bluuebunny/crossref_metadata_2025 huggingface dataset:
A Computational Framework to Identify Metabolic Engineering Strategies for the Co-Production of Metabolites
Authors: Raajaraam Lavanya , Raman Karthik
Published: January 2022

Microbial production of chemicals is a more sustainable alternative to traditional chemical processes. However, the shift to bioprocess is usually accompanied by a drop in economic feasibility. Co-production of more than one chemical can improve the economy of bioprocesses, enhance carbon utilization and also ensure better exploitation of resources. While a number of tools exist for in silico metabolic engineering, there is a dearth of computational tools that can co-optimize the production of multiple metabolites. In this work, we propose co-FSEOF (co-production using Flux Scanning based on Enforced Objective Flux), an algorithm designed to identify intervention strategies to co-optimize the production of a set of metabolites. Co-FSEOF can be used to identify all pairs of products that can be co-optimized with ease using a single intervention. Beyond this, it can also identify higher-order intervention strategies for a given set of metabolites. We have employed this tool on the genome-scale metabolic models of Escherichia coli and Saccharomyces cerevisiae, and identified intervention targets that can co-optimize the production of pairs of metabolites under both aerobic and anaerobic conditions. Anaerobic conditions were found to support the co-production of a higher number of metabolites when compared to aerobic conditions in both organisms. The proposed computational framework will enhance the ease of study of metabolite co-production and thereby aid the design of better bioprocesses.
Acitretin-Conjugated Dextran Nanoparticles Ameliorate Psoriasis-like Skin Disease at Low Dosages
Authors: Lan Jiajia , Li Yuce , Wen Jingjing , Chen Yu , Yang Jing , Zhao Liang , Xia Yuting , Du Hongyao , Tao Juan , Li Yan , Zhu Jintao
Published: January 2022

Psoriasis is a common chronic inflammatory skin disease mainly characterized by keratinocyte hyperproliferation and massive infiltration of inflammatory immune cells. Acitretin (ACT), an FDA-approved first-line systemic drug for psoriasis treatment, could suppress the proliferation of keratinocytes and downregulate the expression of inflammatory cytokines by modulating signal transducer and activator of transcription (STAT) signaling pathways. However, dose-dependent side effects of ACT limit its long-term administration in the clinic. Therefore, improving the therapeutic efficacy of ACT to reduce clinical dosage will benefit the patients. Here, we develop ACT-conjugated dextran nanoparticles (ACT-Dex NPs) and evaluated the potential for psoriasis treatment. Our results indicate that ACT-Dex NPs ameliorate psoriasis-like skin disease significantly at a low dosage which does not cause side effects, while neat ACT drugs at an equivalent dosage provide much less benefit. Moreover, we demonstrate that ACT-Dex NPs suppress keratinocyte proliferation more efficiently than neat ACT by enhancing the inhibitory effect on STAT3 phosphorylation. Thus, the proposed ACT-Dex NPs provide an effective and safe option for psoriasis treatment.
Heterologous Production of Glycine Betaine Using Synechocystis sp. PCC 6803-Based Chassis Lacking Native Compatible Solutes
Authors: Ferreira Eunice A. , Pacheco Catarina C. , Rodrigues João S. , Pinto Filipe , Lamosa Pedro , Fuente David , Urchueguía Javier , Tamagnini Paula
Published: January 2022

Among compatible solutes, glycine betaine has various applications in the fields of nutrition, pharmaceuticals, and cosmetics. Currently, this compound can be extracted from sugar beet plants or obtained by chemical synthesis, resulting in low yields or high carbon footprint, respectively. Hence, in this work we aimed at exploring the production of glycine betaine using the unicellular cyanobacterium Synechocystis sp. PCC 6803 as a photoautotrophic chassis. Synechocystis mutants lacking the native compatible solutes sucrose or/and glucosylglycerol—∆sps, ∆ggpS, and ∆sps∆ggpS—were generated and characterized. Under salt stress conditions, the growth was impaired and accumulation of glycogen decreased by ∼50% whereas the production of compatible solutes and extracellular polymeric substances (capsular and released ones) increased with salinity. These mutants were used as chassis for the implementation of a synthetic device based on the metabolic pathway described for the halophilic cyanobacterium Aphanothece halophytica for the production of the compatible solute glycine betaine. Transcription of ORFs comprising the device was shown to be stable and insulated from Synechocystis’ native regulatory network. Production of glycine betaine was achieved in all chassis tested, and was shown to increase with salinity. The introduction of the glycine betaine synthetic device into the ∆ggpS background improved its growth and enabled survival under 5% NaCl, which was not observed in the absence of the device. The maximum glycine betaine production [64.29 µmol/gDW (1.89 µmol/mg protein)] was reached in the ∆ggpS chassis grown under 3% NaCl. Taking into consideration this production under seawater-like salinity, and the identification of main key players involved in the carbon fluxes, this work paves the way for a feasible production of this, or other compatible solutes, using optimized Synechocystis chassis in a pilot-scale.
An Investigation of Indoor Air Quality in a Recently Refurbished Educational Building
Authors: McLeod R. S. , Mathew M. , Salman D. , Thomas C. L. P.
Published: January 2022

