bluuebunny/crossref_metadata_2025 huggingface dataset:
Additional PD-1 inhibitor improves complete response to induction chemotherapy in locally advanced nasopharyngeal carcinoma
Authors: Yu Yi-Feng , Lu Guan-Zhong , Wang Run-Jie , Song Yu-Kun , Wu San-Gang
Published: June 2024

Purpose

To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma (LANPC).

Methods

Patients with stage III–IVA NPC who received IC or IC + PD-1 inhibitor were included. The chi-square test and multivariate logistic regression analysis were used for statistical analysis.

Results

A total of 225 patients were identified, including 193 (85.8%) and 32 (14.2%) who received IC alone and IC + PD-1 inhibitor, respectively. The addition of PD-1 inhibitor to IC significantly improved the tumor response than those treated with IC alone. The complete response (CR), partial response, stable disease, and progressive disease rates of 4.7% vs. 31.3%, 69.4% vs. 62.5%, 24.9% vs. 6.3%, and 1.0% vs. 0% in patients receiving IC alone and IC + PD-1 inhibitor, respectively (P<0.001). The results of the multivariate logistic regression showed that receiving PD-1 inhibitor was an independent predictor influencing the CR rate of patients (odds ratio 9.814, P<0.001). The most common toxicity by using IC and PD-1 inhibitor was hematological toxicity. In terms of non-hematological toxicity, 7 (21.9%) patients experienced thyroid dysfunction and all of them were hyperthyroidism. No grade 5 toxicities were found. In those who received IC and PD-1 inhibitor, the one-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 100%, 96.9%, 96.9%, and 100%, respectively.

Conclusion

The addition of PD-1 inhibitor to IC has promise as an effective treatment approach for LANPC. More studies are expected to provide further insights into the optimal use of this treatment strategy, paving the way for more personalized and effective treatment options for patients with LANPC.
The potential of bacterial anti-phagocytic proteins in suppressing the clearance of extracellular vesicles mediated by host phagocytosis
Authors: Sun Jiacong , Chen Congcong , Pan Pengpeng , Zhang Keyi , Xu Jinrui , Chen Cheng
Published: June 2024

Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcγ receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by Group A Streptococcus and ImpA secreted by Pseudomonas aeruginosa, as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers αVβ3 on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using pre-loading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EV-based cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation.
Dual role of autoantibodies to heat shock proteins in autoimmune diseases
Authors: Tukaj Stefan
Published: June 2024

Autoimmune diseases are characterized by the recognition of self-antigens (autoantigens) by immune system cells. Loss of immunological tolerance may lead to the generation of autoantibodies and, consequently, tissue damage. It has already been proven that highly immunogenic bacterial and autologous extracellular heat shock proteins (eHsps) interact with immune cells of the innate and adaptive arms of the immune system. The latter interactions may stimulate a humoral (auto)immune response and lead to the generation of anti-Hsps (auto)antibodies. Although circulating levels of anti-Hsps autoantibodies are often elevated in patients suffering from multiple inflammatory and autoimmune diseases, their role in the development of pathological conditions is not fully established. This mini-review presents the dual role of anti-Hsps autoantibodies - protective or pathogenic - in the context of the development of selected autoimmune diseases.
The geographical distribution of the malaria vector Anopheles arabiensis in Cabo Verde, 2016–2023
Authors: Leal Silvânia Da Veiga , Sousa Celivianne de , Monteiro Davidson Daniel Sousa Rocha , Mendonça Maria da Luz Lima , Gonçalves Adéritow Augusto Lopes Macedo , DePina Adilson José
Published: June 2024

Background

Integrated malaria vector control is crucial to eliminate or reduce infection risk. Understanding vector species distribution, behavior, and environmental factors such as climate, topography, and preferred aquatic habitats is essential.

Objectives

Herein, we aim to compile data from 2016 to 2023 on the primary malaria vector in Cabo Verde to support health surveillance and elimination certification.

Materials and methods

Mosquitoes larvae were collected using standard sampling tools, and adults using Biogents Sentinel traps, mechanical aspiration and CDC UV light traps, both indoor and in the surroundings of urban and rural areas.

Results

Six hundred fifty-seven specimens of Anopheles gambiae s.l. were identified by morphological methods and PCR-based techniques as Anopheles arabiensis in 12 municipalities from six of the nine inhabited islands, namely, São Vicente, São Nicolau, Maio, Boavista, Santiago, and Santo Antão.

