bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of healthy lifestyles on the risk of hypertension, type 2 diabetes mellitus, and their comorbidity among subjects with dyslipidemia
Authors: Hu Peng , Zheng Murui , Duan Xueru , Zhou Huanning , Huang Jun , Lao Lixian , Zhao Yue , Li Yi , Xue Meng , Zhao Wenjing , Deng Hai , Liu Xudong
Published: September 2022

Background

Adherence to a healthy lifestyle could reduce the risk of hypertension and diabetes in general populations; however, whether the associations exist in subjects with dyslipidemia remains unclear. This study aimed to investigate the integrated effect of lifestyle factors on the risk of hypertension, type 2 diabetes mellitus (T2DM), and their comorbidity among subjects with dyslipidemia.

Methods

In total of 9,339 subjects with dyslipidemia were recruited from the baseline survey of the Guangzhou Heart Study. A questionnaire survey and medical examination were performed. The healthy lifestyle score (HLS) was derived from five factors: smoking, alcohol drinking, diet, body mass index, and leisure-time physical activity. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated by using the logistic regression model and the multinomial logistic regression after adjusting for confounders.

Results

The prevalence of hypertension, T2DM, and their comorbidity was 47.65, 16.02, and 10.10%, respectively. Subjects with a higher HLS were associated with a lower risk of hypertension, T2DM, and their comorbidity. In comparison to the subjects with 0–2 HLS, the adjusted ORs for subjects with five HLS was 0.48 (95% CI: 0.40–0.57) and 0.67 (95% CI: 0.54–0.84) for hypertension and T2DM. Compared with subjects with 0-2 HLS and neither hypertension nor T2DM, those with five HLS had a lower risk of suffering from only one disease (OR: 0.48, 95% CI: 0.40–0.57) and their comorbidity (OR: 0.35, 95% CI: 0.26–0.47).

Conclusions

The results suggest that the more kinds of healthy lifestyle, the lower the risk of hypertension, T2DM, and their comorbidity among subjects with dyslipidemia. Preventive strategies incorporating lifestyle factors may provide a more feasible approach for the prevention of main chronic diseases.
Circulating metabolites associated with tumor hypoxia and early response to treatment in bevacizumab-refractory glioblastoma after combined bevacizumab and evofosfamide
Authors: Lodi Alessia , Pandey Renu , Chiou Jennifer , Bhattacharya Ayon , Huang Shiliang , Pan Xingxin , Burgman Brandon , Yi S. Stephen , Tiziani Stefano , Brenner Andrew J.
Published: September 2022

Glioblastomas (GBM) are the most common and aggressive form of primary malignant brain tumor in the adult population, and, despite modern therapies, patients often develop recurrent disease, and the disease remains incurable with median survival below 2 years. Resistance to bevacizumab is driven by hypoxia in the tumor and evofosfamide is a hypoxia-activated prodrug, which we tested in a phase 2, dual center (University of Texas Health Science Center in San Antonio and Dana Farber Cancer Institute) clinical trial after bevacizumab failure. Tumor hypoxic volume was quantified by 18F-misonidazole PET. To identify circulating metabolic biomarkers of tumor hypoxia in patients, we used a high-resolution liquid chromatography-mass spectrometry-based approach to profile blood metabolites and their specific enantiomeric forms using untargeted approaches. Moreover, to evaluate early response to treatment, we characterized changes in circulating metabolite levels during treatment with combined bevacizumab and evofosfamide in recurrent GBM after bevacizumab failure. Gamma aminobutyric acid, and glutamic acid as well as its enantiomeric form D-glutamic acid all inversely correlated with tumor hypoxia. Intermediates of the serine synthesis pathway, which is known to be modulated by hypoxia, also correlated with tumor hypoxia (phosphoserine and serine). Moreover, following treatment, lactic acid was modulated by treatment, likely in response to a hypoxia mediated modulation of oxidative vs glycolytic metabolism. In summary, although our results require further validation in larger patients’ cohorts, we have identified candidate metabolic biomarkers that could evaluate the extent of tumor hypoxia and predict the benefit of combined bevacizumab and evofosfamide treatment in GBM following bevacizumab failure.
The emerging therapeutic target of dynamic and reversible N6-methyladenosine modification during cancer development
Authors: Liu Shougeng , Chen Sihong , Tang Chengfang , Zhao Yingxi , Cui Wei , Jia Lina , Wang Lihui
Published: September 2022

As a reversible and dynamic epigenetic modification, N6-methyladenosine (m6A) modification is ubiquitous in eukaryotic cells. m6A methylation is prevalent in almost all RNA metabolism processes that affect the fate of cells, including cancer development. As indicated by the available evidence, targeting m6A regulators may play a crucial role in tumor therapy and multidrug resistance. Currently, many questions remain uncovered. Here, we review recent studies on m6A modification in various aspects of tumor progression, tumor immunity, multidrug resistance, and therapeutic targets to provide new insight into the m6A methylation process.
An easy-to-use nomogram predicting overall survival of adult acute lymphoblastic leukemia
Authors: Liu Yu , Zheng Ruyue , Liu Yajun , Yang Lu , Li Tao , Li Yafei , Jiang Zhongxing , Liu Yanfang , Wang Chong , Wang Shujuan
Published: September 2022

