bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development vision to enhance the eco-therapeutic tourism industry and its impact on urban development in Egypt
Authors: Riad Mohamed Khatab Mohamed Ahmed 
Published: July 2024

AbstractThis study aims to analyze the importance of eco-therapeutic tourism industry in Egypt's development and to create a strategic plan to enhance such type of tourism through collaborative efforts between various stakeholders. The goal is to align with Egypt's Vision 2030 and focus on the third Sustainable Development Goal. The research highlights the positive economic impact of tourism on Egypt's tourism infrastructure, emphasizing the importance of healing, relaxation, and rejuvenation in serene destinations. It discusses the role of infrastructure capacity, programs, and services in maximizing returns from tourism, and examines the potential for growth eco-therapeutic tourism in Egypt. The study finds a correlation between demand , marketing strategies and flexible tourism infrastructure, This research project starts by exploring the fundamental principles of eco-therapeutic tourism in Egypt. It then looks at past experiences to extract important insights. The study also evaluates the potential of health and wellness tourism in Egypt and assesses the country's current performance in this aspect. The research methodology involves using descriptive and analytical inductive methods at various stages. The study found a strong link between the demand for eco-therapeutic tourism industry in Egypt and factors related to development, such as marketing effectiveness and tourism infrastructure. It also emphasized the significance of infrastructure that is not limited to a specific location in reducing costs for providers and patients. Egypt can benefit from these factors to increase revenue and achieve significant economic returns from medical and preventive tourism resorts by relying on nearby villages and cities to reduce costs.
Hydrology Outweighs Temperature in Driving Production and Export of Dissolved Carbon in a Snowy Mountain Catchment
Authors: Kerins Devon , Sadayappan Kayalvizhi , Zhi Wei , Sullivan Pamela L. , Williams Kenneth H. , Carroll Rosemary W. H. , Barnard Holly R. , Sprenger Matthias , Dong Wenming , Perdrial Julia , Li Li 
Published: July 2024

AbstractTerrestrial production and export of dissolved organic and inorganic carbon (DOC and DIC) to streams depends on water flow and biogeochemical processes in and beneath soils. Yet, understanding of these processes in a rapidly changing climate is limited. Using the watershed‐scale reactive‐transport model BioRT‐HBV and stream data from a snow‐dominated catchment in the Rockies, we show deeper groundwater flow averaged about 20% of annual discharge, rising to ∼35% in drier years. DOC and DIC production and export peaked during snowmelt and wet years, driven more by hydrology than temperature. DOC was primarily produced in shallow soils (1.94 ± 1.45 gC/m2/year), stored via sorption, and flushed out during snowmelt. Some DOC was recharged to and further consumed in the deeper subsurface via respiration (−0.27 ± 0.02 gC/m2/year), therefore reducing concentrations in deeper groundwater and stream DOC concentrations at low discharge. Consequently, DOC was primarily exported from the shallow zone (1.62 ± 0.96 gC/m2/year, compared to 0.12 ± 0.02 gC/m2/year from the deeper zone). DIC was produced in both zones but at higher rates in shallow soils (1.34 ± 1.00 gC/m2/year) than in the deep subsurface (0.36 ± 0.02 gC/m2/year). Deep respiration elevated DIC concentrations in the deep zone and stream DIC concentrations at low discharge. In other words, deep respiration is responsible for the commonly‐observed increasing DOC concentrations (flushing) and decreasing DIC concentrations (dilution) with increasing discharge. DIC export from the shallow zone was ~66% of annual export but can drop to ∼53% in drier years. Numerical experiments suggest lower carbon production and export in a warmer, drier future, and a higher proportion from deeper flow and respiration processes. These results underscore the often‐overlooked but growing importance of deeper processes in a warming climate.
Prioritizing Forestation in China Through Incorporating Biogeochemical and Local Biogeophysical Effects
Authors: Li Yu , Zhang Pengyi , Wang Huanhuan , Ma Hui , Zhao Jie , Xu Mengyang , Wang Mengyu , Guo Chenhui , Yue Chao 
Published: July 2024

