bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential oil supplementation in milk replacers: short- and long-term impacts on feed efficiency, the faecal microbiota and the plasma metabolome in dairy calves
Authors: Andrés Sonia , Gini Chiara , Ceciliani Fabrizio , Gutiérrez-Expósito Daniel , Arteche-Villasol Noive , Martín Alba , Cremonesi Paola , Faré Fiorenza , Ghaffari Morteza Hosseini , Giráldez F. Javier , Abdennebi-Najar Latifa
Published: April 2024

Early supplementation with oregano essential oil (EO) in milk replacer (MR) may improve growth, immune responses, the microbiota and the metabolome in dairy calves during pre-weaning and in adulthood. Sixteen female dairy calves (3 days of age) were divided in two groups (n = 8/group): the control group (no EO) and the EO group (0.23 ml of EO in MR during 45 days). After weaning, calves were kept in a feedlot and fed ad libitum. The animals were weighed, and blood and faecal samples were collected on days 3 (T0), 45 (T1) and 370 (T2) to measure the biochemical profile and characterise peripheral blood mononuclear cells (PBMCs; CD4+, CD8+, CD14+, CD21+ and WC1+), the metabolome and microbiota composition. The EO group only had greater average daily weight gain during the suckling (EO supplementation) period (P = 0.030). The EO group showed higher average CD14+ population (monocytes) values, a lower abundance of Ruminococcaceae UCG-014, Faecalibacterium, Blautia and Alloprevotella and increased abundances of Allistipes and Akkermansia. The modification of some metabolites in plasma, such as butyric acid, 3-indole-propionic acid and succinic acid, particularly at T1, are consistent with intestinal microbiota changes. The data suggest that early EO supplementation increases feed efficiency only during the suckling period with notable changes in the microbiota and plasma metabolome; however, not all of these changes can be considered desirable from a gut health point of view. Additional research studies is required to demonstrate that EOs are a viable natural alternative to antibiotics for improving calf growth performance and health.
A systematic review of the neutrophil to lymphocyte and platelet to	lymphocyte ratios in patients with lower extremity arterial	disease
Authors: Bradley Nicholas A. , Roxburgh Campbell S. D. , McMillan Donald C. , Guthrie Graeme J. K.
Published: April 2024

Summary: Lower extremity arterial disease (LEAD) is caused by atherosclerotic plaque in the arterial supply to the lower limbs. The neutrophil to lymphocyte and platelet to lymphocyte ratios (NLR, PLR) are established markers of systemic inflammation which are related to inferior outcomes in multiple clinical conditions, though remain poorly described in patients with LEAD. This review was carried out in accordance with PRISMA guidelines. The MEDLINE database was interrogated for relevant studies. Primary outcome was the prognostic effect of NLR and PLR on clinical outcomes following treatment, and secondary outcomes were the prognostic effect of NLR and PLR on disease severity and technical success following revascularisation. There were 34 studies included in the final review reporting outcomes on a total of 19870 patients. NLR was investigated in 21 studies, PLR was investigated in two studies, and both NLR & PLR were investigated in 11 studies. Relating to increased levels of systemic inflammation, 20 studies (100%) reported inferior clinical outcomes, 13 (92.9%) studies reported increased disease severity, and seven (87.5%) studies reported inferior technical results from revascularisation. The studies included in this review support the role of elevated NLR and PLR as key components influencing the clinical outcomes, severity, and success of treatment in patients with LEAD. The use of these easily accessible, cost effective and routinely available markers is supported by the present review.
Chemistry Contribution to Stratospheric Ozone Depletion After the Unprecedented Water‐Rich Hunga Tonga Eruption
Authors: Zhang Jun , Kinnison Douglas , Zhu Yunqian , Wang Xinyue , Tilmes Simone , Dube Kimberlee , Randel William
Published: April 2024

Following the Hunga Tonga–Hunga Ha'apai (HTHH) eruption in January 2022, stratospheric ozone depletion was observed at Southern Hemisphere mid‐latitudes and over Antarctica during the 2022 austral wintertime and springtime, respectively. The eruption injected sulfur dioxide and unprecedented amounts of water vapor into the stratosphere. This work examines the chemistry contribution of the volcanic materials to ozone depletion using chemistry‐climate model simulations with nudged meteorology. Simulated 2022 ozone and nitrogen oxide (NOx = NO + NO2) anomalies show good agreement with satellite observations. We find that chemistry yields up to 4% ozone destruction at mid‐latitudes near ∼70 hPa in August and up to 20% ozone destruction over Antarctica near ∼80 hPa in October. Most of the ozone depletion is attributed to internal variability and dynamical changes forced by the eruption. Both the modeling and observations show a significant NOx reduction associated with the HTHH aerosol plume, indicating enhanced dinitrogen pentoxide hydrolysis on sulfate aerosol.
Observed Spatiotemporal Variability in the Annual Sea Level Cycle Along the Global Coast
Authors: Barroso A. , Wahl T. , Li S. , Enriquez A. , Morim J. , Dangendorf S. , Piecuch C. , Thompson P.
Published: April 2024

