bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel methylation-related long non-coding RNA clinical outcome prediction method: the clinical phenotype and immune infiltration research in low-grade gliomas
Authors: Li Youjun , Li Xiaobo , Yu Zhengtao
Published: May 2023

Background

Recent studies have suggested that long non-coding RNAs (lncRNAs) may play crucial role in low-grade glioma; however, the underlying mechanisms linking them to epigenetic methylation remain unclear.

Methods

We downloaded expression level data for regulators associated with N1 methyladenosine (m1A), 5-methyladenine (m5C), and N6 methyladenosine (m6A) (M1A/M5C/M6A) methylation from the Cancer Genome Atlas-low-grade glioma (TCGA-LGG) database. We identified the expression patterns of lncRNAs, and selected methylation-related lncRNAs using Pearson correlation coefficient>0.4. Non-negative matrix dimensionality reduction was then used to determine the expression patterns of the methylation-associated lncRNAs. We constructed a weighted gene co-expression network analysis (WGCNA) network to explore the co-expression networks between the two expression patterns. Functional enrichment of the co-expression network was performed to identify biological differences between the expression patterns of different lncRNAs. We also constructed prognostic networks based on the methylation presence in lncRNAs in low-grade gliomas.

Results

We identified 44 regulators by literature review. Using a correlation coefficient greater than 0.4, we identified 2330 lncRNAs, among which 108 lncRNAs with independent prognostic values were further screened using univariate Cox regression at P< 0.05. Functional enrichment of the co-expression networks revealed that regulation of trans-synaptic signaling, modulation of chemical synaptic transmission, calmodulin binding, and SNARE binding were mostly enriched in the blue module. The calcium and CA2 signaling pathways were associated with different methylation-related long non-coding chains. Using the Least Absolute Shrinkage Selector Operator (LASSO) regression analysis, we analyzed a prognostic model containing four lncRNAs. The model’s risk score was 1.12 *AC012063 + 0.74 * AC022382 + 0.32 * AL049712 + 0.16 * GSEC. Gene set variation analysis (GSVA) revealed significant differences in mismatch repair, cell cycle, WNT signaling pathway, NOTCH signaling pathway, Complement and Cascades, and cancer pathways at different GSEC expression levels. Thus, these results suggest that GSEC may be involved in the proliferation and invasion of low-grade glioma, making it a prognostic risk factor for low-grade glioma.

Conclusion

Our analysis identified methylation-related lncRNAs in low-grade gliomas, providing a foundation for further research on lncRNA methylation. We found that GSEC could serve as a candidate methylation marker and a prognostic risk factor for overall survival in low-grade glioma patients. These findings shed light on the underlying mechanisms of low-grade glioma development and may facilitate the development of new treatment strategies.
Rewarming rate of hypothermic neonates in a low-resource setting: a retrospective single-center study
Authors: Rossi Elisa , Maziku Donald Micah , Leluko Dionis Erasto , Guadagno Chiara , Brasili Luca , Azzimonti Gaetano , Putoto Giovanni , Pietravalle Andrea , Cavallin Francesco , Trevisanuto Daniele
Published: May 2023

Background

Hypothermic neonates need to be promptly rewarmed but there is no strong evidence to support a rapid or a slow pace of rewarming. This study aimed to investigate the rewarming rate and its associations with clinical outcomes in hypothermic neonates born in a low-resource setting.

Methods

This retrospective study evaluated the rewarming rate of hypothermic inborn neonates admitted to the Special Care Unit of Tosamaganga Hospital (Tanzania) in 2019–2020. The rewarming rate was calculated as the difference between the first normothermic value (36.5–37.5°C) and the admission temperature, divided by the time elapsed. Neurodevelopmental status at 1 month of age was assessed using the Hammersmith Neonatal Neurological Examination.

Results

Median rewarming rate was 0.22°C/h (IQR: 0.11–0.41) in 344/382 (90%) hypothermic inborn infants, and was inversely correlated to admission temperature (correlation coefficient −0.36, p < 0.001). Rewarming rate was not associated with hypoglycemia (p = 0.16), late onset sepsis (p = 0.10), jaundice (p = 0.85), respiratory distress (p = 0.83), seizures (p = 0.34), length of hospital stay (p = 0.22) or mortality (p = 0.17). In 102/307 survivors who returned at follow-up visit at 1 month of age, rewarming rate was not associated with a potential correlate of cerebral palsy risk.

Conclusions

Our findings did not show any significant association between rewarming rate and mortality, selected complications or abnormal neurologic exam suggestive of cerebral palsy. However, further prospective studies with strong methodological approach are required to provide conclusive evidence on this topic.
Genetic variants of genes involved in thiopurine metabolism pathway are associated with 6-mercaptopurine toxicity in pediatric acute lymphoblastic leukemia patients from Ethiopia
Authors: Ali Awol Mekonnen , Adam Haileyesus , Hailu Daniel , Engidawork Ephrem , Howe Rawleigh , Abula Teferra , Coenen Marieke J. H.
Published: May 2023

Introduction: Genetic variation in the thiopurine S-methyltransferase (TPMT) gene by and large predicts variability in 6-mercaptopurine (6-MP) related toxicities. However, some individuals without genetic variants in TPMT still develop toxicity that necessitates 6-MP dose reduction or interruption. Genetic variants of other genes in the thiopurine pathway have been linked to 6-MP related toxicities previously.

