bluuebunny/crossref_metadata_2025 huggingface dataset:
Sampling and ranking spatial transcriptomics data embeddings to identify tissue architecture
Authors: Lin Yu , Wang Yan , Liang Yanchun , Yu Yang , Li Jingyi , Ma Qin , He Fei , Xu Dong
Published: August 2022

Spatial transcriptomics is an emerging technology widely applied to the analyses of tissue architecture and corresponding biological functions. Substantial computational methods have been developed for analyzing spatial transcriptomics data. These methods generate embeddings from gene expression and spatial locations for spot clustering or tissue architecture segmentation. Although the hyperparameters used to produce an embedding can be tuned for a given training set, a fixed embedding has variable performance from case to case due to data distributions. Therefore, selecting an effective embedding for new data in advance would be useful. For this purpose, we developed an embedding evaluation method named message passing-Moran’s I with maximum filtering (MP-MIM), which combines message passing-based embedding transformation with spatial autocorrelation analysis. We applied a graph convolution to aggregate spatial transcriptomics data and employed global Moran’s I to measure spatial autocorrelation and select the most effective embedding to infer tissue architecture. Sixteen spatial transcriptomics samples generated from the human brain were used to validate our method. The results show that MP-MIM can accurately identify high-quality embeddings that produce a high correlation between the predicted tissue architecture and the ground truth. Overall, our study provides a novel method to select embeddings for new test data and enhance the usability of deep learning tools for spatial transcriptome analyses.
Identification of novel key genes and potential candidate small molecule drugs in diabetic kidney disease using comprehensive bioinformatics analysis
Authors: Li Bin , Ye Siyang , Fan Yuting , Lin Yi , Li Suchun , Peng Huajing , Diao Hui , Chen Wei
Published: August 2022

Objective: The currently established diagnostic and prognostic tools for diabetic kidney disease (DKD) have limitations, which demands the necessity to find new genes and pathways associated with diagnosis and treatment. Our study aims to reveal the gene expression alteration and discover critical genes involved in the development of DKD, thus providing novel diagnostic molecular markers and therapeutic targets.

Materials and methods: The differences of infiltrating immune cells within kidney were compared between healthy living donors and DKD patients. Besides, differentially expressed genes (DEGs) within kidney from healthy living donor, early stage DKD and advanced stage DKD samples were detected. Furthermore, the weighted co-expressed network (WGCNA) and protein-protein interaction (PPI) network were constructed, followed by recognition of core hub genes and module analysis. Receiver operating characteristic (ROC) curve analysis was implemented to determine the diagnostic value of hub genes, correlation analysis was employed to explore the association between hub genes and infiltrating immune cells, and certain hub genes was validated by quantitative real-time PCR and immunohistochemistry staining in cultured tubule cells and diabetic mice kidney. Finally, the candidate small molecules as potential drugs to treat DKD were anticipated through utilizing virtual screening and molecular docking investigation.

Results: Our study revealed significantly higher proportion of infiltrating immune cells within kidney from DKD patients via probing the immune landscape by single-cell transcriptomics. Besides, 126 commonly shared DEGs identified among three group samples were enriched in immune biological process. In addition, the ROC curve analysis demonstrated the strong diagnostic accuracy of recognized hub genes (NFKB1, DYRK2, ATAD2, YAP1, and CHD3) from PPI network. Correlation analysis further confirmed the positive association between these hub genes with infiltrating natural killer cells. More importantly, the mRNA transcripts and protein abundance of YAP1 were significantly higher in high glucose-treated renal tubule cells and diabetic mice kidney, and the small molecules exhibiting the best binding affinities with YAP1 were predicted and acquired.

Conclusion: Our findings for the first time indicate that NFKB1, DYRK2, ATAD2, YAP1, and CHD3 might be potential novel biomarkers and therapeutic targets for DKD, providing insights into the molecular mechanisms underlying the pathogenesis of DKD.
Novel genetic associations with five aesthetic facial traits: A genome-wide association study in the Chinese population
Authors: Wang Peiqi , Sun Xinghan , Miao Qiang , Mi Hao , Cao Minyuan , Zhao Shan , Wang Yiyi , Shu Yang , Li Wei , Xu Heng , Bai Ding , Zhang Yan
Published: August 2022

Background: The aesthetic facial traits are closely related to life quality and strongly influenced by genetic factors, but the genetic predispositions in the Chinese population remain poorly understood.

Methods: A genome-wide association studies (GWAS) and subsequent validations were performed in 26,806 Chinese on five facial traits: widow’s peak, unibrow, double eyelid, earlobe attachment, and freckles. Functional annotation was performed based on the expression quantitative trait loci (eQTL) variants, genome-wide polygenic scores (GPSs) were developed to represent the combined polygenic effects, and single nucleotide polymorphism (SNP) heritability was presented to evaluate the contributions of the variants.

