bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular structure of dinosaur scales reveals retention of reptile-type skin during the evolutionary transition to feathers
Authors: Yang Zixiao , Jiang Baoyu , Xu Jiaxin , McNamara Maria E.
Published: May 2024

Fossil feathers have transformed our understanding of integumentary evolution in vertebrates. The evolution of feathers is associated with novel skin ultrastructures, but the fossil record of these changes is poor and thus the critical transition from scaled to feathered skin is poorly understood. Here we shed light on this issue using preserved skin in the non-avian feathered dinosaur Psittacosaurus. Skin in the non-feathered, scaled torso is three-dimensionally replicated in silica and preserves epidermal layers, corneocytes and melanosomes. The morphology of the preserved stratum corneum is consistent with an original composition rich in corneous beta proteins, rather than (alpha-) keratins as in the feathered skin of birds. The stratum corneum is relatively thin in the ventral torso compared to extant quadrupedal reptiles, reflecting a reduced demand for mechanical protection in an elevated bipedal stance. The distribution of the melanosomes in the fossil skin is consistent with melanin-based colouration in extant crocodilians. Collectively, the fossil evidence supports partitioning of skin development in Psittacosaurus: a reptile-type condition in non-feathered regions and an avian-like condition in feathered regions. Retention of reptile-type skin in non-feathered regions would have ensured essential skin functions during the early, experimental stages of feather evolution.
The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B
Authors: Sun Wenqi , Dong Qianhua , Li Xueqing , Gao Jinxin , Ye Xianwen , Hu Chunyi , Li Fei , Chen Yong
Published: May 2024

Heterochromatin is generally associated with the nuclear periphery, but how the spatial organization of heterochromatin is regulated to ensure epigenetic silencing remains unclear. Here we found that Sad1, an inner nuclear membrane SUN-family protein in fission yeast, interacts with histone H2A-H2B but not H3-H4. We solved the crystal structure of the histone binding motif (HBM) of Sad1 in complex with H2A-H2B, revealing the intimate contacts between Sad1HBM and H2A-H2B. Structure-based mutagenesis studies revealed that the H2A-H2B-binding activity of Sad1 is required for the dynamic distribution of Sad1 throughout the nuclear envelope (NE). The Sad1-H2A-H2B complex mediates tethering telomeres and the mating-type locus to the NE. This complex is also important for heterochromatin silencing. Mechanistically, H2A-H2B enhances the interaction between Sad1 and HDACs, including Clr3 and Sir2, to maintain epigenetic identity of heterochromatin. Interestingly, our results suggest that Sad1 exhibits the histone-enhanced liquid-liquid phase separation property, which helps recruit heterochromatin factors to the NE. Our results uncover an unexpected role of SUN-family proteins in heterochromatin regulation and suggest a nucleosome-independent role of H2A-H2B in regulating Sad1’s functionality.
Ciliary tip actin dynamics regulate photoreceptor outer segment integrity
Authors: Megaw Roly , Moye Abigail , Zhang Zhixian , Newton Fay , McPhie Fraser , Murphy Laura C. , McKie Lisa , He Feng , Jungnickel Melissa K. , von Kriegsheim Alex , Tennant Peter A. , Brotherton Chloe , Gurniak Christine , Gross Alecia K. , Machesky Laura M. , Wensel Theodore G. , Mill Pleasantine
Published: May 2024

As signalling organelles, cilia regulate their G protein-coupled receptor content by ectocytosis, a process requiring localised actin dynamics to alter membrane shape. Photoreceptor outer segments comprise an expanse of folded membranes (discs) at the tip of highly-specialised connecting cilia, into which photosensitive GPCRs are concentrated. Discs are shed and remade daily. Defects in this process, due to mutations, cause retinitis pigmentosa (RP). Whilst fundamental for vision, the mechanism of photoreceptor disc generation is poorly understood. Here, we show membrane deformation required for disc genesis is driven by dynamic actin changes in a process akin to ectocytosis. We show RPGR, a leading RP gene, regulates actin-binding protein activity central to this process. Actin dynamics, required for disc formation, are perturbed in Rpgr mouse models, leading to aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. Actin manipulation partially rescues this, suggesting the pathway could be targeted therapeutically. These findings help define how actin-mediated dynamics control outer segment turnover.
Electrostatic-induced ion-confined partitioning in graphene nanolaminate membrane for breaking anion–cation co-transport to enhance desalination
Authors: Zhang Haiguang , Xing Jiajian , Wei Gaoliang , Wang Xu , Chen Shuo , Quan Xie
Published: May 2024

