bluuebunny/crossref_metadata_2025 huggingface dataset:
Glutathione-responsive and -exhausting metal nanomedicines for robust synergistic cancer therapy
Authors: Liu Peng , Hao Lu , Liu Min , Hu Shuo
Published: March 2023

Due to their rapid and uncontrolled proliferation, cancer cells are characterized by overexpression of glutathione (GSH), which impairs reactive oxygen species (ROS)-based therapy and weakens the chemotherapeutic agent-induced toxification. Extensive efforts have been made in the past few years to improve therapeutic outcomes by depleting intracellular GSH. Special focus has been given to the anticancer applications of varieties of metal nanomedicines with GSH responsiveness and exhaustion capacity. In this review, we introduce several GSH-responsive and -exhausting metal nanomedicines that can specifically ablate tumors based on the high concentration of intracellular GSH in cancer cells. These include inorganic nanomaterials, metal-organic frameworks (MOFs), and platinum-based nanomaterials. We then discuss in detail the metal nanomedicines that have been extensively applied in synergistic cancer therapy, including chemotherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), ferroptotic therapy, and radiotherapy. Finally, we present the horizons and challenges in the field for future development.
Small molecules targeting endocytic uptake and recycling pathways
Authors: Placidi Giampaolo , Mattu Clara , Ciardelli Gianluca , Campa Carlo C.
Published: March 2023

Over the past years a growing number of studies highlighted the pivotal role of intracellular trafficking in cell physiology. Among the distinct transport itineraries connecting the endocytic system, both internalization (endocytosis) and recycling (endocytic recycling) pathways were found fundamental to ensure cellular sensing, cell-to-cell communication, cellular division, and collective cell migration in tissue specific-contexts. Consistently, the dysregulation of endocytic trafficking pathways is correlated with several human diseases including both cancers and neurodegeneration. Aimed at suppress specific intracellular trafficking routes involved in disease onset and progression, huge efforts have been made to identify small molecule inhibitors with suitable pharmacological properties for in vivo administration. Here, we review most used drugs and recently discovered small molecules able to block endocytosis and endocytic recycling pathways. We characterize such pharmacological inhibitors by emphasizing their target specificity, molecular affinity, biological activity and efficacy in both in vitro and in vivo experimental models.
Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing
Authors: Jagtap Yuvraj Anandrao , Kumar Prashant , Kinger Sumit , Dubey Ankur Rakesh , Choudhary Akash , Gutti Ravi Kumar , Singh Sarika , Jha Hem Chandra , Poluri Krishna Mohan , Mishra Amit
Published: March 2023

The disturbance in mitochondrial functions and homeostasis are the major features of neuron degenerative conditions, like Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Alzheimer’s disease, along with protein misfolding. The aberrantly folded proteins are known to link with impaired mitochondrial pathways, further contributing to disease pathogenesis. Despite their central significance, the implications of mitochondrial homeostasis disruption on other organelles and cellular processes remain insufficiently explored. Here, we have reviewed the dysfunction in mitochondrial physiology, under neuron degenerating conditions. The disease misfolded proteins impact quality control mechanisms of mitochondria, such as fission, fusion, mitophagy, and proteasomal clearance, to the detriment of neuron. The adversely affected mitochondrial functional roles, like oxidative phosphorylation, calcium homeostasis, and biomolecule synthesis as well as its axes and contacts with endoplasmic reticulum and lysosomes are also discussed. Mitochondria sense and respond to multiple cytotoxic stress to make cell adapt and survive, though chronic dysfunction leads to cell death. Mitochondria and their proteins can be candidates for biomarkers and therapeutic targets. Investigation of internetworking between mitochondria and neurodegeneration proteins can enhance our holistic understanding of such conditions and help in designing more targeted therapies.
Combining machine learning and structure-based approaches to develop oncogene PIM kinase inhibitors
Authors: Almukadi Haifa , Jadkarim Gada Ali , Mohammed Arif , Almansouri Majid , Sultana Nasreen , Shaik Noor Ahmad , Banaganapalli Babajan
Published: March 2023

Introduction: PIM kinases are targets for therapeutic intervention since they are associated with a number of malignancies by boosting cell survival and proliferation. Over the past years, the rate of new PIM inhibitors discovery has increased significantly, however, new generation of potent molecules with the right pharmacologic profiles were in demand that can probably lead to the development of Pim kinase inhibitors that are effective against human cancer.

Method: In the current study, a machine learning and structure based approaches were used to generate novel and effective chemical therapeutics for PIM-1 kinase. Four different machine learning methods, namely, support vector machine, random forest, k-nearest neighbour and XGBoost have been used for the development of models. Total, 54 Descriptors have been selected using the Boruta method.

Results: SVM, Random Forest and XGBoost shows better performance as compared to k-NN. An ensemble approach was implemented and, finally, four potential molecules (CHEMBL303779, CHEMBL690270, MHC07198, and CHEMBL748285) were found to be effective for the modulation of PIM-1 activity. Molecular docking and molecular dynamic simulation corroborated the potentiality of the selected molecules. The molecular dynamics (MD) simulation study indicated the stability between protein and ligands.

