bluuebunny/crossref_metadata_2025 huggingface dataset:
Illite K-Ar and (U-Th)/He low-temperature thermochronology reveal onset timing of Yadong-Gulu rift in southern Tibetan Plateau
Authors: Wang Shiguang , Shen Xiaoming , Chevalier Marie-Luce , Replumaz Anne , Zheng Yong , Li Haibing , Pan Jiawei , Li Kang , Xu Xiwei
Published: August 2022

Determining the timing of E-W extension across the NS-trending rifts in southern Tibet is key to test the mechanical models of the latest evolution in the collision between India and Asia. We focus on the southern half of the largest of the seven main rifts, the Yadong-Gulu rift (YGR), which, despite being the focus of numerous studies thanks to its easy access, still lacks direct time constraints. Using illite K-Ar ages of fault gouge from the active Yadong normal fault of the YGR, we directly constrain its onset timing at 9 ± 1 Ma. (U-Th)/He dating of the footwall leucogranite reveals a rapid exhumation of the southern YGR since ∼9 Ma, attesting to its onset activity. Such timing is similar to that estimated for the northern half of the YGR at 8 ± 1 Ma, suggesting that the entire YGR formed at approximately the same time. Our synthesis of published initiation ages of the other main rifts in southern Tibet shows that they mostly fall between ∼23 and 8 Ma, suggesting a clear spatial and temporal pattern of old initiation ages to the west and young to the east. In this case, the formation of rifts in southern Tibet is unlikely caused by slab tearing of the underthruting Indian plate or orogenic collapse. Our study supports that E-W extension in Tibetan Plateau is triggered by a combination of eastward propagation of the Karakorum-Jiali fault zone and divergent thrusting along the curved Himalayan arc.
Academic integration in higher education: A review of effective institutional strategies and personal factors
Authors: Abdul-Rahaman Nurudeen , Arkorful Vincent E. , Okereke Tochukwu
Published: August 2022

Globally, there has been a surge in international students, posing challenges to their host institutions. The review aimed to identify institutional strategies and personal factors that promote international students' academic integration. With an independent systematic review of titles, abstracts, and full texts, 64 studies were sampled and analyzed. The study presented findings through a narrative synthesis across all studies. The review results showed that there have been an increasing number of studies on academic integration over the last decade. Institutional strategies like staff and student interaction, student orientation programs, classroom organization, supervisory support, and learning communities are more effective in promoting healthy academic lives and the academic progress of students. Personal factors, which include financial status, language ability, and self-efficacy in students, were revealed to facilitate healthy academic lives and progress on campus. Prioritizing international students' welfare, providing language adaptation support, and increasing the accessibility of academic staff were suggested strategies for improving the academic lives of international students. The study also recommends that tertiary education systems and other stakeholders take these institutional strategies and personal factors into account when developing higher education policies. This will help international students have better academic lives and stay in school.
Evaluating the effectiveness of technological pedagogical content knowledge-based training program in enhancing pre-service teachers’ perceptions of technological pedagogical content knowledge
Authors: Diamah Aodah , Rahmawati Yuli , Paristiowati Maria , Fitriani Ella , Irwanto Irwanto , Dobson Stephen , Sevilla Doyet
Published: August 2022

In this study, we sought to investigate the effect of a 2-week Technological Pedagogical Content Knowledge (TPACK)-based training program on how the pre-service teachers’ TPACK was perceived. To achieve the goal, we used four TPACK activities; Explore-Engage-Reflection-Transformation. The study employed mixed methods with a TPACK questionnaire and open questions. Increased self-efficacy perceptions of TPACK was evaluated using a one-group pre-post-post research design. The sample was 30 pre-service teachers (5 male; 25 female) at a public university in Indonesia. Paired t-test was used to examine the significant difference between pretest and posttest scores and Cohen’s d was calculated to check the strength of the effect size. As a result, the paired t-test showed that the posttest scores were significantly higher than the pretest scores for all TPACK dimensions with large effect sizes. In addition, qualitative data from students’ reflections were analyzed. It found that pre-service teachers understand the role of technology integration in the TPACK framework for creating meaningful learning experiences. Participants reflected on the role as assessment for, and as learning. Professional learning from the New Zealand education system was introduced within a holistic framework to stimulate students to be creative future-directed teachers and agents of change. This indicates that the present training program increased the pre-service teachers’ perceptions of TPACK at the end of the training. We suggest that TPACK training programs that facilitate how pre-service teachers integrate technology, content, and pedagogy to create effective technology-enriched learning environments in their subjects should be included in teacher education programs.
An empirical study on the development of socio-industrial adaptation of vocational education in China: A case of Southwest China
Authors: Xia Zaiming , Wang Hsuan-Po
Published: August 2022

