bluuebunny/crossref_metadata_2025 huggingface dataset:
The time-course augmentation of perivascular space enlargement in the basal ganglia among a community-dwelling elder population
Authors: Sugai Yasuhiro , Hiraka Toshitada , Shibata Akiko , Taketa Ayato , Tanae Taiyo , Moriya Yosuke , Komatsu Masanori , Iseki Chifumi , Ohta Yasuyuki , Kanoto Masafumi
Published: June 2024

Purpose

We examined whether time-course augmentation of perivascular space enlargement in the basal ganglia (BG-PVS) reflected cerebral small vessel disease (CSVD) severity by considering white matter hyperintensity lesion (WMHL) as an indicator for CSVD.

Materials and methods

This study population included 416 older participants from a community-based cohort. They participated in magnetic resonance imaging (MRI) studies more than once during the study period. The grades for BG-PVS and WMHL were evaluated by visual rating scales; BG-PVS time-course augmentation in 4–9 years was also evaluated. At baseline, the participants were asked about their smoking and drinking history, and medical history. They also underwent a blood examination and their office blood pressure (BP) examination. In addition, 24-h ambulatory BP monitoring was also performed within the study period.

Results

Of the 416 participants, 48 participants (11.5%) had BG-PVS time-course augmentation. The participants with BG-PVS augmentation had significantly lower LDL levels, hyper-nighttime BP, and lower nighttime BP fall in univariate analysis (p = 0.03, p = 0.03, p = 0.003, respectively). In multivariate analysis, lower nighttime BP fall and male sex showed significance (p = 0.02, 0.03, respectively). Additionally, BG-PVS time-course augmentation was significantly associated with subsequent WMHL severity in univariate analysis (p < 0.001), which remained significant in multivariate analysis adjusted by imaging and demographic factors (p = 0.03). In multivariate analysis, additionally adjusted by the clinical factors, the significance disappeared (p = 0.07).

Conclusion

This study revealed that the lower nighttime BP fall in ambulatory blood pressure monitoring was a factor significantly associated with BG-PVS augmentation. Moreover, the BG-PVS time-course augmentation would be a notable finding that was associated with the subsequent WMHL.
The newly-adopted Corporate Sustainability Due Diligence Directive: an overview of the lawmaking process and analysis of the final text
Authors: Ciacchi Silvia
Published: June 2024

This article provides an overview of the process leading up to the adoption of the Corporate Sustainability Due Diligence Directive (CSDDD) and delivers a comprehensive analysis of the Directive’s final text. The article contextualises the design process of the CSDDD within the international normative framework on sustainability due diligence and elaborates on key events surrounding the inter-institutional negotiations between the European Commission, the European Parliament and the Council of the European Union on the Directive. The article then delves into the content of the newly adopted text, highlighting key differences between the final version and the Commission’s original proposal.
Sex-Dimorphic Kidney-Brain Connectivity Map of Mice
Authors: Li Xulin , Zhou Yuan , Wang Feng , Wang Liping
Published: June 2024

The kidneys are essential organs that help maintain homeostasis, and their function is regulated by the neural system. Despite the anatomical multi-synaptic connection between the central autonomic nuclei and the kidneys, it remains unclear whether there are any variations in neural connections between the nervous systems and the renal cortex and medulla in male and female mice. Here, we used the pseudorabies virus to map the central innervation network of the renal cortex and medulla in both sexes. The data revealed that specific brain regions displayed either a contralateral-bias or ipsilateral-bias pattern while kidney-innervating neurons distributed symmetrically in the midbrain and hindbrain. Sex differences were observed in the distribution of neurons connected to the left kidney, as well as those connected to the renal cortex and medulla. Our findings provide a comprehensive understanding of the brain-kidney network in both males and females and may help shed light on gender differences in kidney function and disease susceptibility in humans.
Genomic and Phenotypic Safety Assessment of Probiotic Bacillus coagulans Strain JBI-YZ6.3
Authors: Zhang Yongmei , Overbeck Tom J. , Skebba Victoria L. Palmer , Gandhi Neil N.
Published: June 2024

Spore-forming Bacillus coagulans has been widely recognized as an important probiotic, which is commonly used in products for human consumption and animal feeds. B. coagulans exhibits beneficial traits from both Bacillus and lactic acid-producing Lactobacillus. The present study evaluated the safety of the newly isolated B. coagulans strain JBI-YZ6.3, using combined genomic and phenotypic analysis approaches. The taxonomic classification based on genome sequence and biochemical tests identified strain JBI-YZ6.3 as B. coagulans. Comprehensive genome-based analyses established JBI-YZ6.3 as a novel strain of B. coagulans. Antibiotic susceptibility testing showed that the strain JBI-YZ6.3 was sensitive to a panel of fourteen antibiotics, and no genes related to antibiotic resistance were found in its genome. The spores of strain JBI-YZ6.3 exhibited tolerance to acid and bile salts, as well as stability at ambient and elevated conditions of temperature and relative humidity. There were no homologs of Bacillus toxin genes identified in the genome of JBI-YZ6.3, and the strain exhibited no cytotoxicity towards Vero cells and human peripheral blood mononuclear cells. In conclusion, findings from this study support the safety of B. coagulans strain JBI-YZ6.3, which can be developed into new probiotic products for preventive and therapeutic benefits in human and animal hosts.
Public Support for Business, Intermediary Organizations, and Knowledge Transfer: Critical Development and Innovation Policy Bottlenecks
Authors: Chatzinikolaou Dimos , Vlados Charis
Published: June 2024

