bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronous Fracture Expansion Pattern of Hydraulic Fracturing with Different Perforation Spacing
Authors: Jiang Yulong , Wang Kai , Zhang Xiaoqiang , Cai Tingting
Published: January 2024

Using the self-developed “TCHFSM-I” large-size true triaxial fracturing seepage simulation device and fluid injection flow dynamic monitoring device, we studied the crack initiation and expansion law of multi-fractures under different perforation spacing conditions and revealed the mechanism of multi-fractures expanding from non-equilibrium to equilibrium on the basis of the evolution law of the injection pressure and characteristics of the distribution of the injection flow. The results show that when the perforation spacing is small (<60 mm), the central injection fracturing cracks are affected by the extension of the upper and lower injection cracks, and their extension lengths are shorter; on the contrary, the extension lengths of the upper, central and lower injection cracks are basically the same, and the three hydraulically fractured cracks shift from non-equilibrium to equilibrium extension. When the perforation spacing is small, the fracture initiation pressure of the middle perforation is much larger than that of the upper and lower perforations. However, as the perforation spacing increases, the fracture initiation pressure of the middle perforation gradually decreases. Its fracture initiation pressure is basically the same as that of the upper and lower perforations. The expansion of the three hydraulically fractured cracks is independent of each other. In addition, the evolution law of the injection flow rate can better reflect the multi-fracture fracture initiation and expansion pattern, and the evolution pattern of the injection flow rate can better reflect the synchronous fracture initiation and expansion mechanism of multi-fracture fracture. The results of the study can provide technical guidance for efficient coalbed methane extraction.
A Two-Stage Cascade for Increased High-Value Product Accumulation in Chlamydomonas asymmetrica
Authors: Hahm Joachim , Jung Sun-Hwa , Kandaswamy Saikrishnan , Talwar Prakhar , Verma Nikita , Vivekanand Vivekanand , Lindenberger Christoph
Published: January 2024

Cascade systems are used in the large-scale production of astaxanthin, facilitating a successful value-added process despite high accumulating costs. However, their application to other high-value products (HVPs), like lutein, β-carotene, chlorophylls, and fatty acids, remains unexplored. This study investigates Chlamydomonas asymmetica in chemostatic cultures, focusing on the impact of light and dilution rate. A two-stage cascade system is designed, combining high-light growth with low-light pigment accumulation. The results show potential for productivity improvement. Notably, the spacetime yield (STY) of Chlorophyll a increased by 20.96%, reaching 2.73 g·L−1·d−1 at the lowest dilution rate. Lutein maintains a consistent concentration of 22.34 mg·g−1, while β-carotene achieves a maximum STY of 3.60 mg·L·d−1. A cascade modification with a hollow fiber membrane significantly enhances HVP concentrations—Chlorophyll b, Lutein, Chlorophyll a, β-carotene, EPS, and GLA increase 27.23%, 38.95%, 31.88%, 86.19%, 128.7%, and 57.71%, respectively. STY improvements for these HVPs range from 1.78% to 82.96%. This study offers insights into C. asymmetica’s response and proposes a cascade modification for enhanced HVP production and downstream processing efficiency.
Screening, Characterization and Probiotic Properties of Selenium-Enriched Lactic Acid Bacteria
Authors: Zan Lixia , Chen Zhe , Zhang Ben , Zou Xiangyu , Lan Afeng , Zhang Wenyi , Yuan Yahong , Yue Tianli
Published: January 2024

Considerable progress has been achieved in the bioaccumulation and transformation of selenium (Se)-enriched lactic acid bacteria (LAB). However, research on the effects of Se on the structure and probiotic potential of LAB is relatively limited. In this study, six industrial LAB strains, including Lactobacillus plantarum 21,805, Lactobacillus paracasei 20,241, Lactobacillus fermentum 21,828, Lactobacillus casei 23,185, Lactobacillus acidophilus 6064, and Lactobacillus plantarum 6076, were cultured in De Man, Rogosa, and Sharpe (MRS) medium containing Se for three generations. High-Se LAB was screened based on bacterial biomass, viable bacterial count, and Se content. Their structural characteristics were analyzed using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The results indicated that LAB growth was influenced by the Se environment, with high Se (20 μg/mL) inhibiting it. At a Se concentration of 10 μg/mL, LAB maintained integrity and exhibited a high Se enrichment ability, with a Se enrichment of 4.88 ± 0.39 mg/g. The intracellular Se existed in an amorphous or non-crystalline form. Furthermore, Se-enriched LAB exhibited enhanced probiotic properties, including tolerance to simulated gastrointestinal fluids, acid resistance, bile salt resistance, and hydrophobicity. Therefore, Se-enriched LAB are expected to develop new functional foods or dietary supplements for human and animal consumption.
Regional High-Rise Building Fire Risk Assessment Based on the Spatial Markov Chain Model and an Indicator System
Authors: Zhang Yan , Wang Guru , Wang Xuehui , Kong Xin , Jia Hongchen , Zhao Jinlong
Published: January 2024