With the rising strain of job rivalry in the contemporary social climate, the incapacity of recent graduates to adjust to society has become a pressing issue. College vocational education’s social industry adaptability and students’ job development skills are profoundly influenced by the growth direction of colleges, universities, and majors. Accordingly, 616 students and 7 instructors from three institutions in Southwest China serve as the research subjects for this study. The objective is to examine the societal support for colleges and universities in Southwest China, as well as the adaptation of colleges and universities to society, and to establish their link and attempt to prove its psychological capital significance. Moreover, via the investigation of the interview questionnaires of instructors, we can learn the true requirements of students to adjust to social vocations. The findings indicate that (1) social support for colleges and universities may predict social adaption considerably and favorably. (2) Psychological capital has an important beneficial function as an intermediate between societal support for colleges and universities and the adaptation of institutions to society. (3) More attention and resources should be devoted to career preparation for students. Schools, as the primary institution, should build a variety of relationships with social businesses, and the steps taken to facilitate students’ integration into society will assist schools in establishing their reputation. This contributes to the enhancement of the school’s capacity for comprehensive management, so promoting the school’s and society’s virtuous growth cycle.
The tumor microenvironment of hepatocellular carcinoma and its targeting strategy by CAR-T cell immunotherapy
Authors: Guizhen Zhang , Guanchang Ji , Liwen Liu , Huifen Wang , Zhigang Ren , Ranran Sun , Zujiang Yu
Published: August 2022

Hepatocellular carcinoma (HCC) is the major subtype of liver cancer, which ranks sixth in cancer incidence and third in mortality. Although great strides have been made in novel therapy for HCC, such as immunotherapy, the prognosis remains less than satisfactory. Increasing evidence demonstrates that the tumor immune microenvironment (TME) exerts a significant role in the evolution of HCC and has a non-negligible impact on the efficacy of HCC treatment. In the past two decades, the success in hematological malignancies made by chimeric antigen receptor-modified T (CAR-T) cell therapy leveraging it holds great promise for cancer treatment. However, in the face of a hostile TME in solid tumors like HCC, the efficacy of CAR-T cells will be greatly compromised. Here, we provide an overview of TME features in HCC, discuss recent advances and challenges of CAR-T immunotherapy in HCC.
Cross-species comparisons reveal resistance of human skeletal stem cells to inhibition by non-steroidal anti-inflammatory drugs
Authors: Goodnough L. Henry , Ambrosi Thomas H. , Steininger Holly M. , Butler M. Gohazrua K. , Hoover Malachia Y. , Choo HyeRan , Van Rysselberghe Noelle L. , Bellino Michael J. , Bishop Julius A. , Gardner Michael J. , Chan Charles K. F.
Published: August 2022

Fracture healing is highly dependent on an early inflammatory response in which prostaglandin production by cyclo-oxygenases (COX) plays a crucial role. Current patient analgesia regimens favor opioids over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) since the latter have been implicated in delayed fracture healing. While animal studies broadly support a deleterious role of NSAID treatment to bone-regenerative processes, data for human fracture healing remains contradictory. In this study, we prospectively isolated mouse and human skeletal stem cells (SSCs) from fractures and compared the effect of various NSAIDs on their function. We found that osteochondrogenic differentiation of COX2-expressing mouse SSCs was impaired by NSAID treatment. In contrast, human SSCs (hSSC) downregulated COX2 expression during differentiation and showed impaired osteogenic capacity if COX2 was lentivirally overexpressed. Accordingly, short- and long-term treatment of hSSCs with non-selective and selective COX2 inhibitors did not affect colony forming ability, chondrogenic, and osteogenic differentiation potential in vitro. When hSSCs were transplanted ectopically into NSG mice treated with Indomethacin, graft mineralization was unaltered compared to vehicle injected mice. Thus, our results might contribute to understanding species-specific differences in NSAID sensitivity during fracture healing and support emerging clinical data which conflicts with other earlier observations that NSAID administration for post-operative analgesia for treatment of bone fractures are unsafe for patients.
Targeting trafficking as a therapeutic avenue for misfolded GPCRs leading to endocrine diseases
Authors: Ulloa-Aguirre Alfredo , Zariñán Teresa , Gutiérrez-Sagal Rubén , Tao Ya-Xiong
Published: August 2022

