bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae and Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae in China Determined via Mouse Lethality Tests
Authors: Hu Dakang , Chen Wenjie , Zhang Qi , Li Meng , Yang Zehua , Wang Yong , Huang Yunkun , Li Gang , Tian Dongxing , Fu Pan , Wang Weiwen , Ren Ping , Mu Qing , Yu Lianhua , Jiang Xiaofei
Published: June 2022

Objective

To investigate the epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) and hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP).

Methods

Totally 436 K. pneumoniae strains were collected from 7 hospitals in mainland China between 2017.01 and 2018.02. Sequence types, serotypes, antimicrobial-resistance and virulence genes were analyzed. Additionally, string test, capsule stain, Periodic Acid Schiff stain, fitness analysis, quantitative real-time PCR and mouse lethality test were also performed. Molecular combinations were used to screen putative blaKPC(+)-HvKP and Hv-blaKPC(+)-KP, followed by the confirmation of mouse lethality test.

Results

Diverse detection rates were found for the virulence genes, ranging from c-rmpA (0.0%) to entB (100.0%). According to the molecular criteria, 127, 186, 9 and 26 strains were putatively denoted as HvKP, blaKPC(+)-KP, blaKPC(+)-HvKP and Hv-blaKPC(+)-KP. Mouse lethality test confirmed 2 blaKPC(+)-HvKP strains (JS184 and TZ20) and no Hv-blaKPC(+)-KP. JS184 showed K2 serotype, thin capsule, positive exopolysaccharid and string test. TZ20 presented K20 serotype, thin capsule, negative exopolysaccharide and string test. Compared with the positive control NTUH-K2044, equal galF expression and growth curves were confirmed for JS184 and TZ20.

Conclusions

Molecular determination of CR-HvKP and Hv-CRKP brings remarkable bias compared with mouse lethality test. The exact prevalence of CR-HvKP is less than 1.0%, which of Hv-CRKP is much lower.
CRISPR/Cas12a-Based Diagnostic Platform Accurately Detects Nocardia farcinica Targeting a Novel Species-Specific Gene
Authors: Qiu Xiaotong , Xu Shuai , Liu Xueping , Ren Hongtao , Han Lichao , Li Zhenjun
Published: June 2022

Under the COVID-19 pandemic background, nucleic acid detection has become the gold standard to rapidly diagnose the infectious disease. A rapid, low cost, reliable nucleic acid detection platform will be the key to control next potential pandemic. In this study, a nucleic acid detection platform, which combined CRISPR/Cas12a-based detection with loop-mediated isothermal amplification (LAMP), was developed and termed CRISPR-CLA. In the CRISPR-CLA system, LAMP preamplification was employed, and CRISPR/Cas12a-based detection was used to monitor the preamplicons. The forward inner primer (FIP) was engineered with a protospacer adjacent motif (PAM) site TTTA of Cas12a effector at the linker region; thus, the CRISPR-CLA platform can detect any sequence as long as the primer design meets the requirement of LAMP. To demonstrate the validity of the CRISPR-CLA system, it was applied for the molecular diagnosis of nocardiosis caused by Nocardia farcinica (N. farcinica). A highly conserved and species-specific gene pbr1 of N. farcinica, which was first reported in this study, was used as the target of detection. A set of LAMP primers targeting a fragment of pbr1 of the N. farcinica reference strain IFM 10152 was designed according to the principle of CRISPR-CLA. Three CRISPR RNAs (crRNAs) with different lengths were designed, and the most efficient crRNA was screened out. Additionally, three single-strand DNA (ssDNA) probes were tested to further optimize the detection system. As a result, the N. farcinica CRISPR-CLA assay was established, and the whole detection process, including DNA extraction (20 min), LAMP preamplification (70°C, 40 min), and CRISPR/Cas12a-mediated detection (37°C, 8 min), can be completed within 70 min. A fluorescence reader (for fluorescence CRISPR-CLA) or a lateral flow biosensor (for lateral-flow CRISPR-CLA) can be the media of the result readout. Up to 132 strains were used to examine the specificity of N. farcinica CRISPR-CLA assay, and no cross-reaction was observed with non-N. farcinica templates. The limit of detection (LoD) of the N. farcinica CRISPR-CLA assay was 100 fg double-strand DNA per reaction. N. farcinica was detected accurately in 41 sputum specimens using the N. farcinica CRISPR-CLA assay, which showed higher specificity than a real-time qPCR method. Hence, the N. farcinica CRISPR-CLA assay is a rapid, economic and accurate method to diagnose N. farcinica infection.
Analysis of Gut Microbiota Signature and Microbe-Disease Progression Associations in Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Concurrent Chemoradiotherapy
Authors: Xi Yu , Liu FangJie , Qiu Bo , Li Ying , Xie XinQiang , Guo JinYu , Wu Lei , Liang TingTing , Wang DaQuan , Wang Juan , Chen Moutong , Xue Liang , Ding Yu , Zhang Jumei , Wu QingPing , Liu Hui
Published: June 2022

Purpose

To evaluate the association of gut microbiome signature and disease progression in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) by fecal metagenome analysis.

Methods

Metagenome-wide association studies on baseline fecal samples from 18 LA-NSCLC patients before CCRT and 13 controls from healthy first-degree relatives were performed. Among the 18 LA-NSCLC patients, six patients were defined as the long progression-free survival (long-PFS) group (PFS≥11 months) while another 12 were in the short-PFS group (PFS<11 months). Alpha diversity, taxonomic composition, and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways were compared between groups.

