bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ enzymatic control of colloidal phoresis and catalysis through hydrolysis of ATP
Authors: Shandilya Ekta , Rallabandi Bhargav , Maiti Subhabrata
Published: April 2024

The ability to sense chemical gradients and respond with directional motility and chemical activity is a defining feature of complex living systems. There is a strong interest among scientists to design synthetic systems that emulate these properties. Here, we realize and control such behaviors in a synthetic system by tailoring multivalent interactions of adenosine nucleotides with catalytic microbeads. We first show that multivalent interactions of the bead with gradients of adenosine mono-, di- and trinucleotides (AM/D/TP) control both the phoretic motion and a proton-transfer catalytic reaction, and find that both effects are diminished greatly with increasing valence of phosphates. We exploit this behavior by using enzymatic hydrolysis of ATP to AMP, which downregulates multivalent interactivity in situ. This produces a sudden increase in transport of the catalytic microbeads (a phoretic jump), which is accompanied by increased catalytic activity. Finally, we show how this enzymatic activity can be systematically tuned, leading to simultaneous in situ spatial and temporal control of the location of the microbeads, as well as the products of the reaction that they catalyze. These findings open up new avenues for utilizing multivalent interaction-mediated programming of complex chemo-mechanical behaviors into active systems.
All-natural 2D nanofluidics as highly-efficient osmotic energy generators
Authors: Tang Jiadong , Wang Yun , Yang Hongyang , Zhang Qianqian , Wang Ce , Li Leyuan , Zheng Zilong , Jin Yuhong , Wang Hao , Gu Yifan , Zuo Tieyong
Published: April 2024

Two-dimensional nanofluidics based on naturally abundant clay are good candidates for harvesting osmotic energy between the sea and river from the perspective of commercialization and environmental sustainability. However, clay-based nanofluidics outputting long-term considerable osmotic power remains extremely challenging to achieve due to the lack of surface charge and mechanical strength. Here, a two-dimensional all-natural nanofluidic (2D-NNF) is developed as a robust and highly efficient osmotic energy generator based on an interlocking configuration of stacked montmorillonite nanosheets (from natural clay) and their intercalated cellulose nanofibers (from natural wood). The generated nano-confined interlamellar channels with abundant surface and space negative charges facilitate selective and fast hopping transport of cations in the 2D-NNF. This contributes to an osmotic power output of ~8.61 W m−2 by mixing artificial seawater and river water, higher than other reported state-of-the-art 2D nanofluidics. According to detailed life cycle assessments (LCA), the 2D-NNF demonstrates great advantages in resource consumption (1/14), greenhouse gas emissions (1/9), and production costs (1/13) compared with the mainstream 2D nanofluidics, promising good sustainability for large-scale and highly-efficient osmotic power generation.
Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane
Authors: Zeng Junlan , Liu Xiaoqiang , Dong Zhaoyue , Zhang Fangyuan , Qiu Fei , Zhong Mingyu , Zhao Tengfei , Yang Chunxian , Zeng Lingjiang , Lan Xiaozhong , Zhang Hongbo , Zhou Junhui , Chen Min , Tang Kexuan , Liao Zhihua
Published: April 2024

Solanaceous plants produce tropane alkaloids (TAs) via esterification of 3α- and 3β-tropanol. Although littorine synthase is revealed to be responsible for 3α-tropanol esterification that leads to hyoscyamine biosynthesis, the genes associated with 3β-tropanol esterification are unknown. Here, we report that a BAHD acyltransferase from Atropa belladonna, 3β-tigloyloxytropane synthase (TS), catalyzes 3β-tropanol and tigloyl-CoA to form 3β-tigloyloxytropane, the key intermediate in calystegine biosynthesis and a potential drug for treating neurodegenerative disease. Unlike other cytosolic-localized BAHD acyltransferases, TS is localized to mitochondria. The catalytic mechanism of TS is revealed through molecular docking and site-directed mutagenesis. Subsequently, 3β-tigloyloxytropane is synthesized in tobacco. A bacterial CoA ligase (PcICS) is found to synthesize tigloyl-CoA, an acyl donor for 3β-tigloyloxytropane biosynthesis. By expressing TS mutant and PcICS, engineered Escherichia coli synthesizes 3β-tigloyloxytropane from tiglic acid and 3β-tropanol. This study helps to characterize the enzymology and chemodiversity of TAs and provides an approach for producing 3β-tigloyloxytropane.
Integrated 2D multi-fin field-effect transistors
Authors: Yu Mengshi , Tan Congwei , Yin Yuling , Tang Junchuan , Gao Xiaoyin , Liu Hongtao , Ding Feng , Peng Hailin
Published: April 2024