G protein-coupled receptors (GPCRs) are plasma membrane proteins associated with an array of functions. Mutations in these receptors lead to a number of genetic diseases, including diseases involving the endocrine system. A particular subset of loss-of-function mutant GPCRs are misfolded receptors unable to traffic to their site of function (i.e. the cell surface plasma membrane). Endocrine disorders in humans caused by GPCR misfolding include, among others, hypo- and hyper-gonadotropic hypogonadism, morbid obesity, familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, X-linked nephrogenic diabetes insipidus, congenital hypothyroidism, and familial glucocorticoid resistance. Several in vitro and in vivo experimental approaches have been employed to restore function of some misfolded GPCRs linked to endocrine disfunction. The most promising approach is by employing pharmacological chaperones or pharmacoperones, which assist abnormally and incompletely folded proteins to refold correctly and adopt a more stable configuration to pass the scrutiny of the cell’s quality control system, thereby correcting misrouting. This review covers the most important aspects that regulate folding and traffic of newly synthesized proteins, as well as the experimental approaches targeted to overcome protein misfolding, with special focus on GPCRs involved in endocrine diseases.
The relationship between renal function and surgical outcomes of patients with proliferative diabetic retinopathy
Authors: Liu Jin , Zhang Weiwei , Xie Ping , Yuan Songtao , Jiang Lin , Liu Qinghuai , Hu Zizhong
Published: August 2022

Objectives

The relationship between renal function and diabetic retinopathy has been controversial. This study is to investigate the influence of renal function on the complex and surgical outcomes of proliferative diabetic retinopathy (PDR).

Methods

This was a post hoc analysis of the CONCEPT clinical trial. A total of 45 eyes with PDR underwent vitrectomy were included. Based on the estimated glomerular filtration rate (eGFR), they were divided into abnormal renal function group (ARF group) and normal renal function group (NRG group). Baseline PDR complex, intraoperative outcomes (Intraoperative bleeding, frequency of endodiathermy, surgical time, iatrogenic hole, and tamponade) and postoperative outcomes (logMAR best-corrected visual acuity, vitreous re-hemorrhage, and macular edema, follow up at postoperative 1 month and 3 months) were estimated. Vitreous, aqueous humor and serum were collected at the vitrectomy day and Vascular endothelia growth factor-A levels were quantified for all included patients using liquid chip method.

Results

There was no significant difference in baseline PDR complex, intraoperative and postoperative outcomes between ARF group and NRG group (all P > 0.05). At the vitrectomy day, there was also no difference of Vascular endothelia growth factor-A levels in vitreous, aqueous humor and serum between the two groups (all P > 0.05).

Conclusion

Our results showed that the renal function seems not parallel to the severity of PDR, neither to the surgical outcomes. This might be interpreted by the similar Vascular endothelia growth factor-A levels in vitreous, aqueous humor and serum between the two groups.
Second-generation biofuel production from the organic fraction of municipal solid waste
Authors: Kowalski Zygmunt , Kulczycka Joanna , Verhé Roland , Desender Luc , De Clercq Guy , Makara Agnieszka , Generowicz Natalia , Harazin Paulina
Published: August 2022

Biofuels are playing an increasingly important role since they are an attractive alternative to fossil fuels, access to which has been limited. Moreover, they can help the European Union countries meet their climate and energy objectives. There is a growing interest in the production of biofuels from the organic fraction of municipal solid wastes as second-generation biofuels. Such a solution supports a circular economy as an example of an effective approach in terms of effective waste management. The study presents a review of different biofuels with an emphasis on second-generation biofuels from lignocellulose biomass, highlighting the BioRen process, which is one of the waste-to-fuel conversion technologies. It allows for maintaining the value of materials within the economy. All stages of the process are described and material flow is presented. The framework of the BioRen project includes the bio-fermentation of the organic fraction by a two-stage enzymatic process simultaneously into bioethanol and isobutanol, which are then used to produce glycerol tertiary butyl ether. The post-fermentation sludge is treated by the hydrothermal carbonization method increasing the efficiency of the whole waste treatment process and closing the loop. The bio-coal resulting from the process of carbonization can be used as a fuel with a high-calorific value. The remaining fraction undergoes a physical–chemical and catalytic conversion of inorganic particles into their clean, dry, and inert components. The results show that in the BioRen project 78% of the heat that is produced during the process is recovered and used for electricity production. Moreover, 53% of waste is recovered and re-used, because the process is profitable, efficient, environmentally friendly, and maintains high-security standards. Such an example of advanced technology, with a high readiness level, obtained results, and experience may encourage European countries and facilities to implement such an effective solution, which supports the development of bioenergy.
An Experimental and Case Study on the Evaluation of the Partial Shading Impact on PV Module Performance Operating Under the Sudano-Sahelian Climate of Cameroon
Authors: Yaouba  , Bajaj Mohit , Welba Colince , Bernard Kola , Kitmo  , Kamel Salah , El-Naggar Mohamed F.
Published: August 2022

