bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Study on the Road Performance of High Content of Phosphogypsum in the Lime–Fly Ash Mixture
Authors: Qian Guoping , Zhong Yixiong , Li Xi , Peng Huaizhi , Su Ju , Huang Zichao
Published: July 2022

Phosphogypsum (PG), as a by-product of the production of phosphoric acid, faces the problems of large annual output and difficult treatment. There is a large demand for fillers in the process of road paving, which may be an effective method for the utilization of PG resources. In this study, three proportions of phosphogypsum–lime–fly ash (PLF) mixture were designed, first, according to orthogonal tests. The comprehensive performance of the PLF mixture was tested by the compression rebound modulus test, unconfined compressive strength test, flexural tensile strength test, dry shrinkage test, and temperature shrinkage test, respectively. The results show that adding crushed stone to the PLF mixture can effectively improve the compression rebound modulus, unconfined compressive strength, and flexural tensile strength. The high content of PG in the mixture can also improve the dry shrinkage and temperature shrinkage properties of the mixture. According to the road layer requirements, the optimum proportion of the PLF mixture is recommended, which may benefit the road construction and PG resources.
Effects of Ca substitution on the local structure and oxide–ion behavior of layered perovskite lanthanum nickelate
Authors: Kitamura Naoto , Kimura Kazuki , Ishida Naoya , Ishibashi Chiaki , Idemoto Yasushi
Published: July 2022

La2NiO4+δ-based materials with a layered perovskite structure have attracted significant attention as air–electrode materials for use in solid oxide fuel cells. In particular, Ca-substituted materials, La2-xCaxNiO4+δ, have been investigated, as the partial substitution of La with Ca can improve oxide–ion conduction in crystals. However, the local structures around the conducting oxide ion and Ca dopant are not been well understood because their distributions cannot be characterized by a general structure analysis only using Bragg peaks. Therefore, we examine the atomic structure of La1.75Ca0.25NiO4+δ by a combination of molecular dynamics simulations and a reverse Monte Carlo modeling using the Faber–Ziman structure factor, real-space function, and the Bragg profile simultaneously. The results indicate that conducting oxide ions are introduced into rocksalt layers in the crystal and are present around La but not Ca. Furthermore, it is found that ionic diffusion is accompanied by a change in the rocksalt layer volume, which can be suppressed by the partial substitution with Ca. This can be regarded as a major reason why Ca substitution improves oxide–ion diffusion in the La2NiO4+δ layered perovskite.
The numerical analysis of the acoustic streaming effect of a cavity acoustic black hole
Authors: Huang Meilian , Liang Xiao , Su Liang , He Xingyun , Li Danni , Chu Jiaming , Wang Shengsheng , Liang Haofeng , Zhang Yongyan
Published: July 2022

In this study, we use numerical methods to study the acoustic streaming effect of the acoustic black hole (ABH). Firstly, we build an ABH model to study the acoustic streaming effect. By deriving the waves equations and solving the Navier–Stokes equations, we obtain the flow field, sound field, and temperature field under the acoustic excitation. Secondly, the simulation result reveals the mechanism of acoustic streaming effects on the sound transmission characteristics of cavity ABH. The numerical results show that the abrupt decrease in the sound pressure is caused by the great changes in the velocity gradient caused by the catastrophe of cross section. The energy of the sound waves can also be dissipated by the thermal viscous layer at low frequencies. Finally, based on the acoustic streaming effects of the acoustic medium in the ABH, we propose feasible methods to enhance the sound insulation. Increasing the cross section of the cavity in ABH can get a better sound insulation effect at high frequencies, and decreasing the cross section can improve Sound Transmission Loss (STL). Through optimization, STL can reach more than 25 dB at low frequencies.
The numerical simulation of nanosecond-pulsed discharge-assisted ignition in lean-burn natural gas HCCI engines
Authors: Ban Yangyang , Zhang Fan , Zhong Shenghui , Zhu Jiajian
Published: July 2022

A plasma-assisted internal combustion engine model is established based on detailed plasma kinetics, combustion kinetics, and physical compression/expansion processes. The effects of nanosecond repetitively pulsed discharge (NRPD) on plasma-assisted ignition characteristics of mixtures under different fuel concentrations are studied under HCCI engine-relevant conditions. The coupled plasma and chemical kinetic model are validated with experiments. The comparison between NRPD and thermal ignition with a certain amount of input energy is carried out, and the results show that the former can ignite a mixture owing to the kinetic effect of nonequilibrium plasma, but the latter cannot ensure ignition. Path flux analysis shows that excited states and electrons react with fuel, providing O and H directly, increasing the possibility of ignition at a low temperature. The effect of NRPD on combustion performance under various equivalence ratios (φ) is investigated. It was found that in ICEs with NRPD, the ignition delay time under the lean-burn condition (φ = 0.5) is the shortest among three demonstrative cases. Even though the leaner mixture case with φ = 0.2 is more favorable for the production of O and OH during the discharge, after discharge, the heat release in case 2 with φ = 0.5 dramatically increases, resulting in the temperature exceeding that in the ultra-lean case. As the piston moves up, the higher amounts of CH3, HO2, and H2O2 as well as higher temperature for the lean-burn (φ = 0.5) case lead to the rapid increase of OH and O, which accelerates the consumption of methane and finally the earliest hot ignition near TDC. Finally, a series of parameter studies are performed to show the effects of E/N, current density, φ, and discharge timing on the ignition process. The results suggest that discharge parameters E/N and current density together with discharge timings and equivalence ratios can improve ignitability in internal combustion engines.
The regulatory challenges of innovative customized combination products
Authors: Reis Mariana E. , Bettencourt Ana , Ribeiro Helena M.
Published: July 2022

