bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-temporal variations of lower tropospheric pollutants and their relation with meteorological factors in Karachi, Pakistan
Authors: Ahmed Dilshad , Shams Zafar Iqbal , Ahmed Moinuddin , Siddique Muhammad Fahim
Published: December 2021

Despite being one of the most populated cities globally, the air quality of Karachi is hardly ever comprehended. The present paper investigates the outdoor concentrations of 10 air pollutants, viz. NO, NO2, NOx, SO2, CO, O3, CH4, methane carbon, non-methane hydrocarbons, and total hydrocarbons at three different city sites, viz., Sohrab Goth, Defense Housing Authority, and North Nazimabad. The results demonstrate that these pollutants severely affected the city's air quality. The annual mean concentrations of both NO2 and SO2 exceeded the WHO guidelines at some study sites. The city experiences varied concentrations of major air pollutants because three types of fuel, viz. diesel, gasoline, and compressed natural gas, operate the motor vehicles in this conurbation. The study also correlates the various air pollutants with each other and with various meteorological factors. All the three oxides of nitrogen are statistically associated at all three sites with one another, with SO2 at Defense Housing Authority, with CO at North Nazimabad, and with meteorological factors at Sohrab Goth and Defense Housing Authority. Carbon monoxide is statistically associated with the meteorological factors only at North Nazimabad. The study suggests that higher air pollution in the city is due to the adoption of lenient vehicular emission standards because stringent emission standards cannot be adopted due to the non-availability of low or zero sulfur fuel. Moreover, ineffective regulation of exiting standards also contributes to higher vehicular emissions in the city.
Evaluation of Inorganic Phosphate Solubilizing Efficiency and Multiple Plant Growth Promoting Properties of Endophytic Bacteria Isolated From Root Nodules Erythrina Brucei
Authors: Berza Belay , Sekar Jegan , VR Prabavathy , Pagano Marcela C , Assefa Fassil
Published: December 2021

Background: The majority of phosphorous in the soil is fixed and unavailable to plant nutrition, hence in scarcity. Phosphate solubilizing bacteria, the ecological engineers, are considered as the best, sustainable and eco-friendly options. The objectives of this study were to screen and evaluate inorganic phosphate solubilizing efficiency and assess multiple plant growth promoting traits of E. brucei root nodule bacterial endophytes.Results: A total of 304 nodule bacterial endophytes were screened for phosphate solubilization potential on solid PA medium among which 119 (39%) were potential tricalcium phosphate solubilizers. None of these isolates were able to form clearly visible halos on aluminum phosphate (AlPO4), Al-P or iron phosphate (FePO4), Fe-P supplemented PA medium. Out of 119 inorganic phosphate solubilizing endophytes, 40.3% were IAA producers. Based on phosphate solubilization index, the potential bacterial endophytes were identified to Gluconobacter cerinus, Acinetobacter soli, Achromobacter xylosoxidans and Bacillus thuringiensis using the 16S rRNA gene sequences analysis. All the selected isolates were potential solubilizers of the three inorganic phosphates (Al-P, Fe-P and tricalcium phosphate, TCP) included in liquid NBRIP medium. The highest values of solubilized TCP were recorded by isolates AU4 and RG6 (A. soli), 108.96 mg L-1 and 107.48 mg L-1, respectively at sampling day3 and 120.36 mg L-1 and 112.82 mg L-1, respectively at day 6. The highest values of solubilized Al-P and Fe-P were recorded by isolate RG6, 102.14 mg L-1 and 96.07 mg L-1, respectively at sampling days 3 and 6, respectively. The highest IAA, 313.61µg mL-1 was recorded by isolate DM17 (B. thuringiensis). These selected potential isolates were also HCN, NH3, and hydrolytic enzymes producers. The isolates were also varied in tolerance to eco-physiological stressors and exhibited versatility to carbon and nitrogen substrate utilization. Conclusions: The genera and species Gluconobacter cerinus, Acinetobacter soli, Achromobacter xylosoxidans and Bacillus thuringiensis are the first reports from E .brucei root nodules and Gluconobacter is also the first report to the science as phosphate solubilizer. Isolates AU4 and RG (A. soli) could be potential bio-inoculant candidates for the growth enhancement of the host plant for better agro-forestry practices in acidic and alkaline soils in Ethiopia.
GLP-1-mediated delivery of the PPAR𝛼/𝛾 dual-agonist Tesaglitazar improves obesity and glucose metabolism in mice
Authors: Quarta Carmelo , Stemmer Kerstin , Novikoff Aaron , Yang Bin , Klingelhuber Felix , Harger Alexandra , Bakhti Mostafa , Bastidas-Ponce Aimée , Bauge Eric , Clemmensen Christoffer , Colldén Gustav , Cota Perla , Drucker Daniel , García-Cáceres Cristina , Grandl Gerald , Hennuyer Nathalie , Herzig Stephan , Hofmann Susanna , Kulaj Konxhe , Lalloyer Fanny , Lickert Heiko , Maity Gandhari , Perez-Tilve Diego , Sanchez-Garrido Miguel A. , Zhang Qian , Staels Bard , Krahmer Natalie , DiMarchi Richard , Tschoep Matthias , Finan Brian , Müller Timo
Published: December 2021