Young people spend extended periods of time in educational buildings, yet relatively little is known about the air quality in such spaces, or the long-term risks which contaminant exposure places on their health and development. Although standards exist in many countries in relation to indoor air quality in educational buildings, they are rarely subject to detailed post-occupancy evaluation. In this study a novel indoor air quality testing methodology is proposed and demonstrated in the context of assessing the post-occupancy performance of a recently refurbished architecture studio building at Loughborough University, United Kingdom. The approach used provides a monitoring process that was designed to evaluate air quality in accordance with United Kingdom national guidelines (Building Bulletin 101) and international (WELL Building) standards. Additional, scenario-based, testing was incorporated to isolate the presence and source of harmful volatile organic compounds, which were measured using diffusive sampling methods involving analysis by thermal desorption - gas chromatography - mass spectrometry techniques. The findings show that whilst the case-study building appears to perform well in respect to existing national and international standards, these guidelines only assess average CO2 concentrations and total volatile organic compound limits. The results indicate that existing standards, designed to protect the health and wellbeing of students, are likely to be masking potentially serious indoor air quality problems. The presence of numerous harmful VOCs found in this study indicates that an urgent revaluation of educational building procurement and air quality monitoring guidelines is needed.
Epigenetic, Metabolic, and Immune Crosstalk in Germinal-Center-Derived B-Cell Lymphomas: Unveiling New Vulnerabilities for Rational Combination Therapies
Authors: Serganova Inna , Chakraborty Sanjukta , Yamshon Samuel , Isshiki Yusuke , Bucktrout Ryan , Melnick Ari , Béguelin Wendy , Zappasodi Roberta
Published: January 2022

B-cell non-Hodgkin lymphomas (B-NHLs) are highly heterogenous by genetic, phenotypic, and clinical appearance. Next-generation sequencing technologies and multi-dimensional data analyses have further refined the way these diseases can be more precisely classified by specific genomic, epigenomic, and transcriptomic characteristics. The molecular and genetic heterogeneity of B-NHLs may contribute to the poor outcome of some of these diseases, suggesting that more personalized precision-medicine approaches are needed for improved therapeutic efficacy. The germinal center (GC) B-cell like diffuse large B-cell lymphomas (GCB-DLBCLs) and follicular lymphomas (FLs) share specific epigenetic programs. These diseases often remain difficult to treat and surprisingly do not respond advanced immunotherapies, despite arising in secondary lymphoid organs at sites of antigen recognition. Epigenetic dysregulation is a hallmark of GCB-DLBCLs and FLs, with gain-of-function (GOF) mutations in the histone methyltransferaseEZH2, loss-of-function (LOF) mutations in histone acetyl transferasesCREBBPandEP300, and the histone methyltransferaseKMT2Drepresenting the most prevalent genetic lesions driving these diseases. These mutations have the common effect to disrupt the interactions between lymphoma cells and the immune microenvironment, via decreased antigen presentation and responsiveness to IFN-γ and CD40 signaling pathways. This indicates that immune evasion is a key step in GC B-cell lymphomagenesis. EZH2 inhibitors are now approved for the treatment of FL and selective HDAC3 inhibitors counteracting the effects ofCREBBPLOF mutations are under development. These treatments can help restore the immune control of GCB lymphomas, and may represent optimal candidate agents for more effective combination with immunotherapies. Here, we review recent progress in understanding the impact of mutant chromatin modifiers on immune evasion in GCB lymphomas. We provide new insights on how the epigenetic program of these diseases may be regulated at the level of metabolism, discussing the role of metabolic intermediates as cofactors of epigenetic enzymes. In addition, lymphoma metabolic adaptation can negatively influence the immune microenvironment, further contributing to the development of immune cold tumors, poorly infiltrated by effector immune cells. Based on these findings, we discuss relevant candidate epigenetic/metabolic/immune targets for rational combination therapies to investigate as more effective precision-medicine approaches for GCB lymphomas.
Study of Variability of Waste Wood Samples Collected in a Panel Board Industry
Authors: Mancini Manuela , Rinnan Åsmund
Published: January 2022

Waste wood is becoming an appealing alternative material to virgin wood, and the main drivers are the increased demand for waste wood by the panel industry, the introduction of renewable energy policies, and the waste framework directive. In fact, the use of waste wood as a secondary resource is favored over both landfills and combustion. The best reuse and cascading use of the material are linked to its characteristics. That is why it is important to know the chemical composition and the variation in the properties of such a heterogeneous material. In this article, a sampling study was carried out in a panel board company located in the northern part of Italy. In order to investigate the heterogeneity of waste wood, all samples have been analyzed by near-infrared spectroscopy. Nested analysis of variance and principal component analysis have been used to evaluate the heterogeneity and the variation in sample properties. The approach gives information about how to ensure representative measurements and efficiently describe the variability of the material. The results suggest that it is important to have replicates or at least two subsamples for each lot and then measure each of these with at least 100 scans, in order to get representative measurements and describe the variability of the material. The determination of waste wood composition and variability is the focal point for improving the sorting process and increasing the reuse of waste wood, avoiding expensive landfills and risks for human health and the environment.
Copper(II)-Bis-Cyclen Intercalated Graphene Oxide as an Efficient Two-Dimensional Nanocomposite Material for Copper-Catalyzed Azide–Alkyne Cycloaddition Reaction
Authors: Samuel Angel Green , Subramanian Sowmya , Vijendran Vijaikanth , Bhagavathsingh Jebasingh
Published: January 2022

