bluuebunny/crossref_metadata_2025 huggingface dataset:
HUMAN CAPITAL EFFICIENCY AND FIRM VALUE USING PANEL REGRESSION
Authors:   Chukwuemeka Odumegwu Ojukwu University, Anambra State, Nigeria., PETERS Dr. EMEKA, OBIORA , FRANKLINE C.S.A Dr. OKEKE, ,   Department of Accountancy Alex Ekwueme Federal University Ndufu-Alike, Ikwo Ebonyi State Nigeria, IFEOMA GLORIA Dr. DURUZOR, ,   epartment of Accountancy Alex Ekwueme Federal University Ndufu-Alike, Ikwo Ebonyi State Nigeria., LINUS Dr. ADAMA. A. ,   Department of Business Administration Alex Ekwueme Federal University Ndufu-Alike, Ikwo Ebonyi State Nigeria.
Published: June 2022

This study evaluated human capital efficiency and firm value of quoted Non-financial firms in Nigeria. Its core objective is to evaluate the effect human capital efficiency has on firm values. The study employed secondary data and panel regression models which were subjected to descriptive Statistics, Correlation Matrix, and Hausman test for interpretations. Data was collected from (76) quoted Non-financial firms from the year (2011-2020). The study was anchored in Resource-based theory. Findings hold that there is a negative influence of capital employed efficiency as it has positive but not significant influence, firm size (FISZ) has negative and significant influence and firm age (FIRA) has positive and non-significant influence on firm value of non-financial firms in Nigeria. Concluding, only human capital employed efficiency and firm age influenced firm value positively and thus the study recommends that the human capital component of intellectual capital should be trained and educated regularly to build capacity. Firms’ specific growth and sustainability policy should be strongly placed using corporate governance code and other enhanced internal innovative processes to ensure that their existence is not affected by age.
Injectable, Adhesive, and Self-Healing Composite Hydrogels Loaded With Oxybutynin Hydrochloride for the Treatment of Overactive Bladder in Rats
Authors: Sun Peng , Wang Zheng , Wu Tong , Zuo Shishuai , Huang Xiaoyu , Cui Zilian , Zhang Dong
Published: June 2022

Object: The aim of this study was to prepare injectable, adhesive, and self-healing composite hydrogels loaded with oxybutynin hydrochloride and verify its function in the treatment of overactive bladder.

Method: The ultraviolet (UV) absorption of oxybutynin (Oxy) in the solution was detected using a UV spectrophotometer at 233 nm, and the cumulative drug release was calculated using Origin software. L929 mouse fibroblasts were used to test cell adhesion to OCP50 and OCP100 hydrogels. Both FT-IR and NMR overactive bladder demonstrated that Dex was oxidized to PDA with aldehyde groups. Urodynamic examinations were performed 24 h after intraperitoneal injection in the rat model. The relative expression levels of Orai1 and STIM1 were detected by western blot (WB) and QPCR.

Results: After loading Oxy, the shear adhesion under the wet conditions of OCP50 and OCP100 was higher than CP50 and CP100 (p < 0.05), and both were suitable for intravaginal administration. After 72 h of release, oxybutynin released 82.8% in OCP100 hydrogel and 70% in OCP50. Compared to the model, OCP50, CP100, and OCP100 relieved the overactive bladder and inhibited the expression of Orail and STIM1.

Conclusions: Oxybutynin hydrogel could provide relief to overactive bladder by decreasing the expression of Orail and STIM1 in rats.
Does the Heel’s Dissipative Energetic Behavior Affect Its Thermodynamic Responses During Walking?
Authors: Papachatzis Nikolaos , Slivka Dustin R. , Pipinos Iraklis I. , Schmid Kendra K. , Takahashi Kota Z.
Published: June 2022

Most of the terrestrial legged locomotion gaits, like human walking, necessitate energy dissipation upon ground collision. In humans, the heel mostly performs net-negative work during collisions, and it is currently unclear how it dissipates that energy. Based on the laws of thermodynamics, one possibility is that the net-negative collision work may be dissipated as heat. If supported, such a finding would inform the thermoregulation capacity of human feet, which may have implications for understanding foot complications and tissue damage. Here, we examined the correlation between energy dissipation and thermal responses by experimentally increasing the heel’s collisional forces. Twenty healthy young adults walked overground on force plates and for 10 min on a treadmill (both at 1.25 ms−1) while wearing a vest with three different levels of added mass (+0%, +15%, & +30% of their body mass). We estimated the heel’s work using a unified deformable segment analysis during overground walking. We measured the heel’s temperature immediately before and after each treadmill trial. We hypothesized that the heel’s temperature and net-negative work would increase when walking with added mass, and the temperature change is correlated with the increased net-negative work. We found that walking with +30% added mass significantly increased the heel’s temperature change by 0.72 ± 1.91 ℃ (p = 0.009) and the magnitude of net-negative work (extrapolated to 10 min of walking) by 326.94 ± 379.92 J (p = 0.005). However, we found no correlation between the heel’s net-negative work and temperature changes (p = 0.277). While this result refuted our second hypothesis, our findings likely demonstrate the heel’s dynamic thermoregulatory capacity. If all the negative work were dissipated as heat, we would expect excessive skin temperature elevation during prolonged walking, which may cause skin complications. Therefore, our results likely indicate that various heat dissipation mechanisms control the heel’s thermodynamic responses, which may protect the health and integrity of the surrounding tissue. Also, our results indicate that additional mechanical factors, besides energy dissipation, explain the heel’s temperature rise. Therefore, future experiments may explore alternative factors affecting thermodynamic responses, including mechanical (e.g., sound & shear-stress) and physiological mechanisms (e.g., sweating, local metabolic rate, & blood flow).
Parental High-Fat High-Sugar Diet Intake Programming Inflammatory and Oxidative Parameters of Reproductive Health in Male Offspring
Authors: Sertorio Marcela Nascimento , César Helena , de Souza Esther Alves , Mennitti Laís Vales , Santamarina Aline Boveto , De Souza Mesquita Leonardo Mendes , Jucá Andréa , Casagrande Breno Picin , Estadella Debora , Aguiar Odair , Pisani Luciana Pellegrini
Published: June 2022

