/122) were observed LTP. The 1-year and 2-year cumulative intrahepatic progression rates were 38.7% and 52.1% respectively. Patients were divided into subgroups according to tumor size (≥ 30 mm, n = 13; < 30 mm, n = 38) and tumor location (perivascular, n = 20; non-perivascular, n = 31 and subcapsular, n = 36; non-subcapsular, n = 15). The cumulative intrahepatic progression rates were similar between the subgroups regarding tumor size and perivascular location, while significantly higher in the subcapsular group than in the non-subcapsular group (p = 0.021)., Conclusion: Ultrasound fusion imaging-assisted MWA exhibited satisfactory local efficacy for CRLM, especially for non-subcapsular tumors., Competing Interests: Declarations. Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Fungal rhinosinusitis is a significant and growing health concern in arid regions, with an increasing incidence over recent decades. Without timely and appropriate management, it can lead to severe complications, including potential intracranial spread. This study aims to establish efficient and rapid diagnostics for non-invasive fungal rhinosinusitis (FRS), addressing the challenge of its difficult-to-culture diagnosis., Methods: Twenty-eight patients suspected of FRS were studied using endoscopic sinus surgery to obtain tissue samples for histopathology, direct microscopy, fungal culture, quantitative PCR (qPCR) and metagenomic next-generation sequencing (mNGS) detection. A patented qPCR targeting prevalent Aspergillus species was evaluated., Results: The patient cohort had a male-to-female ratio of 9:14, with disease duration up to 50 years. Histopathologically, 23 out of 28 cases were positive. Fungal culture exhibited a sensitivity of 21.74%, with one false positive. qPCR and mNGS showed 100% sensitivity and specificity, with a 100% consistency rate for identification at the species level (23/23), and potential detection of cases with co-infections. The most common pathogen was A. flavus, followed by A. fumigatus and A. niger. Two cases involved mixed infections of A. fumigatus and A. flavus., Conclusion: qPCR and mNGS proved effective in rapidly identifying fungi from fresh sinus tissue that are challenging to culture, surpassing conventional methods. However, further evaluation and optimization with a larger cohort of patients are necessary. Histopathology is still recommended to confirm the clinical significance of the detected fungal species., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Clinical Research Ethics Committee of the Peking University First Hospital. (No.2019 − 330). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Contrast-induced nephropathy (CIN) is an adverse renal event that occurs following the administration of contrast media for diagnostic procedures or therapeutic angiographic intervention. Nevertheless, there is currently no efficacious and safe agents for the treatment of CIN, except for hydration. We aimed to conduct a meta-analysis to verify the potential nephroprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in the prevention of CIN., Methods: The PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases were searched from their respective inception dates up until 26 August 2024. The "Meta" package of R and Stata software was used for data analysis., Results: A total of 12 studies were included in the analysis, comprising 11 single-center retrospective studies and one prospective cohort study. Our meta-analysis determined that SGLT2is significantly decrease CIN (odds ratio (OR) 0.39, 95% confidence interval (CI) (0.31, 0.48), P < 0.0001, I 2  = 0%) and mortality (OR 0.45, 95% CI (0.26, 0.77), P = 0.0039, I 2  = 48%). No notable discrepancy was discerned in continuous renal replacement therapy (CRRT) (OR 0.53, 95% CI (0.15, 1.91), I 2  = 0%) or contrast volume (MD - 9.68, 95% CI (- 19.38, 0.03), I 2  = 71%)., Conclusion: The present study demonstrated that SGLT2is markedly reduce the incidence of contrast-induced nephropathy in diabetic patients. It is recommended that future large-scale randomized controlled trials (RCTs) are required to confirm these findings and to elucidate further the outcomes in patients without diabetes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To investigate the efficacy of three-compartment restriction spectrum imaging (RSI), diffusion kurtosis imaging (DKI), and diffusion-weighted imaging (DWI) in the assessment of lymph node metastases (LNM) in rectal cancer., Methods: A total of 77 patients with rectal cancer who underwent pelvic MRI were enrolled. RSI-derived parameters (f 1 , f 2 , and f 3 ), DKI-derived parameters (D app and K app ), and the DWI-derived parameter (ADC) were calculated and compared using a Mann-Whitney U test or independent samples t-test. Logistic regression (LR) analysis was used to identify independent predictors of LNM status. Area under the receiver operating characteristic curve (AUC) and Delong analysis were performed to assess the diagnostic performance of each parameter., Results: The LNM-positive group exhibited significantly higher f 1 and K app levels and significantly lower f 3 , D app , and ADC levels compared to the LNM-negative group (p < 0.05). There was no difference in f 2 levels between the two groups (p = 0.783). LR analysis showed that D app and K app were independent predictors of a positive LNM status. AUC and Delong analysis showed that DKI (D app  + K app ) exhibited significantly higher diagnostic efficacy (AUC = 0.908; sensitivity = 87.10%; specificity = 86.96%) than RSI (f 1  + f 3 ) and DWI (ADC), with AUCs were 0.842 and 0.771 (Z = 2.113, 3.453; p = 0.035, < 0.001, respectively). The AUC performance between RSI and DWI was also statistically significant (Z = 1.972, p = 0.049)., Conclusion: The RSI model is superior to conventional DWI but inferior to DKI in differentiation between LNM-positive and LNM-negative rectal cancers. Further study is needed before it could serve as a promising biomarker for guiding effective treatment strategies., Critical Relevance Statement: The three-compartment restriction spectrum imaging was able to differentiate between LNM-positive and LNM-negative rectal cancers with high accuracy, which has the potential to serve as a promising biomarker that could guide treatment strategies., Key Points: Three-compartment restriction spectrum imaging could differentiate lymph node metastases in rectal cancer. Diffusion kurtosis imaging and diffusion-weighted were associated with lymph node metastases in rectal cancer. The combination of different parameters has the potential to serve as a promising biomarker., Competing Interests: Declarations. Ethics approval and consent to participate: This prospective study had approval from our hospital’s ethics review committee and each patient provided signed informed consent. Consent for publication: All participants provided written informed consent. Competing interests: K.W., who is an employee of GE Healthcare, gave guidance to this paper in terms of technical parameters and language embellishment. The remaining authors declare no relationships with any companies whose products or services may be related to the subject matter of the article. No conflicts of interest between the two corresponding authors or between the two research projects., (© 2024. The Author(s).)

Purpose: To evaluate the feasibility and efficiency between the two intelligent auto-registrations (based on hepatic vessels or based on liver surface) and manual registration for US-CT/MR fusion imaging of liver tumours., Methods: From May 2017 to December 2017, 30 patients with 30 liver tumours were enrolled in this prospectively study. Two intelligent auto-registrations (based on hepatic vessels or based on liver surface) and manual registration were randomly performed, the registration success rate and efficiency were compared., Results: In terms of success rate, auto-registrations based on the hepatic vessels (80%) was lower than auto-registration base on liver surface and manual registration (96.67%), but with no statistical difference (P = 0.125). In comparison of the registration efficiency, the efficiency of the auto-registration based on the hepatic vessels was superior to auto-registration based on liver surface and manual registration (P < 0.05). The one-step success rate of auto-registration based on the hepatic vessels (53.33%, 16/30) was higher than that of other two registrations (P < 0.05). Stratified analysis showed that, for the lesion with display of hepatic vessels in grade 3, the success rate of auto-registration based on vessels (0%) was lower than that of auto-registration based on liver surface and manual registration (100%) (P = 0.031)., Conclusion: Intelligent auto-registration based on hepatic vessels is a feasible and efficient registration method for US-CT/MR fusion imaging of liver tumours for the patients with clear hepatic vessels. The auto-registration based on liver surface and manual registration can be an effective supplement for cases with poor hepatic vessels display., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The diagnostic value of serum human epididymal secretory protein 4 (HE4) for endometrial cancer (EC) was assessed via evidence-based medicine (EBM) and systematic review (SR) methodologies., Methods: The Cochrane Library, PubMed, Web of Science, Embase, CBM, CNKI, and Wan Fang databases were searched up to April 1st, 2024, to identify relevant literature. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was utilized to evaluate the quality of the selected studies. The meta-analysis was conducted via RevMan 5.3, STATA 16.1, and Meta-disc software., Results: A total of 22 studies comprising 9036 cases (3776 cases in the case group and 5260 cases in the control group) were included. The results revealed that HE4 exhibited a pooled sensitivity of 0.59 [95% CI (0.53, 0.64)], specificity of 0.93 [95% CI (0.88, 0.96)], positive likelihood ratio (PLR) of 6.87 [95% CI (4.57, 10.33)], negative likelihood ratio (NLR) of 0.46 [95% CI (0.39, 0.54)], diagnostic odds ratio (DOR) of 14.36 [95% CI (9.37, 21.17)], and area under the receiver operating characteristic curve (AUC) of 0.78 [95% CI (0.75, 0.82)]., Conclusions: Serum HE4 demonstrates high specificity and moderate sensitivity for diagnosing EC, thus serving as a valuable biomarker for clinicians either alone or in conjunction with other tumour markers., (© 2024. The Author(s).)