Results

The Firmicutes/Bacteroidetes value of long-PFS group was higher than those of short-PFS (p=0.073) and healthy individual groups (p=0.009). Meanwhile, long-PFS group had significantly higher diversities in Fungi, Archaea, and Viruses than short-PFS group. The KEGG pathways overrepresented in short-PFS group included fructose and mannose metabolism (p=0.028), streptomycin biosynthesis (p=0.028), acarbose and validamycin biosynthesis (p=0.013), ribosome biogenesis in eukaryotes (p=0.035), biosynthesis of vancomycin group antibiotics (p=0.004), apoptosis-fly (p=0.044), and tetracycline biosynthesis (p=0.044), while those overrepresented in long-PFS group included fatty acid biosynthesis (p=0.035), fatty acid metabolism (p=0.008), vancomycin resistance (p=0.008), longevity regulating pathway-worm (p=0.028), type II diabetes mellitus (p=0.004), and viral carcinogenesis (p=0.003). Further analysis of antibiotic resistome demonstrated that the short-PFS group had a trend with more antibiotic resistance genes than healthy control (p=0.070) and long-PFS groups (p=0.218). The vancomycin resistance sequences were significantly enriched in the long-PFS group compared to the short-PFS group (p=0.006).

Conclusions

The baseline gut microbiome composition and functionality might be associated with PFS in LA-NSCLC treated with CCRT. The outcome of CCRT might be modulated through bacterial metabolic pathways. The antibiotic resistance genes might play a role in disease progression and provide potential information on the relationship between the use of antibiotics and treatment efficacy of CCRT in LA-NSCLC.
Long-Term Interactions of Salmonella Enteritidis With a Lytic Phage for 21 Days in High Nutrients Media
Authors: Barron-Montenegro Rocio , Rivera Dácil , Serrano María Jesus , García Rodrigo , Álvarez Diana M. , Benavides Julio , Arredondo Fernanda , Álvarez Francisca P. , Bastías Roberto , Ruiz Soledad , Hamilton-West Christopher , Castro-Nallar Eduardo , Moreno-Switt Andrea I.
Published: June 2022

Salmonella spp. is a relevant foodborne pathogen with worldwide distribution. To mitigate Salmonella infections, bacteriophages represent an alternative to antimicrobials and chemicals in food animals and food in general. Bacteriophages (phages) are viruses that infect bacteria, which interact constantly with their host. Importantly, the study of these interactions is crucial for the use of phages as a mitigation strategy. In this study, experimental coevolution of Salmonella Enteritidis (S. Enteritidis) and a lytic phage was conducted in tryptic soy broth for 21 days. Transfer to fresh media was conducted daily and every 24 hours, 2 mL of the sample was collected to quantify Salmonella OD600 and phage titter. Additionally, time-shift experiments were conducted on 20 colonies selected on days 1, 12, and 21 to evaluate the evolution of resistance to past (day 1), present (day 12), and future (day 21) phage populations. The behavior of the dynamics was modeled and simulated with mathematical mass-action models. Bacteria and phage from days 1 and 21 were sequenced to determine the emergence of mutations. We found that S. Enteritidis grew for 21 days in the presence and absence of the phage and developed resistance to the phage from day 1. Also, the phage was also able to survive in the media for 21 days, however, the phage titer decreased in approx. 3 logs PFU/mL. The stability of the lytic phage population was consistent with the leaky resistance model. The time-shift experiments showed resistance to phages from day 1 of at least 85% to the past, present, and future phages. Sequencing of S. Enteritidis showed mutations in genes involved in lipopolysaccharide biosynthesis genes rfbP and rfbN at day 21. The phage showed mutations in the tail phage proteins responsible for recognizing the cell surface receptors. These results suggest that interactions between bacteria and phage in a rich resource media generate a rapid resistance to the infective phage but a fraction of the population remains susceptible. Interactions between Salmonella and lytic phages are an important component for the rational use of phages to control this important foodborne pathogen.
Evaluating Challenges and Adoption Factors for Active Assisted Living Smart Environments
Authors: Lam Lena , Fadrique Laura , Bin Noon Gaya , Shah Aakanksha , Morita Plinio Pelegrini
Published: June 2022

While there have been rapid advancements in individual technologies such as Internet of Things (IoT) and Active Assisted Living (AAL) to address challenges related to an aging population, there remain large gaps in how these technologies can be integrated into the broader ecosystem to support older adults in aging in place. This research provides an overview of 15 solutions available to date around the globe and compares key factors for adoption in each solution, including user acceptance, privacy and security, accessibility, and interoperability. To scale these solutions sustainably and universally, the development and implementation of standards for key factors for adoption in AAL environments is critical. There is also a need for increased and sustainable funding to complement research priorities, to continue advancing AAL technologies.
Single Cell RNA Sequencing Reveals Deep Homology of Dental Cell Types Across Vertebrates
Authors: Gruenhagen George W. , Mubeen Talha , Patil Chinar , Stockert Joseph , Streelman Jeffrey T.
Published: June 2022

