bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment
Authors: Wu Xianbo , Xu Yihua , Liang Qi , Yang Xinwei , Huang Jianli , Wang Jie , Zhang Hong , Shi Jianyou
Published: April 2023

The PI3K-Akt-mTOR pathway is a viable target for cancer treatment and can be used to treat various malignant tumours, including follicular lymphoma and breast cancer. Both enzymes, PI3K and mTOR, are critical in this pathway. Hence, in recent years, an array of inhibitors targeting these two targets have been studied, showing dual PI3K/mTOR inhibition compared with single targeting small molecule inhibitors. Inhibitors not only inhibit cell proliferation but also promote cell apoptosis. These inhibitors show high potency and little drug resistance even at low doses, suggesting that PI3K/mTOR inhibitors are promising cancer drugs. Herein, we summarised the recent research of PI3K/mTOR dual inhibitors—for example, structure-activity relationship, pharmacokinetics, and clinical practice, and briefly commented on them.

Clinical Trial Registration:https://clinicaltrials.gov.
The Antifibrotic and the Anticarcinogenic Activity of Capsaicin in Hot Chili Pepper in Relation to Oral Submucous Fibrosis
Authors: Huang Zoufang , Sharma Mohit , Dave Aparna , Yang Yuqi , Chen Zhe-Sheng , Radhakrishnan Raghu
Published: April 2023

A burning sensation on eating spicy foods purportedly supports the role of capsaicin, an active component of chili peppers, in the etiology of oral submucous fibrosis (OSF). Although the mast cell mediators and activated P2X receptors induce a constant burning sensation through an ATP-dependent mechanism, it is the activation of the transient receptor potential vanilloid 1 (TRPV-1) receptor by capsaicin that aggravates it. The molecular basis for the burning pain in OSF is thus attributable to the activation of TRPV1. There is overwhelming evidence that confirms capsaicin has more of a protective role in attenuating fibrosis and is potentially therapeutic in reversing conditions linked to collagen accumulation. The activation of TRPV-1 by capsaicin increases intracellular calcium ([Ca2+]i), upregulates AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT-1), to enrich endothelium-dependent vasodilation via endothelial nitric oxide synthase (eNOS). The induction of vasodilation induces antifibrotic effects by alleviating hypoxia. The antifibrotic effects of capsaicin are mediated through the upregulation of antioxidant enzymes, downregulation of inflammatory genes and suppression of new collagen fibril formation. Capsaicin also demonstrates an anticarcinogenic effect by upregulating the cytotoxic T cells and downregulating regulatory T cells through the inhibition of angiogenesis and promotion of apoptosis. Judicious administration of capsaicin with an appropriate delivery mechanism may have therapeutic benefits in reducing pain sensation, rendering antifibrotic effects, and preventing the malignant transformation of OSF. This paper provides an overview of the molecular basis of capsaicin and its therapeutic application as an antifibrotic and anticarcinogenic agent for the treatment of OSF.
Modified coptisine derivatives as an inhibitor against pathogenic Rhizomucor miehei, Mycolicibacterium smegmatis (Black Fungus), Monkeypox, and Marburg virus by molecular docking and molecular dynamics simulation-based drug design approach
Authors: Akash Shopnil , Hossain Arafat , Mukerjee Nobendu , Sarker Md. Moklesur Rahman , Khan Mohammad Firoz , Hossain Md. Jamal , Rashid Mohammad A. , Kumer Ajoy , Ghosh Arabinda , León-Figueroa Darwin A. , Barboza Joshuan J. , Padhi Bijaya Kumar , Sah Ranjit
Published: April 2023

During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our in silico investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg viruses.
Xue-Jie-San restricts ferroptosis in Crohn’s disease via inhibiting FGL1/NF-κB/STAT3 positive feedback loop
Authors: Gao Ying , Zhang Zhaozheng , Du Jun , Yang Xiao , Wang Xiaopeng , Wen Ke , Sun Xueliang
Published: April 2023