Partial shading is a factor that influences the performance of a PV module. The study sought to evaluate the impact of partial shading on PV module performance in the Sudano-Sahelian climate conditions of Cameroon. The behavior of the PV module was simulated using MATLAB/Simulink for 12 months with data from the town of Yagoua. The power, current, and voltage losses of the PV module were estimated by varying the partial shading rate from 5.0% to 95.0%, with an increase factor of 5.0%. The results show that, when the shading ranges from 5.0% to 55.0%, the power and current losses are very significant and vary from 3.0% to 52.0% and 3.0%–53.0%, respectively. The voltage in this shading range remains almost invariant. For shading from 60.0% to 95.0%, the power losses increase slightly and reach approximately 60.0%. A very small current loss is observed, varying from 1.0% to 3.0%. Significant voltage losses are noted and vary from 55.0% to 59.0%. From 40.0% shading rate onwards, a mismatch is observed on the power-voltage characteristics curve by the presence of two maximum power points. This method can be used to evaluate the efficiency of different PV array topologies under partial shading. The results show the importance of paying attention to partial shading, however small its occurrence.
Appraising machine learning classifiers for discriminating rotor condition in 50W–12V operational wind turbine for maximizing wind energy production through feature extraction and selection process
Authors: Arockia Dhanraj Joshuva , Alkhawaldeh Rami S. , Van De Pham , Sugumaran V. , Ali Najabat , Lakshmaiya Natrayan , Chaurasiya Prem Kumar , S. Priyadharsini , Velmurugan Karthikeyan , Chowdhury Md Shahariar , Channumsin Sittiporn , Sreesawet Suwat , Fayaz H.
Published: August 2022

Wind energy is one of nature’s most valuable green energy assets, as well as one of the most reliable renewable energy supplies. Wind turbine blades convert wind energy into electric energy. Wind turbine blades range in size from 25 to 120 m, depending on the demands and efficiency necessary. Owing to ambient influences and wide structures, the blades are subject to various friction forces that might harm the blades. As a result, the generation of power and the shutdown of turbines are both affected. Downtimes are reduced when blades are detected on a regular basis, according to structural health management. On the 50-W, 12-V wind turbine, this research investigates the use of vibration signals to anticipate deterioration. The machine learning (ML) method establishes a nonlinear relationship between selected important damage features and the related uniqueness measures. The learning algorithm was trained and tested based on the excellent state of the edge. To forecast blade faults, classifier models, such as naive Bayes (NB), multilayer perceptron (MLP), linear support vector machine (linear_SVM), one-deep convolutional neural network (1DCNN), bagging, random forest (RF), XGBoosts, and decision tree J48 (DT) were used, and the results were compared according to their parameters to propose a better fault diagnostics model.
Collaborative optimal dispatch of microgrid and electric vehicles based on the Stackelberg game
Authors: Bo Wen , Zhang Wenqiang , Du Rongyu , Wang Donglai , Zhao Yan , Li Quanzheng , Zhang Zhen
Published: August 2022

The development of both microgrids and electric vehicles has become an important part of the current energy scenario. Useful complementary advantages can be formed between electric vehicles and microgrids, the consumers of which can utilize renewable energy and narrow the peak–valley differences of the net load curve while ensuring their own pecuniary interests. Based on the idea of the Stackelberg game, an optimal dispatch model of a microgrid with electric vehicles is proposed herein, where the benefits of the state of charge are taken into account. In the upper layer of the model, the charging and discharging behaviors of electric vehicles are guided by the goal of minimizing the operating cost of the microgrid. In the lower layer of the model, electric vehicle users adjust the charging and discharging strategies with the goal of maximizing their individual interests. The study results demonstrate that the proposed model not only reflects the benefits of both the master and slave but also reduces the peak–valley differences of the microgrid load. Further, the charging and discharging times of electric vehicles are reduced, and their state of charge is maintained at a high level.
Efficient whole-process carbon intensity calculation method for power users in active distribution networks
Authors: Shen Zhiheng , Dan Yangqing , Qi Mengxue , Sun Feifei , Sun Yikai , Mei Linjuehao
Published: August 2022

With the tightening restrictions on carbon emission globally, the carbon intensity of the economic is receiving more attention than ever, but the results obtained by conventional methods are not accurate enough for the responsibility division. To change this situation, a power flow tracking method aimed at the distribution networks and an electricity-consumption-based carbon intensity calculation framework are proposed in this paper. Firstly, to overcome the obstacles created by the three-phase asymmetries and the scale expansion of the networks while processing power flow tracing, a phase-split calculation regime and a high-efficiency power flow tracing method are proposed, respectively. On that basis, a whole-process carbon intensity calculation framework is reported. By adding simplified models about industrial production processes, this paper gives the calculation route from the energy consumption to the carbon intensity for each user in the distribution network. Finally, we emulated with the IEEE 34 bus and 123 bus test feeders and analyze the numerical results, to prove the efficiency and effectiveness of the framework proposed.
Heat transfer and flow structures of supercritical n-decane in a regenerative cooling channel loaded with non-uniform heat flux
Authors: Liu Jian , Xu Mengyao , Ma Kai , Liu Chaoyang , Xi Wenxiong
Published: August 2022

