bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders
Authors: Akter Hosneara , Rahman Muhammad Mizanur , Sarker Shaoli , Basiruzzaman Mohammed , Islam Md. Mazharul , Rahaman Md. Atikur , Rahaman Md. Ashiquir , Eshaque Tamannyat Binte , Dity Nushrat Jahan , Sarker Shouvik , Amin Md. Robed , Hossain Mohammad Monir , Lopa Maksuda , Jahan Nargis , Hossain Shafaat , Islam Amirul , Mondol Ashaduzzaman , Faruk Md Omar , Saha Narayan , Kundu Gopen kumar , Kanta Shayla Imam , Kazal Rezaul Karim , Fatema Kanij , Rahman Md. Ashrafur , Hasan Maruf , Hossain Mollah Md. Abid , Hosen Md. Ismail , Karuvantevida Noushad , Begum Ghausia , Zehra Binte , Nassir Nasna , Nabi A. H. M. Nurun , Uddin K. M. Furkan , Uddin Mohammed
Published: March 2023

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh.

Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., “Critical-Exon Genes (CEGs)”] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package.

Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients’ pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability.

Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.
Roles and therapeutic implications of m6A modification in cancer immunotherapy
Authors: Pan Juan , Huang Tuxiong , Deng Zhenjun , Zou Chang
Published: March 2023

Recent studies have demonstrated that N6-methyladenosine (m6A), the most abundant, dynamic, and reversible epigenetic RNA modification in eukaryotes, is regulated by a series of enzymes, including methyltransferases (writers), demethylases (erasers), and m6A recognition proteins (readers). Aberrant regulation of m6A modification is pivotal for tumorigenesis, progression, invasion, metastasis, and apoptosis of malignant tumors. Immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, as recognized by the 2018 Nobel Prize in Medicine and Physiology. However, not all cancer patients response to ICI therapy, which is thought to be the result of intricate immune escape mechanisms. Recently, numerous studies have suggested a novel role for m6A epigenetic modification in the regulation of tumor immune evasion. Herein, we review the relevant mechanisms of m6A regulators in regulating various key signaling pathways in cancer biology and how m6A epigenetic modifications regulate the expression of immune checkpoints, opening a new window to understand the roles and mechanisms of m6A epigenetic modifications in regulating tumor immune evasion. In addition, we highlight the prospects and development directions of future combined immunotherapy strategies based on m6A modification targeting, providing directions for promoting the treatment outcomes of immune checkpoint inhibitors.
Pleiotropic antifibrotic actions of aspirin-triggered resolvin D1 in the lungs
Authors: Guilherme Rafael F. , Silva José Bruno N.F. , Waclawiack Ingrid , Fraga-Junior Vanderlei S. , Nogueira Thaís O. , Pecli Cyntia , Araújo-Silva Carlla A. , Magalhães Nathalia S. , Lemos Felipe S. , Bulant Carlos A. , Blanco Pablo J. , Serra Rafaela , Svensjö Erik , Scharfstein Júlio , Moraes João A. , Canetti Claudio , Benjamim Claudia F.
Published: March 2023

Introduction

Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments.

Methods

Using a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later.

Results and discussion

Assessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-β, and TGF-β. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-β-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-β-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.
PD-1 and CTLA-4 exert additive control of effector regulatory T cells at homeostasis
Authors: Pereira Joseph A. , Lanzar Zachary , Clark Joseph T. , Hart Andrew P. , Douglas Bonnie B. , Shallberg Lindsey , O’Dea Keenan , Christian David A. , Hunter Christopher A.
Published: March 2023

At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in eTreg cells which was associated with increased proliferation, enhanced production of IL-10, and reduced dendritic cell and macrophage expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation.
Abundance and composition of particles and their attached microbiomes along an Atlantic Meridional Transect
Authors: Reintjes Greta , Heins Anneke , Wang Cheng , Amann Rudolf
Published: March 2023

