bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposal for a new N-stage classification system for intrahepatic cholangiocarcinoma
Authors: Liao Shan , Liao Ruizhe , Wu Huaxing , Wang Shijie , Zhou Yanming
Published: August 2023

Background

The number of metastatic lymph nodes (MLNs) is not considered in the nodal status (N classification) of intrahepatic cholangiocarcinoma (ICC) in the current 8thEdition of the American Joint Committee on Cancer (AJCC) staging system. The aim of this study was to find out the optimal cut-off point based on the number of MLNs and establish a modified AJCC staging system for ICC according to the new N category

Methods

A total of 675 ICC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. The optimal cut-off value of MLNs affecting survival was determined by X-tile software. The relative discriminative power was assessed by Harrell’s concordance index (C-index) and Akaike information criterion (AIC).

Results

The proposed new nodal category subdivided patients into three groups (N0, no MLN; N1, 1–3 MLNs; and N2, ≥ 4 MLNs) with significantly different overall survival (P < 0.001). Multivariable analysis revealed that the new nodal category was an independent prognostic factor (P < 0.001). Both the C-index and AIC for our modified staging system were better than those for the 8th AJCC edition (0.574 [95% confidence interval 0.533-0.615] versus 0.570 [95% confidence interval 0.527-0.613], and 853.30 versus 854.21, respectively).

Conclusion

The modified AJCC staging system based on the number of MLNs may prove to be a useful alternative for predicting survival of ICC patients in clinical practice.
Clinical features of COVID-19 in Italian outpatient children and adolescents during Parental, Delta, and Omicron waves: a prospective, observational, cohort study
Authors: Di Chiara Costanza , Boracchini Riccardo , Sturniolo Giulia , Barbieri Alessia , Costenaro Paola , Cozzani Sandra , De Pieri Marica , Liberati Cecilia , Zin Annachiara , Padoan Andrea , Bonfante Francesco , Kakkar Fatima , Cantarutti Anna , Donà Daniele , Giaquinto Carlo
Published: August 2023

Introduction

COVID-19 features changed with the Omicron variant of SARS-CoV-2 in adults. This study aims to describe COVID-19 symptoms in children and adolescents during the Parental, Delta, and Omicron eras

Methods

A single-centre, prospective observational study was conducted on individuals aged 0–20 years attending the University Hospital of Padua (Italy) from April 2020 to December 2022. COVID-19 cases were defined by positive SARS-CoV-2 molecular detection and/or serology; patient/family symptoms and virological positivity were considered to determine the infection onset. Variables were summarized and compared using appropriate tests of descriptive statistics

Results

A total of 509 cases [46% female, median age eight years (IQR: 4–12)] were studied. Three-hundred-eighty-seven (76%), 52 (10%), and 70 (14%) subjects experienced COVID-19 during the Parental, Delta, and Omicron waves, respectively. All subjects developed an asymptomatic/mild COVID-19. Overall, the most frequent symptoms were fever (47%) and rhinitis (21%), which showed a significant increasing incidence from the Parental to Omicron waves (p < 0.001). Conversely, diarrhea was most common during the pre-Omicron eras (p = 0.03). Stratifying symptoms according to the age group, fever, rhinitis, and skin rashes were observed more frequently among infants/toddlers; conversely, fatigue was more common in children older than five years. The duration of symptoms was similar across different SARS-CoV-2 variants of concern (VOCs); conversely, the number of symptoms varied according to the age group (p < 0.0001)

Discussion

This study showed differences in COVID-19 clinical presentation among infants, children, and adolescents and confirmed Omicron infection is more likely to be associated with upper respiratory symptoms. However, further population-based studies are needed to support these findings. In addition, active surveillance will play a crucial role in assessing the disease severity of future VOCs.
Testicular ischemia associated with IgA vasculitis in a child: a case report and literature review
Authors: Zhang Shuya , Wang Qingwen , Li Ziwei , Guo Qingyin
Published: August 2023

Testicular necrosis is a rare and severe complication of immunoglobulin A (IgA) vasculitis (IgAV). Herein, We report a case of a 10-year-old boy who was admitted to the hospital due to skin purpura and intermittent abdominal pain for 10 days and bilateral testicular pain for 2 days. Scrotal ultrasonography indicated right testicle ischemia, right epididymo-orchitis, and bilateral hydrocele of the testis. Scrotal surgical exploration revealed significant swelling and darkening of the right testicle. Conservative treatment led to improvement in his condition, and he was discharged. During 3 months of follow-up, there was no recurrence of skin purpura or pain, and the urine tests were normal. Color ultrasound indicated only partial blood flow signal to the right testicle tissue, which was slightly smaller than the left testicle. This case highlights the need for continuous attention from clinicians to the signs and symptoms of the reproductive system during the diagnosis and treatment of IgAV. Continuous monitoring with ultrasound can aid in early detection, diagnosis, and treatment of reproductive system lesions of IgA vasculitis.
Clinical efficacy of IgM-enriched immunoglobulin as adjunctive therapy in neonatal and pediatric sepsis: a systematic review and meta-analysis
Authors: Dinleyici Ener Cagri , Frey Georg , Kola Ermira , Wippermann Ulrike , Bauhofer Artur , Staus Alexander , Griffiths Peter , Azharry Muhamad , Rohsiswatmo Rinawati
Published: August 2023

Background

Sepsis is a major cause of mortality and morbidity globally, with around one-quarter of all sepsis-related deaths occurring in children under the age of 5. We conducted a meta-analysis and systematic review of the literature to evaluate the clinical effectiveness of an IgM-enriched immunoglobulin preparation in pediatrics patients and neonates with sepsis.

