bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral flow cytometry cluster analysis of therapeutic donor lymphocyte infusions identifies T cell subsets associated with outcome in patients with AML relapse
Authors: Odak Ivan , Sikora Ruth , Riemann Lennart , Bayir Lâle M. , Beck Maleen , Drenker Melanie , Xiao Yankai , Schneider Jessica , Dammann Elke , Stadler Michael , Eder Matthias , Ganser Arnold , Förster Reinhold , Koenecke Christian , Schultze-Florey Christian R.
Published: October 2022

Identification of immune phenotypes linked to durable graft-versus-leukemia (GVL) response following donor lymphocyte infusions (DLI) is of high clinical relevance. In this prospective observational study of 13 AML relapse patients receiving therapeutic DLI, we longitudinally investigated changes in differentiation stages and exhaustion markers of T cell subsets using cluster analysis of 30-color spectral flow cytometry during 24 months follow-up. DLI cell products and patient samples after DLI were analyzed and correlated to the clinical outcome. Analysis of DLI cell products revealed heterogeneity in the proportions of naïve and antigen experienced T cells. Cell products containing lower levels of effector memory (eff/m) cells and higher amounts of naïve CD4+ and CD8+ T cells were associated with long-term remission. Furthermore, investigation of patient blood samples early after DLI showed that patients relapsing during the study period, had higher levels of CD4+ eff/m T cells and expressed a mosaic of surface molecules implying an exhausted functional state. Of note, this observation preceded the clinical diagnosis of relapse by five months. On the other hand, patients with continuous remission retained lower levels of exhausted CD4+ eff/m T cells more than four months post DLI. Moreover, lower frequencies of exhausted CD8+ eff/m T cells as well as higher amounts of CD4+temra CD45RO+ T cells were present in this group. These results imply the formation of functional long-term memory pool of T cells. Finally, unbiased sample analysis showed that DLI cell products with low levels of eff/m cells both in CD4+ and CD8+ T cell subpopulations associate with a lower relapse incidence. Additionally, competing risk analysis of patient samples taken early after DLI revealed that patients with high amounts of exhausted CD4+ eff/m T cells in their blood exhibited significantly higher rates of relapse. In conclusion, differentially activated T cell clusters, both in the DLI product and in patients post infusion, were associated with AML relapse after DLI. Our study suggests that differences in DLI cell product composition might influence GVL. In-depth monitoring of T cell dynamics post DLI might increase safety and efficacy of this immunotherapy, while further studies are needed to assess the functionality of T cells found in the DLI.
Feeding strategy trade-off and selection of marine nocturnal gastropods under predation risk
Authors: Lin Shihui , Gao Xiaolong , Zhang Mo , Lyu Mingxin , Ke Caihuan
Published: October 2022

The circadian rhythm is one of the most crucial and universal biological rhythms in living organisms. As a typical nocturnal creature, the Pacific abalone (Haliotis discus hannai) exhibits rhythmic behaviors in terms of passively selecting whether to avoid predators or to forage, and active adaptation to light cycle changes is regulated by the biological clock. However, no basic data are available to help us to understand these rhythmic behaviors in the abalone species. In the present study, quantification of behavioral data for the abalone and its predator swimming crab Portunus trituberculatus in short-term (24 h) and long-term (40 days) polyculture scenarios suggests that the distance and duration of movement, percentage of feeding individuals, and cumulative duration of feeding of the abalone individuals were significantly lower under the short-term predation risk than the long-term predation risk. The concentrations of 5-hydroxytryptamine (5-HT), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and hexokinase (HK) in hemolymph, and expression levels of 5-HT1A receptor and 5-HT2 receptor in cerebral ganglion were significantly higher under the long-term predation risk than the short-term predation risk. The concentration of lactate dehydrogenase (LDH) and glycogen content in adductor muscle of the abalone was significantly higher under the short-term predation risk than the long-term predation risk, thereby implying their role in anaerobic metabolism and aerobic metabolism as primary energy sources under the short-term and long-term predation risk, respectively. The concentrations of 5-HT and cAMP, and the expression levels of Bmal1 and 5-HT2 receptor exhibited no significant signs of cosine rhythmicity under the short-term predation risk, but changes in the movement and feeding behaviors of the abalone still occurred at the night only. Correlation analysis shows that the expression levels of Bmal1 and Clock had significantly positive correlations with the circadian changes in the movement parameters of the abalone, thereby suggesting a dominant role in the rhythmic expression of endogenous circadian clock genes regulating the rhythmic behavior of the abalone. These findings provide new insights into the origin and evolution of biological rhythms in nocturnal marine animals and a reference for developing rational stock enhancement plans, and would improve protection for marine benthic biodiversity.
Metabolic trade-offs associated with homeostatic adjustments in pelagic and benthic cephalopods: Comparative evaluations of NH4+/H+ transport machinery in gills
Authors: Lin Meng-Wei , Kuan Pou-Long , Sung Po-Hsuan , Tseng Yung-Che
Published: October 2022

