bluuebunny/crossref_metadata_2025 huggingface dataset:
A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma
Authors: Lin Cha , Chen Jian , Su Zhaoying , Liu Pei , Liu Zheyu , Zhu Chenchen , Xu Dan , Lin Zhongda , Xu Pei , Liu Ganqiang , Liu Xinjian
Published: September 2021

Background: Immune checkpoint inhibitors have been successfully used in a variety of tumors, however, the efficacy of immune checkpoint blockade therapy for patients with glioma is limited. In this study, we tried to clarify gene expression signatures related to the prognosis of gliomas and construct a signature to predict the survival of patients with gliomas.

Methods: Calcium-related differential expressed genes (DEGs) between gliomas and normal brain tissues were comprehensively analyzed in two independent databases. Univariate, multivariate Cox regression analysis and proportional hazards model were used to identify the prognostic of calcium-related risk score signature. The CIBERSORT algorithm and association analysis were carried out to evaluate the relationship between calcium-related signature and characteristic clinical features, tumor-infiltrating immune cell signatures as well as immune checkpoint molecules in glioma. A nomogram model was developed for predicting the overall survival for patients with gliomas.

Results: We found the intersection of 415 DEGs between gliomas and normal brain tissues, and identified that an eighteen calcium-related gene panel was significantly enriched in these DEGs. A calcium-related signature derived risk score was developed to divide patients into high- and low-risk groups. Low levels of calcium-related gene expression in high-risk score cases were accompanied with worse outcomes of patients. Calcium-related risk scores were significantly associated with characteristic clinical features, immune infiltrating signatures of tumor microenvironment, and exhausted T cell markers including programmed cell death 1 (PD-1), lymphocyte activating 3 (LAG3), and T cell membrane protein 3 (TIM-3), which contribute to an adverse therapeutic effect of immunotherapy. Calcium-related signature risk score was considered as an independent prognostic parameter to predict the of overall survival of patients with gliomas in nomogram model.

Conclusion: Our study demonstrated that calcium signaling pathway is highly associated with immunosuppression of gliomas and overall survival of patients. Targeting the calcium signaling pathway might be a new strategy to reverse the immunosuppressive microenvironment of gliomas and improve the efficacy of glioma immunotherapy.
The Effect of Smoking on the Immune Microenvironment and Immunogenicity and Its Relationship With the Prognosis of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer
Authors: Sun Yueqin , Yang Qi , Shen Jie , Wei Ting , Shen Weitao , Zhang Nan , Luo Peng , Zhang Jian
Published: September 2021

Background: The emergence of immune checkpoint inhibitors (ICIs) has opened a new chapter for the treatment of non-small cell lung cancer (NSCLC), and the best beneficiaries of ICI treatment are still being explored. Smoking status has been repeatedly confirmed to affect the efficacy of ICIs in NSCLC patients, but the specific mechanism is still unclear.

Methods: We performed analysis on the Memorial Sloan Kettering Cancer Center (MSKCC) clinical NSCLC cohort receiving ICI treatment, The Cancer Genome Atlas (TCGA) Pan-Lung Cancer cohort, and Gene Expression Omnibus (GEO) database GSE41271 lung cancer cohort that did not receive ICI treatment, including survival prognosis, gene mutation, copy number variation, immunogenicity, and immune microenvironment, and explored the impact of smoking status on the prognosis of NSCLC patients treated with ICIs and possible mechanism. In addition, 8 fresh NSCLC surgical tissue samples were collected for mass cytometry (CyTOF) experiments to further characterize the immune characteristics and verify the mechanism.

Result: Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49–0.97, p = 0.031) than those who never smoked. Further analysis of the TCGA and GEO validation cohorts found that the differences in prognosis between different groups may be related to the smoking group’s higher immunogenicity, higher gene mutations, and stronger immune microenvironment. The results of the CyTOF experiment further found that the immune microenvironment of smoking group was characterized by higher expression of immune positive regulatory chemokine, and higher abundance of immune activated cells, including follicular helper CD4+ T cells, gamma delta CD4+ T cells, activated DC, and activated CD8+ T cells. In contrast, the immune microenvironment of non-smoking group was significantly enriched for immunosuppressive related cells, including regulatory T cells and M2 macrophages. Finally, we also found highly enriched CD45RAhighCD4+ T cells and CD45RAhighCD8+ T cells in the non-smoking group.

Conclusion: Our research results suggest that among NSCLC patients receiving ICI treatment, the stronger immunogenicity and activated immune microenvironment of the smoking group make their prognosis better.
Creaming Layers of Nanocellulose Stabilized Water-Based Polystyrene: High-Solids Emulsions for 3D Printing
Authors: Gestranius Marie , Kontturi Katri S. , Mikkelson Atte , Virtanen Tommi , Schirp Claudia , Cranston Emily D. , Kontturi Eero , Tammelin Tekla
Published: September 2021