Conclusions

We believe this is the first scientific report of the presence of An. arabiensis on the island of Santo Antão. The Anopheles arabiensis remains the only species in the An. gambiae complex in the Cabo Verde islands. These results offer vital insights for epidemiological surveillance and effective malaria control, especially in light of the recent WHO certification declaring the country malaria-free. However, it is imperative to conduct further studies that comprehensively address epidemiological and entomological aspects, with a special focus on bionomics, genetic determinants of the parasite-vector association, and the characterization of larval habitats. These investigations have the potential to guide a more informed and strategic implementation of malaria vector control measures in Cabo Verde.
A comparative analysis of growth and nutritional quality of the hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) in a simulated pond system and a recirculating aquaculture system
Authors: Qu Yingsha , Yin Zhendong , Fan Xiangyu , Hu Haiyan , Cui Hongwu , Cui Zhengguo , Qu Keming , Li Hao
Published: June 2024

Groupers, as a popular economic fish species, are now more frequently cultured in land-based facilities, however, traditional pond-farming methods are plagued by frequent disease outbreaks, unstable economic benefits, and environmental pollution. To explore a new farming mode for a grouper, an 80-day cultivation experiment was conducted using both a simulated pond system (SPS) and a recirculating aquaculture system (RAS). The research aims to evaluate the growth performance, health (pathogenic bacteria, intestinal microbiota), off-flavor compounds (geosmin, 2-methylisoborneol), and nutritional component (amino acids, fatty acid composition and content) of a hybrid grouper (Pinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) under different aquaculture systems. The results showed that the hybrid grouper in a RAS exhibited better growth performance; the concentration of Vibrio in the fish tissue in the RAS was significantly lower than that in the SPS. Moreover, the content of fresh amino acids in the RAS was significantly higher, and the levels of saturated fatty acids (SFAs) and ω-6 polyunsaturated fatty acids (ω-6PUFAs) were significantly higher in the RAS. This finding indicates the superior flavor and nutritional value of the grouper. These results prove that the RAS is suitable for the widespread cultivation of grouper.
Evaluation of the Pacific oyster marine aquaculture suitability in Shandong, China based on GIS and remote sensing
Authors: Li Chunlin , Liu Yang , Yin Zixu , Si Zhangqi , Li Qi , Saitoh Sei-Ichi
Published: June 2024

The Pacific oyster (Crassostrea gigas) is a marine aquaculture species with rapid production growth in recent years. China accounts for nearly 90% of global production by 2021, especially in Shandong province. Evaluating suitability is crucial for ensuring the sustainable growth of Pacific oyster marine aquaculture and achieving a blue transition. This study developed a suitability evaluation model for Pacific oyster marine aquaculture using a Geographic Information System (GIS), Maximum Entropy (MaxEnt) model, remote sensing, and reanalysis data. A literature review and Analytic Hierarchy Process (AHP) were used to establish an evaluation model encompassing water quality, hydrology, climate and meteorology, and socioeconomic factors. The results showed that within a 20 km range of the Shandong coast, 49% of the area was highly suitable, 51% was moderately suitable, and the overall annual high score proportion (HSP) fluctuated around 50%, with higher suitability observed in the spring and autumn. The inner bays of the coastal areas (Laizhou, Rongcheng, Jimo) exhibited high suitability (HSP over 80%); in contrast, the offshore areas (Changdao, Rushan) farther from the coast had lower suitability and showed significant monthly variations. The result was consistent with the spatial distribution and temporal variation of Shandong’s existing Pacific oyster marine aquaculture areas. The study also found that El Niño significantly impacts Rongcheng, Rushan, and Jimo during summer. We predicted an overall increase of suitability in the Shandong offshore areas under future climate change scenarios, with a more significant increase of suitability in the north. El Niño-Southern Oscillation (ENSO) influenced the concentration of parameters such as chlorophyll-a (Chl-a) and total suspended sediment (TSS) in the coastal waters through its impact on precipitation (Pr), resulting in suitability fluctuations.
Study on the fountain effect of the bubble plume formed by submarine gas pipeline leakage
Authors: Wang Hao , Jia Yunxin , Liu Xiaolei , Liu Jiahao , Wang Kan , Jiang Jinnan , Xu Hang , Tang Jiamin , Sun Chen
Published: June 2024

The leakage from submarine gas pipelines presents a significant threat to marine ecological environments. Bubble plumes can be formed when gas escapes, which can give rise to the distinctive fountain phenomenon by interacting with the water surface. It is imperative to understand the factors that influence the physical dimensions and temporal characteristics of the resulting fountain to elucidate the formation mechanism of this phenomenon. Gas leakage experiments under various conditions are conducted to investigate the dynamic characteristics of the fountain in the study. The findings reveal the following: The initial kinetic energy of the escaping gas varies significantly under different leakage scenarios, resulting in the positive correlation between the maximum fountain height and width, as well as the leakage pressure and diameter of the leakage hole. Then, the analysis of dimensional indicates that the dynamic equilibrium of the bubbles is intricately tied to both the Froude number (Fr) and Reynolds number (Re). Notably, the effect of leakage pressure on Fr and Re follows similar patterns. However, the trends of Fr and Re values across varying leak hole diameters are opposite. At last, the frequency analysis of the time series data related to the fountain height demonstrates that higher leakage pressure and larger leak hole diameters result in an increase in both the main frequency and bandwidth. The research results offer valuable insights for evaluating the impact of gas leakage intensity on the marine environment by analyzing the size parameters of fountain.
Effect of photoperiod and temperature on bioproduct production from juvenile sporophytes of Macrocystis pyrifera
Authors: Purcell Diane , Wheeler Thomas T. , Hayes Maria , Packer Michael A.
Published: June 2024

