bluuebunny/crossref_metadata_2025 huggingface dataset:
Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis
Authors: Hashimoto Kenji
Published: July 2023

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a serious public health burden worldwide. In addition to respiratory, heart, and gastrointestinal symptoms, patients infected with SARS-CoV-2 experience a number of persistent neurological and psychiatric symptoms, known as long COVID or “brain fog”. Studies of autopsy samples from patients who died from COVID-19 detected SARS-CoV-2 in the brain. Furthermore, increasing evidence shows that Epstein–Barr virus (EBV) reactivation after SARS-CoV-2 infection might play a role in long COVID symptoms. Moreover, alterations in the microbiome after SARS-CoV-2 infection might contribute to acute and long COVID symptoms. In this article, the author reviews the detrimental effects of COVID-19 on the brain, and the biological mechanisms (e.g., EBV reactivation, and changes in the gut, nasal, oral, or lung microbiomes) underlying long COVID. In addition, the author discusses potential therapeutic approaches based on the gut–brain axis, including plant-based diet, probiotics and prebiotics, fecal microbiota transplantation, and vagus nerve stimulation, and sigma-1 receptor agonist fluvoxamine.
The heterogeneous associations between gestational weight gain and adverse pregnancy outcomes in gestational diabetes mellitus according to abnormal glucose metabolism
Authors: Wu Qi , Chen Yunyan , Ma Hao , Zhou Tao , Hu Ying , Liang Zhaoxia , Chen Danqing
Published: July 2023

Objectives

The gestational weight gain (GWG) and hyperglycemia are two key factors affecting adverse pregnancy outcomes among women with gestational diabetes mellitus (GDM). We aimed to investigate the combinatorial effect of abnormal glucose metabolism and GWG on adverse outcomes in GDM.

Methods

This retrospective cohort study included 2611 pregnant women with GDM in Women’s Hospital School of Medicine Zhejiang University. Bases on the OGTT glucose levels, we categorized the GDM cohort into three subgroups: impaired fasting glucose (IFG) group, impaired glucose tolerance (IGT) group, and combined impaired glucose (IFG&IGT) group.

Results

Among pregnant women with IGT, insufficient GWG (IGWG) was an independent protective factor for pregnancy-induced hypertension syndrome (PIH) (aOR 0.55, 95% CI 0.32-0.95), macrosomia (0.38, 0.19-0.74) and large for gestational age (0.45, 0.32-0.62), as well as an independent risk factor for low birth weight infants (2.29, 1.24-4.22) and small for gestational age (1.94, 1.17-3.19); and excessive GWG (EGWG) was related to increased risks of PIH (1.68, 1.12-2.52), preterm delivery (1.82, 1.28-2.58), postpartum hemorrhage (1.85, 1.05–3.28), cesarean delivery (1.84, 1.38-2.46) and low body weight infants (2.36, 1.33-4.20). Moreover, EGWG was positively associated with PIH (3.27, 1.09–9.80) in the IFG group. But there were no significant associations between either IGWG or EGWG and any pregnancy outcomes in women with combined IFG&IGT.

Conclusions

The relationships between GWG and adverse outcomes were modified by abnormal glucose metabolism in women with GDM. Our results suggest that more specific GWG recommendations according to their metabolic state are needed for GDM.
Rational design of PD-1-CD28 immunostimulatory fusion proteins for CAR T cell therapy
Authors: Lorenzini Theo , Cadilha Bruno L. , Obeck Hannah , Benmebarek Mohamed-Reda , Märkl Florian , Michaelides Stefanos , Strzalkowski Thaddäus , Briukhovetska Daria , Müller Philipp Jie , Nandi Sayantan , Winter Pia , Majed Lina , Grünmeier Ruth , Seifert Matthias , Rausch Svenja , Feuchtinger Tobias , Endres Stefan , Kobold Sebastian
Published: July 2023

Background

In many situations, the therapeutic efficacy of CAR T cells is limited due to immune suppression and poor persistence. Immunostimulatory fusion protein (IFP) constructs have been advanced as a tool to convert suppressive signals into stimulation and thus promote the persistence of T cells, but no universal IFP design has been established so far. We now took advantage of a PD-1-CD28 IFP as a clinically relevant structure to define key determinants of IFP activity.

Methods

We compared different PD-1-CD28 IFP variants in a human leukemia model to assess the impact of distinctive design choices on CAR T cell performance in vitro and a xenograft mouse model.

Results

We observed that IFP constructs that putatively exceed the extracellular length of PD-1 induce T-cell response without CAR target recognition, rendering them unsuitable for tumour-specific therapy. IFP variants with physiological PD-1 length ameliorated CAR T cell effector function and proliferation in response to PD-L1+ tumour cells in vitro and prolonged survival in vivo. Transmembrane or extracellular CD28 domains were found to be replaceable by corresponding PD-1 domains for in vivo efficacy.