We report stable and heterogeneous graphene oxide (GO)–intercalated copper as an efficient catalyst for the organic transformations in green solvents. The GO-intercalated copper(II) complex of bis(1,4,7,10-tetraazacyclododecane) [Cu(II)-bis-cyclen] was prepared by a facile synthetic approach with a high dilution technique. The as-prepared GO-Cu(II)-bis-cyclen nanocomposite was used as a click catalyst for the 1,3 dipolar Huisgen cycloaddition reaction of terminal alkyne and azide substrates. On directing a great deal of attention toward the feasibility of the rapid electron transfer rate of the catalyst in proliferating the yield of 1,2,3-triazole products, the click catalyst GO-Cu(II)-bis-cyclen nanocomposite was designed and synthesized via non-covalent functionalization. The presence of a higher coordination site in an efficient 2D nanocomposite promotes the stabilization of Cu(I) L-acetylide intermediate during the catalytic cycle initiated by the addition of reductants. From the XRD analysis, the enhancement in the d-interlayer spacing of 1.04 nm was observed due to the intercalation of the Cu(II)-bis-cyclen complex in between the GO basal planes. It was also characterized by XPS, FT-IR, RAMAN, UV, SEM, AFM, and TGA techniques. The recyclability of the heterogeneous catalyst [GO-Cu(II)-cyclen] with the solvent effect has also been studied. This class of GO-Cu(II)-bis-cyclen nanocomposite paves the way for bioconjugation of macromolecules through the click chemistry approach.
Discovery of a Series of 1,2,3-Triazole-Containing Erlotinib Derivatives With Potent Anti-Tumor Activities Against Non-Small Cell Lung Cancer
Authors: Sun Ge , Mao Longfei , Deng Wenjing , Xu Shuxiang , Zhao Jie , Yang Jianxue , Yao Kaitai , Yuan Miaomiao , Li Wei
Published: January 2022

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are emerging at the vanguard of therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the increasing therapeutic resistance caused by novel mutations or activated bypass pathways has impaired their performance. In this study, we link one of the commercial EGFR-TKIs, Erlotinib, to different azide compounds to synthesize a novel class of 1,2,3-triazole ring-containing Erlotinib derivatives. We discovered that several new compounds show robust antiproliferation activity against diverse NSCLC cells in vitro including PC-9, H460, H1975 and A549. Two of the most potent compounds, e4 and e12 have been found to be more efficient than Erlotinib in all NSCLC cell lines except PC-9. They significantly induce apoptosis and cell cycle arrest in PC-9 and H460 cells. The antitumor efficacy of compound e4 in vivo is close to that of Erlotinib in a PC-9 xenograft mouse model. Most Erlotinib-1,2,3-triazole compounds exhibit moderate to good inhibitory activities toward wild-type EGFR as indicated by enzyme-linked immunosorbent assay (ELISA), and the EGFR phosphorylation was inhibited in H460 and PC-9 cells exposed to e4 or e12. These data suggest that these Erlotinib-1,2,3-triazole compounds are suitable candidates for use against NSCLC and more unknown mechanisms merit further investigation.
Senecavirus A- and Non-Infected Cells at Early Stage of Infection: Comparative Metabolomic Profiles
Authors: Liu Fuxiao , Ni Bo , Wei Rong
Published: January 2022

Senecavirus A (SVA), classified into the genus Senecavirus in the family Picornaviridae, causes an infectious disease in pigs. This virus can efficiently replicate in some non-pig-derived cells, such as the BHK cell line and its derivative (BSR-T7/5 cell line). We had recovered a wild-type SVA from its cDNA clone previously, and then uncovered the proteomic profile of SVA-infected BSR-T7/5 cells at 12 h post inoculation (hpi). In order to explore the cellular metabolomics further, the SVA-inoculated BSR-T7/5 cell monolayer was collected at 12 hpi for assay via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The resultant data set was comprehensively analyzed using bioinformatics tools. A total of 451 metabolites were identified using in-house and public databases. Out of these metabolites, sixty-one showed significantly differential values (p value < 0.05). The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to analyze metabolic pathways of the significantly differential metabolites. There were eighty-one identified KEGG pathways, out of which twenty-seven showed their p values < 0.05. The pyrimidine metabolism revealed the minimum p value and the maximum number of significantly differential metabolites, implying the pyrimidine played a key role in cellular metabolism after SVA infection. SVA replication must rely on the cellular metabolism. The present study on metabolomics would shed light on impacts of SVA-induced multiple interactions among metabolites on cells or even on natural hosts.
Diallyl Disulfide (DADS) Ameliorates Intestinal Candida albicans Infection by Modulating the Gut microbiota and Metabolites and Providing Intestinal Protection in Mice
Authors: Hu Wanchao , Huang Liou , Zhou Ziyang , Yin Liping , Tang Jianguo
Published: January 2022