Methods

Systematic searches of PubMed, the Cochrane Library and Embase databases were performed in November 2022, with no date limitations, to identify studies in which IgM-enriched immunoglobulin was used as adjunctive therapy in neonatal and pediatric patients with sepsis.

Results

In total, 15 studies fulfilled the eligibility criteria, 13 neonatal studies and 2 pediatric studies. Pooled estimates from all studies indicated that mortality rates were significantly lower in patients who received treatment with the IgM-enriched immunoglobulin compared with controls (OR 0.41; 95% CI 0.32–0.55). Further analyses in neonatal studies, alone, showed a significant benefit with longer treatment durations (>3 days) vs. the recommended treatment duration (3 days) (OR 0.32; 95% CI 0.22–0.47) vs. (OR 0.61; 95% CI 0.41–0.92). Treatment with IgM-enriched immunoglobulin was associated with a lower mortality risk compared with controls in prospective studies vs. retrospective analyses (OR 0.37; 95% CI 0.27–0.51) vs. (OR 0.73; 95% CI 0.41–1.30).

Conclusions

This systematic review suggests that adjunctive treatment with IgM-enriched immunoglobulin may reduce the risk of mortality in neonatal and pediatric populations. However, large randomized controlled trials are required to further substantiate and evaluate these findings.
Cost-effectiveness analysis of selexipag for the combined treatment of pulmonary arterial hypertension
Authors: Dong Wenxing , Zhang Zhe , Chu Mingming , Gu Peng , Hu Min , Liu Lulu , Huang Jingbin , Zhang Rong
Published: August 2023

Objective: Adding selexipag to the combined treatment of endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitor (PDE5i) reduces the risk of clinical worsening events in patients with pulmonary arterial hypertension (PAH) but at a considerably higher cost. This study evaluated the cost-effectiveness of adding selexipag to the combined treatment of ERA and PDE5i in patients with PAH from a Chinese healthcare system perspective.

Methods: A Markov model was developed to assess costs and quality-adjusted life years (QALYs) of macitentan + tadalafil + selexipag vs. macitentan + tadalafil for the treatment of PAH. Markov states included WHO Functional Class (FC) (I–IV) and death. Transition probabilities were based on data from the TRITON trial. Mortality rates, costs, and utilities were obtained from published literature and public databases.

Results: In the base case analysis, compared with macitentan + tadalafil, selexipag + macitentan + tadalafil increased costs ($357,807.588 vs. $116,534.543, respectively) and QALYs (7.234 QALYs vs. 6.666 QALYs, respectively). The resulting incremental cost-effectiveness ratio was $424,746.070 per QALY, which was higher than the willingness-to-pay (WTP) of $38,223.339 per QALY. The results were most sensitive to HR for mortality of patients with FC IV relative to the general population, discount rate, and the cost of selexipag. The probability was greater than 50% for the selexipag + macitentan + tadalafil only if the WTP was more significant than $426,019.200 per QALY.

Conclusion: In China, adding selexipag may not be cost-effective for patients with PAH who failed to control their condition after combined treatment of ERA and PDE5i. Results of the analysis can aid discussions on the value and position of selexipag for the combined treatment of PAH.
LC-MS-based metabolomics reveals the mechanism of anti-gouty arthritis effect of Wuwei Shexiang pill
Authors: Lang Jirui , Li Li , Quan Yunyun , Tan Ruirong , Zhao Jinbiao , Li Min , Zeng Jin , Chen Shilong , Wang Ting , Li Yong , Zhao Junning , Yin Zhujun
Published: August 2023

Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1β, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.
Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases
Authors: Yang Yang , Feng Qi , Luan Ying , Liu Hui , Jiao Yuxue , Hao Huijie , Yu Bo , Luan Yi , Ren Kaidi
Published: August 2023

Copper (Cu) is a vital trace element for maintaining human health. Current evidence suggests that genes responsible for regulating copper influx and detoxification help preserve its homeostasis. Adequate Cu levels sustain normal cardiac and blood vessel activity by maintaining mitochondrial function. Cuproptosis, unlike other forms of cell death, is characterized by alterations in mitochondrial enzymes. Therapeutics targeting cuproptosis in cardiovascular diseases (CVDs) mainly include copper chelators, inhibitors of copper chaperone proteins, and copper ionophores. In this review, we expound on the primary mechanisms, critical proteins, and signaling pathways involved in cuproptosis, along with its impact on CVDs and the role it plays in different types of cells. Additionally, we explored the influence of key regulatory proteins and signaling pathways associated with cuproptosis on CVDs and determined whether intervening in copper metabolism and cuproptosis can enhance the outcomes of CVDs. The insights from this review provide a fresh perspective on the pathogenesis of CVDs and new targets for intervention in these diseases.
The effect of cyclic stretch on aortic viscoelasticity and the putative role of smooth muscle focal adhesion
Authors: Neutel Cédric H. G. , Wesley Callan D. , De Meyer Guido R. Y. , Martinet Wim , Guns Pieter-Jan
Published: August 2023