High-rise buildings (HRBs) are prone to high fire hazards due to their high occupant density, limited evacuation routes, and high fire load. The indicator system method, as a systematic evaluation method, is widely applied to assess HRB fire risk. However, the method is subjective because the determination of the indicator weights mainly relies on expert experience. In order to reduce the subjectivity of the indicator system method in assessing the fire risk of HRBs, this study proposes a new assessment method by combining the spatial Markov chain model and the indicator system method. In this new method, fire occurrence probability is calculated by the spatial Markov chain model using historical HRB fire accident data. An indicator system is built to characterize the fire consequence by the structure entropy weight method. Subsequently, HRBs in Beijing are used as a case to illustrate the practicality of this approach. Firstly, the spatial Markov chain model is trained and validated using the chi-square goodness-of-fit test based on fire accident data from 2018 to 2023 in Beijing. It was found that the best performance was achieved with the monthly period and the four-state. Then, the distribution of regional fire occurrence probability in April was predicted based on fire accident data in March 2023 in Beijing. It showed that areas with higher fire occurrence probability are mainly located in the central region, especially in the I District. Then, the indicator system was used to evaluate the HRB fire consequence in the I District. The assessment results showed that the areas with more severe fire consequences are mainly located in the II and IV Districts, due to the poor performance of the fire system or the absence of fire protection systems. Coupling the fire occurrence probability and its consequences shows that HRBs with higher fire risk are mainly located in area II and should be carefully supervised for fire management. This developed method can provide some insights into the fire safety management of HRBs and the layout of the fire stations.
Population-Based Biobanking
Authors: Lieb Wolfgang , Strathmann Eike A. , Röder Christian , Jacobs Gunnar , Gaede Karoline I. , Richter Gesine , Illig Thomas , Krawczak Michael
Published: January 2024

Population-based biobanking is an essential element of medical research that has grown substantially over the last two decades, and many countries are currently pursuing large national biobanking initiatives. The rise of individual biobanks is paralleled by various networking activities in the field at both the national and international level, such as BBMRI-ERIC in the EU. A significant contribution to population-based biobanking comes from large cohort studies and national repositories, including the United Kingdom Biobank (UKBB), the CONSTANCES project in France, the German National Cohort (NAKO), LifeLines in the Netherlands, FinnGen in Finland, and the All of Us project in the U.S. At the same time, hospital-based biobanking has also gained importance in medical research. We describe some of the scientific questions that can be addressed particularly well by the use of population-based biobanks, including the discovery and calibration of biomarkers and the identification of molecular correlates of health parameters and disease states. Despite the tremendous progress made so far, some major challenges to population-based biobanking still remain, including the need to develop strategies for the long-term sustainability of biobanks, the handling of incidental findings, and the linkage of sample-related and sample-derived data to other relevant resources.
Special Issue “Primate Phylogeny and Genetics”
Authors: Radespiel Ute , Roos Christian
Published: January 2024

New phylogenetic tools and population genetics methods have been developed and vastly advanced over the last decade [...]
Preliminary Psychometric Evaluation of Novel Measures of Therapist Practice Related to LGBTQ+ Clients
Authors: Turpin Rodman , Fish Jessica N. , King-Marshall Evelyn , Boekeloo Bradley
Published: January 2024

Background: Culturally competent and equitable mental healthcare for LGBTQ+ people is critical for addressing mental health inequities for this population. Tools to assess therapists’ practice with LGBTQ+ clients are needed for research and clinical efforts related to mental healthcare equity goals. Methods: We conducted a preliminary assessment of the reliability and validity of a novel 28-item self-report measure assessing therapist practice with LGBTQ+ clients. We examined the construct validity using factor analyses, the convergent and criterion validity using intercorrelations with LGBTQ-affirming knowledge, self-efficacy, and attitudes, and the internal consistency using Cronbach alpha. Results: Our overall total LGBTQ+ practice measure demonstrated excellent internal consistency (Cronbach’s alpha = 0.91) and was strongly associated with LGBTQ+ knowledge (rho = 0.377), self-efficacy (rho = 0.633), and LGBTQ+ attitudes (rho = 0.305). We also identified two subscales: “Commitment to Continued Learning” and “Affirmative Practices”, which demonstrated similarly strong internal consistency and tests of validity. Conclusions: Our novel measure of overall LGBTQ+ practice, including two subscales, demonstrated strong reliability and validity. These findings have important implications for practice and research in mental healthcare for LGBTQ+ clients. Future research exploring these measures in relationship to mental healthcare outcomes is recommended.
Examining Anti-Poverty Programs to Address Student’s Unmet Basic Needs at Texas Hispanic-Serving Institutions over the Course of the COVID-19 Pandemic
Authors: Zottarelli Lisa K. , Sunil Thankam , Xu Xiaohe , Chowdhury Shamatanni
Published: January 2024