Particulate organic matter plays a significant role in the marine carbon cycle. Its sinking exports organic carbon from the surface to deep oceans. Using fractionated filtration, we analysed particles of 3 – 10 µm and >10 µm and their microbiomes in thirty-five stations along a latitudinal transect of the Atlantic Ocean and provide new insights into the composition, community dynamics, and catabolic potential of particle-attached bacteria. Samples were taken during an Atlantic Meridional Transect (AMT22), which traversed six distinctive ocean provinces. Using 16S rRNA amplicon sequencing and fluorescence in situ hybridisation, we could show a strong variation between particle-attached and free-living bacterial communities at each station and across the biogeographical provinces – a dynamic likely driven by chlorophyll a concentrations, temperature, and the oxygen content of the respective biogeographical provinces. Whereas the <3 µm fraction was primarily composed of SAR11, SAR86, Prochlorococcus and Bacteroidetes of the NS9 and NS5 clades, particle-attached communities were dominated by other Bacteroidetes (Polaribacter spp.), diverse Gammaproteobacteria including members of the genera Alteromonas and Vibrio, Alphaproteobacteria, Planctomycetes, OM27 and Verrucomicrobia. In three provinces, we quantified particle abundance and analysed their glycan composition using four lectins targeting fucose, galactose, N-acetylgalactosamine and mannose. Particles were mainly composed of fucose glycans with only a minor abundance of the other glycans, and particle abundance was directly correlated with the chlorophyll a concentrations. Functional analysis of 54 metagenome-assembled genomes retrieved from bacterial communities attached to small particles showed that particle-attached Bacteroidetes, Planctomycetes and Verrucomicrobia displayed key roles in the degradation of sulfated fucose-containing polysaccharides. We also identified gene clusters potentially encoding the utilisation of mannan and laminarin, suggesting an adaptation to the glycan composition of the particles, potentially resulting in niche diversification. Together, our results provide insights into particle-attached bacteria and their ecological strategies in the Atlantic.
Reproductive performance of captive-reared Indian white shrimp, Penaeus indicus, broodstocks over two generations
Authors: Anand P. S. Shyne , Balasubramanian C. P. , Aravind R. , Biju I. F. , Rajan R. Vidhu , Vinay T. N. , Panigrahi A. , Sudheer N. S. , Rajamanickam S. , Kumar Sujeet , Antony Jose , Ambasankar K. , Jithendran K. P. , Vijayan K. K.
Published: March 2023

Closing the complex life cycle of closed thelycum shrimp in captivity is one of the fundamental challenges in breeding programs. In the present study, we investigated the sexual maturity, broodstock development, and spawning performance of two generations of captive-reared Indian white shrimp, Penaeus indicus, over 36 months originated from a single stock of wild brooders. The post larvae (GN-1) produced from wild P. indicus (G0) and P.L. (GN-2) produced from captive-reared (GN-1) broodstocks were nursery (1000 PL m-3) and grow-out (12 shrimp m-2) reared, and subsequently raised in broodstock ponds (1 shrimp m-2). The annual salinity and photoperiod in broodstock ponds varied between 20 to 36 ppt, and 11.2 -12.5 L and 11.5-12.8 D hours, respectively. The light intensity varied between 91 ± 6 lux at dusk to 75,358 ± 1719 lux at noon. The size at first impregnation or mating was 16.45 ± 1.7 g (132 DOC) and 17.62 ± 1.9 g (90 DOC), respectively, in GN-1 and GN-2 females. By 220 DOC, 25% of the GN-1 females initiated gonad development, whereas 55% of the GN-2 females recorded developing ovaries or were in stage II at 150 DOC. The broodstock attained an average final body weight of 38.85 ± 1.5 g (GN-1) and 42.65 ± 1.8 g (GN-2) by 360 DOC. The highest (p<0.01) eggs per gram body weight (5137 ± 303 eggs g-1) and hatchability, H (83 ± 0.7%), was recorded in wild broodstocks (G0) followed by GN-2 (1,715 ± 162 eggs g-1; H: 69 ± 2%) and GN-1 (1,476 ± 151 eggs g-1; H: 75 ± 1%). However, captive-reared broodstock had better survival (89-92%) than wild broodstocks (71 ± 0.8%). Further, indoor maturation trial (21 days) using ablated broodstocks (GN-1) revealed 79% of the impregnated broodstocks undergo molting, resulting in the loss of sperm pack and subsequent reduction in mating efficacy to 29%. The average sperm count and percentage of normal sperm also recorded (p<0.05) reduction during the maturation cycle. The data generated in the present investigation can form the baseline information for developing the breeding strategy for the genetic improvement of Indian white shrimp in India.
How to estimate age of old bottlenose dolphins (Tursiops truncatus); by tooth or pectoral flipper?
Authors: Barratclough Ashley , McFee Wayne E. , Stolen Megan , Hohn Aleta A. , Lovewell Gretchen N. , Gomez Forrest M. , Smith Cynthia R. , Garcia-Parraga Daniel , Wells Randall S. , Parry Celeste , Daniels Risa , Ridgway Sam H. , Schwacke Lori
Published: March 2023