Objective: The aim of this study was to evaluate the effect of genetic variants in ITPA, TPMT, NUDT15, XDH, and ABCB1 on 6-MP related toxicities in patients with acute lymphoblastic leukemia (ALL) from Ethiopia.

Methods: Genotyping of ITPA, and XDH was performed using KASP genotyping assay, while that of TPMT, NUDT15, and ABCB1 with TaqMan® SNP genotyping assays. Clinical profile of the patients was collected for the first 6 months of the maintenance phase treatment. The primary outcome was the incidence of grade 4 neutropenia. Bivariable followed by multivariable cox regression analysis was performed to identify genetic variants associated with the development of grade 4 neutropenia within the first 6 months of maintenance treatment.

Results: In this study, genetic variants in XDH and ITPA were associated with 6-MP related grade 4 neutropenia and neutropenic fever, respectively. Multivariable analysis revealed that patients who are homozygous (CC) for XDH rs2281547 were 2.956 times (AHR 2.956, 95% CI = 1.494–5.849, p = 0.002) more likely to develop grade 4 neutropenia than those with the TT genotype.

Conclusion: In conclusion, in this cohort, XDH rs2281547 was identified as a genetic risk factor for grade 4 hematologic toxicities in ALL patients treated with 6-MP. Genetic polymorphisms in enzymes other than TPMT involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.
Millet seed oil activates β–catenin signaling and promotes hair growth
Authors: Lee Eunyoung , Seo Hyo-Deok , Kim Daedong , Park So-Hyun , Kim Soo Ro , Hyun Changhun , Hahm Jeong-Hoon , Ha Tae-Youl , Ahn Jiyun , Jung Chang Hwa
Published: May 2023

Alopecia, regardless of gender, exacerbates psychological stress in those affected. The rising prevalence of alopecia has fueled a research interest in preventing hair loss. This study investigates the potential of millet seed oil (MSO) in promoting the proliferation of hair follicle dermal papilla cells (HFDPC) and stimulating hair growth in animals with testosterone-dependent hair growth inhibition as part of a study on dietary treatments to improve hair growth. MSO-treated HFDPC significantly increased cell proliferation and phosphorylation of AKT, S6K1, and GSK3β proteins. This induces β-catenin, a downstream transcription factor, to translocate to the nucleus and increase the expression of factors related to cell growth. In a C57BL/6 mice model in which hair growth was inhibited by subcutaneous testosterone injection after shaving the dorsal skin, oral administration of MSO stimulated hair growth in the subject mice by increasing the size and number of hair follicles. These results suggest that MSO is a potent agent that may help prevent or treat androgenetic alopecia by promoting hair growth.
Phytochemicals in the treatment of inflammation-associated diseases: the journey from preclinical trials to clinical practice
Authors: Nisar Akib , Jagtap Suresh , Vyavahare Suresh , Deshpande Manasi , Harsulkar Abhay , Ranjekar Prabhakar , Prakash Om
Published: May 2023

Advances in biomedical research have demonstrated that inflammation and its related diseases are the greatest threat to public health. Inflammatory action is the pathological response of the body towards the external stimuli such as infections, environmental factors, and autoimmune conditions to reduce tissue damage and improve patient comfort. However, when detrimental signal-transduction pathways are activated and inflammatory mediators are released over an extended period of time, the inflammatory process continues and a mild but persistent pro-inflammatory state may develop. Numerous degenerative disorders and chronic health issues including arthritis, diabetes, obesity, cancer, and cardiovascular diseases, among others, are associated with the emergence of a low-grade inflammatory state. Though, anti-inflammatory steroidal, as well as non-steroidal drugs, are extensively used against different inflammatory conditions, they show undesirable side effects upon long-term exposure, at times, leading to life-threatening consequences. Thus, drugs targeting chronic inflammation need to be developed to achieve better therapeutic management without or with a fewer side effects. Plants have been well known for their medicinal use for thousands of years due to their pharmacologically active phytochemicals belonging to diverse chemical classes with a number of these demonstrating potent anti-inflammatory activity. Some typical examples include colchicine (alkaloid), escin (triterpenoid saponin), capsaicin (methoxy phenol), bicyclol (lignan), borneol (monoterpene), and quercetin (flavonoid). These phytochemicals often act via regulating molecular mechanisms that synergize the anti-inflammatory pathways such as increased production of anti-inflammatory cytokines or interfere with the inflammatory pathways such as to reduce the production of pro-inflammatory cytokines and other modulators to improve the underlying pathological condition. This review describes the anti-inflammatory properties of a number of biologically active compounds derived from medicinal plants, and their mechanisms of pharmacological intervention to alleviate inflammation-associated diseases. The emphasis is given to information on anti-inflammatory phytochemicals that have been evaluated at the preclinical and clinical levels. Recent trends and gaps in the development of phytochemical-based anti-inflammatory drugs have also been included.
Functional single nucleotide polymorphisms in dopaminergic receptors D2 predict clinical response to Cariprazine
Authors: De Pieri Marco , Ferrari Marco , Marino Franca , Traber Rafael , Bolla Emilio , Cosentino Marco
Published: May 2023

