bluuebunny/crossref_metadata_2025 huggingface dataset:
Inspired by nature: Fiber networks functionalized with tannic acid and condensed tannin-rich extracts of Norway spruce bark show antimicrobial efficacy
Authors: Jyske Tuula , Liimatainen Jaana , Tienaho Jenni , Brännström Hanna , Aoki Dan , Kuroda Katsushi , Reshamwala Dhanik , Kunnas Susan , Halmemies Eelis , Nakayama Eiko , Kilpeläinen Petri , Ora Ari , Kaseva Janne , Hellström Jarkko , Marjomäki Varpu S. , Karonen Maarit , Fukushima Kazuhiko
Published: April 2023

This study demonstrated the antibacterial and antiviral potential of condensed tannins and tannic acid when incorporated into fiber networks tested for functional material purposes. Condensed tannins were extracted from industrial bark of Norway spruce by using pressurized hot water extraction (PHWE), followed by purification of extracts by using XADHP7 treatment to obtain sugar-free extract. The chemical composition of the extracts was analyzed by using HPLC, GC‒MS and UHPLC after thiolytic degradation. The test matrices, i.e., lignocellulosic handsheets, were produced and impregnated with tannin-rich extracts, and tannic acid was used as a commercial reference. The antibacterial and antiviral efficacy of the handsheets were analyzed by using bioluminescent bacterial strains (Staphylococcus aureus RN4220+pAT19 and Escherichia coli K12+pCGLS11) and Enterovirus coxsackievirus B3. Potential bonding of the tannin-rich extract and tannic acid within the fiber matrices was studied by using FTIR-ATR spectroscopy. The deposition characteristics (distribution and accumulation patterns) of tannin compounds and extracts within fiber networks were measured and visualized by direct chemical mapping using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and digital microscopy. Our results demonstrated for the first time, how tannin-rich extracts obtained from spruce bark side streams with green chemistry possess antiviral and antibacterial properties when immobilized into fiber matrices to create substitutes for plastic hygienic products, personal protection materials such as surgical face masks, or food packaging materials to prolong the shelf life of foodstuffs and prevent the spread of infections. However, more research is needed to further develop this proof-of-concept to ensure stable chemical bonding in product prototypes with specific chemistry.
Delivery of AntagomiR-7 through polymer nanoparticles for assisting B Cell to alleviate systemic lupus erythematosus
Authors: Guo Hui , Ma Jiangtao , Zhang Yanli , Mao Yan , Hu Ziwei , Lin Ying , Yu Feng , Wang Wei , Liu Yaling
Published: April 2023

An autoimmune condition known as systemic lupus erythematosus (SLE) is characterized by B cell hyperresponsiveness and persistent generation of pathogenic autoantibodies that cause damage to various organs and tissues. The treatments available today are either ineffective or have adverse effects. The dysregulation of B cell activation is crucial for the emergence of SLE. MiR-7 explicitly targeted PTEN mRNA in B cells. Treatment with antagomiR-7 reduced B cell hyperresponsiveness and prevented the onset of lupus. As a result, inhibiting miR-7 may be used therapeutically to treat SLE. We developed a SA (sialic acid)-poly (D, L-lactide-co-glycolide) (SA-PLGA) nano delivery system to deliver antagomiR-7 into splenic B cells since the stability and targeted delivery of miRNA remain significant challenges in vivo. Results show that SA-PLGA nanoparticles (SA-PLGA@antagomiR-7) loaded with antagomiR-7 display good biocompatibility and shield antagomiR-7 from degradation, extending the miRNA’s duration in circulation in vivo. Additionally, in MRL/Ipr lupus mice, SA-PLGA@antagomiR-7 is successfully delivered to the splenic B cells and preferentially enriched in the diseased spleen in MRL/Ipr lupus mice. The SA-PLGA@antagomiR-7 NPs therapy effectively decreases immunological abnormalities, normalizes splenic B cell subtypes, and suppresses B cell activation. The antagomiR-7 NPs exhibit excellent therapeutic efficiency and high biosafety collectively, which may result in a more effective treatment for SLE.
Transition metal doped CeO2 for photocatalytic removal of 2-chlorophenol in the exposure of indoor white light and antifungal activity
Authors: Qamar M. Tariq , Iqbal Shahid , Aslam M. , Alhujaily Ahmad , Bilal Anum , Rizwan Komal , Farooq Hafiz Muhammad Umer , Sheikh Tahir Ali , Bahadur Ali , Awwad Nasser S. , Ibrahium Hala A. , Almufarij Rasmiah S. , Elkaeed Eslam B.
Published: April 2023

