Batch culture analysis to identify potent organic acids for suppressing ruminal methane production

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Abstract

We performed an in vitro rumen batch culture study to screen 11 commercially available organic acids for methane-suppressing ability and analyzed the rumen microbiota to determine the mode of action of the acids that showed potent methane-suppressing activity. Nine of the 11 acids showed methane-suppressing activity. Maleic anhydride, itaconate, citrate, and fumarate, which showed the highest activity, were further examined. These four acids showed methane-suppressing activity irrespective of the hay-to-concentrate ratios of the substrate. Maleic anhydride and itaconate decreased total gas and short-chain fatty acid production. Maleic anhydride and fumarate increased propionate production, while itaconate increased butyrate production. Maleic anhydride, itaconate, and citrate increased lactate production. Fumarate increased the abundance of bacteria involved in propionate production. Maleic anhydride, itaconate, and citrate increased the abundance of bacteria involved in lactate production. Thus, the results indicate that maleic anhydride, itaconate, and citrate may decrease methane in part by stimulating the acrylate pathway.

Developing models to predict feces and urine excretion in Japanese Black fattening steer by multiple regression analysis

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Abstract

The objective of this study was to develop models for predicting the amount of feces and urine excreted by Japanese Black fattening steer using a dataset of 119 digestion trials for a total of 46 animals. Correlation analysis was used to analyze the relationships between feces and urine excretion and feed intake, feed digestibility, and nitrogen balance. Multiple regression analysis was conducted to develop models for predicting the amount of feces and urine excreted using the explanatory variables selected from various animal and dietary parameters based on P-value (<0.10) and variance inflation factor (<3.0). Resultingly, dry matter intake was a primary predictor of feces excreted. The prediction equation for the amount of feces excretion as a function of body weight, dry matter intake, and calculated total digestible nutrients fits the data well (adjusted coefficient of determination [adj R 2] = 0.519, root mean square error = 1.57). Furthermore, the nitrogen content in the urine was the primary predictor of the urine excretion amount. Thus, the prediction equation for the amount of urine excreted using the nitrogen content in urine yielded a highly accurate model (adj R 2 = 0.813, root mean square error = 4.12).

Phenological growth stages of Astragalus membranaceus var. mongholicus according to the Biologische Bundesanstalt Bundessortenamt and Chemical Industry (BBCH) scale

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Phenological growth stages of Astragalus membranaceus var. mongholicus according to the Biologische Bundesanstalt Bundessortenamt and Chemical Industry (BBCH) scale

Astragalus membraneceus var. monghalicus fruit growth process


Abstract

Astragalus membranaceus var. mongholicus (Astragalus) is a perennial medicinal plant belonging to Leguminosae. Its main agronomic and industrial interest is the accumulation of astragaloside IV and calycosin-7-O-β-D-glucoside in roots, two components that play crucial pharmacological roles in the finished pharmaceutical products. Phenological research is a prerequisite for improving the yield quality of cultivated medicinal plants. However, there are no standardized phenological studies on Astragalus. To expand phenotyping knowledge on this medicinal plant, researchers and breeders need a universal scale to describe the development of this plant. This study aims to define the phenological growth stages of Astragalus, based on the existing Biologische Bundesanstalt, Bundessortenamt und Chemische Industrie (BBCH) scale to provide a standard scale for Astragalus, and grown under temperate conditions of production and climate, proposes a disease and pest control reference. This study was conducted in Inner Mongolia, North China. The existing BBCH scale with a three-digit code was used to define Astragalus's phenological growth codes, supplemented with pictures. Phenological observations were performed twice monthly, based on the developmental stages. The chronology and duration of each stage were also observed and described according to the accumulation of degree days during the growing season. Based on the data obtained, the influence of the average temperature and GDD on the phenophases was evaluated. The phenological description is divided into two principal growth stages: five for vegetative growth (perennating bud, leaf development, formation of branches, main stem elongation and root development), four for reproductive growth (reproductive organ development, flowering, fruit development and fruit maturation), and one for senescence according to the BBCH scale. Seventy secondary growth stages were described within the 10 principal growth stages. Under each secondary growth stage, six mesostages are also taken into account, which contains the distinct patterns of the phenological characteristics in Astragalus varieties and the process of transplanting seedlings. A practical management program for disease and pest control was also proposed by using the BBCH code and the phenological data proposed in this work. Our study presents the first BBCH scale established for Astragalus cultivated in temperate conditions and a chronology of phenological stages based on the accumulation of thermal time, through growing degree day calculation. This work provides a general tool that can be widely used by researchers, breeders, and manufacturers of medicinal materials leading to better agricultural production and scientific communication.

Prognostic value of virtual portal pressure gradient response in compensated cirrhotic patients treated with carvedilol

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Prognostic value of virtual portal pressure gradient response in compensated cirrhotic patients treated with carvedilol

This single-center cohort study has demonstrated the significance of virtual portal pressure gradient (vPPG) response in disease prognosis of cirrhotic patients who require carvedilol to prevent first VH. The computation of vPPG includes the reconstruction of 3D portal vein and application of fluid dynamics analysis. Monocyte chemoattractant protein-1 makes a contribution to vPPG-reducing effects by carvedilol in cirrhotic patients.