AbstractForestation is a key strategy for climate mitigation in China through its biogeochemical (BGC) effect of ecosystem carbon sequestration. Additionally, the BGC effect of forestation can be either reinforced or counteracted by concurrent biogeophysical processes (BGP effect) resulting in local land surface warming or cooling, which can be translated into CO2e (i.e., BGC effect) using a local transient climate response. Previous evaluations of the climate mitigation potential of future forestation in China have, however, focused on the BGC effect only and neglected the BGP effect, potentially leading to suboptimal forestation areas. Here, we determined priority forestation areas in China by incorporating both effects to maximize its global climate mitigation effect. Our results suggest an additional 167.2 Mha potentially suitable for forestation in China, exceeding the largest forestation target (86.8 Mha) possibly assumed by the government in 2060. The forestation‐induced BGP effect (18.7 ± 61.9 tCO2e ha−1) largely reinforces the BGC effect (458.2 ± 92.6 tCO2e ha−1) in China, yielding a total climate mitigation effect of 476.9 ± 114.2 tCO2e ha−1 over 40 years (2021–2060). Under the 2060 forestation target, considering both BGC and BGP effects will displace 17.7% (15.3 Mha) of the forestation area derived by considering the BGC effect alone. Integrating both BGC and BGP effects will lead to a CO2 uptake of 28.8 GtCO2e by 2060, 3.9 GtCO2e higher than the value obtained when considering the BGC effect only. Our results highlight the importance of considering BGP effect when making forestation policies for climate mitigation.
National‐Scale Flood Hazard Data Unfit for Urban Risk Management
Authors: Schubert Jochen E. , Mach Katharine J. , Sanders Brett F. 
Published: July 2024

AbstractExtreme flooding events are becoming more frequent and costly, and impacts have been concentrated in cities where exposure and vulnerability are both heightened. To manage risks, governments, the private sector, and households now rely on flood hazard data from national‐scale models that lack accuracy in urban areas due to unresolved drainage processes and infrastructure. Here we assess the uncertainties of First Street Foundation (FSF) flood hazard data, available across the U.S., using a new model (PRIMo‐Drain) that resolves drainage infrastructure and fine resolution drainage dynamics. Using the case of Los Angeles, California, we find that FSF and PRIMo‐Drain estimates of population and property value exposed to 1%‐ and 5%‐annual‐chance hazards diverge at finer scales of governance, for example, by 4‐ to 18‐fold at the municipal scale. FSF and PRIMo‐Drain data often predict opposite patterns of exposure inequality across social groups (e.g., Black, White, Disadvantaged). Further, at the county scale, we compute a Model Agreement Index of only 24%—a ∼1 in 4 chance of models agreeing upon which properties are at risk. Collectively, these differences point to limited capacity of FSF data to confidently assess which municipalities, social groups, and individual properties are at risk of flooding within urban areas. These results caution that national‐scale model data at present may misinform urban flood risk strategies and lead to maladaptation, underscoring the importance of refined and validated urban models.
Obliquity Pacing of Deep Pacific Carbonate Chemistry During the Plio‐Pleistocene
Authors: Qin Bingbin , Xiong Zhifang , Algeo Thomas J. , Jia Qi , Nürnberg Dirk , Li Tiegang 
Published: July 2024

AbstractReconstruction of the seawater carbonate system is essential for an improved understanding of glacial‐interglacial oceanic carbon cycling and climate change. However, continuous high‐resolution ocean carbonate chemistry data are generally lacking for the Plio‐Pleistocene. Here, we present a deep Pacific carbonate ion saturation state (Δ[CO32−]) record spanning the last 5.1 Myr, reconstructed from the size‐normalized shell weight of planktonic foraminifer in the western tropical Pacific. Deep Pacific Δ[CO32−] has been modulated primarily by orbital obliquity since 5.1 Ma, during which it has exhibited in‐phase behavior with the 40‐Kyr obliquity cycle. Significantly, the amplitude of the 40‐Kyr Δ[CO32−] cycles has responded linearly to obliquity forcing throughout the Plio‐Pleistocene, independent of the late Pliocene intensification of Northern Hemisphere glaciation. We speculate that the obliquity signal in the deep Pacific Δ[CO32−] record reflects an ocean‐atmosphere circulation feedback mediated by migration of the Southern Hemisphere Westerlies.
Factors Controlling DMS Emission and Atmospheric Sulfate Aerosols in the Western Pacific Continental Sea
Authors: Yan Shi‐Bo , Xu Gao‐Bin , Zhang Hong‐Hai , Wang Jian , Xu Feng , Gao Xu‐Xu , Zhang Jia‐Wei , Wu Jin‐Wei , Yang Gui‐Peng 
Published: July 2024