Besides natural sunlight and expensive artificial lights, economical indoor white light can play a significant role in activating a catalyst for photocatalytic removal of organic toxins from contaminated water. In the current effort, CeO2 has been modified with Ni, Cu, and Fe through doping methodology to study the removal of 2-chlorophenol (2-CP) in the illumination of 70 W indoor LED white light. The absence of additional diffractions due to the dopants and few changes such as reduction in peaks’ height, minor peak shift at 2θ (28.525°) and peaks’ broadening in XRD patterns of modified CeO2 verifies the successful doping of CeO2. The solid-state absorption spectra revealed higher absorbance of Cu-doped CeO2 whereas a lower absorption response was observed for Ni-doped CeO2. An interesting observation regarding the lowering of indirect bandgap energy of Fe-doped CeO2 (∼2.7 eV) and an increase in Ni-doped CeO2 (∼3.0 eV) in comparison to pristine CeO2 (∼2.9 eV) was noticed. The process of e-– h+ recombination in the synthesized photocatalysts was also investigated through photoluminescence spectroscopy. The photocatalytic studies revealed the greater photocatalytic activity of Fe-doped CeO2 with a higher rate (∼3.9 × 10−3 min-1) among all other materials. Moreover, kinetic studies also revealed the validation of the Langmuir-Hinshelwood kinetic model (R2 = 0.9839) while removing 2-CP in the exposure of indoor light with a Fe-doped CeO2 photocatalyst. The XPS analysis revealed the existence of Fe3+, Cu2+ and Ni2+ core levels in doped CeO2. Using the agar well-diffusion method, the antifungal activity was assessed against the fungus M. fructicola and F. oxysporum. Compared to CeO2, Ni-doped CeO2, and Cu-doped CeO2 nanoparticles, the Fe-doped CeO2 nanoparticles have outstanding antifungal properties.
Estimated pulse wave velocity is associated with all-cause and cardio-cerebrovascular disease mortality in stroke population: Results from NHANES (2003–2014)
Authors: Huang Huoming , Bu Xiancong , Pan Huachun , Yang Shumin , Cheng Wenke , Shubhra Quazi T. H. , Ma Niya
Published: April 2023

Background

Arterial stiffness is a significant determinant and evaluation of cardio-cerebrovascular disease and all-cause mortality risk in the stroke population. Estimated pulse wave velocity (ePWV) is a well-established indirect measure of arterial stiffness. We examined the association of ePWV with all-cause and cardio-cerebrovascular disease (CCD) mortality in the stroke population in a large sample of US adults.

Methods

The study design was a prospective cohort study with data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014, between the ages of 18–85 years, with follow-up through December 31, 2019. 1,316 individuals with stroke among 58,759 participants were identified and ultimately, 879 stroke patients were included in the analysis. ePWV was calculated from a regression equation using age and mean blood pressure according to the following formula: ePWV = 9.587 − (0.402 × age) + [4.560 × 0.001 × (age2)] − [2.621 × 0.00001 × (age2) × MBP] + (3.176 × 0.001 × age × MBP) − (1.832 × 0.01 × MBP). Survey-weighted Cox regression models were used to assess the association between ePWV and all-cause and CCD mortality risk.

Results

The high ePWV level group had a higher increased risk of all-cause mortality and CCD mortality compared to the low ePWV level group after fully adjusting for covariates. With an increase in ePWV of 1 m/s, the risk of all-cause and CCD mortality increased by 44%–57% and 47%–72% respectively. ePWV levels were linearly correlated with the risk of all-cause mortality (P for nonlinear = 0.187). With each 1 m/s increase in ePWV, the risk of all-cause mortality increased by 44% (HR 1.44, 95% CI: 1.22–1.69; P < 0.001). When ePWV was <12.1 m/s, an increase in ePWV per 1 m/s was associated with a 119% (HR 2.19, 95% CI: 1.43–3.36; P < 0.001) increase in CCD mortality risk; when ePWV was ≥12.1 m/s, an increase in ePWV per 1 m/s was not associated with in CCD mortality risk.

