bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of three-dimensional primary human myospheres as culture model of skeletal muscle cells for metabolic studies
Authors: Dalmao-Fernandez Andrea , Aizenshtadt Aleksandra , Bakke Hege G. , Krauss Stefan , Rustan Arild C. , Thoresen G. Hege , Kase Eili Tranheim
Published: March 2023

Introduction: Skeletal muscle is a major contributor to whole-body energy homeostasis and the utilization of fatty acids and glucose. At present, 2D cell models have been the most used cellular models to study skeletal muscle energy metabolism. However, the transferability of the results to in vivo might be limited. This project aimed to develop and characterize a skeletal muscle 3D cell model (myospheres) as an easy and low-cost tool to study molecular mechanisms of energy metabolism.

Methods and results: We demonstrated that human primary myoblasts form myospheres without external matrix support and carry structural and molecular characteristics of mature skeletal muscle after 10 days of differentiation. We found significant metabolic differences between the 2D myotubes model and myospheres. In particular, myospheres showed increased lipid oxidative metabolism than the 2D myotubes model, which oxidized relatively more glucose and accumulated more oleic acid.

Discussion and conclusion: These analyses demonstrate model differences that can have an impact and should be taken into consideration for studying energy metabolism and metabolic disorders in skeletal muscle.
Causes of permanent vertical deformation at subduction margins: Evidence from late Pleistocene marine terraces of the southern Hikurangi margin, Aotearoa New Zealand
Authors: Ninis Dee , Howell Andy , Little Timothy , Litchfield Nicola
Published: March 2023

Theoretical studies of the seismic cycle at convergent plate boundaries anticipate that most coseismic deformation is recovered, yet significant permanent vertical displacement of the overriding plate is observed at many subduction margins. To understand the mechanisms driving permanent vertical displacement, we investigate tectonic uplift across the southern Hikurangi subduction margin, Aotearoa New Zealand, in the last ∼200 ka. Marine terraces preserved along the Wellington south coast have recently been dated as Marine Isotope Stage (MIS) 5a (∼82 ka), 5c (∼96 ka), 5e (∼123 ka) and 7a (∼196 ka) in age. We use these ages, together with new reconstructions of shoreline angle elevations, to calculate uplift rates across the margin and to examine the processes responsible for their elevation. The highest uplift rate—1.7 ± 0.1 mm/yr–and maximum tilting—2.9° to the west–are observed near Cape Palliser, the closest site to (∼50 km from) the Hikurangi Trough. Uplift rates decrease monotonically westward along the Palliser Bay coast, to 0.2 ± 0.1 mm/yr at Wharekauhau (∼70 km from the trough), defining a gently west-tilted subaerial forearc domain. Locally, active oblique-slip upper-plate faults cause obvious vertical offsets of the marine terraces in the axial ranges (>70 km from the trough). Uplift rates at Baring Head, on the upthrown side of the Wairarapa-Wharekauhau fault system, are ∼0.7–1.6 mm/yr. At Tongue Point, uplift on the upthrown side of the Ōhāriu Fault is 0.6 ± 0.1 mm/yr. Dislocation and flexural-isostatic modelling shows that slip on faults within the overriding plate—specifically the Palliser-Kaiwhata Fault and the Wairarapa-Wharekauhau fault system—may dominate uplift in their immediate hanging walls. Depending on their slip rate and geometry, slip on these two upper-plate fault systems could plausibly cause >80% of late Pleistocene uplift everywhere along the south coast of North Island. Our modelling suggests that subduction of the buoyant Hikurangi Plateau contributes uplift of 0.1–0.2 mm/yr and uplift due to sediment underplating at Tongue Point and Wharekauhau is likely ≤0.6 mm/yr but could be significantly lower. Earthquakes on the subduction interface probably contribute ≤0.4 mm/yr of late Pleistocene uplift, with ≤10% of uplift due to each earthquake being stored permanently, similar to other subduction zones. These results indicate a significant contribution of slip on upper-plate faults to permanent uplift and tilting across the subduction margin and suggest that in regions where upper-plate faults are prevalent, strong constraints on fault geometry and slip rate are necessary to disentangle contributions of deeper-seated processes to uplift.
Dynamic evolution of attribution analysis of runoff based on the complementary Budyko equation in the source area of Lancang river
Authors: Yang Xu , Wang Chao , Du Jun , Qiu Shike , Liu Jiping
Published: March 2023

Analyzing runoff variation characteristics and quantifying the impact of different factors on the runoff variation in the source area of Lancang River, are of significance for scientific response to the ecological protection of the region and Lancang River. The Budyko method is adopted to quantitatively calculate the contribution rate of human factors and climate factors to runoff change in the source area of Lancang River. The results show that: 1) the annual runoff at Qamdo hydrological station decreased significantly during 1961–2018. 2) 1966 is the mutation year of runoff at Qamdo hydrological station from 1961 to 2018. 3) At the Qamdo hydrological station, the contribution rates of precipitation P) to the runoff change are 16.92–72.8% before 1990 and -1.91∼-53.61% after 1990, the contribution rates of potential evaporation (ET0) to the runoff changes are 0.14–39.19%. The contribution rates of human factors ω) to the runoff changes are between 26.9% and 114.42%. This study has important theoretical reference and practical significant for maintaining the integrity and sustainable development of the ecosystems of the Lancang River.
“You have an affiliative leadership style. That's going to be a problem for you.”: Feminized orientations to school leadership and navigating the pipeline
Authors: Odell Sarah Margaret
Published: March 2023

