bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the Eurasian Wave Train on the Interannual Variability of Autumn Precipitation in the Central Region of China
Authors: Jiang Linwei , Ren Baohua , Wang Cen , Zhang Chao 
Published: August 2023

AbstractAutumn precipitation in the central region of China (APCC) can considerably influence on agricultural production and human livelihood. With reanalysis data from 1979 to 2020, it revealed that APCC is significantly affected by the second mode of the meridional wind field at 200 hPa over the Eurasian continent on the interannual scale, which featured a quasi‐barotropic “+‐+” wave‐like pattern from Europe to China (EC pattern) in extratropical zone. When the EC pattern is in a positive phase, central China lags behind the downstream positive geopotential height (anticyclone) anomaly. In this context, the transport of moisture from the south and east is enhanced and the advancement of the southerly monsoon is blocked, providing sufficient water vapor to support the occurrence of APCC. Further diagnosis revealed that local ascending motion is strengthened owing to the warm advection induced by anomalous southerly and positive vorticity advection associated with the anomalous anticyclone over East Asia. Additionally, wave flux analysis and model simulation suggest that the EC pattern results from the propagation of stationary Rossby wave, which could be excited by dipole sea surface temperature anomalies in the North Atlantic. These discoveries will contribute to improving the predictability of APCC.
Stratospheric Ozone Loss Enhances Summer Precipitation Over the Southern Slope of the Tibetan Plateau
Authors: Xia Yan , Hu Yongyun , Huang Yi , Bian Jianchun , Zhao Chuanfeng , Lin Jintai , Xie Fei , Zhou Chunjiang 
Published: August 2023

AbstractHeavy summer precipitation over the southern slope of the Tibetan Plateau has dramatic influences on water resources and hydrological disasters in South Asia. It experienced increasing trends over 1979–1996 and decreasing trends over 1996–2022, which are not yet well understood. Here we show observational and numerical evidence that stratospheric ozone has significant impacts on long‐term trends of summer precipitation in this strong convection area. It is found that stratospheric ozone depletion, by modulating the lower stratospheric temperature and upper‐tropospheric static stability, enhances deep convection and precipitation over the southern slope of the Tibetan Plateau. The results suggest that the ozone recovery in the future may reduce the summer precipitation over the southern slope of the Tibetan Plateau in the first half of the 21st century, which would be imperative for future water resource management in South Asia.
The Relationship Between the Present‐Day Seasonal Cycles of Clouds in the Mid‐Latitudes and Cloud‐Radiative Feedback
Authors: Furtado K. , Tsushima Y. , Field P. R. , Rostron J. , Sexton D. 
Published: August 2023

AbstractWe show that the seasonal cycles of clouds over the mid‐latitude oceans in the Northern Hemisphere are predictors of the responses of clouds to increasing sea‐surface temperatures globally. These regions are therefore “natural laboratories” in which the processes responsible for low‐cloud feedbacks on global scales are observed as seasonal changes in local cloud properties. We use an ensemble of configurations of a global‐climate model to show that the sensitivities of cloud‐radiative anomalies to surface temperature and lower‐tropospheric stability in the “laboratory” regions predict the models' global cloud‐radiative feedbacks. Models with greater changes in low‐clouds between seasons are shown to have stronger negative feedbacks in the mid‐latitudes, and stronger positive feedbacks from the subtropical stratocumulus. The biases in the simulated seasonal cycles, compared to observations, imply that both feedbacks are too weak in the model. The consequences of this for configuring our model to have a lower climate sensitivity are discussed.
Linking ENSO to Synoptic Weather Systems in Eastern Australia
Authors: Gillett Z. E. , Taschetto A. S. , Holgate C. M. , Santoso A. 
Published: August 2023