A harsh and complex thermal environment in the combustor threatens safe working of scramjets. In this study, heat transfer and flow structures of supercritical n-decane under 3 MPa in a regenerative cooling channel loaded with non-uniform heat flux distributions are investigated, including uniform, sinusoidal, increased, and decreased heat flux distributions. A verified k–ω SST turbulence model was employed, and a corresponding mesh independence study was performed. From this work, the fluid temperature at the outlet of the heated channel is only determined by the averaged heat flux, and all the regenerative cooling channels achieve the same temperature although loaded with different heat flux distributions. Compared with the fluid temperature, the wall temperature distribution is more sensitive to the variations of heat flux distribution. The regenerative cooling channels loaded with the sinusoidal heat flux distributions exist in several high-temperature regions, and the channel loaded with linear distributions changes the trend of temperature distribution. A larger temperature gradient is found in the regenerative cooling channel wall with a lower thermal conductivity. This work provides a good insight into the characteristics of the flow and temperature field of regenerative cooling channels loaded with non-uniform heat flux considering the effect of conjugate heat transfer.
Reconstructing the Historical Terrestrial Water Storage Variations in the Huang–Huai–Hai River Basin With Consideration of Water Withdrawals
Authors: Yang Chuanxun , Liu Yangxiaoyue , Yang Ji , Li Yong , Chen Shuisen
Published: August 2022

The Huang-Huai-Hai River Basin in eastern China has suffered from severe water scarcity during recent decades due to the effects of climate change and human activities. Quantifying the changes in the amount of terrestrial freshwater available in this region and their driving factors is important for understanding hydrological processes and developing a sustainable water policy. This study proposed an ensemble learning model to reconstruct historical variations in the terrestrial water storage (TWS) of the Huang-Huai-Hai River Basin, China. The model was trained using the observations of the variations in TWS from the Gravity Recovery and Climate Experiment mission (GRACE) satellites, climatic driving, and human withdrawal datasets produced on a monthly scale. The variations in the reconstructed TWS were compared with the results of several land surface and hydrological models with a variety of in situ measurements of the soil water content. The contributions of the climate and human activity to the ensemble learning model were also quantified. The results show that the proposed approach generally outperforms the land surface and hydrological models examined in this study, matches the patterns in the GRACE solutions, and reconstructs past changes in TWS, which are consistent with the GRACE observations. Climatic variables are the most important in the ensemble learning model, with precipitation over the prior month being a critical factor. The model that includes human intervention tends to perform better than without it. Irrigation, industry, and domestic water withdrawals contribute equally to the model. This study provides a flexible and easily implementable model that can bridge the gap between GRACE observations and past changes in TWS. The model is applicable in areas with intense human activities, and the results have the potential to be assimilated into and enhance hydrological models.
Can the technologically advanced policy achieve green innovation of small and medium-sized enterprises?—The case of China
Authors: Huang Dawei , Chen Gang
Published: August 2022

The purpose of this study is to apply a multidimensional fixed-effects difference-in-differences (DID) model to empirically examine the impact, policy mechanism, and heterogeneity of Technologically Advanced Policy (TAP) on green innovation in small and medium-sized enterprises (SMEs) based on the data of China’s A-share listed companies from 2004 to 2021. The results show that TAP significantly improves the green innovation level of listed companies on the small and medium-sized board, and has a more significant role in promoting technologically advanced enterprises (TAEs). The results of the policy effect are still robust after the placebo test, changing the dependent variable, and controlling for the influence of the environmental inspection system, the emissions trading system (ETS), and the carbon emissions trading system (CETS). Furthermore, we find that the policy effect of TAP is better in state-owned SMEs and SMEs in the eastern, central, and western regions. In addition, further research shows that the green innovation effect of TAP is mainly realized through mechanisms such as government subsidies, tax reduction, credit financing, and market competition. Moreover, state-owned SMEs have obvious advantages in the three mechanisms of government subsidy, tax reduction, and market competition, while private SMEs only have significant advantages in credit financing mechanisms. Overall, our findings show that TAP has achieved policy effects in promoting green innovation for SMEs in China, but state-owned SMEs still receive significant policy preference. It is recommended that future policy reforms favor private SMEs.
Pathway to green growth: A panel-ARDL model of environmental upgrading, environmental regulations, and GVC participation for the Chinese manufacturing industry
Authors: Shahid Rabia , Shijie Li , Yifan Ning , Jian Gao
Published: August 2022