Due to its viscoelastic properties, the aorta aids in dampening blood pressure pulsatility. At the level of resistance-arteries, the pulsatile flow will be transformed into a continuous flow to allow for optimal perfusion of end organs such as the kidneys and the brain. In this study, we investigated the ex vivo viscoelastic properties of different regions of the aorta of healthy C57Bl6/J adult mice as well as the interplay between (altered) cyclic stretch and viscoelasticity. We demonstrated that the viscoelastic parameters increase along the distal aorta and that the effect of altered cyclic stretch is region dependent. Increased cyclic stretch, either by increased pulse pressure or pulse frequency, resulted in decreased aortic viscoelasticity. Furthermore, we identified that the vascular smooth muscle cell (VSMC) is an important modulator of viscoelasticity, as we have shown that VSMC contraction increases viscoelastic parameters by, in part, increasing elastin fiber tortuosity. Interestingly, an acute increase in stretch amplitude reverted the changes in viscoelastic properties induced by VSMC contraction, such as a decreasing contraction-induced elastin fiber tortuosity. Finally, the effects of altered cyclic stretch and VSMC contraction on viscoelasticity were more pronounced in the abdominal infrarenal aorta, compared to both the thoracic ascending and descending aorta, and were attributed to the activity and stability of VSMC focal adhesion. Our results indicate that cyclic stretch is a modulator of aortic viscoelasticity, acting on VSMC focal adhesion. Conditions of (acute) changes in cyclic stretch amplitude and/or frequency, such as physical exercise or hypertension, can alter the viscoelastic properties of the aorta.
Antennal transcriptome analysis of odorant-binding proteins and characterization of GOBP2 in the variegated cutworm Peridroma saucia
Authors: Dong Jun-Feng , Wang Ke , Sun Ya-Lan , Tian Cai-Hong , Wang Shao-Li
Published: August 2023

Odorant-binding proteins (OBPs) are expressed at extremely high concentrations in the chemo-sensilla lymph of insects and have long been thought to be crucial for delivering the semiochemicals to the odorant receptors. They are represented by multiple classes: general odorant-binding proteins (GOBP1 and GOBP2) and pheromone-binding proteins. In the current study, we identified a total of 35 OBPs in the antennal transcriptome of Peridroma saucia, a worldwide pest that causes serious damage to various crops. A gene expression value (TPM, transcripts per million) analysis revealed that seven OBPs (PsauPBP1/2/3, PsauGOBP1/2, PsauOBP6, and PsauOBP8) were highly abundant in the antennae. Next, we focused on the expression and functional characterization of PsauGOBP2. Real-time quantitative-PCR analysis demonstrated that PsauGOBP2 was predominantly expressed in the antennae of both sexes. Fluorescence binding assays showed that the recombinant PsauGOBP2 strongly binds to the female sex pheromone components Z11-16: Ac (Ki = 4.2 μM) and Z9-14: Ac (Ki = 4.9 μM) and binds moderately (6 µM ≤ Ki ≤ 13 µM) to the host plant volatiles phenylethyl acetate, β-myrcene, and dodecanol. Further 3D structural modeling and molecular docking revealed that several crucial amino acid residues are involved in ligand binding. The results not only increase our understanding of the olfactory system of P. saucia but also provide insights into the function of PsauGOBP2 that has implications for developing sustainable approaches for P. saucia management.
Opportunities and challenges in the application of single-cell and spatial transcriptomics in plants
Authors: Chen Ce , Ge Yining , Lu Lingli
Published: August 2023

Single-cell and spatial transcriptomics have diverted researchers’ attention from the multicellular level to the single-cell level and spatial information. Single-cell transcriptomes provide insights into the transcriptome at the single-cell level, whereas spatial transcriptomes help preserve spatial information. Although these two omics technologies are helpful and mature, further research is needed to ensure their widespread applicability in plant studies. Reviewing recent research on plant single-cell or spatial transcriptomics, we compared the different experimental methods used in various plants. The limitations and challenges are clear for both single-cell and spatial transcriptomic analyses, such as the lack of applicability, spatial information, or high resolution. Subsequently, we put forth further applications, such as cross-species analysis of roots at the single-cell level and the idea that single-cell transcriptome analysis needs to be combined with other omics analyses to achieve superiority over individual omics analyses. Overall, the results of this review suggest that combining single-cell transcriptomics, spatial transcriptomics, and spatial element distribution can provide a promising research direction, particularly for plant research.
Approach strategies and application of metabolomics to biotechnology in plants
Authors: Oh Seon-Woo , Imran Muhammad , Kim Eun-Ha , Park Soo-Yun , Lee Sang-Gu , Park Hyoun-Min , Jung Jung-Won , Ryu Tae-Hun
Published: August 2023

