bluuebunny/crossref_metadata_2025 huggingface dataset:
Switching molecular recognition selectivities by temperature in a diffusion-regulatory porous material
Authors: Su Yan , Otake Ken-ichi , Zheng Jia-Jia , Xu Hong , Wang Qing , Liu Haiming , Huang Fei , Wang Ping , Kitagawa Susumu , Gu Cheng
Published: January 2024

Over the long history of evolution, nature has developed a variety of biological systems with switchable recognition functions, such as the ion transmissibility of biological membranes, which can switch their ion selectivities in response to diverse stimuli. However, developing a method in an artificial host-guest system for switchable recognition of specific guests upon the change of external stimuli is a fundamental challenge in chemistry because the order in the host-guest affinity of a given system hardly varies along with environmental conditions. Herein, we report temperature-responsive recognition of two similar gaseous guests, CO2 and C2H2, with selectivities switched by temperature change by a diffusion-regulatory mechanism, which is realized by a dynamic porous crystal featuring ultrasmall pore apertures with flip-flop locally-motive organic moiety. The dynamic local motion regulates the diffusion process of CO2 and C2H2 and amplifies their rate differences, allowing the crystal to selectively adsorb CO2 at low temperatures and C2H2 at high temperatures with separation factors of 498 (CO2/C2H2) and 181 (C2H2/CO2), respectively.
Spectroscopy and dynamics of the hydrated electron at the water/air interface
Authors: Jordan Caleb J. C. , Coons Marc P. , Herbert John M. , Verlet Jan R. R.
Published: January 2024

The hydrated electron, e–(aq), has attracted much attention as a central species in radiation chemistry. However, much less is known about e–(aq) at the water/air surface, despite its fundamental role in electron transfer processes at interfaces. Using time-resolved electronic sum-frequency generation spectroscopy, the electronic spectrum of e–(aq) at the water/air interface and its dynamics are measured here, following photo-oxidation of the phenoxide anion. The spectral maximum agrees with that for bulk e–(aq) and shows that the orbital density resides predominantly within the aqueous phase, in agreement with supporting calculations. In contrast, the chemistry of the interfacial hydrated electron differs from that in bulk water, with e–(aq) diffusing into the bulk and leaving the phenoxyl radical at the surface. Our work resolves long-standing questions about e–(aq) at the water/air interface and highlights its potential role in chemistry at the ubiquitous aqueous interface.
Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1
Authors: Khan Ilyas , Li Sunan , Tao Lihong , Wang Chong , Ye Bowei , Li Huiyu , Liu Xiaoyang , Ahmad Iqbal , Su Wenqiang , Zhong Gongxun , Wen Zhiyuan , Wang Jinliang , Hua Rong-Hong , Ma Ao , Liang Jie , Wan Xiao-Peng , Bu Zhi-Gao , Zheng Yong-Hui
Published: January 2024

SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides. Importantly, NPC1 strongly promotes productive SARS-CoV-2 entry, which we propose is due to its influence on fusion in late endosomes. The Tubeimosides’ antiviral activity and NPC1 function are further confirmed by infection with SARS-CoV-2 variants of concern (VOC), SARS-CoV, and MERS-CoV. Thus, NPC1 is a critical entry co-factor for highly pathogenic human coronaviruses (HCoVs) in the late endosomes, and Tubeimosides hold promise as a new countermeasure for these HCoVs and filoviruses.
A general strategy for recycling polyester wastes into carboxylic acids and hydrocarbons
Authors: Zeng Wei , Zhao Yanfei , Zhang Fengtao , Li Rongxiang , Tang Minhao , Chang Xiaoqian , Wang Ying , Wu Fengtian , Han Buxing , Liu Zhimin
Published: January 2024

Chemical recycling of plastic wastes is of great significance for sustainable development, which also represents a largely untapped opportunity for the synthesis of value-added chemicals. Herein, we report a novel and general strategy to degrade polyesters via directly breaking the Calkoxy-O bond by nucleophilic substitution of halide anion of ionic liquids under mild conditions. Combined with hydrogenation over Pd/C, 1-butyl-2,3-dimethylimidazolium bromide can realize the deconstruction of various polyesters including aromatic and aliphatic ones, copolyesters and polyester mixtures into corresponding carboxylic acids and alkanes; meanwhile, tetrabutylphosphonium bromide can also achieve direct decomposition of the polyesters with β-H into carboxylic acids and alkenes under hydrogen- and metal-free conditions. It is found that the hydrogen-bonding interaction between ionic liquid and ester group in polyester enhances the nucleophilicity of halide anion and activates the Calkoxy-O bond. The findings demonstrate how polyester wastes can be a viable feedstock for the production of carboxylic acids and hydrocarbons.
Efficacy and feasibility of aerobic exercise interventions as an adjunctive treatment for patients with schizophrenia: a meta-Analysis
Authors: Guo Jing , Liu Keju , Liao Yundan , Qin Ying , Yue Weihua
Published: January 2024