Background/aims

Combination products are therapeutic and/or diagnostic products that can combine drugs and medical devices and which increasing complexity has raised new regulatory framework challenges. To reach the market, a combination product must be classified based on the principal mode of action (PMOA). However, research and technological progress has been leading to the development of novel combination products with no clearly defined PMOA, emphasizing the lack of a systematization process, thus challenging the correct classification of these products. To illustrate the regulatory challenge, two case studies are discussed: innovative combination products with PMOA that can change due to an external stimulus, specifically custom-made 3D-printed scaffolds with incorporated medicinal substances.

Methods

Data was collected through computational search engines, regulatory agencies and equally relevant associations. The analysis of the data resulted on this state-of-the-art review, a description of the decision-making process by the regulatory authorities, and case studies analysis that culminated in the proposal of a decision-tree scheme.

Findings

Current regulations do not fully address complex combination products namely personalized 3D-printed scaffolds. Two merged regulatory approaches are suggested along with the schematization of the rational assisted by a decision-tree tool.

Conclusion

Combination products have become increasingly sophisticated, which has furthered the need to develop multidisciplinary collaborations within the health sector to adapt to these innovative healthcare solutions as well as with regulators to overcome the challenges posed for their classification.
New integrated weaning indices from mechanical ventilation: A derivation-validation observational multicenter study
Authors: Vahedian-Azimi Amir , Gohari-Moghadam Keivan , Rahimi-Bashar Farshid , Samim Abbas , Khoshfetrat Masoum , Mohammadi Seyyede Momeneh , de Souza Leonardo Cordeiro , Mahmoodpoor Ata
Published: July 2022

Background

To develop ten new integrated weaning indices that can predict the weaning outcome better than the traditional indices.

Methods

This retrospective-prospective derivation-validation observational multicenter clinical trial (Clinical Trial.Gov, NCT 01779297), was conducted on 1,175 adult patients admitted at 9 academic affiliated intensive care units (ICUs; 4 surgical and 5 medical), from Jan 2013 to Dec 2018. All patients, intubated and mechanically ventilated for at least 24 h and ready for weaning were enrolled. The study had two phases: at first, the threshold values of each index that best discriminate between a successful and an unsuccessful weaning outcome was determined among 208 patients in the derivation group. In the second phase, the predictive performance of these values was prospectively tested in 967 patients in the validation group. In the prospective-validation set we used Bayes’ theorem to assess the probability of each test in predicting weaning.

Results

In the prospective validation group, sensitivity, specificity, diagnostic accuracy, positive and negative predictive values, and finally area under the receiver operator characteristic curves and standard errors for each index (ten formulae) were calculated. Statistical values of ten formulae for aforesaid variables were higher than 87% (0.87–0.99).

Conclusion

The new indices can be used for hospitalized patients in intensive care settings for accurate prediction of the weaning outcome.
Burden of tuberculosis and its association with socio-economic development status in 204 countries and territories, 1990–2019
Authors: Xue Yi , Zhou Jie , Wang Peng , Lan Jun-hong , Lian Wen-qin , Fan Yue-Ying , Xu Bei-Ni , Yin Jia-Peng , Feng Zi-hao , Zhou Jian , Jia Chi-Yu
Published: July 2022

Background

Tuberculosis (TB) always runs in the forefront of the global burden when it comes to infectious diseases. Tuberculosis, which can lead to impairment of quality of life, financial hardship, discrimination, marginalization, and social barriers, is a major public health problem. The assessment of TB burden and trend can provide crucial information for policy decision and planning, and help countries in the world to achieve the goal of sustainable development of ending the epidemic of TB in 2030.

Methods

All data are from the Global Burden of Disease 2019 (GBD 2019) database, which analyzed the burden trend of age-standardized incidence, DALYs, and deaths rate in TB and HIV/AIDS-infected TB over the past 30 years. Also, GBD 2019 not only analyzed the burden distribution of TB in 204 countries and main regions of the world but also analyzed the relationship between the burden of global TB and the socio–demographic Index (SDI).

Results

The age-standardized incidence, age-standardized disability-adjusted life years (DALYs), and age-standardized deaths rate for HIV-negative TB were 10,671.45 (9,395.60–12,194.10), 59,042.45 (53,684.78–64,641.53), and 1,463.62 (1,339.24–1,602.71) (95% CI, per 100,000 person-years) in 2019, respectively. Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of HIV/AIDS-XDR-TB (95% CI, per 1,000 person-years) were 2.10 (1.51–2.90), 64.23 (28.64–117.74), and 1.01 (0.42–1.86), respectively. We found that TB is inversely proportional to SDI, the age-standardized incidence, DALYs, and deaths rate low burden countries were in high SDI areas, while high burden countries were in low SDI areas. The global TB showed a slow decline trend, but the age-standardized incidence of HIV-positive TB was increasing, and mainly distributed in sub-Saharan Africa.