Discussion: Our findings suggest that the selected models are robust and can be potentially useful for facilitating the discovery against PIM kinase.
Recent advances on catalysts for photocatalytic selective hydrogenation of nitrobenzene to aniline
Authors: Guo Jiawen , Liu Huimin , Li Yuqiao , Li Dezheng , He Dehua
Published: March 2023

Selective hydrogenation of nitrobenzene (SHN) is an important approach to synthesize aniline, an essential intermediate with extremely high research significance and value in the fields of textiles, pharmaceuticals and dyes. SHN reaction requires high temperature and high hydrogen pressure via the conventional thermal-driven catalytic process. On the contrary, photocatalysis provides an avenue to achieve high nitrobenzene conversion and high selectivity towards aniline at room temperature and low hydrogen pressure, which is in line with the sustainable development strategies. Designing efficient photocatalysts is a crucial step in SHN. Up to now, several photocatalysts have been explored for photocatalytic SHN, such as TiO2, CdS, Cu/graphene and Eosin Y. In this review, we divide the photocatalysts into three categories based on the characteristics of the light harvesting units, including semiconductors, plasmonic metal-based catalysts and dyes. The recent progress of the three categories of photocatalysts is summarized, the challenges and opportunities are pointed out and the future development prospects are described. It aims to give a clear picture to the catalysis community and stimulate more efforts in this research area.
Relationship between disorders of the intestinal microbiota and heart failure in infants with congenital heart disease
Authors: Zhang Qi-Liang , Chen Xiu-Hua , Zhou Si-Jia , Lei Yu-Qing , Huang Jiang-Shan , Chen Qiang , Cao Hua
Published: March 2023

Purpose

There is a close relationship between the intestinal microbiota and heart failure, but no study has assessed this relationship in infants with congenital heart disease. This study aimed to explore the relationship between heart failure and intestinal microbiota in infants with congenital heart disease.

Methods

Twenty-eight infants with congenital heart disease with heart failure admitted to a provincial children’s hospital from September 2021 to December 2021 were enrolled in this study. A total of 22 infants without heart disease and matched for age, sex, and weight were selected as controls. Faecal samples were collected from every participant and subjected to 16S rDNA gene sequencing.

Results

The composition of the intestinal microbiota was significantly disordered in infants with heart failure caused by congenital heart disease compared with that in infants without heart disease. At the phylum level, the most abundant bacteria in the heart failure group were Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes, and the most abundant bacteria in the control group were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. At the genus level, the most abundant bacteria in the heart failure group were Enterococcus, Bifidobacterium, Subdoligranulum, Shigella, and Streptococcus, and the most abundant bacteria in the control group were Bifidobacterium, Blautia, Bacteroides, Streptococcus, and Ruminococcus. The alpha and beta diversities of the gut bacterial community in the heart failure group were significantly lower than those in the control group (p<0.05). Compared with the control group, retinol metabolism was significantly downregulated in the heart failure group.

Conclusion

Heart failure in infants with congenital heart disease caused intestinal microbiota disorder, which was characterised by an increase in pathogenic bacteria, a decrease in beneficial bacteria, and decreases in diversity and richness. The significant downregulation of retinol metabolism in the intestinal microbiota of infants with heart failure may be related to the progression of heart failure, and further study of the underlying mechanism is needed.
Quantification of primary mitral regurgitation by echocardiography: A practical appraisal
Authors: Altes Alexandre , Vermes Emmanuelle , Levy Franck , Vancraeynest David , Pasquet Agnès , Vincentelli André , Gerber Bernhard L. , Tribouilloy Christophe , Maréchaux Sylvestre
Published: March 2023

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity. However, the use of multiple parameters to grade MR can result in potential discrepancies between one or more of them. Importantly, many factors beyond MR severity impact the values obtained for these parameters including technical settings, anatomic and hemodynamic considerations, patient's characteristics and echocardiographer' skills. Hence, clinicians involved in valvular diseases should be well aware of the respective strengths and pitfalls of each of MR grading methods by echocardiography. Recent literature highlighted the need for a reappraisal of the severity of primary MR from a hemodynamic perspective. The estimation of MR regurgitation fraction by indirect quantitative methods, whenever possible, should be central when grading the severity of these patients. The assessment of the MR effective regurgitant orifice area by the proximal flow convergence method should be used in a semi-quantitative manner. Furthermore, it is crucial to acknowledge specific clinical situations in MR at risk of misevaluation when grading severity such as late-systolic MR, bi-leaflet prolapse with multiple jets or extensive leak, wall-constrained eccentric jet or in older patients with complex MR mechanism. Finally, it is debatable whether the 4-grades classification of MR severity would be still relevant nowadays, since the indication for mitral valve (MV) surgery is discussed in clinical practice for patients with 3+ and 4+ primary MR based on symptoms, specific markers of adverse outcome and MV repair probability. Primary MR grading should be seen as a continuum integrating both quantification of MR and its consequences, even for patients with presumed “moderate” MR.
Echocardiography-based AI for detection and quantification of atrial septal defect
Authors: Lin Xixiang , Yang Feifei , Chen Yixin , Chen Xu , Wang Wenjun , Li Wenxiu , Wang Qiushuang , Zhang Liwei , Li Xin , Deng Yujiao , Pu Haitao , Chen Xiaotian , Wang Xiao , Luo Dong , Zhang Peifang , Burkhoff Daniel , He Kunlun
Published: March 2023