Schizophrenia is a chronic mental disorder primarily treated with antipsychotics, which have limited efficacy for negative symptoms. This study aims to evaluate the effectiveness and feasibility of exercise interventions as adjuncts to pharmacotherapy through a meta-analysis, providing valuable insights for rational intervention design. Four databases were searched, and randomized controlled trials with no language restrictions published up to March 27, 2023, were included. The primary outcome indicator was the Positive and Negative Symptom Scale (PANSS) total score along with its three sub-scales. Secondary outcomes included the Scale for Assessment of Negative Symptoms (SANS) and Body Mass Index (BMI), which were used to assess the efficacy of aerobic exercise interventions in patients with schizophrenia. Subgroup analyses were conducted to explore the impact of intervention duration and total weekly exercise time, while treatment feasibility was assessed through adherence rates. A total of 17 publications involving 973 patients with schizophrenia were deemed eligible and included in the analysis. Compared to other forms of adjunctive interventions, the network meta-analysis of 12 PANSS-based studies revealed that adjunctive aerobic exercise interventions were the most effective in reducing overall PANSS scores in patients with schizophrenia, with statistically significant pooled results (MD = −4.84, 95% CI: −5.72, −3.96). Both the PANSS negative symptom subscale (MD = −2.11, 95% CI: −3.26, −0.95) and SANS (MD = −9.11, 95% CI: −11.94, −6.27) indicated that adjunctive aerobic exercise interventions effectively alleviate negative symptoms. Subgroup meta-analysis indicated that 2-3 month interventions involving 100–220 min of exercise per week were the most effective. Additionally, adherence to the adjunctive aerobic exercise regimen was found to be comparable to that of conventional treatment alone. Aerobic exercise interventions, as adjunctive therapy, are an effective measure for reducing PANSS scores in patients with schizophrenia, contributing to the alleviation of both the positive and negative symptoms, and patients demonstrated strong adherence to aerobic exercise.
A candidate antibody drug for prevention of malaria
Authors: Williams Katherine L. , Guerrero Steve , Flores-Garcia Yevel , Kim Dongkyoon , Williamson Kevin S. , Siska Christine , Smidt Pauline , Jepson Sofia Z. , Li Kan , Dennison S. Moses , Mathis-Torres Shamika , Chen Xiaomu , Wille-Reece Ulrike , MacGill Randall S. , Walker Michael , Jongert Erik , King C. Richter , Ockenhouse Christian , Glanville Jacob , Moon James E. , Regules Jason A. , Tan Yann Chong , Cavet Guy , Lippow Shaun M. , Robinson William H. , Dutta Sheetij , Tomaras Georgia D. , Zavala Fidel , Ketchem Randal R. , Emerling Daniel E.
Published: January 2024

Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important in efforts to eradicate malaria. Here we characterize the circulating B cell repertoires of 45 RTS,S/AS01 vaccinees and discover monoclonal antibodies for development as potential therapeutics. We generated >28,000 antibody sequences and tested 481 antibodies for binding activity and 125 antibodies for antimalaria activity in vivo. Through these analyses we identified correlations suggesting that sequences in Plasmodium falciparum circumsporozoite protein, the target antigen in RTS,S/AS01, may induce immunodominant antibody responses that limit more protective, but subdominant, responses. Using binding studies, mouse malaria models, biomanufacturing assessments and protein stability assays, we selected AB-000224 and AB-007088 for advancement as a clinical lead and backup. We engineered the variable domains (Fv) of both antibodies to enable low-cost manufacturing at scale for distribution to pediatric populations, in alignment with WHO’s preferred product guidelines. The engineered clone with the optimal manufacturing and drug property profile, MAM01, was advanced into clinical development.
Liquid-infused interfacial floatable porous membrane as movable gate for ultrafast immiscible oil/water separation
Authors: Yang Jianlin , Yang Xin , Yu Tianlu , Wang Zhecun
Published: January 2024

Liquid separation methods are widely used in industrial and everyday applications, however, their applicability is often constrained by low efficiency, membrane fouling, and poor energy efficiency. Herein, a conceptually novel liquid-infused interfacial floatable porous membrane (LIIFPM) system for high-performance oil/water separation is proposed. The system functions by allowing a liquid to wet and fill a superamphiphilic porous membrane, thereby creating a stable liquid-infused interface that floats at the oil/water interface and prevents the passage of immiscible liquids. The lower-layer liquid can outflow directly, while the flow of the upper-layer liquid is stopped by the membrane. Remarkably, the efficiency of the LIIFPM system is independent of the membrane pore size, enabling ultrafast immiscible oil/water separation in an energy-saving and antifouling manner.
Efficient extraction of oleoresin from Ferula gummosa roots by natural deep eutectic solvent and its structure and chemical characterizations
Authors: Radmard Javad , Mohamadi Sani Ali , Arianfar Akram , Mahmoodzadeh Vaziri Behrooz
Published: January 2024

