bluuebunny/crossref_metadata_2025 huggingface dataset:
SURF1 Deficiency: Expanding on Disease Phenotype and Assessing Disease Burden by Describing Clinical and Biochemical Phenotype
Authors: Kayani Saima , Daescu Victor , Dahshi Hamza , Messahel Souad , Woleban Kasey , Minassian Berge A. , Ling Qinglan , Gray Steven J.
Published: December 2024

Leigh syndrome, a severe neurological disorder is commonly caused by homozygous or bi‐allelic pathogenic variants in the SURF1 gene. SURF1 deficiency leads to dysfunction of Cytochrome C Oxidase (COX) activity, which is crucial for mitochondrial oxidative phosphorylation. Understanding COX activity's correlation with disease severity is essential for developing SURF1 Leigh Syndrome biomarkers. This study assesses the disease burden in SURF1 Leigh Syndrome and evaluates COX activity as a treatment biomarker. We reviewed records and questionnaires from 17 individuals, classifying them into phenotypic and genotypic groups. We compared COX activity assays in patient fibroblasts to age‐matched controls, clinical data, and neuroimaging findings. Patient COX activity was at most 50% of controls, averaging 32% (p < 0.001). Common clinical features included brainstem abnormalities (93.3%), motor regression (92.3%), bi‐allelic heterozygous SURF1 variants (88.2%), and delayed growth/development (35.7%). Homozygous and heterozygous nonsense/frameshift variants showed more severe phenotypes (p = 0.008) and more MRI abnormalities (p = 0.005). Significant COX activity reduction is linked to SURF1 Leigh Syndrome, with genotype influencing disease severity. Clinical and neuroimaging correlations show potential for prognostic indicators. This study lays the groundwork for future research and clinical application of COX activity as a SURF1 Leigh Syndrome biomarker.
Alkylated Quinolines through Benzylic sp3 C−H Functionalization: Sequential Synthesis and Photophysical Studies
Authors: Suresh Sundararajan , Keerthana Pari , Nawaz Khan Fazlurrahman
Published: December 2024

An efficient method has been developed for the green synthesis of alkylated quinolines via Cu‐TEMPO catalyzed dehydrogenation, and DEP/DES‐assisted benzylic C−H functionalization followed by cross Rauhut‐Currier type reaction. The reaction mechanism is elucidated through control experiments and 1H NMR reaction monitoring. This transformation offers several advantages, including moderate to good yields of the desired products, mild reaction conditions, use of a cost‐effective metal catalyst, good functional group tolerance, and applicability to gram‐scale synthesis. Additionally, the synthetic utility and the photophysical properties of the synthesized alkylated quinoline derivatives were investigated.
Diphenylperylene Isomers as Novel Emissive Organic Semiconductors
Authors: Chen Liangliang , Wang Ying , Liu Zitong
Published: December 2024

Emissive organic semiconductors are crucial for integrated optoelectronic devices, yet only a limited number of materials exhibit high mobility and high photoluminescence quantum yield because of the contradictory requirements for molecular stacking. In this study, two diphenylperylene isomers, 39P‐Ph and 310P‐Ph, were successfully synthesized through a one‐step process by varying the positions of the substituent phenyl groups on the perylene core. Both compounds were comprehensively characterized and demonstrated excellent hole transport capabilities and moderate photoluminescence quantum yield (PLQY), along with long‐wavelength emission, establishing them as effective emissive organic semiconductors. 39P‐Ph emits orange‐yellow fluorescence in crystalline powder with an absolute PLQY of 15.4 % and 310P‐Ph shows orange‐red emission with an emissive wavelength of up to 612 nm in 17.5 % PLQY. Moreover, the carrier mobilities of 39P‐Ph and 310P‐Ph are up to 3.05 cm2 V−1 s−1 and 1.36 cm2 V−1 s−1, respectively, based on the single‐crystal devices. These results reveal that 39P‐Ph and 310P‐Ph are promising candidates as emissive semiconductors, offering a balance between efficient charge transport and light emission for integrated optoelectronic applications.
Computer‐Aided Development of New Nonlinear Optical Materials
Authors: Wang Hongshan , Mutailipu Miriding , Yang Zhihua , Pan Shilie , Li Junjie
Published: December 2024

Exploring new nonlinear optical (NLO) materials is an urgent need for advanced photoelectric technologies. However, the discovery of new materials with targeted properties is time‐consuming, and involves various challenges by the traditional trial‐and‐error experiments. Recently, the theoretical prediction‐guided structural design has been demonstrated as a feasible way for efficiently developing new NLO materials, and a large number of NLO candidates with excellent optical properties have been explored. To promote the development of high‐performance NLO materials, this review provides a summary on the exploration of new NLO materials aided by computer, with a particular emphasis on the state‐of‐the‐art research advances that including crystal structure predictions, optical & thermal property calculations, high‐throughput screening of NLO materials with or without machine learning; and the progress achieved in the computer‐assisted design and development of new deep ultraviolet (DUV), ultraviolet (UV), infrared (IR) NLO materials in various material systems: oxide, chalcogenide, nitride, and halide. Finally, the opportunities and forthcoming challenges in the fascinating field are discussed.
A Highly Efficient Propeller‐Like Organic Radical with Less Solvent Sensitivity and Selective Detection of Aromatic Amines from Aliphatic Amines through Turn‐on Fluorescence
Authors: Ding Zhaoze , Zhu Zihao , Wang Shengjie , Obolda Ablikim , Abdurahman Alim
Published: December 2024