All gender identity is socialized, but anything gendered feminine is marginalized. Up to this point, work on gender and education leadership has remained within the bounds of patriarchy and thus been confined to binary, hierarchical gender definitions. This study pushes past prior work to advance a more complex and messy understanding of how identity impacts aspiring leaders in their careers. The main question for this study is as follows: How do gender identity and gender performance impact the career journeys of aspiring K12 school leaders? Using Carol Gilligan's Listening Guide Method, this study contains the interviews of 18 aspiring K12 school leaders who are graduates of Education University. This study focuses on the key finding that relational leadership, which we come to understand as a feminized orientation to leadership, had a significant impact on aspiring leaders' career journeys. This feminized way of leading, keeping relationships at the center of how school leaders thought about their roles, created obstacles and barriers for them on their way to leadership and for some subjects, once they became school leaders. This study focuses on the interviews of four of the subjects: Rachel, Winston, Taylor, and Charlie. These interviews are representative of the themes around relational leadership. Rachel is a white, heterosexual woman who is at a mid-to-late career stage. She has struggled to advance into school leadership because she thinks about her colleagues first and the institution second. Winston is a white, heterosexual man who was successful in becoming a school leader but has left education all together. He found that the higher he ascended as a school leader, the more he was forced to sever his relationships with faculty and students. Taylor is a gender non-conforming school leader who keeps relationships central to his leadership but has questions about how a non-DEIJ-focused leadership position will enable him to show up. Finally, Charlie is a Black, heterosexual woman school leader who has been able to keep relationships central to her work. All four interviews demonstrate how relational leadership is marginalized, keeping white patriarchy as the framework for school leadership.
Encouraging reflective practice in the teacher education practicum: A dean’s early efforts
Authors: Fuentealba Jara Rodrigo , Russell Tom
Published: March 2023

This article presents an analysis of a dean’s early efforts to encourage reflective practice in the teacher education practicum, in consultation with a critical friend. The focus is on the importance of listening and the identification of assumptions underlying practices. The authors met in 2010 in a week-long seminar focused on the practicum in teacher education programs at a university in Santiago, Chile. A long conversation over dinner one evening revealed a significant interest in each other’s perspectives and experiences. Since that time, more than 20 opportunities to visit each other in Chile and in Canada have established an on-going connection for sharing insights as they emerge from experiences in each other’s country. The authors now consider themselves to be life-long critical friends. In April 2021, Rodrigo was appointed as Dean of Education at Universidad Autónoma in Santiago, with an early focus on encouraging reflective practice by all who are involved in the teacher education practicum—student teachers, mentor teachers and faculty supervisors. Tom retired in 2019 after 42 years in teacher education practice and research at Queen’s University, and he continues to explore the complex issue of how people learn to teach.
Revisions in written composition: Introducing speech-to-text to children with reading and writing difficulties
Authors: Kraft Sanna
Published: March 2023

The ability to perform revisions targeting the content of the text is important for text quality improvement, and it is hypothesized that lower-level transcription processes need to be automatized in order to free up capacity for higher-level processes such as revision. However, for people with reading and writing difficulties due to underlying difficulties with decoding and spelling, the transcription process is rarely automatized because of their troubles with spelling. One possible way to circumvent spelling difficulties, and possibly gaining capacity for higher level processes such as revision, is to write using speech-to-text (STT). This study investigates the revisions performed when children with reading and writing difficulties (n= 16), and a reference group without such difficulties (n= 12), compose text using STT and using a keyboard. More specifically, the study investigates whether, and if so how, revisions at various levels, errors left in the final text product, and text quality differ between conditions and between groups. The compositions were logged using keystroke logging (keyboard) and audio- and screen-recording (STT). The level of revisions were manually coded. The results showed that children with reading and writing difficulties gain more from composing with STT compared to keyboard than the reference group. They leave fewer errors in their final text product when composing by means of STT, even though they need to engage more in the correction of surface errors because of the large number of STT errors. Despite the numerous STT errors, neither the proportion of meaning-related revisions nor text quality decreased in composing with STT (for either of the groups). Taken together, the results suggest, albeit not emphatically, that STT may be appropriate as a facilitatory tool for children with reading and writing difficulties. However, more research is needed to investigate instruction that addresses strategies for STT transcription and highlights the shortcomings of the tool in the target language, and also focuses specifically on higher-level aspects of composition such as planning or revising, in order to gain further knowledge about the feasibility of using STT as a means of composition for children who struggle with writing, and its possible effects over time.
Integrated analysis of genome-wide gene expression and DNA methylation profiles reveals candidate genes in ovary endometriosis
Authors: Lei Lei , Xu Xinxin , Gong Chengchen , Lin Bowen , Li Fang
Published: March 2023

Background

The incidence of endometriosis (EMs), a common disease in gynecology, has increased over the years. Women suffer from the symptoms caused by EMs, such as chronic pelvic pain, dysmenorrhea, and infertility. However, the etiology and pathophysiology of EMs remain unclear. This study aimed to identify candidate genes of endometriosis through integrated analysis of genome-wide gene expression and DNA methylation profiles.