Deep eutectic solvents in the extraction of plant metabolites have found many advantages, such as low toxicity, biodegradability, low cost and ease of preparation over the conventional methods. This work aims to compare natural deep eutectic solvents in extraction and optimization of oleoresin from Ferula gummosa and determining its chemical and structure properties. Box–Behnken design was applied to optimize the extraction of oleoresin from Ferula gummosa using eutectic solvents. The variables of extraction were extraction time, temperature, and ratio of eutectic solvents. Six mixtures of eutectic solvents including choline chloride/urea, acetic acid, lactic acid, formic acid, formamide and glycerol at ratios of 2:1 and 3:1 were evaluated. The highest yields were obtained for choline chloride/formic acid, choline chloride/formamide. The quadratic regression equation was set up as a predictive model with an R2 value of 0.85. The optimum condition was 6 h, 40 °C, and ratio 12.5% (w/v). No significant difference was found between the predicted and experimental yield. The main components of the oleoresin were β-pinene (40.27%), cylcofenchen (11.93%) and α-pinene (7.53%) as characterized by gas chromatography-mass spectrometry. The chemical structure study by spectroscopy showed that no solvents remained in the oleoresin. Therefore, F. gummosa oleoresin can be explored as a novel promising natural pharmaceutical ingredient extracted with eutectic solvents.
Characteristics of physical activity during beginner-level group tennis lessons and the effect daily activity
Authors: Kawakami Ryo , Yamakawa Satoshi , Konda Shoji , Ogasawara Issei , Hasegawa Ryosuke , Yamasaki Keita , Kanamoto Takashi , Yokoyama Teruki , Yoshida Akiyo , Marutani Yoshihiro , Ueda Yuko , Mitsuoka Hideo , Horie Shintaro , Horio Daigo , Nakata Ken
Published: January 2024

Tennis is a popular leisure sport, and studies have indicated that playing tennis regularly provides many health benefits. We aimed to clarify the characteristics of physical activity during beginner-level group tennis lessons and daily physical activity of the participants. Physical activity was measured using an accelerometer sensor device for four weeks, including the 80-min duration tennis lessons held twice a week. Valid data were categorized for tennis and non-tennis days. The mean physical activity intensity during the tennis lesson was 3.37 METs. The mean ratio of short-bout rest periods to the tennis lesson time in 90 and 120 s was 7% and 4%, respectively. The mean physical activity intensity was significantly higher (p < 0.0001) and the duration of vigorous-intensity physical activity (VPA) was increased in 76% of participants on days with tennis lessons compared to without tennis lessons. Beginner-level tennis lesson has characteristics of less short-bout rest physical activity than previously reported competitive tennis match and increased the duration of VPA in daily activity compared to without tennis lessons, suggesting that beginner-level tennis lessons contribute physical activity of health benefits.
Study on improvement of copper sulfide acid soil properties and mechanism of metal ion fixation based on Fe-biochar composite
Authors: Zhang Xiao , Xue Jinchun , Han Huaqin , Wang Yu
Published: January 2024

In this study, Fe modification of bamboo biochar (BC) with ferrate was used to construct a composite soil amendment based on K2FeO4-biochar (Fe-BC) system. Based on soil culture experiments, Fe-BC combined with organic–inorganic materials at the application levels of 3%, 5% and 10% to copper sulfide contaminated acid soil was studied. Adsorption kinetics experiment was used to investigate the adsorption capacity of Fe-modified biochar to heavy metal Cu. The results showed that the pH value of bamboo biochar could be increased by 1.12 units after K2FeO4 modification. Compared with the BC, the adsorption capacity of Cu2+ increased from 190.48 to 276.12 mg/g, which was mainly reflected in single-layer surface adsorption and chemisorption. Pore diffusion, electrostatic interaction and surface interaction are the possible mechanisms of Fe-BC interaction with Cu2+ ions. And the contents of Pb, Cu and Zn in soil leaching state decreased by 59.20%, 65.88% and 57.88%, respectively, at the 10% application level of Fe-BC. In general, the composite modifier based on ferrate and biochar has a positive effect on improving the characteristics of acidic soil in copper mining area.
Identification of hub genes distinguishing subtypes in endometrial stromal sarcoma through comprehensive bioinformatics analysis
Authors: Zhang Ruiqi , Zhao Weilin , Zhu Xingyao , Liu Yuhua , Ding Qi , Yang Caiyun , Zou Hong
Published: January 2024

Diagnosing low-grade and high-grade endometrial stromal sarcoma (LG-ESS and HG-ESS) is a challenge. This study aimed to identify biomarkers. 22 ESS cases were analyzed using Illumina microarrays. Differentially expressed genes (DEGs) were identified via Limma. DEGs were analyzed with String and Cytoscape. Core genes were enriched with GO and KEGG, their pan-cancer implications and immune aspects were studied. 413 DEGs were found by exome sequencing, 2174 by GSE85383 microarray. 36 common genes were identified by Venn analysis, and 10 core genes including RBFOX1, PCDH7, FAT1 were selected. Core gene GO enrichment included cell adhesion, T cell proliferation, and KEGG focused on related pathways. Expression was evaluated across 34 cancers, identifying immune DEGs IGF1 and AVPR1A. Identifying the DEGs not only helps improve our understanding of LG-ESS, HG-ESS but also promises to be potential biomarkers for differential diagnosis between LG-ESS and HG-ESS and new therapeutic targets.
Comparison of intraocular pressure fluctuation and glaucoma progression rate between phakic and pseudophakic eyes in pseudoexfoliation glaucoma
Authors: Kang Edward , Park Ji-Hye , Yoo Chungkwon , Kim Yong Yeon
Published: January 2024