Vertical semiconducting fins integrated with high-κoxide dielectrics have been at the centre of the key device architecture that has promoted advanced transistor scaling during the last decades. Single-fin channels based on two-dimensional (2D) semiconductors are expected to offer unique advantages in achieving sub-1 nm fin-width and atomically flat interfaces, resulting in superior performance and potentially high-density integration. However, multi-fin structures integrated with high-κdielectrics are commonly required to achieve higher electrical performance and integration density. Here we report a ledge-guided epitaxy strategy for growing high-density, mono-oriented 2D Bi2O2Se fin arrays that can be used to fabricate integrated 2D multi-fin field-effect transistors. Aligned substrate steps enabled precise control of both nucleation sites and orientation of 2D fin arrays. Multi-channel 2D fin field-effect transistors based on epitaxially integrated 2D Bi2O2Se/Bi2SeO5fin-oxide heterostructures were fabricated, exhibiting an on/off current ratio greater than 106, high on-state current, low off-state current, and high durability. 2D multi-fin channel arrays integrated with high-κoxide dielectrics offer a strategy to improve the device performance and integration density in ultrascaled 2D electronics.
VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance
Authors: Pichol-Thievend Cathy , Anezo Oceane , Pettiwala Aafrin M. , Bourmeau Guillaume , Montagne Remi , Lyne Anne-Marie , Guichet Pierre-Olivier , Deshors Pauline , Ballestín Alberto , Blanchard Benjamin , Reveilles Juliette , Ravi Vidhya M. , Joseph Kevin , Heiland Dieter H. , Julien Boris , Leboucher Sophie , Besse Laetitia , Legoix Patricia , Dingli Florent , Liva Stephane , Loew Damarys , Giani Elisa , Ribecco Valentino , Furumaya Charita , Marcos-Kovandzic Laura , Masliantsev Konstantin , Daubon Thomas , Wang Lin , Diaz Aaron A. , Schnell Oliver , Beck Jürgen , Servant Nicolas , Karayan-Tapon Lucie , Cavalli Florence M. G. , Seano Giorgio
Published: April 2024

Glioblastoma (GBM) is a highly lethal type of cancer. GBM recurrence following chemoradiation is typically attributed to the regrowth of invasive and resistant cells. Therefore, there is a pressing need to gain a deeper understanding of the mechanisms underlying GBM resistance to chemoradiation and its ability to infiltrate. Using a combination of transcriptomic, proteomic, and phosphoproteomic analyses, longitudinal imaging, organotypic cultures, functional assays, animal studies, and clinical data analyses, we demonstrate that chemoradiation and brain vasculature induce cell transition to a functional state named VC-Resist (vessel co-opting and resistant cell state). This cell state is midway along the transcriptomic axis between proneural and mesenchymal GBM cells and is closer to the AC/MES1-like state. VC-Resist GBM cells are highly vessel co-opting, allowing significant infiltration into the surrounding brain tissue and homing to the perivascular niche, which in turn induces even more VC-Resist transition. The molecular and functional characteristics of this FGFR1-YAP1-dependent GBM cell state, including resistance to DNA damage, enrichment in the G2M phase, and induction of senescence/stemness pathways, contribute to its enhanced resistance to chemoradiation. These findings demonstrate how vessel co-option, perivascular niche, and GBM cell plasticity jointly drive resistance to therapy during GBM recurrence.
Engineering is evolution: a perspective on design processes to engineer biology
Authors: Castle Simeon D. , Stock Michiel , Gorochowski Thomas E.
Published: April 2024

Careful consideration of how we approach design is crucial to all areas of biotechnology. However, choosing or developing an effective design methodology is not always easy as biology, unlike most areas of engineering, is able to adapt and evolve. Here, we put forward that design and evolution follow a similar cyclic process and therefore all design methods, including traditional design, directed evolution, and even random trial and error, exist within an evolutionary design spectrum. This contrasts with conventional views that often place these methods at odds and provides a valuable framework for unifying engineering approaches for challenging biological design problems.
Efficient tandem electroreduction of nitrate into ammonia through coupling Cu single atoms with adjacent Co3O4
Authors: Liu Yan , Wei Jie , Yang Zhengwu , Zheng Lirong , Zhao Jiankang , Song Zhimin , Zhou Yuhan , Cheng Jiajie , Meng Junyang , Geng Zhigang , Zeng Jie
Published: April 2024

The nitrate (NO3−) electroreduction into ammonia (NH3) represents a promising approach for sustainable NH3 synthesis. However, the variation of adsorption configurations renders great difficulties in the simultaneous optimization of binding energy for the intermediates. Though the extensively reported Cu-based electrocatalysts benefit NO3− adsorption, one of the key issues lies in the accumulation of nitrite (NO2−) due to its weak adsorption, resulting in the rapid deactivation of catalysts and sluggish kinetics of subsequent hydrogenation steps. Here we report a tandem electrocatalyst by combining Cu single atoms catalysts with adjacent Co3O4 nanosheets to boost the electroreduction of NO3− to NH3. The obtained tandem catalyst exhibits a yield rate for NH3 of 114.0 mg$${}_{{{{{{\rm{NH}}}}}}_3}$$

NH

3

h−1 cm−2, which exceeds the previous values for the reported Cu-based catalysts. Mechanism investigations unveil that the combination of Co3O4 regulates the adsorption configuration of NO2− and strengthens the binding with NO2−, thus accelerating the electroreduction of NO3− to NH3.
Self-condensation-assisted chemical vapour deposition growth of atomically two-dimensional MOF single-crystals
Authors: Luo Lingxin , Hou Lingxiang , Cui Xueping , Zhan Pengxin , He Ping , Dai Chuying , Li Ruian , Dong Jichen , Zou Ye , Liu Guoming , Liu Yanpeng , Zheng Jian
Published: April 2024