This study explores the challenges of integrating macro, meso, and micro in the articulation of advanced innovation policy and examines, respectively, dimensions of public business support, intermediary organizations, and knowledge transfer. It conducts an integrative review of the pertinent literature and a bibliometric analysis of 440 articles. It reveals three major obstacles that seemingly impede the effective integration of macro, meso, and micro in contemporary policymaking and socioeconomic analyses: entrenched boundaries between different thematic areas, methodological discrepancies, and the relative lack of integrated theoretical models. These factors contribute to the absence of unified functional hubs focused on microlevel interventions. The proposed Institutes of Local Development and Innovation (ILDIs) could mitigate these challenges as they are presented as multilevel policy instruments intended to provide support to businesses—particularly to those facing chronic and structural problems.
Some Remarks on Linear-Quadratic Closed-Loop Games with Many Players
Authors: Cirant Marco , Redaelli Davide Francesco
Published: June 2024

We identify structural assumptions which provide solvability of the Nash system arising from a linear-quadratic closed-loop game, with stable properties with respect to the number of players. In a setting of interactions governed by a sparse graph, both short-time and long-time existence of a classical solution for the Nash system set in infinitely many dimensions are addressed, as well as convergence to the solution to the respective ergodic problem as the time horizon goes to infinity; in addition, equilibria for the infinite-dimensional game are shown to provide $$\epsilon $$
ϵ
-Nash closed-loop equilibria for the N-player game. In a setting of generalized mean-field type (where the number of interactions is large but not necessarily symmetric), directly from the N-player Nash system estimates on the value functions are deduced on an arbitrary large time horizon, which should pave the way for a convergence result as N goes to infinity.
Validation of a non-food or water motivated effort-based foraging task as a measure of motivational state in male mice
Authors: Xeni Foteini , Marangoni Caterina , Jackson Megan G.
Published: June 2024

Disorders of motivation such as apathy syndrome are highly prevalent across neurological disorders but do not yet have an agreed treatment approach. The use of translational behavioural models can provide a route through which to meaningfully screen novel drug targets. Methods that utilise food deprivation in contrived environments may lack the sensitivity to detect deficits in self-initiated behaviour, and may have limited translation to normal behaviour. Animals monitored in more naturalistic environments may display more ethologically-relevant behaviours of greater translational value. Here, we aimed to validate a novel, non-food or water motivated effort-based foraging task as a measure of motivational state in mice. In this task, the mouse can freely choose to exert effort to forage nesting material and shuttle it back to a safe and enclosed environment. The amount of nesting material foraged is used as a readout of motivational state. Acute dopaminergic modulation with haloperidol, amphetamine and methylphenidate, and two phenotypic models known to induce motivational deficits (healthy ageing and chronic administration of corticosterone) were used to validate this task. Consistent with other effort-based decision-making tasks we find that foraging behaviour is sensitive to acute modulation of dopaminergic transmission. We find that both phenotypic models induce differing deficits in various aspects of foraging behaviour suggesting that the task may be used to parse different behavioural profiles from distinct disease phenotypes. Thus, without requiring extended training periods or physiological deprivation, this task may represent a refined and translational preclinical measure of motivation.
NIMH perspectives on future directions in neuroimaging for mental health
Authors: Wijtenburg S. Andrea , Rowland Laura M. , Vicentic Aleksandra , Rossi Andrew F. , Brady Linda S. , Gordon Joshua A. , Lisanby Sarah H.
Published: June 2024

NIMH’s mission is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. New imaging techniques hold great promise for improving our understanding of the pathophysiology of mental illnesses, stratifying patients for treatment selection, and developing a personalized medicine approach. Here, we highlight emerging and promising new technologies that are likely to be vital in helping NIMH accomplish its mission, the potential for utilizing multimodal approaches to study mental illness, and considerations for data analytics and data sharing.
Gut microbiota-mediated activation of GSDMD ignites colorectal tumorigenesis
Authors: Chen Ju , Singh Neha , Ye Xiaoyang , Theune Eileen Victoria , Wang Kepeng
Published: June 2024

Activation of Gasdermin D (GSDMD) results in its cleavage, oligomerization, and subsequent formation of plasma membrane pores, leading to a form of inflammatory cell death denoted as pyroptosis. The roles of GSDMD in inflammation and immune responses to infection are well documented. However, whether GSDMD also plays a role in sporadic cancer development, especially that in the gut epithelium, remains unknown. Here, we show that GSDMD is activated in colorectal tumors of both human and mouse origins. Ablation of GSDMD in a mouse model of sporadic colorectal cancer resulted in reduced tumor formation in the colon and rectum, suggesting a tumor-promoting role of the protein in the gut. Both antibiotic-mediated depletion of gut microbiota and pharmacological inhibition of NLRP3 inflammasome reduced the activation of GSDMD. Loss of GSDMD resulted in reduced infiltration of immature myeloid cells, and increased numbers of macrophages in colorectal tumors. Activation of GSDMD is also accompanied by the aggregation of the endosomal sorting complex required for transport (ESCRT) membrane repair proteins on the membrane of colorectal tumor cells, suggesting that active membrane repairment may prevent pyroptosis induced by the formation of GSDMD pore in tumor cells. Our results show that gut microbiota/NLRP3-mediated activation of GSDMD promotes the development of colorectal tumors, and supports the use of NLRP3 inhibitors to treat colon cancer.
The combination of immune checkpoint inhibitors and antibody-drug conjugates in the treatment of urogenital tumors: a review insights from phase 2 and 3 studies
Authors: Yu Puguang , Zhu Chunming , You Xiangyun , Gu Wen , Wang Xia , Wang Yuan , Bu Renge , Wang Kefeng
Published: June 2024

