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Abstract Urinary tract obstruction during renal development leads to inflammation, leukocyte infiltration, tubular cell death, and interstitial fibrosis. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, produced mainly by monocytes/macrophages and regulatory T-cells. IL-10 inhibits innate and adaptive immune responses. IL-10 has a protective role in the adult model of obstructive uropathy. However, its role in neonatal obstructive uropathy is still unclear which led us to study the role of IL-10 in neonatal mice with unilateral ureteral obstruction (UUO). UUO serves as a model for congenital obstructive nephropathies, a leading cause of kidney failure in children. Newborn Il-10 −/− and C57BL/6 wildtype-mice (WT) were subjected to complete UUO or sham-operation on the 2nd day of life. Neonatal kidneys were harvested at day 3, 7, and 14 of life and analyzed for different leukocyte subpopulations by FACS, for cytokines and chemokines by Luminex assay and ELISA, and for inflammation, programmed cell death, and fibrosis by immunohistochemistry and western blot. Compared to WT mice, Il-10 −/− mice showed reduced infiltration of neutrophils, CD11bhi cells, conventional type 1 dendritic cells, and T-cells following UUO. Il-10 −/− mice with UUO also showed a reduction in pro-inflammatory cytokine and chemokine release compared to WT with UUO, mainly of IP-10, IL-1α, MIP-2α and IL-17A. In addition, Il-10 −/− mice showed less necroptosis after UUO while the rate of apoptosis was not different. Finally, α-SMA and collagen abundance as readout for fibrosis were similar in Il-10 −/− and WT with UUO. Surprisingly and in contrast to adult Il-10 −/− mice undergoing UUO, neonatal Il-10 −/− mice with UUO showed a reduced inflammatory response compared to respective WT control mice with UUO. Notably, long term changes such as renal fibrosis were not different between neonatal Il-10 −/− and neonatal WT mice with UUO suggesting that IL-10 signaling is different in neonates and adults with UUO.

For decades, the evolutionary role of melanism in reptiles has been highly debated. According to the thermal melanism hypothesis, melanistic phenotypes should provide thermal advantages, thus positively impacting various biological aspects of these individuals. Nevertheless, these benefits seem to be countered by environmental constraints and predatory pressure. Here, we mapped for the first time the distribution of the melanistic phenotypes in the highly polymorphic asp viper (Vipera aspis). We focused our research effort on the Italian peninsula, where this species reaches its highest level of taxonomic diversity with three currently described subspecies. Furthermore, we investigated via bioclimatic niche modelling, the influence of a wide array of bioclimatic variables on the distribution of melanism in Italian asp vipers. In general, our results seem to support the implications of the thermal melanism hypothesis, highlighting the central influence of mean annual temperature and elevation on the geographic distribution of melanistic V. aspis. At the finest scale, our analyses have highlighted a distinction in bioclimatic niches among the three assessed subspecies. However, further fine-scale investigations are needed in order to exclude the potential influence of latitude and elevation on the observed the intersubspecific bioclimatic niche segregation pattern.

Educational institutions are transitioning their learning modalities to flexible learning from remote education; educators and staff continuously encounter ambiguous work demands that negatively affect their well-being. Literature indicates the influence of autonomy support, psychological capital, work engagement, and economic factors (i.e., financial preparedness and job insecurity) on well-being. We propose that social, psychological, work, and economic factors influence the well-being of university educators and staff. 315 employees voluntarily completed the autonomy support, work engagement, hope, self-efficacy, job insecurity, and financial preparedness scales. We used IBM SPSS Amos for the confirmatory factor analysis and structural equation modeling. Five separate models were conducted to test the research objective. Results indicate good to excellent model fit indices for the research scales and structural model. We also found that self-efficacy, work engagement, hope, and financial preparedness during emergencies positively predict well-being, while job insecurity is detrimental. Our findings could serve as a basis for mental health programs to address the mental issues of educators and staff.