Inflammation-induced intestinal epithelial barrier (IEB) dysfunction is one of the important reasons for the occurrence and development of intestinal inflammatory-related diseases, including ulcerative colitis (UC), Crohn's disease and necrotizing enterocolitis (NEC). Dragon's blood (DB) is a traditional Chinese medicine and has been clinically used to treat UC. However, the protective mechanism of DB on intestinal inflammatory-related diseases has still not been elucidated. The present study aimed to explore the protection mechanism of DB on IEB dysfunction in rat ileum and human colorectal adenocarcinoma cells (Caco-2)/human umbilical vein endothelial cells (HUVECs) coculture system induced by lipopolysaccharide (LPS). DB could ameliorate rat ileum mucosa morphological injury, reduce the accumulation of lipid-peroxidation products and increase the expression of junction proteins. DB also alleviated LPS-induced Caco-2 cells barrier integrity destruction in Caco-2/ HUVECs coculture system, leading to increased trans-endothelial electrical resistance (TEER), reduced cell permeability, and upregulation of expressions of F-actin and junction proteins. DB contributed to the assembly of actin cytoskeleton by upregulating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway and contributed to the formation of intercellular junctions by downregulating TLR4-MyD88-NF-κB pathway, thus reversing LPS-induced IEB dysfunction. These novel findings illustrated the potential protective mechanism of DB on intestinal inflammatory-related diseases and might be useful for further clinical application of DB., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Purpose: Sunitinib is a recommended drug for metastatic renal cell carcinoma (RCC). However, the therapeutic potential of sunitinib is impaired by toxicity and resistance. Therefore, we seek to explore a combinatorial strategy to improve sunitinib efficacy of low-toxicity dose for better clinical application., Methods: We screen synergistic reagents of sunitinib from a compound library containing 1374 FDA-approved drugs by in vitro cell viability evaluation. The synergistically antiproliferative and proapoptotic effects were demonstrated on in vitro and in vivo models. The molecular mechanism was investigated by phosphoproteomics, co-immunoprecipitation, immunofluorescence and western-blot assays, etc. RESULTS: From the four-step screening, nilotinib stood out as a potential synergistic killer combined with sunitinib. Subsequent functional evaluation demonstrated that nilotinib and sunitinib synergistically inhibit RCC cell proliferation and promote apoptosis in vitro and in vivo. Mechanistically, nilotinib activates E3-ligase HUWE1 and in combination with sunitinib renders MCL-1 for degradation via proteasome pathway, resulting in the release of Beclin-1 from MCL-1/Beclin-1 complex. Subsequently, Beclin-1 induces complete autophagy flux to promote antitumor effect., Conclusion: Our findings revealed that a novel mechanism that nilotinib in combination with sunitinib overcomes sunitinib resistance in RCC. Therefore, this novel rational combination regimen provides a promising therapeutic avenue for metastatic RCC and rationale for evaluating this combination clinically., (© 2024. Springer Nature Switzerland AG.)

Cardiac hypertrophy is the main adaptive response of the heart to chronic loads; however, prolonged or excessive hypertrophy promotes myocardial interstitial fibrosis, systolic dysfunction, and cardiomyocyte death, especially aseptic inflammation mediated by NLRP3 inflammasome, which can aggravate ventricular remodeling and myocardial damage, which is an important mechanism for the progression of heart failure. Various cardiac overloads can cause mitochondrial damage. In recent years, the mitochondria have been demonstrated to be involved in the inflammatory response during the development of cardiac hypertrophy in vitro and in vivo. As the NLRP3 inflammasome and mitochondria are regulators of inflammation and cardiac hypertrophy, we explored the potential functions of the NLRP3 inflammasome and mitochondrial dysfunction in cardiac hypertrophy. In particular, we proposed that the induction of mitochondrial dysfunction in cardiomyocytes may promote NLRP3-dependent inflammation during myocardial hypertrophy. Further in-depth studies could prompt valuable discoveries regarding the underlying molecular mechanisms of cardiac hypertrophy, reveal novel anti-inflammatory therapies for cardiac hypertrophy, and provide more desirable therapeutic outcomes for patients with cardiac hypertrophy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Diagnostic imaging plays an important role in the pre-treatment workup of knee osteoarthritis (OA) and rheumatoid arthritis (RA). Herein, we identified a useful MRI sign of infrapatellar fat pad (IPFP) to improve diagnosis., Methods: Eighty-one age- and sex-matched RA and OA patients each, with pathological diagnosis and pre-treatment MRI were retrospectively evaluated. All randomized MR images were blinded and independently reviewed by two radiologists. The assessment process included initial diagnosis, sign evaluation, and final diagnosis, with a 3-week interval between each assessment. Broken-fat pad (BFP) sign was assessed on sagittal T2-weighted-imaging in routine MRI. The area under the curve and Cohen's kappa (κ) were used to assess the classification performance. Two shape features were extracted from IPFP for quantitative interpretation., Results: The median age of the study population was 57.6 years (range: 31.0-78.0 years). The BFP sign was detected more frequently in patients with RA (72.8%) than those with OA (21.0%). Both radiologists achieved better performance by referring to the BFP sign, with accuracies increasing from 58.0 to 75.9% and 72.8 to 79.6%, respectively. The inter-reader correlation coefficient showed an increase from fair (κ = 0.30) to substantial (κ = 0.75) upon the consideration of the BFP sign. For quantitative analysis, the IPFP of RA had significantly lower sphericity (0.54 ± 0.04 vs. 0.59 ± 0.03, p < 0.01). Despite larger surface-volume-ratio of RA (0.38 ± 0.05 vs. 0.37 ± 0.04, p = 0.25) than that of OA, there was no statistical difference., Conclusions: The BFP sign is a potentially important diagnostic clue for differentiating RA from OA with routine MRI and reducing misdiagnosis., Critical Relevance Statement: With the simple and feasible broken-fat pad sign, clinicians can help more patients with early accurate diagnosis and proper treatment, which may be a valuable addition to the diagnostic workup of knee MRI assessment., Key Points: • Detailed identification of infrapatellar fat pad alterations of patients may be currently ignored in routine evaluation. • Broken-fat pad sign is helpful for differentiating rheumatoid arthritis and osteoarthritis. • The quantitative shape features of the infrapatellar fat pad may provide a possible explanation of the signs. • This sign has good inter-reader agreements and is feasible for clinical application., (© 2024. The Author(s).)