Two-dimensional metal-organic frameworks (MOFs) have a wide variety of applications in molecular separation and other emerging technologies, including atomically thin electronics. However, due to the inherent fragility and strong interlayer interactions, high-quality MOF crystals of atomic thickness, especially isolated MOF crystal monolayers, have not been easy to prepare. Here, we report the self-condensation-assisted chemical vapour deposition growth of atomically thin MOF single-crystals, yielding monolayer single-crystals of poly[Fe(benzimidazole)2] up to 62 μm in grain sizes. By using transmission electron microscopy and high-resolution atomic force microscopy, high crystallinity and atomic-scale single-crystal structure are verified in the atomically MOF flakes. Moreover, integrating such MOFs with MoS2 to construct ultrathin van der Waals heterostructures is achieved by direct growth of atomically MOF single-crystals onto monolayer MoS2, and enables a highly selective ammonia sensing. These demonstrations signify the great potential of the method in facilitating the development of the fabrication and application of atomically thin MOF crystals.
Optimal quantum key distribution networks: capacitance versus security
Authors: Cirigliano Lorenzo , Brosco Valentina , Castellano Claudio , Conti Claudio , Pilozzi Laura
Published: April 2024

The rate and security of quantum communications between users placed at arbitrary points of a quantum communication network depend on the structure of the network, on its extension and on the nature of the communication channels. In this work we propose a strategy for the optimization of trusted-relays based networks that intertwines classical network approaches and quantum information theory. Specifically, by suitably defining a quantum communication efficiency functional, we identify the optimal quantum communication connections through the network by balancing security and the quantum communication rate. The optimized network is then constructed as the network of the maximal quantum communication efficiency connections and its performance is evaluated by studying the scaling of average properties as functions of the number of nodes and of the network spatial extension.
Hunting for quantum-classical crossover in condensed matter problems
Authors: Yoshioka Nobuyuki , Okubo Tsuyoshi , Suzuki Yasunari , Koizumi Yuki , Mizukami Wataru
Published: April 2024

The intensive pursuit for quantum advantage in terms of computational complexity has further led to a modernized crucial question of when and how will quantum computers outperform classical computers. The next milestone is undoubtedly the realization of quantum acceleration in practical problems. Here we provide a clear evidence and arguments that the primary target is likely to be condensed matter physics. Our primary contributions are summarized as follows: 1) Proposal of systematic error/runtime analysis on state-of-the-art classical algorithm based on tensor networks; 2) Dedicated and high-resolution analysis on quantum resource performed at the level of executable logical instructions; 3) Clarification of quantum-classical crosspoint for ground-state simulation to be within runtime of hours using only a few hundreds of thousand physical qubits for 2d Heisenberg and 2d Fermi-Hubbard models, assuming that logical qubits are encoded via the surface code with the physical error rate of p = 10−3. To our knowledge, we argue that condensed matter problems offer the earliest platform for demonstration of practical quantum advantage that is order-of-magnitude more feasible than ever known candidates, in terms of both qubit counts and total runtime.
Structural, angiogenic, and immune responses influencing myocardial regeneration: a glimpse into the crucible
Authors: Baccouche Basil M. , Elde Stefan , Wang Hanjay , Woo Y. Joseph
Published: April 2024

Complete cardiac regeneration remains an elusive therapeutic goal. Although much attention has been focused on cardiomyocyte proliferation, especially in neonatal mammals, recent investigations have unearthed mechanisms by which non-cardiomyocytes, such as endothelial cells, fibroblasts, macrophages, and other immune cells, play critical roles in modulating the regenerative capacity of the injured heart. The degree to which each of these cell types influence cardiac regeneration, however, remains incompletely understood. This review highlights the roles of these non-cardiomyocytes and their respective contributions to cardiac regeneration, with emphasis on natural heart regeneration after cardiac injury during the neonatal period.
Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant
Authors: de Oliveira Raphaela M. , Paiva Mariana U. B. , Picossi Carolina R. C. , Paiva Diego V. N. , Ricart Carlos A. O. , Ruperez Francisco J. , Barbas Coral , Atik Fernando A. , Martins Aline M. A.
Published: April 2024

Heart failure (HF) studies typically focus on ischemic and idiopathic heart diseases. Chronic chagasic cardiomyopathy (CCC) is a progressive degenerative inflammatory condition highly prevalent in Latin America that leads to a disturbance of cardiac conduction system. Despite its clinical and epidemiological importance, CCC molecular pathogenesis is poorly understood. Here we characterize and discriminate the plasma metabolomic profile of 15 patients with advanced HF referred for heart transplantation – 8 patients with CCC and 7 with idiopathic dilated cardiomyopathy (IDC) – using gas chromatography/quadrupole time-of-flight mass spectrometry. Compared to the 12 heart donor individuals, also included to represent the control (CTRL) scenario, patients with advanced HF exhibited a metabolic imbalance with 21 discriminating metabolites, mostly indicative of accumulation of fatty acids, amino acids and important components of the tricarboxylic acid (TCA) cycle. CCC vs. IDC analyses revealed a metabolic disparity between conditions, with 12 CCC distinctive metabolites vs. 11 IDC representative metabolites. Disturbances were mainly related to amino acid metabolism profile. Although mitochondrial dysfunction and loss of metabolic flexibility may be a central mechanistic event in advanced HF, metabolic imbalance differs between CCC and IDC populations, possibly explaining the dissimilar clinical course of Chagas’ patients.
Gross morphology and adhesion-associated physical properties of Drosophila larval salivary gland glue secretion
Authors: Beňo Milan , Beňová-Liszeková Denisa , Kostič Ivan , Šerý Michal , Mentelová Lucia , Procházka Michal , Šoltýs Ján , Trusinová Ludmila , Ritomský Mário , Orovčík Lubomír , Jerigová Monika , Velič Dušan , Machata Peter , Omastová Mária , Chase Bruce A. , Farkaš Robert
Published: April 2024