Cariprazine (CAR) is an antipsychotic drug for the treatment of schizophrenia (SCZ) and bipolar disorder (BD), and it acts as a partial agonist on the dopamine receptors (DR), D2, and D3. Although many single nucleotide polymorphisms (SNPs) in genes coding for these receptors are known to influence response to antipsychotics, to date, no study on CAR pharmacogenetics exists. In this pilot study, we investigated the relationship between SNPs in DRD2 (rs1800497 and rs6277) and DRD3 (rs6280), and response to CAR treatment, evaluated by the psychometric Brief Psychiatric Rating Scale (BPRS), in a cohort of Caucasian patients. We found a significant association between DRD2 rs1800497 and rs6277 and response to CAR treatment. When genotypes were combined into an arbitrary score, the receiver operating characteristic curve analysis showed that using a cut-off value of −2.5 the response to CAR treatment could be predicted with a positive likelihood ratio of 8.0. Our study report, for the first time, a correlation between SNPs in DRD2 and response to CAR treatment. After confirmation in a larger cohort of patients, our results could open the way for the identification of new tools for the provision of response to CAR treatment.
Assessment of the effectiveness and efficiency of the economic community of West African States Medicines Regulatory Harmonization initiative by the pharmaceutical industry
Authors: Owusu-Asante Mercy , Darko Delese Mimi , Walker Stuart , Salek Sam
Published: May 2023

Background: Following the establishment of Economic Community of West African States Medicines Regulatory Harmonization (ECOWAS-MRH) initiative in 2017, it was considered timely to carry out an evaluation of the current status of the initiative’s operating model by the pharmaceutical industry users. This study examined the challenges being encountered and identified strategies that would strengthen the ECOWAS-MRH initiative moving forward.

Methods: The Process Effectiveness and Efficiency Rating (PEER) questionnaire was used to collect data from manufacturers who have submitted applications to the joint assessment procedure and had identified recommendations for improving the performance of the ECOWAS-MRH initiative.

Results: Ten pharmaceutical manufacturer participants (innovator, generic foreign, generic local) all reported that harmonisation of registration requirements was a major benefit, allowing submission of the same dossier to multiple countries, reducing the application burden and saving time and resources. Additionally, receipt of the same list of questions from several countries enables the compilation of a single response package, resulting in shorter timelines for approvals compared to the individualised country responses. Another benefit of a harmonised registration process was the simultaneous accessibility of medicines in various markets. Key challenges included a lack of centralised submission and tracking, differences in regulatory performance of the national medical regulatory authorities, a lack of detailed information for applicants and a low motivation to use the ECOWAS-MRH route with a preference for other regulatory pathways in the ECOWAS member states.

Conclusion: This study identified several approaches to increase the effectiveness of this initiative: the implementation of risk-based approaches such as use of reliance pathways; establishment of a robust information technology systems, building assessor capacity to facilitate processing and monitoring applications; and priority review of ECOWAS-MRH products.
Evaluating efficacy and safety of sub-anesthetic dose esketamine as an adjuvant to propofol/remifentanil analgosedation and spontaneous respiration for children flexible fibreoptic bronchoscopy: a prospective, double-blinded, randomized, and placebo-controlled clinical trial
Authors: Zhong Yu , Jiang Min , Wang Yunshi , Su Tingting , Lv Yuanzhi , Fan Zhiqing , Ning Hengyi , Yang Yilan , Chen Yanhua , Xie Yubo
Published: May 2023

Background: Flexible fiberoptic bronchoscopy (FFB) for children is widely performed under sedation. Currently, the optimal sedation regimen remains unclear. Esketamine is an N-methyl-D-aspartic acid (NMDA) receptor antagonist, which has stronger sedative and analgesic effects and exerts less cardiorespiratory depression than other sedatives. The purpose of this study was to evaluate whether a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous ventilation compared with control reduces the procedural and anesthesia-related complications of FFB in children.

Materials and methods: Seventy-two children ≤ 12 years of age who were scheduled for FFB were randomly assigned, in a 1:1 ratio, to the esketamine-propofol/remifentanil (Group S, n = 36) or to the propofol/remifentanil group (Group C, n = 36). All children were retained spontaneous ventilation. The primary outcome was the incidence of oxygen desaturation (respiratory depression). Perioperative hemodynamic variables, blood oxygen saturation (SPO2), end-tidal partial pressure of carbon dioxide (PetCO2), respiratory rate (R), and the Bispectral index (BIS), induction time, procedural time, recovery time, the time to the ward from the recovery room, consumption of propofol and remifentanil during the procedure and the appearance of adverse events, including paradoxical agitation following midazolam administration, injection pain, laryngospasm, bronchospasm, PONV, vertigo, and hallucination were also compared.