AbstractEl Niño‐Southern Oscillation (ENSO) is the main driver of interannual east Australian rainfall variability, but its link with rain‐producing synoptic weather systems is unclear. By tracking low pressure systems in ERA5 over 1979 to 2021, we find that springtime cyclones are linked to variations in the large‐scale atmospheric circulation during ENSO events. On spring days with a cyclone during La Niña, a pressure dipole occurs with a strong anticyclonic anomaly southeast of Australia and a cyclonic anomaly over eastern Australia. The northeasterly circulation directs tropical moisture toward eastern Australia, and coupled with induced ascent, promotes rainfall in this region. Both dynamical and thermodynamical changes are important for the rainfall response. An almost opposite circulation response occurs on cyclone days during El Niño events: high‐pressure over the Australian continent reduces rainfall in eastern Australia. These synoptic setups resemble the seasonal‐mean Rossby wave teleconnections, indicating a link between weather systems and ENSO.
How Unusual Is the 2022 European Compound Drought and Heatwave Event?
Authors: Tripathy Kumar Puran , Mishra Ashok Kumar 
Published: August 2023

AbstractThe 2022 Compound Drought and Heatwave (CDHW) caused widespread crop damage, water shortages, and wildfires across Europe. Our study analyzed this event’s severity and return period (RP) and compared it with past mega CDHWs in Europe. The hardest‐hit areas were Iberian Peninsula, France, and Italy, where temperatures exceeded 2.5°C above normal, and severe droughts persisted from May to August. Using a Bayesian approach, we estimated the RP for the 2022 CDHW event, which was unprecedented in Northern Italy, Iberian Peninsula, and western parts of France, with RPs of 354, 420, and 280 years, respectively. The reduced soil moisture due to precipitation deficits and high temperatures contributed to the persistence and severity of drought, creating a positive feedback loop where dry soils led to even drier conditions. In light of our findings, it is evident that global warming poses increased risks of severe CDHW events, which are likely to increase.
Light people: Nobel Laureate Prof. Eric Betzig
Authors: Wang Hui , Yu Cun 
Published: August 2023

EditorialSuper-resolution microscopy illuminated the hazy molecular world like a beacon, bringing significant changes to the fields of biology, optics and chemistry. Eric Betzig, who shared the 2014 Nobel Prize of Chemistry with Stefan Hell and William Moerner, is one of the inventors of this fantastic scientific tool. Working originally on near field optics, Dr. Betzig made a series of stunning achievements at Bell Labs before turning 35. Yet he quit, seemingly at the top of his game, to become a hands-on dad and joined the machinery business. Eventually, he missed science so much that he made a comeback and wowed everyone instantly with his work. He defies the conventional definition of “persistence” by demonstrating an alternative route to success. Plain-speaking and earnest, Dr. Betzig is sometimes honest to almost a fault, and always believes in doing practical things. He puts his heart and soul into everything he does, because he says he wants to truly live rather than simply pass through life. In science work, he is meticulous, yet he embraces risks and believes they can bring the best out of oneself. In life, he is a loving father who is always ready to take time from his busy research work to take his children to school or tennis lessons, and a caring teacher who never forgets to command the hard work of his postdocs. Please join us for a glimpse of the Nobel laureate Eric Betzig and his extraordinary life.
Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1
Authors: Hou Yiming , Yu Wenqian , Wu Gaoyi , Wang Zhaoling , Leng Shuai , Dong Ming , Li Na , Chen Lei 
Published: August 2023

AbstractOral squamous cell carcinoma (OSCC) is the most prevalent cancer of the mouth, characterised by rapid progression and poor prognosis. Hence, an urgent need exists for the development of predictive targets for early diagnosis, prognosis determination, and clinical therapy. Dysregulation of lymphoid enhancer-binding factor 1 (LEF1), an important transcription factor involved in the Wnt-β-catenin pathway, contributes to the poor prognosis of OSCC. Herein, we aimed to explore the correlation between LEF1 and histone lysine demethylase 4 A (KDM4A). Results show that the KDM4A complex is recruited by LEF1 and specifically binds the LATS2 promoter region, thereby inhibiting its expression, and consequently promoting cell proliferation and impeding apoptosis in OSCC. We also established NOD/SCID mouse xenograft models using CAL-27 cells to conduct an in vivo analysis of the roles of LEF1 and KDM4A in tumour growth, and our findings show that cells stably suppressing LEF1 or KDM4A have markedly decreased tumour-initiating capacity. Overall, the results of this study demonstrate that LEF1 plays a pivotal role in OSCC development and has potential to serve as a target for early diagnosis and treatment of OSCC.
p53 isoform expression promotes a stemness phenotype and inhibits doxorubicin sensitivity in breast cancer
Authors: Steffens Reinhardt Luiza , Groen Kira , Zhang Xiajie , Morten Brianna C. , Wawruszak Anna , Avery-Kiejda Kelly A. 
Published: August 2023