AbstractThe western Pacific continental sea significantly influences the regulation of climate‐active gases budget and the burden of sulfate aerosols. An underway shipboard measurement device was used to determine the dimethyl sulfide (DMS) in the surface seawater and overlying atmosphere in the East China Continental Sea. The average concentration of DMS in atmosphere and seawater was 122.8 ± 86.2pptv and 6.47 ± 3.58 nmol L−1, respectively. The variation trend of surface water DMS in the western Pacific continental sea was influenced by the abundance and composition of phytoplankton under different ocean current systems, with a significant impact from eddies on DMS production in the South China Sea. By eliminating the influence of terrestrial sources and limiting air mass transport within the marine boundary layer, strong correlations were established between atmospheric DMS and air mass exposure to chlorophyll (Echl), as well as between aerosol methanesulfonic acid (MSA) and Echl. During the aerosol sampling period, the atmospheric DMS levels (1,057 ± 371 ng/m3) were significantly higher than MSA levels (46.3 ± 59.8 ng/m3) in the East China Sea, where the conversion of DMS to MSA was not affected by changes in DMS concentration. The sea‐to‐air fluxes of DMS varied over a wide range, from 0.02 to 156.0 μmol m−2 d−1, with an average of 14.35 ± 18.58 μmol m−2 d−1. Marine DMS emissions play a critical role in the formation of sulfur aerosols on the western Pacific continental shelf, accounting for 24.6 ± 7.6% (14.8%–37.8%) of the total sulfate aerosols.
Decrease in UCP1 by sustained high lipid promotes NK cell necroptosis to exacerbate nonalcoholic liver fibrosis
Authors: Gu Min , Zhang Yu , Lin Zhijie , Hu Xiangyu , Zhu Yaqin , Xiao Weiming , Jia Xiaoqin , Chen Weiwei , Lu Guotao , Gong Weijuan 
Published: July 2024

AbstractUncoupling protein 1 (UCP1) catalyzes the leak of protons across the mitochondrial inner membrane for thermogenesis. Compromised NK cell activity is involved in the occurrence of nonalcoholic liver fibrosis. Here, decreased UCP1 in NK cells was identified in patients with advanced nonalcoholic fatty liver disease. Although no obvious changes were observed in the NK cells of physiologic UCP1−/− mice (8–10 weeks old), impaired NK cell bioactivity was shown in methionine–choline-diet (MCD)-fed UCP1−/− mice and involved in the acerbation of nonalcoholic steatohepatitis (NASH) progress to liver fibrosis. Moreover, UCP1-deficient NK cells were responsible for the aggravation of liver fibrosis, as confirmed in MCD-fed UCP1flox/flox-NCR1cre mice. Acerbation of liver fibrosis was also seen in wild-type mice when their endogenous NK cells were replaced with UCP1−/− NK cells. Transcriptions of mitophagy-associated molecules in UCP1−/− NK cells were enhanced according to RNA-seq. Electron microscopic results showed mitochondrial injuries and autophagic vesicles in MCD-fed NKWT cells, PA-treated NKWT cells, or physiologic NKKO cells. However, the co-existence of UCP1 deficiency and high lipid can synergistically induce NK cell necroptosis via DRP1S616 accompanied with reduced mitophagy. Finally, The UCP1 in NK cells was downregulated when treated by sustained high PA (600 μM) via the PPARγ/ATF2 axis. Thus, persistent high-lipid treatment not only decreases UCP1 expression but also combines with reduced UCP1 to promote NK cell necroptosis, and it is involved in NASH progression to fibrosis.
ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I
Authors: Li Chunya , Wang Boyu , Tu Jingyao , Liu Chaofan , Wang Yuan , Chen Junjie , Huang Yongbiao , Liu Bo , Yuan Xianglin 
Published: July 2024