Conclusion

PD-1-CD28 IFP constructs must mimic the physiological interaction of PD-1 with PD-L1 to retain selectivity and mediate CAR-conditional therapeutic activity.
Altered muscle niche contributes to myogenic deficit in the D2-mdx model of severe DMD
Authors: Mázala Davi A. G. , Hindupur Ravi , Moon Young Jae , Shaikh Fatima , Gamu Iteoluwakishi H. , Alladi Dhruv , Panci Georgiana , Weiss-Gayet Michèle , Chazaud Bénédicte , Partridge Terence A. , Novak James S. , Jaiswal Jyoti K.
Published: July 2023

Lack of dystrophin expression is the underlying genetic basis for Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2-mdx is a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2-mdx muscles is associated with an enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports the excessive accumulation of fibroadipogenic progenitors (FAPs), leading to increased fibrosis. Unexpectedly, the extent of damage and degeneration in juvenile D2-mdx muscle is significantly reduced in adults, and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance regenerative myogenesis in the adult D2-mdx muscle, reaching levels comparable to the milder B10-mdx model of DMD. Ex vivo co-culture of healthy satellite cells (SCs) with juvenile D2-mdx FAPs reduces their fusion efficacy. Wild-type juvenile D2 mice also manifest regenerative myogenic deficit and glucocorticoid treatment improves their muscle regeneration. Our findings indicate that aberrant stromal cell responses contribute to poor regenerative myogenesis and greater muscle degeneration in juvenile D2-mdx muscles and reversal of this reduces pathology in adult D2-mdx muscle, identifying these responses as a potential therapeutic target for the treatment of DMD.
Impaired vision in children prenatally exposed to methadone: an observational cohort study
Authors: Hamilton R. , Mulvihill A. , Butler L. , Chow A. , Irving E. , McCulloch D. L. , McNeil A. , Michael K. , Spowart K. M. , Waterson-Wilson J. , Mactier H.
Published: July 2023

Background/objectives

To examine prevalence of failed visual assessment at 8–10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure.

Subjects/methods

Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a ‘fail’. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables.

Results

33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual ‘fail’ outcome, adjusted odds ratio 2.6, 95% CI 1.1–6.2; adjusted relative risk 1.8 (95% CI 1.1–3.4). Visual ‘fail’ outcome rates did not differ between methadone-exposed children who had (n = 47) or had not (n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference—11–27%).

Conclusions

Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure.

Trial registration

The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301.
Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates
Authors: Limorenko Galina , Tatli Meltem , Kolla Rajasekhar , Nazarov Sergey , Weil Marie-Theres , Schöndorf David C. , Geist Daniela , Reinhardt Peter , Ehrnhoefer Dagmar E. , Stahlberg Henning , Gasparini Laura , Lashuel Hilal A.
Published: July 2023

Tau protein fibrillization is implicated in the pathogenesis of several neurodegenerative diseases collectively known as Tauopathies. For decades, investigating Tau fibrillization in vitro has required the addition of polyanions or other co-factors to induce its misfolding and aggregation, with heparin being the most commonly used. However, heparin-induced Tau fibrils exhibit high morphological heterogeneity and a striking structural divergence from Tau fibrils isolated from Tauopathies patients’ brains at ultra- and macro-structural levels. To address these limitations, we developed a quick, cheap, and effective method for producing completely co-factor-free fibrils from all full-length Tau isoforms and mixtures thereof. We show that Tau fibrils generated using this ClearTau method – ClearTau fibrils - exhibit amyloid-like features, possess seeding activity in biosensor cells and hiPSC-derived neurons, retain RNA-binding capacity, and have morphological properties and structures more reminiscent of the properties of the brain-derived Tau fibrils. We present the proof-of-concept implementation of the ClearTau platform for screening Tau aggregation-modifying compounds. We demonstrate that these advances open opportunities to investigate the pathophysiology of disease-relevant Tau aggregates and will facilitate the development of Tau pathology-targeting and modifying therapies and PET tracers that can distinguish between different Tauopathies.
Joint analysis of phenotype-effect-generation identifies loci associated with grain quality traits in rice hybrids
Authors: Li Lanzhi , Zheng Xingfei , Wang Jiabo , Zhang Xueli , He Xiaogang , Xiong Liwen , Song Shufeng , Su Jing , Diao Ying , Yuan Zheming , Zhang Zhiwu , Hu Zhongli
Published: July 2023

Genetic improvement of grain quality is more challenging in hybrid rice than in inbred rice due to additional nonadditive effects such as dominance. Here, we describe a pipeline developed for joint analysis of phenotypes, effects, and generations (JPEG). As a demonstration, we analyze 12 grain quality traits of 113 inbred lines (male parents), five tester lines (female parents), and 565 (113×5) of their hybrids. We sequence the parents for single nucleotide polymorphisms calling and infer the genotypes of the hybrids. Genome-wide association studies with JPEG identify 128 loci associated with at least one of the 12 traits, including 44, 97, and 13 loci with additive effects, dominant effects, and both additive and dominant effects, respectively. These loci together explain more than 30% of the genetic variation in hybrid performance for each of the traits. The JEPG statistical pipeline can help to identify superior crosses for breeding rice hybrids with improved grain quality.
Extensive diversity in RNA termination and regulation revealed by transcriptome mapping for the Lyme pathogen Borrelia burgdorferi
Authors: Petroni Emily , Esnault Caroline , Tetreault Daniel , Dale Ryan K. , Storz Gisela , Adams Philip P.
Published: July 2023

