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Transition metal-based electrocatalytic materials for hydrogen production through water splitting offer advantages in terms of price and availability compared to noble metal-based catalysts, among which, Fe-, Co-, and Ni-based compounds are the most typical and widely studied materials. Utilizing the synergistic effects between composite components in compounds containing multiple metal elements is an important way to improve the catalytic performance of catalysts, so developing ternary or multiple active center catalysts containing Fe, Co, and Ni is a promising direction. In this mini-review, we provide an summary of the latest achievements of water splitting catalyst materials simultaneously containing Fe, Co, and Ni elements. It was summarized according to several groups including compounds of boron-/carbon-/nitrogen-/phosphorus-/oxygen-group elements, metal-organic framework-based compounds, and compounds in situ grown from alloy matrix. Also challenges that need to be addressed are presented at the end of the article., (© 2024 Wiley-VCH GmbH.)

Primary Sjögren's Syndrome (PSS) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms between PSS and psoriasis remain poorly defined. In this study, we conducted bidirectional MR analysis to explore the causal relationship between PSS and psoriasis using four MR methods: inversevariance weighted, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses were carried out, employing different models and testing methods for comparison to assess the influence of heterogeneity and pleiotropy on our findings and to confirm the robustness of these results. We primarily employed the Inverse Variance Weighting (IVW) method for our analysis. A p-value of less than 0.05 indicates a significant causal relationship, while a p-value greater than 0.05 suggests the absence of such a relationship. The IVW analysis confirmed a causal relationship between psoriasis and primary Sjögren's syndrome (PSS) (OR: 3.149E-10, 95% CI 1.114E-18-0.089, P = 0.028), with the weighted median yielding similar results. Conversely, there was no causal association found between PSS and the risk of developing psoriasis (OR: 1.000, 95% CI 0.999-1.000, P = 0.328). This study reveals a causal relationship between primary Sjögren's syndrome (PSS) and psoriasis, demonstrating that psoriasis increases the risk of developing PSS, while the reverse is not true. This potential causal link offers new insights into the etiology of both PSS and psoriasis., Competing Interests: Declarations. Conflict of interest: The authors declare that there are no conflicts of interest., (© 2025. The Author(s).)

The textile industry's high-salinity wastewater presents a significant difficulty for fractioning salts and dyes. To fractionate the dyes and salts, a high-performance CPVC composite loose nanofiltration membrane (LNM) was fabricated by interfacial polymerization. The organic phase was obtained by crosslinking polyethylenimine (PEI) with tannic acid (TA) and gallic acid (GA) using TMC. The resultant composite LNM performance was enhanced by adjusting the coating parameters, which included TA and GA concentrations as well as coating time. The study examined the effects of the total content of TA/PEI and GA/PEI concentrations on the chemical structure, surface roughness, and microstructure of the selective layer of LNM using SEM, AFM, FTIR, and water contact angle measurements. It also investigated the filtration performance of the membrane's selective layer, including pure water flux, PEG800 rejection rate, and membrane fouling analysis. However, the resultant membrane treated simulated reactive black 5 (RB5) dye wastewater. When the total content of TA/PEI is 4 kg L -1 , the permeability of pure water flux is high at 7.5 L per m 2 per h per bar when the total content of GA/PEI is 14 kg L -1 and the pure water flux is high at 8.8 L per m 2 per h per bar. The overall PEG800 rejection rates were 97-98.98%. The optimal TA : PEI ratios reached a good pure water permeability up to 6.4 L per (m 2 per h per bar) with a high rejection rate of 99.69% for a ratio 1/3 to dye, and GA : PEI ratios reached a good water permeability at 5.5 and 6.5 L per (m 2 per h per bar) with rejection rates of 99.21% and 98.88% for ratio 1/3 and 3.5/10.5 for simulated RB5 dye, and the NaCl retention rate gradually decreased from 4% to 3%. The resultant LNM demonstrated promising applications in dye and salt fractionation., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

ClpA is a widely conserved protease in bacteria that plays a key role in virulence. To investigate its specific mechanism of action in the pathogenicity of Paracidovorax citrulli (formerly Acidovorax citrulli) , we constructed a ClpA deletion mutant, Δ ClpA . The Δ ClpA mutant of P. citrulli displayed reduced virulence on melon seedlings, and reduced motility, swarming ability, and antioxidant capacity. On the other hand, the ClpA deletion of P. citrulli mutant reduced the resistance to elevated temperature and enhanced biofilm formation ability. Using qRT-PCR, we observed that ClpA negatively regulates the expression of the virulence-related genes virB , pilR , pilA , and fliM , while positively regulating hrpG , hrcQ , and trbC . Bacterial double hybrid and Glutathione-S-transferase pulldown (GST-pulldown) results showed that ClpA interacts directly with RepA, and negatively regulates the expression of RepA . After deletion of the RepA gene, the pathogenicity of P. citrulli was lost, biofilm formation ability was enhanced, and the expression of hrpG , pilR , and trbC was positively regulated. These results indicate that ClpA plays a key role in the regulation of several virulence traits of P. citrulli , paving the way for future studies to better elucidate the virulence mechanisms of this bacterial plant pathogen., 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 © 2024 Ziye, Yuqiang, Shitong, Ling, Chenchao, Jun, Weirong, Yanli and Baishi.)

Objective: To investigate the effects of motivational interview education on psychological status, compliance behavior and quality of life in patients with malignant tumors combined with diabetes mellitus., Methods: This is a retrospective study. Eighty patients with malignant tumors combined with diabetes mellitus admitted at The Fourth Hospital of Hebei Medical University from January 2021 to June 2022 were included as subjects and divided into observation group and control group according to the intervention measures. Patients in the control group were given routine health education intervention, while those in the observation group were given motivational interviewing intervention on the basis of the control group. We compared the prognosis, cognitive function, quality of life, relief of cancer pain before intervention and three months after the intervention of the two groups were compared., Results: At three months after the intervention, the total remission rate of cancer pain in the observation group was higher than that in the control group(p<0.05), while the levels of FBG and 2hPG in the observation group were significantly lower than those in the control group(p<0.05). Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) scores decreased in both groups three months after the intervention, with the level of reduction in the observation group being higher than that in the control group(p<0.05). The overall compliance was higher in the observation group than in the control group(p<0.05)., Conclusion: Motivational interviewing leads to alleviate negative emotions, improve the psychological status, enhance compliance behavior and improve quality of life in patients with malignant tumors combined with diabetes mellitus., Competing Interests: Declaration of conflicting interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: -Recent evidence suggests that hyperuricemia may act as independent risk factors for erectile dysfunction (ED), in addition to the already established factors. The current evidence supporting this relationship remains insufficient., Methods and Results: -A total of 3,810 participants from the NHANES pool between 2001 and 2004 were included in our study, comprising 1,093 individuals with ED and 2,717 individuals without ED. Univariable and multivariable logistic regression analyses were conducted to examine the relationship between uric acid (UA) and the prevalence of ED. In the fully adjusted model, no significant association was observed between UA and ED (OR = 1.02, 95% CI: 0.84-1.24), and no significant differences were noted among the various UA levels (p = 0.5). In our sensitivity analyses, employing a stricter definition for ED, no significant results were found in the fully adjusted model (OR = 0.85, 95% CI: 0.60-1.19). Furthermore, no significant differences were observed among the various UA levels (p = 0.083)., Conclusions: -Our study did not establish a correlation between UA levels and ED. Nonetheless, further research with larger sample cohorts is required to verify these findings., (© 2024. The Author(s).)