Parental nutrition can impact the health of future generations, programming the offspring for the development of diseases. The developing germ cells of the offspring could be damaged by the maternal or the paternal environment. The germ cells in development and their function could be affected by nutritional adversity and therefore, harm the health of subsequent generations. The paternal or maternal intake of high-fat diets has been shown to affect the reproductive health of male offspring, leading to imbalance in hypothalamic-pituitary-gonadal axis, testicular oxidative stress, low testosterone production, and changes in sperm count, viability, motility, and morphology. There is a need for studies that address the combined effects of diets with a high-fat and high-sugar (H) content by both progenitors on male reproduction. In this context, our study evaluated epigenetic parameters and the inflammatory response that could be associated to oxidative stress in testis and epididymis of adult offspring. 90 days-old male rats were divided according to the combination of the parental diet: CD (control paternal and maternal diet), HP (H paternal diet and control maternal diet), HM (H maternal diet and control paternal diet) and HPM (H paternal and maternal diet).We evaluated serum levels of testosterone and FSH; testicular gene expression of steroidogenic enzymes Star and Hsd17b3 and epigenetic markers Dnmt1, Dnmt3a, Dnmt3b, and Mecp2; testicular and epididymal levels of TNF-α, IL-6, IL-10, and IL-1β; testicular and epididymal activity of SOD, CAT, and GST; the oxidative markers MDA and CP; the daily sperm production, sperm transit time, and sperm morphology. Testicular epigenetic parameter, inflammatory response, oxidative balance, and daily sperm production of the offspring were affected by the maternal diet; paternal diet influenced serum testosterone levels, and lower daily sperm production was exacerbated by the interaction effect of both parental intake of high-fat high-sugar diet in the testis. There was isolated maternal and paternal effect in the antioxidant enzyme activity in the cauda epididymis, and an interaction effect of both parents in protein oxidative marker. Maternal effect could also be observed in cytokine production of cauda epididymis, and no morphological effects were observed in the sperm. The potential programming effects of isolated or combined intake of a high-fat high-sugar diet by the progenitors could be observed at a molecular level in the reproductive health of male offspring in early adulthood.
Low Temperature Aluminothermic Reduction of Natural Sepiolite to High-Performance Si Nanofibers for Li-Ion Batteries
Authors: Zhao Mingyuan , Yang Shaobin , Dong Wei
Published: June 2022

Nanostructure silicon is one of the most promising anode materials for the next-generation lithium-ion battery, but the complicated synthesis process and high cost limit its large-scale commercial application. Herein, a simple and low-cost method was proposed to prepare silicon nanofibers (SNF) using natural sepiolite as a template via a low-temperature aluminum reduction process. The low temperature of 260°C during the reduction process not only reduced the production cost but also avoided the destruction of the natural sepiolite structure caused by the high temperature above 600°C in the traditional magnesium thermal reduction process, leading to a more complete nanofiber structure in the final product. For the first time, the important role of Mg-O octahedral structure in the maintenance of nanofiber structure during the process of low-temperature aluminothermic reduction was verified by experiments. When used as an anode for lithium-ion batteries, SNF yield a high reversible capacity of 2005.4 mAh g−1 at 0.5 A g−1 after 50 cycles and 1017.6 mAh g−1 at 2 A g−1 after 200 cycles, remarkably outperforming commercial Si material. With a low-cost precursor and facile approach, this work provides a new strategy for the synthesis of a commercial high-capacity Si anode.
Pyrrolopyrrole-Based Aza-BODIPY Small Molecules for Organic Field-Effect Transistors
Authors: Zhang Daohai , Liang Dongxu , Gu Liang , Zhang Haichang
Published: June 2022

Diketopyrrolopyrrole (DPP), due to its good planarity, π-conjugate structure, thermal stability, and structural modifiability, has received much attention from the scientific community as an excellent semiconductor material for its applications in the field of optoelectronics, such as organic solar cells, organic photovoltaics, and organic field effect transistors. In this study, a new small molecule, pyrrolopyrrole aza-BODIPY (PPAB), based on the thiophene-substituted DPP structure was developed using the Schiff-base formation reaction of DPP and heteroaromatic amines. Absorption spectroscopy, electrochemistry, X-ray diffraction, molecular theoretical simulation calculation were performed, and organic field-effect transistor properties based on PPAB were investigated. It was found that PPAB exhibits a broad absorption range in the visible and near-infrared regions, which is attributed to its long-range conjugate structure. In addition, it is worth noting that PPAB has multiple F atoms resulting in the low LUMO level, which is conducive to the injection and transportation of charge carriers between the semiconductor layer and the electrode. Meanwhile, its hole carrier mobility is up to 1.3 × 10−3 cm2 V−1 s−1 due to its large conjugate structure, good intramolecular charge transfer effect, and high degree of coplanarity. In this study, a new chromophore with electron-deficient ability for designing high-performance semiconductors was successfully synthesized.
Effects of Exosomes Derived From Helicobacter pylori Outer Membrane Vesicle-Infected Hepatocytes on Hepatic Stellate Cell Activation and Liver Fibrosis Induction
Authors: Zahmatkesh Masoumeh Ebadi , Jahanbakhsh Mariyeh , Hoseini Negin , Shegefti Saina , Peymani Amir , Dabin Hossein , Samimi Rasoul , Bolori Shahin
Published: June 2022