Diallyl disulfide (DADS), a garlic extract also known as allicin, has been reported to have numerous biological activities, including anticancer, antifungal, and inflammation-inhibiting activities, among others. Although many studies have assessed whether DADS can treat Candida albicans infection in vitro, its in vivo function and the underlying mechanism are still not clear. Accumulated evidence has implicated the gut microbiota as an important factor in the colonization and invasion of C. albicans. Thus, this study aimed to identify the mechanism by which DADS ameliorates dextran sulfate (DSS)-induced intestinal C. albicans infection based on the systematic analysis of the gut microbiota and metabolomics in mice. Here, we determined the body weight, survival, colon length, histological score, and inflammatory cytokine levels in the serum and intestines of experimental mice. Fecal samples were collected for gut microbiota and metabolite analysis by 16S rRNA gene sequencing and LC–MS metabolomics, respectively. DADS significantly alleviated DSS-induced intestinal C. albicans infection and altered the gut microbial community structure and metabolic profile in the mice. The abundances of some pathogenic bacteria, such as Proteobacteria, Escherichia–Shigella, and Streptococcus, were notably decreased after treatment with DADS. In contrast, SCFA-producing bacteria, namely, Ruminiclostridium, Oscillibacter, and Ruminococcaceae_UCG−013, greatly increased in number. The perturbance of metabolites in infectious mice was improved by DADS, with increases in secondary bile acids, arachidonic acid, indoles and their derivatives, which were highly related to the multiple differentially altered metabolic pathways, namely, bile secretion, arachidonic acid metabolism, and tryptophan metabolism. This study indicated that DADS could modulate gut microbiota and metabolites and protect the gut barrier to alleviate DSS-induced intestinal C. albicans infection in mice. Moreover, this work might also provide novel insight into the treatment of C. albicans infection using DADS.
Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy
Authors: Li Jingjing , Xu Yajuan , Cai Yanjun , Zhang Miao , Sun Zongzong , Ban Yanjie , Zhai Shanshan , Hao Yingqi , Ouyang Qian , Wu Bo , Wang Mengqi , Wang Wentao
Published: January 2022

Objective

To investigate the association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism (SCH) during pregnancy.

Methods

The plasma of pregnant women in the SCH group and control group was analyzed by liquid chromatography-mass spectrometry (LC-MS), obtaining differential metabolites. Then, methane and hydrogen breath tests were performed in both groups, and basic clinical data and maternal outcome information were collected. Finally, differential metabolites were analyzed for small intestinal bacterial overgrowth (SIBO) and pregnancy outcomes using Spearman correlation analysis.

Results

(1) Multivariate statistics: There were 564 different metabolites in positive ion mode and 226 different metabolites in negative ion mode. (2) The positive rate of the methane hydrogen breath test in the SCH group was higher than that in the control group (p<0.05). (3) KEGG pathway analysis revealed that differential metabolites were mainly involved in bile secretion, cholesterol metabolism, and other pathways. (4) Serum cholesterol (TC) and triglyceride (TG) levels and hypertensive disorder complicating pregnancy (HDCP) were higher in the SCH group (p<0.05), and newborn birth weight (BW) was lower than that in the control group (p<0.05). (5) SIBO was negatively correlated with glycocholic acid and BW, and positively correlated with TC. Glycocholic acid was negatively correlated with TG but positively correlated with BW. TG was positively correlated with HDCP.

Conclusion

Differential metabolites in the SCH group during pregnancy were disordered with small intestinal bacteria, which may affect pregnancy outcomes, and bile acids and cholesterol may be potential biomarkers for studying their mechanism of action.
An Empirical Shear Model of Interface Between the Loess and Hipparion Red Clay in a Loess Landslide
Authors: Zhu Yanbo , Miao Shuaisheng , Li Hongfei , Han Yutao , Lan Hengxing
Published: January 2022

Quaternary loess is widely distributed over the tertiary Hipparion red clay on the Loess Plateau of China. Large-scale loess landslides often occur along the weak contact interface between these two sediment materials. To investigate the failure mode and shear strength characteristics of the loess–Hipparion red clay contact interface, a series of shearing experiments were performed on interface specimens using purpose-built shear equipment. In this article, the relationship between shear strength and interface morphology is discussed, and an empirical shear model of the interface is proposed based on the experimental results and theoretical work. The results indicate that discontinuities between the loess and the Hipparion red clay reduce the shear strength of specimens significantly. The contribution of the contact interface to shear performance including failure mode, shear deformation, and shear strength varies with the interface morphology and the applied normal stress. With low interface roughness or normal stress, sliding failure is likely to occur. With increasing interface roughness and normal stress, the peak strength increases rapidly. With further increase in the interface roughness and normal stress, the increment of peak strength decreases gradually as the failure mode transitions from sliding mode to cutoff mode. A staged shear model that takes the failure mode into consideration is developed to express the non-linear change in the interface shear strength. The shear model’s capability is validated by comparing model estimates with experimental data. This work improves our understanding of shear mechanisms and the importance of considering the effects of interfacial properties in the mechanical behavior of contact interfaces.
High-Contrast Lumbar Spinal Bone Imaging Using a 3D Slab-Selective UTE Sequence
Authors: Afsahi Amir Masoud , Lombardi Alecio F. , Wei Zhao , Carl Michael , Athertya Jiyo , Masuda Koichi , Wallace Mark , Lee Roland R. , Ma Ya-Jun
Published: January 2022

