bluuebunny/crossref_metadata_2025_split huggingface dataset:
Warming and Drought Weaken the Carbon Sink Capacity of an Endangered Paleoendemic Temperate Rainforest in South America
Authors: Perez‐Quezada Jorge F. , Barichivich Jonathan , Urrutia‐Jalabert Rocío , Carrasco Enrique , Aguilera David , Bacour Cédric , Lara Antonio 
Published: March 2023

AbstractMeasurements of ecosystem carbon (C) fluxes in temperate forests are concentrated in the Northern Hemisphere, leaving the functionally diverse temperate forests in the Southern Hemisphere underrepresented. Here, we report 3 years (February 2018 to January 2021) of C fluxes, studied with eddy‐covariance and closed chamber techniques, in an endangered temperate evergreen rainforest of the long‐lived paleoendemic South American conifer Fitzroya cupressoides. Using classification and regression trees, we analyzed the most relevant drivers and thresholds of daily net ecosystem exchange (NEE) and soil respiration. The annual NEE showed that the forest was a moderate C sink during the period analyzed (−287 ± 38 g C m−2 year −1). We found that the capacity to capture C of the Fitzroya rainforests in the Coastal Range of southern Chile is optimal under cool and rainy conditions in the early austral spring (October–November) and decreases rapidly toward the summer dry season (January–February) and autumn. Although the studied forest type has a narrow geographical coverage, the gross primary productivity measured at the tower was highly representative of Fitzroya and other rainforests in the region. Our results suggest that C fluxes in paleoendemic cool F. cupressoides forests may be negatively affected by the warming and drying predicted by climate change models, reinforcing the importance of maintaining this and other long‐term ecological research sites in the Southern Hemisphere.
Higher Frozen Soil Permeability Represented in a Hydrological Model Improves Spring Streamflow Prediction From River Basin to Continental Scales
Authors: Agnihotri Jetal , Behrangi Ali , Tavakoly Ahmad , Geheran Matthew , Farmani Mohammad A. , Niu Guo‐Yue 
Published: March 2023

AbstractDespite plentiful evidence of frozen ground effects on snowmelt infiltration from lab experiments at pedon scales, streamflow observations show a weaker or no effect in terms of timing and magnitude at larger scales. We aim to understand this conflicting phenomenon through modeling using the Noah land surface model with multi‐physics (MP; Noah‐MP) options and the Routing Application for Parallel computatIon of Discharge (RAPID) over the Mississippi River Basin. We conduct 16 experiments with combinations of two supercooled liquid water (SLW) parameterization schemes and four soil hydraulic property schemes in Noah‐MP driven by two gridded precipitation products of the North American Land Data Assimilation System (NLDAS) and the Integrated Multi‐satellitE Retrievals for GPM (IMERG) Final. We then use RAPID to route Noah‐MP modeled surface runoff and groundwater discharge to predict daily streamflow at 52 United States Geological Survey gauges from 2015 to 2019. A model with the highest permeability performs better than other schemes on daily streamflow predictions by 20%–57% throughout a water year and 29%–113% for the spring as measured by the mean Kling‐Gupta Efficiency of the 52 gauges. Different SLW schemes demonstrate negligible effects on streamflow predictions. Models forced by IMERG show a better prediction skill compared with those forced by NLDAS at most of the gauges. Both precipitation products confirm that a scheme of higher permeability yields more accurate streamflow predictions over frozen ground. Future models should represent preferential flows through macropore networks to improve the understanding of frozen soil effects on infiltration and discharge across scales.
Corticosteroids reduce pathologic interferon responses by downregulating STAT1 in patients with high-risk COVID-19
Authors: Jeong Hyun-Woo , Lee Jeong Seok , Ko Jae-Hoon , Hong Seunghee , Oh Sang Taek , Choi Seongkyun , Peck Kyong Ran , Yang Ji Hun , Chung Seok , Kim Sung-Han , Kim Yeon-Sook , Shin Eui-Cheol 
Published: March 2023

