bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of IHMT-MST1-39 as a novel MST1 kinase inhibitor and AMPK activator for the treatment of diabetes mellitus
Authors: Wang Junjie , Qi Ziping , Wu Yun , Wang Aoli , Liu Qingwang , Zou Fengming , Wang Beilei , Qi Shuang , Cao Jiangyan , Hu Chen , Shi Chenliang , Liang Qianmao , Wang Li , Liu Jing , Wang Wenchao , Liu Qingsong 
Published: April 2023

AbstractInsulin-producing pancreatic β cell death is the fundamental cause of type 1 diabetes (T1D) and a contributing factor to type 2 diabetes (T2D). Moreover, metabolic disorder is another hallmark of T2D. Mammalian sterile 20-like kinase 1 (MST1) contributes to the progression of diabetes mellitus through apoptosis induction and acceleration of pancreatic β cell dysfunction. AMP-activated protein kinase (AMPK) is an energy sensing kinase and its activation has been suggested as a treatment option for metabolic diseases. Thus, pharmacological inhibition of MST1 and activation of AMPK simultaneously represents a promising approach for diabetes therapy. Here, we discovered a novel selective MST1 kinase inhibitor IHMT-MST1-39, which exhibits anti-apoptosis efficacy and improves the survival of pancreatic β cells under diabetogenic conditions, as well as primary pancreatic islets in an ex vivo disease model. Mechanistically, IHMT-MST1-39 activated AMPK signaling pathway in hepatocytes in vitro, combination of IHMT-MST1-39 and metformin synergistically prevented hyperglycemia and significantly ameliorated glucose tolerance and insulin resistance in diabetic mice. Taken together, IHMT-MST1-39 is a promising anti-diabetic candidate as a single agent or in combination therapy for both T1D and T2D.
The temporal dynamics of transition to psychosis in individuals at clinical high-risk (CHR-P) shows negative prognostic effects of baseline antipsychotic exposure: a meta-analysis
Authors: Raballo Andrea , Poletti Michele , Preti Antonio 
Published: April 2023

AbstractMeta-analytic evidence indicates that baseline exposure to antipsychotics (AP) in individuals at clinical high-risk for psychosis (CHR-P) is associated with an even higher risk of transition to psychosis. However, the temporal dynamics of such prognostic effect have not been clarified yet. This study was therefore designed to address this knowledge gap. We performed a systematic review and meta-analysis of all longitudinal studies published up to 31 December 2021 on CHR-P individuals identified according to a validated diagnostic procedure and reporting numeric data of transition to psychosis according to baseline antipsychotic exposure. 28 studies covering a total of 2405 CHR-P were included. 554 (23.0%) were exposed to AP at baseline, whereas 1851 (77.0%) were not. At follow-up (12 to 72 months), 182 individuals among AP-exposed (32.9%; 95% CI: 29.4% to 37.8%) and 382 among AP-naive CHR-P (20.6%; 18.8% to 22.8%) developed psychosis. Transition rates increased over time, with the best-fit for an ascending curve peaking at 24 months and reaching then a plateau, with a further increase at 48 months. Baseline AP-exposed CHR-P had higher transition risk at 12 months and then again at 36 and 48 months, with an overall higher risk of transition (fixed-effect model: risk ratio = 1.56 [95% CI: 1.32–1.85]; z = 5.32; p < 0.0001; Random-effect model: risk ratio = 1.56 [95% CI: 1.07–2.26]; z = 2.54; p = 0.0196). In conclusion, the temporal dynamics of transition to psychosis differ in AP-exposed vs. AP-naive CHR-P. Baseline AP exposure in CHR-P is associated with a persistently higher risk of transition at follow up, supporting the rationale for more stringent clinical monitoring in AP-exposed CHR-P. The insufficiency of more granular information in available primary literature (e.g., temporal and quantitative details of AP exposure as well as psychopathological dimensions in CHR-P) did not allow the testing of causal hypotheses on this negative prognostic association.
FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells
Authors: Wang Chen , Sun Hui , Davis John S. , Wang Xiaojie , Huo Lijun , Sun Nan , Huang Qianzhi , Lv Xiangmin , Wang Cheng , He Chunbo , He Changjiu , Zhou Yang , Wu Jiyun , Yang Liguo , Hua Guohua 
Published: April 2023