Cephalopods are ancient mollusks that can be found in many different ecological niches in the ocean ranging from the intertidal zone to the deep-sea abyss. In order to adapt to a lifestyle in various habitats, cephalopods have evolved a variety of locomotory modes to accommodate their respective habitats. Most cephalopods have relatively high metabolic rates due to their less efficient swimming mode by jet propulsion. This lifestyle is characterized by a high level of energy expenditure, fueled exclusively by protein diets that are rapidly digested and may produce metabolic nitrogenous waste NH3/NH4 +accumulation and acid-base disturbances. This study observed that the NH4 +transport rate in pelagic bigfin reef squid (Sepioteuthis lessoniana) is two times faster than benthic common octopus (Octopus vulgaris). Inhibition of Na+/H+ exchangers (NHEs) showed significant disruption of NH4 + and H+ excretory processes in gills of octopus but not in squid. However, inhibition of vacuolar-type H+-ATPase (VHA) significantly disrupts NH4 + and H+ transport rates in gills of both animals. Accordingly, for NH4 + and H+ homeostasis, benthic octopus with lower aerobic respiration rates utilize both active and Na+-driven secondary transport machinery. In order to avoid NH4 + accumulated in the blood, pelagic squids with higher aerobic respiration rates prefer active NH4 + and H+ transport mechanisms that consume ATP intensively.
Value of transbronchial needle aspiration combined with a rapid on-site evaluation of cytology in the diagnosis of pulmonary lesions
Authors: Liang Long , Duan Hongxia , Zhu Huiyuan , Yang Huiqiong , Li Xuan , Wang Changhui , Xie Shuanshuan
Published: October 2022

Background

The diagnostic value of rapid on-site evaluation (ROSE) of cytology during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains controversial. The purpose of this study was to validate the value of ROSE during the EUBS-TBNA procedure in the diagnosis of pulmonary lesions (PLs).

Methods

Enrolled in this study were 260 patients with nodules, masses, cavities, or inflammatory lesions on pulmonary CT images. They were assigned to undergo EBUS-TBNA with ROSE (n = 134) or without ROSE (n = 126). The diagnostic results of ROSE during EBUS-TBNA and the final pathologic reports were analyzed and compared by utilizing SPSS21.0 software to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we further explored whether the ROSE method during EBUS-TBNA would improve the diagnostic yield and reduce the incidence of complications.

Results

The overall diagnostic yield of EBUS-TBNA for malignant diseases in the ROSE and the non-ROSE group were 29.9 and 11.1%, respectively. The sensitivity, specificity, PPV and NPV of the ROSE method during EBUS-TBNA were 97.4, 96.9, 92.5, and 98.90%, respectively. The result of the chi-square test effectively proved that ROSE operation during EBUS-TBNA contributes to the diagnosis of malignancy compared with the non-ROSE group (χ2 = 13.858, P < 0.001). The number of punctures in the ROSE group was significantly lower than that in the non-ROSE group (P < 0.001).

Conclusion

ROSE examination during EBUS-TBNA could effectively improve the diagnostic yield of malignant diseases compared with the non-ROSE group and reduce the number of intraoperative punctures, which is a clinical application worth popularizing.
Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose
Authors: Zhu Jing , Pan Fei , Cai Huawei , Pan Lili , Li Yalun , Li Lin , Li YunChun , Wu Xiaoai , Fan Hong
Published: October 2022

Lung cancer has been the leading cause of cancer-related mortality in China in recent decades. Positron emission tomography-computer tomography (PET/CT) has been established in the diagnosis of lung cancer. 18F-FDG is the most widely used PET tracer in foci diagnosis, tumor staging, treatment planning, and prognosis assessment by monitoring abnormally exuberant glucose metabolism in tumors. However, with the increasing knowledge on tumor heterogeneity and biological characteristics in lung cancer, a variety of novel radiotracers beyond 18F-FDG for PET imaging have been developed. For example, PET tracers that target cellular proliferation, amino acid metabolism and transportation, tumor hypoxia, angiogenesis, pulmonary NETs and other targets, such as tyrosine kinases and cancer-associated fibroblasts, have been reported, evaluated in animal models or under clinical investigations in recent years and play increasing roles in lung cancer diagnosis. Thus, we perform a comprehensive literature review of the radiopharmaceuticals and recent progress in PET tracers for the study of lung cancer biological characteristics beyond glucose metabolism.
Ephedrine vs. phenylephrine effect on sublingual microcirculation in elderly patients undergoing laparoscopic rectal cancer surgery
Authors: Zhang Yanbing , Jin Limin , Liu Huayue , Meng Xiaowen , Ji Fuhai
Published: October 2022

Background

The effects of anesthesia administration on sublingual microcirculation are unknown. It is unclear how sublingual microcirculation responds to ephedrine or phenylephrine administration. We hypothesized that microvascular perfusion is impaired under anesthesia.

Materials and methods

We randomly divided 100 elderly patients undergoing laparoscopic rectal cancer surgery into phenylephrine and ephedrine groups in a 1:1 ratio. Ephedrine or phenylephrine was administered when MAP was < 80% for > 1 min. The heart rate (HR) and mean arterial pressure (MAP) were recorded every 5 min. Lactic acid was tested both pre- and postoperatively. The sublingual microcirculation characteristics of the microvascular flow index, the percentage of perfused vessels, the density of perfused vessels, and the heterogeneity index were monitored using a sidestream dark field imaging device.