AbstractWe do not yet understand exactly how corticosteroids attenuate hyperinflammatory responses and alleviate high-risk coronavirus disease 2019 (COVID-19). We aimed to reveal the molecular mechanisms of hyperinflammation in COVID-19 and the anti-inflammatory effects of corticosteroids in patients with high-risk COVID-19. We performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from three independent COVID-19 cohorts: cohort 1 was used for comparative analysis of high-risk and low-risk COVID-19 (47 PBMC samples from 28 patients), cohort 2 for longitudinal analysis during COVID-19 (57 PBMC samples from 15 patients), and cohort 3 for investigating the effects of corticosteroid treatment in patients with high-risk COVID-19 (55 PBMC samples from 13 patients). PBMC samples from healthy donors (12 PBMC samples from 12 donors) were also included. Cohort 1 revealed a significant increase in the proportion of monocytes expressing the long noncoding RNAs NEAT1 and MALAT1 in high-risk patients. Cohort 2 showed that genes encoding inflammatory chemokines and their receptors were upregulated during aggravation, whereas genes related to angiogenesis were upregulated during improvement. Cohort 3 demonstrated downregulation of interferon-stimulated genes (ISGs), including STAT1, in monocytes after corticosteroid treatment. In particular, unphosphorylated STAT-dependent ISGs enriched in monocytes from lupus patients were selectively downregulated by corticosteroid treatment in patients with high-risk COVID-19. Corticosteroid treatment suppresses pathologic interferon responses in monocytes by downregulating STAT1 in patients with high-risk COVID-19. Our study provides insights into the mechanisms underlying COVID-19 aggravation and improvement and the effects of corticosteroid treatment.
Enhanced ion acceleration from transparency-driven foils demonstrated at two ultraintense laser facilities
Authors: Dover Nicholas P. , Ziegler Tim , Assenbaum Stefan , Bernert Constantin , Bock Stefan , Brack Florian-Emanuel , Cowan Thomas E. , Ditter Emma J. , Garten Marco , Gaus Lennart , Goethel Ilja , Hicks George S. , Kiriyama Hiromitsu , Kluge Thomas , Koga James K. , Kon Akira , Kondo Kotaro , Kraft Stephan , Kroll Florian , Lowe Hazel F. , Metzkes-Ng Josefine , Miyatake Tatsuhiko , Najmudin Zulfikar , Püschel Thomas , Rehwald Martin , Reimold Marvin , Sakaki Hironao , Schlenvoigt Hans-Peter , Shiokawa Keiichiro , Umlandt Marvin E. P. , Schramm Ulrich , Zeil Karl , Nishiuchi Mamiko 
Published: March 2023

AbstractLaser-driven ion sources are a rapidly developing technology producing high energy, high peak current beams. Their suitability for applications, such as compact medical accelerators, motivates development of robust acceleration schemes using widely available repetitive ultraintense femtosecond lasers. These applications not only require high beam energy, but also place demanding requirements on the source stability and controllability. This can be seriously affected by the laser temporal contrast, precluding the replication of ion acceleration performance on independent laser systems with otherwise similar parameters. Here, we present the experimental generation of >60 MeV protons and >30 MeV u−1 carbon ions from sub-micrometre thickness Formvar foils irradiated with laser intensities >1021 Wcm2. Ions are accelerated by an extreme localised space charge field ≳30 TVm−1, over a million times higher than used in conventional accelerators. The field is formed by a rapid expulsion of electrons from the target bulk due to relativistically induced transparency, in which relativistic corrections to the refractive index enables laser transmission through normally opaque plasma. We replicate the mechanism on two different laser facilities and show that the optimum target thickness decreases with improved laser contrast due to reduced pre-expansion. Our demonstration that energetic ions can be accelerated by this mechanism at different contrast levels relaxes laser requirements and indicates interaction parameters for realising application-specific beam delivery.
Efficient ultrafast laser writing with elliptical polarization
Authors: Lei Yuhao , Shayeganrad Gholamreza , Wang Huijun , Sakakura Masaaki , Yu Yanhao , Wang Lei , Kliukin Dmitrii , Skuja Linards , Svirko Yuri , Kazansky Peter G. 
Published: March 2023