Results: In total, 21 genetic associations were identified, of which ten were novel: GMDS-AS1 (rs4959669, p = 1.29 × 10−49) and SPRED2 (rs13423753, p = 2.99 × 10−14) for widow’s peak, a previously unreported trait; FARSB (rs36015125, p = 1.96 × 10−21) for unibrow; KIF26B (rs7549180, p = 2.41 × 10−15), CASC2 (rs79852633, p = 4.78 × 10−11), RPGRIP1L (rs6499632, p = 9.15 × 10−11), and PAX1 (rs147581439, p = 3.07 × 10−8) for double eyelid; ZFHX3 (rs74030209, p = 9.77 × 10−14) and LINC01107 (rs10211400, p = 6.25 × 10−10) for earlobe attachment; and SPATA33 (rs35415928, p = 1.08 × 10−8) for freckles. Functionally, seven identified SNPs tag the missense variants and six may function as eQTLs. The combined polygenic effect of the associations was represented by GPSs and contributions of the variants were evaluated using SNP heritability.

Conclusion: These identifications may facilitate a better understanding of the genetic basis of features in the Chinese population and hopefully inspire further genetic research on facial development.
Nature vs. nurture: FOXP3, genetics, and tissue environment shape Treg function
Authors: Raugh Arielle , Allard Denise , Bettini Maria
Published: August 2022

The importance of regulatory T cells (Tregs) in preventing autoimmunity has been well established; however, the precise alterations in Treg function in autoimmune individuals and how underlying genetic associations impact the development and function of Tregs is still not well understood. Polygenetic susceptibly is a key driving factor in the development of autoimmunity, and many of the pathways implicated in genetic association studies point to a potential alteration or defect in regulatory T cell function. In this review transcriptomic control of Treg development and function is highlighted with a focus on how these pathways are altered during autoimmunity. In combination, observations from autoimmune mouse models and human patients now provide insights into epigenetic control of Treg function and stability. How tissue microenvironment influences Treg function, lineage stability, and functional plasticity is also explored. In conclusion, the current efficacy and future direction of Treg-based therapies for Type 1 Diabetes and other autoimmune diseases is discussed. In total, this review examines Treg function with focuses on genetic, epigenetic, and environmental mechanisms and how Treg functions are altered within the context of autoimmunity.
Identification of prognostic gene expression signatures based on the tumor microenvironment characterization of gastric cancer
Authors: Sang Qingqing , Dai Wentao , Yu Junxian , Chen Yunqin , Fan Zhiyuan , Liu Jixiang , Li Fangyuan , Li Jianfang , Wu Xiongyan , Hou Junyi , Yu Beiqin , Feng Haoran , Zhu Zheng-Gang , Su Liping , Li Yuan-Yuan , Liu Bingya
Published: August 2022

Increasing evidence has elucidated that the tumor microenvironment (TME) shows a strong association with tumor progression and therapeutic outcome. We comprehensively estimated the TME infiltration patterns of 111 gastric cancer (GC) and 21 normal stomach mucosa samples based on bulk transcriptomic profiles based on which GC could be clustered as three subtypes, TME-Stromal, TME-Mix, and TME-Immune. The expression data of TME-relevant genes were utilized to build a GC prognostic model—GC_Score. Among the three GC TME subtypes, TME-Stomal displayed the worst prognosis and the highest GC_Score, while TME-Immune had the best prognosis and the lowest GC_Score. Connective tissue growth factor (CTGF), the highest weighted gene in the GC_Score, was found to be overexpressed in GC. In addition, CTGF exhibited a significant correlation with the abundance of fibroblasts. CTGF has the potential to induce transdifferentiation of peritumoral fibroblasts (PTFs) to cancer-associated fibroblasts (CAFs). Beyond characterizing TME subtypes associated with clinical outcomes, we correlated TME infiltration to molecular features and explored their functional relevance, which helps to get a better understanding of carcinogenesis and therapeutic response and provide novel strategies for tumor treatments.
Lung and gut microbiomes in pulmonary aspergillosis: Exploring adjunctive therapies to combat the disease
Authors: Cai Liuyang , Gao Peigen , Wang Zeyu , Dai Chenyang , Ning Ye , Ilkit Macit , Xue Xiaochun , Xiao Jinzhou , Chen Chang
Published: August 2022

Species within the Aspergillus spp. cause a wide range of infections in humans, including invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis, and are associated with high mortality rates. The incidence of pulmonary aspergillosis (PA) is on the rise, and the emergence of triazole-resistant Aspergillus spp. isolates, especially Aspergillus fumigatus, limits the efficacy of mold-active triazoles. Therefore, host-directed and novel adjunctive therapies are required to more effectively combat PA. In this review, we focus on PA from a microbiome perspective. We provide a general overview of the effects of the lung and gut microbiomes on the growth of Aspergillus spp. and host immunity. We highlight the potential of the microbiome as a therapeutic target for PA.
Being ECR in marine science: Results of a survey among early-career marine scientists and conservationists
Authors: Osiecka Anna N. , Wróbel Aleksandra , Hendricks Ida-Wenona , Osiecka-Brzeska Katarzyna
Published: August 2022

