bluuebunny/crossref_metadata_2025_split huggingface dataset:
Water Recycling in the Deep Earth: Insights From Integrated μ‐XRF, THz‐TDS Spectroscopy, TG, and DCS of High‐Pressure Granulite
Authors: Li Shan‐Shan , Qiu Kun‐Feng , Hernández‐Uribe David , Gao Yi‐Xue , Santosh M. , Huang Hao‐Chong , Zheng Zhi‐Yuan , Zhang Zi‐Li , Gao Shi‐Chen 
Published: February 2023

AbstractSubduction‐related dehydration and exhumation‐related rehydration play an important role in water recycling on Earth. Water can be transported to the deep mantle through crustal subduction, whereas the behavior of water in the subducted crust during exhumation remains enigmatic. Here, we use an integrated micro X‐ray fluorescence spectrometry, transmission terahertz time‐domain, thermogravimetry, and differential scanning calorimetry approach for the first time on high‐pressure mafic granulite and amphibolite to investigate the water species and contents, as well as exhumation rehydration reactions. Our study demonstrates that garnet, hornblende, and ilmenite contain considerable amounts, and plagioclase contains minor amounts of water as molecular and structural species, whereas quartz contains only a minor amount of structural water. Water released from garnet and external fluids from the grain boundary will either migrate into hornblende, plagioclase, ilmenite, and quartz, or stored in the mantle wedge, or further subducted into the deep mantle. We suggest that water recycling between the Earth's surface and deep mantle is an unequilibrium process, and the lower crust and mantle may store a significant amount of water in deep Earth and can function as a container to feed and maintain the water recycling balance.
Soil Moisture and Atmospheric Aridity Impact Spatio‐Temporal Changes in Evapotranspiration at a Global Scale
Authors: Zhang Wenmin , Koch Julian , Wei Fangli , Zeng Zhenzhong , Fang Zhongxiang , Fensholt Rasmus 
Published: February 2023

AbstractEvapotranspiration (ET) constitutes the water exchange from land to the atmosphere, which in turn modulates precipitation and soil moisture (SM). Multiple lines of evidence document complex feedbacks between changes in ET and temperature, atmospheric CO2 and vegetation greening. However, the existing analyses on global changes in ET do not account for the direct effects of SM supply and atmospheric water demand, expressed by vapor pressure deficit (VPD), while considering multiple environmental variables. Here we evaluated the performance of ET products using 140 flux towers included in the FLUXNET database. All ET products show reasonable performance, with an overall correlation higher than 0.7 and better performance at a higher latitude. From analysis of the ensemble mean of annual ET, we show insignificant (P = 0.06) trends in global ET during 1982–2020 and a significantly (P < 0.01) increasing trend during 2002–2020. Changes in GLEAM ET generally exert a positive response to changes in SM and a negative response to changes in VPD. Yet, these effects are not globally consistent and are largely determined by changes in vegetation transpiration. Using our finding as a benchmark, Earth System Models mostly reproduce the positive response of ET to SM with less coupling strength, while showing negative effects of VPD on ET with stronger coupling strength. Our study highlights that concurrent soil drying and atmospheric aridity could intensify water exchanges and the importance of realistically representing SM‐VPD‐ET interactions in models for accurate predictions of the hydrological cycle.
Differential global distribution of marine picocyanobacteria gene clusters reveals distinct niche-related adaptive strategies
Authors: Doré Hugo , Guyet Ulysse , Leconte Jade , Farrant Gregory K , Alric Benjamin , Ratin Morgane , Ostrowski Martin , Ferrieux Mathilde , Brillet-Guéguen Loraine , Hoebeke Mark , Siltanen Jukka , Le Corguillé Gildas , Corre Erwan , Wincker Patrick , Scanlan David J , Eveillard Damien , Partensky Frédéric , Garczarek Laurence 
Published: February 2023