Since the opening up of China, its manufacturing sector contributed significantly toward economic development on one hand and caused elevated environmental pollution and heavy resource consumption problems on the other hand. Green productivity is an essential means of addressing environmental problems and promoting sustainable environmental performance and long-term economic growth. When the factors affecting the green total factor energy productivity (GTFEP) are studied in recent years, the hitherto literature lacks the relationship between GTFEP, environmental regulations, and global value chain (GVC) participation. Using GTFEP as a proxy of environmental upgrading for the Chinese manufacturing industry, this study investigates the nexus between the GTFEP, environmental regulation index (ERI), and total production length index (TPLI). Based on panel data 18 industries from 2000 to 2014, the current study employed the panel pool mean group estimators for the auto-regressive distributed lag model (ARDL) and estimated the long-run relationship between variables. Findings revealed the positive effect of ERI and GVC participation (TPLI) on the GTFEP of the Chinese manufacturing industry. Furthermore, pairwise panel causativeness analysis indicated unidirectional causality between GTFEP and ERI, running from GTFEP to ERI. Based on research findings, some conclusions and policy implications are derived, such as strict enforcement of environmental regulations, industry-specific policies, promotion of clean energy resources, and acceleration of the country’s further opening-up and reforms. All of these will help promulgate the GTFEP and environmental upgrading of the Chinese manufacturing sector, thus leading to sustainable economic development decoupled from environmental pollution.
Ecological restoration of the Los Angeles River provides natural and human benefits as part of a virtuous socioecological cycle
Authors: Katagi Wendy , Butler Nate , Keith Anthony , Backlar Shelly , Orr Bruce
Published: August 2022

Ecological restoration in the Los Angeles (LA) River watershed is proceeding on multiple fronts with the support and engagement of diverse stakeholder groups. Pilot projects to restore habitat, reintroduce native species, and design science-based ecosystem enhancements have produced real benefits to nature and people and demonstrated the potential for additional benefits. The pilot projects, which are in various stages of collaborative planning and implementation, have generated increased interest and financial support to further their implementation and maximize socioecological co-benefits. This self-reinforcing positive feedback is an example of a virtuous cycle established through a combination of long-term environmental planning, community-building, and watershed-scale scientific study to gain the support of stakeholders and align ecological intervention (i.e., restoration) with the plans and policies of governments, resource managers, conservation groups, and grassroots advocacy groups. Conservation and restoration projects targeting iconic and protected focal species can be an effective means of leveraging these interests and building support. For example, the LA River Fish Passage and Habitat Structures project addresses a critical limiting factor for the recovery of endangered steelhead trout (Oncorhynchus mykiss) while also enhancing urban biodiversity and providing recreational opportunities and other beneficial uses (e.g., ecosystem services) for the surrounding communities. Through these efforts, our planners, ecologists, and engineers are using place-based conservation to demonstrate solutions to problems that affect people and nature in other urban landscapes. Here, we show how this work can provide socioecological benefits in disadvantaged communities and also generate public awareness and motivation to perpetuate the cycle of positive feedback.
Terrigenous subsidies in lakes support zooplankton production mainly via a green food chain and not the brown food chain
Authors: Hirama Fumiya , Urabe Jotaro , Doi Hideyuki , Kazama Takehiro , Noguchi Takumi , Tappenbeck Tyler H. , Katano Izumi , Yamamichi Masato , Yoshida Takehito , Elser James J.
Published: August 2022

Terrestrial organic matter (t-OM) has been recognized as an important cross-boundary subsidy to aquatic ecosystems. However, recent evidence has shown that t-OM contributes little to promote secondary production in lakes because it is a low-quality food for aquatic consumers. To resolve this conflict, we performed a field experiment using leaf litter as t-OM. In the experiment, we monitored zooplankton biomass in enclosures with and without addition of leaf litter under shaded and unshaded conditions and assessed food web changes with stable isotope analyses. We then examined whether or not leaf litter indeed stimulates lake secondary production and, if it does, which food chain, the detritus-originated food chain (“brown” food chain) or the algae-originated food chain (“green” food chain), contributes more to this increase. Analyses with stable isotopes showed the importance of t-OM in supporting secondary production under ambient lake conditions. However, the addition of the leaf litter increased the zooplankton biomass under unshaded conditions but not under shaded conditions. We found that phosphorus was leached from leaf litter at much faster rate than organic carbon and nitrogen despite its low content in the leaf litter. These results showed that leaf litter stimulated the increase in zooplankton biomass mainly through the green food chain rather than the brown food chain because the leaf litter supplied limiting nutrients (i.e., phosphorus) for primary producers.Our results indicate that the functional stoichiometry of the subsidized organic matter plays a crucial role in determining the relative importance of brown and green food chains in promoting production at higher trophic levels in recipient ecosystems.
Rapid acquisition of microorganisms and microbial genes can help explain punctuated evolution
Authors: Rosenberg Eugene
Published: August 2022