Adult acute lymphoblastic leukemia (ALL) is heterogeneous both biologically and clinically. The outcomes of ALL have been improved with the application of children-like regimens and novel agents including immune therapy in young adults. The refractory to therapy and relapse of ALL have occurred in most adult cases. Factors affecting the prognosis of ALL include age and white blood cell (WBC) count at diagnosis. The clinical implications of genetic biomarkers, including chromosome translocation and gene mutation, have been explored in ALL. The interactions of these factors on the prediction of prognosis have not been evaluated in adult ALL. A prognostic model based on clinical and genetic abnormalities is necessary for clinical practice in the management of adult ALL. The newly diagnosed adult ALL patients were divided into the training and the validation cohort at 7:3 ratio. Factors associated with overall survival (OS) were assessed by univariate/multivariate Cox regression analyses and a signature score was assigned to each independent factor. A nomogram based on the signature score was developed and validated. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to assess the performance of the nomogram model. This study included a total of 229 newly diagnosed ALL patients. Five independent variables including age, WBC, bone marrow (BM) blasts, MLL rearrangement, and ICT gene mutations (carried any positive mutation of IKZF1, CREBBP and TP53) were identified as independent adverse factors for OS evaluated by the univariate, Kaplan-Meier survival and multivariate Cox regression analyses. A prognostic nomogram was built based on these factors. The areas under the ROC curve and calibration curve showed good accuracy between the predicted and observed values. The DCA curve showed that the performance of our model was superior to current risk factors. A nomogram was developed and validated based on the clinical and laboratory factors in newly diagnosed ALL patients. This model is effective to predict the overall survival of adult ALL. It is a simple and easy-to-use model that could efficiently predict the prognosis of adult ALL and is useful for decision making of treatment.
A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs
Authors: Villarreal-García Valeria , Estupiñan-Jiménez José Roberto , Vivas-Mejía Pablo E. , Gonzalez-Villasana Vianey , Vázquez-Guillén José Manuel , Reséndez-Pérez Diana
Published: September 2022

Breast cancer (BC) is the most common cancer in women worldwide. This highly heterogeneous disease is molecularly stratified into luminal A, luminal B, HER2, triple-negative/basal-like, and normal-like subtypes. An important aspect in BC progression is the activation of inflammatory processes. The activation of CD8+/Th1, NK, and M1 tumor associated macrophages (TAMs), leads to tumor destruction. In contrast, an anti-inflammatory response mediated by CD4+/Th2 and M2 TAMs will favor tumor progression. Inflammation also stimulates the production of inflammatory mediators like reactive oxygen species (ROS). In chronic inflammation, ROS activates oxidative stress and endothelial dysfunction. In cancer, ROS plays a dual role with anti-tumorigenic and pro-tumorigenic effects in cell signaling pathways that control proliferation, survival, apoptosis, and inflammation. MicroRNAs (miRNAs), which are known to be involved in BC progression and inflammation, can be regulated by ROS. At the same time, miRNAs regulate the expression of genes modulating oxidative stress. In this review, we will discuss the interplay between inflammation, ROS, and miRNAs as anticancer and tumor promoter molecules in BC. A clear understanding of the role of miRNAs in the regulation of ROS production and inflammation, may lead to new opportunities for therapy in BC.
Transcriptome analysis of childhood Guillain–Barré syndrome associated with supportive care
Authors: Hu Ke , Liu Wanli , Gan Yi , Huang Zhaoxuan
Published: September 2022

Childhood Guillain–Barré syndrome (GBS) is a rare neurological disease. Early diagnosis followed by precise treatment can reduce mortality. In this study, we collected two transcriptome data between GBS and controls from the publicly available databases (GEO dataset). We identified two distinct down-regulated genes (PTGDS and AR) in GBS by transcriptome analysis (n = 20). Based on the two distinct down-regulated genes in the GBS group, a two-gene diagnostic signature was developed. Moreover, gene expression analysis for the two-gene was performed on a patient with GBS before and after Supportive Care. RT–PCR results show that the expression of PTGDS increased after the patient was given supportive care. Therefore, PTGDS might be considered as a potential target for therapeutic target in GBS.
Analysis of non-retinopathy of prematurity (ROP)–related fundus hemorrhage in preterm infants in China
Authors: Yaoyao Sun , Kaixin Deng , Xiaoxin Li , Min Zhao , Yanrong Jiang , Hong Yin , Huijun Qi , Tong Qian , Dandan Linghu , Wenzhen Yu , Mingwei Zhao , Jianhong Liang
Published: September 2022

Objective

To determine the incidence of fundus hemorrhage (FH) not associated with retinopathy of prematurity (ROP) during ocular screening and report their clinical features, risk factors, therapies, and prognosis in a large population of premature newborns.

Methods

The medical records of all preterm newborns admitted to the Department of Ophthalmology, Peking University People's Hospital, Beijing, from January 1, 2016 through August 31, 2021 were retrospectively reviewed. Fundus examinations were carried out by experienced retinal experts. Examination under anesthesia was carried out in newborns with abnormal fundus including vitreous hemorrhage (VH) or retinal hemorrhage (RH) >2 disks' diameter by a Retcam 2 system. A lens-preserving vitrectomy was performed in infants requiring a vitrectomy. A comprehensive medical history was also recorded and analyzed.

Results

During the 5-year period, a total of 7,260 preterm babies were screened. There were 82 (1.13%) newborns and 104 (0.72) eyes with FH, including VH or RH.