Metabolomics refers to the technology for the comprehensive analysis of metabolites and low-molecular-weight compounds in a biological system, such as cells or tissues. Metabolites play an important role in biological phenomena through their direct involvement in the regulation of physiological mechanisms, such as maintaining cell homeostasis or signal transmission through protein–protein interactions. The current review aims provide a framework for how the integrated analysis of metabolites, their functional actions and inherent biological information can be used to understand biological phenomena related to the regulation of metabolites and how this information can be applied to safety assessments of crops created using biotechnology. Advancement in technology and analytical instrumentation have led new ways to examine the convergence between biology and chemistry, which has yielded a deeper understanding of complex biological phenomena. Metabolomics can be utilized and applied to safety assessments of biotechnology products through a systematic approach using metabolite-level data processing algorithms, statistical techniques, and database development. The integration of metabolomics data with sequencing data is a key step towards improving additional phenotypical evidence to elucidate the degree of environmental affects for variants found in genome associated with metabolic processes. Moreover, information analysis technology such as big data, machine learning, and IT investment must be introduced to establish a system for data extraction, selection, and metabolomic data analysis for the interpretation of biological implications of biotechnology innovations. This review outlines the integrity of metabolomics assessments in determining the consequences of genetic engineering and biotechnology in plants.
Foliar application of salicylic acid inhibits the cadmium uptake and accumulation in lettuce (Lactuca sativa L.)
Authors: Tang Wen , Liang Le , Xie Yongdong , Li Xiaomei , Lin Lijin , Huang Zhi , Sun Bo , Sun Guochao , Tu Lihua , Li Huanxiu , Tang Yi
Published: August 2023

Introduction

Salicylic acid (SA) is a multi-functional endogenous phytohormone implicated in the growth, development, and metabolism of many plant species.

Methods

This study evaluated the effects of different concentrations of SA (0, 25, 100, 200, and 500 mg/L) on the growth and cadmium (Cd) content of lettuce (Lactuca sativa L.) under Cd stress. The different concentrations of SA treatments were administered through foliar application.

Results

Our results showed that 100-200 mg/L SA significantly increased the plant height and biomass of lettuce under Cd stress. When SA concentration was 200 mg/L, the plant height and root length of lettuce increased by 19.42% and 22.77%, respectively, compared with Cd treatment alone. Moreover, 200 mg/L and 500mg/L SA concentrations could reduce peroxidase (POD) and superoxide dismutase (SOD) activities caused by Cd stress. When the concentration of exogenous SA was 500 mg/L, the POD and SOD activities of lettuce leaves decreased by 15.51% and 19.91%, respectively, compared with Cd treatment. A certain concentration of SA reduced the uptake of Cd by the lettuce root system and the transport of Cd from the lettuce root system to shoots by down-regulating the expression of Nramp5, HMA4, and SAMT, thus reducing the Cd content of lettuce shoots. When the concentration of SA was 100 mg/L, 200 mg/L, and 500 mg/L, the Cd contents of lettuce shoots were 11.28%, 22.70%, and 18.16%, respectively, lower than that of Cd treatment alone. Furthermore, principal component and correlation analyses showed that the Cd content of lettuce shoots was correlated with plant height, root length, biomass, antioxidant enzymes, and the expression level of genes related to Cd uptake.

Discussion

In general, these results provide a reference for the mechanism by which SA reduces the Cd accumulation in vegetables and a theoretical basis for developing heavy metal blockers with SA components.
Clonal dominant grass Leymus chinensis benefits more from physiological integration in sexual reproduction than its main companions in a meadow
Authors: Guo Jian , Li Haiyan , Yang Yunfei , Yang Xuechen
Published: August 2023

The bioecological characteristics of plants determine their status and role in the community. The advantages of dominant species in the community compared with companion species in terms of physiological and ecological characteristics remain unclear. When both dominant and companion species in grassland plant communities are clonal, these plants are able to share resources within clones (physiological integration). However, it is unclear how the clonal dominant and companion species differ in the effect of their physiological integration on sexual reproduction. We chose Leymus chinensis, the dominant species of the most widespread meadow plant communities in the semiarid and arid regions of northern China, and its main companion species L. secalinus, Calamagrostis ripidula, C. pseudophragmites, and C. epigeios and conducted a series of in situ field experiments in a homogeneous environment, including the determination of the phenotypic characteristics of reproductive ramets with connected (allowing physiological integration) and disconnected (preventing integration) tillering nodes for each species, as well as 15N leaf labeling of ramet pairs at the milk-ripe stage. In the clonal populations of the five grasses, physiological integration between vegetative ramets and reproductive ramets interconnected by tillering nodes significantly increased the leaf, stem, inflorescence and ramet biomasses of reproductive ramets, and relative changes in ramet biomass were greatest in L. chinensis. 15N labeling showed that vegetative ramets supplied nutrients to reproductive ramets through tillering nodes; the amount of translocated 15N per unit of reproductive ramet biomass was highest in L. chinensis. Overall, our results indicate that in the five clonal grasses, physiological integration between functionally different ramets under tillering node connections had a significant positive effect on sexual reproduction, indicating interspecific consistency in the contribution of physiological integration to sexual reproduction between the dominant and companion species, but this positive effect was greater in the dominant species L. chinensis than in the four main companion species. Therefore, differences in the physiological integration ability between the dominant and main companion species, identified for the first time in this study, may explain, at least partly, the dominance of L. chinensis in the community.
Applying productivity and phytonutrient profile criteria in modelling species selection of microgreens as Space crops for astronaut consumption
Authors: Izzo Luigi Gennaro , El Nakhel Christophe , Rouphael Youssef , Proietti Simona , Paglialunga Gabriele , Moscatello Stefano , Battistelli Alberto , Iovane Maurizio , Romano Leone Ermes , De Pascale Stefania , Aronne Giovanna
Published: August 2023