Like most mammals, humans replace their teeth once throughout their lives and have limited regenerative capabilities. In contrast, mice continually renew tissues lost due to gnawing through a well characterized population of stem cells on the labial surface of the incisor. Most non-mammalian vertebrates replace teeth throughout life; the cellular and molecular mechanisms of successional tooth replacement are largely unknown. Here we use single nuclei RNA sequencing (snRNA-seq) of replacement teeth and adjacent oral lamina in Lake Malawi cichlids, species with lifelong whole–tooth replacement, to make two main discoveries. First, despite hundreds of millions of years of evolution, we demonstrate conservation of cell type gene expression across vertebrate teeth (fish, mouse, human). Second, we used an approach that combines marker gene expression and developmental potential of dental cells to uncover the transcriptional signature of stem-like cells in regenerating teeth. Our work underscores the importance of a comparative framework in the study of vertebrate oral and regenerative biology.
Leadership Within the Phenomenological Structure of Teacher Creativity
Authors: Žydžiūnaitė Vilma , Butanavičius Valentinas , Jurgilė Vaida , Kaminskienė Lina
Published: June 2022

Few studies have investigated the relationship between teachers’ leadership and creativity, and thus far, no quantitative or qualitative studies have been undertaken focusing on teacher leadership in the context of teacher creativity and, more specifically, in the context of the phenomenological structure of teacher creativity. Thus, the study presented in this article draws attention to the phenomenological relationship between teacher creativity and leadership. The research question used as a guide for this study was as follows: What does a teacher’s leadership in the phenomenological structure of teacher creativity mean? The study aimed to describe teacher leadership as a component of the phenomenological structure of teacher creativity. Phenomenology is the study of structures of consciousness as experienced from the first-person (teacher’s) point of view. In the study, integral phenomenology as a specific approach to design was applied. Unstructured in-depth phenomenological interviews were conducted with non-art discipline teachers. This means school teachers who do not teach arts (music, dance, theatre) but other subjects such as physics, mathematics, chemistry, geography, informatics, languages, biology, communication, psychology and, etc. This article presents the results of 19 analysed interviews. Findings showed that the phenomenological structure of teacher creativity consisted of eighteen themes covering specific sub-themes; one theme represented teacher leadership, encompassing innovativeness, influence, and collegiality. The teacher leadership within the phenomenological structure of teacher creativity was related to the following themes: being curious, being brave, being in relationship, being a citizen, motivating, and opening up. It could be concluded that the complex phenomenological structure of teacher creativity proves that neither teacher creativity nor leadership are individual elements or individual competencies that are acquired separately – teacher creativity is always accompanied by teacher leadership and vice versa. Findings provide opportunities to change our conceptions of teacher leadership in relation to teacher creativity. This study shows that teacher leadership does not play a key role in her/his creativity.
Professional Vision and the Compensatory Effect of a Minimal Instructional Intervention: A Quasi-Experimental Eye-Tracking Study With Novice and Expert Teachers
Authors: Grub Ann-Sophie , Biermann Antje , Lewalter Doris , Brünken Roland
Published: June 2022

The early recognition of potential disruptions in learning environments is of great importance for the proactive control of the teaching process and maximizing learning outcomes. The professional competence of (prospective) teachers is required for successful classroom management. Teachers’ professional vision (PV) serves as a link between their knowledge and classroom management behavior. Expertise research in different domains has shown that experts and novices show differences in visual perception based on their expertise level; however, research results to date are heterogeneous and often based on small samples. An eye-tracking study using a quasi-randomized experimental design was performed to investigate how German prospective (n = 29) and experienced (n = 35) teachers perceived different teaching situations. The goal of the study was to determine whether previous results from expertise research could be replicated in a standardized experimental setting. Moreover, the impact of a minimal intervention (specific instruction) on PV of potential classroom disruptions was investigated. In contrast to the hypotheses, no expertise-dependent differences on various eye-tracking parameters can be found. Furthermore, the minimal intervention does not lead to an improvement in PV for experts or novices. The results are discussed with regard to the discrepancy with previously published findings and possible explanations are offered (e.g., the salience of disruptions, internal personal factors, and external environmental influences).
Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism
Authors: Hu Hua , Zhao Meng , Li Zhaoyang , Nie Hongli , He Jia , Chen Zhuo , Yuan Jing , Guo Huan , Zhang Xiaomin , Yang Handong , Wu Tangchun , He Meian
Published: June 2022

Objective

To explore differentially expressed miRNAs in type 2 diabetes and their potential cellular functions.

Methods

We screened plasma miRNAs by miRNA array analysis and validated them by TaqMan real-time PCR in 113 newly diagnosed, untreated type 2 diabetes cases and 113 healthy controls. Low-abundance plasma proteins encoded by miR-193b-3p target genes were explored in this study population. We further investigated the potential cellular functions of the differentially expressed miRNAs in HepG2 cells.

Results

miR-193b-3p was differentially expressed in type 2 diabetes cases compared to healthy controls (fold change = 2.01, P = 0.006). Plasma levels of triosephosphate isomerase (TPI1, a protein involved in the glycolytic pathway) decreased in type 2 diabetes cases (fold change = 1.37, P = 0.002). The effect of miR-193b-3p on TPI1 was verified by transfection of miR-193b-3p into HepG2 cells. miR-193b-3p inhibited the expression of YWHAZ/14-3-3ζ in the PI3K-AKT pathway, subsequently altering the expression of FOXO1 and PCK1. After transfection, cells were incubated in glucose-free medium for another 4 h. Glucose levels in medium from cells with elevated miR-193b-3p levels were significantly higher than those in medium from negative control cells (P = 0.016). In addition, elevated miR-193b-3p reduced glucose uptake by inhibiting insulin receptor (IR) and GLUT2 expression.