Red dragon fruit is gaining popularity globally due to its nutritional value and bioactive components. The study aimed to assess the phytochemical, nutritional composition, antioxidant, antibacterial, and cytotoxic properties of extracts from the South Chinese red dragon fruit peel, flesh, and seeds. Extract fractions with increasing polarity (ethyl acetate50 values ranging from 3.25-8.30 μg/mL. The flesh MT and ET extract fractions demonstrated substantial inhibitory effects, with MIC 50 ranging 73.62-98.85 μg/mL, against several multidrug-resistant bacteria. Cytotoxicity assays revealed no adverse effects of the crude extract fractions on human keratinocytes (HaCaT) cells (from adult human skin). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) analyses unveiled a wide array of compounds with known and unknown antibacterial and antioxidant activities. Thereafter, pharmacological property screening and molecular docking were performed. The results identified four active compounds, baicalein, quercetin, morin, and isorhamnetin, which demonstrated strong binding affinity with the selected target proteins and complied with most of the pharmacological parameters. In conclusion, this study provides essential information on the key nutrients present in the peel, flesh, and seeds of the red dragon fruit from Southern-China. Furthermore, it highlights the potential of ET and MT fractions, which contain compounds with promising antibacterial properties., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A YOLOv5-based YOLOv5-KE unmanned aerial vehicle (UAV) image detection algorithm is proposed to address the low detection accuracy caused by the small size, high density, and overlapping leaves of Ambrosia trifida targets in UAV images. The YOLOv5-KE algorithm builds upon the YOLOv5 algorithm by adding a micro-scale detection layer, adjusting the hierarchical detection settings based on k-Means for Anchor Box, improving the loss function of CIoU, reselecting and improving the detection box fusion algorithm. Comparative validation experiments of the YOLOv5-KE algorithm for Ambrosia trifida recognition were conducted using a self-built dataset. The experimental results show that the best detection accuracy of Ambrosia trifida in UAV images is 93.9%, which is 15.2% higher than the original YOLOv5. Furthermore, this algorithm also outperforms other existing object detection algorithms such as YOLOv7, DC-YOLOv8, YOLO-NAS, RT-DETR, Faster RCNN, SSD, and Retina Net. Therefore, YOLOv5-KE is a practical algorithm for detecting Ambrosia trifida under complex field conditions. This algorithm shows good potential in detecting weeds of small, high-density, and overlapping leafy targets in UAV images, it could provide technical reference for the detection of similar plants., 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 © 2024 Xiaoming, Tianzeng, Haomin, Ziqi, Dehua, Jianchao and Jun.)

Employing the Complex Adaptive System (CAS) framework, we analyzed the evolution of digitally transformed financial networks, underscoring the pivotal role of adaptation and learning among network participants. Government funds supporting banks and platforms in digital transformation prove more effective than direct subsidies to SMEs. Achieving sustainable development requires an optimal balance between investment and efficiency due to the impact of digitalization costs on constructing digital financial networks. The study advocates for a long-term microcredit financing mode tailored to SMEs, aiding them in maintaining financial stability. Additionally, intermediary nodes within the network, such as credit rating companies, can facilitate information sharing, thereby fostering the growth of digital financial networks. This heightened information sharing enhances the payoff for each subject and reduces financing constraints. Furthermore, the study establishes that digital financial networks can alleviate the repercussions of unforeseen events, such as the COVID-19 pandemic. Finally, empirical analysis of the Beijing University Inclusive Finance Index data and financial records of Chinese SMEs listed on the New Third Board from 2016 to 2018 confirms that digital finance can alleviate the financing constraints of SMEs. In summary, the progression of digital financial networks is intricate, necessitating a thorough comprehension of diverse factors. The government is encouraged to guide the enhancement of relevant systems and regulations, bolstering supervision, and facilitating the high-quality development of digital finance networks., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wang Jun reports financial support was provided by Sichuan Science and Technology Plan Project. Wang Jun reports financial support was provided by Humanities and Social Sciences Research project of Ministry of Education of China. If there are other authors, they 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 Authors. Published by Elsevier Ltd.)

Background: Children with special health care needs (CSHCN) require long-term and ongoing rehabilitation interventions supporting their development. Telerehabilitation can provide continuous rehabilitation services for CSHCN. However, few studies have explored the intention of CSHCN and their caregivers to use telerehabilitation and its impact on them. Objective: The objective of this study was to identify factors that influence the intention to use telerehabilitation among CSHCN and their caregivers. Methods: This study was a cross-sectional study. Based on the unified theory of acceptance and use of technology, extended with additional predictors (trust and perceived risk [PR]), this study developed a research model and proposed 10 hypotheses. A structured questionnaire was distributed to 176 caregivers. Data were analyzed and research hypotheses were tested using partial least squares structural equation modeling to better understand the factors influencing the use of telerehabilitation. Results: A total of 164 valid questionnaires were collected. CSHCN and their caregivers were overall satisfied with this telerehabilitation medical service. The results of the structural model analysis indicated that social influence (SI), facilitating conditions (FC), and trust had significant effects on behavioral intention (BI) to use telerehabilitation, while the paths between performance expectancy (PE), effort expectancy (EE), and PR and BI were not significant. PE, EE, and SI had a significant effect on trust. Moreover, EE and SI had indirect effects on BI, with trust as the mediator. Conclusions: The results indicated that SI, FC, and trust are significant factors influencing CSHCN and their caregivers' use of telerehabilitation. Trust is also an important mediator for the intention and highly influenced by PE, EE, and SI.

Cold stress (CS) significantly limits cucumber yield. However, it remains unclear whether and how sodium nitrophenolate (CSN) regulates plant responses to cold stress. Here, H 2 O, CSN, 24-epibrassinolide (EBR), and CSN + EBR were sprayed on cucumber seedlings before or after CS, and on control plants. We found that CSN, EBR, or EBR + CSN pre-treatment improved seedling growth under normal conditions (control condition) and cold tolerance under CS conditions. EBR pre-treatment promoted the expression of approximately half of the genes involved in BR synthesis and signaling and CsICE-CsCBF-CsCOR under CS. However, CSN pre-treatment promoted almost all the expression of BR synthesis and signaling genes, and CsICE-CsCBF-CsCOR genes, which showed the highest expression in early CS, remarkably improving the cold tolerance of cucumber. Interestingly, EBR and CSN had a superimposed effect on the expression of BR synthesis and signaling and CsICE-CsCBF-CsCOR genes, which rapidly increased their expression under normal temperature. Spraying EBR after CS accelerated seedling recovery, whereas CSN had the opposite effect. However, spraying CSN combined with EBR accelerated the recovery of CS-injured seedlings and was better than spraying EBR alone. Although CS-injured seedlings were negatively influenced by CSN, pre-treatment with CSN accelerated seedling growth and increased cold tolerance, suggesting that the effect of CSN was related to whether the seedlings were damaged by CS. In conclusion, we firstly found that CSN enhanced cold tolerance by activating BR signaling, contributing to the gene expression of ICE-CBF-COR and that CSN + EBR contributed to cold tolerance and CS-injured seedling recovery in cucumber., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Immune checkpoint inhibitors (ICIs) have improved the long-term survival of NSCLC patients. However, the efficacy of ICIs in elderly NSCLC patients remains controversial. We conducted a retrospective study and meta-analysis exploring the efficacy of ICIs in those patients using public databases and RCTs. NSCLC patients were identified into elderly and non-elderly groups by age 75 years. The retrospective study showed significant differences in OS and PFS between non-elderly and elderly patients treated with ICIs (P= 0.029 and 0.027), with reduced efficacy in elderly NSCLC patients. ECOG PS also negatively affected OS in elderly NSCLC patients (P= 0.007). In meta-analysis, the HR for OS in the non-elderly and elderly groups were 0.74 and 0.90, respectively, and the difference between the two age groups was statistically significant (P= 0.025). ICIs resulted in a lower incidence of all-grade (OR= 0.47) and high-grade TRAEs (OR= 0.38) than chemotherapy. Our findings revealed that the survival benefit of ICIs in elderly patients (≥ 75 years) may be lower than in non-elderly patients. In addition, the incidence of TRAEs induced by ICIs was lower than chemotherapy.

Background: DNA methylation is a form of epigenetic modification that impacts gene expression without modifying the DNA sequence, thereby exerting control over gene function and cellular development. The prediction of DNA methylation is vital for understanding and exploring gene regulatory mechanisms. Currently, machine learning algorithms are primarily used for model construction. However, several challenges remain to be addressed, including limited prediction accuracy, constrained generalization capability, and insufficient learning capacity., Results: In response to the aforementioned challenges, this paper leverages the similarities between DNA sequences and time series to introduce a time series-based hybrid ensemble learning model, called Multi2-Con-CAPSO-LSTM. The model utilizes multivariate and multidimensional encoding approach, combining three types of time series encodings with three kinds of genetic feature encodings, resulting in a total of nine types of feature encoding matrices. Convolutional Neural Networks are utilized to extract features from DNA sequences, including temporal, positional, physicochemical, and genetic information, thereby creating a comprehensive feature matrix. The Long Short-Term Memory model is then optimized using the Chaotic Accelerated Particle Swarm Optimization algorithm for predicting DNA methylation., Conclusions: Through cross-validation experiments conducted on 17 species involving three types of DNA methylation (6 mA, 5hmC, and 4mC), the results demonstrate the robust predictive capabilities of the Multi2-Con-CAPSO-LSTM model in DNA methylation prediction across various types and species. Compared with other benchmark models, the Multi2-Con-CAPSO-LSTM model demonstrates significant advantages in sensitivity, specificity, accuracy, and correlation. The model proposed in this paper provides valuable insights and inspiration across various disciplines, including sequence alignment, genetic evolution, time series analysis, and structure-activity relationships., (© 2023. The Author(s).)