Multiple techniques have been used for estimating age in bottlenose dolphins (Tursiops truncatus). The longest established technique is via counts of growth later groups (GLGs) in the longitudinal section of an extracted mandibular tooth. Previous studies to validate GLGs have primarily used younger dolphins (less than 16yrs old) due to the limited number of known age older animals. This study assessed the accuracy of age estimates for bottlenose dolphins using both GLG analysis and a newer technique, pectoral flipper radiography (PFR) for dolphins ranging from 0 to 58yrs, with a majority of samples (70%) over 16yrs. GLGs were assessed by two expert independent readers on tooth sections from 52 different dolphins (85% over 16yrs, maximum age 58yrs), and assessments of PFRs were performed by two experienced veterinarians on 37 dolphins (54% over 16yrs, maximum age 54yrs). Results demonstrated both techniques became less accurate in older dolphins, particularly those > 30yrs, with errors as large as 37yrs for GLG estimates. The root mean squared error (RMSE) for age estimation using GLGs for dolphins ≤15 years of age was 1.46yrs compared to 1.58yrs using PFRs demonstrating the accuracy of both techniques in this age bracket. For dolphins >30yrs, RMSE increased to 17yrs in GLG aging and 8.25yrs in PFR. Challenges in obtaining accurate age estimates in GLGs were primarily due to sectioning and staining difficulties in visualizing the newest GLG layers, in the very old animals. Complications in reading the layers included obtaining a good section, the presence of accessory layers, GLG compression, and tooth curvature or wear removing the neonatal line influencing aging biases. In pectoral flipper aging, the primary challenge was obtaining a true dorsoventral radiograph in a live dolphin during a health assessment, as well as the subjective assessment of scoring and reliance on degenerative changes accurately estimate age in geriatric dolphins. While access to the radiography equipment can be a limiting factor, the improved accuracy for age estimation in adult dolphins, the less invasive nature, and reduced processing time to results make pectoral radiography a preferred alternative technique for estimating age in live dolphins.
Age-adjusted Charlson comorbidity index predicts postoperative mortality in elderly patients with hip fracture: A prospective cohort
Authors: Zhang Dan-Long , Cong Yu-Xuan , Zhuang Yan , Xu Xin , Zhang Bin-Fei
Published: March 2023

Background

This study aimed to evaluate the clinical association between the age-adjusted Charlson comorbidity index (aCCI) and postoperative mortality in elderly patients.

Materials and methods

Elderly patients with hip fractures were screened from January 2015 to September 2019. After demographic and clinical characteristics were collected, linear and non-linear multivariate Cox regression models were used to identify the association between the aCCI and mortality. All analyses were performed using EmpowerStats and R software.

Results

A total of 2,657 patients were included in the study, and the mean follow-up duration was of 38.97 months. The mean aCCI score was 4.24 ± 1.09, and 977 (34.14%) died of all-cause mortality. The fully-adjusted linear multivariate Cox regression models showed the aCCI to be associated with mortality [hazard ratio (HR) = 1.31, 95% confidence interval (CI):1.21–1.41, P < 0.0001]. Patients in Q2 showed greater mortality (HR = 1.60, 95% CI: 1.23–2.09; P = 0.0005) than those in Q1; patients in Q3 showed greater mortality (HR = 2.18, 95% CI: 1.66–2.87; P < 0.001) than those in Q1. In addition, the P-value for the trend also showed a linear association in the three models (P < 0.0001). In the sensitivity analysis, propensity score matching was used, and the results were stable.

Conclusion

The mortality risk of hip fractures increased by 31% when the aCCI increased by one unit. aCCI score was shown to be a good predictor of three-year mortality following hip fracture.

Clinical trial registration

http://www.chictr.org.cn/showproj.aspx?proj=152919, identifier ChiCTR2200057323.
Effectiveness of small-angle episiotomy on incisional laceration rate, suturing time, and incisional bleeding in primigravida: A meta-analysis
Authors: Zhang Yan , Zhang Jiaoyan , Zhao Liang , Xiao Lin , Tian Jinhui , Fan Wei
Published: March 2023

Objective

To investigate the effect of small-angle lateral perineal incision on postoperative perineal rehabilitation in primiparous women.

Method

The Cochrane Library, PubMed, Embase, CINAHL, CNKI, WanFang, VIP, and the Chinese Biomedical Literature Database were searched for randomized controlled trials (RCTs) on the effect of small-angle episiotomy on postoperative maternal perineal wound rehabilitation in puerpera until April 3, 2022. Two researchers independently performed literature screening, data extraction and evaluation of risk of bias in the included literature, and statistical analysis of the data was performed using RevMan 5.4 and Stata 12.0 software.

Result

A total of 25 RCTs were included, with a total sample of 6,366 cases. Meta-analysis results showed that the use of small-angle episiotomy reduced incisional tearing [OR = 0.32, 95% CI (0.26, 0.39)], shortened incisional suture time [MD = −4.58 min, 95% CI (−6.02, −3.14)] and reduced incisional bleeding [MD = −19.08 mL, 95% CI (−19.53, −18.63)], with statistically significant differences (all p < 0.05). There was no significant difference in the rate of severe laceration between the two groups [OR = 2.32, 95% CI (0.70, 7.70), p > 0.05].

Conclusion

The use of a small-angle episiotomy during vaginal delivery can reduce the incision tear rate without increasing the incidence of severe perineal laceration, while shortening the incisional suturing time and reducing incisional bleeding. It can be used clinically according to birth canal conditions of the maternal, the intrauterine condition of the fetus and maternal needs.