Conclusion

Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of TB is related to SDI, and the burden of low SDI countries is lighter than that of high SDI countries. Without effective measures, it will be difficult for countries around the world to achieve the goal of ending the TB epidemic by 2030. Effective control of the spread of TB requires concerted efforts from all countries in the world, especially in the countries with low SDI, which need to improve the diagnosis and preventive measures of TB and improve the control of HIV/AIDS-TB.
What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis?
Authors: Raine Charles , Giles Ian
Published: July 2022

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease and has a female predominance of around 3:1. The relationship between sex hormones and RA has been of great interest to researchers ever since Philip Hench's observations in the 1930's regarding spontaneous disease amelioration in pregnancy. Extensive basic scientific work has demonstrated the immunomodulatory actions of sex hormones but this therapeutic potential has not to date resulted in successful clinical trials in RA. Epidemiological data regarding both endogenous and exogenous hormonal factors are inconsistent, but declining estrogen and/or progesterone levels in the menopause and post-partum appear to increase the risk and severity of RA. This review assimilates basic scientific, epidemiological and clinical trial data to provide an overview of the current understanding of the relationship between sex hormones and RA, focusing on estrogen, progesterone and androgens.
Delay in accessing definitive care for patients with microbial keratitis in Nepal
Authors: Hoffman Jeremy J. , Yadav Reena , Das Sanyam Sandip , Chaudhary Pankaj , Roshan Abhishek , Singh Sanjay K. , Mishra Sailesh K. , Arunga Simon , Hu Victor H. , Macleod David , Leck Astrid , Burton Matthew J.
Published: July 2022

Background

The aim of this study was to describe the health-seeking journey for patients with microbial keratitis (MK) in Nepal and identify factors associated with delay.

Methods

Prospective cohort study where MK patients attending a large, tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. We collected demographic details, clinical history, and examination findings. Care-seeking journey details were captured including places attended, number of journeys, time from symptom onset, and costs. We compared “direct” with “indirect” presenters, analyzing for predictors of delay.

Results

We enrolled 643 patients with MK. The majority (96%) self-referred. “Direct” attenders accounted for only 23.6% (152/643) of patients, the majority of “indirect” patients initially presented to a pharmacy (255/491). Over half (328/643) of all cases presented after at least 7 days. The total cost of care increased with increasing numbers of facilities visited (p < 0.001). Those living furthest away were least likely to present directly (p < 0.001). Factors independently associated with delayed presentation included distance >50 km from the eye hospital [aOR 5.760 (95% CI 1.829–18.14, p = 0.003)], previous antifungal use [aOR 4.706 (95% CI 3.139–5.360)], and two or more previous journeys [aOR 1.442 (95% CI 1.111–3.255)].

Conclusions

Most patients visited at least one facility prior to our institution, with time to presentation and costs increasing with the number of prior journeys. Distance to the eye hospital is a significant barrier to prompt, direct presentation. Based on these findings, improving access to eye care services, strengthening referral networks and encouraging early appropriate treatment are recommended to reduce delay, ultimately improving clinical outcomes.
Human IgG antibody responses to severe acute respiratory syndrome coronavirus 2 viral antigens receptor-binding domain, spike, and nucleocapsid, in vaccinated adults from Merida, Mexico
Authors: Puerta-Guardo Henry , Parra-Cardeña Manuel , Peña-Miranda Fernando , Flores-Quintal Felipe , Granja-Pérez Pilar , Villanueva-Jorge Salha , González-Losa Refugio , Conde-Ferraez Laura , Gómez-Carballo Jesus , Vazquez-Prokopec Gonzalo , Earnest James T. , Manrique-Saide Pablo , Ayora-Talavera Guadalupe
Published: July 2022

Several vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been approved for controlling the coronavirus disease 2019 (COVID-19) pandemic worldwide. Antibody response is essential to understand the immune response to different viral targets after vaccination with different vaccine platforms. Thus, the main aim of this study was to describe how vaccination with two distinct SARS-CoV-2 vaccine preparations elicit IgG antibody specific responses against two antigenically relevant SARS-CoV-2 viral proteins: the receptor-binding domain (RBD) and the full-length spike (S). To do so, SARS-CoV-2 protein specific in-house enzyme-linked immunosorbent assays (ELISAs) were standardized and tested against serum samples collected from 89 adults, recipients of either a single-dose of the Spike-encoding mRNA-based Pfizer/BioNTech (Pf-BNT) (70%, 62/89) or the Spike-encoding-Adenovirus-5-based CanSino Biologics Inc. (CSBIO) (30%, 27/89) in Merida, Mexico. Overall, we identified an IgG seroconversion rate of 88% (68/78) in all vaccinees after more than 25 days post-vaccination (dpv). Anti-RBD IgG-specific responses ranged from 90% (46/51) in the Pf-BNT vaccine at 25 dpv to 74% (20/27) in the CSBIO vaccine at 42 dpv. Compared to the S, the RBD IgG reactivity was significantly higher in both Pf-BNT (p < 0.004) and CSBIO (p < 0.003) vaccinees. Interestingly, in more than 50% of vaccine recipients, with no history of COVID-19 infection, antibodies against the nucleocapsid (N) protein were detected. Thus, participants were grouped either as naïve or pre-exposed vaccinees. Seroconversion rates after 25 and more dpv varies between 100% in Pf-BNT (22/22) and 75% (9/12) in CSBIO pre-exposed vaccinees, and 89% (26/29) and 73% (11/15) in Pf-BNT and CSBIO naïve vaccine recipients, respectively. In summary, observed seroconversion rates varied depending on the type of vaccine, previous infection with SARS-CoV-2, and the target viral antigen. Our results indicate that both vaccine preparations can induce detectable levels of IgG against the RBD or Spike in both naïve and SARS-CoV-2 pre-exposed vaccinees. Our study provides valuable and novel information about the serodiagnosis and the antibody response to vaccines in Mexico.
Occurrence and Effects on Weaning From Mechanical Ventilation of Intensive Care Unit Acquired and Diaphragm Weakness: A Pilot Study
Authors: Bertoni Michele , Piva Simone , Beretta Alessandra , Bongiovanni Federica , Contarino Riccardo , Artigas Ricard Mellado , Ceresoli Lucia , Marchesi Mattia , Falappi Michele , Belleri Marta , Goffi Alberto , Pozzi Matteo , Rasulo Frank Antonio , Latronico Nicola
Published: July 2022