The giant kelp (Macrocystis pyrifera (Linnaeus) C. Agardh 1820) is a habitat-forming brown seaweed in temperate systems with an unexplored potential as a source of seaweed bioproducts. This study used M. pyrifera sporophytes sourced in Tasmania, Australia, to investigate the effect of photoperiod and temperature on growth rates and the nutritional characteristics of the resulting juvenile biomass. Four cultivation treatments combined growth temperatures of 12 °C, 15 °C, 18 °C with light:dark (L:D) of 12:12 and 16:8 (L:D) photoperiods, (12 °C – (12:12); 12 °C – (16:8); 15 °C – (12:12); 18 °C – (12:12) to investigate their effect on the number and size of sporophytes, biomass accumulation and nutritional composition. After 60 days of cultivation the 12 °C – (12:12) treatment had the greatest number of juvenile sporophytes, and the greatest biomass of 14 ± 1.3 g dry weight (DW). The lowest biomass of 1 g DW, was obtained from the 18 °C – (12:12) treatment. The protein content across all treatments ranged from 16-22.48% DW, with the 12 °C (12:12) treatment having largest range, then the 12°C (16:18) treatment was next with 18.48-22.48% DW, and the 15°C (12:12) treatment had the lowest protein range with 16.48-18% DW. These results are in the range of protein content previously reported for brown seaweeds of 5-20%. Total polysaccharide content ranged from 9.6-16.2% DW with the highest content of 16.2% DW obtained for the 15 °C – (12:12) treatment, and the lowest total polysaccharide content of 9.6% DW obtained for the 12 °C (16:18) treatment. After 66 days of cultivation, the highest yield of sulphated polysaccharides of 0.4% DW was obtained for the 12 °C (12:12) treatment. Total fatty acids were analysed, with the highest polyunsaturated fatty acid content of 60.4% detected in the 12 °C (12:12) treatment. This study demonstrates that temperature and photoperiod are factors impacting juvenile sporophyte growth, biomass accumulation and biochemical composition. The study showed the least stressed sporophytes produced the most potentially beneficial nutritional or bioactive profile.
On the thermal performance of radiative stagnation-point hybrid nanofluid flow across a wedge with heat source/sink effects and sensitivity analysis
Authors: Chakraborty Anomitra , Saadeh Rania , Qazza Ahmad , Zomot Naser , Janapatla Pranitha , Khan Umair , Qraywi Mohammad , Muhammad Taseer
Published: June 2024

The present article aims to examine the thermal performance and the sensitivity analysis of a GO−TiO2/water hybrid nanofluid in the presence of different nanoparticle shapes along with heat absorption and thermal radiation effects over a wedge geometry. Analyzing the effects of heat generation and radiation effects is one of the key studies conducted by researchers in various nanofluid flows over some required geometries. However, a combined study of these effects has yet to be studied over a moving wedge, and that combination defines the novelty of the work. Similarity transformations are implemented to the governing equations to obtain the final set of nondimensional equations, which are solved using the bvp4c code in MATLAB. The results obtained were in close agreement with the published results. The Nusselt number decreased with an increase in the heat source parameter Q, and it increased with an increasing Hartree pressure gradient β and thermal radiation parameter Rd. The sensitivity is statistically analyzed for the variations in radiation effect, heat source, and pressure gradient parameters on the Nusselt number. The high values for R2=99.99% and Adj R2=99.96% validate the ANOVA results obtained using a Box–Behnken design (BBD) model in the response surface methodology (RSM) with 14 degrees of freedom. The input parameters Rd and β show positive sensitivity, while Q shows negative sensitivity toward the skin friction. The Nusselt number proves to be most sensitive toward the pressure gradient parameter. TiO2, graphene (Gr), and the derivative forms of graphene, are gaining much importance due to their wide applications in the oil and petroleum industries. Thus, this study contributes to lubrication purposes, emulsion stabilizers, oxalic acid removal, anti-corrosive properties, etc.
Combined coagulation and inflammation markers as predictors of venous thrombo-embolism and death in COVID-19
Authors: Zhu Jaja , Bouzid Raïda , Travert Benoît , Géri Guillaume , Cohen Yves , Picod Adrien , Heming Nicholas , Rottman Martin , Joly-Laffargue Bérangère , Veyradier Agnès , Capron Claude , Coppo Paul
Published: June 2024

Background

The COVID-19 pandemic related to SARS-CoV-2 virus was responsible for global pandemic. The severe form of the disease was linked to excessive activation of immune pathways together with a systemic cytokine storm response and thrombotic venous or arterial complications. Factors predicting severe outcomes including venous and/or pulmonary thrombosis (VT) and death were identified, but the prognostic role of their combination was not addressed extensively.

Objectives

We investigated the role of prognostic factors from the coagulation or inflammatory pathways to better understand the outcome of the disease.

Methods

For this, we prospectively studied 167 SARS-CoV-2-positive patients from admission in intensive care units (ICU) or emergency departments from four academic hospitals over a 14-month period. Besides standard biology, we assessed serum concentrations of inflammatory markers, coagulation factors and peripheral blood cells immunophenotyping.