Conclusion

ePWV is an independent risk factor for all-cause and CCD mortality in stroke patients. Higher levels of ePWV are associated with higher all-cause mortality and CCD mortality in stroke patients.
Insulinoma in childhood: a retrospective review of 22 patients from one referral centre
Authors: Melikyan Maria , Gubaeva Diliara , Shadrina Anna , Bolmasova Anna , Kareva Maria , Tiulpakov Anatoly , Efremenkov Artem , Sokolov Yuri , Brusgaard Klaus , Christesen Henrik T. , Andersen Kirstine , Stepanov Alexey , Averyanova Julia , Makarov Sergey , Gurevich Larisa
Published: April 2023

Background

Insulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1).

Methods

We conducted a retrospective review of patients diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained.

Results

A total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1–46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry MEN1 mutations, inherited n=5, de novo n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations.

Conclusions

In this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation.
Sperm morphological abnormalities in autosomal dominant polycystic kidney disease are associated with the Hippo signaling pathway via PC1
Authors: Shi Wei-Hui , Zhou Zhi-Yang , Ye Mu-Jin , Qin Ning-Xin , Jiang Zi-Ru , Zhou Xuan-You , Xu Nai-Xin , Cao Xian-Lin , Chen Song-Chang , Huang He-Feng , Xu Chen-Ming
Published: April 2023

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder mostly caused by mutations in PKD1 or PKD2 genes. Here, we report thirteen ADPKD males with infertility and investigated the sperm morphological defects associated with PC1 disruption.

Methods

Targeted next-generation sequencing was performed to detect PKD1 variants in patients. Sperm morphology was observed by immunostaining and transmission electron microscopy, and the sperm motility was assessed using the computer-assisted sperm analysis system. The Hippo signaling pathway was analyzed with by quantitative reverse transcription polymerase chain reaction (qPCR) and western blotting in vitro.

Results

The ADPKD patients were infertile and their sperm tails showed morphological abnormalities, including coiled flagella, absent central microtubules, and irregular peripheral doublets. In addition, the length of sperm flagella was shorter in patients than in controls of in in. In vitro, ciliogenesis was impaired in Pkd1-depleted mouse kidney tubule cells. The absence of PC1 resulted in a reduction of MST1 and LATS1, leading to nuclear accumulation of YAP/TAZ and consequently increased transcription of Aurka. which might promote HDAC6-mediated ciliary disassembly.

Conclusion

Our results suggest the dysregulated Hippo signaling significantly contributes to ciliary abnormalities in and may be associated with flagellar defects in spermatozoa from ADPKD patients.
Is routine drainage necessary after thyroid surgery? A randomized controlled trial study
Authors: Wang Ziming , Qi Peng , Zhang Lixi , Zhang Ben , Liu Xuyao , Shi Qi , Zhang Qiang
Published: April 2023

Objective

To evaluate whether no drainage has an advantage over routine drainage in patients with thyroid carcinoma after unilateral thyroid lobectomy and central neck dissection.

Methods

A total of 104 patients with thyroid cancer who underwent unilateral thyroid lobectomy and central lymph node dissection were randomly assigned into no drainage tube (n=52) and routine drainage tube (n=52) placement groups. General information of each patient was recorded, including the postoperative drainage volume/residual cavity fluid volume, postoperative complications, incision area comfort, and other data, and the thyroid cancer-specific quality of life questionnaire (THYCA-QoL) and patient and observer scar assessment scale (POSAS) were evaluated after surgery. At the 3–6 month follow-up exam, the differences between the two groups were compared based on univariate analysis.