AbstractFemale subfertility is an increasing reproductive issue worldwide, which is partially related to abnormal ovarian follicular development. Granulosa cells (GCs), by providing the necessary physical support and microenvironment for follicular development, play critical roles in maintaining female fertility. We previously showed that ectopic expression of four and a half LIM domains 2 (FHL2) promoted ovarian granulosa cell tumor progression. However, its function in follicular development and fertility remains unknown. Here, we confirmed that FHL2 is highly expressed in human and mouse ovaries. FHL2 immunosignals were predominantly expressed in ovarian GCs. A Fhl2 knockout (KO) mouse model was generated to examine its roles in follicular development and fertility. Compared with wildtype, knockout of Fhl2 significantly decreased female litter size and offspring number. Furthermore, Fhl2 deficiency reduced ovarian size and impaired follicular development. RNA-sequencing analysis of GCs isolated from either KO or WT mice revealed that, Fhl2 deletion impaired multiple biological functions and signaling pathways, such as Ovarian Putative Early Atresia Granulosa Cell, ErbB, Hippo/YAP, etc. In vitro studies confirmed that FHL2 silencing suppressed GCs growth and EGF-induced GCs proliferation, while its overexpression promoted GC proliferation and decreased apoptosis. Mechanistic studies indicated that FHL2, via forming complexes with transcriptional factors AP-1 or NF-κB, regulated Egf and Egfr expression, respectively. Besides, FHL2 depletion decreased YAP1 expression, especially the active form of YAP1 (nuclear YAP1) in GCs of growing follicles. EGF, serving as an autocrine/paracrine factor, not only induced FHL2 expression and nuclear accumulation, but also stimulated YAP1 expression and activation. Collectively, our study suggests that FHL2 interacts with EGFR and Hippo/YAP signaling to regulate follicular development and maintain fertility. This study illuminates a novel mechanism for follicular development and a potential therapeutic target to address subfertility.
IL-33 promotes double negative T cell survival via the NF-κB pathway
Authors: Sun Xiaojing , Zhang Chunpan , Sun Fanqi , Li Shuxiang , Wang Yaning , Wang Tingting , Li Li 
Published: April 2023

AbstractIL-33, which is a crucial modulator of adaptive immune responses far beyond type 2 response, can enhance the function of several T cell subsets and maintain the immune homeostasis. However, the contribution of IL-33 to double negative T (DNT) cell remains unappreciated. Here, we demonstrated that the IL-33 receptor ST2 was expressed on DNT cells, and that IL-33 stimulation increased DNT cells proliferation and survival in vivo and in vitro. Transcriptome sequencing analysis also demonstrated that IL-33 enhanced the biological function of DNT cells, especially effects on proliferation and survival. IL-33 promoted DNT cells survival by regulating Bcl-2, Bcl-xl and Survivin expression. IL-33-TRAF4/6-NF-κB axis activation promoted the transmission of essential division and survival signals in DNT cells. However, IL-33 failed to enhance the expression of immunoregulatory molecules in DNT cells. DNT cells therapy combined with IL-33 inhibited T cells survival and further ameliorated ConA-induced liver injury, which mainly depended on the proliferative effect of IL-33 on DNT cells in vivo. Finally, we stimulated human DNT cells with IL-33, and similar results were observed. In conclusion, we revealed a cell intrinsic role of IL-33 in the regulation of DNT cells, thereby identifying a previously unappreciated pathway supporting the expansion of DNT cells in the immune environment.
Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line
Authors: Noguchi Masafumi , Kohno Susumu , Pellattiero Anna , Machida Yukino , Shibata Keitaro , Shintani Norihito , Kohno Takashi , Gotoh Noriko , Takahashi Chiaki , Hirao Atsushi , Scorrano Luca , Kasahara Atsuko 
Published: April 2023