The management of patients with concurrent pseudoexfoliation glaucoma (PXG) and cataract is challenging given its worse prognosis compared to other glaucoma types and the increased risk associated with cataract surgery. In this retrospective study, we investigated the long-term outcomes of cataract surgery in patients with PXG. We enrolled patients with PXG who had undergone cataract surgery at least 2 years previously and compared them with mean deviation (MD) matched patients with phakic eyes. The results showed that both groups experienced a decrease in MD, with the group of pseudophakic eyes exhibiting a significantly higher rate of decline (−2.15 ± 2.66 dB/year vs. −0.86 ± 0.95 dB/year; P = 0.040). Similarly, there was a trend towards more rapid thinning of the retinal nerve fiber layer in the pseudophakic group (−2.92 ± 2.34 μm/year vs. −1.79 ± 1.71 μm/year; P = 0.074). No significant differences in the intraocular pressure parameters were observed between the two groups. Multivariate analysis revealed that pseudophakic lens status was significantly associated with a faster rate of MD decline in patients with PXG (regression coefficient, −1.391; P = 0.022). These findings underscore the importance of close monitoring of patients with pseudophakic PXG to effectively manage glaucoma progression.
Domain-general and language-specific contributions to speech production in a second language: an fMRI study using functional localizers
Authors: Wolna Agata , Szewczyk Jakub , Diaz Michele , Domagalik Aleksandra , Szwed Marcin , Wodniecka Zofia
Published: January 2024

For bilinguals, speaking in a second language (L2) compared to the native language (L1) is usually more difficult. In this study we asked whether the difficulty in L2 production reflects increased demands imposed on domain-general or core language mechanisms. We compared the brain response to speech production in L1 and L2 within two functionally-defined networks in the brain: the Multiple Demand (MD) network and the language network. We found that speech production in L2 was linked to a widespread increase of brain activity in the domain-general MD network. The language network did not show a similarly robust differences in processing speech in the two languages, however, we found increased response to L2 production in the language-specific portion of the left inferior frontal gyrus (IFG). To further explore our results, we have looked at domain-general and language-specific response within the brain structures postulated to form a Bilingual Language Control (BLC) network. Within this network, we found a robust increase in response to L2 in the domain-general, but also in some language-specific voxels including in the left IFG. Our findings show that L2 production strongly engages domain-general mechanisms, but only affects language sensitive portions of the left IFG. These results put constraints on the current model of bilingual language control by precisely disentangling the domain-general and language-specific contributions to the difficulty in speech production in L2.
Individual differences in the neural architecture in semantic processing
Authors: Liu Xin , Hu Yiwen , Hao Yaokun , Yang Liu
Published: January 2024

Neural mechanisms underlying semantic processing have been extensively studied by using functional magnetic resonance imaging, nevertheless, the individual differences of it are yet to be unveiled. To further our understanding of functional and anatomical brain organization underlying semantic processing to the level of individual humans, we used out-of-scanner language behavioral data, T1, resting-state, and story comprehension task-evoked functional image data in the Human Connectome Project, to investigate individual variability in the task-evoked semantic processing network, and attempted to predict individuals’ language skills based on task and intrinsic functional connectivity of highly variable regions, by employing a machine-learning framework. Our findings first confirmed that individual variability in both functional and anatomical markers were heterogeneously distributed throughout the semantic processing network, and that the variability increased towards higher levels in the processing hierarchy. Furthermore, intrinsic functional connectivities among these highly variable regions were found to contribute to predict individual reading decoding abilities. The contributing nodes in the overall network were distributed in the left superior, inferior frontal, and temporo-parietal cortices. Our results suggested that the individual differences of neurobiological markers were heterogeneously distributed in the semantic processing network, and that neurobiological markers of highly variable areas are not only linked to individual variability in language skills, but can predict language skills at the individual level.
3D density imaging using gravity and gravity gradient in the wavenumber domain and its application in the Decorah
Authors: He Huiyou , Fang Jian , Guo Dongmei , Cui Ronghua , Xue Zhixin
Published: January 2024

Density imaging is a method that uses the inversion of the gravity and gravity gradient spectra in the wavenumber domain to create accurate 3D reconstructions of subsurface density distributions. This approach offers computational efficiency and rapid calculations. This research used preliminary inversions to examine the spectral characteristics of gravity and gravity gradient anomalies, as well as the resulting models, were scrutinized through preliminary inversions. 3D density imaging of gravity and gravity gradient was performed in the wavenumber domain using depth weighting on both noise-added and theoretical data, producing a density model that was consistent with the theoretical one. The technique was then used in the Decorah region of the United States, where 3D density imaging was performed and an examination of the properties of gravity and gravity gradient anomalies was conducted. The results showed where high-density Decorah complexes, low-density siliceous intrusive rocks, and high-density intrusive rock masses, were the distributed within the surrounding rock. Each of these provided comprehensive insights into the intrusive pathways to the rock mass. Thus, the appropriateness and effectiveness of the density imaging method were confirmed, supporting a deeper understanding of the structural division and geological evolution in the region.
Integrated whole transcriptome profiling revealed a convoluted circular RNA-based competing endogenous RNAs regulatory network in colorectal cancer
Authors: Mollanoori Hasan , Ghelmani Yaser , Hassani Bita , Dehghani Mohammadreza
Published: January 2024