Abstract

Aim

This study aimed to assess the prognostic significance of virtual portal pressure gradient (vPPG) response to carvedilol in patients with compensated cirrhosis (CC).

Methods

Compensated cirrhosis patients with high-risk varices were prospectively enrolled to receive carvedilol for prevention of first variceal hemorrhage (VH) and followed up for 1 year. The vPPG response was defined as a reduction of vPPG >10% from baseline after 1-month therapy. Logistic and Cox regression analyses were performed to identify independent predictors for vPPG response and first decompensation, respectively. Competitive risk models were constructed to predict disease progression, and validated using the C-index, Kaplan–Meier analysis, competitive risk analysis, and calibration curves.

Results

A total of 129 patients completed this study, of whom 56 (43.4%) achieved vPPG response and were referred as vPPG responders. Baseline vPPG, red color sign, Model for End-stage Liver Disease score, serum monocyte chemoattractant protein-1 (MCP-1), and laminin levels significantly correlated with vPPG response, which itself was further documented as an independent predictor of VH, ascites, and overall decompensation events in CC. Moreover, the red color sign or Child–Turcotte–Pugh score effectively predicted VH, while ascites correlated well with portal flow velocity or MCP-1. The predictive models for VH and ascites showed a good discrimination with C-index values of 0.747 and 0.689 respectively, and the high consistency on calibration curves.

Conclusion

The vPPG response could be used as a noninvasive tool for prediction of disease progression in patients with CC.

Magnetic resonance imaging‐based risk factors of hepatocellular carcinoma after direct‐acting antiviral therapy: A multicenter observational study

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Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study

According to the multivariate analysis, age, male sex, history of hepatocellular carcinoma, and hepatobiliary phase hypointense nodule without arterial phase hyperenhancement were independent risk factors significantly associated with the development of hypervascular hepatocellular carcinoma (p < 0.001–0.04). The incidence rate of hypervascular hepatocellular carcinoma was significantly higher among patients with a history of hepatocellular carcinoma than in those without a history of hepatocellular carcinoma (p < 0.001). The 1-, 3-, and 5-year cumulative hypervascular hepatocellular carcinoma development rates were 11.7%, 46.9%, and 71.9%, respectively, among patients with a history of hepatocellular carcinoma, whereas the rates were 2.0%, 8.0%, and 9.7%, respectively, in the patients without a history of hepatocellular carcinoma. The incidence rate of hypervascular hepatocellular carcinoma was significantly higher among patients with hepatobiliary phase hypointense nodule without arterial phase hyperenhancement than in those without that nodule (p < 0.001). The 1-, 3-, and 5-year cumulative hypervascular hepatocellular carcinoma development rates were 10.9%, 44.2%, and 61.6%, respectively, in the patients with hepatobiliary phase hypointense nodule without arterial phase hyperenhancement, whereas the rates were 2.5%, 9.9%, and 15.9%, respectively, in the patients without that nodule.


Abstract

Aim

To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy.

Methods

We enrolled patients with chronic hepatitis C who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan–Meier method, and differences between groups were assessed using the log-rank test.

Results

The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p < 0.001–0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively).

Conclusion

History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.

Characterisation of IL‐1 family members in Sweet syndrome highlights the overexpression of IL‐1β and IL‐1R3 as possible therapeutic targets

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Abstract

Sweet syndrome (SS) as a prototypic neutrophilic dermatosis (NDs) shares certain clinical and histologic features with monogenic auto-inflammatory disorders in which interleukin (IL)-1 cytokine family members play an important role. This has led to the proposal that NDs are polygenic auto-inflammatory diseases and has fuelled research to further understand the role of IL-1 family members in the pathogenesis of NDs. The aim of this study was to characterise the expression of the IL-1 family members IL-1β, IL-36γ, IL-33 and IL-1R3 (IL-1RaP) in SS. The expression profile of IL-1β, IL-33, IL-36γ and their common co-receptor IL-1R3 was analysed by immunohistochemistry, in situ hybridisation and double immunofluorescence (IF) in healthy control skin (HC) and lesional skin samples of SS. Marked overexpression of IL-1β in the dermis of SS (p < 0.001), and a non-significant increase in dermal (p = 0.087) and epidermal (p = 0.345) IL-36γ expression compared to HC was observed. Significantly increased IL-1R3 expression within the dermal infiltrate of SS skin samples (p = 0.02) was also observed, whereas no difference in IL-33 expression was found between SS and HC (p = 0.7139). In situ hybridisation revealed a good correlation between gene expression levels and the above protein expression levels. Double IF identifies neutrophils and macrophages as the predominant sources of IL-1β. This study shows that IL-1β produced by macrophages and neutrophils and IL-1R3 are significantly overexpressed in SS, thereby indicating a potential pathogenic role for this cytokine and receptor in SS.