Oil-in-water emulsions stabilized using cellulose nanofibrils (CNF) form extremely stable and high-volume creaming layers which do not coalesce over extended periods of time. The stability is a result of the synergistic action of Pickering stabilization and the formation of a CNF percolation network in the continuous phase. The use of methyl cellulose (MC) as a co-emulsifier together with CNF further increases the viscosity of the system and is known to affect the droplet size distribution of the formed emulsion. Here, we utilize these highly stable creaming layer systems for in situ polymerization of styrene with the aim to prepare an emulsion-based dope for additive manufacturing. We show that the approach exploiting the creaming layer enables the effortless water removal yielding a paste-like material consisting of polystyrene beads decorated with CNF and MC. Further, we report comprehensive characterization that reveals the properties and the performance of the creaming layer. Solid-state NMR measurements confirmed the successful polymerization taking place inside the nanocellulosic network, and size exclusion chromatography revealed average molecular weight (Mw) of polystyrene as approximately 700,000 Da. Moreover, the amount of the leftover monomer was found to be less than 1% as detected by gas chromatography. The dry solids content of the paste was ∼20% which is a significant increase compared to the solids content of the original CNF dispersion (1.7 wt%). The shrinkage of the CNF, MC and polystyrene structures upon drying—an often-faced challenge—was found to be acceptable for this composite containing highly hygroscopic biobased materials. At best, the two dimensional shrinkage was no more than ca. 20% which is significantly lower than the shrinkage of pure CNF being as high as 50%. The paste, which is a composite of biobased materials and a synthetic polymer, was demonstrated in direct-ink-writing to print small objects. With further optimization of the formulation, we find the emulsion templating approach as a promising route to prepare composite materials.
En Bloc Arch Reconstruction With the Frozen Elephant Trunk Technique for Acute Type a Aortic Dissection
Authors: Liu Penghong , Wen Bing , Liu Chao , Xu Huashan , Zhao Guochang , Sun Fuqiang , Zhang Hang , Yao Xingxing
Published: September 2021

Objective: The study objective was to evaluate the effect of en bloc arch reconstruction with frozen elephant trunk (FET) technique for acute type A aortic dissection.

Methods: 41 patients with acute Stanford type A dissection underwent en bloc arch reconstruction combined with FET implantation between April 2018 and August 2020. The mean age of the patients was 46 ± 13 years, and 9 patients were female. One patient had Marfan syndrome. Six patients had pericardial tamponade, 9 had pleural effusion, 5 had transient cerebral ischemic attack, and 3 had chronic kidney disease.

Results: The hospital mortality rate was 9.8% (4 patients). 2 (4.9%) patients had stroke, 23 (56.1%) had acute kidney injury, and 5 (12.2%) had renal failure requiring hemodialysis. During follow-up, the rate of complete false lumen thrombosis was 91.6% (33/36) around the FET, 69.4% (25/36) at the diaphragmatic level, and 27.8% (10/36) at the superior mesenteric artery level. The true lumen diameter at the same three levels of the descending aorta increased significantly while the false lumen diameter reduced at the two levels: pulmonary bifurcation and the diaphragm. The 1-, 2-and 3-year actuarial survival rates were 90.2% [95% confidence interval (CI), 81.2–99.2], 84.2% (95% CI, 70.1–98.3) and 70.2% (95% CI, 42.2–98), respectively.

Conclusions: In patients with acute type A dissection, en bloc arch reconstruction with FET technique appeared to be feasible and effective with early clinical follow-up results. Future studies including a large sample size and long-term follow-up are required to evaluate the efficacy.
Prognostic Factors of Survival in Pancreatic Cancer Metastasis to Liver at Different Ages of Diagnosis: A SEER Population-Based Cohort Study
Authors: Liu Meiqi , Wang Moran , Li Sheng
Published: September 2021

Background: Liver is a common metastatic organ for most malignancies, especially the pancreas. However, evidence for prognostic factors of pancreatic cancer metastasis to the liver at different ages is lacking. Thus, we aimed to evaluate the predictors of patients with pancreatic cancer metastasis to liver grouped by age of diagnosis.

Methods: We chose the patients diagnosed between 2004 and 2015 from the SEER database. The primary lesions of metastatic liver cancer between sexes were compared using the Pearson’s chi-square test for categorical variables. The overall survival (OS) and cancer-specific survival (CSS) were the endpoint of the study. The prognostic factors were analyzed with the Kaplan-Meier method and log-rank test, and Cox proportional-hazards regression model.

Results: The main primary sites of metastatic liver cancer for our patients are lung and brunchu, sigmoid colon, pancreas, which in males are lung and bronchu, sigmoid colon and pancreas, while breast, lung and bronchu, sigmoid colon in females. Furthermore, we explored the prognostic factors of pancreatic cancer metastasis to liver grouped by age at diagnosis. Tumor grade, histology and treatment are valid prognostic factors in all age groups. Additionally, gender and AJCC N stage in age<52 years old, while race and AJCC N stage in age >69 years old were predictors. Surgery alone was the optimal treatment in group age>69 years old, whereas surgery combined with chemotherapy was the best option in the other groups.

Conclusion: Our study evaluated the predictors of patients with pancreatic cancer metastasis to liver at various ages of diagnosis.
Association of Urinary Sodium Excretion and Left Ventricular Hypertrophy in People With Type 2 Diabetes Mellitus: A Cross-Sectional Study
Authors: Liu Jianfang , Yang Xiaoyu , Zhang Peizhen , Guo Dan , Xu Bingyan , Huang Chensihan , Xue Yaoming , Zhang Huijie
Published: September 2021

Background

It has been well documented that left ventricular hypertrophy (LVH) is highly associated with the incidence of cardiovascular disease (CVD). Evidence indicated that high sodium intake was closely related with LVH in general population. However, information is not available regarding the association between urinary sodium excretion and LVH in patients with type 2 diabetes mellitus (T2DM). This study aimed to explore the association between urinary sodium excretion and LVH in patients with T2DM.

