bluuebunny/crossref_metadata_2025 huggingface dataset:
The “Biological Weapons” of Ehrlichia chaffeensis: Novel Molecules and Mechanisms to Subjugate Host Cells
Authors: Rikihisa Yasuko
Published: January 2022

Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes human monocytic ehrlichiosis, an emerging, potentially fatal tick-borne infectious disease. The bacterium enters human cells via the binding of its unique outer-membrane invasin EtpE to the cognate receptor DNase X on the host-cell plasma membrane; this triggers actin polymerization and filopodia formation at the site of E. chaffeensis binding, and blocks activation of phagocyte NADPH oxidase that catalyzes the generation of microbicidal reactive oxygen species. Subsequently, the bacterium replicates by hijacking/dysregulating host-cell functions using Type IV secretion effectors. For example, the Ehrlichia translocated factor (Etf)-1 enters mitochondria and inhibits mitochondria-mediated apoptosis of host cells. Etf-1 also induces autophagy mediated by the small GTPase RAB5, the result being the liberation of catabolites for proliferation inside host cells. Moreover, Etf-2 competes with the RAB5 GTPase-activating protein, for binding to RAB5-GTP on the surface of E. chaffeensis inclusions, which blocks GTP hydrolysis and consequently prevents the fusion of inclusions with host-cell lysosomes. Etf-3 binds ferritin light chain to induce ferritinophagy to obtain intracellular iron. To enable E. chaffeensis to rapidly adapt to the host environment and proliferate, the bacterium must acquire host membrane cholesterol and glycerophospholipids for the purpose of producing large amounts of its own membrane. Future studies on the arsenal of unique Ehrlichia molecules and their interplay with host-cell components will undoubtedly advance our understanding of the molecular mechanisms of obligatory intracellular infection and may identify hitherto unrecognized signaling pathways of human hosts. Such data could be exploited for development of treatment and control measures for ehrlichiosis as well as other ailments that potentially could involve the same host-cell signaling pathways that are appropriated by E. chaffeensis.
Development Trend and Stability Analysis of Creep Landslide With Obvious Slip Zone Under Rainfall-Taking Xinchang Xiashan Basalt Slope as an Example
Authors: Bao Chunyan , Zhan Lingtao , Xia Yingjie , Huang Yongliang , Zhao Zhenxing
Published: January 2022

The creep slope is a dynamic development process, from stable deformation to instability failure. For the slope with sliding zone, it generally creeps along the sliding zone. If the sliding zone controlling the slope sliding does not have obvious displacement, and the slope has unexpected instability without warning, the harm and potential safety hazard are often much greater than the visible creep. Studying the development trend of this kind of landslide is of great significance to slope treatment and landslide early warning. Taking Xiashan village landslide in Huishan Town, Xinchang County, Zhejiang Province as an example, the landslide point was determined by numerical simulation in 2006. Generally, the landslide is a typical long-term slow deformation towards the free direction. Based on a new round of investigation and monitoring, this paper shows that there are signs of creeping on the surface of the landslide since 2003, and there is no creep on the deep sliding surface. The joint fissures in the landslide area are relatively developed, and rainfall infiltration will soften the soft rock and soil layer and greatly reduce its stability. This paper collects and arranges the rainfall data of the landslide area in recent 30 years, constructs the slope finite element model considering rainfall conditions through ANSYS finite element software, and carries out numerical simulation stability analysis. The results show that if cracks appear below or above the slope’s sliding surface, or are artificially damaged, the sliding surface may develop into weak cracks. Then, the plastic zone of penetration is offset; In the case of heavy rain, the slope can unload itself under the action of rainfall. At this time, the slope was unstable and the landslide happened suddenly.
Potential Role of the Renal Arterial Resistance Index in the Differential Diagnosis of Diabetic Kidney Disease
Authors: Li Haiyang , Shen Yunzhu , Yu Zhikai , Huang Yinghui , He Ting , Xiao Tangli , Li Yan , Xiong Jiachuan , Zhao Jinghong
Published: January 2022

Aims

To investigate the potential role of renal arterial resistance index (RI) in the differential diagnosis between diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) and establish a better-quantified differential diagnostic model.

Materials and Methods

We consecutively reviewed 469 type 2 diabetes patients who underwent renal biopsy in our center. According to the renal biopsy results, eligible patients were classified into the DKD group and the NDKD group. The diagnostic significance of RI was evaluated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis was used to search for independent risk factors associated with DKD. Then a novel diagnostic model was established using multivariate logistic regression analysis.