Highly efficient red luminescent organic radicals with less solvent sensitivity are much more attractive due to their wide application in various fields, especially in fluorescence sensing, and bioimaging. In this work, we synthesized a three δ‐carboline‐capped highly efficient propeller‐like organic radical TTM‐3δPyID with a D−A structure. The radical showed pure red emission with PLQY of 77.3 % in cyclohexane and kept 35.2 % even in the polar solvent dichloromethane, indicating potential applications in fluorescence sensing. Radical TTM‐3δPyID also showed stepwise proton‐responsive properties and different emissions at the different states. Furthermore, by taking advantage of the nitrogen site of the radical, we have achieved a fluorescent‐quenched radical derivative TTM‐3δPyID‐AB by introducing of 2‐bromoethyl chain through a quaternary ammonium salt reaction. The radical TTM‐3δPyID‐AB showed turn‐on fluorescence in the presence of primary organic amines. Finally, this turn‐on fluorescent property is successfully used to distinguish aliphatic amines from aromatic amines.
Subregion‐specific thalamocortical functional connectivity, executive function, and social behavior in children with autism spectrum disorders
Authors: Chuah Jasmine Si Min , Manahan Aisleen M. A. , Chan Shi Yu , Ngoh Zhen Ming , Huang Pei , Tan Ai Peng
Published: December 2024

The thalamus has extensive cortical connections and is an integrative hub for cognitive functions governing social behavior. This study examined (1) associations between thalamocortical resting‐state functional connectivity (RSFC) and social behavior in children and (2) how various executive function (EF) subdomains mediate the association between thalamocortical RSFC and social behavior. Children from the autism brain imaging data exchange (ABIDE) initiative with neuroimaging, behavioral, and demographic data were included in our study (age < 14, ASD; n = 207, typically developing; n = 259). Thalamocortical RSFC was examined for associations with social communication and interaction (SCI) scores (SRS; social responsiveness scale) using Spearman's rank‐order correlation, first in ASD children and then in typically developing children. This was followed by a more granular analysis at the thalamic subregion level. We then examined the mediating roles of eight EF subdomains in ASD children (n = 139). Right thalamus‐default mode network (DMN) RSFC was significantly associated with SCI scores in ASD children (ρ = 0.23, pFDR = 0.012), primarily driven by the medial (ρ = 0.22, pFDR = 0.013), ventral (ρ = 0.17, pFDR = 0.036), and intralaminar (ρ = 0.17, pFDR = 0.036) thalamic subregions. Cognitive flexibility (ACME = 0.13, punc = 0.016) and emotional control (ACME = 0.08, punc = 0.020) significantly mediated the association between right thalamus‐DMN RSFC and SCI scores. This study provided novel insights into the association between thalamocortical RSFC and social behavior in ASD children at the thalamic subregion level, providing higher levels of precision in brain‐behavior mapping. Cognitive flexibility and emotion regulation were highlighted as potential targets to ameliorate the downstream effects of altered thalamocortical connectivity to improve social outcomes in ASD children.
Towards Next Generation Protein Sequencing
Authors: Yi Yakun , Li Ziyi , Liu Lei , Wu Hai‐Chen
Published: December 2024

Understanding the structure and function of proteins is a critical objective in the life sciences. Protein sequencing, a central aspect of this endeavor, was first accomplished through Edman degradation in the 1950s. Since the late 20th century, mass spectrometry has emerged as a prominent method for protein sequencing. In recent years, single‐molecule technologies have increasingly been applied to this field, yielding numerous innovative results. Among these, nanopore sensing has proven to be a reliable single‐molecule technology, enabling advancements in amino acid recognition, short peptide differentiation, and peptide sequence reading. These developments are set to elevate protein sequencing technology to new heights. The next generation of protein sequencing technologies is anticipated to revolutionize our understanding of molecular mechanisms in biological processes and significantly enhance clinical diagnostics and treatments.
Nanomaterial‐Enhanced Red Blood Cell Biopreservation: From Refrigeration to Cryopreservation
Authors: Xu Jun , Lei Chuanyi , Zhu Wei
Published: December 2024

Red blood cell (RBC) transfusions represent a cornerstone of clinical practice, with RBCs constituting the primary component in transfusion therapy. Extending the preservation of RBCs while maintaining their functional integrity would offer considerable advancements for both transfusion medicine and military healthcare. Despite decades of research, progress in achieving long‐term RBC preservation has been limited. A key challenge is the range of physical and biochemical damage RBCs incur during storage, leading to marked changes in their morphology, physiological function, and viability. While traditional preservation techniques have provided partial mitigation of these damages, their efficacy remains suboptimal. In contrast, nanomaterials, with their distinctive spatial architectures and surface properties, offer a promising avenue for minimizing storage‐related damage and extending RBC preservation. This review provides an overview of the major categories of damage encountered during RBC biopreservation, classified into storage lesions and cryolesions. We also highlight the key role of nanomaterials in enhancing the storage quality of RBCs and prolonging their preservation duration. Finally, we discuss the current challenges and pressing issues faced by nanomaterial‐based RBCs biopreservation.
ZnIn2S4 with a hybrid reaction mechanism and sulfur vacancies for sustainable sodium storage
Authors: Wang Yu , Zhang He He , Wen Zi , Sun Chang Ning , Wang Guo Yong , Wang Ming‐Sheng , Yang Chun Cheng , Jiang Qing
Published: December 2024

