bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair
Authors: Zujur Denise , Al-Akashi Ziadoon , Nakamura Anna , Zhao Chengzhu , Takahashi Kazuma , Aritomi Shizuka , Theoputra William , Kamiya Daisuke , Nakayama Koichi , Ikeya Makoto
Published: May 2023

Background: To date, there is no effective long-lasting treatment for cartilage tissue repair. Primary chondrocytes and mesenchymal stem/stromal cells are the most commonly used cell sources in regenerative medicine. However, both cell types have limitations, such as dedifferentiation, donor morbidity, and limited expansion. Here, we report a stepwise differentiation method to generate matrix-rich cartilage spheroids from induced pluripotent stem cell-derived mesenchymal stem/stromal cells (iMSCs) via the induction of neural crest cells under xeno-free conditions.

Methods: The genes and signaling pathways regulating the chondrogenic susceptibility of iMSCs generated under different conditions were studied. Enhanced chondrogenic differentiation was achieved using a combination of growth factors and small-molecule inducers.

Results: We demonstrated that the use of a thienoindazole derivative, TD-198946, synergistically improves chondrogenesis in iMSCs. The proposed strategy produced controlled-size spheroids and increased cartilage extracellular matrix production with no signs of dedifferentiation, fibrotic cartilage formation, or hypertrophy in vivo.

Conclusion: These findings provide a novel cell source for stem cell-based cartilage repair. Furthermore, since chondrogenic spheroids have the potential to fuse within a few days, they can be used as building blocks for biofabrication of larger cartilage tissues using technologies such as the Kenzan Bioprinting method.
Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases
Authors: Chaudhary Priya , Janmeda Pracheta , Docea Anca Oana , Yeskaliyeva Balakyz , Abdull Razis Ahmad Faizal , Modu Babagana , Calina Daniela , Sharifi-Rad Javad
Published: May 2023

Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions that take place in the human body. Under normal conditions, they are removed from the body by antioxidant processes. If these natural mechanisms are disrupted, radicals accumulate in excess and contribute to the development of many diseases.

Methodology: Relevant recent information on oxidative stress, free radicals, reactive oxidative species, and natural and synthetic antioxidants was collected by researching electronic databases such as PubMed / Medline, Web of Science, and Science Direct.

Results: According to the analysed studies, this comprehensive review provided a recent update on oxidative stress, free radicals and antioxidants and their impact on the pathophysiology of human diseases.

Discussion: To counteract the condition of oxidative stress, synthetic antioxidants must be provided from external sources to supplement the antioxidant defense mechanism internally. Because of their therapeutic potential and natural origin, medicinal plants have been reported as the main source of natural antioxidants phytocompounds. Some non-enzymatic phytocompounds such as flavonoids, polyphenols, and glutathione, along with some vitamins have been reported to possess strong antioxidant activities in vivo and in vitro studies. Thus, the present review describes, in brief, the overview of oxidative stress-directed cellular damage and the unction of dietary antioxidants in the management of different diseases. The therapeutic limitations in correlating the antioxidant activity of foods to human health were also discussed.
Clinical characteristics and outcomes of children with Kawasaki disease combined with sepsis in the pediatric intensive care unit
Authors: Yang Yufan , Huang Jiaotian , Yan Haipeng , Li Xun , Liu Pingping , Zhou Wu , Zhang Xinping , Lu Xiulan , Xiao Zhenghui
Published: May 2023

Background

Kawasaki disease (KD) is a vascular inflammatory disease with unknown pathogenesis. There are few studies on KD combined with sepsis worldwide.

Purpose

To provide valuable data regarding clinical characteristics and outcomes related to pediatric patients with KD combined with sepsis in pediatric intensive care unit (PICU).

Methods

We retrospectively analyzed the clinical data of 44 pediatric patients admitted in PICU at Hunan Children’s Hospital with KD combined with sepsis between January 2018 and July 2021.

Results

Of the 44 pediatric patients (mean age, 28.18 ± 24.28 months), 29 were males and 15 were female. We further divided the 44 patients into two groups: KD combined with severe sepsis (n=19) and KD combined with non-severe sepsis (n=25). There were no significant between-group differences in leukocyte, C-reactive protein, and erythrocyte sedimentation rate. Interleukin-6, interleukin-2, interleukin-4 and procalcitonin in KD with severe sepsis group were significantly higher than those in KD with non-severe sepsis group. And the percentage of suppressor T lymphocyte and natural killer cell in severe sepsis group were significantly higher than those in non-severe group, while the CD4+/CD8+ T lymphocyte ratio was significantly lower in KD with severe sepsis group than in KD with non-severe sepsis group. All 44 children survived and were successfully treated after intravenous immune globulin (IVIG) combined with antibiotics.

Conclusion

Children who develop with KD combined with sepsis have different degrees of inflammatory response and cellular immunosuppression, and the degree of inflammatory response and cellular immunosuppression is significantly correlated with the severity of the disease.
Different phenotype of left atrial function impairment in patients with hypertrophic cardiomyopathy and hypertension: comparison of healthy controls
Authors: Li Hongwen , Wang Haibao , Wang Tingting , Jin Chaolong , Lu Minjie , Liu Bin
Published: May 2023

Background

The impairment of atrial function and atrial-ventricular coupling in diseases with left ventricular (LV) hypertrophy has been increasingly recognized. This study compares left atrium (LA) and right atrium (RA) function, as well as LA-LV coupling, in patients with hypertrophic cardiomyopathy (HCM) and hypertension (HTN) with preserved LV ejection fraction (EF), using cardiovascular magnetic resonance feature tracking (CMR-FT).