One of the major functions of the larval salivary glands (SGs) of many Drosophila species is to produce a massive secretion during puparium formation. This so-called proteinaceous glue is exocytosed into the centrally located lumen, and subsequently expectorated, serving as an adhesive to attach the puparial case to a solid substrate during metamorphosis. Although this was first described almost 70 years ago, a detailed description of the morphology and mechanical properties of the glue is largely missing. Its main known physical property is that it is released as a watery liquid that quickly hardens into a solid cement. Here, we provide a detailed morphological and topological analysis of the solidified glue. We demonstrated that it forms a distinctive enamel-like plaque that is composed of a central fingerprint surrounded by a cascade of laterally layered terraces. The solidifying glue rapidly produces crystals of KCl on these alluvial-like terraces. Since the properties of the glue affect the adhesion of the puparium to its substrate, and so can influence the success of metamorphosis, we evaluated over 80 different materials for their ability to adhere to the glue to determine which properties favor strong adhesion. We found that the alkaline Sgs-glue adheres strongly to wettable and positively charged surfaces but not to neutral or negatively charged and hydrophobic surfaces. Puparia formed on unfavored materials can be removed easily without leaving fingerprints or cascading terraces. For successful adhesion of the Sgs-glue, the material surface must display a specific type of triboelectric charge. Interestingly, the expectorated glue can move upwards against gravity on the surface of freshly formed puparia via specific, unique and novel anatomical structures present in the puparial’s lateral abdominal segments that we have named bidentia.
Aerobic vaginitis, bacterial vaginosis, and vaginal candidiasis among women of reproductive age in Arba Minch, southern Ethiopia
Authors: Aklilu Addis , Woldemariam Melat , Manilal Aseer , Koira Getahun , Alahmadi Reham M. , Raman Gurusamy , Idhayadhulla Akbar , Yihune Manaye
Published: April 2024

Reproductive tract infections (RTIs) are a persistent public health threat worldwide, particularly among women in low-income countries of Africa, including Ethiopia, where drug resistance is also a growing problem. It is crucial to address this problem to ensure women's health and well-being. A cross-sectional study was carried out among a cohort of 398 women of reproductive age who sought medical attention at the Gynecology Department of the Arba Minch General Hospital, southern Ethiopia, from January to June 2020. They were chosen through systematic random sampling, and a pre-tested structured questionnaire was used to collect the data. The collection of vaginal and/or cervical swabs were done to diagnose bacterial vaginosis (BV) and aerobic vaginitis (AV) using Nugent and AV score analyses, respectively. The swabs were subjected to standard microbiological culture techniques to detect the isolates causing AV and vaginal candidiasis (VC). The susceptibility profiles of the causative agents of AV were checked by the Kirby-Bauer disc diffusion technique. Descriptive and inferential statistical analyses were also done. Aerobic vaginitis was the predominantly diagnosed RTI (n = 122, 30.7%), followed by BV (n = 117, 29.4%) and VC (n = 111, 27.9%). The prominent bacteria of AV were Escherichia coli (n = 36, 34.2%) and Klebsiella pneumoniae (n = 30, 28.5%). The overall rate of multidrug-resistant (MDR) bacteria was 65.71% (n = 69). History of abortion (p = 0.01; AOR = 4.0, 95% CI = 2.1, 7.7) and the habit of using vaginal pH-altering contraceptives (p = 0.01; AOR = 4.7, 95% CI = 2.5, 8.8) have the greatest odds of RTI. The high prevalence of RTIs in our study warrants an urgent intervention to minimize the associated morbidities and complications. The overall rate of MDR bacterial isolates necessitates the implementation of an effective surveillance program in the study setting.
Phylogenetic relationships, selective pressure and molecular markers development of six species in subfamily Polygonoideae based on complete chloroplast genomes
Authors: Feng Zhan , Zheng Yan , Jiang Yuan , Pei Jin , Huang Linfang
Published: April 2024

The subfamily Polygonoideae encompasses a diverse array of medicinal and horticultural plants that hold significant economic value. However, due to the lack of a robust taxonomy based on phylogenetic relationships, the classification within this family is perplexing, and there is also a scarcity of reports on the chloroplast genomes of many plants falling under this classification. In this study, we conducted a comprehensive analysis by sequencing and characterizing the complete chloroplast genomes of six Polygonoideae plants, namely Pteroxygonum denticulatum, Pleuropterus multiflorus, Pleuropterus ciliinervis, Fallopia aubertii, Fallopia dentatoalata, and Fallopia convolvulus. Our findings revealed that these six plants possess chloroplast genomes with a typical quadripartite structure, averaging 162,931 bp in length. Comparative chloroplast analysis, codon usage analysis, and repetitive sequence analysis demonstrated a high level of conservation within the chloroplast genomes of these plants. Furthermore, phylogenetic analysis unveiled a distinct clade occupied by P. denticulatum, while P. ciliinrvis displayed a closer relationship to the three plants belonging to the Fallopia genus. Selective pressure analysis based on maximum likelihood trees showed that a total of 14 protein-coding genes exhibited positive selection, with psbB and ycf1 having the highest number of positive amino acid sites. Additionally, we identified four molecular markers, namely petN-psbM, psal-ycf4, ycf3-trnS-GGA, and trnL-UAG-ccsA, which exhibit high variability and can be utilized for the identification of these six plants.
Comparing the efficacy of concomitant treatment of resistance exercise and creatine monohydrate versus multiple individual therapies in age related sarcopenia
Authors: Elgizawy Eman I. , Amer Ghada S. , Ali Eman A. , Alqalashy Fatma S. , Ibrahim Marwa M. , Latif Asmaa A. Abdel , Shaban Anwar M.
Published: April 2024