AbstractDrug resistance limits the efficacy of chemotherapy and targeted cancer treatments, calling for the identification of druggable targets to overcome it. Here we show that the mitochondria-shaping protein Opa1 participates in resistance against the tyrosine kinase inhibitor gefitinib in a lung adenocarcinoma cell line. Respiratory profiling revealed that oxidative metabolism was increased in this gefitinib-resistant lung cancer cell line. Accordingly, resistant cells depended on mitochondrial ATP generation, and their mitochondria were elongated with narrower cristae. In the resistant cells, levels of Opa1 were increased and its genetic or pharmacological inhibition reverted the mitochondrial morphology changes and sensitized them to gefitinib-induced cytochrome c release and apoptosis. In vivo, the size of gefitinib-resistant lung orthotopic tumors was reduced when gefitinib was combined with the specific Opa1 inhibitor MYLS22. The combo gefitinib-MYLS22 treatment increased tumor apoptosis and reduced its proliferation. Thus, the mitochondrial protein Opa1 participates in gefitinib resistance and can be targeted to overcome it.
Autophagy in hepatic ischemia–reperfusion injury
Authors: Mao Benliang , Yuan Wei , Wu Fan , Yan Yong , Wang Bailin 
Published: April 2023

AbstractHepatic ischemia–reperfusion injury (HIRI) is a major complication of liver resection or liver transplantation that can seriously affect patient’s prognosis. There is currently no definitive and effective treatment strategy for HIRI. Autophagy is an intracellular self-digestion pathway initiated to remove damaged organelles and proteins, which maintains cell survival, differentiation, and homeostasis. Recent studies have shown that autophagy is involved in the regulation of HIRI. Numerous drugs and treatments can change the outcome of HIRI by controlling the pathways of autophagy. This review mainly discusses the occurrence and development of autophagy, the selection of experimental models for HIRI, and the specific regulatory pathways of autophagy in HIRI. Autophagy has considerable potential in the treatment of HIRI.
Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRASG12D mutated pancreatic cancer in vivo model
Authors: Panebianco Concetta , Pisati Federica , Villani Annacandida , Andolfo Annapaola , Ulaszewska Marynka , Bellini Edoardo , Ferro Carmelapia , Lombardi Renato , Orsenigo Fabrizio , Latiano Tiziana Pia , Belmonte Beatrice , Tripodo Claudio , Perri Francesco , Pazienza Valerio 
Published: April 2023

AbstractPancreatic cancer (PC) has a very low survival rate mainly due to late diagnosis and refractoriness to therapies. The latter also cause adverse effects negatively affecting the patients’ quality of life, often requiring dose reduction or discontinuation of scheduled treatments, compromising the chances of cure. We explored the effects of a specific probiotic blend on PC mice xenografted with KRAS wild-type or KRASG12D mutated cell lines alone or together with gemcitabine+nab-paclitaxel treatment to then assess tumor volume and clinical pathological variables. Beside a semi-quantitative histopathological evaluation of murine tumor and large intestine samples, histochemical and immunohistochemical analyses were carried out to evaluate collagen deposition, proliferation index Ki67, immunological microenvironment tumor-associated, DNA damage markers and also mucin production. Blood cellular and biochemical parameters and serum metabolomics were further analyzed. 16S sequencing was performed to analyze the composition of fecal microbiota. Gemcitabine+nab-paclitaxel treatment impaired gut microbial profile in KRAS wild-type and KRASG12D mice. Counteracting gemcitabine+nab-paclitaxel- induced dysbiosis through the administration of probiotics ameliorated chemotherapy side effects and decreased cancer-associated stromatogenesis. Milder intestinal damage and improved blood count were also observed upon probiotics treatment as well as a positive effect on fecal microbiota, yielding an increase in species richness and in short chain fatty acids producing- bacteria. Mice’ serum metabolomic profiles revealed significant drops in many amino acids upon probiotics administration in KRAS wild-type mice while in animals transplanted with PANC-1 KRASG12D mutated all treated groups showed a sharp decline in serum levels of bile acids with respect to control mice. These results suggest that counteracting gemcitabine+nab-paclitaxel-induced dysbiosis ameliorates chemotherapy side effects by restoring a favorable microbiota composition. Relieving adverse effects of the chemotherapy through microbiota manipulation could be a desirable strategy in order to improve pancreatic cancer patients’ quality of life and to increase the chance of cure.
Using conservation genetics to prioritise management options for an endangered songbird
Authors: Alves Fernanda , Banks Sam C. , Edworthy Max , Stojanovic Dejan , Langmore Naomi E. , Heinsohn Robert 
Published: April 2023