Results

Their MAP showed an evident decrease of > 20%. At this point, the HR, microvascular flow index, perfused vessel density, and proportion of perfused vessels decreased similarly in ephedrine and phenylephrine groups. Conversely, the heterogeneity index increased in both groups. After phenylephrine and ephedrine administration, ephedrine treatment significantly increased the proportion of perfused vessels, microvascular flow index, and HR compared with phenylephrine treatment.

Conclusion

General anesthesia was associated with reduced MAP, HR, and sublingual microcirculation in elderly patients undergoing laparoscopic rectal cancer surgery. The results of ephedrine treatment were better than those of phenylephrine treatment in terms of HR, increased the proportion of perfused vessels, and microvascular flow index of sublingual microcirculation.

Clinical trial registration

[www.ClinicalTrials.gov], identifier [ChiCTR-2000035959].
Unsupervised clustering reveals phenotypes of AKI in ICU COVID-19 patients
Authors: Legouis David , Criton Gilles , Assouline Benjamin , Le Terrier Christophe , Sgardello Sebastian , Pugin Jérôme , Marchi Elisa , Sangla Frédéric
Published: October 2022

Background

Acute Kidney Injury (AKI) is a very frequent condition, occurring in about one in three patients admitted to an intensive care unit (ICU). AKI is a syndrome defined as a sudden decrease in glomerular filtration rate. However, this unified definition does not reflect the various mechanisms involved in AKI pathophysiology, each with its own characteristics and sensitivity to therapy. In this study, we aimed at developing an innovative machine learning based method able to subphenotype AKI according to its pattern of risk factors.

Methods

We adopted a three-step pipeline of analyses. First, we looked for factors associated with AKI using a generalized additive model. Second, we calculated the importance of each identified AKI related factor in the estimated AKI risk to find the main risk factor for AKI, at the single patient level. Lastly, we clusterized AKI patients according to their profile of risk factors and compared the clinical characteristics and outcome of every cluster. We applied this method to a cohort of severe COVID-19 patients hospitalized in the ICU of the Geneva University Hospitals.

Results

Among the 248 patients analyzed, we found 7 factors associated with AKI development. Using the individual expression of these factors, we identified three groups of AKI patients, based on the use of Lopinavir/Ritonavir, baseline eGFR, use of dexamethasone and AKI severity. The three clusters expressed distinct characteristics in terms of AKI severity and recovery, metabolic patterns and hospital mortality.

Conclusion

We propose here a new method to phenotype AKI patients according to their most important individual risk factors for AKI development. When applied to an ICU cohort of COVID-19 patients, we were able to differentiate three groups of patients. Each expressed specific AKI characteristics and outcomes, which probably reflect a distinct pathophysiology.
D-dimer levels and characteristics of lymphocyte subsets, cytokine profiles in peripheral blood of patients with severe COVID-19: A systematic review and meta-analysis
Authors: Zhang Haiyue , Wu Huajun , Pan Dongli , Shen Weifeng
Published: October 2022

Purpose

A series of complications caused by severe COVID-19 can significantly affect short-term results. Therefore, early diagnosis is essential for critically COVID-19 patients. we aimed to investigate the correlation among D-dimer levels, lymphocyte subsets, cytokines, and disease severity in COVID-19 patients.

Methods

Systematic review and meta- analysis of PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Embase, clinical trials, and China National Knowledge Infrastructure (CNKI) until 1 August 2022. We considered case-control, and cohort studies that compared laboratory parameters between patients with severe or non-serious diseases or between survivors and non-survivors. Pooled data was assessed by use of a random-effects model and used I2 to test heterogeneity. We assessed the risk of bias using the Newcastle- Ottawa Scale.

Results

Of the 5,561 identified studies, 32 were eligible and included in our analysis (N = 3,337 participants). Random-effect results indicated that patients with COVID-19 in severe group had higher levels for D-dimer (WMD = 1.217 mg/L, 95%CI=[0.788, 1.646], P < 0.001), neutrophil-to-lymphocyte ratio (NLR) (WMD = 6.939, 95%CI = [4.581, 9.297], P < 0.001), IL-2 (WMD = 0.371 pg/ml, 95%CI = [−0.190, 0.932], P = 0.004), IL-4 (WMD = 0.139 pg/ml, 95%CI = [0.060, 0.219], P = 0.717), IL-6 (WMD = 44.251 pg/ml, 95%CI = [27.010, 61.493], P < 0.001), IL-10 (WMD = 3.718 pg/ml, 95%CI = [2.648, 4.788], P < 0.001) as well as lower levels of lymphocytes (WMD = −0.468( × 109/L), 95%CI = [−0.543, −0.394], P < 0.001), T cells (WMD = −446.746(/μL), 95%CI = [−619.607, −273.885], P < 0.001), B cells (WMD = −60.616(/μL), 95%CI = [−96.452, −24.780], P < 0.001), NK cells (WMD = −68.297(/μL), 95%CI = [−90.600, −45.994], P < 0.001), CD3+T cells (WMD = −487.870(/μL), 95%CI = [−627.248, −348.492], P < 0.001), CD4+T cells (WMD = −290.134(/μL), 95%CI = [−370.834, −209.435], P < 0.001), CD8+T cells (WMD = −188.781(/μL), 95%CI = [−227.806, −149.757], P < 0.001).