AbstractAccumulating evidence supports the concept that DNA damage response targeted therapies can improve antitumor immune response by increasing the immunogenicity of tumor cells and improving the tumor immune microenvironment. Ataxia telangiectasia mutated (ATM) is a core component of the DNA repair system. Although the ATM gene has a significant mutation rate in many human cancers, including colorectal, prostate, lung, and breast, it remains understudied compared with other DDR-involved molecules such as PARP and ATR. Here, we found that either gene knockout or drug intervention, ATM inhibition activated the cGAS/STING pathway and augmented MHC class I in CRC cells, and these effects could be amplified by radiation. Furthermore, we found that MHC class I upregulation induced by ATM inhibition is dependent on the activation of the NFκB/IRF1/NLRC5 pathway and independent of STING. Animal experiments have shown increasing infiltration and cytotoxic function of T cells and better survival in ATM-deficient tumors. This work indicated that ATM nonsense mutation predicted the clinical benefits of radiotherapy combined with immune checkpoint blockade for patients with CRC. It also provides a molecular mechanism rationale for ATM-targeted agents for patients with CRC.
Progression of m6A in the tumor microenvironment: hypoxia, immune and metabolic reprogramming
Authors: Han Xuan , Zhu Yu , Ke Juan , Zhai Yufeng , Huang Min , Zhang Xin , He Hongjie , Zhang Xiaojing , Zhao Xuehong , Guo Kaikai , Li Xianglin , Han Zhongyu , Zhang Yanming 
Published: July 2024

AbstractRecently, N6-methyladenosine (m6A) has aroused widespread discussion in the scientific community as a mode of RNA modification. m6A comprises writers, erasers, and readers, which regulates RNA production, nuclear export, and translation and is very important for human health. A large number of studies have found that the regulation of m6A is closely related to the occurrence and invasion of tumors, while the homeostasis and function of the tumor microenvironment (TME) determine the occurrence and development of tumors to some extent. TME is composed of a variety of immune cells (T cells, B cells, etc.) and nonimmune cells (tumor-associated mesenchymal stem cells (TA-MSCs), cancer-associated fibroblasts (CAFs), etc.). Current studies suggest that m6A is involved in regulating the function of various cells in the TME, thereby affecting tumor progression. In this manuscript, we present the composition of m6A and TME, the relationship between m6A methylation and characteristic changes in TME, the role of m6A methylation in TME, and potential therapeutic strategies to provide new perspectives for better treatment of tumors in clinical work.
Family with sequence similarity 83, member A (FAM83A) inhibits ferroptosis via the Wnt/β-catenin pathway in lung squamous cell cancer
Authors: Wang Cong , Zhang Jing , Wang Hongjiao , Chen Ruixue , Lu Ming 
Published: July 2024

AbstractThe function of Family With Sequence Similarity 83, Member A (FAM83A) in lung squamous cell carcinoma (LUSC) is largely unknown. Here, we detected its prognostic and regulation roles in LUSC. Bioinformatics methods were applied initially to predict the expression level and prognostic value of FAM83A mRNA in LUSC. In vitro experiments, such as western blot, colony formation and cell viability assay, lipid Reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG), and 4-hydroxy-2-nonenal (4-HNE) assay, were used to investigate its mechanism. In vivo experiments were further conducted to validate the mechanism. Results from TCGA and Oncomine databases revealed significantly higher FAM83A mRNA expression levels in LUSC than in normal lung tissue. TCGA and GEO databases and our database revealed that FAM83A expression level was an independent prognostic factor for both overall survival and progression-free survival. Besides, FAM83A was significantly associated with a higher ability of growth and clonogenicity. Mechanistically, in vitro and in vivo experiments revealed that FAM83A could promote LUSC cell growth by inhibiting ferroptosis via activating the Wnt/β-catenin signaling pathway. The rescue experiment demonstrated that inhibition of the Wnt/β-catenin pathway counteracted the function of FAM83A. FAM83A is overexpressed in LUSC and could serve as a prognosis prediction biomarker for LUSC. FAM83A promotes LUSC cell growth by inhibiting ferroptosis via activating the Wnt/β-catenin signaling pathway, which provides a new potential therapeutic target for LUSC treatment.
Structure and exfoliation mechanism of two-dimensional boron nanosheets
Authors: Chung Jing-Yang , Yuan Yanwen , Mishra Tara P. , Joseph Chithralekha , Canepa Pieremanuele , Ranjan Pranay , Sadki El Hadi S. , Gradečak Silvija , Garaj Slaven 
Published: July 2024