Objectives

We developed and tested a deep learning (DL) framework applicable to color Doppler echocardiography for automatic detection and quantification of atrial septal defects (ASDs).

Background

Color Doppler echocardiography is the most commonly used non-invasive imaging tool for detection of ASDs. While prior studies have used DL to detect the presence of ASDs from standard 2D echocardiographic views, no study has yet reported automatic interpretation of color Doppler videos for detection and quantification of ASD.

Methods

A total of 821 examinations from two tertiary care hospitals were collected as the training and external testing dataset. We developed DL models to automatically process color Doppler echocardiograms, including view selection, ASD detection and identification of the endpoints of the atrial septum and of the defect to quantify the size of defect and the residual rim.

Results

The view selection model achieved an average accuracy of 99% in identifying four standard views required for evaluating ASD. In the external testing dataset, the ASD detection model achieved an area under the curve (AUC) of 0.92 with 88% sensitivity and 89% specificity. The final model automatically measured the size of defect and residual rim, with the mean biases of 1.9 mm and 2.2 mm, respectively.

Conclusion

We demonstrated the feasibility of using a deep learning model for automated detection and quantification of ASD from color Doppler echocardiography. This model has the potential to improve the accuracy and efficiency of using color Doppler in clinical practice for screening and quantification of ASDs, that are required for clinical decision making.
Teaching and quality of teaching: Conceptions of higher education professors in Sao Tome and Principe
Authors: Grácio Luísa , Aguiar Helga , Pires Heldemerina , Carapeto Maria João
Published: March 2023

Higher education is a fundamental resource to achieve the 2030’ Sustainable Development Goals (SDG) defined by the United Nations. Specifically, SDG4 advocates the access to quality education for all, including tertiary education. Besides, higher education is expected to be an important condition for achieving other SDGs. Developing countries face particularly important challenges to accomplish these higher education goals. Thus, it is crucial to understand how to promote quality in higher education in the specific context of each country. Among the most important factors influencing higher education quality are professors’ conceptions of teaching. These conceptions influence teaching action and have a direct impact on students’ own academic performance and learning outcomes. Teaching conceptions seems to be strongly influenced by cultural values and social norms and in African countries there is little research in this field. This study aims to characterize and understand both the conceptions of teaching and on facilitating factors and barriers to university teaching held by the University of Sao Tome and Principe (USTP) faculty. The data were obtained through semi-structured interviews to 19 university professors and analyzed through qualitative and quantitative methodologies. The results suggest the prevalence of teacher-centered/transmission-oriented and student-centered/learning-oriented conceptions of university teaching. In addition, other conceptions highlight professors’ competences and the relationship between teaching and context variables. Organizational aspects of the education system, material resources and facilities, characteristics and training of the faculty, teaching action, and students’ characteristics, are mentioned both as facilitators and barriers to university teaching. Some contributions emerged from the professors’ conceptions that could inspire improvements at the USTP teaching, therefore contributing to facing changes and challenges of a society in development.
Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk
Authors: Degroote Cathy , von Känel Roland , Thomas Livia , Zuccarella-Hackl Claudia , Messerli-Bürgy Nadine , Saner Hugo , Wiest Roland , Wirtz Petra H.
Published: March 2023

Background

Coronary heart disease (CHD) and its major risk factor hypertension have both been associated with altered activity of the hypothalamus-pituitary-adrenal (HPA)-axis but the biological mechanisms underlying prospective associations with adverse disease outcomes are unclear. We investigated diurnal HPA-axis activity in CHD-patients, hypertensive (HT) and healthy normotensive men (NT) and tested for prospective associations with biological CHD risk factors.

Methods

Eighty-three male CHD-patients, 54 HT and 54 NT men repeatedly measured salivary cortisol over two consecutive days. Prospective CHD risk was assessed by changes between baseline and follow-up in the prothrombotic factors D-dimer and fibrinogen, the pro-inflammatory measures interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and acute phase protein C-reactive protein (CRP), as well as blood lipids in terms of total cholesterol (tChol)/high-density-lipoprotein cholesterol (HDL)-ratio. We aggregated coagulation and inflammatory measures to respective indices.