Purpose

Limb intensive care unit (ICU)-acquired weakness (ICUAW) and ICU acquired diaphragm weakness (DW) occur frequently in mechanically ventilated (MV) patients; their coexistence in cooperative and uncooperative patients is unknown. This study was designed to (1) describe the co-occurrence of the two conditions (2) evaluate the impact of ICUAW and DW on the ventilator-free days (VFDs) at 28 days and weaning success, and (3) assess the correlation between maximal inspiratory pressure (MIP) and thickening fraction (TFdi) in patients with DW.

Methods

This prospective pilot study was conducted in a single-center on 73 critically ill MV patients. Muscle weakness was defined as a Medical Research Council score < 48 in cooperative patients or a bilateral mean simplified peroneal nerve test < 5.26 mV in uncooperative patients. Diaphragm dysfunction was defined as MIP < 30 cm H2O or as a TFdi < 29%. Weaning success was defined according to weaning according to a new definition (WIND).

Results

Fifty-seven patients (78%) had ICUAW and 59 (81%) had DW. The coexistence of the two conditions occurred in 48 patients (65%), without association (χ2 = 1.06, p = 0.304). In the adjusted analysis, ICUAW was independently related to VFDs at 28-days (estimate difference 6 days, p = 0.016), and WIND (OR of 3.62 for having WIND different than short weaning), whereas DW was not. The linear mixed model showed a significant but weak correlation between MIP and TFdi (p < 0.001).

Conclusion

This pilot study is the first to explore the coexistence of ICUAW and DW in both cooperative and uncooperative patients; a lack of association was found between DW and ICUAW when considering both cooperative and uncooperative patients. We found a strong correlation between ICUAW but not DW with the VFDs at 28 days and weaning success. A future larger study is warranted in order to confirm our results, and should also investigate the use of transdiaphragmatic twitch pressure measurement during bilateral anterior magnetic phrenic nerve stimulation for the diagnosis of DW.
Comparative analysis of neutrophil to lymphocyte ratio and derived neutrophil to lymphocyte ratio with respect to outcomes of in-hospital coronavirus disease 2019 patients: A retrospective study
Authors: Asghar Muhammad Sohaib , Akram Mohammed , Yasmin Farah , Najeeb Hala , Naeem Unaiza , Gaddam Mrunanjali , Jafri Muhammad Saad , Tahir Muhammad Junaid , Yasin Iqra , Mahmood Hamid , Mehmood Qasim , Marzo Roy Rillera
Published: July 2022

Introduction and objectives

In patients with coronavirus disease 2019 (COVID-19), several abnormal hematological biomarkers have been reported. The current study aimed to find out the association of neutrophil to lymphocyte ratio (NLR) and derived NLR (dNLR) with COVID-19. The objective was to compare the accuracy of both of these markers in predicting the severity of the disease.

Materials and methods

The study was conducted in a single-center having patients with COVID-19 with a considerable hospital stay. NLR is easily calculated by dividing the absolute neutrophil count (ANC) with the absolute lymphocyte count (ALC) {ANC/ALC}, while dNLR is calculated by ANC divided by total leukocyte count minus ANC {ANC/(WBC-ANC)}. Medians and interquartile ranges (IQR) were represented by box plots. Multivariable logistic regression was performed obtaining an odds ratio (OR), 95% CI, and further adjusted to discover the independent predictors and risk factors associated with elevated NLR and dNLR.

Results

A total of 1,000 patients with COVID-19 were included. The baseline NLR and dNLR were 5.00 (2.91–10.46) and 4.00 (2.33–6.14), respectively. A cut-off value of 4.23 for NLR and 2.63 for dNLR were set by receiver operating characteristic (ROC) analysis. Significant associations of NLR were obtained by binary logistic regression for dependent outcome variables as ICU stay (p < 0.001), death (p < 0.001), and invasive ventilation (p < 0.001) while that of dNLR with ICU stay (p = 0.002), death (p < 0.001), and invasive ventilation (p = 0.002) on multivariate analysis when adjusted for age, gender, and a wave of pandemics. Moreover, the indices were found correlating with other inflammatory markers such as C-reactive protein (CRP), D-dimer, and procalcitonin (PCT).