Results

A total of 332 DKD and 137 NDKD patients were enrolled for analysis. RI was significantly higher in the DKD group compared with those in the NDKD group (0.70 vs. 0.63, p< 0.001). The optimum cutoff value of RI for predicting DKD was 0.66 with sensitivity (69.2%) and specificity (80.9%). Diabetic retinopathy, diabetes duration ≥ 60 months, HbA1c ≥ 7.0(%), RI ≥ 0.66, and body mass index showed statistical significance in the multivariate logistic regression analysis. Then, we constructed a new diagnostic model based on these results. And the validation tests indicated that the new model had good sensitivity (81.5%) and specificity (78.6%).

Conclusions

RI has a potential role in discriminating DKD from NDKD. The RI-based predicting model can be helpful for differential diagnosis of DKD and NDKD.
Environmental Performance Assessment of Energy-Consuming Sectors Through Novel Data Envelopment Analysis
Authors: Xue Yangang , Mohsin Muhammad , Taghizadeh-Hesary Farhad , Iqbal Nadeem
Published: January 2022

This study evaluates the role of information in the environmental performance index (EPI) in different energy-consuming sectors in Pakistan through a novel slack-based data envelopment analysis (DEA). The index combines energy consumption as the primary input and gross domestic product (GDP) as the desirable output and CO2 emissions as the undesirable output. Yale’s EPI measures the efficiency of the sectoral level environmental performance of primary energy consumption in the country. Performance analysis was conducted from 2009 to 2018. The sectors were assigned scores between one and zero, with zero indicating maximum decision-making unit (DMU) inefficiency and one indicating maximum DMU efficiency. Despite being in the top-performing sector, agriculture scored only 0.51 in 2018, and the electricity sector obtained 0.412. Results also show that even the best-performing sector operates below the efficiency level. The mining and quarrying sector ranked second by obtaining 0.623 EPI and 0.035 SBEPI. Results also show that much of the energy supply of Pakistan (60.17%) is focused on fossil fuels, supplemented by hydropower (33%), while nuclear, wind, biogas, and solar power account for 5.15%, 0.47%, 0.32%, and 0.03%, respectively. Nonetheless, the overall results for both measures remained reasonably consistent. According to the literature and the energy crisis and climate instability dilemma, the authors conclude that changes to a diverse green power network are a possibility and an imminent need. Similarly, the government should penalize companies with poor performance. Furthermore, to ensure the capacity development and stability of environmental management and associated actions in the country, providing access to knowledge and training to groom human resources and achieve the highest performance is crucial.
Organic Phosphorus Mineralization Dominates the Release of Internal Phosphorus in a Macrophyte-Dominated Eutrophication Lake
Authors: Yu Wei , Yang Haiquan , Chen Jingan , Liao Peng , Chen Quan , Yang Yongqiong , Liu Yong
Published: January 2022

Macrophyte-dominated eutrophication (MDE) lakes have attracted wide attention due to the high phosphorus (P) loading in sediments that poses a wide spread risk for P release and pollution management. However, because of the superior productivity characteristics, the role of organic P mineralization in sediments in the internal P loading of MDE lake is still under debate. This study investigated the release dynamic of P in the sediments of Lake Caohai, a MDE lake in southwest of China, using a combination of the modified Huffer sequential extraction method, 31P nuclear magnetic resonance spectroscopy (NMR), and composite diffusive gradient in thin films (DGT) technology. Results showed that the apparent P diffusion flux at the sediment-water interface was remarkably high, with a mean value of 0.37 mg m−2 d−1. The phosphate ester organophosphorus components (i.e., Mono-P and Diester-P) continuously deposited and degraded in the sediments maintained the high productivity of the lake, and the mineralization process plays a critical role in the release of internal P. Although the content of inorganic P in sediment is relatively high (accounting for approximately 60% of total P), the reductive mechanism based on P-containing iron oxide/hydroxide has a low contribution to the internal P loading, as was indicated by the low release rate of P-combination iron-manganese (Fe-Mn)/iron-aluminum (Fe-Al) (BD-P and NaOH-P) and the insignificant positive correlations between DGT-labile P and DGT-labile Fe in the sediment cores. Additionally, organic P in sediments could transfer to P-combination Fe-Al/Fe-Mn. However, in severely expropriated environments, the enrichment of P-combination Fe-Al/Fe-Mn in surface sediments inhibited the mineralization of monophosphate to some degree. Taken together, this study emphasized the impact of sediment organic P loading on the release of internal P in lake, highlighting that organic P is also the valuable objects for avoiding eutrophication of MDE lakes.
Gene Expression in Embryos From Norwegian Red Bulls With High or Low Non Return Rate: An RNA-Seq Study of in vivo-Produced Single Embryos
Authors: Diaz-Lundahl Sofia , Sundaram Arvind Y.M. , Gillund Per , Gilfillan Gregor Duncan , Olsaker Ingrid , Krogenæs Anette
Published: January 2022