With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.
Hard-Flaccid syndrome: a survey of sexual medicine practitioners’ knowledge and experience
Authors: Gryzinski Gustavo , Hammad Muhammed Moukhtar , Alzweri Laith , Azad Babak , Barham David , Lumbiganon Supanut , Serefoglu Ege Can , Yafi Faysal
Published: June 2024

Hard-flaccid syndrome (HFS) is a poorly understood condition of male sexual dysfunction (MSD) that has more recently become a new topic of discussion in online forums and sexual medicine conferences. There has been limited research looking into HFS and consequently there are no evidence-based guidelines for its work-up and management. In order to identify the current level of understanding of HFS in the sexual medicine community, a survey was distributed at a national urologic conference focusing on pertinent management strategies employed by practitioners, and their own thoughts on HFS. This showed that nearly one-third of those surveyed had never seen HFS in their practice. Of those that had, diagnosis was mainly made via clinical history as well as patient self-diagnosis. Additionally, only about half of the respondents who had seen HFS were confident in its legitimacy as a real medical syndrome. This analysis is one of the first of its kind, and highlights the ongoing lack of familiarity of HFS among the sexual medicine community. There were limitations, most notably its survey format as well as low sample size, however, it importantly emphasizes the critical need for continued education and research into HFS to improve diagnostic accuracy, enhance patient care, and develop effective treatment strategies.
Interplay of two small RNAs fine-tunes hierarchical flagella gene expression in Campylobacter jejuni
Authors: König Fabian , Svensson Sarah L. , Sharma Cynthia M.
Published: June 2024

Like for many bacteria, flagella are crucial for Campylobacter jejuni motility and virulence. Biogenesis of the flagellar machinery requires hierarchical transcription of early, middle (RpoN-dependent), and late (FliA-dependent) genes. However, little is known about post-transcriptional regulation of flagellar biogenesis by small RNAs (sRNAs). Here, we characterized two sRNAs with opposing effects on C. jejuni filament assembly and motility. We demonstrate that CJnc230 sRNA (FlmE), encoded downstream of the flagellar hook protein, is processed from the RpoN-dependent flgE mRNA by RNase III, RNase Y, and PNPase. We identify mRNAs encoding a flagella-interaction regulator and the anti-sigma factor FlgM as direct targets of CJnc230 repression. CJnc230 overexpression upregulates late genes, including the flagellin flaA, culminating in longer flagella and increased motility. In contrast, overexpression of the FliA-dependent sRNA CJnc170 (FlmR) reduces flagellar length and motility. Overall, our study demonstrates how the interplay of two sRNAs post-transcriptionally fine-tunes flagellar biogenesis through balancing of the hierarchically-expressed components.
The association of maternal factors with the neonatal microbiota and health
Authors: Zhu Bin , Edwards David J. , Spaine Katherine M. , Edupuganti Laahirie , Matveyev Andrey , Serrano Myrna G. , Buck Gregory A.
Published: June 2024

The human microbiome plays a crucial role in human health. However, the influence of maternal factors on the neonatal microbiota remains obscure. Herein, our observations suggest that the neonatal microbiotas, particularly the buccal microbiota, change rapidly within 24–48 h of birth but begin to stabilize by 48–72 h after parturition. Network analysis clustered over 200 maternal factors into thirteen distinct groups, and most associated factors were in the same group. Multiple maternal factor groups were associated with the neonatal buccal, rectal, and stool microbiotas. Particularly, a higher maternal inflammatory state and a lower maternal socioeconomic position were associated with a higher alpha diversity of the neonatal buccal microbiota and beta diversity of the neonatal stool microbiota was influenced by maternal diet and cesarean section by 24–72 h postpartum. The risk of admission of a neonate to the newborn intensive care unit was associated with preterm birth as well as higher cytokine levels and probably higher alpha diversity of the maternal buccal microbiota.
The hexosamine biosynthetic pathway rescues lysosomal dysfunction in Parkinson’s disease patient iPSC derived midbrain neurons
Authors: Wani Willayat Y. , Zunke Friederike , Belur Nandkishore R. , Mazzulli Joseph R.
Published: June 2024