Twelve (14.63%) newborns (16 eyes, 15.38%) had VH; 56 (68.29%) (74 eyes, 71.15%) had flame-shaped, superficial hemorrhages; six (7.31%) (6 eyes, 5.77%) had small, round, deep hemorrhages (<2 disk diameters in size); and eight (9.76%) (8 eyes, 7.69%) had large, round hemorrhages (>2 disk diameters). In all, there were 10 (12.20%) cases of intracranial hemorrhage. The mode of delivery was not found to be a significant factor in the occurrence of birth-related retinal hemorrhage (P = 0.22).

Six newborns (eyes) with large, round retinal hemorrhage at the posterior pole while the macular was not impacted and 11 cases (15 eyes) with vitreous hemorrhage were required to receive close follow-up with average follow-up time of 105 days. A lens-sparing vitreous surgery was conducted in three patients without any complications.

Conclusion

Preterm newborns with FH that are not caused by ROP are more likely to have superficial, peripheral hemorrhages. Vaginal delivery compression and forceps may be associated with hemorrhage. A lens-preserving vitrectomy is required and considered safe for dense FH involving the refractive media.
Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO
Authors: Bai Lu , Sun Siwen , Su Wenmei , Chen Chaoqun , Lv Yuesheng , Zhang Jinrui , Zhao Jinyao , Li Man , Qi Yangfan , Zhang Wenjing , Wang Yang
Published: September 2022

Hepatocellular carcinoma (HCC) is one of the most common primary cancers with limited therapeutic options. Melatonin, a neuroendocrine hormone produced primarily by the pineal gland, demonstrates an anti-cancer effect on a myriad of cancers including HCC. However, whether melatonin could suppress tumor growth through regulating RNA alternative splicing remains largely unknown. Here we demonstrated that melatonin could inhibit the growth of HCC. Mechanistically, melatonin induced transcriptional alterations of genes, which are involved in DNA replication, DNA metabolic process, DNA repair, response to wounding, steroid metabolic process, and extracellular matrix functions. Importantly, melatonin controlled numerous cancer-related RNA alternative splicing events, regulating mitotic cell cycle, microtubule-based process, kinase activity, DNA metabolic process, GTPase regulator activity functions. The regulatory effect of melatonin on alternative splicing is partially mediated by melatonin receptor MT1. Specifically, melatonin regulates the splicing of IKBKG (NEMO), an essential modulator of NF-κB. In brief, melatonin increased the production of the long isoform of NEMO-L with exon 5 inclusion, thereby inhibiting the growth of HepG2 cells. Collectively, our study provides a novel mechanism of melatonin in regulating RNA alternative splicing, and offers a new perspective for melatonin in the inhibition of cancer progression.
Vegetable glycerin e-cigarette aerosols cause airway inflammation and ion channel dysfunction
Authors: Kim Michael D. , Chung Samuel , Dennis John S. , Yoshida Makoto , Aguiar Carolina , Aller Sheyla P. , Mendes Eliana S. , Schmid Andreas , Sabater Juan , Baumlin Nathalie , Salathe Matthias
Published: September 2022

Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days. Markers of inflammation, including interleukin-6 (IL6), interleukin-8 (IL8) and matrix metalloproteinase-9 (MMP9) mRNAs, as well as MMP-9 activity and mucin 5AC (MUC5AC) expression levels, were also elevated in nasal samples from volunteers who vaped VG-containing e-liquids. In sheep, exposures to VG e-cig aerosols for five days increased mucus concentrations and MMP-9 activity in tracheal secretions and plasma levels of transforming growth factor-beta 1 (TGF-β1). In vitro exposure of HBECs to VG e-cig aerosols for five days decreased ciliary beating and increased mucus concentrations. VG e-cig aerosols also reduced CFTR function in HBECs, mechanistically by reducing membrane fluidity. Although VG e-cig aerosols did not increase MMP9 mRNA expression, expression levels of IL6, IL8, TGFB1, and MUC5AC mRNAs were significantly increased in HBECs after seven days of exposure. Thus, VG e-cig aerosols can potentially cause harm in the airway by inducing inflammation and ion channel dysfunction with consequent mucus hyperconcentration.
Idiosyncratic liver injury induced by bolus combination treatment with emodin and 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside in rats
Authors: Li Dan , Lyu Yuanfeng , Song Qianbo , Lai Yuen Sze , Zuo Zhong
Published: September 2022

Polygoni Multiflori Radix (PMR) is a commonly used traditional Chinese medicine in clinical practice, while adverse effects of hepatotoxicity related to PMR have been frequently reported. The clinical case reports indicated that PMR hepatotoxicity could occur under both overdose medication/long-term exposure and low doses with short-duration (idiosyncratic) conditions. The combination treatment with emodin and 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG), two major PMR components, was reported to contribute to PMR hepatotoxicity after long-term treatment. However, the role of the combination treatment of these two components in PMR-induced idiosyncratic liver injury has not been clearly clarified. In this study, the LPS-mediated inflammatory stress model rats were adopted to explore the idiosyncratic liver injury induced by the bolus combination treatment with emodin and TSG. After a bolus oral administration with TSG (165 mg/kg), emodin (5 mg/kg) or their combination in both normal and LPS-mediated inflammatory stress model rats, the systemic/hepatic concentrations of emodin, emodin glucuronides and bile acids were determined; the hepatotoxicity assessments were conducted via monitoring histopathological changes and liver injury biomarkers (ALT and AST). Moreover, the protein expressions of bile acid homeostasis- and apoptosis-related proteins were examined. No liver damage was observed in the normal rats after a bolus dose with the individual or combination treatment, while the bolus combination treatment with emodin and TSG induced liver injury in the LPS-mediated inflammatory stress model rats, evidenced by the elevated plasma levels of alanine aminotransferase (∼66%) and aspartate aminotransferase (∼72%) accompanied by severe inflammatory cell infiltration and apoptotic hepatocytes in liver tissue. Moreover, such combination treatment at a bolus dose in the LPS-mediated inflammatory stress model rats could significantly elevate the hepatic TBA levels by about 45% via up-regulating the hepatic protein expression levels of bile acid synthesis enzymes and inhibiting that of bile acid efflux transporters and the expression levels of apoptosis-related proteins. Our study for the first time proved the major contribution of the combination treatment with emodin and TSG in PMR-induced idiosyncratic liver injury.
SGLT2 inhibitors suppress epithelial–mesenchymal transition in podocytes under diabetic conditions via downregulating the IGF1R/PI3K pathway
Authors: Guo Ruixue , Wang Peipei , Zheng Xuejun , Cui Wen , Shang Jin , Zhao Zhanzheng
Published: September 2022

