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Objective The purpose of this study was to evaluate the diagnostic accuracy of 6 different imaging modalities for differentiating glioma recurrence from postradiotherapy changes by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more imaging techniques.Data sources PubMed, Scopus, EMBASE, the Web of Science and the Cochrane Library were searched from inception to August 2021. The Confidence In Network Meta-Analysis (CINeMA) tool was used to evaluate the quality of the included studies with the criterion for study inclusion being direct comparison using 2 or more imaging modalities.Data extraction and synthesis The consistency was evaluated by examining the agreement between direct and indirect effects. NMA was performed and the surface under the the cumulative ranking curve (SUCRA) values was obtained to calculate the probability of each imaging modality being the most effective diagnostic method. The CINeMA tool was used to evaluate the quality of the included studies.Main outcomes and measures Direct comparison, inconsistency test, NMA and SUCRA values.Results A total of 8853 potentially relevant articles were retrieved and 15 articles met the inclusion criteria. 18F-FET showed the highest SUCRA values for sensitivity, specificity, positive predictive value and accuracy, followed by 18F-FDOPA. The quality of the included evidence is classified as moderate.Conclusion and relevance This review indicates that 18F-FET and 18F-FDOPA may have greater diagnostic value for glioma recurrence relative to other imaging modalities (Grading of Recommendations, Assessment, Development and Evaluations B).PROSPERO registration number CRD42021293075.

Tapinarof is an aryl hydrocarbon receptor (AHR) ligand which is used to treat plaque psoriasis in adults. However, the underlying mechanism is not yet fully understood. In this study, we applied two of the most studied psoriasis mouse models: topical application of imiquimod (IMQ) and subcutaneous injection of IL‐23. Although both models successfully induced psoriasis‐like lesions in mice, tapinarof had a completely opposite effect on the two models. Tapinarof decreased the expression of multiple essential cytokines involved in the pathological IL‐23/IL‐17/IL‐22 axis and ameliorated IMQ‐induced psoriatic dermatitis, inhibiting keratinocyte proliferation and abnormal differentiation. However, in the IL‐23‐injection‐model, tapinarof instead aggravated the disease. Here, tapinarof increased epidermal thickness and differentiated epidermal dysplasia in mice. Our data suggest that tapinarof may have different effects on varied types of psoriasis. [ABSTRACT FROM AUTHOR]