During the last decade, paternal effects on embryo development have been found to have greater importance than previously believed. In domestic cattle, embryo mortality is an issue of concern, causing huge economical losses for the dairy cattle industry. In attempts to reveal the paternal influence on embryo death, recent approaches have used transcriptome profiling of the embryo to find genes and pathways affected by different phenotypes in the bull. For practical and economic reasons, most such studies have used in vitro produced embryos. The aim of the present study was to investigate the differences in the global transcriptome of in vivo produced embryos, derived from sires with either high or low field fertility measured as the non-return rate (NRR) on day 56 after first AI of the inseminated cows. Superovulated heifers (n = 14) in the age span of 12–15 months were artificially inseminated with semen from either high fertility (n = 6) or low fertility (n = 6) bulls. On day seven after insemination, embryos were retrieved through uterine flushing. Embryos with first grade quality and IETS stage 5 (early blastocyst), 6 (blastocyst) or 7 (expanded blastocyst) were selected for further processing. In total, RNA extracted from 24 embryos was sequenced using Illumina sequencing, followed by differential expression analysis and gene set enrichment analysis. We found 62 genes differentially expressed between the two groups (adj.p-value<0.05), of which several genes and their linked pathways could explain the different developmental capacity. Transcripts highly expressed in the embryos from low fertility bulls were related to sterol metabolism and terpenoid backbone synthesis, while transcripts highly expressed in the high fertility embryos were linked to anti-apoptosis and the regulation of cytokine signaling. The leukocyte transendothelial migration and insulin signaling pathways were associated with enrichments in both groups. We also found some highly expressed transcripts in both groups which can be considered as new candidates in the regulation of embryo development. The present study is an important step in defining the paternal influence in embryonic development. Our results suggest that the sire’s genetic contribution affects several important processes linked to pre-and peri implantation regulation in the developing embryo.
Whole Blood Holding Time Prior to Plasma Processing Alters microRNA Expression Profile
Authors: Kim Sung Hye , MacIntyre David A. , Sykes Lynne , Arianoglou Maria , Bennett Phillip R. , Terzidou Vasso
Published: January 2022

MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied sample collection protocols, storage times/conditions, sample processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood samples were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.
Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study
Authors: Endmayr Verena , Tunc Cansu , Ergin Lara , De Rosa Anna , Weng Rosa , Wagner Lukas , Yu Thin-Yau , Fichtenbaum Andreas , Perkmann Thomas , Haslacher Helmuth , Kozakowski Nicolas , Schwaiger Carmen , Ricken Gerda , Hametner Simon , Klotz Sigrid , Dutra Lívia Almeida , Lechner Christian , de Simoni Désirée , Poppert Kai-Nicolas , Müller Georg Johannes , Pirker Susanne , Pirker Walter , Angelovski Aleksandra , Valach Matus , Maestri Michelangelo , Guida Melania , Ricciardi Roberta , Frommlet Florian , Sieghart Daniela , Pinter Miklos , Kircher Karl , Artacker Gottfried , Höftberger Romana , Koneczny Inga
Published: January 2022

Background

IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features.

Methods

We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD.

Results

A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%,p= .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p= .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+plasma cells, which are diagnostic hallmarks of IgG4-RLD.

Conclusion

Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.
Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients
Authors: Liu Jinhui , Cui Guoliang , Shen Shuning , Gao Feng , Zhu Hongjun , Xu Yinghua
Published: January 2022

Backgrounds

Epithelial–mesenchymal transition (EMT) is a sequential process where tumor cells develop from the epithelial state to the mesenchymal state. EMT contributes to various tumor functions including initiation, propagating potential, and resistance to therapy, thus affecting the survival time of patients. The aim of this research is to set up an EMT-related prognostic signature for endometrial cancer (EC).

Methods

EMT-related gene (ERG) expression and clinical data were acquired from The Cancer Genome Atlas (TCGA). The entire set was randomly divided into two sets, one for contributing the risk model (risk score) and the other for validating. Univariate and multivariate Cox proportional hazards regression analyses were applied to the training set to select the prognostic ERGs. The expression of 10 ERGs was confirmed by qRT-PCR in clinical samples. Then, we developed a nomogram predicting 1-/3-/5-year survival possibility combining the risk score and clinical factors. The entire set was stratified into the high- and low-risk groups, which was used to analyze the immune infiltrating, tumorigenesis pathways, and response to drugs.