Disrupted glucose metabolism and protein misfolding are key characteristics of age-related neurodegenerative disorders including Parkinson’s disease, however their mechanistic linkage is largely unexplored. The hexosamine biosynthetic pathway utilizes glucose and uridine-5’-triphosphate to generate N-linked glycans required for protein folding in the endoplasmic reticulum. Here we find that Parkinson’s patient midbrain cultures accumulate glucose and uridine-5’-triphosphate, while N-glycan synthesis rates are reduced. Impaired glucose flux occurred by selective reduction of the rate-limiting enzyme, GFPT2, through disrupted signaling between the unfolded protein response and the hexosamine pathway. Failure of the unfolded protein response and reduced N-glycosylation caused immature lysosomal hydrolases to misfold and accumulate, while accelerating glucose flux through the hexosamine pathway rescued hydrolase function and reduced pathological α-synuclein. Our data indicate that the hexosamine pathway integrates glucose metabolism with lysosomal activity, and its failure in Parkinson’s disease occurs by uncoupling of the unfolded protein response-hexosamine pathway axis. These findings offer new methods to restore proteostasis by hexosamine pathway enhancement.
A spatial perturbation framework to validate implantation of the epileptogenic zone
Authors: Jaber Kassem , Avigdor Tamir , Mansilla Daniel , Ho Alyssa , Thomas John , Abdallah Chifaou , Chabardes Stephan , Hall Jeff , Minotti Lorella , Kahane Philippe , Grova Christophe , Gotman Jean , Frauscher Birgit
Published: June 2024

Stereo-electroencephalography (SEEG) is the gold standard to delineate surgical targets in focal drug-resistant epilepsy. SEEG uses electrodes placed directly into the brain to identify the seizure-onset zone (SOZ). However, its major constraint is limited brain coverage, potentially leading to misidentification of the ‘true’ SOZ. Here, we propose a framework to assess adequate SEEG sampling by coupling epileptic biomarkers with their spatial distribution and measuring the system’s response to a perturbation of this coupling. We demonstrate that the system’s response is strongest in well-sampled patients when virtually removing the measured SOZ. We then introduce the spatial perturbation map, a tool that enables qualitative assessment of the implantation coverage. Probability modelling reveals a higher likelihood of well-implanted SOZs in seizure-free patients or non-seizure free patients with incomplete SOZ resections, compared to non-seizure-free patients with complete resections. This highlights the framework’s value in sparing patients from unsuccessful surgeries resulting from poor SEEG coverage.
Identification of endothelial and mesenchymal FOXF1 enhancers involved in alveolar capillary dysplasia
Authors: Wang Guolun , Wen Bingqiang , Guo Minzhe , Li Enhong , Zhang Yufang , Whitsett Jeffrey A. , Kalin Tanya V. , Kalinichenko Vladimir V.
Published: June 2024

Mutations in the FOXF1 gene, a key transcriptional regulator of pulmonary vascular development, cause Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins, a lethal lung disease affecting newborns and infants. Identification of new FOXF1 upstream regulatory elements is critical to explain why frequent non-coding FOXF1 deletions are linked to the disease. Herein, we use multiome single-nuclei RNA and ATAC sequencing of mouse and human patient lungs to identify four conserved endothelial and mesenchymal FOXF1 enhancers. We demonstrate that endothelial FOXF1 enhancers are autoactivated, whereas mesenchymal FOXF1 enhancers are regulated by EBF1 and GLI1. The cell-specificity of FOXF1 enhancers is validated by disrupting these enhancers in mouse embryonic stem cells using CRISPR/Cpf1 genome editing followed by lineage-tracing of mutant embryonic stem cells in mouse embryos using blastocyst complementation. This study resolves an important clinical question why frequent non-coding FOXF1 deletions that interfere with endothelial and mesenchymal enhancers can lead to the disease.
Arabidopsis CaLB1 undergoes phase separation with the ESCRT protein ALIX and modulates autophagosome maturation
Authors: Mosesso Niccolò , Lerner Niharika Savant , Bläske Tobias , Groh Felix , Maguire Shane , Niedermeier Marie Laura , Landwehr Eliane , Vogel Karin , Meergans Konstanze , Nagel Marie-Kristin , Drescher Malte , Stengel Florian , Hauser Karin , Isono Erika
Published: June 2024

Autophagy is relevant for diverse processes in eukaryotic cells, making its regulation of fundamental importance. The formation and maturation of autophagosomes require a complex choreography of numerous factors. The endosomal sorting complex required for transport (ESCRT) is implicated in the final step of autophagosomal maturation by sealing of the phagophore membrane. ESCRT-III components were shown to mediate membrane scission by forming filaments that interact with cellular membranes. However, the molecular mechanisms underlying the recruitment of ESCRTs to non-endosomal membranes remain largely unknown. Here we focus on the ESCRT-associated protein ALG2-interacting protein X (ALIX) and identify Ca2+-dependent lipid binding protein 1 (CaLB1) as its interactor. Our findings demonstrate that CaLB1 interacts with AUTOPHAGY8 (ATG8) and PI(3)P, a phospholipid found in autophagosomal membranes. Moreover, CaLB1 and ALIX localize with ATG8 on autophagosomes upon salt treatment and assemble together into condensates. The depletion of CaLB1 impacts the maturation of salt-induced autophagosomes and leads to reduced delivery of autophagosomes to the vacuole. Here, we propose a crucial role of CaLB1 in augmenting phase separation of ALIX, facilitating the recruitment of ESCRT-III to the site of phagophore closure thereby ensuring efficient maturation of autophagosomes.
Structural basis for IL-33 recognition and its antagonism by the helminth effector protein HpARI2
Authors: Jamwal Abhishek , Colomb Florent , McSorley Henry J. , Higgins Matthew K.
Published: June 2024