Methods

Fifty-eight HCM patients, 44 HTN patients, and 25 healthy controls were retrospectively enrolled. LA and RA functions were compared among the three groups. LA-LV correlations were evaluated in the HCM and HTN groups.

Results

LA reservoir (LA total EF, ɛs, and SRs), conduit (LA passive EF, ɛe, SRe), and booster pump (LA booster EF, ɛa, SRa) functions were significantly impaired in HCM and HTN patients compared to healthy controls (HCM vs. HTN vs. healthy controls: ɛs, 24.8 ± 9.8% vs. 31.3 ± 9.3% vs. 25.2 ± 7.2%; ɛe, 11.7 ± 6.7% vs. 16.8 ± 6.9% vs. 25.5 ± 7.5%; ɛa, 13.1 ± 5.8% vs. 14.6 ± 5.5% vs. 16.5 ± 4.5%, p < 0.05). Reservoir and conduit functions were more impaired in HCM patients compared to HTN patients (p < 0.05). LA strains demonstrated significant correlations with LV EF, LV mass index, LV MWT, global longitudinal strain parameters, and native T1 in HCM patients (p < 0.05). The only correlations in HTN were observed between LA reservoir strain (ɛs) and booster pump strain (ɛa) with LV GLS (p < 0.05). RA reservoir function (RA ɛs, SRs) and conduit function (RA ɛe, SRe) were significantly impaired in HCM and HTN patients (p < 0.05), while RA booster pump function (RA ɛa, SRa) was preserved.

Conclusions

LA functions were impaired in HCM and HTN patients with preserved LV EF, with reservoir and conduit functions more affected in HCM patients. Moreover, different LA-LV couplings were apparent in two different diseases, and abnormal LA-LV coupling was emphasized in HTN. Decreased RA reservoir and conduit strains were evident in both HCM and HTN, while booster pump strain was preserved.
The critical role of mode of action studies in kinetoplastid drug discovery
Authors: Fairlamb Alan H. , Wyllie Susan
Published: May 2023

Understanding the target and mode of action of compounds identified by phenotypic screening can greatly facilitate the process of drug discovery and development. Here, we outline the tools currently available for target identification against the neglected tropical diseases, human African trypanosomiasis, visceral leishmaniasis and Chagas’ disease. We provide examples how these tools can be used to identify and triage undesirable mechanisms, to identify potential toxic liabilities in patients and to manage a balanced portfolio of target-based campaigns. We review the primary targets of drugs that are currently in clinical development that were initially identified via phenotypic screening, and whose modes of action affect protein turnover, RNA trans-splicing or signalling in these protozoan parasites.
Apatite geochemistry as a proxy for porphyry-skarn Cu genesis: a case study from the Sanjiang region of SW China
Authors: Liu Qian , Pan Li-Chuan , Wang Xin-Song , Yan Jun , Xing Lang-Zhang
Published: May 2023

In view of the importance of the magmatic oxidation state and volatile composition (H2O-S-Cl) in porphyry Cu mineralization, identification of magmatic information has become the basis for the evaluation of the Cu-mineralization potential of porphyries. Apatite, as a common accessory mineral in porphyry, is recognized as an effective petrogenetic and metallogenic indicator. In this study, we analyze the in situ major and trace elements and Nd isotope content of apatite from four granitic plutons in the Yidun Terrane, SW China, in order to provide new insights into the identification of the magmatic features of Cu-mineralized plutons. The plutons investigated in this study are a Cu-mineralized pluton (Hongshan) and three non-mineralized plutons (Cilincuo, Rongyicuo, and Hagela). Chemical composition and textural analysis indicate that the apatites are all of magmatic origin and have not been altered. Our results show that apatite δCe values rather than δEu and Ga values are more valid indicators of the magma oxidation state of the four plutons. Based on apatite δCe values and zircon compositions, the parental magma of the Hongshan pluton is identified as having been more oxidized than those of the other three plutons. Moreover, the higher Cl content (0.06–0.23 wt%) in the Hongshan apatite compared to that in apatite from the other three plutons (0.01–0.09 wt%), indicates that the parental magma of the former pluton was more enriched in Cl. Apatite from the Hongshan pluton contains more SO3 (average 0.05 wt%) than that from the other three plutons (SO3 content mostly lower than the detection limit of electron probe micro-analysis), which may be related to higher magmatic oxygen fugacity of the Hongshan pluton. In addition, the Nd isotopic composition of apatite [εNd(t): −13.6−5.9] demonstrates that the Cu-mineralized and non-mineralized plutons were derived from the melting of ancient lower crust. Furthermore, based on the geochemical signature of adakite revealed by apatite Sr/Y and δEu values, the Hongshan pluton can be considered to have been produced as the result of partial melting of the thickened lower crust. Finally, an index system consisting of apatite δCe, Sr/Y, and F/Cl values is established to distinguish between the Cu-mineralized and non-mineralized plutons.
Hyaluronan regulates sperm-induced inflammatory response by enhancing sperm attachment to bovine endometrial epithelial cells via CD44: in-silico and in-vitro approaches
Authors: Ezz Mohamed Aboul , Mansouri Alireza , Akthar Ihshan , Yousef Mohamed Samy , Kowsar Rasoul , Miyamoto Akio
Published: May 2023