Dual-agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPAR𝛼/𝛾) have shown beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to unfavorable cardiovascular and/or renal effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPAR𝛼/𝛾 dual-agonist Tesaglitazar to GLP-1 to allow for the GLP-1 receptor-dependent delivery of Tesaglitazar. GLP-1/Tesaglitazar does not differ from matched GLP-1 in GLP-1R signaling, but shows GLP-1R-dependent PPAR𝛾-RXR heterodimerization with enhanced efficacy to improve body weight, food intake, and glucose metabolism relative to GLP-1 or Tesaglitazar in mice with diet- and genetically-induced obesity. The conjugate fails to affect body weight and glucose metabolism in GLP-1R knockout (ko) mice and shows preserved effects in DIO mice at doses subthreshold for GLP-1 and Tesaglitazar to improve metabolism. Consistent with the GLP-1R expression pattern, LC/MS-based proteomics identified a series of novel PPAR protein targets in the hypothalamus that are acutely upregulated by Tesaglitazar and by GLP-1/Tesaglitazar, but not by treatment with GLP-1. Collectively, our data show that GLP-1/Tesaglitazar improves energy and glucose metabolism with superior efficacy to GLP-1 or Tesaglitazar alone and suggest that this conjugate holds therapeutic value to treat hyperglycemia and insulin resistance.
Specifically Binding of D-Amino Neuraminic Acid to Ganglioside Studied in Prostate Cancer Cells
Authors: Demir Kenan , Aktug Huseyin , Yigitturk Gurkan , Acikgoz Eda , Guler Gunnur , Rouhrazi Hadi , Oktem Gulperi
Published: December 2021

Aims: The aim of this study was to investigate the cellular binding site of human KDN (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid). The KDN molecule is a member of the sialic acid family, and its expression increases in cancer cells. Although KDN has been shown to bind to GM3 (Monosialodihexosyl Ganglioside) in trout sperm.Methods and Results: Prostate cancer cell line (DU145) was used in this study. Each experimental group was divided into 3 groups: control, GCS (Glucosylceramide synthase) enzyme inhibitor Genz-123346 treated, and GM3 synthesis inhibitor Triptolide treated. Each group was stained using the immunocytochemical method for GM3, GD3 (Disialosyllactosylceramide) and KDN. The FTIR (Fourier Transform Infrared Spectroscopy) analysis was performed to elucidate the cellular changes upon treatment. The non-treated number 1 cell group stained positive with all of GM3, GD3 and KDN, the GCS enzyme blocked with Genz-123346 number 2 cell groups stained positive with only KDN. Furthermore, GD3 Synthase inhibitor Triptolide treated number 3 cell group stained positive with GM3 and KDN. Measurements with FTIR showed apoptotic features with Triptolide while Genz-123346 had no negative effect on the cell viability. The decrease in sugar constructions was revealed and the results that we obtained with staining were reinforced.Conclusions: Determining the location of bounded KDN is important in selecting new targets for cancer treatment researches. It has been shown that KDN is not inhibited by both GM3 inhibition and GD3 inhibition, and thus, KDN might also bind to different places, be specific, and not only attached to any of gangliosides of the GM or GD series.
Liana functional assembly along the hydrological gradient in Central Amazonia
Authors: Rocha Elisangela da Xavier , Nogueira Anselmo , Costa Flávia , Burnham Robyn , Gerolamo Caian , Honorato Cibelly , Schietti Juliana
Published: December 2021

Soil hydrology, nutrient availability and forest disturbance determine the variation of tropical tree species composition locally. However, most habitat filtering is explained by tree species' hydraulic traits along the hydrological gradient. We asked whether these patterns apply to lianas. At the community level, we investigated: (i) whether the hydrological gradient, soil fertility and forest disturbance explain liana species composition; and (ii) whether differences in leaf and stem wood functional traits were linked to species composition along ecological gradients. We sampled liana species composition in 18 1-ha plots across a 64 km² landscape in Central Amazonia and measured ten leaves and stem wood traits across 115 liana species in 2,000 individuals. We correlated liana species composition summarized with PCoA with the functional composition summarized by PCA, considering the species mean values of traits at the plot level. We tested the relationship between ordination axes and the environmental gradients. Liana species composition was highly correlated with functional composition. Taxonomic (PCoA) and functional (PCA) composition were strongly associated with the hydrological gradient, with a slight impact of forest disturbance on functional composition. Species at valley areas had higher stomata size and higher proportions of self-supporting xylem than plateau. Differently, lianas on plateaus invest more in fast-growing leaves (higher SLA), although with a higher wood density. Our study reveals that lianas use different functional solutions in dealing with each end of the hydrological gradient and that the relationships between habitat preferences and traits explain lianas species distributions not straightforwardly as previously found for trees.
The cytosolic role of EZH2-IMPDH2 complex in melanoma progression and metastasis via GTP regulation
Authors: Abali Gamze Kuser , Noguchi Fumihito , Szeto Pacman , Zhang Youfang , Huang Cheng , Barlow Christopher , Pomilio Giovanna , Chew Christopher , Moghaddam Samar Masoumi , Zhao Peinan , Andrews Miles , Leece Isobel , Cheung Jen , Ameratunga Malaka , Wong Nicholas , Schittenhelm Ralf , Wei Andrew () , Shackleton Mark
Published: December 2021