Conventional monometallic sulfides are usually conversion or conversion‐alloying‐dominated anodes, while the sluggish kinetics and severe volume variation greatly hamper their electrochemical properties in sodium‐ion batteries. Herein, bimetallic sulfides (Vs‐ZnIn2S4) are developed with S vacancies, which are verified via electron paramagnetic resonance. A possible reaction mechanism (intercalation–conversion–alloying) is proposed, which is characterized by in situ X‐ray diffraction. In addition, the small volume change during (de)sodiation of Vs‐ZnIn2S4 is also observed by in situ transmission electron microscopy. The Vs‐ZnIn2S4 anode shows ultrastable and superfast sodium storage performance, such as outstanding long‐term cycling durability at 10 A g−1 (349.6 mAh g−1 after 2000 cycles) and rate property at 80 A g−1 (222.7 mAh g−1). Moreover, the full cell [Vs‐ZnIn2S4//Na3V2(PO4)3/C] achieves an excellent property after 300 cycles (185.9 mAh g−1) at 5 A g−1, showing significant potential for real‐world applications.
Photocatalytic CeCl3‐Promoted C−H Alkenylation and Alkynylation of Alkanes
Authors: Stini Naya A. , Gkizis Petros L. , Triandafillidi Ierasia , Kokotos Christoforos G.
Published: December 2024

The reemerging field of photoredox catalysis offers numerous advantages towards the development of novel, sustainable and easy‐to‐execute organic transformations. Herein, we report a light‐triggered application of cerium complexes towards the C−H alkenylation and alkynylation of alkanes. An indirect HAT‐mediated photocatalytic protocol was developed, using a cerium salt (CeCl3 ⋅ 7H2O) and a chlorine source (TBACl) as the catalytic system. A variety of cyclic and linear hydrocarbons were utilized, delivering the corresponding alkenylation or alkynylation products in good to high yields, displaying high regioselectivity. A series of mechanistic experiments were conducted.
Fine Needle Aspiration Cytological Diagnosis of Primary Breast Large‐Cell Neuroendocrine Carcinoma/Squamous Cell Carcinoma
Authors: Cui Wenjing , Yang Changwei , Ding Xiaochen , Liu Jiayan , Zhang Hongjuan , Xu Hong
Published: December 2024

Primary breast large‐cell neuroendocrine carcinoma (LCNEC)/squamous cell carcinoma (SCC), also referred to as mixed neuroendocrine/non‐neuroendocrine neoplasms of the breast (Br‐MiNENs), represents an exceedingly rare malignancy. We report the first case of primary breast LCNEC/SCC diagnosed via ultrasound‐guided fine‐needle aspiration (FNA) biopsy of the left supraclavicular and left internal mammary lymph nodes. The patient, a 40‐year‐old female, underwent a lumpectomy followed by breast‐conserving surgery and was diagnosed with primary breast LCNEC. Notably, within merely four months following the breast‐conserving surgery, PET‐CT revealed lymph node enlargement, prompting the performance of FNA. FNA cytology of metastatic lymph nodes revealed two distinct tumor components, allowing for clear differentiation between LCNEC and SCC in the smear. The diagnosis was further corroborated by immunocytochemical (ICC) staining of the cell blocks. Subsequently, histopathological re‐examination of the breast mass revealed occult SCC components comprising less than 1% of the tumor cells. Additionally, the case exhibited triple‐negative breast cancer, with PIK3CA, TP53, RB1, and BCL2L11 mutations identified through next‐generation sequencing (NGS). Br‐MiNEN is exceedingly rare, and its cytological diagnosis poses significant challenges. It is recommended that a detailed and objective description of each tumor component and its proportion be provided. This report provides the first detailed description of the FNA cytology of LCNEC/SCC, thereby enhancing cytopathologists' comprehension of this tumor. Auxiliary studies, including ICC staining and molecular biology assays, are crucial for accurate diagnosis, therapy, and prognosis.
Survey of Latin American ketogenic diet centers: Challenges and success for “La Terapia Cetogénica”
Authors: Armeno Marisa , Kossoff Eric H. , Guilhoto Laura , Caraballo Roberto
Published: December 2024

Objective

Despite growing recognition of the efficacy of ketogenic diet therapies (KDT) in reducing seizure frequency and improving the quality of life for individuals with epilepsy, several factors hinder their widespread adoption across Latin America. Specific challenges in the region have been discussed but not formally studied. Currently, no data exist on the availability and operation of KDT teams in the region. To address this gap, we conducted a survey of KDT centers across Latin American countries in the framework of the biannual International Ketogenic Diet Conference in September 2023.

Methods

A seven‐question survey was distributed via email to neurologists, dietitians, or through indexed publications.

Results

Of the 16 centers approached, 14 (87.5%) responded, identifying 98 KDT centers. Nearly half (49%) are public institutions, primarily in Brazil, Chile, and Mexico; 44 are private; and 5 are mixed. Core teams in all centers included a neurologist and dietitian, with some teams in Argentina, Chile, and Paraguay also involving a medical nutritionist. None of the centers reported a protocol for transitioning to adult care, and consistent data on Glut1 patients and protocols were lacking.

Significance

Over the past two decades, the KDT landscape in Latin America has improved, with established centers expanding and new ones emerging. However, continued efforts are needed to promote KDT adoption in countries where it is not yet practiced and in regions with limited resources and expertise.
Preventing epileptogenesis by interaction between inositol isomers and proteins
Authors: Tsverava Lia , Kharkhelauri Luka , Lagani Vincenzo , Gamkrelidze Giorgi , Bokuchava Veriko , Kiguradze Tamar , Kokaia Merab , Solomonia Revaz
Published: December 2024

Objective

Inositols play significant roles in biological systems. Myo‐inositol (MI), the most prevalent isomer, functions as an osmolyte and mediates cell signal transduction. Other notable isomers include Scyllo‐inositol (SCI) and D‐Chiro‐inositol (DCHI). Our previous investigations have highlighted MI's potential antiepileptogenic effects, although its exact mechanisms of action during epileptogenesis remain unclear. A critical, unexplored area is how inositols interact with proteins. Additionally, the antiepileptogenic capabilities of SCI and DCHI have yet to be determined. This study seeks to address these gaps.

