bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure and Tensile Properties of HPDC Mg–RE Alloys with Varying Y Additions
Authors: Feng Lingyun , Dong Xixi , Cai Qing , Ji Shouxun
Published: February 2024

High-pressure die-casting Mg–2.6RE–xY (EW) alloys with Y contents between 0 and 3% (in wt%) were investigated for their microstructure and tensile properties. In the Y-containing alloy, the intermetallic phases at the grain boundaries consisted of skeletal Mg12RE phase, bulk Mg24Y5 phase and irregular Mg3Y phase, while {011} twins were observed in the Mg12RE phase. The yield strength was improved by Y addition at both room temperature and high temperatures. Compared with Y-free alloy, the yield strength of 3% Y alloy increased from 143.1 to 174.8 MPa and improved by 22.2% at room temperature, while it was increased from 72.2 to 104.6 MPa and enhanced by 44.9% at 300 °C. The area fraction of intermetallic phase increased dramatically from 14.5 to 18.4% with 3% Y addition. Second phase strengthening was the major contributor to the yield strength increase at ambient temperature. The increment of the area fraction of the high-thermally stable Mg–RE intermetallic phases with Y addition contributed to the consequent improvement in yield strength at high temperatures. At ambient temperature, the mechanism for the fracture of EW alloys was a ductile and quasi-cleavage fracture blend.
Task-Oriented and Change-Preserving Data Classification for Multi-Temporal Choropleth Maps
Authors: Schiewe Jochen
Published: February 2024

Series or animations of classified choropleth maps are an important form of reproducing multi-temporal, cardinally scaled data sets, especially in media. However, there are problems with such representations that are not taken into account by the known methods of data classification (such as equidistant grouping or quantiles), and therefore lead to visualizations that are not sufficiently suitable for use. On the one hand, different questions and change analysis tasks are not explicitly considered in the process of making these maps. In the following, typical change tasks are singled out (i.e. show absolute differences, absolute percentage changes, positive changes and deviations from the trend) and the corresponding metrics for quantitative description are proposed. On the other hand, there are no measures in the usual procedures to avoid the loss of significant changes after classification (i.e. the regions belong to the same class). In the following, a procedure is therefore proposed that begins with rules for assigning value differences to class differences (e.g. based on statistical significance). Based on this, a preservation measure is defined that describes the success of obtaining the desired class differences after applying the classification. This measure can also be used to guide a new classification procedure. Using two multi-temporal data sets, the effects of the developed measures and methods are demonstrated both numerically and visually in corresponding choropleth maps.
Differences in spine growth potential for Sanders maturation stages 7A and 7B have implications for treatment of idiopathic scoliosis
Authors: Hori Yusuke , Kaymaz Burak , da Silva Luiz Carlos Almeida , Rogers Kenneth J. , Yorgova Petya K. , Gabos Peter G. , Shah Suken A.
Published: February 2024

Purpose

This study aimed to clarify the differences in spine and total body height growth and curve progression between Sanders maturation stage (SMS) 7A and 7B in patients with adolescent idiopathic scoliosis (AIS).

Methods

This retrospective case–control study involving patients with AIS at SMS 7 evaluated the differential gains in the spine (T1-S1) and total body height and curve progression between SMS 7A and 7B. A validated formula was used to calculate the corrected height, accounting for height loss due to scoliosis. A multivariable non-linear and logistic regression model was applied to assess the distinct growth and curve progression patterns between the SMS 7 subtypes, adjusting for potential confounders.

Results

A total of 231 AIS patients (83% girls, mean age 13.9 ± 1.2 years) were included, with follow-up averaging 3.0 years. Patients at SMS 7A exhibited larger gains in spine height (9.9 mm vs. 6.3 mm) and total body height (19.8 mm vs. 13.4 mm) compared with SMS 7B. These findings remained consistent even after adjustments for curve magnitude. Non-linear regression models showed continued spine and total body height increases plateauing after 2 years, significantly greater in SMS 7A. More SMS 7A patients had curve progression over 10°, with an adjusted odds ratio of 3.31.

Conclusion

This study revealed that patients staged SMS 7A exhibited more spine and total body growth and a greater incidence of substantial curve progression than those at 7B. These findings imply that delaying brace discontinuation until reaching 7B could be beneficial, particularly for those with larger curves.