Recently, we reported that sperm induce cluster of differentiation 44 (CD44) expression and Toll-like receptor 2 (TLR2)-mediated inflammatory response in bovine uterus. In the present study, we hypothesized that the interaction between CD44 of bovine endometrial epithelial cells (BEECs) and hyaluronan (HA) affects sperm attachment and thereby enhancing TLR2-mediated inflammation. To test our hypothesis, at first, in-silico approaches were employed to define the binding affinity of HA for CD44 and TLR2. Further, an in-vitro experiment using the sperm-BEECs co-culture model was applied to investigate the effect of HA on sperm attachment and inflammatory response. Here, low molecular weight (LMW) HA at different concentrations (0, 0.1, 1, or 10 µg/mL) was incubated with BEECs for 2 h followed by the co-culture without- or with non-capacitated washed sperm (106/ml) for additional 3 h was performed. The present in-silico model clarified that CD44 is a high-affinity receptor for HA. Moreover, TLR2 interactions with HA oligomer (4- and 8-mers) target a different subdomain (h-bonds) compared to TLR2-agonist (PAM3) which targets a central hydrophobic pocket. However, the interaction of LMW HA (32-mers) with TLR2 revealed no stability of HA at any pocket of TLR2. Notably, the immunofluorescence analysis revealed the HA localization in both endometrial stroma and epithelia of ex-vivo endometrial explant. Moreover, ELISA showed significant levels of HA in BEECs culture media. Importantly, BEECs pretreatment with HA prior to sperm exposure increased the number of attached sperm to BEECs, and upregulated the transcriptional levels of pro-inflammatory genes (TNFA, IL-1B, IL-8, and PGES) in BEECs in response to sperm. However, BEECs treated with HA only (no sperm exposure) did not show any significant effect on the transcript abundance of pro-inflammatory genes when compared to the non-treated BEECs. Altogether, our findings strongly suggest a possible cross-talk between sperm and endometrial epithelial cells via HA and HA binding receptors (CD44 and TLR2) to induce a pro-inflammatory response in bovine uterus.
Weight cycling and risk of clinical adverse events in patients with heart failure with preserved ejection fraction: a post-hoc analysis of TOPCAT
Authors: Tan Yi , Guo Hang , Zhang Ning , Zheng Keyang , Liu Guifang
Published: May 2023

Background

Previous studies hardly evaluated the association of variability of body mass index (BMI) or waist circumference with clinical adverse events and investigated whether weight cycling had an effect on the prognosis of patients with heart failure with preserved ejection fraction (HFpEF).

Methods

This study was a post-hoc analysis of TOPCAT. Three outcomes were evaluated: the primary endpoint, cardiovascular disease (CVD) death, and heart failure hospitalization. Among them, CVD death and hospitalization were outcomes of heart failure. Kaplan–Meier curves were used to describe the cumulative risk of outcome and were tested using the log-rank test. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95%CIs for outcomes. We also performed a subgroup analysis, and several subgroups were compared.

Results

A total of 3,146 patients were included. In the Kaplan–Meier curves, the coefficients of variation of both BMI and waist circumference were grouped according to quartiles, with the Q4 group having the highest cumulative risk (log-rank P < 0.001). In the coefficient of BMI variation and the outcomes, the HRs for group Q4 of coefficient of variation of BMI were 2.35 (95%CI: 1.82, 3.03) for the primary endpoint, 2.40 (95%CI: 1.69, 3.40) for death, and 2.33 (95%CI: 1.68, 3.22) for HF hospitalization in model 3 (fully adjusted model) compared with group Q1. In the coefficient of waist circumference variation and the outcomes, group Q4 had increased hazard of the primary endpoint [HR: 2.39 (95%CI: 1.84, 3.12)], CVD death [HR: 3.29 (95%CI: 2.28, 4.77)], and HF hospitalization [HR: 1.98 (95%CI 1.43, 2.75)] in model 3 (fully adjusted model) compared with group Q1. In the subgroup analysis, there was a significant interaction in the diabetes mellitus subgroup (P for interaction = 0.0234).

Conclusion

Weight cycling had a negative effect on the prognosis of patients with HFpEF. The presence of comorbid diabetes weakened the relationship between waist circumference variability and clinical adverse events.
Redesigning carbon emissions reduction policies for China’s manufacturing industry: a dynamic stochastic general equilibrium approach
Authors: Lei Yutao , Zhang Xuan , Yao Canzhong , Peng Wenxiang
Published: May 2023

The design of China’s industrial carbon reduction policies is still in its early stages, so currently, comparing the effectiveness of various emission reduction policies can help China design emission reduction policies. This paper develops a dynamic stochastic general equilibrium (DSGE) model of China’s manufacturing industry and investigates the impact of innovation on environmental protection technology, the carbon emissions tax, and government emissions reduction expenditures on the output and carbon emissions reduction of China’s manufacturing industry. Unlike previous studies that examined one policy using a single model, by focusing on the differences between three shocks it is possible to make the policies more comparable, and the comparison is more convincing. The results indicate that updating environmental protection technology can promote the development of the manufacturing industry and reduce carbon emissions in the short term. Carbon emissions taxes have a negative effect on manufacturing output in the short term and a significant and lasting effect on the reduction of carbon emissions in the long term. The government’s emissions reduction expenditures have a positive effect on manufacturing output in the short term, but a non-significant negative effect in the long term. The Chinese government should take the lead in implementing carbon emissions tax policies in heavily polluting industries and regions while lowering but stabilizing emissions reduction expenditures.
Post deposition annealing effect on properties of CdS films and its impact on CdS/Sb2Se3 solar cells performance
Authors: Vadakkedath Gopi Sajeesh , Spalatu Nicolae , Basnayaka Madhawa , Krautmann Robert , Katerski Atanas , Josepson Raavo , Grzibovskis Raitis , Vembris Aivars , Krunks Malle , Oja Acik Ilona
Published: May 2023