Methods

This cross-sectional analysis included baseline data from 1,556 individuals with T2DM enrolled in the NanFang Prospective Diabetes Study (NFPDS). Urinary sodium excretion levels were measured from 24-hour urine samples of inpatients and morning fasting urine samples of outpatients. Left ventricular dimensions were assessed by echocardiography. The associations between urinary sodium excretion and the risks of cardiovascular events, LVH and left ventricular mass index (LVMI) were examined using linear regression analysis, logistic regression and restricted cubic splines (RCS).

Results

Urinary sodium excretion levels were positively associated with cardiometabolic risk factors, including systolic blood pressure, body mass index, waist circumference and LVMI (All P<0.001). Odds ratios of the highest quartile of urinary sodium excretion compared with the lowest quartile were 1.80 (95% CI, 1.28-2.54; P=0.001) for LVH and 1.77 (95% CI, 1.06-2.94; P=0.028) for CVD, after adjusted for demographics, lifestyle risk factors and cardiovascular risk factors. Multivariable-adjusted RCS analysis of the association between urinary sodium excretion and LVMI showed a significant association (P=0.001) and lacked evidence of a nonlinear association (P=0.406).

Conclusion

This study indicated that high urinary sodium excretion was independently associated with increased risk of LVH and CVD in patients with T2DM, suggesting that control of sodium intake may be valuable for the prevention of diabetic cardiovascular complications.
Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis
Authors: Muley Carolin , Kotschi Stefan , Bartelt Alexander
Published: September 2021

The acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate targeting and proteasomal degradation. However, whether ubiquilins participate in brown adipocyte function has not been investigated so far. Here, we determine the role of ubiquilins for proteostasis and non-shivering thermogenesis in brown adipocytes. We found that Ubqln1, 2 and 4 are highly expressed in BAT and their expression was induced by cold and proteasomal inhibition. Surprisingly, silencing of ubiquilin gene expression (one or multiple in combinations) did not lead to aggravated ER stress or inflammation. Moreover, ubiquitin level and proteasomal activity under basal conditions were not impacted by loss of ubiquilins. Also, non-shivering thermogenesis measured by norepinephrine-induced respiration remained intact after loss of ubiquilins. In conclusion, ubiquilin proteins are highly abundant in BAT and regulated by cold, but they are dispensable for brown adipocyte proteostasis and thermogenesis.
High Genetic Diversity but Absence of Population Structure in Local Chickens of Sri Lanka Inferred by Microsatellite Markers
Authors: Samaraweera Amali Malshani , Liyanage Ranga , Ibrahim Mohamed Nawaz , Okeyo Ally Mwai , Han Jianlin , Silva Pradeepa
Published: September 2021

Local chicken populations belonging to five villages in two geographically separated provinces of Sri Lanka were analyzed using 20 microsatellite markers to determine the genetic diversity of local chickens. Population genetic parameters were estimated separately for five populations based on geographic locations and for eight populations based on phenotypes, such as naked neck, long legged, crested or crown, frizzle feathered, Giriraj, commercial layer, crossbreds, and non-descript chicken. The analysis revealed that there was a high genetic diversity among local chickens with high number of unique alleles, mean number of alleles per locus (MNA), and total number of alleles per locus per population. A total of 185 microsatellite alleles were detected in 192 samples, indicating a high allelic diversity. The MNA ranged from 8.10 (non-descript village chicken) to 3.50 (Giriraj) among phenotypes and from 7.30 (Tabbowa) to 6.50 (Labunoruwa) among village populations. In phenotypic groups, positive inbreeding coefficient (FIS) values indicated the existence of population substructure with evidence of inbreeding. In commercial layers, a high expected heterozygosity He = 0.640 ± 0.042) and a negative FIS were observed. The positive FIS and high He estimates observed in village populations were due to the heterogeneity of samples, owing to free mating facilitated by communal feeding patterns. Highly admixed nature of phenotypes was explained as a result of rearing many phenotypes by households (58%) and interactions of chickens among neighboring households (53%). A weak substructure was evident due to the mating system, which disregarded the phenotypes. Based on genetic distances, crown chickens had the highest distance to other phenotypes, while the highest similarity was observed between non-descript village chickens and naked neck birds. The finding confirms the genetic wealth conserved within the populations as a result of the breeding system commonly practiced by chicken owners. Thus, the existing local chicken populations should be considered as a harbor of gene pool, which can be readily utilized in developing locally adapted and improved chicken breeds in the future.
Small Molecule Potentiator of Adjuvant Activity Enhancing Survival to Influenza Viral Challenge
Authors: Saito Tetsuya , Sako Yukiya , Sato-Kaneko Fumi , Hosoya Tadashi , Yao Shiyin , Lao Fitzgerald S. , Shpigelman Jonathan , Messer Karen , Pu Minya , Shukla Nikunj M. , Chan Michael , Chu Paul J. , Cottam Howard B. , Hayashi Tomoko , Carson Dennis A. , Corr Maripat
Published: September 2021