Biological sequence data mining is hot spot in bioinformatics. A biological sequence can be regarded as a set of characters. Time series is similar to biological sequences in terms of both representation and mechanism. Therefore, in the article, biological sequences are represented with time series to obtain biological time sequence (BTS). Hybrid ensemble learning framework (SaPt-CNN-LSTM-AR-EA) for BTS is proposed. Single-sequence and multi-sequence models are respectively constructed with self-adaption pre-training one-dimensional convolutional recurrent neural network and autoregressive fractional integrated moving average fused evolutionary algorithm. In DNA sequence experiments with six viruses, SaPt-CNN-LSTM-AR-EA realized the good overall prediction performance and the prediction accuracy and correlation respectively reached 1.7073 and 0.9186. SaPt-CNN-LSTM-AR-EA was compared with other five benchmark models so as to verify its effectiveness and stability. SaPt-CNN-LSTM-AR-EA increased the average accuracy by about 30%. The framework proposed in this article is significant in biology, biomedicine, and computer science, and can be widely applied in sequence splicing, computational biology, bioinformation, and other fields., Competing Interests: The authors declare that they have no competing interests., (© 2023 Yan et al.)

Objective: To evaluate the effects of Sanren Tang (SRT, ) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice and to investigate the hepatic transcriptome regulated by SRT., Methods: The primary SRT components were identified using ultra-high-performance liquid chromatography-high-resolution accurate mass spectrometry. The SRT-induced pharmacological effects on HFD-induced NAFLD were evaluated in mice for 16 weeks. Obeticholic acid was used as a control drug. Body weight, food intake, and homeostatic model assessment for insulin resistance (HOMA-IR) index were analysed. Hepatic histological changes were observed in haematoxylin and eosin-stained sections and quantified using the NAFLD activity score (NAS). Serum alanine aminotransferase (ALT) and hepatic triglyceride (TG) levels were measured. Lipids in hepatocytes were visualised by Oil red staining. RNA-sequencing was performed to determine the transcriptome profile of the liver tissue. The differentially expressed genes were validated using real-time polymerase chain reaction and Western blotting., Results: Four principal compounds were identified in the SRT: adenosine, amygdalin, luteoloside, and magnolol. SRT ameliorated hepatic histology and lipid deposition in the NAFLD mice, and decreased HOMA-IR, NAS and ALT, and hepatic TG levels. Hepatic transcriptome analysis revealed 232 HFD-regulated genes that were reversed by SRT simultaneously. Retinol metabolism, cytokine-cytokine receptor interaction, and peroxisome proliferator-activated receptor (PPAR) γ signalling were the top three SRT-regulated pathways in NAFLD., Conclusions: SRT significantly ameliorated HFD-induced NAFLD, which was correlated with the regulation of genes enriched in the retinol metabolism, cytokine-cytokine receptor interaction, and PPARγ signalling pathways.

Lung cancer is one of the leading causes of cancer-related death. Most advanced lung adenocarcinoma (LUAD) patients have poor survival because of drug resistance and relapse. Neglecting intratumoral heterogeneity might be one of the reasons for treatment insensitivity, while single-cell RNA sequencing (scRNA-seq) technologies can provide transcriptome information at the single-cell level. Herein, we combined scRNA-seq and bulk RNA-seq data of LUAD and identified a novel cluster of malignant epithelial cells - KRT81 + malignant epithelial cells - associated with worse prognoses. Further analysis revealed that the hypoxia and EMT pathways of these cells were activated to predispose them to differentiate into metastatic lung adenocarcinoma cells. Finally, we also studied the role of these tumor cells in the immune microenvironment and their role in the classification and prognosis prediction of lung adenocarcinoma patients., 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., (© 2023 The Authors.)

Objectives: To study the levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 199, CA724, CA242, pepsinogen (PG) I, PGII, gastrin-17 (G-17), the PGI/PGII ratio (PGR), as well as the expression of p27 and Ki67, in patients suffering from early gastric cancer and intraepithelial neoplasia and to provide new markers for the diagnosis of early gastric cancer and precancerous lesions., Methods: A retrospective study where the blood serum concentration of CEA, CA199, CA724, CA242, PGI, PGII, G-17 and PGR were tested and also the protein expression of p27 and Ki67 was detected in patients tissues by immunohistochemistry in the Gastrointestinal Endoscopy Center of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China, from March 2018 to March 2021., Results: Carbohydrate antigen 242 and CA199 levels in tumor tissue significantly differed among the groups. Pepsinogen I levels decreased with increasing disease severity, G-17 levels increased with the aggravation of severity, and p27 expression decreased with the severity., Conclusion: The combination of serum gastric function markers (PGI and G-17) and p27 digestive tumor indices can serve as markers for the diagnosis of early gastric cancer and intraepithelial neoplasia., (Copyright: © Saudi Medical Journal.)

Objective: The effect of fecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome remains unclear. This systematic review employed a meta-analysis of RCTs for assessment on the role of FMT in treating obesity and metabolic syndrome, and its impact on clinically relevant parameters., Method: Major databases and grey literatures were searched identifying RCTs comparing FMT of lean donors with placebo in obese/metabolic syndrome patients. Studies using any form of placebo were included. Variations in the parameters before and after treatment were calculated followed by meta-analyses., Result: Ten studies met the inclusion criteria and a total of 334 patients were included for further analysis. Clinically significant parameters associated with obesity and metabolic syndrome were explored and FMT was identified significantly and negatively associated with most indices of abdominal adiposity including caloric intake, fasting glucose, HOMA-IR, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL, LDL, triglycerides and CRP, Obesity parameters including fasting glucose and acetic acid were increased following FMT., Conclusion: FMT is more advantageous for obese patients with elevated blood pressure, disordered glucose and insulin metabolism, and elevated blood lipids. The study of metabolic factors in obese patients will be our starting point in the future., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As observed in recent genetic studies, PITX2 is one of the most popular genes with atrial fibrillation; single nucleotide polymorphism (rs2200733) at chromosome 4q25 (near PITX2) is found to be strongly associated with atrial fibrillation, but it has a difference among Chinese Han population. The basic aim of conducting this study is to find the correlation between PITX2 gene polymorphism and the risk of atrial fibrillation and to identify the possibility for early diagnosis of silent atrial fibrillation and high-risk atrial fibrillation., Methods: The study included 98 cases of atrial fibrillation patients and 88 non-atrial fibrillation patients in Affiliated Hospital of Yangzhou University were enrolled in a case-control study. The single nucleotide polymorphism of rs2200733 at 4q25 near PITX2 was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis., Results: A total of 98 patients with atrial fibrillation were genotyped, and the following frequencies were included in genotype percentages (44.9%, 50%, and 5.1%) while distribution of significant single nucleotide polymorphism rs2200733 consisted (29.55%, 53.41%, and 17.05%) which showed (χ2 = 9.159, P =.01). There was no significant difference in TC genotype frequency (P =.642), frequency of T allele (χ2 = 7.447, P =.006), and T allele was 1.806 times that of the control group (odds ratio = 1.806, 95% CI = 1.179-2.766, P =.006). According to logistic regression analysis, following results were concluded for TC genotype (odds ratio = 3.128, 95% CI = 1.053-9.287, P =.04), or TT genotype (odds ratio = 5.077, 95% CI = 1.653-15.595, P =.005) increased the risk of atrial fibrillation., Conclusions: The genotype and allele frequency distribution of rs2200733 (T/C) near PITX2 is different in the atrial fibrillation group and the control group. The T allele is a risk factor for atrial fibrillation. Compared with the CC genotype, the TT genotype increased the risk of atrial fibrillation.

Quinolone derivatives, represented by fluoroquinolones, have emerged as the most commonly prescribed antibacterials for the treatment of various bacterial infections. In particular, the combination of a quinolone moiety with other antibacterial pharmacophores has the potential to act on different drug targets, which in turn, overcome drug resistance. Accordingly, quinolone hybrids are useful prototypes for fighting drug-resistant pathogens. The purpose of the present review is to provide an emphasis on the current scenario of quinolone hybrids with potential antibacterial activity against drug-resistant pathogens, covering articles published in the past 10 years. The structure-activity relationships, various aspects of rational design and mechanisms of action are also discussed to facilitate further rational development of more effective candidates.