Crohn’s disease (CD) is an incurable inflammatory bowel disease due to unclear etiology and pathogenesis. Accumulating evidences have shown the harmful role of ferroptosis in CD onset and development. Additionally, fibrinogen-like protein 1 (FGL1) has been verified to be a potential therapeutic target of CD. Xue-Jie-San (XJS) is an effective prescription for treating CD. However, its therapeutic mechanism has not been fully elucidated. This study aimed to determine whether XJS alleviating CD via regulating ferroptosis and FGL1 expression. A colitis rat model was induced by 2,4,6-trinitrobenzene sulfonic acid and treated with XJS. The disease activity indices of the colitis rats were scored. Histopathological damage was assessed using HE staining. ELISA was performed to examine inflammatory cytokines. Transmission electron microscopy was utilized to observe ultrastructure changes in intestinal epithelial cells (IECs). Iron load was evaluated by examining iron concentrations, the expressions of FPN, FTH and FTL. Lipid peroxidation was investigated through detecting the levels of ROS, 4-HNE, MDA and PTGS2. Furthermore, the SLC7A11/GSH/GPX4 antioxidant system and FGL1/NF-κB/STAT3 signaling pathway were examined. The results showed that colitis was dramatically ameliorated in the XJS-treated rats as evidenced by relief of clinical symptoms and histopathological damages, downregulation of pro-inflammatory cytokines IL-6, IL-17 and TNF-α, and upregulation of anti-inflammatory cytokine IL-10. Furthermore, XJS administration led to ferroptosis inhibition in IECs by reducing iron overload and lipid peroxidation. Mechanistically, XJS enhanced the SLC7A11/GSH/GPX4 antioxidant system negatively regulated by the FGL1/NF-κB/STAT3 positive feedback loop. In conclusion, XJS might restrain ferroptosis in IECs to ameliorate experimental colitis by inhibition of FGL1/NF-κB/STAT3 positive feedback loop.
The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms
Authors: Rezaee Malihe , Mohammadi Fatemeh , Keshavarzmotamed Atoosa , Yahyazadeh Sheida , Vakili Omid , Milasi Yaser Eshaghi , Veisi Vida , Dehmordi Rohollah Mousavi , Asadi Sepideh , Ghorbanhosseini Seyedeh Sara , Rostami Mehdi , Alimohammadi Mina , Azadi Abbas , Moussavi Nushin , Asemi Zatollah , Aminianfar Azadeh , Mirzaei Hamed , Mafi Alireza
Published: April 2023

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.
Cerebroprotein hydrolysate attenuates neurodegenerative changes in Alzheimer’s mice model via ferroptosis pathway
Authors: Chen Moxi , Song Wei , Chen Zhengju , Shi Xiaodong , Wang Xue , Li Rongrong , Hao Honglin , Chen Wei
Published: April 2023

Introduction:Cerebroprotein hydrolysate has been proven to improve cognitive function in patients with Alzheimer’s disease (AD). We explored the safety and effectiveness of the clinical administration of oral cerebroprotein hydrolysate in AD, and possible mechanisms related to the neuronal ferroptosis pathway.

Methods:Three-month-old male APP/PS1 double-transgenic mice were randomly divided into AD model (n = 8) and intervention (n = 8) groups. Eight non-transgenic wild-type (WT) C57 mice were used as age-matched controls. The experiments were started at the age of 6 months. The intervention group was then administered cerebroprotein hydrolysate nutrient solution (11.9 mg/kg/day)viachronic gavage, the other groups received an identical volume of distilled water. Behavioural experiments were performed after 90 days of continuous administration. Serum and hippocampal tissues were then collected for histomorphological observation, tau and p-tau expression, and ferroptosis markers analysis.

Results:Cerebroprotein hydrolysate simplified movement trajectories and shortened escape latencies of APP/PS1 mice in the Morris water maze test. Neuronal morphologies were restored in hippocampal tissues on haematoxylin-eosin staining. In the AD-model group, Aβ protein and p-tau/tau expression levels were elevated, plasma Fe2+and malondialdehyde levels were elevated, GXP4 protein expression and plasma glutathione levels declined than controls. All indices improved after cerebroprotein hydrolysate intervention.

Conclusion:Cerebroprotein hydrolysate improves learning and memory function, alleviates neuronal damage, and reduces the deposition of pathological AD markers in AD mice, which may be related to the inhibition of neuronal ferroptosis.
High-resolution characterization of the coagulation and drying processes of whole blood based on optical coherence tomography
Authors: Zhuo Shufeng , Li Meifang , Lu Zenghai , Chen Kaihong
Published: April 2023

Introduction: Escaping whole blood exhibits biochemical and physical coupled mechanisms such as coagulation and drying. However, there is no method for simultaneously monitoring the coagulation and drying procedure.

Methods: In this study, a new method based on optical coherence tomography (OCT) combined with speckle variance and thickness is presented for simultaneously capturing spatially high-resolved characteristics of coagulation and drying of whole blood during the procedure. Deep learning based on a convolutional neural network (CNN) is employed for collecting OCT images with a resolution of micron order and quantitatively obtaining pixel-wise information of whole blood.

Results and discussion: Then, the pixel-wise thickness map provides high-resolved temporal–spatial dynamics of whole blood during the drying procedure, and the corresponding speckle variance can uncover information of whole blood coagulation. The results demonstrate that coagulation and drying of whole blood have spatially inhomogeneous features. This method could provide the potential for revealing the coupling mechanism between coagulation and drying.
Association between gut microbiota and bone metabolism: Insights from bibliometric analysis
Authors: Zhang Zhanrong , Zhang Zheng , Shu Haoming , Meng Yichen , Lin Tao , Ma Jun , Zhao Jianquan , Zhou Xuhui
Published: April 2023