Recently, it has been identified that circRNAs can act as miRNA sponge to regulate gene expression in various types of cancers, associating them with cancer initiation and progression. The present study aims to identify colorectal cancer-related circRNAs and the underpinning mechanisms of circRNA/miRNA/mRNA networks in the development and progress of Colorectal Cancer. Differentially expressed circRNAs, miRNAs, and mRNAs were identified in GEO microarray datasets using the Limma package of R. The analysis of differentially expressed circRNAs resulted in 23 upregulated and 31 downregulated circRNAs. CeRNAs networks were constructed by intersecting the results of predicted and experimentally validated databases, circbank and miRWalk, and by performing DEMs and DEGs analysis using Cytoscape. Next, functional enrichment analysis was performed for DEGs included in ceRNA networks. Followed by survival analysis, expression profile assessment using TCGA and GEO data, and ROC curve analysis we identified a ceRNA sub-networks that revealed the potential regulatory effect of hsa_circ_0001955 and hsa_circ_0071681 on survival-related genes, namely KLF4, MYC, CCNA2, RACGAP1, and CD44. Overall, we constructed a convoluted regulatory network and outlined its likely mechanisms of action in CRC, which may contribute to the development of more effective approaches for early diagnosis, prognosis, and treatment of CRC.
Clinical outcome post treatment of anemia in pregnancy with intravenous versus oral iron therapy: a systematic review and meta-analysis
Authors: Pandey Anuj Kumar , Gautam Diksha , Tolani Himanshu , Neogi Sutapa Bandyopadhyay
Published: January 2024

Oral iron therapy is often the most common way of treating anaemia; however intravenous iron is considered effective due to rapid iron replenishment. We have dearth of evidence on clinical outcomes post treatment of anaemia. We have searched studies published in English in PubMed, Cochrane, Scopus, ProQuest, and Google Scholar. Our study analysed the clinical outcomes amongst neonates and mother and the adverse events post treatment and assessed the mean change in maternal haemoglobin concentration in both the groups. Forest plots for the clinical outcomes are presented. From a total of 370 studies, 34 Randomized and quasi experimental studies comparing clinical outcomes post-treatment of anaemia in pregnancy were included for quantitative evidence synthesis. Pooled results of maternal clinical outcomes using random effect model [OR: 0.79 (95% CI 0.66; 0.95); 10 outcomes; 17 studies] showed statistically significant difference among both the groups [Moderate quality evidence]; however no significant difference [OR: 0.99 (95% CI 0.86; 1.14); 7 outcomes; 8 studies] have been observed for neonatal complications [Low quality evidence]. The study found that pregnant women receiving IV iron were significantly less likely to experience adverse events as compared with those receiving oral iron [OR 0.39;  (95% CI 0.26–0.60)]; 34 studies; 13,909 women; [Low quality evidence]. Findings from meta-regression analysis showed that IV iron is more likely to reduce maternal complications by 21% compared to oral iron. Increase in odds of adverse maternal outcomes was observed due to increase in gestational age and publication year but no effect for the type of drug used. IV iron increases Hb more and at a higher pace than oral iron. Intravenous iron is more likely to avert adverse maternal outcomes and adverse reactions. However, there is no conclusive evidence on its effectiveness on individual maternal outcome or neonatal outcome/s. Protocol registered with PROSPERO CRD42022368346).
MicroRNAs modulate immunological and inflammatory responses in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis
Authors: Badia-Bringué Gerard , Canive María , Blanco-Vázquez Cristina , Torremocha Rosana , Ovalle Susana , Ramos-Ruiz Ricardo , Casais Rosa , Alonso-Hearn Marta
Published: January 2024

MicroRNAs (miRNAs) regulate the post-transcriptional expression of genes by binding to their target mRNAs. In this study, whole miRNA sequencing was used to compare the expression of miRNAs in ileocecal valve (ICV) and peripheral blood (PB) samples of cows with focal or diffuse paratuberculosis (PTB)-associated lesions in gut tissues versus (vs) control cows without lesions. Among the eight miRNAs differentially expressed in the PB samples from cows with diffuse lesions vs controls, three (miR-19a, miR-144, miR32) were also down-regulated in cows with diffuse vs focal lesions. In the ICV samples, we identified a total of 4, 5, and 18 miRNAs differentially expressed in cows with focal lesions vs controls, diffuse lesions vs controls, and diffuse vs focal lesions, respectively. The differential expression of five microRNAs (miR-19a, miR-144, miR-2425-3p, miR-139, miR-101) was confirmed by RT-qPCR. Next, mRNA target prediction was performed for each differentially expressed miRNA. A functional analysis using the predicted gene targets revealed a significant enrichment of the RNA polymerase and MAPK signaling pathways in the comparison of cows with focal vs no lesions and with diffuse vs focal lesions, respectively. The identified miRNAs could be used for the development of novel diagnostic and therapeutical tools for PTB control.
Unraveling the surface marker signature of cell-derived vesicles via proteome analysis and nanoparticle flow cytometry
Authors: Lau Hui-Chong , Passalacqua Ilaria , Jung Jik-Han , Kwon Yerim , Zocco Davide , Park Sung-Soo , Oh Seung Wook
Published: January 2024