Background: The application of traditional Chinese herbal medicine has been officially recommended and strongly promoted in China as an important complement to conventional prevention and treatment for COVID-19. Capturing the practices, knowledge and attitudes of young adult population toward using Chinese herbs for COVID-19 is important for understanding the future of Chinese herbal medicine over the coming decades., Methods: This cross-sectional questionnaire-based study was conducted from May to June, 2022, among 313 student volunteers in Wuhan University of Science and Technology, a provincial comprehensive university in China., Results: Results showed that only 18% of students had used Chinese herbs to prevent COVID-19. The main information sources were social media, the students' family members, relatives, friends, etc. as well as the healthcare professionals. However, most students only sometimes paid close attention to related reports and news articles in social media. Clear pharmacological and toxicological properties of herbs were considered by 43% students as the most important factor to promote their own application of Chinese herbs to fight COVID-19. The mean knowledge score was 1.64 out of 5. Students' overall attitudes toward application of Chinese herbal medicine to fight COVID-19 were very positive., Conclusion: These data suggests most university young adults had a positive attitude but lack of practices and knowledge towards traditional Chinese herbal medicine for COVID-19 control., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Li et al.)

Background: The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown., Methods: We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases Lats1 and Lats2 using the tamoxifen-inducible, cardiac conduction system-specific Cre driver Hcn4 CreERT2 with Lats1 and Lats2 conditional knockout alleles. In addition, the Hippo-signaling effectors Yap and Taz were conditionally inactivated in the SAN. To determine the function of Hippo signaling in the SAN and other cardiac conduction system components, we conducted a series of physiological and molecular experiments, including telemetry ECG recording, echocardiography, Masson Trichrome staining, calcium imaging, immunostaining, RNAscope, cleavage under targets and tagmentation sequencing using antibodies against Yap1 or H3K4me3, quantitative real-time polymerase chain reaction, and Western blotting. We also performed comprehensive bioinformatics analyses of various datasets., Results: We found that Lats1/2 inactivation caused severe sinus node dysfunction. Compared with the controls, Lats1/2 conditional knockout mutants exhibited dysregulated calcium handling and increased fibrosis in the SAN, indicating that Lats1/2 function through both cell-autonomous and non-cell-autonomous mechanisms. It is notable that the Lats1/2 conditional knockout phenotype was rescued by genetic deletion of Yap and Taz in the cardiac conduction system. These rescued mice had normal sinus rhythm and reduced fibrosis of the SAN, indicating that Lats1/2 function through Yap and Taz. Cleavage Under Targets and Tagmentation sequencing data showed that Yap potentially regulates genes critical for calcium homeostasis such as Ryr2 and genes encoding paracrine factors important in intercellular communication and fibrosis induction such as Tgfb1 and Tgfb3 . Consistent with this, Lats1/2 conditional knockout mutants had decreased Ryr2 expression and increased Tgfb1 and Tgfb3 expression compared with control mice., Conclusions: We reveal, for the first time to our knowledge, that the canonical Hippo-Yap pathway plays a pivotal role in maintaining SAN homeostasis.

Background: Robot-assisted thoracic surgery has gradually been accepted as an alternative treatment for early-stage non-small-cell lung cancer (NSCLC) owing to its advantages. However, severe incomplete interlobar fissure may lead to a high rate of conversion and postoperative morbidity. This retrospective study was conducted to assess the safety and efficiency of robot-assisted lung resection for patients with incomplete fissures (IFs)., Methods: A retrospective review of medical records was performed in our institution from March 2021 to November 2021, and 207 patients with NSCLC who underwent robot-assisted anatomic lung resection were included in this study. Patients were divided into the IF group and the complete fissure (CF) group according to the level of fissure, which was determined based on the anatomical classification of pulmonary fissures., Results: The number of patients in the IF and CF groups was 87 and 120, respectively. In univariate analysis, there were no statistically significant differences between the two groups in terms of operative time (p = 0.66), intraoperative blood loss (p = 0.26), chest tube duration (p = 0.41), incidence of prolonged air leakage (PAL, p = 0.49), or length of postoperative hospital stay (p = 0.25). No patients experienced bronchopleural fistula, pneumonia, or cardiovascular complications. The total cost in the IF group was higher than that in the CF group (¥83,655 ± 13,314 versus ¥78,211 ± 11,980, p = 0.002)., Conclusion: IF does not increase the difficulty of lung cancer surgery with robotic platforms. Robot-assisted anatomic lung resection using the tunnel technique is an effective and safe method for IF patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients affected by senile vascular dementia (VaD) suffer from a gradual deterioration in their cognitive expressions as well as the ability of taking care for themselves. This study aimed to investigate the clinical efficacy and safety of improving cognitive function and daily life activities of patients with VaD by transplanting human umbilical cord mesenchymal stem cells (HUCMSCs)., Methods: A total number of 11 patients with senile VaD, who were admitted through outpatient treatment and hospitalized between February 2013 and February 2016, were selected. The diagnosis was based on CT and MRI examinations. The cultivated HUCMSCs (10 6 /kg) were injected by intravenous (i.v.) infusion on three occasions. Patients were evaluated for the Mini-Mental State Examination (MMSE) with 25-30 as normal, 21-24 as mild dementia, 10-20 as moderate dementia, and 0-9 as severe dementia. In addition, the Barthel index (BI) was used for a standardized activities of daily living (ADLs) with 0-20 as total dependence, 21-60 as severe dependence, 61-90 as moderate dependence, and 91-95 slight dependence. The t-test was performed to compare statistical significance., Results: The study included 11 subjects, one of whom fell out due to an event unrelated to the study. The results show descriptive statistics at different time points. No matter MMSE score or Barthel index, the difference between before treatment and after treatment or follow-up was statistically significant (P < 0.001).Result interpretation: this intervention method has a significant therapeutic effect, and in the 3-month follow-up period, the intervention effect is still significant compared with that before treatment., Conclusions: Our preliminary clinical observations suggest that the i.v. infusion of HUCMSCs significantly improved the cognitive function (MMSE) and daily life activities (BI) of patients with senile VaD. This approach may prove to be safe and relatively simple method to be applied for the treatment of senile VaD., (Copyright © 2022. Published by Elsevier B.V.)

Background: Bowen's disease is a cutaneous squamous cell carcinoma (CSCC) in situ. If left untreated, BD may progress to invasive CSCC. CSCC is one of the most common cutaneous carcinoma in the elderly and the advanced, metastasis CSCC usually have a poor outcomes. However, the mechanisms of invasion and metastasis from Bowen's disease to CSCC is complicated and still unclear., Objectives: The aim of this study was to explore the biomarkers and molecular alterations in Bowen's disease development process via analyzing the proteomics changes in tissues of CSCC, Bowen disease and healthy skin., Methods: A total of 7 individuals with CSCC (5 for proteomics study and 2 for validation), 7 individuals with Bowen disease (5 for proteomics study and 2 for validation) and 7 healthy controls (5 for proteomics study and 2 for validation) presented to the Department of Dermatology, Yijishan Hospital, the First Affiliated Hospital of Wannan Medical College between January 2021 and December 2021 were enrolled. The proteomics analysis was performed to screen differentially expressed proteins/gens (DEPs/DEGs) in the lesions of CSCC, Bowen disease and healthy skin tissues. The transcriptomic data (GSE32628) of CSCC was selected and downloaded from the GEO database. The common DEGs in our proteomics results and GSE32628 between CSCC and healthy skin tissues were selected. And then, the common DEGs which significantly up or down-regulated between CSCC and Bowen disease in our proteomics results were further screened to identify using Western blot methods in the validation group. CSCC A431 cells were transfected with SERPINB1 small interfering RNA (si-SERPINB1) or small interfering RNA negative control (si-NC). To explore the effect of SERPINB1 silencing on migration and invasion ability of A431 cells., Results: A total of 501 proteins were differentially expressed between the CSCC and healthy skin tissues, with 332 up-regulated and 169 down-regulated at least 1.5-fold with a P value < 0.05. These DEPs involved multiple biological functions such as protein binding process, immune, inflammation, ribosome, protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway and others. A total of 20 common DEGs (COL3A1, LUM, TNC, COL1A1, ALDH3A2, FSCN1, SERPINB4, SERPINB1, CD36, COL4A1, CSTB, GPX3, S100A7, ACTN1, SERPINB3, S100A8, RAB31, STAT1, SPRR1B, S100A9) between CSCC and healthy skin tissues in GSE32628 and our proteomics results were found. Besides, the proteins of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in CSCC were significantly up-regulated, while COL3A1, COL1A1 and CD36 were significantly down-regulated relative to Bowen disease in proteomics results. These proteins were mainly involved in multiple pathways, including Focal adhesion, ECM-receptor interaction, Human papillomavirus infection, PI3K-Akt signaling pathway, PPAR signaling pathway, AMPK signaling pathway and others. These eight proteins were selected for further validation. According to the Western blotting analysis, when compared with the Bowen disease and healthy skin tissues, we found that the relative expression levels of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in the CSCC were significantly increased, while COL1A1 and CD36 were significantly decreased, and the differences were statistically significant (P < 0.05). Furthermore, the relative expression levels of TNC, FSCN1, SERPINB1 in the Bowen disease were also significantly increased, while the COL3A1 were also significantly decreased relative to the healthy control. SERPINB1 siRNA inhibited the expression of SERPINB1 at mRNA and protein levels in the A431 cells. After interfering with the expression of SERPINB1, the migration and invasion ability in the A431 cells were significantly decreased (P < 0.05)., Conclusions: This study highlights that eight proteins, TNC, FSCN1, SERPINB1, ACTN1, RAB31, COL3A1, COL1A1, CD36, were significantly associated with the mechanisms of invasion and metastasis in Bowen's disease., (© 2022. The Author(s).)