Ocean research and conservation are still largely exclusive fields, with ongoing issues of racial, gender, class, and geographic underrepresentation. To improve accessibility and retention within these fields, we need to create equitable, just, and welcoming study and work environments. It is therefore crucial to listen to the voices of students and early career ocean professionals (ECOP). We conducted an online survey on the study- and workplace experiences of ECOP, focusing on social obstacles, such as economic strain, unpaid work, and workplace discrimination and abuse. Strong economic barriers to education access were evident in certain geographic areas. Almost half of the reported work time in the field was uncompensated, yet unpaid work rarely translated into career advancement and was often associated with workplace abuse. Dissatisfaction and burn-out rates at the earliest career stages were alarming, and experienced hardship and mental health issues were particularly dire for women and non-binary persons. While most respondents were white and from the global north, meaning the results may not reflect experiences of ECOP in other regions, this study highlights some of the barriers to equity as well as work ethics issues that should be urgently addressed within the field.
Satellite assessment of coastal plume variability and its relation to environmental variables in the Sofala Bank
Authors: Machaieie Helder Arlindo , Nehama Fialho Paloge Juma , Silva Cleverson Guizan , de Oliveira Eduardo Negri
Published: August 2022

Monthly composites of remote sensing reflectance at 555 nm wavelength (Rrs555) from ocean color imagery of the MODIS sensor onboard the Aqua platform were used to characterize the spatial and temporal variability of coastal plume in the Sofala Bank and its relation to river discharge, local rainfall, and wind speed. To achieve the objective, maps of monthly composites of Rrs555 over the Sofala Bank were inspected and statistical analysis was performed, including correlation, analysis of variance, and wavelet coherence between environmental variables and both plume area and Rrs555. Climatology of Rrs555 revealed that both plume dispersion and Rrs555 values are higher during June to December and lower during January to May. A positive correlation (r = 0.77) between wind speed and monthly time series of Rrs555, and a negative correlation between the Zambezi river discharge (r = −0.21) and rainfall (r = −0.67) with Rrs555 were found. These results suggest that variation of suspended matter in the Sofala Bank is mainly controlled by erosion and re-suspension by winds rather than the input of terrigenous matter by the Zambezi River discharge and rainfall, assuming that Rrs555 can be a valid proxy for the inorganic suspended matter. The southern portion of the Sofala Bank (i.e., near the mouths of the Pungue and Buzi Rivers) presented higher values of Rrs555 if compared to the center region near Zambezi river mouth and the northern region near Licungo river mouth. The higher Rrs555 values in the southern region might be associated with higher re-suspension rates due to increased tide mixing, dredging activities, and the shallower nature of bathymetry in the southern region. The dominance of wind in controlling the variability of suspended sediments and the eventual relatively greater contribution of Pungue and Buzi River than the Zambezi in supplying sediments could represent an evidence of weakening of Zambezi River supply of sediments, a process that might have started after damming the Zambezi Catchment.
Women and adaptive capacity to climate change in East African seascapes – Zanzibar as an example
Authors: de la Torre-Castro Maricela , Lindström Lars , Jiddawi Narriman S. , Pike Felicity , Max Astrid
Published: August 2022

As the climate crisis persists, there is a crucial need to increase knowledge on adaptive capacity and the underlying factors building it. This is particularly important for disadvantaged groups, such as coastal women in East Africa. Women’s livelihoods in these seascapes are and will be more severely affected by climate change and the capacity of East African states to deal with these challenges is limited in terms of financial and human capital. In this research, we investigated the underlying factors building the adaptive capacity of coastal women in Zanzibar (Unguja Island), Tanzania. Coastal women (N=117) were interviewed in villages around the island to gather information about potential factors supporting adaptive capacity. This was analysed applying Cinner et al (2018) five domains typology for adaptive capacity, i.e. assets, flexibility, organizations, learning and agency. The results show that women had relatively low adaptive capacity, extended poverty and very high dependence on seaweed farming of red algae, a livelihood providing low income and already being seriously affected by climate variability and change. Women’s observations of key variables related to environmental changes corresponded to most scientific findings. It was, however, unclear how that knowledge is useful and enhances adaptive capacity. Adaptive capacity was generally low but individual differences were found in which ten women had a high income. The results show that the factors underlying adaptive capacity are complex and interact with each other, being positive, negative and unclear. Many of the identified factors deserve future research. This study adds to the pool of knowledge by addressing women (not only men); coastal ecosystems (as land and freshwater systems are more studied) and the individual level (since most studies focus on national and community levels). The study illustrates that institutional renewal, bridging and cooperation is possible in Zanzibar bringing good news to the region.
‘Out of sight, out of mind’ - towards a greater acknowledgment of submerged prehistoric resources in Australian science-policy as part of a common heritage
Authors: Ward Ingrid , Elliott Michael , Guilfoyle David
Published: August 2022

There is growing awareness of the need for greater acknowledgement of underwater prehistoric cultural resources as part of management and regulation of the seabed around many maritime countries, especially those with large indigenous populations and history such as Australia. Prehistoric cultural places and landscapes inundated by Post-glacial sea-level rise on Australia’s continental shelf remain largely out-of-sight and out-of-mind, hence awareness and hence legal protection of this resource is lacking. There is a clear need for greater integration of archaeology and cultural heritage management within the marine sciences as well as a greater awareness of this resource as part of a common heritage more generally. This paper explores some of the dichotomies between Western and Indigenous cultures in valuing and managing the seabed. We argue that in developing science-policy, an attempt at least needs to be made to bridge both the gap between the nature and culture perspectives, and the jurisdictional divide between land and sea. Part of the answer lies in a convergence of Indigenous knowledge with Western science approaches, focused around our understanding of physical processes impacting past and present coastal landscapes and on the seabed itself. We explore several case studies from northern and Western Australia that are trying to do this, and which are helping to provide a greater appreciation of the inundated landscapes of the inner shelf as part of a common heritage.
Postoperative day 1 serum cystatin C level predicts postoperative delayed graft function after kidney transplantation
Authors: Li Yajuan , Wang Bo , Wang Le , Shi Kewei , Zhao Wangcheng , Gao Sai , Chen Jiayu , Ding Chenguang , Du Junkai , Gao Wei
Published: August 2022

Background

Delayed graft function (DGF) commonly occurs after kidney transplantation, but no clinical predictors for guiding post-transplant management are available.