The enhancer of zeste homolog 2 (EZH2) oncogene is a histone methyltransferase that functions canonically as a catalytic subunit of the polycomb repressive complex 2 (PRC2) to tri-methylate histone H3 at Lys 27 (H3K27me3). Although targeting of EZH2 methyltransferase is a promising therapeutic strategy against cancer, methyltransferase-independent oncogenic functions of EZH2 are also described. Moreover, pharmacological EZH2 methyltransferase inhibition was only variably effective in pre-clinical and clinical studies, suggesting that targeting EZH2 methyltransferase alone may be insufficient. Here, we demonstrate a non-canonical mechanism of EZH2’s oncogenic activity through interactions with inosine monophosphate dehydrogenase 2 (IMPDH2) and downstream promotion of guanosine-5'-triphosphate (GTP) production. Liquid Chromatography-Mass Spectrometry (LC-MS) of EZH2 immunoprecipitates from melanoma cell lines and human patient-derived xenografts (PDXs) revealed EZH2-IMPDH2 interactions that were verified to occur between the N-terminal EED-binding domain of cytosolic EZH2 and the CBS domain of IMPDH2 in a PRC2- and methylation-independent manner. EZH2 silencing reduced cellular GTP, ribosome biogenesis, RhoA-mediated actomyosin contractility and melanoma cell proliferation and invasion by impeding the activity and cytosolic localization of IMPDH2. Guanosine, which replenishes GTP, reversed these effects and thereby promoted invasive and clonogenic cell states even in EZH2 silenced cells. IMPDH2 silencing antagonized the proliferative and invasive effects of EZH2, also in a guanosine-reversible manner. In human melanomas, high cytosolic EZH2 and IMPDH2 expression were associated with nucleolar enlargement, a marker for ribosome biogenesis. We also identified EZH2-IMPDH2 complexes in a range of cancers in which Sappanone A (SA), which inhibits EZH2-IMPDH2 interactions and thereby IMPDH2 tetramerization, was anti-tumorigenic, although notably non-toxic in normal human melanocytes and bone marrow derived blood progenitor cells that lacked observable EZH2-IMPDH2 interactions. These findings illuminate a previously unrecognized, non-canonical, methyltransferase-independent, but GTP-dependent mechanism by which EZH2 regulates tumorigenicity in melanoma and other cancers, opening new avenues for development of anti-EZH2 therapeutics.
Gene Expression of the Endocannabinoid System in Endometrium Through Menstrual Cycle
Authors: Tanaka Keisuke , Amoako Akwasi , Mortlock Sally , Rogers Peter , Holdsworth-Carson Sarah , Donoghue Jacqueline , Teh Wan , Montgomery Grant , McKinnon Brett
Published: December 2021

Endocannabinoids mediate cellular functions and their activity is controlled by a complex system of enzymes, membrane receptors and transport molecules. Endocannabinoids are present in endometrium, a cyclical regenerative tissue requiring tightly regulated cellular mechanisms for maturation. The objective of this study was to chart the gene expression of key elements involved in the endocannabinoid system across the menstrual cycle. RNA was isolated from endometrial tissue and genome-wide gene expression datasets were generated using RNA-sequencing. An a priori set of 70 genes associated with endocannabinoid system were selected from published literature. Gene expression across the menstrual cycle was analyzed using a moderated t test, corrected for multiple testing with Bonferroni’s method. A total of 40 of the 70 genes were present in >90% of the samples, and significant differential gene expression identified for 29 genes. We identified 4 distinct regulation patterns for synthesizing enzymes, as well as a distinct regulation pattern for degradations and transporting enzymes. This study charts the expression of endometrial endocannabinoid system genes across the menstrual cycle. Altered expression of genes that control endocannabinoid may allow fine control over endocannabinoid concentrations and their influence on cellular function, maturation and differentiation as the endometrium matures through the menstrual cycle.
Novel SOX2 Mutation in Autosomal Dominant Cataract-Microcornea Syndrome
Authors: Lin Zhi-Bo , Li Jin , Sun Hai-Sen , Yu A-Yong , Chen Shi-Hao , Li Fen-Fen
Published: December 2021

Background: Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. Purpose: To unravel the genetic cause of autosomal dominant family with CCMC.Methods: All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. Results: Four CCMC patients from a Chinese family, and five unaffected family members were enrolled in this study. Using whole-exome sequencing, missense mutation c.295G>T (p.a99s, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level.Conclusions: A novel missense mutation (c.295G>T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study firstly determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.
How to Integrate Palliative Care Within Primary Healthcare- Perspectives of People Living With Serious Illnesses, Their Family Caregivers and Primary Healthcare Professionals in Nigeria
Authors: Afolabi Oladayo A , Nkhoma Kennedy , Soyannwo Olaitan , Aje Akinyemi , Ogunniyi Adesola , Harding Richard , Maddocks Matthew
Published: December 2021