Antimony selenide (Sb2Se3) is one of the emerging photovoltaic absorber materials possessing abundance and non-toxicity as the main attributes. Following CdTe technology, CdS is a widely used partner layer for Sb2Se3 solar cells. Related to CdS/Sb2Se3 device configuration, a number of studies reported findings and challenges regarding the intermixing phenomenon at the main interface and suitability of various annealing for CdS (and related interface) and still, significant room remains in developing strategies for interface optimization and understanding of the physiochemistry behind. In this perspective, this work provides a systematic investigation of the effect of vacuum and air annealing at temperatures between 200 and 400°C on the properties of CdS deposited by chemical bath deposition and combined with Sb2Se3 absorber obtained by close-spaced sublimation the direct impact of the CdS annealing on the device performance is illustrated. It is found that by varying the annealing temperature from 200 to 400°C in both, vacuum and air ambient, the morphology of CdS changes from highly dispersed small grain structure to sintered dense grains, the band gap decreases from 2.43 to 2.35 eV and the electron density drops from ∼1018 to ∼1011 cm−3. These changes were correlated with the changes in the CdS lattice and connected with the mobility of the OH group and the presence of secondary phases in CdS layers. 200°C air annealing of CdS was found as an optimal treatment resulting in 2.8% Sb2Se3/CdS cell efficiency - a 60% boost compared to the 1.8% performance of the device with as-deposited CdS. Material and device characterization analysis is performed, providing complementary insights on the interrelation between the physicochemical mechanism of the CdS annealing processes and device functionality.
Estimates of woody biomass and mixed effects improve isoscape predictions across a northern mixed forest
Authors: Berini John L. , Runck Bryan , Vogeler Jody , Fox David L. , Forester James D.
Published: May 2023

Contemporary methods used to predict isotopic variation at regional scales have yet to include underlying distributions of the abundance of isotopic substrates. Additionally, traditional kriging methods fail to account for the potential influences of environmental grouping factors (i.e., random effects) that may reduce prediction error. We aim to improve upon traditional isoscape modeling techniques by accounting for variation in the abundances of isotopic substrates and evaluating the efficacy of a mixed-effects, regression kriging approach. We analyzed common moose forage from northeast Minnesota for δ13C and δ15N and estimated the isotopic landscape using regression kriging, both with and without random effects. We then compared these predictions to isoscape estimates informed by spatial variation in above-ground biomass. Finally, we kriged the regression residuals of our best-fitting models, added them to our isoscape predictions, and compared model performance using spatial hold-one-out cross validation. Isoscape predictions driven by uninformed and biomass-informed models varied by as much as 10‰. Compared to traditional methods, incorporating biomass estimates improved RMSE values by as much as 0.12 and 1.00% for δ13C and δ15N, respectively, while random effects improved r2 values by as much as 0.15 for δ13C and 0.87 for δ15N. Our findings illustrate how field-collected data, ancillary geospatial data, and novel spatial interpolation techniques can be used to more accurately estimate the isotopic landscape. Regression kriging using mixed-effects models and the refinement of model predictions using measures of abundance, provides a flexible, yet mechanistically driven approach to modeling isotopic variation across space.
Half of a forest bird community infected with haemosporidian parasites
Authors: Strehmann Finja , Becker Marcel , Lindner Kim , Masello Juan F. , Quillfeldt Petra , Schumm Yvonne R. , Farwig Nina , Schabo Dana G. , Rösner Sascha
Published: May 2023

Introduction

Parasites play important roles in ecosystems. Through their interactions with host and vector species, they are capable of changing the behavior and population dynamics of their host species, and the shape of entire communities. Over the past years, many studies have acknowledged the role of parasitism for host populations and communities and discovered their important regulatory functions for many vertebrate populations. Although birds are a well-studied group of vertebrates, the infection patterns of endoparasites at the community level are not fully understood. Some bird species and families are known to have a higher susceptibility to certain endoparasites than others, which may be driven by their abundance in the community.

Methods

Over the course of four consecutive breeding seasons (2019–2022), we monitored the patterns of endoparasite infections in a bird community of a temperate forest ecosystem. We sampled 483 birds belonging to 29 Palearctic species and investigated the prevalence of blood parasites (haemosporidian parasites) andTrichomonasspp. using molecular methods.

Results

We found an overall prevalence of 48.1% of haemosporidians belonging to 53 genetic lineages of the three generaHaemoproteus,Leucocytozoon, andPlasmodiumspp. While the bird families Turdidae (94%) and Paridae (76%) showed a high prevalence of haemosporidians, Certhiidae, and Picidae were not infected (0%). Host–parasite network analysis detected high variability in interactions. Infections withTrichomonasspp. were not observed in the forest bird community.