As viruses continue to mutate the need for rapid high titer neutralizing antibody responses has been highlighted. To meet these emerging threats, agents that enhance vaccine adjuvant activity are needed that are safe with minimal local or systemic side effects. To respond to this demand, we sought small molecules that would sustain and improve the protective effect of a currently approved adjuvant, monophosphoryl lipid A (MPLA), a Toll-like receptor 4 (TLR4) agonist. A lead molecule from a high-throughput screen, (N-(4-(2,5-dimethylphenyl)thiazol-2-yl)-4-(piperidin-1-ylsulfonyl)benzamide, was identified as a hit compound that sustained NF-κB activation by a TLR4 ligand, lipopolysaccharide (LPS), after an extended incubation (16 h). In vitro, the resynthesized compound (2D216) enhanced TLR4 ligand-induced innate immune activation and antigen presenting function in primary murine bone marrow-derived dendritic cells without direct activation of T cells. In vivo murine vaccination studies demonstrated that compound 2D216 acted as a potent co-adjuvant when used in combination with MPLA that enhanced antigen-specific IgG equivalent to that of AS01B. The combination adjuvant MPLA/2D216 produced Th1 dominant immune responses and importantly protected mice from lethal influenza virus challenge. 2D216 alone or 2D216/MPLA demonstrated minimal local reactogenicity and no systemic inflammatory response. In summary, 2D216 augmented the beneficial protective immune responses of MPLA as a co-adjuvant and showed an excellent safety profile.
Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages
Authors: Diaz-del-Olmo Ines , Worboys Jonathan , Martin-Sanchez Fatima , Gritsenko Anna , Ambrose Ashley R. , Tannahill Gillian M. , Nichols Eva-Maria , Lopez-Castejon Gloria , Davis Daniel M.
Published: September 2021

Interleukin 1β (IL-1β) plays a major role in inflammation and is secreted by immune cells, such as macrophages, upon recognition of danger signals. Its secretion is regulated by the inflammasome, the assembly of which results in caspase 1 activation leading to gasdermin D (GSDMD) pore formation and IL-1β release. During inflammation, danger signals also activate the complement cascade, resulting in the formation of the membrane attack complex (MAC). Here, we report that stimulation of LPS-primed human macrophages with sub-lytic levels of MAC results in activation of the NOD-like receptor 3 (NLRP3) inflammasome and GSDMD-mediated IL-1β release. The MAC is first internalized into endosomes and then colocalizes with inflammasome components; adapter protein apoptosis associated speck-like protein containing a CARD (ASC) and NLRP3. Pharmacological inhibitors established that MAC-triggered activation of the NLRP3 inflammasome was dependent on MAC endocytosis. Internalization of the MAC also caused dispersion of the trans-Golgi network. Thus, these data uncover a role for the MAC in activating the inflammasome and triggering IL-1β release in human macrophages.
Shrimp Parvovirus Circular DNA Fragments Arise From Both Endogenous Viral Elements and the Infecting Virus
Authors: Taengchaiyaphum Suparat , Buathongkam Phasini , Sukthaworn Suchitraporn , Wongkhaluang Prapatsorn , Sritunyalucksana Kallaya , Flegel Timothy William
Published: September 2021

Some insects use endogenous reverse transcriptase (RT) to make variable viral copy DNA (vcDNA) fragments from viral RNA in linear (lvcDNA) and circular (cvcDNA) forms. The latter form is easy to extract selectively. The vcDNA produces small interfering RNA (siRNA) variants that inhibit viral replication via the RNA interference (RNAi) pathway. The vcDNA is also autonomously inserted into the host genome as endogenous viral elements (EVE) that can also result in RNAi. We hypothesized that similar mechanisms occurred in shrimp. We used the insect methods to extract circular viral copy DNA (cvcDNA) from the giant tiger shrimp (Penaeus monodon) infected with a virus originally named infectious hypodermal and hematopoietic necrosis virus (IHHNV). Simultaneous injection of the extracted cvcDNA plus IHHNV into whiteleg shrimp (Penaeus vannamei) resulted in a significant reduction in IHHNV replication when compared to shrimp injected with IHHNV only. Next generation sequencing (NGS) revealed that the extract contained a mixture of two general IHHNV-cvcDNA types. One showed 98 to 99% sequence identity to GenBank record AF218266 from an extant type of infectious IHHNV. The other type showed 98% sequence identity to GenBank record DQ228358, an EVE formerly called non-infectious IHHNV. The startling discovery that EVE could also give rise to cvcDNA revealed that cvcDNA provided an easy means to identify and characterize EVE in shrimp and perhaps other organisms. These studies open the way for identification, characterization and use of protective cvcDNA as a potential shrimp vaccine and as a tool to identify, characterize and select naturally protective EVE to improve shrimp tolerance to homologous viruses in breeding programs.
Serum CD203c+ Extracellular Vesicle Serves as a Novel Diagnostic and Prognostic Biomarker for Succinylated Gelatin Induced Perioperative Hypersensitive Reaction
Authors: Qi Zheng , Xue Qiong , Wang Haitao , Cao Bin , Su Yu , Xing Qinghe , Yang Jian-Jun
Published: September 2021

Background

Perioperative hypersensitivity reaction (HR) is an IgE-FcϵRI-mediated hypersensitivity reaction with degranulation and activation of mast cells and basophils. Several studies have focused on assessing the degranulation and activation of mast cells and basophils to diagnose and predict the prognosis of drug induced HR. However, it is challenging to isolate sufficiently pure mast cells and basophils from human sources to investigate. Effective biomarkers to assess mast cells and basophils activationin vivocould potentially have high diagnostic and prognostic values. In the present study, we investigated EVs pelleted from serum in patients with succinylated gelatin induced HR.

Methods

Extracellular vesicles (EVs) were isolated using a total exosome isolation kit and ultracentrifugation, characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. Basophils were isolated from fresh peripheral blood by negative selection using Basophil Isolation Kit II. Human mast cell line was stimulated with IL4. The expression levels of proteins related to the hypersensitive response were evaluated by Western blotting and flow Cytometer. Histamine and tryptase levels were tested using a commercial ELISA kit, and gene expression of inflammatory mediators was evaluated by qRT-PCR. The receiver operating characteristic (ROC) curve was used to evaluate the specificity and sensitivity of biomarker in predicting HR.