Conclusions

There is a correlation among higher levels of D-dimer, cytokines, lower levels of lymphocyte subsets, and disease severity in COVID-19 patients. These effective biomarkers may help clinicians to evaluate the severity and prognosis of COVID-19. This study is registered with PROSPERO, number CRD42020196659.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=196659; PROSPERO registration number: CRD42020196659.
Subdiaphragmatic bronchogenic cysts: Case series and literature review
Authors: Xiao Jianchun , Zhang Xueyang , Zhou Hongru , Hong Tao , Li Binglu , He Xiaodong , Liu Wei
Published: October 2022

Bronchogenic cysts are congenital malformations caused by aberrant foregut budding. They major occur in the thorax, with subdiaphragmatic cases being uncommon. Here, we present a series of 19 patients diagnosed with subdiaphragmatic bronchogenic cysts histopathologically at a single institution in China from 2012 to 2021. A literature review was also conducted by searching the PubMed database using keywords related to “bronchogenic cysts” and “subdiaphragmatic,” yielding 107 cases. Taken together, the 126 cases had a median age of 41.0 years (interquartile range, 30.0–51.0 years) and 62 of them were male (49.2%). The cysts were most commonly detected in the left adrenal region (36.2%), followed by the pancreatic region (11.5%) and gastric cardia/lesser curvature of the stomach (9.2%). All patients except two underwent surgery for a definite diagnosis, symptom alleviation, and (or) malignancy prevention. Most patients recovered fast and were discharged from the hospital within 1 week after surgery, and the surgical complications were infrequent. The prognosis was generally favorable, as no recurrence was reported during the follow-up as long as 77 months.
SARS-CoV-2 variants impact RBD conformational dynamics and ACE2 accessibility
Authors: Valério Mariana , Borges-Araújo Luís , Melo Manuel N. , Lousa Diana , Soares Cláudio M.
Published: October 2022

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed over 6 million people and is having a devastating social and economic impact around the world. The rise of new variants of concern (VOCs) represents a difficult challenge due to the loss of vaccine and natural immunity, as well as increased transmissibility. All VOCs contain mutations in the spike glycoprotein, which mediates fusion between the viral and host cell membranes. The spike glycoprotein binds to angiotensin-converting enzyme 2 (ACE2) via its receptor binding domain (RBD) initiating the infection process. Attempting to understand the effect of RBD mutations in VOCs, a lot of attention has been given to the RBD-ACE2 interaction. However, this type of analysis ignores more indirect effects, such as the conformational dynamics of the RBD itself. Observing that some mutations occur in residues that are not in direct contact with ACE2, we hypothesized that they could affect the RBD conformational dynamics. To test this, we performed long atomistic (AA) molecular dynamics (MD) simulations to investigate the structural dynamics of wt RBD, and that of four VOCs (Alpha, Beta, Delta, and Omicron). Our results show that the wt RBD presents two distinct conformations: an “open” conformation where it is free to bind ACE2; and a “closed” conformation, where the RBM ridge blocks the binding surface. The Alpha and Beta variants shift the open/closed equilibrium towards the open conformation by roughly 20%, likely increasing ACE2 binding affinity. Simulations of the Delta and Omicron variants showed extreme results, with the closed conformation being rarely observed. The Delta variant also differed substantially from the other variants, alternating between the open conformation and an alternative “reversed” one, with a significantly changed orientation of the RBM ridge. This alternate conformation could provide a fitness advantage due to increased availability for ACE2 binding, and by aiding antibody escape through epitope occlusion. These results support the hypothesis that VOCs, and particularly the Omicron and Delta variants, impact RBD conformational dynamics in a direction that promotes efficient binding to ACE2 and, in the case of Delta, may assist antibody escape.
Comparative Metabolic Pathways Analysis and Subtractive Genomics Profiling to Prioritize Potential Drug Targets Against Streptococcus pneumoniae
Authors: Khan Kanwal , Jalal Khurshid , Khan Ajmal , Al-Harrasi Ahmed , Uddin Reaz
Published: October 2022

Graphical Abstract
Green synthesis of biogenetic Te(0) nanoparticles by high tellurite tolerance fungus Mortierella sp. AB1 with antibacterial activity
Authors: Ao Bo , He Fei , Lv Jing , Tu Junming , Tan Zheng , Jiang Honglin , Shi Xiaoshan , Li Jingjing , Hou Jianjun , Hu Yuanliang , Xia Xian
Published: October 2022

Tellurite [Te(IV)] is a high-toxicity metalloid. In this study, a fungus with high Te(IV) resistance was isolated. Strain AB1 could efficiently reduce highly toxic Te(IV) to less toxic Te(0). The reduced products formed rod-shaped biogenetic Te(0) nanoparticles (Bio-TeNPs) intracellularly. Further TEM-element mapping, FTIR, and XPS analysis showed that the extracted Bio-TeNPs ranged from 100 to 500 nm and consisted of Te(0), proteins, lipids, aromatic compounds, and carbohydrates. Moreover, Bio-TeNPs exhibited excellent antibacterial ability against Shigella dysenteriae, Escherichia coli, Enterobacter sakazakii, and Salmonella typhimurium according to inhibition zone tests. Further growth and live/dead staining experiments showed that E. coli and S. typhimurium were significantly inhibited by Bio-TeNPs, and cells were broken or shriveled after treatment with Bio-TeNPs based on SEM observation. Additionally, the antioxidant and cytotoxicity tests showed that the Bio-TeNPs exhibited excellent antioxidant capacity with no cytotoxicity. All these results suggested that strain AB1 showed great potential in bioremediation and Bio-TeNPs were excellent antibacterial nanomaterials with no cytotoxicity.
Enterovirus 71 non-structural protein 3A hijacks vacuolar protein sorting 25 to boost exosome biogenesis to facilitate viral replication
Authors: Ruan Zhihui , Liang Yicong , Chen Zicong , Yin Jialing , Li Chengcheng , Pan Pan , Zhang Qiwei , Wu Jianguo , Luo Zhen
Published: October 2022