IL-33 plays a significant role in inflammation, allergy, and host defence against parasitic helminths. The model gastrointestinal nematode Heligmosomoides polygyrus bakeri secretes the Alarmin Release Inhibitor HpARI2, an effector protein that suppresses protective immune responses and asthma in its host by inhibiting IL-33 signalling. Here we reveal the structure of HpARI2 bound to mouse IL-33. HpARI2 contains three CCP-like domains, and we show that it contacts IL-33 primarily through the second and third of these. A large loop which emerges from CCP3 directly contacts IL-33 and structural comparison shows that this overlaps with the binding site on IL-33 for its receptor, ST2, preventing formation of a signalling complex. Truncations of HpARI2 which lack the large loop from CCP3 are not able to block IL-33-mediated signalling in a cell-based assay and in an in vivo female mouse model of asthma. This shows that direct competition between HpARI2 and ST2 is responsible for suppression of IL-33-dependent responses.
Photoelectrochemical Fe/Ni cocatalyzed C−C functionalization of alcohols
Authors: Zou Long , Sun Rui , Tao Yongsheng , Wang Xiaofan , Zheng Xinyue , Lu Qingquan
Published: June 2024

The simultaneous activation of reactants on the anode and cathode via paired electrocatalysis has not been extensively demonstrated. This report presents a paired oxidative and reductive catalysis based on earth-abundant iron/nickel cocatalyzed C–C functionalization of ubiquitous alcohols. A variety of alcohols (i.e., primary, secondary, tertiary, or unstrained cyclic alcohols) can be activated at very low oxidation potential of (~0.30 V vs. Ag/AgCl) via photoelectrocatalysis coupled with versatile electrophiles. This reactivity yields a wide range of structurally diverse molecules with broad functional group compatibility (more than 50 examples).
DNA replication in early mammalian embryos is patterned, predisposing lamina-associated regions to fragility
Authors: Xu Shuangyi , Wang Ning , Zuccaro Michael V. , Gerhardt Jeannine , Iyyappan Rajan , Scatolin Giovanna Nascimento , Jiang Zongliang , Baslan Timour , Koren Amnon , Egli Dieter
Published: June 2024

DNA replication in differentiated cells follows a defined program, but when and how it is established during mammalian development is not known. Here we show using single-cell sequencing, that late replicating regions are established in association with the B compartment and the nuclear lamina from the first cell cycle after fertilization on both maternal and paternal genomes. Late replicating regions contain a relative paucity of active origins and few but long genes and low G/C content. In both bovine and mouse embryos, replication timing patterns are established prior to embryonic genome activation. Chromosome breaks, which form spontaneously in bovine embryos at sites concordant with human embryos, preferentially locate to late replicating regions. In mice, late replicating regions show enhanced fragility due to a sparsity of dormant origins that can be activated under conditions of replication stress. This pattern predisposes regions with long neuronal genes to fragility and genetic change prior to separation of soma and germ cell lineages. Our studies show that the segregation of early and late replicating regions is among the first layers of genome organization established after fertilization.
Dynamic stereomutation of vinylcyclopropanes with metalloradicals
Authors: Mendel Marvin , Karl Teresa M. , Hamm Jegor , Kaldas Sherif J. , Sperger Theresa , Mondal Bhaskar , Schoenebeck Franziska
Published: June 2024

The ever increasing demands for greater sustainability and lower energy usage in chemical processes call for fundamentally new approaches and reactivity principles. In this context, the pronounced prevalence of odd-oxidation states in less precious metals bears untapped potential for fundamentally distinct reactivity modes via metalloradical catalysis1–3. Contrary to the well-established reactivity paradigm that organic free radicals, upon addition to a vinylcyclopropane, lead to rapid ring opening under strain release—a transformation that serves widely as a mechanistic probe (radical clock)4 for the intermediacy of radicals5—we herein show that a metal-based radical, that is, a Ni(I) metalloradical, triggers reversible cis/trans isomerization instead of opening. The isomerization proceeds under chiral inversion and, depending on the substitution pattern, occurs at room temperature in less than 5 min, requiring solely the addition of the non-precious catalyst. Our combined computational and experimental mechanistic studies support metalloradical catalysis as origin of this profound reactivity, rationalize the observed stereoinversion and reveal key reactivity features of the process, including its reversibility. These insights enabled the iterative thermodynamic enrichment of enantiopure cis/trans mixtures towards a single diastereomer through multiple Ni(I) catalysis rounds and also extensions to divinylcyclopropanes, which constitute strategic motifs in natural product- and total syntheses6. While the trans-isomer usually requires heating at approximately 200 °C to trigger thermal isomerization under racemization to cis-divinylcyclopropane, which then undergoes facile Cope-type rearrangement, the analogous contra-thermodynamic process is herein shown to proceed under Ni(I) metalloradical catalysis under mild conditions without any loss of stereochemical integrity, enabling a mild and stereochemically pure access to seven-membered rings, fused ring systems and spirocycles.
Computational design of soluble and functional membrane protein analogues
Authors: Goverde Casper A. , Pacesa Martin , Goldbach Nicolas , Dornfeld Lars J. , Balbi Petra E. M. , Georgeon Sandrine , Rosset Stéphane , Kapoor Srajan , Choudhury Jagrity , Dauparas Justas , Schellhaas Christian , Kozlov Simon , Baker David , Ovchinnikov Sergey , Vecchio Alex J. , Correia Bruno E.
Published: June 2024