Results

The concentration of EVs and protein expression level of CD63, FcϵRI, CD203c and tryptase were significantly (p< 0.05) increased in HR samples. The expression level of mast cell/basophil specific CD203c were significantly increased in EVs derived from serum and basophils of HR patients, and the CD203c+-EVs production in mast cells is dramatically increased in the presence of IL4, which positively correlated with histamine, tryptase and inflammatory mediators. Moreover, the ROC curve of EVs concentration and CD203c expression indicated that CD203c+-EVs had a strong diagnostic ability for HR.

Conclusion

Serum CD203c+-EVs serves as a novel diagnostic and prognostic biomarker for HR.
Characterising the Phenotypic Diversity of Antigen-Specific Memory B Cells Before and After Vaccination
Authors: Tjiam M. Christian , Fernandez Sonia , French Martyn A.
Published: September 2021

The diversity of B cell subsets and their contribution to vaccine-induced immunity in humans are not well elucidated but hold important implications for rational vaccine design. Prior studies demonstrate that B cell subsets distinguished by immunoglobulin (Ig) isotype expression exhibit divergent activation-induced fates. Here, the antigen-specific B cell response to tetanus toxoid (TTd) booster vaccination was examined in healthy adults, using a dual-TTd tetramer staining flow cytometry protocol. Unsupervised analyses of the data revealed that prior to vaccination, IgM-expressing CD27+ B cells accounted for the majority of TTd-binding B cells. 7 days following vaccination, there was an acute expansion of TTd-binding plasmablasts (PB) predominantly expressing IgG, and a minority expressing IgA or IgM. Frequencies of all PB subsets returned to baseline at days 14 and 21. TTd-binding IgG+ and IgA+ memory B cells (MBC) exhibited a steady and delayed maximal expansion compared to PB, peaking in frequencies at day 14. In contrast, the number of TTd-binding IgM+IgD+CD27+ B cells and IgM-only CD27+ B cells remain unchanged following vaccination. To examine TTd-binding capacity of IgG+ MBC and IgM+IgD+CD27+ B cells, surface TTd-tetramer was normalised to expression of the B cell receptor-associated CD79b subunit. CD79b-normalised TTd binding increased in IgG+ MBC, but remained unchanged in IgM+IgD+CD27+ B cells, and correlated with the functional affinity index of plasma TTd-specific IgG antibodies, following vaccination. Finally, frequencies of activated (PD-1+ICOS+) circulating follicular helper T cells (cTFH), particularly of the CXCR3-CCR6- cTFH2 cell phenotype, at their peak expansion, strongly predicted antigen-binding capacity of IgG+ MBC. These data highlight the phenotypic and functional diversity of the B cell memory compartment, in their temporal kinetics, antigen-binding capacities and association with cTFH cells, and are important parameters for consideration in assessing vaccine-induced immune responses.
High-Sustained Concentrations of Organisms at Very low Oxygen Concentration Indicated by Acoustic Profiles in the Oxygen Deficit Region Off Peru
Authors: Paulmier Aurelien , Eldin Gerard , Ochoa José , Dewitte Boris , Sudre Joël , Garçon Véronique , Grelet Jaques , Mosquera-Vásquez Kobi , Vergara Oscar , Maske Helmut
Published: September 2021

The oxygen deficient mesopelagic layer (ODL) off Peru has concentrations below 5 μmol O2 kg–1 and is delimited by a shallow upper oxycline with strong vertical gradient and a more gradual lower oxycline (lOx). Some regions show a narrow band of slightly increased oxygen concentrations within the ODL, an intermediate oxygen layer (iO2). CTD, oxygen and lowered Acoustic Doppler Current Profiler (LADCP, 300 kHz) profiles were taken on the shelf edge and outside down to mostly 2000 m. We evaluate here the acoustic volume backscatter strength of the LADCP signal representing organisms of about 5 mm size. Dominant features of the backscatter profiles were a minimum backscatter strength within the ODL, and just below the lOx a marked backscatter increase reaching a maximum at less than 3.0 μmol O2 kg–1. Below this maximum, the acoustic backscatter strength gradually decreased down to 1000 m below the lOx. The backscatter strength also increased at the iO2 in parallel to the oxygen concentration perturbations marking the iO2. These stable backscatter features were independent of the time of day and the organisms represented by the backscatter had to be adapted to live in this microaerobic environment. During daylight, these stable structures were overlapped by migrating backscatter peaks. Outstanding features of the stable backscatter were that at very low oxygen concentrations, the volume backscatter was linearly related to the oxygen concentration, reaching half peak maximum at less than 2.0 μmol O2 kg–1 below the lOx, and the depth-integrated backscatter of the peak below the lOx was higher than the integral above the Ox. Both features suggest that sufficient organic material produced at the surface reaches to below the ODL to sustain the major fraction of the volume backscatter-producing organisms in the water column. These organisms are adapted to the microaerobic environment so they can position themselves close to the lower oxycline to take advantage of the organic particles sinking out of the ODL.
Climate-Biogeochemistry Interactions in the Tropical Ocean: Data Collection and Legacy
Authors: Krahmann Gerd , Arévalo-Martínez Damian L. , Dale Andrew W. , Dengler Marcus , Engel Anja , Glock Nicolaas , Grasse Patricia , Hahn Johannes , Hauss Helena , Hopwood Mark J. , Kiko Rainer , Loginova Alexandra N. , Löscher Carolin R. , Maßmig Marie , Roy Alexandra-Sophie , Salvatteci Renato , Sommer Stefan , Tanhua Toste , Mehrtens Hela
Published: September 2021