Human enterovirus 71 (EV71) is one of the major agents of the hand, foot, and mouth disease (HFMD), and occasionally causes severe neurological complications. There is clinical evidence that EV71 infection increases the exosomes in the serum of severe HFMD patients, suggesting a role of exosomes in EV71 pathogenesis. However, the relationship between exosomes and EV71 replication remains elusive. In this study, we initially found that EV71 infection elevated exosome biogenesis in the cultured cells. Among EV71 non-structural proteins, we identified EV71 3A, but not 3B, constitutively promoted exosome secretion. In detail, EV71 3A protein interacted with vacuolar protein sorting 25 (VPS25), while knock-down of VPS25 reduced EV71 3A protein- and EV71-induced exosome production. Further studies revealed VPS25 located on exosomes and its expression correlated to the exosome production. During EV71 infection, knock-down of VPS25 decreased exosome biogenesis to attenuate viral replication. Consistently, GW4869, an exosome inhibitor, exerted an obviously antiviral activity against EV71 replication companied with the decrease of exosome secretion or formation. These findings suggest the binding of EV71 3A and VPS25 benefited exosome biogenesis, thereby boosting viral replication. This study uncovers a novel mechanism underlying EV71-mediated exosomes in the regulation of viral replication, which provides potential anti-viral strategies against the EV71 infection and transmission in HFMD.
Metatranscriptomic and metataxonomic insights into the ultra-small microbiome of the Korean fermented vegetable, kimchi
Authors: Lee Hae-Won , Yoon So-Ra , Dang Yun-Mi , Yun Ji-Hyun , Jeong Hoibin , Kim Kil-Nam , Bae Jin-Woo , Ha Ji-Hyoung
Published: October 2022

Presently, pertinent information on the ultra-small microbiome (USM) in fermented vegetables is still lacking. This study analyzed the metatranscriptome and metataxonome for the USM of kimchi. Tangential flow filtration was used to obtain a USM with a size of 0.2 μm or less from kimchi. The microbial diversity in the USM was compared with that of the normal microbiome (NM). Alpha diversity was higher in the USM than in NM, and the diversity of bacterial members of the NM was higher than that of the USM. At the phylum level, both USM and NM were dominated by Firmicutes. At the genus level, the USM and NM were dominated by Lactobacillus, Leuconostoc, and Weissella, belonging to lactic acid bacteria. However, as alpha diversity is higher in the USM than in the NM, the genus Akkermansia, belonging to the phylum Verrucomicrobia, was detected only in the USM. Compared to the NM, the USM showed a relatively higher ratio of transcripts related to “protein metabolism,” and the USM was suspected to be involved with the viable-but-nonculturable (VBNC) state. When comparing the sub-transcripts related to the “cell wall and capsule” of USM and NM, USM showed a proportion of transcripts suspected of being VBNC. In addition, the RNA virome was also identified, and both the USM and NM were confirmed to be dominated by pepper mild mottle virus (PMMoV). Additionally, the correlation between metataxonome and metatranscriptome identified USM and NM was estimated, however, only limited correlations between metataxonome and metatranscriptome were estimated. This study provided insights into the relationship between the potential metabolic activities of the USM of kimchi and the NM.
Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome
Authors: Mesnage Robin , Panzacchi Simona , Bourne Emma , Mein Charles A. , Perry Melissa J. , Hu Jianzhong , Chen Jia , Mandrioli Daniele , Belpoggi Fiorella , Antoniou Michael N.
Published: October 2022

The potential health consequences of glyphosate-induced gut microbiome alterations have become a matter of intense debate. As part of a multifaceted study investigating toxicity, carcinogenicity and multigenerational effects of glyphosate and its commercial herbicide formulations, we assessed changes in bacterial and fungal populations in the caecum microbiota of rats exposed prenatally until adulthood (13 weeks after weaning) to three doses of glyphosate (0.5, 5, 50 mg/kg body weight/day), or to the formulated herbicide products Roundup Bioflow and RangerPro at the same glyphosate-equivalent doses. Caecum bacterial microbiota were evaluated by 16S rRNA sequencing whilst the fungal population was determined by ITS2 amplicon sequencing. Results showed that both fungal and bacterial diversity were affected by the Roundup formulations in a dose-dependent manner, whilst glyphosate alone significantly altered only bacterial diversity. At taxa level, a reduction in Bacteroidota abundance, marked by alterations in the levels of Alloprevotella, Prevotella and Prevotellaceae UCG-003, was concomitant to increased levels of Firmicutes (e.g., Romboutsia, Dubosiella, Eubacterium brachy group or Christensenellaceae) and Actinobacteria (e.g., Enterorhabdus, Adlercreutzia, or Asaccharobacter). Treponema and Mycoplasma also had their levels reduced by the pesticide treatments. Analysis of fungal composition indicated that the abundance of the rat gut commensal Ascomycota Kazachstania was reduced while the abundance of Gibberella, Penicillium, Claviceps, Cornuvesica, Candida, Trichoderma and Sarocladium were increased by exposure to the Roundup formulations, but not to glyphosate. Altogether, our data suggest that glyphosate and its Roundup RangerPro and Bioflow caused profound changes in caecum microbiome composition by affecting the fitness of major commensals, which in turn reduced competition and allowed opportunistic fungi to grow in the gut, in particular in animals exposed to the herbicide formulations. This further indicates that changes in gut microbiome composition might influence the long-term toxicity, carcinogenicity and multigenerational effects of glyphosate-based herbicides.
Complete genome sequencing and in silico genome mining reveal the promising metabolic potential in Streptomyces strain CS-7
Authors: Alam Khorshed , Hao Jinfang , Zhong Lin , Fan Guoqing , Ouyang Qing , Islam Md. Mahmudul , Islam Saiful , Sun Hongluan , Zhang Youming , Li Ruijuan , Li Aiying
Published: October 2022