The cell-derived vesicles (CDVs) obtained using a proprietary extrusion process are the foundation of BioDrone platform technology. With superior productivity and versatility, this technology has garnered increasing attention in broad applications, particularly as a drug delivery vehicle. Previously, we showed that CDVs exhibited varying levels of expression for tetraspanin and organelle membrane markers while revealing no discernible differences in physical characteristics compared to naturally produced extracellular vesicles (EVs). To further understand and utilize the therapeutic potentials of CDVs, a more comprehensive study of membrane protein profiles is necessary. In addition, it is crucial to validate that the CDVs produced from extrusion are indeed intact lipid vesicles rather than other impurities. Here, we produced multiple batches of CDVs and EVs from HEK293 cells. CDVs and EVs were subjected to the same purification processes for subsequent proteome and particle analyses. The proteome analyses revealed unique proteome signatures between CDVs, EVs, and parental cells. Extensive proteome analyses identified the nine most prominent membrane markers that are abundant in CDVs compared to cells and EVs. Subsequent western blotting and nanoparticle flow cytometry analyses confirmed that CD63, lysosome-associated membrane glycoprotein 1 (LAMP1), and nicastrin (NCSTN) are highly enriched in CDVs, whereas CD81, CD9, and prostaglandin F2 receptor negative regulator (PTGFRN) are more abundant in EVs. This highlights the unique membrane composition and marker signature of CDVs that are distinct from EVs. Lastly, we demonstrated that more than 90% of the CDVs are genuine lipid vesicles by combining two different classes of vesicle labeling dyes and detergents to disrupt lipid membranes. This indicates that our proprietary extrusion technology is highly compatible with other well-characterized EV production methods. The robust CDV markers identified in this study will also facilitate the engineering of CDVs to achieve enhanced therapeutic effects or tissue-selective cargo delivery.
Growth performance, histological and physiological responses of heat-stressed broilers in response to short periods of incubation during egg storage and thermal conditioning
Authors: Abdel-Fattah Sayed A. , Madkour Mahmoud , Hemida Mona A. , Shourrap Mohamed
Published: January 2024

The short periods of incubation during egg storage (SPIDES) method enhances the quality of chicks and improves hatching rates. Additionally, embryonic thermal conditioning (TC) is a technique used to enhance thermotolerance in birds. Previous studies have evaluated the effects of SPIDES and embryonic TC separately. Yet, our hypothesis postulated that a synergistic effect could be achieved by integrating TC and SPIDES, thereby enhancing the broilers' resilience to thermal stress. We conducted an experiment involving 800 Ross broiler eggs, divided into two groups. The first group, referred to as S0, was maintained under standard storage room conditions and acted as our control group. The second group, known as S1, underwent a process called SPIDES for 5 h at a temperature of 37.8 ± 0.1 °C, on three occasions: days 5, 10, and 15 following egg collection. Upon reaching the 14th day of incubation (DOI), each of these primary groups was randomly subdivided into two equal subgroups. The control subgroup, designated as TC0, remained in the usual incubation conditions. Meanwhile, the other subgroup, TC1, was subjected to prenatal heat conditioning at a temperature of 39.5 ± 0.1 °C for 6 h per day, commencing on the 14th embryonic day (E) and extending until the 18th embryonic day (E). This experimental setup resulted in four distinct experimental subgroups: S0TC0, S1TC0, S0TC1, and S1TC1. The findings indicated that the combined application of SPIDES and TC had a significant positive effect on chick performance after hatching. Specifically, the (S1TC1) group exhibited the heaviest live body weight (LBW) and body weight gain (BWG) at the marketing age in comparison to the other groups. Furthermore, both SPIDES and TC had a positive influence on the relative weights of breast muscles and their histological measurements. The (S1TC1) group displayed significantly higher values in terms of the relative weight of breast muscles and the number of myocytes. In conclusion, SPIDES and TC have beneficial effects on pre- and post-hatch characteristics of broiler chicks up until the marketing age. Additionally, TC techniques improve chick performance, particularly under conditions of heat stress, and enhance the yield of breast muscle in later stages of life.
Framework for assessing bridges construction impact on work zone traffic using BrIM
Authors: Marzouk Mohamed , Elsayed Ahmed
Published: January 2024

This research presents a framework for visualizing bridge construction impact on work zone traffic using Bridge Information Modelling (BrIM) and Google Maps API. The framework consists of four modules. The first module contains the construction data of the bridge by reporting the construction's daily progress. The second module is designated to model traffic data of the work zone using Google Maps API, traffic Survey counting, and Google Earth Images. The third module performs a traffic simulation for the work zone, and calculating the user cost of different stages. The fourth module visualizes the bridge's construction using Bridge Information Modelling (BrIM) and virtual reality in the Twinmotion engine to demonstrate the construction stages and the corresponding traffic states. An actual case study of El-Nahas Bridge in Cairo city-Egypt is presented to demonstrate the main features of the developed framework and its practical aspects. The case study results reveal that the impact of the construction stages varies on work zone traffic throughout the project period. The impact greatly influences the traffic status at the beginning of the project associated with high user costs. Then, the impact declines in later stages depending on the type of construction activities in each stage.
Lack of fitness costs associated with resistance to permethrin in Musca domestica
Authors: Khan Hafiz Azhar Ali
Published: January 2024