Results

Significant differences were not observed in the general and pathological information (including sex, age, body weight, body mass index (BMI), incision length, specimen volume, Hashimoto’s thyroiditis, and number of lymph nodes dissected), operation time, and postoperative complications (postoperative bleeding, incision infection, lymphatic leakage, and temporary hypoparathyroidism) between the two groups. The patients in the non-drainage group had a shorter hospital stay (2.11 ± 0.33 d) than the patients in the drainage group (3.38 ± 0.90 d) (P<0.001). The amount of cervical effusion in patients in the non-drainage group (postoperative 24h: 2.20 ± 1.24 ml/48 h: 1.53 ± 1.07 ml) was significantly less than that in the drainage group (postoperative 24 hours: 22.58 ± 5.81 ml/48 h: 36.15 ± 7.61 ml) (all P<0.001). The proportion of incision exudation and incision numbness in the non-drainage group was lower than that in the drainage group (all P<0.05), and the pain score (VAS) and neck foreign body sensation score (FBST) decreased significantly (P<0.05). During the 3- and 6-month follow-up exams, significant differences were not observed between the THYCA-QoL and drainage groups and the non-drainage group, although the scarring and POSAS values were lower than those in the drainage group. In addition, the length of stay and cost of hospitalization in the non-drainage group were lower than those in the drainage group (P<0.05).

Conclusion

Routine drainage tube insertion is not needed in patients with unilateral thyroid lobectomy and central neck dissection.
Permanent hypothyroidism following immune checkpoint inhibitors induced thyroiditis may be associated with improved survival: results of an exploratory study
Authors: Lee Hanna J. , Manavalan Anjali , Stefan-Lifshitz Mihaela , Schechter Clyde , Maity Aloke , Tomer Yaron
Published: April 2023

Background

Immune-related endocrinopathies are common after immune checkpoint inhibitor (ICI) therapy, among which destructive thyroiditis is the most prevalent. Improved survival outcomes have been associated with immune-related adverse events. We aimed to compare the clinical course and biochemical parameters of two subtypes of ICI-related destructive thyroiditis: a transient thyrotoxicosis that reverts to either euthyroidism (TT; transient thyroiditis) versus progression to permanent hypothyroidism (PH), and to identify prognostic markers in cancer patients receiving ICI therapy who developed DT.

Methods

This retrospective observational study included 124 patients who developed a transient thyrotoxicosis due to a destructive thyroiditis after ICI therapy from January 1, 2016 to April 30, 2021 at the Montefiore Medical Center. Patients were categorized as either TT or PH based on spontaneous renormalization of the TSH or the permanent need for thyroid hormone replacement, respectively. Thyroid hormone and antibody levels, serum inflammatory markers, eosinophils, and metabolic uptake of the thyroid on PET imaging, each corresponding closest to a suppressed TSH, were characterized. Survival from TT and PH were also analyzed.

Results

Of the 124 patients, 53 developed PH and 71 developed TT. The PH group developed thyrotoxicosis at a median of 42 days from the first ICI dose while the TT group took significantly longer at 56 days. Thyroidal PET uptake was increased in 18.9% of the PH group versus 6.0% of the TT group (P=0.04). Three different survival models consistently demonstrated a trend towards increased survival in the PH group, compared to the TT group.

Conclusion

Our results suggest that PH developing after ICI-induced destructive thyroiditis may be associated with a more robust inflammatory and antitumor response to ICI therapy. The results suggests that PH may be a potential clinical predictor of improved survival.
Effect of continuous glucose monitoring compared with self-monitoring of blood glucose in gestational diabetes patients with HbA1c<6%: a randomized controlled trial
Authors: Lai Mengyu , Weng Jianrong , Yang Jiaying , Gong Yujia , Fang Fang , Li Na , Kang Mei , Xu Xianming , Wang Yufan
Published: April 2023

Objective

This study evaluated the effect of continuous glucose monitoring (CGM) versus self-monitored blood glucose (SMGB) in gestational diabetes mellitus (GDM) with hemoglobin A1c (HbA1c) <6%.