Constructing nanolaminate membranes made of two-dimensional graphene oxide nanosheets has gained enormous interest in recent decades. However, a key challenge facing current graphene-based membranes is their poor rejection for monovalent salts due to the swelling-induced weak nanoconfinement and the transmembrane co-transport of anions and cations. Herein, we propose a strategy of electrostatic-induced ion-confined partitioning in a reduced graphene oxide membrane for breaking the correlation of anions and cations to suppress anion-cation co-transport, substantially improving the desalination performance. The membrane demonstrates a rejection of 95.5% for NaCl with a water permeance of 48.6 L m−2 h−1 bar−1 in pressure-driven process, and it also exhibits a salt rejection of 99.7% and a water flux of 47.0 L m−2 h−1 under osmosis-driven condition, outperforming the performance of reported graphene-based membranes. The simulation and calculation results unveil that the strong electrostatic attraction of membrane forces the hydrated Na+ to undergo dehydration and be exclusively confined in the nanochannels, strengthening the intra-nanochannel anion/cation partitioning, which refrains from the dynamical anion-cation correlations and thereby prevents anions and cations from co-transporting through the membrane. This study provides guidance for designing advanced desalination membranes and inspires the future development of membrane-based separation technologies.
Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization
Authors: Kant Aayush , Guo Zixian , Vinayak Vinayak , Neguembor Maria Victoria , Li Wing Shun , Agrawal Vasundhara , Pujadas Emily , Almassalha Luay , Backman Vadim , Lakadamyali Melike , Cosma Maria Pia , Shenoy Vivek B.
Published: May 2024

In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence of transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, histone modifications, and chromatin extrusion. We predict that the size of heterochromatic domains is governed by a balance among the diffusive flux of methylated histones sustaining them and the acetylation reactions in the domains and the process of loop extrusion via supercoiling by RNAPII at their periphery, which contributes to size reduction. Super-resolution and nano-imaging of five distinct cell lines confirm the predictions indicating that the absence of transcription leads to larger heterochromatin domains. Furthermore, the model accurately reproduces the findings regarding how transcription-mediated supercoiling loss can mitigate the impacts of excessive cohesin loading. Our findings shed light on the role of transcription in genome organization, offering insights into chromatin dynamics and potential therapeutic targets.
Cell-free biosynthesis and engineering of ribosomally synthesized lanthipeptides
Authors: Liu Wan-Qiu , Ji Xiangyang , Ba Fang , Zhang Yufei , Xu Huiling , Huang Shuhui , Zheng Xiao , Liu Yifan , Ling Shengjie , Jewett Michael C. , Li Jian
Published: May 2024

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with diverse chemical structures and potent biological activities. A vast majority of RiPP gene clusters remain unexplored in microbial genomes, which is partially due to the lack of rapid and efficient heterologous expression systems for RiPP characterization and biosynthesis. Here, we report a unified biocatalysis (UniBioCat) system based on cell-free gene expression for rapid biosynthesis and engineering of RiPPs. We demonstrate UniBioCat by reconstituting a full biosynthetic pathway for de novo biosynthesis of salivaricin B, a lanthipeptide RiPP. Next, we delete several protease/peptidase genes from the source strain to enhance the performance of UniBioCat, which then can synthesize and screen salivaricin B variants with enhanced antimicrobial activity. Finally, we show that UniBioCat is generalizable by synthesizing and evaluating the bioactivity of ten uncharacterized lanthipeptides. We expect UniBioCat to accelerate the discovery, characterization, and synthesis of RiPPs.
Lightweight and drift-free magnetically actuated millirobots via asymmetric laser-induced graphene
Authors: Chen Yun , Guo Yuanhui , Xie Bin , Jin Fujun , Ma Li , Zhang Hao , Li Yihao , Chen Xin , Hou Maoxiang , Gao Jian , Liu Huilong , Lu Yu-Jing , Wong Ching-Ping , Zhao Ni
Published: May 2024

Millirobots must have low cost, efficient locomotion, and the ability to track target trajectories precisely if they are to be widely deployed. With current materials and fabrication methods, achieving all of these features in one millirobot remains difficult. We develop a series of graphene-based helical millirobots by introducing asymmetric light pattern distortion to a laser-induced polymer-to-graphene conversion process; this distortion resulted in the spontaneous twisting and peeling off of graphene sheets from the polymer substrate. The lightweight nature of graphene in combine with the laser-induced porous microstructure provides a millirobot scaffold with a low density and high surface hydrophobicity. Magnetically driven nickel-coated graphene-based helical millirobots with rapid locomotion, excellent trajectory tracking, and precise drug delivery ability were fabricated from the scaffold. Importantly, such high-performance millirobots are fabricated at a speed of 77 scaffolds per second, demonstrating their potential in high-throughput and large-scale production. By using drug delivery for gastric cancer treatment as an example, we demonstrate the advantages of the graphene-based helical millirobots in terms of their long-distance locomotion and drug transport in a physiological environment. This study demonstrates the potential of the graphene-based helical millirobots to meet performance, versatility, scalability, and cost-effectiveness requirements simultaneously.
A stem cell-based assay platform demonstrates alpha-synuclein dependent synaptic dysfunction in patient-derived cortical neurons
Authors: White Andrew J. , Clark Karis A. , Alexander Kellianne D. , Ramalingam Nagendran , Young-Pearse Tracy L. , Dettmer Ulf , Selkoe Dennis J. , Ho Gary P. H.
Published: May 2024

Alpha-synuclein (αS)-rich Lewy bodies and neurites in the cerebral cortex correlate with the presence of dementia in Parkinson disease (PD) and Dementia with Lewy bodies (DLB), but whether αS influences synaptic vesicle dynamics in human cortical neurons is unknown. Using a new iPSC-based assay platform for measuring synaptic vesicle cycling, we found that in human cortical glutamatergic neurons, increased αS from either transgenic expression or triplication of the endogenous locus in patient-derived neurons reduced synaptic vesicle cycling under both stimulated and spontaneous conditions. Thus, using a robust, easily adopted assay platform, we show for the first time αS-induced synaptic dysfunction in human cortical neurons, a key cellular substrate for PD dementia and DLB.
Enhancing therapeutic efficacy: sustained delivery of 5-fluorouracil (5-FU) via thiolated chitosan nanoparticles targeting CD44 in triple-negative breast cancer
Authors: Anjum Sadia , Naseer Faiza , Ahmad Tahir , Jahan Faryal , Qadir Halima , Gul Rabia , Kousar Kousain , Sarwar Atif , Shabbir Abdallah
Published: May 2024