Liver fibrosis is a multifactorial disease with microbial and non-microbial causes. In recent years, Helicobacter pylori infection has been thought to play a critical role in some extra-gastrointestinal manifestations especially liver disorders. Outer membrane vesicles (OMVs) are one of the most important discussed H. pylori virulence factors. In the current study, four different clinical strains of H. pylori were collected and their OMVs were purified using ultra-centrifugation. To investigate their effects on liver cell exosomes, co-incubation with hepatocytes was applied. After a while, hepatocyte-derived exosomes were extracted and incubated with hepatic stellate cells (HSCs) to investigate the HSC activation and fibrosis marker induction. The expression of α-SMA, TIMP-1, β-catenin, vimentin, and e-cadherin messenger RNAs (mRNA) was assessed using real-time RT-PCR, and the protein expression of α-SMA, TIMP-1, β-catenin, vimentin, and e-cadherin was evaluated by Western blotting. Our results showed that infected hepatocyte-derived exosomes induced the expression of α-SMA, TIMP-1, β-catenin, and vimentin in HSCs and e-cadherin gene and protein expression was downregulated. In the current study, we found that H. pylori-derived OMVs may aid the exosome alternation and modified exosomes may have a possible role in HSC activation and liver fibrosis progression.
Development and Use of a Monoclonal Antibody Specific for the Candida albicans Cell-Surface Protein Hwp1
Authors: Oh Soon-Hwan , Martin-Yken Hélène , Coleman David A. , Dague Etienne , Hoyer Lois L.
Published: June 2022

The Candida albicans cell-surface protein Hwp1 functions in adhesion to the host and in biofilm formation. A peptide from the Gln-Pro-rich adhesive domain of Hwp1 was used to raise monoclonal antibody (MAb) 2-E8. MAb 2-E8 specificity for Hwp1 was demonstrated using a hwp1/hwp1 C. albicans isolate and strains that expressed at least one HWP1 allele. Immunofluorescence and atomic force microscopy experiments using MAb 2-E8 confirmed C. albicans germ-tube-specific detection of the Hwp1 protein. MAb 2-E8 also immunolabeled the tips of some Candida dubliniensis germ tubes grown under conditions that maximized HWP1 expression. The phylogeny of HWP1 and closely related genes suggested that the Gln-Pro-rich adhesive domain was unique to C. albicans and C. dubliniensis focusing the utility of MAb 2-E8 on these species. This new reagent can be used to address unanswered questions about Hwp1 and its interactions with other proteins in the context of C. albicans biology and pathogenesis.
Patients With Multiple Myeloma Have a Disbalanced Whole Blood Thrombin Generation Profile
Authors: Li Li , Roest Mark , Sang Yaqiu , Remijn Jasper A. , Fijnheer Rob , Smit Karel , Huskens Dana , Wan Jun , de Laat Bas , Konings Joke
Published: June 2022

Background

Multiple myeloma (MM) is associated with a high prevalence of bleeding and an increased risk of thrombo-embolism. MM patients have reduced platelet- and red blood cell (RBC) numbers in blood, which may indicate that the paradoxical hemostasis profile is a consequence of a disturbed platelet and RBC homeostasis.

Objectives

To get better insight in the disbalanced hemostasis of MM patients.

Methods

We conducted a case-control study on the whole blood (WB) coagulation profiles of 21 MM patients and 21 controls. We measured thrombin generation (TG) in WB and platelet poor plasma (PPP) of MM patients and controls.

Results

In WB-TG, we observed that the median time to the thrombin Peak was 52% longer in MM patients than in controls, while the median endogenous thrombin potential until the Peak (ETPp) was 39% higher in MM-patients than in controls. In line with these findings, the levels of platelets, RBCs, white blood cells and agonist induced platelet activation were decreased in MM patients compared to controls. The plasma TG experiments showed no differences between MM-patients and controls.

Conclusion

Patients with MM have a disturbed blood cell metabolism and a disbalanced WB-TG profile. This disbalance may explain the paradoxically high prevalence of bleeding symptoms in MM patients vs. an increased thrombosis risk. There was no disturbance observed in plasma TG, indicating that blood cells are the major determinants for the disbalanced hemostasis in MM patients.
Investigating the Impact of Globalization on Environmental Degradation in Kazakhstan
Authors: Primbetova Madina , Sharipov Kongratbay , Allayarov Piratdin , Haq Ihtisham ul
Published: June 2022