Ultra-short echo time (UTE) MRI with post-processing is a promising technique in bone imaging that produces a similar contrast to computed tomography (CT). Here, we propose a 3D slab-selective ultrashort echo time (UTE) sequence together with image post-processing to image bone structures in the lumbar spine. We also explore the intermodality agreement between the UTE and CT images. The lumbar spines of two healthy volunteers were imaged with 3D UTE using five different resolutions to determine the best imaging protocol. Then, four patients with low back pain were imaged with both the 3D UTE sequence and CT to investigate agreement between the imaging methods. Two other patients with low back pain were then imaged with the 3D UTE sequence and clinical conventional T1-weighted and T2-weighted fast spin-echo (FSE) MRI sequences for qualitative comparison. The 3D UTE sequence together with post-processing showed high contrast images of bone and high intermodality agreement with CT images. In conclusion, post-processed slab-selective UTE imaging is a feasible approach for highlighting bone structures in the lumbar spine and demonstrates significant anatomical correlation with CT images.
A Hybrid Model for Power Consumption Forecasting Using VMD-Based the Long Short-Term Memory Neural Network
Authors: Ruan Yingjun , Wang Gang , Meng Hua , Qian Fanyue
Published: January 2022

Energy consumption prediction is a popular research field in computational intelligence. However, it is difficult for general machine learning models to handle complex time series data such as building energy consumption data, and the results are often unsatisfactory. To address this difficulty, a hybrid prediction model based on modal decomposition was proposed in this paper. For data preprocessing, the variational mode decomposition (VMD) technique was used to used to decompose the original sequence into more robust subsequences. In the feature selection, the maximum relevance minimum redundancy (mRMR) algorithm was chosen to analyse the correlation between each component and the individual features while eliminating the redundancy between individual features. In the forecasting module, the long short-term memory (LSTM) neural network model was used to predict power consumption. In order to verify the performance of the proposed model, three categories of contrast methods were applied: 1) Comparing the hybrid model to a single predictive model, 2) Comparing the hybrid model with the backpropagation neural network (BPNN) to the hybrid model with the LSTM and 3) Comparing the hybrid model using mRMR and the hybrid model using mutual information maximization (MIM). The experimental results on the measured data of an office building in Qingdao show that the proposed hybrid model can improve the prediction accuracy and has better robustness compared to VMD-MIM-LSTM. In the three control groups mentioned above, the R2 value of the hybrid model improved by 10, 3 and 3%, respectively, the values of the mean absolute error (MAE) decreased by 48.9, 41.4 and 35.6%, respectively, and the root mean square error (RMSE) decreased by 54.7, 35.5 and 34.1%, respectively.
Can the Target Responsibility System of Air Pollution Control Achieve a Win-Win Situation of Pollution Reduction and Efficiency Enhancement?
Authors: Wang Jie , Xu Hao , Xu Jingxuan
Published: January 2022

Whether the environmental target responsibility system, a typical mandatory environmental regulation, can realize the coordinated development of environmental protection and economic growth has attracted widespread attention. With the difference-in-differences (DID) method, this paper utilizes a policy, “China’s Key Cities for Air Pollution Control to Meet the Standards within the Time Limit (APCMS),” as a quasi-natural experiment to empirically examine the target responsibility system of air pollution control’s effect on both firms’ pollutant emissions and their total factor productivity (TFP). The corresponding mechanisms are also investigated. The results show: 1) The policy not only significantly decreases firms’ pollutant emissions, but also improves their TFP. The results are robust to the exclusion of the impact of other policies in the same period, propensity score matching DID (PSM-DID) test, the adoption of alternative dependent variables, and altering sample interval; 2) The dynamic analysis shows that the policy effect on reducing pollutant emissions has increased over years after a lag of 2 years; 3) The policy reduces pollutant emissions mainly through stimulating the internal innovation rather than end-pipe treatment or production cuts. 4) Capital-intensive and private firms and firms in regions with a high degree of marketization or strong environmental law enforcement are found more responsive to the environmental target responsibility system.
Data-Driven Forest Cover Change and Its Driving Factors Analysis in Africa
Authors: Xiao Han , Liu Jianbo , He Guojin , Zhang Xiaomei , Wang Hua , Long Tengfei , Zhang Zhaoming , Wang Wei , Yin Ranyu , Guo Yantao , Cheng Bo , Cao Qianqian
Published: January 2022