Abstract
The ever-increasing number of available microbial genomes and metagenomes provides new opportunities to investigate the links between niche partitioning and genome evolution in the ocean, especially for the abundant and ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Here, by combining metagenome analyses of the Tara Oceans dataset with comparative genomics, including phyletic patterns and genomic context of individual genes from 256 reference genomes, we show that picocyanobacterial communities thriving in different niches possess distinct gene repertoires. We also identify clusters of adjacent genes that display specific distribution patterns in the field (eCAGs) and are thus potentially involved in the same metabolic pathway and may have a key role in niche adaptation. Several eCAGs are likely involved in the uptake or incorporation of complex organic forms of nutrients, such as guanidine, cyanate, cyanide, pyrimidine, or phosphonates, which might be either directly used by cells, for example for the biosynthesis of proteins or DNA, or degraded to inorganic nitrogen and/or phosphorus forms. We also highlight the enrichment of eCAGs involved in polysaccharide capsule biosynthesis in Synechococcus populations thriving in both nitrogen- and phosphorus-depleted areas vs. low-iron (Fe) regions, suggesting that the complexes they encode may be too energy-consuming for picocyanobacteria thriving in the latter areas. In contrast, Prochlorococcus populations thriving in Fe-depleted areas specifically possess an alternative respiratory terminal oxidase, potentially involved in the reduction of Fe(III) to Fe(II). Altogether, this study provides insights into how phytoplankton communities populate oceanic ecosystems, which is relevant to understanding their capacity to respond to ongoing climate change.
Comorbidities in autism spectrum disorder and their etiologies
Authors: Khachadourian Vahe , Mahjani Behrang , Sandin Sven , Kolevzon Alexander , Buxbaum Joseph D. , Reichenberg Abraham , Janecka Magdalena 
Published: February 2023

AbstractIndividuals with autism spectrum disorder (ASD), in addition to the core features of the disease, experience a higher burden of co-occurring medical conditions. This study sought to describe the frequency and distribution of comorbidit conditions in individuals with ASD, and systematically evaluate the possibility that pre- and postnatal exposures (e.g., preterm birth, hypoxia at birth, traumatic brain injury, and fetal alcohol syndrome) associated with ASD may also be linked with distinct comorbidities. We used the SPARK study database, launched by the Simons Foundation Autism Research Initiative (SFARI). Comorbidities considered in the study included neurological, cognitive, psychiatric, and physical conditions. The study sample consisted of 42,569 individuals with ASD and their 11,389 non-ASD siblings (full and half siblings). Majority (74%) of individuals with ASD had at least one comorbidity, and had a greater average number of comorbidities than their non-ASD siblings. Preterm birth and hypoxia at birth were the most common peri-natal exposures in the sample. In logistic regression models adjusted for covariates, these exposures were associated with several distinct comorbidities in ASD cases, including attention and behavior problems, psychiatric and neurological disorders, and growth conditions. A similar pattern of association was also observed in non-ASD siblings. Our findings underscore that individuals with ASD experience a greater burden of comorbidities, which could be partly attributable to the higher rates of perinatal exposures compared to their non-ASD siblings. Study findings, if replicated in other samples, can inform the etiology of comorbidity in ASD.
Randomised controlled trial of breast cancer and multiple disease prevention weight loss programmes vs written advice amongst women attending a breast cancer family history clinic
Authors: Harvie Michelle , French David P. , Pegington Mary , Lombardelli Cheryl , Krizak Suzy , Sellers Katharine , Barrett Emma , Gareth Evans D. , Cutress Ramsey , Wilding RGN Andrea , Graves Lee , Howell Anthony 
Published: February 2023

Background
Overweight and obesity are common amongst women attending breast cancer Family History, Risk and Prevention Clinics (FHRPCs). Overweight increases risk of breast cancer (BC) and conditions including1 cardiovascular disease (CVD) and type-2 diabetes (T2D). Clinics provide written health behaviour advice with is likely to have minimal effects. We assessed efficacy of two remotely delivered weight loss programmes vs. written advice.

Method
210 women with overweight or obesity attending three UK FHRPCs were randomised to either a BC prevention programme (BCPP) framed to reduce risk of BC (n = 86), a multiple disease prevention programme (MDPP) framed to reduce risk of BC, CVD and T2D (n = 87), or written advice (n = 37). Change in weight and health behaviours were assessed at 12-months.

Results
Weight loss at 12 months was −6.3% (−8.2, −4.5) in BCPP, −6.0% (−7.9, −4.2) in MDPP and −3.3% (−6.2, −0.5) in the written group (p = 0.451 across groups). The percentage losing ≥10% weight in these groups were respectively 34%, 23% and 14% (p = 0.038 across groups).