Materials and methods

Data including demographics, surgery, anesthesia, postoperative day 1 serum cystatin C (S-CysC) level, kidney functions, and postoperative complications in 603 kidney transplant recipients who met the enrollment criteria from January 2017 to December 2018 were collected and analyzed to form the Intention-To-Treat (ITT) set. All perioperative data were screened using the least absolute shrinkage and selection operator. The discrimination, calibration, and clinical effectiveness of the predictor were verified with area under curve (AUC), calibration plot, clinical decision curve, and impact curve. The predictor was trained in Per-Protocol set, validated in the ITT set, and its stability was further tested in the bootstrap resample data.

Result

Patients with DGF had significantly higher postoperative day 1 S-CysC level (4.2 ± 1.2 vs. 2.8 ± 0.9 mg/L; P < 0.001), serum creatinine level (821.1 ± 301.7 vs. 554.3 ± 223.2 μmol/L; P < 0.001) and dialysis postoperative (74 [82.2%] vs. 25 [5.9%]; P < 0.001) compared with patients without DGF. Among 41 potential predictors, S-CysC was the most effective in the parsimonious model, and its diagnostic cut-off value was 3.80 mg/L with the risk score (OR, 13.45; 95% CI, 8.02–22.57; P < 0.001). Its specificity and sensitivity indicated by AUC was 0.832 (95% CI, 0.779–0.884; P < 0.001) with well fit calibration. S-CysC yielded up to 50% of clinical benefit rate with 1:4 of cost/benefit ratio.

Conclusion

The postoperative day 1 S-CysC level predicts DGF and may be used as a predictor of DGF but warrants further study.
Intralipid fails to rescue bupivacaine-induced cardiotoxicity in late-pregnant rats
Authors: Sherman Caitlin , Koons Natalie , Zargari Michael , Cha Catherine , Hirsch Jason , Hong Richard , Eghbali Mansoureh , Umar Soban
Published: August 2022

Background

Females routinely receive bupivacaine for obstetric and regional anesthesia. An accidental overdose of bupivacaine can result in cardiotoxicity and cardiac arrest. Intralipid (ILP) rescues bupivacaine-induced cardiotoxicity in male rats. However, bupivacaine cardiotoxicity and ILP rescue have not been studied in non-pregnant and late-pregnant female rats. Here, we tested the hypothesis that an appropriate dose of ILP would rescue non-pregnant and late-pregnant rats from bupivacaine-induced cardiotoxicity.

Methods

Non-pregnant (n = 6) and late-pregnant (n = 7) female rats received intravenous bupivacaine (10-mg/kg bolus) to induce asystole. Resuscitation with 20% ILP (5-ml/kg actual body weight, single bolus, and 0.5-ml/kg/min maintenance) and chest compressions were continued for 10-min. Serial heart rate (HR), left ventricular ejection-fraction (LVEF%), and LV-fractional shortening (LVFS%) were recorded at baseline and 10-min after bupivacaine-induced cardiac arrest. Data are mean ± SD followed by 95% CI. P-values < 0.05 were considered statistically significant.

Results

All rats developed cardiac arrest within a few seconds after bupivacaine. All non-pregnant rats were successfully rescued by ILP, with a HR of 280 ± 32 bpm at baseline vs. 212 ± 18 bpm at 10-min post ILP (p < 0.01), LVEF of 70 ± 6% vs. 68 ± 5% (p = ns), and LVFS of 41 ± 5% vs. 39 ± 4% (p = ns). Interestingly, 6 out of 7 late-pregnant rats did not recover with ILP. Baseline HR, LVEF and LVFS for late-pregnant rats were 330 ± 40 bpm, 66 ± 5% and 38 ± 4%, respectively. At 10-min post ILP, the HR, LVEF, and LVFS were 39 ± 102 bpm (p < 0.0001), 8 ± 22% (p < 0.0001), and 5 ± 12% (p < 0.001), respectively.

Conclusions

ILP successfully rescued bupivacaine-induced cardiac arrest in non-pregnant rats, but failed to rescue late-pregnant rats.
Dupilumab modulates specific IgE mite responses at the molecular level in severe T2-high atopic dermatitis: A real-world experience
Authors: González-Pérez Ruperto , Poza-Guedes Paloma , Mederos-Luis Elena , Sánchez-Machín Inmaculada
Published: August 2022

Background

Atopic dermatitis (AD) is regarded as a chronic systemic disease which is characterized by a robust overexpression of type 2 related cytokines, with increased total IgE levels and a concomitant sensitization to common allergens. Dupilumab, a fully human monoclonal antibody (mAb) to IL-4Rα that inhibits both IL-4 and IL-13 signaling, has previously shown a marked and rapid improvement when treating the moderate-to-severe forms of AD. We sought to evaluate the real-world evidence (RWE) of dupilumab in the modulation of total and specific IgE (sIgE) serum levels to a panel of molecular house dust mites (HDM) and storage mites (SM) allergens in patients with severe AD.