Gut microbiota has been reported to participate in bone metabolism. However, no article has quantitatively and qualitatively analyzed this crossing field. The present study aims to analyze the current international research trends and demonstrate possible hotspots in the recent decade through bibliometrics. We screened out 938 articles meeting the standards from 2001 to 2021 in the Web of Science Core Collection database. Bibliometric analyses were performed and visualized using Excel, Citespace, and VOSviewer. Generally, the annual number of published literatures in this field shows an escalating trend. The United States has the largest number of publications, accounting for 30.4% of the total. Michigan State University and Sichuan University have the largest number of publications, while Michigan State University has the highest average number of citations at 60.00. Nutrients published 49 articles, ranking first, while the Journal of Bone and Mineral Research had the highest average number of citations at 13.36. Narayanan Parameswaran from Michigan State University, Roberto Pacifici from Emory University, and Christopher Hernandez from Cornell University were the three professors who made the largest contribution to this field. Frequency analysis showed that inflammation (148), obesity (86), and probiotics (81) are keywords with the highest focus. Moreover, keywords cluster analysis and keywords burst analysis showed that “inflammation”, “obesity”, and “probiotics” were the most researched topics in the field of gut microbiota and bone metabolism. Scientific publications related to gut microbiota and bone metabolism have continuously risen from 2001 to 2021. The underlying mechanism has been widely studied in the past few years, and factors affecting the alterations of the gut microbiota, as well as probiotic treatment, are emerging as new research trends.
De novo transcriptome sequencing and gene co-expression reveal a genomic basis for drought sensitivity and evidence of a rapid local adaptation on Atlas cedar (Cedrus atlantica)
Authors: Cobo-Simón Irene , Gómez-Garrido Jèssica , Esteve-Codina Anna , Dabad Marc , Alioto Tyler , Maloof Julin N. , Méndez-Cea Belén , Seco José Ignacio , Linares Juan Carlos , Gallego Francisco Javier
Published: April 2023

Introduction

Understanding the adaptive capacity to current climate change of drought-sensitive tree species is mandatory, given their limited prospect of migration and adaptation as long-lived, sessile organisms. Knowledge about the molecular and eco-physiological mechanisms that control drought resilience is thus key, since water shortage appears as one of the main abiotic factors threatening forests ecosystems. However, our current background is scarce, especially in conifers, due to their huge and complex genomes.

Methods

Here we investigated the eco-physiological and transcriptomic basis of drought response of the climate change-threatened conifer Cedrus atlantica. We studied C. atlantica seedlings from two locations with contrasting drought conditions to investigate a local adaptation. Seedlings were subjected to experimental drought conditions, and were monitored at immediate (24 hours) and extended (20 days) times. In addition, post-drought recovery was investigated, depicting two contrasting responses in both locations (drought resilient and non-resilient). Single nucleotide polymorphisms (SNPs) were also studied to characterize the genomic basis of drought resilience and investigate a rapid local adaptation of C. atlantica.

Results

De novo transcriptome assembly was performed for the first time in this species, providing differences in gene expression between the immediate and extended treatments, as well as among the post-drought recovery phenotypes. Weighted gene co-expression network analysis showed a regulation of stomatal closing and photosynthetic activity during the immediate drought, consistent with an isohydric dynamic. During the extended drought, growth and flavonoid biosynthesis inhibition mechanisms prevailed, probably to increase root-to-shoot ratio and to limit the energy-intensive biosynthesis of secondary metabolites. Drought sensitive individuals failed in metabolism and photosynthesis regulation under drought stress, and in limiting secondary metabolite production. Moreover, genomic differences (SNPs) were found between drought resilient and sensitive seedlings, and between the two studied locations, which were mostly related to transposable elements.

Discussion

This work provides novel insights into the transcriptomic basis of drought response of C. atlantica, a set of candidate genes mechanistically involved in its drought sensitivity and evidence of a rapid local adaptation. Our results may help guide conservation programs for this threatened conifer, contribute to advance drought-resilience research and shed light on trees’ adaptive potential to current climate change.
Transcriptome profiling, physiological, and biochemical analyses provide new insights towards drought stress response in sugar maple (Acer saccharum Marshall) saplings
Authors: Mulozi Lungowe , Vennapusa Amaranatha R. , Elavarthi Sathya , Jacobs Oluwatomi E. , Kulkarni Krishnanand P. , Natarajan Purushothaman , Reddy Umesh K. , Melmaiee Kalpalatha
Published: April 2023