Results

Thirty-nine patients (23.3%) developed VT and 30 patients (18%) died. By univariate analysis, C-reactive protein (CRP) level > 150 mg/L, interleukin-6 (IL-6) ≥ 20 pg/mL, D-dimers > 1,500 μg/L, ADAMTS13 activity ≤ 50%, Von

Conclusion

A combination of coagulation and inflammatory markers can refine the prognostication of severe outcome in COVID-19, and could be useful for the initial evaluation of other types of viral infection.
Unveiling shared biomarkers and therapeutic targets between systemic lupus erythematosus and heart failure through bioinformatics analysis
Authors: Zhou Ting , Pan Jing , Yan Chenghui , Yuan Jing , Song Haixu , Han Yaling
Published: June 2024

Background

Systemic lupus erythematosus (SLE) is frequently accompanied by various complications, with cardiovascular diseases being particularly concerning due to their high mortality rate. Although there is clinical evidence suggesting a potential correlation between SLE and heart failure (HF), the underlying shared mechanism is not fully understood. Therefore, it is imperative to explore the potential mechanisms and shared therapeutic targets between SLE and HF.

Methods

The SLE and HF datasets were downloaded from the NCBI Gene Expression Omnibus database. Differentially expressed genes (DEGs) in both SLE and HF were performed using “limma” R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) analyses were conducted to analyze the enriched functions and pathways of DEGs in both SLE and HF datasets. Protein–Protein Interaction network (PPI) and the molecular complex detection (MCODE) plugins in the Cytoscape software were performed to identify the shared hub genes between SLE and HF datasets. R package “limma” was utilized to validate the expression of hub genes based on SLE (GSE122459) and HF (GSE196656) datasets. CIBERSORT algorithm was utilized to analyze the immune cell infiltration of SLE and HF samples based on SLE (GSE112087) and HF (GSE116250) datasets. A weighted gene co-expression network analysis (WGCNA) network was established to further validate the hub genes based on HF dataset (GSE116250). Molecular biology techniques were conducted to validate the hub genes.

Results

999 shared DGEs were identified between SLE and HF datasets, which were mainly enriched in pathways related to Th17 cell differentiation. 5 shared hub genes among the common DGEs between SLE and HF datasets were screened and validated, including HSP90AB1, NEDD8, RPLP0, UBB, and UBC. Additionally, 5 hub genes were identified in the central part of the MEbrown module, showing the strongest correlation with dilated cardiomyopathy. HSP90AB1 and UBC were upregulated in failing hearts compared to non-failing hearts, while UBB, NEDD8, and RPLP0 did not show significant changes.

Conclusion

HSP90AB1 and UBC are closely related to the co-pathogenesis of SLE and HF mediated by immune cell infiltration. They serve as promising molecular markers and potential therapeutic targets for the treatment of SLE combined with HF.
Global prevalence of mutation in the mgrB gene among clinical isolates of colistin-resistant Klebsiella pneumoniae: a systematic review and meta-analysis
Authors: Khoshbayan Amin , Narimisa Negar , Elahi Zahra , Bostanghadiri Narjess , Razavi Shabnam , Shariati Aref
Published: June 2024

Background

Colistin is used as a last resort for managing infections caused by multidrug-resistant bacteria. However, the high emergence of colistin-resistant strains has restricted the clinical use of this antibiotic in the clinical setting. In the present study, we evaluated the global prevalence of the mutation in the mgrB gene, one of the most important mechanisms of colistin resistance in Klebsiella pneumoniae.

Methods

Several databases, including Scopus, Medline (via PubMed), and Web of Science, were searched (until August 2023) to identify those studies that address the mgrB mutation in clinical isolates of K. pneumoniae. Using Stata software, the pooled prevalence of mgrB mutation and subgroup analyses for the year of publication, country, continent, mgrB mutation types, and detection methods of mgrB mutation were analyzed.

Results

Out of the 115 studies included in the analysis, the prevalence of mgrB mutations in colistin-resistant K. pneumoniae isolates was estimated at 65% of isolates, and mgrB variations with insertional inactivation had the highest prevalence among the five investigated mutations with 69%. The year subgroup analysis indicated an increase in mutated mgrB from 46% in 2014 to 61% in 2022. Europe had the highest prevalence of mutated mgrB at 73%, while Africa had the lowest at 54%.

Conclusion

Mutations in the mgrB gene are reported as one of the most common mechanisms of colistin resistance in K. pneumoniae, and the results of the present study showed that 65% of the reported colistin-resistant K. pneumoniae had a mutation in this gene.
Removal of metals and emergent contaminants from liquid digestates in constructed wetlands for agricultural reuse
Authors: Porras-Socias Pau , Tomasino Maria Paola , Fernandes Joana P. , De Menezes Alexandre B. , Fernández Belén , Collins Gavin , Alves Maria João , Castro Ricardo , Gomes Carlos R. , Almeida C. Marisa R. , Mucha Ana Paula
Published: June 2024