Introduction

Long-duration missions in outer Space will require technologies to regenerate environmental resources such as air and water and to produce food while recycling consumables and waste. Plants are considered the most promising biological regenerators to accomplish these functions, due to their complementary relationship with humans. Plant cultivation for Space starts with small plant growth units to produce fresh food to supplement stowed food for astronauts’ onboard spacecrafts and orbital platforms. The choice of crops must be based on limiting factors such as time, energy, and volume. Consequently, small, fast-growing crops are needed to grow in microgravity and to provide astronauts with fresh food rich in functional compounds. Microgreens are functional food crops recently valued for their color and flavor enhancing properties, their rich phytonutrient content and short production cycle. Candidate species of microgreens to be harvested and eaten fresh by crew members, belong to the families Brassicaceae, Asteraceae, Chenopodiaceae, Lamiaceae, Apiaceae, Amarillydaceae, Amaranthaceae, and Cucurbitaceae.

Methods

In this study we developed and applied an algorithm to objectively compare numerous genotypes of microgreens intending to select those with the best productivity and phytonutrient profile for cultivation in Space. The selection process consisted of two subsequent phases. The first selection was based on literature data including 39 genotypes and 25 parameters related to growth, phytonutrients (e.g., tocopherol, phylloquinone, ascorbic acid, polyphenols, lutein, carotenoids, violaxanthin), and mineral elements. Parameters were implemented in a mathematical model with prioritization criteria to generate a ranking list of microgreens. The second phase was based on germination and cultivation tests specifically designed for this study and performed on the six top species resulting from the first ranking list. For the second selection, experimental data on phytonutrients were expressed as metabolite production per day per square meter.

Results and discussion

In the final ranking list radish and savoy cabbage resulted with the highest scores based on their productivity and phytonutrient profile. Overall, the algorithm with prioritization criteria allowed us to objectively compare candidate species and obtain a ranking list based on the combination of numerous parameters measured in the different species. This method can be also adapted to new species, parameters, or re-prioritizing the parameters for specific selection purposes.
A sword or a buffet: plant endomembrane system in viral infections
Authors: Jovanović Ivana , Frantová Nicole , Zouhar Jan
Published: August 2023

The plant endomembrane system is an elaborate collection of membrane-bound compartments that perform distinct tasks in plant growth and development, and in responses to abiotic and biotic stresses. Most plant viruses are positive-strand RNA viruses that remodel the host endomembrane system to establish intricate replication compartments. Their fundamental role is to create optimal conditions for viral replication, and to protect replication complexes and the cell-to-cell movement machinery from host defenses. In addition to the intracellular antiviral defense, represented mainly by RNA interference and effector-triggered immunity, recent findings indicate that plant antiviral immunity also includes membrane-localized receptor-like kinases that detect viral molecular patterns and trigger immune responses, which are similar to those observed for bacterial and fungal pathogens. Another recently identified part of plant antiviral defenses is executed by selective autophagy that mediates a specific degradation of viral proteins, resulting in an infection arrest. In a perpetual tug-of-war, certain host autophagy components may be exploited by viral proteins to support or protect an effective viral replication. In this review, we present recent advances in the understanding of the molecular interplay between viral components and plant endomembrane-associated pathways.
Cultivar-dependent phenotypic and chemotypic responses of drug-type Cannabis sativa L. to polyploidization
Authors: Fernandes Hocelayne Paulino , Choi Young Hae , Vrieling Klaas , de Bresser Maikel , Sewalt Bobbie , Tonolo Francesco
Published: August 2023