Conclusion

Both markers are equally reliable and sensitive for predicting in-hospital outcomes of patients with COVID-19. Early detection and predictive analysis of these markers can allow physicians to risk assessment and prompt management of these patients.
Oral isotretinoin for acne vulgaris side effects on the ocular surface: Hyaluronic acid and galacto-xyloglucan as treatment for dry eye disease signs and symptoms
Authors: Sánchez-González María Carmen , De-Hita-Cantalejo Concepción , Martínez-Lara Concepción , Sánchez-González José-María
Published: July 2022

The purpose was to assess the efficacy of 0.4% hyaluronic acid and 0.2% galacto-xyloglucan on the subjective symptoms of dry eye disease and invasive and non-invasive tear film signs in oral isotretinoin for acne vulgaris treatment. A prospective, longitudinal, single-blind, clinical study was performed in oral isotretinoin for the acne vulgaris consumer population. Subjective dry eye disease questionnaires and invasive and non-invasive tear film assessments were reported prior to and after 6 weeks of hyaluronic acid with galacto-xyloglucan (HA-GX) treatment vs. hyaluronic acid alone (HA). Participants in the HA-GX group reported a higher decrease in the ocular surface disease index (17.01 ± 11.36 score points) compared to the variation in participants in the HA group (11.61 ± 11.18 score points). Standard patient evaluation of eye dryness also decreased more in participants in the HA-GX group (4.06 ± 5.50 score points) than in participants who received HA alone (0.70 ± 3.16). Regarding non-invasive break-up time (NIBUT), participants in the HA-GX group first NIBUT achieved an increase of 1.75 ± 1.16 s while participants in the HA-alone group demonstrated an increase of only 0.54 ± 1.01 s. The HA-GX group mean NIBUT increased by of 3.72 ± 5.69 s; however, the value for the HA-alone group was 2.19 ± 5.26 s. Hyaluronic acid in combination with galacto-xyloglucan significantly decreased limbal and bulbar conjunctival redness classification and SPEED test outcomes. The inclusion of galacto-xyloglucan also increased BUT and mean NIBUT values compared to those obtained with hyaluronic acid alone.
SARS-CoV-2 Nucleocapsid Protein Has DNA-Melting and Strand-Annealing Activities With Different Properties From SARS-CoV-2 Nsp13
Authors: Zhang Bo , Xie Yan , Lan Zhaoling , Li Dayu , Tian Junjie , Zhang Qintao , Tian Hongji , Yang Jiali , Zhou Xinnan , Qiu Shuyi , Lu Keyu , Liu Yang
Published: July 2022

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world and has had a devastating impact on health and economy. The biochemical characterization of SARS-CoV-2 proteins is important for drug design and development. In this study, we discovered that the SARS-CoV-2 nucleocapsid protein can melt double-stranded DNA (dsDNA) in the 5′-3′ direction, similar to SARS-CoV-2 nonstructural protein 13. However, the unwinding activity of SARS-CoV-2 nucleocapsid protein was found to be more than 22 times weaker than that of SARS-CoV-2 nonstructural protein 13, and the melting process was independent of nucleoside triphosphates and Mg2+. Interestingly, at low concentrations, the SARS-CoV-2 nucleocapsid protein exhibited a stronger annealing activity than SARS-CoV-2 nonstructural protein 13; however, at high concentrations, it promoted the melting of dsDNA. These findings have deepened our understanding of the SARS-CoV-2 nucleocapsid protein and will help provide novel insights into antiviral drug development.
A metacommunity ecology approach to understanding microbial community assembly in developing plant seeds
Authors: Bergmann Gillian E. , Leveau Johan H. J.
Published: July 2022

Microorganisms have the potential to affect plant seed germination and seedling fitness, ultimately impacting plant health and community dynamics. Because seed-associated microbiota are highly variable across individual plants, plant species, and environments, it is challenging to identify the dominant processes that underlie the assembly, composition, and influence of these communities. We propose here that metacommunity ecology provides a conceptually useful framework for studying the microbiota of developing seeds, by the application of metacommunity principles of filtering, species interactions, and dispersal at multiple scales. Many studies in seed microbial ecology already describe individual assembly processes in a pattern-based manner, such as correlating seed microbiome composition with genotype or tracking diversity metrics across treatments in dispersal limitation experiments. But we see a lot of opportunities to examine understudied aspects of seed microbiology, including trait-based research on mechanisms of filtering and dispersal at the micro-scale, the use of pollination exclusion experiments in macro-scale seed studies, and an in-depth evaluation of how these processes interact via priority effect experiments and joint species distribution modeling.
Niche-Neutral Continuum Seems to Explain the Global Niche Differentiation and Local Drift of the Human Digestive Tract Microbiome
Authors: Chen Hongju (Daisy) , Ma Zhanshan (Sam)
Published: July 2022