Our current study reports the successful synthesis of thiolated chitosan-based nanoparticles for targeted drug delivery of 5-Fluorouracil. This process was achieved through the ionic gelation technique, aiming to improve the efficacy of the chemotherapeutic moiety by modifying the surface of the nanoparticles (NPs) with a ligand. We coated these NPs with hyaluronic acid (HA) to actively target the CD44 receptor, which is frequently overexpressed in various solid malignancies, including breast cancer. XRD, FTIR, SEM, and TEM were used for the physicochemical analysis of the NPs. These 5-Fluorouracil (5-FU) loaded NPs were evaluated on MDA-MB-231 (a triple-negative breast cell line) and MCF-10A (normal epithelial breast cells) to determine their in vitro efficacy. The developed 5-FU-loaded NPs exhibited a particle size within a favorable range (< 300 nm). The positive zeta potential of these nanoparticles facilitated their uptake by negatively charged cancer cells. Moreover, they demonstrated robust stability and achieved high encapsulation efficiency. These nanoparticles exhibited significant cytotoxicity compared to the crude drug (p < 0.05) and displayed a promising release pattern consistent with the basic diffusion model. These traits improve the pharmacokinetic profile, efficacy, and ability to precisely target these nanoparticles, offering a potentially successful anticancer treatment for breast cancer. However, additional in vivo assessments of these formulations are obligatory to confirm these findings.
Mesoporous Mn-substituted MnxZn1−xCo2O4 ternary spinel microspheres with enhanced electrochemical performance for supercapacitor applications
Authors: Dolla Tarekegn Heliso , Lawal Isiaka Ayobamidele , Kifle Gizachew Wendimu , Jikamo Samuel Chufamo , Matthews Thabo , Maxakato Nobanathi Wendy , Liu Xinying , Mathe Mkhulu , Billing David Gordon , Ndungu Patrick
Published: May 2024

Extensive investigations have been carried out on spinel mixed transition metal oxide-based materials for high-performance electrochemical energy storage applications. In this study, mesoporous Mn-substituted MnxZn1−xCo2O4 (ZMC) ternary oxide microspheres (x = 0, 0.3, 0.5, 0.7, and 1) were fabricated as electrode materials for supercapacitors through a facile coprecipitation method. Electron microscopy analysis revealed the formation of microspheres comprising interconnected aggregates of nanoparticles. Furthermore, the substitution of Mn into ZnCo2O4 significantly improved the surface area of the synthesized samples. The electrochemical test results demonstrate that the ZMC3 oxide microspheres with an optimal Mn substitution exhibited enhanced performance, displaying the largest specific capacitance of 589.9 F g−1 at 1 A g−1. Additionally, the ZMC3 electrode maintained a capacitance retention of 92.1% after 1000 cycles and exhibited a significant rate capability at a current density of 10 A g−1. This improved performance can be ascribed to the synergistic effects of multiple metals resulting from Mn substitution, along with an increase in the surface area, which tailors the redox behavior of ZnCo2O4 (ZC) and facilitates charge transfer. These findings indicate that the incorporation of Mn into mixed transition metal oxides holds promise as an effective strategy for designing high-performance electrodes for energy storage applications.
Gamma radiation assisted green synthesis of hesperidin-reduced graphene oxide nanocomposite targeted JNK/SMAD4/MMP2 signaling pathway
Authors: Kodous Ahmad S. , Taha Eman. O. , El-Maghraby Dina F. , Hassana Asmaa A. , Atta M. M.
Published: May 2024

In this study, a novel method for the fabrication of hesperidin/reduced graphene oxide nanocomposite (RGOH) with the assistance of gamma rays is reported. The different RGOHs were obtained by varying hesperidin concentrations (25, 50, 100, and 200 wt.%) in graphene oxide (GO) solution. Hesperidin concentrations (25, 50, 100, and 200 wt.%) in graphene oxide (GO) were varied to produce the various RGOHs. Upon irradiation with 80 kGy from γ-Ray, the successful reduction of GO occurred in the presence of hesperidin. The reduction process was confirmed by different characterization techniques such as FTIR, XRD, HRTEM, and Raman Spectroscopy. A cytotoxicity study using the MTT method was performed to evaluate the cytotoxic-anticancer effects of arbitrary RGOH on Wi38, CaCo2, and HepG2 cell lines. The assessment of RGOH’s anti-inflammatory activity, including the monitoring of IL-1B and IL-6 activities as well as NF-kB gene expression was done. In addition, the anti-invasive and antimetastatic properties of RGOH, ICAM, and VCAM were assessed. Additionally, the expression of the MMP2-9 gene was quantified. The assessment of apoptotic activity was conducted by the detection of gene expressions related to BCl2 and P53. The documentation of the JNK/SMAD4/MMP2 signaling pathway was ultimately accomplished. The findings of our study indicate that RGOH therapy has significant inhibitory effects on the JNK/SMAD4/MMP2 pathway. This suggests that it could be a potential therapeutic option for cancer.
Multi-proxy record of the Austrian Upper Triassic Polzberg Konservat-Lagerstätte in light of the Carnian Pluvial Episode
Authors: Lukeneder Alexander , Lukeneder Petra , Sachsenhofer Reinhard F. , Roghi Guido , Rigo Manuel
Published: May 2024