Results

A total of 220 genes were screened out from 1,316 ERGs for their differential expression in tumor versus normal. Next, 10 genes were found to be associated with overall survival (OS) in EC, and the expression was validated by qRT-PCR using clinical samples, so we constructed a 10-ERG-based risk score to distinguish high-/low-risk patients and a nomogram to predict survival rate. The calibration plots proved the predictive value of our model. Gene Set Enrichment Analysis (GSEA) discovered that in the low-risk group, immune-related pathways were enriched; in the high-risk group, tumorigenesis pathways were enriched. The low-risk group showed more immune activities, higher tumor mutational burden (TMB), and higher CTAL4/PD1 expression, which was in line with a better response to immune checkpoint inhibitors. Nevertheless, response to chemotherapeutic drugs turned out better in the high-risk group. The high-risk group had higher N6-methyladenosine (m6A) RNA expression, microsatellite instability level, and stemness indices.

Conclusion

We constructed the ERG-related signature model to predict the prognosis of EC patients. What is more, it might offer a reference for predicting individualized response to immune checkpoint inhibitors and chemotherapeutic drugs.
Use of a Clostridioides difficile Murine Immunization and Challenge Model to Evaluate Single and Combination Vaccine Adjuvants Consisting of Alum and NKT Cell-Activating Ligands
Authors: Lang Gillian A. , Norman Kaylee , Amadou Amani Souwelimatou , Shadid Tyler M. , Ballard Jimmy D. , Lang Mark L.
Published: January 2022

Adjuvant combinations may enhance or broaden the expression of immune responses to vaccine antigens. Information on whether established Alum type adjuvants can be combined with experimental CD1d ligand adjuvants is currently lacking. In this study, we used a murine Clostridioides difficile immunization and challenge model to evaluate Alum (Alhydrogel™), α-galactosylceramide (α-GC), and one of its analogs 7DW8-5 singly and in combination as vaccine adjuvants. We observed that the Alum/α-GC combination caused modest enhancement of vaccine antigen-specific IgG1 and IgG2b responses, and a broadening to include IgG2c that did not significantly impact overall protection. Similar observations were made using the Alum/7DW8-5 combination. Examination of the impact of adjuvants on NKT cells revealed expansion of invariant NKT (iNKT) cells with modest expansion of their iNKTfh subset and little effect on diverse NKT (dNKT) cells. Side effects of the adjuvants was determined and revealed transient hepatotoxicity when Alum/α-GC was used in combination but not singly. In summary these results showed that the Alum/α-GC or the Alum/7DW8-5 combination could exert distinct effects on the NKT cell compartment and on isotype switch to produce Th1-driven IgG subclasses in addition to Alum/Th2-driven subclasses. While Alum alone was efficacious in stimulating IgG-mediated protection, and α-GC offered no apparent additional benefit in the C. difficile challenge model, the work herein reveals immune response features that could be optimized and harnessed in other vaccine contexts.
HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection
Authors: Zhang Hui , Cao Shuang , Gao Yang , Sun Xiao , Jiang Fanming , Zhao Bin , Ding Haibo , Dong Tao , Han Xiaoxu , Shang Hong
Published: January 2022

A series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a recombination structure analysis of the gag, pol, and nef genes from longitudinal samples of patient LNA819. A total of 9 pol and 5 nef CRF01_AE/CRF07_BC recombinants were detected. The quasispecies makeup and the composition of the pol and nef gene recombinants changed continuously, suggestive of continuous evolution in vivo. T-cell responses targeting peptides of the primary strain and the recombination regions were screened. The results showed that Pol-LY10, Pol-RY9, and Nef-GL9 were the immunodominant epitopes. Pol-LY10 overlapped with the recombination breakpoints in multiple recombinants. For the LY10 epitope, escape from T-cell responses was mediated by both recombination with a CRF07_BC insertion carrying the T467E/T472V variants and T467N/T472V mutations originating in the CRF01_AE strain. In pol recombinants R8 and R9, the recombination breakpoints were located ~23 amino acids upstream of the RY9 epitope. The appearance of new recombination breakpoints harboring a CRF07_BC insertion carrying a R984K variant was associated with escape from RY9-specific T-cell responses. Although the Nef-GL9 epitope was located either within or 10~11 amino acids downstream of the recombination breakpoints, no variant of this epitope was observed in the nef recombinants. Instead, a F85V mutation originating in the CRF01_AE strain was the main immune escape mechanism. Understanding the cellular immune pressure on recombination is critical for monitoring the new circulating recombinant forms of HIV and designing epitope-based vaccines. Vaccines targeting antigens that are less likely to escape immune pressure by recombination and/or mutation are likely to be of benefit to patients with HIV-1.
Human Dermcidin Protects Mice Against Hepatic Ischemia-Reperfusion–Induced Local and Remote Inflammatory Injury
Authors: Qiang Xiaoling , Li Jianhua , Zhu Shu , He Mingzhu , Chen Weiqiang , Al-Abed Yousef , Brenner Max , Tracey Kevin J. , Wang Ping , Wang Haichao
Published: January 2022

Background

Hepatic ischemia and reperfusion (I/R) injury is commonly associated with surgical liver resection or transplantation, and represents a major cause of liver damage and graft failure. Currently, there are no effective therapies to prevent hepatic I/R injury other than ischemic preconditioning and some preventative strategies. Previously, we have revealed the anti-inflammatory activity of a sweat gland-derived peptide, dermcidin (DCD), in macrophage/monocyte cultures. Here, we sought to explore its therapeutic potential and protective mechanisms in a murine model of hepatic I/R.