AbstractPhotosensitivity in nature is commonly associated with stronger light absorption. It is also believed that artificial optical anisotropy to be the strongest when created by light with linear polarization. Contrary to intuition, ultrafast laser direct writing with elliptical polarization in silica glass, while nonlinear absorption is about 2.5 times weaker, results in form birefringence about twice that of linearly polarized light. Moreover, a larger concentration of anisotropic nanopores created by elliptically polarized light pulses is observed. The phenomenon is interpreted in terms of enhanced interaction of circularly polarized light with a network of randomly oriented bonds and hole polarons in silica glass, as well as efficient tunneling ionization produced by circular polarization. Applications to multiplexed optical data storage and birefringence patterning in silica glass are demonstrated.
MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage
Authors: Chen Kelie , Yuan Xiaoyu , Wang Shengchao , Zheng Fang , Fu Zhiqin , Shen Zhangjin , Cheng Xiaodong , Wang Yuwei , Tang Song , Ni Heng , Wang Fang , Lu Guang , Wu Yihua , Xia Dajing , Lu Weiguo 
Published: March 2023

AbstractPeritoneal metastasis is a key feature of advanced ovarian cancer, but the critical protein required for ovarian cancer metastasis and progression is yet to be defined. Thus, an unbiased high throughput and in-depth study is warranted to unmask the mechanism. Transcriptomic sequencing of paired primary ovarian tumors and metastases unveiled that MAP4K4, a serine/threonine kinase belongs to the Ste20 family of kinases, was highly expressed in metastatic sites. Increased MAP4K4 expression in metastasis was further validated in other independent patients, with higher MAP4K4 expression associated with poorer survival, higher level of CA125 and more advanced FIGO stage. Down regulation of MAP4K4 inhibited cancer cell adhesion, migration, and invasion. Notably, MAP4K4 was found to stabilize N-cadherin. Further results showed that MAP4K4 mediated phosphorylation of ADAM10 at Ser436 results in suppression of N-cadherin cleavage by ADAM10, leading to N-cadherin stabilization. Pharmacologic inhibition of MAP4K4 abrogated peritoneal metastases. Overall, our data reveal MAP4K4 as a significant promoter in ovarian cancer metastasis. Targeting MAP4K4 may be a potential therapeutic approach for ovarian cancer patients.
Synthetic biology-inspired cell engineering in diagnosis, treatment and drug development
Authors: Zhao Ninglin , Song Yingjie , Xie Xiangqian , Zhu Ziqi , Duan Chenxi , Nong Cheng , Wang Huan , Bao Rui 
Published: March 2023

AbstractThe fast-developing synthetic biology (SB) has provided many genetic tools to reprogram and engineer cells for improved performance, novel functions, and diverse applications. Such cell engineering resources can play a critical role in the research and development of novel therapeutics. However, there are certain limitations and challenges in applying genetically engineered cells in clinical practice. This literature review updates the recent advances in biomedical applications, including diagnosis, treatment, and drug development, of SB-inspired cell engineering. It describes technologies and relevant examples in a clinical and experimental setup that may significantly impact the biomedicine field. At last, this review concludes the results with future directions to optimize the performances of synthetic gene circuits to regulate the therapeutic activities of cell-based tools in specific diseases.
Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications
Authors: Xie Saiyang , Xu Si-Chi , Deng Wei , Tang Qizhu 
Published: March 2023

AbstractCardiac aging is evident by a reduction in function which subsequently contributes to heart failure. The metabolic microenvironment has been identified as a hallmark of malignancy, but recent studies have shed light on its role in cardiovascular diseases (CVDs). Various metabolic pathways in cardiomyocytes and noncardiomyocytes determine cellular senescence in the aging heart. Metabolic alteration is a common process throughout cardiac degeneration. Importantly, the involvement of cellular senescence in cardiac injuries, including heart failure and myocardial ischemia and infarction, has been reported. However, metabolic complexity among human aging hearts hinders the development of strategies that targets metabolic susceptibility. Advances over the past decade have linked cellular senescence and function with their metabolic reprogramming pathway in cardiac aging, including autophagy, oxidative stress, epigenetic modifications, chronic inflammation, and myocyte systolic phenotype regulation. In addition, metabolic status is involved in crucial aspects of myocardial biology, from fibrosis to hypertrophy and chronic inflammation. However, further elucidation of the metabolism involvement in cardiac degeneration is still needed. Thus, deciphering the mechanisms underlying how metabolic reprogramming impacts cardiac aging is thought to contribute to the novel interventions to protect or even restore cardiac function in aging hearts. Here, we summarize emerging concepts about metabolic landscapes of cardiac aging, with specific focuses on why metabolic profile alters during cardiac degeneration and how we could utilize the current knowledge to improve the management of cardiac aging.
A new generation Mpro inhibitor with potent activity against SARS-CoV-2 Omicron variants
Authors: Huang Chong , Shuai Huiping , Qiao Jingxin , Hou Yuxin , Zeng Rui , Xia Anjie , Xie Lingwan , Fang Zhen , Li Yueyue , Yoon Chaemin , Huang Qiao , Hu Bingjie , You Jing , Quan Baoxue , Zhao Xiu , Guo Nihong , Zhang Shiyu , Ma Ronggang , Zhang Jiahao , Wang Yifei , Yang Ruicheng , Zhang Shanshan , Nan Jinshan , Xu Haixing , Wang Falu , Lei Jian , Chu Hin , Yang Shengyong 
Published: March 2023

AbstractEmerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health. Small molecule antivirals are an effective treatment strategy to fight against the virus. However, the first-generation antivirals either show limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of these drugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a new generation antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (Mpro). This compound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, but also other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2 mouse model, oral treatment with SY110 significantly lowered the viral burdens in lung and alleviated the virus-induced pathology. Importantly, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstanding safety profile. Furthermore, SY110 exhibited sensitivity to several drug-resistance Mpro mutations. Collectively, this investigation provides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.
The feasibility of using mouthpiece ventilation in the intensive care unit for post-extubation breathing support after acute tetraplegia
Authors: Wadsworth Brooke M. , Kruger Peter S. , Hukins Craig A. , Modderman Gabrielle A. , Brown Duncan , Paratz Jennifer D. 
Published: March 2023

Abstract
Study design
A prospective cohort of patients with acute tetraplegia.

Objectives
This study aimed to determine the feasibility of using mouthpiece ventilation (MPV) in the intensive care unit (ICU) for patients who are extubated after suffering an acute cervical spinal cord injury (CSCI).

Setting
ICU, Princess Alexandra Hospital, Brisbane Australia.

Methods
New admissions to ICU in the 14 months between April 2017 and June 2018 with a CSCI who underwent intubation were assessed for inclusion. MPV was provided to consenting participants (who were deemed likely to be able to maintain ventilation on their own) at the time of extubation and was utilised in addition to standard care while participants were awake. MPV settings, usage, and support hours to educate and facilitate MPV were collected. Feedback from participants and clinical staff was gathered throughout the study. Pre- and post-extubation measures of forced vital capacity (FVC), the frequency of endotracheal suction of sputum, and gas exchange using ventilation-perfusion ratios were recorded along with the incidence of reintubation.

Results
Fourteen participated in utilising MPV with 16 episodes of extubation. The average time per participant to have MPV titrated and bedside data collected was 178 minutes. Data from 16 episodes of extubation have been included. Three of the 14 participants failed initial extubation. Feedback from participants and clinicians has been positive and constructive, enabling MPV settings to be adapted to the person with acute CSCI during this pilot study.

Conclusion
MPV is feasible to use post-extubation for people with CSCI in ICU. Pressure control mode MPV was deemed the most suitable for newly extubated acute CSCI patients. Intensive clinical support is required initially to provide education prior to MPV, and at the time of extubation for both patient and treating clinicians. Both report it to be a useful adjunct to ICU treatment.
Global prevalence of mild cognitive impairment among older adults living in nursing homes: a meta-analysis and systematic review of epidemiological surveys
Authors: Chen Pan , Cai Hong , Bai Wei , Su Zhaohui , Tang Yi-Lang , Ungvari Gabor S. , Ng Chee H. , Zhang Qinge , Xiang Yu-Tao 
Published: March 2023