Results

Eutopic and ectopic endometrial tissues were collected from patients who were diagnosed as ovarian EMs. Genome-wide methylation profiling identified 17551 differentially methylated loci, with 9777 hypermethylated and 7774 hypomethylated loci. Differentially methylated loci were mainly concentrated in the gene body and intergenic regions. Genome-wide gene expression profiling identified 1837 differentially expressed genes (DEGs), with 1079 genes upregulated and 758 downregulated in ectopic groups. Integrated analysis revealed that DNA methylation was negatively correlated to gene expression in most genomic regions, such as exon, 3’UTR, 5’UTR, and promoter. We also identified promoter-related (53 downregulated and 113 upregulated) and enhancer-related DMGs (212 downregulated and 232 upregulated), which were significantly correlated to the gene expression. Further validation of the top-ranked genes belonging to differentially methylated genes (DMGs) and DEGs revealed that TMEM184A, GREM2, SFN, KIR3DX1, HPGD, ESR1, BST2, PIK3CG and RNASE1 were significant candidate genes in ovarian endometriosis.

Conclusion

Our study revealed the significance of DNA methylation in the gene expression in ovary endometriosis, which provides new insights and a molecular foundation for understanding the underlying mechanisms of endometriosis.
Impact of GLP-1 receptor agonist versus omega-3 fatty acids supplement on obesity-induced alterations of mitochondrial respiration
Authors: Jansen Kirsten M. , Dahdah Norma , Gama-Perez Pau , Schots Pauke C. , Larsen Terje S. , Garcia-Roves Pablo M.
Published: March 2023

Objective

To compare administration of the glucagon-like peptide-1 (GLP-1) analogue, exenatide, versus dietary supplementation with the omega-3 fatty acid-rich Calanus oil on obesity-induced alterations in mitochondrial respiration.

Methods

Six-week-old female C57BL/6JOlaHSD mice were given high fat diet (HFD, 45% energy from fat) for 12 weeks to induce obesity. Thereafter, they were divided in three groups where one received exenatide (10 μg/kg/day) via subcutaneously implanted mini-osmotic pumps, a second group received 2% Calanus oil as dietary supplement, while the third group received HFD without any treatment. Animals were sacrificed after 8 weeks of treatment and tissues (skeletal muscle, liver, and white adipose tissue) were collected for measurement of mitochondrial respiratory activity by high-resolution respirometry, using an Oroboros Oxygraph-2k (Oroboros instruments, Innsbruck, Austria).

Results

It was found that high-fat feeding led to a marked reduction of mitochondrial respiration in adipose tissue during all three states investigated – LEAK, OXPHOS and ETS. This response was to some extent attenuated by exenatide treatment, but not with Calanus oil treatment. High-fat feeding had no major effect on hepatic mitochondrial respiration, but exenatide treatment resulted in a significant increase in the various respiratory states in liver. Mitochondrial respiration in skeletal muscle was not significantly influenced by high-fat diet or any of the treatments. The precise evaluation of mitochondrial respiration considering absolute oxygen flux and ratios to assess flux control efficiency avoided misinterpretation of the results.

Conclusions

Exenatide increased hepatic mitochondrial respiration in high-fat fed mice, but no clear beneficial effect was observed in skeletal muscle or fat tissue. Calanus oil did not negatively affect respiratory activity in these tissues, which maintains its potential as a dietary supplement, due to its previously reported benefits on cardiac function
The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model
Authors: Wu Dongming , Zhang Zhenyuan , Sun Wenxiu , Yan Yong , Jing Mengzhe , Ma Shizhan
Published: March 2023

Background

Previous research has shown a tight relationship between the G0/G1 switch gene 2 (G0S2) and metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and obesity and diabetes, and insulin resistance has been shown as the major risk factor for both NAFLD and T2DM. However, the mechanisms underlying the relationship between G0S2 and insulin resistance remain incompletely understood. Our study aimed to confirm the effect of G0S2 on insulin resistance, and determine whether the insulin resistance in mice fed a high-fat diet (HFD) results from G0S2 elevation.

Methods

In this study, we extracted livers from mice that consumed HFD and received tail vein injections of AD-G0S2/Ad-LacZ, and performed a proteomics analysis.