Given the increasing pressure on water bodies, it is imperative to explore sustainable methodologies for wastewater treatment and reuse. The simultaneous presence of multiples contaminants in complex wastewater, such as the liquid effluents from biogas plants, can compromise biological treatment effectiveness for reclaiming water. Vertical subsurface flow constructed wetlands were established as low-cost decentralized wastewater treatment technologies to treat the liquid fraction of digestate from municipal organic waste with metals, antibiotics, and antibiotic resistance genes, to allow its reuse in irrigation. Twelve lab-scale planted constructed wetlands were assembled with gravel, light expanded clay aggregate and sand, testing four different treating conditions (liquid digestate spiked with oxytetracycline, sulfadiazine, or ofloxacin, at 100 μg/ L, or without dosing) during 3 months. Physicochemical parameters (pH, chemical oxygen demand (COD), nutrients, metals, and antibiotics), the microbial communities dynamics (through 16S high-throughput sequencing) and antibiotic resistance genes removal (qPCR) were monitored in influents and effluents. Systems removed 85.8%–96.9% of organic matter (as COD), over 98.1% of ammonium and phosphate ions, and 69.3%–99.4% of nitrate and nitrite ions, with no significant differences between the presence or absence of antibiotics. Removal of Fe, Mn, Zn, Cu, Pb and Cr exceeded 82% in all treatment cycles. The treatment also removed oxytetracycline, sulfadiazine and ofloxacin over 99%, and decreased intl1, tetA, tetW, sul1 and qnrS gene copies. Nonetheless, after 3 months of ofloxacin dosing, qnrS gene started being detected. Removal processes relied on high HRT (14 days) and various mechanisms including sorption, biodegradation, and precipitation. Microbial community diversity in liquid digestate changed significantly after treatment in constructed wetlands with a decrease in the initial Firmicutes dominance, but with no clear effect of antibiotics on the microbial community structure. Removals above 85% and 94% were observed for Streptococcus and Clostridium, respectively. Results suggest that vertical subsurface flow constructed wetlands were a suitable technology for treating the liquid digestate to reuse it in irrigation agricultural systems, contributing to the circular bioeconomy concept. However, a more profound understanding of effective wastewater treatment strategies is needed to avoid antibiotic resistance genes dissemination.
Formic acid enhances whole-plant mulberry silage fermentation by boosting lactic acid production and inhibiting harmful bacteria
Authors: Hao Lihong , Jiang Fugui , Wang Yanping , Wang Huaizhong , Hu Hongmei , You Wei , Hu Xin , Cheng Haijian , Wang Cheng , Song Enliang
Published: June 2024

Mulberry has also been regarded as a valuable source of forage for ruminants. This study was developed to investigate the impact of four additives and combinations thereof on fermentation quality and bacterial communities associated with whole-plant mulberry silage. Control fresh material (FM) was left untreated, while other groups were treated with glucose (G, 20 g/kg FM), a mixture of Lactobacillus plantarum and L. buchneri (L, 106 CFU/g FM), formic acid (A, 5 mL/kg FM), salts including sodium benzoate and potassium sorbate (S, 1.5 g/kg FM), a combination of G and L (GL), a combination of G and A (GA), or a combination of G and S (GS), followed by ensiling for 90 days. Dry matter content in the A, S, GA, and GS groups was elevated relative to the other groups (p < 0.01). Relative to the C group, all additives and combinations thereof were associated with reductions in pH and NH3-N content (p < 0.01). The A groups exhibited the lowest pH and NH3-N content at 4.23 and 3.27 g/kg DM, respectively (p < 0.01), whereas the C groups demonstrated the highest values at 4.43 and 4.44 g/kg DM, respectively (p < 0.01). The highest levels of lactic acid were observed in the GA and A groups (70.99 and 69.14 g/kg DM, respectively; p < 0.01), followed by the GL, L, and GS groups (66.88, 64.17 and 63.68 g/kg DM, respectively), with all of these values being higher than those for the C group (53.27 g/kg DM; p < 0.01). Lactobacillus were the predominant bacteria associated with each of these samples, but the overall composition of the bacterial community was significantly impacted by different additives. For example, Lactobacillus levels were higher in the G, A, and GA groups (p < 0.01), while those of Weissella levels were raised in the L, GL, and GS groups (p < 0.01), Pediococcus levels were higher in the A and GA groups (p < 0.01), Enterococcus levels were higher in the G and S groups (p < 0.01), and Lactococcus levels were raised in the S group (p < 0.01). Relative to the C group, a reduction in the levels of undesirable Enterobacter was evident in all groups treated with additives (p < 0.01), with the greatest reductions being evident in the A, S, GA, and GS groups. The additives utilized in this study can thus improve the quality of whole-plant mulberry silage to varying extents through the modification of the associated bacterial community, with A and GA addition achieving the most efficient reductions in pH together with increases in lactic acid content and the suppression of undesirable bacterial growth.
Association of coagulase-negative staphylococci with orthopedic infections detected by in-house multiplex real-time PCR
Authors: Wang Ying , Liu Chao , Xia Wenbo , Cui Yanxiang , Yu Linhong , Zhao Dan , Guan Xiaoxuan , Wang Yingdi , Wang Yani , Li Yisong , Hu Jianqiang , Liu Jie
Published: June 2024

Introduction

Clinical significance of coagulase-negative staphylococci (CoNS) has been gradually acknowledged in both healthcare and clinical research, but approaches for their precise discrimination at the species level remain scarce. The current study aimed to evaluate the association of CoNS with orthopedic infections, where accurate and prompt identification of etiology is crucial for appropriate diagnosis and treatment decision-making.