Aging-related sarcopenia is a degenerative loss of strength and skeletal muscle mass that impairs quality of life. Evaluating NUDT3 gene and myogenin expression as new diagnostic tools in sarcopenia. Also, comparing the concomitant treatment of resistance exercise (EX) and creatine monohydrate (CrM) versus single therapy by EX, coenzyme Q10 (CoQ10), and CrM using aged rats. Sixty male rats were equally divided into groups. The control group, aging group, EX-treated group, the CoQ10 group were administered (500 mg/kg) of CoQ10, the CrM group supplied (0.3 mg/kg of CrM), and a group of CrM concomitant with resistance exercise. Serum lipid profiles, certain antioxidant markers, electromyography (EMG), nudix hydrolase 3 (NUDT3) expression, creatine kinase (CK), and sarcopenic index markers were measured after 12 weeks. The gastrocnemius muscle was stained with hematoxylin–eosin (H&E) and myogenin. The EX-CrM combination showed significant improvement in serum lipid profile, antioxidant markers, EMG, NUDT3 gene, myogenin expression, CK, and sarcopenic index markers from other groups. The NUDT3 gene and myogenin expression have proven efficient as diagnostic tools for sarcopenia. Concomitant treatment of CrM and EX is preferable to individual therapy because it reduces inflammation, improves the lipid serum profile, promotes muscle regeneration, and thus has the potential to improve sarcopenia.
Mechanical stimulation of induced pluripotent stem cell derived cardiac fibroblasts
Authors: Bekedam Fjodor T. , Smal Rowan , Smit Marisa C. , Aman Jurjan , Vonk-Noordegraaf Anton , Bogaard Harm Jan , Goumans Marie José , De Man Frances S. , Llucià-Valldeperas Aida
Published: April 2024

Cardiac fibrosis contributes to the development of heart failure, and is the response of cardiac fibroblasts (CFs) to pressure or volume overload. Limiting factors in CFs research are the poor availability of human cells and the tendency of CFs to transdifferentiate into myofibroblasts when cultured in vitro. The possibility to generate CFs from induced pluripotent stem cells (iPSC), providing a nearly unlimited cell source, opens new possibilities. However, the behaviour of iPSC-CFs under mechanical stimulation has not been studied yet. Our study aimed to assess the behaviour of iPSC-CFs under mechanical stretch and pro-fibrotic conditions. First, we confirm that iPSC-CFs are comparable to primary CFs at gene, protein and functional level. Furthermore, iPSC-derived CFs adopt a pro-fibrotic response to transforming growth factor beta (TGF-β). In addition, mechanical stretch inhibits TGF-β-induced fibroblast activation in iPSC-CFs. Thus, the responsiveness to cytokines and mechanical stimulation of iPSC-CFs demonstrates they possess key characteristics of primary CFs and may be useful for disease modelling.
The positive impact of smoking cessation on fracture risk in a nationwide cohort study
Authors: Park Jin-Sung , Kang Kyung-Chung , Park Se-Jun , Kim Jeong-Keun , Han Kyungdo , Hong Jae-Young
Published: April 2024

Many studies sought to demonstrate the association between smoking and fracture risk. However, the correlation between smoking and fractures remains controversial. This study aimed to examine the impact of smoking and smoking cessation on the occurrence of fractures using prospective nationwide cohort data. We enrolled those who underwent a National Health Insurance Service (NHIS) health checkup in 2009–2010 who had a previous health checkup 4-year prior (2005–2006). The study population of 4,028,559 subjects was classified into three groups (non-smoker, smoking cessation, current smoker). The study population was also analyzed according to fracture type (all fractures, vertebral fracture, hip fracture). Lastly, the smoking cessation group and current smoker group were divided into four subgroups based on a lifetime smoking amount cut-off of 20 pack-years (PY). Multivariate-adjusted hazard ratios (HRs) of fracture were examined through a Cox proportional hazards model. After multivariable adjustment, non-smokers showed the lowest risk of fracture (HR = 0.818, CI 0.807–0.828, p < 0.0001) and smoking cessation significantly lowered the risk of fracture (HR 0.938, 95% CI 0.917–0.959, p < 0.0001) compared to current smokers. Regardless of 20PY, all smoking cessation subgroups showed significantly less risk of fractures than current smokers with ≥ 20PYs. Smoking increases the risk of fracture, and smoking cessation lowers the risk of fracture.
Cognitive profile in multiple sclerosis and post-COVID condition: a comparative study using a unified taxonomy
Authors: Delgado-Alonso Cristina , Delgado-Alvarez Alfonso , Díez-Cirarda María , Oliver-Mas Silvia , Cuevas Constanza , Montero-Escribano Paloma , Ramos-Leví Ana Maria , Gil-Moreno María José , López-Carbonero Juan Ignacio , Hermann Bruce P. , Matias-Guiu Jorge , Matias-Guiu Jordi A.
Published: April 2024

Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.
Lead and copper removal from sterile dumps by phytoremediation with Robinia pseudoacacia
Authors: Chirilă Băbău Adriana Mihaela , Micle Valer , Damian Gianina Elena , Sur Ioana Monica
Published: April 2024

In Romania, huge quantities of gangue material from the mining activity practiced in the past were improperly stored and led to the pollution of the environment. Thus, this work is framed to manage the sterile dump of the “Radeș” mine (Alba, Romania) through a 12-week phytoremediation process. The efficient use of Robinia pseudoacacia was studied through the implementation, at the laboratory level, of a phytoremediation experiment based on various variants prepared by mixtures of gangue material, uncontaminated soil, and dehydrated sludge. The prepared variants, all planted with R. pseudoacacia, were watered with tap water, potassium monobasic phosphate, and enzyme solution. The bioconcentration and translocation factors for lead showed values ˂ 1, which indicates a potential presence of an exclusion system for Pb or a reduced Pb bioavailability since the R. pseudoacacia accumulates high concentrations of metals absorbed on and inside the roots. For copper, both factors had values > 1 indicating the suitability of R. pseudoacacia to readily translocate copper into the epigean organs. In the investigated experimental conditions, the highest efficiency in the removal of copper (93.0%) and lead (66.4%) by plants was obtained when gangue material was not mixed with other materials and wetted with enzymatic solution.
Effects of trimer repeats on Psidium guajava L. gene expression and prospection of functional microsatellite markers
Authors: Pires Giovanna Pinto , Fioresi Vinicius Sartori , Canal Drielli , Canal Dener Cezati , Fernandes Miquéias , Brustolini Otávio José Bernardes , de Avelar Carpinetti Paola , Ferreira Adésio , da Silva Ferreira Marcia Flores
Published: April 2024

Most research on trinucleotide repeats (TRs) focuses on human diseases, with few on the impact of TR expansions on plant gene expression. This work investigates TRs' effect on global gene expression in Psidium guajava L., a plant species with widespread distribution and significant relevance in the food, pharmacology, and economics sectors. We analyzed TR-containing coding sequences in 1,107 transcripts from 2,256 genes across root, shoot, young leaf, old leaf, and flower bud tissues of the Brazilian guava cultivars Cortibel RM and Paluma. Structural analysis revealed TR sequences with small repeat numbers (5–9) starting with cytosine or guanine or containing these bases. Functional annotation indicated TR-containing genes' involvement in cellular structures and processes (especially cell membranes and signal recognition), stress response, and resistance. Gene expression analysis showed significant variation, with a subset of highly expressed genes in both cultivars. Differential expression highlighted numerous down-regulated genes in Cortibel RM tissues, but not in Paluma, suggesting interplay between tissues and cultivars. Among 72 differentially expressed genes with TRs, 24 form miRNAs, 13 encode transcription factors, and 11 are associated with transposable elements. In addition, a set of 20 SSR-annotated, transcribed, and differentially expressed genes with TRs was selected as phenotypic markers for Psidium guajava and, potentially for closely related species as well.
A high efficiency precision genome editing method with CRISPR in iPSCs
Authors: Singh Avinash , Smedley G. Dalton , Rose Jamee-Grace , Fredriksen Kristina , Zhang Ying , Li Ling , Yuan Shauna H.
Published: April 2024

The use of genetic engineering to generate point mutations in induced pluripotent stem cells (iPSCs) is essential for studying a specific genetic effect in an isogenic background. We demonstrate that a combination of p53 inhibition and pro-survival small molecules achieves a homologous recombination rate higher than 90% using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in human iPSCs. Our protocol reduces the effort and time required to create isogenic lines.
Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C–H bond activation
Authors: Hu Xia , Cheng-Sánchez Iván , Kong Wangqing , Molander Gary A. , Nevado Cristina
Published: April 2024

The development of novel strategies to rapidly construct complex chiral molecules from readily available feedstocks is a long-term pursuit in the chemistry community. Radical-mediated alkene difunctionalizations represent an excellent platform towards this goal. However, asymmetric versions remain highly challenging, and more importantly, examples featuring simple hydrocarbons as reaction partners are elusive. Here we report an asymmetric three-component alkene dicarbofunctionalization capitalizing on the direct activation of C(sp3)–H bonds through the combination of photocatalysed hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for installing two vicinal carbon–carbon bonds across alkenes in an atom-economic fashion, providing a wide array of high-value chiral α-aryl/alkenyl carbonyls and phosphonates, as well as 1,1-diarylalkanes from ubiquitous alkane, ether and alcohol feedstocks. This method exhibits operational simplicity, broad substrate scope and excellent regioselectivity, chemoselectivity and enantioselectivity. The compatibility with bioactive motifs and expedient synthesis of pharmaceutically relevant molecules highlight the synthetic potential of this protocol.
Cold-shock proteome of myoblasts reveals role of RBM3 in promotion of mitochondrial metabolism and myoblast differentiation
Authors: Dey Paulami , Rajalaxmi Srujanika , Saha Pushpita , Thakur Purvi Singh , Hashmi Maroof Athar , Lal Heera , Saini Nistha , Singh Nirpendra , Ramanathan Arvind
Published: April 2024