As a consequence of globalization, the world’s economies are merging; nonetheless, concerns about how globalization trends may harm the environment locally and worldwide are growing. The globalization-environment nexus has now become a contentious issue among policymakers. As a result, several empirical research studies on the globalization-environment nexus have been conducted. In the context of the environmental Kuznets curve theory, this study explores the influence of globalization on environmental deterioration in Kazakhstan (EKC). Furthermore, energy is a control variable in this research. Unit roots and structural break are used to solve the issue of non-stationarity in time series. The autoregressive distributed lagged (ARDL) model is used in this research for long run relationships between variables as well as to estimate long run and short run coefficients. Income, energy, and globalization are discovered to have a long-term link. Furthermore, the findings revealed that long-term environmental deterioration was exacerbated by economic, political, and social globalization, since these factors were shown to have a positive impact on carbon emissions in Kazakhstan. Energy is to blame for environmental damage both in the short and long term. Furthermore, this research reveals that the EKC theory exists in Kazakhstan. On the basis of the findings, policy suggestions are made.
Adsorption of Methyl Orange and Cr (VI) Onto Poultry Manure-Derived Biochar From Aqueous Solution
Authors: Ghani Usman , Jiang Wenjia , Hina Kiran , Idrees Atif , Iqbal Meenal , Ibrahim Muhammad , Saeed Rashid , Irshad M. Kashif , Aslam Imran
Published: June 2022

In recent years, heavy metals and other organic compound pollution has increased and become a considerable global problem due to its direct impacts on the aquatic ecosystem. This study is aimed to see how efficient the poultry manure-derived biochar is in removing chromium (VI) and methyl orange simultaneously from the aqueous solutions through adsorption. Chromium present in the form of reactive ions such as HCrO4− and Cr2O72− at pH 2–6 values and in stable form, CrO4− at alkaline pH. In this study, biochar was synthesized by the slow pyrolysis of feedstock in a muffle furnace at 550°C temperature with 2 mm particle size. This study provided the biochar with SBET 16.0921 m2/g rough stomata-like pores with a volume of 0.0074 cm³/g, pore diameter 1.84 nm, aromatic groups, and structural diversity. A batch adsorption experiment was conducted to investigate the adsorption efficiency, and mechanism was elucidated by fitting isotherm and kinetic models and result analysis along with the thermodynamics. From the linear Langmuir fit results the maximum adsorption capacity (qmax) of biochar reached up to 20.8 and 19.09 mg g−1 for MO and Cr, respectively. Different operational factors like reaction time, pollutant initial concentration, effect of temperature, and sorbent material dose were studied at pH 4 and initial concentration of 100 mg/L using 2 g of the adsorbent dose. The linear Langmuir well fitted with the experimental data having R2 value of 0.99 and 0.99 for MO and Cr, respectively. From the obtained results, the highest adsorption efficiency reached 88.80% and 90.231% for MO and Cr, respectively.From kinetics study, non-linear pseudo–second-order (PSO) model are highly fitted with the obtained data with R2 of 0.97 and 0.974 for MO and Cr, respectively. The result analysis revealed that HCrO4− and Cr2O72− ions compete with the SO3− to attach on the surface of the sorbent which leads to competitive adsorption of Cr (VI) and MO onto BC. Thermodynamic study presents that the change in Gibbs free energy ΔG° is negative, indicates that the whole process was favorable and completed. The adsorption process was monolayer physisorption, irreversible, and endothermic. Hence, it can be said that this material is environmental friendly and an economical sorbent for high adsorption efficiency.
Spring Freeze–Thaw Stimulates Greenhouse Gas Emissions From Agricultural Soil
Authors: Badewa Emmanuel A. , Yeung Chun C. , Rezanezhad Fereidoun , Whalen Joann K. , Oelbermann Maren
Published: June 2022

In temperate cold regions, the gradual resurgence of soil microbial activity during spring freeze-thaw events is frequently associated with greenhouse gas emissions. Enhanced greenhouse gas fluxes during spring freeze-thaw are related to the mineralization of bioavailable substrates, which may be elevated when soil is amended with organic residues (e.g., biobased residues such as compost, digestate, biosolids). The objective of this study was to determine the impact of biobased residues, compared to urea fertilizer, on greenhouse gas emissions during spring freeze-thaw events. The field treatments included urea (170 kg N ha−1 y−1), composted food waste (240 kg N ha−1 y−1), hydrolyzed biosolids (215 kg N ha−1 y−1), and anaerobic digestate (231 kg N ha−1 y−1). Headspace gases were sampled from a closed static chamber in each replicate plot (n = 4) and categorized with three transient spring freeze-thaw phases (waterlogged, wet, and dry). Among the treatments, nitrous oxide (N2O) flux was significantly different (p < 0.05) where compost had the highest emission and digestate lowest while carbon dioxide (CO2) and methane (CH4) fluxes were not significantly different (p > 0.05). The greenhouse gas fluxes were significantly different among the freeze-thaw events (p < 0.05) likely due to intense microbial activity and anaerobic conditions. The CO2 and CH4 emissions were related to N2O emission (p < 0.05), and soil temperature strongly correlated with CO2 fluxes. This suggested that soil warming driven by ambient conditions as well as the type and quantity of carbon input influenced soil microbial activity, leading to greenhouse gases production. Therefore, soil amended with biobased residues may either increase or reduce greenhouse gas fluxes during spring freeze-thaw events depending on the source and production method of the organic material.
Suboptimal Embryonic Incubation Temperature Has Long-Term, Sex-Specific Consequences on Beak Coloration and the Behavioral Stress Response in Zebra Finches
Authors: Choi Madeline P. , Rubin Alexander M. , Wada Haruka
Published: June 2022