Conclusion

Plasma miR-193b-3p levels increased in type 2 diabetes cases, and TPI1 levels decreased in both plasma and HepG2 cells with increased miR-193b-3p levels, while extracellular lactate levels did not significantly changed. Moreover, miR-193b-3p may affect glucose metabolism by directly targeting YWHAZ/14-3-3ζ and upregulating the transcription factor FOXO1 downstream of the PI3K-AKT pathway.
Vitamin D Supplementation Improves Handgrip Strength in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhang Jia-Li , Poon Christina Chui-Wa , Wong Man-Sau , Li Wen-Xiong , Guo Yi-Xun , Zhang Yan
Published: June 2022

Introduction

In postmenopausal women, vitamin D deficiency (as defined by the circulating level of 25(OH)D being below 20 ng/ml (50 nmol/L)) is a regular occurrence. The effect of vitamin D supplementation on the muscle function of postmenopausal women has been controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines and summarizes the effects of vitamin D supplementation on the muscular strength and mobility of postmenopausal women.

Methods

RCTs that met the inclusion criteria for this study were identified by searching PubMed, EMBASE, and the Cochrane Library. Postmenopausal women who were included in the study were exposed to RCTs assessing the effectiveness of vitamin D supplements. Meta-analysis data were extracted by two independent reviewers and screened for methodological quality. RCTs that did not meet the minimum requirement for assessment were excluded. In the meta-analysis, the effect size (weighted mean differences, WMD) of handgrip strength (HGS) and timed-up and go test (TUG) with a 95% confidence interval (CI) was obtained to compare reported results across the included RCTs.

Results

A total of 19 trials were included in this systematic review, among which 13 trials were eligible for the meta-analysis. In the 13 included studies, supplementing with vitamin D produced a weighted mean difference of 0.876 kg (95% CI = 0.180 to 1.571, P = 0.014, I2 = 68.5%) for HGS, a measurement of muscle strength. However, an insignificant decrease of 0.044 s was observed after analyzing the TUG (95% CI = -0.979 to 0.892, P = 0.927, I2 = 95%). According to subgroup analysis, vitamin D supplementation increased HGS in patients over the age of 60 (P = 0.001), in those without calcium supplementation (P = 0.032), and in those whose baseline vitamin D level was greater than 75 nmol/L (30 ng/ml) (P = 0.003).

Conclusions

Taking into account the studies in this systematic review, vitamin D supplementation improved muscle strength in postmenopausal women. However, an insignificant result was demonstrated in terms of mobility after vitamin D supplementation.
Risk Factors for Cardiac Complications in Patients With Pheochromocytoma and Paraganglioma: A Retrospective Single-Center Study
Authors: Zhao Lin , Meng Xu , Mei QiMin , Fan Hua , Liu YeCheng , Zhou XianLiang , Zhu HuaDong , Zhang ShuYang
Published: June 2022

Background

Catecholamine excess arising from pheochromocytomas and paragangliomas (PPGLs) can cause a wide spectrum of cardiac manifestations. Although there are reviews of reported cases, these reviews lack detailed data, which makes it impossible to perform an accurate analysis. In this study, we conducted a comprehensive analysis of cardiovascular complications (CCs), including PPGL-related myocardial injury, cardiogenic shock, and arrhythmias requiring antiarrhythmic therapy, in a large cohort of patients with PPGL.

Methods

We retrospectively analyzed the clinical data of consecutive patients with PPGL admitted between January 2018 and June 2020. The prevalence and the characteristics of patients with CCs were investigated. Moreover, comparisons were made between patients with and without CCs.

Results

Compared with the non-CC group, the percentage of men was significantly lower (14/41 vs.92/175, 34.1% vs. 52.6%, p = 0.034) and the proportion of patients with paroxysmal hypertension was significantly higher (13/41 vs.29/173, 31.7% vs.16.8%, p = 0.03) in the CC group. More patients showed excessive sweating (19/41 vs 64/175, 46.3% vs. 24.0%, p = 0.004) and PPGL crisis (7/41 vs. 10/175, 17.1% vs.5.7%, p=0.035) in the CC group. In terms of laboratory findings, higher white blood cell [7.36 (6.49, 20.23) vs. 5.95 (5.1, 6.97)×109/L, p<0.001] and platelet [339.28 ± 108.54 vs. 250.66 ± 70.83(×109/L), p = 0.021] counts were more common in the CC group. There was also a higher prevalence of combination-producing PPGL in the CC group (13/24 vs.20/149, 54.2% vs.13.4%, p<0.001). However, the tumor size, invasive behavior on histology, and hemorrhage or necrosis on histology did not differ between the two groups. Platelet count [odds ratio (OR): 1.009; 95% confidence interval (CI) 1.001–1.016; p=0.023] and combination-secreting PPGL (OR: 5.009; 95% CI 1.365–18.38; p=0.015) are independent risk factors for CCs in patients with PPGL.

Conclusions

In patients with PPGL, even in the absence of signs and symptoms of CCs, a work up of cardiology should be strongly considered. Importantly, if patients with PPGLs have higher platelet counts and the combination-secreting pattern, they are more likely to have CCs. Thus, a careful cardiac evaluation should be performed.
Activation of GIPR Exerts Analgesic and Anxiolytic-Like Effects in the Anterior Cingulate Cortex of Mice
Authors: Wang Xin-shang , Jiang Yong-li , Lu Liang , Feng Ban , Ma Xue , Zhang Kun , Guan Shao-yu , Yang Le , Fan Qing-yu , Zhu Xiao-chen , Yang Fan , Qi Jing-yu , Yang Liu-kun , Li Xu-bo , Zhao Ming-gao , Jiang Wen , Tian Zhen , Liu Shui-bing
Published: June 2022

Background

Chronic pain is defined as pain that persists typically for a period of over six months. Chronic pain is often accompanied by an anxiety disorder, and these two tend to exacerbate each other. This can make the treatment of these conditions more difficult. Glucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family and plays a critical role in glucose metabolism. Previous research has demonstrated the multiple roles of GIP in both physiological and pathological processes. In the central nervous system (CNS), studies of GIP are mainly focused on neurodegenerative diseases; hence, little is known about the functions of GIP in chronic pain and pain-related anxiety disorders.