Breast cancer is a major threat to safety and health of women. The breast cancer stem cells (BCSCs) have multi-drug resistance to chemotherapy drugs, which leads to chemotherapy failure. We proposed a strategy of delivery of tumor-killing drugs and a resistance reversal agent, to enhance inhibition of BCSCs. Here, schisandrin B (SchB)/AP NPs are constructed using acid-grafted-poly (β-amino ester) (ATRA-g-PBAE, AP) grafted polymer nanoparticle encapsulated SchB, with pH-sensitive release function. This drug delivery system has good pharmacological properties and can increase the SchB release with the decrease of pH. The NPs showed cytotoxic effects in reversing ATRA resistance to BCSCs. Lysosomal escape was achieved when the nanoparticles were taken up by BCSCs. In addition, we found that NPs may reverse MDR by inhibiting the expression of P-glycoprotein (P-gp) and affecting the energy supply of drug efflux. This study provides a nanodelivery therapy strategy that reverses BCSCs multidrug resistance (MDR) and demonstrates that it did so by interfering with cancer cell energy metabolism. Therefore, the co-delivery strategy of ATRA and SchB provides a new option for the treatment of breast cancer., (© 2024. The Author(s).)

Previous epidemiological studies have linked short-term exposure to particulate matter with outpatient visits for respiratory diseases. However, evidence on ultrafine particle (UFP) is still scarce in China. To investigate the association between short-term UFP exposure and outpatient visits for respiratory diseases as well as the corresponding lag patterns, information on outpatient visits for main respiratory diseases during January 1, 2017, to December 31, 2019 was collected from electronic medical records of two large tertiary hospitals in Shanghai, China. Generalized additive models employing a Quasi-Poisson distribution were employed to investigate the relationships between UFP and respiratory diseases. We computed the percentage change and its corresponding 95% confidence interval (CI) for outpatient visits related to respiratory diseases per interquartile range (IQR) increase in UFP concentrations. Based on a total of 1,034,394 hospital visits for respiratory diseases in Shanghai, China, we found that the strongest associations of total UFP with acute upper respiratory tract infection (AURTI), bronchitis, chronic obstructive pulmonary disease (COPD), and pneumonia occurred at lag 03, 03, 0, and 03 days, respectively. Each IQR increase in the total UFP concentrations was associated with increments of 9.02% (95% CI: 8.64-9.40%), 3.94% (95% CI: 2.84-5.06%), 4.10% (95% CI: 3.01-5.20%), and 10.15% (95% CI: 9.32-10.99%) for AURTI, bronchitis, COPD, and pneumonia, respectively. Almost linear concentration-response relationship curves without apparent thresholds were observed between total UFP and outpatient-department visits for four respiratory diseases. Stratified analyses illustrated significantly stronger associations of total UFP with AURTI, bronchitis, and pneumonia among female patients, while that with COPD was stronger among male patients. After adjustment of criteria air pollutants, these associations all remained robust. This time-series study indicates that short-term exposure to UFP was associated with increased risk of hospital visits for respiratory diseases, underscoring the importance of reducing ambient UFP concentrations for respiratory diseases control and prevention., (© 2023. The Author(s).)

Water-coal interactions are dominant factors that affect water quality in coal mines. Using lixiviation, the effects of water-coal interactions on pH, salinity, and hazardous elemental enrichment in coal mine water and associated trends were simulated and analyzed. The salinity and hazardous element contents were low in the alkaline solution filtrate. However, the salinity and contents of hazardous elements (As, Cr, Zn, Cu, Mn, Co, Ni, Cd, Pb, U, and Be) in acid solution filtrate increased significantly with a decrease in pH. The pH of the solution filtrate was affected by the mineral composition of the coal, wherein the pyrite content could generally determine the pH. In addition, the spatial distribution and utilization potential of coal mine water quality in China was determined based on water quality data surveys. For water-deficient regions in northern China, particularly in the northwest, the local mine water had high salinity, a high pH, and a low content of hazardous elements; therefore, the reuse of mine water for water consumption is feasible. Conversely, the mine water in the southwest region had high salinity and a low pH and was enriched in harmful elements with potential ecological and health risks. The actual water quality characteristics of the coal mine water matched the results of the laboratory simulation analysis, confirming the effect from water-coal interactions. This work provides a reference for understanding the determinants of coal mine water quality and the potential for water environment protection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Conventional magnetic resonance imaging (MRI) features have difficulty distinguishing glioma true tumor recurrence (TuR) from treatment-related effects (TrE). We aimed to develop a machine-learning model based on multimodality MRI radiomics to help improve the efficiency of identifying glioma TuR., Methods: A total of 131 patients were enrolled and randomly divided into the training set (n = 91) and the test set (n = 40). Radiomic features were extracted from the postoperative enhancement (PoE) region and edema (ED) region from four routine MRI sequences. After analyses of Spearman's rank correlation coefficient, and least absolute shrinkage and selection operator, the key radiomic features were selected to construct support vector machine (SVM) and k-nearest neighbor (KNN) models. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to analyze the performance., Results: The PoE model had a significantly higher area under curve (AUC) than the ED model (p < 0.05). Among the models constructed with a single sequence, the model using PoE regional features from CE-T1WI was superior to other models, with an AUC of 0.905 for SVM and 0.899 for KNN. In multimodality models, the PoE model outperformed the ED model with an AUC of 0.931 for SVM and 0.896 for KNN. The multimodality model, which combined routine sequences and the whole regional features, showed a slightly better performance with an AUC of 0.965 for SVM and 0.955 for KNN. Decision curve analysis showed the good clinical utility of multimodal radiomics models., Conclusions: Multimodality radiomics can identify glioma TuR and TrE, potentially aiding clinical decision-making for individualized treatment. And edematous regions may provide useful information for recognizing recurrence., Retrospectively Registered: 2021.04.15, No:2020039., (© 2023. The Author(s).)