We present a multi-proxy investigation of a lower Carnian basinal succession from Polzberg in the Northern Calcareous Alps (Lower Austria). A section comprising a unique Konservat-Lagerstätte was studied based on bio- and chemostratigraphy along with geophysical methods, yielding a detailed and robust stratigraphic calibration of the Polzberg succession. The Polzberg section revealed the paleoceanographic history and helped to identify a global climatic reversal, the Carnian Pluvial Episode. The age of the Upper Triassic Reingraben formation in the Northern Calcareous Alps is refined as the Austrotrachyceras austriacum Zone within the lower Carnian (Julian 2). Ammonoids and conodonts provide a detailed biostratigraphic subdivision that serves as a basis for analyses of the faunal distribution and the paleoenvironmental evolution of the Upper Triassic Reifling Basin. The succession includes lithological and facies changes similar to those of coeval units in the Tethys. The Carnian was characterized by a weak (~ 1‰) positive δ13C trend, punctuated by a negative shift during the lower Carnian corresponding to the initiation of the Carnian Pluvial Episode, a period representing the onset of early/late Carnian transitional global greenhouse conditions. Organic maturity parameters and the conodont alteration index (CAI) show that the thermal overprint of the Polzberg section is low. Biomarker proxies suggest that the organic matter of the uppermost Göstling formation is a mixture of marine and terrestrial material deposited in a dysoxic environment. Within the overlaying Reingraben formation, the amount of marine biomass decreased gradually upwards. Oxygen-depleted conditions, probably due to water-column stratification, continued during deposition of the Reingraben formation. Bacterial sulfate reduction played a major role in organic matter degradation.
Optimization of preparation conditions and performance of a new degradable soil water retaining agent
Authors: Yumang Zhang , Yongheng Wang , Chengyu Wang , Yunhang Gao , Shuxia Liu , Zhonglei Xie , Hongyan Chang
Published: May 2024

Using polyaspartic acid (PAsp) and bentonite (BT) as the main raw materials, a new type of degradable soil water retaining agent (PAsp-AA/BT) was synthesized by microwave radiation. The optimum synthesis conditions and comprehensive properties of PAsp-AA/BT were discussed and the structure and surface characteristics of PAspsp-AA/BT were characterized by FTIR, SEM, XRD and TGA in the paper. The results showed that the optimum synthesis conditions of PAsp-AA/BT were as follows: the dosages of polyaspartic acid (PAsp), bentonite (BT), initiator potassium persulfate, crosslinking agent N,N′-methylene bisacrylamide was 5, 3, 0.3, 0.03%, respectively, the neutralization degree of acrylic acid was 75%, and the microwave power was 490W. Under this condition, the absorption ratio of the synthesized PAspsp-AA/BT in deionized water and 0.9% NaCl solution was 953 and 164 g/g, respectively. The synthesized PAsp-AA/BT had a high water absorption rate, good water retention and repeated water absorption, and the degradation rate in soil within 30 days reached 32.75%, with good degradation effect. The analysis of SEM, FT-IR, XRD and TGA showed that: the surface of PAsp-AA/BT was rough and had obvious pore structure, which was conducive to the diffusion of water molecules; polyaspartic acid, bentonite and acrylic acid were polymerized; the cross-linking structure was formed between polyaspartic acid, bentonite and acrylic acid; the product of PASP-AA/BT had good thermal stability. This study provides a new soil water retaining agent, which is helpful for the better development of soil water retaining agent research.
Risk factor analysis and nomogram development and verification for medullary carcinoma of the colon using SEER database
Authors: Yang Lu , Yu Lei , Zhou Qiang , Liu Li , Shen Na , Li Na
Published: May 2024

Medullary Carcinoma of the Colon (MCC) is a rare histological subtype of colon cancer, and there is currently no recognized optimal treatment plan for it, with its prognosis remaining unclear. The aim of this study is to analyze the independent prognostic factors for MCC patients and develop and validate nomograms to predict overall survival (OS). A total of 760 patients newly diagnosed with MCC from 2004 to 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to a training group and a validation group in a 7:3 ratio. Univariate and multivariable Cox regression analyses were conducted to identify prognostic factors and construct nomograms. The nomogram prediction model was evaluated and validated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The study found that elderly women are more susceptible to MCC, and the ascending colon and cecum are the most common sites of involvement. MCC is poorly differentiated, with stages II and III being the most common. Surgery is the primary treatment for MCC. The prognosis for patients with stage IV MCC is poor, with a median survival time of only 10 months. Independent prognostic factors for MCC include age, N stage, M stage, surgery, chemotherapy, and tumor size. Among them, age < 75 years and completion of chemotherapy were protective factors for colon medullary carcinoma, while N2 (HR = 2.18, 95%CI 1.40–3.38), M1 (HR = 3.31, 95%CI 2.01–5.46), no surgery (HR = 27.94, 95%CI 3.69–211.75), and tumor diameter > 7 cm (HR = 1.66, 95%CI 1.20–2.30) were risk factors for colon medullary carcinoma. The results of ROC, AUC, calibration curves, and DCA demonstrate that the nomogram prediction model exhibits good predictive performance. We have updated the demographic characteristics of colon medullary carcinoma and identified age, N staging, M staging, surgery, chemotherapy and tumor size as independent prognostic factors for colon medullary carcinoma. Additionally, we have established nomograms for prognostic prediction. These nomograms can provide personalized predictions and serve as valuable references for clinical decision-making.
Multi-disciplinary strategy to optimize irrigation efficiency in irrigated agriculture
Authors: Batisha Ayman
Published: May 2024