Changes in the seasonal sea level cycle can modulate the flooding risk along coastlines. Here, we use harmonic analysis to quantify changes in the amplitude and phase of the annual component of the sea level cycle at 798 tide gauge locations along the global coastline where long records are available. We identify coastal hotspots by applying clustering methods revealing coherent regions with similar patterns of variability in the annual sea level cycle. Results show that for most tide gauges the annual amplitude reached its maximum after 1970 and its peak typically occurs during the fall season of the respective hemisphere. Many tide gauges exhibit non‐stationarity in the annual cycle in terms of amplitude and/or phase. For example, at 226 tide gauges we find significant trends in the amplitude (either increasing or decreasing) for the time period after 1970; while several sites (50 in total), mostly in the Mediterranean and around Pacific islands, experienced phase changes leading to shifts in the timing of the peak of the annual cycle by more than a month over their entire record. Our results highlight the importance of accounting for potential non‐stationarity in seasonal mean sea level cycles along coastlines.
Analyzing the Instabilities in the Venus Atmosphere Using Bred Vectors
Authors: Liang Jianyu , Sugimoto Norihiko , Miyoshi Takemasa
Published: April 2024

Barotropic, baroclinic, and Rossby‐Kelvin instabilities exist in the Venus atmosphere, as revealed by previous studies using numerical models. This study aims to deepen our understanding of the instabilities in the Venus atmosphere using the breeding of growing modes (BGM) method for the first time. We conducted a 1‐year model simulation as the control run. First, we conducted identical twin experiments in which random perturbations were added to the control run at the initial time, and they grew freely. Perturbations in the upper layer (UL, 70–100 km altitudes) grow faster at the beginning but saturate earlier at a low value compared to those in the lower layer (LL, 40–70 km altitudes). Next, we implemented the BGM method and conducted multiple breeding cycle experiments with different rescaling amplitudes and intervals, the two parameters of the BGM method. The bred vectors (BVs) from these experiments identified instabilities in various regions. With large rescaling amplitudes, the structure and amplitude of the BVs in the LL closely resembled the deviations in the control run, indicating the growth of BVs due to barotropic, baroclinic, and Rossby‐Kelvin instabilities. Composite mean analysis shows larger BV amplitudes in the morning hemisphere at the 60–70 km altitudes in the mid‐latitudes, indicating enhanced baroclinic instability by the thermal tide. Finally, we estimated the intrinsic predictability related to baroclinic instability for Venus is >1 month, which would be longer than that for the Earth of ∼2 weeks.
Effects of Seasonal Variations in Seagrass Density and Storms on Sediment Retention and Connectivity Between Subtidal Flats and Intertidal Marsh
Authors: Zhu Qingguang , Wiberg Patricia L.
Published: April 2024

Both submerged aquatic vegetation and salt marsh are important coastal ecosystems known for their effectiveness in sediment trapping and carbon burial. However, their proximity can lead to competition for limited sediment resources, potentially compromising their capacity to facilitate sufficient sediment deposition to withstand sea‐level rise. Here we applied the Delft3D flow and sediment transport model in a shallow coastal bay to assess how seasonal variations in seagrass density and storms modulate sediment retention and connectivity between subtidal flats and intertidal marsh. Results show that submerged seagrass meadows acted as temporary storage for fine sediment and altered the timing of sediment transport to an adjacent marsh through seasonal growth cycles. When seagrass occupied subtidal flats, sediment flux to the marsh was controlled by seasonal seagrass density variations, with peak fluxes during winter senescence. In contrast, wave‐induced sediment resuspension on the flats was the major contributor for marsh sediment input in the simulation with no seagrass, with peak storm‐driven fluxes in summer/autumn. Overall, seagrass meadows significantly increased annual sediment accumulation on the vegetated subtidal flats by tenfold, while reducing annual marsh sediment flux and edge erosion by 20%. Seagrass meadows and marsh were both able to maintain a sediment deposition rate comparable to the rapid sea‐level rise at the study site despite the absence of terrestrial sediment sources. Our findings highlight the strong seasonal control subtidal aquatic vegetation has in the vertical and horizontal dynamics of tidal flat‐marsh systems and provide insights that can inform wetland restoration and management strategies in similar systems.
Entosis: the core mechanism and crosstalk with other cell death programs
Authors: Kim Sunghoon , Lee Donghyuk , Kim Sung Eun , Overholtzer Michael
Published: April 2024