Transcription termination is an essential and dynamic process that can tune gene expression in response to diverse molecular signals. Yet, the genomic positions, molecular mechanisms, and regulatory consequences of termination have only been studied thoroughly in model bacteria. Here, we use several RNA-seq approaches to map RNA ends for the transcriptome of the spirochete Borrelia burgdorferi – the etiological agent of Lyme disease. We identify complex gene arrangements and operons, untranslated regions and small RNAs. We predict intrinsic terminators and experimentally test examples of Rho-dependent transcription termination. Remarkably, 63% of RNA 3′ ends map upstream of or internal to open reading frames (ORFs), including genes involved in the unique infectious cycle of B. burgdorferi. We suggest these RNAs result from premature termination, processing and regulatory events such as cis-acting regulation. Furthermore, the polyamine spermidine globally influences the generation of truncated mRNAs. Collectively, our findings provide insights into transcription termination and uncover an abundance of potential RNA regulators in B. burgdorferi.
Chronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity
Authors: Flaherty Stephen E. , Bezy Olivier , Zheng Wei , Yan Dong , Li Xiangping , Jagarlapudi Srinath , Albuquerque Bina , Esquejo Ryan M. , Peloquin Matthew , Semache Meriem , Mancini Arturo , Kang Liya , Drujan Doreen , Breitkopf Susanne B. , Griffin John D. , Jean Beltran Pierre M. , Xue Liang , Stansfield John , Pashos Evanthia , Shakey Quazi , Pehmøller Christian , Monetti Mara , Birnbaum Morris J. , Fortin Jean-Philippe , Wu Zhidan
Published: July 2023

Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone receptor 2 (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of UCN2 induces systemic insulin resistance in male mice and skeletal muscle. Inversely, chronic elevation of UCN2 by injection with adenovirus encoding UCN2 resolves metabolic complications, improving glucose tolerance. CRHR2 recruits Gs in response to low concentrations of UCN2, as well as Gi and β-Arrestin at high concentrations of UCN2. Pre-treating cells and skeletal muscle ex vivo with UCN2 leads to internalization of CRHR2, dampened ligand-dependent increases in cAMP, and blunted reductions in insulin signaling. These results provide mechanistic insights into how UCN2 regulates insulin sensitivity and glucose metabolism in skeletal muscle and in vivo. Importantly, a working model was derived from these results that unifies the contradictory metabolic effects of UCN2.
Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome
Authors: Menzel Jan Philipp , Young Reuben S. E. , Benfield Aurélie H. , Scott Julia S. , Wongsomboon Puttandon , Cudlman Lukáš , Cvačka Josef , Butler Lisa M. , Henriques Sónia T. , Poad Berwyck L. J. , Blanksby Stephen J.
Published: July 2023

Fatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acids are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow, to discover unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds. The workflow encompasses semi-automated data analysis and enables de novo identification in complex media including human plasma, cancer cell lines and vernix caseosa. The targeted analysis including ozonolysis enables structural assignment over a dynamic range of five orders of magnitude, even in instances of incomplete chromatographic separation. Thereby we expand the number of identified plasma fatty acids two-fold, including non-methylene-interrupted fatty acids. Detection, without prior knowledge, allows discovery of non-canonical double bond positions. Changes in relative isomer abundances reflect underlying perturbations in lipid metabolism.
High-speed scanless entire bandwidth mid-infrared chemical imaging
Authors: Zhao Yue , Kusama Shota , Furutani Yuji , Huang Wei-Hong , Luo Chih-Wei , Fuji Takao
Published: July 2023

Mid-infrared spectroscopy probes molecular vibrations to identify chemical species and functional groups. Therefore, mid-infrared hyperspectral imaging is one of the most powerful and promising candidates for chemical imaging using optical methods. Yet high-speed and entire bandwidth mid-infrared hyperspectral imaging has not been realized. Here we report a mid-infrared hyperspectral chemical imaging technique that uses chirped pulse upconversion of sub-cycle pulses at the image plane. This technique offers a lateral resolution of 15 µm, and the field of view is adjustable between 800 µm × 600 µm to 12 mm × 9 mm. The hyperspectral imaging produces a 640 × 480 pixel image in 8 s, which covers a spectral range of 640–3015 cm–1, comprising 1069 wavelength points and offering a wavenumber resolution of 2.6–3.7 cm–1. For discrete frequency mid-infrared imaging, the measurement speed reaches a frame rate of 5 kHz, the repetition rate of the laser. As a demonstration, we effectively identified and mapped different components in a microfluidic device, plant cell, and mouse embryo section. The great capacity and latent force of this technique in chemical imaging promise to be applied to many fields such as chemical analysis, biology, and medicine.
Polar Solomon rings in ferroelectric nanocrystals
Authors: Wang Jing , Liang Deshan , Ma Jing , Fan Yuanyuan , Ma Ji , Jafri Hasnain Mehdi , Yang Huayu , Zhang Qinghua , Wang Yue , Guo Changqing , Dong Shouzhe , Liu Di , Wang Xueyun , Hong Jiawang , Zhang Nan , Gu Lin , Yi Di , Zhang Jinxing , Lin Yuanhua , Chen Long-Qing , Huang Houbing , Nan Ce-Wen
Published: July 2023

Solomon rings, upholding the symbol of wisdom with profound historical roots, were widely used as decorations in ancient architecture and clothing. However, it was only recently discovered that such topological structures can be formed by self-organization in biological/chemical molecules, liquid crystals, etc. Here, we report the observation of polar Solomon rings in a ferroelectric nanocrystal, which consist of two intertwined vortices and are mathematically equivalent to a $${4}_{1}^{2}$$

4

1

2

link in topology. By combining piezoresponse force microscopy observations and phase-field simulations, we demonstrate the reversible switching between polar Solomon rings and vertex textures by an electric field. The two types of topological polar textures exhibit distinct absorption of terahertz infrared waves, which can be exploited in infrared displays with a nanoscale resolution. Our study establishes, both experimentally and computationally, the existence and electrical manipulation of polar Solomon rings, a new form of topological polar structures that may provide a simple way for fast, robust, and high-resolution optoelectronic devices.
A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity
Authors: Zhang Mingfeng , Shan Yuanyue , Cox Charles D. , Pei Duanqing
Published: July 2023