Many post-secondary institutions have implemented anti-poverty programs to address students’ basic needs insecurities. This study examined the provision of 17 types of basic needs programs at Texas Hispanic-serving institutions over the course of the COVID-19 pandemic with the aim to identify changes in the number and types of programs offered as well as factors that may influence the presence of specific types of basic needs programs on campus. While the average number of basic needs programs per institution varied little over time, the specific types of programs that were offered changed. Institution type as a 2-year or 4-year institution was associated with providing on-campus mental health services, on-campus physical health services, and after-school care for students’ children at pre-pandemic and anticipated post-pandemic time points and employing students and free food or meal vouchers at the pre-pandemic time point. The percentage of students receiving Pell Grants was associated with basic needs programs to assist students applying for public services and referrals to off-campus health services pre-pandemic and anticipated post-pandemic. The presence of an on-campus free food pantry was associated with the percentage of students receiving Pell Grants at the anticipated post-pandemic time point only. Over the course of the pandemic, there were changes to the types of basic needs programs offered. Some types of basic needs programs were associated with institutional and/or student characteristics. Given the continued presence of basic needs programs through the course of the pandemic and into the post-pandemic period, the use of these kinds of programs and services to support students, while influenced by external factors such as the pandemic, appears institutionally established as a way to facilitate going to college for students in need.
A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
Authors: Anguita Raul , Prats-Ejarque Guillem , Moussaoui Mohammed , Becknell Brian , Boix Ester
Published: January 2024

Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP, resulting in a G to A substitution that determines an arginine (R) to glutamine (Q) transversion at position 66 in the protein sequence. By structural analysis we observed that R66Q substitution significantly reduces the positive electrostatic charge at the protein surface. Here, we generated both recombinant RNase 6-R66 and -Q66 protein variants and determined their antimicrobial activity toward uropathogenic Escherichia coli (UPEC), the most common cause of UTI. We found that the R66 variant, encoded by the major SNP rs1045922 allele, exhibited superior bactericidal activity in comparison to the Q66 variant. The higher bactericidal activity of R66 variant correlated with an increase in the protein lipopolysaccharide binding and bacterial agglutination abilities, while retaining the same enzymatic efficiency. These findings encourage further work to evaluate RNASE6 SNP distribution and its impact in UTI susceptibility.
Pigment Diversity in Leaves of Caladium × hortulanum Birdsey and Transcriptomic and Metabolic Comparisons between Red and White Leaves
Authors: Zhou Yiwei , Xu Yechun , Zhu Gen-Fa , Tan Jianjun , Lin Jingyi , Huang Lishan , Ye Yuanjun , Liu Jinmei
Published: January 2024

Leaf color is a key ornamental characteristic of cultivated caladium (Caladium × hortulanum Birdsey), a plant with diverse leaf colors. However, the genetic improvement of leaf color in cultivated caladium is hindered by the limited understanding of leaf color diversity and regulation. In this study, the chlorophyll and anthocyanin content of 137 germplasm resources were measured to explore the diversity and mechanism of leaf color formation in cultivated caladium. Association analysis of EST-SSR markers and pigment traits was performed, as well as metabolomics and transcriptomics analysis of a red leaf variety and its white leaf mutant. We found significant differences in chlorophyll and anthocyanin content among different color groups of cultivated caladium, and identified three, eight, three, and seven EST-SSR loci significantly associated with chlorophyll-a, chlorophyll-b, total chlorophyll and total anthocyanins content, respectively. The results further revealed that the white leaf mutation was caused by the down-regulation of various anthocyanins (such as cyanidin-3-O-rutinoside, quercetin-3-O-glucoside, and others). This change in concentration is likely due to the down-regulation of key genes (four PAL, four CHS, six CHI, eight F3H, one F3′H, one FLS, one LAR, four DFR, one ANS and two UFGT) involved in anthocyanin biosynthesis. Concurrently, the up-regulation of certain genes (one FLS and one LAR) that divert the anthocyanin precursors to other pathways was noted. Additionally, a significant change in the expression of numerous transcription factors (12 NAC, 12 bZIP, 23 ERF, 23 bHLH, 19 MYB_related, etc.) was observed. These results revealed the genetic and metabolic basis of leaf color diversity and change in cultivated caladium, and provided valuable information for molecular marker-assisted selection and breeding of leaf color in this ornamental plant.
Metabolic Response of Peach Fruit to Invasive Brown Marmorated Stink Bug (Halyomorpha halys Stål.)’s Infestation
Authors: Gacnik Sasa , Rusjan Denis , Mikulic-Petkovsek Maja
Published: January 2024

The brown marmorated stink bug (BMSB; Halyomorpha halys Stål.) is a highly destructive and polyphagous invasive pest that poses a serious threat to more than a hundred reported host plants. In the current study, the metabolic response of peach fruit of two cultivars—‘Maria Marta’ and ‘Redhaven’—to BMSB infestation was studied using high-performance liquid chromatography (HPLC) and mass spectrometry (MS). In general, a strong phenolic response to BMSB infestation in peach flesh in the injury zone was observed, with flavanol content increasing by 2.4-fold, hydroxycinnamic acid content by 5.0-fold, flavonol content by 3.2-fold, flavanone content by 11.3-fold, and dihydrochalcones content by 3.2-fold compared with the undamaged tissue in the cultivar ‘Maria Marta’. The phenolic response in the ‘Redhaven’ cultivar was even stronger. Consequently, the total phenolic content in the injured flesh also increased, 3.3-fold in ‘Maria Marta’ and 6.9-fold in ‘Redhaven’, compared with the uninjured flesh. Infestation with BMSB induced the synthesis of cyanidin-3-glucoside, which is not normally present in peach flesh. In comparison, the phenolic response was lower in peach peel, especially in the cultivar ‘Maria Marta’. The study showed that both peach cultivars reacted to BMSB infestation with an increase in phenolic content in the peach flesh, but in a limited area of injury.
AtSNP_TATAdb: Candidate Molecular Markers of Plant Advantages Related to Single Nucleotide Polymorphisms within Proximal Promoters of Arabidopsis thaliana L.
Authors: Bogomolov Anton , Zolotareva Karina , Filonov Sergey , Chadaeva Irina , Rasskazov Dmitry , Sharypova Ekaterina , Podkolodnyy Nikolay , Ponomarenko Petr , Savinkova Ludmila , Tverdokhleb Natalya , Khandaev Bato , Kondratyuk Ekaterina , Podkolodnaya Olga , Zemlyanskaya Elena , Kolchanov Nikolay A. , Ponomarenko Mikhail
Published: January 2024