Results

The groups differed in repeated daytime cortisol (dayCort) secretion (p=.005,η2p=.03,f=0.18) and cortisol awakening response (CAR) (p=.006,η2p=.03,f=0.18), with similarly lower overall dayCort and CAR in CHD-patients and HT, as compared to NT. The groups differed further in cortisol at awakening (p=.015,η2p=.04,f=0.20) with highest levels in HT (p´s≤.050), and in diurnal slope between waking and evening cortisol (p=.033,η2p=.04,f=0.20) with steepest slopes in HT (p´s≤.039), although in part not independent of confounders. Lower aggregated dayCort and CAR in terms of area-under-the-curve (AUC) independently predicted increases in future overall CHD risk (AUCdayCort: p=.021,η2p=.10,f=0.33;AUCCAR: p=.028,η2p=.09,f=0.31) 3.00 ± 0.06(SEM) years later, with risk prediction most pronounced in fibrinogen (AUCdayCort: p=.017,ΔR2= 0.12;AUCCAR: p=.082).

Conclusion

We found evidence for an HPA-axis hypoactivity in CHD and HT with lower diurnal HPA-axis activity predicting increases in cardiovascular risk as evidenced by increases in circulating levels of biomarkers of atherothrombotic risk. Down-regulation of basal HPA-axis activity may contribute to the pathogenesis of atherosclerosis and thrombosis in CHD via effects on coagulation.
Concomitant downregulation of neuropeptide genes in a marine snail with consecutive sexual maturation after a nuclear disaster in Japan
Authors: Morishita Fumihiro , Horiguchi Toshihiro , Akuta Hiroto , Ueki Tatsuya , Imamura Takuya
Published: March 2023

Consecutive sexual maturation (CSM), an abnormal reproductive phenomenon of a marine snail, Reishia clavigera, has occurred since 2017 in the vicinity of the Fukushima Daiichi Nuclear Power Plant after the nuclear disaster there. We hypothesized that alterations in animal physiology mediated through genetic/epigenetic changes could sensitively reflect environmental pollution. Understanding the mechanism of this rapid biological response should enable us to quantitatively evaluate long-lasting effects of the nuclear disaster. To determine the molecular basis for CSM, we conducted transcriptome profiling in the ganglia of normal and CSM snails. We assembled the short-read cDNA sequences obtained by Illumina sequencing, and succeeded in characterizing more than 60,000 gene models that include 88 kinds of neuropeptide precursors by BLAST search and experimental curation. GO-enrichment analysis of the differentially expressed genes demonstrated that severe downregulation of neuropeptide-related genes occurred concomitantly with CSM. In particular, significant decreases of the transcripts of 37 genes among 88 neuropeptide precursor genes, including those for myomodulin, PentaFVamide, maturation-associated peptide-5A and conopressin, were commonly observed in female and male CSM snails. By contrast, microseminoprotein precursor was the only exceptional case where the expression was increased in CSM snails. These results indicate that down-regulation of neuropeptide precursors is a remarkable feature of CSM. We also found that factors involved in epigenetic modification rather than transcription factors showed altered patterns of expression upon CSM. Comprehensive expression panels of snail neuropeptide precursors made in this study will be useful tools for environmental assessment as well as for studying marine reproductive biology.
Optimal real-time tuning of autonomous distributed power systems using modern techniques
Authors: Chatterjee Shamik , Mohammed Ahmed Nura , Mishra Sachin , Sharma Naveen Kumar , Selim Ali , Bajaj Mohit , Rihan Mahmoud , Kamel Salah
Published: March 2023

This work considers using a novel heuristic population-based evolutionary algorithm [viz., the moth flame optimization (MFO) algorithm] to regulate the conventional controller installed in an autonomous power system (APS). The moth flame optimization algorithm intends to produce the optimal magnitudes of the proportional-integral-derivative plus second derivative (PIDD2) controller parameters along with its first- and second-order low-pass filter constraints (installed in the investigated autonomous power system). The present task includes a comparison of the voltage response profiles of the investigated system obtained by the proposed moth flame optimization-based proportional-integral-derivative plus second derivative controller and those obtained by other algorithms (conveyed in current state-of-the-art literature) based on a proportional-integral controller. A fast-acting Sugeno fuzzy logic (SFL) technique is used to achieve the dynamic online results of the investigated autonomous power system model for online, off-nominal operational circumstances. Under step perturbations, the time-domain transient investigation in reference to voltage and/or mandate of load for the proposed autonomous power system model is inspected. Additionally, the robustness of the proposed moth flame optimization-based proportional-integral-derivative plus second derivative controller is investigated to test its behavior. An investigation has been provided by varying the model components of the studied autonomous power system model. It may be reported, as per the results obtained from the simulation, that the proposed moth flame optimization-based proportional-integral-derivative plus second derivative controller is an effective control strategy for the autonomous power system. The current research effort indicates that the proposed moth flame optimization algorithm, along with Sugeno fuzzy logic, may be useful for the actual time process of an autonomous power system.
State of energy estimation of the echelon-use lithium-ion battery based on Takagi–Sugeno fuzzy optimization
Authors: Hou Enguang , Wang Zhen , Wang Zhixue , Qiao Xin , Liu Guangmin
Published: March 2023