Cell death pathways play critical roles in organism development and homeostasis as well as in the pathogenesis of various diseases. While studies over the last decade have elucidated numerous different forms of cell death that can eliminate cells in various contexts, how certain mechanisms impact physiology is still not well understood. Moreover, recent studies have shown that multiple forms cell death can occur in a cell population, with different forms of death eliminating individual cells. Here, we aim to describe the known molecular mechanisms of entosis, a non-apoptotic cell engulfment process, and discuss signaling mechanisms that control its induction as well as its possible crosstalk with other cell death mechanisms.
Mass-produced and uniformly luminescent photochromic fibers toward future interactive wearable displays
Authors: Li Yan , Su Yikai
Published: April 2024

Enabling flexible fibers with light-emitting capabilities has the potential to revolutionize the design of smart wearable interactive devices. A recent publication in Light Science & Application, an interdisciplinary team of scientists led by Prof. Yan-Qing Lu and Prof. Guangming Tao has realized a highly flexible, uniformly luminescent photochromic fiber based on a mass-produced thermal drawing method. It overcomes the shortcomings of existing commercial light-diffusing fibers, exhibiting outstanding one-dimensional linear illumination performance. The research team integrated controllable photochromic fibers into various wearable interaction interfaces, providing a novel approach and insights to enable human-computer interaction.
Knowledge and attitudes toward anaphylaxis to local anesthetics in dental practice
Authors: Cherrez-Ojeda Ivan , Gallardo-Bastidas Juan C. , Borrero Gabriela Rouillon , Mautong Hans , Silva Paola Andrea Mena , Sarfraz Zouina , Sarfraz Azza , Cano Leonardo , Robles-Velasco Karla
Published: April 2024

Objective/aim

The absence of a comprehensive understanding of potential anaphylactic reactions to local anesthetics (LAs) and management can result in grave consequences. For this reason we aim to assess Latin American dentists’ knowledge, preparedness, and competency in managing anaphylactic reactions to LAs.

Materials and Methods

Design: A cross-sectional study was conducted from November 2021 to February 2022. Board-certified dentists answered a survey comprising 26 structured questions. Chi-square tests and logistic regression models were performed in Stata 17.0. Setting: Argentina, Brazil, Colombia, Costa Rica, Ecuador, Honduras, Mexico, Peru, Venezuela, and other Latin American countries.

Results

Of 507 respondents, lidocaine was the most frequently used LA (88.1%). While 85.2% could identify dyspnea as a symptom of anaphylaxis, only 50.1% knew the correct route for epinephrine administration, and just 43.5% had epinephrine in their emergency kits. Confidence in managing anaphylactic reactions was low (9.6%). Older age was inversely related to both knowledge of anaphylaxis management and the possession of epinephrine (P = 0.003 and P = 0.0001, respectively).

Discussion

Our study highlights a concerning discrepancy between the practical readiness of Latin American dentists in handling anaphylaxis.

Conclusion

The study’s findings underscore the need for educational interventions to improve the readiness to identify and handle anaphylactic emergencies in dental practice.
Cellular metabolism regulates the differentiation and function of T-cell subsets
Authors: Ma Sicong , Ming Yanan , Wu Jingxia , Cui Guoliang
Published: April 2024

T cells are an important component of adaptive immunity and protect the host from infectious diseases and cancers. However, uncontrolled T cell immunity may cause autoimmune disorders. In both situations, antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens. Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion. Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets. The realm of immunometabolism research is undergoing swift advancements. Encapsulating all the recent progress within this concise review in not possible. Instead, our objective is to provide a succinct introduction to this swiftly progressing research, concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids, glucose, and amino acids—in T cells. We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells. Moreover, we delve into the prospect of “editing” metabolic pathways within T cells using pharmacological or genetic approaches, with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.
De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy
Authors: Sajan Samin A. , Gradisch Ralph , Vogel Florian D. , Coffey Alison J. , Salyakina Daria , Soler Diana , Jayakar Parul , Jayakar Anuj , Bianconi Simona E. , Cooper Annina H. , Liu Shuxi , William Nancy , Benkel-Herrenbrück Ira , Maiwald Robert , Heller Corina , Biskup Saskia , Leiz Steffen , Westphal Dominik S. , Wagner Matias , Clarke Amy , Stockner Thomas , Ernst Margot , Kesari Akanchha , Krenn Martin
Published: April 2024