Methods

Inositol interacting proteins were identified by cellular thermal shift assay. Status epilepticus (SE) in rats was induced using kainic acid (KA), followed by a 28‐day treatment with either MI, SCI, DCHI, or saline. The duration and frequencies of behavioral spontaneous recurrent seizures (SRS) were scored for 8 weeks by 24 h video monitoring system. The effects of inositol treatment on spatial learning and memory deficits associated with epileptogenesis were evaluated by Morris water maze test. The changes in protein amounts were studied by Western immunoblotting.

Results

We identified several proteins that interact with inositols, noting both commonalities and isomer‐specific associations. For the first time, we demonstrated that the treatment with SCI and DCHI, alongside MI, significantly reduces the frequency and duration of behavioral SRS in a KA‐induced post‐status epilepsy model in rats. This reduction persisted for 4 weeks post‐treatment. Moreover, all three inositol isomers mitigated spatial learning and memory deficits associated with epileptogenesis. Alterations in the inositol interacting proteins: alpha synuclein and 14‐3‐3 theta were further examined 8 weeks post‐SE in the hippocampus and neocortex of rats.

Significance

Myo‐inositol, SCI and DCHI interact with a number of proteins involved in different biological pathways. All studied inositol isomers express long‐term beneficial effects on KA‐induced SRS and the associated comorbidities. Inositols can be successfully used in the future for translational research.

Plain Language Summary

Epilepsy is a common neurological disorder characterized by spontaneous recurrent seizures and a range of associated comorbidities. The process that leads to the development of epilepsy is called epileptogenesis, and currently, no medication can effectively prevent it. Our study investigated the effects of a group of compounds—myo‐inositol, scyllo‐inositol, and D‐chiro‐inositol—that have potential antiepileptogenic properties on epilepsy induced by kainic acid. We found that: (i) the three inositol isomers share some common target proteins and also have unique ones and (ii) all of them counteract epileptogenesis and the related cognitive impairments.
Comparative Analysis of Flavour Profile and Aroma Components of Shanxi Aged Vinegar From China
Authors: Wang Yuqian , Wang Junyi , Sun Linjia , Zhang Jihang , Zhang Ning
Published: December 2024

Shanxi aged vinegar (SAV) is a traditional vinegar produced mainly in southern China from rice and wheat, undergoing prolonged fermentation for maturation, which distinguishes it from other vinegar. To explore its flavour, a selection of 12 SAV varieties was meticulously chosen for in‐depth aroma analysis. Sensory analysis and electronic nose (E‐nose) were used to compare flavour profiles. Volatile components were extracted via liquid–liquid extraction (LLE) with solvent‐assisted flavour evaporation (SAFE), analysed by gas chromatography–mass spectrometry (GC–MS) and gas chromatography olfactometry‐mass spectrometry (GC‐O‐MS). The results revealed 145 volatile compounds, predominantly acids, alcohols, ketones and heterocycles, with acids as the most prevalent (ranging from 960.17 to 1231.78 μg/mL). Additionally, 90 aroma‐active compounds were identified, notably acetic acid, furfuryl alcohol, 2,3‐dimethylpyrazine, lactic acid, phenol, propyl acetate, ethyl propionate and 2(5H)‐furanone. Accordingly, a flavour wheel was constructed highlighting dominant volatile components, featuring acidic, alcohol, tangerine peel‐like and yeasty aromas. Partial least squares regression (PLSR) analysis showed that the acidity note in SAV positively correlates with acetic acid, isovaleric acid, hexanoic acid, phenethyl alcohol and butyric acid. Understanding the flavour composition of SAV provides vital insight for flavour research and product quality control.
The Effects of Adding Probiotic, Alone and in Combination With Zinc, to Routine Treatment on Recurrence of Hepatic Encephalopathy, Quality of Life, and Sleep Quality in Patients With Cirrhosis: An Open‐Label Randomized Controlled Trial
Authors: Amooyi Leila , Alizadeh Leila , Sarbakhsh Parvin , Shojaei‐Zarghani Sara , Gharekhani Afshin
Published: December 2024

Overt hepatic encephalopathy (OHE) is a common complication of decompensated cirrhosis. This study aimed to assess the effects of probiotic, alone and in combination with zinc, on OHE recurrence, Model for End‐stage Liver Disease (MELD) score, ammonia level, health‐related quality of life (HRQoL), and sleep quality in patients with cirrhosis. We performed an open‐label randomized controlled trial on patients with decompensated cirrhosis with a previous history of OHE. Eligible patients (n = 45) were divided randomly into three equal groups to receive 30–45 mL lactulose syrup (2–4 times/day), lactulose and probiotic (4.5 × 1011 CFU of bacteria, 2 times/day), or a combination of lactulose, probiotic, and zinc (25 mg) for 3 months. In this study, probiotic, alone or in combination with zinc, had no effect on OHE recurrence, ammonia levels, and MELD score. Mental aspects and total score of HRQoL were improved following probiotic and its combination with zinc, even after adjustment for baseline values, age, and sex. However, physical aspects of HRQoL and sleep quality were only improved by probiotic and zinc combination compared to the lactulose alone. Our findings showed improved HRQoL after treatment with probiotic, alone or in combination with zinc. However, sleep quality was influenced only by probiotic and zinc combination.

Trail Registration: This study has been registered in the Iranian registry of clinical trials (IRCT20170609034406N9).
Profiling Social Detachment in Older People in Taiwan: A Cluster Analysis
Authors: Tu Chao‐Ying , Wu Chi‐Shin , Yen Chia‐Ming , Chang Hung‐Yeh , Yu Chih‐Yuan , Chang Kai‐Chieh , Chen Hsin‐Shui , Chang Chin‐Kai , Hwang Juey‐Jen , Huang Su‐Hua , Chen Yung‐Ming , Cheng Bor‐Wen , Weng Min‐Hsiu , Hsu Chih‐Cheng , Huang Wei‐Lieh
Published: December 2024

Objectives

The Social Detachment Questionnaire for the Older Population (SDQO) is a validated tool that assesses various dimensions of social relationships. This study aimed to profile social detachment among older people in Taiwan using the SDQO and explore its use in distinguishing groups with varying levels of social engagement.