From 2008 to 2019, a comprehensive research project, ‘SFB 754, Climate – Biogeochemistry Interactions in the Tropical Ocean,’ was funded by the German Research Foundation to investigate the climate-biogeochemistry interactions in the tropical ocean with a particular emphasis on the processes determining the oxygen distribution. During three 4-year long funding phases, a consortium of more than 150 scientists conducted or participated in 34 major research cruises and collected a wealth of physical, biological, chemical, and meteorological data. A common data policy agreed upon at the initiation of the project provided the basis for the open publication of all data. Here we provide an inventory of this unique data set and briefly summarize the various data acquisition and processing methods used.
Development of a Quantitative PCR Method for Specific and Quantitative Detection of Enterocytospora artemiae, a Microsporidian Parasite of Chinese Grass Shrimp (Palaemonetes sinensis)
Authors: Jiang Hongbo , Bao Jie , Liu Jinghui , Chen Yuwen , Feng Chengcheng , Li Xiaodong , Huang Shuai , Chen Qijun
Published: September 2021

Enterocytospora artemiae (EAM) mainly parasitizes the hepatopancreas of Palaemonetes sinensis. Serious infection leads to hepatopancreatic lesions, which greatly reduce the vitality of P. sinensis. Currently, EAM is detected via conventional PCR methods. However, conventional PCR has low sensitivity and cannot be used for accurate quantitative detection of EAM or its parasitic activity in host tissues. In this study, we designed a pair of specific primers based on the sequence of the ribosomal protein S9 gene (RPS9; GenBank accession number: MZ420734) to establish and optimize a SYBR Green I real-time fluorescent quantitative PCR detection method for EAM. Only EAM appeared as a bright and single target band, whereas other microorganisms did not, indicating that the primer for RPS9 had high specificity. This method displayed optimum amplification effects at an annealing temperature of 55°C, and the melting curve of the product produced a single peak. The established method showed a good linear relationship from 2.2 × 108 to 2.2 × 101 copies/μL. The relationship between the number of cycle thresholds (Ct) and the logarithm of the initial template amount (x) conformed to Ct = −3.281 log x + 36.543 (R2 = 0.998). Amplification efficiency was 101.737%, and the lower limit of detection sensitivity was 2.2 × 101 copies/μL. Good intra- and inter-group repeatability was observed within the linear range. The sensitivity of this method was more than 200 times higher than that of nested PCR. Thus, detection data obtained using this method may be useful as a technical reference for rapid and accurate identification of EAM infection and for the prevention and control of EAM during P. sinensis breeding.
Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy
Authors: Wu Guanrong , Liu Baoyi , Wu Qiaowei , Tang Changting , Du Zijing , Fang Ying , Hu Yijun , Yu Honghua
Published: September 2021

Purpose: To investigate the expression of various angiogenesis and inflammation mediators in the vitreous fluid of eyes with proliferative diabetic retinopathy (PDR).

Methods: A total of 38 eyes with PDR and 37 control eyes were included. Vitreous fluid was collected during vitrectomy. Vitreous levels of colony stimulating factor-1 receptor (CSF-1R), syndecan-1, placental growth factor (PIGF), and angiopoietin-like protein 4 (ANGPTL-4) were measured by multiplex immunoassay. Vitreous levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were measured by cytometric beads array. Levels of these mediators were compared between the PDR and control eyes. Correlations between levels of different mediators and between these mediators and kidney function metrics in the PDR group were also analyzed.

Results: Vitreous levels of syndecan-1, PIGF, ANGPTL-4, VEGF, and IL-8 were significantly higher in the PDR group compared to the control group (all p < 0.05). Levels of VEGF were significantly correlated with levels of syndecan-1, PIGF, and ANGPTL-4 (r = 0.370 to 0.497, all p < 0.05). Significant positive correlations were detected between levels of any two of the following mediators including syndecan-1, PIGF, ANGPTL-4, and IL-8 (r = 0.370 to 0.906, all p < 0.05). Apart from VEGF, levels of these mediators were positively correlated with serum creatinine and blood urea nitrogen (r = 0.328 to 0.638, all p < 0.05), and negatively correlated with fasting blood glucose and estimated glomerular filtration rate (r = −0.325 to −0.603, all p < 0.05).

Conclusions: Correlations between different angiogenesis and inflammation mediators were observed in eyes with PDR, suggesting cross-talks of different angiogenesis and inflammation pathways in the pathogenesis of PDR. The levels of angiogenesis and inflammation in PDR are correlated with kidney damage, indicating possible common pathways in diabetic retinopathy and nephropathy.
Increased Risk of Retinal Vasculitis in Patients With Systemic Lupus Erythematosus: A Nationwide Population-Based Cohort Study
Authors: Chen Xiao-Huan , Shi Jia-Cheng , Wei James Cheng-Chung , Chen Hsin-Hua , Mo Han-You
Published: September 2021

Objectives: To evaluate the relationship between systemic lupus erythematosus (SLE) and the risk of retinal vasculitis (RV) using a population-based database.