The human digestive tract (DT) is differentiated into diverse niches and harbors the greatest microbiome diversity of our bodies. Segata et al. (2012) found that the microbiome of diverse habitats along the DT may be classified as four categories or niches with different microbial compositions and metabolic potentials. Nonetheless, few studies have offered theoretical interpretations of the observed patterns, not to mention quantitative mechanistic parameters. Such parameters should capture the essence of the fundamental processes that shape the microbiome distribution, beyond simple ecological metrics such as diversity or composition descriptors, which only capture the manifestations of the mechanisms. Here, we aim to get educated guesses for such parameters by adopting an integrated approach with multisite neutral (MSN) and niche-neutral hybrid (NNH) modeling, via reanalyzing Segata’s 16s-rRNA samples covering 10 DT-sites from over 200 healthy individuals. We evaluate the relative importance of the four essential processes (drift, dispersal, speciation, and selection) in shaping the microbiome distribution and dynamics along DT, which are assumed to form a niche-neutral continuum. Furthermore, the continuum seems to be hierarchical: the selection or niche differentiations seem to play a predominant role (> 90% based on NNH) at the global (the DT metacommunity) level, but the neutral drifts seem to be prevalent (> 90% based on MSN/NNH) at the local sites except for the gut site. An additional finding is that the DT appears to have a fifth niche for the DT microbiome, namely, Keratinized gingival (KG), while in Segata’s original study, only four niches were identified. Specifically, in Segata’s study, KG was classified into the same niche type including buccal mucosa (BM), hard palate (HP), and KG. However, it should be emphasized that the proposal of the fifth niche of KG requires additional verification in the future studies.
Infectious bursal disease virus replication is inhibited by avain T cell chemoattractant chemokine CCL19
Authors: Wang Qiuxia , Chu Fuming , Zhang Xin , Hu Huilong , Lu Lang , Wang Fang , Yu Yan , Zhang Yanhong , Ma Jinyou , Xu Zhiyong , Eldemery Fatma , Ou Changbo , Liu Xingyou
Published: July 2022

Chemokine CCL19, together with its receptor CCR7, is one of the most important factors recruiting immune cells into target organ during virus infection. Our previous study has shown that CCL19 played a vital role in the process of T cell trafficking into bursae during bursal disease virus (IBDV) infection. In this study, we hypothesized that CCL19 could exert direct influences on IBDV replication other than recruiting immune cells. A eukaryotic expression vector of pEGFP-N1/CCL19 was successfully constructed and identified by PCR, double enzymes digestion, and sequencing. Different concentrations of pEGFP-N1/CCL19 plasmids were transfected into DF1 cells and CCL19 protein was highly expressed. Then, DF1 cells were infected with IBDV B87 strain post-transfection. Based on PCR and Western blot results, CCL19 could obviously decrease the gene levels of VP1 and VP2 and the protein levels of VP2 and VP3. When CCL19 was knocked down, the gene levels of VP1 and VP2 were significantly upregulated. Moreover, indirect immunostaining revealed that the IBDV content was largely decreased after CCL19 overexpression. Additionally, CCL19 inhibitory effects might rely on activation of the JNK signal pathway. Taken together, chemokine CCL19 directly blocks IBDV replication in DF1 cells, indicating that CCL19 could play crucial functions other than recruiting T cells during the pathogenesis of IBDV.
The Future of Synbiotics: Rational Formulation and Design
Authors: Gomez Quintero David F. , Kok Car Reen , Hutkins Robert
Published: July 2022

Synbiotics, mixtures of live microbes and substrates selectively utilized by host organisms, are of considerable interest due to their ability to improve gastrointestinal health. However, formulating synbiotics remains challenging, due in part, to the absence of rational strategies to assess these products for synbiotic activities prior to clinical trials. Currently, synbiotics are formulated as either complementary or synergistic. Complementary synbiotics are made by combining probiotics and prebiotics, with each component acting independently and with the combination shown to provide a clinical health benefit. Most commercial synbiotics as well as those used in clinical trials have been of the complementary type. In contrast, synergistic synbiotics require that the added microbe is specifically stimulated or it’s persistence or activity are enhanced by the cognate substrate. Although several innovative examples have been described in the past few years based on this principle, in practice, relatively few synbiotic studies have tested for synergism. In this review, selected recent examples of complementary and synergistic synbiotics and the rationale for their formulation will be described. In addition, pre-clinical experimental approaches for identifying combinations that provide a basis for satisfying the requirements for synergism will be discussed.
Recent advances in the study of NADC34-like porcine reproductive and respiratory syndrome virus in China
Authors: Zhao Hong-zhe , Wang Feng-xue , Han Xiao-yu , Guo Hao , Liu Chun-yu , Hou Li-na , Wang Ya-xin , Zheng Hui , Wang Lu , Wen Yong-jun
Published: July 2022

Since porcine reproductive and respiratory syndrome virus (PRRSV) was first described in China in 1996, several genetically distinct strains of PRRSV have emerged with varying pathogenicity and severity, thereby making the prevention and control of PRRS more difficult in China and worldwide. Between 2017 and 2021, the detection rate of NADC34-like strain in China increased. To date, NADC34-like strains have spread to 10 Chinese provinces and have thus developed different degrees of pathogenicity and mortality. In this review, we summarize the history of NADC34-like strains in China and clarify the prevalence, genomic characteristics, restriction fragment length polymorphisms, recombination, pathogenicity, and vaccine status of this strain in China. In so doing, this study aims to provide a basis for the further development of prevention and control measures targeting the NADC34-like strain.
Biocontrol activity and action mechanism of Paenibacillus polymyxa strain Nl4 against pear Valsa canker caused by Valsa pyri
Authors: Yuan Hongbo , Yuan Mengjia , Shi Bingke , Wang Zhuoni , Huang Tianxiang , Qin Genhong , Hou Hui , Wang Li , Tu Hongtao
Published: July 2022