Nine out of 19 genes encoding GABAA receptor subunits have been linked to monogenic syndromes characterized by seizures and developmental disorders. Previously, we reported the de novo variant p.(Thr300Ile) in GABRA4 in a patient with epilepsy and neurodevelopmental abnormalities. However, no new cases have been reported since then. Through an international collaboration, we collected molecular and phenotype data of individuals carrying de novo variants in GABRA4. Patients and their parents were investigated either by exome or genome sequencing, followed by targeted Sanger sequencing in some cases. All variants within the transmembrane domain, including the previously reported p.(Thr300Ile) variant, were characterized in silico and analyzed by molecular dynamics (MD) simulation studies. We identified three novel de novo missense variants in GABRA4 (NM_000809.4): c.797 C > T, p.(Pro266Leu), c.899 C > A, p.(Thr300Asn), and c.634 G > A, p.(Val212Ile). The p.(Thr300Asn) variant impacts the same codon as the previously reported variant p.(Thr300Ile) and likely arose post-zygotically as evidenced by sequencing oral mucosal cells. Overlapping phenotypes among affected individuals included developmental delay (4/4), epileptiform EEG abnormalities (3/4), attention deficits (3/4), seizures (2/4), autistic features (2/4) and structural brain abnormalities (2/4). MD simulations of the three variants within the transmembrane domain of the receptor indicate that sub-microsecond scale dynamics differ between wild-type and mutated subunits. Taken together, our findings further corroborate an association between GABRA4 and a neurological phenotype including variable neurodevelopmental, behavioral and epileptic abnormalities.
Archaeological and molecular evidence for ancient chickens in Central Asia
Authors: Peters Carli , Richter Kristine K. , Wilkin Shevan , Stark Sören , Mir-Makhamad Basira , Fernandes Ricardo , Maksudov Farhod , Mirzaakhmedov Sirojidin , Rahmonov Husniddin , Schirmer Stefanie , Ashastina Kseniia , Begmatov Alisher , Frachetti Michael , Kurbanov Sharof , Shenkar Michael , Hermes Taylor , Kidd Fiona , Omelchenko Andrey , Huber Barbara , Boivin Nicole , Wang Shujing , Lurje Pavel , von Baeyer Madelynn , Dal Martello Rita , Spengler Robert N.
Published: April 2024

The origins and dispersal of the chicken across the ancient world remains one of the most enigmatic questions regarding Eurasian domesticated animals. The lack of agreement concerning timing and centers of origin is due to issues with morphological identifications, a lack of direct dating, and poor preservation of thin, brittle bird bones. Here we show that chickens were widely raised across southern Central Asia from the fourth century BC through medieval periods, likely dispersing along the ancient Silk Road. We present archaeological and molecular evidence for the raising of chickens for egg production, based on material from 12 different archaeological sites spanning a millennium and a half. These eggshells were recovered in high abundance at all of these sites, suggesting that chickens may have been an important part of the overall diet and that chickens may have lost seasonal egg-laying
Experimentally realized physical-model-based frugal wave control in metasurface-programmable complex media
Authors: Sol Jérôme , Prod’homme Hugo , Le Magoarou Luc , del Hougne Philipp
Published: April 2024

Metasurface-programmable radio environments are considered a key ingredient of next-generation wireless networks. Yet, identifying a metasurface configuration that yields a desired wireless functionality in an unknown complex environment was so far only achieved with closed-loop iterative feedback schemes. Here, we introduce open-loop wave control in metasurface-programmable complex media by estimating the parameters of a compact physics-based forward model. Our experiments demonstrate orders-of-magnitude advantages over deep-learning-based digital-twin benchmarks in terms of accuracy, compactness and required calibration examples. Strikingly, our parameter estimation also works without phase information and without providing measurements for all considered scattering coefficients. These unique generalization capabilities of our pure-physics model unlock unforeseen and previously inaccessible frugal wave control protocols that significantly alleviate the measurement complexity. For instance, we achieve coherent wave control (focusing or perfect absorption) and phase-shift-keying backscatter communications in metasurface-programmable complex media with intensity-only measurements. Our approach is also directly relevant to dynamic metasurface antennas, microwave-based signal processors and emerging in situ reconfigurable nanophotonic, optical and room-acoustical systems.
Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation
Authors: Tsutsumi Ryouhei , Ueberheide Beatrix , Liang Feng-Xia , Neel Benjamin G. , Sakai Ryuichi , Saito Yoshiro
Published: April 2024

Glycolysis is a fundamental cellular process, yet its regulatory mechanisms remain incompletely understood. Here, we show that a subset of glucose transporter 1 (GLUT1/SLC2A1) co-endocytoses with platelet-derived growth factor (PDGF) receptor (PDGFR) upon PDGF-stimulation. Furthermore, multiple glycolytic enzymes localize to these endocytosed PDGFR/GLUT1-containing vesicles adjacent to mitochondria. Contrary to current models, which emphasize the importance of glucose transporters on the cell surface, we find that PDGF-stimulated glucose uptake depends on receptor/transporter endocytosis. Our results suggest that growth factors generate glucose-loaded endocytic vesicles that deliver glucose to the glycolytic machinery in proximity to mitochondria, and argue for a new layer of regulation for glycolytic control governed by cellular membrane dynamics.
Janus electronic state of supported iridium nanoclusters for sustainable alkaline water electrolysis
Authors: Liu Yaoda , Li Lei , Wang Li , Li Na , Zhao Xiaoxu , Chen Ya , Sakthivel Thangavel , Dai Zhengfei
Published: April 2024