Short-term memory is implicated in a range of cognitive abilities and is critical for understanding primate cognitive evolution. To investigate the effects of phylogeny, ecology and sociality on short-term memory, we tested the largest and most diverse primate sample to date (421 non-human primates across 41 species) in an experimental delayed-response task. Our results confirm previous findings that longer delays decrease memory performance across species and taxa. Our analyses demonstrate a considerable contribution of phylogeny over ecological and social factors on the distribution of short-term memory performance in primates; closely related species had more similar short-term memory abilities. Overall, individuals in the branch of Hominoidea performed better compared to Cercopithecoidea, who in turn performed above Platyrrhini and Strepsirrhini. Interdependencies between phylogeny and socioecology of a given species presented an obstacle to disentangling the effects of each of these factors on the evolution of short-term memory capacity. However, this study offers an important step forward in understanding the interspecies and individual variation in short-term memory ability by providing the first phylogenetic reconstruction of this trait’s evolutionary history. The dataset constitutes a unique resource for studying the evolution of primate cognition and the role of short-term memory in other cognitive abilities.

Human evolutionary success is often argued to be rooted in specialized social skills and motivations that result in more prosocial, rational and cooperative decisions. One manifestation of human ultra-sociality is the tendency to engage in social comparison. While social comparison studies typically focus on cooperative behaviour and emphasize concern for fairness and equality, here we investigate the competitive dimension of social comparison: a preference for getting more than others, expressed in a willingness to maximize relative payoff at the cost of absolute payoff. Chimpanzees and human children (5-6- and 9-10-year-olds) could decide between an option that maximized their absolute payoff (but put their partner at an advantage) and an option that maximized their relative payoff (but decreased their own and their partner's payoff). Results show that, in contrast to chimpanzees and young children, who consistently selected the rational and payoff-maximizing option, older children paid a cost to reduce their partner's payoff to a level below their own. This finding demonstrates that uniquely human social skills and motivations do not necessarily lead to more prosocial, rational and cooperative decision-making.

Yong Zhou,1,* Yongfei Fan,1,* Binzhe Qiu,1 Ming Lou,1 Xiaoshuang Liu,2 Kai Yuan,1,3 Jichun Tong1 1The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Nanjing Jinling Hospital: East Region Military Command General Hospital, Nanjing, People’s Republic of China; 3Heart and Lung Disease Laboratory, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jichun Tong; Kai Yuan, Email tongjichun2021@163.com; yuankai202001@163.comBackground: NSCLC (non-small cell lung cancer) has become the malignancy with the highest incidence and mortality rate worldwide. Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a key regulator of glycolysis with both kinase and phosphatase activities. The Warburg effect, or increased glycolysis in tumors, provides the metabolic basis for cancer cell proliferation and metastasis, and the Warburg pathway enzyme PFKFB4 is a newly identified important kinase. This study aimed to elucidate the poor prognostic relevance of PFKFB4 in non-small cell lung cancer tissues and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints.Methods: In this study, immunohistochemical methods were used to assess PFKFB4 expression levels in 140 surgical specimens from patients with histologically confirmed non-small cell lung cancer and to investigate the relationship between PFKFB4 expression levels and the patients’ clinicopathological characteristics. The impact of PFKFB4 expression on prognosis was evaluated using Kaplan–Meier survival analysis and Cox regression analysis.Results: When compared to normal paracrine tissues, PFKFB4 expression was enhanced in lung cancer tissues, and Kaplan–Meier survival analysis revealed that patients with high PFKFB4 expression had a worse prognosis. In NSCLC, PFKFB4 was found to be associated with immune cell infiltration and immunological checkpoints.Conclusion: PFKFB4 expression may be upregulated as a sign of poor prognosis in NSCLC, and PFKFB4 may be implicated not only in the genesis and progression of NSCLC but also in its immunological control.Keywords: PFKFB4, NSCLC, prognostic marker, immune cells