AbstractExfoliation of two-dimensional (2D) nanosheets from three-dimensional (3D) non-layered, non-van der Waals crystals represents an emerging strategy for materials engineering that could significantly increase the library of 2D materials. Yet, the exfoliation mechanism in which nanosheets are derived from crystals that are not intrinsically layered remains unclear. Here, we show that planar defects in the starting 3D boron material promote the exfoliation of 2D boron sheets—by combining liquid-phase exfoliation, aberration-corrected scanning transmission electron microscopy, Raman spectroscopy, and density functional theory calculations. We demonstrate that 2D boron nanosheets consist of a planar arrangement of icosahedral sub-units cleaved along the {001} planes of β-rhombohedral boron. Correspondingly, intrinsic stacking faults in 3D boron form parallel layers of faulted planes in the same orientation as the exfoliated nanosheets, reducing the {001} cleavage energy. Planar defects represent a potential engineerable pathway for exfoliating 2D sheets from 3D boron and, more broadly, the other covalently bonded materials.
Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency
Authors: Tesla Rachel , Guhl Charlotte , Werthmann Gordon C. , Dixon Danielle , Cenik Basar , Addepalli Yesu , Liang Jue , Fass Daniel M. , Rosenthal Zachary , Haggarty Stephen J. , Williams Noelle S. , Posner Bruce A. , Ready Joseph M. , Herz Joachim 
Published: July 2024

AbstractHeterozygous loss-of-function mutations in the GRN gene are a major cause of hereditary frontotemporal dementia. The mechanisms linking frontotemporal dementia pathogenesis to progranulin deficiency are not well understood, and there is currently no treatment. Our strategy to prevent the onset and progression of frontotemporal dementia in patients with GRN mutations is to utilize small molecule positive regulators of GRN expression to boost progranulin levels from the remaining functional GRN allele, thus restoring progranulin levels back to normal within the brain. This work describes a series of blood-brain-barrier-penetrant small molecules which significantly increase progranulin protein levels in human cellular models, correct progranulin protein deficiency in Grn+/− mouse brains, and reverse lysosomal proteome aberrations, a phenotypic hallmark of frontotemporal dementia, more efficiently than the previously described small molecule suberoylanilide hydroxamic acid. These molecules will allow further elucidation of the cellular functions of progranulin and its role in frontotemporal dementia and will also serve as lead structures for further drug development.
Characterization of a Salmonella enterica serovar Typhimurium lineage with rough colony morphology and multidrug resistance
Authors: Xiang Ying , Zhu Kunpeng , Min Kaiyuan , Zhang Yaowen , Liu Jiangfeng , Liu Kangkang , Han Yiran , Li Xinge , Du Xinying , Wang Xin , Huang Ying , Li Xinping , Peng Yuqian , Yang Chaojie , Liu Hongbo , Liu HONGBO , Li Xiaoying , Wang Hui , Wang Chao , Wang Qi , Jia Huiqun , Yang Mingjuan , Wang Ligui , Wu Yarong , Cui Yujun , Chen Fei , Yang Haiyan , Baker Stephen , Xu Xuebin , Yang Juntao , Song Hongbin , Qiu Shaofu 
Published: July 2024

AbstractSalmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (−44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.
Catalyst-free selective oxidation of C(sp3)-H bonds in toluene on water
Authors: Lee Kyoungmun , Cho Yumi , Kim Jin Chul , Choi Chiyoung , Kim Jiwon , Lee Jae Kyoo , Li Sheng , Kwak Sang Kyu , Choi Siyoung Q. 
Published: July 2024

AbstractThe anisotropic water interfaces provide an environment to drive various chemical reactions not seen in bulk solutions. However, catalytic reactions by the aqueous interfaces are still in their infancy, with the emphasis being on the reaction rate acceleration on water. Here, we report that the oil-water interface activates and oxidizes C(sp3)-H bonds in toluene, yielding benzaldehyde with high selectivity (>99%) and conversion (>99%) under mild, catalyst-free conditions. Collision at the interface between oil-dissolved toluene and hydroxyl radicals spontaneously generated near the water-side interfaces is responsible for the unexpectedly high selectivity. Protrusion of free OH groups from interfacial water destabilizes the transition state of the OH-addition by forming π-hydrogen bonds with toluene, while the H-abstraction remains unchanged to effectively activate C(sp3)-H bonds. Moreover, the exposed free OH groups form hydrogen bonds with the produced benzaldehyde, suppressing it from being overoxidized. Our investigation shows that the oil-water interface has considerable promise for chemoselective redox reactions on water without any catalysts.