Methods

A telephone‐based survey was conducted, collecting demographic data and responses to the SDQO and Brief Symptom Rating Scale‐5 (BSRS‐5). Cluster analysis based on SDQO dimension scores was performed to identify groupings. Regression analyses examined the association between social engagement clusters, demographic variables, and BSRS‐5 scores. A receiver operating characteristic curve was established and the area under the curve was calculated to identify the cutoff for distinguishing individuals with high and low social engagement.

Results

In a representative sample of 2549 individuals aged 55 and above in Taiwan, cluster analysis identified two groups based on social engagement levels as measured by the SDQO. The low social engagement cluster, indicating higher social detachment, was more likely to consist of older individuals (≥ 75 years), those without children, and those with lower education levels (≤ 9 years). After adjusting for demographics, the low social engagement cluster was associated with higher BSRS‐5 scores. The optimal SDQO cutoff for identifying low social engagement was 27/28.

Conclusions

The SDQO can identify socially detached older people, who are more likely to experience increased psychological distress. Screening older individuals with demographic risk factors using the SDQO could help identify those most vulnerable to adverse health outcomes related to social detachment.
Comparing Outcomes Between CPX‐351 and Fludarabine‐Based Induction in Secondary Acute Myeloid Leukemia in the Real‐World Setting: The Prognostic Role of Measurable Residual Disease
Authors: Riva Carola , Minetto Paola , Chies Maria , Vernarecci Chiara , Colombo Nicoletta , Rosellini Sara , Parodi Alessia , Tedone Elisabetta , Carminati Enrico , Nurra Clara , Puglisi Francesco , Frello Michela , Maio Elena , Ferro Beatrice , Zecchetti Giada , Fugazza Giuseppina , Nozza Paolo , Cea Michele , Lemoli Roberto Massimo , Guolo Fabio
Published: December 2024

Secondary acute myeloid leukemia (s‐AML) is associated with inferior outcomes with conventional chemotherapy, and fludarabine combinations (FLAG‐Ida) have been tested to improve results. More recently, CPX‐351 resulted superior to conventional 3 + 7 in s‐AML patients. In the UK NCRI AML19 trial, AML patients were randomized to receive either FLAG‐Ida or CPX‐351. Subgroup analysis revealed better overall survival (OS) with CPX‐351 in patients with MDS‐related gene mutations. Unfortunately, minimal residual disease (MRD) was evaluated only in a minority of patients. The aim of this study was to further disclose the mechanisms of higher efficacy of CPX‐351 in s‐AML, with a focus on MRD. We analyzed 183 consecutive s‐AML elderly patients (median age 69, range 60–77) treated with CPX‐351 (n = 82) or receiving FLAG‐Ida (n = 101). Complete remission (CR) rate and MRD negativity probability were higher among patients receiving CPX‐351 (MRD negative CR rate of 40/64, 62.5%, compared to 25/55, 45% in patients who received FLAG‐Ida, p < 0.05). Extra‐hematological toxicity was lower in CPX‐351 arm, and 30 days mortality was 3.6% and 8% in patients receiving CPX‐351 or FLAG‐Ida, respectively. Notably, 21/64 (32.8%) CR patients treated with CPX 351 underwent allogeneic stem cell transplantation (HSCT), compared to 5/55 with FLAG‐Ida (9%, p < 0.05). Overall, CPX‐351 treatment resulted in higher OS (median OS 17.7 vs. 11.2 months with FLAG‐Ida, p < 0.05). The better outcome of CPX‐351 compared to FLAG‐Ida in our cohort may be explained by a greater probability of MRD negativity, alongside with an improved tolerance, enabling more s‐AML patients to undergo HSCT.
Maintenance of Cardiac Microenvironmental Homeostasis: A Joint Battle of Multiple Cells
Authors: Yao Jiayu , Zhang Youtao , Wang Ziwen , Chen Yuejun , Shi Xingjuan
Published: December 2024

Various cells such as cardiomyocytes, fibroblasts and endothelial cells constitute integral components of cardiac tissue. The health and stability of cardiac ecosystem are ensured by the action of a certain type of cell and the intricate interactions between multiple cell types. The dysfunctional cells exert a profound impact on the development of cardiovascular diseases by involving in the pathological process. In this paper, we introduce the dynamic activity, cell surface markers as well as biological function of the various cells in the heart. Besides, we discuss the multiple signaling pathways involved in the cardiac injury including Hippo/YAP, TGF‐β/Smads, PI3K/Akt, and MAPK signaling. The complexity of different cell types poses a great challenge to the disease treatment. By characterizing the roles of various cell types in cardiovascular diseases, we sought to discuss the potential strategies for preventing and treating cardiovascular diseases.
The Cyclic and Episodic Transition of Strong El Niño and Implications for South American Precipitation During Their Peak and Decay Stages
Authors: Mamani Leonardo , Andreoli Rita V. , de Souza Itamara Parente , Kayano Mary Toshie , Cevalho Wallace , Sales Djanir , Ferreira de Souza Rodrigo A.
Published: December 2024