Elevated carbon‐dioxide effects on wheat grain quality differed under contrasting nitrogen and phosphorus fertiliser supply

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Abstract

Global atmospheric carbon-dioxide concentration ([CO2]) is increasing rapidly, but its interactions with nitrogen (N) and phosphorus (P) fertiliser on wheat grain quality are not well understood. In two experiments, we investigated the effects of ambient [CO2] (aCO2; ∼410 ppm) and elevated [CO2] (eCO2; 760 ppm) on shoot macro-nutrient content, nutrient harvest index (NuHI) and grain nutrient concentration of wheat supplied low and optimum rates of N and P fertilisers. Elevated [CO2] increased biomass, grain yield and grain nutrient accumulation in Experiment 1, resulting in reduced grain N, S, Ca and Mg concentration. This was attributed to nutrient ‘dilution’ due to increased carbohydrate content in the grain. In contrast, in Experiment 2, measured variables were unaffected by eCO2, but grain N, K, Ca and Mg concentrations decreased with increasing [CO2]. This was attributed to reduced remobilisation of nutrients to the grain during reproductive development at eCO2. Fertiliser deficiency reduced straw and grain yield by 61–86% across CO2 treatments and experiments. The element HIs were unaffected by eCO2, except for MgHI. Our results point to a compensatory and symmetrical interactions between N, P and CO2 that changes in one element rapidly altering the availability of the other. Furthermore, the results highlight the need for selecting cultivars that are productive and yet maintain suitable quality characteristics under eCO2.

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Single‐cell analysis of human dermal fibroblasts isolated from a single male donor over 35 years

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Single-cell analysis of human dermal fibroblasts isolated from a single male donor over 35 years

The effect of ageing of the same donor on dermal fibroblast heterogeneity was tested in a dermal fibroblast lineage (ASF-4 cell lineage) isolated from the inner side of the upper arm of a healthy male donor (age 36) for 35 years. Single-cell RNA sequencing of cultured cells frozen at Passage 10 at the age of 36 and 72 years showed that genes involved in extracellular matrix remodelling were downregulated with donor ageing, which is a different observation from those reported in the previous studies. Based on the scRNA-Seq results, we identified a cellular senescence-associated gene EFEMP2.


Abstract

The aim of this study is to examine the effects of ageing on dermal fibroblast heterogeneity based on samples obtained from the same donor. We used a dermal fibroblast lineage (named ASF-4 cell lines) isolated from the inner side of the upper arm of a healthy male donor over a 35-year period, beginning at 36 years of age. Because clonal analysis of ASF-4 cell lines demonstrated a donor age-dependent loss of proliferative capacity and acquisition of senescent traits at the single-cell level, cultured cells frozen at passage 10 at ages 36 and 72 years were subjected to single-cell RNA sequencing. Transcriptome analysis revealed an increase in senescent fibroblasts and downregulation of genes associated with extracellular matrix remodelling with ageing. In addition, two putative differentiation pathways, with one endpoint consisting of senescent fibroblasts and the other without, were speculated using a pseudo-time analysis. Knockdown of the characteristic gene of the non-senescent fibroblast cluster endpoint, EFEMP2, accelerated cellular senescence. This was also confirmed in two other normal human dermal fibroblast cell lines. The detection of a common cellular senescence-related gene from single-donor analysis is notable. This study provides new insights into the behaviour of dermal fibroblasts during skin ageing.

A 2‐week time‐restricted feeding attenuates psoriasis‐like lesions with reduced inflammatory cytokines and immunosenescence in mice

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Abstract

Psoriasis, a well-established T-cell mediated dermatosis, exhibits a robust correlation with obesity and systemic inflammation, manifesting psoriasis skin lesions and premature immunosenescence within the peripheral blood and lesion. Intermittent fasting (IF) has exhibited various beneficial effects in reducing inflammation, resisting oxidative stress and slowing ageing, as well as losing weight. A form of IF known as time-restricted feeding (TRF) restricts daily caloric intake within 4–8 h. Nonetheless, the advantageous impacts of TRF on psoriasis still require further verification. We measured the acanthosis in Imiquimod (IMQ)-induced psoriasis mice and evaluated their pathological phenotypes. Our study examined the effects of a 2-week TRF on body weight and metabolic parameters. The subsets of T cells in spleens and skin lesions were accessed by flow cytometry. Cytokines and senescence-associated genes were evaluated by immunofluorescence and RT-qPCR. RNA sequencing was conducted on skin lesions. According to our findings, a 2-week TRF attenuates psoriasis-like lesions in mice with reduced inflammatory cytokines and mitigated immunosenescence. TRF increased the counts of CD4+ Treg cells in skin lesions while reducing the counts of Th2 and Th17 cells in spleens. Furthermore, the administration of TRF resulted in a decrease in the population of CD4+ senescent T cells in both the dermis and spleens, concomitant with the expression of senescence-associated genes in spleen CD4+ T cells. The outcomes mentioned above provide valuable evidence in support of TRF for the management of psoriasis.

Cutaneous findings and treatments in deficiency of interleukin‐36 receptor antagonist (DITRA): A review of the literature

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Abstract

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.