Loss of podocyte is a characteristic pathological change of diabetic nephropathy (DN) which is associated with increased proteinuria. Many studies have shown that novel inhibitors of sodium–glucose cotransporter 2 (SGLT2-is), such as dapagliflozin, exert nephroprotective effect on delaying DN progression. However, the mechanisms underlying SGLT2-associated podocyte injury are still not fully elucidated. Here, we generated streptozotocin-induced DN models and treated them with dapagliflozin to explore the possible mechanisms underlying SGLT2 regulation. Compared to mice with DN, dapagliflozin-treated mice exhibited remission of pathological lesions, including glomerular sclerosis, thickening of the glomerular basement membrane (GBM), podocyte injury in the glomeruli, and decreased nephrotoxin levels accompanied by decreased SGLT2 expression. The mRNA expression profiles of these treated mice revealed the significance of the insulin-like growth factor-1 receptor (IGF1R)/PI3K regulatory axis in glomerular injury. KEGG analysis confirmed that the phosphatidylinositol signaling system and insulin signaling pathway were enriched. Western blotting showed that SGLT2-is inhibited the increase of mesenchymal markers (α-SMA, SNAI-1, and ZEB2) and the loss of podocyte markers (nephrin and E-cad). Additionally, SGLT2, IGF1R, phosphorylated PI3K, α-SMA, SNAI-1, and ZEB2 protein levels were increased in high glucose-stimulated human podocytes (HPC) and significantly decreased in dapagliflozin-treated (50 nM and 100 nM) or OSI-906-treated (inhibitor of IGF1R, 60 nM) groups. However, the use of both inhibitors did not enhance this protective effect. Next, we analyzed urine and plasma samples from a cohort consisting of 13 healthy people and 19 DN patients who were administered with (n = 9) or without (n = 10) SGLT2 inhibitors. ELISA results showed decreased circulating levels of IGF1 and IGF2 in SGLT2-is-treated DN patients compared with DN patients. Taken together, our study reported the key role of SGLT2/IGF1R/PI3K signaling in regulating podocyte epithelial–mesenchymal transition (EMT). Modulating IGF1R expression may be a novel approach for DN therapy.
Comprehensive analysis for cellular senescence-related immunogenic characteristics and immunotherapy prediction of acute myeloid leukemia
Authors: Mao Yan , Xu Jinwen , Xu Xuejiao , Qiu Jiayun , Hu Zhengyun , Jiang Feng , Zhou Guoping
Published: September 2022

In malignancies, cellular senescence is critical for carcinogenesis, development, and immunological regulation. Patients with acute myeloid leukemia (AML) have not investigated a reliable cellular senescence-associated profile and its significance in outcomes and therapeutic response. Cellular senescence-related genes were acquired from the CellAge database, while AML data were obtained from the GEO and TCGA databases. The TCGA-AML group served as a training set to construct a prognostic risk score signature, while the GSE71014 set was used as a testing set to validate the accuracy of the signature. Through exploring the expression profiles of cellular senescence-related genes (SRGs) in AML patients, we used Lasso and Cox regression analysis to establish the SRG-based signature (SRGS), which was validated as an independent prognostic predictor for AML patients via clinical correlation. Survival analysis showed that AML patients in the low-risk score group had a longer survival time. Tumor immune infiltration and functional enrichment analysis demonstrated that AML patients with low-risk scores had higher immune infiltration and active immune-related pathways. Meanwhile, drug sensitivity analysis and the TIDE algorithm showed that the low-risk score group was more susceptible to chemotherapy and immunotherapy. Cell line analysis in vitro further confirmed that the SRGs in the proposed signature played roles in the susceptibility to cytarabine and YM155. Our results indicated that SRGS, which regulates the immunological microenvironment, is a reliable predictor of the clinical outcome and immunotherapeutic response in AML.
Influenza vaccination and risk of atrial fibrillation in patients with gout: A nationwide population-based cohort study
Authors: Chen Chun-Chao , Chiu Chun-Chih , Chen Nai-Hsuan , Yang Tsung-Yeh , Lin Cheng-Hsin , Fang Yu-Ann , Jian William , Lei Meng-Huan , Yeh Hsien-Tang , Hsu Min-Huei , Hao Wen-Rui , Liu Ju-Chi
Published: September 2022

Objective: Although influenza vaccination reduces the risk of atrial fibrillation (AF), its protective effect in patients with gout remains unclear. The present study aimed to evaluate the protective effect of influenza vaccination in patients with gout.