Pear Valsa canker caused by Valsa pyri is among the most destructive diseases of pear, which causes significant economic loss. The present study was developed to explore the biocontrol efficiency and underlying antagonistic mechanism of Paenibacillus polymyxa strain Nl4 against V. pyri. P. polymyxa strain Nl4, one of the 120 different endophytic bacterial strains from pear branches, exhibited strong inhibitory effects against the mycelial growth of V. pyri and caused hyphal malformation. Culture filtrate derived from strain Nl4 was able to effectively suppress mycelial growth of V. pyri, and was found to exhibit strong protease, cellulase and β-1, 3-glucanase activity. Through re-isolation assay, strain Nl4 was confirmed to be capable of colonizing and surviving in pear branch. Treatment with strain NI4 effectively protected against pear Valsa canker symptoms on detached pear twigs inoculated with V. pyri. Moreover, strain Nl4 promoted enhanced plant growth probably through the solubilization of phosphorus. Comparative transcriptomic analyses revealed that strain NI4 was able to suppress V. pyri growth in large part through the regulation of the expression of membrane- and energy metabolism-related genes in this pathogen. Further transcriptomic analyses of pear trees indicated that strain NI4 inoculation was associated with changes in the expression of genes associated with secondary metabolite biosynthesis, signal transduction, and cutin, suberine, and wax biosynthesis. Together, these data highlighted P. polymyxa strain Nl4 as a promising biocontrol agent against pear Valsa canker and investigated the possible mechanisms of strain Nl4 on control of this devastating disease.
Therapeutic Mechanisms of Berberine to Improve the Intestinal Barrier Function via Modulating Gut Microbiota, TLR4/NF-κ B/MTORC Pathway and Autophagy in Cats
Authors: Cao JingWen , Chen MiaoYu , Xu Ran , Guo MengYao
Published: July 2022

Background

Inflammatory bowel disease (IBD), a disease that seriously harms human and animal health, has attracted many researchers’ attention because of its complexity and difficulty in treatment. Most research has involved rats and dogs, and very little was cats. We should know that gut microbiota varies significantly from animal to animal. Traditional Chinese Medicine and its monomer component have many advantages compared with antibiotics used in pet clinics. Numerous studies have shown berberine (berberine hydrochloride) therapeutic value for IBD. However, the specific mechanism remains to consider.

Results

We assessed gut pathology and analyzed fecal bacterial composition using Histological staining and 16S rRNA sequence. Dioctyl sodium sulfosuccinate (DSS) administration destroyed intestinal mucosal structure and changed the diversity of intestinal flora relative to control. RT-PCR and western blot confirmed specific molecular mechanisms that trigger acute inflammation and intestinal mucosal barrier function disruption after DSS treatment. And autophagy inhibition is typical pathogenesis of IBD. Interestingly, berberine ameliorates inflammation during the development of the intestinal by modulating the toll-like receptors 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and activating autophagy. Berberine significantly reduces tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β expression in cats’ serum. Enhancing the antioxidant effect of IBD cats is one of the protective mechanisms of berberine. We demonstrated that berberine repairs intestinal barrier function by activating the mammalian target of rapamycin (mTOR) complex (MTORC), which inhibits autophagy.

Conclusion

Berberine can restore intestinal microbiota homeostasis and regulate the TLR4/NF-κB pathway, thereby controlling inflammatory responses. We propose a novel mechanism of berberine therapy for IBD, namely, berberine therapy can simultaneously activate MTORC and autophagy to restore intestinal mucosal barrier function in cats, which should be further studied to shed light on berberine to IBD.
Electrochemical impedance spectroscopy applied to microbial fuel cells: A review
Authors: Wang Hui , Long Xizi , Sun Yingying , Wang Dongqi , Wang Zhe , Meng Haiyu , Jiang Chunbo , Dong Wen , Lu Nan
Published: July 2022

Electrochemical impedance spectroscopy (EIS) is an efficient and non-destructive test for analyzing the bioelectrochemical processes of microbial fuel cells (MFCs). The key factors limiting the output performance of an MFC can be identified by quantifying the contribution of its various internal parts to the total impedance. However, little attention has been paid to the measurement conditions and diagrammatic processes of the EIS for MFC. This review, starting with the analysis of admittance of bioelectrode, introduces conditions for the EIS measurement and summarizes the representative equivalent circuit plots for MFC. Despite the impedance from electron transfer and diffusion process, the effect of unnoticeable capacitance obtained from the Nyquist plot on MFCs performance is evaluated. Furthermore, given that distribution of relaxation times (DRT) is an emerging method for deconvoluting EIS data in the field of fuel cell, the application of DRT-analysis to MFC is reviewed here to get insight into bioelectrode reactions and monitor the biofilm formation. Generally, EIS measurement is expected to optimize the construction and compositions of MFCs to overcome the low power generation.
Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex
Authors: Ahmed Wesam S. , Philip Angelin M. , Biswas Kabir H.
Published: July 2022