The mainstream of the post-genome target-assisted breeding in crop plant species includes biofortification such as high-throughput phenotyping along with genome-based selection. Therefore, in this work, we used the Web-service Plant_SNP_TATA_Z-tester, which we have previously developed, to run a uniform in silico analysis of the transcriptional alterations of 54,013 protein-coding transcripts from 32,833 Arabidopsis thaliana L. genes caused by 871,707 SNPs located in the proximal promoter region. The analysis identified 54,993 SNPs as significantly decreasing or increasing gene expression through changes in TATA-binding protein affinity to the promoters. The existence of these SNPs in highly conserved proximal promoters may be explained as intraspecific diversity kept by the stabilizing natural selection. To support this, we hand-annotated papers on some of the Arabidopsis genes possessing these SNPs or on their orthologs in other plant species and demonstrated the effects of changes in these gene expressions on plant vital traits. We integrated in silico estimates of the TBP-promoter affinity in the AtSNP_TATAdb knowledge base and showed their significant correlations with independent in vivo experimental data. These correlations appeared to be robust to variations in statistical criteria, genomic environment of TATA box regions, plants species and growing conditions.
Exploring the Multiple Roles of Notch1 in Biological Development: An Analysis and Study Based on Phylogenetics and Transcriptomics
Authors: Zhou Yuesi , Yan Zihao , Pang Ya , Jiang Yao , Zhuang Ruyu , Zhang Shuyuan , Nurmamat Ayqeqan , Xiu Min , Li Ding , Zhao Liang , Liu Xin , Li Qingwei , Han Yinglun
Published: January 2024

At present, there is a research gap concerning the specific functions and mechanisms of the Notch gene family and its signaling pathway in jawless vertebrates. In this study, we identified a Notch1 homologue (Lr. Notch1) in the Lethenteron reissneri database. Through bioinformatics analysis, we identified Lr. Notch1 as the likely common ancestor gene of the Notch gene family in higher vertebrates, indicating a high degree of conservation in the Notch gene family and its signaling pathways. To validate the biological function of Lr. Notch1, we conducted targeted silencing of Lr. Notch1 in L. reissneri and analyzed the resultant gene expression profile before and after silencing using transcriptome analysis. Our findings revealed that the silencing of Lr. Notch1 resulted in differential expression of pathways and genes associated with signal transduction, immune regulation, and metabolic regulation, mirroring the biological function of the Notch signaling pathway in higher vertebrates. This article systematically elucidated the origin and evolution of the Notch gene family while also validating the biological function of Lr. Notch1. These insights offer valuable clues for understanding the evolution of the Notch signaling pathway and establish a foundation for future research on the origin of the Notch signaling pathway, as well as its implications in human diseases and immunomodulation.
Genome-Wide Identification and Expression Profiling of Heavy Metal ATPase (HMA) Genes in Peanut: Potential Roles in Heavy Metal Transport
Authors: Li Jinxiu , Zhang Zheng , Shi Gangrong
Published: January 2024

The heavy metal ATPase (HMA) family belongs to the P-type ATPase superfamily and plays an essential role in the regulation of metal homeostasis in plants. However, the gene family has not been fully investigated in peanut. Here, a genome-wide identification and bioinformatics analysis was performed on AhHMA genes in peanut, and the expression of 12 AhHMA genes in response to Cu, Zn, and Cd was evaluated in two peanut cultivars (Silihong and Fenghua 1) differing in Cd accumulation. A total of 21 AhHMA genes were identified in the peanut genome, including ten paralogous gene pairs derived from whole-genome duplication, and an additional gene resulting from tandem duplication. AhHMA proteins could be divided into six groups (I–VI), belonging to two clades (Zn/Co/Cd/Pb-ATPases and Cu/Ag-ATPases). Most AhHMA proteins within the same clade or group generally have a similar structure. However, significant divergence exists in the exon/intron organization even between duplicated gene pairs. RNA-seq data showed that most AhHMA genes are preferentially expressed in roots, shoots, and reproductive tissues. qRT-PCR results revealed that AhHMA1.1/1.2, AhHMA3.1/3.2, AhHMA7.1/7.4, and AhHMA8.1 might be involved in Zn transport in peanut plants, while AhHMA3.2 and AhHMA7.5 might be involved in Cd transport. Our findings provide clues to further characterize the functions of AhHMA genes in metal uptake and translocation in peanut plants.
Phosphoramidate Azole Oligonucleotides for Single Nucleotide Polymorphism Detection by PCR
Authors: Chubarov Alexey S. , Baranovskaya Elizaveta E. , Oscorbin Igor P. , Yushin Ivan I. , Filipenko Maxim L. , Pyshnyi Dmitrii V. , Vasilyeva Svetlana V. , Lomzov Alexander A.
Published: January 2024