Methods: A total of 26,243 patients with gout, aged 55 and older, were enrolled from the National Health Insurance Research Database (NHIRD) between 1 January 2001, and 31 December 2012. The patients were divided into vaccinated (n = 13,201) and unvaccinated groups (n = 13,042). After adjusting comorbidities, medications, sociodemographic characteristics, the risk of AF during follow-up period was analyzed.

Results: In influenza, non-influenza seasons and all seasons, the risk of AF was significantly lower in vaccinated than in unvaccinated patients (Adjust hazard ratio [aHR]: 0.59, 95% confidence interval [CI]: 0.50–0.68; aHR: 0.50, 95% CI: 0.42–0.63; aHR: 0.55, 95% CI: 0.49–0.62, respectively). In addition, the risk of AF significantly decreased with increased influenza vaccination (aHR: 0.85, 95% CI: 0.69–1.04; aHR: 0.72, 95% CI: 0.60–0.87; aHR: 0.40, 95% CI: 0.33–0.49, after first, 2–3 times, and ≥4 times of vaccination, respectively). Furthermore, sensitivity analysis indicated that the risk of AF significantly decreased after influenza vaccination for patients with different sexes, medication histories, and comorbidities.

Conclusions: Influenza vaccination is associated with a lower risk of AF in patients with gout. This potentially protective effect seems to depend on the dose administered.
Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling
Authors: Song Sang-Hoon , Jang Won-Jun , Jang Eun Young , Kim Oc-Hee , Kim Haesoo , Son Taekwon , Choi Dong-Young , Lee Sooyeun , Jeong Chul-Ho
Published: September 2022

MicroRNA (miRNA)-mediated striatal gene regulation may play an important role in methamphetamine (METH) addiction. This study aimed to identify changes in novel miRNAs and their target genes during METH self-administration and investigate their roles in METH-induced locomotion. RNA sequencing analysis revealed that mir-183-5p was upregulated in the striatum of METH self-administered rats, and target gene prediction revealed that the glucocorticoid receptor (GR) gene, Nr3c1, was a potential target gene for mir-183-5p. We confirmed that single and repeated METH administrations increased METH-induced locomotion and plasma corticosterone levels in rats. Additionally, increased miR-185-5p expression and decreased GR gene expression were observed only in the repeated-METH-injection group but not in the single-injection group. We then investigated the effects of miR-183-5p on METH-induced locomotion using a miR-183-5p mimic and inhibitor. Injection of a mir-183-5p mimic in the striatum of rats attenuated METH-induced locomotion, whereas injection of a miR-183-5p inhibitor enhanced the locomotor activity in METH-administered rats. Furthermore, the miR-183-5p mimic reduced the phosphorylation of tyrosine hydroxylase (TH) whereas the inhibitor increased it. Taken together, these results indicate that repeated METH injections increase striatal miR-183-5p expression and regulate METH-induced locomotion by regulating GR expression in rats, thereby suggesting a potential role of miR-183-5p as a novel regulator of METH-induced locomotion.
Experimental characterization of diffuse speckle pulsatile flowmetry system
Authors: Choo Tristan Wen Jie , Zhang Ruochong , Bi Renzhe , Olivo Malini
Published: September 2022

The recently developed Diffuse Speckle Pulsatile Flowmetry (DSPF) technique offers high measurement rates of around 300 Hz for non-invasive blood flow measurement of blood flow in deep tissue (up to a depth of approximately 15 mm), showing promising potential for the monitoring of various pathologies associated with abnormal blood flow. The effects of various parameters associated with this technique such as speckle size and exposure time on the measured flow readings, however, have yet to be studied. In this work, we examine these relationships experimentally, observing that the number of pixels per speckle (a measure of speckle size) and exposure time have a strong inverse relationship and a positive relationship respectively with the measured DSPF readings in no-flow setups using both static single light scattering and multiple light scattering mediums. We also studied how the sensitivity of DSPF readings to flow is affected by these parameters, finding that the number of pixels per speckle and exposure time have an inverse relationship and strong positive linear relationship respectively with the gradient of the regression line between the actual and measured flow rates in a dynamic setup using a tissue-mimicking flow phantom. It is hoped that these results would enable researchers using the DSPF technique to select and utilize the most optimized settings for their specific use applications.
Effective magnetic monopole mechanism for localized electron pairing in HTS
Authors: Diamantini M. C. , Trugenberger C. A. , Vinokur V. M.
Published: September 2022

The mechanism responsible for spatially localized strong coupling electron pairing characteristic of high-temperature superconductors (HTS) remains elusive and is a subject of hot debate. Here we propose a new HTS pairing mechanism which is the binding of two electrons residing in adjacent conducting planes of layered HTS materials by effective magnetic monopoles forming between these planes. The pairs localized near the monopoles form real-space seeds for superconducting droplets and strong coupling is due to the topological Dirac quantization condition. The pairing occurs well above the superconducting transition temperature Tc. Localized electron pairing around effective monopoles promotes, upon cooling, the formation of superconducting droplets connected by Josephson links. Global superconductivity arises when strongly coupled granules form an infinite cluster, and global superconducting phase coherence sets in. The resulting Tc is estimated to fall in the range from hundred to thousand Kelvins. Our findings pave the way for tailoring materials with elevated superconducting transition temperatures.
Diet and exercise interventions reduce serum asprosin and the corresponding hypothalamic– pituitary–gonad-axis dysfunction in obese men
Authors: Yao Tingting , Song Chenglin , Yu Yajie , Cheng Yang , Lu Hongyan , Li Jing , Yang Yang , Tang Donghui , Yi Xuejie
Published: September 2022

Background: Asprosin (ASP) is a recently discovered adipocyte factor that participates in glucose metabolism and inflammatory reactions. Recent findings suggest that it may be involved in the regulation of sex hormone secretion in the hypothalamic-pituitary-gonad (HPG) axis, but no studies have been reported in related populations. The purpose of this study was to evaluate the changes in serum ASP levels in healthy men and obese men, as well as before and after exercise weight loss, and to investigate male hypogonadism, insulin resistance, inflammatory response, and relationships induced by ASP and obesity.