De novo design of complex protein folds using solely computational means remains a substantial challenge1. Here we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, such as those from G-protein-coupled receptors2, are not found in the soluble proteome, and we demonstrate that their structural features can be recapitulated in solution. Biophysical analyses demonstrate the high thermal stability of the designs, and experimental structures show remarkable design accuracy. The soluble analogues were functionalized with native structural motifs, as a proof of concept for bringing membrane protein functions to the soluble proteome, potentially enabling new approaches in drug discovery. In summary, we have designed complex protein topologies and enriched them with functionalities from membrane proteins, with high experimental success rates, leading to a de facto expansion of the functional soluble fold space.
Research on the influence of pits on the propagation law of explosion shock waves
Authors: Fei Shang , Liangquan Wang
Published: June 2024

To study the influence of pits on shock wave propagation and the propagation of shock waves within pits, numerical simulations were used to calculate the distribution of overpressure peak values at the bottom and rear of the pits at 5 depths and 5 explosion center distances. The results indicate that diffraction occurs when the explosion shock wave passes through the edge of the crater; The peak overpressure of the shock wave at the bottom of the pit exhibits a "spoon shaped" distribution, and the peak overpressure on the right side is significantly higher than that on the left side; There are two distinct boundary regions for the overpressure of the shock wave behind the crater due to the influence of the crater; The distance between the explosion centers has little effect on the distribution trend of the overpressure peak of the shock wave at the bottom and rear of the pit, mainly affecting the magnitude of the overpressure peak. The research results provide theoretical support for the analysis of the propagation law of explosion shock waves and guidance for the design of protective engineering structures, with significant engineering application value.
Sol–gel derived ceramic nanoparticles as an alternative material for microstrip patch antenna in WLAN applications
Authors: Didde Sekhar , Dubey R. S.
Published: June 2024

In the fast-evolving realm of communication technology, microstrip patch antennas (MPAs) are in high demand owing to their compact size, lightweight, inexpensive, ease of integration, and compatibility with modern electronic devices. This research focuses on the synthesis of ZnAl2O4Ca (ZAC) ceramic nanoparticles using an economical sol–gel method suitable for microstrip patch antenna applications. The structural analysis study of ZAC nanoparticles confirmed the polycrystalline nature with 8.1 nm of crystallite size whereas an investigation of functional groups showed the corresponding vibration modes. Morphological investigation revealed the spherical grains having their mean diameter of 12.32 nm. The dielectric property’s examination, revealed the dielectric permittivity of 13, loss tangent of 0.02, and conductivity of 67 μΩ−1 cm−1. Furthermore, a prototype patch antenna fabricated using ZAC ceramics demonstrated a dual-band performance at frequencies 2.8 GHz and 4.8 GHz, with return losses of − 25.78 dB and − 28.5 dB, respectively. This work suggests the suitability of ZAC ceramic nanoparticles for use in WLAN applications.
PLX038A, a long-acting SN-38, penetrates the blood-tumor-brain-barrier, accumulates and releases SN-38 in brain tumors to increase survival of tumor bearing mice
Authors: Jung Jinkyu , Schneider Eric L. , Zhang Wei , Song Hua , Zhang Meili , Chou William , Meher Niranjan , VanBrocklin Henry F. , Barcellos-Hoff Mary Helen , Ozawa Tomoko , Gilbert Mark R. , Santi Daniel V.
Published: June 2024

Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between  ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a “Trojan horse” to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors.
Increased ERCP-related adverse event from premature urgent ERCP following symptom onset in acute biliary pancreatitis with cholangitis
Authors: Lee See Young , Park Sang Ho , Do Min Young , Lee Dong Ki , Jang Sung Ill , Cho Jae Hee
Published: June 2024

Acute biliary pancreatitis (ABP) with cholangitis requires endoscopic retrograde cholangiopancreatography (ERCP) within 24 h to resolve ductal obstruction. However, this recommendation is based on the timing of emergency room (ER) visits. We wanted to determine the optimal timing of ERCP for ABP based on the timing of symptom onset, not the timing of the ER visit. We retrospectively reviewed 162 patients with ABP with cholangitis who underwent urgent ERCP (within 24 h of ER admission). Area under the receiver operating characteristic (ROC) curve (AUC) was analyzed to determine differences in complication rates according to time from symptom onset. A difference in ERCP-related adverse events (AEs) was identified, and Youden’s J statistic was used to determine a cutoff time from symptom onset (18 h). We compared mortality and complications based on this cutoff. Based on time to symptom onset, significantly higher rates of aspiration pneumonia (odds ratio [OR] 4.00, 95% confidence interval [CI] 1.15–13.92, P = 0.021) and post-ERCP hypotension (OR 11.9, 95% CI 1.39–101.33, P = 0.005) were observed in the ≤ 18-h group than in the > 18-h group. The study found that patients who underwent ERCP within 18 h of symptom onset is associated with an increased risk of ERCP-related AEs.
Chemical Pedagogy
Authors: Taber Keith S
Published: June 2024

How should chemistry be taught in schools, colleges, and universities? Chemical Pedagogy discusses teaching approaches and techniques, the reasoning behind them, and the evidence for their effectiveness.