Results: The incidence of oxygen desaturation was significantly lower in Group S (8.3%) compared to Group C (36.1%, p = 0.005). The perioperative hemodynamic profile including SBP, DBP, and HR were more stable in Group S than that in Group C (p < 0.05). Consumption of propofol and remifentanil was lower in Group S than in Group C (p < 0.05). Furthermore, PAED scores, cough scores and injection pain were lower in the Group S than in Group C (p < 0.05). The recovery time of Group S was slightly longer than that of Group C (p < 0.05). Nobody happened paradoxical agitation following midazolam administration, PONV, vertigo, and hallucinations in both groups (p > 0.05).

Conclusion: Our findings indicate that a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous respiration is an effective regimen for children undergoing FFB. Our findings will provide a reference for clinical sedation practice during these procedures in children.

Clinical Trail Registration: Chinese clinicaltrials.gov registry (identifier: ChiCTR2100053302).
An impact-insensitive fiber optic current transformer based on polarization maintaining photonic crystal fiber delay coil
Authors: Gao Hongze , Wang Guochen , Gao Wei , Zhao Bo , Zhang Runfeng , Zhang Boya , Yang Fan
Published: May 2023

When the polarization-maintaining fiber (PMF) delay coil of a fiber optic current transformer (FOCT) is impacted, external forces on the optical fibers and change of their birefringence may lead to extra phase errors during the propagation of optical signals in the fibers. These errors increase the error in current measurement. In the paper, the environmental impact mechanisms influencing the PMF delay coil of FOCT were investigated with a mathematical error model. The method of replacing PMF with a polarization-maintaining photonic crystal fiber (PCF) as the delay coil was proposed. Also, the relationship between structural parameters of air holes and linear birefringence of the polarization maintaining PCF subjected to stress was investigated. The structural parameters of optical fibers were also optimized subsequently. Simulated impact experiments of FOCT with polarization-maintaining PCF and PMF as the delay coil, respectively, demonstrated the effective impact resistance of FOCT with polarization-maintaining PCF delay coil after the optimization of its structural parameters. The current measurement errors of the FOCTs with polarization maintaining PCF delay coil reduced by approximately 35% with respect to the FOCT with PMF delay coil.
On QSAR-based cardiotoxicity modeling with the expressiveness-enhanced graph learning model and dual-threshold scheme
Authors: Wang Huijia , Zhu Guangxian , Izu Leighton T. , Chen-Izu Ye , Ono Naoaki , Altaf-Ul-Amin MD , Kanaya Shigehiko , Huang Ming
Published: May 2023

Introduction: Given the direct association with malignant ventricular arrhythmias, cardiotoxicity is a major concern in drug design. In the past decades, computational models based on the quantitative structure–activity relationship have been proposed to screen out cardiotoxic compounds and have shown promising results. The combination of molecular fingerprint and the machine learning model shows stable performance for a wide spectrum of problems; however, not long after the advent of the graph neural network (GNN) deep learning model and its variant (e.g., graph transformer), it has become the principal way of quantitative structure–activity relationship-based modeling for its high flexibility in feature extraction and decision rule generation. Despite all these progresses, the expressiveness (the ability of a program to identify non-isomorphic graph structures) of the GNN model is bounded by the WL isomorphism test, and a suitable thresholding scheme that relates directly to the sensitivity and credibility of a model is still an open question.

Methods: In this research, we further improved the expressiveness of the GNN model by introducing the substructure-aware bias by the graph subgraph transformer network model. Moreover, to propose the most appropriate thresholding scheme, a comprehensive comparison of the thresholding schemes was conducted.

Results: Based on these improvements, the best model attains performance with 90.4% precision, 90.4% recall, and 90.5% F1-score with a dual-threshold scheme (active: <1μM; non-active: >30μM). The improved pipeline (graph subgraph transformer network model and thresholding scheme) also shows its advantages in terms of the activity cliff problem and model interpretability.
Lung diffusing capacity for nitric oxide in space: microgravity gas density interactions
Authors: Karlsson Lars L. , Van Muylem Alain , Linnarsson Dag
Published: May 2023

Introduction: During manned space exploration lung health is threatened by toxic planetary dust and radiation. Thus, tests such as lung diffusing capacity (DL) are likely be used in planetary habitats to monitor lung health. During a DL maneuver the rate of uptake of an inspired blood-soluble gas such as nitric oxide (NO) is determined (DLNO). The aim of this study was to investigate the influence of altered gravity and reduced atmospheric pressure on the test results, since the atmospheric pressure in a habitat on the moon or on Mars is planned to be lower than on Earth. Changes of gravity are known to alter the blood filling of the lungs which in turn may modify the rate of gas uptake into the blood, and changes of atmospheric pressure may alter the speed of gas transport in the gas phase.

Methods: DLNO was determined in 11 subjects on the ground and in microgravity on the International Space Station. Experiments were performed at both normal (1.0 atm absolute, ata) and reduced (0.7 ata) atmospheric pressures.

Results: On the ground, DLNO did not differ between pressures, but in microgravity DLNO was increased by 9.8% (9.5) (mean [SD]) and 18.3% (15.8) at 1.0 and 0.7 ata respectively, compared to normal gravity, 1.0 ata. There was a significant interaction between pressure and gravity (p = 0.0135).