Methods

A 16S rRNA-based quantitative PCR (qPCR) assay was developed for the detection of Staphylococcus genus and two panels of 3-plex qPCR assays for further differentiation of six CoNS species with remarkable clinical significance, including S. epidermidis, S. haemolyticus, S. simulans, S. hominis, S. capitis, and S. caprae. All the assays exhibited excellent analytical performance. ΔCq (quantification cycle) between 16S rRNA and CoNS species-specific targets was established to determine the primary CoNS. These methods were applied to detect CoNS in wound samples from orthopedic patients with and without infection.

Results and discussion

Overall, CoNS were detected in 17.8% (21/118) of patients with clinically suspected infection and in 9.8% (12/123) of patients without any infection symptom (p < 0.05). Moreover, the association with infection was found to be bacterial quantity dependent. S. epidermidis was identified as the predominant species, followed by S. simulans, S. haemolyticus, and S. hominis. Male sex, open injury, trauma, and lower extremity were determined as risk factors for CoNS infections. CoNS-positive patients had significantly longer hospitalization duration (20 days (15, 33) versus 13 days (7, 22) for Staphylococcus-negative patients, p = 0.003), which could be a considerable burden for healthcare and individual patients. Considering the complex characteristics and devastating consequences of orthopedic infections, further expanding the detection scope for CoNS may be pursued to better understand the etiology of orthopedic infections and to improve therapeutic strategies.
Are there double knots in proteins? Prediction and in vitro verification based on TrmD-Tm1570 fusion from C. nitroreducens
Authors: Perlinska Agata P. , Nguyen Mai Lan , Pilla Smita P. , Staszor Emilia , Lewandowska Iwona , Bernat Agata , Purta Elżbieta , Augustyniak Rafal , Bujnicki Janusz M. , Sulkowska Joanna I.
Published: June 2024

We have been aware of the existence of knotted proteins for over 30 years—but it is hard to predict what is the most complicated knot that can be formed in proteins. Here, we show new and the most complex knotted topologies recorded to date—double trefoil knots (31#31). We found five domain arrangements (architectures) that result in a doubly knotted structure in almost a thousand proteins. The double knot topology is found in knotted membrane proteins from the CaCA family, that function as ion transporters, in the group of carbonic anhydrases that catalyze the hydration of carbon dioxide, and in the proteins from the SPOUT superfamily that gathers 31 knotted methyltransferases with the active site-forming knot. For each family, we predict the presence of a double knot using AlphaFold and RoseTTaFold structure prediction. In the case of the TrmD-Tm1570 protein, which is a member of SPOUT superfamily, we show that it folds in vitro and is biologically active. Our results show that this protein forms a homodimeric structure and retains the ability to modify tRNA, which is the function of the single-domain TrmD protein. However, how the protein folds and is degraded remains unknown.
Therapeutic potential of mesenchymal stem cell-derived exosomes in skeletal diseases
Authors: Yang Xiaobo , Zhang Shaodian , Lu Jinwei , Chen Xiaoling , Zheng Tian , He Rongxin , Ye Chenyi , Xu Jianbin
Published: June 2024

Skeletal diseases impose a considerable burden on society. The clinical and tissue-engineering therapies applied to alleviate such diseases frequently result in complications and are inadequately effective. Research has shifted from conventional therapies based on mesenchymal stem cells (MSCs) to exosomes derived from MSCs. Exosomes are natural nanocarriers of endogenous DNA, RNA, proteins, and lipids and have a low immune clearance rate and good barrier penetration and allow targeted delivery of therapeutics. MSC-derived exosomes (MSC-exosomes) have the characteristics of both MSCs and exosomes, and so they can have both immunosuppressive and tissue-regenerative effects. Despite advances in our knowledge of MSC-exosomes, their regulatory mechanisms and functionalities are unclear. Here we review the therapeutic potential of MSC-exosomes for skeletal diseases.
Breed and timepoint-based analysis of chicken harderian gland transcriptome during Newcastle disease virus challenge
Authors: Vanamamalai Venkata Krishna , Priyanka E. , Kannaki T. R. , Sharma Shailesh
Published: June 2024

Introduction: Newcastle disease is a highly infectious disease caused by the Newcastle Disease Virus (NDV) and has a devastating financial impact on the global chicken industry. It was previously established that Leghorn and Fayoumi breeds of chicken exhibit variable resistance against NDV infection. The harderian gland is the less studied tissue of the chicken, known to play an essential role in the immune response.

Methods: Our previous study, we reported differential gene expression and long noncoding RNAs (lncRNAs) between challenged and non-challenged chickens in the Harderian gland transcriptomic data. Now, we report the analysis of the same data studying the differential expression patterns between Leghorn and Fayoumi and between different timepoints during disease. First, the pipeline FHSpipe was used for identification of lncRNAs, followed by differential expression analysis by edgeR (GLM), functional annotation by OmicsBox, co-expression analysis using WGCNA and finally validation of selected lncRNAs and co-expressing genes using qRT-PCR.