Discussion
BCPP and MDPP programmes resulted in more women achieving ≥10% weight loss, but no evidence of additional benefits of MDPP. A multicentre RCT to test the BCPP across UK FHRPCs is warranted.
Clinical Trial Registration ISRCTN16431108.
NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation
Authors: Zhang Peng , Chen Liang , Zhou Fenfang , He Zhiwen , Wang Gang , Luo Yongwen 
Published: February 2023

AbstractProstate cancer (PCa) is the most common malignant tumor with a high global incidence in males. The mechanism underlying PCa progression is still not clear. This study observed that NRP1 was highly expressed in PCa and associated with poor prognosis in PCa patients. Functionally, NRP1 depletion attenuated the proliferation and migration ability of PCa cells in vitro and in vivo, while NRP1 overexpression promoted PCa cell proliferation and migration. Moreover, it was observed that NRP1 depletion induced G1 phase arrest in PCa cells. Mechanistically, HIF1α is bound to the specific promoter region of NRP1, thereby regulating its transcriptional activation. Subsequently, NRP1 interacted with EGFR, leading to EGFR phosphorylation. This study also provided evidence that the b1/b2 domain of NRP1 was responsible for the interaction with the extracellular domain of EGFR. Moreover, EGFR mediated NRP1-induced activation of the AKT signaling pathway, which promoted the malignant progression of PCa. In addition, the administration of NRP1 inhibitor EG01377 significantly inactivated the EGFR/AKT signaling axis, thereby suppressing PCa progression. In conclusion, the findings from this study highlighted the molecular mechanism underlying NRP1 expression in PCa and provide a potential predictor and therapeutic target for clinical prognosis and treatment of PCa.
MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury
Authors: Yan Yan , Tian Liu-yang , Jia Qian , Han Yang , Tian Yu , Chen Hui-ning , Cui Sai-jia , Xi Jie , Yao Yong-ming , Zhao Xiao-jing 
Published: February 2023

AbstractUnderstanding the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is an urgent problem in clinical trials. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating mitochondria-related gene expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a significantly increased in acute myocardial infarction (AMI) patients and myocardial I/R rats. MiR-130a could downregulate the viability of cardiomyocytes and the knockdown of miR-130a could protect the viability of cardiomyocytes under hypoxia-reoxygenation (HR). Over-expression of miR-130a resulted in mitochondrial dysfunction. It was evidenced by decreases in mitochondrial ATP production, mitochondrial membrane potential (MMP), and an increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect against mitochondrial damage, show elevation of mitochondrial ATP production rate and MMP, and reduce ROS production. We further explored the effect of miR-130a on the mitochondrial quality control (QMC) system by determining mitochondrial-protein-specific proteases and analyzed mitochondrial morphology by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targeted mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a targeted GJA1, and GJA1 rescued IRI by enhancing ATP production rate and oxidative phosphorylation, meanwhile protecting cell viability, MMP, and activating mitophagy. In addition, the knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while the knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.
The mechanism of programmed death and endoplasmic reticulum stress in pulmonary hypertension
Authors: Sun Yang , Liu Shasha , Chen Chen , Yang Songwei , Pei Gang , Lin Meiyu , Wang Ting , Long Junpeng , Yan Qian , Yao Jiao , Lin Yuting , Yi Fan , Meng Lei , Tan Yong , Ai Qidi , Chen Naihong , Yang Yantao 
Published: February 2023

AbstractPulmonary hypertension (PH) was a cardiovascular disease with high morbidity and mortality. PH was a chronic disease with complicated pathogenesis and uncontrollable factors. PH was divided into five groups according to its pathogenesis and clinical manifestations. Although the treatment and diagnosis of PH has made great progress in the past ten years. However, the diagnosis and prognosis of the PAH had a great contrast, which was not conducive to the diagnosis and treatment of PH. If not treated properly, it will lead to right ventricular failure or even death. Therefore, it was necessary to explore the pathogenesis of PH. The problem we urgently need to solve was to find and develop drugs for the treatment of PH. We reviewed the PH articles in the past 10 years or so as well as systematically summarized the recent advance. We summarized the latest research on the key regulatory factors (pyroptosis, apoptosis, necroptosis, ferroptosis, and endoplasmic reticulum stress) involved in PH. To provide theoretical basis and basis for finding new therapeutic targets and research directions of PH.
Bioinspired crowding directs supramolecular polymerisation
Authors: Bäumer Nils , Castellanos Eduardo , Soberats Bartolome , Fernández Gustavo 
Published: February 2023