Mechanosensitive (MS) ion channels are a ubiquitous type of molecular force sensor sensing forces from the surrounding bilayer. The profound structural diversity in these channels suggests that the molecular mechanisms of force sensing follow unique structural blueprints. Here we determine the structures of plant and mammalian OSCA/TMEM63 proteins, allowing us to identify essential elements for mechanotransduction and propose roles for putative bound lipids in OSCA/TMEM63 mechanosensation. Briefly, the central cavity created by the dimer interface couples each subunit and modulates dimeric OSCA/TMEM63 channel mechanosensitivity through the modulating lipids while the cytosolic side of the pore is gated by a plug lipid that prevents the ion permeation. Our results suggest that the gating mechanism of OSCA/TMEM63 channels may combine structural aspects of the ‘lipid-gated’ mechanism of MscS and TRAAK channels and the calcium-induced gating mechanism of the TMEM16 family, which may provide insights into the structural rearrangements of TMEM16/TMC superfamilies.
A soft, self-sensing tensile valve for perceptive soft robots
Authors: Choe Jun Kyu , Kim Junsoo , Song Hyeonseo , Bae Joonbum , Kim Jiyun
Published: July 2023

Soft inflatable robots are a promising paradigm for applications that benefit from their inherent safety and adaptability. However, for perception, complex connections of rigid electronics both in hardware and software remain the mainstay. Although recent efforts have created soft analogs of individual rigid components, the integration of sensing and control systems is challenging to achieve without compromising the complete softness, form factor, or capabilities. Here, we report a soft self-sensing tensile valve that integrates the functional capabilities of sensors and control valves to directly transform applied tensile strain into distinctive steady-state output pressure states using only a single, constant pressure source. By harnessing a unique mechanism, “helical pinching”, we derive physical sharing of both sensing and control valve structures, achieving all-in-one integration in a compact form factor. We demonstrate programmability and applicability of our platform, illustrating a pathway towards fully soft, electronics-free, untethered, and autonomous robotic systems.
In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir
Authors: Kiso Maki , Furusawa Yuri , Uraki Ryuta , Imai Masaki , Yamayoshi Seiya , Kawaoka Yoshihiro
Published: July 2023

Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal antibody therapies, potential SARS-CoV-2 resistance to nirmatrelvir is a major public health concern. Several amino acid substitutions have been identified as being responsible for reduced susceptibility to nirmatrelvir. Among them, we selected L50F/E166V and L50F/E166A/L167F in the 3CLpro because these combinations of substitutions are unlikely to affect virus fitness. We prepared and characterized delta variants possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F. Both mutant viruses showed decreased susceptibility to nirmatrelvir and their growth in VeroE6/TMPRSS2 cells was delayed. Both mutant viruses showed attenuated phenotypes in a male hamster infection model, maintained airborne transmissibility, and were outcompeted by wild-type virus in co-infection experiments in the absence of nirmatrelvir, but less so in the presence of the drug. These results suggest that viruses possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F do not become dominant in nature. However, it is important to closely monitor the emergence of nirmatrelvir-resistant SARS-CoV-2 variants because resistant viruses with additional compensatory mutations could emerge, outcompete the wild-type virus, and become dominant.
Generation of the transgene-free canker-resistant Citrus sinensis using Cas12a/crRNA ribonucleoprotein in the T0 generation
Authors: Su Hang , Wang Yuanchun , Xu Jin , Omar Ahmad A. , Grosser Jude W. , Calovic Milica , Zhang Liyang , Feng Yu , Vakulskas Christopher A. , Wang Nian
Published: July 2023

Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is a destructive citrus disease worldwide. Generating disease-resistant cultivars is the most effective, environmentally friendly and economic approach for disease control. However, citrus traditional breeding is lengthy and laborious. Here, we develop transgene-free canker-resistant Citrus sinensis lines in the T0 generation within 10 months through transformation of embryogenic protoplasts with Cas12a/crRNA ribonucleoprotein to edit the canker susceptibility gene CsLOB1. Among the 39 regenerated lines, 38 are biallelic/homozygous mutants, demonstrating a 97.4% biallelic/homozygous mutation rate. No off-target mutations are detected in the edited lines. Canker resistance of the cslob1-edited lines results from both abolishing canker symptoms and inhibiting Xcc growth. The transgene-free canker-resistant C. sinensis lines have received regulatory approval by USDA APHIS and are exempted from EPA regulation. This study provides a sustainable and efficient citrus canker control solution and presents an efficient transgene-free genome-editing strategy for citrus and other crops.
An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo
Authors: Tsuji Moriya , Nair Manoj S. , Masuda Kazuya , Castagna Candace , Chong Zhenlu , Darling Tamarand L. , Seehra Kuljeet , Hwang Youngmin , Ribeiro Ágata Lopes , Ferreira Geovane Marques , Corredor Laura , Coelho-dos-Reis Jordana Grazziela Alves , Tsuji Yukiko , Mori Munemasa , Boon Adrianus C. M. , Diamond Michael S. , Huang Yaoxing , Ho David D.
Published: July 2023