Methods: Using the 1997–2013 Taiwanese National Health Insurance Database, we identified newly diagnosed SLE patients between 2001 and 2012 as the SLE group. We matched the SLE group with non-SLE individuals selected from a representative one million sample of the population in a 1:20 ratio for age, sex, and the year of the index date. After adjusting for potential confounders, including urbanization of the patient's residence, the level of the payroll-related insured amount, and selected comorbidities, we examined the association between SLE and the risk of RV using the Cox proportional hazard model shown as hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses were conducted using various definitions of RV.

Results: We included 11,586 patients with SLE and 231,720 matched non-SLE individuals. The mean age of the study participants was 36.7 ± 16.9 years, and the female-to-male ratio was 6.8:1. The incidence rates of RV were 56.39 cases per 100,000 person-years and 2.45 cases per 100,000 person-years, respectively. After adjusting for potential confounders, the incidence rate of RV in the SLE cohort was 22.99 times higher than that in the non-SLE cohort (56.39 vs. 2.45 per 100,000 person-years). The adjusted HR for RV in the SLE group was 23.61 (95% CI, 14.94–37.32). The results remained robust in the sensitivity analysis.

Conclusion: This nationwide population-based study revealed that SLE patients had a significantly higher risk of RV than non-SLE individuals.
The Gut Microbiome and Sex Hormone-Related Diseases
Authors: He Song , Li Hao , Yu Zehui , Zhang Faming , Liang Sicheng , Liu Hang , Chen Hongwei , Lü MuHan
Published: September 2021

The role of the gut microbiome has been a hot topic in recent years. One aim of this review is to shed light on the crosstalk between sex hormones and the gut microbiome. Researchers have observed a sex bias of the composition of the gut microbiome in mice and have proved that sex differences influence the composition of the gut microbiome, although the influence is usually obscured by genetic variations. Via cell studies, animal studies and some observational studies in humans, researchers have confirmed that the gut microbiome can be shaped by the hormonal environment. On other hand, some theories suggest that the gut microbiota regulates the levels of sex hormones via interactions among its metabolites, the immune system, chronic inflammation and some nerve-endocrine axes, such as the gut-brain axis. In addition, bidirectional interactions between the microbiome and the hormonal system have also been observed, and the mechanisms of these interactions are being explored. We further describe the role of the gut microbiome in sex hormone-related diseases, such as ovarian cancer, postmenopausal osteoporosis (PMOP), polycystic ovary syndrome and type 1 diabetes. Among these diseases, PMOP is described in detail. Finally, we discuss the treatments of these diseases and the application prospects of microbial intervention.
Artificial Intelligence Systems for Diagnosis and Clinical Classification of COVID-19
Authors: Yu Lan , Shi Xiaoli , Liu Xiaoling , Jin Wen , Jia Xiaoqing , Xi Shuxue , Wang Ailan , Li Tianbao , Zhang Xiao , Tian Geng , Sun Dejun
Published: September 2021

Objectives: COVID-19 is highly infectious and has been widely spread worldwide, with more than 159 million confirmed cases and more than 3 million deaths as of May 11, 2021. It has become a serious public health event threatening people’s lives and safety. Due to the rapid transmission and long incubation period, shortage of medical resources would easily occur in the short term of discovering disease cases. Therefore, we aimed to construct an artificial intelligent framework to rapidly distinguish patients with COVID-19 from common pneumonia and non-pneumonia populations based on computed tomography (CT) images. Furthermore, we explored artificial intelligence (AI) algorithms to integrate CT features and laboratory findings on admission to predict the clinical classification of COVID-19. This will ease the burden of doctors in this emergency period and aid them to perform timely and appropriate treatment on patients.

Methods: We collected all CT images and clinical data of novel coronavirus pneumonia cases in Inner Mongolia, including domestic cases and those imported from abroad; then, three models based on transfer learning to distinguish COVID-19 from other pneumonia and non-pneumonia population were developed. In addition, CT features and laboratory findings on admission were combined to predict clinical types of COVID-19 using AI algorithms. Lastly, Spearman’s correlation test was applied to study correlations of CT characteristics and laboratory findings.

Results: Among three models to distinguish COVID-19 based on CT, vgg19 showed excellent diagnostic performance, with area under the curve (AUC) of the receiver operating characteristic (ROC) curve at 95%. Together with laboratory findings, we were able to predict clinical types of COVID-19 with AUC of the ROC curve at 90%. Furthermore, biochemical markers, such as C-reactive protein (CRP), LYM, and lactic dehydrogenase (LDH) were identified and correlated with CT features.

Conclusion: We developed an AI model to identify patients who were positive for COVID-19 according to the results of the first CT examination after admission and predict the progression combined with laboratory findings. In addition, we obtained important clinical characteristics that correlated with the CT image features. Together, our AI system could rapidly diagnose COVID-19 and predict clinical types to assist clinicians perform appropriate clinical management.
DexA70, the Truncated Form of a Self-Produced Dextranase, Effectively Disrupts Streptococcus mutans Biofilm
Authors: Liu Nan , Li Xin , Wang Maofeng , Zhang Fengyu , Wang Chuandong , Zhang Kundi , Wang Hongwei , Xu Sujuan , Hu Wei , Gu Lichuan
Published: September 2021