Sugar maple (Acer saccharum Marshall) is a temperate tree species in the northeastern parts of the United States and is economically important for its hardwood and syrup production. Sugar maple trees are highly vulnerable to changing climatic conditions, especially drought, so understanding the physiological, biochemical, and molecular responses is critical. The sugar maple saplings were subjected to drought stress for 7, 14, and 21 days and physiological data collected at 7, 14, and 21 days after stress (DAS) showed significantly reduced chlorophyll and Normalized Difference Vegetation Index with increasing drought stress time. The drought stress-induced biochemical changes revealed a higher accumulation of malondialdehyde, proline, and peroxidase activity in response to drought stress. Transcriptome analysis identified a total of 14,099 differentially expressed genes (DEGs); 328 were common among all stress periods. Among the DEGs, transcription factors (including NAC, HSF, ZFPs, GRFs, and ERF), chloroplast-related and stress-responsive genes such as peroxidases, membrane transporters, kinases, and protein detoxifiers were predominant. GO enrichment and KEGG pathway analysis revealed significantly enriched processes related to protein phosphorylation, transmembrane transport, nucleic acids, and metabolic, secondary metabolite biosynthesis pathways, circadian rhythm-plant, and carotenoid biosynthesis in response to drought stress. Time-series transcriptomic analysis revealed changes in gene regulation patterns in eight different clusters, and pathway analysis by individual clusters revealed a hub of stress-responsive pathways. In addition, qRT-PCR validation of selected DEGs revealed that the expression patterns were consistent with transcriptome analysis. The results from this study provide insights into the dynamics of physiological, biochemical, and gene responses to progressive drought stress and reveal the important stress-adaptive mechanisms of sugar maple saplings in response to drought stress.
Bioreactor systems for micropropagation of plants: present scenario and future prospects
Authors: Murthy Hosakatte Niranjana , Joseph Kadanthottu Sebastian , Paek Kee Yoeup , Park So Young
Published: April 2023

Plant micropropagation has been adapted in the fields of agriculture, horticulture, forestry, and other related fields for large-scale production of elite plants. The use of liquid media and adoption of bioreactors have escalated the production of healthy plants. Several liquid-phase, gas-phase, temporary immersion, and other modified bioreactors have been used for plant propagation. The design, principle, operational mode, merits, and demerits of various bioreactors used for the regeneration of propagules, such as bulblets, cormlets, rhizomes, microtubers, shoots (subsequent rooting), and somatic embryos, are discussed here. In addition, various parameters that affect plant regeneration are discussed with suitable examples.
Unfolding molecular switches for salt stress resilience in soybean: recent advances and prospects for salt-tolerant smart plant production
Authors: Feng Chen , Gao Hongtao , Zhou Yonggang , Jing Yan , Li Senquan , Yan Zhao , Xu Keheng , Zhou Fangxue , Zhang Wenping , Yang Xinquan , Hussain Muhammad Azhar , Li Haiyan
Published: April 2023

The increasing sodium salts (NaCl, NaHCO3, NaSO4 etc.) in agricultural soil is a serious global concern for sustainable agricultural production and food security. Soybean is an important food crop, and their cultivation is severely challenged by high salt concentration in soils. Classical transgenic and innovative breeding technologies are immediately needed to engineer salt tolerant soybean plants. Additionally, unfolding the molecular switches and the key components of the soybean salt tolerance network are crucial for soybean salt tolerance improvement. Here we review our understandings of the core salt stress response mechanism in soybean. Recent findings described that salt stress sensing, signalling, ionic homeostasis (Na+/K+) and osmotic stress adjustment might be important in regulating the soybean salinity stress response. We also evaluated the importance of antiporters and transporters such as Arabidopsis K+ Transporter 1 (AKT1) potassium channel and the impact of epigenetic modification on soybean salt tolerance. We also review key phytohormones, and osmo-protectants and their role in salt tolerance in soybean. In addition, we discuss the progress of omics technologies for identifying salt stress responsive molecular switches and their targeted engineering for salt tolerance in soybean. This review summarizes recent progress in soybean salt stress functional genomics and way forward for molecular breeding for developing salt-tolerant soybean plant.
Theoretical and experimental studies on the oil-based emulsion spray
Authors: Gong Chen , Chen Fujun , Kang Can
Published: April 2023

Oil-based emulsion is a common herbicide formulation in agricultural spray, and its atomization mechanism is different from that of water spray. In this paper, a theoretical model based on the characteristics of spray sheets was proposed to predict the spray droplet size for oil-based emulsion spray. An image processing method was used to measure droplet size distributions for different spray pressures and nozzle configurations, and the measured results were used to validate the theoretical model. The results show that oil-based emulsion spray is characterized by the web structure constituted by perforations. The liquid originally occupied by spray sheets eventually gathers in these web structures. The proposed theoretical model is based on the size of the nozzle exit, the angle of spray sheets, and the perforation number in the web structure, which are relatively easy to obtain. The theoretical droplet size is in inverse proportion to the square root of the perforation number in the web structure while in proportion to the square root of the area of the nozzle exit. The captured images of spray sheets and the measured droplet size distribution show consistency with the theoretical prediction. The difference between theoretical results and measured volumetric median diameter is less than 10% for different spray pressures and nozzles.
Productivity model and experiment of field crop spraying by plant protection unmanned aircraft
Authors: Qin Weicai , Chen Panyang , Wang Baokun
Published: April 2023