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as well as by respiratory syncytial virus and influenza virus, in mice or hamsters. We also found that this protective antiviral effect is both host-directed and mechanism-specific, requiring both the CD1d molecule and interferon-$$\gamma$$
γ
. A chemical compound like 7DW8-5 that is easy to administer and cheap to manufacture may be useful not only in slowing the spread of COVID-19 but also in responding to future pandemics long before vaccines or drugs are developed.
Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism
Authors: Nayak Smruti Ranjan , Joseph Deepthi , Höfner Georg , Dakua Archishman , Athreya Arunabh , Wanner Klaus T. , Kanner Baruch I. , Penmatsa Aravind
Published: July 2023

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is cleared from the synaptic cleft by the sodium- and chloride-coupled GABA transporter GAT1. Inhibition of GAT1 prolongs the GABAergic signaling at the synapse and is a strategy to treat certain forms of epilepsy. In this study, we present the cryo-electron microscopy structure of Rattus norvegicus GABA transporter 1 (rGAT1) at a resolution of 3.1 Å. The structure elucidation was facilitated by epitope transfer of a fragment-antigen binding (Fab) interaction site from the Drosophila dopamine transporter (dDAT) to rGAT1. The structure reveals rGAT1 in a cytosol-facing conformation, with a linear density in the primary binding site that accommodates a molecule of GABA, a displaced ion density proximal to Na site 1 and a bound chloride ion. A unique insertion in TM10 aids the formation of a compact, closed extracellular gate. Besides yielding mechanistic insights into ion and substrate recognition, our study will enable the rational design of specific antiepileptics.
Extracellular tau stimulates phagocytosis of living neurons by activated microglia via Toll-like 4 receptor–NLRP3 inflammasome–caspase-1 signalling axis
Authors: Pampuscenko Katryna , Morkuniene Ramune , Krasauskas Lukas , Smirnovas Vytautas , Brown Guy C. , Borutaite Vilmante
Published: July 2023

In tauopathies, abnormal deposition of intracellular tau protein followed by gradual elevation of tau in cerebrospinal fluids and neuronal loss has been documented, however, the mechanism how actually neurons die under tau pathology is largely unknown. We have previously shown that extracellular tau protein (2N4R isoform) can stimulate microglia to phagocytose live neurons, i.e. cause neuronal death by primary phagocytosis, also known as phagoptosis. Here we show that tau protein induced caspase-1 activation in microglial cells via ‘Toll-like’ 4 (TLR4) receptors and neutral sphingomyelinase. Tau-induced neuronal loss was blocked by caspase-1 inhibitors (Ac-YVAD-CHO and VX-765) as well as by TLR4 antibodies. Inhibition of caspase-1 by Ac-YVAD-CHO prevented tau-induced exposure of phosphatidylserine on the outer leaflet of neuronal membranes and reduced microglial phagocytic activity. We also show that suppression of NLRP3 inflammasome, which is down-stream of TLR4 receptors and mediates caspase-1 activation, by a specific inhibitor (MCC550) also prevented tau-induced neuronal loss. Moreover, NADPH oxidase is also involved in tau-induced neurotoxicity since neuronal loss was abolished by its pharmacological inhibitor. Overall, our data indicate that extracellular tau protein stimulates microglia to phagocytose live neurons via Toll-like 4 receptor–NLRP3 inflammasome–caspase-1 axis and NADPH oxidase, each of which may serve as a potential molecular target for pharmacological treatment of tauopathies.
An explorative cross-sectional analysis of mental health shame and help-seeking intentions in different lifestyles
Authors: Helmert Claudia , Fleischer Toni , Speerforck Sven , Ulke Christine , Altweck Laura , Hahm Stefanie , Muehlan Holger , Schmidt Silke , Grabe Hans J. , Völzke Henry , Schomerus Georg
Published: July 2023

To identify und support particular target groups for mental health prevention, we explore the links between shame and help-seeking intentions concerning mental health in different lifestyles (based on socioeconomic status as well as health-related behaviors). Lifestyles were operationalized by nine confirmatory, homogenous clusters of the sample. These clusters are based on individuals’ similarities in sociodemographic aspects and health behavior. Analyses included t tests, Chi-square, ANOVA, regressions investigating in sociodemographic characteristics. Hierarchical linear models examining cross-sectional associations of shame and willingness to seek help for different lifestyles of participants of the Study of Health in Pomerania (SHIP-START-1 and SHIP-START-3, data collected 2002–2006 and 2014–2016; n = 1630). Hierarchical linear models showed small context effects for lifestyle-related associations of shame and willingness to seek help. For younger as well as male participants, lifestyles indicated different associations of shame and help-seeking intentions: Especially the lifestyles with unhealthy behaviors and high as well as low socioeconomic status resulted in higher shame being associated with low help-seeking intentions in case of mental illness. Lifestyle clusters might be a useful tool to identify marginalized groups with unhealthy behaviors, which should be addressed by interventions and prevention programs.
Homozygosity mapping in the Kazakh national dog breed Tazy
Authors: Perfilyeva Anastassiya , Bespalova Kira , Bespalov Sergey , Begmanova Mamura , Kuzovleva Yelena , Vishnyakova Olga , Nazarenko Inna , Abylkassymova Gulnar , Perfilyeva Yuliya , Plakhov Konstantin , Djansugurova Leyla , Bekmanov Bakhytzhan
Published: July 2023