Methods: Thirty-eight young male volunteers were recruited and divided into a normal group (n = 20) and an obese group (n = 18) according to their body mass index. Fourteen of the obese men underwent a 14-week exercise and diet intervention (first 8 weeks of aerobic exercise at 60%–70% HRmax for 30–50 min/4 days a week). Beginning at week 9, the intensity was increased to 75% HRmax. Participants in the obese groups maintained a calorie-restricted diet throughout the study period.

Results: Serum ASP levels in the obese group were significantly higher than those in the normal group, and serum gonadotropin-releasing hormone (GnRh), luteinizing hormone (LH), and testosterone (T) levels were decreased. After 14 weeks of exercise and diet intervention, serum ASP decreased significantly, the levels of body weight, lean body weight, body fat rate, fasting insulin (FINS), homeostatic model assessment for insulin resistance, TNF-α, IL-6, and IL-1β decreased significantly, and the serum GnRH, LH, and T levels increased significantly. ASP was positively correlated with body weight, body fat percentage, FINS, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β and negatively correlated with relative lean body weight and serum LH and T levels.

Conclusion: The serum ASP levels were increased in obese men compared with those of normal weight individuals, resulting in a chronic inflammatory reaction, high serum insulin, and HPG axis injury. Fourteen weeks of exercise and diet intervention effectively alleviated this phenomenon. It has been speculated that ASP might regulate male reproductive function by regulating the inflammatory response and insulin sensitivity.
A high-throughput drug discovery pipeline to optimize kidney normothermic machine perfusion
Authors: Hofmann Smilla , Grahammer Florian , Edenhofer Ilka , Puelles Victor G. , Huber Tobias B. , Czogalla Jan
Published: September 2022

Kidney transplantation is the only definitive therapy for end-stage kidney disease. The shortage of organs for transplantation is the main limitation of this life-saving treatment. Normothermic machine perfusion (NMP) is a novel preservation technique with the potential to increase the number of transplantable kidneys through reducing delayed graft function and organ evaluation under physiological conditions. To date, the cellular effects and possible pharmacological interventions during machine perfusion are incompletely understood. A major limitation is the technically complex, time-consuming, and small-scale replication of NMP in rodent models. To overcome this, we developed a 3D-printed, high throughput ex-vivo mouse kidney slice incubator (KSI) mimicking mouse kidney NMP by working under closely resembling conditions. KSI significantly reduced the time per experiment and increased the sample throughput (theoretical: 54 incubations with n = 500/day). The model recapitulated the cellular responses during NMP, namely increased endoplasmic reticulum stress (ER stress). Using KSI, five pharmacological interventions against ER stress taken from the literature were tested. While four were ineffective and excluded, one, β-Nicotinamide-adenine-dinucleotide (NADH), ameliorated ER stress significantly during KSI. The test of NADH in mouse kidney NMP replicated the positive effects against ER stress. This suggests that testing the addition of NADH during clinical kidney NMP might be warranted.
Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies
Authors: Kawana Masataka , Spudich James A. , Ruppel Kathleen M.
Published: September 2022

Hypertrophic cardiomyopathy (HCM) affects more than 1 in 500 people in the general population with an extensive burden of morbidity in the form of arrhythmia, heart failure, and sudden death. More than 25 years since the discovery of the genetic underpinnings of HCM, the field has unveiled significant insights into the primary effects of these genetic mutations, especially for the myosin heavy chain gene, which is one of the most commonly mutated genes. Our group has studied the molecular effects of HCM mutations on human β-cardiac myosin heavy chain using state-of-the-art biochemical and biophysical tools for the past 10 years, combining insights from clinical genetics and structural analyses of cardiac myosin. The overarching hypothesis is that HCM-causing mutations in sarcomere proteins cause hypercontractility at the sarcomere level, and we have shown that an increase in the number of myosin molecules available for interaction with actin is a primary driver. Recently, two pharmaceutical companies have developed small molecule inhibitors of human cardiac myosin to counteract the molecular consequences of HCM pathogenesis. One of these inhibitors (mavacamten) has recently been approved by the FDA after completing a successful phase III trial in HCM patients, and the other (aficamten) is currently being evaluated in a phase III trial. Myosin inhibitors will be the first class of medication used to treat HCM that has both robust clinical trial evidence of efficacy and that targets the fundamental mechanism of HCM pathogenesis. The success of myosin inhibitors in HCM opens the door to finding other new drugs that target the sarcomere directly, as we learn more about the genetics and fundamental mechanisms of this disease.
Transcriptome analysis of megalurothrips usitatus (Bagnall) identifies olfactory genes with ligands binding characteristics of MusiOBP1 and MusiCSP1
Authors: Li Zhaoyang , Chen Weiyi , Wang Xiaoshuang , Sang Wen , Pan Huipeng , Ali Shaukat , Tang Liangde , Wu Jianhui
Published: September 2022