The book surveys a wide range of different pedagogic strategies and tactics that have been recommended to better engage learners and provide more effective chemistry teaching. These accounts are supported by an initial introduction to some key ideas and debates about pedagogy - the science of teaching.

Chemical Pedagogy discusses how teaching innovations can be tested to inform research-based practice. Through this book, the author explores the challenges of carrying out valid experimental studies in education, and the impediments to generalising study results to diverse teaching and learning contexts. As a result, the author highlights both the need to read published studies critically and the value of teachers and lecturers testing out recommended innovations in their own classrooms.

Chemical Pedagogy introduces core principles – from research into human cognition and learning – to provide a theoretical perspective on how to best teach for engagement and understanding. An examination of some of the more contentious debates about pedagogy leads to the advice to seek ‘optimally guided instruction’ which balances the challenge offered to learners with the level of support provided. This provides a framework for discussing a wide range of teaching approaches and techniques that have been recommended to those teaching chemistry across educational levels, including both those intended to replace ‘teaching from the front’ and others that can be built into traditional lecture courses to enhance the learning experience.
Detection and identification of SARS-CoV-2 and influenza a based on microfluidic technology
Authors: Liu Yujie , Yu Guanliu , Liang Hongkun , Sun Wenbo , Zhang Lulu , Mauk Michael G. , Li Hua , Chen Lei
Published: June 2024

We developed a system that integrates RPA-CRISPR Cas12a with microfluidic chip, allowing for the rapid, highly specific, and sensitive detection and differentiation of SARS-CoV-2, H1N1, and H3N2.
Highly tunable emission properties of solid-state supramolecular compounds based on Eu mixed-lanthanide complexes and cucurbit[6]uril
Authors: Rakhmanova Mariana , Sukhikh Taisiya , Kovalenko Ekaterina
Published: June 2024

A supramolecular approach for emission control.
Exploring flat-band properties in two-dimensional M3QX7 compounds
Authors: Wang Hai-Chen , Rauch Tomáš , Tellez-Mora Andres , Wirtz Ludger , Romero Aldo H. , Marques Miguel A. L.
Published: June 2024

The electronic band structure, the breathing Kagome lattice, and the Raman spectrum of Nb3SBr7 monolayer.
Deep eutectic solvents towards green polymeric materials
Authors: Weerasinghe Udyani Aloka , Wu Tingting , Chee Pei Lin , Yew Pek Yin Michelle , Lee Hiang Kwee , Loh Xian Jun , Dan Kai
Published: June 2024

Solvents are essential for chemical synthesis and material preparation; however, traditional solvents face challenges in meeting safety and sustainability standards.
Superwetting Ag@Cu2O anchored copper mesh for efficient oil/water separation and visible-light driven removal of organic pollutants
Authors: Zhao Jianchao , Yang Zhengqiang , Liu Na , Wang Rui , Deng Siqi , Cao Haijie
Published: June 2024

A multifunctional Ag@Cu2O anchored mesh with high oil–water separation efficiency and effective removal of organic pollutants.
A review on surface modulation of MXenes and the impact on their work functions and stability
Authors: Pang Yuchen , Li Junxiao , Lv Kangle , Tang Dingguo , Li Qin
Published: June 2024

The objective of this review is to systematically investigate the methodologies for modulating the surface terminations of MXenes and explore the impact on their properties.
Asymmetric ion transport through “Janus” MoSSe sub-nanometer pores
Authors: Chakraborty Rajat , Crawford-Eng Henry T. , Leburton Jean-Pierre
Published: June 2024

Janus MoSSe sub-nm pore exhibits polarity-driven ion adsorption and charge-induced transport dynamics, yielding asymmetrical I–V curves, with potential nanofluidics applications.
Advances in nanoporous materials for next-generation battery applications
Authors: Sheng Li , He Xiangming , Xu Hong
Published: June 2024

The tunable nanoporous features in metal–organic frameworks and covalent organic frameworks show great potential for batteries, such as promoting lithium-ion conduction and stabilising lithium metal anodes/high nickel cathodes.
Supramolecular polymerization of [6]helicene-based cyano-luminogens: on the overall efficiency of self-assembled circularly polarized emitters
Authors: López-Gandul Lucia , Rodríguez Rafael , Vanthuyne Nicolas , Crassous Jeanne , Sánchez Luis
Published: June 2024

The supramolecular polymerization of the [6]helicene-based luminophores 1 and 2, showing a rich dichroic pattern, is reported. The inherent chirality of both the monomeric and aggregated species of 1 and 2 provides the systems with a remarkable overall CPL-efficiency.
Expression of concern: An integrated salinity-driven workflow for rapid lipid enhancement in green microalgae for biodiesel application
Authors: Satpati Gour Gopal , Gorain Prakash Chandra , Paul Ishita , Pal Ruma
Published: June 2024