AbstractCrowding effects are crucial to maintaining functionality in biological systems, but little is known about their role in analogous artificial counterparts. Within the growing field of supramolecular polymer science, crowding effects have hitherto remained underappreciated. Herein, we show that crowding effects exhibit strong and distinct control over the kinetics, accessible pathways and final outcomes of supramolecular polymerisation processes. In the presence of a pre-formed supramolecular polymer as crowding agent, a model supramolecular polymer dramatically changes its self-assembly behaviour and undergoes a morphological transformation from bundled fibres into flower-like hierarchical assemblies, despite no co-assembly taking place. Notably, this new pathway can only be accessed in crowded environments and when the crowding agent exhibits a one-dimensional morphology. These results allow accessing diverse morphologies and properties in supramolecular polymers and pave the way towards a better understanding of high-precision self-assembly in nature.
Climate-induced range shifts drive adaptive response via spatio-temporal sieving of alleles
Authors: Luqman Hirzi , Wegmann Daniel , Fior Simone , Widmer Alex 
Published: February 2023

AbstractQuaternary climate fluctuations drove many species to shift their geographic ranges, in turn shaping their genetic structures. Recently, it has been argued that adaptation may have accompanied species range shifts via the “sieving” of genotypes during colonisation and establishment. However, this has not been directly demonstrated, and knowledge remains limited on how different evolutionary forces, which are typically investigated separately, interacted to jointly mediate species responses to past climatic change. Here, through whole-genome re-sequencing of over 1200 individuals of the carnation Dianthus sylvestris coupled with integrated population genomic and gene-environment models, we reconstruct the past neutral and adaptive landscape of this species as it was shaped by the Quaternary glacial cycles. We show that adaptive responses emerged concomitantly with the post-glacial range shifts and expansions of this species in the last 20 thousand years. This was due to the heterogenous sieving of adaptive alleles across space and time, as populations expanded out of restrictive glacial refugia into the broader and more heterogeneous range of habitats available in the present-day inter-glacial. Our findings reveal a tightly-linked interplay of migration and adaptation under past climate-induced range shifts, which we show is key to understanding the spatial patterns of adaptive variation we see in species today.
The crucial role of adhesion in the transmigration of active droplets through interstitial orifices
Authors: Tiribocchi A. , Durve M. , Lauricella M. , Montessori A. , Marenduzzo D. , Succi S. 
Published: February 2023

AbstractActive fluid droplets are a class of soft materials exhibiting autonomous motion sustained by an energy supply. Such systems have been shown to capture motility regimes typical of biological cells and are ideal candidates as building-block for the fabrication of soft biomimetic materials of interest in pharmacology, tissue engineering and lab on chip devices. While their behavior is well established in unconstrained environments, much less is known about their dynamics under strong confinement. Here, we numerically study the physics of a droplet of active polar fluid migrating within a microchannel hosting a constriction with adhesive properties, and report evidence of a striking variety of dynamic regimes and morphological features, whose properties crucially depend upon droplet speed and elasticity, degree of confinement within the constriction and adhesiveness to the pore. Our results suggest that non-uniform adhesion forces are instrumental in enabling the crossing through narrow orifices, in contrast to larger gaps where a careful balance between speed and elasticity is sufficient to guarantee the transition. These observations may be useful for improving the design of artificial micro-swimmers, of interest in material science and pharmaceutics, and potentially for cell sorting in microfluidic devices.
Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice
Authors: Qiao Sen , Alasmi Samer , Wyatt Amanda , Wartenberg Philipp , Wang Hongmei , Candlish Michael , Das Debajyoti , Aoki Mari , Grünewald Ramona , Zhou Ziyue , Tian Qinghai , Yu Qiang , Götz Viktoria , Belkacemi Anouar , Raza Ahsan , Ectors Fabien , Kattler Kathrin , Gasparoni Gilles , Walter Jörn , Lipp Peter , Mollard Patrice , Bernard Daniel J. , Karatayli Ersin , Karatayli Senem Ceren , Lammert Frank , Boehm Ulrich 
Published: February 2023