Results

Proteomic analysis revealed that there was a total of 125 differentially expressed proteins (DEPs) (56 increased and 69 decreased proteins) among the identified 3583 proteins. Functional enrichment analysis revealed that four insulin signaling pathway-associated proteins were significantly upregulated and five insulin signaling pathway -associated proteins were significantly downregulated.

Conclusion

These findings show that the DEPs, which were associated with insulin resistance, are generally consistent with enhanced insulin resistance in G0S2 overexpression mice. Collectively, this study demonstrates that G0S2 may be a potential target gene for the treatment of obesity, NAFLD, and diabetes.
Metagenomics reveals the diversity and role of surface-water microbes in biogeochemical cycles in lakes at different terrain ladders
Authors: Zhao Aiwen , Lu Yuntao , Li Qi , Li Tao , Zhao Jindong
Published: March 2023

As the most important component of ecosystems, microbial communities play a significant role in global biogeochemical cycles. Geographical barriers created by topographic differences are proposed as one of the main factors to shape microbial diversity, functional composition and their evolution across aquatic ecosystem. There are few studies that compare the microbial community structure and functional potential of lakes with different terrain ladders (terrains of contrasting elevation levels), especially those involving Qinghai-Tibet Plateau. This study compared microbial 16S rRNA data from 51 lakes with different terrain ladders, showing that the composition of the dominant microbial community was similar, but the microbial abundance was quite different in different terrain ladders. Actinobacteria, Proteobacteria, Cyanobacteria, Planctomycete, Verrucomicrobia and Bacteroidetes were the dominant taxa. Through the correlation analysis between environmental factors and the microbial community structure, it was found that two environmental factors (elevation and salinity) had significant contributions to the microbial composition. Metagenomics of six representative lakes revealed the relationship between microbial composition and metabolic processes related to carbon, nitrogen and sulfur cycles. The comparative analysis of genes related to metabolism cycles showed that functional processes such as aerobic respiration, nitrogen assimilation, the mineralization of nitrogen and sulfur had highest metabolic potential in the ecosystems. The analysis of indicator species based on the metabolic process in the carbon, nitrogen and sulfur cycles showed that the microbial community structure is related to the dominant metabolic functions within biogeochemical cycles. Different dominant species play an important and distinct role in lakes with different gradients. Actinobacteria, Cyanobacteria and Proteobacteria were the most important indicator species on the Qinghai-Tibet Plateau, Yunnan-Guizhou Plateau and the middle and lower reaches of the Yangtze River Plain, respectively. In general, this study explored the functional distribution patterns of the dominant microbial communities in the lakes in biogeocycles.
Preliminary study on microplastic abundance in mangrove sediment cores at Mae Klong River, upper Gulf of Thailand
Authors: Chaisanguansuk Pattraporn , Phantuwongraj Sumet , Jirapinyakul Akkaneewut , Assawincharoenkij Thitiphan
Published: March 2023

Microplastics have polluted our environment, particularly mangrove ecosystems, the barriers between land and sea that trap sediments and pollutants. The abundance of microplastics has increased in microplastic deposition and is expected to rise in the future. In this study, mangrove sediment cores were collected from the Mae Klong River mouth and Queen Sirikit Park (shoreline), Samut Songkhram province. The microplastics were analyzed using a modified flotation method, then recasted and removed organic matter. Fiber microplastics is composed of 92% and 82% of the total microplastics that found in the Mae Klong River mouth and Queen Sirikit Park, respectively. There were significant changes in the abundance of microplastics in relation to the sediment particle size (p < 0.05). The difference in location between the Queen Sirikit Park and Mae Klong River mouth sites was significant (p < 0.01). The accumulation of microplastics in the sediments was influenced by grain size and location. The polymer types of microplastics were those normally used in textiles, indicating human activity. Moreover, micro-Fourier transform infrared (µ-FTIR) spectroscopy analysis identified compounds of other small particles, including tire rubber, pigment, paint, dyes, and flame retardant. These results imply that microplastics and microparticles have polluted the mangrove sediment in the Mae Klong River basin, which is an important fishery area in the upper Gulf of Thailand.
Outcomes associated with translocation of mule deer (Odocoileus hemionus): Influence of age, release timing, and year on survival
Authors: Smedley David C. , McMillan Brock R. , Hersey Kent R. , Shannon Justin M. , Larsen Randy T.
Published: March 2023