Gram-positive Streptomyces bacteria can produce valuable secondary metabolites. Streptomyces genomes include huge unknown silent natural product (NP) biosynthetic gene clusters (BGCs), making them a potential drug discovery repository. To collect antibiotic-producing bacteria from unexplored areas, we identified Streptomyces sp. CS-7 from mountain soil samples in Changsha, P.R. China, which showed strong antibacterial activity. Complete genome sequencing and prediction in silico revealed that its 8.4 Mbp genome contains a total of 36 BGCs for NPs. We purified two important antibiotics from this strain, which were structurally elucidated to be mayamycin and mayamycin B active against Staphylococcus aureus. We identified functionally a BGC for the biosynthesis of these two compounds by BGC direct cloning and heterologous expression in Streptomyces albus. The data here supported this Streptomyces species, especially from unexplored habitats, having a high potential for new NPs.
Enzymatic properties and biological activity of resuscitation-promoting factor B of Rhodococcus sp. (GX12401)
Authors: Gong Xu , Lu Huijiao , Wu Jiafa , Zhou Yan , Yang Lifang , Wang Yibing , Shen Naikun , Jiang Mingguo
Published: October 2022

Resuscitation-promoting factor B (RpfB) is one of the five members of Rpf-like family in Mycobacteriales, which have the resuscitation-promoting activity. Most strains of Rhodococcus also have RpfB gene, but the study of rpfB gene in Rhodococcus is not thorough. Here, we amplified the rpfB gene of intact Rhodococcus sp. (GX12401) and cloned it into pET30a (+) expression vector. Then a recombinant form of soluble RpfB was expressed in Escherichia coli BL21. The soluble recombinant RpfB was purified by Ni–Sepharose affinity chromatography and molecular weight of the protein was 55 kDa, determined by 12% SDS–PAGE stained with Coomassie brilliant blue R-250. When 4-methylumbelliferyl-β-D-N,N′,N″-triacetylchitoside was used as enzyme substrate to test lysozyme activity, the recombinant protein RpfB had good stability and enzyme activity, and the lysozyme activity was low (4.74 U), among which Mg2+, Na+, Al3+ and DMSO could significantly increase the activity of RpfB. The purified recombinant protein was added to Rhodococcus VBNC cells, and the VBNC cells were resuscitated at the concentration of 1 picomolar concentrations, which increased by 18% compared with the control, while the cell resuscitation was inhibited at the concentration of 1,000 picomolar concentrations. Therefore, RpfB can improve the survival ability of Rhodococcus in extreme or harsh environment and enhance the corresponding biological activity.
Impact of Weissella cibaria BYL4.2 and its supernatants on Penicillium chrysogenum metabolism
Authors: Yao Di , Wang Xiaoyu , Ma Lixue , Wu Mengna , Xu Lei , Yu Qiaoru , Zhang Liyuan , Zheng Xiqun
Published: October 2022

Lactic acid bacteria (LAB) can produce a vast spectrum of antifungal metabolites to inhibit fungal growth. The purpose of this study was to elucidate the antifungal effect of isolated Weissella cibaria BYL4.2 on Penicillium chrysogenum, the antifungal activity of W. cibaria BYL4.2 against P. chrysogenum was evaluated by the superposition method, results showed that it had obviously antifungal activity against P. chrysogenum. Studying the probiotic properties of BYL4.2 and determining it as beneficial bacteria. Furtherly, different treatments were carried out to characterize the antifungal activity of cell-free supernatant (CFS) produced by W. cibaria BYL4.2, and it was shown that the CFS was pH-dependent, partly heat-sensitive, and was not influenced by proteinaceous treatment. The CFS of W. cibaria BYL4.2 was analyzed by high-performance liquid chromatography (HPLC) and found the highest content of lactic acid. Screening of metabolic markers by a non-targeted metabolomics approach based liquid chromatography-mass spectrometry (LC-MS). The results speculated that organic acid especially detected D-tartaric acid was the main antifungal substance of CFS, which could cause the down-regulation of metabolites in the ABC transporters pathway, thereby inhibiting the growth of P. chrysogenum. Therefore, this study may provide important information for the inhibitory mechanism of W. cibaria BYL4.2 on P. chrysogenum, and provide a basis for further research on the antifungal effect of Weissella.
MTDeepM6A-2S: A two-stage multi-task deep learning method for predicting RNA N6-methyladenosine sites of Saccharomyces cerevisiae
Authors: Wang Hong , Zhao Shihao , Cheng Yinchu , Bi Shoudong , Zhu Xiaolei
Published: October 2022