Metal-support electronic interactions play crucial roles in triggering the hydrogen spillover (HSo) to boost hydrogen evolution reaction (HER). It requires the supported metal of electron-rich state to facilitate the proton adsorption/spillover. However, this electron-rich metal state contradicts the traditional metal→support electron transfer protocol and is not compatible with the electron-donating oxygen evolution reaction (OER), especially in proton-poor alkaline conditions. Here we profile an Ir/NiPS3 support structure to study the Ir electronic states and performances in HSo/OER-integrated alkaline water electrolysis. The supported Ir is evidenced with Janus electron-rich and electron-poor states at the tip and interface regions to respectively facilitate the HSo and OER processes. Resultantly, the water electrolysis (WE) is efficiently implemented with 1.51 V at 10 mA cm–2 for 1000 h in 1 M KOH and 1.44 V in urea-KOH electrolyte. This research clarifies the Janus electronic state as fundamental in rationalizing efficient metal-support WE catalysts.
Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche
Authors: González-Iglesias Ainara , Arcas Aida , Domingo-Muelas Ana , Mancini Estefania , Galcerán Joan , Valcárcel Juan , Fariñas Isabel , Nieto M. Angela
Published: April 2024

The adult mammalian brain retains some capacity to replenish neurons and glia, holding promise for brain regeneration. Thus, understanding the mechanisms controlling adult neural stem cell (NSC) differentiation is crucial. Paradoxically, adult NSCs in the subependymal zone transcribe genes associated with both multipotency maintenance and neural differentiation, but the mechanism that prevents conflicts in fate decisions due to these opposing transcriptional programmes is unknown. Here we describe intron detention as such control mechanism. In NSCs, while multiple mRNAs from stemness genes are spliced and exported to the cytoplasm, transcripts from differentiation genes remain unspliced and detained in the nucleus, and the opposite is true under neural differentiation conditions. We also show that m6A methylation is the mechanism that releases intron detention and triggers nuclear export, enabling rapid and synchronized responses. m6A RNA methylation operates as an on/off switch for transcripts with antagonistic functions, tightly controlling the timing of NSCs commitment to differentiation.
Ultraviolet light blocking optically clear adhesives for foldable displays via highly efficient visible-light curing
Authors: Kwon Yonghwan , Lee Seokju , Kim Junkyu , Jun Jinwon , Jeon Woojin , Park Youngjoo , Kim Hyun-Joong , Gierschner Johannes , Lee Jaesang , Kim Youngdo , Kwon Min Sang
Published: April 2024

In developing an organic light-emitting diode (OLED) panel for a foldable smartphone (specifically, a color filter on encapsulation) aimed at reducing power consumption, the use of a new optically clear adhesive (OCA) that blocks UV light was crucial. However, the incorporation of a UV-blocking agent within the OCA presented a challenge, as it restricted the traditional UV-curing methods commonly used in the manufacturing process. Although a visible-light curing technique for producing UV-blocking OCA was proposed, its slow curing speed posed a barrier to commercialization. Our study introduces a highly efficient photo-initiating system (PIS) for the rapid production of UV-blocking OCAs utilizing visible light. We have carefully selected the photocatalyst (PC) to minimize electron and energy transfer to UV-blocking agents and have chosen co-initiators that allow for faster electron transfer and more rapid PC regeneration compared to previously established amine-based co-initiators. This advancement enabled a tenfold increase in the production speed of UV-blocking OCAs, while maintaining their essential protective, transparent, and flexible properties. When applied to OLED devices, this OCA demonstrated UV protection, suggesting its potential for broader application in the safeguarding of various smart devices.
Pianno: a probabilistic framework automating semantic annotation for spatial transcriptomics
Authors: Zhou Yuqiu , He Wei , Hou Weizhen , Zhu Ying
Published: April 2024

Spatial transcriptomics has revolutionized the study of gene expression within tissues, while preserving spatial context. However, annotating spatial spots’ biological identity remains a challenge. To tackle this, we introduce Pianno, a Bayesian framework automating structural semantics annotation based on marker genes. Comprehensive evaluations underscore Pianno’s remarkable prowess in precisely annotating a wide array of spatial semantics, ranging from diverse anatomical structures to intricate tumor microenvironments, as well as in estimating cell type distributions, across data generated from various spatial transcriptomics platforms. Furthermore, Pianno, in conjunction with clustering approaches, uncovers a region- and species-specific excitatory neuron subtype in the deep layer 3 of the human neocortex, shedding light on cellular evolution in the human neocortex. Overall, Pianno equips researchers with a robust and efficient tool for annotating diverse biological structures, offering new perspectives on spatial transcriptomics data.
Umpolung reactivity of strained C–C σ-bonds without transition-metal catalysis
Authors: Bai Dachang , Guo Xiuli , Wang Xinghua , Xu Wenjie , Cheng Ruoshi , Wei Donghui , Lan Yu , Chang Junbiao
Published: April 2024