AbstractGenetic data can be highly informative for answering questions relevant to practical conservation efforts, but remain one of the most neglected aspects of species recovery plans. Framing genetic questions with reference to practical and tractable conservation objectives can help bypass this limitation of the application of genetics in conservation. Using a single-nucleotide polymorphism dataset from reduced-representation sequencing (DArTSeq), we conducted a genetic assessment of remnant populations of the endangered forty-spotted pardalote (Pardalotus quadragintus), a songbird endemic to Tasmania, Australia. Our objectives were to inform strategies for the conservation of genetic diversity in the species and estimate effective population sizes and patterns of inter-population movement to identify management units relevant to population conservation and habitat restoration. We show population genetic structure and identify two small populations on mainland Tasmania as ‘satellites’ of larger Bruny Island populations connected by migration. Our data identify management units for conservation objectives relating to genetic diversity and habitat restoration. Although our results do not indicate the immediate need to genetically manage populations, the small effective population sizes we estimated for some populations indicate that they are vulnerable to genetic drift, highlighting the urgent need to implement habitat restoration to increase population size and to conduct genetic monitoring. We discuss how our genetic assessment can be used to inform management interventions for the forty-spotted pardalote and show that by assessing contemporary genetic aspects, valuable information for conservation planning and decision-making can be produced to guide actions that account for genetic diversity and increase chances of recovery in species of conservation concern.
Variability conceals emerging trend in 100yr projections of UK local hourly rainfall extremes
Authors: Kendon Elizabeth J. , Fischer Erich M. , Short Chris J. 
Published: April 2023

AbstractExtreme precipitation is projected to intensify with warming, but how this will manifest locally through time is uncertain. Here, we exploit an ensemble of convection-permitting transient simulations to examine the emerging signal in local hourly rainfall extremes over 100-years. We show rainfall events in the UK exceeding 20 mm/h that can cause flash floods are 4-times as frequent by 2070s under high emissions; in contrast, a coarser resolution regional model shows only a 2.6x increase. With every degree of regional warming, the intensity of extreme downpours increases by 5-15%. Regional records of local hourly rainfall occur 40% more often than in the absence of warming. However, these changes are not realised as a smooth trend. Instead, as a result of internal variability, extreme years with record-breaking events may be followed by multiple decades with no new local rainfall records. The tendency for extreme years to cluster poses key challenges for communities trying to adapt.
Hematopoietic stem-cell gene therapy is associated with restored white matter microvascular function in cerebral adrenoleukodystrophy
Authors: Lauer Arne , Speroni Samantha L. , Choi Myoung , Da Xiao , Duncan Christine , McCarthy Siobhan , Krishnan Vijai , Lusk Cole A. , Rohde David , Hansen Mikkel Bo , Kalpathy-Cramer Jayashree , Loes Daniel J. , Caruso Paul A. , Williams David A. , Mouridsen Kim , Emblem Kyrre E. , Eichler Florian S. , Musolino Patricia L. 
Published: April 2023

AbstractBlood-brain barrier disruption marks the onset of cerebral adrenoleukodystrophy (CALD), a devastating cerebral demyelinating disease caused by loss of ABCD1 gene function. The underlying mechanism are not well understood, but evidence suggests that microvascular dysfunction is involved. We analyzed cerebral perfusion imaging in boys with CALD treated with autologous hematopoietic stem-cells transduced with the Lenti-D lentiviral vector that contains ABCD1 cDNA as part of a single group, open-label phase 2-3 safety and efficacy study (NCT01896102) and patients treated with allogeneic hematopoietic stem cell transplantation. We found widespread and sustained normalization of white matter permeability and microvascular flow. We demonstrate that ABCD1 functional bone marrow-derived cells can engraft in the cerebral vascular and perivascular space. Inverse correlation between gene dosage and lesion growth suggests that corrected cells contribute long-term to remodeling of brain microvascular function. Further studies are needed to explore the longevity of these effects.
Long distance multiplexed quantum teleportation from a telecom photon to a solid-state qubit
Authors: Lago-Rivera Dario , Rakonjac Jelena V. , Grandi Samuele , Riedmatten Hugues de 
Published: April 2023