Detection of the Kirsten rat sarcoma gene (KRAS) mutational status is an important factor for the treatment of various malignancies. The most common KRAS-activating mutations are caused by single-nucleotide mutations, which are usually determined by using PCR, using allele-specific DNA primers. Oligonucleotide primers with uncharged or partially charged internucleotide phosphate modification have proved their ability to increase the sensitivity and specificity of various single nucleotide mutation detection. To enhance the specificity of single nucleotide mutation detection, the novel oligonucleotides with four types of uncharged and partially charged internucleotide phosphates modification, phosphoramide benzoazole (PABA) oligonucleotides (PABAO), was used to prove the concept on the KRAS mutation model. The molecular effects of different types of site-specific PABA modification in a primer or a template on a synthesis of full-length elongation product and PCR efficiency were evaluated. The allele-specific PCR (AS-PCR) on plasmid templates showed a significant increase in analysis specificity without changes in Cq values compared with unmodified primer. PABA modification is a universal mismatch-like disturbance, which can be used for single nucleotide polymorphism discrimination for various applications. The molecular insights of the PABA site-specific modification in a primer and a template affect PCR, structural features of four types of PABAO in connection with AS-PCR results, and improvements of AS-PCR specificity support the further design of novel PCR platforms for various biological targets testing.
Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review
Authors: Molinaro Monica , Torrente Yvan , Villa Chiara , Farini Andrea
Published: January 2024

Mounting evidence underscores the intricate interplay between the immune system and skeletal muscles in Duchenne muscular dystrophy (DMD), as well as during regular muscle regeneration. While immune cell infiltration into skeletal muscles stands out as a prominent feature in the disease pathophysiology, a myriad of secondary defects involving metabolic and inflammatory pathways persist, with the key players yet to be fully elucidated. Steroids, currently the sole effective therapy for delaying onset and symptom control, come with adverse side effects, limiting their widespread use. Preliminary evidence spotlighting the distinctive features of T cell profiling in DMD prompts the immuno-characterization of circulating cells. A molecular analysis of their transcriptome and secretome holds the promise of identifying a subpopulation of cells suitable as disease biomarkers. Furthermore, it provides a gateway to unraveling new pathological pathways and pinpointing potential therapeutic targets. Simultaneously, the last decade has witnessed the emergence of novel approaches. The development and equilibrium of both innate and adaptive immune systems are intricately linked to the gut microbiota. Modulating microbiota-derived metabolites could potentially exacerbate muscle damage through immune system activation. Concurrently, genome sequencing has conferred clinical utility for rare disease diagnosis since innovative methodologies have been deployed to interpret the functional consequences of genomic variations. Despite numerous genes falling short as clinical targets for MD, the exploration of Tdark genes holds promise for unearthing novel and uncharted therapeutic insights. In the quest to expedite the translation of fundamental knowledge into clinical applications, the identification of novel biomarkers and disease targets is paramount. This initiative not only advances our understanding but also paves the way for the design of innovative therapeutic strategies, contributing to enhanced care for individuals grappling with these incapacitating diseases.
Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555
Authors: Guan Yuntian , Zhang Mei , Lacy Christie , Shah Soham , Epstein Frederick H. , Yan Zhen
Published: January 2024

Millions of diabetic patients suffer from cardiovascular complications. One of the earliest signs of diabetic complications in the heart is diastolic dysfunction. Regular exercise is a highly effective preventive/therapeutic intervention against diastolic dysfunction in diabetes, but the underlying mechanism(s) remain poorly understood. Studies have shown that the accumulation of damaged or dysfunctional mitochondria in the myocardium is at the center of this pathology. Here, we employed a mouse model of diabetes to test the hypothesis that endurance exercise training mitigates diastolic dysfunction by promoting cardiac mitophagy (the clearance of mitochondria via autophagy) via S555 phosphorylation of Ulk1. High-fat diet (HFD) feeding and streptozotocin (STZ) injection in mice led to reduced endurance capacity, impaired diastolic function, increased myocardial oxidative stress, and compromised mitochondrial structure and function, which were all ameliorated by 6 weeks of voluntary wheel running. Using CRISPR/Cas9-mediated gene editing, we generated non-phosphorylatable Ulk1 (S555A) mutant mice and showed the requirement of p-Ulk1at S555 for exercise-induced mitophagy in the myocardium. However, diabetic Ulk1 (S555A) mice retained the benefits of exercise intervention. We conclude that endurance exercise training mitigates diabetes-induced diastolic dysfunction independent of Ulk1 phosphorylation at S555.
Lidocaine–Liposomes—A Promising Frontier for Transdermal Pain Management
Authors: Leon Maria Magdalena , Maștaleru Alexandra , Oancea Andra , Alexa-Stratulat Teodora , Peptu Cătălina Anișoara , Tamba Bogdan-Ionel , Harabagiu Valeria , Grosu Cristina , Alexa Anisia Iuliana , Cojocaru Elena
Published: January 2024