Mingqiang Gong,1,2,* Yunxia Shen,2,* Wenbin Liang,2 Zhen Zhang,3 Chunxue He,4 Mingwu Lou,2 ZiYu Xu2 1Department of Acupuncture and Moxibustion, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang Central Hospital, Shenzhen, People’s Republic of China; 3Department of Radiology, The Third People’s Hospital of Longgang District, Shenzhen, People’s Republic of China; 4Department of Radiology, Shenzhen Clinical Medicine College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingwu Lou; ZiYu Xu, Department of Radiology, Longgang Central Hospital, No. 6082, Longgang Avenue, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86 13808854650 ; +86 13824321925, Email mingwulou@sina.com; xuziyu82@163.comPurpose: Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment.Methods: Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively.Results: Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs.Conclusion: Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.Keywords: methamphetamine, abstinence, network, Granger causality analysis, independent component analysis

Chunxue He,1,2,&ast; Mingqiang Gong,3,4,&ast; Gengxiao Li,1,2 Yunxia Shen,2 Longyin Han,5 Bin Han,6 Mingwu Lou2 1Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang District Central Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 4Department of Acupuncture, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China; 5Department of Neurology, Beijing Longfu Hospital, Beijing, People’s Republic of China; 6Department of Rehabilitation Medicine, Longgang District Central Hospital of Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Han; Mingwu Lou, Tel +86 13928488998 ; +86 13808854650, Email hhbb08@163.com; mingwulou@sina.comPurpose: To investigate white matter alterations in post-stroke cognitive impairment (PSCI) patients at the subacute stage employing diffusion kurtosis and tensor imaging.Methods: Thirty PSCI patients at the subacute phase and 30 healthy controls (HC) underwent diffusion kurtosis imaging (DKI) scans and neuropsychological assessments. Based on the tract-based spatial statistics and atlas-based ROI analysis, fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), kurtosis fractional anisotropy (KFA), axial kurtosis (AK), and radial kurtosis (RK) were compared in specific white matter fiber bundles between the groups (with family-wise error correction). Adjusting for age and gender, a partial correlation was conducted between neurocognitive assessments and DKI metrics in the PSCI group.Results: In comparison with the HC, PSCI patients significantly showed decreased MK, RK, and FA and increased MD values in the genu of corpus callosum, anterior limb internal capsule, and left superior corona radiata. In addition, DKI detected more white matter region changes in MK (31/48), KFA (40/48), and RK (25/48) than DTI with FA (28/48) and MD (21/48), which primarily consisted of the right cingulum, right superior longitudinal fasciculus, and left posterior limb of internal capsule. In the left anterior limb of internal capsule, MK and RK values were significantly negatively correlated with TMT-B (r = − 0.435 and − 0.414, P < 0.05), and KFA values (r = − 0.385, P < 0.05) of corpus callosum negatively associated with TMT-B.Conclusion: Combing DTI, DKI, and neuropsychological tests, we found extensive damaged white matter microstructure and poor execution performance in subacute PSCI patients. DKI could detect more subtle white matter changes than DTI metrics. Our findings provide added information for exploring the mechanisms of PSCI and conducting cognitive rehabilitation in the subacute stage.Keywords: diffusion kurtosis imaging, diffusion tensor imaging, subacute ischemic stroke, cognitive impairment