The olfactory system is an important component of insect behavior and is vital for survival and reproduction. However, the genomic characterization and molecular basis of the olfactory response of Megalurothrips usitatus remain relatively unknown. RNA sequencing-built developmental transcriptomes of nymphs, pupae, and adult M. usitatus were examined in order to establish the sequence-based background of M. usitatus olfactory responses. A total of 56,669 unigenes were annotated using GO, NR, Pfam, eggNOG, SwissProt, and KEGG. The number of differentially expressed genes between pupae and nymphs, males and nymphs, and females and nymphs were 10,498, 9,235, and 10,964, respectively. One odorant-binding protein (MusiOBP1) and one chemosensory protein (MusiCSP1) were selected from the transcriptome, and their full-length sequences were obtained using RACE PCR. The relative expression of MusiOBP1 was the highest in primordial females, whereas the relative expression of MusiCSP1 was the highest in primordial pupae. The strongest binding ability to the odor-binding protein MusiOBP1 was observed for β-citronellol. 3-Hydroxy-2-methyl-4-pyrone showed the strongest binding affinity to MusiCSP1. Our analysis suggests that MusiOBP1 and MusiCSP1 may play significant roles in mediating M. usitatus host recognition. This research will improve our knowledge of odorant-binding proteins and chemosensory proteins, which will in turn improve our understanding of insect olfactory systems.
Integrated analysis of multi-omics and fine-mapping reveals a candidate gene regulating pericarp color and flavonoids accumulation in wax gourd (Benincasa hispida)
Authors: Xie Lingling , Wang Jin , Liu Feng , Zhou Huoqiang , Chen Ying , Pan Luzhao , Xiao Wei , Luo Yin , Mi Baobin , Sun Xiaowu , Xiong Cheng
Published: September 2022

Wax gourd (Benincasa hispida), a popular fruit of the Cucurbitaceae (cucurbits) family, contains many nutrients with health benefits and is widely grown in China and other tropical areas. In this study, a wax gourd mutant hfc12 with light-color pericarp was obtained through ethane methylsulfonate (EMS) mutagenesis. Integrative analysis of the metabolome and transcriptome identified 31 differentially accumulated flavonoids (DAFs; flavonoids or flavonoid glycosides) and 828 differentially expressed genes (DEGs) between the hfc12 mutant and wild-type ‘BWT’. Furthermore, BSA-seq and kompetitive allele specific PCR (KASP) analysis suggested that the light-color pericarp and higher flavonoid content was controlled by a single gene BhiPRR6 (Bhi12M000742), a typical two-component system (TCS) pseudo-response regulator (PRR). Genetic analysis detected only one nonsynonymous mutation (C-T) in the second exon region of the BhiPRR6. Weighted correlation network analysis (WGCNA) identified the downstream target genes of BhiPRR6, probably regulated by light and were intermediated in the regulatory enzyme reaction of flavonoid biosynthetic pathway. Thus, these results speculated that the transcription factor BhiPRR6, interacting with multiple genes, regulates the absorption of light signals and thereby changes the pericarp color and synthesis of flavonoids in wax gourd.
Response of leaf stoichiometry of Potentilla anserina to elevation in China's Qilian Mountains
Authors: Zhang Xiaofang , Feng Qi , Cao Jianjun , Biswas Asim , Su Haohai , Liu Wei , Qin Yanyan , Zhu Meng
Published: September 2022

Plants adapt to changes in elevation by regulating their leaf ecological stoichiometry.Potentilla anserinaL. that grows rapidly under poor or even bare soil conditions has become an important ground cover plant for ecological restoration. However, its leaf ecological stoichiometry has been given little attention, resulting in an insufficient understanding of its environmental adaptability and growth strategies. The objective of this study was to compare the leaf stoichiometry ofP. anserinaat different elevations (2,400, 2,600, 2,800, 3,000, 3,200, 3,500, and 3,800 m) in the middle eastern part of Qilian Mountains. With an increase in elevation, leaf carbon concentration [(C)leaf] significantly decreased, with the maximum value of 446.04 g·kg−1(2,400 m) and the minimum value of 396.78 g·kg−1(3,500 m). Leaf nitrogen concentration [(N)leaf] also increased with an increase in elevation, and its maximum and minimum values were 37.57 g·kg−1(3,500 m) and 23.71 g·kg−1(2,800 m), respectively. Leaf phosphorus concentration [(P)leaf] was the highest (2.79 g·kg−1) at 2,400 m and the lowest (0.91 g·kg−1) at 2,800 m. The [C]leaf/[N]leafdecreased with an increase in elevation, while [N]leaf/[P]leafshowed an opposite trend. The mean annual temperature, mean annual precipitation, soil pH, organic carbon, nitrogen, and phosphorus at different elevations mainly affected [C]leaf, [N]leaf, and [P]leaf. The growth ofP. anserinain the study area was mainly limited by P, and this limitation was stronger with increased elevation. Progressively reducing P loss at high elevation is of great significance to the survival ofP. anserinain this specific region.
Rice cellulose synthase-like protein OsCSLD4 coordinates the trade-off between plant growth and defense
Authors: Liu Xiong , Yin Zhongliang , Wang Yubo , Cao Sai , Yao Wei , Liu Jinling , Lu Xuedan , Wang Feng , Zhang Guilian , Xiao Yunhua , Tang Wenbang , Deng Huabing
Published: September 2022