Results: Here, we observed that Leghorn showed a higher number of upregulated immune-related genes than Fayoumi in timepoint-based analysis, especially during the initial stages. Surprisingly, Fayoumi, being comparatively resistant, showed little difference between challenged and non-challenged conditions and different time points of the challenge. The breed-based analysis, which compared Leghorn with Fayoumi in both challenged and non-challenged conditions separately, identified several immune-related genes and positive co-expressing cis lncRNAs to be upregulated in Fayoumi when compared to Leghorn in both challenged and non-challenged conditions.

Discussion: The current study shows that Leghorn, being comparatively more susceptible to NDV than Fayoumi, showed several immune-related genes and positive co-expressing cis lncRNAs upregulated in challenged Leghorn when compared to non-challenged Leghorn and also in different timepoints during challenge. While, breed-based analysis showed that there were more upregulated immune genes and positive cis-lncRNAs in Fayoumi than Leghorn. This result clearly shows that the differences in the expression of genes annotated with immune-related GO terms and pathways, i.e., immune-related genes and the co-expressing cis-lncRNAs between Leghorn and Fayoumi, and their role in the presence of differences in the resistance of Leghorn and Fayoumi chicken against NDV.

Conclusion: These immune-genes and cis-lncRNAs could play a role in Fayoumi being comparatively more resistant to NDV than Leghorn. Our study elucidated the importance of lncRNAs during the host defense against NDV infection, paving the way for future research on the mechanisms governing the genetic improvement of chicken breeds.
Dysregulation of arginine methylation in tumorigenesis
Authors: Li Xiao , Song Yaqiong , Mu Weiwei , Hou Xiaoli , Ba Te , Ji Shaoping
Published: June 2024

Protein methylation, similar to DNA methylation, primarily involves post-translational modification (PTM) targeting residues of nitrogen-containing side-chains and other residues. Protein arginine methylation, occurred on arginine residue, is mainly mediated by protein arginine methyltransferases (PRMTs), which are ubiquitously present in a multitude of organisms and are intricately involved in the regulation of numerous biological processes. Specifically, PRMTs are pivotal in the process of gene transcription regulation, and protein function modulation. Abnormal arginine methylation, particularly in histones, can induce dysregulation of gene expression, thereby leading to the development of cancer. The recent advancements in modification mediated by PRMTs and cancer research have had a profound impact on our understanding of the abnormal modification involved in carcinogenesis and progression. This review will provide a defined overview of these recent progression, with the aim of augmenting our knowledge on the role of PRMTs in progression and their potential application in cancer therapy.
Downregulation of Ripk1 and Nsf mediated by CRISPR-CasRx ameliorates stroke volume and neurological deficits after ischemia stroke in mice
Authors: Song Xincheng , Lan Yang , Lv Shuang , Wang Yuye , Chen Leian , Lu Tao , Liu Fei , Peng Dantao
Published: June 2024

Necroptosis is implicated in the pathogenesis of ischemic stroke. However, the mechanism underlying the sequential recruitment of receptor-interacting protein kinase 1 (RIPK1) and N-ethylmaleimide-sensitive fusion ATPase (NSF) in initiating necroptosis remains poorly understood, and the role of NSF in ischemic stroke is a subject of controversy. Here, we utilized a recently emerging RNA-targeting CRISPR system known as CasRx, delivered by AAVs, to knockdown Ripk1 mRNA and Nsf mRNA around the ischemic brain tissue. This approach resulted in a reduction in infarct and edema volume, as well as an improvement in neurological deficits assessed by Bederson score, RotaRod test, and Adhesive removal test, which were achieved by RIPK1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein signaling pathway involved in neuronal necroptosis. In conclusion, the downregulation of Ripk1 mRNA and Nsf mRNA mediated by CRISPR-CasRx holds promise for future therapeutic applications aimed at ameliorating cerebral lesions and neurological deficits following the ischemic stroke.
Resting-state networks and anosognosia in Alzheimer’s disease
Authors: Tondelli Manuela , Ballotta Daniela , Maramotti Riccardo , Carbone Chiara , Gallingani Chiara , MacKay Clare , Pagnoni Giuseppe , Chiari Annalisa , Zamboni Giovanna
Published: June 2024

Background

Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer’s Disease (AD) may be explained by a disconnection between brain regions involved in accessing and monitoring information regarding self and others. It has been demonstrated that AD patients with anosognosia have reduced connectivity within the default mode network (DMN) and that anosognosia in people with prodromal AD is positively associated with bilateral anterior cingulate cortex (ACC), suggesting a possible role of this region in mechanisms of awareness in the early phase of disease. We hypothesized that anosognosia in AD is associated with an imbalance between the activity of large-scale resting-state functional magnetic resonance imaging (fMRI) networks, in particular the DMN, the salience network (SN), and the frontoparietal network (FPN).