Cannabis sativa L. is a plant with a wide range of potential medicinal applications. In recent years, polyploidy has gained attention as a potential strategy for rapidly improving C. sativa, which, unlike other modern crops, has not yet benefitted from this established biotechnological application. Currently, no reports on high THCA and CBDA drug-type polyploid cultivars have been published. Moreover, it still needs to be clarified if different cultivars react similarly to polyploidization. For these reasons, we set out to evaluate and compare the phenotype and chemotype of three high Δ9-tetrahydrocannabinolic acid (THCA) and one high cannabidiolic acid (CBDA) drug-type cultivars in their diploid, triploid and tetraploid state through agronomic and metabolomic approaches. Our observations on plant morphology revealed a significant increase in plant height and leaf size with increasing ploidy levels in a cultivar-dependent manner. In contrast, cannabinoids were negatively affected by polyploidization, with the concentration of total cannabinoids, THCA, CBDA and cannabigerolic acid (CBGA) decreasing significantly in higher ploidy levels across all four cultivars. Headspace analysis of volatiles revealed that total volatile content decreased in triploids. On the other hand, tetraploids reacted differently depending on the cultivars. Two THCA dominant cultivars showed an increase in concentrations, while in the other two cultivars, concentrations decreased. Additionally, several rare compounds not present in diploids appeared in higher ploidy levels. Moreover, in one high THCA cultivar, a couple of elite tetraploid genotypes for cannabinoid and volatile production were identified, highlighting the role of cultivar and genotypic variability as an important factor in Cannabis sativa L. polyploids. Overall, our observations on plant morphology align with the giga phenotype observed in polyploids of other plant species. The decrease in cannabinoids and volatiles production in triploids have relevant implications regarding their commercial use. On the other hand, this study found that tetraploidization is a suitable approach to improve Cannabis sativa L. medicinal potential, although the response is cultivar and genotype-dependent. This work lays the ground for further improving, evaluating and harnessing Cannabis sativa L. chemical diversity by the breeding, biotechnological and pharmaceutical sectors.
Functional characterization and allelic mining of OsGLR genes for potential uses in rice improvement
Authors: Zeng Wei , Li Hua , Zhang Fanlin , Wang Xinchen , Rehman Shamsur , Huang Shiji , Zhang Chenyang , Wu Fengcai , Li Jianfeng , Lv Yamei , Zhang Chaopu , Li Min , Li Zhikang , Shi Yingyao
Published: August 2023

Glutamate-like receptor (GLR) genes are a group of regulatory genes involved in many physiological processes of plants. With 26 members in the rice genome, the functionalities of most rice GLR genes remain unknown. To facilitate their potential uses in rice improvement, an integrated strategy involving CRISPR-Cas9 mediated knockouts, deep mining and analyses of transcriptomic responses to different abiotic stresses/hormone treatments and gene CDS haplotype (gcHap) diversity in 3,010 rice genomes was taken to understand the functionalities of the 26 rice GLR genes, which led us to two conclusions. First, the expansion of rice GLR genes into a large gene family during evolution had gone through repeated gene duplication events occurred primarily in two large GLR gene clusters on rice chromosomes 9 and 6, which was accompanied with considerable functional differentiation. Secondly, except for two extremely conserved ones (OsGLR6.2 and OsGLR6.3), rich gcHap diversity exists at the remaining GLR genes which played important roles in rice population differentiation and rice improvement, evidenced by their very strong sub-specific and population differentiation, by their differentiated responses to day-length and different abiotic stresses, by the large phenotypic effects of five GLR gene knockout mutants on rice yield traits, by the significant association of major gcHaps at most GLR loci with yield traits, and by the strong genetic bottleneck effects and artificial selection on the gcHap diversity in populations Xian (indica) and Geng (japonica) during modern breeding. Our results suggest the potential values of the natural variation at most rice GLR loci for improving the productivity and tolerances to abiotic stresses. Additional efforts are needed to determine the phenotypic effects of major gcHaps at these GLR loci in order to identify ‘favorable’ alleles at specific GLR loci specific target traits in specific environments to facilitate their application to rice improvement in future.
Cotyledon peeling method for passion fruit protoplasts: a versatile cell system for transient gene expression in passion fruit (Passiflora edulis)
Authors: Wang Linxi , Liu Haobin , Liu Peilan , Wu Guanwei , Shen Wentao , Cui Hongguang , Dai Zhaoji
Published: August 2023

Passion fruit (Passiflora edulis) is a perennial evergreen vine that grows mainly in tropical and subtropical regions due to its nutritional, medicinal and ornamental values. However, the molecular biology study of passion fruit is extremely hindered by the lack of an easy and efficient method for transformation. The protoplast transformation system plays a vital role in plant regeneration, gene function analysis and genome editing. Here, we present a new method (‘Cotyledon Peeling Method’) for simple and efficient passion fruit protoplast isolation using cotyledon as the source tissue. A high yield (2.3 × 107 protoplasts per gram of fresh tissues) and viability (76%) of protoplasts were obtained upon incubation in the enzyme solution [1% (w/v) cellulase R10, 0.25% (w/v) macerozyme R10, 0.4 M mannitol, 10 mM CaCl2, 20 mM KCl, 20 mM MES and 0.1% (w/v) BSA, pH 5.7] for 2 hours. In addition, we achieved high transfection efficiency of 83% via the polyethylene glycol (PEG)-mediated transformation with a green fluorescent protein (GFP)-tagged plasmid upon optimization. The crucial factors affecting transformation efficiency were optimized as follows: 3 μg of plasmid DNA, 5 min transfection time, PEG concentration at 40% and protoplast density of 100 × 104 cells/ml. Furthermore, the established protoplast system was successfully applied for subcellular localization analysis of multiple fluorescent organelle markers and protein-protein interaction study. Taken together, we report a simple and efficient passion fruit protoplast isolation and transformation system, and demonstrate its usage in transient gene expression for the first time in passion fruit. The protoplast system would provide essential support for various passion fruit biology studies, including genome editing, gene function analysis and whole plant regeneration.
It’s a helluva journey: a qualitative study of patient and clinician experiences of nausea and vomiting syndromes
Authors: Sebaratnam Gabrielle , Law Mikaela , Broadbent Elizabeth , Gharibans Armen A. , Andrews Christopher N. , Daker Charlotte , O’Grady Greg , Calder Stefan , Keane Celia
Published: August 2023

Background

Chronic gastroduodenal disorders including, chronic nausea and vomiting syndrome, gastroparesis, and functional dyspepsia, are challenging to diagnose and manage. The diagnostic and treatment pathways for these disorders are complex, costly and overlap substantially; however, experiences of this pathway have not been thoroughly investigated. This study therefore aimed to explore clinician and patient perspectives on the current clinical pathway.