Discussion

We found that the prevalence and lineage diversity of haemosporidian parasites differed between avian families and that the parasite prevalence of a family could not serve as a predictor of lineage diversity. To further assess the consequences of these host–parasite interactions for bird communities, future research should aim to disentangle the infection pathways in different ecosystems while also considering the vector community and environmental factors.
The Belt and Road Initiative and enterprise green innovation: evidence from Chinese manufacturing enterprises
Authors: Cao Xin , Zhao Feng , Wang Yuanyuan , Deng Yin , Zhang Heng , Huang Xiaozhi
Published: May 2023

Building a green silk road is an important path toward implementation of the UN 2030 sustainable development goals. The purpose of the paper is to discuss the sustainable development goals of the “Belt and Road” Initiative (BRI) by evaluating the relationship between the BRI and enterprise green innovation. Employing the technology–organization–environment (TOE) framework to build a theoretical model based on the micro data of Chinese manufacturing enterprises from 2011 to 2018, and using the difference-in-differences method, this paper analyzes the BRI’s influence on the green innovation of enterprises. The research results indicate that the BRI has significantly enhanced the level of green innovation in Chinese manufacturing enterprises. This effect is still robust after the analysis of PSM-DID excluding the interference of policies in the same period and heterogeneity analysis. The results of the mechanism analysis show that the percentage of R&D employees, policy support and R&D expenditure can enhance the positive effects of the BRI’s influence on enterprise green innovation. The marginal contribution of this paper is to identify the causal relationship between the BRI and green innovation, add a new micro perspective to the research on the relationship between the BRI and sustainable development, and reveal a new micro mechanism.
Floral response to the Late Triassic Carnian Pluvial Episode
Authors: Zhang Peixin , Yang Minfang , Lu Jing , Jiang Zhongfeng , Zhou Kai , Xu Xiaotao , Wang Ye , Wu Li , Chen Huijuan , Zhu Xuran , Guo Yanghang , Ye Huajun , Shao Longyi , Hilton Jason
Published: May 2023

The Late Triassic Carnian Pluvial Episode (CPE; ca. 234–232 Ma) was characterized by dramatic global temperature and humidity increases, which in many terrestrial settings was accompanied by changes from arid to humid vegetation types. This study reviews current evidence of terrestrial floral composition and distribution during the CPE and analyzes spatial and temporal variation with relation to potential environmental driving mechanisms. Available evidence suggests the CPE was a globally significant event that triggered significant increases in the abundance of ferns and hygrophytes in terrestrial floras and freshwater algae in fluvial and lacustrine settings. These changes ended a long interval of relatively arid terrestrial climatic conditions since the Early Triassic and are linked temporally with eruptions of the oceanic plateau Wrangellia Large Igneous Province (LIP). The massive release of greenhouse gasses including isotopically light CO2 during 3–4 distinct pulses of Wrangellia volcanism appears to have been the main driver of CPE climate change. Each pulse enhanced global atmospheric circulation and the hydrological cycle and resulted in changes from arid to humid conditions that affected floral abundance and composition. Higher terrestrial primary productivity in humid phases facilitated increased burial of terrestrial organic carbon and led to the recommencement of peat accumulation, ending the coal gap that had persisted since the Earliest Triassic times. Enhanced movement of carbon from the atmosphere through the biosphere into the geosphere may have counteracted the warming effects of Wrangellia volcanic greenhouse gas emissions and ultimately led to the return of a steady climate state that terminated the warm and humid conditions of the CPE.
Wildfire promotes the invasion of Robinia pseudoacacia in the unmanaged Mediterranean Castanea sativa coppice forests
Authors: Saulino Luigi , Rita Angelo , Stinca Adriano , Liuzzi Greta , Silvestro Roberto , Rossi Sergio , Saracino Antonio
Published: May 2023

In the Mediterranean region of southern Europe, Castanea sativa Mill. (Castanea) coppice stands are being invaded by non-native pioneer tree species due to recurrent coppicing and wildfire disturbances. There is a need to control the spread of non-native tree species in Castanea coppices due to their pivotal socio-economic role, however, to facilitate this, further research into invasive strategies and their interactions with disturbances is required. The non-native Robinia pseudoacacia L. (Robinia) has widely colonized the overaged and unmanaged Castanea coppice forests in Vesuvius National Park, which were disturbed by the low-severity fires in the summer of 2017. Here, we aimed to assess the functional traits conferring a competitive advantage to the Robinia over Castanea and the changes in spatial stand patterns driven by wildfire disturbance. To achieve this we assessed the spatial stem patterns, regeneration strategies, and conducted field-assessments and remote sensing of the spring leaf phenology of both Castanea and Robinia in five 300–600 m2 plots. After the 2017 wildfire, root suckers constituted 72% (±12) of the Robinia vegetative living sprouts and occurred up to a distance of 10 m from the adult parent trees under the canopy of the Castanea trees. NDVI-based estimates at the start of the growing season (sos) in Castanea occurred over a 7 day period, from DOY 118–124, increasing at a rate (rsp) of 0.10–0.16, in agreement with the field-based assessment of spring leaf phenology. In Robinia, the sos estimated at DOY 109 from the NDVI seasonal trajectory disagreed with the field-based observations, which started later than Castanea, after approximately DOY 133. Here, the high percentage cover (∼90%) of the understory species influenced NDVI-based estimates of Robinia leaf spring phenology. The results suggest that low-severity wildfires increased the invasiveness of Robinia, and that vegetative regeneration strategies, rather than earlier spring phenology, conferred a competitive advantage in the fire-disturbed Castanea coppice stands. The results thus suggest that appropriate management of invasive Robinia trees to conserve the continuous canopy cover of Castanea stands should guide nature-based solutions to control the spread of non-native tree species.
Identification and validation of hub genes and pathways associated with mitochondrial dysfunction in hypertrophy of ligamentum flavum
Authors: Gu Yifei , Yu Wenchao , Qi Min , Hu Jinquan , Jin Qianmei , Wang Xinwei , Wang Chen , Chen Yu , Yuan Wen
Published: May 2023

Background: Lumbar spinal stenosis which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy of ligamentum flavum (HLF). Recent studies have indicated that mitochondrial dysfunction may contribute to the development of HLF. However, the underlying mechanism is still unclear.