The Tazy is a breed of sighthound common in Kazakhstan. The identification of runs of homozygosity (ROH) is an informative approach to assessing the history and possible patterns of directional selection pressure. To our knowledge, the present study is the first to provide an overview of the ROH pattern in the Tazy dogs from a genome-wide perspective. The ROH of the Tazy was found to be mainly composed of shorter segments (1–2 Mb), accounting for approximately 67% of the total ROH. The estimated ROH-based inbreeding coefficients (FROH) ranged from 0.028 to 0.058 with a mean of 0.057. Five genomic regions under positive selection were identified on chromosomes 18, 22, and 25. The regions on chromosomes 18 and 22 may be breed specific, while the region on chromosome 22 overlaps with regions of hunting traits in other hunting dog breeds. Among the 12 candidate genes located in these regions, the gene CAB39L may be a candidate that affects running speed and endurance of the Tazy dog. Eight genes could belong to an evolutionarily conserved complex as they were clustered in a large protein network with strong linkages. The results may enable effective interventions when incorporated into conservation planning and selection of the Tazy breed.
Thickness-stiffness trade-off improves lodging resistance in rice
Authors: Tsugawa Satoru , Shima Hiroyuki , Ishimoto Yukitaka , Ishikawa Kazuya
Published: July 2023

Lodging of cereal crops significantly reduces grain yield and quality, making lodging resistance a prime target for breeding programs. However, lodging resistance among different rice (Oryza sativa L.) cultivars in the field remains largely unknown, as is the relationship between the major properties of culms such as their morphological and mechanical properties. Here, we investigated the morphological and mechanical properties of 12 rice cultivars by considering different internodes within culms. We detected variation in these two traits among cultivars: one set of cultivars had thicker but softer culms (thickness-type), while the other set of cultivars showed stiffer but thinner culms (stiffness-type). We designate this variation as a thickness-stiffness trade-off. We then constructed a mechanical model to dissect the mechanical and/or morphological constraints of rice culms subjected to their own weight (self-weight load). Through modeling, we discovered that ear weight and the morphology of the highest internode were important for reducing deflection, which may be important factors to achieve higher lodging resistance. The mechanical theory devised in this study could be used to predict the deflection of rice culms and may open new avenues for novel mechanics-based breeding techniques.
The role of water in the laboratory thermal advancement of immature type I kerogen from the Cretaceous Qingshankou Formation in China
Authors: Safaei-Farouji Majid , Gentzis Thomas , Liu Bo , Ma Zhongliang , Wang Liu , Xu Yaohui , Ostadhassan Mehdi
Published: July 2023

To understand variations in geochemistry, organic petrology, and chemical composition of crude oil and byproducts, an immature sample from the Cretaceous Qingshankou Formation in the Songliao Basin, China, was analyzed by anhydrous and hydrous pyrolysis (AHP/HP) at a wide range of temperatures ranging from 300 °C to 450 °C. The geochemical parameters: TOC, S2, HI, and Tmax obtained from Rock–Eval pyrolysis showed both a decrease and an increase as thermal maturity progressed under HP and AHP conditions. Gas chromatography (GC) analysis showed the presence of n-alkanes in the C14 to C36 range in both expelled and residual byproducts, a Delta-shaped configuration although many samples had a gradually reducing (tapering) trend toward the high range. Gas chromatography-mass spectrometry (GC–MS) analysis revealed both an increase and a decrease in biomarker and very small changes in aromatic compound variations with increasing temperature during pyrolysis. To be more specific, C29Ts biomarker increased with temperature for the expelled byproduct, while the opposite trend was observed for the residual one. Next, The Ts/Tm ratio initially increased and then decreased with temperature while the C29H/C30H ratio fluctuated for the expelled byproduct but increased for the residual. Moreover, the GI and C30 rearranged hopane to C30 hopane ratio remained unchanged whereas the C23 tricyclic terpane/C24 tetracyclic terpane ratio and the C23/C24 tricyclic terpane ratio showed varying trends with maturity alike the C19/C23 and C20/C23 tricyclic terpane. Ultimately, based on organic petrography observations, increasing the temperature resulted in higher bitumen reflectance (%Bro, r) and optical and structural alterations in the macerals. The findings of this study provide valuable insights for future exploration endeavors in the studied region. Moreover, they contribute to our understanding of the significant role of water in the generation and expulsion of petroleum and associated byproducts, thereby facilitating the development of updated models in this field.
Scaffolds with high oxygen content support osteogenic cell survival under hypoxia
Authors: Augustine Robin , Camci-Unal Gulden
Published: July 2023

Novel oxygen-generating scaffold with a controlled oxygen release profile can support osteogenic cells under hypoxia and is a promising solution for bone tissue engineering.
Green biomanufacturing in recombinant collagen biosynthesis: trends and selection in various expression systems
Authors: Zhao Zilong , Deng Jianjun , Fan Daidi
Published: July 2023

The rapid development of synthetic biology allows us to perform a heterologous expression of recombinant collagens in diverse expression systems (prokaryotic organisms, yeasts, plants, insects, mammalian and human cells,etc.).
Strong metal–support bonding enhanced thermal stability in Au–Al2O3 core–shell nanowires characterized by in situ transmission electron microscopy
Authors: Yang Haotian , Ridge Claron J. , Overdeep Kyle , Lindsay C. Michael , Tong Xiao , Orlov Alexander
Published: July 2023

Ultra-clean Au–Al2O3 nanowire with enhanced thermal stability.
Proline-conditioning and chemically-programmed ice nucleation protects spheroids during cryopreservation
Authors: Gao Yanan , Bissoyi Akalabya , Kinney Nina L. H. , Whale Thomas F. , Guo Qiongyu , Gibson Matthew I.
Published: July 2023