AbstractInter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to regulate gonadal function and control fertility. Whether FSH and LH also act on organs other than the gonads is debated. Here, we find that gonadotrope depletion in adult female mice triggers profound hypogonadism, obesity, glucose intolerance, fatty liver, and bone loss. The absence of sex steroids precipitates these phenotypes, with the notable exception of fatty liver, which results from ovary-independent actions of FSH. We uncover paracrine FSH action on pituitary corticotropes as a mechanism to restrain the production of corticosterone and prevent hepatic steatosis. Our data demonstrate that functional communication of two distinct hormone-secreting cell populations in the pituitary regulates hepatic lipid metabolism.
Cobalt(III)-catalyzed asymmetric ring-opening of 7-oxabenzonorbornadienes via indole C–H functionalization
Authors: Zheng Yang , Zhang Wen-Yun , Gu Qing , Zheng Chao , You Shu-Li 
Published: February 2023

AbstractAsymmetric ring-opening of 7-oxabenzonorbornadienes is achieved via Co-catalyzed indole C–H functionalization. The utilization of chiral Co-catalyst consisting of a binaphthyl-derived trisubstituted cyclopentadienyl ligand resulted in high yields (up to 99%) and excellent enantioselectivity (>99% ee) for the target products with tolerance for diverse functional groups. Opposite diastereoselectivities are obtained with chiral Co-catalyst or Cp*CoI2CO. Combined experimental and computational studies suggest β-oxygen elimination being the selectivity-determining step of the reaction. Meanwhile, the reactions of 7-azabenzonorbornadiene could also be executed in a diastereodivergent manner.
Identification of SARS-CoV-2 Mpro inhibitors containing P1’ 4-fluorobenzothiazole moiety highly active against SARS-CoV-2
Authors: Higashi-Kuwata Nobuyo , Tsuji Kohei , Hayashi Hironori , Bulut Haydar , Kiso Maki , Imai Masaki , Ogata-Aoki Hiromi , Ishii Takahiro , Kobayakawa Takuya , Nakano Kenta , Takamune Nobutoki , Kishimoto Naoki , Hattori Shin-ichiro , Das Debananda , Uemura Yukari , Shimizu Yosuke , Aoki Manabu , Hasegawa Kazuya , Suzuki Satoshi , Nishiyama Akie , Saruwatari Junji , Shimizu Yukiko , Sukenaga Yoshikazu , Takamatsu Yuki , Tsuchiya Kiyoto , Maeda Kenji , Yoshimura Kazuhisa , Iida Shun , Ozono Seiya , Suzuki Tadaki , Okamura Tadashi , Misumi Shogo , Kawaoka Yoshihiro , Tamamura Hirokazu , Mitsuya Hiroaki 
Published: February 2023

Abstract
COVID-19 caused by SARS-CoV-2 has continually been serious threat to public health worldwide. While a few anti-SARS-CoV-2 therapeutics are currently available, their antiviral potency is not sufficient. Here, we identify two orally available 4-fluoro-benzothiazole-containing small molecules, TKB245 and TKB248, which specifically inhibit the enzymatic activity of main protease (Mpro) of SARS-CoV-2 and significantly more potently block the infectivity and replication of various SARS-CoV-2 strains than nirmatrelvir, molnupiravir, and ensitrelvir in cell-based assays employing various target cells. Both compounds also block the replication of Delta and Omicron variants in human-ACE2-knocked-in mice. Native mass spectrometric analysis reveals that both compounds bind to dimer Mpro, apparently promoting Mpro dimerization. X-ray crystallographic analysis shows that both compounds bind to Mpro’s active-site cavity, forming a covalent bond with the catalytic amino acid Cys-145 with the 4-fluorine of the benzothiazole moiety pointed to solvent. The data suggest that TKB245 and TKB248 might serve as potential therapeutics for COVID-19 and shed light upon further optimization to develop more potent and safer anti-SARS-CoV-2 therapeutics.