AbstractQuantum teleportation is an essential capability for quantum networks, allowing the transmission of quantum bits (qubits) without a direct exchange of quantum information. Its implementation between distant parties requires teleportation of the quantum information to matter qubits that store it for long enough to allow users to perform further processing. Here we demonstrate long distance quantum teleportation from a photonic qubit at telecom wavelength to a matter qubit, stored as a collective excitation in a solid-state quantum memory. Our system encompasses an active feed-forward scheme, implementing a conditional phase shift on the qubit retrieved from the memory, as required by the protocol. Moreover, our approach is time-multiplexed, allowing for an increase in the teleportation rate, and is directly compatible with the deployed telecommunication networks, two key features for its scalability and practical implementation, that will play a pivotal role in the development of long-distance quantum communication.
Ring-closing C–O/C–O metathesis of ethers with primary aliphatic alcohols
Authors: Liu Hongmei , Huang Qing , Liao Rong-zhen , Li Man , Xie Youwei 
Published: April 2023

AbstractIn canonical organic chemistry textbooks, the widely adopted mechanism for the classic transetherifications between ethers and alcohols starts with the activation of the ether in order to weaken the C–O bond, followed by the nucleophilic attack by the alcohol hydroxy group, resulting in a net C–O/O–H σ-bond metathesis. In this manuscript, our experimental and computational investigation of a Re2O7mediated ring-closing transetherification challenges the fundamental tenets of the traditional transetherification mechanism. Instead of ether activation, the alternative activation of the hydroxy group followed by nucleophilic attack of ether is realized by commercially available Re2O7through the formation of perrhenate ester intermediate in hexafluoroisopropanol (HFIP), which results in an unusual C–O/C–O σ-bond metathesis. Due to the preference for the activation of alcohol rather than ether, this intramolecular transetherification reaction is therefore suitable for substrates bearing multiple ether moieties, unparalleled by any previous methods.
Mining of lattice distortion, strength, and intrinsic ductility of refractory high entropy alloys
Authors: Tandoc Christopher , Hu Yong-Jie , Qi Liang , Liaw Peter K. 
Published: April 2023

AbstractSevere lattice distortion is a prominent feature of high-entropy alloys (HEAs) considered a reason for many of those alloys’ properties. Nevertheless, accurate characterizations of lattice distortion are still scarce to only cover a tiny fraction of HEA’s giant composition space due to the expensive experimental or computational costs. Here we present a physics-informed statistical model to efficiently produce high-throughput lattice distortion predictions for refractory non-dilute/high-entropy alloys (RHEAs) in a 10-element composition space. The model offers improved accuracy over conventional methods for fast estimates of lattice distortion by making predictions based on physical properties of interatomic bonding rather than atomic size mismatch of pure elements. The modeling of lattice distortion also implements a predictive model for yield strengths of RHEAs validated by various sets of experimental data. Combining our previous model on intrinsic ductility, a data mining design framework is demonstrated for efficient exploration of strong and ductile single-phase RHEAs.
A general-purpose material property data extraction pipeline from large polymer corpora using natural language processing
Authors: Shetty Pranav , Rajan Arunkumar Chitteth , Kuenneth Chris , Gupta Sonakshi , Panchumarti Lakshmi Prerana , Holm Lauren , Zhang Chao , Ramprasad Rampi 
Published: April 2023

AbstractThe ever-increasing number of materials science articles makes it hard to infer chemistry-structure-property relations from literature. We used natural language processing methods to automatically extract material property data from the abstracts of polymer literature. As a component of our pipeline, we trained MaterialsBERT, a language model, using 2.4 million materials science abstracts, which outperforms other baseline models in three out of five named entity recognition datasets. Using this pipeline, we obtained ~300,000 material property records from ~130,000 abstracts in 60 hours. The extracted data was analyzed for a diverse range of applications such as fuel cells, supercapacitors, and polymer solar cells to recover non-trivial insights. The data extracted through our pipeline is made available at polymerscholar.org which can be used to locate material property data recorded in abstracts. This work demonstrates the feasibility of an automatic pipeline that starts from published literature and ends with extracted material property information.