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs.
An all-in-one tetrazine reagent for cysteine-selective labeling and bioorthogonal activable prodrug construction
Authors: He Xinyu , Li Jie , Liang Xinxin , Mao Wuyu , Deng Xinglong , Qin Meng , Su Hao , Wu Haoxing
Published: April 2024

The prodrug design strategy offers a potent solution for improving therapeutic index and expanding drug targets. However, current prodrug activation designs are mainly responsive to endogenous stimuli, resulting in unintended drug release and systemic toxicity. In this study, we introduce 3-vinyl-6-oxymethyl-tetrazine (voTz) as an all-in-one reagent for modular preparation of tetrazine-caged prodrugs and chemoselective labeling peptides to produce bioorthogonal activable peptide-prodrug conjugates. These stable prodrugs can selectively bind to target cells, facilitating cellular uptake. Subsequent bioorthogonal cleavage reactions trigger prodrug activation, significantly boosting potency against tumor cells while maintaining exceptional off-target safety for normal cells. In vivo studies demonstrate the therapeutic efficacy and safety of this prodrug design approach. Given the broad applicability of functional groups and labeling versatility with voTz, we foresee that this strategy will offer a versatile solution to enhance the therapeutic range of cytotoxic agents and facilitate the development of bioorthogonal activatable biopharmaceuticals and biomaterials.
Trialkoxysilane-Induced Iridium-Catalyzed para-Selective C–H Bond Borylation of Arenes
Authors: Ju Guodong , Huang Zhibin , Zhao Yingsheng
Published: April 2024

An ideal approach for the construction of aryl boron compounds is to selectively replace a C–H bond in arenes with a C–B bond, and controlling regioselectivity is one of the most challenging aspects of these transformations. Herein, we report an iridium-catalyzed trialkoxysilane protecting group-assisted regioselective C–H borylation of arenes, including derivatives of benzaldehydes, acetophenones, benzoic acids, benzyl alcohols, phenols, aryl silanes, benzyl silanes, and multi-functionalized aromatic rings are all well tolerated and gave the para -selective C–H borylation products in a short time without the requirement of inert gases atmosphere. The site-selective C–H borylation can be adjustable by installing the developed trialkoxysilane protecting group on different functional groups on one aromatic ring. Importantly, the preparation process of the trialkoxychlorosilane is efficient and scalable. Mechanistic and computational studies reveal that the steric hindrance of the trialkoxysilane protecting group plays a key role in dictating the para-selectivity.
PARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress
Authors: Muoio Daniela , Laspata Natalie , Dannenberg Rachel L. , Curry Caroline , Darkoa-Larbi Simone , Hedglin Mark , Uttam Shikhar , Fouquerel Elise
Published: April 2024

PARP2 is a DNA-dependent ADP-ribosyl transferase (ARTs) enzyme with Poly(ADP-ribosyl)ation activity that is triggered by DNA breaks. It plays a role in the Base Excision Repair pathway, where it has overlapping functions with PARP1. However, additional roles for PARP2 have emerged in the response of cells to replication stress. In this study, we demonstrate that PARP2 promotes replication stress-induced telomere fragility and prevents telomere loss following chronic induction of oxidative DNA lesions and BLM helicase depletion. Telomere fragility results from the activity of the break-induced replication pathway (BIR). During this process, PARP2 promotes DNA end resection, strand invasion and BIR-dependent mitotic DNA synthesis by orchestrating POLD3 recruitment and activity. Our study has identified a role for PARP2 in the response to replication stress. This finding may lead to the development of therapeutic approaches that target DNA-dependent ART enzymes, particularly in cancer cells with high levels of replication stress.
Verifying the security of a continuous variable quantum communication protocol via quantum metrology
Authors: Conlon Lorcán O. , Shajilal Biveen , Walsh Angus , Zhao Jie , Janousek Jiri , Lam Ping Koy , Assad Syed M.
Published: April 2024

Quantum mechanics offers the possibility of unconditionally secure communication between multiple remote parties. Security proofs for such protocols typically rely on bounding the capacity of the quantum channel in use. In a similar manner, Cramér-Rao bounds in quantum metrology place limits on how much information can be extracted from a given quantum state about some unknown parameters of interest. In this work we establish a connection between these two areas. We first demonstrate a three-party sensing protocol, where the attainable precision is dependent on how many parties work together. This protocol is then mapped to a secure access protocol, where only by working together can the parties gain access to some high security asset. Finally, we map the same task to a communication protocol where we demonstrate that a higher mutual information can be achieved when the parties work collaboratively compared to any party working in isolation.
Fostering inclusion in EEG measures of pediatric brain activity
Authors: Adams Eryn J. , Scott Molly E. , Amarante Melina , Ramírez Chanel A. , Rowley Stephanie J. , Noble Kimberly G. , Troller-Renfree Sonya V.
Published: April 2024