Discussion: Estimates of the membrane (DmNO) and gas phase (DgNO) components of DLNO suggested that at normal gravity a reduced pressure led to opposing effects in convective and diffusive transport in the gas phase, with no net effect of pressure. In contrast, a DLNO increase with reduced pressure at microgravity is compatible with a substantial increase of DmNO partially offset by reduced DgNO, the latter being compatible with interstitial edema. In microgravity therefore, DmNO would be proportionally underestimated from DLNO. We also conclude that normal values for DL in anticipation of planetary exploration should be determined not only on the ground but also at the gravity and pressure conditions of a future planetary habitat.
Transcriptional time course after rotator cuff repair in 6 month old female rabbits
Authors: Vasquez-Bolanos Laura S. , Gibbons Michael C. , Ruoss Severin , Wu Isabella T. , Esparza Mary C. , Fithian Donald C. , Lane John G. , Singh Anshuman , Nasamran Chanond A. , Fisch Kathleen M. , Ward Samuel R.
Published: May 2023

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes.

Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae.

Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways.

Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks post-repair.
RNAi-mediated gene silencing of Phlebotomus papatasi defensins favors Leishmania major infection
Authors: Vomáčková Kykalová Barbora , Sassù Fabiana , Volf Petr , Telleria Erich Loza
Published: May 2023

Introduction: Production of different antimicrobial peptides (AMPs) is one of the insect’s prominent defense strategies, regulated mainly by Toll and immune deficiency (IMD) humoral pathways. Here we focused mainly on two AMPs of Phlebotomus papatasi, vector of Leishmania major parasites, their association with the relish transcription factor and the effective participation on Leishmania infection.

Methods and results: We further characterized the role of previously described gut-specific P. papatasi defensin (PpDef1) and identified the second defensin (PpDef2) expressed in various sand fly tissues. Using the RNAi-mediated gene silencing, we report that the silencing of PpDef1 gene or simultaneous silencing of both defensin genes (PpDef1 and PpDef2) resulted in increased parasite levels in the sand fly (detectable by PCR) and higher sand fly mortality. In addition, we knocked down relish, the sole transcription factor of the IMD pathway, to evaluate the association of the IMD pathway with AMPs expression in P. papatasi. We demonstrated that the relish gene knockdown reduced the expression of PpDef2 and attacin, another AMP abundantly expressed in the sand fly body.

Conclusions: Altogether, our experiments show the importance of defensins in the sand fly response toward L. major and the role of the IMD pathway in regulating AMPs in P. papatasi.
Compartmentalised cAMP signalling in the primary cilium
Authors: Paolocci Ester , Zaccolo Manuela
Published: May 2023

cAMP is a universal second messenger that relies on precise spatio-temporal regulation to control varied, and often opposing, cellular functions. This is achieved via selective activation of effectors embedded in multiprotein complexes, or signalosomes, that reside at distinct subcellular locations. cAMP is also one of many pathways known to operate within the primary cilium. Dysfunction of ciliary signaling leads to a class of diseases known as ciliopathies. In Autosomal Dominant Polycystic Kidney Disease (ADPKD), a ciliopathy characterized by the formation of fluid-filled kidney cysts, upregulation of cAMP signaling is known to drive cystogenesis. For decades it has been debated whether the primary cilium is an independent cAMP sub-compartment, or whether it shares a diffusible pool of cAMP with the cell body. Recent studies now suggest it is a specific pool of cAMP generated in the cilium that propels cyst formation in ADPKD, supporting the notion that this antenna-like organelle is a compartment within which cAMP signaling occurs independently from cAMP signaling in the bulk cytosol. Here we present examples of cAMP function in the cilium which suggest this mysterious organelle is home to more than one cAMP signalosome. We review evidence that ciliary membrane localization of G-Protein Coupled Receptors (GPCRs) determines their downstream function and discuss how optogenetic tools have contributed to establish that cAMP generated in the primary cilium can drive cystogenesis.
Molecular changes in phenolic compounds in Euglena gracilis cells grown under metal stress
Authors: Bernard Eve , Guéguen Céline
Published: May 2023

Metal presence in the aquatic ecosystem has increased and diversified over the last decades due to anthropogenic sources. These contaminants cause abiotic stress on living organisms that lead to the production of oxidizing molecules. Phenolic compounds are part of the defense mechanisms countering metal toxicity. In this study, the production of phenolic compounds by Euglena gracilis under three different metal stressors (i.e. cadmium, copper, or cobalt) at sub-lethal concentration was assessed using an untargeted metabolomic approach by mass spectrometry combined with neuronal network analysis (i.e. Cytoscape). The metal stress had a greater impact on molecular diversity than on the number of phenolic compounds. The prevalence of sulfur- and nitrogen-rich phenolic compounds were found in Cd- and Cu-amended cultures. Together these results confirm the impact of metallic stress on phenolic compounds production, which could be utilized to assess the metal contamination in natural waters.
Explore the soil factors driving soil microbial community and structure in Songnen alkaline salt degraded grassland
Authors: Bai Zhenyin , Jia Aomei , Li Haixian , Wang Mingjun , Qu Shanmin
Published: May 2023

Introduction

Saline-alkali degradation in grassland significantly affects plant community composition and soil physical and chemical properties. However, it remains unclear whether different degradation gradients affect soil microbial community and the main soil driving factors. Therefore, it is important to elucidate the effects of saline-alkali degradation on soil microbial community and the soil factors affecting soil microbial community in order to develop effective solutions to restore the degraded grassland ecosystem.