Systematic Review Registration

PROSPERO International Prospective Register of Systematic Reviews [CRD42022369698]; [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369698].
Mechanisms of macular edema
Authors: Haydinger Cameron D. , Ferreira Lisia Barros , Williams Keryn A. , Smith Justine R.
Published: March 2023

Macular edema is the pathological accumulation of fluid in the central retina. It is a complication of many retinal diseases, including diabetic retinopathy, retinal vascular occlusions and uveitis, among others. Macular edema causes decreased visual acuity and, when chronic or refractory, can cause severe and permanent visual impairment and blindness. In most instances, it develops due to dysregulation of the blood-retinal barrier which permits infiltration of the retinal tissue by proteins and other solutes that are normally retained in the blood. The increase in osmotic pressure in the tissue drives fluid accumulation. Current treatments include vascular endothelial growth factor blockers, corticosteroids, and non-steroidal anti-inflammatory drugs. These treatments target vasoactive and inflammatory mediators that cause disruption to the blood-retinal barrier. In this review, a clinical overview of macular edema is provided, mechanisms of disease are discussed, highlighting processes targeted by current treatments, and areas of opportunity for future research are identified.
Synergistic antifungal interaction of N-(butylcarbamothioyl) benzamide and amphotericin B against Cryptococcus neoformans
Authors: Andriani Gabriella Maria , Spoladori Lais Fernanda de Almeida , Fabris Marciéli , Camargo Priscila Goes , Pereira Patrícia Morais Lopes , Santos Jussevania Pereira , Bartolomeu-Gonçalves Guilherme , Alonso Lais , Lancheros Cesar Armando Contreras , Alonso Antonio , Nakamura Celso Vataru , Macedo Fernando , Pinge-Filho Phileno , Yamauchi Lucy Megumi , Bispo Marcelle de Lima Ferreira , Tavares Eliandro Reis , Yamada-Ogatta Sueli Fumie
Published: March 2023

Introduction

Cryptococcus neoformans is one of the leading causes of invasive fungal infections worldwide. Cryptococcal meningoencephalitis is the main challenge of antifungal therapy due to high morbidity and mortality rates, especially in low- and middle-income countries. This can be partly attributed to the lack of specific diagnosis difficulty accessing treatment, antifungal resistance and antifungal toxicity.

Methods

In the present study, the effect of the synthetic thiourea derivative N-(butylcarbamothioyl) benzamide (BTU-01), alone and combined with amphotericin B (AmB), was evaluated in planktonic and sessile (biofilm) cells of C. neoformans.

Results

BTU-01 alone exhibited a fungistatic activity with minimal inhibitory concentrations (MICs) ranging from 31.25 to 62.5 μg/mL for planktonic cells; and sessile MICs ranging from 125.0 to 1000.0 μg/mL. BTU-01 caused a concentration-dependent inhibitory activity on cryptococcal urease and did not interfere with plasma membrane fluidity. Molecular docking was performed on Canavalia ensiformis urease, and BTU-01 showed relevant interactions with the enzyme. The combination of BTU-01 and AmB exhibited synergistic fungicidal activity against planktonic and sessile cells of C. neoformans. Microscopic analysis of C. neoformans treated with BTU-01, alone or combined with AmB, revealed a reduction in cell and capsule sizes, changes in the morphology of planktonic cells; a significant decrease in the number of cells within the biofilm; and absence of exopolymeric matrix surrounding the sessile cells. Neither hemolytic activity nor cytotoxicity to mammalian cells was detected for BTU-01, alone or combined with AmB, at concentrations that exhibited antifungal activity. BTU-01 also displayed drug-likeness properties.

Conclusion

These results indicate the potential of BTU-01, for the development of new strategies for controlling C. neoformans infections.
Assessment of adaptive immune responses of dairy cows with Burkholderia contaminans-induced mastitis
Authors: Zhang Zhipeng , Yao Yiyang , Yang Jiayu , Jiang Hui , Meng Ye , Cao Wenqiang , Zhou Fuzhen , Wang Kun , Yang Zhangping , Yang Chunhua , Sun Jie , Yang Yi
Published: March 2023

Burkholderia contaminans, an emerging pathogen related to cystic fibrosis, is known to cause potentially fatal infections in humans and ruminants, especially in immunocompromised individuals. However, the immune responses in cows following its infection have not been fully elucidated. In this study, T- and B-lymphocytes-mediated immune responses were evaluated in 15 B. contaminans-induced mastitis cows and 15 healthy cows with multi-parameter flow cytometry. The results showed that infection with B. contaminans was associated with a significant decrease in the number and percentage of B lymphocytes but with a significant increase in the proportion of IgG+CD27+ B lymphocytes. This indicated that humoral immune response may not be adequate to fight intracellular infection, which could contribute to the persistent bacterial infection. In addition, B. contaminans infection induced significant increase of γδ T cells and double positive (DP) CD4+CD8+ T cells but not CD4+ or CD8+ (single positive) T cells in blood. Phenotypic analysis showed that the percentages of activated WC1+ γδ T cells in peripheral blood were increased in the B. contaminans infected cows. Interestingly, intracellular cytokine staining showed that cattle naturally infected with B. contaminans exhibited multifunctional TNF-α+IFN-γ+IL-2+B. contaminans-specific DP T cells. Our results, for the first time, revealed a potential role of IgG+CD27+ B cells, CD4+CD8+ T cells and WC1+ γδ T cells in the defense of B. contaminans-induced mastitis in cows.
Effects of rice blast biocontrol strain Pseudomonas alcaliphila Ej2 on the endophytic microbiome and proteome of rice under salt stress
Authors: Zeng Qingchao , Man Xiaowu , Huang Zeyang , Zhuang Lubo , Yang Hanmeng , Sha Yuexia
Published: March 2023