As an essential factor in the prognosis of systemic lupus erythematosus (SLE), lupus nephritis (LN) can accelerate the rate at which patients with SLE can transition to chronic kidney disease or even end‐stage renal disease. Podocytes now appear to be a possible direct target in LN in addition to being prone to collateral damage from glomerular capillary lesions induces by immune complexes and inflammatory processes. The NLRP3 inflammasome is regulated by CCAAT/enhancer‐binding protein β (C/EBPβ), which is involved in the pathogenesis of SLE. However, the role and mechanism of C/EBPβ in LN remain unclear. In this investigation, glomerular podocytes treated with LN serum and MRL/lpr mice were employed as in vivo and in vitro models of LN, respectively. In vivo, the expression of C/EBPβ isoforms was detected in kidney specimens of humans and mice with LN. Then we assessed the effect of C/EBPβ inhibition on renal structure and function by injecting RNAi adeno‐associated virus of C/EBPβ shRNA into MRL/lpr mice. In vitro, glomerular podocytes were treated with LN serum and C/EBPβ siRNA to explore the role of C/EBPβ in the activation of the AIM2 inflammasome and podocyte injury. C/EBPβ‐LAP and C/EBPβ‐LIP were significantly overexpressed in kidney tissue samples from LN patients and mice, and C/EBPβ inhibition significantly alleviated renal function damage and ameliorated renal structural deficiencies. Inflammatory pathways downstream from the AIM2 inflammasome could be suppressed by C/EBPβ knockdown. Furthermore, the upregulation of C/EBPβ‐LAP could activate the AIM2 inflammasome and podocyte pyroptosis by binding to the promoters of AIM2 and CASPASE1 to enhance their expression, and the knockdown of AIM2 or (and) caspase‐1 reversed the effects of C/EBPβ‐LAP overexpression. Interestingly, C/EBPβ‐LIP overexpression could transcriptionally inhibit IRAG and promote Ca2+ release‐mediated activation of the AIM2 inflammasome. This finding suggests that C/EBPβ is not only involved in the regulation of the expression of key proteins of the AIM2 inflammasome but also affects the polymerization of key proteins of the AIM2 inflammasome through the regulation of Ca2+ release. In conclusion, this study provides a new idea for studying the regulatory mechanism of C/EBPβ and provides a theoretical basis for the early diagnosis and treatment of LN in the future. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Objective: The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different concentrations of albumin on reducing the mortality rate of theses patients by meta-analysis. Materials and Methods: PubMed, EMBASE, and Web of Science databases were used for screening the relevant studies. Randomized controlled trials (RCTs) were eligible if they compared the effects of albumin with crystalloid on mortality in patients with sepsis and septic shock. Data were examined and extracted by two reviewers independently. Any disagreements were resolved by consensus with or without the help from a third reviewer. Data including mortality, sample size of the patients, and resuscitation endpoints were extracted. Meta-analysis was carried based on the corresponding odds ratios with 95% confidence intervals. Results: Eight studies with a total of 5124 septic patients and 3482 septic shock patients were included in this study. Compared with crystalloid, the use of albumin may represent a trend toward reduced the 90-day mortality of septic patients (OR 0.91 [0.80, 1.02]; P =.11) and significantly improved the outcome of septic shock patients (OR 0.85 [0.74, 0.99]; P =.04). Further analysis showed a potentially beneficial role of both 4% to 5% and 20% albumin on reducing the mortality of septic patients. The use of 20% albumin significantly decreased the 90-day mortality of septic shock patients (OR 0.81 [0.67, 0.98]; P =.03), which was better than 4% to 5% albumin and crystalloid. Conclusions: Albumin treatment, particularly 20% albumin, significantly reduced the 90-day mortality in septic shock patients. Both 4% to 5% and 20% of albumin may work better than crystalloid in improving the survival rate of patients with sepsis, but more relative RCTs are required for validation. [ABSTRACT FROM AUTHOR]

Studies have revealed that miR-21 is abnormally expressed in breast cancer patients, suggesting that miR-21 could be exploited as a possible diagnostic biomarker for clinical applications. In order to provide clinical evidence that is supported by research, we investigate the diagnostic utility of miR-21 in breast cancer in this study. From their inception to 23 January 2022, the PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases were searched for all pertinent English literature. QUADAS-2 for literature quality assessment, GRADE for evidence grading. Statistical analyses were performed using the R 4.0.1 and Revman 5.3. The results were validated using Stata 15.1 software. Subgroup analysis was also performed according to the source of miR-21 and miR-21 combinations. Nine publications with 2048 patients were reviewed for inclusion. All of the included studies are of moderate-high quality. Meta-analysis was performed using a mixed-effects model. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (NLR) and positive likelihood ratio (PLR) were 0.91 [95% CI (0.86, 0.95)], 0.85 [95% CI (0.77, 0.91)], 56.62 [95% CI (21.00, 184.83)], 0.11 [95% CI (0.05, 0.18)] and 6.35 [95% CI (3.66, 11.16)], respectively. The GRADE classification for miR-21 was A, indicating a strong recommendation for breast cancer screening. The available evidence suggests that miR-21 has sufficient diagnostic value as a biomarker for breast cancer. Its diagnostic precision can be further improved by combining it with other miRNAs. Based on the GRADE review, miR-21 is strongly recommended for breast cancer screening. [ABSTRACT FROM AUTHOR]