Methods

In this study, Illumina high-throughput sequencing technology was used to study the effects of different saline-alkali degradation gradients on soil microbial diversity and composition. Three different gradients were qualitatively selected, which were the light degradation gradient (LD), the moderate degradation gradient (MD) and the severe degradation gradient (SD).

Results

The results showed that salt and alkali degradation decreased the diversity of soil bacterial and fungal communities, and changed the composition of bacterial and fungal communities. Different degradation gradients had different adaptability and tolerance species. With the deterioration of salinity in grassland, the relative abundance of Actinobacteriota and Chytridiomycota showed a decreasing trend. EC, pH and AP were the main drivers of soil bacterial community composition, while EC, pH and SOC were the main drivers of soil fungal community composition. Different microorganisms are affected by different soil properties. The changes of plant community and soil environment are the main factors limiting the diversity and composition of soil microbial community.

Discussion

The results show that saline-alkali degradation of grassland has a negative effect on microbial biodiversity, so it is important to develop effective solutions to restore degraded grassland to maintain biodiversity and ecosystem function.
Artificial hybridization techniques in small millets—A review
Authors: Nagaraja T. E. , Nandini C.  , Bhat Sujata , Parveen S. Gazala
Published: May 2023

Small millets are nutri-rich, climate-resilient food and fodder crops. They include finger millet, proso millet, foxtail millet, little millet, kodo millet, browntop millet, and barnyard millet. They are self-pollinated crops and belong to the family Poaceae. Hence, to widen the genetic base, the creation of variation through artificial hybridization is a prerequisite. Floral morphology, size, and anthesis behavior cause major hindrances in recombination breeding through hybridization. Manual emasculation of florets is practically very difficult; therefore, the contact method of hybridization is widely followed. However, the success rate of obtaining true F1s is 2% to 3%. In finger millet, hot water treatment (52°C) for 3 to 5 min causes temporal male sterility. Chemicals such as maleic hydrazide, gibberellic acid, and ethrel at different concentrations aid in inducing male sterility in finger millet. Partial-sterile (PS) lines developed at the Project Coordinating Unit, Small Millets, Bengaluru are also in use. The percent seed set in crosses derived from PS lines ranged from 27.4 to 49.4, with an average of 40.10%. In proso millet, little millet, and browntop millet, apart from contact method, hot water treatment, hand emasculation, and the USSR method of hybridization are also followed. A newly developed modified crossing method known as the Small Millets University of Agricultural Sciences Bengaluru (SMUASB) method in proso and little millets has a success rate of 56% to 60% in obtaining true hybrids. Hand emasculation and pollination under the greenhouse and growth chamber in foxtail millet with a success rate of 75% seed set is suggested. In barnyard millet, hot water treatment (48°C to 52°C) for 5 min followed by the contact method is often practiced. Kodo millet being cleistogamous, mutation breeding is widely followed to create variation. Most commonly, hot water treatment is followed in finger millet and barnyard millet, SMUASB in proso, and little millet. Although no specific method is suitable for all small millets, it is essential to identify a trouble-free technique that produces maximum crossed seeds in all the small millets.
Capturing agro-morphological variability for tolerance to terminal heat and combined heat–drought stress in landraces and elite cultivar collection of wheat
Authors: Kumar Shubham , Kumar Hitesh , Gupta Vikas , Kumar Adesh , Singh Chandra Mohan , Kumar Mukul , Singh Ajay Kumar , Panwar Gurusharan Singh , Kumar Sujit , Singh Akhilesh Kumar , Kumar Rahul
Published: May 2023

Climate change has resulted in extreme temperature and drought around the globe, which poses serious threat to food security. Both heat and drought stress affects the production and productivity of wheat crop. The present study was undertaken to evaluate 34 landraces and elite cultivars ofTriticumspp. for phenological and yield-related traits under optimum, heat, and combined heat–drought stress environments during 2020–2021 and 2021–2022. The pooled analysis of variance showed significant genotype × environment interaction, suggesting an influence of stress on trait expression. The trait performance of genotypes exhibited significant reduction under combined heat–drought stress as compared to optimum and heat stress environments. The maximum seed yield penalty was observed under combined heat–drought stress environment as compared to heat stress alone. Regression analysis indicated significant contribution of number of grains per spike towards stress tolerance. Based on Stress Tolerance Index (STI), genotypes Local-17, PDW 274, HI-8802, and HI-8713 were identified to be tolerant to both heat and combined heat and drought stress at Banda, whereas genotypes DBW 187, HI-8777, Raj 4120, and PDW 274 were tolerant at Jhansi location. The genotype PDW 274 showed stress tolerance under all treatments at both the locations. The genotypes PDW 233 and PDW 291 showed highest stress susceptibility index (SSI) across the environments. The number of grains per spike and test kernel weight were positively associated with seed yield across the environments and locations. The selected genotypes Local-17, HI 8802, and PDW 274 were identified to be the potential sources of heat and combined heat–drought tolerance, which may be utilized in hybridization to develop tolerant wheat genotypes and also for mapping of underlying genes/quantitative trait loci (QTLs).
Metabolic profiling of Chimonanthus grammatus via UHPLC-HRMS-MS with computer-assisted structure elucidation and its antimicrobial activity
Authors: Hu Haibo , Tekin Volkan , Hu Bin , Yaghoobi Mahdi , Khan Ajmal , Ghosh Alokesh Kumar , Panda Sujogya Kumar , Huang Hao , Luyten Walter
Published: May 2023