Methods

Male C57BL/6 mice were subjected to hepatic ischemia by clamping the hepatic artery and portal vein for 60 min, which was then removed to initiate reperfusion. At the beginning of reperfusion, 0.2 ml saline control or solution of DCD (0.5 mg/kg BW) or DCD-C34S analog (0.25 or 0.5 mg/kg BW) containing a Cys (C)→Ser (S) substitution at residue 34 was injected via the internal jugular vein. For survival experiments, mice were subjected to additional resection to remove non-ischemic liver lobes, and animal survival was monitored for 10 days. For mechanistic studies, blood and tissue samples were collected at 24 h after the onset of reperfusion, and subjected to measurements of various markers of inflammation and tissue injury by real-time RT-PCR, immunoassays, and histological analysis.

Results

Recombinant DCD or DCD-C34S analog conferred a significant protection against lethal hepatic I/R when given intravenously at the beginning of reperfusion. This protection was associated with a significant reduction in hepatic injury, neutrophilic CXC chemokine (Mip-2) expression, neutrophil infiltration, and associated inflammation. Furthermore, the administration of DCD also resulted in a significant attenuation of remote lung inflammatory injury. Mechanistically, DCD interacted with epidermal growth factor receptor (EGFR), a key regulator of liver inflammation, and significantly inhibited hepatic I/R-induced phosphorylation of EGFR as well as a downstream signaling molecule, protein kinase B (AKT). The suppression of EGFR expression by transducing Egfr-specific shRNA plasmid into macrophages abrogated the DCD-mediated inhibition of nitric oxide (NO) production induced by a damage-associated molecular pattern (DAMP), cold-inducible RNA-binding protein, CIRP.

Conclusions

The present study suggests that human DCD and its analog may be developed as novel therapeutics to attenuate hepatic I/R-induced inflammatory injury possibly by impairing EGFR signaling.
Effect of Nitrogen Concentration on the Alkalophilic Microalga Nitzschia sp. NW129-a Promising Feedstock for the Integrated Production of Lipids and Fucoxanthin in Biorefinery
Authors: Cao Zihao , Shen Xiaotong , Wang Xujing , Zhu Baohua , Pan Kehou , Li Yun
Published: January 2022

Microalgae are considered promising resources for producing a variety of high-value-added products, especially for lipids and pigments. Alkalophilic microalgae have more advantages than other microalgae when cultured outdoors on a large scale. The present study investigated the comprehensive effects of different nitrogen concentrations on fucoxanthin (Fx), lipids accumulation and the fatty acid profile of the alkaliphilic microalgae Nitzschia sp. NW129 to evaluate the potential for simultaneous production of Fx and biofuels. Fx and Lipids amassed in a coordinated growth-dependent manner in response to various concentrations, reaching 18.18 mg g–1 and 40.67% dry weight (DW), respectively. The biomass of Nitzschia sp. NW129 was 0.58 ± 0.02 g L–1 in the medium at the concentration of 117.65 mM. The highest productivities of Fx (1.44 mg L–1 d–1) and lipid (19.95 ± 1.29 mg L–1 d–1) were obtained concurrently at this concentration. Furthermore, the fatty acid methyl esters revealed excellent biofuel properties with an appropriate value of the degree unsaturation (49.97), cetane number (62.72), and cold filter plugging point (2.37), which met the European standards for biofuel production (EN14214). These results provided a reliable strategy for further industrialization and comprehensive production of biofuel and Fx by using the alkaliphilic microalgal Nitzschia sp. NW129.
Ocular Manifestations of Acute Secondary Angle Closure Associated With Lens Subluxation
Authors: Jing Qinghe , Chen Tianhui , Chen Zexu , Lan Lina , Zhao Chen , Jiang Yongxiang
Published: January 2022

Purpose:

To evaluate the clinical characteristics and ocular features of patients with acute secondary angle closure, associated with lens subluxation (ASAC-LS).

Methods:

We performed a retrospective study at the EENT Hospital of Fudan University, Shanghai, China. A total of 41 affected eyes from 41 patients were enrolled in this study. Furthermore, 20 affected eyes were part of the ASAC-LS cohort and 21 affected eyes were included in the acute primary angle closure (APAC) cohort. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), axial length (AL), minimum corneal curvature (K1), maximum corneal curvature (K2), and anterior chamber depth (ACD) were measured and compared between the 2 cohorts. In addition, inter-eye (intraindividual) comparison was performed.