Forest cover plays an important role in sustaining ecological security to realize Sustainable Development Goals (SDGs). The research target area is composed of the African region which is experiencing unprecedented deforestation based on the data collection from 54 countries and regions between 2000 and 2020. Spatial autocorrelation analysis, global principal component analysis, and geographic detector model have been used as the core research tool. The temporal and spatial patterns of forest cover change in Africa and the driving effects of population growth, economic and trade, social development, arable land expansion, and other factors on forest cover change in different periods have been demonstrated. The findings are as follows: 1) extremely unequal distribution of Africa forest has caused forest area reduction in 20 years. The reduction quantity of forest has been illustrated from strong to weak: Central Africa (strongest), East Africa (higher strong), West Africa (medium), South Africa (higher weak), and North Africa (weakest). However, the forest reduction area in West Africa with the original ratio is the most significant. More than 80% of the forest area reduction in Africa has occurred in 14 countries, just five national forest areas to achieve the net growth, but the increase amount was only 1% of loss amount. 2) The spatial pattern of forest cover change in Africa contracted and clustered gradually, especially after 2012. Algeria was the hotspot cluster of Morocco and Tunisia, forming the increase area of forest cover in North Africa. Zambia, the coldest point, gathers Angola significantly, while the Democratic Republic of the Congo and Tanzania form a significantly reduced forest cover area. 3) Total population, land area, cultivated land, urban population, consumer price index, and birth rate are the main factors influencing the temporal evolution of forest cover change in Africa. It can be divided into four stages to interpret the different explanations and significance of each factor for forest cover change in the study area.
Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations
Authors: Lv Weigang , Liang Lili , Chen Xin , Li Zhuo , Liang Desheng , Zhu Huimin , Teng Yanling , Wu Weijuan , Wu Lingqian , Han Lianshu
Published: January 2022

Noninvasive prenatal testing (NIPT) for monogenic disorders has been developed in recent years; however, there are still significant technical and analytical challenges for clinical use. The clinical feasibility of NIPT for methylmalonic acidemia cblC type (cblC type MMA) was investigated using our circulating single-molecule amplification and re-sequencing technology (cSMART). Trios molecular diagnosis was performed in 29 cblC type MMA-affected children and their parents by traditional Sanger sequencing. In the second pregnancy, invasive prenatal diagnosis (IPD) of the pathogenic MMACHC gene was used to determine fetal genotypes, and NIPT was performed using a novel MMACHC gene–specific cSMART assay. Maternal–fetal genotypes were deduced based on the mutation ratio in maternal plasma DNA. Concordance of fetal genotypes between IPD and NIPT, and the sensitivity and specificity of NIPT were determined. After removing two cases with a low P value or reads, the concordance ratio for NIPT and IPD was 100.00% (27/27), and the sensitivity and specificity were 100.00% (54.07–100.00%) and 100.00% (83.89–100.00%), respectively. This study demonstrates that NIPT using the cSMART assay for cblC type MMA was accurate in detecting fetal genotypes. cSMART has a potential clinical application as a prenatal diagnosis and screening tool for carrier and low-risk genotypes of cblC type MMA and other monogenic diseases.
ECG Changes Through Immunosuppressive Therapy Indicate Cardiac Abnormality in Anti-MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis
Authors: Matsuo Takashi , Sasai Tsuneo , Nakashima Ran , Kuwabara Yoshihiro , Kato Eri Toda , Murakami Isao , Onizawa Hideo , Akizuki Shuji , Murakami Kosaku , Hashimoto Motomu , Yoshifuji Hajime , Tanaka Masao , Morinobu Akio , Mimori Tsuneyo
Published: January 2022

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a dermatomyositis (DM)-specific antibody, is strongly associated with interstitial lung disease (ILD). Patients with idiopathic inflammatory myopathy (IIM) who are anti-MDA5 antibody positive [anti-MDA5 (+)] often experience chest symptoms during the active disease phase. These symptoms are primarily explained by respiratory failure; nevertheless, cardiac involvement can also be symptomatic. Thus, the aim of this study was to investigate cardiac involvement in anti-MDA5 (+) DM. A total of 63 patients with IIM who underwent electrocardiography (ECG) and ultrasound cardiography (UCG) during the active disease phase from 2016 to 2021 [anti-MDA5 (+) group, n = 21; anti-MDA5-negative (-) group, n = 42] were enrolled in the study, and their clinical charts were retrospectively reviewed. The ECG and UCG findings were compared between the anti-MDA5 (+) and anti-MDA5 (-) groups. All anti-MDA5 (+) patients had DM with ILD. The anti-MDA5 (+) group showed more frequent skin ulcerations and lower levels of leukocytes, muscle enzymes, and electrolytes (Na, K, Cl, and Ca) than the anti-MDA5 (-) group. According to the ECG findings obtained during the active disease phase, the T wave amplitudes were significantly lower for the anti-MDA5 (+) group than for the anti-MDA5 (-) group (I, II, and V4–6 lead;p< 0.01; aVF and V3, p < 0.05). However, the lower amplitudes were restored during the remission phase. Except for the E wave, A wave and Sep e’, the UCG results showed no significant differences between the groups. Four patients with anti-MDA5 (+) DM had many leads with lower T wave and cardiac abnormalities (heart failure, diastolic dysfunction, myocarditis) on and after admission. Though anti-MDA5 (+) patients clinically improved after immunosuppressive therapy, some of their ECG findings did not fully recover in remission phase. In conclusion, anti-MDA5 (+) DM appears to show cardiac involvement (electrical activity and function) during the active phase. Further studies are necessary to clarify the actual cardiac condition and mechanism of these findings in patients with anti-MDA5 (+) DM.
A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis
Authors: Xie Yi-Zi , Peng Chen-Wen , Su Zu-Qing , Huang Hui-Ting , Liu Xiao-Hong , Zhan Shao-Feng , Huang Xiu-Fang
Published: January 2022

Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein–protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K–AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible “dangerous liaison” between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.
Trace Metal Dynamics in Shallow Hydrothermal Plumes at the Kermadec Arc
Authors: Kleint Charlotte , Zitoun Rebecca , Neuholz René , Walter Maren , Schnetger Bernhard , Klose Lukas , Chiswell Stephen M. , Middag Rob , Laan Patrick , Sander Sylvia G. , Koschinsky Andrea
Published: January 2022

Hydrothermal vents are a source of many trace metals to the oceans. Compared to mid-ocean ridges, hydrothermal vent systems at arcs occur in shallower water depth and are much more diverse in fluid composition, resulting in highly variable water column trace metal concentrations. However, only few studies have focused on trace metal dynamics in hydrothermal plumes at volcanic arcs. During R/V Sonne cruise SO253 in 2016/2017, hydrothermal plumes from two hydrothermally active submarine volcanoes along the Kermadec arc in the Southwest Pacific Ocean were sampled: (1) Macauley, a magmatic dominated vent site located in water depths between 300 and 680 m, and (2) Brothers, located between 1,200 and 1,600 m water depth, where hydrothermalism influenced by water rock interactions and magmatically influenced vent sites occur near each other. Surface currents estimated from satellite-altimeter derived currents and direct measurements at the sites using lowered acoustic Doppler current profilers indicate the oceanic regime is dominated by mesoscale eddies. At both volcanoes, results indicated strong plumes of dissolved trace metals, notably Mn, Fe, Co, Ni, Cu, Zn, Cd, La, and Pb, some of which are essential micronutrients. Dissolved metal concentrations commonly decreased with distance from the vents, as to be expected, however, certain element/Fe ratios increased, suggesting a higher solubility of these elements and/or their stronger stabilization (e.g., for Zn compared to Fe). Our data indicate that at the magmatically influenced Macauley and Brothers cone sites, the transport of trace metals is strongly controlled by sulfide nanoparticles, while at the Brothers NW caldera wall site iron oxyhydroxides seem to dominate the trace metal transport over sulfides. Solution stabilization of trace metals by organic complexation appears to compete with particle adsorption processes. As well as extending the generally sparse data set for hydrothermal plumes at volcanic arc systems, our study presents the first data on several dissolved trace metals in the Macauley system, and extends the existing plume dataset of Brothers volcano. Our data further indicate that chemical signatures and processes at arc volcanoes are highly diverse, even on small scales.
Validity of the Fisher Community Knowledge-Based Economic Valuation of the Local Ecosystem for Oyster Farming: A Case Study in Japan
Authors: Shinji Junpei , Kamiyama Ryutaro , Nakamura Tsubasa , Yamanaka Kenshiro , Matsui Takahiro
Published: January 2022

The importance of local knowledge as a relevant information resource for ecosystem conditions has recently been the focus of sustainable ecosystem management. However, the accuracy of economic evaluation based on local knowledge regarding ecosystems has not yet been discussed, despite most activities in human society, including ecological conservation, being monetarily mediated. This study reports the correspondence between the economic value estimated by the fisher community and the analyzed environmental factors in the marine areas sectioned for oyster farming in Japan. At the study site, community-agreed usage fees for the area sections showed a gradient from the inner to the outer part of the bay. Our numerical modeling showed that the gradient of the economic value correlated with oyster feeding efficiency, indicating that a better location for feeding was empirically evaluated at a high price by the local fisher community. This suggests that the economic evaluation based on the local knowledge was biologically reasonable and could be a reliable information source for the aim of the area use in the study site.
Effect of Hyperinsulinemia and Insulin Resistance on Endocrine, Metabolic, and Reproductive Outcomes in Non-PCOS Women Undergoing Assisted Reproduction: A Retrospective Cohort Study
Authors: Cai Wang-Yu , Luo Xi , Song Jianyuan , Ji Danpin , Zhu Jun , Duan Cuicui , Wu Wei , Wu Xiao-Ke , Xu Jian
Published: January 2022

Objective: To evaluate the effect of hyperinsulinemia (HI) and insulin resistance (IR) on endocrine, metabolic, and reproductive outcomes in women without polycystic ovary syndrome (PCOS) undergoing assisted reproduction.

Materials and Methods: The study included 1,104 non-PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection-fresh embryo transfer. HI was evaluated by serum fasting insulin (FIN), and IR was evaluated by homeostatic model assessment of insulin resistance index (HOMA-IR). In addition, biometric, sex hormone, and metabolic parameters were measured. Independent t-test, linear, and logistic regression examined associations between HI, IR, and endocrine, metabolic, ovarian stimulation characteristics, and reproductive outcomes.