Secondary sex characteristics, like beak color in some avian species, have indirect impacts on reproductive success, as they are considered to be honest indicators of condition, immunocompetence, and developmental history. However, little is known about the long-term effects of environmental perturbations on the production and maintenance of these secondary sex characteristics in avian species. In zebra finches (Taeniopygia guttata), redder beaks indicate increased carotenoid expression and implantation into beak tissue, and female zebra finches prefer males with pronounced bright red beaks as a mate. The present study examines the long-term effects of embryonic incubation temperature on the maturation of beak color in zebra finches. We also investigated the effects of embryonic incubation temperature on sensitivity to a handling and restraint stressor in adulthood. Specifically, the aims of this study were to examine: (1) whether suboptimal incubation temperatures affect the timing of beak color development and color characteristics before and after sexual maturity, (2) if repeated handling causes short-term changes in beak color and whether color changes are related to embryonic thermal environment, and (3) how thermal stress during incubation alters future responses to a repeated handling stressor. Zebra finch eggs were randomly assigned to one of three incubators: “Control,” “Low,” or “Periodic Cooling.” Beak color (hue, saturation, and value) was quantified before [45, 60, 75 days post-hatch (dph)] and after sexual maturity (95 dph), as well as after repeated handling stress later in adulthood (avg of 386 dph). We found that there were age- and sex- specific effects of incubation treatment on beak hue, where females from periodically cooled eggs had decreased hues (redder) in adulthood. Additionally, eggs laid later in a clutch had decreased beak saturation levels throughout life regardless of incubation environment. We found that females had lower beak hue and saturation following a capture and restraint stressor, while males showed increased beak saturation. Lastly, males subjected to the Low incubation treatment had relatively higher activity levels during restraint than those in the Control group. Overall, these findings suggest that fluctuating incubation temperatures combined with repeated, short-term stressors can have significant, sex-specific effects on sexual ornamentation and behavior.
IFNAR1 Deficiency Impairs Immunostimulatory Properties of Neutrophils in Tumor-Draining Lymph Nodes
Authors: Hussain Timon , Domnich Maksim , Bordbari Sharareh , Pylaeva Ekaterina , Siakaeva Elena , Spyra Ilona , Ozel Irem , Droege Freya , Squire Anthony , Lienenklaus Stefan , Sutter Kathrin , Hasenberg Anja , Gunzer Matthias , Lang Stephan , Jablonska Jadwiga
Published: June 2022

Tumor-draining lymph nodes (TDLNs) are the first organs where the metastatic spread of different types of cancer, including head and neck cancer (HNC), occurs and have therefore high prognostic relevance. Moreover, first anti-cancer immune responses have been shown to be initiated in such LNs via tumor-educated myeloid cells. Among myeloid cells present in TDLNs, neutrophils represent a valuable population and considerably participate in the activation of effector lymphocytes there. Tumor-supportive or tumor-inhibiting activity of neutrophils strongly depends on the surrounding microenvironment. Thus, type I interferon (IFN) availability has been shown to prime anti-tumor activity of these cells. In accordance, mice deficient in type I IFNs show elevated tumor growth and metastatic spread, accompanied by the pro-tumoral neutrophil bias. To reveal the mechanism responsible for this phenomenon, we have studied here the influence of defective type I IFN signaling on the immunoregulatory activity of neutrophils in TDLNs. Live imaging of such LNs was performed using two-photon microscopy in a transplantable murine HNC model. CatchupIVM-red and Ifnar1-/- (type I IFN receptor- deficient) CatchupIVM-red mice were used to visualize neutrophils and to assess their interaction with T-cells in vivo. We have evaluated spatiotemporal patterns of neutrophil/T-cell interactions in LNs in the context of type I interferon receptor (IFNAR1) availability in tumor-free and tumor-bearing animals. Moreover, phenotypic and functional analyses were performed to further characterize the mechanisms regulating neutrophil immunoregulatory capacity. We demonstrated that inactive IFNAR1 leads to elevated accumulation of neutrophils in TDLNs. However, these neutrophils show significantly impaired capacity to interact with and to stimulate T-cells. As a result, a significant reduction of contacts between neutrophils and T lymphocytes is observed, with further impairment of T-cell proliferation and activation. This possibly contributes to the enhanced tumor growth in Ifnar1-/- mice. In agreement with this, IFNAR1-independent activation of downstream IFN signaling using IFN-λ improved the immunostimulatory capacity of neutrophils in TDLNs and contributed to the suppression of tumor growth. Our results suggest that functional type I IFN signaling is essential for neutrophil immunostimulatory capacity and that stimulation of this signaling may provide a therapeutic opportunity in head and neck cancer patients.
Lnc90386 Sponges miR-33-5p to Mediate Mycoplasma gallisepticum-Induced Inflammation and Apoptosis in Chickens via the JNK Pathway
Authors: Sun Yingfei , Wang Yingjie , Zou Mengyun , Wang Tengfei , Wang Lulu , Peng Xiuli
Published: June 2022

Mycoplasma gallisepticum(MG) is one of the most important pathogens, that causes chronic respiratory disease (CRD) in chickens. Long non-coding RNAs (lncRNAs) are emerging as new regulators for many diseases and some lncRNAs can function as competing endogenous RNAs (ceRNAs) to regulate mRNAs by competitively binding to miRNAs. Here, we found that miR-33-5p was significantly up-regulated both in MG-infected chicken embryonic lungs and chicken embryo fibroblast cells (DF-1), and Lnc90386 negatively correlated with miR-33-5p. miR-33-5p, as a new regulator for MG infection, repressed apoptosis, inflammatory factors in DF-1 cells by targeting JNK1. Further analyses showed that Lnc90386 sponged miR-33-5p to weaken its inhibitory effect on JNK1, forming the ceRNA regulatory network. Furthermore, knockdown of Lnc90386 significantly inhibited apoptosis and inflammatory factors, and promoted DF-1 cells proliferation. However, co-treatment with miR-33-5p inhibitor and Lnc90386 siRNA showed that knockdown of Lnc90386 could partially eliminate the inhibiting effect of miR-33-5p inhibitor on inflammation, cell apoptosis and proliferation. In conclusion, Lnc90386 sponges miR-33-5p to defend against MG infection by inhibiting the JNK signaling pathway.
Heterogeneity and Function of Kupffer Cells in Liver Injury
Authors: Li Weiyang , Chang Na , Li Liying
Published: June 2022