T-cell acute lymphoblastic leukemia (T-ALL) is a serious hematological tumor derived from early T-cell progenitors, which is extremely resistant to chemotherapy. Classically, doxorubicin (DOX) is an effective first-line drug for the treatment of T-ALL; however, DOX resistance limits its clinical effect. The DEK proto-oncogene (DEK) has been involved in neoplasms but remains unexplored in T-ALL. We silenced DEK on Jurkat cells and detected cell proliferation with cell counting and colony formation assay. Then, we detected DEK's drug sensitivity to DOX with CCK-8, cell cycle, and apoptosis with DOX treatment. Western blot analysis was performed to determine protein expression of apoptosis and cell cycle-related genes, including BCL2L1, caspase-3, and cyclin-dependent kinases (CDK). Finally, the tumorigenic ability of DEK was analyzed using a BALB/C nude mouse model. In this study, DEK was highly expressed in Jurkat cells. Inhibition of DEK can lead to decreased cell proliferation and proportion of S-phase cells in the cell cycle and more cell apoptosis, and the effect is more obvious after DOX treatment. Western blot results showed that DOX treatment leads to cell cycle arrest, reduction of cyclin-dependent kinase 6 (CDK6) protein, accumulation of CDKN1A protein, and DOX-induced apoptosis accompanied by reductions in protein levels of BCL2L1, as well as increases in protein level of caspase-3. Furthermore, DEK-silenced Jurkat cells generated a significantly smaller tumor mass in mice. Our study found that DEK is a novel, potential therapeutic target for overcoming DOX resistance in T-ALL. [ABSTRACT FROM AUTHOR]

The AID/APOBEC family which converts cytidine to uridine on RNA or DNA experienced dynamic expansion in primates in order to resist exogenous viruses and endogenous retrotransposons. Recently, expansion of AID/APOBEC-like homologs has also been observed in the extant jawless vertebrate lamprey. To reveal what causes such expansion and leads to the functional diversification of lamprey cytosine deaminases (CDAs), we reassessed the CDA genes in Lethenteron japonicum (Lj). We first confirmed the expansion of LjCDA1L1 (CDA1-like 1) genes and found the expression correlation of LjCDA2 and LjCDA1L2 with LjVLRs (variable lymphocyte receptors). Among up to 14 LjCDA1L1 proteins, LjCDA1L1_4a has an extremely high deamination activity on ssDNA and buDNA and, unexpectedly, on dsDNA. LjCDA1L1s can also restrict the infection of HSV-1 particles. Thus, the arms race between the host and pathogens along with the recruitment by VLR assembly may participate together to form a driving force in the expansion and diversification of the lamprey AID/APOBEC family. [ABSTRACT FROM AUTHOR]

Rearrangement of the mixed lineage leukemia (MLL; also known as lysine methyltransferase 2A) gene is a recurrent genomic aberration in acute myeloid leukemia (AML). MLLT3, super elongation complex subunit (AF9) is one of the most common MLL fusion partners in AML. The present study aimed to explore the aberrant expression of genes associated with the MLL-AF9 translocation and identified potential new targets for the therapy of AML with MLL-AF9 translocation. The transcriptomic and epigenetic datasets were downloaded from National Center of Biotechnology Information Gene Expression Omnibus (GEO) database. Differentially expressed genes were obtained from two independent datasets (GSE68643 and GSE73457). Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. MLL-AF9-associated chromatin immunoprecipitation sequencing (ChIP-Seq) data was analyzed and identified binding sites for MLL-AF9 and wild type MLL (MLL WT). The ChIP-Seq of histone modification data was downloaded from the GEO database, including histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 79 dimethylation (H3K79me2) and histone 3 lysine 27 acetylation (H3K27ac), was used for comparing histone modification marks between the MLL-AF9 leukemia cells and normal hematopoietic cells at MLL-AF9 and MLL WT binding sites. The differentially expressed genes with the same trend in H3K79me2, H3K27ac and H3K4me3 alteration were identified as potential MLL-AF9 direct target genes. Upon validation using RNA-Seq data from the Therapeutically Applicable Research to Generate Effective Treatments AML project, eight potential direct target genes of MLL-AF9 were identified and further confirmed in MLL-AF9 mouse model using reverse transcription-quantitative polymerase chain reaction. These genes may have a critical role in AML with MLL-AF9 translocation. [ABSTRACT FROM AUTHOR]