Introduction

Soil salinity is a prevalent environmental stress in agricultural production. Microbial inoculants could effectively help plants to alleviate salt stress. However, there is little knowledge of the biocontrol strain Pseudomonas alcaliphila Ej2 mechanisms aiding rice plants to reduce the adverse effects caused by salt stress.

Methods

We performed integrated field and greenhouse experiments, microbial community profiling, and rice proteomic analysis to systematically investigate the Ej2 mechanism of action.

Results

The results displayed that biocontrol strain Ej2 increased shoot/root length and fresh/dry weight compared with control under salt stress. Meanwhile, strain Ej2 has the ability to control rice blast disease and promote rice growth. Furthermore, the microbial community analysis revealed that the alpha-diversity of Ej2-inoculated plants was higher than the control plants, expect the Shannon index of the bacterial microbiome and the Ej2-inoculated samples clustered and separated from the control samples based on beta-diversity analysis. Importantly, the enriched and specific OTUs after Ej2 inoculation at the genus level were Streptomyces, Pseudomonas, Flavobacterium, and Bacillus. Moreover, we observed that Ej2 inoculation influenced the rice proteomic profile, including metabolism, plant-pathogen interactions, and biosynthesis of unsaturated fatty acids. These results provide comprehensive evidence that Ej2 inoculation induced the rice endophytic microbiome and proteomic profiles to promote plant growth under salt stress.

Discussion

Understanding the biocontrol strain effects on the endophytic microbiome and rice proteomics will help us better understand the complex interactions between plants and microorganisms under salt stress. Furthermore, unraveling the mechanisms underlying salt tolerance will help us more efficiently ameliorate saline soils.
Biocontrol potential of wine yeasts against four grape phytopathogenic fungi disclosed by time-course monitoring of inhibitory activities
Authors: Esteves Marcos , Lage Patrícia , Sousa João , Centeno Filipe , de Fátima Teixeira Maria , Tenreiro Rogério , Mendes-Ferreira Ana
Published: March 2023

Grapes’ infection by phytopathogenic fungi may often lead to rot and impair the quality and safety of the final product. Due to the concerns associated with the extensive use of chemicals to control these fungi, including their toxicity for environment and human health, bio-based products are being highly preferred, as eco-friendlier and safer alternatives. Specifically, yeasts have shown to possess antagonistic activity against fungi, being promising for the formulation of new biocontrol products.In this work 397 wine yeasts, isolated from Portuguese wine regions, were studied for their biocontrol potential against common grapes phytopathogenic fungal genera: Aspergillus, Botrytis, Mucor and Penicillium. This set comprised strains affiliated to 32 species distributed among 20 genera. Time-course monitoring of mold growth was performed to assess the inhibitory activity resulting from either diffusible or volatile compounds produced by each yeast strain. All yeasts displayed antagonistic activity against at least one of the mold targets. Mucor was the most affected being strongly inhibited by 68% of the tested strains, followed by Botrytis (20%), Aspergillus (19%) and Penicillium (7%). More notably, the approach used allowed the detection of a wide array of yeast-induced mold response profiles encompassing, besides the decrease of mold growth, the inhibition or delay of spore germination and the complete arrest of mycelial extension, and even its stimulation at different phases. Each factor considered (taxonomic affiliation, mode of action and fungal target) as well as their interactions significantly affected the antagonistic activity of the yeast isolates. The highest inhibitions were mediated by volatile compounds. Total inhibition of Penicillium was achieved by a strain of Metschnikowia pulcherrima, while the best performing yeasts against Mucor, Aspergillus and Botrytis, belong to Lachancea thermotolerans, Hanseniaspora uvarum and Starmerella bacillaris, respectively. Notwithstanding the wide diversity of yeasts tested, only three strains were found to possess a broad spectrum of antagonistic activity, displaying strong or very strong inhibition against the four fungal targets tested. Our results confirm the potential of wine yeasts as biocontrol agents, while highlighting the need for the establishment of fit-for-purpose selection programs depending on the mold target, the timing, and the mode of application.
DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
Authors: Hu Wei , Li Ping , Zeng Nianju , Tan Sheng
Published: March 2023

Objective

Ischemic stroke (IS) is a common disease that causes severe and long-term neurological disability in people worldwide. Although rehabilitation is indispensable to promote neurological recovery in ischemic stroke, it is limited to providing a timely and efficient reference for developing and adjusting treatment strategies because neurological assessment after stroke treatment is mostly performed using scales and imaging. Therefore, there is an urgent need to find biomarkers that can help us evaluate and optimize the treatment plan.