Yongfei Fan,1 Yong Zhou,1 Ming Lou,1 Xinwei Li,2 Xudong Zhu,1 Kai Yuan1,3 1Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Department of Gastroenterology, Affiliated Cancer Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 3Heart and Lung Disease Laboratory, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Kai Yuan, Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, No. 29 Xinglong Lane, Changzhou, 213003, Jiangsu Province, People’s Republic of China, Tel +86-13915890721, Email yuankai1978@163.comPurpose: The role of RNA N6-methyladenosine (m6A) modification in the progression of multiple tumours and the tumour microenvironment (TME) has been progressively demonstrated and promises a new direction for tumour therapy. However, there have been no reports on systematic analyses of RNA m6A modification in TME in non-small cell lung cancer (NSCLC).Patients and Methods: In this study, we used unsupervised cluster analysis to identify three m6A modification patterns of 28 m6A regulators and three m6A gene signature subgroups of commonly differentially expressed genes (co-DEGs) in the three m6A modification patterns. Quantifying these subtypes using the ssGSEA and ESTIMATE algorithms to characterise the tumour immune microenvironment (TIME) in NSCLC. Based on the principal component analysis (PCA), we used co-DEGs to construct m6A scores to analyse the characteristics of m6A modifications in individual patients and assessed the practical clinical utility of m6A scores using a nomogram for survival prediction.Results: A total of 28 m6A regulators in 1210 NSCLC samples were mainly enriched in RNA modification and metabolic biological processes. The three following m6A modification patterns were identified based on the role of the 28 m6A regulators in TME: immune inflammation, immune evasion and immune desert. The m6A scores calculated based on co-DEGs in these modification patterns were significantly positively correlated with immune infiltration and significantly negatively correlated with tumour mutational burden (TMB). Survival was significantly better in the high-m6A-score group than in the low-m6A-score group, and the m6A score could be used as an independent favourable prognostic factor. In addition, assessment of both immune checkpoint inhibitors (ICIs) and immunophenoscore (IPS) revealed a better immunotherapeutic effect in the high-m6A-score group.Conclusion: The modification characteristics of 28 m6A regulators in the TIME of NSCLC were analysed from a comprehensive to an individual basis, which may facilitate the development of more effective clinical immunotherapeutic strategies.Graphical Abstract: Keywords: immunophenotype, immunotherapy, m6A modification, non-small cell lung cancer, tumour microenvironment

The Sardinian grass snake, Natrix helvetica cetti, is an endangered endemic snake subspecies with a restricted and highly fragmented geographic distribution. Information on its ecology and detailed geographic distribution are scarce and may negatively impact on its conservation status. Therefore, a literature review on its taxonomy, morphology, ecology, and conservation is presented here. Moreover, field records from the authors, citizen science and the existing literature provide an updated geographic distribution highlighting its presence within 13 new and 7 historic 10 × 10 km cells. Bioclimatic niche modelling was then applied to explore patterns of habitat suitability and phenotypic variation within N. h. cetti. The geographic distribution of the species was found to be positively correlated with altitude and precipitation values, whereas temperature showed a negative correlation. Taken together, these outcomes may explain the snake’s presence, particularly in eastern Sardinia. In addition, analysis of distribution overlap with the competing viperine snake (N. maura) and the urodeles as possible overlooked trophic resources (Speleomantes spp. and Euproctus platycephalus) showed overlaps of 66% and 79%, respectively. Finally, geographical or bioclimatic correlations did not explain phenotypic variation patterns observed in this highly polymorphic taxon. Perspectives on future research to investigate N. h. cetti’s decline and support effective conservation measures are discussed.

Two experiments were conducted in a naturally lit research greenhouse to validate our modified strategy for delivering nutrients to sub-irrigated chrysanthemum plants. A split-plot design was used with four blocks arranged randomly, three nutrient rates as the main plot, and two contrasting cultivars as the subplot. The entire nutrient supply was removed at bud break and markedly reduced during vegetative growth, compared to common commercial fertilizer formulations, without adversely affecting tissue nutrient levels and plant/inflorescence quality, indicating that the plants were functioning in the low nutrient sufficiency zone. Specific nutrients (Nt) were more likely to exhibit improved uptake efficiency (shoot Nt content/Nt supply) than improved utilization efficiency (inflorescence DM/shoot Nt content) with decreasing nutrient supply. Thus, the common practice of delivering superfluous nutrient levels to greenhouse-grown chrysanthemum has little scientific merit in terms of nutrient accumulation and plant longevity. Applying a low‐input nutrient delivery strategy to the cultivation of indoor-grown, potted ornamental plants would improve the overall sustainability of the Canadian floricultural industry. [ABSTRACT FROM AUTHOR]