Methods

The chronic inflammatory pain model was established by hind paw injection with complete Freund’s adjuvant (CFA) in C57BL/6 mice. GIP receptor (GIPR) agonist (D-Ala2-GIP) and antagonist (Pro3-GIP) were given by intraperitoneal injection or anterior cingulate cortex (ACC) local microinjection. Von Frey filaments and radiant heat were employed to assess the mechanical and thermal hypersensitivity. Anxiety-like behaviors were detected by open field and elevated plus maze tests. The underlying mechanisms in the peripheral nervous system and CNS were explored by GIPR shRNA knockdown in the ACC, enzyme-linked immunosorbent assay, western blot analysis, whole-cell patch-clamp recording, immunofluorescence staining and quantitative real-time PCR.

Results

In the present study, we found that hind paw injection with CFA induced pain sensitization and anxiety-like behaviors in mice. The expression of GIPR in the ACC was significantly higher in CFA-injected mice. D-Ala2-GIP administration by intraperitoneal or ACC local microinjection produced analgesic and anxiolytic effects; these were blocked by Pro3-GIP and GIPR shRNA knockdown in the ACC. Activation of GIPR inhibited neuroinflammation and activation of microglia, reversed the upregulation of NMDA and AMPA receptors, and suppressed the enhancement of excitatory neurotransmission in the ACC of model mice.

Conclusions

GIPR activation was found to produce analgesic and anxiolytic effects, which were partially due to attenuation of neuroinflammation and inhibition of excitatory transmission in the ACC. GIPR may be a suitable target for treatment of chronic inflammatory pain and pain-related anxiety.
Circulating Ism1 Reduces the Risk of Type 2 Diabetes but not Diabetes-Associated NAFLD
Authors: Wang Jiajia , Du Juan , Ge Xiaoxu , Peng Wenfang , Guo Xirong , Li Wenyi , Huang Shan
Published: June 2022

Purpose

To examine the association of serum Ism1, a new adipokine that can regulate glucose uptake, with type 2 diabetes (T2D) in a Chinese population. Considering high prevalence of Nonalcoholic Fatty Liver Disease in patients with type 2 diabetes and the regulating role of Ism1 on glucose uptake of peripheral tissues, we further explored the association between Ism1 and diabetes-associated nonalcoholic fatty liver disease.

Methods

A total of 120 newly diagnosed T2D patients and 60 control subjects with normal glucose were recruited in the case-control study. Serum Ism1 concentrations were determined by ELISA. Multivariate logistic regression analysis was used to evaluate the independent association of serum Ism1 concentration with the risk of T2D. The 120 newly diagnosed T2D patients were divided into uncomplicated T2D group and diabetes-associated NAFLD group according to the FLI score.

Results

The Ism1 level of normoglycemic controls was higher than that of T2D patients (3.91 ± 0.24 ng/ml vs 3.01 ± 0.16 ng/ml, P=0.001). Based on quartile analysis of Ism1 level, the proportion of high circulating Ism1 levels in the control group increased while T2D group decreased, and the distribution difference was statistically significant (P=0.015). Logistic regression analysis indicated that the serum Ism1 level was an independent protective factor of type 2 diabetes (OR=0.69, 95%CI: 0.54-0.89). The decrease of Ism1 level did not increase the risk of non-alcoholic fatty liver disease in diabetic patients by Binary logistic regression analysis (OR=1.08, 95% CI: 0.69-1.69).

Conclusions

The increase of serum Ism1 was associated with a decreased risk of diabetes, and it did not reduce the risk of non-alcoholic fatty liver disease in diabetic patients.
Association Between Serum Uric Acid and Carotid Intima-Media Thickness in Different Fasting Blood Glucose Patterns: A Case-Control Study
Authors: Gao Yuanyuan , Xu Baofeng , Yang Yanyan , Zhang Mei , Yu Tian , Zhang Qiujuan , Sun Jianwei , Liu Rui
Published: June 2022