Traditional agricultural production requires numerous human and material resources; however, agricultural production efficiency is low. The successful development of plant protection unmanned aerial vehicles (UAVs) has changed the operation mode of traditional agricultural production, saving human, material, and financial resources and significantly improving production efficiency. To summarize the process of improving the productivity of plant protection UAVs, this study established a productivity calculation model of UAVs based on the time composition of the UAV agricultural plant protection process, including spraying, turning, replenishment, and transfer times. The time required for the unmanned aircraft application process was counted through years of tracking the application process of eight different plant protection unmanned aircraft. Plot lengths of 100, 300, 500, 700, 1,000, 1,500, 2,000, 2,500, 3,000, and 3,500 m were established to calculate the theoretical productivity. The results showed that the productivity of different types of plant protection UAVs increased with an increase in plot length in the range of 100 to 1,500 m; however, when the plot length reached a certain value, the productivity growth rate slowed down or even decreased slightly. Simultaneously, based on the working area per 10,000 mu, the recommended plot length and the number of configured models for different models were recommended. If the plant protection UAV was distinguished by electric and oil power, the time utilization rate of electric plant protection UAVs was 72.7%, and the labor productivity was 56.4 mu/person·h. In contrast, the time utilization rate of the heavy load oil-powered plant protection unmanned aircraft was 86%, and the labor productivity was 63.5 mu/person ·h. This study can support plant protection UAV enterprises to optimize equipment efficiency, provide evaluation methods for the operation efficiency assessment of plant protection UAVs, provide a reference for the selection of plant protection UAVs, and provide a basis for field planning.
The leisure basis of caring
Authors: Stebbins Robert A.
Published: April 2023

The social science literature on caring is long on application and short on concepts about its nature. In this latter capacity leisure is seldom mentioned as a context within which people care for others. This article examines the relationship of caring and compassion as expressed during free time in leisure activities. This has never been done, with the result that many contextual and motivational properties unique to leisure have been overlooked, and consequently, have been unavailable to both the theoretic and the practical sides of the sociology and psychology of compassion. The present article attempts to demonstrate that such oversight has denied this field some useful conceptual tools.
Comparison of peripheral blood T, B, and NK lymphocytes between frontline medical workers for treating patients of COVID-19 and normal outpatient and emergency medical workers in China
Authors: He Weijian , Ma Piyong , Li Xiuying , Wang Yali , Zhang Yucheng
Published: April 2023

The outbreak of the novel coronavirus disease 2019 (COVID-19) has led to significant mental stress for frontline medical workers treating patients with confirmed COVID-19 in China. Psychological stress has an impact on the immune system. The number and percentage of lymphocyte subsets are standard indicators of cellular immune detection. Here, we reported the differences in CD3, CD4, CD8, CD19, and CD56 lymphocytes between 158 frontline medical workers and 24 controls from medical staffs of the outpatient and emergency departments. We found that frontline medical workers had significantly lower absolute values and percentages of CD19+ B cells, especially in the female and the aged ≥40 years subgroup. Stratification analysis showed that the absolute values of CD4+ T cells were significantly lower in the aged <40 years subgroup, while percentages of CD8+ T cells were lower and percentages of CD56+ NK cells were higher in the aged ≥40 years subgroup. In summary, this study suggests paying more attention to frontline medical workers’ mental health and immune function, and properly providing them with psychological interventions and measures of care.
An updated review of the salient geomedical aspects of mercury for enhancement of data quality in simulation modelling and other prognostic applications: Africa case descriptions
Authors: Davies Theophilus C.
Published: April 2023

Mercury (Hg) pollution is of global concern. Despite the prolificity of research in the past two decades or so, there are still several uncertainties and variabilities in our knowledge of both the element’s exposure dynamics and its health effects. Understanding the intricacies of the element’s emissions-to-impact path, for instance, is rendered intractable by its varied environmental fate and the overarching influence of environmental, geochemical, biological and socioeconomic drivers. In this paper, an updated synopsis of the relevant and more important geomedical characteristics of Hg is considered to constitute part of the provision of high-quality input data needed in Hg simulation modelling studies, and other applications such as the provision of long-term data necessary for evaluating the effectiveness of regulatory measures at various scales. A critical overview is presented on the importance of data quality in parameterisation, and validation of Hg simulation models and other related applications. In this connection, the dearth of modern measurements of Hg abundance in crustal rocks and other Earth materials which needs to be set prior to simulation as well as in modelling source to sink transfers in the Hg cycle, is highlighted. An improved input data quality would also foster the production of model outcomes that are accurate enough for applications in design of better exposure-limiting strategies; and in providing insights on how the course of diagnosis and treatment currently proffered by physicians for Hg-induced maladies, can be revised or expanded. Model results derived from high-quality input datasets also have a high potential for providing forecasting capabilities to inform policy.
“PrEP protects us”: Behavioural, normative, and control beliefs influencing pre-exposure prophylaxis uptake among pregnant and breastfeeding women in Zambia
Authors: Hamoonga Twaambo Euphemia , Mutale Wilbroad , Hill Lauren M. , Igumbor Jude , Chi Benjamin H.
Published: April 2023

Background

Although pre-exposure prophylaxis (PrEP) is recommended for pregnant and breastfeeding women at elevated HIV risk, uptake has been low in Zambia.