The punctuated mode of evolution posits that evolution occurs in rare bursts of rapid evolutionary change followed by long periods of genetic stability (stasis). The accepted cause for the rapid changes in punctuated evolution is special ecological circumstances – selection forces brought about by changes in the environment. This article presents a complementary explanation for punctuated evolution by the rapid formation of genetic variants in animals and plants by the acquisition of microorganisms from the environment into microbiomes and microbial genes into host genomes by horizontal gene transfer. Several examples of major evolutionary events driven by microorganisms are discussed, including the formation of the first eukaryotic cell, the ability of some animals to digest cellulose and other plant cell-wall complex polysaccharides, dynamics of root system architecture, and the formation of placental mammals. These changes by cooperation were quantum leaps in the evolutionary development of complex bilolgical systems and can contribute to an understanding of the mechanisms underlying punctuated evolution.
Comprehensive analysis reveals a 5-gene signature and immune cell infiltration in Alzheimer’s disease with qPCR validation
Authors: Jin Fanmao , Xi Yuemei , Xie De , Wang Qiang
Published: August 2022

Over 50 million people around the world currently are suffering from Alzheimer’s disease (AD) without any effective therapy. Neuroinflammation plays a pivotal role in AD, which leads us to probe the profile of immune cell infiltration in AD. Here, we analyzed a microarray dataset (GSE44770) containing 115 AD and 115 control samples to determine biomarkers and immune infiltration characteristics of AD by multiple bioinformatics methods. First, we identified 3,840 DEGs (1892 upregulated and 1948 downregulated) by using the limma package and 2,697 hub genes by constructing a weighted gene correlation network, and they had a total of 2,167 intersecting genes. Second, combining the LASSO logistic regression and SVM-RFE, we obtained five biomarkers (DGKG, MAP3K7IP2, NFKBIE, VIP, and PCCB), which may reveal the key pathogenetic features of AD and serve as diagnostic markers assessed by the ROC curve (AUC = 0.9716) and validation of another AD dataset (GSE33000) (AUC = 0.9388). Third, immune cell infiltration analysis revealed that compared with control samples, plasma cells, CD8 T cells, T follicular helper cells, and activated NK cells infiltrated less in AD; Monocytes, M2 macrophages, and neutrophils infiltrated more in AD. Neutrophils and activated NK cells demonstrated the most significant and negative correlation. Then, Spearman correlation analysis between the five biomarkers and immune infiltrating cells revealed that all of them were significantly associated with plasma cells. Finally, mRNA levels of VIP and PCCB were conformed in a murine AD model. In conclusion, DGKG, MAP3K7IP2, NFKBIE, VIP, and PCCB may be used as diagnostic markers of AD, and the disruption of the delicate immune balance may be a key process in the onset and development of AD.
Network analysis of hepatocellular carcinoma liquid biopsies augmented by single-cell sequencing data
Authors: Safrastyan Aram , Wollny Damian
Published: August 2022

Liquid biopsy, the analysis of body fluids, represents a promising approach for disease diagnosis and prognosis with minimal intervention. Sequencing cell-free RNA derived from liquid biopsies has been very promising for the diagnosis of several diseases. Cancer research, in particular, has emerged as a prominent candidate since early diagnosis has been shown to be a critical determinant of disease prognosis. Although high-throughput analysis of liquid biopsies has uncovered many differentially expressed genes in the context of cancer, the functional connection between these genes is not investigated in depth. An important approach to remedy this issue is the construction of gene networks which describes the correlation patterns between different genes, thereby allowing to infer their functional organization. In this study, we aimed at characterizing extracellular transcriptome gene networks of hepatocellular carcinoma patients compared to healthy controls. Our analysis revealed a number of genes previously associated with hepatocellular carcinoma and uncovered their association network in the blood. Our study thus demonstrates the feasibility of performing gene co-expression network analysis from cell-free RNA data and its utility in studying hepatocellular carcinoma. Furthermore, we augmented cell-free RNA network analysis with single-cell RNA sequencing data which enables the contextualization of the identified network modules with cell-type specific transcriptomes from the liver.
Methylation associated with long- or short-term survival in glioblastoma patients from the Nordic phase 3 trial
Authors: Łysiak Małgorzata , Das Jyotirmoy , Malmström Annika , Söderkvist Peter
Published: August 2022