Translocation of large mammals has become common practice for wildlife managers charged with conservation of animals and their genetic integrity on increasingly modified landscapes. Translocations of ungulates have occurred around the world with varying outcomes. Although translocations have been used to manage mule deer (Odocoileus hemionus) in western North America, only recently have the outcomes associated with this management practice been documented. Our objective was to evaluate survival of translocated mule deer in comparison to resident mule deer over multiple years following release and provide information useful in judging the relative value of translocation as a conservation strategy for this species. In January and March 2013, the Utah Division of Wildlife Resources (UDWR) captured and translocated 102 mule deer from winter range near Parowan, Utah to winter range near Holden, Utah (approximately 145 kilometers north of capture location). We fitted each deer with a radio transmitter (n = 102 total: 21 GPS collars, 81 VHF collars) prior to release. We also captured and marked a total of 70 resident deer (9 GPS collars, 61 VHF collars) to serve as a reference group. Survival of translocated deer in the first year was similar among release dates in January (0.51; 95% CI = 0.40–0.63) and March (0.53; 95% CI = 0.40–0.66). Annual survival of translocated deer, however, was lower than survival of resident deer (0.83; 95% CI = 0.72–0.90) in the first year after release. During the second year following release, however, survival of translocated animals (0.85; 95% CI = 0.71–0.93) was not different from that of resident deer (0.80; 95% CI = 0.69–0.88). Additionally, age strongly influenced the survival of translocated deer; young deer (e.g., 1.5  year olds) were more than twice as likely as old deer (e.g., 7.5  year olds) to survive the initial year following translocation. These data highlight the need to monitor translocated animals for multiple years following release and suggest that wildlife managers should expect to see higher survival rates during the second year following translocation and higher survival rates in younger deer compared to older deer.
Outer membrane vesicles of Dinoroseobacter shibae transport a volatile aldehyde
Authors: Koteska Diana , Wang Hui , Wagner-Döbler Irene , Schulz Stefan
Published: March 2023

Outer Membrane Vesicles (OMVs) of the Gram-negative marine bacterium Dinoroseobacter shibae, a member of the Roseobacteraceae, were investigated for the presence of volatile organic compounds (VOCs). Extracts of vesicles were analyzed by gas chromatography/mass spectrometry (GC/MS). In these analyses the short fatty acid (Z)-5-dodecenoic acid (1) and the related, more volatile aldehyde (Z)-5-dodecenal (8) were identified as VOCs of the OMVs. The aldehyde 8 has not yet been reported before from bacteria. Due to their possible function as signaling molecules, both compounds were tested for Quorum Sensing (QS) inhibition in a bioassay against the QS sensor strain Pseudomonas putida F117 (pKRC12) responsive to long-chain N-acylhomoserine lactones, the effectors of the sensor. Both compounds showed QS inhibitory activity. The potential function of VOCs in OMVs which has not been observed previously is discussed.
Gelsolin: A comprehensive pan-cancer analysis of potential prognosis, diagnostic, and immune biomarkers
Authors: Wang Yiyang , Bi Xiaojuan , Luo Zhiwen , Wang Haiyan , Ismtula Dilimulati , Guo Chenming
Published: March 2023

Introduction: Gelsolin (GSN), a calcium-regulated actin-binding protein, is out of balance in various cancers. It can mediate cytoskeletal remodeling and regulate epithelial-mesenchymal conversion (EMT), but the studies on GSN function in pan-cancer are limited.

Methods: We studied the transcription level, prognostic impact, diagnostic value, genetic, epigenetic modification, methylation level and immune significance of GSN in pan-cancer to fully comprehend the function of GSN in various malignancies based on multiple databases like The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).

Results: Pan-cancer research showed that GSN was downregulated in most tumors and expressed differently in immunological and molecular subtypes of many cancers. GSN had varying impacts on the prognosis of various tumor types. However, all had moderate to high diagnostic efficiency, and serum GSN had good diagnostic value in breast cancer patients (AUC = 0.947). Moreover, GSN was a distinguishing prognosis factor for some specific cancer types. The GSN protein was hypophosphorylated, and its promoter was hypermethylated in most cancers. GSN was linked to the infiltration level of several immunity cells and was essential in anti-tumor immune cell infiltration. KEGG and GSEA analyses showed that GSN was vital in the functions and proteoglycans processes in cancer, chemokine signaling pathway and other immune-related pathways, DNA methylation and cell cycle.

Discussion: In conclusion, GSN possesses the ability to be a predictive, diagnostic, and immune indicator in pan-cancer.
A novel signature combing cuproptosis- and ferroptosis-related genes in sepsis-induced cardiomyopathy
Authors: Song Juanjuan , Ren Kairui , Zhang Dexin , Lv Xinpeng , Sun Lin , Deng Ying , Zhu Huadong
Published: March 2023

Objective: Cardiac dysfunction caused by sepsis, usually termed sepsis-induced cardiomyopathy (SIC), is one of the most serious complications of sepsis, and ferroptosis can play a key role in this disease. In this study, we identified key cuproptosis- and ferroptosis-related genes involved in SIC and further explored drug candidates for the treatment of SIC.

Methods: The GSE79962 gene expression profile of SIC patients was downloaded from the Gene Expression Omnibus database (GEO). The data was used to identify differentially expressed genes (DEGs) and to perform weighted correlation network analysis (WGCNA). Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Then, gene set enrichment analysis (GSEA) was applied to further analyze pathway regulation, with an adjusted p-value <0.05 and a false discovery rate (FDR) <0.25. Ferroptosis-related genes were obtained from the FerrDb V2 database, and cuproptosis-related genes were obtained from the literature. We constructed a novel signature (CRF) by combing cuproptosis-related genes with ferroptosis-related genes using the STRING website. The SIC hub genes were obtained by overlapping DEGs, WGCNA-based hub genes and CRF genes, and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of hub genes. A transcription factor-microRNA-hub gene network was also constructed based on the miRnet database. Finally, potential therapeutic compounds for SIC were predicted based on the Drug Gene Interaction Database.