Chimonanthus grammatus is used as Hakka traditional herb to treat cold, flu, etc. So far, the phytochemistry and antimicrobial compounds have not been well investigated. In this study, the orbitrap-ion trap MS was used to characterize its metabolites, combined with a computer-assisted structure elucidation method, and the antimicrobial activities were assessed by a broth dilution method against 21 human pathogens, as well as the bioassay-guided purification work to clarify its main antimicrobial compounds. A total of 83 compounds were identified with their fragmentation patterns, including terpenoids, coumarins, flavonoids, organic acids, alkaloids, and others. The plant extracts can strongly inhibit the growth of three Gram-positive and four Gram-negative bacteria, and nine active compounds were bioassay-guided isolated, including homalomenol C, jasmonic acid, isofraxidin, quercitrin, stigmasta-7,22-diene-3β,5α,6α-triol, quercetin, 4-hydroxy-1,10-secocadin-5-ene-1,10-dione, kaempferol, and E-4-(4,8-dimethylnona-3,7-dienyl)furan-2(5H)-one. Among them, isofraxidin, kaempferol, and quercitrin showed significant activity against planktonic Staphylococcus aureus (IC50 = 13.51, 18.08 and 15.86 µg/ml). Moreover, their antibiofilm activities of S. aureus (BIC50 = 15.43, 17.31, 18.86 µg/ml; BEC50 = 45.86, ≥62.50, and 57.62 µg/ml) are higher than ciprofloxacin. The results demonstrated that the isolated antimicrobial compounds played the key role of this herb in combating microbes and provided benefits for its development and quality control, and the computer-assisted structure elucidation method was a powerful tool for chemical analysis, especially for distinguishing isomers with similar structures, which can be used for other complex samples.
Combined analysis of metabolome and transcriptome of wheat kernels reveals constitutive defense mechanism against maize weevils
Authors: Lv Liangjie , Guo Xiaorui , Zhao Aiju , Liu Yuping , Li Hui , Chen Xiyong
Published: May 2023

Sitophilus zeamais (maize weevil) is one of the most destructive pests that seriously affects the quantity and quality of wheat (Triticum aestivum L.). However, little is known about the constitutive defense mechanism of wheat kernels against maize weevils. In this study, we obtained a highly resistant variety RIL-116 and a highly susceptible variety after two years of screening. The morphological observations and germination rates of wheat kernels after feeding ad libitum showed that the degree of infection in RIL-116 was far less than that in RIL-72. The combined analysis of metabolome and transcriptome of RIL-116 and RIL-72 wheat kernels revealed differentially accumulated metabolites were mainly enriched in flavonoids biosynthesis-related pathway, followed by glyoxylate and dicarboxylate metabolism, and benzoxazinoid biosynthesis. Several flavonoids metabolites were significantly up-accumulated in resistant variety RIL-116. In addition, the expression of structural genes and transcription factors (TFs) related to flavonoids biosynthesis were up-regulated to varying degrees in RIL-116 than RIL-72. Taken together, these results indicated that the biosynthesis and accumulation of flavonoids contributes the most to wheat kernels defense against maize weevils. This study not only provides insights into the constitutive defense mechanism of wheat kernels against maize weevils, but may also play an important role in the breeding of resistant varieties.
Targeting the Aspergillus flavus p2c gene through host-induced gene silencing reduces A. flavus infection and aflatoxin contamination in transgenic maize
Authors: Raruang Yenjit , Omolehin Olanike , Hu Dongfang , Wei Qijian , Promyou Surassawadee , Parekattil Lidiya J. , Rajasekaran Kanniah , Cary Jeffrey W. , Wang Kan , Chen Zhi-Yuan
Published: May 2023