(1) Background: We aim to develop novel gel formulations for transdermal drug delivery systems in acute and inflammatory pain therapy. (2) Methods: We induced inflammation by the injection of λ-carrageenan on the hind paw of 80 Wistar male rats. The animals were randomized into eight groups of 10 rats each: C (placebo gel), E (EMLATM), L (lidocaine 2%), L-CD (lidocaine + cyclodextrin 2.5%), L-LP (lidocaine + liposomes 1.7%), L-CS (lidocaine + chitosan 4%), L-CSh (lidocaine + chitosan hydrochloride), and L-CS-LP (lidocaine + chitosan + liposomes). The behavior response was determined with a hot plate, cold plate, and algesimeter, each being performed at 30, 60, 120, 180, and 240 min after pain induction. At the end of the experiment, tissue samples were collected for histological assessment. (3) Results: L-LP had the greatest anesthetic effects, which was proven on the cold plate test compared to placebo and EMLATM (all p ≤ 0.001). L-CS-LP had a significant effect on cold plate evaluation compared to placebo (p ≤ 0.001) and on hot plate evaluation compared to EMLATM (p = 0.018). (4) Conclusions: L-LP is a new substance with a substantial analgesic effect demonstrated by the cold plate in the first 120 min. Further studies with more animals are needed to determine the maximum doses that can be applied for a better analgesia with minimum side effects.
Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia
Authors: Costa Alessandro , Abruzzese Elisabetta , Latagliata Roberto , Mulas Olga , Carmosino Ida , Scalzulli Emilia , Bisegna Maria Laura , Ielo Claudia , Martelli Maurizio , Caocci Giovanni , Breccia Massimo
Published: January 2024

Background: While the outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly population (i.e., aged ≥ 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs). In this retrospective study, we sought to evaluate the safety and efficacy of TKIs in this particular setting of patients. Methods: We conducted a retrospective analysis of a multicenter cohort of 123 newly diagnosed CP-CML very elderly patients. Results: The median age at diagnosis was 80 years (range: 75–96). In the first line, 86.1% of patients received imatinib, 7.1% dasatinib, 5.6% nilotinib, and 0.81% received bosutinib. A total of 31 patients (25.2%) switched to second-line therapy, nine patients to a third line, and one patient to a fourth line of therapy. Resistance to treatment was the primary reason for switching therapy in both the first (64.5%) and second lines (77.7%). At diagnosis, reduced doses were administered in 36.5% of patients, in 61.2% in the second line, and in all patients in subsequent lines of therapy. In the first-line setting, 71.9% of patients achieved an early molecular response (EMR, i.e., 3-month BCR::ABL1IS < 10%); at 6, 12, and 24 months, MR3 was reached by 35.7%, 55.7%, and 75.0% of patients, respectively, with 16.6%, 35.7%, and 51.7% achieving a deep molecular response (DMR) at the same time points. Treatment-free remission (TFR) was successfully attempted in 11 patients. During the follow-up period, adverse events (AEs) were observed in 78.8% of patients, including 22 cases of cardiovascular AEs. Toxicity grade ≥ 3 was more commonly observed in patients treated with standard doses of TKIs compared to reduced doses (p = 0.033). Overall, the median follow-up was 46.62 months (range: 1.8–206.2), and 43 patients died due to non-CML-related causes. Three patients died due to disease progression to advanced (n = 1) and blastic (n = 2) phases. The 5-year overall survival (OS) for the entire cohort was 71.9% (95% CI: 0.63–0.81), with no significant difference between the patients treated with standard doses of TKIs compared to those treated with reduced doses (p = 0.35). Conclusions: TKIs appear to be safe and effective even in very elderly CML patients, and dose optimization strategies yield satisfactory molecular responses for adequate disease control with an improved safety profile.
Comparative Assessment of Habitat Suitability and Niche Overlap of Three Cytospora Species in China
Authors: Yan Chengcai , Hao Haiting , Sha Shuaishuai , Wang Zhe , Huang Lili , Kang Zhensheng , Wang Lan , Feng Hongzu
Published: January 2024

The plant pathogenic fungus Cytospora is notoriously known for causing woody plant canker diseases, resulting in substantial economic losses to biological forests and fruit trees worldwide. Despite their strong negative ecological impact, the existing and prospective distribution patterns of these plant pathogens in China, according to climate change, have received little attention. In this study, we chose three widely dispersed and seriously damaging species, namely, Cytospora chrysosperma, Cytospora mali, and Cytospora nivea, which are the most common species that damage the Juglans regia, Malus domestica, Eucalyptus, Pyrus sinkiangensis, Populus spp., and Salix spp. in China. We utilized ecological niche modeling to forecast their regional distribution in China under four climate change scenarios (present, SSP 126, SSP 370, and SSP 585). The results show that temperature-related climate factors limit the current distribution ranges of the three species. Currently, the three studied species are highly suitable for northeast, northwest, north, and southwest China. Under future climate scenarios, the distribution ranges of the three species are projected to increase, and the centers of the adequate distribution areas of the three species are expected to shift to high-latitude regions. The three species coexist in China, primarily in the northwest and north regions. The ecological niches of C. chrysosperma and C. nivea are more similar. The distribution range of C. mali can reach the warmer and wetter eastern region, whereas C. chrysosperma and C. nivea are primarily found in drought-prone areas with little rainfall. Our findings can help farmers and planners develop methods to avoid the spread of Cytospora spp. and calculate the costs of applying pesticides to reduce contamination and boost yields.
Intentional Characteristics and Public Perceived Preferences of Lake Parks Based on Machine Learning Models
Authors: Wang Dandan , Min Hyun , Rui Donggen
Published: January 2024