Equilibrium among water, food, energy, and climate actions is necessary for life to exist, quality, and sustainability. This article explored how to ensure sustainability, and equilibrium in the irrigation processes by proposing irrigation equilibrium indicators (IEIs) for sustainable irrigated agriculture (SIA). The primary purpose of IEIs is to achieve a state of sustainable climate and environmental balance. The pressures driving agriculture and irrigation professionals to enhance the irrigation scheme performance are tremendous in all agricultural communities. Monitoring, assessment, and improvement of agriculture practices and irrigation schemes for enhancing the Climate, water, food, and energy (CWFE) nexus is a must. As an auspicious climate action, IEIs were developed to enhance the irrigation scheme’s efficiency, within the scope of SIA. Subsequently, water, agricultural, food, and energy productivity could be optimized. Then, the appropriate equilibrium indicators could identify the actual performance of the CWFE nexus as a whole and the performance of each component. The effective irrigation scheme is the backbone of SIA. IEIs could measure the degree of achieving the overall and specific objectives and designated irrigation processes. The ultimate measure of equilibrium is optimizing sustainable agricultural yields and productivity, ensuring environmental balance, strengthening life quality, and maximizing economic returns.
Autologous bone marrow derived mesenchymal stem cells are safe for the treatment of Achilles tendinopathy
Authors: Goldberg Andrew J. , Masci Lorenzo , O’Donnell Paul , Green Ruth , Brooking Deirdre , Bassett Paul , Lowdell Mark W. , Smith Roger K. W.
Published: May 2024

Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 106, range 5–19 × 106 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.
Oscillating latent dynamics in robot systems during walking and reaching
Authors: Parker Jones Oiwi , Mitchell Alexander L. , Yamada Jun , Merkt Wolfgang , Geisert Mathieu , Havoutis Ioannis , Posner Ingmar
Published: May 2024

Sensorimotor control of complex, dynamic systems such as humanoids or quadrupedal robots is notoriously difficult. While artificial systems traditionally employ hierarchical optimisation approaches or black-box policies, recent results in systems neuroscience suggest that complex behaviours such as locomotion and reaching are correlated with limit cycles in the primate motor cortex. A recent result suggests that, when applied to a learned latent space, oscillating patterns of activation can be used to control locomotion in a physical robot. While reminiscent of limit cycles observed in primate motor cortex, these dynamics are unsurprising given the cyclic nature of the robot’s behaviour (walking). In this preliminary investigation, we consider how a similar approach extends to a less obviously cyclic behaviour (reaching). This has been explored in prior work using computational simulations. But simulations necessarily make simplifying assumptions that do not necessarily correspond to reality, so do not trivially transfer to real robot platforms. Our primary contribution is to demonstrate that we can infer and control real robot states in a learnt representation using oscillatory dynamics during reaching tasks. We further show that the learned latent representation encodes interpretable movements in the robot’s workspace. Compared to robot locomotion, the dynamics that we observe for reaching are not fully cyclic, as they do not begin and end at the same position of latent space. However, they do begin to trace out the shape of a cycle, and, by construction, they are driven by the same underlying oscillatory mechanics.
Increased risk of fetal left–right asymmetry disorders associated with maternal SARS-CoV-2 infection during the first trimester
Authors: Li Yang , Wang Yuemei , Wu Haifang , Li Qi , Li Shizhen , Qiu Chunli , Qiu Shuo , Niu Qingfang , Zhang Xianmei , Xiong Yi , Tao Guowei
Published: May 2024

Our center has observed a substantial increase in the detection rate of fetal left–right(LR) asymmetry disorders between March and May 2023. This finding has raised concerns because these pregnant women experienced the peak outbreak of SARS-CoV-2 in China during their first trimester. To explore the relationship between maternal SARS-CoV-2 infection and fetal LR asymmetry disorders. A retrospective collection of clinical and ultrasound data diagnosed as fetal LR asymmetry disorders was conducted from January 2018 to December 2023. The case–control study involved fetuses with LR asymmetry disorders and normal fetuses in a 1:1 ratio. We evaluated and compared the clinical and fetal ultrasound findings in pregnant women with SARS-CoV-2 infection and pregnant women without infection. The Student t-test was utilized to compare continuous variables, while the chi-squared test was employed for univariable analyses. The incidence rate of LR asymmetry disorders from 2018 to 2023 was as follows: 0.17‰, 0.63‰, 0.61‰, 0.57‰, 0.59‰, and 3.24‰, respectively. A total of 30 fetuses with LR asymmetry disorders and 30 normal fetuses were included. This case–control study found that SARS-CoV-2 infection (96.67% vs 3.33%, P = .026) and infection during the first trimester (96.55% vs 3.45%, P = .008) were identified as risk factors. The odds ratio values were 10.545 (95% CI 1.227, 90.662) and 13.067 (95% CI 1.467, 116.419) respectively. In cases of SARS-CoV-2 infection in the first trimester, the majority of infections (88.1%, 37/42) occurred between 5 and 6 weeks of gestation. We found that 43.7% (66/151) of fetuses with LR asymmetry disorder had associated malformations, 90.9% (60/66) exhibited cardiac malformations. SARS-CoV-2 infection during the first trimester significantly increases the risk of fetal LR asymmetry disorders, particularly when the infection occurs between 5 and 6 gestation weeks. The most common associated malformation is heart malformation.
RAS/RAF mutations and microsatellite instability status in primary colorectal cancers according to HER2 amplification
Authors: Lee Sun Mi , Oh Hyunjoo
Published: May 2024