Resistance to permethrin has been reported in Pakistani strains of Musca domestica. The present study explored the performance of biological traits and analyzed life tables to determine whether there is any detrimental effect of permethrin resistance on the fitness of permethrin-resistant strains [an isogenic resistant strain (Perm-R) and a field strain (Perm-F)] compared to a susceptible strain (Perm-S). Perm-R and Perm-F exhibited 233.93- and 6.87-fold resistance to permethrin, respectively. Life table analyses revealed that the Perm-R strain had a significantly shorter preadult duration, longer longevity, shorter preoviposition period, higher fecundity, finite rate of increase, intrinsic rate of increase, net reproductive rate and a shorter mean generation time, followed by the Perm-F strain when compared to the Perm-S strain. Data of the performance of biological traits reveled that permethrin resistance strains had a better fit than that of the Perm-S strain. The enhanced fitness of resistant strains of M. domestica may accelerate resistance development to permethrin and other pyrethroids in Pakistan. Some possible measures to manage M. domestica and permethrin resistance in situations of fitness advantage are discussed.
Number of medically prescribed pharmaceutical agents as predictor of mortality risk: a longitudinal, time-variable analysis in the EPIC-Heidelberg cohort
Authors: Katzke Verena A. , Bajracharya Rashmita , Nasser Mohamad I. , Schöttker Ben , Kaaks Rudolf
Published: January 2024

The number of prescribed medications might be used as proxy indicator for general health status, in models to predict mortality risk. To estimate the time-varying association between active pharmaceutical ingredient (API) count and all-cause mortality, we analyzed data from a population cohort in Heidelberg (Germany), including 25,546 participants with information on medication use collected at 3-yearly intervals from baseline recruitment (1994–1998) until end of 2014. A total of 4548 deaths were recorded until May 2019. Time-dependent modeling was used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for all-cause mortality in relation to number of APIs used, within three strata of age (≤ 60, > 60 to  ≤ 70 and > 70 years) and adjusting for lifestyle-related risk factors. For participants reporting commonly used APIs only (i.e., API types accounting for up to 80% of medication time in the population) total API counts showed no association with mortality risk within any age stratum. However, when at least one of the APIs was less common, the total API count showed a strong relationship with all-cause mortality especially up to age ≤ 60, with HR up to 3.70 (95% CI 2.30–5.94) with 5 or 6 medications and 8.19 (5.61–11.97) for 7 or more APIs (versus none). Between > 60 and 70 years of age this risk association was weaker, with HR up to 3.96 (3.14–4.98) for 7 or more APIs, and above 70 years it was weakened further (HR up to 1.54 (1.34–1.79)). Multiple API-use may predict mortality risk in middle-aged and women and men ≤ 70 years, but only if it includes at least one less frequently used API type. With advancing age, and multiple medication becomes increasingly prevalent, the association of API count with risk of death progressively attenuates, suggesting an increasing complexity with age of underlying mortality determinants.
Comparison of mid-outcome among bare metal stent, atherectomy with or without drug-coated balloon angioplasty for femoropopliteal arterial occlusion
Authors: Yang Lin , Quan Jianjun , Dong Jian , Ding Ningning , Han Yang , Cong Longlong , Lin Yuhao , Liu Jianlin
Published: January 2024

This study evaluated the outcomes of a bare metal stent (BMS), DCB alone, atherectomy plus a drug-coated balloon (AT + DCB) and AT alone for the treatment of femoropopliteal artery occlusion. Four groups were included in this retrospective cohort study: 119 patients underwent the BMS procedure, 89 patients underwent DCB alone, 52 patients underwent AT + DCB, and 61 patients underwent AT alone. Patients were followed-up at 1, 6, 12 and 24 months after the procedure, the clinical outcomes and complications were assessed, and the primary outcomes were primary patency and restenosis. AT + DCB showed a lower bailout stent, and BMS displayed a higher retrograde puncture, flow-limiting dissection and postdilation (p < 0.05). For all procedures, the walking distance, ABI and pain score post-procedure were significantly improved compared with the pre-procedure values (p < 0.001). The restenosis rate was higher in BMS (21.0%) and AT alone (24.6%) than in DCB (10.1%) alone and AT + DCB (11.5%) (p = 0.04); there was no difference in amputation or clinically driven target lesion revascularization among procedures. The primary patency rates were 77.7%, 89.4%, 88.0% and 73.7% in the BMS, DCB alone, AT + DCB and AT alone groups at 24 months, respectively (p = 0.03), while the secondary patency and main adverse events (stroke, MI and death) were similar. Proximal concavity, proximal target vessel diameter ≥ 5 mm, runoff number ≥ 2 and DCB use were protective factors for primary patency. Our results suggested that AT + DCB and DCB alone were associated with higher primary patency, and DCB devices (combined with/without AT) should be the preferred choice for FP lesions.
Association between high-density lipoprotein cholesterol and reversion to normoglycemia from prediabetes: an analysis based on data from a retrospective cohort study
Authors: Mo Zihe , Hu Haofei , Han Yong , Cao Changchun , Zheng Xiaodan
Published: January 2024