Results: We identified 173 DEGs in SIC patients. Four hub modules and 411 hub genes were identified by WGCNA. A total of 144 genes were found in the CRF. Then, POR, SLC7A5 and STAT3 were identified as intersecting hub genes and their diagnostic values were confirmed with ROC curves. Drug screening identified 15 candidates for SIC treatment.

Conclusion: We revealed that the cuproptosis- and ferroptosis-related genes, POR, SLC7A5 and STAT3, were significantly correlated with SIC and we also predicted therapeutic drugs for these targets. The findings from this study will make contributions to the development of treatments for SIC.
Dissected subgroups predict the risk of recurrence of stage II colorectal cancer and select rational treatment
Authors: Wang Fulong , Lu Shixun , Zhou Xin , Di Xiaotang , Wu Rujia , Chen Gong , Tian Sun
Published: March 2023

Background

Stage II colorectal cancer(CRC) patients after surgery alone have a five-year survival rate of ~60-80%; the incremental benefit of adjuvant chemotherapy is <5%. Predicting risk of recurrence and selecting effective personalized adjuvant drugs for stage II CRC using formalin-fixed, paraffin-embedded(FFPE) samples is a major challenge.

Methods

1319 stage II CRC patients who enrolled in 2011-2019 at Sun Yat-sen University Cancer Center were screened. RNAseq data of FFPE tumor samples of 222 stage II microsatellite stable(MSS) CRC patients(recurrence (n=47), norecurrence (n=175), median follow-up=41 months) were used to develop a method TFunctionalProg for dissecting heterogeneous subgroups of recurrence and predicting risk of recurrence.

Results

TFunctionalProg showed significant predictive values in 222 stage II MSS CRCs. The TFunctionalProg low-risk group had significantly better recurrence free survival (validation set: HR=4.78, p-value=1e-4, low-risk group three-year recurrence free survival=92.6%, high-risk group three-year recurrence free survival=59.7%). TFunctionalProg dissected two subgroups of transition states of stage II MSS CRCs at a high risk of recurrence; each state displays distinct levels of hybrid epithelial-mesenchymal traits, CD8+ T cell suppression mechanisms and FOLFOX resistance. Based on mechanisms in two subgroups, TFunctionalProg proposed personalized rational adjuvant drug combinations of immunotherapy, chemotherapy and repurposed CNS drugs. TFunctionalProg provides different utilities from ctDNA-based prognostic biomarkers.

Conclusion

TFunctionalProg was validated using FFPE samples to predict the risk of recurrence and propose rational adjuvant drug combinations for stage II CRC.
Design and preclinical evaluation of a universal SARS-CoV-2 mRNA vaccine
Authors: Qin Jane , Jeon Ju Hyeong , Xu Jiangsheng , Langston Laura Katherine , Marasini Ramesh , Mou Stephanie , Montoya Brian , Melo-Silva Carolina R. , Jeon Hyo Jin , Zhu Tianyi , Sigal Luis J. , Xu Renhuan , Zhu Huabin
Published: March 2023

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated lipid nanoparticle (LNP) formulated mRNA vaccines that induce only T cell responses or both T cell and neutralizing antibody responses by using two mRNAs. One mRNA encodes SARS-CoV-2 Omicron Spike protein in prefusion conformation for induction of neutralizing antibodies. The other mRNA encodes over one hundred T cell epitopes (multi-T cell epitope or MTE) derived from non-Spike but conserved regions of the SARS-CoV-2. We show immunization with MTE mRNA alone protected mice from lethal challenge with the SARS-CoV-2 Delta variant or a mouse-adapted virus MA30. Immunization with both mRNAs induced the best protection with the lowest viral titer in the lung. These results demonstrate that induction of T cell responses, in the absence of preexisting antibodies, is sufficient to confer protection against severe disease, and that a vaccine containing mRNAs encoding both the Spike and MTE could be further developed as a universal SARS-CoV-2 vaccine.
Monoacylglycerol lipase regulates macrophage polarization and cancer progression in uveal melanoma and pan-cancer
Authors: Tan Yao , Pan Juan , Deng Zhenjun , Chen Tao , Xia Jinquan , Liu Ziling , Zou Chang , Qin Bo
Published: March 2023

Background

Although lipid metabolism has been proven to play a key role in the development of cancer, its significance in uveal melanoma (UM) has not yet been elucidated in the available literature.