Adaptation to hypothermia is important for skeletal muscle cells under physiological stress and is used for therapeutic hypothermia (mild hypothermia at 32  °C). We show that hypothermic preconditioning at 32  °C for 72 hours improves the differentiation of skeletal muscle myoblasts using both C2C12 and primary myoblasts isolated from 3 month and 18-month-old mice. We analyzed the cold-shock proteome of myoblasts exposed to hypothermia (32  °C for 6 and 48 h) and identified significant changes in pathways related to RNA processing and central carbon, fatty acid, and redox metabolism. The analysis revealed that levels of the cold-shock protein RBM3, an RNA-binding protein, increases with both acute and chronic exposure to hypothermic stress, and is necessary for the enhanced differentiation and maintenance of mitochondrial metabolism. We also show that overexpression of RBM3 at 37  °C is sufficient to promote mitochondrial metabolism, cellular proliferation, and differentiation of C2C12 and primary myoblasts. Proteomic analysis of C2C12 myoblasts overexpressing RBM3 show significant enrichment of pathways involved in fatty acid metabolism, RNA metabolism and the electron transport chain. Overall, we show that the cold-shock protein RBM3 is a critical factor that can be used for controlling the metabolic network of myoblasts.
Wnt/β-catenin signaling regulates amino acid metabolism through the suppression of CEBPA and FOXA1 in liver cancer cells
Authors: Nakagawa Saya , Yamaguchi Kiyoshi , Takane Kiyoko , Tabata Sho , Ikenoue Tsuneo , Furukawa Yoichi
Published: April 2024

Deregulation of the Wnt/β-catenin pathway is associated with the development of human cancer including colorectal and liver cancer. Although we previously showed that histidine ammonia lyase (HAL) was transcriptionally reduced by the β-catenin/TCF complex in liver cancer cells, the mechanism(s) of its down-regulation by the complex remain to be clarified. In this study, we search for the transcription factor(s) regulating HAL, and identify CEBPA and FOXA1, two factors whose expression is suppressed by the knockdown of β-catenin or TCF7L2. In addition, RNA-seq analysis coupled with genome-wide mapping of CEBPA- and FOXA1-binding regions reveals that these two factors also increase the expression of arginase 1 (ARG1) that catalyzes the hydrolysis of arginine. Metabolome analysis discloses that activated Wnt signaling augments intracellular concentrations of histidine and arginine, and that the signal also increases the level of lactic acid suggesting the induction of the Warburg effect in liver cancer cells. Further analysis reveals that the levels of metabolites of the urea cycle and genes coding its related enzymes are also modulated by the Wnt signaling. These findings shed light on the altered cellular metabolism in the liver by the Wnt/β-catenin pathway through the suppression of liver-enriched transcription factors including CEBPA and FOXA1.
Integrative analysis of yeast colony growth
Authors: Gaizer Tünde , Juhász János , Pillér Bíborka , Szakadáti Helga , Pongor Csaba I. , Csikász-Nagy Attila
Published: April 2024

Yeast colonies are routinely grown on agar plates in everyday experimental settings to understand basic molecular processes, produce novel drugs, improve health, and so on. Standardized conditions ensure these colonies grow in a reproducible fashion, while in nature microbes are under a constantly changing environment. Here we combine the power of computational simulations and laboratory experiments to investigate the impact of non-standard environmental factors on colony growth. We present the developement and parameterization of a quantitative agent-based model for yeast colony growth to reproduce measurements on colony size and cell number in a colony at non-standard environmental conditions. Specifically, we establish experimental conditions that mimic the effects of humidity changes and nutrient gradients. Our results show how colony growth is affected by moisture changes, nutrient availability, and initial colony inoculation conditions. We show that initial colony spread, not initial cell number have higher impact on the final size and cell number of colonies. Parameters of the model were identified by fitting these experiments and the fitted model gives guidance to establish conditions which enable unlimited growth of yeast colonies.
Reconstruction of unstable heavy particles using deep symmetry-preserving attention networks
Authors: Fenton Michael James , Shmakov Alexander , Okawa Hideki , Li Yuji , Hsiao Ko-Yang , Hsu Shih-Chieh , Whiteson Daniel , Baldi Pierre
Published: April 2024

Reconstructing unstable heavy particles requires sophisticated techniques to sift through the large number of possible permutations for assignment of detector objects to the underlying partons. An approach based on a generalized attention mechanism, symmetry preserving attention networks (SPA-NET), has been previously applied to top quark pair decays at the Large Hadron Collider which produce only hadronic jets. Here we extend the SPA-NET architecture to consider multiple input object types, such as leptons, as well as global event features, such as the missing transverse momentum. In addition, we provide regression and classification outputs to supplement the parton assignment. We explore the performance of the extended capability of SPA-NET in the context of semi-leptonic decays of top quark pairs as well as top quark pairs produced in association with a Higgs boson. We find significant improvements in the power of three representative studies: a search for $$t\bar{t}H$$
t

t

¯

H
, a measurement of the top quark mass, and a search for a heavy $${Z}^{{\prime} }$$

Z

′

decaying to top quark pairs. We present ablation studies to provide insight on what the network has learned in each case.
Alternative routes to electron hydrodynamics
Authors: Estrada-Álvarez Jorge , Domínguez-Adame Francisco , Díaz Elena
Published: April 2024