In this study, a thin 2D fluidized bed was used to investigate the effect of mixing state of the binary particles on bubble behavior through the analysis of images captured by a high-speed digital camera. Experimental results show that the mixing index increases gradually with increasing gas velocity and the binary particles are in different mixing states though they are in the steady fluidization state. The maximal bubble number is near the interface of the bed when the binary particles are in the segregation state, whereas the maximal bubble number is at the bottom when the binary particles are in the well mixing state. The small bubbles are position at the bottom and are adjacent to the bed wall, while the large bubbles are mainly located in the central regions of the bed. The average bubble diameter shows the different variation trends with the different mixing states of the binary particles. The correlations estimating bubble diameter according to the mixing state of the binary particles are developed, and the computing value agrees well with the experimental data. [ABSTRACT FROM AUTHOR]

Long non‑coding RNAs (lncRNAs) are transcripts characterized by >200 nucleotides, without validated protein production. Previous studies have demonstrated that certain lncRNAs have a critical role in the initiation and development of acute myeloid leukemia (AML). In the present study, the subtype‑specific lncRNAs in AML was identified. Following the exclusion of the subtype‑specific lncRNAs, the prognostic value of lncRNAs was investigated and a three‑lncRNA expression‑based risk score [long intergenic non‑protein coding RNA 926, family with sequence similarity 30 member A and LRRC75A antisense RNA 1 (LRRC75A‑AS1)] was developed for AML patient prognosis prediction by analyzing the RNA‑seq data of AML patients from Therapeutically Available Research to Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) projects. In the training set obtained from TARGET, patients were divided into poor and favorable prognosis groups by the median risk score. The prognostic effectiveness of this lncRNA risk score was confirmed in the validation set obtained from TCGA by the same cut‑off. Furthermore, the lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis. As further verification of the independent prognostic power of the lncRNA risk score, stratified analysis was performed by a cytogenetics risk group and revealed a consistent result. The prognostic predictive ability of the risk score was compared with the cytogenetics risk group by time‑dependent receiver operating characteristic curves analysis. It was revealed that the combination of the lncRNA risk score and cytogenetics risk group provided a higher prognostic value than a single prognostic factor. The present study also performed co‑expression analysis to predict the potential regulatory mechanisms of these lncRNAs in a cis/trans/competing endogenous RNA manner. The results suggested that LRRC75A‑AS1 was highly associated with the target genes of transcription factors tumor protein 53 and ETS variant 6. Overall, these results highlighted the use of the three‑lncRNA expression‑based risk score as a potential molecular biomarker to predict the prognosis in AML patients. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Leaves of six main tree species from the Pearl River Delta (PRD) in Southern China were collected to identify the interspecific variability, the spatial variability and the seasonal variations of polycyclic aromatic hydrocarbons'' (PAHs) concentrations, and to calculate the amount of PAHs removed by leaves. PAHs concentrations in pine needles were much higher than in broad-leaves and leaves from urban/industrial areas (Baiyunshan and Heshan) exhibited two times greater concentrations than leaves from the rural area (Dinghushan). Seasonal variations of PAHs in leaves occurred with lesser concentrations in September. Leaves in PRD scavenged 3.7±0.9t PAHsy−1, accounting for about 10% of the total amount emitted in this region. This result suggests that forests play an important role in the fate of PAHs. [Copyright &y& Elsevier]

Mol Med Rep 21: 883-893, 2020, DOI: 10.3892/mmr.2019.10849 Following the publication of this paper, the authors have realized that the final article did not indicate in the Authors' Contribution section that Fangce Wang and Zheng Li made equal contributions to this work (FW and ZL performed most of the statistical analyses and drafted the initial version of the manuscript). The authors and the Editor apologize for any inconvenience caused. [Extracted from the article]