Background
Palliative care should be integrated into primary healthcare systems within low- and middle-income countries to achieve Universal Health Coverage goals. We aimed to identify preferences and expectations for primary healthcare support among people living with serious illness and their families in Nigeria, and to determine feasible steps palliative care integration within the health system.
Methods
Qualitative interview study with 48 participants including people living with serious illnesses (n=21) and their family caregivers (n=15) recruited from specialist clinics at a Teaching hospital in Nigeria; and healthcare providers (n=12) recruited from three primary healthcare facilities in Nigeria. Data were analysed using thematic analysis.
Results
Three major themes were identified. 1) Balancing patients and families’ expectations and preferences for easily accessible service and opportunities for social interaction and adequate communication with available human resource. 2) Engaging patients requires existing trust and bonds from their current use of primary healthcare and support to develop patients’ agency. 3) Development of healthcare providers is needed to ensure an appropriate clinical response, manage interprofessional trust and ensure clear role delineation.
Conclusions
Palliative care integration within primary healthcare in Nigeria can be achieved through building information and communication skills of healthcare providers, engaging and empowering patients to exercise their agency in care decisions, and adequately delineating healthcare providers’ roles to ensure staff work within their competencies and training.
Osteoprotegerin And MTHFR Gene Variations In Rheumatoid Arthritis: Association With Disease Susceptibility And Markers of Subclinical Atherosclerosis
Authors: Arida Aikaterini , Nezos Adrianos , Papadaki Ioanna , Sfikakis Petros P. , Mavragani Clio P.
Published: December 2021

Objective: To explore whether the osteoprotegerin (OPG) rs2073618 gene variant and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133 polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis.Methods: 283 RA patients and 595 healthy controls (HC) were genotyped for OPG and MTHFR gene variants using PCR based assays. Clinical, laboratory parameters and markers of subclinical atherosclerosis (Carotid/Femoral intima media thickness/plaque formation) along with traditional risk factors for atherosclerosis were assessed in RA patients and 280HC.Results: Increased prevalence of the rs2073618CC genotype was detected in RA patients vs HC (p=0.04), especially in RA patients with high serum titers of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibodies compared to HC (p-values:0.0029 and 0.0077, respectively). This genotype was also associated with higher carotid-IMT scores (p=0.01) and marginally with higher rates of carotid plaque formation (p=0.06). MTHFR 1298CC genotype was more prevalent in the anti-CCP positive group compared to HC, with no associations detected with markers of subclinical atherosclerosis. Reduced rates of carotid/femoral plaque formation were detected among RA patients harboring the MTHFR 677TT genotype (p=0.009).Conclusion: OPG and MTHFR gene variations seem to increase susceptibility for seropositive RA and potentially contribute to subclinical atherosclerosis linked to RA.
Can Green Finance Optimize Energy Structure: A Spatial Econometric Analysis based on China's Traditional and Renewable Energy Consumption
Authors: Wang Hui , Jiang Lili , Duan Hongjun , Wang Yifeng , Jiang Yichen
Published: December 2021

This paper studies the impact of the development of green finance on China’s energy consumption structure. In terms of the construction of the green finance index (GFI), this paper selects 17 basic indexes from the three aspects of economy, finance, and environment, uses the improved entropy weight method to construct the GFI, and studies the spatial spillover effect of the GFI of China's provinces. This paper further studies the impact of green finance on traditional and renewable energy consumption. We first uses panel regression to determine that the development of green finance has a positive effect on the slowdown of traditional energy consumption and acceleration of renewable energy consumption, and then further studies the spatial characteristics of green finance development on energy consumption by using spatial Durbin model. The results show that there is a positive spatial spillover effect in the development of green finance among provinces in China. The development of green finance contributes to the conversion of traditional to renewable energy consumption. The effect of green finance on the transformation of energy consumption structure is mainly reflected in the direct effect. Therefore, the government should support the green finance, reduce traditional energy consumption and increase renewable energy consumption.
Difficult Airway Prediction Score for Intubation in Emergency Departments: A Retrospective Cohort Study
Authors: Savatmongkorngul Sorravit , Pitakwong Panrikan , Srichar Pungkava , Yuksen Chaiyaporn , Jenpanitpong Chetsadakon , watcharakitpaisan Sorawich
Published: December 2021

Objective: Difficult intubation is associated with an increasing number of endotracheal intubation attempts. Repeated endotracheal intubation attempts are in turn associated with an increased risk of adverse events. Clinical prediction tools to predict difficult airway have limited application in emergency airway situations. This study was performed to develop a new model for predicting difficult intubation in the emergency department.Methods: This retrospective study was conducted using an exploratory model at the Emergency Medicine of Ramathibodi Hospital, a university-affiliated super-tertiary care hospital in Bangkok, Thailand. The study was conducted from June 2018 to July 2020. The inclusion criteria were an age of ≥15 years and treatment by emergency intubation in the emergency department. Difficult intubation was defined as a Cormack–Lehane grade III or IV laryngoscopic view. The predictive model and prediction score for detecting difficult intubation were developed by multivariable regression analysis.Results: During the study period, 617 patients met the inclusion criteria; of these, 83 (13.45%) had difficult intubation. Five independent factors were predictive of difficult intubation. The difficult airway assessment score that we developed to predict difficult airway intubation had an accuracy of 89%. A score of >4 increased the likelihood ratio of difficult intubation by 7.62 times.Conclusion: A difficult airway assessment score of >4 was associated with difficult intubation.
Corporate Carbon Disclosure, Financing Structure and Total Factor Productivity: Evidence from Chinese Heavy Polluting Listed Corporates
Authors: Yuan Sai , Pan Xiongfeng
Published: December 2021