Methods

Sixty patients with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D), a measure of anosognosia based on a discrepancy score between patient’s and carer’s judgments. After having applied Independent Component Analysis (ICA) to resting fMRI data we performed: (i) correlations between the AQ-D score and functional connectivity in the DMN, SN, and FPN, and (ii) comparisons between aware and unaware patients of the DMN, SN, and FPN functional connectivity.

Results

We found that anosognosia was associated with (i) weak functional connectivity within the DMN, in posterior and middle cingulate cortex particularly, (ii) strong functional connectivity within the SN in ACC, and between the SN and basal ganglia, and (iii) a heterogenous effect concerning the functional connectivity of the FPN, with a weak connectivity between the FPN and PCC, and a strong connectivity between the FPN and ACC. The observed effects were controlled for differences in severity of cognitive impairment and age.

Conclusion

Anosognosia in the AD continuum is associated with a dysregulation of the functional connectivity of three large-scale networks, namely the DMN, SN, and FPN.
Developmental effect of RASopathy mutations on neuronal network activity on a chip
Authors: Weiss Eva-Maria , Guhathakurta Debarpan , Petrušková Aneta , Hundrup Verena , Zenker Martin , Fejtová Anna
Published: June 2024

RASopathies are a group of genetic disorders caused by mutations in genes encoding components and regulators of the RAS/MAPK signaling pathway, resulting in overactivation of signaling. RASopathy patients exhibit distinctive facial features, cardiopathies, growth and skeletal abnormalities, and varying degrees of neurocognitive impairments including neurodevelopmental delay, intellectual disabilities, or attention deficits. At present, it is unclear how RASopathy mutations cause neurocognitive impairment and what their neuron-specific cellular and network phenotypes are. Here, we investigated the effect of RASopathy mutations on the establishment and functional maturation of neuronal networks. We isolated cortical neurons from RASopathy mouse models, cultured them on multielectrode arrays and performed longitudinal recordings of spontaneous activity in developing networks as well as recordings of evoked responses in mature neurons. To facilitate the analysis of large and complex data sets resulting from long-term multielectrode recordings, we developed MATLAB-based tools for data processing, analysis, and statistical evaluation. Longitudinal analysis of spontaneous network activity revealed a convergent developmental phenotype in neurons carrying the gain-of-function Noonan syndrome-related mutations Ptpn11D61Y and KrasV14l. The phenotype was more pronounced at the earlier time points and faded out over time, suggesting the emergence of compensatory mechanisms during network maturation. Nevertheless, persistent differences in excitatory/inhibitory balance and network excitability were observed in mature networks. This study improves the understanding of the complex relationship between genetic mutations and clinical manifestations in RASopathies by adding insights into functional network processes as an additional piece of the puzzle.
A systematic review and meta-analysis of acupuncture in aspiration caused by post-stroke dysphagia
Authors: Li Hongwei , Li Jie , Wang Xu , Zhang Zhilong
Published: June 2024

Objective

This systematic review and meta-analysis aims to systematically evaluate the effectiveness and safety of acupuncture in the treatment of aspiration caused by post-stroke dysphagia.

Methods

A computer search was conducted in nine databases, including the China National Knowledge Infrastructure (CNKI), China Science and Technology Journal (VIP), Wan-fang Database, China Biomedical Literature Database (CBM), PubMed, Web of Science, Cochrane Library, Embase, and Chinese Clinical Trial Registry (ChiCTR), from their inception until April 2024. Clinical randomized controlled trials comparing acupuncture combined therapy or single therapy with control interventions for the treatment of aspiration caused by post-stroke dysphagia were included. The primary outcome measure was the Penetration Aspiration Scale (PAS), and secondary outcome measures included the overall effective rate, video fluoroscopic swallowing study (VFSS), and hyoid bone displacement. The statistical analysis was performed using RevMan 5.3 and Stata 16.0.

Results

A total of 16 articles involving 1,284 patients were included. The meta-analysis results showed that acupuncture combined therapy or single therapy was more effective in improving PAS scores compared to conventional rehabilitation therapy or balloon dilation of the catheter [WMD = −1.05, 95% CI (−1.30, −0.80), Z = 0.82, p = 0.00 < 0.05]. It was also more effective in improving VFSS scores [WMD = 1.32, 95% CI (0.08, 2.55), Z = 2.09, p = 0.04 < 0.05] and hyoid bone displacement [WMD = 2.02, 95% CI (0.86, 3.18), Z = 3.41, p = 0.00 < 0.05]. Additionally, acupuncture had a higher overall effective rate [WMD = 1.21, 95% CI (1.14, 1.29), Z = 5.76, p = 0.00 < 0.05] and a lower incidence of adverse events. Sensitivity analysis indicated that the literature had minimal impact on the results, and bias tests showed no publication bias.

Conclusion

Acupuncture combined therapy and acupuncture single therapy can effectively improve aspiration caused by post-stroke dysphagia with a low incidence of adverse events. However, due to the low quality of the included literature, more high-quality randomized controlled trials are still needed to confirm the effectiveness and safety of acupuncture in the treatment of aspiration caused by post-stroke dysphagia.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023462707, identifier CRD42023462707