Cr (VI) is still of great concern due to its high toxicity, solubility, and mobility. The transformation of waste biomass to biochar is favorable for sustainable development. Hazelnut shell, an agriculture waste, was utilized as precursor to prepare biochar at 700 °C and firstly conducted for Cr (VI) removal. Nearly all 50 mg L -1 of Cr (VI) was removed from aqueous media in 180 min under the optimal conditions. The best compliance with pseudo-second-order kinetic model (R 2 = 0.999) and Langmuir isotherm model (R 2 = 0.999) indicated Cr (VI) removal was a monolayer chemisorption process. The hazelnut shell biochar exhibited superior performance on Cr (VI) removal at low pH (2.0) and Cr (VI) concentrations (≤ 50 mg L -1 ). Various techniques illustrated that the predominant mechanism of Cr (VI) removal by hazelnut shell biochar involved electrostatic attraction, reduction, and complexation. This study provides a promising low-cost alternative for Cr (VI) elimination from acidic wastewater and groundwater after extraction following by pH adjustment to 2.0., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chemical composition, surface morphology characteristics, and mineralogical characteristics of feed coals from six power plants were studied in this paper, as well as alteration behavior of mineral phase, functional groups, and trace elements during combustion. The apparent morphology of feed coals is different in compactness and order, while sharing a similar lamellar shape. Quartz, kaolinite, calcite, and illite are the main minerals in feed coals. There are obvious differences in the calorific value and temperature range in volatiles stages or coke combustion stages for feed coals. Peak positions for the main functional groups in feed coals are similar. After burning at 800 ℃, most organic functional groups in feed coals were lost in products, but the group of -CH 2 on the side chain skeleton of n-alkane and the aromatic hydrocarbon bond (Ar-H) still existed in the ash, and the vibration of Si-O-Si bond and Al-OH bond in inorganic functional groups was strengthened. During combustion, Pb and Cr in feed coals will be accumulated in the mineral residues, unburned carbon, and residual ferromanganese minerals, along with the loss of organic matter and sulfide or the decomposition of carbonate. Pb and Cr are more easily adsorbed by the fine-graded coal combustion products. Occasionally, the abnormal phenomenon occurred in a medium-graded ash but with the maximum adsorption of Pb and Cr, which is mainly caused by the collision and agglomeration of the combustion products, or the adsorption capacity of different mineral components. The effects of diameter, coal species and feed coal on the forms of Pb and Cr in combustion products were also analyzed in this study. The study has some guiding significance for understanding the behavior track and alteration mechanism of Pb and Cr during coal combustion., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Exploring alternative fuels and advanced vehicle technology is a crucial strategy for vehicle emission reduction. Fuel cell heavy-duty trucks (FC-HDTs) have a promising application prospect to alleviate the high energy consumption and emissions of road freight, but their environmental performance during the fuel life cycle should be further studied. This study is aimed at evaluating the fossil fuel consumption and GHG emissions of FC-HDTs in China using the updated GREET model. The results show that (1) comparing various hydrogen production pathways, it is found that the coke oven gas (COG) pathway can provide the best environmental performance, while the energy consumption and greenhouse gas (GHG) emissions of the coal gasification (CG) and grid power water electrolysis (GPWE) pathways will be significantly decreased in the future. (2) Among the involved vehicles in China, FC-HDT with GVWR18 has the greatest energy-saving and emission-reduction potential. (3) The application of carbon capture and storage (CCS) technology in hydrogen production is conducive to improving the emission-reduction effect of FC-HDT while increasing its energy consumption slightly. The key to achieving upstream carbon neutrality is to optimize the hydrogen production structure and electricity mix, along with adjusting the hydrogen production process and transportation mode. Furthermore, the fuel economy and payload of the FC-HDT affect its environmental performance, indicating the importance of improving the technology of the drivetrain, fuel cell, and hydrogen storage tank., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Kdm6b, a specific histone 3 lysine 27 (H3K27) demethylase, has been reported to be implicated in a variety of developmental processes including cell differentiation and cell fate determination and multiple organogenesis. Here, we regulated the transcript level of kdm6bb to study the potential role in controlling the hearing organ development of zebrafish., Methods: A morpholino antisense oligonucleotide (MO) strategy was used to induce Kdm6b deficiency; immunohistochemical staining and in situ hybridization analysis were conducted to figure out the morphologic alterations and embryonic mechanisms., Results: Kdm6bb is expressed in the primordium and neuromasts at the early stage of zebrafish embryogenesis, suggesting a potential function of Kdm6b in the development of mechanosensory organs. Knockdown of kdm6bb severely influences the cell migration and proliferation in posterior lateral line primordium, abates the number of neuromasts along the trunk, and mRNA-mediated rescue test can partially renew the neuromasts. Loss of kdm6bb might be related to aberrant expressions of chemokine genes encompassing cxcl12a and cxcr4b/cxcr7b in the migrating primordium. Moreover, inhibition of kdm6bb reduces the expression of genes in Fgf signaling pathway, while it increases the axin2 and lef1 expression level of Wnt/β-catenin signaling during the migrating stage., Conclusions: Collectively, our results revealed that Kdm6b plays an essential role in guiding the migration of primordium and in regulating the deposition of zebrafish neuromasts by mediating the gene expression of chemokines and Wnt and Fgf signaling pathway. Since histone methylation and demethylation are reversible, targeting Kdm6b may present as a novel therapeutic regimen for hearing disorders., (© 2021. The Author(s).)

To achieve net zero emissions, the global transportation sector needs to reduce emissions by 90% from 2020 to 2050, and road freight has a significant potential to reduce emissions. In this context, emission reduction paths should be explored for road freight over the fuel life cycle. Based on panel data from 2015 to 2020 in China, China's version of the GREET model was established to evaluate the impact of crude oil mix, electricity mix, and vehicle technology on China's reduction in road freight emissions. The results show that the import share of China's crude oil has increased from 2015 to 2020, resulting in an increase in the greenhouse gas (GHG) emission intensity of ICETs in the well-to-tank (WTT) stage by 7.3% in 2020 compared with 2015. Second, the share of China's coal-fired electricity in the electricity mix decreased from 2015 to 2020, reducing the GHG emission intensity of battery electric trucks (BETs), by approximately 6.5% in 2020 compared to 2015. Third, different vehicle classes and types of BETs and fuel cell electric trucks (FCETs) have different emission reduction effects, and their potentials for energy-saving and emission reduction at various stages of the fuel life cycle are different. In addition, in a comparative study of vehicle technology, the results show that (1) for medium-duty trucks (MDTs) and heavy-duty trucks (HDTs), FCETs have lower GHG emission intensity than BETs, and replacing diesel-ICETs can significantly reduce GHG emissions from road freight; (2) for light-duty trucks (LDTs), BETs and FCETs have the highest GHG emission reduction potential; thus, improving technologies such as electricity generation, hydrogen fuel production, hydrogen fuel storage, and transportation will help to improve the emission reduction capabilities of BETs and FCETs. Therefore, policymakers should develop emission standards for road freight based on vehicle class, type, and technology., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Olverembatinib represents the third-generation breakpoint cluster region protein-Abelson-murine leukemia 1 (BCR-ABL1) tyrosine kinase inhibitor with oral bioavailability, which can be used to overcome the T315I mutation in Philadelphia chromosome-positive (Ph +) leukemia. BCR-ABL-independent resistance to olverembatinib has been reported among patients in various clinical cases. However, the mechanism of olverembatinib resistance has rarely been reported. This study has illustrated bone marrow cell transcriptome and metabolome profiles among Ph + acute lymphoblastic leukemias (ALL) cases pre- and post-olverembatinib resistance. The transcriptome studies demonstrated that PI3K/AKT, purine metabolism, and other signaling pathways could play a vital role in olverembatinib resistance. As suggested by metabolomics, olverembatinib resistance in Ph + ALL was associated with purine metabolism alterations. Subsequently, high-performance liquid chromatography along with real-time quantitative PCR was utilized to measure purine metabolism-related mRNA levels and metabolism expression levels between olverembatinib resistance and sensitive cell lines. Our results elucidate the mechanism of olverembatinib resistance in Ph + ALL at transcriptome and metabolome levels, which facilitate a better understanding of olverembatinib resistance and hence may prove crucial in identifying novel drugs to tackle this conundrum., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The all-vanadium redox flow battery (VRFB) is becoming a promising technology for large-scale energy storage due to its advantages such as scalability and flexibility. In recent years, the VRFB has been successfully developed and put into use in many countries. It is expected that the abandoned VRFB will generate a large amount of vanadium waste. To our knowledge, there are few reports on the disposal of spent VRFBs. Herein, chitosan-coated nano-zero-valent iron (CS-Fe 0 ) is proposed for the first time as adsorbents for the treatment of spent VRFBs. It can provide a new approach to deal with the upcoming large number of spent VRFBs. The calculated maximum adsorption capacity for V(V) of chitosan and CS-Fe 0 reached 209.5 and 511.3 mg/g at 288 K, respectively. CS-Fe 0 showed better adsorption performance than chitosan under different pH conditions and is easy to be separated from the liquid phase. The Freundlich isotherm was suitable for the adsorption process of chitosan, and CS-Fe 0 was more consistent with the Langmuir isotherm. Ionic strength (0.05-0.5 M) had a positive effect on the adsorption capacity of CS-Fe 0 , and the influence of coexisting anions on CS-Fe 0 could be negligible. FTIR and XPS analyses revealed that the primary mechanisms were the electrostatic attraction of chitosan and redox of Fe 0 . The present study confirmed that CS-Fe 0 could be a potential material to efficiently trap V(V) from the VRFB electrolyte., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the risk factors for adverse pregnancy outcomes (APOs) in women with rheumatoid arthritis (RA) and the influence on their offspring health., Methods: Pregnant women with RA (n = 67) who were hospitalized in the Department of Obstetrics, Peking University People's Hospital between January 2007 and September 2021 were included in this study. Participants were evaluated at least once in each trimester and postpartum. Fetal outcomes and RA disease activity were extracted from medical records, and the offspring of enrolled patients were followed up. Associations between RA disease activity, medication use, and pregnancy outcomes were analyzed., Results: The incidence of APOs in our cohort was 43.3%. Postpartum hemorrhage (20.9%) was the commonest complication, followed by premature delivery (11.9%). Previous miscarriages [odds ratio (OR): 1.869, 95% confidence interval (CI): 1.053-3.318, P = 0.033] and antinuclear antibody (ANA) positivity (OR:3.168, 95% CI: 1.068-9.768, P = 0.045) were risk factors for APOs. Compared to patients with APOs, the remission rate of disease activity during pregnancy was higher in patients without APOs (P = 0.027). There were no significant differences between patients with and without APOs with respect to daily and cumulative doses of prednisone (P > 0.05). The average age of the offspring was 4.9 years (range 0.3-14 years). Long-term follow-up showed no significant differences in offspring health between the two groups (P > 0.05)., Conclusion: Previous miscarriages and ANA positivity are independent risk factors for APOs in RA patients, while adverse pregnancy outcomes and low-dose prednisone have no effect on offspring health. Key points • Previous miscarriages and ANA positivity are risk factors for APOs in RA patients. • Adverse pregnancy outcomes and low-dose prednisone during pregnancy have no effect on offspring health., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