Plant cell wall is a complex and changeable structure, which is very important for plant growth and development. It is clear that cell wall polysaccharide synthases have critical functions in rice growth and abiotic stress, yet their role in plant response to pathogen invasion is poorly understood. Here, we describe a dwarf and narrowed leaf in Hejiang 19 (dnl19) mutant in rice, which shows multiple growth defects such as reduced plant height, enlarged lamina joint angle, curled leaf morphology, and a decrease in panicle length and seed setting. MutMap analysis, genetic complementation and gene knockout mutant show that cellulose synthase-like D4 (OsCSLD4) is the causal gene for DNL19. Loss function of OsCSLD4 leads to a constitutive activation of defense response in rice. After inoculation with rice blast and bacterial blight, dnl19 displays an enhanced disease resistance. Widely targeted metabolomics analysis reveals that disruption of OsCSLD4 in dnl19 resulted in significant increase of L-valine, L-asparagine, L-histidine, L-alanine, gentisic acid, but significant decrease of L-aspartic acid, malic acid, 6-phosphogluconic acid, glucose 6-phosphate, galactose 1-phosphate, gluconic acid, D-aspartic acid. Collectively, our data reveals the importance of OsCSLD4 in balancing the trade-off between rice growth and defense.
Combined physiological and transcriptome analysis revealed the response mechanism of Pogostemon cablin roots to p-hydroxybenzoic acid
Authors: Yan Wuping , Cao Shijia , Liu Xiaofeng , Yao Guanglong , Yu Jing , Zhang Junfeng , Bian Tengfei , Yu Wengang , Wu Yougen
Published: September 2022

Pogostemon cablin (patchouli) cultivation is challenged by serious soil sickness, of which autotoxins accumulation is a major cause. p-hydroxybenzoic acid (p-HBA) is one of the main autotoxins of patchouli. However, the molecular mechanism underlying the response of patchouli to p-HBA remains unclear. In this study, RNA-sequencing combined with physiological analysis was used to monitor the dynamic transcriptomic and physiological changes in patchouli seedlings 0, 6, 12, 24, 48, and 96 h after p-HBA treatment. p-HBA stress inhibited root biomass accumulation, induced excessive hydrogen peroxide accumulation and lipid peroxidation, and activated most antioxidant enzymes. Compared with that of the control, the osmotic adjustment substance content was elevated with treatment. Subsequently, 15,532, 8,217, 8,946, 2,489, and 5,843 differentially expressed genes (DEGs) at 6, 12, 24, 48, and 96 h after p-HBA treatment, respectively, were identified in patchouli roots. GO functional enrichment analysis showed that the DEGs were enriched mainly in plasma membrane, defense response, response to chitin, DNA-binding transcription factor activity and abscisic acid-activated signaling pathway. The upregulated genes were involved in glycolysis/gluconeogenesis, cysteine and methionine metabolism, starch and sucrose metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. Genes associated with MAPK signaling pathway-plant, plant-pathogen interaction, plant hormone signal transduction were downregulated with p-HBA treatment. These pathways are related to root browning and rotting, leading to plant death.
Developing a mechanism of construction project manager’s emotional intelligence on project success: A grounded theory research based in China
Authors: Zhang Qi , Hao Shengyue
Published: September 2022

A project manager’s emotional intelligence (EI) is essential to project success. However, the mechanism in this cause and effect remains a black box in extant literature. China is now the world’s largest construction market, and figuring out the mechanism of construction project manager’s (CPM’s) EI on project success is meaningful for developing the global construction market. This study conducted an in-depth interview with 24 CPMs with more than 5-year experience in construction project management. The grounded theory was employed to profile the application of CPM’s EI and to build the multilevel mechanism that explains the influence of CPM’s EI on project success. The mechanism framework conforms to the existed input–process–output (IPO) theory. It consists of a team-level mechanism (including the positive team atmosphere, shared vision, and team cohesion) and an individual-level mechanism (i.e., organizational citizenship behavior directed at the organization, perceived supervisor support, trust in leader, and subordinate’s psychological and emotional health). This study further proposed that the effect of this mechanism does not work immediately but develops with time passing. Implications for further research and project management practice are discussed in the end.
Environmental preferences of adolescents within a low ecological footprint country
Authors: Bogner Franz X. , Suarez Bosque Rafael
Published: September 2022

As Cuba achieves one of the lowest per capita ecological footprints in the world, the country’s overshoot day was on 1 December 2019, while some European countries already reach this limit in February (e.g., Luxembourg), monitoring the environmental preferences of the Cuban younger generation may offer valuable behavioral or pedagogical insights into such a society. As accepted standardized measures exist in the scales of 2-Major Environmental Values (2-MEV) and the General Ecological Behavior (GEB), both measures are following the necessary psychometric requirement, as they have the unique advantage of repeated independent confirmation (and thus provide an external validity). These captured 40 items of reported behavior originating in six subscales that total in a single main cover score. The first one (2-MEV) monitors individual biocentric and anthropocentric preferences with a 20 item-set by relying upon these two higher-order factors of “Preservation” (PRE) and “Utilization” (UTL). Although many language versions already exist (33 in the case of the 2-MEV) for verifying validities and reliabilities of both scales, a country such as Cuba may affirm that this is due to expected cultural differences as well as their exceptionally low global footprint. Additionally, neither the individual connectedness with nature nor the diurnal preferences within the linear structural model showed a substantial relationship to PRE or UTL. Nevertheless, all the regression scores follow the expected positive or negative directions, albeit not all the fit scores turned out as satisfactorily. Apparently, the applied measures secure a good basis for measuring the attitudinal and behavioral framework, but will need further fine tuning to completely monitor the environmental preferences of Cuban adolescents.