The past two decades have seen a rapid increase in neuroscientific evidence being used to characterize how contextual, structural, and societal factors shape cognition and school readiness. Measures of functional brain activity are increasingly viewed as markers of child development and biomarkers that could be employed to track the impact of interventions. While electroencephalography (EEG) provides a promising tool to understand educational inequities, traditional EEG data acquisition is commonly limited in some racial and ethnic groups due to hair types and styles. This ultimately constitutes unintentional systemic racism by disproportionately excluding participants from certain racial and ethnic groups from participation and representation in neuroscience research. Here, we provide a comprehensive review of how cultural considerations surrounding hair density, texture, and styling consistently skew samples to be less representative by disproportionately excluding Black and Latinx participants. We also provide recommendations and materials to promote best practices.
Climbing fibers provide essential instructive signals for associative learning
Authors: Silva N. Tatiana , Ramírez-Buriticá Jorge , Pritchett Dominique L. , Carey Megan R.
Published: April 2024

Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber (CF) inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. In the present study we used cell-type-specific perturbations of various cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning in mice. Our findings reveal that, although optogenetic stimulation of either CFs or Purkinje cells can drive learning under some conditions, even subtle reductions in CF signaling completely block learning to natural stimuli. We conclude that CFs and corresponding Purkinje cell complex spike events provide essential instructive signals for associative cerebellar learning.
South American Archaeological Isotopic Database, a regional-scale multi-isotope data compendium for research
Authors: Pezo-Lanfranco Luis , Mut Patricia , Chávez Juan , Fossile Thiago , Colonese André Carlo , Fernandes Ricardo
Published: April 2024

The South American Archaeological Isotopic Database (SAAID) is a comprehensive open-access resource that aggregates all available bioarchaeological stable and radiogenic isotope measurements, encompassing data from human individuals, animals, and plants across South America. Resulting from a collaborative effort of scholars who work with stable isotopes in this region, SAAID contains 53,781 isotopic measurements across 24,507 entries from individuals/specimens spanning over 12,000 years. SAAID includes valuable contextual information on archaeological samples and respective sites, such as chronology, geographical region, biome, and spatial coordinates, biological details like estimated sex and age for human individuals, and taxonomic description for fauna and flora. SAAID is hosted at the PACHAMAMA community within the Pandora data platform and the CORA repository to facilitate easy access. Because of its rich data structure, SAAID is particularly well-suited for conducting spatiotemporal meta-analyses. It serves as a valuable tool for addressing a variety of research topics, including the spread, adoption, and consumption intensification of food items, paleo-environmental reconstruction, as well as the exploration of mobility patterns across extensive geographic regions.
The antihyperglycemic potential of pyrazolobenzothiazine 1, 1-dioxide novel derivative in mice using integrated molecular pharmacological approach
Authors: Taj Saman , Ashfaq Usman Ali , Ahmad Matloob , Noor Hasnat , Ikram Ayesha , Ahmed Rashid , Tariq Muhammad , Masoud Muhammad Shareef , Hasan Anwarul
Published: April 2024

Diabetes Mellitus is a metabolic disease characterized by elevated blood sugar levels caused by inadequate insulin production, which subsequently leads to hyperglycemia. This study was aimed to investigate the antidiabetic potential of pyrazolobenzothiazine derivatives in silico, in vitro, and in vivo. Molecular docking of pyrazolobenzothiazine derivatives was performed against α-glucosidase and α-amylase and compounds were selected based on docking score, bonding interactions and low root mean square deviation (RMSD). Enzyme inhibition assay against α-glucosidase and α-amylase was performed in vitro using p-nitrophenyl-α-D-glucopyranoside (PNPG) and starch substrate. Synthetic compound pyrazolobenzothiazine (S1) exhibited minimal conformational changes during the 100 ns MD simulation run. S1 also revealed effective IC50 values for α-glucosidase (3.91 µM) and α-amylase (8.89 µM) and an enzyme kinetic study showed low ki (− 0.186 µM, − 1.267 µM) and ki′ (− 0.691 µM, − 1.78 µM) values with the competitive type of inhibition for both enzymes α-glucosidase and α-amylase, respectively. Moreover, studies were conducted to check the effect of the synthetic compound in a mouse model. A low necrosis rate was observed in the liver, kidney, and pancreas through histology analysis performed on mice. Compound S1 also exhibited a good biochemical profile with lower sugar level (110–115 mg/dL), increased insulin level (25–30 μM/L), and low level of cholesterol (85 mg/dL) and creatinine (0.6 mg/dL) in blood. The treated mice group also exhibited a low % of glycated haemoglobin (3%). This study concludes that S1 is a new antidiabetic-agent that helps lower blood glucose levels and minimizes the complications associated with type-II diabetes.
Comparative study on numerical simulation of temperature field of farm house with different roof forms
Authors: Pan Zhichao , Zhao Wenjuan , Wang Haidong
Published: April 2024