Addressing both biochemical and biophysical mechanisms of cryo-damage through proline preconditioning and induced ice nucleation rescues spheroids from cryopreservation damage.
A computational study on bifunctional 1T-MnS2 with an adsorption-catalysis effect for lithium–sulfur batteries
Authors: Duan Shaorong , Liu Mingyi , Cao Chuanzhao , Liu Haitao , Ye Meng , Duan Wenhui
Published: July 2023

1T-MnS2 exhibits excellent adsorption-catalysis activity for Li–S batteries, which can enhance the adsorption for polysulfides and accelerate the oxidation of Li2S and sulfur reduction reaction.
Refinement of nanoporous copper by dealloying the Al–Cu alloy in NaOH solution containing sodium dodecyl sulfate
Authors: Li Jie , Yi Zhi-Bin , Li Nuo-Tong , Yu Na-Na , Geng Hao-Ran
Published: July 2023

Nanoporous copper (NPC) is fabricated by sodium dodecyl sulfate (SDS)-mediated dealloying. SDS adsorbs on alloy surfaces and suppresses adatom diffusivity and thus refines the ligaments. SDS–alloy interactions are modeled by MD simulations.
Fascinating chiral information transfer to titania/silica from near to racemic compound self-organized from polyethyleneimine and tartaric acid
Authors: Oota Kei , Jin Ren-Hua
Published: July 2023

Crystalline aggregates (P/T) self-organized from polyethyleneimine (P) and enantiomeric excess (ee = ±4%, d/l = 52/48 and 48/52) of tartaric acid (T) could serve as chiral catalytic templates to effectively give chiroptical hybrids of TiO2/SiO2.
Flavonol dioxygenation catalysed by cobalt(ii) complexes supported with 3N(COO) and 4N donor ligands: a comparative study to assess the carboxylate effects on quercetin 2,4-dioxygenase-like reactivity
Authors: Podder Nirmalya , Saha Anannya , Barman Suman K. , Mandal Sukanta
Published: July 2023

This paper describes the model studies of quercetin 2,4-dioxygenase, mainly focusing on the role of the carboxylate group at the enzyme active site by comparing the catalytic activities of Co(ii) complexes supported with 3N(COO) and 4N donor ligands.
Tetraphenylporphyrin electrocatalysts for the hydrogen evolution reaction: applicability of molecular volcano plots to experimental operating conditions
Authors: Zaar Felicia , Moyses Araujo C. , Emanuelsson Rikard , Strømme Maria , Sjödin Martin
Published: July 2023

Recent years have seen an increasing interest in molecular electrocatalysts for the hydrogen evolution reaction (HER).
Co-adsorption and Fenton-like oxidation in the efficient removal of methylene blue by MIL-88B@UiO-66 nanoflowers
Authors: Teng Pingping , Liu Ying , Sun Zhongqiao , Meng Hao , Han Yide , Zhang Xia
Published: July 2023

For the first time, MIL-88B@UiO-66 nanoflower was applied in co-adsorption and Fenton-like oxidation to remove methylene-blue dye.
Ligand leaching enabling improved electrocatalytic oxygen evolution performance
Authors: Zhou Hongbo , Wei Zi , Nyaaba Albert Akeno , Kang Ziliang , Liu Yashu , Chen Caiyao , Zhu Jun , Ji Xiafang , Zhu Guoxing
Published: July 2023

Nanosheet-like organic frameworks composed by [Fe(CN)6]3− and amine coordinated Ni ions were prepared, the ligand leaching of which induced improved catalytic activity for oxygen evolution.
A eutectic electrolyte for an ultralong-lived Zn//V2O5cell: anin situgenerated gradient solid-electrolyte interphase
Authors: Meng Chao , He Wei-Dong , Tan Hao , Wu Xing-Long , Liu Hong , Wang Jian-Jun
Published: July 2023

This study achieved dendrite-free Zn metal anodes for Zn-ion batteriesviaanin situgenerated gradient organic/inorganic hybrid solid–electrolyte interphase enabled by a eutectic electrolyte.
Occurrence, distribution and environmental risk of 19 anthelmintic drugs in river water and sediment from the Jinjiang River, China
Authors: Yang Sheng , Liao Mengxi , Su Shijun , Ding Sanglan , Li Yiwen , Gan Zhiwei
Published: July 2023

This study explored the occurrence and distribution of 19 common anthelmintic drugs (ADs) in river water and sediment of the Jinjiang River in Sichuan, China, during summer and winter seasons.
Electrochemical inactivation of enteric viruses MS2, T4, and Phi6 using doped laser-induced graphene electrodes and filters
Authors: Nair Akhila M. , Kumar Ashish , Barbhuiya Najmul H. , Singh Swatantra P.
Published: July 2023

Titanium suboxide-doped laser-induced graphene holds great potential to inactivate model enteric viruses MS2, T4, and Phi6. The mechanism of inactivation was recognized as the combination of electric field-induced effects and electrooxidation.
Synthesis and functionalization of zinc phosphate@polyglycidyl methacrylate composites for antimicrobial drug immobilization and controlled release: an in vitro study
Authors: Shathi Tonmoye Sarkar , Rahman Md. Abdur , Rahman Md. Ataur , Nasiruddin Md. , Alim Al-Bari Md. Abdul , Pande Sagar , Komeda Tadahiro , Ul-Hamid Anwar , Ahmad Hasan , Karim Md. Rabiul
Published: July 2023

Functionalized polyglycidyl methacrylate coated ZnPPs with enhanced surface properties were synthesized for physical immobilization, and sustained release of antibacterial drug under physiological and slightly acidic media.
Synthesis of bimetallic aluminum–iron oxide nanorice, nanocubes and nanospheres
Authors: Hoque Abdul , Huseinov Artur , Nawarathne Chaminda P. , Alvarez Noe T.
Published: July 2023