Level of evidence

Level III (Case–control study).
A Novel Training Approach in Deep Spiking Neural Network Based on Fuzzy Weighting and Meta-heuristic Algorithm
Authors: Hamian Melika , Faez Karim , Nazari Soheila , Sabeti Malihe
Published: February 2024

The challenge of supervised learning in spiking neural networks (SNNs) for digit classification from speech signals is examined in this study. Meta-heuristic algorithms and a fuzzy logic framework are used to train SNNs. Using gray wolf optimization (GWO), the features obtained from audio signals are reduced depending on the dispersion of each feature. Then, it combines fuzzy weighting system (FWS) and spike time-dependent flexibility (STDP) approach to implement the learning rule in SNN. The FWS rule produces a uniformly distributed random weight in the STDP flexibility window, so that the system requires fewer training parameters. Finally, these neurons are fed data to estimate the training weights and threshold values of the neurons using wild horse algorithm (WHO). With the parameters given, these rule weights are applied to appropriately display the class's share in extracting the relevant feature. The suggested network can classify speech signals into categories with 97.17% accuracy. The dataset was obtained using neurons operating at sparse biological rates below 600 Hz in the TIDIGITS test database. The suggested method has been evaluated on the IRIS and Trip Data datasets, where the classification results showed a 98.93% and 97.36% efficiency, respectively. Compared to earlier efforts, this study's results demonstrate that the strategy is both computationally simpler and more accurate. The accuracy of classification of digits, IRIS and Trip Data has increased by 4.9, 3.46 and 1.24%, respectively. The principal goal of this research is to improve the accuracy of SNN by developing a new high-precision training method.
Algorithm Optimization of Computer Simulation Vehicle Driving Simulation System Based on Virtual Reality Technology
Authors: Zou Lan , Liang Tianhui
Published: February 2024

The traditional automobile driving simulation system has the problems of low calculation efficiency and lack of realism. The traditional automobile driving simulation system with low computational efficiency and lack of realism limits the learning effect. Through virtual reality technology, vehicle driving can be simulated. By optimizing the algorithm of simulating vehicle driving simulation system, the preference of testers for driving style is investigated and the driver's preference style is determined. Finally, through the automatic driving simulation test method based on genetic algorithm, the key scenes can be divided into 11 different types, and the Euclidean distance of these 11 types is analyzed. Most drivers prefer a more conservative autonomous driving style. When analyzing 11 key scenario types, the Euclidean distance between scenario 2 and scenario 3 is the smallest, which is 33 m, and the maximum Euclidean distance between scenario 6 and scenario 11 is 91 m. The difference between scene 2 and scene 3 is the smallest, while the difference between scene 6 and scene 11 is the largest, and there are differences between each scene. Through virtual reality technology and algorithm optimization, the performance and user experience of driving simulation system are improved.
The Relation Between Cigarette Smoking and Development of Sepsis: A 10-Year Follow-Up Study of Four Million Adults from the National Health Screening Program
Authors: Lee Eun Hwa , Lee Kyoung Hwa , Lee Kyu-na , Park Yebin , Do Han Kyung , Han Sang Hoon
Published: February 2024

Background

Sepsis remains a growing global health concern with soaring mortality and no direct anti-sepsis drug. Although smoking has distinct deleterious effects on chronic inflammatory illnesses and can impair immune function, a comprehensive analysis of the connection between sepsis and smoking is lacking.

Methods

This large-scale longitudinal cohort study retrospectively assessed adults aged ≥ 20 years who underwent national health checkups under the Korean National Health Insurance Service between January and December 2009 (N = 4,234,415) and were followed up for 10 years. Sepsis was identified based on the International Classification of Diseases, 10th Revision codes, and smoking status, including accumulated amount, was collected through a self-administered questionnaire. The Cox proportional hazard regression model was used, adjusting for age, sex, household income, body mass index, drinking, exercise, diabetes, hypertension, dyslipidemia, and chronic renal disease.

Results

After excluding cases with sepsis occurring before follow-up or after ≤ 1 year of follow-up, 3,881,958 participants, including non-smokers (N = 2,342,841), former smokers (N = 539,850), and active smokers (N = 999,267), were included. Compared to non-smokers, all active smokers (adjust hazard ratio: 1.41, 95% confidence interval 1.38–1.44) and former smokers (1.10, 1.07–1.14) with ≥ 20 pack-years exhibited a significantly higher risk of sepsis (p < 0.001). Smoking of ≥ 30 pack-years in former and active smokers groups significantly increased sepsis incidence (adjust hazard ratio [95% confidence interval] 1.34 [1.31–1.38], p < 0.001).

Conclusions

Smoking is closely associated with the incidence of sepsis. Smoking cessation may help in the primary prevention of sepsis.
The Causal Association Between Blood Lead and Sleep Disorders: Evidence from National Health and Nutrition Examination Survey and Mendelian Randomization Analysis
Authors: Chen Shengnan , Zhang Ming , Zhang Weisong , Shao Xiaolong , Yang Xiaobin , Yang Zhi , Nan Kai
Published: February 2024

Background

Poor sleep quality is a global public health concern. This study aimed to identify the risk factors for sleep disorders and clarify their causal effects.

Methods

Data were obtained from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR)-Base databases. Baseline characteristics of individuals with and without sleep disorders were compared. A multivariate logistic regression analysis was performed to calculate the effects of each variable on sleep disorders. Causal effects of blood lead levels and hypertension on sleep disorders were assessed using MR analysis.