In recent years, the issue of energy consumption in farm buildings has received much attention. The roofs of farm buildings in Northwest China have a variety of roof forms. This paper presents the implementation of first fully confirmed the indoor thermal environment of different roof construction was significantly effected by periodic thermogenesis. In order to determine the indoor temperature distribution of the farmhouse in summer in Ningxia Hui Autonomous Region, we provided the heat transfer coefficient data of the farmhouse envelope, also detailed in the manuscript. Model of Thermal Mass Transport enables fast and accurately simulates the indoor temperature distribution of farmhouses with different roof forms on the same day, taking into account the climate zone of the region. This is despite the phase delay time of indoor temperatures for different roof forms caused by periodic initial temperature boundaries ranged from 1.55 to 2.78$$\text{h}$$
h
, and the phase delay angle ranged from 23.25$$^{\circ }$$

∘

to 41.7$$^{\circ }$$

∘

. Extensive simulated results revealed individual variability in the role of roof form, demonstrating indoor temperatures in farmhouses corresponding to different climatic zones. In addition, by analyzing and discussing the indoor temperature phase delay angle and delay time for each type of roof forms, statistical results identified the advantages of Non-equal-sloped roof as a local farmhouse roof.
Chronic phase advances reduces recognition memory and increases vascular cognitive dementia-like impairments in aged mice
Authors: Liu Jennifer A. , Bumgarner Jacob R. , Walker William H. , Meléndez-Fernández O. Hecmarie , Walton James C. , DeVries A. Courtney , Nelson Randy J.
Published: April 2024

Disrupted or atypical light–dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression.
Graphical user interface-based convolutional neural network models for detecting nasopalatine duct cysts using panoramic radiography
Authors: Ito Kotaro , Hirahara Naohisa , Muraoka Hirotaka , Sawada Eri , Tokunaga Satoshi , Komatsu Tomohiro , Kaneda Takashi
Published: April 2024

Nasopalatine duct cysts are difficult to detect on panoramic radiographs due to obstructive shadows and are often overlooked. Therefore, sensitive detection using panoramic radiography is clinically important. This study aimed to create a trained model to detect nasopalatine duct cysts from panoramic radiographs in a graphical user interface-based environment. This study was conducted on panoramic radiographs and CT images of 115 patients with nasopalatine duct cysts. As controls, 230 age- and sex-matched patients without cysts were selected from the same database. The 345 pre-processed panoramic radiographs were divided into 216 training data sets, 54 validation data sets, and 75 test data sets. Deep learning was performed for 400 epochs using pretrained-LeNet and pretrained-VGG16 as the convolutional neural networks to classify the cysts. The deep learning system's accuracy, sensitivity, and specificity using LeNet and VGG16 were calculated. LeNet and VGG16 showed an accuracy rate of 85.3% and 88.0%, respectively. A simple deep learning method using a graphical user interface-based Windows machine was able to create a trained model to detect nasopalatine duct cysts from panoramic radiographs, and may be used to prevent such cysts being overlooked during imaging.
Genetic improvement of Egyptian cotton (Gossypium barbadense L.) for high yield and fiber quality properties under semi arid conditions
Authors: Lamlom Sobhi F. , Yehia W. M. B. , Kotb H. M. K. , Abdelghany Ahmed M. , Shah Adnan Noor , Salama Ehab A. A. , Abdelhamid Mohamed M. A. , Abdelsalam Nader R.
Published: April 2024

Between 2016 and 2018, the Agriculture Research Center's Sakha Agriculture Research Station conducted two rounds of pedigree selection on a segregating population of cotton (Gossypium barbadenseL.) using the F2, F3, and F4generations resulting from crossing Giza 94 and Suvin. In 2016, the top 5% of plants from the F2population were selected based on specific criteria. The superior families from the F3generation were then selected to produce the F4families in 2017, which were grown in the 2018 summer season in single plant progeny rows and bulk experiments with a randomized complete block design of three replications. Over time, most traits showed increased mean values in the population, with the F2generation having higher Genotypic Coefficient of Variance (GCV) and Phenotypic Coefficient of Variance (PCV) values compared to the succeeding generations for the studied traits. The magnitude of GCV and PCV in the F3and F4generations was similar, indicating that genotype had played a greater role than the environment. Moreover, the mean values of heritability in the broad sense increased from generation to generation. Selection criteria I2, I4, and I5 were effective in improving most of the yield and its component traits, while selection criterion I1 was efficient in improving earliness traits. Most of the yield and its component traits showed a positive and significant correlation with each other, highlighting their importance in cotton yield. This suggests that selecting to improveone or more of these traits would improve the others. Families number 9, 13, 19, 20, and 21 were the best genotypes for relevant yield characters, surpassing the better parent, check variety, and giving the best values for most characters. Therefore, the breeder could continue to use these families in further generations as breeding genotypes to develop varieties with high yields and its components.