Patients with glioblastoma (GBM) have a poor outcome, but even among patients receiving the same therapies and with good prognostic factors, one can find those with exceptionally short and long survival. From the Nordic trial, which randomized GBM patients of 60 years or older between two radiotherapy arms (60 Gy or 34 Gy) or temozolomide (TMZ), we selected 59 with good prognostic factors. These selected GBM patients were equally distributed according to treatment and MGMT promoter methylation status but had long or short survival. Methylation profiling with the Illumina Infinium Methylation EPIC BeadChip arrays was performed and utilized for methylation-based CNS tumor classification, and pathway enrichment analysis of differentially methylated CpG sites (DMCs), as well as calculation of epigenetic age acceleration with three different algorithms, to compare the long and short survival groups. Samples identified by the classifier as non-GBM IDH wildtype were excluded. DMCs between long- and short-term survivors were found in patients with methylated MGMT promoter treated with TMZ (123,510), those with unmethylated MGMT treated with 60Gy radiotherapy (4,086), and with methylated MGMT promoter treated with 34Gy radiotherapy (39,649). Long-term survivors with methylated MGMT promoter treated with TMZ exhibited hypermethylation of the Wnt signaling and the platelet activation, signaling, and aggregation pathways. The joint analysis of radiotherapy arms revealed 319 DMCs between long- and short-term survivors with unmethylated MGMT and none for samples with methylated MGMT promoter. An analysis comparing epigenetic age acceleration between patients with long- and short-term survival across all treatment arms showed a decreased epigenetic age acceleration for the latter. We identified DMCs for both TMZ and RT-treated patients and epigenetic age acceleration as a potential prognostic marker, but further systematic analysis of larger patient cohorts is necessary for confirmation of their prognostic and/or predictive properties.
Identification and validation of a novel cellular senescence-related lncRNA prognostic signature for predicting immunotherapy response in stomach adenocarcinoma
Authors: Zeng Cheng , Liu Yu , He Rong , Lu Xiaohuan , Dai Yuyang , Qi Guoping , Liu Jingsong , Deng Jianzhong , Lu Wenbin , Jin Jianhua , Liu Qian
Published: August 2022

Background: Cellular senescence is a novel hallmark of cancer associated with patient outcomes and tumor immunotherapy. However, the value of cellular senescence-related long non-coding RNAs (lncRNAs) in predicting prognosis and immunotherapy response for stomach adenocarcinoma (STAD) patients needs further investigation.

Methods: The transcriptome and corresponding clinical information of STAD and cellular senescence-related genes were, respectively, downloaded from the Cancer Genome Atlas (TCGA) and CellAge databases. Differential expression analysis and coexpression analysis were performed to obtain cellular senescence-related lncRNAs. Univariate regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were conducted to establish the cellular senescence-related lncRNA prognostic signature (CSLPS). Next, the survival curve, ROC curve, and nomogram were developed to assess the capacity of predictive models. Moreover, principal component analysis (PCA), gene set enrichment analysis (GSEA), tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion (TIDE) score analysis were performed between high- and low-risk groups.

Results: A novel CSLPS involving fifteen lncRNAs (REPIN1-AS1, AL355574.1, AC104695.3, AL033527.2, AC083902.1, TYMSOS, LINC00460, AC005165.1, AL136115.1, AC007405.2, AL391152.1, SCAT1, AC129507.1, AL121748.1, and ADAMTS9-AS1) was developed. According to the nomogram, the risk model based on the CSLPS was an independent prognostic factor and could predict 1-, 3-, and 5-year overall survival for STAD patients. GSEA suggested that the high-risk group was mainly associated with Toll-like receptor, JAK/STAT, NOD-like receptor, and chemokine signaling pathways. Further analysis revealed that STAD patients in the low-risk group with better clinical outcomes had a higher TMB, higher proportion of high microsatellite instability (MSI-H), better immune infiltration, and lower TIDE scores.

Conclusion: A fifteen-CSlncRNA prognostic signature could predict survival outcomes, and patients in the low-risk group may be more sensitive to immunotherapy.
A novel prognostic and therapeutic target biomarker based on necroptosis-related gene signature and immune microenvironment infiltration in gastric cancer
Authors: Xin Dao , Man Yuxin , Yang Yalan , Wang Feng
Published: August 2022

Background: Gastric cancer is a major global public health burden worldwide. Although treatment strategies are continuously improving, the overall prognosis remains poor. Necroptosis is a newly discovered form of cell death associated with anti-tumor immunity.

Methods: Gastric cancer (GC) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were downloaded. Bioinformatics analysis was performed to construct a necroptosis-related risk model and to establish cancer subtypes. Potential associations of the tumor immune microenvironment and immunotherapy response with necroptosis-related prognostic risk score (NRG risk score) were comprehensively explored. 16 GC and paired normal tissues were collected and RT-PCR was performed to examine expression of NRG related genes.

Results: GC samples were stratified into three subtypes according to prognostic necroptosis gene expression. A necroptosis risk model based on 12 genes (NPC1L1, GAL, RNASE1, PCDH7, NOX4, GJA4, SLC39A4, BASP1, BLVRA, NCF1, PNOC, and CCR5) was constructed and validated. The model was significantly associated with the OS and PFS of GC patients and the tumor immune microenvironment including immune cell infiltration, microsatellite instability (MSI) status, tumor mutational burden (TMB) score, immune checkpoint, and human leukocyte antigen (HLA) gene expression. A prognostic nomogram based on the NRG_score was additionally constructed. A low NRG risk score was correlated with high tumor immunogenicity and might benefit from immunotherapy.

Conclusion: We have identified a useful prognostic model based on necroptosis-related genes in GC and comprehensively the relationship between necroptosis and tumor immunity. Predicting value to immunotherapy response is promising, and further research to validate the model in clinical practice is needed.