Our objective was to analyze the correlation between serum uric acid (SUA) levels and carotid intima-media thickness (CIMT) and explore the relationship between SUA and carotid atherosclerosis in different glucose metabolism patterns. A total of 614 patients were enrolled in this case-control study, including 406 in the normouricemia group and 208 in the hyperuricemia group. The two groups were each divided into three groups according to fasting blood glucose (FBG) level: normal, impaired fasting glucose (IFG), and diabetes mellitus (DM). CIMT and the CIMT thickening rate in the hyperuricemia group were significantly higher than those in the normouricemia group: 0.17 (0.11–0.24) cm vs. 0.12 (0.08–0.15) cm and 73.56% vs. 51.97% (p < 0.001). Pearson’s correlation analysis showed that age, systolic blood pressure (SBP), diastolic blood pressure, FBG, triglyceride, SUA, creatinine, and blood urea nitrogen were positively correlated with CIMT, whereas high-density lipoprotein cholesterol and total cholesterol were negatively correlated with CIMT. Multiple linear regression analysis showed that age, SUA, FBG, and SBP were independent factors that affected CIMT. Furthermore, age and SBP were independent factors in the normouricemia group, and FBG was an independent factor that affected CIMT in the hyperuricemia group (p < 0.05). In the hyperuricemia group, CIMT in the DM group was significantly higher than that in the normal group [0.20 (0.14–0.25)cm vs. 0.15 (0.1–0.25); p < 0.05], and the CIMT thickening rate in the DM group was significantly higher than those in the IFG and normal groups (90.38% vs. 78.38%, 90.38% vs. 65.81%; p < 0.05). The ROC curve analysis showed that uric acid combined with age, SBP, and FBG had the highest area under the curve (AUC) for predicting CIMT thickening [0.855 (95% confidence interval (CI): 0.804–0.906)], followed by uric acid combined with FBG [AUC: 0.767 (95% CI: 0.726–0.808)]. In conclusion, SUA was closely associated with an increase in CIMT in patients with specific FBG metabolic patterns and may be an independent risk factor for carotid atherosclerosis. SUA, especially in combination with other factors (such as age, SBP, FBG), may serve as a specific model to help predict the incidence of CIMT thickening. Clinical Trial Registration:http://www.chictr.org.cn, identifier ChiCTR2000039124.
Cultivation Mechanism of Green Technology Innovation in Manufacturing Enterprises Under Environmental Regulations in China
Authors: Zhang Tong-Jian , Zhou Jian-Ya , Wang Min , Ren Kai , Imran Muhammad , Wang Rongyu
Published: June 2022

The rapid development of China’s economy is increasing the pressure on the country’s ecological environment. As the largest developing country in the world, China’s environmental crisis is bound to cause global ecological risks. Therefore, green technology innovation is imperative for sustainable development as manufacturing enterprises are heavily affected by the Chinese environment. Through green technology, innovation to help China get rid of the environmental crisis, and then achieve new breakthroughs in the global economy. The Porter hypothesis notes that environmental regulation can promote the growth of green technology innovation capabilities, although the effects have not entirely been felt by China’s manufacturing enterprises. This study is based on the structural equation model and considers a sample of China’s manufacturing enterprises to empirically test the promotion mechanism of environmental regulation underlying green technology innovation capability. Command-based environmental regulation has the strongest effect on promoting green technology innovation capability, followed by incentive-based environmental regulation. Voluntary environmental regulation has the weakest effect. Green product innovation capability has been well cultivated in the field of green technology innovation capability, followed by green process innovation capability. Terminal technology governance capability is the least developed.
Modeling the Impact of Climate Change on Cervid Chronic Wasting Disease in Semi-Arid South Texas
Authors: Islam Md Rafiul , Bulut Ummugul , Feria-Arroyo Teresa Patricia , Tyshenko Michael G. , Oraby Tamer
Published: June 2022

Chronic wasting disease (CWD) is a spongiform encephalopathy disease caused by the transmission of infectious prion agents. CWD is a fatal disease that affects wild and farmed cervids in North America with few cases reported overseas. Social interaction of cervids, feeding practices by wildlife keepers and climate effects on the environmental carrying capacity all can affect CWD transmission in deer. Wildlife deer game hunting is economically important to the semi-arid South Texas region and is affected by climate change. In this paper, we model and investigate the effect of climate change on the spread of CWD using typical climate scenarios. We use a system of impulsive differential equations to depict the transmission of CWD between different age groups and gender of cervids. The carrying capacity and contact rates are assumed to depend on climate. Due to the polygamy of bucks, we use mating rates that depend on the number of bucks and does. We analyze the stability of the model and use simulations to study the effect of harvesting (culling) on eradicating the disease, given the climate of South Texas. We use typical climate change scenarios based on published data and our assumptions. For the climate indicator, we calculated and utilized the Standard Precipitation Evapotranspiration Index (SPEI). We found that climate change might hinder the efforts to reduce and effectively manage CWD as it becomes endemic to South Texas. The model shows the extinction of the deer population from this region is a likely outcome.
Spatial Distribution and Conservation Strategies of Large Carnivores in Human-Dominated Landscape: A Case Study of Asiatic Black Bear in Jilin, China
Authors: Hairong Du , Xiaoliang Zhi , Minghai Zhang , Xiangdong Ruan , Lee Tien Ming
Published: June 2022

Large carnivores maintain the balance of ecosystems. Understanding distribution and population changes are necessary prerequisites for scientific conservation strategy. The east of Jilin Province is the habitat of endangered Amur tiger (Panthera tigris altaica). The Chinese government has focused the monitoring on protecting the Amur tiger. However, little is known about Asiatic black bear (ABB, Ursus thibetanus) distribution, population dynamics in the wild, and protection awareness of local residents in Jilin Province, China. We conducted a integrative survey in mountain areas of eastern Jilin to determine ABB distribution. We explored the drivers of the distribution of ABB in Jilin using logstic regression, we further predicted the habitat suitability and potential suitable habitat of the ABB. Totally, we surveyed 112 grids (15 km × 15 km) from November 2015 to January 2019. Logistic regression analysis revealed that the main factors driving ABB distribution in Jilin are forest coverage, distance from protected areas, distance from main roads (railways and highways), and distance from water bodies. The results of questionnaire survey showed that the local residents’ understanding of ABB distribution is congruent with our field research. They believed that the number of ABBs has gradually increased in the past ten years. Nevertheless, the local residents have a negative attitude toward the ABBs, which may adversely affect efforts to protect them, possibly leading to more conflicts between humans and bears. Therefore, there is a need to consider ways to change the attitude of the locals through the strengthening of the protection propaganda and advocating management as being critical for the protection of ABBs. Our research provides a scientific basis for future conservation planning. We recommend taking local people’s attitude into consideration during conservation management strategy making to reduce human-bear conflicts and promote the coexistence of humans and bears.
Necroptosis-Related miRNA Biomarkers for Predicting Overall Survival Outcomes for Endometrial Cancer
Authors: Song Hualin , Li Tianjie , Sheng Jindong , Li Dan , Liu Xiangyu , Xiao Huiting , Yu Hu , Liu Wenxin , Wang Ke , Chen Ying
Published: June 2022