The mechanisms associated with the transitions of strong El Niño (EN) events and their implications for the South American precipitation were investigated for the 1950–2023 period. Strong EN events exhibit cyclic or episodic characteristics in their transitions. Cyclic EN events are both preceded and followed by La Niña (LN) conditions, whereas episodic EN events are preceded by neutral conditions, with a more uncertain transition following. For cyclic EN, tropical Pacific mechanisms initiates and peak warming in the eastern tropical Pacific from austral winter to early summer. In contrast, for episodic EN, coupled subtropical and tropical Pacific mechanisms, respectively, initiate and peak warming in the central tropical Pacific from autumn to late summer. The Pacific Decadal Oscillation (PDO) mean state modulates EN's decay stage. During the +PDO mean state, cyclones in the eastern subtropical Pacific of both hemispheres sustain the warming of episodic EN, whereas during the −PDO mean state, anticyclones in the eastern subtropical Pacific accelerate the decay of cyclic EN, favouring its transition to an LN. These mechanisms explain why episodic EN initiates earlier, peaks later, is more intense and decays more slowly than cyclic EN. During an episodic EN summer, the strengthened atmospheric circulation maintains the Atlantic Intertropical Convergence Zone (ITCZ) north of the equator, causing persistent negative precipitation anomalies in north–northeastern South America (SA) until the following winter, while positive precipitation anomalies in southeastern SA are driven by south–southeastward moisture transport from equatorial Atlantic. Conversely, during a cyclic EN summer, negative (positive) precipitation anomalies impact north–northwestern (southeastern) SA; however, the anomalous atmospheric circulation and precipitation in SA quickly return to normal conditions in the autumn, and positive precipitation anomalies appear in northern SA in the following winter. Understanding these mechanisms is crucial for predicting EN's future changes and, consequently, their potential socio‐economic impacts globally.
Desertification Reduces Organic Carbon Content and Nutrient Availability in Dryland Soils: Evidence From a Survey in the Amu Darya River Basin
Authors: Zhang Peng , He Mingzhu , Wang Jin , Huang Lei , Yang Haotian , Song Guang , Zhao Jiecai , Li Xinrong
Published: December 2024

Desertification degrades drylands, undermining ecosystem services and human well‐being as a serious global issue. Assessing desertification impacts on soil organic carbon (SOC) and properties aids in preserving drylands and combating desertification. However, knowledge gaps persist regarding desertification effects on SOC and soil in Central Asia's Amu Darya River Basin. Surveys across ~1000 km in this region showed that desertification decreased SOC by ~52% versus natural vegetation. Desertification also reduced nutrient availability and altered hydrothermal conditions, pH, stoichiometry, and herbaceous richness. In particular, it decreased soil clay and silt while increasing sand content. Regional climate change and prolonged grazing are primary desertification drivers here. These pronounced impacts on soils and vegetation may threaten ecological processes and services. Our findings contribute to dryland restoration efforts and resilience against desertification.
Seagrasses under stress: Independent negative effects of elevated temperature and light reduction at multiple levels of organization
Authors: Bass Alissa V. , Falkenberg Laura J. , Thibodeau Benoit
Published: December 2024

Seagrasses are important foundation species, which support coastal biodiversity and provide socioeconomic benefits. However, seagrasses are threatened by anthropogenic changes, including the elevated temperature associated with marine heatwaves (MHWs) and light limitation from eutrophication or increased sedimentation. In this experiment, we exposed the seagrass Halophila ovalis to 10‐d of elevated temperature, simulating a MHW, and three light intensities to examine the impacts on multiple levels of organization, that is, growth, productivity, nitrogen cycling, and leaf microbiome. We found that both the MHW temperature and decreased light independently negatively impacted seagrass growth of new leaves, with decreased light also reducing new leaf area and rhizome elongation rate, and the occurrence of MHW temperatures increasing the rate of leaf loss. Similarly, chlorophyll concentration was altered by both stressors independently, with a common response to reduced light (increased chlorophyll concentration) significantly lower under the MHW temperature. Nitrogen assimilation rate into the leaves also decreased under both MHW temperature and reduced light availability. The leaf microbiome shifted in response to the MHW temperature and lower light, with these conditions prompting relatively more anaerobic microbes but less oxidative stress‐tolerant bacteria, and less prokaryotes performing phototrophy and (oxygenic) photoautotrophy. In conclusion, we show elevated temperature representing a MHW and light limitation can drive decreased seagrass growth, chlorophyll concentration, and cause shifts in leaf microbial functional groups, although there was little interaction between stressors. It is therefore important that good water clarity and habitat health is maintained to reduce the susceptibility of seagrasses to extreme climatic events.
Structural Insight on the Selectivity of Calyx[4]Arene‐Based Inhibitors of Mg2+−Dependent Atp‐Hydrolases
Authors: Rayevsky Alexey , Platonov Maksym , Elijah Bulgakov , Volochnyuk Dmytro , Veklich Tetyana , Cherenok Sergiy , Rodik Roman , Kalchenko Vitaliy , Kosterin Sergiy
Published: December 2024