HER2 amplification-associated molecular alterations and clinicopathologic features in colorectal cancers (CRCs) have not been well established. In this study, we assessed the prevalence of HER2 amplification and microsatellite instability (MSI) status of 992 patients with primary CRC. In addition, molecular alterations of HER2 amplified and unamplified CRCs were examined and compared by next-generation sequencing. HER2 amplifications were found in 41 (4.1%) of 992 primary CRCs. HER2 amplification was identified in 1.0% of the right colonic tumors, 5.1% of the left colonic tumors, and 4.8% of the rectal tumors. Approximately 95% of HER2 amplification was observed in the left colon and rectum. Seven (87.5%) of eight metastatic tumors showed HER2 amplification. Most clinicopathologic features were unrelated to HER2 amplification except tumor size and MSI status. All 41 HER2 amplified CRCs were microsatellite stable. In a molecular analysis of frequently identified somatic mutations in CRCs, HER2 amplified CRCs showed a lower rate of KRAS mutations (24.4%) but a higher rate of TP53 mutations (83%) than unamplified CRCs. No BRAF and NRAS mutations were identified in HER2 amplified CRCs. Our study suggests that HER2 amplified CRCs are mutually exclusive of MSI and harbor less frequent KRAS/NRAS/BRAF mutations but frequent T53 mutations.
TPMS-based auxetic structure for high-performance airless tires with variable stiffness depending on deformation
Authors: Kim Do-Yeon , Kim Hong-Seok , Kamath Sarath Suresh , Hou Xiangying , Choi Jae-Won , Park Sang-Hu
Published: May 2024

A novel auxetic structure applicable to airless tire spokes is designed based on the primitive-type triply periodic minimal surface (P-TPMS) to have higher stiffness through deformation under compressive force. For becoming higher stiffness by deformation, an unit cell of auxetic structure is proposed and its characteristics according to design parameters are studied. Based on the parametric study, a rotated primitive-type auxetic structure (RPAS) is designed, and the deformative behaviors of an airless tire with the RPAS spokes are compared with a generally used honeycomb spoke. Simulation and experiment results show that the designed RPAS tire exhibits more stable behavior through higher rigidity depending on the deformation state when compressed on flat ground and obstacles. This variable stiffness characteristic of RPAS tires can be advantageous for shock absorption and prevention of large local deformations. Also, the manufacturability of the designed auxetic structure is evaluated using real rubber-based additive manufacturing processes for practical application in the tire manufacturing industry.
The role of breastfeeding and formula feeding regarding depressive symptoms and an impaired mother child bonding
Authors: Carvalho Hilje Clara , Bauer Nicola H. , Reis Daniela , Kapp Claudia , Ostermann Thomas , Vöhler Franziska , Längler Alfred
Published: May 2024

Associations between depressive symptoms and breastfeeding are well documented. However, evidence is lacking for subdivisions of feeding styles, namely exclusive breastfeeding, exclusive formula feeding and a mixed feeding style (breastfeeding and formula feeding). In addition, studies examining associations between mother-child-bonding and breastfeeding have yielded mixed results. The aim of this study is to provide a more profound understanding of the different feeding styles and their associations with maternal mental health and mother-child-bonding. Data from 307 women were collected longitudinally in person (prenatally) and by telephone (3 months postnatally) using validated self-report measures, and analyzed using correlational analyses, unpaired group comparisons and regression analyses. Our results from a multinomial regression analysis revealed that impaired mother-child-bonding was positively associated with mixed feeding style (p = .003) and depressive symptoms prenatal were positively associated with exclusive formula feeding (p = .013). Further studies could investigate whether information about the underlying reasons we found for mixed feeding, such as insufficient weight gain of the child or the feeling that the child is unsatiated, could help prevent impaired mother-child-bonding. Overall, the results of this study have promising new implications for research and practice, regarding at-risk populations and implications for preventive measures regarding postpartum depression and an impaired mother-child-bonding.
Establishment of an efficient regeneration system of ‘ZiKui’ tea with hypocotyl as explants
Authors: Jin Jiongyi , Chen Yulu , Cai Ju , Lv Litang , Zeng Xiaofang , Li Jianrong , Asghar Sumeera , Li Yan
Published: May 2024