Endometrial cancer (EC) is the gynecological tumor with the highest incidence. In recent years, it has been proved that necroptosis is a method of cell death related to EC. However, the expression of necroptosis-related miRNA in EC and its correlation with prognosis still ill-defined. Use the Cancer Genome Atlas (TCGA) cohort to obtain prognostic data and related clinical data for ECs and normal endometrium tissues. In this study, we identified three necroptotic regulatory miRNAs that are necroptosis-related and survival-related miRNAs (DENSMs) between normal endometrium tissues and EC from 13 necroptosis-related miRNAs. The three DENSMs signature was built to develop prognostic model and classified all EC patients into a high or low risk group. EC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (p = 0.0242), and the risk score was found to be an independent prognosis factor for predicting the OS of EC patients (p = 0.0254) in multivariate Cox regression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed dephosphorylation, microtubule, protein serine/threonine kinase activity, PI3K-Akt signaling pathway and MAPK signaling pathway are closely related to it. In conclusion, the risk prediction model based on necroptosis-related miRNAs can effectively predict the prognosis of EC patients.
Phenotypic and Genetic Complexity in Pediatric Movement Disorders
Authors: Kim Min-Jee , Yum Mi-Sun , Seo Go Hun , Ko Tae-Sung , Lee Beom Hee
Published: June 2022

The complex and evolving nature of clinical phenotypes have made genetically diagnosing pediatric patients with movement disorders difficult. Here, we describe this diverse complexity in the clinical and genetic features of a pediatric cohort examined by whole-exome sequencing (WES) and demonstrate the clinical benefit of WES as a diagnostic tool in a pediatric cohort. We evaluated 75 patients with diverse single or combined movement phenomenologies using WES. WES identified 42 variants in 37 genes (56.0%). The detection rate was highest in patients with dystonia (11/13, 84.6%), followed by ataxia (21/38, 55.3%), myoclonus (3/6, 50.0%), unspecified dyskinesia (1/4, 25.0%), tremor (1/1, 100%), respectively. Most genetically diagnosed patients (90.5%) were affected by other neurologic or systemic manifestations; congenital hypotonia (66.7%), and epilepsy (42.9%) were the most common phenotypes. The genetic diagnosis changed the clinical management for five patients (6.7%), including treatments targeting molecular abnormalities, and other systemic surveillance such as cancer screening. Early application of WES yields a high diagnostic rate in pediatric movement disorders, which can overcome the limitations of the traditional phenotype-driven strategies due to the diverse phenotypic and genetic complexity. Additionally, this early genetic diagnosis expands the patient’s clinical spectrum and provides an opportunity for tailored treatment.
A Major Downregulation of Circulating microRNAs in Zika Acutely Infected Patients: Potential Implications in Innate and Adaptive Immune Response Signaling Pathways
Authors: Carvalho-Silva Ana Carolina , Da Silva Junior Almir Ribeiro , Rigaud Vagner Oliveira-Carvalho , Martins Waleska Kerllen , Coelho Verônica , Pfrimer Irmtraut Araci Hoffmann , Kalil Jorge , Fonseca Simone Gonçalves , Cunha-Neto Edecio , Ferreira Ludmila Rodrigues Pinto
Published: June 2022

Zika virus (ZIKV) is an arbovirus mainly transmitted by mosquitos of the genus Aedes. The first cases of ZIKV infection in South America occurred in Brazil in 2015. The infection in humans causes diverse symptoms from asymptomatic to a syndrome-like dengue infection with fever, arthralgia, and myalgia. Furthermore, ZIKV infection during pregnancy is associated with fetal microcephaly and neurological disorders. The identification of host molecular mechanisms responsible for the modulation of different signaling pathways in response to ZIKV is the first step to finding potential biomarkers and therapeutic targets and understanding disease outcomes. In the last decade, it has been shown that microRNAs (miRNAs) are important post-transcriptional regulators involved in virtually all cellular processes. miRNAs present in body fluids can not only serve as key biomarkers for diagnostics and prognosis of human disorders but also contribute to cellular signaling offering new insights into pathological mechanisms. Here, we describe for the first time ZIKV-induced changes in miRNA plasma levels in patients during the acute and recovery phases of infection. We observed that during ZIKV acute infection, among the dysregulated miRNAs (DMs), the majority is with decreased levels when compared to convalescent and control patients. We used systems biology tools to build and highlight biological interactions between miRNAs and their multiple direct and indirect target molecules. Among the 24 DMs identified in ZIKV + patients, miR-146, miR-125a-5p, miR-30-5p, and miR-142-3p were related to signaling pathways modulated during infection and immune response. The results presented here are an effort to open new vistas for the key roles of miRNAs during ZIKV infection.
Identification of CD8+ T Cell Related Biomarkers in Ovarian Cancer
Authors: Li Ling , Chen Dian , Luo Xiaolin , Wang Zhengkun , Yu Hanjie , Gao Weicheng , Zhong Weiqiang
Published: June 2022

Background: Immunotherapy is a promising strategy for ovarian cancer (OC), and this study aims to identify biomarkers related to CD8+ T cell infiltration to further discover the potential therapeutic target.