Methods

We used data-independent acquisition (DIA) technology to screen differentially expressed proteins (DEPs) before and after ischemic stroke rehabilitation treatment, and then performed Gene Ontology (GO) and pathway enrichment analysis of DEPs using bioinformatics tools such as KEGG pathway and Reactome. In addition, the protein–protein interaction (PPI) network and modularity analysis of DEPs were integrated to identify the hub proteins (genes) and hub signaling pathways for neurological recovery in ischemic stroke. PRM-targeted proteomics was also used to validate some of the screened proteins of interest.

Results

Analyzing the serum protein expression profiles before and after rehabilitation, we identified 22 DEPs that were upregulated and downregulated each. Through GO and pathway enrichment analysis and subsequent PPI network analysis constructed using STRING data and subsequent Cytoscape MCODE analysis, we identified that complement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammatory and immune pathways are the major pathways involved in the improvement of neurological function after stroke rehabilitation.

Conclusion

Complement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammation and immunity pathways are not only key pathways in the pathogenesis of ischemic stroke but also the main pathways of action of rehabilitation therapy. In addition, IGHA1, LRG1, IGHV3-64D, and CP are upregulated in patients with ischemic stroke and downregulated after rehabilitation, which may be used as biomarkers to monitor neurological impairment and recovery after stroke.
Measuring white matter microstructure in 1,457 cannabis users and 1,441 controls: A systematic review of diffusion-weighted MRI studies
Authors: Robinson Emily Anne , Gleeson John , Arun Arush Honnedevasthana , Clemente Adam , Gaillard Alexandra , Rossetti Maria Gloria , Brambilla Paolo , Bellani Marcella , Crisanti Camilla , Curran H. Valerie , Lorenzetti Valentina
Published: March 2023

Introduction

Cannabis is the most widely used regulated substance by youth and adults. Cannabis use has been associated with psychosocial problems, which have been partly ascribed to neurobiological changes. Emerging evidence to date from diffusion-MRI studies shows that cannabis users compared to controls show poorer integrity of white matter fibre tracts, which structurally connect distinct brain regions to facilitate neural communication. However, the most recent evidence from diffusion-MRI studies thus far has yet to be integrated. Therefore, it is unclear if white matter differences in cannabis users are evident consistently in selected locations, in specific diffusion-MRI metrics, and whether these differences in metrics are associated with cannabis exposure levels.

Methods

We systematically reviewed the results from diffusion-MRI imaging studies that compared white matter differences between cannabis users and controls. We also examined the associations between cannabis exposure and other behavioral variables due to changes in white matter. Our review was pre-registered in PROSPERO (ID: 258250; https://www.crd.york.ac.uk/prospero/).

Results

We identified 30 diffusion-MRI studies including 1,457 cannabis users and 1,441 controls aged 16-to-45 years. All but 6 studies reported group differences in white matter integrity. The most consistent differences between cannabis users and controls were lower fractional anisotropy within the arcuate/superior longitudinal fasciculus (7 studies), and lower fractional anisotropy of the corpus callosum (6 studies) as well as higher mean diffusivity and trace (4 studies). Differences in fractional anisotropy were associated with cannabis use onset (4 studies), especially in the corpus callosum (3 studies).

Discussion

The mechanisms underscoring white matter differences are unclear, and they may include effects of cannabis use onset during youth, neurotoxic effects or neuro adaptations from regular exposure to tetrahydrocannabinol (THC), which exerts its effects by binding to brain receptors, or a neurobiological vulnerability predating the onset of cannabis use. Future multimodal neuroimaging studies, including recently developed advanced diffusion-MRI metrics, can be used to track cannabis users over time and to define with precision when and which region of the brain the white matter changes commence in youth cannabis users, and whether cessation of use recovers white matter differences.

Systematic review registration

www.crd.york.ac.uk/prospero/, identifier: 258250.
Testing effects of trigeminal stimulation on binary odor mixture quality in rats
Authors: Li Huibo , Lee Clara , Kay Leslie M.
Published: March 2023