This research aimed to analyze and understand the perceived landscape preferences of lake parks (LPs) and how the public perceives and prefers these elements within the context of lake parks. The objective was to provide insights beneficial for landscape design, urban planning, and the creation of more appealing and sustainable lake parks. To achieve this, two primary methods were employed in this study: the Automated Machine Learning (Auto ML) model and the DeepLab v3+ model. To gather data for the research, 46,444 images were collected from 20 different lake parks from 2019 to 2022. Social media platforms such as Instagram, Flickr, and specific lake park community groups were tapped to source photographs from both professional photographers and the general public. According to the experimental findings, the perceived frequency of natural landscapes was 69.27%, which was higher than that of humanistic landscapes by 30.73%. The perceived intensity was also maintained between 0.09 and 0.25. The perceived frequency of water body landscapes was much greater on a macro-scale, at 73.02%, and the public had various plant preferences throughout the year. Aquatic plant landscapes with low-to-medium green visibility were preferred by the public, according to the landscape share characterization, while amusement rides with medium-to-high openness were preferred. The sky visibility of amusement rides was between 0 and 0.1 and between 0.3 and 0.5, indicating that the public preferred amusement rides with medium-to-high openness. In lake parks, the populace chose settings with less obvious architectural features. When combined, the two models used in this study are useful for identifying and analyzing the intended traits and preferences of lake parks among the general public. They also have theoretical and practical application value for directing the development of lake parks and urban landscapes.
Urban Green Spaces in Bamako and Sikasso, Mali: Land Use Changes and Perceptions
Authors: Fomba Mohamed , Osunde Zinash Delebo , Traoré Souleymane Sidi , Okhimamhe Appollonia , Kleemann Janina , Fürst Christine
Published: January 2024

Increasing land use and land cover change and climate change have considerable impacts on urban green spaces and their ecosystem services. These impacts result in a loss of urban green space and particularly weaken the climate resilience of urban populations. Landsat imagery data from 1990 to 2020 were used to track the spatio-temporal dynamics of urban sprawl and its influence on the loss of urban green space in Bamako and Sikasso in Mali. Furthermore, a survey of local stakeholders was conducted to capture the perceptions of the status of urban green space. The results of the land use/land cover analysis of the cities between 1990 and 2020 showed that most of the vegetation classes, mainly urban green spaces, have been converted into built-up and bare land in both cities during the last 30 years. In Bamako, built-up land has risen from 5421 hectares in 1990 to 13,350 hectares in 2020, and in Sikasso, from 929 hectares in 1990 to 2213 hectares in 2020. Respondents mentioned street trees as the prevalent type of urban green spaces in both cities (20% of the respondents in Bamako and 24% in Sikasso). In addition, the majority of respondents perceived urban green spaces in Sikasso as having a good status and in Bamako as having a good or moderate status. This study recommends improving the number and quality of urban green spaces, which are crucial for the provision of ecosystem services and for the resilience of cities against climate change.
An Improved Super-Twisting Sliding Mode Composite Control for Quadcopter UAV Formation
Authors: Ye Yulong , Hu Song , Zhu Xingyu , Sun Zhenxing
Published: January 2024

Aiming at the nonlinear and multiple disturbances in the multi-quadcopter UAV system, this paper proposes a leader–follower composite formation control strategy based on an improved super-twisted sliding mode controller (ISTSMC) and a finite-time extended state observer (FTESO). For the designed sliding mode control algorithm, the integral term’s switching function is replaced with a non-smooth term to reduce the vibration in the control, further improving the overall performance of the system. For external disturbances, the finite-time extended state observer achieves rapid and accurate observation of external disturbances. Finally, through formation control experiments, the reliability and superiority of the proposed composite formation controller (CFC) is validated.
Instance Segmentation Frustum–PointPillars: A Lightweight Fusion Algorithm for Camera–LiDAR Perception in Autonomous Driving
Authors: Wang Yongsheng , Han Xiaobo , Wei Xiaoxu , Luo Jie
Published: January 2024