Methods

To identify the expression patterns of lipid metabolism in 80 UM patients from the TCGA database, 47 genes involved in lipid metabolism were analyzed. Consensus clustering revealed two distinct molecular groups. ESTIMATE, TIMER, and ssGSEA analyses were done to identify the differences between the two subgroups in tumor microenvironment (TME) and immune state. Using Cox regression and Lasso regression analysis, a risk model based on differentially expressed genes (DEGs) was developed. To validate the expression of monoacylglycerol lipase (MGLL) and immune infiltration in diverse malignancies, a pan-cancer cohort from the UCSC database was utilized. Next, a single-cell sequencing analysis on UM patients from the GEO data was used to characterize the lipid metabolism in TME and the role of MGLL in UM. Finally, in vitro investigations were utilized to study the involvement of MGLL in UM.

Results

Two molecular subgroups of UM patients have considerably varied survival rates. The majority of DEGs between the two subgroups were associated with immune-related pathways. Low immune scores, high tumor purity, a low number of immune infiltrating cells, and a comparatively low immunological state were associated with a more favorable prognosis. An examination of GO and KEGG data demonstrated that the risk model based on genes involved with lipid metabolism can accurately predict survival in patients with UM. It has been demonstrated that MGLL, a crucial gene in this paradigm, promotes the proliferation, invasion, and migration of UM cells. In addition, we discovered that MGLL is strongly expressed in macrophages, specifically M2 macrophages, which may play a function in the M2 polarization of macrophages and M2 macrophage activation in cancer cells.

Conclusion

This study demonstrates that the risk model based on lipid metabolism may be useful for predicting the prognosis of patients with UM. By promoting macrophage M2 polarization, MGLL contributes to the evolution of malignancy in UM, suggesting that it may be a therapeutic target for UM.
Chlorophyll response to wind and terrestrial nitrate in the western and southern continental shelves of the Gulf of Mexico
Authors: González-Ramírez Javier , Parés-Sierra Alejandro , Cepeda-Morales Jushiro
Published: March 2023

In Mexico, 16 rivers directly discharge into the Gulf of Mexico. The Mexican rivers and those coming from the United States generate large regions in which phytoplanktonic primary production possesses a seasonal component that is linked to these nutrient-rich freshwater inputs. In the present study, new simulated flow and daily nutrient data were obtained for the largest Mexican rivers. These data were integrated as forcings in a configuration of the hydrodynamic Coastal and Regional Ocean COmmunity model coupled to an N2PZD2 biogeochemical model. We present a 21 year simulation using two different configurations. The first included river forcing, and the second did not consider their influence. The results were validated with satellite images of the surface chlorophyll concentration and discussed with data presented in previous studies. The model was able to realistically reproduce the seasonal dynamics of primary production in the Gulf of Mexico based on the concentration and distribution of chlorophyll, both at the surface and in the water column. We found significant differences in the response of chlorophyll to the input of nitrate from the rivers between both model configurations. The largest and most evident in the northern region of the continental shelf followed by the Bay of Campeche and Tamaulipas-Veracruz shelves. Finally, using the configuration with the river forcing, the physical processes that influence the dynamics of chlorophyll concentration in the deep region and continental shelf of the gulf were determined. In the deep region, primary production was driven by vertical mixing induced by the passage of cold fronts during winter and mesoscale structures. On the continental shelf, such dynamics were driven by coastal upwelling and fluvial nutrient contributions.
First Maximum Sustainable Yield advice for the Nephrops norvegicus stocks of the Northwest Iberian coast using stochastic Surplus Production model in Continuous Time (SPiCT)
Authors: González Herraiz Isabel , Vila Yolanda , Cardinale Massimiliano , Berg Casper W. , Winker Henning , Azevedo Manuela , Mildenberger Tobias K. , Kokkalis Alexandros , Vázquez Vilamea A. Armando , Morlán Roberto , Somavilla Raquel , Pennino Maria Grazia
Published: March 2023

The assessment of the status of fisheries resources is pivotal due to the importance of marine resources in global food security and to halt the ongoing decline in marine biodiversity. Norway lobster (Nephrops norvegicus) is one of the most valuable resources in the Northeast Atlantic. However, overfishing has caused the decline of several Nephrops stocks over the last decades, particularly in the Nephrops Functional Units (FUs) 25 (NW Spain), 26-27 (NW Spain and North Portugal) and 31 (Cantabrian Sea, North Spain). Since 2003, the information provided by the very low level of landings and fishing effort of these three stocks was insufficient to carry out an adequate analytical assessment, so the base of the assessment has been the trends from commercial catch per unit effort (CPUE). The objective of this study was to carry out the first assessment of these three stocks with an analytical MSY-based model. A review of the available data was made and the stochastic Surplus Production Model in Continuous Time (SPiCT) was fitted for each FU. The results indicate an extremely low biomass for FUs 25 and 26-27 since the mid-nineties well below the reference points. For FU 31, on the other hand, estimated biomass is larger. Our findings also identified long-term temporal and spatial changes in the population dynamic of Nephrops in the Northwest Iberian coast. The results were compare with those obtained in the same stocks with other data-limited methods. Also the role of abiotic factors on the observed dynamic of the stocks was explored. The results of this study are not only relevant for the sustainable exploitation of Norway lobster stocks off the Northwest Iberian coast but provide valuable insights into the suitability and limitations of production models for the assessment of crustacean stocks in general.
Spatial distribution and seasonal variation of fish larvae in the upper 200 m of the Philippine Sea
Authors: Fang Chen , Wang Xiaogu , Sun Dong , Zhai Hongchang , Zhang Dongsheng , Liao Guanghong , Wang Chunsheng
Published: March 2023