Synthesis of bimetallic oxide nanorice, nanocube and nanosphere particles made of AlOx–Fe2O3. The amorphous AlOx goes into phase transformation into γ-Al2O3 and α-Al2O3 at high-temperatures while the crystallinity of Fe2O3 is maintained.
Atomically precise chiral silver clusters based on non-chiral ligands for acid/base stimulated luminescence response
Authors: Wang Shuaibo , He Weimiao , Cui Yujia , Zhou Zhan , Ma Lufang , Zang Shuang-Quan
Published: July 2023

Spontaneous crystalline chiral resolution of homochiral clusters in Ag6-Rac clusters with acid–base stimulated fluorescence response.
Prolinamides containing 2-(2-aminocyclohexyl)phenols as highly enantioselective organocatalysts for aldol reactions
Authors: Yeşil Tolga A. , Atalar Taner , Yavuz Mustafa , Ertürk Erkan
Published: July 2023

Novel prolinamides containing a phenol OH as the H-bond donor group have been reported as conformationally flexible organocatalysts.
Recent advances in radical-mediated intermolecular (4 + 2) cycloaddition
Authors: Cai Xue-Er , Wang Zi-Ying , Tian Wen-Chan , Liu Hongxin , Wei Wen-Ting , Lei Ke-Wei
Published: July 2023

On the basis of the types of radicals that initiate different intermolecular (4 + 2) cycloaddition processes, we classify them into five types, and this review places special emphasis on the reaction design and mechanisms.
GSH-triggered disintegrable hyperbranched polymer prodrug as unimolecular micelles for tumor-specific chemotherapy
Authors: Li Jie , Yang Yubin , Liu Peng
Published: July 2023

A GSH-triggered disintegrable hyperbranched polymer prodrug was designed for tumor-specific chemotherapy, to solve the conflict between the stability and drug release of its unimolecular micelles.
Chemical recycling to monomer: thermodynamic and kinetic control of the ring-closing depolymerization of aliphatic polyesters and polycarbonates
Authors: Cederholm Linnea , Olsén Peter , Hakkarainen Minna , Odelius Karin
Published: July 2023

The study investigates the potential in solvent triggered chemical recycling and how the power of the solvent effect is influenced by the monomer structure. Catalyst selectivity is utilized to demonstrate chemical recycling of mixed polymer waste.
Copper-catalyzed multicomponent cascade synthesis of polyfunctionalized β-ketone sulfones
Authors: Luo Chun-Mei , Sun Yong-Bin , Wang Ling-Tao , Dai Nan-Nan , Li Jiao-Zhe , Zhang Jianfeng , Chen Jin-Yang , Wei Wen-Ting , Ge Guo-Ping
Published: July 2023

Polyfunctionalized β-ketone sulfones are prepared in one-pot through a series of processes including radical relay, radical addition, hydrogen abstraction, hydrolysis or oxidation.
Aptamer-based colorimetric and lateral flow assay approaches for the detection of toxic metal ions, thallium(i) and lead(ii)
Authors: Srinivasan Sathya , Ranganathan Velu , McConnell Erin M. , Murari Bhaskar Mohan , DeRosa Maria C.
Published: July 2023

Simple colorimetric and lateral flow sensing for the heavy metal ions, thallium(i) and lead(ii), using aptamers.
Entropy stabilized cubic Li7La3Zr2O12 with reduced lithium diffusion activation energy: studied using solid-state NMR spectroscopy
Authors: Fan Juntian , Wang Tao , Bridges Craig A. , Borisevich Albina Y. , Steren Carlos A. , Li Pengzhen , Thapaliya Bishnu P. , Do-Thanh Chi-Linh , Yang Zhenzhen , Yuan Yating , Dai Sheng
Published: July 2023

A high-entropy strategy at Zr sites was achieved to stabilize cubic Li7La3Zr2O12 and reduce lithium diffusion activation energy, demonstrated by SSNMR.
Highly efficient and selective CO2 capture of Li2CO3- and (Li–K)2CO3-based porous carbon composites
Authors: Li Honghao , Nasiman Tuerxun
Published: July 2023

In this study, adsorbents containing Li were synthesized, which have excellent carbon dioxide adsorption capacity, adsorption selectivity and reproducibility, and have great application prospects in the field of CO2 adsorption.
Design, synthesis and antitumor activity of Ascaphin-8 derived stapled peptides based on halogen–sulfhydryl click chemical reactions
Authors: Kong Xianglong , Zhang Nan , Shen Huaxing , Wang Nan , Cong Wei , Liu Chao , Hu Hong-gang
Published: July 2023

Ascaphin-8 (GFKDLLKGAAKALVKTVLF-NH2) and its derived stapled peptides based on halogen–sulfhydryl click chemical reactions.
Copper borate (CuB4O7)-promoted multi-component green synthesis of 2,4,5-triarylimidazole derivatives and evidence of in situ conversion of copper borate (CuB4O7) into Cu(OAc)2 in the presence of NH4OAc
Authors: Chettri Sailesh , Tamang Sumiran , Pradhan Kiran , Sinha Biswajit , Brahman Dhiraj
Published: July 2023

A green, efficient, and straightforward methodology for the three-component synthesis of 2,4,5-triarylimidazole has been developed under solvent-free conditions using unconventional CuB4O7 as a promoter.