Methods

In in-depth interviews, we explored beliefs about PrEP among 24 HIV-negative pregnant and breastfeeding Zambian women. Thematic analysis was used to identify behavioural, normative and control beliefs likely to influence PrEP uptake.

Results

Most women viewed PrEP as a good method of protecting themselves and their babies from HIV infection. Partners were cited as key referents in decision making about PrEP use. Many women felt that PrEP use was not entirely in their control. Most reported that they would not use PrEP if their partners did not approve. Health care providers with negative attitudes, long distance to clinics, and extended waiting times were cited as barriers to PrEP uptake.

Conclusion

HIV-negative pregnant and breastfeeding women had a positive attitude towards PrEP but barriers to uptake are multifaceted.
Systematic hybrid laparoscopic and endovascular treatment of median arcuate ligament syndrome: A single-center experience
Authors: Schneider Michael , Longchamp Justine , Uldry Emilie , Corpataux Jean-Marc , Kefleyesus Amaniel , Halkic Nermin
Published: April 2023

Background

Median arcuate ligament syndrome (MALS) is caused by celiac trunk (CT) compression by the median arcuate ligament. Clinically, this pathology varies from postprandial pain (Dunbar syndrome) to a life-threatening hemorrhage because of a rupture of a gastroduodenal artery aneurysm (GAA). Due to the low prevalence of this disease, there is no standard management for MALS.

Material and method

This was a single-center, retrospective study of 13 patients. Two groups were identified on the basis of the initial clinical presentation: those operated for a GAA rupture (bleeding group—BG) and those operated electively for Dunbar syndrome (Dunbar syndrome group—DG). The primary endpoint was 30-day postoperative complications of a systematic laparoscopic release of the median arcuate ligament and stenting during the same procedure.

Results

Seven patients (54%) underwent elective surgery. Six patients (46%) underwent semiurgent repair under elective conditions post-embolization for GAA bleeding. The total operative time was longer in the BG (p = 0.06). Two patients in the BG suffered early major complications and needed reintervention, and those in the DG had a lower comprehensive complication index. No mortality was reported at 30 days. Overall median length of stay was 5 days (IQR: 3.5–15.3). Patients in the DG had a significantly shorter length of stay (p = 0.02). At 6 months, the primary and secondary CT stent patencies were 82% and 100%, respectively. There were no high-flow GAA recurrences.

Conclusions

A combined approach of laparoscopic release of the median arcuate ligament and stenting during the same procedure is feasible and safe, and this approach must be systematically discussed in symptomatic patients.
A Review on Recent Advances in Piezoelectric Ceramic 3D Printing
Authors: Park Jiwon , Lee Dong-Gyu , Hur Sunghoon , Baik Jeong Min , Kim Hyun Soo , Song Hyun-Cheol
Published: April 2023

Piezoelectric materials are a class of materials that can generate an electric charge when subjected to mechanical stress, or vice versa. These materials have a wide range of applications, from sensors and actuators to energy-harvesting devices and medical implants. Recently, there has been growing interest in using 3D printing to fabricate piezoelectric materials with complex geometries and tailored properties. Three-dimensional printing allows for the precise control of the material’s composition, microstructure, and shape, which can significantly enhance piezoelectric materials’ performance. Three-dimensional printing has emerged as a promising technique for fabricating piezoelectric materials with tailored properties and complex geometries. The development of high-performance piezoelectric materials using 3D printing could have significant implications for various applications, including sensors, energy harvesting, and medical devices. In this review paper, 3D printing methods for piezoelectric materials, their advantages and disadvantages, representative piezoelectric ceramics, and examples of 3D printing are presented. Furthermore, the applications utilizing these materials are summarized.
Simulated Ecosystem and Farm-Level Economic Impacts of Conservation Tillage in a Northeastern Iowa County
Authors: Osei Edward , Jafri Syed H. , Gassman Philip W. , Saleh Ali
Published: April 2023

While the ecological benefits of no-till are largely indisputable, the economic impacts are less certain, and the latter may be partly to blame for lower-than-expected adoption of no-till. In this study, we contribute to a better understanding of the ecosystem and farm-level economic impacts of no-till, with Buchanan County in the northeastern region of the U.S. State of Iowa as the backdrop due to previously established data and model validation efforts in that region. Using the Agricultural Policy Environmental eXtender (APEX) and Farm Economic Model (FEM), we simulated two tillage scenarios—a conservation tillage baseline and no-till—for continuous corn and corn–soybean rotations in Buchanan County using gridded historical climate data. We find that no-till provides clear ecosystem benefits, except that soluble nutrient losses might actually rise. We also find that under current commodity prices for corn and soybeans, no-till is not as profitable as the conservation tillage baseline. For no-till to be at least as profitable as the baseline under current commodity prices, the yield penalty associated with no-till cannot be higher than 1.5% for corn and 0.8% for soybeans, or similar combinations that entail a revenue penalty of about $24,000 for an 809-hectare continuous corn or corn–soybean operation. Given the simulated yield penalties associated with no-till, corn and soybean prices would have to be substantially lower in order for no-till to break even. Consequently, incentives for conservation practice implementation may need to be tied to commodity prices and yield penalties in order to elicit greater adoption rates.
Effects of Yellow Mealworm (Tenebrio molitor) on Growth Performance, Hepatic Health and Digestibility in Juvenile Largemouth Bass (Micropterus salmoides)
Authors: Chen Haijie , Yu Jiao , Ran Xudong , Wu Jiaxuan , Chen Yongjun , Tan Beiping , Lin Shimei
Published: April 2023