Methods: The dataset GSE113212 was obtained from the Gene Expression Omnibus database, and the differentially expressed genes were identified. The intersection of DEGs and mitochondrial dysfunction-related genes were identified as mitochondrial dysfunction-related DEGs. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis were performed. Protein-protein interaction network was constructed, and miRNAs and transcriptional factors of the hub genes were predicted via the miRNet database. Small molecule drugs targeted to these hub genes were predicted via PubChem. Immune infiltration analysis was performed to evaluate the infiltration level of immune cells and their correlation with the hub genes. In final, we measured the mitochondrial function and oxidative stress in vitro and verified the expression of hub genes by qPCR experiments.

Results: In total, 43 genes were identified as MDRDEGs. These genes were mainly involved in cellular oxidation, catabolic processes, and the integrity of mitochondrial structure and function. The top hub genes were screened, including LONP1, TK2, SCO2, DBT, TFAM, MFN2. The most significant enriched pathways include cytokine-cytokine receptor interaction, focal adhesion, etc. Besides, SP1, PPARGC1A, YY1, MYC, PPARG, and STAT1 were predicted transcriptional factors of these hub genes. Additionally, increased immune infiltration was demonstrated in HLF, with a close correlation between hub genes and immune cells found. The mitochondrial dysfunction and the expression of hub genes were validated by evaluation of mitochondrial DNA, oxidative stress markers and quantitative real-time PCR.

Conclusion: This study applied the integrative bioinformatics analysis and revealed the mitochondrial dysfunction-related key genes, regulatory pathways, TFs, miRNAs, and small molecules underlying the development of HLF, which improved the understanding of molecular mechanisms and the development of novel therapeutic targets for HLF.
Genomic study of TEX15 variants: prevalence and allelic heterogeneity in men with spermatogenic failure
Authors: Qureshi Sidra , Hardy Jimmaline J. , Pombar Christopher , Berman Andrea J. , Malcher Agnieszka , Gingrich Tara , Hvasta Rachel , Kuong Jannah , Munyoki Sarah , Hwang Kathleen , Orwig Kyle E. , Ahmed Jawad , Olszewska Marta , Kurpisz Maciej , Conrad Donald F. , Jaseem Khan Muhammad , Yatsenko Alexander N.
Published: May 2023

Introduction: Human spermatogenesis is a highly intricate process that requires the input of thousands of testis-specific genes. Defects in any of them at any stage of the process can have detrimental effects on sperm production and/or viability. In particular, the function of many meiotic proteins encoded by germ cell specific genes is critical for maturation of haploid spermatids and viable spermatozoa, necessary for fertilization, and is also extremely sensitive to even the slightest change in coding DNA.

Methods: Here, using whole exome and genome approaches, we identified and reported novel, clinically significant variants in testis-expressed gene 15 (TEX15), in unrelated men with spermatogenic failure (SPGF).

Results: TEX15 mediates double strand break repair during meiosis. Recessive loss-of-function (LOF) TEX15 mutations are associated with SPGF in humans and knockout male mice are infertile. We expand earlier reports documenting heterogeneous allelic pathogenic TEX15 variants that cause a range of SPGF phenotypes from oligozoospermia (low sperm) to nonobstructive azoospermia (no sperm) with meiotic arrest and report the prevalence of 0.6% of TEX15 variants in our patient cohort. Among identified possible LOF variants, one homozygous missense substitution c.6835G>A (p.Ala2279Thr) co-segregated with cryptozoospermia in a family with SPGF. Additionally, we observed numerous cases of inferred in trans compound heterozygous variants in TEX15 among unrelated individuals with varying degrees of SPGF. Variants included splice site, insertions/deletions (indels), and missense substitutions, many of which resulted in LOF effects (i.e., frameshift, premature stop, alternative splicing, or potentially altered posttranslational modification sites).

Conclusion: In conclusion, we performed an extensive genomic study of familial and sporadic SPGF and identified potentially damaging TEX15 variants in 7 of 1097 individuals of our combined cohorts. We hypothesize that SPGF phenotype severity is dictated by individual TEX15 variant’s impact on structure and function. Resultant LOFs likely have deleterious effects on crossover/recombination in meiosis. Our findings support the notion of increased gene variant frequency in SPGF and its genetic and allelic heterogeneity as it relates to complex disease such as male infertility.
Development and validation of an immune infiltration/tumor proliferation-related Notch3 nomogram for predicting survival in patients with primary glioblastoma
Authors: Zheng Zong-Qing , Zhang Guo-Guo , Yuan Gui-Qiang , Hao Jia-Hui , Nie Qian-Qian , Zheng Ming-Cheng , Wang Zhong
Published: May 2023

Background: Notch receptors (Notch 1/2/3/4), the critical effectors of the Notch pathway, participate in the tumorigenesis and progression of many malignancies. However, the clinical roles of Notch receptors in primary glioblastoma (GBM) have not been fully elucidated.