Objective: To analyze the ultrasonic characteristics of false-negative and false-positive results of shear wave elastography (SWE) in the diagnosis of thyroid nodules to clarify the influence of nodular characteristics on SWE and to guide the clinical application of SWE., Methods: A total of 435 thyroid nodules from 343 patients with the diagnosis confirmed by surgical pathology were analyzed. Preoperative ultrasonography and SWE were conducted. The conventional ultrasound characteristics of thyroid nodules and the maximum Young's modulus were recorded. The false negativity and false positivity of SWE for the diagnosis of thyroid nodules were calculated. The ultrasonic characteristics of thyroid nodules with SWE false results were analyzed, and logistic regression analysis was adopted to determine the ultrasonic characteristics associated with SWE false results of thyroid nodules., Results: Among 323 malignant nodules, the SWE false negativity was 27.2% (88/323). The false positivity of SWE in 112 benign nodules was 19.6% (22/112). Regression analysis showed that an increase in the nodule volume increased the risk of SWE false-positive results (odds ratio [OR] 3.286; 95% confidence interval [CI]: 1.572-6.871; P = 0.002) and decreased the risk of false-negative results (OR 0.238; 95% CI: 0.115-0.493; P < 0.001). Nodules with coarse calcification had an increased risk of SWE false-positive results compared with those without calcification (OR 5.303; 95% CI: 1.098-25.619; P = 0.038). However, nodules with scattered hyperechoic foci had a reduced risk of SWE false-negative results (OR 0.515; 95% CI: 0.280-0.951; P = 0.034)., Conclusion: Nodular size and calcification were correlated with SWE false results, and the clinical application of SWE should be combined with conventional ultrasound features. Fine needle aspiration or a puncture biopsy should be conducted if necessary., 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 Xue, Kang, Miao, Zhang, Li, Yao and Kang.)

Rhododendron henanense subsp. lingbaoense (hereafter referred to as R. henanense) is an endemic species naturally distributed in the Henan province, China, with high horticultural, ornamental and medicinal value. Herein, we report a de novo genome assembly for R. henanense using a combination of PacBio long read and Illumina short read sequencing technologies. In total, we assembled 634.07 Mb with a contig N50 of 2.5 Mb, representing ~96.93% of the estimated genome size. By applying Hi-C data, 13 pseudochromosomes of R. henanense genome were assembled, covering ~98.21% of the genome assembly. The genome was composed of ~65.76% repetitive sequences and 31,098 protein-coding genes, 88.77% of which could be functionally annotated. Rhododendron henanense displayed a high level of synteny with other Rhododendron species from the Hymenanthes subgenus. Our data also suggests that R. henanense genes related to stress responses have undergone expansion, which may underly the unique abiotic and biotic stress resistance of the species. This alpine Rhododendron chromosome-scale genome assembly provides fundamental molecular resources for germplasm conservation, breeding efforts, evolutionary studies, and elucidating the unique biological characteristics of R. henanense., (© 2021 John Wiley & Sons Ltd.)

Sustainable supply chain management (SSCM) has been a tough challenge for developing economies like Saudi Arabia. Implementation of SSCM practices in the manufacturing industry has been prone to multiple risk factors that need to be identified, evaluated, and prioritized especially considering the dynamics of the manufacturing industry in a developing economy. Moreover, it is also imperative to trace out feasible and sustainable strategies to overcome the risks to SSCM practices adoption. This study serves this purpose and identifies, evaluates, prioritizes the risk factors, sub-factors, and strategies to overcome these risk factors in the implementation of SSCM practices in the manufacturing industry in Saudi Arabia. An integrated multi-criteria decision analysis approach by combining fuzzy AHP and fuzzy WASPAS methods is employed for the analyses. The fuzzy AHP analysis results show that economic risks are dominant risks followed by the managerial policy risks and environmental risks in implementing SSCM. Industrial emissions are the leading risk factors in the overall ranking of the sustainable supply chain sub-risk factors followed by market dynamics, management policy failures, financial constraints, and credit uncertainty. While evaluating the sustainable supply chain strategies using fuzzy WASPAS, it is concluded that commitment and support of top, middle, and lower level management is the most pivotal strategy to deal with the risks to SSCM in Saudi Arabia followed by establishing environmental policies and goals to adopt SSCM, and provision of the financial resources and subsidies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study is aimed at exploring the association between autophagy and tumor immune infiltration (TII) in colorectal cancer (CRC)., Methods and Materials: We downloaded the transcriptome profiling and clinical data for CRC from The Cancer Genome Atlas (TCGA) database and obtained the normal colon transcriptome profiling data from Genotype-Tissue Expression Project (GTEx) database. The list of autophagy-related signatures was obtained from the Human Autophagy Database. We isolated the autophagy-related genes from the CRC gene expression matrix and constructed an autophagy-related prognostic (ARP) risk model. Then, we constructed a multiROC curve to validate the prognostic ability of the ARP risk model. CIBERSORT was used to determine the fractions of 22 immune cells in each CRC sample, and the association between these TII cells and CRC clinical variables was further investigated. Finally, we estimated the association of 3 hub-ARP signatures and 20 different types of TII cell distribution., Results: We classified 447 CRC patients into 224 low-risk and 223 high-risk patients using the median ARP risk score. According to the univariate survival test results, except for gender ( P = 0.672), age ( P = 0.008), cancer stage, and pathological stage T, M, and N were closely correlated with the prognosis of CRC patients ( P < 0.001). Multivariate survival analysis results indicate that age and rescore were the only independent prognostic indicators with significant differences ( P < 0.05). After merging the immune cell distribution (by CIBERSORT) with the CRC clinical data, the results indicate that activated macrophage M0 cells exhibited the highest clinical response, which included cancer stage and stage T, N, and M. Additionally, six immune cells were closely associated with cancer stage, including regulatory T cells (Tregs), gamma delta T cells, follicular helper T cells, activated memory CD4 T cells, activated NK cells, and resting dendritic cells. Finally, we evaluated the correlation of ARP signatures with TII cell distribution. Compared with the other correlation, NRG1 and plasma cells (↑), risk score and macrophage M1 (↑), NRG1 and dendritic cell activated (↑), CDKN2A and T cell CD4 memory resting (↓), risk score and T cell CD8 (↑), risk score and T cell CD4 memory resting (↓), and DAPK1 and T cell CD4 memory activated (↓) exhibited a stronger association ( P < 0.0001)., Conclusions: In summary, we explored the correlation between the risk of autophagy and the TII microenvironment in CRC patients. Furthermore, we integrated different CAR signatures with tumor-infiltrating immune cells and found robust associations between different levels of CAR signature expression and immune cell infiltrating density., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yu Bian-fang et al.)

Background: Urogenital small foreign bodies (FBs) have rarely been reported in children, and their management is still challenging. This study aimed to describe the characteristics and treatment of spherical FBs no larger than 0.6 cm in the children's genitourinary tracts.  METHODS : The clinical data of spherical FBs removed in our hospital from June 2013 to June 2020 were recorded and retrospectively analyzed, including demographics, location, symptoms, imaging examinations and treatment methods., Results: A total of 10 patients were enrolled: 6 girls and 4 boys. Their ages ranged from 5.1 to 16.8 years old, with a mean age of 9.2 years. The course of the disease ranged from 3 h to 1 year, and symptoms recurred in some cases. Their imaging characteristics were reviewed and analyzed, 6 patients underwent color Doppler ultrasonography, 1 patient was suspected to have an FB in the vagina, 7 patients underwent an X-ray examination, and FBs were revealed in 6 patients. All FBs were removed under endoscopic minimally invasive surgery. Six vaginal FBs were successfully retrieved via vaginoscopy, and in the other four cases, removal by transurethral cystoscopy failed because of mutual attraction, which was eliminated by laparoscopy under pneumovesicum. Postoperative recovery was uneventful; in a follow-up of 3 months to 2 years, there was no perforation or fistula formation, and there were no urethral strictures in boys., Conclusion: Small spherical FBs are clinically rare; they are sometimes difficult to detect by imaging examinations and can be easily overlooked. Minimally invasive endoscopy remains the first-line approach for the diagnosis and removal of genitourinary spherical FBs., (© 2022. The Author(s).)