Low-carbon economy has become the current global economic development trend, and Corporate carbon disclosure has attracted more and more attention from scholars and investors. This paper creatively explores the mechanism of corporate carbon disclosure quality on total factor productivity with financing structure as a mediating variable. The content analysis method is used to construct a carbon disclosure evaluation index system that is suitable for Chinese companies. Through the mediating effect model and Sobel test, the internal mechanism of carbon disclosure quality affecting total factor productivity is analyzed, with Chinese heavy polluting listed corporates from 2015 to 2018 as research samples. The empirical results show that, Firstly, the Quality of carbon disclosure has a positive effect on the improvement of total factor productivity. The effect of monetary carbon disclosure quality on the improvement of total factor productivity is higher than that of non-monetary carbon disclosure quality. Secondly, the financing structure has a mediating effect on the quality of carbon disclosure and total factor productivity, and the mediating effect of internal financing capabilities is better than those of external financing costs. Finally, external financing costs and internal financing capabilities have mediating effects in both heterogeneous carbon disclosure quality and total factor productivity. The mediating effect of internal financing capabilities is significantly higher than the mediating effect of external financing costs. Meanwhile, the effect of monetary carbon disclosure quality on total factor productivity indirectly through internal financing capabilities is higher than that of non-monetary carbon disclosure quality.
An osmium-peroxo complex for photoactive therapy of hypoxic tumors
Authors: Lu Nong , Deng Zhihong , Gao Jing , Liang Chao , Xia Haiping , Zhang Pingyu
Published: December 2021

Its limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy (PDT). Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but upon light irradiation, can release a peroxo ligand O2•−, and is transformed into a cytotoxic osmium complex (Os1). The osmium-peroxo complex Os2 produces O2•− under light irradiation even in the absence of oxygen, and retains its phototoxicity in hypoxic tumors. Os1 is cytotoxic in the presence or absence of irradiation, behaves as a chemotherapeutic drug. The light-activated Os2 induces distinct ferroptosis, which is mediated by GSH degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4 (GPX4). In addition, Os2 causes photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide (NADH) in living cancer cells, leading to ferroptosis. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A new strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.
Development of Epoxy Resin-Based Elastomeric Microfluidic Devices Using CO2 Laser Ablation for DNA-Amplification Point-Of-Care (POC) Applications: Assessment of Microchannels' Dimensions and Quality
Authors: Mansour Heba , El-Bab Ahmed M.R. Fath , Soliman Emad A. , Abdel-Mawgood Ahmed L.
Published: December 2021

Microfluidic devices are a rising technology to automatize chemical and biological operations. In this context, laser ablation has significant potential for polymer-based microfluidic platforms' fast and economical manufacturing. Nevertheless, the manufacturing of epoxy-based microfluidic chips is considered highly cost full due to demand for cleanroom facilities that utilize expensive equipment and lengthy processes. Therefore, this study targeted investigating the feasibility of epoxy resins to be fabricated as a lab-on-chip using carbon dioxide laser ablation. The chemical structural properties and thermal stability of the plain epoxy resins were characterized by Fourier transform infrared spectral analysis (FT-IR) and thermogravimetric analysis (TGA). Moreover, a specific migration test was performed to quantify potential migrants by gas chromatography coupled to mass spectrometry (GC-MS) to prove that the cured epoxy resin would not release unreacted monomers to the biological solution test, which caused inhibition of the sensitive biological reactions. By investigating the impact of this process on microchannels' dimensions and quality, a laser technique using CO2 laser was used in vector mode to engrave into a transparent epoxy resin chip. The resulting microchannels were characterized using 3D Laser microscopy. The outcomes of this study showed considerable potential for laser ablation in machining the epoxy-based chips, whereas the microchannels were produced with minor bulges' height (0.027 µm) with no clogging. Moreover, a reasonable depth of 99.31 µm with roughness (Ra) of 14.52 µm was obtained at a laser speed of 5 mm/s and laser power of 1.8 W. This process can produce epoxy resin-based microfluidic chips without the need for cleanroom facilities that require expensive equipment and lengthy process.
The position of geochemical variables as causal co-factors of diseases of unknown aetiology
Authors: Davies Theophilus Clavell
Published: December 2021

The term diseases of unknown aetiology (DUA) or idiopathic diseases refers to diseases that are of uncertain or unknown cause or origin. Among plausible geoenvironmental (co-)factors in causation of DUA, this article focusses on the entry of trace elements, including metals and metalloids into biological systems, and their involvement in humoral and cellular immune responses, representing potentially toxic agents with implications as co-factors for certain DUA. Several trace elements/metals/metalloids (micronutrients) play vital roles as cofactors for essential enzymes and antioxidant molecules, thus, conferring protection against disease. However, inborn errors of trace element/metal/metalloid metabolisms can occur to produce toxicity, such as when there are basic defects in the element transport mechanism. Ultimately, it is the amount of trace element, metal or metalloid that is taken up, its mode of accumulation in human tissues, and related geomedical attributes such as the chemical form and bioavailability that decisively determine whether the exerted effects are toxic or beneficial. Several case descriptions of DUA that are common worldwide are given to illustrate our knowledge so far of how trace element/metal/metalloid interactions in the immune system may engender its dysregulation and be implicated as causal co-factors of DUA.
GPER/β-Alanine Positive Interaction in The Dorsal Root Ganglion Uncovers Potential Mechanisms: Mediating Continuous Neuronal Sensitisation and Neuroinflammation Responses in Neuropathic Pain
Authors: Xu Zhenzhen , Xie Wanli , Feng Yiqi , Wang Yanting , He Yuyao , Chen Lu , Xiong Yue , Li Xia , Liu Jie , Liu Guoyang , Wu Qingping
Published: December 2021