The Philippine Sea, owing to its complicated circulation pattern and the presence of numerous seamounts, is considered to be a hotspot for biodiversity and an important fishing ground. However, to date, few studies on ichthyoplankton in the Philippine Sea have been conducted. During the summer, autumn, and winter of 2020–2021, a series of investigations were conducted to study the spatial and temporal structure of fish larvae in the Philippine Sea. A total of 65 samples were collected by vertical hauling from a depth of 200 m to the surface. A total of 882 fish larvae representing 81 distinct taxa, 49 genera, and 23 families were identified. A seasonal pattern was also observed based on the differences in abundance and dominant taxa. The abundance of fish larvae was 11.35 ± 12.46 ind./100 m3 (mean ± sd.) in summer, 5.83 ± 7.03 ind./100 m3 in autumn, and 2.57 ± 2.73 ind./100 m3 in winter. The dominant species were Vinciguerria nimbaria, Encrasicholina punctifer, and Cyclothone sp. in summer, V. nimbaria, and Ceratoscopelus warmingii in autumn, and Diaphus spp., D. garmani, and Sigmops sp. in winter. A significant latitudinal variation in fish larvae assemblages was found via cluster analysis, and two geographic groups were separated by the northern boundary of the North Equatorial Current. In addition, the fish larvae species diversity also showed a significant latitudinal gradient in autumn, which disappeared in summer. Canonical correspondence analysis indicated that the structure of fish larvae assemblages was affected by average temperature, salinity, and net primary productivity in the upper ocean and sea level anomaly. All dominant species were associated with specific niche environments. This study suggests that latitudinal zonation of fish larvae also occurs in the oligotrophic low latitude Pacific Ocean and is enhanced in autumn. These results provide multi-seasonal baseline data of fish larvae assemblage in the upper Philippine Sea, being an important reference for the planning of marine protected areas in the high seas.
Underwater target detection algorithm based on improved YOLOv4 with SemiDSConv and FIoU loss function
Authors: Zhang Chengpengfei , Zhang Guoyin , Li Heng , Liu Hui , Tan Jie , Xue Xiaojun
Published: March 2023

Underwater target detection is an indispensable part of marine environmental engineering and a fast and accurate method of detecting underwater targets is essential. Although many target detection algorithms have achieved great accuracy in daily scenes, there are issues of low-quality images due to the complex underwater environment, which makes applying these deep learning algorithms directly to process underwater target detection tasks difficult. In this paper, we presented an algorithm for underwater target detection based on improved You Only Look Once (YOLO) v4 in response to the underwater environment. First, we developed a new convolution module and network structure. Second, a new intersection over union loss was defined to substitute the original loss function. Finally, we integrated some other useful strategies to achieve more improvement, such as adding one more prediction head to detect targets of varying sizes, integrating the channel attention into the network, utilizing K-means++ to cluster anchor box, and utilizing different activation functions. The experimental results indicate that, in comparison with YOLOv4, our proposed algorithm improved the average accuracy of the underwater dataset detection by 10.9%, achieving 91.1%, with a detection speed of 58.1 frames per second. Therefore, compared to other mainstream target detection algorithms, it is superior and feasible for applications in intricate underwater environments.
Case report: Dermatosis neglecta mimicking pemphigus foliaceus in association with obsessive–compulsive disorder
Authors: Wattanawinitchai Kantarat , Suchonwanit Poonkiat
Published: March 2023

Dermatosis neglecta (DN) is a frequently underrecognized skin disorder that occurs due to unconscious or conscious neglect of self-cleaning, causing the accumulation of keratin, sweat, sebum, and impurities. It is characterized by asymptomatic yellowish-to-brownish, waxy, adherent papules or plaques with cornflake-like scales that mimic several dermatological conditions. DN awareness is crucial for avoiding unnecessary invasive diagnostic procedures. Its lesions can be removed with some difficulty by ordinary cleansing and efficiently cleared with ethyl or isopropyl alcohol. Individuals with underlying physical or mental disabilities or psychiatric conditions are highly associated with DN. Nevertheless, supportive evidence for the coexistence of DN and psychological conditions is sparse, and most individuals with mental problems usually deny having psychiatric issues. Here, we present a case of DN resembling pemphigus foliaceus on the face with obsessive–compulsive disorder in a 16-years old male. The definitive diagnosis of DN in this patient was confirmed via histopathological examination. The lesions completely disappeared after appropriate facial cleansing and psychiatric management. DN may reveal underlying psychiatric disorders in patients.