Results

In total, 3660 individuals were enrolled in the study. The prevalence of self-reported sleep disorders was 26.21%. Serum lead level, serum mercury level, serum retinol level, prevalence of hypertension, and daily vigorous work duration were significantly higher for those in the sleep disorders group than the control group. After adjusting for various covariates, the effects of serum lead and hypertension on sleep disorders were stable from logistic regression models 1–4. MR analysis showed that blood lead levels were causally related to the risk of sleep disorders (odds ratio (OR) = 1.09, 95% confidence interval (CI) 1.01–1.17, P = 0.030). There was no causal link between elevated blood pressure and sleep disorders (OR = 0.99, 95% CI 0.94–1.04, P = 0.757). Goodness-of-fit tests and sensitivity analyses were used to verify the reliability of the results.

Conclusions

Blood lead is positively and causally associated with an increased risk of sleep disorders. These findings provide a novel perspective regarding sleep protection. Taking effective measures to reduce lead exposure may significantly improve sleep health.
Reviving the lecture: using visually dynamic approaches to teach physiological concepts
Authors: Cork Simon C. , Yhnell Emma
Published: February 2024

The educational benefit of the traditional didactic lecture to learners in Higher Education is hotly debated. Given increasing student numbers, existing technical set ups and many logistical concerns, lectures remain the norm in many Higher Education Institutions (HEIs). In this personal view piece, we discuss the benefits, opportunities, and challenges of incorporating dynamic teaching approaches, including “draw-alongs” and animations into undergraduate lectures, typically with large class sizes, to create more engaging and interactive lectures for learners.
Utilizing gamification to promote pro-sustainable behavior among information technology students
Authors: Charkova Denitza Anguelova
Published: February 2024

Higher education institutions (HEIs) have made substantial strides towards incorporating sustainability into their curricula. However, the methodology of education for sustainable development (ESD) needs to be more performance-oriented and grounded in practical experience in order to foster behavioral changes towards environmental protection. The objective of this study was to assess the efficacy of a gamification-driven strategy in encouraging students of information technology (IT) to adopt sustainable practices. The data was gathered from the digital records and survey responses of 75 information technology (IT) students as a component of their English language course. The results of the study suggested that the gamified method successfully encouraged students to adopt sustainable practices in their personal lives and future workplaces. The students' viewpoints regarding the accountability of individual employers and citizens for the well-being of our planet underwent a substantial transformation in support of sustainable development. The method described is applicable to various academic fields, including the humanities, sciences, medical studies, and others.
The Almoravid Maghrib
Authors: Gómez-Rivas Camilo
Published: February 2024

The Almoravid Maghrib uncovers the richness and complexity of a neglected past. A pivotal moment in the history of North Africa, the rise of the Almoravids brought a corner of the Maghrib into closer contact with the world around. From the Cid to the Seljuqs, the Almoravids impressed contemporaries in ways no Maghribi regime had, signalling a transformation of western North Africa through burgeoning trans-Saharan and trans-Mediterranean commerce, urbanization (two of Morocco's four imperial cities were founded), and the epic encounter with the Christian, Muslim, and Jewish cultures of Iberia. The Almoravids witnessed a series of key transformations and beginnings, including the introduction of one of the area's most successful gold currencies, the formulation of a new religious orthodoxy, the parallel rise of counter-movements (popular, messianic, and spiritual), and the inception of pan-Maghribi-Andalusi artistic, literary, and architectural styles.
(Re)negotiating State Authority: How Hinterland Protests against Global Capital Impact the Mediating Role of Traditional Rulers in Postcolonial Sierra Leone
Authors: Sesay Mohamed
Published: February 2024

Sesay draws from three hinterland protests against multinational corporations in the mining and agricultural sectors to examine how global capital influences central/local politics in postcolonial Sierra Leone. Focusing specifically on the mediating role of traditional rulers—a strong legacy of British colonial indirect rule—Sesay argues that hinterland protests not only enable the relative autonomy of rural citizens to (re)negotiate with the state outside existing political arrangements but also challenge the broker authority of these rulers in center/peripheral relations. While some protests form new alignment of interest with traditional rulers, others allow rural citizens to bypass their chiefs to summon the attention of central authorities. In either of these processes, the local constituents question the position of chiefs in the indirect governance system and shape the governing strategies adopted by the central government to rule over the hinterland.
Exploring East Asia's Successful Early-Stage Covid-19 Response: An Empirical Investigation
Authors: Chung Kee Hoon , Jung Haeil , Jung Miyeun
Published: February 2024