Results:

The ASAC-LS cohort exhibited younger ages, more frequent trauma history (35%), lower IOP (27.43 ± 13.86 mmHg vs. 41.27 ± 10.36 mmHg), longer AL (23.96 ± 2.60 vs. 22.49 ± 0.77 mm), shallower ACD (1.28 ± 0.38 vs. 1.58 ± 0.23 mm), and bigger ACD differences (0.99 ± 0.52 vs. 0.15 ± 0.19 mm), as compared with the APAC cohort (all p < 0.05). Moreover, eyes from the lens subluxation cohort experienced worse BCVA, higher IOP, and shallower ACD than their matched unaffected eyes (all p < 0.05). Although longer AL, shallower ACD, and bigger ACD differences were strongly correlated with lens subluxation in a univariate logistic regression analysis, only the ACD difference remained significant in the multivariate model (p = 0.004, OR = 1,510.50). Additionally, according to the receiver operating characteristic (ROC) curve analysis, both ACD and ACD differences had greater value in the differential diagnosis of ASAC-LS and APAC, with a cut-off value of 1.4 and 0.63 mm, respectively.

Conclusions:

Shallower ACD and larger ACD differences provide the promising diagnostic potential for patients with ASAC-LS.
Five-Minute Apgar Score and the Risk of Mental Disorders During the First Four Decades of Life: A Nationwide Registry-Based Cohort Study in Denmark
Authors: He Hua , Yu Yongfu , Wang Hui , Obel Carsten Lyng , Li Fei , Li Jiong
Published: January 2022

Objectives:

The associations of long-term risks of the full spectrum of mental disorders with clinically reassuring but suboptimal score range 7–9 remain unclear. This study investigated these associations during up to 38 years of follow-up.

Methods:

In a nationwide cohort study of 2,213,822 singletons born in Denmark during 1978–2015, we used cox regression to estimate the hazard ratio (HR) of mental disorders with a 95% CI.

Results:

A total of 3,00,679 (13.6%) individuals were diagnosed with mental disorders. The associations between suboptimal Apgar score 7–9 and mental disorders differed by attained age. In childhood (≤ 18 years), declining Apgar scores were associated with increased risks of overall mental disorders with HRs (95% CI) of 1.13(1.11-1.15), 1.34 (1.27–1.41), and 1.48 (1.31–1.67) for Apgar scores of 7–9, 4–6, and 1–3, respectively, compared with a score of 10. A dose-response association was seen even within the score range from 9 to 7 (HR 1.11 [95% CI: 1.08–1.13], 1.14 [1.10–1.18], and 1.20 [1.14–1.27], respectively). Of note, individuals with scores of 7–9 had increased risks of organic disorders (HR: 1.27, 95% CI: 1.05–1.53), neurotic disorders (HR: 1.07, 95% CI: 1.03–1.11), and a wide range of neurodevelopmental disorders, such as intellectual disability (1.87, 1.76–1.98), childhood autism (1.13, 1.05–1.22) and attention deficit hyperactivity disorder (1.10, 1.06–1.15). In early adulthood (19–39 years), suboptimal Apgar scores 7–9 were not associated with the risks of overall and specific mental disorders.

Conclusion:

Infants born with clinically reassuring but suboptimal 5-min scores 7–9 are at increased risks of a wide spectrum of mental disorders in childhood.
The Role of miRNAs as New Molecular Biomarkers for Dating the Age of Wound Production: A Systematic Review
Authors: De Simone Stefania , Giacani Elena , Bosco Maria Antonella , Vittorio Simona , Ferrara Michela , Bertozzi Giuseppe , Cipolloni Luigi , La Russa Raffaele
Published: January 2022

Background:

The timing of wounds production is a significant issue in forensic pathology. Although various methods have been evaluated, obtaining an accurate dating of lesions is still a challenge. The pathologist uses many parameters to value wound age, such as histological and immunohistochemical. In recent years, there have been many studies regarding the use of miRNAs in wound-age estimation; indeed, miRNAs have multiple potential uses in forensic pathology.

Scope:

This review aims to verify the efficacy and feasibility of miRNAs as a tool for determining the timing of lesions.

Materials and Methods:

The authors conducted the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was used as a search engine to find articles published between January, 1st 2016 and October, 1st 2021, to evaluate the current state of the art regarding wound-age estimation.

Results:

A total of 256 articles were collected; after screening according to PRISMA guidelines, the systematic review included 8 articles. The studies included in this review were all Original articles evaluating the use of biomarkers for wound-age determination.