The study verified the role that different interface designs and users' educational backgrounds play in the task performance and subjective evaluation of mobile terminal customization system. Interface type (based on scroll, alternative, and attribute) and user group (college students and industrial workers) were employed as the variables. A total of 72 users were included in the study, and an analysis of 3 × 2 between-participants design indicated that (1) Different interface designs of customization systems had a significant difference in task performance, the alternative based interface had the best results in the task performance, and there was no significant difference between the attribute-based and scroll-based interfaces in task performance; (2) The matching between educational background and interface type will affect the users' evaluation on system usability. Industrial workers thought that the scroll-based and alternative-based interfaces were more useable, while college students preferred attribute-based interface design; (3) Different interfaces had a significant difference in user task load. The scroll-based interface had the lowest mental demand on the users, while alternative-based had the lowest physical demand on the users, though it consumed more effort; (4) Different educational backgrounds had a significant difference in user task load. Industrial workers showed lower effort in the scroll-based and alternative-based interfaces, while college students had lower effort in the attribution-based interface; (5) A correlation analysis showed that there was a significant negative correlation between the system usability score and the effort in task load. This study results have a positive significance for interface design. With educational background and layout as two important factors in our interface design, we may obtain the most appropriate design principles for enhancing the online customization experiences of different groups of consumers. The more important is that this study is based on the actual needs of the industry. For the first time, we take suitcase as an online customized product, which may not only help local manufacturers to extend their traditional offline distribution channels to online, but also provide a constructive thinking concerning interface design for customization of a single product. [ABSTRACT FROM AUTHOR]

Hydrophobic zinc oxide (ZnO) nanoparticles were produced through grafting aminopropyltriethoxysilane (APS) and oleic acid (OA), which was activated by N,N′-carbonyldiimidazole (CDI). The functional group containing ZnO nanoparticles were incorporated into unsaturated polyester (UP) resin, and their dispersibility in the UP matrix and effects on the properties of UP/ZnO nanocomposites were investigated. ZnO nanoparticles modified by APS and OA activated by CDI, (CDI–OA–APS–ZnO), can be homogeneously dispersed as supported by transmission electron microscopy (TEM) investigations and had been encapsulated in the UP resin. CDI–OA–APS–ZnO nanoparticles were embedded in the net structure of the UP composites through chemical bonds between oleic acid, styrene, and polyester resin, which significantly influence the cure reaction of UP resin and the properties of UP composites. Thermogravimetric analysis (TGA) results show that the incorporation of ZnO nanoparticles could improve the thermal stability of UP when thermal cracking temperature exceeds 365 °C. The exothermic peak and the initial temperature of cure reaction of the UP resin decreased with increasing ZnO content. The tensile strength and bending strength of UP/CDI–OA–APS–ZnO nanocomposites increased by 91.4% and 71.3% when 3 wt % CDI–OA–APS–ZnO nanoparticles was added into the composites, respectively, compared with pure UP resin. [ABSTRACT FROM AUTHOR]