Methods

Demographic and clinical data for severe AD adult patients receiving dupilumab treatment (300 mg every 2 weeks) were reviewed. Mean (standard deviations SD) values and percent changes from baseline in total and sIgE to the complete HDM and SM extracts, and 14 individual molecular allergens were measured over 52 weeks.

Results

Significant (p < 0.05) changes in mean total IgE levels were observed from baseline to week-52 after treatment with dupilumab. Despite no changes were found in sIgE against the extract of HDM during the 52-week treatment with dupilumab, baseline mean levels from 7 out of 14 individual molecular mite allergens -Der p 1, Der p 2, Der p 5, Der p 7, Der p 21, Der p 23, and Lep d 2- were significantly (p < 0.05) decreased—after 52 weeks of treatment with dupilumab.

Conclusions

Dupilumab therapy for 52 weeks resulted in a profound reduction in blood levels of total IgE and allergen-specific IgE to both HDM and SM at the molecular level in adults with severe AD under RWE conditions. The potential benefits of these concomitant immunomodulatory effects after treatment with dupilumab should be explored to a greater extent.
Frailty index, mortality, and length of stay in a geriatric short-stay unit in Guadeloupe
Authors: Vainqueur Larissa , Simo-Tabue Nadine , Villeneuve Roxane , Dagonia Dorice , Bhakkan-Mambir Bernard , Mounsamy Ludwig , Delacroix Vaynome , Tabue-Teguo Maturin
Published: August 2022

Context

The COVID-19 pandemic has placed a tremendous stress on healthcare systems and caused reorganization. As the pandemic intensifies, identifying the profile of patients with COVID-19 was primordial in order to predict negative outcomes and organize healthcare resources. Age is associated with COVID-19’s mortality, but for obvious ethical reasons, chronological age cannot be the sole criterion for predicting negative outcomes.

Objective

The objective of this study was to determine the relationship between frailty index (FI) and length of hospital stay, and death in a non-COVID population of patients aged 75 years old and above.

Methods and design

A retrospective, analytical, single-centered observational study was performed in the geriatric short-stay accommodation unit at Guadeloupe University Hospital. For this study, 158 patients who were at least 75 years old were recruited from November 2020 to May 2021. FI was calculated as the number of deficits in a participant divided by the total number of deficits considered (the cut-off of FI is.25 in outpatient). Multivariate logistics regression analyses were conducted to assess the association between frailty and death, and length of stay.

Results

The average age of the participants was 85.7 ± 6.74 with a range of 75–104. Twenty-four of the patients died during hospitalization. FI was only significantly associated with mortality even after adjustment for age and gender (HR 26.3, 95% CI 1.7–413.4, P = 0.021). The association was stronger in the highest tertile of the FI (age- and gender-adjusted HR 4.6, 95% CI 1.39–15.11, P = 0.01). There was no significant interaction between FI and length of stay.

Conclusion

Our study shows an association between FI (in terms of age-related deficit accumulation) and mortality in a non-COVID geriatric short-stay unit in Guadeloupe. The FI seems to have a lower capacity to catch events such as length of stay in this very complex population. Further research studies have to be conducted for better understanding and investigation of our findings.
Psychologic interventions in patients with the chronic dermatologic itch in atopic dermatitis and psoriasis: A step forward with family constellations seminars
Authors: Capec Szergej , Petrek Martin , Capec Gabriella , Yaremkevych Roman , Andrashko Yuriy
Published: August 2022

Chronic itch is a complex psychophysiological sensation, which can severely affect the quality of life in patients with atopic dermatitis and psoriasis. Itch depends on the irritation of receptors in the skin and the processing of sensory information in the central nervous system. Severe itch leads to activation and later on to disruption of the stress response, resulting in disorders of skin repair, functional and microstructural changes in the areas of the central nervous system that are responsible for the perception of itch. Psychosocial stress can be an essential factor, activating neurohumoral mechanisms which lead to increased itch and scratch, exacerbating skin damage. Patients with chronic itch often have sleep disorders, increased irritability, and depletion of the nervous system. They are characterized by disrupting social relationships, high incidence of anxiety, depressive disorders, and suicidal tendencies. Psychological methods of intervention can effectively influence various mechanisms in the pathogenesis of itch and scratch and improve social functioning in patients with chronic dermatological itch. In this mini-review, we discuss family constellation seminars as an effective method of psychological intervention that can reduce the intensity of itch, and improve sleep and performance in patients with atopic dermatitis and psoriasis. This method is insufficiently described in previous reviews of psychological interventions in atopic dermatitis and psoriasis patients. The positive impact of family constellations seminars in patients with chronic dermatological itch may be related to reducing stress by improving understanding of the family situation, appropriate management of family secrets, and enhancing interactions with the social environment.
Overexpression of enzymes in glycolysis and energy metabolic pathways to enhance coenzyme Q10 production in Rhodobacter sphaeroides VK-2-3
Authors: Zhang Long , Li Yong-li , Hu Jian-hua , Liu Zhan-ying
Published: August 2022