Kupffer cells (KCs) are key regulators of liver immunity composing the principal part of hepatic macrophages even body tissue macrophages. They reside in liver sinusoids towards portal vein. The micro-environment shapes KCs unique immunosuppressive features and functions. KCs express specific surface markers that distinguish from other liver macrophages. By engulfing gut-derived foreign products and apoptotic cells without triggering excessive inflammation, KCs maintain homeostasis of liver and body. Heterogeneity of KCs has been identified in different studies. In terms of the origin, adult KCs are derived from progenitors of both embryo and adult bone marrow. Embryo-derived KCs compose the majority of KCs in healthy and maintain by self-renewal. Bone marrow monocytes replenish massively when embryo-derived KC proliferation are impaired. The phenotype of KCs is also beyond the traditional dogma of M1-M2. Functionally, KCs play central roles in pathogenesis of acute and chronic liver injury. They contribute to each pathological stage of liver disease. By initiating inflammation, regulating fibrosis, cirrhosis and tumor cell proliferation, KCs contribute to the resolution of liver injury and restoration of tissue architecture. The underlying mechanism varied by damage factors and pathology. Understanding the characteristics and functions of KCs may provide opportunities for the therapy of liver injury. Herein, we attempt to afford insights on heterogeneity and functions of KCs in liver injury using the existing findings.
Gut Microbiota, Leaky Gut, and Autoimmune Diseases
Authors: Christovich Anna , Luo Xin M.
Published: June 2022

With the rising prevalence of autoimmune diseases, the role of the environment, specifically the gut microbiota, in disease development has grown to be a major area of study. Recent advances show a relationship and possible cause and effect between the gut microbiota and the initiation or exacerbation of autoimmune diseases. Furthermore, microbial dysbiosis and leaky gut are frequent phenomena in both human autoimmune diseases and the murine autoimmunity models. This review will focus on literature in recent years concerning the gut microbiota and leaky gut in relation to the autoimmune diseases, including systemic lupus erythematosus, type 1 diabetes, and multiple sclerosis.
Vulnerable, but Still Poorly Known, Marine Ecosystems: How to Make Distribution Models More Relevant and Impactful for Conservation and Management of VMEs?
Authors: Gros Charley , Jansen Jan , Dunstan Piers K. , Welsford Dirk C. , Hill Nicole A.
Published: June 2022

Human activity puts our oceans under multiple stresses, whose impacts are already significantly affecting biodiversity and physicochemical properties. Consequently, there is an increased international focus on the conservation and sustainable use of oceans, including the protection of fragile benthic biodiversity hotspots in the deep sea, identified as vulnerable marine ecosystems (VMEs). International VME risk assessment and conservation efforts are hampered because we largely do not know where VMEs are located. VME distribution modelling has increasingly been recommended to extend our knowledge beyond sparse observations. Nevertheless, the adoption of VME distribution models in spatial management planning and conservation remains limited. This work critically reviews VME distribution modelling studies, and recommends promising avenues to make VME models more relevant and impactful for policy and management decision making. First, there is an important interplay between the type of VME data used to build models and how the generated maps can be used in making management decisions, which is often ignored by model-builders. Overall, there is a need for more precise VME data for production of reliable models. We provide specific guidelines for seven common applications of VME distribution modelling to improve the matching between the modelling and the user need. Second, the current criteria to identify VME often rely on subjective thresholds, which limits the transparency, transferability and effective applicability of distribution models in protection measures. We encourage scientists towards founding their models on: (i) specific and quantitative definitions of what constitute a VME, (ii) site conservation value assessment in relation to VME multi-taxon spatial predictions, and (iii) explicitly mapping vulnerability. Along with the recent increase in both deep-sea biological and environmental data quality and quantity, these modelling recommendations can lead towards more cohesive summaries of VME’s spatial distributions and their relative vulnerability, which should facilitate a more effective protection of these ecosystems, as has been mandated by numerous international agreements.
Impacts of Human Activities and Environmental Changes on Spatial-Seasonal Variations of Metals in Surface Sediments of Zhanjiang Bay, China
Authors: Zhou Fengxia , Xiong Mengqi , Wang Shuangling , Tian Sheng , Jin Guangzhe , Chen Fajin , Chen Chunqing , Lu Xuan , Zhu Qingmei , Meng Yafei
Published: June 2022