Ferroptosis is one of the main mechanisms involved in different forms of acute kidney injury (AKI), including cisplatin-induced AKI. However, it is not clear whether Cx43 has a regulatory effect on ferroptosis caused by cisplatin. In this study, we investigate the regulatory effects of Cx43 on cisplatin-induced ferroptosis and its mechanism. In vivo and in vitro studies showed that the expression level of Cx43 was significantly upregulated in the cisplatin-induced kidney injury model. In HK2 cells, cisplatin significantly induced ferroptosis. Adding shRNA-Cx43 and gap27 to the HK2 cells downregulated the expression of Cx43 and blocked the effects of cisplatin, resulting in a significantly improved survival rate of HK2 cells. Our primary data suggested that downregulating Cx43 not only inhibits ferroptosis, but also inhibits apoptosis. Through mechanistic studies, we confirmed that downregulating the expression of Cx43 by increasing SLC7A11 can increase the GSH content to inhibit cisplatin-induced ferroptosis. In vivo experiments showed that downregulation of Cx43 expression by gap27 reduced AKI in the animal model by inhibiting cisplatin-induced ferroptosis. Therefore, our results indicated that downregulation of Cx43 can inhibit ferroptosis by restoring the level of SLC7A11 in the system x c‾ transporter and alleviate cisplatin-induced AKI. • Ferroptosis is involved in cisplatin-induced acute kidney injury. • Cx43 significantly enhanced in cisplatin-induced kidney injury model. • Downregulating Cx43 can reverse the ferroptosis induced by cisplatin. • Cx43 regulates cisplatin-induced ferroptosis by affecting SLC7A11. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of 18 F-fluorodeoxyglucose(FDG) PET/CT multi-time points imaging (MTPI) on the differential diagnosis between lung cancer (LC) and tuberculosis (TB)., Methods: Sixty-four patients underwent 18 F-FDG PET/CT MTPI. The stdSUVmax, stdSUVavg, retention index, metabolic tumor volume, total lesion glycolysis at four-time points and slope of metabolic curve were measured and calculated, and the sex, age, and uniformity of FDG uptake were recorded. The difference in each index between LC and TB was analyzed, and dynamic metabolic curves (DMCs) of LC and TB were fitted by significance indexes. Artificial neural network (ANN) prediction models were established between squamous cell carcinoma (SCC) and TB, as well as between adenocarcinomas and TB., Results: Differences between SCC and TB, stdSUVmax/avg at four-time points, total lesion glycolysis, stdSUVmax/avg slope (1-2 h,1-3 h and 1-4 h), uniformity of FDG uptake and age were significant. stdSUVavg has the largest area under the 4 h curve; age was only significant between adenocarcinomas and TB. DMCs at 1-4 h fitted by stdSUVavg were more helpful in differentiating LC and TB than stdSUVmax. stdSUVavg(1 h and 4 h), stdSUVavg slope 1-4 h, age, and uniformity of FDG uptake were selected to establish an ANN prediction model between SCC and TB; the area under the curve (AUC) was 100.0%. The same indices were used to establish the prediction model between adenocarcinomas and TB; the AUC was up to 83.5, and after adding stdSUVavg (2 and 4 h) to adenocarcinomas and TB models, the AUC was 87.7%., Conclusion: 18 F-FDG PET/CT MTPI fitting DMCs and establishing an ANN prediction model would distinguish SCC from TB relatively accurately and provide certain help in the differentiation between adenocarcinomas and TB., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although cardiac disorder-related adverse events (AEs) have been reported in patients treated with aryl hydrocarbon receptor (AHR) agonists, their safety profiles remain unknown. Here, we identified significant cardiac disorders associated with AHR agonists and further evaluated their relevance., Research Design and Methods: Database queries were performed using OpenVigil 2.1 and AEs voluntarily submitted to Food and Drug Administration Adverse Event Reporting System (FAERS) between 2004 and 2020 were included. This study based on the Medical Dictionary for Regulatory Activities and the standardized MedDRA Queries to define the preferred terms, and we used reporting odd ratio to detect signals., Results: In the FAERS database, 14,078 cardiac disorder-related AEs were identified in patients receiving AHR agonists. Among all AHR agonists, the number of cardiac disorder-related PTs with positive signals for AHR agonists was 93. Peripheral swelling (n = 1572) and atrial fibrillation (n = 1277) were the most reported cardiac disorder-related AEs among AHR agonists in disproportionately reported PTs. Moreover, several AHR agonists were highly associated with tachyarrhythmia., Conclusions: By mining the FAERS database, we provided more information on the association between AHR agonist use and cardiac disorder-related AEs.