Background: The pathogenesis of neuropathic pain and the reasons for the prolonged unhealing are still unknown. Increasing evidence suggests that estrogen sex differences play a role in pain sensitivity, but few studies focused on the role of estrogen receptor which maybe an important molecular component contributing to peripheral pain transduction. We aimed to investigate the impact of oestrogen receptors in nociceptive neuronal response in the dorsal root ganglion (DRG) and spinal dorsal horn using a spared nerve injury (SNI) rat model of chronic pain. Methods: We used a class of estrogen receptors antagonists and agonists intrathecal (i.t.) administrated to male rats with SNI or normal rats to identify the main receptor. Moreover, we applied genes identified through genomic metabolic analysis to determine the key metabolism point and elucidate potential mechanisms mediating continuous neuronal sensitisation and neuroinflammation responses in neuropathic pain. The excitability of DRG neurons was detected using the patch clamp technique. Immunohistochemistry, Western blotting, qPCR and behavioral testing were used to assess the expressions, cellular distributions, and actions of main receptor and its related signaling molecules.Results: Increasing the expression and function of G protein-coupled estrogen receptor (GPER), but not estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), in the DRG, but not the dorsal spinal cord, contributed to SNI-induced neuronal sensitisation. Inhibiting GPER expression in the DRG alleviated SNI-induced pain behaviours and neuroinflammation by downregulating IL-1β and IL-6 expression as well as restoring GABAα2 expression simultaneously. Additionally, the positive interaction between GPER and β-alanine, β-alanine accumulation enhances pain sensation and promotes chronic pain development. Conclusion: GPER activation in the DRG causes a positive interaction of β-alanine with IL-1β and IL-6 expression and represses GABAα2 involved in post-SNI neuropathic pain development. Blocking GPER and eliminating β-alanine in the DRG may prevent neuropathic pain development.
Rare Disease Curative Care Expenditure- Financing Scheme-Health Provider- Beneficiary Group Analysis — An Empirical Study in Sichuan Province, China
Authors: Li Jia , Yang Lian , Zhang Yitong , Liao Hailun , Ma Yuan , Sun Qun
Published: December 2021

Background: Rare diseases impose heavy economic burdens on patients’ families and society worldwide. This study has used the samples from Sichuan Province of China to estimate the curative care expenditure(CCE) of ten rare diseases to provide reference and support for the prioritization of rare disease health policies. Methods: The multi-stage cluster sampling method was adopted to conduct a survey of 9714 rare disease patients from 1,556 medical institutions in Sichuan Province in 2018. Based on System of Health Accounts 2011, the study estimated the total curative care expenditure on rare diseases and identified financing sources and their allocation among different health institutions and the patient population. Results: In 2018, the total CCE of the ten rare diseases in Sichuan Province was 19.001 million US dollars; the top three rare diseases in terms of CCE were Hemophilia ($4.3786 million), Young-onset Parkinson Disease ($2.9627 million) , and Systemic Sclerosis ($2.4457 million); household out-of-pocket expenditure (86.00% for outpatients, 41.60% for inpatients) and social health insurance (7.85% for outpatients; 39.58% for inpatients) were the main sources of financing. The out-of-pocket expenditures for patients with Young-onset Parkinson Disease, Congenital Scoliosis, Autoimmune accounted for more than 60% of the total CCE. More than 80% of the rare disease CCE was incurred in general hospitals. The 40-59 age group consumed the highest percentage of CCE (38.70%) while men spent slightly more (55.37%) than women (44.64%). Conclusions: Since rare disease treatment is costly and household out-of-pocket expenditure is high, we suggest taking steps to include rare disease drugs in the National Reimbursement Drug List, scientifically design insurance coverage range. It is also necessary to explore a multi-tiered Healthcare Security System to pay for the CCE of rare diseases and to reduce the economic burdens of patients.
Postoperative Antibiotics And Time To Reach Discharge Criteria After Appendectomy For Complex Appendicitis
Authors: Boom A.L. van den , de Wijkerslooth E.M.L. , Giesen L. J. X. , Rossem C. C. van , Toorenvliet B. R. , Wijnhoven B. P. L.
Published: December 2021