Prior attempts at forming theoretical predictions regarding the quality of binary odor mixtures have failed to find any consistent predictor for overshadowing of one component in a binary mixture by the other. We test here the hypothesis that trigeminality contributes to overshadowing effects in binary mixture perception. Most odorants stimulate the trigeminal nerve in the nasal sensory epithelium. In the current study we test rats’ ability to detect component odorants in four binary odor sets chosen for their relative trigeminality. We predicted that the difference in trigeminal intensity would predict the degree of overshadowing by boosting or suppressing perceptual intensity of these odorants during learning or during mixture perception. We used a two-alternative choice (TAC) task in which rats were trained to recognize the two components of each mixture and tested on a range of mixtures of the two without reinforcement. We found that even though odorant concentrations were adjusted to balance volatility, all odor sets produced asymmetric psychometric curves. Odor pairs with the greatest difference in trigeminality showed overshadowing by the odorant with weaker trigeminal properties. Odor sets with more evenly matched trigeminal properties also showed asymmetry that was not predicted by either small differences in volatility or trigeminality. Thus, trigeminal properties may influence overshadowing in odor mixtures, but other factors are also likely involved. These mixed results further support the need to test each odor mixture to determine its odor quality and underscore recent results at the level of olfactory receptor neurons that show massive and unpredictable inhibition among odorants in complex mixtures.
Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer
Authors: Ni Rui , Li Ziwei , Li Li , Peng Dan , Ming Yue , Li Lin , Liu Yao
Published: March 2023

Glutamine, the most abundant non-essential amino acid in human blood, is crucial for cancer cell growth and cancer progression. Glutamine mainly functions as a carbon and nitrogen source for biosynthesis, energy metabolism, and redox homeostasis maintenance in cancer cells. Dysregulated glutamine metabolism is a notable metabolic characteristic of cancer cells. Some carcinogen-driven cancers exhibit a marked dependence on glutamine, also known as glutamine addiction, which has rendered the glutamine metabolic pathway a breakpoint in cancer therapeutics. However, some cancer cells can adapt to the glutamine unavailability by reprogramming metabolism, thus limiting the success of this therapeutic approach. Given the complexity of metabolic networks and the limited impact of inhibiting glutamine metabolism alone, the combination of glutamine metabolism inhibition and other therapeutic methods may outperform corresponding monotherapies in the treatment of cancers. This review summarizes the uptake, transport, and metabolic characteristics of glutamine, as well as the regulation of glutamine dependence by some important oncogenes in various cancers to emphasize the therapeutic potential of targeting glutamine metabolism. Furthermore, we discuss a glutamine metabolic pathway, the glutaminase II pathway, that has been substantially overlooked. Finally, we discuss the applicability of polytherapeutic strategies targeting glutamine metabolism to provide a new perspective on cancer therapeutics.
Development of a nomogram based on serum cytokine-related riskscore in breast cancer
Authors: Zhu Ye , He Yang , Chen Chong , Zhang Jingyi , Yang Xin , Lu Yuqing , Chen Yong-Zi , Zhao Weipeng
Published: March 2023

Background

Cytokines are involved in many inflammatory diseases and thus play an important role in tumor immune regulation. In recent years, researchers have found that breast cancer is not only related to genetic and environmental factors, but also to the chronic inflammation and immunity. However, the correlation between serum cytokines and blood tests indicators remain unclear.

Methods

A total of 84 serum samples and clinicopathological data of breast cancer patients from Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, P. R. China were collected. The expression levels of the 12 cytokines were detected by immunofluorescence method. Blood tests results were obtained from medical records. By stepwise Cox regression analysis, a cytokine-related gene signature was generated. Univariate and multivariate Cox regression were used to analyze the influence on the prognosis of patients. A nomogram was constructed to illustrate the cytokine-related riskscore predicting 5-year OS, which was further evaluated and validated by C-index and ROC curve. The correlation between the expression of cytokines in serum and other blood indicators was studied by using Spearman’s test.

Results

The riskscore was calculated as IL-4×0.99069 + TNF-α×0.03683. Patients were divided into high and low risk groups according to the median riskscore, with the high-risk group has a shorter survival time by log-rank test (training set, P=0.017; validation set, P=0.013). Combined with the clinical characteristics, the riskscore was found to be an independent factor for predicting the OS of breast cancer patients in both training cohort (HR=1.2, P<0.01) and validation cohort (HR=1.6, P=0.023). The 5-year C-index and AUC of the nomogram were 0.78 and 0.68, respectively. IL-4 was further found to be negatively correlated with ALB.

Conclusion

In summary, we have developed a nomogram based on two cytokines including IL-4 and TNF-α to predict OS of breast cancer and investigated their correlation with blood test indicators.
A bibliometric study of the top 100 most-cited papers in neuroendocrine prostate cancer
Authors: Gan Yu , He Qiangrong , Li Chao , Alsharafi Bassam Lutf Mohammed , Zhou Hengfeng , Long Zhi
Published: March 2023

Background

This study used bibliometrics to define and analyze the characteristics of the first 100 most cited papers on the topic of neuroendocrine prostate cancer (NEPC).

Methods

We explored the Web of Science Core Collection database, and screened the top 100 most frequently cited articles and reviews with the title NEPC or small cell prostate cancer (SCPC). We conducted bibliometrics research on the screening results to identify the most influential journals and authors in the field of NEPC.

Results

The first 100 most cited papers have been cited a total of 14,795 times, from 73 to 833 times (mean ± standard deviation, 147.95 ± 101.68). All top 100 most cited papers were published from 1984 to 2019, and the total number of citations for papers published in 2016 was significantly higher than that for papers published in other years. The journal with the largest number of published papers is “Prostate” (n=8). “Neuroendocrine differentiation” has become the most frequently used author keyword. “Oncology” is the most popular topic in the field of NEPC.