Objective: To investigate the value of dynamic metabolic curves and artificial neural network prediction models based on 18F-FDG PET multiphase imaging in differentiating nonspecific solitary pulmonary lesions., Methods: This study enrolled 71 patients with solitary pulmonary lesions (48 malignant and 23 benign lesions) who underwent multiphase 18F-fluorodeoxyglucose (18F-FDG)-PET/CT imaging. We recorded information on age, sex and uniformity of FDG uptake, measured standardized uptake value, metabolic tumor volume and total lesion glycolysis at various time points, and calculated individual standardized uptake values, retention index (RI) and slope of metabolic curve. Variables with high diagnostic efficiency were selected to fit dynamic metabolic curves for various lesions and establish different artificial neural network prediction models., Results: There were no significant differences in the retention index, metabolic tumor volume, total lesion glycolysis or sex between benign and malignant lesions; standardized uptake values, the slopes of five metabolic curves, uniformity of FDG uptake, and age showed significant differences. Dynamic metabolic curves for various solitary pulmonary lesions exhibited characteristic findings. Model-1 was established using metabolic parameters with high diagnostic efficacy (area under the curve, 83.3%). Model-2 was constructed as Model-1 + age (area under the curve, 86.7%), whereas Model-3 was established by optimizing Model-2 (area under the curve, 86.0%)., Conclusions: Dynamic metabolic curves showed varying characteristics for different lesions. Referring to these findings in clinical work may facilitate the differential diagnosis of nonspecific solitary pulmonary lesions. Establishing an artificial neural network prediction model would further improve diagnostic efficiency., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In our previous study of 2,130 Chinese patients with coronary heart disease (CHD), we found that tryptophan (TRP) metabolites contributed to elevated risks of death. Many TRP-derived metabolites require the participation of intestinal bacteria to produce, and they play an important role in the pathogenesis of metabolic diseases such as CHD. So it is necessary to metabolize TRP into beneficial metabolites against CHD or prevent the production of harmful metabolites through external intervention. Indole-3-butyric acid (IBA) may be a key point of gut microbiota that causes TRP metabolism disorder and affects major adverse cardiovascular events in CHD. Therefore, this study aimed to develop a method based on in vitro culture bacteria to evaluate the effects of IBA on specific microbial metabolites quickly. We detected the concentrations of TRP and its metabolites in 11 bacterial strains isolated from feces using liquid chromatography-mass spectrometry, and selected Clostridium sporogenes as the model strain. Then, IBA was used in our model to explore its effect on TRP metabolism. Results demonstrated that the optimal culture conditions of C. sporogenes were as follows: initial pH, 6.8; culture temperature, 37°C; and inoculum amount, 2%. Furthermore, we found that IBA increases the production of TRP and 5-HIAA by intervening TRP metabolism, and inhibits the production of KYNA. This new bacteria-specific in vitro model provides a flexible, reproducible, and cost-effective tool for identifying harmful agents that can decrease the levels of beneficial TRP metabolites. It will be helpful for researchers when developing innovative strategies for studying gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Wu, Duan, Zhou, Li, Zheng, Lai, Zhang, Cao and Zhong.)

Calpain-1, a calcium-activated neutral cysteine proteases, has been reported to be involved in the formation of pulmonary hypertension. HIF-1α, an oxygen-sensitive transcription factor, has been reported to activate genes involved in cell proliferation and extracellular matrix recombination. This study was designed to investigate the effect of calpain-1 in hypoxic pulmonary hypertension (HPH) and to explore whether there is a relationship between calpain-1 and HIF-1α in this disease. In the hypoxia-induced model of HPH, we found that hypoxia resulted in increased right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodelling and collagen deposition in lung tissues of mice. The levels of calpain-1 and HIF-1α were up-regulated in the lung tissues of hypoxia-treated mice and pulmonary arterial smooth muscle cells (PASMCs). Knock-out of calpain-1 restrained haemodynamic and histological changes induced by chronic hypoxia in mice, and inhibition of calpain-1 also repressed the abnormal proliferation and migration of PASMCs. Besides, knock-out or inhibition of calpain-1 suppressed hypoxia-induced expression of HIF-1α, VEGF, PCNA, TGF-β1, MMP2 and collagen I in vivo and in vitro. While inhibition of HIF-1α abolished the above effects of calpain-1. Furthermore, we found that calpain-1 mediates the expression of HIF-1α through NF-κB (P65) under hypoxia conditions. In conclusion, our results suggest that calpain-1 plays a pivotal role in hypoxia-induced pulmonary vascular remodelling and fibrosis through HIF-1α, providing a better understanding of the pathogenesis of HPH., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.