Methods

From January 2019 to February 2021, 154 GDM patients with HbA1c<6% at 24–28 gestational weeks were recruited and assigned randomly to either SMBG only or CGM in addition to SMBG, with 77 participants in each group. CGM was used in combination with fingertip blood glucose monitoring every four weeks until antepartum in the CGM group, while in the SMBG group, fingertip blood glucose monitoring was applied. The CGM metrics were evaluated after 8 weeks, HbA1c levels before delivery, gestational weight gain (GWG), adverse pregnancy outcomes and CGM medical costs were compared between the two groups.

Results

Compared with patients in the SMBG group, the CGM group patients had similar times in range (TIRs) after 8 weeks (100.00% (93.75-100.00%) versus 99.14% (90.97-100.00%), p=0.183) and HbA1c levels before delivery (5.31 ± 0.06% versus 5.35 ± 0.06%, p=0.599). The proportion with GWG within recommendations was higher in the CGM group (59.7% versus 40.3%, p=0.046), and the newborn birth weight was lower (3123.79 ± 369.58 g versus 3291.56 ± 386.59 g, p=0.015). There were no significant differences in prenatal or obstetric outcomes, e.g., cesarean delivery rate, hypertensive disorders, preterm births, macrosomia, hyperbilirubinemia, neonatal hypoglycemia, respiratory distress, and neonatal intensive care unit admission >24 h, between the two groups. Considering glucose monitoring, SMBG group patients showed a lower cost than CGM group patients.

Conclusions

For GDM patients with HbA1c<6%, regular SMBG is a more economical blood glucose monitoring method and can achieve a similar performance in glycemic control as CGM, while CGM is beneficial for ideal GWG.
Crosstalk of disulfidptosis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in bladder cancer based on a machine learning survival framework
Authors: Zhao Songyun , Wang Lanyu , Ding Wei , Ye Bicheng , Cheng Chao , Shao Jianfeng , Liu Jinhui , Zhou Hongyi
Published: April 2023

Background

Bladder cancer (BLCA) is the most common malignancy of the urinary tract. On the other hand, disulfidptosis, a mechanism of disulfide stress-induced cell death, is closely associated with tumorigenesis and progression. Here, we investigated the impact of disulfidptosis-related genes (DRGs) on the prognosis of BLCA, identified various DRG clusters, and developed a risk model to assess patient prognosis, immunological profile, and treatment response.

Methods

The expression and mutational characteristics of four DRGs were first analyzed in bulk RNA-Seq and single-cell RNA sequencing data, IHC staining identified the role of DRGs in BLCA progression, and two DRG clusters were identified by consensus clustering. Using the differentially expressed genes (DEGs) from these two clusters, we transformed ten machine learning algorithms into more than 80 combinations and finally selected the best algorithm to construct a disulfidptosis-related prognostic signature (DRPS). We based this selection on the mean C-index of three BLCA cohorts. Furthermore, we explored the differences in clinical characteristics, mutational landscape, immune cell infiltration, and predicted efficacy of immunotherapy between high and low-risk groups. To visually depict the clinical value of DRPS, we employed nomograms. Additionally, we verified whether DRPS predicts response to immunotherapy in BLCA patients by utilizing the Tumour Immune Dysfunction and Rejection (TIDE) and IMvigor 210 cohorts.

Results

In the integrated cohort, we identified several DRG clusters and DRG gene clusters that differed significantly in overall survival (OS) and tumor microenvironment. After the integration of clinicopathological features, DRPS showed robust predictive power. Based on the median risk score associated with disulfidptosis, BLCA patients were divided into low-risk (LR) and high-risk (HR) groups, with patients in the LR group having a better prognosis, a higher tumor mutational load and being more sensitive to immunotherapy and chemotherapy.