Objective: To evaluate the clinical value of qualitative shear wave elastography (SWE) color in the differential diagnosis of benign and malignant thyroid nodules., Methods: From January 2017 to July 2018, 241 patients with 261 thyroid nodules, who underwent conventional ultrasonography and SWE examination before surgical resection, were enrolled. The nodules were also evaluated by histopathologic analyses. The SWE color characteristics that could differentiate malignant and benign thyroid nodules were selected and scored based on the malignancy rate. The diagnostic performances were evaluated by receiver operating characteristic (ROC) curves analysis., Results: Among the 261 thyroid nodules, 58 were benign, and 203 were malignant. Malignancy was associated with orange or red as the color of maximum hardness inside a nodule, green as the primary color, with a "stiff rim," inhomogeneous internal color, and inhomogeneous color between the nodules and its surrounding areas. The SWE color scores for benign thyroid nodules were mainly 0 and 1, while 4 and 5 were for malignant thyroid nodules. The area under the ROC curve (AUC) of the SWE color score ≥3 for the diagnosis of malignant thyroid nodules was 0.828 (95% CI: 0.764, 0.891) with a sensitivity of 82.8%, a specificity of 82.8%, and an accuracy of 83.1%. Additionally, conventional ultrasound combined with SWE color scores had a higher diagnostic performance than conventional ultrasound (AUC 0.820 vs AUC 0.796, P = 0.04)., Conclusion: The SWE color scores might be a convenient and effective method to assist in differentiating thyroid nodules., Competing Interests: The authors declared that there was no conflict of interest., (© 2021 Zhang et al.)

Rhododendron henanense subsp. lingbaoense is endemic in China. The cpDNA of R. henanense subsp. lingbaoense is a typical quadripartite structure with a length of 208,015 bp, including a large single-copy region of 110,593 bp and a small single-copy region of 2606 bp separated by a pair of identical inverted repeat regions of 47,408 bp each. The chloroplast genome contains 119 genes, including 86 protein-coding genes, four ribosomal RNA genes, and 29 transfer RNA genes. The phylogenetic analysis of R. henanense subsp. lingbaoense showed a relatively close relationship with Rhododendron delavayi ., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

It has been demonstrated that circ&#95;0001874 and circ&#95;0001971 are potential biomarkers for the diagnosis of oral squamous carcinoma (OSCC). MiR-186 was reported to serve as a tumor suppressor in OSCC, and the down-regulation of miR-186 was reported to lead to higher expression of oncogenic factor SHP2 and the activation of growth promoting signaling. In this study, we aimed to explore the possible molecular role of circ&#95;0001874 and circ&#95;0001971 signaling in the pathogenesis of OSCC. RT-qPCR, Western blot, online bioinformatics tools and luciferase assay were utilized to study the molecular signaling pathways of circ&#95;0001874 and circ&#95;0001971. MTT assay and FCM assay were performed to investigate the synergistic effect of circ&#95;0001971 and circ&#95;0001874 on cell proliferation and apoptosis. By observing the effect of different miRNAs on the levels of circ&#95;0001847 and circ&#95;0001971, it was identified that circ&#95;0001847 and circ&#95;0001971 respectively sponged the expression of miR-296 and miR-186 via binding to these miRNAs. Also, SHP2 mRNA and PLK1 mRNA were respectively targeted by miR-186 and miR-296-5p. We also established two signaling pathways, i.e., circ&#95;0001971/miR-186/SHP2 and circ&#95;0001874/miR-296-5p/PLK1, and validated the synergistic effect of circ&#95;0001971 and circ&#95;0001874 via observing their positive effect on cell proliferation and negative effect on cell apoptosis. The expression of miR-186 and miR-296-5p was generally lower in saliva of OSCC patients compared with that in OLK patients, while the expression of miR-186 and miR-296-5p was specifically up-regulated in saliva of OSCC patients. In conclusion, the finding of this study demonstrated that the relative level of hsa&#95;circ&#95;0001971 and hsa&#95;circ&#95;0001874 were different in the saliva of OSCC patients and could be used as predictive biomarkers for the development of OSCC. Furthermore, oncogenic effects of hsa&#95;circ&#95;0001971 and hsa&#95;circ&#95;0001874 in the development of OSCC might be, at least partially, mediated by its downstream signaling pathways including hsa&#95;circ&#95;0001971/microRNA-186/SHP2 and hsa&#95;circ&#95;0001874/microRNA-297/PLK1., (© 2021. The Author(s).)

In order to explore the influence of electrode spacing on the performance of the enhanced bioretention system, four bioretention cells with microbial fuel cell (BRC-MFC) systems with different electrode spacing were designed, and the effect of electrode spacing on system performance was revealed by analysing its water treatment capacity and electricity production efficiency. The results showed that BRC-MFC had good water treatment capacity and could produce electricity simultaneously. Compared with other BRC-MFC systems with spacing, the BRC3 system (with an electrode spacing of 30 cm) had significant water treatment capacity under different organic loads, especially under high organic load (C/N = 10) operation, COD removal rate was as high as 98.49%, NH 4 + - N removal rate was as high as 97%, and it had a higher output voltage of 170.46 ± 6.17 mV. It could be seen that proper electrode spacing can effectively improve the water treatment capacity of the BRC-MFC system. This study provided a feasible method for improving the performance of the BRC-MFC system, and revealed the relevant mechanism. A proper electrode spacing with sufficient carbon sources could effectively improve the water treatment capacity of the BRC-MFC system., (© 2021 The Authors.)

Innovative product design is essentially an activity involving creative cognitive thinking. Therefore, research on the innovative design process and of methods, computer-aided innovation tools should be conducted based on systematic exploration based on the principles of innovative cognitive thinking. We aim to uncover some general principles that can serve as a systematic thinking framework for product designers, provide a feasible framework and method of innovative thinking for designers, and provide theoretical and methodological support for further development of computer-aided innovation platforms. This paper summarizes the sources and content of studies on the idea generation and design processes behind product innovation. Specifically, we break down the general innovative design process of products, outlining the cognitive mechanisms and propose an integrated application strategy that incorporates multiple methods. And taking "the solution program to the coking of oily sludge pyrolysis equipment" as an example, this paper demonstrated and verified the effectiveness and practicability of the method and strategy proposed. Based on the results on improvements in the equipment, the designers put forward some creative and implementable design schemes. The entire thinking process was relatively smooth and efficient. The example presented in this paper shows that the proposed method can effectively guide/assist/motivate designers to think creatively.

Background: Our recent studies demonstrated that both nintedanib, an FDA-approved quadruple kinase inhibitor, and gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, protect against obstructive kidney disease. It remains unknown whether they have a synergistic effect., Methods: In this study, we investigated the effect of combined administration of nintedanib and gefitinib on renal fibrosis in a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO)., Results: Combined treatment with nintedanib and gefitinib after UUO resulted in a greater antifibrotic effect compared with their individual application. Mechanistically, administration of nintedanib blocked UUO-induced phosphorylation of multiple kinase receptors associated renal fibrosis, including platelet-derived growth factor receptors, fibroblast growth factor receptors, vascular endothelial growth factor receptors, and Src family kinase, while gefitinib inhibited EGFR phosphorylation. Their combination also exhibited a more pronounced effect in reducing expression of tissue inhibitors of metalloproteinase-2 (TIMP-2), increasing expression of matrix metalloproteinase-2 (MMP-2), and suppressing renal proinflammatory cytokine expression and macrophage infiltration in the injured kidney. Furthermore, simultaneous administration of nintedanib and gefitinib was more potent in inhibiting UUO-induced renal phosphorylation of signal transducer and activator of transcription-3 (STAT3), nuclear factor-κB, and Smad-3 compared with monotherapy. In cultured renal interstitial fibroblasts, cotreatment with these 2 inhibitors also had synergistic effects in abrogating transforming growth factor β1-induced activation of renal fibroblasts and phosphorylation of Akt, STAT3, and Smad3., Conclusions: Combined application of nintedanib and gefitinib has a synergistic antifibrotic effect in the kidney and may hold translational potential for the treatment of chronic kidney disease., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