Results: Women with HI and IR had lower levels of progesterone, luteinizing hormone, follicle-stimulating hormone, estradiol, high-density lipoproteins, and increased levels of triglycerides low-density lipoproteins. For ovarian stimulation characteristics, those with HI and IR had a longer duration of stimulation, a higher total gonadotropin dose, and a lower peak estradiol level. Linear regression confirmed these associations. For reproductive outcomes, HI and IR were not associated with clinical pregnancy, live birth, and miscarriage.

Conclusions: HI and IR did not impair reproductive outcomes in non-PCOS women undergoing assisted reproduction.
Genome Sequencing Reveals a Mixed Picture of SARS-CoV-2 Variant of Concern Circulation in Eastern Uttar Pradesh, India
Authors: Deval Hirawati , Nyayanit Dimpal A. , Mishra Shailendra Kumar , Yadav Pragya D. , Zaman Kamran , Shankar Prem , Misra Brij R. , Behera Sthita Pragnya , Kumar Niraj , Kumar Abhinendra , Bhardwaj Pooja , Dwivedi Gaurav Raj , Singh Rajeev , Shete Anita M. , Pandit Priyanka , Pandey Ashok K. , Yadav Girijesh Kumar , Gupta Shashi , Kumar Manoj , Kavathekar Asif , Singh Ravi Shankar , Prajapati Sanjay , Kant Rajni
Published: January 2022

Uttar Pradesh is the densely populated state of India and is the sixth highest COVID-19 affected state with 22,904 deaths recorded on November 12, 2021. Whole-genome sequencing (WGS) is being used as a potential approach to investigate genomic evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, a total of 87 SARS-CoV-2 genomes−49 genomes from the first wave (March 2020 to February 2021) and 38 genomes from the second wave (March 2021 to July 2021) from Eastern Uttar Pradesh (E-UP) were sequenced and analyzed to understand its evolutionary pattern and variants against publicaly available sequences. The complete genome analysis of SARS-CoV-2 during the first wave in E-UP largely reported transmission of G, GR, and GH clades with specific mutations. In contrast, variants of concerns (VOCs) such as Delta (71.0%) followed by Delta AY.1 (21.05%) and Kappa (7.9%) lineages belong to G clade with prominent signature amino acids were introduced in the second wave. Signature substitution at positions S:L452R, S:P681R, and S:D614G were commonly detected in the Delta, Delta AY.1, and Kappa variants whereas S:T19R and S:T478K were confined to Delta and Delta AY.1 variants only. Vaccine breakthrough infections showed unique mutational changes at position S:D574Y in the case of the Delta variant, whereas position S:T95 was conserved among Kappa variants compared to the Wuhan isolate. During the transition from the first to second waves, a shift in the predominant clade from GH to G clade was observed. The identified spike protein mutations in the SARS-CoV-2 genome could be used as the potential target for vaccine and drug development to combat the effects of the COVID-19 disease.
Improving Imaging Modalities in Early Psoriatic Arthritis: The Role of Ultrasound in Early Diagnosis of Psoriatic Arthritis
Authors: Gudu Tania , Ng Beverly , Jethwa Hannah , Graham Catherine , Kudva Veda , Rammanohar Jashmitha , Zhang Chen , Sapsford Mark , Jadon Deepak R.
Published: January 2022

Objective: Despite recent advances, early diagnosis of psoriatic arthritis (PsA) remains a challenge in clinical practice. Ultrasound (US) could be a useful tool for the diagnosis and management of PsA. The objective of this review was to determine the role of US in early diagnosis of PsA.

Methods: We have performed a literature review aiming to evaluate studies on US findings in psoriasis and their predictive value of progression to PsA, as well as studies on US features specific for PsA in comparison with other conditions.

Results: A total of 40 studies were included. Sixteen studies assessed US findings in psoriasis, of which only 3 prospectively evaluated the role of US in predicting progression to PsA. Patients with PsA had a greater frequency of US abnormalities, in particular enthesitis and Power Doppler(PD) signal compared to patients with psoriasis only. In the longitudinal studies, psoriatic patients with higher enthesopathy scores at baseline were more likely to progress to PsA. Twenty-four studies evaluated US abnormalities in PsA and compared them to other conditions. Most specific US features that distinguish PsA from psoriasis were PD signal and erosions in joints and entheses. Extra-synovial changes, including peri-tendinous dermal soft tissue oedema with associated PD signal and flexor tendon enthesopathy, as well as thickening of the pulleys in the flexor tendons were highly characteristic for PsA, as they were frequently found in PsA patients, but in none of the RA patients. US-detected entheseal abnormalities in particular erosions and PD signal were more frequent in patients with PsA compared to fibromyalgia.

Conclusion: Despite the wide use of US in PsA, more research is needed to identify predictive factors of progression to PsA in patients with psoriasis, as well as to determine most specific US features that differentiate PsA from other conditions.