In order to improve the recovery ratio of valuable metals in stainless steel dust, reduce environmental pollution, and promote solid waste resource recovery and sustainable development of industry, the synergistic reduction process for preparing Fe-Cr-Ni-C alloy was studied in detail by changing the addition of laterite nickel ore and reduction process conditions. The results show that with the addition of laterite nickel ore, the basicity of raw materials is reduced, the precipitation and aggregation of metal particles are promoted, the separation effect of metals and slags from reduction products is improved, and the metal recovery ratio also improved in the synergistic reduction process. When the ratio of stainless steel dust to laterite nickel ore is 94%:6%, reduction temperature is 1400 °C, reduction time is 20 min, and FC/O is 0.8, the metals and slags of the reduction product can be separated naturally after cooling; the recoveries of Fe, Cr, and Ni are 90.6%, 90.1%, and 91.2%, respectively. The grades of Fe, Cr, and Ni in the Fe-Cr-Ni-C alloy are 62.7%, 18.9%, and 4.1%, respectively. The content of harmful elements S and P in the alloy is low, so it can be directly used as raw material for stainless steel smelting., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper investigates volatility spillovers between the global crude oil market and the stock markets of the global oil stock markets (Russian, Canada, China, Kuwait, and the USA) pre and after the COVID-19 pandemic. We use wavelet Granger causality methods to study the volatility spillovers between global oil stock markets, mainly from January 1, 2019, to March 31, 2021. Our Results (1) shows that WTI and Brent oil prices had a negative mean return before COVID-19 but a positive mean return during the pandemic spread. Other Results (2) find the positive, significantly lowest, and highest frequency during the COVID-19 outbreak for all selected countries. The results also show that the link between oil WTI & Brent prices and stock markets return in the lowest (33-66 days) and highest frequency range (4-16) before the Covid-19 epidemic, especially in the first quarter of 2020. Before the COVID-19 period, the Russian oil stock market is seriously prejudiced with oil prices on a modest scale, but not after the pandemic's start. This study also perceives direction opposite between the COVID-19 period. The Canadian and United States America oil and stock markets influence the lowest scale in the previous COVID-19 sample for the U.S. market. Moreover, this paper exposed that oil marketing highest oil futures in their portfolios than stock shares for all times. We found that oil price shocks had a more significant impact on the stock markets of the United States and Canada than on the stock markets of other countries., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To determine the sensitivity of the 18 F-radiolabelled dihydroethidine analogue ([ 18 F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress., Procedures: The sensitivity of [ 18 F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [ 18 F]DHE (50-150 kBq.min -1 ) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress., Results: [ 18 F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [ 18 F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation., Conclusion: [ 18 F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics., (© 2021. Crown.)

Purpose: Carotid artery atherosclerotic stenosis accounts for 18-25% of ischemic stroke. In the evaluation of carotid atherosclerotic lesions, the automatic, accurate and rapid segmentation of the carotid artery is a priority issue that needs to be addressed urgently. However, the carotid artery area occupies a small target in computed tomography angiography (CTA) images, which affect the segmentation accuracy., Methods: We proposed a coarse-to-fine segmentation pipeline with the Multiplanar D-SEA UNet to achieve fully automatic carotid artery segmentation on the entire 3D CTA images, and compared with other four neural networks (3D-UNet, RA-UNet, Isensee-UNet, Multiplanar-UNet) by assessing Dice, Jaccard similarity coefficient, sensitivity, area under the curve and average hausdorff distance., Results: Our proposed method can achieve a mean Dice score of 91.51% on the 68 neck CTA scans from Beijing Hospital, which remarkably outperforms state-of-the-art 3D image segmentation methods. And the C2F segmentation pipeline can effectively improve segmentation accuracy while avoiding resolution loss., Conclusion: The proposed segmentation method can realize the fully automatic segmentation of the carotid artery and has robust performance with segmentation accuracy, which can be applied into plaque exfoliation and interventional surgery services. In addition, our method is easy to extend to other medical segmentation tasks with appropriate parameter settings., (© 2021. CARS.)

The 38 kDa protein is a major antigen of mycobacterium tuberculosis and has been widely used in TB serodiagnosis, due to its highly sensitivity and specificity. Here we attempt to establish a production platform of recombinant 38 kDa protein in mammalian cells and to evaluate the potential value of 38 kDa protein in TB serodiagnosis. The 38 kDa gene is synthesized and cloned into a lentiviral expressing vector. Recombinant lentiviral vector LV-CMV-38 kDa-eGFP was packaged, titered, and then transduced into HEK 293 T cells. Recombinant cell lines were selected by limiting dilution. Supernatants were collected and purified by HisTrapTM HP column. Western blot showed a molecular weight of approximate 38 kDa in cell supernatants as expected. ELISA assay confirmed the immunological specificity of the obtained protein in the presence of MTB-infected human serum samples. In all, we have obtained a stable cell line with long-term and robust expression of secretory MTB 38 kDa protein, which may provide a promising candidate antigen for the development of TB serological diagnosis., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

A timely and effective evaluation of the suicidal ideation bears practical meaning, particularly for the depressive who tend to disguise the real suicide intent and without obvious symptoms. Measuring individual ideation of the depression with uncertain or transient suicide crisis is the purpose. Resting-state fMRI data were collected from 78 depressed patients with variable clinical suicidal crisis. Thirty subjects were well labeled as extremely serious individuals with suicide attempters or as without suicidal ideation. A feature mask was constructed via the two sample t-test on their regional conncectivities. Then, a semi-supervised machine learning frame using the feature mask was designed to assist in clarifying gradation of suicidal susceptibility for the residual forty-eight vaguely defined subjects, by a way of Iterative Self-Organizing Data analysis techniques (ISODATA). Such semi-supervised model was designed purposely to block out the effect of disease itself on the suicide intendancy evaluation. The vague-labeled patients were divided into another two different stages relating to their suicidal susceptibility. The distance ratio of each subject to the two well-defined extreme groups in the feature space can be utilized as the suicide risk index. The re-evaluation of the Nurses' Global Assessment of Suicide Risk (NGASR) via experts blind to original HAM-D rates was significantly correlated with the model estimation. The constructed model suggested its potential to examine the risk of suicidal in an objective way. The functional connectivity, locating mostly within the frontal-temporal circuit and involving the default mode network (DMN), were well integrated to discriminative the gradual susceptibility of suicidal., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Electronic cigarettes (e-cigarettes), since they do not require tobacco combustion, have traditionally been considered less harmful than conventional cigarettes (c-cigarettes). In recent years, however, researchers have found many toxic compounds in the aerosols of e-cigarettes, and numerous studies have shown that e-cigarettes can adversely affect the human epigenome. In this review, we provide an update on recent findings regarding epigenetic outcomes of e-cigarette aerosols. Moreover, we discussed the effects of several typical e-cigarette ingredients (nicotine, tobacco-specific nitrosamines, volatile organic compounds, carbonyl compounds, and toxic metals) on DNA methylation, histone modifications, and noncoding RNA expression. These epigenetic effects could explain some of the diseases caused by e-cigarettes. It also reminds the public that like c-cigarettes, inhaling e-cigarette aerosols could also be accompanied with potential epigenotoxicity on the human body.