Viscous flow of interacting electrons in two dimensional materials features a bunch of exotic effects. A model resembling the Navier-Stokes equation for classical fluids accounts for them in the so called hydrodynamic regime. We perform a detailed analysis of the physical conditions to achieve electron hydrodynamic transport and find alternative routes: the application of a magnetic field or a high-frequency electric field in the absence of very frequent inelastic collisions. As a major conclusion, we show that the conventional requirement of frequent electron-electron collisions is too restrictive and, as a consequence, materials and phenomena to be described using hydrodynamics are widened. In view of our results, we discuss recent experimental evidence on viscous flow and point out alternative avenues to reduce electric dissipation in optimized devices.
Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity
Authors: Jiang Shan , Yuan Taolin , Rosenberger Florian A. , Mourier Arnaud , Dragano Nathalia R. V. , Kremer Laura S. , Rubalcava-Gracia Diana , Hansen Fynn M. , Borg Melissa , Mennuni Mara , Filograna Roberta , Alsina David , Misic Jelena , Koolmeister Camilla , Papadea Polyxeni , de Angelis Martin Hrabe , Ren Lipeng , Andersson Olov , Unger Anke , Bergbrede Tim , Di Lucrezia Raffaella , Wibom Rolf , Zierath Juleen R. , Krook Anna , Giavalisco Patrick , Mann Matthias , Larsson Nils-Göran
Published: April 2024

The oxidative phosphorylation system1 in mammalian mitochondria plays a key role in transducing energy from ingested nutrients2. Mitochondrial metabolism is dynamic and can be reprogrammed to support both catabolic and anabolic reactions, depending on physiological demands or disease states. Rewiring of mitochondrial metabolism is intricately linked to metabolic diseases and promotes tumour growth3–5. Here, we demonstrate that oral treatment with an inhibitor of mitochondrial transcription (IMT)6 shifts whole-animal metabolism towards fatty acid oxidation, which, in turn, leads to rapid normalization of body weight, reversal of hepatosteatosis and restoration of normal glucose tolerance in male mice on a high-fat diet. Paradoxically, the IMT treatment causes a severe reduction of oxidative phosphorylation capacity concomitant with marked upregulation of fatty acid oxidation in the liver, as determined by proteomics and metabolomics analyses. The IMT treatment leads to a marked reduction of complex I, the main dehydrogenase feeding electrons into the ubiquinone (Q) pool, whereas the levels of electron transfer flavoprotein dehydrogenase and other dehydrogenases connected to the Q pool are increased. This rewiring of metabolism caused by reduced mtDNA expression in the liver provides a principle for drug treatment of obesity and obesity-related pathology.
Supporting the Paris Agreement through international cooperation: potential contributions, institutional robustness, and progress of Glasgow climate initiatives
Authors: Kuramochi Takeshi , Deneault Andrew , Chan Sander , Smit Sybrig , Pelekh Natalie
Published: April 2024

Many sector-level cooperative initiatives involving both national governments and non-state actors were launched around the 2021 Glasgow climate conference (COP26). However, there have been questions about whether and to what extent these initiatives could substantially contribute to achieving the Paris Agreement’s goal to limit global warming to 1.5 °C. To this end, this paper examines the prospects of the 14 Glasgow sector initiatives by investigating their aggregate mitigation ambition under current national signatories and the institutional robustness of each initiative. We find that the additional emission reduction ambition of the current national government signatories would, even if fully implemented, only fill about a quarter of the emissions gap in 2030 between the aggregate of existing national targets (nationally determined contributions: NDCs) and the required emission levels consistent with keeping warming below 1.5 °C, while the institutional robustness varied considerably across the initiatives. We also find that most national government signatories did not mention Glasgow initiatives in their updated NDCs submitted after COP26. Expansion of the national government participation, national government signatories’ incorporation of the initiatives’ goals into their updated NDCs by setting quantifiable domestic targets, and enhanced institutional capacity are key to successful emission reduction outcomes.
Interpersonal physiological and psychological synchrony predict the social transmission of nocebo hyperalgesia between individuals
Authors: Mostafa Rodela , McNair Nicolas Andrew , Tan Winston , Saunders Cosette , Colagiuri Ben , Barnes Kirsten
Published: April 2024

Witnessing another’s pain can heighten pain in the observer. However, research has focused on the observer’s intrapersonal experience. Here, a social transmission-chain explored the spread of socially-acquired nocebo hyperalgesia. Dyads of genuine participants were randomised to ‘Generations’ (G1–G3). G1-Demonstrators, observed by G2-Observers, experienced high/low thermal pain contingent on supposed activity/inactivity of a sham-treatment. G2 became Demonstrators, witnessed by G3-Observers. They experienced fixed low-temperature stimuli irrespective of sham-treatment ‘activity’. G3 then Demonstrated for G4-Observers (a confederate), also experiencing low-temperature stimuli only. Pain ratings, electrodermal activity, and facial action units were measured. G1’s treatment-related pain propagated throughout the chain. G2 and G3 participants showed heightened subjective and physiological response to sham-treatment, despite equivalent stimulus temperatures, and G3 never witnessing the initial pain-event. Dyadic interpersonal physiological synchrony (electrodermal activity) and psychological synchrony (Observer’s ability to predict the Demonstrator’s pain), predicted subsequent socially-acquired pain. Implications relate to the interpersonal spread of maladaptive pain experiences.