Located in plasma membranes, ATP hydrolases are involved in several dynamic transport processes, helping to control the movement of ions across cell membranes. ATP hydrolase acts as a transport protein, converting energy from ATP hydrolysis into transport molecules against their concentration gradients. In addition to energy metabolism and active transport, ATP hydrolase is essential for maintaining cellular homeostasis and cell function. This study focused on the domain architecture model of P‐type ATPases, which participate in the reaction cycles of ATP hydrolysis carried out by membrane transport systems – Na+, K+‐ATPase and Ca2+, Mg2+‐ATPase. Targeted modulation of Na+, K+‐ATPase and Ca2+, Mg2+‐ATPase by unnatural drugs is of greatest interest due to the lack of known effectors. This new discovery presents a convenient model based on our recent experimental studies of the membrane structures and myocytes of the uterine smooth muscle, the myometrium. This current study strongly supports the fact that nanosized calix[4]arenes functionalised on the upper rings of the macrocycle with biologically active phosphonic acid fragments can serve as selective and potent inhibitors of cation‐transporting electroenzymes. This is how we discovered that calix[4]arene of methylenebisphosphonic acid C‐97 and calix[4]arene of bis‐aminophosphonic acid C‐107 selectively and effectively (I0.5 <100 nM) inhibit the activity of Mg2+, ATP‐dependent electrogenic Na+ K+ plasma membrane pump. As drug discovery in the field of Mg2+‐ATPase inhibitors is uncharted territory, basic research holds the key to explaining and predicting the mechanism of interaction and action of different classes of compounds. In light of the presented results, new calix[4]arene compounds can be used as potent inhibitors of Mg2+, ATP‐dependent electrogenic ion pumps.
GLP‐1 enhances β‐cell response to protein ingestion and bariatric surgery amplifies it
Authors: Rayas Maria , Pezzica Samantha , Honka Henri , Carli Fabrizia , Peterson Richard , DeFronzo Ralph , Gastaldelli Amalia , Salehi Marzieh
Published: December 2024

Objective

The glycemic‐independent actions of glucagon‐like peptide‐1 (GLP‐1) in the prandial state in humans are unknown. We examined the contribution of GLP‐1 to β‐cell secretory response (primary endpoint) and glucose metabolism during protein ingestion under basal glycemia, as well as whether these responses are affected by rerouted gut after gastric bypass (GB) or sleeve gastrectomy (SG).

Methods

Insulin secretion rate (ISR) and glucose fluxes during a 50‐g oral protein load were compared among 10 nondiabetic individuals with GB, 9 with SG, and 7 non‐operated controls (CN), with and without intravenous infusion of exendin(9‐39) (Ex‐9), a GLP‐1 receptor (GLP‐1R) antagonist.

Results

Blocking GLP‐1R increased glucose before and after protein ingestion and decreased β‐cell sensitivity to glucose in the first 30 min of protein ingestion in all three groups (p < 0.05). Reduction in the premeal ISR by Ex‐9 infusion was only observed in CN, whereas diminished prandial ISR3h by GLP‐1R blockade was only observed in GB and SG (p < 0.05 for interaction). GLP‐1R blockade enhanced post‐protein insulin action in GB and SG, but not in CN, and exaggerated endogenous glucose production only GB (p < 0.05 for interaction).

Conclusions

These findings are consistent with both pancreatic and extra‐pancreatic roles for GLP‐1 during protein ingestion in humans that are exaggerated by bariatric surgery.

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Long‐Term Stability and Oxidation of Ferroelectric AlScN Devices: An Operando Hard X‐ray Photoelectron Spectroscopy Study
Authors: Rehm Oliver , Baumgarten Lutz , Guido Roberto , Düring Pia Maria , Gloskovskii Andrei , Schlueter Christoph , Mikolajick Thomas , Schroeder Uwe , Müller Martina
Published: December 2024

Aluminum scandium nitride (Al1−xScxN) is a promising material for ferroelectric devices due to its large remanent polarization, scalability, and compatibility with semiconductor technology. By doping AlN with Sc, the bonds in the polar AlN structure are weakened, which enables ferroelectric switching below the dielectric breakdown field. However, one disadvantage of Sc doping is that it increases the material's tendency toward oxidation. Herein, the oxidation process of tungsten‐capped and uncapped Al0.83Sc0.17N thin films is investigated by hard X‐ray photoelectron spectroscopy (HAXPES). The samples is exposed to air for either 2 weeks or 6 months. HAXPES spectra indicate the replacement of nitrogen by oxygen and the tendency of oxygen to favor oxidation with Sc rather than Al. The appearance of an N2 spectral feature thus can be directly related to the oxidation process. An oxidation model that mimics these spectroscopic results of the element‐specific oxidation processes within Al1−xScxN is presented. Finally, in operando HAXPES data of uncapped and capped AlScN‐capacitor stacks are interpreted using the proposed model.
Event‐Triggered Control for Stabilization of Semilinear N‐D Reaction‐Convection‐Diffusion PDE by Switching
Authors: Kang Wen , Fridman Emilia , Zhang Jing , Wang Jun‐Min
Published: December 2024

This paper addresses a switched sampled‐data control design for stabilization of the N‐dimensional (N‐D) semilinear heat equation with a mobile actuator. It is supposed that discrete‐time averaged measurements are available. The system is known to be stabilizable by the static output‐feedback employing several distributed in space actuators and sensors, but is not stabilizable by only one of the actuator‐sensor pairs. Does there exist a switching stabilizing static output‐feedback such that at all times, only one actuator‐sensor pair is active? In our recent paper we gave a positive answer and found the appropriate switching sampled‐data time‐triggered control law for the one‐dimensional (1‐D) case. In this paper, to enlarge the time between switching (which means to reduce the frequency of actuator moving to the active domain), we present an event‐triggered control for stabilization by switching. Moreover, we extend the results for stabilization by switching to the N‐D case. Numerical examples show that the switching‐based event‐triggered controller essentially decreases the frequency of the actuator moving compared to the time‐triggered controller, reducing operating costs.
Type I Porous Liquids with Super‐Low Viscosities: the Construction through a Rather Simple One‐Step Covalent Linkage Strategy and Its Facile Regulation by a Mixed‐Ligand Strategy
Authors: Wang Dechao , Xin Yangyang , Fan Wendi , Li Peipei , Zhou Wenwu , Liu Jianwei , Qian Libing , Ning Hailong , Zhang Yating , Ying Yunpan , Yao Dongdong , Yang Zhiyuan , Zheng Yaping
Published: December 2024