Discussion and Conclusion:

The literature review showed that analysis of miRNA is an innovative field of study with significant potentiality in forensic pathology. There are few studies, and almost all of them are at an early stage. The challenge is to understand how to standardize the samples' selection to obtain reliable experimental data. This observation represents a necessary prerequisite to planning further clinical trials.
The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy
Authors: Honorato Layla , Witkin Steven S. , Mendes-Correa Maria Cássia , Conde Toscano Ana Luiza Castro , Linhares Iara Moreno , de Paula Anderson Vicente , Paião Heuder Gustavo Oliveira , de Paula Vanessa Salete , Lopes Amanda de Oliveira , Lima Silvia Helena , Raymundi Vanessa de Cássia , Ferreira Noely Evangelista , da Silva Junior Almir Ribeiro , Abrahim Karim Yaqub , Braz-Silva Paulo Henrique , Tozetto-Mendoza Tania Regina
Published: January 2022

Introduction

Torque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer.

Methods

Saliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review.

Results

TTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001).

Conclusion

The TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.
Human Microbiota in Esophageal Adenocarcinoma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Implications
Authors: Dan Wanyue , Peng Lihua , Yan Bin , Li Zhengpeng , Pan Fei
Published: January 2022

Esophageal adenocarcinoma (EAC) is one of the main subtypes of esophageal cancer. The incidence rate of EAC increased progressively while the 5-year relative survival rates were poor in the past two decades. The mechanism of EAC has been studied extensively in relation to genetic factors, but less so with respect to human microbiota. Currently, researches about the relationship between EAC and the human microbiota is a newly emerging field of study. Herein, we present the current state of knowledge linking human microbiota to esophageal adenocarcinoma and its precursor lesion—gastroesophageal reflux disease and Barrett’s esophagus. There are specific human bacterial alternations in the process of esophageal carcinogenesis. And bacterial dysbiosis plays an important role in the process of esophageal carcinogenesis via inflammation, microbial metabolism and genotoxicity. Based on the human microbiota alternation in the EAC cascade, it provides potential microbiome-based clinical application. This review is focused on novel targets in prevention, diagnosis, prognosis, and therapy for esophageal adenocarcinoma.
Isolation and Complete Genome Sequence Analysis of Kosakonia cowanii Pa82, a Novel Pathogen Causing Bacterial Wilt on Patchouli
Authors: Zhang Yong , Wang Bangwei , Li Qiao , Huang Derui , Zhang Yuyao , Li Guangwei , He Hong
Published: January 2022

Pogostemon cablin (patchouli), an important medicinal and aromatic plant, is widely used in traditional Chinese medicine as well as in perfume industry. Patchouli plants are susceptible to bacterial wilt disease, which causes significant economic losses by reduction in yield and quality of the plant products. However, few studies focus on the pathogens causing bacterial wilt on patchouli. In this study, strain Pa82 was isolated from diseased patchouli plants with typical bacterial wilt symptoms in Guangdong province, China, and was confirmed to be a highly virulent pathogen of patchouli bacterial wilt. Comparative sequence analysis of 16S rRNA gene showed that the strain was closely related to Kosakonia sp. CCTCC M2018092 (99.9% similarity) and Kosakonia cowanii Esp_Z (99.8% similarity). Moreover, phylogenetic tree based on 16S rRNA gene sequences showed that the strain was affiliated with genus Kosakonia. Further, the whole genome of strain Pa82 was sequenced, and the sequences were assembled and annotated. The complete genome of the strain consists of one chromosome and three plasmids. Average nucleotide identity (ANI) and phylogenetic analysis revealed that the strain belongs to Kosakonia cowanii (designated Kosakonia cowanii Pa82). Virulence-related genes of the strain involved in adherence, biofilm formation, endotoxin and other virulence factors were predicted. Among them, vgrG gene that encodes one of the type VI secretion system components was functionally validated as a virulence factor in Kosakonia cowanii Pa82 through construction of Tn5 insertion mutants and identification of mutant defective in virulence.
From Acid Activation Mechanisms of Proton Conduction to Design of Inhibitors of the M2 Proton Channel of Influenza A Virus
Authors: Aledavood Elnaz , Selmi Beatrice , Estarellas Carolina , Masetti Matteo , Luque F. Javier
Published: January 2022

With an estimated 1 billion people affected across the globe, influenza is one of the most serious health concerns worldwide. Therapeutic treatments have encompassed a number of key functional viral proteins, mainly focused on the M2 proton channel and neuraminidase. This review highlights the efforts spent in targeting the M2 proton channel, which mediates the proton transport toward the interior of the viral particle as a preliminary step leading to the release of the fusion peptide in hemagglutinin and the fusion of the viral and endosomal membranes. Besides the structural and mechanistic aspects of the M2 proton channel, attention is paid to the challenges posed by the development of efficient small molecule inhibitors and the evolution toward novel ligands and scaffolds motivated by the emergence of resistant strains.
Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States
Authors: Cao Ning , Li Shuping , Xu Aimin , Li Manlin , Zou Xiaoguang , Ke Zunji , Deng Gang , Cheng Xuemei , Wang Changhong
Published: January 2022

Objective

Several β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease mouse models. They can be found in some plants, common foodstuffs, and blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remain unclear.