Methods

Semi-structured interviews were conducted between June 2020 and June 2022 with 11 patients with chronic nausea and vomiting syndrome alone (based on Rome IV criteria) and nine gastroenterologists who treat these conditions. Interviews were recorded, transcribed, and thematically analyzed using a reflexive, iterative, inductive approach. Five key patient themes were identified: (1) the impacts of their chronic gastroduodenal symptoms, (2) the complexity of the clinical journey, (3) their interactions with healthcare providers, (4) the need for advocacy, and (5) their experience of treatments. Five key clinician themes were also identified: (1) these conditions were seen as clinically complex, (2) there is an uncertain and variable clinical pathway, (3) the nuance of investigations, (4) these conditions were difficult to therapeutically manage, and (5) there are barriers to developing a therapeutic relationship.

Conclusion

Findings indicate that both patients and clinicians are dissatisfied with the current clinical care pathways for nausea and vomiting syndromes. Recommendations included the development of more clinically relevant and discriminant tests, standardization of the diagnostic journey, and the adoption of a multidisciplinary approach to diagnosis and treatment.
Causal relationship between particulate matter 2.5 and diabetes: two sample Mendelian randomization
Authors: Kim Joyce Mary , Kim Eunji , Song Do Kyeong , Kim Yi-Jun , Lee Ji Hyen , Ha Eunhee
Published: August 2023

Backgrounds

Many studies have shown particulate matter has emerged as one of the major environmental risk factors for diabetes; however, studies on the causal relationship between particulate matter 2.5 (PM2.5) and diabetes based on genetic approaches are scarce. The study estimated the causal relationship between diabetes and PM2.5 using two sample mendelian randomization (TSMR).

Methods

We collected genetic data from European ancestry publicly available genome wide association studies (GWAS) summary data through the MR-BASE repository. The IEU GWAS information output PM2.5 from the Single nucleotide polymorphisms (SNPs) GWAS pipeline using pheasant-derived variables (Consortium = MRC-IEU, sample size: 423,796). The annual relationship of PM2.5 (2010) were modeled for each address using a Land Use Regression model developed as part of the European Study of Cohorts for Air Pollution Effects. Diabetes GWAS information (Consortium = MRC-IEU, sample size: 461,578) were used, and the genetic variants were used as the instrumental variables (IVs). We performed three representative Mendelian Randomization (MR) methods: Inverse Variance Weighted regression (IVW), Egger, and weighted median for causal relationship using genetic variants. Furthermore, we used a novel method called MR Mixture to identify outlier SNPs.

Results

From the IVW method, we revealed the causal relationship between PM2.5 and diabetes (Odds ratio [OR]: 1.041, 95% CI: 1.008–1.076, P = 0.016), and the finding was substantiated by the absence of any directional horizontal pleiotropy through MR-Egger regression (β = 0.016, P = 0.687). From the IVW fixed-effect method (i.e., one of the MR machine learning mixture methods), we excluded outlier SNP (rs1537371) and showed the best predictive model (AUC = 0.72) with a causal relationship between PM2.5 and diabetes (OR: 1.028, 95% CI: 1.006–1.049, P = 0.012).

Conclusion

We identified the hypothesis that there is a causal relationship between PM2.5 and diabetes in the European population, using MR methods.
Analysis of risk factors for surgical site infection after colorectal surgery: a cross-sectional study in the east of China pre-COVID-19
Authors: Sun Hui , Jiang Hua , Jiang Zhi-Wei , Fang Ge , Dai Zheng-Xiang , Wang Zhiguo , Sun Xiang , Wang Wen
Published: August 2023

Background

The occurrence of surgical site infection (SSI) can prolong the postoperative hospital stay, increase the economic burden of patients, and even endanger their lives. The purpose of this study was to investigate the incidence, risk factors, and microbiology of SSI after colorectal surgery (CRS) and to provide a basis for the prevention and control of SSI.

Methods

A single-center, prospective, cross-sectional study of adult patients undergoing CRS was conducted from 2010–2019. Univariate and multivariate logistic regression models were used to collect and analyze demographic information, hospital characteristics, and potential perioperative risk factors of SSI.

Results

A total of 3,302 eligible patients were included in this study, with 213 cases experiencing SSIs, resulting in an infection rate of 6.45%. Notably, the incidence of SSI decreased from 13.33% in 2010 to 3.56% in 2019 (Ptrend < 0.001). Escherichia coli accounted for the majority of isolated microorganisms (37.09%), with 49 strains exhibiting resistance to one or more antibiotics (35.25%). Multivariate analysis showed that diabetes, anastomosis leakage, wound classification (contaminated/dirty), operation duration, blood loss greater than 200 ml, and NNIS risk index score for 2 or 3 were independent risk factors. Conversely, laparoscopic approach, preoperative bowel preparation and preoperative albumin levels emerged as protective factors against SSI after CRS. Furthermore, compared to non-SSI patients, SSI patients had a significantly higher 30-day mortality rate following surgery (0.23% vs. 2.35%, p < 0.05).