The aim of this paper was to investigate the effect of flavonoids of Sophorae Fructus on the proliferation, migration and invasion of hepatocellular carcinoma cells and analyze the regulatory mechanism of LncRNA FBXL19-AS1/miR-342-3 p pathway. MTT assay and plate cloning assay were used to detect the effect of flavonoids of Sophorae Fructus at different concentrations(1, 5, 10 mg·mL~(-1)) on the proliferation of liver cancer Huh7 cells. The effect of flavonoids of Sophorae Fructus on the migration and invasion of Huh7 cells was examined by Transwell chamber assay. qRT-PCR was used to detect the effect of flavonoids of Sophorae Fructus on the expression levels of FBXL19-AS1 and miR-342-3 p in Huh7 cells. The dual luciferase reporter assay was used to detect whether FBXL19-AS1 targeted at miR-342-3 p. The effect on the inhibition of FBXL19-AS1 expression or FBXL19-AS1 overexpression and then the proliferation, migration and invasion of Huh7 cells were examined by the above methods. Gelatin zymography was used to detect the activities of MMP-2 and MMP-9. The expression levels of cyclinD1, p21, MMP-2 and MMP-9 proteins were detected by Western blot. Flavonoids of Sophorae Fructus significantly inhibited the proliferation, migration and invasion of Huh7 cells(P&lt;0.05), promoted the expression of p21 protein(P&lt;0.05), and inhibited the expressions of cyclinD1, MMP-2 and MMP-9(P&lt;0.05) in a dose-dependent manner, and could reduce the activity of MMP-2 and MMP-9(P&lt;0.05). The expression level of FBXL19-AS1 was significantly decreased in Huh7 cells treated with flavonoids of Sophorae Fructus(P&lt;0.05), whereas the expression level of miR-342-3 p was significantly increased(P&lt;0.05). The dual luciferase reporter assay confirmed that FBXL19-AS1 targeted at the inhibition of miR-342-3 p expression. After inhibiting the expression of FBXL19-AS1, the inhibition rate of cell proliferation was significantly increased(P&lt;0.05), the number of cell clone formation was significantly reduced(P&lt;0.05), the number of migrated cells and the number of invasive cells were significantly decreased(P&lt;0.05), and the expression levels of cyclinD1, MMP-2 and MMP-9 were significantly decreased(P&lt;0.05), the activities of MMP-2 and MMP-9 were significantly reduced(P&lt;0.05), while the expression level of p21 protein was significantly increased(P&lt;0.05). The overexpression of FBXL19-AS1 reversed the inhibitory effect of flavonoids of Sophorae Fructus on the proliferation, migration and invasion of Huh7 cells. Flavonoids of Sophorae Fructus could inhibite the proliferation, migration and invasion of hepatoma cells by regulating LncRNA FBXL19-AS1/miR-342-3 p pathway.

Rationale: Low-grade malignant fibrous myxoid sarcoma (LGFMS) is a malignant tumor that originates from soft tissues and has specific clinical and histopathological characteristics. Paravertebral LGFMS is rarely reported., Patient Concerns: A 60-year-old woman had pain in the lower back and right anterior thigh for more than 3 years., Diagnosis: Paravertebral LGFMS., Interventions: Tumor resection, vertebral canal decompression and pedicle screw fixation., Outcomes: The tumor was excised, and the vertebral arch was fixed with pedicle screws at the root. Chemoradiotherapy was not performed. Her postoperative visual analogue scale (VAS) score decreased from 7 points at admission to 2 points at follow-up. The patient was discharged at postoperative day 13, and no recurrence was observed at the 6-month follow-up., Lessons: Although LGFMS is rare, it should be considered in differential diagnosis of other soft tissue tumors to avoid misdiagnosis and inappropriate treatment.

Precipitation is projected to change intensity and seasonal regime under current global projections. However, little is known about how seasonal precipitation changes will affect soil respiration, especially in seasonally dry tropical forests. In a seasonally dry tropical forest in South China, we conducted a precipitation manipulation experiment to simulate a delayed wet season (DW) and a wetter wet season (WW) over a three-year period. In DW, we reduced 60% throughfall in April and May to delay the onset of the wet season and irrigated the same amount water into the plots in October and November to extend the end of the wet season. In WW, we irrigated 25% annual precipitation into plots in July and August. A control treatment (CT) receiving ambient precipitation was also established. Compared with CT, DW significantly increased soil moisture by 54% during October to November, and by 30% during December to April. The treatment of WW did not significantly affect monthly measured soil moisture. In 2015, DW significantly increased leaf area index and soil microbial biomass but decreased fine root biomass. In contrast, WW significantly decreased fine root biomass and forest floor litter stocks. Soil respiration was not affected by DW, which could be attributed to the increased microbial biomass offsetting the decrease in fine root biomass. In contrast, WW significantly increased soil respiration from 3.40 to 3.90 μmol m -2  s -1 in the third year, mainly due to the increased litter decomposition and soil pH (from 4.48 to 4.68). The present study suggests that both a delayed wet season and a wetter wet season will have significant impacts on soil respiration-associated ecosystem components. However, the ecosystem components can respond in different directions to the same change in precipitation, which ultimately affected soil respiration., Competing Interests: None declared., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Objectives: The purpose of this study was to reveal the correlation between superior mesenteric artery (SMA) blood flow in the first 12 hours of life and the risk of necrotizing enterocolitis (NEC) in preterm neonates., Methods: We conducted a prospective study. There were 104 preterm neonates included in our study. The SMA blood flow of each neonate was measured during the first 12 hours of life if the hemodynamic situation was stable. The results of Doppler ultrasound were confidential to the neonatologists and nurses. All of the demographics, comorbidities, and outcomes were recorded and analyzed., Results: Among all of the demographics and comorbidities, the gestational age was related to the measurements of SMA blood flow. We conducted a single-factor analysis of the occurrence of NEC, including the peak systolic velocity (PSV), end-diastolic velocity, time-averaged mean velocity, differential velocity (DV), resistive index, and pulsatility index. A higher PSV (median [interquartile range], 54.165 [42.423-68.463] versus 42.195 [34.278-48.553] cm/s; P = .027) and DV (median [interquartile range], 47.445 [35.010-60.043] versus 32.565 [27.545-39.073] cm/s; P = .020) were significantly related to the risk of NEC. In the logistic analysis including gestational age, PSV, and DV, NEC was significantly associated with gestational age (odds ratio [95% confidence interval], 0.644 [0.456-0.908]; P = .012) and DV (odds ratio [95% confidence interval], 1.144 [1.058-1.237]; P < .01). The area under the receiver operating characteristic curve for the DV was 0.768, with sensitivity 0.875 and specificity 0.604. The cutoff value of the DV was 34.835 cm/s., Conclusions: From this single-center study, we can see the promising value of Doppler ultrasound for the prediction of NEC, but further research is needed., (© 2019 by the American Institute of Ultrasound in Medicine.)

Study Design: Retrospective single-center study., Objective: We want to know whether interleukin (IL)-10-secreting regulatory T cells (Treg) promote the new bone formation (NBF) through suppressing TH17 in ankylosing spondylitis (AS)., Summary of Background Data: NBF in AS is unknown. Since there are balances of bone remodeling in human body and proinflammatory helper T cells TH17 promoted bone resorption., Methods: Eighteen AS patients with or without NBF (both nine cases) and nine healthy individuals were selected and the demographic data, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), MRI sacroiliitis score (MRISIS), and computer tomography sacroiliitis score (CTSIS) were recorded. Removed hip ligament tissue in the lesions after arthroplasty was collected and the lymphocytes and the peripheral blood mononuclear cells were prepared. Second, pathological section in hematoxylin-eosin stain were analyzed and flow cytometry and quantitative polymerase chain reaction analyses were carried out to detect the levels of TH17, Treg, IL-10, and nuclear factor (NF)-κB, and the relevance between them. The effect of Treg on TH17 was further analyzed by using Transwell coculturing., Results: Compared to AS patients without NBF, AS patients with NBF had significantly higher CTSIS and complications (P < 0.05 and 0.01, respectively), but significantly lower BASDAI (3.0 ± 0.4) and MRISIS (3.3 ± 0.8) (P < 0.01 and 0.05, respectively) and no acute inflammation in HE stain for hip joint. Compared to healthy donors, the ratio of TH17/Treg was significantly higher in AS patients without NBF and lower in AS patient with NBF (both P < 0.01) in flow cytometry analysis (FCA). Furthermore, TH17 significantly decreased after indirectly coculturing with Treg in FCA (P < 0.01). Finally, IL-10 had significantly higher mRNA expression in AS patients with NBF (P < 0.01), and NF-κB had significantly higher mRNA expression in AS patients without NBF (P < 0.05) than healthy donors. Only the mRNA expression of IL-10 was significantly correlated to the ratio of TH17/Treg (r = -0.93, P < 0.01)., Conclusion: Treg-induced NBF of AS through suppressing TH17 by secreting IL10 and declining of the ratio of TH17/Treg indicated the development of NBF. This is important not only for screening development of NBF, but also for control of NBF of AS by immune therapy., Level of Evidence: N/A.