Owing to the degradation of an echelon-use lithium-ion battery (EULIB), the Ohmic internal resistance (OIR) and actual capacity (AE) have both changed greatly, and the state of energy (SOE) can more accurately represent the state of a EULIB than the state of charge (SOC) because of the working voltage. To improve the accuracy and adaptability of SOE estimation, in the paper, we study the energy state estimation of a EULIB. First, the four-order resistor–capacitance equivalent model of a EULIB is established, and an unscented transformation is introduced to further improve the estimation accuracy of the SOE. Second, a EULIB’s SOE is estimated based on adaptive unscented Kalman filter (AUKF), and the OIR and AE of a EULIB are estimated based on the AUKF. Third, a Takagi–Sugeno fuzzy model is introduced to optimize the OIR and AE of the EULIB, and the SOE estimation method is established based on an adaptive dual unscented Kalman filter (ADUKF). Through simulation experiments, verification, and comparison, energy decayed to 80%, 60%, and 40% of the rated energy, respectively, even with a large initial error; with the initial value of the SOE starting at 100%, 60%, or 20%, the estimated SOE can track the actual value. It can be seen that the method has a strong adaptive ability, and the estimation accuracy error is less than 1.0%, indicating that the algorithm has high accuracy. The method presented in this paper provides a new perspective for SOE estimation of EULIBs.
The development of micro and small modular reactor in the future energy market
Authors: Tan Shaojie , Cheng Songbai , Wang Kai , Liu Xiaoxing , Cheng Hui , Wang Jun
Published: March 2023

Micro and Small Modular Reactor (MSMR) is an emerging energy technology that meets the requirements of market demand, safety, efficiency, and sustainability. This paper summarizes the advantages, application scenarios, and advanced technologies to support MSMR. Now that the energy market is more flexible and the requirements are more complex, while MSMR can meet the market demand and has a lower cost compared with other clean energies such as wind and solar photovoltaic. The United States is vigorously developing MSMRs into residential energy markets. The MSMR developed around the world has more than three generations of safety characteristics that have adopted passive safety features. MSMR can be manufactured in the factory which reduces construction schedule, cost, and waste. The nuclear fuel supply chain for MSMR is complete and perfect, including the front end and back end. An increasing number of advanced technologies support the development of MSMR, including advanced materials (TRISO fuel and accident-tolerance fuel), advanced control knowledges (DI&C, cybersecurity, and AI), and an advanced computational platform (MOOSE framework).
The effect of environmental governance in quality improvement of urbanization—Evidence from China 2000–2017
Authors: Tang Zhiguo , Tian Yanping , Yu Shuyi
Published: March 2023

Introduction: The promotion effect of environmental governance on improving the quality of urbanization is yet to be fully understood. No consensus exists on the concept of urbanization quality, and the exploration of the promotion effect of` environmental governance focuses on the economic dimension. Since 2000, high-quality and distinctive urbanization has been an important part of China’s social development, and environmental governance has been a primary aspect of this pursuit. Therefore, Chinese practice is a suitable research object to help enrich the exploration of the academic community.

Material and Methods: This paper constructs an evaluation index system for urbanization quality based on a new development philosophy by the Chinese government and adopts the entropy value method to investigate the effect of environmental governance using provincial panel data from 2000 to 2017.

Results: Firstly, the overall effect of environmental governance on improving the quality of urbanization is significant, however, among the environmental governance effects of the five dimensions of urbanization quality, it is conducive to innovation and coordinated development but not conducive to shared development. Secondly, the role of the three governance mechanisms in the environmental governance system is not balanced. The contributions of market governance are much higher than that of government governance and public governance, And there is a large room for improvement in the effectiveness of collaborative governance. In terms of the improvement of specific dimensions of urbanization quality, government governance contributes significantly to innovative development but restricts open and shared development; market governance promotes green and shared development but inhibits open development; public governance plays a positive role in coordinated and open development but hinders innovative, green and shared development. Thirdly, the role of environmental governance has significant regional differences. The eastern region is high, the northeast and central regions are second, and the western region is a negative effect. Within the environmental governance system, government governance has a significant promoting effect on all regions, market governance has a significant promoting effect on eastern, western, and northeastern regions. And public governance has the largest promoting effect on eastern and central regions, while it has an inhibiting effect on western and northeastern regions.