Conclusion

SSI after CRS was susceptible to many factors, and the pathogen of SSI was mainly Escherichia coli. In clinical practice, measures such as correcting preoperative hypoproteinemia, choosing laparoscopic surgery, preoperative bowel preparation and shortening the duration of surgery should be taken to reduce the incidence of SSI.
Neuromelanin-sensitive MRI correlates of cognitive and motor function in Parkinson's disease with freezing of gait
Authors: Huddleston Daniel E. , Chen Xiangchuan , Hwang Kristy , Langley Jason , Tripathi Richa , Tucker Kelsey , McKay J. Lucas , Hu Xiaoping , Factor Stewart A.
Published: August 2023

Substantia nigra pars compacta (SNc) and locus coeruleus (LC) are neuromelanin-rich nuclei implicated in diverse cognitive and motor processes in normal brain function and disease. However, their roles in aging and neurodegenerative disease mechanisms have remained unclear due to a lack of tools to study them in vivo. Preclinical and post-mortem human investigations indicate that the relationship between tissue neuromelanin content and neurodegeneration is complex. Neuromelanin exhibits both neuroprotective and cytotoxic characteristics, and tissue neuromelanin content varies across the lifespan, exhibiting an inverted U-shaped relationship with age. Neuromelanin-sensitive MRI (NM-MRI) is an emerging modality that allows measurement of neuromelanin-associated contrast in SNc and LC in humans. NM-MRI robustly detects disease effects in these structures in neurodegenerative conditions, including Parkinson's disease (PD). Previous NM-MRI studies of PD have largely focused on detecting disease group effects, but few studies have reported NM-MRI correlations with phenotype. Because neuromelanin dynamics are complex, we hypothesize that they are best interpreted in the context of both disease stage and aging, with neuromelanin loss correlating with symptoms most clearly in advanced stages where neuromelanin loss and neurodegeneration are coupled. We tested this hypothesis using NM-MRI to measure SNc and LC volumes in healthy older adult control individuals and in PD patients with and without freezing of gait (FOG), a severe and disabling PD symptom. We assessed for group differences and correlations between NM-MRI measures and aging, cognition and motor deficits. SNc volume was significantly decreased in PD with FOG compared to controls. SNc volume correlated significantly with motor symptoms and cognitive measures in PD with FOG, but not in PD without FOG. SNc volume correlated significantly with aging in PD. When PD patients were stratified by disease duration, SNc volume correlated with aging, cognition, and motor deficits only in PD with disease duration >5 years. We conclude that in severe or advanced PD, identified by either FOG or disease duration >5 years, the observed correlations between SNc volume and aging, cognition, and motor function may reflect the coupling of neuromelanin loss with neurodegeneration and the associated emergence of a linear relationship between NM-MRI measures and phenotype.
Health disparities in the detection and prevalence of pediatric obstructive sleep apnea
Authors: McQuillan Maureen E. , Jones Ian C. , Abu Mayyaleh Haneen F. , Khan Shajna , Honaker Sarah M.
Published: August 2023

Introduction

Pediatric Obstructive Sleep Apnea (OSA) is associated with negative health outcomes, behavior problems, and poor academic performance when left untreated. Prior research has shown that children from racial and ethnic minority backgrounds and those living in lower socioeconomic status (SES) homes or neighborhoods have higher prevalence of OSA but lower likelihood of receiving evidence-based care for OSA. Disparities in pediatric OSA detection (e.g., timely assessment and diagnosis) likely contribute to this observed inequity in receiving treatment. A polysomnogram (PSG) is the gold standard for diagnosing OSA but completing PSG can be challenging. Study aims were to examine racial, ethnic, and SES differences in (1) OSA prevalence and severity and (2) OSA detection, specifically PSG completion rates, timing since referral, and age of diagnosis.

Methods

Children (aged 1–18, N = 1,860, 56% male) were referred for PSG during a 6-month period. Participants' racial/ethnic background were as follows: 64.8% White non-Hispanic, 23.5% Black non-Hispanic, 9.4% White Hispanic, and 2.4% other. Children predominantly had Medicaid insurance (64.5%). SES was measured by insurance type and neighborhood SES using the Distressed Communities Index (DCI) for each participant's zip code (Economic Innovations Group; https://eig.org/dc). Covariates included child age and sex, BMI, premature birth status, and smoke exposure in the home.

Results

We replicated previous research by showing that children from minority racial/ethnic backgrounds and lower SES backgrounds had higher prevalence rates of OSA and worse disease severity. Across racial, ethnic, and socioeconomic backgrounds, only 31.6% of the children referred successfully completed PSG. Insurance coverage (Medicaid or private vs. self-pay), was an important factor in predicting earlier timing and better completion rates of PSG, which is essential for successful diagnosis and treatment of pediatric OSA.