Expression of concern for ‘An integrated salinity-driven workflow for rapid lipid enhancement in green microalgae for biodiesel application’ by Gour Gopal Satpati et al., RSC Adv., 2016, 6, 112340–112355, https://doi.org/10.1039/C6RA23933A.
Mechanisms of controlled stabilizer-free synthesis of gold nanoparticles in liquid aerosol containing plasma
Authors: Nam Jae Hyun , Nayak Gaurav , Exarhos Stephen , Mueller Chelsea M. , Xu Dongxuan , Schatz George C. , Bruggeman Peter J.
Published: June 2024

A fast gold nanoparticle synthesis without stabilizer in plasma–microdroplet interaction is identified.
Internal strain-driven bond manipulation and band engineering in Bi2−xSbxYO4Cl photocatalysts with triple fluorite layers
Authors: Gabov Artem , Kato Daichi , Ubukata Hiroki , Aso Ryotaro , Kakudou Naoji , Fujita Koji , Suzuki Hajime , Tomita Osamu , Saeki Akinori , Abe Ryu , Karazhanov Smagul Zh , Kageyama Hiroshi
Published: June 2024

Internal strain within the triple fluorite layer of Bi2−xSbxYO4Cl explains bond breaking and allows bandgap engineering.
1,3-Dipolar cyclisation reactions of nitriles with sterically encumbered cyclic triphosphanes: synthesis and electronic structure of phosphorus-rich heterocycles with tunable colour
Authors: Nascimento Mitchell A. , LaPierre Etienne A. , Patrick Brian O. , Watson Jade E. T. , Watanabe Lara , Rawson Jeremy , Hering-Junghans Christian , Manners Ian
Published: June 2024

The acid-mediated cyclisation of sterically encumbered cyclic triphosphanes with nitriles provides access to five-membered cationic and neutral P3CN heterocycles with tuneable colour.
An integrated “rigid–flexible” strategy by side chain engineering towards high ion-conduction cationic covalent organic framework electrolytes
Authors: Song Jian , Lin Li , Cui Fengchao , Wang Heng-Guo , Tian Yuyang , Zhu Guangshan
Published: June 2024

An integrated “rigid–flexible” dual-functional strategy promotes the dissociation of lithium salts and fast transport of Li+. The COF solid-state electrolyte shows decent electrochemical properties at both high and low temperatures.
Machine learning approach of multi‐RAT selection for travelling users in 5G NSA networks
Authors: Salau Nurudeen O. , Manzoor Sanaullah , Shakir Muhammad Z.
Published: June 2024

The rapid increment of mobile device usage and the corresponding huge data volume generated afterwards, necessitated the utilisation of the 5G network spectrum. This is deployed today in terrestrial communication in a non‐stand‐alone (NSA) architectural mode; where 5G networks are supported by 4G LTE networks. Hence, the current 5G implementation with the gargantuan number of mobile subscribers, poses challenges to the choice of network Radio Access Technology (RAT) selection between 4G and 5G networks, among available multiple base‐stations to mobile (travelling) users, with respect to their location, bandwidth requirement, and mobility style. Hence, to address the scenario presented above, the authors record live signal measurements of 4G and 5G networks by a travelling user, that transversed multiple 5G NSA base stations. RAT selection implementations were carried out with support vector machine (SVM), deep neural network (DNN), and eXtreme Gradient Boosting (XGBoost) algorithms to select an appropriate RAT between 4G and 5G RATs, for effective resource allocation for travelling users’ requirements. Evaluation of results with standard classification metrics shows XGBoost with overall outstanding accuracy performance at 99.64%.
An overview of the evolution of the internal hellenides (Albania, Republic of North Macedonia, Greek Central Macedonia): obductions, collisions and North Aegean extension
Authors: Vergély Pierre , Mercier Jacques Louis
Published: June 2024

The geological analysis of the Albanian-Macedonian transect constraints a framework of the Internal Hellenides in which 3 or 4 Jurassic oceanic basins opened at 174–160 Ma; they bordered the Western European Continent. During the Late Jurassic, the oceanic crusts subducted eastward, the Mirdita basin below the Pelagonian continent, the Almopias basin below the Malarupa-Veles continent and the Thessaloniki ophiolitic basin below the Continental Margin of the basin. A Paikon Volcanic tholeiitic Island Arc formed above the Almopias subduction and subsequently subducted below the rhyolitic volcanic centre of the Arc; the Guevgueli ophiolitic back-arc basin opened above the subduction of the Paikon Volcanic Arc (164–160 Ma). The top-to-the-W Late Jurassic obduction of the oceanic crusts (D1event) is followed by a gravitational exhumation (D2event). A new Mid-Late Cretaceous Almopias marine basin formed; the Late Cretaceous-Palaeocene continental subduction (=collisions, D3-4events) re-activated the Jurassic subductions and a dacitic Paikon Volcanic Arc formed in the Palaeocene-Early Eocene (56–45 Ma). The Vardar Trough opened at 45 Ma in the back of the dacitic Paikon Volcanic Arc, above the subduction of Vardar and Apulia units; it was submitted in the Late Priabonian to a tectonic event (D5event, 36–34 Ma) and to the Early Miocene compression (D6event). The N. Aegean WNW-ESE extension began at ∼21–20 Ma; change from the WNW to the NE-SW/N-S extensional directions occurred between the Tortonian (∼12 Ma) and the Pliocene (∼6 Ma); it was probably driven by hundreds kms of NE-SW/N-S stretching of the Central and Southern Aegean basins.