Methods: Three datasets with OC transcriptomic data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Two immunotherapy treated cohorts were obtained from the Single Cell Portal and Mariathasan’s study. The infiltration fraction of immune cells was quantified using three different algorithms, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and microenvironment cell populations counter (MCPcounter), and single-sample GSEA (ssGSEA). Weighted gene co-expression network analysis (WGCNA) was applied to identify the co-expression modules and related genes. The nonnegative matrix factorization (NMF) method was proposed for sample classification. The mutation analysis was conducted using the “maftools” R package. Key molecular markers with implications for prognosis were screened by univariate COX regression analysis and K-M survival analysis, which were further determined by the receiver operating characteristic (ROC) curve.

Results: A total of 313 candidate CD8+ T cell-related genes were identified by taking the intersection from the TCGA-OV and GSE140082 cohorts. The NMF clustering analysis suggested that patients in the TCGA-OV cohort were divided into two clusters and the Cluster 1 group showed a worse prognosis. In contrast, Cluster 2 had higher amounts of immune cell infiltration, elevated ssGSEA scores in immunotherapy, and a higher mutation burden. CSMD3, MACF1, PDE4DIP, and OBSCN were more frequently mutated in Cluster 1, while SYNE2 was more frequently mutated in Cluster 2. CD38 and CXCL13 were identified by univariate COX regression analysis and K-M survival analysis in the TCGA-OV cohort, which were further externally validated in GSE140082 and GSE32062. Of note, patients with lower CXCL13 expression showed a worse prognosis and the CR/PR group had a higher expression of CXCL13 in two immunotherapy treated cohorts.

Conclusion: OC patients with different CD8+ T cell infiltration had distinct clinical prognoses. CXCL13 might be a potential therapeutic target for the treatment of OC.
Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia
Authors: Peng Yu , Zheng Yu , Deng Zifeng , Zhang Shuju , Tan Yilan , Hu Zhengmao , Tao Lijuan , Luo Yulin
Published: June 2022

Background: Congenital cataract is one of the most common causes of blindness in children. A rapid and accurate genetic diagnosis benefit the patients in the pediatric department. The current study aims to identify the genetic defects in a congenital cataract patient without a family history.

Case presentation: A congenital cataract patient with microphthalmia and nystagmus was recruited for this study. Trio-based whole-exome sequencing revealed a de novo variant (c.394delG, p.V132Sfs*15) in CRYGC gene. According to the American College of Medical Genetics and Genomics (ACMG) criteria, the variant could be annontated as pathogenic.

Conclusion: Our findings provide new knowledge of the variant spectrum of CRYGC gene and are essential for understanding the heterogeneity of cataracts in the Chinese population.
Detection and Validation of Circular DNA Fragments Using Nanopore Sequencing
Authors: Tüns Alicia Isabell , Hartmann Till , Magin Simon , González Rocío Chamorro , Henssen Anton George , Rahmann Sven , Schramm Alexander , Köster Johannes
Published: June 2022

Occurrence of extra-chromosomal circular DNA is a phenomenon frequently observed in tumor cells, and the presence of such DNA has been recognized as a marker of adverse outcome across cancer types. We here describe a computational workflow for identification of DNA circles from long-read sequencing data. The workflow is implemented based on the Snakemake workflow management system. Its key step uses a graph-theoretic approach to identify putative circular fragments validated on simulated reads. We then demonstrate robustness of our approach using nanopore sequencing of selectively enriched circular DNA by highly sensitive and specific recovery of plasmids and the mitochondrial genome, which is the only circular DNA in normal human cells. Finally, we show that the workflow facilitates detection of larger circular DNA fragments containing extrachromosomal copies of the MYCN oncogene and the respective breakpoints, which is a potentially useful application in disease monitoring of several cancer types.
CNTN-1 Upregulation Induced by Low-Dose Cisplatin Promotes Malignant Progression of Lung Adenocarcinoma Cells via Activation of Epithelial-Mesenchymal Transition
Authors: Zhang Ruijie , Li Shengjin , Lan Jian , Li Changyi , Du Xianzhi , Dong Weijie , Yu Qian , Wang Daoxin
Published: June 2022

Tumor metastasis and invasion are the main impediments to lung adenocarcinoma successful treatment. Previous studies demonstrate that chemotherapeutic agents can elevate the malignancy of cancer cells other than their therapeutic effects. In this study, the effects of transient low-dose cisplatin treatment on the malignant development of lung adenocarcinoma cells (A549) were detected, and the underlying epigenetic mechanisms were investigated. The findings showed that A549 cells exhibited epithelial-mesenchymal transition (EMT)-like phenotype along with malignant progression under the transient low-dose cisplatin treatment. Meanwhile, low-dose cisplatin was found to induce contactin-1 (CNTN-1) upregulation in A549 cells. Subsequently, we found that further overexpressing CNTN-1 in A549 cells obviously activated the EMT process in vitro and in vivo, and caused malignant development of A549 cells in vitro. Taken together, we conclude that low-dose cisplatin can activate the EMT process and resulting malignant progression through upregulating CNTN-1 in A549 cells. The findings provided new evidence that a low concentration of chemotherapeutic agents could facilitate the malignancy of carcinoma cells via activating the EMT process other than their therapeutic effects.