The present study examined the relationship between age of acquisition (AoA) and bilingual development for native Chinese children who learned English as a foreign language. A composite test measuring different aspects of language and cognitive skills in Chinese and English was administered on 85 Chinese native primary schoolers, who received bilingual instruction at different points of development (for Chinese, 0 ≤ AoA ≤ 7 years; for English, 2 ≤ AoA ≤ 10 years). Results found AoA constraints on the outcomes of L1 Chinese acquisition are significantly different from those for L2 English. Not all domains of bilingual skills follow the pattern of "the earlier, the better" in language development. Additionally, L1 AoA made unique contributions to L2 English learning. These findings contribute to our understanding on the nature of the AoA effect on bilingual learning.

Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disease. The major clinical features of SchS are urticarial rash and monoclonal gammopathy, accompanied by fever, joint pain, and lymphadenopathy. There were few reports about SchS in Chinese population. Herein, we describe two patients with SchS in China and conducted a systematic literature review about SchS. Two Chinese Han patients were diagnosed as SchS in our department from 2017 to 2019. Their phenotype and genotype were carefully documented and studied. We also conducted a systematic literature review about SchS. There was one man (66 years old) and one woman (49 years old). Recurrent fever and urticarial rash occurred in both of them during the febrile attacks and normalized in asymptomatic intervals. Other manifestations included arthralgia, lymphadenopathy, and hearing loss. Hepatic cirrhosis and epilepsy were seen in the male patient. None of them had bone pain or family histories. Serum monoclonal IgM gammopathy was found in both patients. MyD88 gene mutation L258P was identified in the female patient. They were treated with tocilizumab and tripterygium wilfordii Hook F (TwHF) respectively, and both showed good response. The rarity and diversity of SchS make it difficult to be recognized. Anti-IL-6 agents may be alternative therapies when anti-IL-1 therapy is unresponsive or unavailable. Due to the case report, the effect of TwHF in the treatment of SchS should be further studied.

Atherosclerosis is the common vascular disease. Vascular smooth muscle cell proliferation and vascular endothelial cell (VEC) dysfunction are involved in the causes of atherosclerosis. And oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cells (VECs) are suitable models for studying atherosclerosis development. Paeonol was reported to repress ox-LDL-induced VEC progression. However, its detailed mechanism was not fully reported. MicroRNAs (miRNAs) acted as regulators in multiple diseases. Previous findings found that microRNA-338-3p (miR-338-3p) was overexpressed in Atherosclerosis process. However, the function and underlying mechanism of miR-338-3p in ox-LDL-treated VECs needed to be elucidated. The purpose of this research was to reveal the role of miR-338-3p in paeonol-regulated ox-LDL-induced VEC progression. Cell counting kit-8 (CCK-8) and flow cytometry were employed to determine cell viability and apoptosis, respectively. Moreover, the levels of IL-6 and IL-1β were analyzed using enzyme-linked immunosorbent assay, as well as the contents of reactive oxygen species, lactate dehydrogenase, and malonic dialdehyde were investigated using related kits. Furthermore, quantitative real-time polymerase chain reaction was carried out to determine the expression of miR-338-3p. Western blot assay was conducted to detect the level of tet methylcytosine dioxygenase 2 (TET2). Besides, the interaction between miR-338-3p and TET2 was predicted by DIANA, and then confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. Ox-LDL repressed mice VEC viability, and promoted apoptosis, inflammatory response, and oxidative injury. Paeonol inhibited the effect of ox-LDL on the growth of the VECs. Furthermore, paeonol regulated VEC development via downregulating miR-338-3p expression. Interestingly, miR-338-3p targeted TET2 and inhibited TET2 expression. MiR-338-3p modulated ox-LDL-treated VEC growth through suppressing TET2 expression. We demonstrated that paeonol attenuated the effect of ox-LDL on the development of mice VECs via modulating miR-338-3p/TET2 axis, providing a theoretical basis for the treatment of AS.

Although structural and functional brain abnormalities have been observed in depressed suicide attempters (DS), structural deficits and functional impairments together with their relationship in DS remain unclear. To clarify this issue, we aimed to examine the differences in gray matter (GM) alteration, corresponding functional connectivity (FC) change, and their relationship between DS and depressed non-suicide attempters (NDS). Sixty-eight DS, 119 NDS and 103 healthy controls were enrolled and subjected to magnetic resonance imaging scans. The patients were evaluated using the 17-item Hamilton Rating Scale for Depression (HRSD) and Nurses' Global Assessment of Suicide Risk (NGASR) scale. Both voxel-based morphometry and resting-state FC analyses were performed based on functional and structural imaging data. Compared with NDS, the DS group showed reduced GM volume in the right inferior frontal orbital gyrus (IFOG) and left caudate (CAU) but increased GM volume in the left calcarine fissure, weaker negative right IFOG-left rectus gyrus (REG) FC, and weaker positive right IFOG-left inferior parietal lobule (IPL) FC. In DS, the GM volume of the right IFOG and left CAU was negatively correlated with NGASR and HRSD scores, respectively; the right IFOG-left IPL FC was negatively correlated with cognitive factor scores; and the GM volume of the right IFOG was positively correlated with IFOG-REG and IFOG-IPL FC. Our findings indicate that structural deficit with its related functional alterations in brain circuits converged in right IFOG centralized pathways and may play a central role in suicidal behaviors in depression.

Perylenequinones (PQ), a class of naturally occurring polypeptides, are widely used as a clinical drug for treating skin diseases and as a photodynamic therapy against cancers and viruses. In this study, the effects of different carbon sources on PQ biosynthesis by Shiraia sp. Slf14 were compared, and the underlying molecular mechanism of fructose as the sole carbon to enhance PQ production was investigated by transcriptome analysis. The results indicated that fructose enhanced PQ yield to 1753.64 mg/L, which was 1.73-fold higher than that obtained with glucose. Comparative transcriptome analysis demonstrated that most of the upregulated genes were related to transport systems, energy and central carbon metabolism in Shiraia sp. Slf14 cultured in fructose. The genes involved in glycolysis and pentose phosphate pathways, and encoding citrate synthase, ATP-citrate lyase, and acetyl-CoA carboxylase were substantially upregulated, resulting in increased overall acetyl-CoA and malonyl-CoA production. However, genes involved in gluconeogenesis, glyoxylate cycle pathway, and fatty acid synthesis were significantly downregulated, resulting in higher acetyl-CoA influx for PQ formation. In particular, the putative PQ biosynthetic cluster was upregulated in Shiraia sp. Slf14 cultured in fructose, leading to a significant increase in PQ production. The results of real-time qRT-PCR and related enzyme activities were also consistent with those of transcriptome analysis. These findings provide a remarkable insight into the underlying mechanism of PQ biosynthesis and pave the way for improvements in PQ production by Shiraia sp. Slf14., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2020.)