AbstractIn breast cancer, dysregulatedTP53expression signatures are a better predictor of chemotherapy response and survival outcomes thanTP53mutations. Our previous studies have shown that high levels of Δ40p53 are associated with worse disease-free survival and disruption of p53-induced DNA damage response in breast cancers. Here, we further investigated the in vitro and in vivo implications of Δ40p53 expression in breast cancer. We have shown that genes associated with cell differentiation are downregulated while those associated with stem cell regulation are upregulated in invasive ductal carcinomas expressing high levels of Δ40p53. In contrast to p53, endogenous ∆40p53 co-localised with the stem cell markers Sox2, Oct4, and Nanog in MCF-7 and ZR75-1 cell lines. ∆40p53 and Sox2 co-localisation was also detected in breast cancer specimens. Further, in cells expressing a high ∆40p53:p53 ratio, increased expression of stem cell markers, greater mammosphere and colony formation capacities, and downregulation ofmiR-145andmiR-200(p53-target microRNAs that repress stemness) were observed compared to the control subline. In vivo, a high ∆40p53:p53 ratio led to increased tumour growth, Ki67 and Sox2 expression, and blood microvessel areas in the vehicle-treated mice. High expression of ∆40p53 also reduced tumour sensitivity to doxorubicin compared to control tumours. Enhanced therapeutic efficacy of doxorubicin was observed when transiently targeting Δ40p53 or when treating cells with OTSSP167 with concomitant chemotherapy. Taken together, high Δ40p53 levels induce tumour growth and may promote chemoresistance by inducing a stemness phenotype in breast cancer; thus, targeting Δ40p53 in tumours that have a high Δ40p53:p53 ratio could enhance the efficacy of standard-of-care therapies such as doxorubicin.
Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells
Authors: Wang Xuan , Ji Yuting , Qi Jingyi , Zhou Shuaishuai , Wan Sitong , Fan Chang , Gu Zhenglong , An Peng , Luo Yongting , Luo Junjie 
Published: August 2023

AbstractCervical cancer is one of the leading causes of cancer death in women. Mitochondrial-mediated ferroptosis (MMF) is a recently discovered form of cancer cell death. However, the role and the underlying mechanism of MMF in cervical cancer remain elusive. Here, using an unbiased screening for mitochondrial transmembrane candidates, we identified mitochondrial carrier 1 (MTCH1) as a central mediator of MMF in cervical cancers. MTCH1-deficiency disrupted mitochondrial oxidative phosphorylation while elevated mitochondrial reactive oxygen species (ROS) by decreasing NAD+ levels. This mitochondrial autonomous event initiated a mitochondria-to-nucleus retrograde signaling involving reduced FoxO1 nuclear translocation and subsequently downregulation of the transcription and activity of a key anti-ferroptosis enzyme glutathione peroxidase 4 (GPX4), thereby elevating ROS and ultimately triggering ferroptosis. Strikingly, targeting MTCH1 in combination with Sorafenib effectively and synergistically inhibited the growth of cervical cancer in a nude mouse xenograft model by actively inducing ferroptosis. In conclusion, these findings enriched our understanding of the mechanisms of MMF in which MTCH1 governed ferroptosis though retrograde signaling to FoxO1-GPX4 axis, and provided a potential therapeutic target for treating cervical cancer.
Risk factors for inpatient mortality among children with severe acute malnutrition in Zimbabwe and Zambia
Authors: Sturgeon Jonathan P. , Mufukari Wadzanai , Tome Joice , Dumbura Cherlynn , Majo Florence D. , Ngosa Deophine , Chandwe Kanta , Kapoma Chanda , Mutasa Kuda , Nathoo Kusum J. , Bourke Claire D. , Ntozini Robert , Bwakura-Dangarembizi Mutsa , Amadi Beatrice , Kelly Paul , Prendergast Andrew J. ,   the HOPE-SAM study team, Sturgeon Jonathan P. 
Published: August 2023

Abstract
Background/Objectives
Malnutrition underlies 45% of deaths in children under-5 years annually. Children hospitalised with complicated severe acute malnutrition (SAM) have unacceptably high mortality. We aimed to identify variables from early hospital admission (baseline factors) independently associated with inpatient mortality in this cohort to identify those most at risk.