This study investigated the total concentrations and geochemical compositions of metals (Cd, Cr, Cu, Ni, Pb, Zn, Fe and Mn) in surface sediments of Zhanjiang Bay (ZJB) in spring and summer, to assess the contamination status, mobility and influencing factors of spatial-seasonal changes of these metals. The average total concentration for each studied metal in the surface sediments of ZJB was 0.173 μg/g for Cd, 58.25 μg/g for Cr, 17.11 μg/g for Cu, 16.89 μg/g for Ni, 28.70 μg/g for Pb, 67.91 μg/g for Zn, 30.18 mg/g for Fe, and 275.5 μg/g for Mn during the investigation period. Generally higher total concentrations of metals were found in the channel and coastal sediments of ZJB compared with those in the central ZJB, which may be probably resulted by the input of Suixi river, domestic sewage and industrial wastewater. The grain size compositions and TOC contents also had influences on the distributions of metals in ZJB. In the channel, total metals and reducible and bioavailable fractions of metals generally showed decreased concentrations in summer compared with those in spring, suggesting the release of metals from sediments. Organic matter degradation and Fe and Mn (hydr)oxides reduction processes may contribute much to this phenomenon. Relatively high proportions of Cd and Zn (average of 21.7% and 14.6%, respectively) were associated with the acid soluble fraction, indicating their high risk to the environment. The combined assessment results of enrichment factor, contaminated factor and the percentages of acid soluble fraction indicated that Cd and Zn in the surface sediments of ZJB were generally contaminated and they had medium to high risk to the environment. The average values of pollution load index in the channel, coastal and central ZJB were 1.28, 0.93 and 0.81, respectively, indicating the deterioration of surface sediments in the channel of ZJB. More attention should be paid on the metals in surface sediments of the channel of ZJB.
Developing a New qFIBS Model Assessing Histological Features in Pediatric Patients With Non-alcoholic Steatohepatitis
Authors: Liu Feng , Wei Lai , Leow Wei Qiang , Liu Shu-Hong , Ren Ya-Yun , Wang Xiao-Xiao , Li Xiao-He , Rao Hui-Ying , Huang Rui , Wu Nan , Wee Aileen , Zhao Jing-Min
Published: June 2022

Background

The evolution of pediatric non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is associated with unique histological features. Pathological evaluation of liver specimen is often hindered by observer variability and diagnostic consensus is not always attainable. We investigated whether the qFIBS technique derived from adult NASH could be applied to pediatric NASH.

Materials and Methods

102 pediatric patients (<18 years old) with liver biopsy-proven NASH were included. The liver biopsies were serially sectioned for hematoxylin-eosin and Masson trichrome staining for histological scoring, and for second harmonic generation (SHG) imaging. qFIBS-automated measure of fibrosis, inflammation, hepatocyte ballooning, and steatosis was estabilshed by using the NASH CRN scoring system as the reference standard.

Results

qFIBS showed the best correlation with steatosis (r = 0.84, P < 0.001); with ability to distinguish different grades of steatosis (AUROCs 0.90 and 0.98, sensitivity 0.71 and 0.93, and specificity 0.90 and 0.90). qFIBS correlation with fibrosis (r = 0.72, P < 0.001) was good with high AUROC values [qFibrosis (AUC) > 0.85 (0.85–0.95)] and ability to distinguish different stages of fibrosis. qFIBS showed weak correlation with ballooning (r = 0.38, P = 0.028) and inflammation (r = 0.46, P = 0.005); however, it could distinguish different grades of ballooning (AUROCs 0.73, sensitivity 0.36, and specificity 0.92) and inflammation (AUROCs 0.77, sensitivity 0.83, and specificity 0.53).

Conclusion

It was demonstrated that when qFIBS derived from adult NASH was performed on pediatric NASH, it could best distinguish the various histological grades of steatosis and fibrosis.
Genotype-Specific Recruitment of Rhizosphere Bacteria From Sandy Loam Soil for Growth Promotion of Cucumis sativus var. hardwickii
Authors: Li Zeyang , Zheng Yingying , Li Yansu , Cheng Xu , Huang Sanwen , Yang Xueyong , Qin Yuxuan
Published: June 2022

The composition and structure of the rhizosphere microbiome is affected by many factors, including soil type, genotype, and cultivation time of the plant. However, the interaction mechanisms among these factors are largely unclear. We use culture-independent 16S rRNA amplicon sequencing to investigate the rhizosphere bacterial composition and the structure of cultivated cucumber Xintaimici (XT) and wild-type cucumber Cucumis sativus var. hardwickii (HD) in four kinds of soils. We found that soil type, cultivation time, and genotype affected the composition and structure of cucumber rhizosphere bacterial communities. Notably, HD showed better physiological features in sandy soil and sandy loam soil than it did in black soil and farm soil at 50 days post-sowing, which was due to its stronger recruitment ability to Nitrospira, Nocardioides, Bacillus, and Gaiella in sandy soil, and more Tumebacillus, Nitrospira, and Paenibacillus in sandy loam soil. Meanwhile, we also found that HD showed a better recruiting capacity for these bacterial genera than XT in both sandy soil and sandy loam soil. Functional predictions indicated that these bacteria might have had stronger root colonization ability and then promoted the growth of cucumbers by enhancing nitrogen metabolism and active metabolite secretion. In this study, our findings provided a better insight into the relationship between cucumber phenotype, genotype, and the rhizosphere bacterial community, which will offer valuable theoretical references for rhizosphere microbiota studies and its future application in agriculture.
Microbial Community Analysis in Sichuan South-road Dark Tea Piled Center at Pile-Fermentation Metaphase and Insight Into Organoleptic Quality Development Mediated by Aspergillus niger M10
Authors: Zou Yao , Zhang Ying , Tian Yun , Liu Minqiang , Yuan Yue , Lai Yuqing , Liu Xuyi , Xu Wei , Tan Liqiang , Tang Qian , Li Pinwu , Xu Jingyi
Published: June 2022