This study examines whether a degree of autocracy and high quality of bureaucracy—two mechanisms often discussed in the context of Covid-19 responses—provide a meaningful explanation for East Asia's relative success compared to the rest of the world at the beginning of the Covid pandemic. Our multiple regression analysis for 111 countries supports our expectation, as East Asia as a region is significantly and negatively associated with confirmed Covid-19 cases and deaths compared to the rest of the world, and its interaction with the quality of bureaucracy further contributes to the negative association. In sum, this research highlights the important role of East Asia's regional characteristics in pandemic responses.
Chinese stalagmite δ18O records reveal the diverse moisture trajectories during the middle to late last glacial period
Authors: Yang Huihui , Chou Yu-Min , Jiang Xiuyang , Zheng Wei , He Yaoqi , Banerjee Yogaraj , Shen Chuan-Chou , Yu Tsai-Luen , Zhong Yi , Humbert Fabien , Liu Qingsong
Published: February 2024

Based on 30 high-resolution U-Th dating controls, we reconstruct stalagmite δ18O records from 45 to 15 thousand years ago (ka B.P., before AD 1950) from the Shizhu Cave, which is located in southwestern China under the influence of both the Indian Summer Monsoon (ISM) and the East Asian Summer Monsoon (EASM). By integrating with the other stalagmite δ18O records in Asia during the middle to late last glacial, our results reveal two main moisture trajectories: one from the Indian Ocean, through the Shizhu Cave towards central China, and the other from the Pacific Ocean to central and northern China. The systematic decrease of the average values of stalagmite δ18O records from oceans to inland China reveals a spatial pattern of water vapour fractionation and moisture trajectory during the middle to late last glacial. In contrast, the variation amplitude, which is defined as the departures apart from the background δ18O records during Heinrich stadials 1 to 4 (HS1–HS4), show an increasing trend from the coastal oceans to mid-latitude inland China, presenting a ‘coastal-inland’ pattern, which can be interpreted by the enhanced East Asian Winter Monsoon (EAWM) and the weakened EASM. More specifically, the enriched stalagmite δ18O records in the EASM region during HS1 to HS4 are caused by the decreased summer rainfall amount or/and the increased proportion of summer moisture resources from the Pacific Ocean. These new observations deepen our understanding of the complicated stalagmite δ18O records in the EASM region.
Characterization of variables related to high stability of raw cow milk
Authors: Martins Fernanda Antunes , Marinho Marina Tolentino , Fischer Vivian , Pereira João Ricardo Alves , Los Paulo Ricardo , Martins Adriana de Souza
Published: February 2024

This research paper analyzes the stability of raw cow milk in the alcohol test and seeks to understand to know the factors that influence milk stability and the occurrence of unstable non-acid milk. Milk samples were collected from the cooling tanks of rural farmers in the state of Paraná twice in summer and twice in winter. The farms were classified according to the production system: pasture with supplementation and feedlot. The following variables were analyzed: stability in the alcohol test, titratable acidity, ionized calcium concentration (iCa), chemical composition of milk, somatic cell count and standard plate count. The results showed that milk stability was greater in winter vs. summer, when the milk contained higher iCa, and in the feedlot vs. pasture system. The Pearson Correlation between variables (ethanol stability, milk composition, iCa, cooling tank temperature, milk volume, number of milking, number of cows milked, fat/protein ratio, distance and travel time) were analyzed. Stability was negatively correlated with iCa concentration and positively with lactose content. Logistic regression of the risk of unstable non-acid milk at 72% alcohol (UNAM72) showed that only iCa and lactose were determinants, while evaluation of the same risk at 78% alcohol revealed iCa, titratable acidity, lactose and milk urea nitrogen as risk factors. Under the dairy farming conditions of Paraná state, the frequency of UNAM72 was low (12.16%) and was higher in summer and in pasture systems with supplementation. In conclusion, in dairy herds bred with high technological level, with adequate nutritional and health management, the frequency of UNAM is low and is related to nutritional management abnd, perhaps, heat stress, factors that alter iCa and lactose levels.
Humanist Missteps, A Black Studies Critique of Posthumanist Archaeologies
Authors: Greer Matthew C.
Published: February 2024

Posthumanist archaeologies have attempted to move beyond humanist conceptions of the human for over a decade. But they have done so by primarily focusing on the ontological split between humans and non-human things. This only addresses one part of humanism, as Black studies scholars have long argued that it also equates humanity writ large with white, economically privileged, cis-gendered, heterosexual men, thereby excluding everyone else from the category of the human. They further argue that the violence and oppression inflicted on those excluded from humanism's definition of the human allows this ontological category to come into being. This article introduces Black studies’ critiques of humanism and applies them to posthumanist archaeologies. Ultimately, it argues that by not attending to the critiques raised by Black studies scholars, posthumanist archaeologies have inadvertently made humanist missteps wherein they continue using elements of humanism's definition of the human in their attempts to move beyond humanism.
What would it look like? Visualizing a future US Corn Belt landscape with more table food production
Authors: Stone Tiffanie F. , Thompson Janette R. , Zimmerman Emily , Brighenti Tassia M. , Liebman Matt
Published: February 2024