We subjected the components of the glycolysis and energy metabolism pathways of Rhodobacter sphaeroides (R. sphaeroides) to metabolic engineering to improve the titer and yield of coenzyme Q10 (CoQ10). Phosphofructokinase (PFK), cyclic adenylate-dependent protein kinase (PKAC), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and adenosine triphosphate hydrolase (KdpC) were overexpressed in R. sphaeroides VK-2-3 (VK-2-3). The strains were labeled R. sphaeroides PFK (RS.PFK), RS.PKAC, RS.PFK–PKAC, RS.KdpC, RS.GAPDH, and RS.KdpC–GAPDH. Results showed that the CoQ10 titers of RS.PFK, RS.PKAC, and RS.PFK–PKAC were 300.96 ± 0.87, 405.94 ± 4.77, and 379.94 ± 0.42 mg/l, respectively. The CoQ10 titers of RS.PFK and VK-2-3 were not significantly different; however, those for RS.PKAC and RS.PFK–PKAC were 13 and 6% higher than that of VK-2-3, respectively. Further, the titers of RS.KdpC, RS.GAPDH, and RS.KdpC–GAPDH were 360.17 ± 0.39, 409.79 ± 0.76, and 359.87 ± 1.14 mg/l, respectively. The titers of RS.KdpC and RS.KdpC–GAPDH were not significantly different from that for VK-2-3, whereas that for RS.GAPDH was 14% higher than that of VK-2-3. Finally, when the cultures of RS.GAPDH and VK-2-3 were scaled up in 5-L fermenters, the CoQ10 titers and RS.GAPDH yields increased by 44.3 and 37.8%, respectively, compared with VK-2-3.To the best of our knowledge, the glycolysis pathway of R. sphaeroides was studied for the first time in this study. We genetically modified the components of the energy metabolism pathway to obtain the strain with high yield of CoQ10 mutant RS.GAPDH. The findings of this study can serve as a basis for future studies involving metabolic engineering of CoQ10-producing strains.
Effects of salinomycin and ethanamizuril on the three microbial communities in vivo and in vitro
Authors: Cheng Xiaolei , Zheng Haihong , Wang Chunmei , Wang Xiaoyang , Fei Chenzhong , Zhou Wen , Zhang Keyu
Published: August 2022

The fate of a drug is not only the process of drug metabolism in vivo and in vitro but also the homeostasis of drug-exposed microbial communities may be disturbed. Anticoccidial drugs are widely used to combat the detrimental effects of protozoan parasites in the poultry industry. Salinomycin and ethanamizuril belong to two different classes of anticoccidial drugs. The effect of salinomycin and ethanamizuril on the microbiota of cecal content, manure compost, and soil remains unknown. Our results showed that although both salinomycin and ethanamizuril treatments suppressed some opportunistic pathogens, they failed to repair the great changes in chicken cecal microbial compositions caused by coccidia infection. Subsequently, the metabolite5 profiling of cecal content by LC-MS/MS analyses confirmed the great impact of coccidia infection on chicken cecum and showed that histidine metabolism may be the main action pathway of salinomycin, and aminoacyl tRNA biosynthesis may be the major regulatory mechanism of ethanamizuril. The microbial community of manure compost showed a mild response to ethanamizuril treatment, but ethanamizuril in soil could promote Actinobacteria reproduction, which may inhibit other taxonomic bacteria. When the soil and manure were exposed to salinomycin, the Proteobacteria abundance of microbial communities showed a significant increase, which suggested that salinomycin may improve the ability of the microbiota to utilize carbon sources. This hypothesis was confirmed by a BIOLOG ECO microplate analysis. In the animal model of coccidia infection, the treatment of salinomycin and ethanamizuril may reconstruct a new equilibrium of the intestinal microbiota. In an in vitro environment, the effect of ethanamizuril on composting and soil microbiota seems to be slight. However, salinomycin has a great impact on the microbial communities of manure composting and soil. In particular, the promoting effect of salinomycin on Proteobacteria phylum should be further concerned. In general, salinomycin and ethanamizuril have diverse effects on various microbial communities.
Genomic and phenotypic characterization of Streptococcus mutans isolates suggests key gene clusters in regulating its interaction with Streptococcus gordonii
Authors: Liu Shanshan , Sun Yu , Liu Yudong , Hu Fuyong , Xu Li , Zheng Qingwei , Wang Qinglong , Zeng Guojin , Zhang Kai
Published: August 2022

Streptococcus mutans (S. mutans) is one of the primary pathogens responsible for dental caries. Streptococcus gordonii (S. gordonii) is one of the early colonizers of dental plaque and can compete with S. mutans for growth. In the present analysis, we explored key target genes against S. gordonii in S. mutans using 80 S. mutans clinical isolates with varying capabilities against S. gordonii. A principal coordinate analysis revealed significant genetic diversity differences between antagonistic and non-antagonistic groups. Genomic comparisons revealed 33 and 61 genes that were, respectively, positively and negatively correlated with S. mutans against S. gordonii, with RNA-sequencing (RNA-seq) highlighting 11 and 43 genes that were, respectively, upregulated and downregulated in the antagonistic group. Through a combination of these results and antiSMASH analysis, we selected 16 genes for qRT-PCR validation in which the expression levels of SMU_137 (malate dehydrogenase, mleS), SMU_138 (malate permease, mleP), SMU_139 (oxalate decarboxylase, oxdC), and SMU_140 (glutathione reductase) were consistent with RNA-seq results. SMU_1315c-1317c (SMU_1315c transport-related gene) and SMU_1908c-1909c were, respectively, downregulated and upregulated in the antagonistic group. The expression patterns of adjacent genes were closely related, with correlation coefficient values greater than 0.9. These data reveal new targets (SMU_137–140, SMU_1315c-1317c, and SMU_1908c-1909c) for investigating the critical gene clusters against S. gordonii in S. mutans clinical isolates.
Natural products from traditional medicine as promising agents targeting at different stages of oral biofilm development
Authors: Chi Yaqi , Wang Ye , Ji Mengzhen , Li Yanyao , Zhu Hualing , Yan Yujia , Fu Di , Zou Ling , Ren Biao
Published: August 2022