Conclusion

We analyzed the first 100 most cited papers in the NEPC field by collecting detailed information, which provide guiding opinions for finding the most influential journals and authors in NEPC-related fields. We hope to help researchers and readers in this field improve their understanding of NEPC research trends and provide ideas for future research from a unique perspective.
The proportion of C1q-high and ISG15-high monocytes in the skin of patients with Behçet disease
Authors: Liu Yangtengyu , Bao Ding , Meng Meng , Lu Lixia , Zhu Honglin
Published: March 2023

Behçet disease (BD) is a chronic systemic vasculitis that is clinically characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin lesions. Here, we conducted bulk RNA-seq of skin samples from 4 BD patients and 4 normal controls (NCs). A total of 260 differentially expressed genes (DEGs), including 99 upregulated and 161 downregulated genes, were detected in the skin lesions of BD patients compared to NCs. These DEGs were mainly enriched in the following biological processes: the activation and migration of immune cells, the release of proinflammatory factors, and the IFN-γ signaling pathway. The top upregulated DEGs were CXCL10, CXCL9, FCGR3A, GBP5, GBP4, LILRB2, ADIPOQ, PLIN1, SLC43A2, and MYO1G. Using the deconvolution method CIBERSORT, we analyzed the immune cells subtypes in the skin of BD by integrating the single cell RNA-seq data from PBMC (GSE198616) and bulk RNA-seq data of skin. There was a higher proportion of C1q+ and ISG15 + monocyte subtypes in skin of BD. IHC staining of CD14 and CD16 showed that the monocyte number increased in the skin of BD. IF staining confirmed there was a higher proportion of the C1Q + Mono and ISG15 + Mono subsets in the skin of BD patients. Moreover, we analyzed the average expression level of the top upregulated genes in immune cell types found in PBMC from BD patients and NCs. Almost all the top upregulated genes expressed in monocytes. CXCL10 was specifically expressed in ISG15 + monocyte, and GBP5, GBP4 and IFI44L were expressed more strongly in ISG15 + monocytes. LILRB2 was expressed more strongly in CD16+ monocytes and C1Q + monocytes. In conclusion, our study identified that the IFN-γ pathway was activated in skin of BD and the proportion of C1q+ and ISG15 + monocyte subtype increased in the skin of BD.
Recent advances in the development of RIPK2 modulators for the treatment of inflammatory diseases
Authors: Pham Anh-Tuan , Ghilardi Amanda Franceschini , Sun Lijun
Published: March 2023

Receptor-interacting serine/threonine kinase 2 (RIPK2) is a vital immunomodulator that plays critical roles in nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs) signaling. Stimulated NOD1 and NOD2 interact with RIPK2 and lead to the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK), followed by the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23. Defects in NOD/RIPK2 signaling are associated with numerous inflammatory diseases, including asthma, sarcoidosis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), multiple sclerosis, and Blau syndrome. As RIPK2 is a crucial element of innate immunity, small molecules regulating RIPK2 functions are attractive to establish novel immunotherapies. The increased interest in developing RIPK2 inhibitors has led to the clinical investigations of novel drug candidates. In this review, we attempt to summarize recent advances in the development of RIPK2 inhibitors and degraders.
Numerical simulations of MHD generalized Newtonian fluid flow effects on a stretching sheet in the presence of permeable media: A finite difference-based study
Authors: Irshad Sadia , Majeed Afraz Hussain , Jahan Shah , Riaz Arshad , Eldin Sayed M. , Shahzad Hasan
Published: March 2023

Casson–Williamson (CW) nanofluid flows and mass transfer characteristics are explored in this study. Furthermore, the velocity slip condition and viscous dissipation affect or are taken to examine the changes in mass and heat transfer caused by a stretching surface integrated into permeable media with heat conversion beneath the effect of a magnetic field and consistent thermal radiation. All the physicochemical characteristics of the non-linear fluids are regarded massive. Whether or not the concentration of nanofluids remains stable is investigated. When particles of a nanofluid are in motion, chemical reactions can occur, and this motion can be used to study the concentration of the nanofluid. One must first examine a set of non-linear partial differential equations with boundary conditions as a base equation to obtain the necessary BVP mathematical model. The approximate solution for differential equations was found using the finite difference method, which also considered the necessary boundary conditions. The numerical analysis results are then represented visually to demonstrate how different governing parameters affect velocity, temperature, and concentration. Although the heat transmission exhibits a reverse manner, the non-Newtonian nanofluid moves more quickly in the non-appearance of a magnetic domain than it does in one. Additionally, as the porosity parameter increased, the heat transmission rate decreased, whereas the skin friction coefficient increased. The novel parts of this study come from the simulation findings of a non-Newtonian CW nanofluid model in porous media subjected to a magnetic field, heat radiation, and slip velocity phenomena.