Coronavirus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a massive health crisis across the globe, with some genetic variants gaining enhanced infectivity and competitive fitness, and thus significantly aggravating the global health concern. In this regard, the recent SARS-CoV-2 alpha, beta, and gamma variants (B.1.1.7, B.1.351, and P.1 lineages, respectively) are of great significance in that they contain several mutations that increase their transmission rates as evident from clinical reports. By the end of March 2021, these variants were accounting for about two-thirds of SARS-CoV-2 variants circulating worldwide. Specifically, the N501Y mutation in the S1 spike receptor binding domain (S1-RBD) of these variants have been reported to increase its affinity for ACE2, although the basis for this is not entirely clear yet. Here, we dissect the mechanism underlying the increased binding affinity of the N501Y mutant for ACE2 using molecular dynamics (MD) simulations of the available ACE2-S1-RBD complex structure (6M0J) and show a prolonged and stable interfacial interaction of the N501Y mutant S1-RBD with ACE2 compared to the wild type S1-RBD. Additionally, we find that the N501Y mutant S1-RBD displays altered dynamics that likely aids in its enhanced interaction with ACE2. By elucidating a mechanistic basis for the increased affinity of the N501Y mutant S1-RBD for ACE2, we believe that the results presented here will aid in developing therapeutic strategies against SARS-CoV-2 including designing of therapeutic agents targeting the ACE2-S1-RBD interaction.
Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway
Authors: Zhang Qin , Yan Liming , Lu Jingwen , Zhou Xiaoming
Published: July 2022

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder manifested as chronic airway inflammation and persistent airflow limitation with the essential mechanism as inflammatory response and oxidative stress induced by toxic exposures such as cigarette smoke (CS). Glycyl-L-histidyl-L-lysine (GHK) is a nontoxic tripeptide involved in the process of healing and regeneration as a natural product. With the combination of Cu(II), glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) improves antioxidative and anti-inflammatory bioavailability, and they might offer potential therapeutic properties for COPD. Thus, the present study aimed to identify the potential effects of GHK-Cu on emphysema induced by cigarette smoke.

Methods: In the in vivo experiment, C57BL/6J mice were exposed to CS for 12 weeks to induce pulmonary emphysema. GHK-Cu was injected intraperitoneally at doses of 0.2, 2 and 20 μg/g/day in 100 µl of saline on alternative days from the 1st day after CS exposure. The effects of GHK-Cu on the morphology of CS-induced emphysema, the inflammatory response and oxidative stress were evaluated. The antioxidative effect of GHK-Cu on human alveolar epithelial A549 cells was assessed in vitro.

Results: GHK-Cu treatment attenuated the CS-induced emphysematous changes and partially reversed the matrix metalloprotein -9 (MMP-9)/tissue inhibitor of metalloproteinases-1 (TIMP-1) imbalance in the lung tissue. GHK-Cu reduced the inflammation and oxidation by decreasing the expression of inflammatory cytokines (IL-1β and TNF-α) in the bronchoalveolar lavage and the enzymatic activity of MPO and MDA in the lung homogenate while restoring the T-AOC and GSH content. Furthermore, administration of GHK-Cu reversed the increase in NF-κB expression induced by CS and increased the Nrf2 level, as an antioxidant defense component, in mice with chronic CS exposure. In CSE-exposed human alveolar epithelial A549 cells, GHK-Cu also inhibited oxidative stress by suppressing MDA levels and restoring T-AOC and GSH levels, which were modulated by upregulating Nrf2 expression.

Conclusion: GHK-Cu treatment attenuated CS-induced emphysema by anti-inflammation by downregulating NF-κB and antioxidation via upregulation of the Nrf2/Keap1 in lung tissues.
Hydrogen Sulfide Inhibits Ferroptosis in Cardiomyocytes to Protect Cardiac Function in Aging Rats
Authors: Liang Zihui , Miao Yuxin , Teng Xu , Xiao Lin , Guo Qi , Xue Hongmei , Tian Danyang , Jin Sheng , Wu Yuming
Published: July 2022

Aging contributes significantly to cardiovascular diseases and cardiac dysfunction. To explore the reasons for the decline in cardiac function in the elderly, we collected clinical data and blood samples from 231 individuals. Our results indicated that aging was accompanied by a decline in cardiac function and remodeling of the left ventricle, and cardiac function was negatively correlated with age. Serum hydrogen sulfide (H2S) decreased, while serum malondialdehyde (MDA) and iron increased with aging in healthy individuals. A rat model of aging and iron overload was constructed for in vivo research. In the animal model, we found that the expression of endogenous H2S-producing enzymes decreased, and endogenous H2S levels decreased, while oxidative stress levels rose. The regulation of iron metabolism and the maintenance of iron homeostasis declined. The accumulation of MDA and iron led to ferroptotic cell death and subsequent myocardial injury and deterioration. A high-iron diet accelerated the aging process and death in rats. The decline of cardiac function in aging rats and iron-overload rats may be caused by cardiomyocyte ferroptosis. Exogenous H2S enhanced the expression of endogenous H2S synthase, promoted endogenous H2S production, regulated iron metabolism, and reduced oxidative stress levels. The protective effects of H2S on cardiac function in aging rats and iron-overload rats may be partly due to the inhibition of cardiomyocyte ferroptosis. We demonstrated that cardiac dysfunction associated with aging was closely related to decreased endogenous H2S levels and cardiomyocyte ferroptosis. H2S-regulated iron metabolism reduced oxidative stress levels in cardiomyocytes, inhibited cardiomyocyte ferroptosis, and protected cardiac function in aging rats.