This study investigated the effects of yellow mealworm meal (TM) on growth performance, hepatic health and digestibility in juvenile largemouth bass (Micropterus salmoides). The fish were fed with the basic feed and the test feed (70% basic feed and 30% raw materials) containing Cr2O3, and feces were collected for digestibility determination. The fish were fed with five isonitrogenous (47% crude protein) and isolipidic (13% crude lipid) diets, in which fishmeal (FM) was replaced with 0% (TM0), 12% (TM12), 24% (TM24), 36% (TM36) and 48% (TM48) TM. The fish were reared in cylindrical plastic tanks in a recirculating aquaculture system for 11 weeks. The apparent digestibility coefficients (ADC), of dry matter, crude protein and crude lipid, in largemouth bass of TM were 74.66%, 91.03% and 90.91%, respectively. The ADC of total amino acid (TAA) of TM in largemouth bass was 92.89%, and the ADC of essential amino acid (EAA) in TM in largemouth bass was 93.86%. The final body weight (FBW), weight gain rate (WGR) and specific growth rate (SGR) in the TM24 group were significantly higher than those in other groups. Similarly, the highest mRNA expression levels of hepatic protein metabolism genes (pi3k, mtor, 4ebp2 and got) and antioxidant enzyme (glutathione peroxidase, Gpx; catalase, Cat) activities were observed in the TM24 group. Moreover, the expression levels of anti-inflammatory factors (il-10 and tgf) in liver were up-regulated and the expression levels of pro-inflammatory factors (il-8 and il-1β) in liver were down-regulated. Quadratic regression model analysis, based on weight gain rate (WGR) against dietary TM level, indicated that the optimum level of dietary TM replacing FM in largemouth bass diet was 19.52%. Appropriate replacement levels (less than 36%) of FM by TM in the diets can enhance the antioxidant capacity and immunity of largemouth bass. However, high levels of FM substitution with TM (more than 48%) in the feeds can damage the liver health and inhibit the growth of largemouth bass. Notably, largemouth bass has high ADC and high utilization of TM, which indicates that it is feasible to use TM as feed protein source for largemouth bass.
Studying and Analyzing Humane Endpoints in the Fructose-Fed and Streptozotocin-Injected Rat Model of Diabetes
Authors: Silva-Reis Rita , Faustino-Rocha Ana I. , Silva Jéssica , Valada Abigaël , Azevedo Tiago , Anjos Lara , Gonçalves Lio , Pinto Maria de Lurdes , Ferreira Rita , Silva Artur M. S. , Cardoso Susana M. , Oliveira Paula A.
Published: April 2023

This work aimed to define a humane endpoint scoring system able to objectively identify signs of animal suffering in a rat model of type 2 diabetes. Sprague-Dawley male rats were divided into control and induced group. The induced animals drink a 10% fructose solution for 14 days. Then, received an administration of streptozotocin (40 mg/kg). Animals’ body weight, water and food consumption were recorded weekly. To evaluate animal welfare, a score sheet with 14 parameters was employed. Blood glucose levels were measured at three time points. After seven weeks of initiating the protocol, the rats were euthanized. The induced animals showed weight loss, polyuria, polyphagia, and polydipsia. According to our humane endpoints table, changes in animal welfare became noticeable after the STZ administration. None of the animals hit the critical score limit (four). Data showed that the most effective parameters to assess welfare in this type 2 diabetes rat induction model were dehydration, grooming, posture, abdominal visualization, and stool appearance. The glycemia was significantly higher in the induced group when compared to the controls (p < 0.01). Induced animals’ murinometric and nutritional parameters were significantly lower than the controls (p < 0.01). Our findings suggest that in this rat model of type 2 diabetes with STZ-induced following fructose consumption, our list of humane endpoints is suitable for monitoring the animals’ welfare.
Recovery of Spinal Walking in Paraplegic Dogs Using Physiotherapy and Supportive Devices to Maintain the Standing Position
Authors: Henea Mădălina Elena , Șindilar Eusebiu Viorel , Burtan Liviu Cătălin , Mihai Iuliana , Grecu Mariana , Anton Alina , Solcan Gheorghe
Published: April 2023