Discussion: It is necessary to build an environmental governance system adapted to the regional reality, play the leading role of government environmental regulation, and optimize the collaborative mechanism of the government, enterprises and the public in the environmental governance system with the guidance of market governance.
Soil moisture and salinity dynamics of drip irrigation in saline-alkali soil of Yellow River basin
Authors: Wang Yaqi , Gao Ming , Chen Heting , Fu Xiaoke , Wang Lei , Wang Rui
Published: March 2023

Soil secondary salinization in the Yellow River Diversion Irrigation Area of Northwest China seriously threatens local agricultural production. Drip irrigation technology is one of the largest contributors to low-yielding saline-alkali land; however, research on the high spatio-temporal scale variability of soil moisture and salinity in drip irrigation is still lacking. Herein, four treatments, CK (flood irrigation, 900 mm), W1 (small volume drip irrigation, 360 mm), W2 (medium volume drip irrigation, 450 mm), and W3 (large volume drip irrigation, 540 mm), were set up to investigate the characteristics and laws of soil moisture and salinity under different irrigation methods. The results showed that the soil moisture of drip irrigation was 5.02%–17.88% (W1), 7.36%–21.06% (W2), and 13.79%–27.88% (W3) higher than that of flood irrigation, resulting in a vertical distribution of soil moisture being low at the top and high at the bottom. Under drip irrigation, the soil salinity formed a desalination zone centered on the drip emitter and this zone gradually expanded to deeper soil with continuous drip irrigation, gradually transforming the soil from surface aggregation type to the bottom accumulation type. The desalination rates of W1, W2, and W3 were 18.46%, 20.84%, and 22.94%, respectively, whereas the salt leaching rate of CK was slower and the salt distribution was not uniform; therefore, the desalination rate was only 5.32%. By precisely controlling the irrigation water volume and flow, drip irrigation significantly reduced surface evaporation and subsurface leakage of water and improved water use efficiency, thus increasing grain yield. Compared with flood irrigation, the yield increase rates of W1, W2, and W3 were 6.6%, 16.18%, and 18.32%, respectively. Therefore, drip irrigation with an appropriate irrigation volume in the saline land in northern Ningxia can improve water saving, salt suppression, and maize yield.
A comprehensive pan-cancer analysis unveiling the oncogenic effect of plant homeodomain finger protein 14 (PHF14) in human tumors
Authors: Cao Zhiyou , Zhan Haibo , Wu Weiwei , Kuang Zhihui , Mo Fengbo , Liu Xuqiang , Dai Min
Published: March 2023

The plant homeodomain (PHD) finger refers to a protein motif that plays a key role in the recognition and translation of histone modification marks by promoting gene transcriptional activation and silencing. As an important member of the PHD family, the plant homeodomain finger protein 14 (PHF14) affects the biological behavior of cells as a regulatory factor. Several emerging studies have demonstrated that PHF14 expression is closely associated with the development of some cancers, but there is still no feasible pan-cancer analysis. Based on existing datasets from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we performed a systematic analysis of the oncogenic role of the PHF14 gene in 33 human cancers. The expression level of PHF14 was significantly different between different types of tumors and adjacent normal tissues, and the expression or genetic alteration of PHF14 gene was closely related to the prognosis of most cancer patients. Levels of cancer-associated fibroblasts (CAFs) infiltration in various cancer types were also observed to correlate with PHF14 expression. In some tumors, PFH14 may play a role in tumor immunity by regulating the expression levels of immune checkpoint genes. In addition, the results of enrichment analysis showed that the main biological activities of PHF14 were related to various signaling pathways or chromatin complex effects. In conclusion, our pan-cancer research shows that the expression level of PHF14 is closely related to the carcinogenesis and prognosis of certain tumors, which needs to be further verified by more experiments and more in-depth mechanism exploration.
Genetic diversity and population structure of a Peruvian cattle herd using SNP data
Authors: Corredor Flor-Anita , Figueroa Deyanira , Estrada Richard , Salazar Wilian , Quilcate Carlos , Vásquez Héctor V. , Gonzales Jhony , Maicelo Jorge L. , Medina Percy , Arbizu Carlos I.
Published: March 2023

New-generation sequencing technologies, among them SNP chips for massive genotyping, are useful for the effective management of genetic resources. To date, molecular studies in Peruvian cattle are still scarce. For the first time, the genetic diversity and population structure of a reproductive nucleus cattle herd of four commercial breeds from a Peruvian institution were determined. This nucleus comprises Brahman (N = 9), Braunvieh (N = 9), Gyr (N = 5), and Simmental (N = 15) breeds. Additionally, samples from a locally adapted creole cattle, the Arequipa Fighting Bull (AFB, N = 9), were incorporated. Female individuals were genotyped with the GGPBovine100K and males with the BovineHD. Quality control, and the proportion of polymorphic SNPs, minor allele frequency, expected heterozygosity, observed heterozygosity, and inbreeding coefficient were estimated for the five breeds. Admixture, principal component analysis (PCA), and discriminant analysis of principal components (DAPC) were performed. Also, a dendrogram was constructed using the Neighbor-Joining clustering algorithm. The genetic diversity indices in all breeds showed a high proportion of polymorphic SNPs, varying from 51.42% in Gyr to 97.58% in AFB. Also, AFB showed the highest expected heterozygosity estimate (0.41 ± 0.01), while Brahman the lowest (0.33 ± 0.01). Besides, Braunvieh possessed the highest observed heterozygosity (0.43 ± 0.01), while Brahman the lowest (0.37 ± 0.02), indicating that Brahman was less diverse. According to the molecular variance analysis, 75.71% of the variance occurs within individuals, whereas 24.29% occurs among populations. The pairwise genetic differentiation estimates (FST) between breeds showed values that ranged from 0.08 (Braunvieh vs. AFB) to 0.37 (Brahman vs. Braunvieh). Similarly, pairwise Reynold’s distance ranged from 0.09 (Braunvieh vs. AFB) to 0.46 (Brahman vs. Braunvieh). The dendrogram, similar to the PCA, identified two groups, showing a clear separation between Bos indicus (Brahman and Gyr) and B. taurus breeds (Braunvieh, Simmental, and AFB). Simmental and Braunvieh grouped closely with the AFB cattle. Similar results were obtained for the population structure analysis with K = 2. The results from this study would contribute to the appropriate management, avoiding loss of genetic variability in these breeds and for future improvements in this nucleus. Additional work is needed to speed up the breeding process in the Peruvian cattle system.
Leveraging transcriptomics for precision diagnosis: Lessons learned from cancer and sepsis
Authors: Tsakiroglou Maria , Evans Anthony , Pirmohamed Munir
Published: March 2023