Abstract Background Fibrinogen concentrate (FC) is frequently used to treat bleeding trauma patients, although the clinical effects are not well known. In this study we describe demographic and clinical outcome data in a cohort of trauma patients receiving FC, compared to a matched control group, who did not receive FC. Methods This retrospective, single-center, observational study included adult trauma patients admitted to a level 1-trauma center in Sweden between January 2013 and June 2015. The study population consisted of patients to whom FC was administrated within 24 h (n = 138, “Fib+”). Patients with Injury Severity Score (ISS) > 49 and/or deceased within 1 h from arrival were excluded (n = 30). Controls (n = 108) were matched for age, gender and ISS (“Fib-“). Primary outcome was mortality (24 h−/30 days−/1 year-), and secondary outcomes were blood transfusions, thromboembolic events and organ failure. Results The Fib+ group, despite having similar ISS as Fib-, had higher prevalence of penetrating trauma and lower Glasgow Coma Scale (GCS), indicating more severe injuries. Patients receiving FC had a higher mortality after 24 h/ 30 days/ 1 year compared to controls (Fib-). However, in a propensity score matched model, the differences in mortality between Fib+ and Fib- were no longer significant. Blood transfusions were more common in the Fib+ group, but no difference was observed in thromboembolic events or organ failure. In both groups, low as well as high P-fibrinogen levels at arrival were associated with increased mortality, with the lowest mortality observed at P-fibrinogen values of 2–3 g/l. Conclusions Despite equal ISS, patients receiving FC had a higher mortality compared to the control group, presumably associated to the fact that these patients were bleeding and physiologically deranged on arrival. When applying a propensity score matching approach, the difference in mortality between the groups was no longer significant. No differences were observed between the groups regarding thromboembolic events or organ failure, despite higher transfusion volumes in patients receiving FC.

Background Severe disease due to the novel coronavirus disease 2019 (COVID-19) has been shown to be associated with hypercoagulation. The aim of this study was to assess the Rotational Thromboelastometry (ROTEM) as a marker of coagulopathy in hospitalized COVID-19 patients. Methods This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model, including variables ROTEM EXTEM-MCF (Maximum Clot Firmness) which in previous data has been suggested a suitable marker of hypercoagulation, age, and respiratory frequency, was developed using logistic regression to evaluate the probability of death. Results Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age, and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM–coagulation time (CT) was observed, supporting a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) effect on prolonged initiation of coagulation. Conclusion Here, we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.

For decades, the evolutionary role of melanism in reptiles has been highly debated. According to the thermal melanism hypothesis, melanistic phenotypes should provide thermal advantages, thus positively impacting various biological aspects of these individuals. Nevertheless, these benefits seem to be countered by environmental constraints and predatory pressure. Here, we mapped for the first time the distribution of the melanistic phenotypes in the highly polymorphic asp viper (Vipera aspis). We focused our research effort on the Italian peninsula, where this species reaches its highest level of taxonomic diversity with three currently described subspecies. Furthermore, we investigated via bioclimatic niche modelling, the influence of a wide array of bioclimatic variables on the distribution of melanism in Italian asp vipers. In general, our results seem to support the implications of the thermal melanism hypothesis, highlighting the central influence of mean annual temperature and elevation on the geographic distribution of melanistic V. aspis. At the finest scale, our analyses have highlighted a distinction in bioclimatic niches among the three assessed subspecies. However, further fine-scale investigations are needed in order to exclude the potential influence of latitude and elevation on the observed the intersubspecific bioclimatic niche segregation pattern. [ABSTRACT FROM AUTHOR]