The fusion of camera and LiDAR perception has become a research focal point in the autonomous driving field. Existing image–point cloud fusion algorithms are overly complex, and processing large amounts of 3D LiDAR point cloud data requires high computational power, which poses challenges for practical applications. To overcome the above problems, herein, we propose an Instance Segmentation Frustum (ISF)–PointPillars method. Within the framework of our method, input data are derived from both a camera and LiDAR. RGB images are processed using an enhanced 2D object detection network based on YOLOv8, thereby yielding rectangular bounding boxes and edge contours of the objects present within the scenes. Subsequently, the rectangular boxes are extended into 3D space as frustums, and the 3D points located outside them are removed. Afterward, the 2D edge contours are also extended to frustums to filter the remaining points from the preceding stage. Finally, the retained points are sent to our improved 3D object detection network based on PointPillars, and this network infers crucial information, such as object category, scale, and spatial position. In pursuit of a lightweight model, we incorporate attention modules into the 2D detector, thereby refining the focus on essential features, minimizing redundant computations, and enhancing model accuracy and efficiency. Moreover, the point filtering algorithm substantially diminishes the volume of point cloud data while concurrently reducing their dimensionality, thereby ultimately achieving lightweight 3D data. Through comparative experiments on the KITTI dataset, our method outperforms traditional approaches, achieving an average precision (AP) of 88.94% and bird’s-eye view (BEV) accuracy of 90.89% in car detection.
On the Bessel Solution of Kepler’s Equation
Authors: Borghi Riccardo
Published: January 2024

Since its introduction in 1650, Kepler’s equation has never ceased to fascinate mathematicians, scientists, and engineers. Over the course of five centuries, a large number of different solution strategies have been devised and implemented. Among them, the one originally proposed by J. L. Lagrange and later by F. W. Bessel still continue to be a source of mathematical treasures. Here, the Bessel solution of the elliptic Kepler equation is explored from a new perspective offered by the theory of the Stieltjes series. In particular, it has been proven that a complex Kapteyn series obtained directly by the Bessel expansion is a Stieltjes series. This mathematical result, to the best of our knowledge, is a new integral representation of the KE solution. Some considerations on possible extensions of our results to more general classes of the Kapteyn series are also presented.
Ethnic Disparities in Lipid Metabolism and Clinical Outcomes between Dutch South Asians and Dutch White Caucasians with Type 2 Diabetes Mellitus
Authors: Yuan Lushun , Verhoeven Aswin , Blomberg Niek , van Eyk Huub J. , Bizino Maurice B. , Rensen Patrick C. N. , Jazet Ingrid M. , Lamb Hildo J. , Rabelink Ton J. , Giera Martin , van den Berg Bernard M.
Published: January 2024

Type 2 diabetes mellitus (T2DM) poses a higher risk for complications in South Asian individuals compared to other ethnic groups. To shed light on potential mediating factors, we investigated lipidomic changes in plasma of Dutch South Asians (DSA) and Dutch white Caucasians (DwC) with and without T2DM and explore their associations with clinical features. Using a targeted quantitative lipidomics platform, monitoring over 1000 lipids across 17 classes, along with 1H NMR based lipoprotein analysis, we studied 51 healthy participants (21 DSA, 30 DwC) and 92 T2DM patients (47 DSA, 45 DwC) from the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction in type 2 dIAbetes mellitus (MAGNA VICTORIA) study. This comprehensive mapping of the circulating lipidome allowed us to identify relevant lipid modules through unbiased weighted correlation network analysis, as well as disease and ethnicity related key mediatory lipids. Significant differences in lipidomic profiles, encompassing various lipid classes and species, were observed between T2DM patients and healthy controls in both the DSA and DwC populations. Our analyses revealed that healthy DSA, but not DwC, controls already exhibited a lipid profile prone to develop T2DM. Particularly, in DSA-T2DM patients, specific lipid changes correlated with clinical features, particularly diacylglycerols (DGs), showing significant associations with glycemic control and renal function. Our findings highlight an ethnic distinction in lipid modules influencing clinical outcomes in renal health. We discover distinctive ethnic disparities of the circulating lipidome and identify ethnicity-specific lipid markers. Jointly, our discoveries show great potential as personalized biomarkers for the assessment of glycemic control and renal function in DSA-T2DM individuals.
Simulation on an Advanced Double-Sided Cooling Flip-Chip Packaging with Diamond Material for Gallium Oxide Devices
Authors: Guan He , Wang Dong , Li Wentao , Liu Duo , Deng Borui , Qu Xiang
Published: January 2024

Gallium oxide (Ga2O3) devices have shown remarkable potential for high-voltage, high-power, and low-loss power applications. However, thermal management of packaging for Ga2O3 devices becomes challenging due to the significant self-heating effect. In this paper, an advanced double-sided cooling flip-chip packaging structure for Ga2O3 devices was proposed and the overall packaging of Ga2O3 chips was researched by simulation in detail. The advanced double-sided cooling flip-chip packaging structure was formed by adding a layer of diamond material on top of the device based on the single-sided flip-chip structure. With a power density of 3.2 W/mm, it was observed that the maximum temperature of the Ga2O3 chip with the advanced double-sided cooling flip-chip packaging structure was 103 °C. Compared with traditional wire bonding packaging and single-sided cooling flip-chip packaging, the maximum temperature was reduced by about 12 °C and 7 °C, respectively. When the maximum temperature of the chip was controlled at 200 °C, the Ga2O3 chip with double-sided cooling packaging could reach a power density of 6.8 W/mm. Finally, by equipping the top of the package with additional water-cooling equipment, the maximum temperature was reduced to 186 °C. These findings highlight the effectiveness of the proposed flip-chip design with double-sided cooling in enhancing the heat dissipation capability of Ga2O3 chips, suggesting promising prospects for this advanced packaging structure.