Most farmland in the US Corn Belt is used to grow row crops at large scales (e.g., corn, soybean) that are highly processed before entering the human food stream rather than specialty crops grown in smaller areas and meant for direct human consumption (table food). Bolstering local table food production close to urban populations in this region through peri-urban agriculture (PUA) could enhance sustainability and resilience. Understanding factors influencing PUA producers' preferences and willingness to produce table food would enable supportive planning and policy efforts. This study combined land use visualization and survey data to examine the potential for increased local table food production for the US Corn Belt. We developed a spatial visualization of current agricultural land use and a future scenario with increased table food production designed to meet 50% of dietary requirements for a metropolitan population in 2050. A survey was administered to row crop (1360) and specialty crop (55) producers near Des Moines, Iowa, US to understand current and intended agricultural land use and factors influencing production. Responses from 316 row crop and 25 specialty crop producers were eligible for this analysis. A future scenario with increased table food production would require less than 3% of available agricultural land and some additional producers (approximately 130, primarily for grain production). Survey responses indicated PUA producers planned small increases in table food production in the next three to five years. Producer plans, including land rental for table food production, could provide approximately 25% of residents' fruit, vegetables, and grains, an increase from the baseline of 2%. Row crop producers ranked food safety regulations, and specialty producers ranked labor concerns as strong influences on their decision-making. Both groups indicated that crop insurance and processing facilities were also important. Increasing table food production by clustering mid-scale operations to increase economies of scale and strengthening supply chains and production infrastructure could provide new profitable opportunities for farmers and more resilient food systems for growing urban regions in the US Corn Belt. Continuing to address producer factors and landscape-scale environmental impacts will be critical in considering food system sustainability challenges holistically.
Between War, Politics, and “Something Nice Back Home”: Uncovering the First Mozambican Experiences within the “World Music” Market (1987–1994)
Authors: FREITAS MARCO ROQUE DE
Published: February 2024

This article analyzes the internationalization of Mozambican music within the “World Music” market during the country’s transitional period from a single-party socialist-led system to a multiparty, liberal one (1987–1994) in relation to the country’s nation-building process. The comparative examination of three cases—Orchestra Marrabenta Star de Moçambique, the song “Baila Maria” by Grupo RM (Amoya), and Real World Records’ albums by Eyuphuro and Ghorwane—shows that the “World Music” market not only served as an escape valve from the country’s lethargic phonographic industry but also emerged as a privileged channel to promote Mozambique’s official musical policy abroad during a crucial civil war-torn period.
Constraints on Lateral Variations of Martian Crustal Thickness From Seismological and Gravity Field Measurements
Authors: Drilleau Mélanie , Samuel Henri , Garcia Raphaël F. , Rivoldini Attilio , Perrin Clément , Wieczorek Mark , Lognonné Philippe , Banerdt William B.
Published: February 2024

Using body wave arrival times from 31 seismic events recorded on Mars by the InSight mission, combined with topography and gravity field modeling, we constrained lateral variations of crustal thickness through a Bayesian inversion approach. The parameterization of the seismic structure relies on quantities that influence the thermochemical evolution of Mars, enabling the seismic velocities and densities in the different planetary envelopes to be consistently linked through common physical assumptions. Compared to a 1D structure, models with lateral variations of crustal thickness show two possible interpretations of the thermal evolution of Mars, with either a hot or cold scenario at the present‐day. We found the hot scenario to be more compatible with InSight's radiotracking data and the tidal Love number. We relocated the marsquakes and derived maps of seismicity recorded by InSight, which is mostly located along or North of the boundary between the Northern lowlands and the Southern highlands.
Present‐Day 3D Crustal Deformation of the Northeastern Tibetan Plateau From Space Geodesy
Authors: Wu Dong‐Lin , Ge Wei‐Peng , Liu Shao‐Zhuo , Yuan Dao‐Yang , Zhang Bo , Wei Cong‐Min
Published: February 2024

High‐resolution present‐day earth surface deformation maps from satellites provide important data constraints, which help us better understand tectonic processes and analyze seismic hazards. Here, we use Sentinel‐1 Radar images (2014–2020) and accurate positioning measurements (2009–2019) to get a high‐resolution three‐dimensional earth surface velocity map for the northeastern Tibetan Plateau, and we invert the slip rate and coupling ratio of major regional faults. We find ∼4 mm/yr uplift along an arc from the Qilianshan to Lajishan, relative to the neighboring low‐elevation area to the east, which indicates ongoing rapid orogeny. We find transient deformation along the Laohushan and 1920 M8.5 Haiyuan rupture segments of the Haiyuan fault, whereas the western Haiyuan, southern Liupanshan, central Lajishan and central‐western West Qinling faults are essentially locked above 15–20 km, suggesting a potentially high seismic hazard.
PRX1-positive mesenchymal stem cells drive molar morphogenesis
Authors: Xu Xiaoqiao , Gong Xuyan , Zhang Lei , Zhang Han , Sun Yao
Published: February 2024

Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+ cells within M1. These PRX1+ cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1+ cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.
FSP1 inhibition enhances olaparib sensitivity in BRCA-proficient ovarian cancer patients via a nonferroptosis mechanism
Authors: Miao Huixian , Meng Huangyang , Zhang Yashuang , Chen Tian , Zhang Lin , Cheng Wenjun
Published: February 2024

Poly ADP-ribose polymerase inhibitors (PARPis) exhibit promising efficacy in patients with BRCA mutations or homologous repair deficiency (HRD) in ovarian cancer (OC). However, less than 40% of patients have HRD, it is vital to expand the indications for PARPis in BRCA-proficient patients. Ferroptosis suppressor protein 1 (FSP1) is a key protein in a newly identified ferroptosis-protective mechanism that occurs in parallel with the GPX4-mediated pathway and is associated with chemoresistance in several cancers. Herein, FSP1 is reported to be negatively correlated with the prognosis in OC patients. Combination therapy comprising olaparib and iFSP1 (a FSP1 inhibitor) strongly inhibited tumour proliferation in BRCA-proficient OC cell lines, patient-derived organoids (PDOs) and xenograft mouse models. Surprisingly, the synergistic killing effect could not be reversed by ferroptosis inhibitors, indicating that mechanisms other than ferroptosis were responsible for the synergistic lethality. In addition, cotreatment was shown to induce increased γH2A.X foci and to impair nonhomologous end joining (NHEJ) activity to a greater extent than did any single drug. Mass spectrometry and immunoprecipitation analyses revealed that FSP1 interacted with Ku70, a classical component recruited to and occupying the end of double-strand breaks (DSBs) in the NHEJ process. FSP1 inhibition decreased Ku70 PARylation, impaired subsequent DNA-PKcs recruitment to the Ku complex at DSB sites and was rescued by restoring PARylation. These findings unprecedentedly reveal a novel role of FSP1 in DNA damage repair and provide new insights into how to sensitize OC patients to PARPi treatment.
Epigenomic analyses identify FOXM1 as a key regulator of anti-tumor immune response in esophageal adenocarcinoma
Authors: Ziman Benjamin , Yang Qian , Zheng Yueyuan , Sheth Megha , Nam Chehyun , Zhao Hua , Zhang Le , Hu Boyan , Bhowmick Neil A. , Sinha Uttam K. , Lin De-Chen
Published: February 2024

Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in the western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify the transcription factor (TF) FOXM1 as an important epigenetic regulator of EAC. FOXM1 plays a critical role in cellular proliferation and tumor growth in EAC patient-derived organoids and cell line models. We identify ERBB2 as an upstream regulator of the expression and transcriptional activity of FOXM1. Unexpectedly, gene set enrichment analysis (GSEA) unbiased screen reveals a prominent anti-correlation between FOXM1 and immune response pathways. Indeed, syngeneic mouse models show that FOXM1 inhibits the infiltration of CD8+ T cells into the tumor microenvironment. Consistently, FOXM1 suppresses CD8+ T cell chemotaxis in vitro and antigen-dependent CD8+ T cell killing. This study characterizes FOXM1 as a significant EAC-promoting TF and elucidates its novel function in regulating anti-tumor immune response.
Fumarate induces LncRNA-MIR4435-2HG to regulate glutamine metabolism remodeling and promote the development of FH-deficient renal cell carcinoma
Authors: Zhu Liangsong , Hong Yilun , Zhu Ziran , Huang Jiwei , Wang Jianfeng , Li Ge , Wu Xiaoyu , Chen Yonghui , Xu Yunze , Zheng Liang , Huang Yiran , Kong Wen , Xue Wei , Zhang Jin
Published: February 2024

Fumarate hydratase (FH) deficient renal cell carcinoma (RCC) is a type of tumor with definite metabolic disorder, but the mechanism of metabolic remodeling is still unclear. LncRNA was reported to closely correlate with cancer metabolism, however the biological role of LncRNA in the development of progression of FH-deficent RCC was not well studied either. FH-deficient RCC samples were collected in my hospital and used for RNA-sequencing and Mass spectrometry analysis. FH-deficient RCC cell line UOK262 and control pFH cells were used for in vitro experiments, including proliferation assay, transwell assay, western-blot, mass spectrometry and so on. PDX mouse model was used for further drug inhibition experiments in vivo. In this study, we analyzed the profiles of LncRNA and mRNA in FH-deficienct RCC samples, and we found that the LncRNA-MIR4435-2GH was specifically highly expressed in FH-deficient RCC compared with ccRCC. In vitro experiments demonstrated that MIR4435-2HG was regulated by Fumarate through histone demethylation, and the deletion of this gene could inhibit glutamine metabolism. RNA-pulldown experiments showed that MIR4435-2HG specifically binds to STAT1, which can transcriptionally activate GLS1. GLS1 inhibitor CB-839 could significantly suppress tumor growth in PDX tumor models. This study analyzed the molecular mechanism of MIR4435-2HG in regulating metabolic remodeling of FH-deficient RCC in clinical samples, cells and animal models by combining transcriptional and metabolic methods. We found that that GLS1 was a therapeutic target for this tumor, and MIR4435-2HG can be used as a drug sensitivity marker.
8-Br-cGMP activates HSPB6 and increases the antineoplastic activity of quinidine in prostate cancer
Authors: Feng Yuankang , Huang Zhenlin , Lu Fubo , Song Liang , Liu Ruoyang , Zhang Yu , Li Ningyang , Han Xu , Li Xiang , Li Keqiang , Huang Budeng , Xie Guoqing , Guo Abao , Yang Jinjian , Jia Zhankui
Published: February 2024