Methods: The genetic alteration-related prognostic values of Notch receptors were determined in the GBM dataset from The Cancer Genome Atlas (TCGA). Two GBM datasets from TCGA and Chinese Glioma Genome Atlas (CGGA) were used to explore the differential expression between Notch receptors and IDH mutation status, and GBM subtypes. The biological functions of Notch Receptors were explored by Gene Ontology and KEGG analysis. The expression and prognostic significance of Notch receptors were determined in the TCGA and CGGA datasets and further validated in a clinical GBM cohort by immunostaining. A Notch3-based nomogram/predictive risk model was constructed in the TCGA dataset and validated in the CGGA dataset. The model performance was evaluated by receiver operating curves, calibration curves, and decision curve analyses. The Notch3-related phenotypes were analyzed via CancerSEA and TIMER. The proliferative role of Notch3 in GBM was validated in U251/U87 glioma cells by Western blot and immunostaining.

Results: Notch receptors with genetic alterations were associated with poor survival of GBM patients. Notch receptors were all upregulated in GBM of TCGA and CGGA databases and closely related to the regulation of transcription, protein-lysine N-methyltransferase activity, lysine N-methyltransferase activity, and focal adhesion. Notch receptors were associated with Classical, Mesenchymal, and Proneural subtypes. Notch1 and Notch3 were closely correlated with IDH mutation status and G-CIMP subtype. Notch receptors displayed the differential expression at the protein level and Notch3 showed a prognostic significance in a clinical GBM cohort. Notch3 presented an independent prognostic role for primary GBM (IDH1 mutant/wildtype). A Notch3-based predictive risk model presented favorable accuracy, reliability, and net benefits for predicting the survival of GBM patients (IDH1 mutant/wildtype and IDH1 wildtype). Notch3 was closely related to immune infiltration (macrophages, CD4+ T cells, and dendritic cells) and tumor proliferation.

Conclusion: Notch3-based nomogram served as a practical tool for anticipating the survival of GBM patients, which was related to immune-cell infiltration and tumor proliferation.
miRNA expression profiles of peripheral white blood cells from beef heifers with varying reproductive potential
Authors: Banerjee Priyanka , Diniz Wellison J. S. , Rodning Soren P. , Dyce Paul W.
Published: May 2023

Reproductive performance is the most critical factor affecting production efficiency in the cow-calf industry. Heifers with low reproductive efficiency may fail to become pregnant during the breeding season or maintain a pregnancy. The cause of reproductive failure often remains unknown, and the non-pregnant heifers are not identified until several weeks after the breeding season. Therefore, improving heifer fertility utilizing genomic information has become increasingly important. One approach is using microRNAs (miRNA) in the maternal blood that play an important role in regulating the target genes underlying pregnancy success and thereby in selecting reproductively efficient heifers. Therefore, the current study hypothesized that miRNA expression profiles from peripheral white blood cells (PWBC) at weaning could predict the future reproductive outcome of beef heifers. To this end, we measured the miRNA profiles using small RNA-sequencing in Angus-Simmental crossbred heifers sampled at weaning and retrospectively classified as fertile (FH, n = 7) or subfertile (SFH, n = 7). In addition to differentially expressed miRNAs (DEMIs), their target genes were predicted from TargetScan. The PWBC gene expression from the same heifers were retrieved and co-expression networks were constructed between DEMIs and their target genes. We identified 16 differentially expressed miRNAs between the groups (p-value ≤0.05 and absolute (log2 fold change ≥0.05)). Interestingly, based on a strong negative correlation identified from miRNA-gene network analysis with PCIT (partial correlation and information theory), we identified miRNA-target genes in the SFH group. Additionally, TargetScan predictions and differential expression analysis identified bta-miR-1839 with ESR1, bta-miR-92b with KLF4 and KAT2B, bta-miR-2419-5p with LILRA4, bta-miR-1260b with UBE2E1, SKAP2 and CLEC4D, and bta-let-7a-5p with GATM, MXD1 as miRNA-gene targets. The miRNA-target gene pairs in the FH group are over-represented for MAPK, ErbB, HIF-1, FoxO, p53, mTOR, T-cell receptor, insulin and GnRH signaling pathways, while those in the SFH group include cell cycle, p53 signaling pathway and apoptosis. Some miRNAs, miRNA-target genes and regulated pathways identified in this study have a potential role in fertility; other targets are identified as novel and need to be validated in a bigger cohort that could help to predict the future reproductive outcomes of beef heifers.
Response of some mango-infesting fruit flies to aqueous solutions of the basil plant Ocimum tenuiflorum L
Authors: Niassy Saliou , Mohamed Samira Abuelgasim , Cheseto Xavier , Omuse Evanson Rigan , Ochola John Bwire , Khamis Fathiya Mbarak , Badji Boubacar , Ndlela Sheppard , Ombura Levi , Okun Noelah Leah , Kupesa David Mfuti , Dubois Thomas , Belayneh Yeneneh Taye , Subramanian Sevgan , Ekesi Sunday
Published: May 2023

Introduction

Horticulture is an important sub-sector for many African countries. Tephritid fruit flies continue to cause serious direct and indirect damage to the sub-sector. The male annihilation technique (MAT) using methyl eugenol (ME) is among the most revered techniques in fruit fly management. However, ME-based lures are only available to some farmers in Africa. Several basils of the genus Ocimum produce ME.

Methods

In laboratory experiments, we used a dual choice olfactometer to assess the attraction of adult oriental fruit fly Bactrocera dorsalis to intact plants, 100 µL commercial methyl eugenol (ME) (positive control), 10 mg/mL of O. tenuiflorum aqueous extract (Otae), and a negative control (blank). Large arena experiments were conducted to compare the responses of four fruit fly species of economic importance in Africa to Otae-baited traps.