N6-methyladenosine (m6A) is one of the most important RNA modifications, which is involved in many biological activities. Computational methods have been developed to detect m6A sites due to their high efficiency and low costs. As one of the most widely utilized model organisms, many methods have been developed for predicting m6A sites of Saccharomyces cerevisiae. However, the generalization of these methods was hampered by the limited size of the benchmark datasets. On the other hand, over 60,000 low resolution m6A sites and more than 10,000 base resolution m6A sites of Saccharomyces cerevisiae are recorded in RMBase and m6A-Atlas, respectively. The base resolution m6A sites are often obtained from low resolution results by post calibration. In view of these, we proposed a two-stage deep learning method, named MTDeepM6A-2S, to predict RNA m6A sites of Saccharomyces cerevisiae based on RNA sequence information. In the first stage, a multi-task model with convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) deep framework was built to not only detect the low resolution m6A sites but also assign a reasonable probability for the predicted site. In the second stage, a transfer-learning strategy was used to build the model to predict the base resolution m6A sites from those low resolution m6A sites. The effectiveness of our model was validated on both training and independent test sets. The results show that our model outperforms other state-of-the-art models on the independent test set, which indicates that our model holds high potential to become a useful tool for epitranscriptomics analysis.
Lysolipids regulate raft size distribution
Authors: Krasnobaev Vladimir D. , Galimzyanov Timur R. , Akimov Sergey A. , Batishchev Oleg V.
Published: October 2022

The lipid matrix of cellular membranes, directly and indirectly, regulates many vital functions of the cell. The diversity of lipids in membranes leads to the formation of ordered domains called rafts, which play a crucial role in signal transduction, protein sorting and other cellular processes. Rafts are believed to impact the development of different neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s ones, amyotrophic lateral sclerosis, some types of cancer, etc. These diseases correlate with the change in the membrane lipid composition resulting from an oxidative stress, age-related processes, dysfunction of proteins, and many others. In particular, a lot of studies report a significant rise in the level of lysolipids. Physicochemical properties of rafts are determined by membrane composition, in particular, by the content of lysolipids. Lysolipids may thus regulate raft-involving processes. However, the exact mechanism of such regulation is unknown. Although studying rafts in vivo still seems to be rather complicated, liquid-ordered domains are well observed in model systems. In the present study, we used atomic force microscopy (AFM) to examine how lysophospholipids influence the liquid-ordered domains in model ternary membranes. We demonstrated that even a small amount of lysolipids in a membrane significantly impacts domain size depending on the saturation of the lysolipid hydrocarbon tails and the amount of cholesterol. The mixture with the bigger relative fraction of cholesterol was more susceptible to the action of lysolipids. This data helped us to generalize our previous theoretical model of the domain size regulation by lipids with particular molecular shape expanding it to the case of lysolipids and dioleoylglycerol.
Metric magnetic resonance imaging analysis reveals pronounced substantia-innominata atrophy in dementia with Lewy bodies with a psychiatric onset
Authors: Hansen Niels , Müller Sebastian Johannes , Khadhraoui Eya , Riedel Christian Heiner , Langer Philip , Wiltfang Jens , Timäus Charles-Arnold , Bouter Caroline , Ernst Marielle , Lange Claudia
Published: October 2022

Background

Dementia with Lewy bodies (DLB) is a type of dementia often diagnosed in older patients. Since its initial symptoms range from delirium to psychiatric and cognitive symptoms, the diagnosis is often delayed.

Objectives

In our study, we evaluated the magnetic resonance imaging (MRI) of patients suffering from DLB in correlation with their initial symptoms taking a new pragmatic approach entailing manual measurements in addition to an automated volumetric analysis of MRI.

Methods

A total of 63 patients with diagnosed DLB and valid 3D data sets were retrospectively and blinded evaluated. We assessed atrophy patterns (1) manually for the substantia innominata and (2) via FastSurfer for the most common supratentorial regions. Initial symptoms were categorized by (1) mild cognitive impairment (MCI), (2) psychiatric episodes, and (3) delirium.

Results

Manual metric MRI measurements revealed moderate, but significant substantia-innominata (SI) atrophy in patients with a psychiatric onset. FastSurfer analysis revealed no regional volumetric differences between groups.