Diagnostics require precision and predictive ability to be clinically useful. Integration of multi-omic with clinical data is crucial to our understanding of disease pathogenesis and diagnosis. However, interpretation of overwhelming amounts of information at the individual level requires sophisticated computational tools for extraction of clinically meaningful outputs. Moreover, evolution of technical and analytical methods often outpaces standardisation strategies. RNA is the most dynamic component of all -omics technologies carrying an abundance of regulatory information that is least harnessed for use in clinical diagnostics. Gene expression-based tests capture genetic and non-genetic heterogeneity and have been implemented in certain diseases. For example patients with early breast cancer are spared toxic unnecessary treatments with scores based on the expression of a set of genes (e.g., Oncotype DX). The ability of transcriptomics to portray the transcriptional status at a moment in time has also been used in diagnosis of dynamic diseases such as sepsis. Gene expression profiles identify endotypes in sepsis patients with prognostic value and a potential to discriminate between viral and bacterial infection. The application of transcriptomics for patient stratification in clinical environments and clinical trials thus holds promise. In this review, we discuss the current clinical application in the fields of cancer and infection. We use these paradigms to highlight the impediments in identifying useful diagnostic and prognostic biomarkers and propose approaches to overcome them and aid efforts towards clinical implementation.
The multifaceted biology of lncR-Meg3 in cardio-cerebrovascular diseases
Authors: Li Jing , Liu Wenxiu , Peng Fu , Cao Xiaoyu , Xie Xiaofang , Peng Cheng
Published: March 2023

Cardio-cerebrovascular disease, related to high mortality and morbidity worldwide, is a type of cardiovascular or cerebrovascular dysfunction involved in various processes. Therefore, it is imperative to conduct additional research into the pathogenesis and new therapeutic targets of cardiovascular and cerebrovascular disorders. Long non-coding RNAs (lncRNAs) have multiple functions and are involved in nearly all cellular biological processes, including translation, transcription, signal transduction, and cell cycle control. LncR-Meg3 is one of them and is becoming increasingly popular. By binding proteins or directly or competitively binding miRNAs, LncR-Meg3 is involved in apoptosis, inflammation, oxidative stress, endoplasmic reticulum stress, epithelial-mesenchymal transition, and other processes. Recent research has shown that LncR-Meg3 is associated with acute myocardial infarction and can be used to diagnose this condition. This article examines the current state of knowledge regarding the expression and regulatory function of LncR-Meg3 in relation to cardiovascular and cerebrovascular diseases. The abnormal expression of LncR-Meg3 can influence neuronal cell death, inflammation, apoptosis, smooth muscle cell proliferation, etc., thereby aggravating or promoting the disease. In addition, we review the bioactive components that target lncR-Meg3 and propose some potential delivery vectors. A comprehensive and in-depth analysis of LncR-Meg3’s role in cardiovascular disease suggests that targeting LncR-Meg3 may be an alternative therapy in the near future, providing new options for slowing the progression of cardiovascular disease.
Recent advances in antigen targeting to antigen-presenting cells in veterinary medicine
Authors: Melgoza-González Edgar Alonso , Bustamante-Córdova Lorena , Hernández Jesús
Published: March 2023