The available evidence on the connection between high-density lipoprotein cholesterol (HDL-C) levels and the reversion from prediabetes (Pre-DM) to normoglycemia is currently limited. The present research sought to examine the connection between HDL-C levels and the regression from Pre-DM to normoglycemia in a population of Chinese adults. This historical cohort study collected 15,420 Pre-DM patients in China who underwent health screening between 2010 and 2016. The present research used the Cox proportional hazards regression model to investigate the connection between HDL-C levels and reversion from Pre-DM to normoglycemia. The Cox proportional hazards regression model with cubic spline functions and smooth curve fitting was employed to ascertain the nonlinear association between HDL-C and reversion from Pre-DM to normoglycemia. Furthermore, a set of sensitivity analyses and subgroup analyses were employed. Following the adjustment of covariates, the findings revealed a positive connection between HDL-C levels and the likelihood of reversion from Pre-DM to normoglycemia (HR 1.898, 95% CI 1.758–2.048, P < 0.001). Furthermore, there was a non-linear relationship between HDL-C and the reversion from Pre-DM to normoglycemia in both genders, and the inflection point of HDL-C was 1.540 mmol/L in males and 1.620 mmol/L in females. We found a strong positive correlation between HDL-C and the reversion from Pre-DM to normoglycemia on the left of the inflection point (Male: HR 2.783, 95% CI 2.373–3.263; Female: HR 2.217, 95% CI 1.802–2.727). Our sensitivity analysis confirmed the robustness of these findings. Subgroup analyses indicated that patients with SBP < 140 mmHg and ever smoker exhibited a more pronounced correlation between HDL-C levels and the reversion from Pre-DM to normoglycemia. In contrast, a less robust correlation was observed among patients with SBP ≥ 140 mmHg, current and never smokers. This study provides evidence of a positive and nonlinear association between HDL-C levels and the reversion from Pre-DM to normoglycemia in Chinese patients. Implementing intensified intervention measures to control the HDL-C levels of patients with Pre-DM around the inflection point may substantially enhance the likelihood of regression to normoglycemia.
Discovering biomarkers associated and predicting cardiovascular disease with high accuracy using a novel nexus of machine learning techniques for precision medicine
Authors: DeGroat William , Abdelhalim Habiba , Patel Kush , Mendhe Dinesh , Zeeshan Saman , Ahmed Zeeshan
Published: January 2024

Personalized interventions are deemed vital given the intricate characteristics, advancement, inherent genetic composition, and diversity of cardiovascular diseases (CVDs). The appropriate utilization of artificial intelligence (AI) and machine learning (ML) methodologies can yield novel understandings of CVDs, enabling improved personalized treatments through predictive analysis and deep phenotyping. In this study, we proposed and employed a novel approach combining traditional statistics and a nexus of cutting-edge AI/ML techniques to identify significant biomarkers for our predictive engine by analyzing the complete transcriptome of CVD patients. After robust gene expression data pre-processing, we utilized three statistical tests (Pearson correlation, Chi-square test, and ANOVA) to assess the differences in transcriptomic expression and clinical characteristics between healthy individuals and CVD patients. Next, the recursive feature elimination classifier assigned rankings to transcriptomic features based on their relation to the case–control variable. The top ten percent of commonly observed significant biomarkers were evaluated using four unique ML classifiers (Random Forest, Support Vector Machine, Xtreme Gradient Boosting Decision Trees, and k-Nearest Neighbors). After optimizing hyperparameters, the ensembled models, which were implemented using a soft voting classifier, accurately differentiated between patients and healthy individuals. We have uncovered 18 transcriptomic biomarkers that are highly significant in the CVD population that were used to predict disease with up to 96% accuracy. Additionally, we cross-validated our results with clinical records collected from patients in our cohort. The identified biomarkers served as potential indicators for early detection of CVDs. With its successful implementation, our newly developed predictive engine provides a valuable framework for identifying patients with CVDs based on their biomarker profiles.
Analysis of microbial communities in solid and liquid pig manure during the fertilization process
Authors: Kim Soo-Ryang , Lee Junkyung , Lee Myung Gyu , Sung Ha Guyn , Hwang Sun-Goo
Published: January 2024

Utilizing livestock manure as organic fertilizer in sustainable agriculture is crucial and should be developed through an appropriate manufacturing process. Solid–liquid separation contributes to reducing odor, managing nutrients in livestock excretions, and lowering the cost of transporting manure to arable soil. To investigate the impact of fermentation after solid–liquid separation, we examined the specific correlation between chemical properties and bacterial communities in solid–liquid manures before and after the fermentation process. In terms of chemical properties before fermentation, the levels of electrical conductivity, nitrogen, ammonium nitrogen (NH4+-N), potassium, sodium, and chloride were higher in the liquid sample than in the solid sample. However, the chemical components of the liquid sample decreased during fermentation, which could be attributed to the low organic matter content. Many chemical components increased in the solid samples during fermentation. Fifty-six bacterial species were significantly correlated with NH4+-N and phosphorus. Following fermentation, their abundance increased in the solid samples and decreased in the liquid samples, indicating the potential for NH4+-N release or phosphorus mineralization from organic matter. These results provide information regarding changes in nutrient and bacterial formation when applying the fermentation process after solid–liquid separation.