AbstractMild cognitive impairment (MCI) is the early stage of cognitive impairment between the expected cognitive decline of normal aging and the more serious decline of dementia. This meta-analysis and systematic review explored the pooled global prevalence of MCI among older adults living in nursing homes and its relevant factors. The review protocol was registered in INPLASY (INPLASY202250098). PubMed, Web of Science, Embase, PsycINFO, and CINAHL databases were systematically searched from their respective inception dates to 8 January 2022. The inclusion criteria were made based on the PICOS acronym, as follows: Participants (P): Older adults living in nursing homes; Intervention (I): not applicable; Comparison (C): not applicable; Outcome (O): prevalence of MCI or the data can generate the prevalence of MCI according to study-defined criteria; Study design (S): cohort studies (only baseline data were extracted) and cross-sectional studies with accessible data published in a peer-reviewed journal. Studies involving mixed resources, reviews, systematic reviews, meta-analyses, case studies, and commentaries were excluded. Data analyses were performed using Stata Version 15.0. Random effects model was used to synthesize the overall prevalence of MCI. An 8-item instrument for epidemiological studies was used to assess the quality of included studies. A total of 53 articles were included involving 376,039 participants with a mean age ranging from 64.42 to 86.90 years from 17 countries. The pooled prevalence of MCI in older adults in nursing homes was 21.2% (95% CI: 18.7–23.6%). Subgroup and meta-regression analyses revealed that the screening tools used were significantly associated with MCI prevalence. Studies using the Montreal Cognitive Assessment (49.8%) had a higher prevalence of MCI than those using other instruments. No significant publication bias was found. Several limitations warrant attention in this study; for example, significant heterogeneity between studies remained and some factors associated with the prevalence of MCI were not examined due to insufficient data. Adequate screening measures and allocation of resources are needed to address the high global prevalence of MCI among older adults living in nursing homes.
Conditional deletion of Neurexin-2 alters neuronal network activity in hippocampal circuitries and leads to spontaneous seizures
Authors: Haile Mulatwa T. , Khoja Sheraz , de Carvalho Gregory , Hunt Robert F. , Chen Lulu Y. 
Published: March 2023

AbstractNeurexins (Nrxns) have been extensively studied for their role in synapse organization and have been linked to many neuropsychiatric disorders, including autism spectrum disorder (ASD), and epilepsy. However, no studies have provided direct evidence that Nrxns may be the key regulator in the shared pathogenesis of these conditions largely due to complexities among Nrxns and their non-canonical functions in different synapses. Recent studies identified NRXN2 mutations in ASD and epilepsy, but little is known about Nrxn2’s role in a circuit-specific manner. Here, we report that conditional deletion of Nrxn2 from the hippocampus and cortex (Nrxn2 cKO) results in behavioral abnormalities, including reduced social preference and increased nestlet shredding behavior. Electrophysiological recordings identified an overall increase in hippocampal CA3→CA1 network activity in Nrxn2 cKO mice. Using intracranial electroencephalogram recordings, we observed unprovoked spontaneous reoccurring electrographic and behavioral seizures in Nrxn2 cKO mice. This study provides the first evidence that conditional deletion of Nrxn2 induces increased network activity that manifests into spontaneous recurrent seizures and behavioral impairments.
Functional characterization and in vitro pharmacological rescue of KCNQ2 pore mutations associated with epileptic encephalopathy
Authors: Yang Gui-mei , Tian Fu-yun , Shen Yan-wen , Yang Chuan-yan , Yuan Hui , Li Ping , Gao Zhao-bing 
Published: March 2023

AbstractMutations in the KCNQ2 gene encoding KV7.2 subunit that mediates neuronal M-current cause a severe form of developmental and epileptic encephalopathy (DEE). Electrophysiological evaluation of KCNQ2 mutations has been proved clinically useful in improving outcome prediction and choosing rational anti-seizure medications (ASMs). In this study we described the clinical characteristics, electrophysiological phenotypes and the in vitro response to KCNQ openers of five KCNQ2 pore mutations (V250A, N258Y, H260P, A265T and G290S) from seven patients diagnosed with KCNQ2-DEE. The KCNQ2 variants were transfected into Chinese hamster ovary (CHO) cells alone, in combination with KCNQ3 (1:1) or with wild-type KCNQ2 (KCNQ2-WT) and KCNQ3 in a ratio of 1:1:2, respectively. Their expression and electrophysiological function were assessed. When transfected alone or in combination with KCNQ3, none of these mutations affected the membrane expression of KCNQ2, but most failed to induce a potassium current except A265T, in which trace currents were observed when co-transfected with KCNQ3. When co-expressed with KCNQ2-WT and KCNQ3 (1:1:2), the currents at 0 mV of these mutations were decreased by 30%-70% compared to the KCNQ2/3 channel, which could be significantly rescued by applying KCNQ openers including the approved antiepileptic drug retigabine (RTG, 10 μM), as well as two candidates subjected to clinical trials, pynegabine (HN37, 1 μM) and XEN1101 (1 μM). These newly identified pathologic variants enrich the KCNQ2-DEE mutation hotspots in the pore-forming domain. This electrophysiological study provides a rational basis for personalized therapy with KCNQ openers in DEE patients carrying loss-of-function (LOF) mutations in KCNQ2.