Conclusion

The SI in patients with DLB and a psychiatric-onset is more atrophied than that in patients with initial MCI. Our results suggest potential differences in SI between DLB subtypes at the prodromal stage, which are useful when taking a differential-diagnostic approach. This finding should be confirmed in larger patient cohorts.
The effect of fish density and tank size on the behavior of adult zebrafish: A systematic analysis
Authors: Shishis Stephanie , Tsang Benjamin , Gerlai Robert
Published: October 2022

The zebrafish has been employed in several fields of biology due to its translational relevance and its simplicity and ease of maintenance. As a result, zebrafish are kept in thousands of laboratories around the world. Current industry standards favor keeping the largest possible number of fish in the smallest possible volume of water to increase efficiency and reduce costs. However, physiological and psychological stress resulting from such crowding may impact a variety of phenotypes, from brain function and behavior to cardiovascular function and cancer. Nevertheless, surprisingly little is known about what constitutes an optimal housing environment for the zebrafish, e.g., no systematic analyses have been performed to test the role of housing density and tank volume despite recent sporadic reports implying negative effects of the standard practice of crowding. Here, we conduct the first proof of concept analysis examining the potential impact of housing density and tank volume on the behavior of zebrafish. We randomly assigned adult zebrafish to one of three tank sizes (1.5, 10, or 50 L) with one of three housing densities (1, 2, or 4 fish/L), a 3 × 3 between subject experimental design, and maintained the fish in their corresponding condition for 2 weeks. Subsequently, we tested the behavior of the fish singly in a novel open tank for 12 min and quantified several of their swim path parameters using a video-tracking system. We found significant additive and interacting effects of tank size and/or housing density on swim path parameters including immobility, swim speed, turn angle, and distance to bottom and to stimulus. Although we had only three fish densities and three tank sizes and we did not explore the effects of more extreme conditions and although the interpretation of the above behavioral effects is speculative at this point, the results already demonstrate that both tank size and housing density exerts significant effects on the zebrafish and thus should be considered in zebrafish husbandry.
Prevalence of chronic non-specific low back pain among caregivers of stroke survivors in Kano, Nigeria and factors associated with it: A cross-sectional study
Authors: Abdullahi Auwal , Aliyu Kamilu , Hassan Auwal Bello , Sokunbi Ganiyu Oluwaleke , Bello Bashir , Saeys Wim , Truijen Steven
Published: October 2022

Purpose

Low back pain (LBP) may have a specific or non-specific cause such as abnormal posture or repetitive tasks. For instance, lifting and transferring patients during caregiving for stroke survivors may predispose the caregivers to LBP.

Objectives

The aim of this study is to determine the prevalence of chronic non-specific LBP and factors associated with it in caregivers of stroke survivors.

Method

The research design used is cross-sectional study design. Participants of the study were caregivers of stroke survivors in Kano, Nigeria who were at least 18 years old. They were included if they had at least one-month experience with caregiving for at least 1 h per day. Presence of LBP and level of disability were assessed using participants' self-report and Rolland Morris Low Back Pain Disability Questionnaire respectively. The data collected was analyzed using descriptive, Chi-square statistics and Binary Logistics Regression.

Result

Three hundred caregivers with mean age, 33.24 ± 10.32 years in which 207 and 93 were males and females respectively, participated in the study. The results showed that, there was a high prevalence (64.7%) of LBP among the caregivers. The prevalence was significantly associated with gender (p < 0.001), age (p = 0.029), occupation (p < 0.001) and duration of caregiving (p < 0.001) of the study participants. In addition, the result of the regression model showed that, being a female (p = 0.001), a civil servant (p = 0.031), a trader (p = 0.013), and a complete caregiver (0.001); and caregiving for a duration of 5 h or more per day (p = 0.024) are significant predictors of having LBP. Similarly, level of disability due to the presence of LBP among the study participants was significantly associated with gender (p < 0.001), occupation (p < 0.001), duration of caregiving (p = 0.025), and the nature of the caregiving (p < 0.001).

Conclusion

Informal caregiving for stroke survivors may result in developing chronic non-specific LBP, especially among females, Civil servants, traders, complete caregivers and those with long duration of caregiving. This can add an additional burden on the family in terms of cost of care, result in reduced quality of caregiving and cause psychological stress. Thus, it is important the health of the caregivers of stroke survivors is considered during stroke rehabilitation.
Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients
Authors: Satani Nikunj , Parsha Kaushik , Davis Courtney , Gee Adrian , Olson Scott D. , Aronowski Jaroslaw , Savitz Sean I.
Published: October 2022

Background

Systemic administration of marrow stromal cells (MSCs) leads to the release of a broad range of factors mediating recovery in rodent stroke models. The release of these factors could depend on the various cell types within the peripheral blood as they contact systemically administered MSCs. In this study, we assessed the immunomodulatory interactions of MSCs with peripheral blood derived monocytes (Mϕ) collected from acute stroke patients.

Methods

Peripheral blood from stroke patients was collected at 5–7 days (N = 5) after symptom onset and from age-matched healthy controls (N = 5) using mononuclear cell preparation (CPT) tubes. After processing, plasma and other cellular fractions were removed, and Mϕ were isolated from the mononuclear fraction using CD14 microbeads. Mϕ were then either cultured alone or co-cultured with MSCs in a trans-well cell-culture system. Secretomes were analyzed after 24 h of co-cultures using a MAGPIX reader.

Results

Our results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5–7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared to the secretions from monocytes alone. When MSCs were added to monocytes from stroke patients, they decreased the levels of IL-1β, and increased the levels of IL-10 significantly more as compared to when they were added to monocytes from control patients.

Conclusion

The systemic circulation of stroke patients may differentially interact with MSCs to release soluble factors integral to their paracrine mechanisms of benefit. Our study finds that the effect of MSCs on Mϕ is different on those derived from stroke patients blood as compared to healthy controls. These findings suggest immunomodulation of peripheral immune cells as a therapeutic target for MSCs in patients with acute stroke.