Methods

The exposure levels of βCBs and of neurotransmitters in plasma and tissues of pup rats, aging rats, mice of different physiological states, and healthy volunteers were detected by using UPLC-MS/MS. Plasma and tissue samples from 110 newborn rats up to 29 days old at 11 sampling points were collected and were analyzed to determine the concentration variation of βCBs in the developmental phase of newborn rats. The plasma of rats aged 2 to 18 months was used to detect the variation trend of βCBs and with some neurotransmitters. The plasma samples of normal C57BL/6 mice, APP/PS1 double transgenic mice, and scopolamine-induced memory impairment mice were collected and were analyzed to compare the difference of βCBs in different physiological states. The exposure levels of βCBs such as harmine, harmaline, and harmane in plasma of 550 healthy volunteers were also detected and analyzed on the basis of gender, race, and age.

Results

Results showed that harmine was the main compound found in rats, mice, and human, which can be detected in a newborn rat plasma (0.16 ± 0.03 ng/ml) and brain (0.33 ± 0.14 ng/g) without any exogenous consumption. The concentration of harmine in rat plasma showed a decreasing trend similar to the exposure levels of neurotransmitters such as 5-hydroxytryptamine, acetylcholine chloride, glutamic acid, tyrosine, and phenylalanine during the growth period of 18 months. The harmine exposure in rats and human indicates high dependence on the physiological and pathological status such as aging, gender, and race.

Conclusion

The dynamic changes of harmine exposure in different animals and human, in vivo, at developmental and physiological states indicate that harmine is a naturally and widely distributed endogenous substance in different mammals and human. In addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals, which should be verified by further experiment.
Response Calls Evoked by Playback of Natural 50-kHz Ultrasonic Vocalizations in Rats
Authors: Berz Annuska C. , Wöhr Markus , Schwarting Rainer K. W.
Published: January 2022

Rats are highly social animals known to communicate with ultrasonic vocalizations (USV) of different frequencies. Calls around 50 kHz are thought to represent a positive affective state, whereas calls around 22 kHz are believed to serve as alarm or distress calls. During playback of natural 50-kHz USV, rats show a reliable and strong social approach response toward the sound source. While this response has been studied in great detail in numerous publications, little is known about the emission of USV in response to natural 50-kHz USV playback. To close this gap, we capitalized on three data sets previously obtained and analyzed USV evoked by natural 50-kHz USV playback in male juvenile rats. We compared different rat stocks, namely Wistar (WI) and Sprague-Dawley (SD) and investigated the pharmacological treatment with the dopaminergic D2 receptor antagonist haloperidol. These response calls were found to vary broadly inter-individually in numbers, mean peak frequencies, durations and frequency modulations. Despite the large variability, the results showed no major differences between experimental conditions regarding call likelihood or call parameters, representing a robust phenomenon. However, most response calls had clearly lower frequencies and were longer than typical 50-kHz calls, i.e., around 30 kHz and lasting generally around 0.3 s. These calls resemble aversive 22-kHz USV of adult rats but were of higher frequencies and shorter durations. Moreover, blockade of dopamine D2 receptors did not substantially affect the emission of response calls suggesting that they are not dependent on the D2 receptor function. Taken together, this study provides a detailed analysis of response calls toward playback of 50-kHz USV in juvenile WI and SD rats. This includes calls representing 50-kHz USV, but mostly calls with lower frequencies that are not clearly categorizable within the so far known two main groups of USV in adult rats. We discuss the possible functions of these response calls addressing their communicative functions like contact or appeasing calls, and whether they may reflect a state of frustration. In future studies, response calls might also serve as a new read-out in rat models for neuropsychiatric disorders, where acoustic communication is impaired, such as autism spectrum disorder.
A Bionic Spatial Cognition Model and Method for Robots Based on the Hippocampus Mechanism
Authors: Yuan Jinsheng , Guo Wei , Zha Fusheng , Wang Pengfei , Li Mantian , Sun Lining
Published: January 2022

The hippocampus and its accessory are the main areas for spatial cognition. It can integrate paths and form environmental cognition based on motion information and then realize positioning and navigation. Learning from the hippocampus mechanism is a crucial way forward for research in robot perception, so it is crucial to building a calculation method that conforms to the biological principle. In addition, it should be easy to implement on a robot. This paper proposes a bionic cognition model and method for mobile robots, which can realize precise path integration and cognition of space. Our research can provide the basis for the cognition of the environment and autonomous navigation for bionic robots.