Porous liquids (PLs) are a novel class of flowing liquid systems that possess accessible permanent porosity, exhibiting great prospects in gas capture and separation. Nevertheless, the further development of PLs lies in the facile synthesis and regulation of PLs with low viscosities. Herein, a novel strategy of preparing type I PLs with super‐low viscosity is proposed through a simple one‐step covalent linkage reaction using UiO‐66‐NH2 as the pore generator and monoglycidyl ether terminated polydimethylsiloxane (E‐PDMS) as the sterically hindered solvent, respectively. More importantly, the idea that PLs can be regulated like advanced porous materials (APMs) is proposed and demonstrated, that is, PLs can be regulated by modulating pore generators with the mixed‐ligands method. As expected, the resultant PLs not only demonstrate a promising potential in CO2 sorption as a flowing sorbent but also exhibit a superior CO2/N2 selective separation. Meanwhile, positron annihilation lifetime spectrum (PALS) and molecular dynamics (MD) simulations further verify the accessible permanent porosity and the favorable CO2 selective sorption. This work provides a simple and facile method to prepare type I PLs with super‐low viscosities, shedding light on the precise regulation of PLs toward task‐specific applications.
Precision Control of Cell Type‐Specific Behavior via RNA Sensing and Editing
Authors: Xiao Lulu , Qin Bo , Zhang Xinyue , Yao Yufeng , Dou Xiaoyan , Liu Yuchen , Duan Xuanchu
Published: December 2024

In the realms of bioengineering and biopharmaceuticals, there exists a critical demand for advanced genetic tools that can interact with specific cell signaling pathways to accurately identify and target various cell types. This research introduces the innovative CRISPR‐ADAReader system, which enables precise manipulation of cell activity through sensing target RNA. Featuring both positive and negative feedback loops, the system allows for tailored regulation across different cell types in response to various internal signals, showcasing exceptional programmability, specificity, and sensitivity. By choosing distinct RNAs as activation signals, the CRISPR‐ADAReader efficiently monitors and alters targeted cell behaviors. In a case study focusing on retinoblastoma treatment, the system distinctively initiates positive feedback and self‐silencing actions by detecting MCYN and Rb transcripts, thus safeguarding normal retinal pigment epithelial cells while promoting apoptosis in cancer cells. Moreover, the CRISPR‐ADAReader demonstrates significant anti‐tumor effectiveness in live models, markedly reducing retinoblastoma cell proliferation through the activation of several cancer‐suppression pathways, outperforming the capabilities of the ADAR‐sensor. Notably, the system also shows an excellent in vivo safety profile. In conclusion, the CRISPR‐ADAReader system represents a groundbreaking method for the detection and editing of RNA, offering a potent instrument for the customized and precise governance of cell behavior.
Beyond Core–Shell Micellar Structures: Complex Structures in Simple Surfactants
Authors: Cezar Henrique Musseli , Bjørnestad Victoria Ariel , Prévost Sylvain , Lund Reidar , Cascella Michele
Published: December 2024

Small‐angle X‐ray/neutron scattering (SAXS/SANS) techniques provide valuable nanostructural information of self‐assembling molecules. However, extracting the information from these experiments can be a challenging task, usually relying on predetermined assumptions. Conventional models for surfactant micelles consider a core–shell structure with a hydrophobic tail encapsulated by the hydrophilic part. This approach is successful in many cases but can fail even for common surfactants such as Triton X‐100 (TX‐100). SAXS and SANS combined with Metainference molecular simulations are employed to investigate TX‐100 assemblies, showing how more complex models, with diffuse core–shell boundaries, multilayering, and polydispersity, are needed to explain the aggregation. This is the first time that Metainference is employed with SAXS and SANS simultaneously to obtain the structural ensemble of assemblies. Compared to regular micelles formed by chemically similar C12EO10 molecules, the role of the hydrophobic core in micellization is discussed, finding that the relatively shorter and less hydrophobic tail of TX‐100 favors polymorphism.
Reparaturschweißen an Brücken im Betrieb
Authors: Begemann Florian , Unglaub Julian , Hensel Jonas , Thiele Klaus
Published: December 2024

An Stahlbrücken treten infolge von zunehmenden Verkehrsbelastungen sowie Konstruktions‐ und Ausführungsmängeln immer wieder Ermüdungsschäden in Schweißnähten auf. Zur Ausführung der Instandsetzungsarbeiten muss die Brücke beim Neuverschweißen für den Verkehr gesperrt werden, um Bewegungen an den Rissflanken zu vermeiden. Schweißarbeiten bei laufendem Verkehr sind nach heutigem Stand der Technik noch nicht zulässig, da bisher nur unzureichende Kenntnisse über erreichbare Nahtgüten und Schwingfestigkeiten betriebsgeschweißter Schweißnähte vorlagen. Ziel ist es, sichere Methoden bereitzustellen, die Schweißarbeiten an Stahlkonstruktionen unter fließendem Verkehr bzw. unter zyklischer Belastung erlauben. Als Grundlage wurden Messungen an einer repräsentativen Stahlbrücke durchgeführt, um realitätsnahe Spaltöffnungsparameter für umfangreiche Schweißversuche unter zyklischer Belastung abzuleiten. Dabei stellt die Beschreibung des Rissverhaltens und der Kraftumverteilung beim Betriebsschweißen eine besondere Herausforderung im Labor dar. Zur Quantifizierung des Einflusses unterschiedlicher Schweißrandbedingungen wurden die experimentellen Untersuchungen unter reiner Weg‐ sowie Kraftregelung umgesetzt. In beiden Grenzfällen konnten normgerechte Schweißnahtqualitäten und Ermüdungsfestigkeiten erreicht werden, die die technische Umsetzbarkeit von Betriebsschweißungen unter Einhaltung definierter Randbedingungen belegen.