Heat shock protein family B [small] member 6 (HSPB6), widely found in various muscles, has been recently identified as a tumor suppressor gene. However, its role in prostate cancer remains unexplored. Herein, we investigated the expression of HSPB6 in prostate cancer and its association with prognosis. Our findings revealed that HSPB6 downregulation in prostate cancer correlated with a poor prognosis. Moreover, we discovered that HSPB6 can be phosphorylated and activated by 8-Br-cGMP, leading to apoptosis in prostate cancer cells by activating Cofilin. Additionally, we demonstrated that knocking down E2F1 by quinidine administration enhances the transcriptional level of HSPB6. Furthermore, we evaluated the combination of quinidine and 8-Br-cGMP as a potential therapeutic strategy for prostate cancer. Our results revealed that the combined treatment was more effective than either treatment alone in inhibiting the growth of prostate cancer through the HSPB6 pathway, both in vitro and in vivo. Overall, our study provides compelling evidence that HSPB6 suppresses malignant behavior in prostate cancer by inducing apoptosis. The combination of quinidine and 8-Br-cGMP emerges as a promising approach for the treatment of prostate cancer.
Liquid Madelung energy accounts for the huge potential shift in electrochemical systems
Authors: Takenaka Norio , Ko Seongjae , Kitada Atsushi , Yamada Atsuo
Published: February 2024

Achievement of carbon neutrality requires the development of electrochemical technologies suitable for practical energy storage and conversion. In any electrochemical system, electrode potential is the central variable that regulates the driving force of redox reactions. However, quantitative understanding of the electrolyte dependence has been limited to the classic Debye-Hückel theory that approximates the Coulombic interactions in the electrolyte under the dilute limit conditions. Therefore, accurate expression of electrode potential for practical electrochemical systems has been a holy grail of electrochemistry research for over a century. Here we show that the ‘liquid Madelung potential’ based on the conventional explicit treatment of solid-state Coulombic interactions enables quantitatively accurate expression of the electrode potential, with the Madelung shift obtained from molecular dynamics reproducing a hitherto-unexplained huge experimental shift for the lithium metal electrode. Thus, a long-awaited method for the description of the electrode potential in any electrochemical system is now available.
Complexation-driven assembly of imine-linked helical receptors showing adaptive folding and temperature-dependent guest selection
Authors: Song Geunmoo , Lee Seungwon , Jeong Kyu-Sung
Published: February 2024

The development of synthetic receptors capable of selectively binding guests with diverse structures and multiple functional groups poses a significant challenge. Here, we present the efficient assembly of foldamer-based receptors for monosaccharides, utilising the principles of complexation-induced equilibrium shifting and adaptive folding. Diimine 4 can be quantitatively assembled from smaller components when d-galactose is added as a guest among monosaccharides we examined. During this assembly, dual complexation-induced equilibrium shifts toward both the formation of diimine 4 and the conversion of d-galactose into α-d-galactofuranose are observed. Diimine 6 is quantitatively assembled in the presence of two different guests, methyl β-d-glucopyranoside and methyl β-d-galactopyranoside, resulting in the formation of two dimeric complexes: (6-MP)2⊃(methyl β-d-glucopyranoside)2 and (6-MM)2⊃(methyl β-d-galactopyranoside∙2H2O)2, respectively. These two complexes exhibit distinct folding structures with domain-swapping cavities depending on the bound guest and temperature. Interestingly, (6-MM)2⊃(methyl β-d-galactopyranoside∙2H2O)2 is exclusively formed at lower temperatures, while (6-MP)2⊃(methyl β-d-glucopyranoside)2 is only formed at higher temperatures.
A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution
Authors: Ng Michael T. H. , Borst Rowie , Gacaferi Hamez , Davidson Sarah , Ackerman Jessica E. , Johnson Peter A. , Machado Caio C. , Reekie Ian , Attar Moustafa , Windell Dylan , Kurowska-Stolarska Mariola , MacDonald Lucy , Alivernini Stefano , Garvilles Micon , Jansen Kathrin , Bhalla Ananya , Lee Angela , Charlesworth James , Chowdhury Rajat , Klenerman Paul , Powell Kate , Hackstein Carl-Philip ,   ICECAP Consortium, Rangan Amar , Gwilym Stephen , Little Christopher , Titchener Andrew , Chaudhury Salma , Holland Philip , Wheway Kim , Watkins Bridget , Beazley Debra , Vesty-Edwards Lois , Appleton Louise , Atkinson Marc , Kottam Lucksy , James Juliet , Clark Natalie , Furniss Dominic , Rees Jonathan , Gilroy Derek , Coles Mark , Carr Andrew J. , Sansom Stephen N. , Buckley Christopher D. , Dakin Stephanie G.
Published: February 2024

Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.
Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer
Authors: Wang Shixiang , Wu Chen-Yi , He Ming-Ming , Yong Jia-Xin , Chen Yan-Xing , Qian Li-Mei , Zhang Jin-Ling , Zeng Zhao-Lei , Xu Rui-Hua , Wang Feng , Zhao Qi
Published: February 2024

The clinical implications of extrachromosomal DNA (ecDNA) in cancer therapy remain largely elusive. Here, we present a comprehensive analysis of ecDNA amplification spectra and their association with clinical and molecular features in multiple cohorts comprising over 13,000 pan-cancer patients. Using our developed computational framework, GCAP, and validating it with multifaceted approaches, we reveal a consistent pan-cancer pattern of mutual exclusivity between ecDNA amplification and microsatellite instability (MSI). In addition, we establish the role of ecDNA amplification as a risk factor and refine genomic subtypes in a cohort from 1015 colorectal cancer patients. Importantly, our investigation incorporates data from four clinical trials focused on anti-PD-1 immunotherapy, demonstrating the pivotal role of ecDNA amplification as a biomarker for guiding checkpoint blockade immunotherapy in gastrointestinal cancer. This finding represents clinical evidence linking ecDNA amplification to the effectiveness of immunotherapeutic interventions. Overall, our study provides a proof-of-concept of identifying ecDNA amplification from cancer whole-exome sequencing (WES) data, highlighting the potential of ecDNA amplification as a valuable biomarker for facilitating personalized cancer treatment.
PIBF1 regulates trophoblast syncytialization and promotes cardiovascular development
Authors: Lee Jong Geol , Yon Jung-Min , Kim Globinna , Lee Seul-Gi , Kim C-Yoon , Cheong Seung-A , Kim Hyun-Yi , Yu Jiyoung , Kim Kyunggon , Sung Young Hoon , Yoo Hyun Ju , Woo Dong-Cheol , Rho Jin Kyung , Ha Chang Hoon , Pack Chan-Gi , Oh Seak Hee , Lim Joon Seo , Han Yu Mi , Hong Eui-Ju , Seong Je Kyung , Lee Han-Woong , Lee Sang-Wook , Lee Ki-Up , Kim Chong Jai , Nam Sang-Yoon , Cho You Sook , Baek In-Jeoung
Published: February 2024

Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that PIBF1 promotes the development of cardiovascular characteristics in heart organoids. Our findings show how SynTs organize the barrier and imply their possible roles in supporting embryogenesis, including cardiovascular development. SynT-derived factors and SynT within the placenta may play critical roles in ensuring proper organogenesis of other organs in the embryo.
Molecular co-assembled strategy tuning protein conformation for cartilage regeneration
Authors: Zhao Chengkun , Li Xing , Han Xiaowen , Li Zhulian , Bian Shaoquan , Zeng Weinan , Ding Mingming , Liang Jie , Jiang Qing , Zhou Zongke , Fan Yujiang , Zhang Xingdong , Sun Yong
Published: February 2024

The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a “molecular velcro”-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered β-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials.
Self-supervised dynamic learning for long-term high-fidelity image transmission through unstabilized diffusive media
Authors: Li Ziwei , Zhou Wei , Zhou Zhanhong , Zhang Shuqi , Shi Jianyang , Shen Chao , Zhang Junwen , Chi Nan , Dai Qionghai
Published: February 2024

Multimode fiber (MMF) which supports parallel transmission of spatially distributed information is a promising platform for remote imaging and capacity-enhanced optical communication. However, the variability of the scattering MMF channel poses a challenge for achieving long-term accurate transmission over long distances, of which static optical propagation modeling with calibrated transmission matrix or data-driven learning will inevitably degenerate. In this paper, we present a self-supervised dynamic learning approach that achieves long-term, high-fidelity transmission of arbitrary optical fields through unstabilized MMFs. Multiple networks carrying both long- and short-term memory of the propagation model variations are adaptively updated and ensembled to achieve robust image recovery. We demonstrate >99.9% accuracy in the transmission of 1024 spatial degree-of-freedom over 1 km length MMFs lasting over 1000 seconds. The long-term high-fidelity capability enables compressive encoded transfer of high-resolution video with orders of throughput enhancement, offering insights for artificial intelligence promoted diffusive spatial transmission in practical applications.