Aspergillus flavus is an opportunistic fungal pathogen that infects maize and produces aflatoxins. Using biocontrol or developing resistant cultivars to reduce aflatoxin contamination has only achieved limited success. Here, the A. flavus polygalacturonase gene (p2c) was targeted for suppression through host-induced gene silencing (HIGS) to reduce aflatoxin contamination in maize. An RNAi vector carrying a portion of the p2c gene was constructed and transformed into maize B104. Thirteen out of fifteen independent transformation events were confirmed to contain p2c. The T2 generation kernels containing the p2c transgene had less aflatoxin than those without the transgene in six out of eleven events we examined. Homozygous T3 transgenic kernels from four events produced significantly less aflatoxins (P ≤ 0.02) than the kernels from the null or B104 controls under field inoculation conditions. The F1 kernels from the crosses between six elite inbred lines with P2c5 and P2c13 also supported significantly less aflatoxins (P ≤ 0.02) than those from the crosses with null plants. The reduction in aflatoxin ranged from 93.7% to 30.3%. Transgenic leaf (T0 and T3) and kernel tissues (T4) were also found to have significantly higher levels of p2c gene-specific small RNAs. Further, homozygous transgenic maize kernels had significantly less fungal growth (27~40 fold) than the null control kernels 10 days after fungal inoculation in the field. The calculated suppression of p2c gene expression based on RNAseq data was 57.6% and 83.0% in P2c5 and P2c13 events, respectively. These results indicate clearly that the reduced aflatoxin production in the transgenic kernels is due to RNAi-based suppression of p2c expression, which results in reduced fungal growth and toxin production.
Distribution patterns of fern species richness along elevations the Tibetan Plateau in China: regional differences and effects of climate change variables
Authors: Umair Muhammad , Hu Xiaofei , Cheng Qi , Ali Shahzad , Ni Jian
Published: May 2023

Because of its distinct geological history, frigid temperature, and rich biodiversity, the Tibetan Plateau gives an excellent opportunity to assess the effect of climate change on determining species richness. The distribution patterns of fern species richness and their underlying processes have long been a matter of debate in ecology research, with various hypotheses suggested over the years. Here, we explore richness patterns of fern species in Xizang on the southern and western Tibetan Plateau along an elevational gradient (100–5300 m a.s.l.) and evaluate climatic factors causing the spatial decrease and increase of fern species richness. We used regression and correlation analyses to relate the species richness with elevation and climatic variables. Throughout our research, we identified 441 fern species from 97 genera and 30 families. The Dryopteridaceae family (S = 97) has the highest number of species. All energy-temperature and moisture variables except drought index (DI) had a significant correlation with elevation. The altitude has a unimodal relationship with fern species, and the species richness is the largest at an altitude of 2500 m. The horizontal richness pattern of fern species on the Tibetan Plateau also showed that areas of extremely high species richness are mainly distributed in Zayü and Mêdog County, with an average elevation of 2800 m and 2500 m, respectively. The richness of fern species has a log-linear relationship with moisture-related factors such as moisture index (MI), mean annual precipitation (MAP), and drought index (DI). Because the peak corresponds spatially with the MI index, the unimodal patterns confirm the significance of moisture on fern distributions. Our results showed that mid-altitudes have the highest species richness (high MI), but high elevations have lower richness due to high solar radiation, and low elevations have lower richness due to high temperatures and low precipitation. Twenty-two of the total species are classified as nearly threatened, vulnerable or critically endangered, and varied in elevation from 800 m to 4200 m. Such relationships between the distribution and richness of fern species and climates on the Tibetan Plateau can provide data support for future predictions of the impacts of climate change scenarios on fern species, the ecological protection of representative fern species, and references for the planning and construction of nature reserves in the future.
Intervention with EMDR on a sample of healthcare workers in the nephrology and dialysis service during the COVID-19 emergency: from immediate treatment effect to long-term maintenance
Authors: Belvedere Caterina , Fabbrini Paolo , Alberghini Elena , Ghedini Simona Anna , Fernandez Isabel , Maslovaric Giada , Pagani Marco , Gallina Eugenio
Published: May 2023

Background

During the COVID-19 pandemic, psychological support was provided to healthcare workers in Nephrology and Dialysis Operative Unit of the Azienda Ospedaliera Bassini using an EMDR group protocol to decrease posttraumatic stress symptoms in the medium and long term. The aim of this study was to demonstrate the effectiveness of EMDR treatment to reduce post-traumatic stress symptoms at the end of the first pandemic wave and its progress over time in the subsequent phases of the health emergency.

Methods

The sample of study consisted of 43 healthcare workers from the Nephrology and Dialysis Service who spontaneously decided to take part in the Brief EMDR treatment. Statistical analyses were carried out to compare the data collected with the IES-R, the Emotion Thermometer and the Post-Traumatic Growth Scale. The comparisons covered pre-treatment, post-treatment and follow-up.

Results

The results show a significant clinical improvement in reducing PTSD symptoms following the Brief EMDR group treatment. The comparison between PRE and POST treatment (DELTA1) regarding the scores from IES-R and Emotion Thermometer, highlighted the important statistically change that occurred in terms of symptomatology reduction (p < 0.001). By comparing POST and FU (DELTA2), it was observed that all variables except avoidance show a significant weakening of the effect with time (p < 0.001), but the magnitude of this effect is much smaller than the improvement found in DELTA1. DELTA 3 analysis finally made it possible to highlight how the treatment effect is maintained almost intact at follow-up. In fact, the maintenance of a better situation at follow-up was observed, in the course of re-traumatization linked to the new wave, compared to the initial data (p < 0.001).

Conclusion

The COVID-19 health emergency has significantly impacted hospital healthcare workers, leading to a high risk of developing PTSD symptoms. A psychological intervention aimed at the operators themselves is therefore of great importance.