Paraplegic patients have always been ideal candidates for physiotherapy due to their body’s inability to recover on its own. Regardless of the cause that led to the onset of paraplegia (traumatic or degenerative), physiotherapy helps these patients with devices and methods designed to restore the proper functioning of their motility, as well as their quality of life. A total of 60 paraplegic dogs without deep pain in the hindlimbs caused by intervertebral disc extrusion or thoracolumbar fractures underwent physiotherapy sessions: manual therapy (massage), electrostimulation (10–20 min with possible repetition on the same day), ultrasound therapy, laser therapy, hydrotherapy, and assisted gait in supportive devices or on treadmills to stimulate and relearn walking, which was the main focus of the study. To maintain the standing position over time, we developed different devices adapted for each patient depending on the degree of damage and the possible associated pathologies: harnesses, trolleys, straps, exercise rollers, balancing platforms and mattresses, physio balls and rollers for recovery of proprioception. The main objective of our study was to demonstrate that physiotherapy and assisted gait in supportive devices to maintain the standing position may help paraplegic dogs to develop spinal walking. Concurrent pathologies (skin wounds, urinary infections, etc.) were managed concomitantly. Recovery of SW was evaluated by progression in regaining the reflectivity, nociception, gait score, and quality of life. After 125 to 320 physiotherapy sessions (25 to 64 weeks), 35 dogs (58.33%) developed spinal walking and were able to walk without falling or falling only sometimes in the case of a quick look (gait score 11.6 ± 1.57, with 14 considered normal), with a lack of coordination between the thoracic and pelvic limbs or difficulties in turning, especially when changing direction, but with the recovery of the quadrupedal position in less than 30 s. The majority of dogs recovering SW were of small size, with a median weight of 6.83 kg (range: 1.5–15.7), mixed breed (n = 9; 25.71%), Teckel (n = 4; 11.43%), Bichon (n = 5; 14.28%), Pekingese (n = 4; 11.43%), and Caniche (n = 2; 5.71%), while those who did not recover SW were larger in size, 15.59 kg (range: 5.5–45.2), and mixed breed (n = 16; 64%).
Proteinuria and Electrophoretic Pattern in Dogs with Comorbidities Associated with Chronic Kidney Disease
Authors: Pérez-Sánchez Alicia Pamela , Perini-Perera Sofía , Del-Angel-Caraza Javier , Quijano-Hernández Israel Alejandro , Recillas-Morales Sergio
Published: April 2023

In animals with chronic pathologies, the detection of proteinuria via the proteinuria: creatininuria ratio (UPC) and urinary protein electrophoresis allows for the early diagnosis of chronic kidney disease (CKD). The objective of this work was to identify and determine the magnitude of proteinuria and its electrophoretic pattern characterization in dogs with chronic diseases pathophysiologically related to proteinuria. With the studied patients, five groups were formed. The control group (CG) contained non-proteinuric cases. The cases with proteinuria were classified into four groups according to the concurrent disease: chronic inflammatory diseases (IG), neoplasms (NG), heart diseases (HG), and endocrine diseases (EG). For the statistical analysis, descriptive statistics and non-parametric tests were used. Data from 264 dogs were obtained; in the disease groups, proteinuria was observed in more than 30% as the only finding of kidney disease, evidencing a greater risk factor for proteinuria in the HG group (OR 4.047, CI 1.894–8.644, p < 0.0001). In the HG, NG, and EG groups, a higher frequency of glomerular pattern (GEP) related to glomerular hypertension was observed; in the IG, a higher frequency of mixed pattern (MEP) was observed. These findings are secondary to the hyperfiltration process that affects the glomerulus and the renal tubule.
The Epidemiology of Antibiotic-Related Adverse Events in the Treatment of Diabetic Foot Infections: A Narrative Review of the Literature
Authors: Soldevila-Boixader Laura , Murillo Oscar , Waibel Felix W. A. , Huber Tanja , Schöni Madlaina , Lalji Rahim , Uçkay Ilker
Published: April 2023

The use of antibiotics for the treatment of diabetic foot infections (DFIs) over an extended period of time has been shown to be associated with adverse events (AEs), whereas interactions with concomitant patient medications must also be considered. The objective of this narrative review was to summarize the most frequent and most severe AEs reported in prospective trials and observational studies at the global level in DFI. Gastrointestinal intolerances were the most frequent AEs, from 5% to 22% among all therapies; this was more common when prolonged antibiotic administration was combined with oral beta-lactam or clindamycin or a higher dose of tetracyclines. The proportion of symptomatic colitis due to Clostridium difficile was variable depending on the antibiotic used (0.5% to 8%). Noteworthy serious AEs included hepatotoxicity due to beta-lactams (5% to 17%) or quinolones (3%); cytopenia’s related to linezolid (5%) and beta-lactams (6%); nausea under rifampicin, and renal failure under cotrimoxazole. Skin rash was found to rarely occur and was commonly associated with the use of penicillins or cotrimoxazole. AEs from prolonged antibiotic use in patients with DFI are costly in terms of longer hospitalization or additional monitoring care and can trigger additional investigations. The best way to prevent AEs is to keep the duration of antibiotic treatment short and with the lowest dose clinically necessary.