Subjects/Methods
Observational study of 745 children aged 0–59 months admitted with complicated SAM at three hospitals in Zimbabwe/Zambia. Children underwent anthropometry and clinical assessment by a study physician within 72 h of enrolment, and caregivers provided sociodemographic data. Children were followed-up daily until discharge/death. A multivariable survival analysis identified the baseline factors independently associated with mortality.

Results
70/745 (9.4%) children died in hospital. Age between 6–23 months [aHR 6.53, 95%CI 2.24–19.02], higher mid-upper arm circumference [aHR 0.73, 95%CI 0.59–0.89], presence of oedema [aHR 2.22, 95%CI 1.23–4.05], shock [aHR 8.18, 95%CI 3.79–17.65], sepsis [aHR 3.13, 95%CI 1.44–6.80], persistent diarrhoea [aHR 2.27, 95%CI 1.18–4.37], lack of a toilet at home [aHR 4.35, 95%CI 1.65–11.47], and recruitment at one Harare site [aHR 0.38, 95%CI 0.18–0.83] were all independently associated with inpatient mortality. Oedematous children had a significantly higher birthweight [2987 g vs 2757 g, p < 0.001] than those without oedema; higher birthweight was weakly associated with mortality [aHR 1.50 95%CI 0.97–2.31].

Conclusions
Children with oedema, low MUAC, baseline infections, shock and lack of home sanitation had a significantly increased risk of inpatient mortality following hospitalisation for complicated SAM. Children with high-risk features may require additional care. A better understanding of the pathophysiology of SAM is needed to identify adjunctive interventions.
Hyaluronic acid-bilirubin nanomedicine-based combination chemoimmunotherapy
Authors: Lee Yonghyun , Shinn Jongyoon , Xu Cheng , Dobson Hannah E. , Neamati Nouri , Moon James J. 
Published: August 2023

AbstractDespite significant advances in immune checkpoint blockade (ICB), immunosuppression mediated by tumor-associated myeloid cells (TAMCs) poses a major barrier to cancer immunotherapy. In addition, while immunogenic cell death (ICD) provides a viable approach to inducing anti-tumor immune response, it remains unknown how to effectively trigger ICD while addressing immunosuppressive TAMCs. Here, we show that SC144, a gp130 inhibitor that blocks the IL-6/gp130/STAT3 pathway, induces ICD of tumor cells and polarizes macrophages to M1-phenotype in vitro. However, as SC144 also induces killing of CD8+ T-cells, we sought to deliver SC144 selectively to tumor cells and TAMCs. Toward this goal, we have developed hyaluronic acid-bilirubin nanoparticles (HABN) that accumulate in CD44hi tumor cells and TAMCs. Systemic administration of SC144 loaded in HABN (SC144@HABN) induces apoptosis and ICD of tumor cells, increases the ratio of M1-like to M2-like macrophages, and decreases the frequency of myeloid-derived suppressor cells and CD4+ regulatory T-cells, while promoting anti-tumor CD8+ T-cells. Moreover, SC144@HABN combined with anti-PD-L1 ICB efficiently eliminates MC38 tumors and ICB-resistant 4T1 tumors. Overall, our work demonstrates a therapeutic strategy based on coordinated ICD induction and TAMC modulation and highlights the potential of combination chemoimmunotherapy.
spinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content
Authors: De Jonghe Joachim , Kaminski Tomasz S. , Morse David B. , Tabaka Marcin , Ellermann Anna L. , Kohler Timo N. , Amadei Gianluca , Handford Charlotte E. , Findlay Gregory M. , Zernicka-Goetz Magdalena , Teichmann Sarah A. , Hollfelder Florian 
Published: August 2023