Advances in antigen targeting in veterinary medicine have gained traction over the years as an alternative approach for diseases that remain a challenge for traditional vaccines. In addition to the nature of the immunogen, antigen-targeting success relies heavily on the chosen receptor for its direct influence on the elicited response that will ensue after antigen uptake. Different approaches using antibodies, natural or synthetic ligands, fused proteins, and DNA vaccines have been explored in various veterinary species, with pigs, cattle, sheep, and poultry as the most frequent models. Antigen-presenting cells can be targeted using a generic approach, such as broadly expressed receptors such as MHC-II, CD80/86, CD40, CD83, etc., or focused on specific cell populations such as dendritic cells or macrophages (Langerin, DC-SIGN, XCR1, DC peptides, sialoadhesin, mannose receptors, etc.) with contrasting results. Interestingly, DC peptides show high specificity to DCs, boosting activation, stimulating cellular and humoral responses, and a higher rate of clinical protection. Likewise, MHC-II targeting shows consistent results in enhancing both immune responses; an example of this strategy of targeting is the approved vaccine against the bovine viral diarrhea virus in South America. This significant milestone opens the door to continuing efforts toward antigen-targeting vaccines to benefit animal health. This review discusses the recent advances in antigen targeting to antigen-presenting cells in veterinary medicine, with a special interest in pigs, sheep, cattle, poultry, and dogs.
Next-generation humanized NSG-SGM3 mice are highly susceptible to Staphylococcus aureus infection
Authors: Hung Sophia , Kasperkowitz Amelie , Kurz Florian , Dreher Liane , Diessner Joachim , Ibrahim Eslam S. , Schwarz Stefan , Ohlsen Knut , Hertlein Tobias
Published: March 2023

Humanized hemato-lymphoid system mice, or humanized mice, emerged in recent years as a promising model to study the course of infection of human-adapted or human-specific pathogens. Though Staphylococcus aureus infects and colonizes a variety of species, it has nonetheless become one of the most successful human pathogens of our time with a wide armory of human-adapted virulence factors. Humanized mice showed increased vulnerability to S. aureus compared to wild type mice in a variety of clinically relevant disease models. Most of these studies employed humanized NSG (NOD-scid IL2Rgnull) mice which are widely used in the scientific community, but show poor human myeloid cell reconstitution. Since this immune cell compartment plays a decisive role in the defense of the human immune system against S. aureus, we asked whether next-generation humanized mice, like NSG-SGM3 (NOD-scid IL2Rgnull-3/GM/SF) with improved myeloid reconstitution, would prove to be more resistant to infection. To our surprise, we found the contrary when we infected humanized NSG-SGM3 (huSGM3) mice with S. aureus: although they had stronger human immune cell engraftment than humanized NSG mice, particularly in the myeloid compartment, they displayed even more pronounced vulnerability to S. aureus infection. HuSGM3 mice had overall higher numbers of human T cells, B cells, neutrophils and monocytes in the blood and the spleen. This was accompanied by elevated levels of pro-inflammatory human cytokines in the blood of huSGM3 mice. We further identified that the impaired survival of huSGM3 mice was not linked to higher bacterial burden nor to differences in the murine immune cell repertoire. Conversely, we could demonstrate a correlation of the rate of humanization and the severity of infection. Collectively, this study suggests a detrimental effect of the human immune system in humanized mice upon encounter with S. aureus which might help to guide future therapy approaches and analysis of virulence mechanisms.
Active ingredients of traditional Chinese medicine for enhancing the effect of tumor immunotherapy
Authors: Yang Chao , Li Dan , Ko Chung-Nga , Wang Kai , Wang Haiyong
Published: March 2023

Immunotherapy is a type of treatment that uses our own immune system to fight cancer. Studies have shown that traditional Chinese medicine (TCM) has antitumor activity and can enhance host immunity. This article briefly describes the immunomodulatory and escape mechanisms in tumors, as well as highlights and summarizes the antitumor immunomodulatory activities of some representative active ingredients of TCM. Finally, this article puts forward some opinions on the future research and clinical application of TCM, aiming to promote the clinical applications of TCM in tumor immunotherapy and to provide new ideas for the research of tumor immunotherapy using TCM.
Cervical cancer immune infiltration microenvironment identification, construction of immune scores, assisting patient prognosis and immunotherapy
Authors: Yao Shijie , Zhao Liyang , Chen Siming , Wang Hua , Gao Yang , Shao Ning-Yi , Dai Mengyuan , Cai Hongbing
Published: March 2023

Background

The immune microenvironment is of great significance in cervical cancer. However, there is still a lack of systematic research on the immune infiltration environment of cervical cancer.

Methods

We obtained cervical cancer transcriptome data and clinical information from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, evaluated the immune microenvironment of cervical cancer, determined immune subsets, constructed an immune cell infiltration scoring system, screened key immune-related genes, and performed single-cell data analysis and cell function analysis of key genes.

Results

We combined the TCGA and GEO data sets and obtained three different immune cell populations. We obtained two gene clusters, extracted 119 differential genes, and established an immune cell infiltration (ICI) scoring system. Finally, three key genes, IL1B, CST7, and ITGA5, were identified, and single-cell sequencing data were mined to distribute these key genes in different cell types. By up-regulating CST7 and down-regulating IL1B and ITGA5, cervical cancer cells’ proliferation ability and invasion ability were successfully reduced.

Conclusion

We conducted a comprehensive assessment of the state of the tumor immune microenvironment in cervical cancer, constructed the ICI scoring system, and identified the ICI scoring system as a potential indicator of susceptibility to immunotherapy for cervical cancer, identifying key genes suggesting that IL1B, CST7, and ITGA5 play an essential role in cervical cancer.