Purpose: Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus and one of the most important causes of end-stage renal disease, but its pathogenesis has not been elucidated so far, and there is no effective treatment., Methods: DN models of rats and MPC-5 cells were established with streptozotocin (STZ) and high glucose (HG) in vivo and in vitro, respectively. Cell markers desmin and nephrin in foot kidney tissue were detected by Western blot. CCNG1 level in vitro was analyzed by Western blot and immunohistochemistry. CCK-8 assay and flow cytometry were conducted to analyze the effect of CCNG1 on HG-treated MPC-5 cells. Apoptosis-related proteins (Bcl-2, Bax and p53), CCNG1, and MDM2 were determined by RT-qPCR and Western blot., Results: The level of nephrin was decreased, while desmin was increased in STZ-induced DN rats and CCNG1 level was also enhanced by STZ. In vitro experiments indicated that MPC-5 cell viability was inhibited and apoptosis was induced by HG and we also found that CCNG1 expression was up-regulated by HG and negatively correlated with MDM2 level. The effects of HG on MPC-5 cell viability, apoptosis, and cell cycle were reversed by silencing CCNG1, but further deteriorated by overexpression of CCNG1. Furthermore, overexpression of MDM2 inhibited HG-induced MPC-5 cell injury and CCNG1 expression., Conclusions: These findings revealed that down-regulation of CCNG1 has protection effects in DN that is mechanistically linked to MDM2-p53 pathways.

Agricultural wastes have promising potential for the production of low-cost and sustainable adsorbents for heavy metals, while the characteristics of those biosorbents and the stability of the passivated heavy metals under natural conditions need to be studied further. In this paper, the oilseed rape plant after seed harvesting was divided into three parts: root (RT), stem (ST), and pod (PD). The isotherm adsorption of cadmium (Cd(II)) on the biomass was conducted. In practice, the biomass was aged in the Cd(II)-contaminated soil, and the concentration of Cd(II) in the leachate was measured after the continuous eluent of typical acid rain. The components and elements of the biomass were determined for the analysis of the differences between the immobilization abilities of the biomass. Results showed the CC (corn cob, as a comparison), ST, RT, and PD had the adsorption capacities of 6.34, 7.58, 9.22, and 9.87 mg/g for Cd(II) through the Langmuir fitting of the isothermal adsorption experiments, respectively. The leached Cd(II) were reduced 1063, 2073, 2824, and 3621 μg by CC, ST, RT, and PD biomass aging, respectively. Compared that by CC, the immobilization differences between the biomass in soil were much greater than that in isotherm adsorption, indicating the biosorption ability of rape biomass was enlarged during the 30 days of aging. Nitrogen, phosphorus, and sulfur contents showed sequences as pod>root>stem and had high correlations with the reduced amount of leached Cd(II), which indicated protein might be beneficial for the enhancement of adsorption/immobilization in the soil.

Due to rising development costs and stagnant product outputs of traditional drug discovery methods, drug repositioning, which discovers new indications for existing drugs, has attracted increasing interest. Computational drug repositioning can integrate prioritization information and accelerate time lines even further. However, most existing methods for predicting drug repositioning have low precisions. The present article proposed a new method named DDAPRED (https://github.com/nongdaxiaofeng/DDAPRED) for drug repositioning prediction. The method integrated multiple sources of drug similarity and disease similarity information, and it used the regularized logistic matrix decomposition method to significantly improve the prediction performance. In 5-fold cross-validation, the areas under the receiver operating characteristic curve (AUROC) and the precision-recall curve (AUPRC) of DDAPRED reached 0.932 and 0.438, respectively, exceeding other methods. The present study also analyzed the parameters influencing the model performance and the effect of different drug similarity information in-depth, and it verified the treatment relationship of the top 50 predictions with unknown relationships in the training set, further demonstrating the practicability of our method.

Background: The safety of nucleos(t)ide analogue (NA) treatment cessation remains one of the most controversial topics in the management of chronic hepatitis B (CHB) patients. This study investigated the efficiency of 48-week pegylated-interferon (peg-IFN) alfa-2a consolidation therapy on viral relapse after discontinued NA treatment in CHB patients who achieved hepatitis B e antigen (HBeAg) seroconversion for > 1 year., Methods: NA-treated HBeAg-positive patients who achieved the standard of discontinued NA treatment (i.e. time of HBeAg seroconversion > 1 year) were randomly assigned to receive peg-IFN consolidation (n = 24) treatment or continue original NA therapy (n = 24) for 48 weeks. The treatments were then discontinued, and the patients were observed up to 144 weeks. The primary endpoint was the proportion of patients with viral relapse at week 144 among those who received at least one dose of study drug or had at least one study visit [modified intention-to-treat population (mITT)]., Results: Of the 24 patients who received peg-IFN treatment, 6 (25%) experienced viral relapse and 8 (36.3%) showed HBsAg loss during 96 weeks of treatment-free follow-up. Of the patients who underwent NA consolidation treatment, only 1 (4.3%) of 23 patients showed HBsAg loss and 14 (58.3%) of 24 patients experienced viral relapse during follow-up. HBsAg level decline < 0.25 log 10 IU/mL at week 96 was significantly associated with viral relapse., Conclusion: A 48-week peg-IFN alfa-2a consolidation therapy increased the rate of HBsAg loss and sustained viral replication suppression in HBeAg-positive patients who achieved HBeAg seroconversion for > 1 year after NA treatment discontinuation.

Introduction: Traditional high-resolution MS1 based untargeted metabolomics suffers from low sensitivity, while low-resolution MS/MS based multiple reaction monitoring increases sensitivity at the cost of metabolite coverage and the mass accuracy., Objectives: To evaluate and apply the high-resolution MS/MS level untargeted metabolomics., Methods: SWATH based data-independent acquisition (DIA) was optimized to obtain MS/MS of all precursor ions., Results: SWATH-MS/MS could rescue MS1 obscured or saturated metabolites and potentially provide diagnostic fragments to differentiate isomers. For SWATH-MS/MS, 4944 out of 21492 (23.0%) and 2289 out of 12831 (17.8%) fragment ion features significantly changed (Fold change > 1.5, P < 0.05) between Normal and experimental acute ulcerative colitis (UC) groups in positive and negative ion mode, respectively. For SWATH-MS1, 1022 out of 4818 (21.2%) and 353 out of 2266 (15.6%) features significantly changed in positive and negative ion mode, respectively. By deciphering the metabolite profiles with high-resolution MS/MS, it allows versatile post-acquisition data mining such as open detection of different sub-metabolome. The method revealed a global urinary metabolic alteration and increased glucuronide and sulfate sub-metabolome in UC. The major limitation of untargeted SWATH-MS/MS is increased interferences derived from wider Q1 isolation window., Conclusions: SWATH-MS/MS is a versatile metabolomics strategy, merging the coverage of high-resolution untargeted metabolomics and the sensitivity of MS/MS.

Myocardial damage is responsible for the high mortality of sepsis. However, the underlying mechanism is not well understood. Cardiomyocyte autophagy alleviates the cardiac injury caused by myocardial infarction. Enhanced cardiomyocyte autophagy also has protective effects against cardiomyocyte mitochondrial injury. Minocycline enhances autophagy in many types of cells under different types of pathological stress and can be easily taken up by cardiomyocytes. The present study investigated whether minocycline prevented myocardial injury caused by sepsis and whether cardiomyocyte autophagy participated in this process. The results indicated that minocycline enhanced cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy and improved myocardial mitochondrial and cardiac function. Minocycline upregulated protein kinase B (Akt) phosphorylation, inhibited mTORC1 expression and enhanced mTORC2 expression. In conclusion, minocycline enhanced cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy and improved cardiac function. The underlying mechanisms were associated with mTORC1 inhibition and mTORC2 activation. Thus, our findings suggest that minocycline may represent a potential approach for treating myocardial injury and provide novel insights into the underlying mechanisms of myocardial injury and dysfunction after sepsis.

Four new flavonoid glucosides, 2″-O-(6‴-O-caffeoyl)-galactopyranosylvitexin (1), 2″-O-(6‴-O-veratroyl)-galactopyranosylvitexin (2), 2″-O-(6‴-O-feruloyl)-galactopyranosylorientin (3), 2″-O-(2‴-O-methylbutyryl)-glucopyranosylisoswertisin (4), along with three known compounds were isolated from the flowers of Trollius chinensis Bunge. Their structures were determined by extensive spectroscopic analyses.