Billions of people suffer from dental caries every year in spite of the effort to reduce the prevalence over the past few decades. Streptococcus mutans is the leading member of a specific group of cariogenic bacteria that cause dental caries. S. mutans forms biofilm, which is highly resistant to harsh environment, host immunity, and antimicrobial treatments. In this study, we found that S. mutans biofilm is highly resistant to both antimicrobial agents and lysozyme. DexA70, the truncated form of DexA (amino acids 100–732), a dextranase in S. mutans, prevents S. mutans biofilm formation and disassembles existing biofilms within minutes at nanomolar concentrations when supplied exogenously. DexA70 treatment markedly enhances biofilm sensitivity to antimicrobial agents and lysozyme, indicating its great potential in combating biofilm-related dental caries.
Molecular Characterization of a Tolerant Saline-Alkali Chlorella Phosphatidate Phosphatase That Confers NaCl and Sorbitol Tolerance
Authors: Wang Jingang , Shan Qinghua , Ran Ye , Sun Dexiang , Zhang Haizhen , Zhang Jinzhu , Gong Shufang , Zhou Aimin , Qiao Kun
Published: September 2021

The gene encoding a putative phosphatidate phosphatase (PAP) from tolerant saline-alkali (TSA) Chlorella, ChPAP, was identified from a yeast cDNA library constructed from TSA Chlorella after a NaCl treatment. ChPAP expressed in yeast enhanced its tolerance to NaCl and sorbitol. The ChPAP protein from a GFP-tagged construct localized to the plasma membrane and the lumen of vacuoles. The relative transcript levels of ChPAP in Chlorella cells were strongly induced by NaCl and sorbitol as assessed by northern blot analyses. Thus, ChPAP may play important roles in promoting Na-ion movement into the cell and maintaining the cytoplasmic ion balance. In addition, ChPAP may catalyze diacylglycerol pyrophosphate to phosphatidate in vacuoles.
Penicillium simplicissimum NL-Z1 Induced an Imposed Effect to Promote the Leguminous Plant Growth
Authors: Zhuang Jiayao , Liu Chao , Wang Xiaoxue , Xu Tongxin , Yang Hao
Published: September 2021

It is found effective for phytoremediation of the guest soil spraying method by adding microbes to promote the growth of arbor leguminous plant on a high and steep rock slope. However, its underlying mechanisms remain elusive. Here, some experiments were conducted to explore the multifunctions of Penicillium simplicissimum NL-Z1 on rock weathering, nodule growth, and beneficial microbial regulation. The results show that P. simplicissimum NL-Z1 significantly increased the release of phosphorus, potassium, calcium, and magnesium from the rock by 226, 29, 24, and 95%, respectively, compared with that of the control. A significant increase of 153% in Indigofera pseudotinctoria Matsum nodule biomass, accompanied by an increase of 37% in the leguminous plant biomass was observed in the P. simplicissimum NL-Z1 treatment than in the control treatment. Interestingly, even though P. simplicissimum NL-Z1 itself became a minor microbial community in the soil, it induced a significant increase in Mortierella, which, as a beneficial microbe, can promote phosphate-solubilizing and plant growth. The results suggest that P. simplicissimum NL-Z1 could induce an imposed effect to promote leguminous plant growth, which may be conducive to the development of the phytoremediation technique for high and steep rock slope. The study provides a novel thought of using the indirect effect of microbes, i.e., promoting other beneficial microbes, to improve soil environment.
Advances in Studies on Microbiota Involved in Nitrogen Removal Processes and Their Applications in Wastewater Treatment
Authors: Mai Wenning , Chen Jiamin , Liu Hai , Liang Jiawei , Tang Jinfeng , Wei Yongjun
Published: September 2021

The discharge of excess nitrogenous pollutants in rivers or other water bodies often leads to serious ecological problems and results in the collapse of aquatic ecosystems. Nitrogenous pollutants are often derived from the inefficient treatment of industrial wastewater. The biological treatment of industrial wastewater for the removal of nitrogen pollution is a green and efficient strategy. In the initial stage of the nitrogen removal process, the nitrogenous pollutants are converted to ammonia. Traditionally, nitrification and denitrification processes have been used for nitrogen removal in industrial wastewater; while currently, more efficient processes, such as simultaneous nitrification-denitrification, partial nitrification-anammox, and partial denitrification-anammox processes, are used. The microorganisms participating in nitrogen pollutant removal processes are diverse, but information about them is limited. In this review, we summarize the microbiota participating in nitrogen removal processes, their pathways, and associated functional genes. We have also discussed the design of efficient industrial wastewater treatment processes for the removal of nitrogenous pollutants and the application of microbiome engineering technology and synthetic biology strategies in the modulation of the nitrogen removal process. This review thus provides insights that would help in improving the efficiency of nitrogen pollutant removal from industrial wastewater.
Application of Computational Methods in Understanding Mutations in Mycobacterium tuberculosis Drug Resistance
Authors: Mugumbate Grace , Nyathi Brilliant , Zindoga Albert , Munyuki Gadzikano
Published: September 2021

The emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) impedes the End TB Strategy by the World Health Organization aiming for zero deaths, disease, and suffering at the hands of tuberculosis (TB). Mutations within anti-TB drug targets play a major role in conferring drug resistance within Mtb; hence, computational methods and tools are being used to understand the mechanisms by which they facilitate drug resistance. In this article, computational techniques such as molecular docking and molecular dynamics are applied to explore point mutations and their roles in affecting binding affinities for anti-TB drugs, often times lowering the protein’s affinity for the drug. Advances and adoption of computational techniques, chemoinformatics, and bioinformatics in molecular biosciences and resources supporting machine learning techniques are in abundance, and this has seen a spike in its use to predict mutations in Mtb. This article highlights the importance of molecular modeling in deducing how point mutations in proteins confer resistance through destabilizing binding sites of drugs and effectively inhibiting the drug action.