Zikui (Camellia sinensis cv. Zikui) is a recently discovered cultivar of local purple tea in Guizhou, China. It is a purple leaf bud mutation material of Meitan Taicha (Camellia sinensis cv. ‘Meitan-taicha’) ‘N61’ strain, which is an important local germplasm resource in Guizhou. It is also a model plant for the study of anthocyanins, but the limited germplasm resources and the limitation of traditional reproduction hinder its application. Here, an efficient regeneration system is established by using hypocotyl as explants for the first time. Different plant growth regulators (PGRs) are evaluated during different regeneration processes including callus and root induction. According to our findings, using the optimal disinfection conditions, the seed embryo contamination rate is 17.58%. Additionally, the mortality rate is 9.69%, while the survival rate is measured as 72.73%. Moreover, the highest germination rate of 93.64% is observed under MS + 2.40 mg/L GA3 medium conditions. The optimal callus induction rate is 95.19%, while the optimal adventitious bud differentiation rate is 20.74%, Medium with 1.6 mg/L IBA achieved 68.6% rooting of the adventitious shoots. The survival rate is more than 65% after 6 days growth in the cultivated matrix. In summary, our research aims to establish a regeneration system for Zikui tea plants and design a transformation system for tea plant tissue seedlings. This will enable transfer of the target gene and ultimately facilitate the cultivation of new tea varieties with unique characteristics.
Exploring the evolution of bacterial cellulose precursors and their potential use as cellulose-based building blocks
Authors: Mauro Francesca , Corrado Brunella , De Gregorio Vincenza , Lagreca Elena , Di Natale Concetta , Vecchione Raffaele , Netti Paolo Antonio
Published: May 2024

Natural polymers have found increased use in a wider range of applications due to their less harmful effects. Notably, bacterial cellulose has gained significant consideration due to its exceptional physical and chemical properties and its substantial biocompatibility, which makes it an attractive candidate for several biomedical applications. This study attempts to thoroughly unravel the microstructure of bacterial cellulose precursors, known as bioflocculants, which to date have been poorly characterised, by employing both electron and optical microscopy techniques. Here, starting from bioflocculants from Symbiotic Culture of Bacteria and Yeast (SCOBY), we proved that their microstructural features, such as porosity percentage, cellulose assembly degree, fibres’ density and fraction, change in a spatio-temporal manner during their rising toward the liquid–air interface. Furthermore, our research identified a correlation between electron and optical microscopy parameters, enabling the assessment of bioflocculants' microstructure without necessitating offline sample preparation procedures. The ultimate goal was to determine their potential suitability as a novel cellulose-based building block material with tuneable structural properties. Our investigations substantiate the capability of SCOBY bioflocculants, characterized by distinct microstructures, to successfully assemble within a microfluidic device, thereby generating a cellulose sheet endowed with specific and purposefully designed structural features.
Promoter hypermethylation as a novel regulator of ANO1 expression and function in prostate cancer bone metastasis
Authors: Shin Yonghwan , Kim Sungmin , An Woojin
Published: May 2024

Despite growing evidence implicating the calcium-activated chloride channel anoctamin1 (ANO1) in cancer metastasis, its direct impact on the metastatic potential of prostate cancer and the possible significance of epigenetic alteration in this process are not fully understood. Here, we show that ANO1 is minimally expressed in LNCap and DU145 prostate cancer cell lines with low metastatic potential but overexpressed in high metastatic PC3 prostate cancer cell line. The treatment of LNCap and DU145 cells with DNMT inhibitor 5-aza-2′-deoxycytidine (5-Aza-CdR) potentiates ANO1 expression, suggesting that DNA methylation is one of the mechanisms controlling ANO1 expression. Consistent with this notion, hypermethylation was detected at the CpG island of ANO1 promoter region in LNCap and DU145 cells, and 5-Aza-CdR treatment resulted in a drastic demethylation at promoter CpG methylation sites. Upon 5-Aza-CdR treatment, metastatic indexes, such as cell motility, invasion, and metastasis-related gene expression, were significantly altered in LNCap and DU145 cells. These 5-Aza-CdR-induced metastatic hallmarks were, however, almost completely ablated by stable knockdown of ANO1. These in vitro discoveries were further supported by our in vivo observation that ANO1 expression in xenograft mouse models enhances the metastatic dissemination of prostate cancer cells into tibial bone and the development of osteolytic lesions. Collectively, our results help elucidate the critical role of ANO1 expression in prostate cancer bone metastases, which is epigenetically modulated by promoter CpG methylation.
Cloning and functional characterization of the peptide deformylase encoding gene EuPDF1B from Eucommia ulmoides Oliv
Authors: Wang Yumei , Zhao De-Gang
Published: May 2024