Oral cavity is an ideal habitat for more than 1,000 species of microorganisms. The diverse oral microbes form biofilms over the hard and soft tissues in the oral cavity, affecting the oral ecological balance and the development of oral diseases, such as caries, apical periodontitis, and periodontitis. Currently, antibiotics are the primary agents against infectious diseases; however, the emergence of drug resistance and the disruption of oral microecology have challenged their applications. The discovery of new antibiotic-independent agents is a promising strategy against biofilm-induced infections. Natural products from traditional medicine have shown potential antibiofilm activities in the oral cavity with high safety, cost-effectiveness, and minimal adverse drug reactions. Aiming to highlight the importance and functions of natural products from traditional medicine against oral biofilms, here we summarized and discussed the antibiofilm effects of natural products targeting at different stages of the biofilm formation process, including adhesion, proliferation, maturation, and dispersion, and their effects on multi-species biofilms. The perspective of antibiofilm agents for oral infectious diseases to restore the balance of oral microecology is also discussed.
Metabolic responses of thermophilic endospores to sudden heat-induced perturbation in marine sediment samples
Authors: Chakraborty Anirban , Rattray Jayne E. , Drake Sienna S. , Matthews Stuart , Li Carmen , Jørgensen Bo Barker , Hubert Casey R. J.
Published: August 2022

Microbially mediated processes in a given habitat tend to be catalyzed by abundant populations that are ecologically adapted to exploit specific environmental characteristics. Typically, metabolic activities of rare populations are limited but may be stimulated in response to acute environmental stressors. Community responses to sudden changes in temperature and pressure can include suppression and activation of different populations, but these dynamics remain poorly understood. The permanently cold ocean floor hosts countless low-abundance microbes including endospores of thermophilic bacteria. Incubating sediments at high temperature resuscitates viable spores, causing the proliferation of bacterial populations. This presents a tractable system for investigating changes in a microbiome's community structure in response to dramatic environmental perturbations. Incubating permanently cold Arctic fjord sediments at 50°C for 216 h with and without volatile fatty acid amendment provoked major changes in community structure. Germination of thermophilic spores from the sediment rare biosphere was tracked using mass spectrometry-based metabolomics, radiotracer-based sulfate reduction rate measurements, and high-throughput 16S rRNA gene sequencing. Comparing community similarity at different intervals of the incubations showed distinct temporal shifts in microbial populations, depending on organic substrate amendment. Metabolite patterns indicated that amino acids and other sediment-derived organics were decomposed by fermentative Clostridia within the first 12–48 h. This fueled early and late phases of exponential increases in sulfate reduction, highlighting the cross-feeding of volatile fatty acids as electron donors for different sulfate-reducing Desulfotomaculia populations. The succession of germinated endospores triggered by sudden exposure to high temperature and controlled by nutrient availability offers a model for understanding the ecological response of dormant microbial communities following major environmental perturbations.
Manure applications alter the abundance, community structure and assembly process of diazotrophs in an acidic Ultisol
Authors: Lin Yongxin , Ye Guiping , Hu Hang-Wei , Fan Jianbo , He Ji-Zheng
Published: August 2022

The excessive usage of nitrogen (N) fertilizers can accelerate the tendency of global climate change. Biological N fixation by diazotrophs contributes substantially to N input and is a viable solution to sustainable agriculture via reducing inorganic N fertilization. However, how manure application influences the abundance, community structure and assembly process of diazotrophs in soil aggregates is not fully understood. Here, we investigated the effect of manure amendment on diazotrophic communities in soil aggregates of an arable soil. Manure application increased soil aggregation, crop yield and the abundance of nifH genes. The abundance of nifH genes increased with aggregate sizes, indicating that diazotrophs prefer to live in larger aggregates. The abundance of nifH genes in large macroaggregates, rather than in microaggregates and silt and clay, was positively associated with plant biomass and crop yield. Both manure application and aggregate size did not alter the Shannon diversity of diazotrophs but significantly changed the diazotrophic community structure. The variation of diazotrophic community structure explained by manure application was greater than that by aggregate size. Manure application promoted the relative abundance of Firmicutes but reduced that of α-Proteobacteria. Stochastic processes played a dominant role in the assembly of diazotrophs in the control treatment. Low-rate manure (9 Mg ha−1) application, rather than medium-rate (18 Mg ha−1) and high-rate (27 Mg ha−1) manure, significantly increased the relative importance of deterministic processes in diazotrophic community assembly. Taken together, our findings demonstrated that long-term manure application increased nifH gene abundance and altered the community structure and assembly process of diazotrophs in soil aggregates, which advanced our understanding of the ecophysiology and functionality of diazotrophs in acidic Ultisols.
Osmotic stress tolerance and transcriptome analysis of Gluconobacter oxydans to extra-high titers of glucose
Authors: Liu Xinlu , Wang Zhiwei , Xiao Jianjian , Zhou Xin , Xu Yong
Published: August 2022