Background: Postoperative antibiotic treatment is indicated for 3 – 5 days following appendectomy for complex appendicitis. However, meeting discharge criteria may allow for safe discontinuation of antibiotics and discharge. This study assessed the association between time to reach discharge criteria and duration of postoperative antibiotic use and length of hospital stay. Methods: This was a multicenter retrospective cohort study including patients who underwent appendectomy for complex appendicitis and received postoperative antibiotics for >24 hours. Main outcome measures were time to reach discharge criteria, duration of postoperative antibiotic use, length of hospital stay and postoperative infectious complications. Discharge criteria were defined as absence of fever (temperature ≤38°C) for 24 hours, ability to tolerate oral intake and pain controlled by oral analgesics.Results: A total of 124 patients were included between May 2014 and January 2015. Median time to reach discharge criteria was 2 days (interquartile range 1 – 3). Postoperative antibiotics duration and hospital stay were 5 (IQR 3 – 5) and 5 (IQR 4 – 6) days, respectively. Infectious complications occurred in 15 of 124 patients (12%) and was not different between patients reaching discharge criteria before or after 2 postoperative days.Conclusions: Discharge criteria were met by a median of 2 days after appendectomy for complex appendicitis. This suggests that postoperative antibiotics and hospital stay can be reduced without an increase in infectious complications. In daily practice this is not done, prescribed antibiotics are not reduced in total days given. Prospective studies that evaluate limited postoperative antibiotic use, based on these criteria, are necessary.
Intelligent Physical Exercise Training (IPET) in the Offshore Wind Industry: a Feasibility Study With an Adjusted Conceptual Model
Authors: Oestergaard Anne Skov , Sandal Louise Fleng , Smidt Trine Fernando , Søgaard Karen
Published: December 2021

Background: Good physical health and capacity is a requirement for offshore wind service technicians (WTs) who have substantial physical work demands and are exposed to numerous health hazards. Workplace physical exercise has shown promising results as a strategy for maintaining and improving physical health and work ability among various types of workers. Therefore, we aimed to assess the feasibility and preliminary efficacy of the Intelligent Physical Exercise Training (IPET) concept among WTs in the offshore wind industry.Methods: The present study used a within-subject design to assess the feasibility and preliminary efficacy of IPET (one hour/week individualized exercise during working hours). The intervention period was 12 weeks, with the first eight weeks performed on site as supervised or partly supervised exercise during work hours and the last four weeks planned as home-administered exercise after termination of the seasonal offshore service period. Three assessments, T1 (six months prior to intervention start), T2 (start of intervention) and T3 (end of intervention), of physical health and capacity (self-reported and objective measurements) were conducted and the period between T1 and T2 served as a within-subject control period. Primary outcome was feasibility measured as compliance, adherence, adverse events, and participant acceptability. Descriptive statistics were used to present feasibility outcomes and pairwise comparisons were performed to assess for differences in outcomes between T1, T2 and T3. Results: All WTs at the included wind farm (n=24, age: 40 years (SD±8)) participated in the study. No serious adverse events were reported. Compliance and adherence of 95 and 80% respectively, were reached in the eight-week supervised part, but lower when exercise was home-administered (<20%). Acceptability was high for the supervised part, with 83% indicating that the exercise program worked well and 100% that exercise should be implemented as an integrated part of the working structure. Physical capacity and health parameters collected at T1, T2 and T3 increased before and during the intervention period, indicating seasonal fluctuations in addition to possible improvements caused by the intervention.Conclusion: Implementation of Intelligent Physical Exercise Training on site and during working hours seems to be feasible and well received among WTs in the offshore wind industry.Trial registration: ClinicalTrials.gov (Identifier: NCT04995718). Retrospectively registered on August 6, 2021, https://clinicaltrials.gov/ct2/show/NCT04995718?term=NCT04995718&draw=2&rank=1
Immune Characteristics-Related Typing of Colorectal Cancer and the Establishment of 14-Gene Prognostic Model
Authors: Ma Jianxing , Wang Chen
Published: December 2021

This study is to establish NMF (nonnegative matrix factorization) typing related to the tumor microenvironment (TME) of colorectal cancer (CRC) and to construct a gene model related to prognosis to be able to more accurately estimate the prognosis of CRC patients. NMF algorithm was used to classify samples merged clinical data of differentially expressed genes (DEGs) of TCGA that are related to the TME shared in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and survival differences between subtype groups were compared. By using createData Partition command, TCGA database samples were randomly divided into train group and test group. Then the univariate Cox analysis, Lasso regression and multivariate Cox regression models were used to obtain risk model formula, which is used to score the samples in the train group, test group and GEO database, and to divide the samples of each group into high-risk and low-risk groups, according to the median score of the train group. After that, the model was validated. Patients with CRC were divided into 2, 3, 5 subtypes respectively. The comparison of patients with overall survival (OS) and progression-free survival (PFS) showed that the method of typing with the rank set to 5 was the most statistically significant (p=0.007, p<0.001, respectively). Moreover, the model constructed containing 14 immune-related genes (PPARGC1A, CXCL11, PCOLCE2, GABRD, TRAF5, FOXD1, NXPH4, ALPK3, KCNJ11, NPR1, F2RL2, CD36, CCNF, DUSP14) can be used as an independent prognostic factor, which is superior to some previous models in terms of patient prognosis. The 5-type typing of CRC patients and the 14 immune-related genes model constructed by us can accurately estimate the prognosis of patients with CRC.
Arabidopsis CPR5 Plays a Role in Regulating Nucleocytoplasmic Transport of mRNAs in Ethylene Signaling Pathway
Authors: Chen Jiacai , Sui Xinying , Ma Binran , Li Yuetong , Li Na , Qiao Longfei , Yu Yanchong , Dong Chun-Hai
Published: December 2021