Peptide deformylase can catalyse the removal of formyl groups from the N-terminal formyl methionine of the primary polypeptide chain. The peptide deformylase genes of a few herbaceous plants have been studied to some extent, but the peptide deformylase genes of woody plants have not been studied. In this study, we isolated EuPDF1B from Eucommia ulmoides Oliv. The full-length sequence of EuPDF1B is 1176 bp long with a poly-A tail and contains an open reading frame of 831 bp that encodes a protein of 276 amino acids. EuPDF1B was localized to the chloroplast. qRT‒PCR analysis revealed that this gene was expressed in almost all tissues tested but mainly in mature leaves. Moreover, the expression of EuPDF1B was enhanced by ABA, MeJA and GA and inhibited by shading treatment. The expression pattern of EuPDF1B was further confirmed in EuPDF1Bp: GUS transgenic tobacco plants. Among all the transgenic tobacco plants, EuPDF1Bp-3 showed the highest GUS histochemical staining and activity in different tissues. This difference may be related to the presence of enhancer elements in the region from − 891 bp to − 236 bp of the EuPDF1B promoter. In addition, the expression of the chloroplast gene psbA and the net photosynthetic rate, fresh weight and height of tobacco plants overexpressing EuPDF1B were greater than those of the wild-type tobacco plants, suggesting that EuPDF1B may promote the growth of transgenic tobacco plants. This is the first time that PDF and its promoter have been cloned from woody plants, laying a foundation for further analysis of the function of PDF and the regulation of its expression.
Stacked neural network for predicting polygenic risk score
Authors: Kim Sun bin , Kang Joon Ho , Cheon MyeongJae , Kim Dong Jun , Lee Byung-Chul
Published: May 2024

In recent years, the utility of polygenic risk scores (PRS) in forecasting disease susceptibility from genome-wide association studies (GWAS) results has been widely recognised. Yet, these models face limitations due to overfitting and the potential overestimation of effect sizes in correlated variants. To surmount these obstacles, we devised the Stacked Neural Network Polygenic Risk Score (SNPRS). This novel approach synthesises outputs from multiple neural network models, each calibrated using genetic variants chosen based on diverse p-value thresholds. By doing so, SNPRS captures a broader array of genetic variants, enabling a more nuanced interpretation of the combined effects of these variants. We assessed the efficacy of SNPRS using the UK Biobank data, focusing on the genetic risks associated with breast and prostate cancers, as well as quantitative traits like height and BMI. We also extended our analysis to the Korea Genome and Epidemiology Study (KoGES) dataset. Impressively, our results indicate that SNPRS surpasses traditional PRS models and an isolated deep neural network in terms of accuracy, highlighting its promise in refining the efficacy and relevance of PRS in genetic studies.
Enhancing electrocatalytic N2 reduction to NH3 by introducing Ni heteroatoms into NiCuOx electrocatalyst
Authors: Han Xinxin , Zhou Weizhen , Huang Xin , Yu Haoming , Yang Fangqi , Chen Shixia , Wang Jun
Published: May 2024

The Ni dopant enhances the local electronic density surrounding Cu sites, which is favorable for reducing the energy barrier of the rate-determining (*N2 to *NNH) step of the NRR as well as depressing the competing HER.
The impact of secondary operating temperature on in-line coagulation/flocculation and fouling of membranes used in tertiary treatment
Authors: Tao Chen , Parker Wayne , Bérubé Pierre
Published: May 2024

The preferred coagulant dosage and mechanisms of tertiary fouling mitigation with the effect of secondary operating temperature were comprehensively studied.
Chelate-functionalized poly(2-oxazoline) for the destruction of bacterial cell membranes
Authors: Bochenek Marcelina , Mendrek Barbara , Wałach Wojciech , Foryś Aleksander , Kubacki Jerzy , Jałowiecki Łukasz , Borgulat Jacek , Płaza Grażyna , Klama-Baryła Agnieszka , Sitkowska Anna , Kowalczuk Agnieszka , Oleszko-Torbus Natalia
Published: May 2024

In this work we study the conjugate of the copolymer of 2-substituted-2-oxazoline and a chelating compound, which may potentially entrap the ions responsible for stabilizing the bacterial outer membrane (OM).
A Chemist's guide to multi-objective optimization solvers for reaction optimization
Authors: Senthil Vel Aravind , Cortés-Borda Daniel , Felpin François-Xavier
Published: May 2024

This paper presents a chemist's guide for selecting multi-objective optimization algorithms for reaction optimization.
Engineering of bespoke photosensitiser–microbe interfaces for enhanced semi-artificial photosynthesis
Authors: Bishara Robertson Imogen L. , Zhang Huijie , Reisner Erwin , Butt Julea N. , Jeuken Lars J. C.
Published: May 2024

To maximise performance and scalability of biohybrid systems for solar fuel generation, we emphasise the need for rational design of the biotic–abiotic interface, taking into consideration two important aspects: attachment and electron transfer.
Efficient and stabilized molecular doping of hole-transporting materials driven by a cyclic-anion strategy for perovskite solar cells
Authors: Zeng Huaibiao , Lin Fangyan , Wan Zhongquan , Yang Hua , Lu Hui , Jiang Shaoliang , Zhu Jinqing , Yin Haomiao , Wei Runmin , Wang Yuanxi , Luo Junsheng , Jia Chunyang
Published: May 2024

A cyclic-anion dopant (Li-CYCLIC) with high doping performance and intrinsic stability was used for efficient and stable perovskite solar cells.
Influence of anaerobic digestion process parameters on the amount of volatile fatty acids formed in wastewater
Authors: Reshetova Anna , Gulshin Igor , Gogina Elena
Published: May 2024

The limiting indicator for the course of biological wastewater treatment is easily obtainable organic matter. If the wastewater entering the sewage treatment plant is depleted in terms of the content of easily accessible organic matter, then a set of measures aimed at their enrichment is required. Prefermentation of raw sludge was considered as a method of increasing the proportion of readily available organic matter. The influence of the main technological parameters of anaerobic digestion on the amount of volatile fatty acids formed was studied.