MicroRNAs are members of the family of non-coding small RNAs that regulate gene expression either by inhibiting mRNA translation or by promoting mRNA degradation at the post-transcriptional level. They play an important role in the differentiation of human bone marrow mesenchymal stem cells (hMSCs) into adipocytes. However, the role of microRNAs in this process remains to be poorly understood. Here, we observed that miR-377-3p expression was markedly decreased during adipogenic differentiation of hMSCs. Overexpression of miR-377-3p decreased adipocyte differentiation and downregulated the expression of adipogenic markers. Meanwhile, bioinformatics-based studies suggested that LIFR is a target of miR-377-3p. Further analysis confirmed that expression of LIFR present markedly increased during adipogenic differentiation of hMSCs. In addition, downregulation expression of LIFR significantly inhibited the process of adipocyte differentiation. To confirm the relation between miR-377-3p and LIFR, luciferase reporter assays were carried out. The results indicated that miR-377-3p bound directly to the 3'-untranslated region of LIFR. These data indicate that miR-377-3p suppressed adipogenesis of hMSCs by targeting LIFR, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.

Extracellular ATP (eATP) plays an essential role in plant growth, development, and stress tolerance. Here, we report that eATP participated in Nicotiana tabacum pollen germination (PG) and pollen tube growth (PTG) by regulating K + and Ca 2+ influx. Exogenous ATP or ADP effectively promoted PG and PTG in a dose-dependent manner; weakly hydrolysable ATP analog (ATPγS) showed a similar effect. AMP, adenosine, adenine, and phosphate did not affect PG or PTG. Within a certain range, higher concentrations of K + or Ca 2+ in the medium increased the effect of ATP in promoting PG and PTG. However, in mediums containing K + or Ca 2+ concentrations above this range, the effect of ATP was reversed, resulting in PG and PTG inhibition. Ca 2+ chelators (EGTA), Ca 2+ channel blockers, and K + channel blockers suppressed ATP-promoted PG and PTG. Results from a patch clamp showed that ATP activated a K + and Ca 2+ influx in pollen protoplasts. These results suggest that, as an apoplastic signal, eATP may be involved in PG and PTG via regulating Ca 2+ and K + absorption.

Frataxin is the protein responsible for the genetically-inherited neurodegenerative disease Friedreich's ataxia caused by partial silencing of the protein and loss of function. Although the frataxin function is not yet entirely clear, it has been associated to the machine that builds iron-sulfur clusters, essential prosthetic groups involved in several processes and is strongly conserved in organisms from bacteria to humans. Two of its important molecular partners are the protein NFS1 (or IscS in bacteria), that is the desulfurase which converts cysteine to alanine and produces sulfur, and ISU (or IscU), the scaffold protein which transiently accepts the cluster. While bacterial frataxin has been extensively characterized, only few eukaryotic frataxins have been described. Here we report the 1 H, 13 C and 15 N backbone and side-chain chemical shift assignments of frataxin from Chaetomium thermophilum, a thermophile increasingly used by virtue of its stability.

Resistant non-segmental vitiligo is difficult to be treated. Ablative erbium-YAG (Er:YAG) laser has been used in the treatment of vitiligo, but the ablation of entire epidermis frustrated the compliance of patients. The purpose of this study is to investigate the effects of fractional Er:YAG laser followed by topical betamethasone and narrow band ultraviolet B (NB-UVB) therapy in the treatment of resistant non-segmental vitiligo. The vitiligo lesions of each enrolled patient were divided into four treatment parts, which were all irradiated with NB-UVB. Three parts were, respectively, treated with low, medium, or high energy of Er:YAG laser, followed by topical betamethasone solution application. A control part was spared with laser treatment and topical betamethasone. The treatment period lasted 6 months. The efficacy was assessed by two blinded dermatologists. Treatment protocol with high energy of 1800 mJ/P of fractional Er:YAG laser followed by topical betamethasone solution and in combination with NB-UVB made 60% patients achieve marked to excellent improvement in white patches. The protocol with medium energy of 1200 mJ/P of laser assisted approximate 36% patients achieve such improvement. The two protocols, respectively, showed better efficacies than NB-UVB only protocol. However, fractional Er:YAG laser at low energy of 600 mJ/P did not provide such contributions to the treatment of vitiligo. The fractional Er:YAG laser in combination with topical betamethasone solution and NB-UVB was suitable for resistant non-segmental vitiligo. The energy of laser was preferred to be set at relatively high level.

Purpose: To evaluate histologic differentiation of hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) using apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM)-derived metrics and to compare findings with alpha-fetoprotein (AFP) levels alone and in combination., Materials and Method: One hundred and six chronic HBV-related HCC patients who underwent IVIM diffusion-weighted magnetic resonance imaging with eleven b values were enrolled. Mean ADC, diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were determined for all detected lesions. The metrics and AFP levels of different histologically differentiated groups were compared. Spearman's rank correlation was used to assess the statistical dependence among the histologically differentiated HCCs. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance of these metrics and AFP levels alone and in combination., Results: ADC, D, and f values and AFP levels were significantly different among well-, moderately, and poorly differentiated HCCs. The four metrics were significantly correlated with histologic differentiation. The area under the ROC curve (AUC-ROC) of ADC, D, f, and AFP for diagnosing well-differentiated HCCs was 0.903, 0.84, 0.782, and 0.806, respectively, and the AUC-ROC of above metrics for diagnosing poorly differentiated HCCs was 0.787, 0.726, 0.624, and 0.633, respectively. The combination of ADC and AFP provided an AUC-ROC of 0.945 for well-differentiated HCC. However, this did not provide better performance for diagnosing poorly differentiated HCC., Conclusion: ADC, IVIM metrics, and AFP levels may be useful for evaluating histologic differentiation of HBV-related HCCs, and the combination of ADC and AFP provides better diagnostic performance for well-differentiated HCC.

Two new compounds, 2″-O-feruloylisoswertiajaponin (1) and (2E)-2-methyl-1-O-vaniloyl-4-β-D-glucopyranoside-2-butene (2), along with one indole alkaloid and five known flavonoids, were isolated from the flowers of Trollius chinensis Bunge. Their structures were elucidated on the basis of spectroscopic evidence (UV, IR, HR-ESI-MS, NMR).

BRCA1 and BRCA2 mutations confer an increased lifetime risk of breast cancer; however, the associations of microRNA (miRNA) binding site single nucleotide polymorphisms (SNPs) in 3' untranslated region (3'-UTR) of BRCA1 and BRCA2 with breast cancer (BC) risk were rarely reported. In this case-control study (498 BC patients and 498 matched controls), three SNPs (rs8176318, rs12516 and rs15869) were selected in the 3'-UTR of BRCA1 and BRCA2 genes, which were within miRNA-binding seed regions and might have potential function to regulate the expression of BRCA1/BRCA2. Unconditional logistic regression model was used to analyze the association between three SNPs and BC risk with adjustment of reproductive factors, and Student's t test was performed to assess relative expression of BRCA2 in human breast cancer cell lines. Multifactor dimensionality reduction method was applied to calculate gene-reproductive factors interactions. A novel finding showed that AC [odds ratio (OR) 1.524; 95% confidence interval (CI) 1.141-2.035] genotype of rs15869 in BRCA2 could increase the risk of BC and recombinant plasmid-pGenesil-1-miR-627 could negatively regulate the expression of BRCA2 in MCF-7 and MDA-MB-231 cells. Gene-reproductive factors interactions analysis revealed that rs15869 together with age at menarche and number of pregnancy could increase the risk of BC by 2.39-fold and TT genotype (OR 0.316; 95% CI 0.130-0.767) of rs8176318 had a significant association with progesterone receptor status in BC patients. Our findings suggest that the miRNA-binding SNPs in BRCA1/BRCA2 and their interaction with reproductive factors might contribute to BC risk, and miR-627 might down-regulate BRCA2 expression in MCF-7 and MDA-MB-231 cells.