The ETR1 receptor plays a predominant role in ethylene signaling in Arabidopsis thaliana. Previous studies showed that both RTE1 and CPR5 can directly bind to the ETR1 receptor and regulate ethylene signaling. RTE1 was suggested to promote the ETR1 receptor signaling by influencing its conformation, but little is known about the regulatory mechanism of CPR5 in ethylene signaling. In this study, we presented data showing that both RTE1 and CPR5 bound to the N-terminal domains of ETR1, and regulated ethylene signaling via the ethylene receptor. On the other hand, the research provided evidence indicating that CPR5 could act as a nucleoporin to regulate the ethylene-related mRNAs export out of the nucleus, while RTE1 or its homolog (RTH) had no effect on the nucleocytoplasmic transport of mRNAs. Nuclear qRT-PCR analysis and poly(A)-mRNA in situ hybridization showed that defect of CPR5 restricted nucleocytoplasmic transport of mRNAs. These results advance our understanding of the regulatory mechanism of CPR5 in ethylene signaling.
Degumming of Hemp Fibers Using Combined Microwave Energy and Deep Eutectic Solvent Treatment
Authors: Ahmed Bulbul , Wu Qinglin , Gwon Jaegyoung , Negulescu Ioan , Cameron Bruce
Published: December 2021

Hemp bast fibers were degummed using combined microwave energy (MWE) and deep eutectic solvent (DES) to generate pure hemp cellulose fibers for potential textile applications. The properties of the obtained fibers were investigated and compared with those from the traditional alkali-based process using several analytical techniques. Results revealed that hemp fiber surface underwent dramatic structural disruption during the pretreatment, due to the removal of “gummy” compounds (i.e., lignin, pectin, oil, and wax) and amorphous cellulose. Ultraviolet (UV) protection factor (UPF) of DES-treated fibers with 1:20 fiber-DES ratio (i.e., 183.67) were significantly higher than those from the traditional alkali-treated (140.75) and untreated raw hemp fibers (127.47). The treated fibers also had higher thermal stability. Chemical composition analysis showed that the cellulose content in the treated fiber samples increased to 49.95% which was comparable with the cellulose content of the alkali-treated fibers (49.49%). The study demonstrates a potentially effective, less time-consuming, and environmentally sustainable protocol for manufacturing purified hemp cellulose fibers using combined MWE-DES treatment.
Dendritic cell targeting virus-like particle delivers mRNA for in vivo immunization
Authors: Yin Di , Ling Sikai , Tian Xiaolong , Li Yang , Xu Zhijue , Jiang Hewei , Zhang Xue , Wang Xiaoyuan , Shi Yi , Wang Quanjun , Xu Jianjiang , Hong Wei , Xue Heng , yang hang , Zhang Yan , Da Lintai , Han Ze-Guang , Tao Sheng-ce , Hong Jiaxu , Ying Tianlei , Cai Yujia
Published: December 2021

mRNA vaccine was approved clinically in 2020. Future development includes delivering mRNA to dendritic cells (DCs) specifically to improve effectiveness and avoid off-target cytotoxicity. Here, we developed virus-like particles (VLPs) as a DC tropic mRNA vaccine vector and showed the prophylactic effects in both SARS-CoV-2 and HSV-1 infection models. The VLP mRNA vaccine elicited strong cytotoxic T cell immunity and durable antibody response with the spike-specific antibodies that lasted for more than 9 months. Importantly, we were able to target mRNA to DCs by pseudotyping VLP with engineered Sindbis virus glycoprotein and found the DC-targeting mRNA vaccine significantly enhanced the titer of antigen-specific IgG, protecting the hACE-2 mice from SARS-CoV-2 infection. Additionally, we showed DC-targeted mRNA vaccine also protected mice from HSV-1 infection when co-delivering the gB and gD mRNA. Thus, the VLP may serve as an in situ DC vaccine and accelerate the further development of mRNA vaccines.
Feline Herpesvirus Infection of Snow Leopard
Authors: Wu Qiaoxing , Wu Hongchao , He Shunfu , Liu Yuxiu , Chen Yalei , Qi Xinzhang , Gu Xiangyang , Wen Yifan , Jin Xuelin , Jin Yipeng , Tian Kegong
Published: December 2021

Feline herpesvirus type 1 (FHV-1) is a common causative agent of domestic cats rhinotracheitis and gradually threatens the wild felid worldwide. The endangered snow leopard belongs to the family Felidae and is also the top predator on the Tibetan Plateau. Herein, FHV-1 was identified and isolated from three dead snow leopards with symptom of sneezing and rhinorrhea. To explore the relationship between FHV-1 and their death, histopathology and molecular biology was performed. The organs and nasal swabs were collected for examinations of histopathology, the nucleic acid of the pathogen, viral isolation, and sequence analysis. The results reveal that all three snow leopards were infected with FHV-1. The first case primarily died of old cerebral infarction and secondary non-suppurative meningoencephalitis probably caused by FHV-1. The second case mainly died of renal failure accompanied by interstitial pneumonia caused by FHV-1. The third case was doubted to be related to the reactivation of latency of FHV-1. The gD and gE gene sequence alignment of the FHV-1 isolate strain revealed that the isolated strain originated from a domestic cat. Therefore, FHV-1 infection can cause different lesions of snow leopards and shows a high risk for the wild felid. We should focus more on protecting felid against threatening of FHV-1 infection originating from domestic cats.