Memory is a dynamic brain function that is continually processed after encoding. Although psychologic concepts of mental schema are now well established, they have rarely been considered in animal studies. We used a behavior paradigm of multiple flavor-place paired associates (PAs) and showed that memory schema facilitates fast acquisition of new PAs in a single trial. The hippocampus is necessary for the encoding of new PAs and for memory retrieval within a certain time window-24 h following new PA consolidation. Whereas the anterior cingulate cortex (ACC) plays a critical role for dynamic PA learning and consolidation during training sessions, ACC is essential in schema representation and activation. New myelin generation is essential for learning. Neural activity in the cortical regions impacts myelination by regulating oligodendrocyte (OL) proliferation, differentiation, and myelin formation. Here, we show that newly formed OL progenitor cells and mature OLs are increased following repeated PA learning and that establishment of the memory schema is associated with enhanced myelin strength in the ACC region. Furthermore, to ensure that myelination is necessary for the acquisition of paired-associate learning, ACC lysolecithin-induced demyelination revealed impaired PA learning associated with decrease in ACC θ band power and reduced spike-field coherence and phase-locking in ACC.-Hasan, M., Kanna, M. S., Jun, W., Ramkrishnan, A. S., Iqbal, Z., Lee, Y., Li, Y. Schema-like learning and memory consolidation acting through myelination.

Background: Based on the association of common GLIS3 variants with various forms of diabetes and the biological role of GLIS3 in beta-cells, we sequenced GLIS3 in non-diabetic and diabetic Danes to investigate the effect of rare missense variants on glucose metabolism., Methods: We sequenced 53 patients with maturity-onset diabetes of the young (MODY), 5,726 non-diabetic participants, 2,930 patients with newly diagnosed type 2 diabetes and 206 patients with glutamic acid decarboxylase antibody (GADA) -positive diabetes., Results: In total we identified 86 rare (minor allele frequency < 0.1%) missense variants. None was considered causal for the presence of MODY. Among patients with type 2 diabetes, we observed a higher prevalence of rare GLIS3 missense variants (2.5%) compared to non-diabetic individuals (1.8%) (odds ratio of 1.37 (interquartile range:1.01-1.88, p = 0.04)). A significantly increased HbA1c was found among patients with type 2 diabetes and with GADA-positive diabetes carrying rare GLIS3 variants compared to non-carriers of rare GLIS3 variants with diabetes (p = 0.02 and p = 0.004, respectively). One variant (p.I28V) was found to have a minor allele frequency of only 0.03% among patients with type 2 diabetes compared to 0.2% among non-diabetic individuals suggesting a protective function (odds ratio of 0.20 (interquartile range: 0.005-1.4, p = 0.1)), an effect which was supported by publically available data. This variant was also associated with a lower level of fasting plasma glucose among non-diabetic individuals (p = 0.046)., Conclusion: Rare missense variants in GLIS3 associates nominally with increased level of HbA1c and increased risk of developing type 2 diabetes. In contrast, the rare p.I28V variant associate with reduced level of fasting plasma glucose and may be protective against type 2 diabetes., Competing Interests: The authors declare no competing interest. JS and KK are has received support from BGI and WJ from iCarbonX, however, these affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials.

Macrophage migration inhibitory factor (MIF), a type of pleiotropic immunoregulatory cytokine with a specific structure, participates in the regulation of host cell growth and migration and immune responses. Following parasitic infections, hosts may produce MIF and then participate in the parasite-host interactions. In addition, parasites may secrete parasite-derived MIF, and they jointly participate in parasite-host interactions. This paper reviews the regulation of MIF gene expression following parasitic infections, the role of MIF in parasite-host immune system interactions, and important signaling pathways of MIF-mediated immune responses.

Background: Sorafenib is one of the most commonly used systemic therapies for hepatocellular carcinoma (HCC), but the acquired resistance towards sorafenib found in HCC patients usually led to failure of treatment and poor prognosis. Therefore, there is an urgent need to study the molecular mechanism caused by the acquired resistance. Previous studies demonstrated that P62 plays an important role in tumor cell resistance towards systemic therapies including chemotherapy and targeted therapy. However, the role of P62 in acquired resistance to sorafenib in HCC has not been clearly investigated., Materials and Methods: In this study we screened the most sensitive HCC cell lines towards sorafenib using CCK8. Then on this cell line, we analyzed the relationship between P62 expression level and the sensitivity towards sorafenib by western blot and CCK8. After knockdown and overexpression of P62 in HCC cells, cells were then treated with sorafenib. After that, we detect changes of sensitivity towards sorafenib. HCC samples were used to investigate the expression of P62 and their survival time., Results: Among four HCC cell lines in our lab, HepG2 cell line with the highest sensitivity to sorafenib was screened and selected. After treatment with sorafenib, the expression of P62 was significantly increased. In HCC cells, we found that significant up-regulation of P62 was correlated with the reduction of sorafenib sensitivity. In HCC samples, we found that the expression of P62 was associated with sorafenib resistance and a shorter survival time., Conclusion: The up-regulation of P62 could reduce the sensitivity of HCC towards sorafenib. Thus, P62 could be therapeutic target to overcome sorafenib acquired resistance in the future., Competing Interests: None., (IJCEP Copyright © 2019.)

Nuclear factor 45 (NF-45) has been found to be markedly upregulated in several cancers, including esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms underlying its functions remain unclear. In this study, we confirm that overexpression of NF45 was frequently detected in ESCC tissues and was associated with poor outcome. Overexpression studies revealed that NF-45 promoted cell growth and invasion and upregulated Rac1/Tiam1 signalling via 14-3-3ε protein in ESCC cell lines. This novel mechanism linking upregulated NF45 expression to increased 14-3-3ε/Rac1/Tiam1 signalling and subsequent growth and invasion in ESCC may aid in identification of new therapeutic targets for this disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical effects of continuous intravenous infusion with high-dose furosemide on early acute kidney injury (AKI) complicated with acute lung edema., Methods: Ninety patients who had been treated by furosemide at routine dose for 12 hour but with unsatisfactory outcomes were selected and subjected to continuous intravenous infusion with high-dose furosemide. The dose was adjusted according to hourly urine output. Serum levels of urea nitrogen, creatinine and potassium, pH, oxygenation index and mechanical ventilation time before and 6, 12, 24, 48 and 72 hour after treatment were compared., Results: The urine outputs before and 6, 12, 24, 48 and 72 hour after treatment were (10.71 ± 1.81), (164.52 ± 21.42), (189.71 ± 29.61), (181.33 ± 23.52), (176.82 ± 24.80) and (164.52 ± 18.91) ml/h respectively. Compared with data before treatment, the serum levels of urea nitrogen, creatinine and potassium significantly decreased while pH and oxygenation index significantly increased after six hour of treatment (P<0.05). After treatment, the kidney functions of 80 patients (88.9%) were completely recovered, without obvious adverse reactions., Conclusion: For patients with early AKI complicated with acute pulmonary edema who cannot be cured by diuretic agent at routine dose, high-dose furosemide increases urine output and improves success rate., Competing Interests: Conflict of interest: None.

Background: This study was conducted to evaluate the performance of multislice computed tomography (MSCT) to diagnose high-density thymic cysts and thymomas in lesions measuring < 3 cm., Methods: The records of 42 patients admitted to Ningbo No. 2 Hospital with an anterior mediastinal mass (diameter < 3 cm) suspected of carcinoma originating from the thymus were retrospectively analyzed. All patients underwent surgery and pathological examination. Twenty-eight were diagnosed with thymic cysts and 14 with thymoma. The features of thymic cysts and thymomas revealed on MSCT were compared., Results: Mediastinal masses with a triangular or teardrop shape and a straight mediastina-lung border were more likely to be diagnosed as thymic cysts (P < 0.05), while those with a bulging nodule-lung border were more likely thymomas (P < 0.05). Using the CT value as a reference for differential diagnosis, the diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve for CT values of non-contrast CT images, enhanced CT values, and ΔCT values were 0.65 (0.47-0.84), 0.95(0.86-1.00), and 0.96 (0.89-1.00), respectively., Conclusion: MSCT of high-density thymus gland nodules (maximum diameter ≤ 3 cm) can reveal specific features that could be helpful for differential diagnosis., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)