Results

In dual choice olfactometer assay, more B. dorsalis males (78.6%) than females (23.8%) were attracted to Otae. Most B. dorsalis males were attracted to the positive control (90.5%) and 10 mg/mL Otae (88.5%) compared to the whole plant (84.0%). In large arena experiments, Otae attracted the most B. dorsalis males (47.7%), followed by Zeugodacus cucurbitae males (25.1%), while males of Ceratitis species were the least attracted. The analysis of headspace volatiles from aerial plants, Otae and essential oil using gas chromatography-mass spectrometry detected 97 compounds. The intact plant without flowers, intact plant with flowers, Otae, and the O. tenuiflorum essential oil contributed 76, 62, 33 and 28 compounds, respectively. ME comprised the top three most abundant compounds, especially in the essential oil.

Discussion

Our study confirms the potential of O. tenuiflorum as a source of ME for tephritid fruit fly integrated management in Africa. Otae, a readily available alternative to commercial ME, can be used to develop fruit fly-baited traps, particularly for smallholder farmers.
Comprehensive analysis of FOXM1 immune infiltrates, m6a, glycolysis and ceRNA network in human hepatocellular carcinoma
Authors: Xu Ziwu , Pei Chaozhu , Cheng Haojie , Song Kaixin , Yang Junting , Li Yuhang , He Yue , Liang Wenxuan , Liu Biyuan , Tan Wen , Li Xia , Pan Xue , Meng Lei
Published: May 2023

Background

Forkhead box M1 (FOXM1) is a member of the Forkhead box (Fox) transcription factor family. It regulates cell mitosis, cell proliferation, and genome stability. However, the relationship between the expression of FOXM1 and the levels of m6a modification, immune infiltration, glycolysis, and ketone body metabolism in HCC has yet to be fully elucidated.

Methods

Transcriptome and somatic mutation profiles of HCC were downloaded from the TCGA database. Somatic mutations were analyzed by maftools R package and visualized in oncoplots. GO, KEGG and GSEA function enrichment was performed on FOXM1 co-expression using R. We used Cox regression and machine learning algorithms (CIBERSORT, LASSO, random forest, and SVM-RFE) to study the prognostic value of FOXM1 and immune infiltrating characteristic immune cells in HCC. The relationship between FOXM1 and m6A modification, glycolysis, and ketone body metabolism were analyzed by RNA-seq and CHIP-seq. The competing endogenous RNA (ceRNA) network construction relies on the multiMiR R package, ENCORI, and miRNET platforms.

Results

FOXM1 is highly expressed in HCC and is associated with a poorer prognosis. At the same time, the expression level of FOXM1 is significantly related to the T, N, and stage. Subsequently, based on the machine learning strategies, we found that the infiltration level of T follicular helper cells (Tfh) was a risk factor affecting the prognosis of HCC patients. The high infiltration of Tfh was significantly related to the poor overall survival rate of HCC. Besides, the CHIP-seq demonstrated that FOXM1 regulates m6a modification by binding to the promoter of IGF2BP3 and affects the glycolytic process by initiating the transcription of HK2 and PKM in HCC. A ceRNA network was successfully obtained, including FOXM1 - has-miR-125-5p – DANCR/MIR4435-2HG ceRNA network related to the prognosis of HCC.

Conclusion

Our study implicates that the aberrant infiltration of Tfh associated with FOXM1 is a crucial prognostic factor for HCC patients. FOXM1 regulates genes related to m6a modification and glycolysis at the transcriptional level. Furthermore, the specific ceRNA network can be used as a potential therapeutic target for HCC.
TMBserval: a statistical explainable learning model reveals weighted tumor mutation burden better categorizing therapeutic benefits
Authors: Wang Yixuan , Wang Jiayin , Fang Wenfeng , Xiao Xiao , Wang Quan , Zhao Jian , Liu Jingjing , Yang Shuanying , Liu Yuqian , Lai Xin , Song Xiaofeng
Published: May 2023

A high tumor mutation burden (TMB) is known to drive the response to immune checkpoint inhibitors (ICI) and is associated with favorable prognoses. However, because it is a one-dimensional numerical representation of non-synonymous genetic alterations, TMB suffers from clinical challenges due to its equal quantification. Since not all mutations elicit the same antitumor rejection, the effect on immunity of neoantigens encoded by different types or locations of somatic mutations may vary. In addition, other typical genomic features, including complex structural variants, are not captured by the conventional TMB metric. Given the diversity of cancer subtypes and the complexity of treatment regimens, this paper proposes that tumor mutations capable of causing various degrees of immunogenicity should be calculated separately. TMB should therefore, be segmented into more exact, higher dimensional feature vectors to exhaustively measure the foreignness of tumors. We systematically reviewed patients’ multifaceted efficacy based on a refined TMB metric, investigated the association between multidimensional mutations and integrative immunotherapy outcomes, and developed a convergent categorical decision-making framework, TMBserval (Statistical Explainable machine learning with Regression-based VALidation). TMBserval integrates a multiple-instance learning concept with statistics to create a statistically interpretable model that addresses the broad interdependencies between multidimensional mutation burdens and decision endpoints. TMBserval is a pan-cancer-oriented many-to-many nonlinear regression model with discrimination and calibration power. Simulations and experimental analyses using data from 137 actual patients both demonstrated that our method could discriminate between patient groups in a high-dimensional feature space, thereby rationally expanding the beneficiary population of immunotherapy.