Gluconobacter oxydans has been widely acknowledged as an ideal strain for industrial bio-oxidations with fantastic yield and productivity. Even 600 g/L xylose can be catalyzed efficiently in a sealed and compressed oxygen-supplying bioreactor. Therefore, the present study seeks to explore the osmotic stress tolerance against extra-high titer of representative lignocellulosic sugars like glucose. Gluconobacter oxydans can well adapted and fermented with initial 600 g/L glucose, exhibiting the highest bio-tolerance in prokaryotic strains and the comparability to the eukaryotic strain of Saccharomyces cerevisiae. 1,432 differentially expressed genes corresponding to osmotic pressure are detected through transcriptome analysis, involving several genes related to the probable compatible solutes (trehalose and arginine). Gluconobacter oxydans obtains more energy by enhancing the substrate-level phosphorylation, resulting in the increased glucose consumption rate after fermentation adaption phase. This study will provide insights into further investigation of biological tolerance and response to extra-high titers of glucose of G. oxydans.
Investigating the role of GLUL as a survival factor in cellular adaptation to glutamine depletion via targeted stable isotope resolved metabolomics
Authors: Bayram Șafak , Razzaque Yasmin Sophiya , Geisberger Sabrina , Pietzke Matthias , Fürst Susanne , Vechiatto Carolina , Forbes Martin , Mastrobuoni Guido , Kempa Stefan
Published: August 2022

Cellular glutamine synthesis is thought to be an important resistance factor in protecting cells from nutrient deprivation and may also contribute to drug resistance. The application of ‟targeted stable isotope resolved metabolomics” allowed to directly measure the activity of glutamine synthetase in the cell. With the help of this method, the fate of glutamine derived nitrogen within the biochemical network of the cells was traced. The application of stable isotope labelled substrates and analyses of isotope enrichment in metabolic intermediates allows the determination of metabolic activity and flux in biological systems. In our study we used stable isotope labelled substrates of glutamine synthetase to demonstrate its role in the starvation response of cancer cells. We applied 13C labelled glutamate and 15N labelled ammonium and determined the enrichment of both isotopes in glutamine and nucleotide species. Our results show that the metabolic compensatory pathways to overcome glutamine depletion depend on the ability to synthesise glutamine via glutamine synthetase. We demonstrate that the application of dual-isotope tracing can be used to address specific reactions within the biochemical network directly. Our study highlights the potential of concurrent isotope tracing methods in medical research.
Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects
Authors: Zighan Madleen , Arkadir David , Douiev Liza , Keller Guy , Miller Chaya , Saada Ann
Published: August 2022

Omaveloxolone (RTA408) is a second-generation oleanane triterpenoid Nrf2 inducer with antioxidant and anti-inflammatory properties and was reported to improve mitochondrial bioenergetics. It is currently being tested in medical trials for Friedrich ataxia, a genetic, multi-organ disease involving mitochondrial dysfunction. Thus, omaveloxolone could potentially be beneficial for additional disorders involving mitochondrial dysfunction. To this end, we investigated its effect on primary fibroblasts derived from patients with mitochondrial complex I deficiency, mitochondrial cytochrome oxidase deficiency, and two recessive forms of Parkinson’s disease. Patients and control cells were incubated in the presence or absence of 50 nM omaveloxolone for 72 h prior to measurements. Generally, growth on galactose medium and ATP production were unaltered. Mitochondrial membrane potential was slightly but significantly decreased, while reactive oxygen species (ROS) production was variably decreased. Mitochondrial mass and mitochondrial DNA (mtDNA) contents were significantly increased in the patient’s cells. These results were partially confirmed by the results of oxygen consumption studies which disclosed increased maximal oxygen consumption rates in most cells and increased energy status in all treated cells. Further investigation is required to explore the precise effect of omaveloxolone on mitochondrial function in disease.
Improve the Colorectal Cancer Diagnosis Using Gut Microbiome Data
Authors: Zhou Yi-Hui , Sun George
Published: August 2022

In the United States, colorectal cancer is the second largest cause of cancer death, and accurate early detection and identification of high-risk patients is a high priority. Although fecal screening tests are available, the close relationship between colorectal cancer and the gut microbiome has generated considerable interest. We describe a machine learning method for gut microbiome data to assist in diagnosing colorectal cancer. Our methodology integrates feature engineering, mediation analysis, statistical modeling, and network analysis into a novel unified pipeline. Simulation results illustrate the value of the method in comparison to existing methods. For predicting colorectal cancer in two real datasets, this pipeline showed an 8.7% higher prediction accuracy and 13% higher area under the receiver operator characteristic curve than other published work. Additionally, the approach highlights important colorectal cancer-related taxa for prioritization, such as high levels of Bacteroides fragilis, which can help elucidate disease pathology. Our algorithms and approach can be widely applied for Colorectal cancer prediction using either 16 S rRNA or shotgun metagenomics data.