AbstractDroplet microfluidic methods have massively increased the throughput of single-cell sequencing campaigns. The benefit of scale-up is, however, accompanied by increased background noise when processing challenging samples and the overall RNA capture efficiency is lower. These drawbacks stem from the lack of strategies to enrich for high-quality material or specific cell types at the moment of cell encapsulation and the absence of implementable multi-step enzymatic processes that increase capture. Here we alleviate both bottlenecks using fluorescence-activated droplet sorting to enrich for droplets that contain single viable cells, intact nuclei, fixed cells or target cell types and use reagent addition to droplets by picoinjection to perform multi-step lysis and reverse transcription. Our methodology increases gene detection rates fivefold, while reducing background noise by up to half. We harness these properties to deliver a high-quality molecular atlas of mouse brain development, despite starting with highly damaged input material, and provide an atlas of nascent RNA transcription during mouse organogenesis. Our method is broadly applicable to other droplet-based workflows to deliver sensitive and accurate single-cell profiling at a reduced cost.
Modulation of translational decoding by m6A modification of mRNA
Authors: Jain Sakshi , Koziej Lukasz , Poulis Panagiotis , Kaczmarczyk Igor , Gaik Monika , Rawski Michal , Ranjan Namit , Glatt Sebastian , Rodnina Marina V. 
Published: August 2023

AbstractN6-methyladenosine (m6A) is an abundant, dynamic mRNA modification that regulates key steps of cellular mRNA metabolism. m6A in the mRNA coding regions inhibits translation elongation. Here, we show how m6A modulates decoding in the bacterial translation system using a combination of rapid kinetics, smFRET and single-particle cryo-EM. We show that, while the modification does not impair the initial binding of aminoacyl-tRNA to the ribosome, in the presence of m6A fewer ribosomes complete the decoding process due to the lower stability of the complexes and enhanced tRNA drop-off. The mRNA codon adopts a π-stacked codon conformation that is remodeled upon aminoacyl-tRNA binding. m6A does not exclude canonical codon-anticodon geometry, but favors alternative more dynamic conformations that are rejected by the ribosome. These results highlight how modifications outside the Watson-Crick edge can still interfere with codon-anticodon base pairing and complex recognition by the ribosome, thereby modulating the translational efficiency of modified mRNAs.
Proteomics and constraint-based modelling reveal enzyme kinetic properties of Chlamydomonas reinhardtii on a genome scale
Authors: Arend Marius , Zimmer David , Xu Rudan , Sommer Frederik , Mühlhaus Timo , Nikoloski Zoran 
Published: August 2023

AbstractMetabolic engineering of microalgae offers a promising solution for sustainable biofuel production, and rational design of engineering strategies can be improved by employing metabolic models that integrate enzyme turnover numbers. However, the coverage of turnover numbers for Chlamydomonas reinhardtii, a model eukaryotic microalga accessible to metabolic engineering, is 17-fold smaller compared to the heterotrophic cell factory Saccharomyces cerevisiae. Here we generate quantitative protein abundance data of Chlamydomonas covering 2337 to 3708 proteins in various growth conditions to estimate in vivo maximum apparent turnover numbers. Using constrained-based modeling we provide proxies for in vivo turnover numbers of 568 reactions, representing a 10-fold increase over the in vitro data for Chlamydomonas. Integration of the in vivo estimates instead of in vitro values in a metabolic model of Chlamydomonas improved the accuracy of enzyme usage predictions. Our results help in extending the knowledge on uncharacterized enzymes and improve biotechnological applications of Chlamydomonas.
A conserved membrane curvature-generating protein is crucial for autophagosome formation in fission yeast
Authors: Wang Ning , Shibata Yoko , Paulo Joao A. , Gygi Steven P. , Rapoport Tom A. 
Published: August 2023

AbstractOrganelles are shaped by curvature-generating proteins, which include the reticulons and REEPs that are involved in forming the endoplasmic reticulum (ER). A conserved REEP subfamily differs from the ER-shaping REEPs in abundance and membrane topology and has unidentified functions. Here, we show that Rop1, the single member of this family in the fission yeast Schizosacharomyces pombe, is crucial for the macroautophagy of organelles and cytosolic proteins. Rop1 is needed for the formation of phagophores, cup-like structures consisting of two closely apposed membrane sheets that encapsulate cargo. It is recruited at early stages to phagophores and is required for their maturation into autophagosomes. Rop1 function relies on its ability to generate high membrane curvature and on its colocalization with the autophagy component Atg2 that is thought to reside at the phagophore rim. We propose that Rop1 facilitates the formation and growth of the double-membrane structure of the autophagosome.