Microbes are critical in the Sichuan South-road Dark Tea (SSDT) organoleptic quality development during pile-fermentation. Piled tea center at fermenting metaphase is crucial for the conversion of its quality components. In this study, we investigated the microbial community of piled SSDT center below the stacked tea surface of 15 cm (SSDTB), 50 cm (SSDTX), and 85 cm (SSDTH) on the second turning time of pile-fermentation, respectively. Results showed that SSDTH and SSDTB had a higher similarity in the microbial community. Pantoea (36.8%), Klebsiella (67.7%), and Aspergillus (35.3%) were the most abundant in SSDTH, SSDTB, and SSDTX, respectively. We found 895 species were common among all samples, but 86, 293, and 36 species were unique to SSDTB, SSDTX, and SSDTH, respectively. Aspergillus niger showed high co-occurrence and was positively correlated with numerous microbes in SSDT samples, and Aspergillus niger M10 isolated from SSDTX was excellent at enhancing soluble sugar (SS), amino acids (AAs), theaflavin (TF), and thearubigins (TR) contents, while decreasing catechin (Cat), tea polyphenols (TPs)/AA, Caf/SS, Cat/SS, TPs/SS, and (TPs + Caf)/SS levels in AM10 post-fermentation, as compared with the control. Moreover, it also produced a noticeable difference in the CIELab parameters in dried, liquor, and infused tea colors between AM10 and control during fermentation. When it was further inoculated on differential mediums, we detected glycoside hydrolases, namely, β-glucosidase, mannosidase, pectinase, cellulase, amylase, and α-galactosidase being secreted by Aspergillus niger M10. Taken together, SSDXT presented a more unique microbial community. Aspergillus niger M10 probably improved the sweet and mellow taste, and the yellow brightness and red color of SSDT during fermentation. It also provided new insights into the microbial profile and organoleptic quality development mechanism of SSDT during pile-fermentation.
The Big Picture of Neurodegeneration: A Meta Study to Extract the Essential Evidence on Neurodegenerative Diseases in a Network-Based Approach
Authors: Ruffini Nicolas , Klingenberg Susanne , Heese Raoul , Schweiger Susann , Gerber Susanne
Published: June 2022

The common features of all neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease, are the accumulation of aggregated and misfolded proteins and the progressive loss of neurons, leading to cognitive decline and locomotive dysfunction. Still, they differ in their ultimate manifestation, the affected brain region, and the kind of proteinopathy. In the last decades, a vast number of processes have been described as associated with neurodegenerative diseases, making it increasingly harder to keep an overview of the big picture forming from all those data. In this meta-study, we analyzed genomic, transcriptomic, proteomic, and epigenomic data of the aforementioned diseases using the data of 234 studies in a network-based approach to study significant general coherences but also specific processes in individual diseases or omics levels. In the analysis part, we focus on only some of the emerging findings, but trust that the meta-study provided here will be a valuable resource for various other researchers focusing on specific processes or genes contributing to the development of neurodegeneration.
OzEAN Study to Collect Real-World Evidence of Persistent Use, Effectiveness, and Safety of Ozanimod Over 5 Years in Patients With Relapsing-Remitting Multiple Sclerosis in Germany
Authors: Ziemssen Tjalf , Richter Stephan , Mäurer Mathias , Buttmann Mathias , Kreusel Boris , Poehler Anne-Maria , Lampl Maren , Linker Ralf A.
Published: June 2022

Background:

Ozanimod, a sphingosine 1-phosphate receptor 1 and 5 modulator, was approved as a disease-modifying therapy for active relapsing-remitting multiple sclerosis (RRMS) in 2020 and for active ulcerative colitis in 2021. Long-term, real-world studies in a nonselective population are needed. OzEAN is an ongoing study to assess the real-world persistent use, effectiveness, and safety of ozanimod and its impact on quality of life (QoL) in patients with RRMS over a 5-year period.

Methods

This prospective, noninterventional, postmarketing authorization study will enroll ~1,300 patients (≥18 years of age) with active RRMS. The decision to initiate ozanimod must have been made before and independent from study participation. Enrollment began in March 2021. Recruitment is ongoing and will last for 36 months across 140 sites in Germany. Treatment-naive patients or those having prior experience with a disease-modifying therapy receive oral ozanimod 0.92 mg/day after an initial dose escalation, per the summary of product characteristics recommendations, for up to 60 months. Persistence with ozanimod treatment (primary endpoint) is assessed at month 60. Secondary endpoints include additional physician-reported outcomes [persistence at earlier time points, annualized relapse rate, Expanded Disability Status Scale score, cognition (Symbol Digit Modalities Test), and incidence of adverse events], and patient-reported outcomes assessing patient satisfaction, adherence, and treatment modalities (Treatment Satisfaction Questionnaire for Medication, v1.4), disability (United Kingdom Neurological Disability Rating Scale), QoL (MSQOL-54 questionnaire), fatigue (Fatigue Scale for Motor and Cognitive Functions), and health economics [Work Productivity and Activity Impairment Questionnaire for Multiple Sclerosis (German v2.1); Multiple Sclerosis Health Resource Survey, v3.0]. A Multiple Sclerosis Documentation System with an internet-based e-health portal allows patients to view files and complete questionnaires. A safety follow-up will occur 3–8 months after the last ozanimod dose for patients who discontinue treatment early. Long-term results are anticipated after study completion in 2029. Yearly interim analyses are planned after enrollment has reached 25%.

Conclusion

This is the first long-term, real-world study of ozanimod in patients with RRMS and, to our knowledge, the first noninterventional study utilizing a patient portal. These data will add to the safety/efficacy profile of ozanimod demonstrated in phase 3 trials.

Clinical Trial Registration

Clinicaltrials.gov, identifier: NCT05335031.