Conclusion

Our study, therefore, provides a valuable tool to further guide clinical management and tailor the treatment of BLCA patients, offering new insights into individualized treatment.
Educational fields of higher education graduates in European Union
Authors: Angheluță Petrică Sorin , Dobrea Cătălin Răzvan , Crețu Florentina Raluca , Ganea Otilia , Breaz Teodora Odett , Popescu (Groaznicu) Nicoleta Luminița
Published: April 2023

The processes of automation and globalization are resizing workplaces through their changes. A picture of the labor market can be provided by the educational fields of the graduates. Thus, depending on the educational field, the situation regarding the distribution of bachelor’s graduates is analyzed in the article. The importance of the quality of the education and vocational training processes can be considered to be the basis of addressing the major challenges that are manifesting worldwide. Economic and social pressures influence the development of skills and competencies even for higher education. Training for the purpose of employment also contributes to increasing employability. The degree of access to jobs is higher when the level of education is higher. For the age group 15 to 64, this article presents the share of graduates having an education level between 5 and 8. Quality education can contribute to sustainable development. Thus, to identify solutions to problems that may arise in a community, the contribution of education can increase by increasing the life quality of the members from that community. In this context, for the 30–34 age group, at European level, the evolution of graduates with a tertiary level of education is analyzed. For employers, it is very important to know both the level of education and especially the fields in which they are trained. This is one of the reasons why the authors of the study carried out this analysis. Taking into account the classification of graduates according to the educational field, the research presents the situation for each of the five fields for which in 2020 there were the most numerous bachelor’s graduates.
Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice
Authors: Krysko Olga , Korsakova Darya , Teufelberger Andrea , De Meyer Amse , Steels Jill , De Ruyck Natalie , van Ovost Judith , Van Nevel Sharon , Holtappels Gabriele , Coppieters Frauke , Ivanchenko Mikhail , Braun Harald , Vedunova Maria , Krysko Dmitri V. , Bachert Claus
Published: April 2023

Background

Recent in vitro studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in the cleavage of IL-33 cytokine, and their contribution to allergic airway inflammation.

Results

In vitro, full-length IL-33 protein was efficiently degraded by mast cell supernatants of BALB/c mice in contrast to the mast cell supernatants from C57BL/6 mice. RNAseq analysis indicated major differences in the gene expression profiles of bone marrow-derived mast cells from C57BL/6 and BALB/c mice. In Alternaria alternata (Alt) - treated C57BL/6 mice the full-length form of IL-33 was mainly present, while in BALB/c mice, the processed shorter form of IL-33 was more prominent. The observed cleavage pattern of IL-33 was associated with a nearly complete lack of mast cells and their proteases in the lungs of C57BL/6 mice. While most inflammatory cells were similarly increased in Alt-treated C57BL/6 and BALB/c mice, C57BL/6 mice had significantly more eosinophils in the bronchoalveolar lavage fluid and IL-5 protein levels in their lungs than BALB/c mice.

Conclusion

Our study demonstrates that lung mast cells differ in number and protease content between the two tested mouse strains and could affect the processing of IL-33 and inflammatory outcome of Alt -induced airway inflammation. We suggest that mast cells and their proteases play a regulatory role in IL-33-induced lung inflammation by limiting its proinflammatory effect via the IL-33/ST2 signaling pathway.
Dissecting order amidst chaos of programmed cell deaths: construction of a diagnostic model for KIRC using transcriptomic information in blood-derived exosomes and single-cell multi-omics data in tumor microenvironment
Authors: Wang Chengbang , He Yuan , Zheng Jie , Wang Xiang , Chen Shaohua
Published: April 2023

Background

Kidney renal clear cell carcinoma (KIRC) is the most frequently diagnosed subtype of renal cell carcinoma (RCC); however, the pathogenesis and diagnostic approaches for KIRC remain elusive. Using single-cell transcriptomic information of KIRC, we constructed a diagnostic model depicting the landscape of programmed cell death (PCD)-associated genes, namely cell death-related genes (CDRGs).

Methods

In this study, six CDRG categories, including apoptosis, necroptosis, autophagy, pyroptosis, ferroptosis, and cuproptosis, were collected. RNA sequencing (RNA-seq) data of blood-derived exosomes from the exoRBase database, RNA-seq data of tissues from The Cancer Genome Atlas (TCGA) combined with control samples from the GTEx databases, and single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database were downloaded. Next, we intersected the differentially expressed genes (DEGs) of the KIRC cohort from exoRBase and the TCGA databases with CDRGs and DEGs obtained from single-cell datasets, further screening out the candidate biomarker genes using clinical indicators and machine learning methods and thus constructing a diagnostic model for KIRC. Finally, we investigated the underlying mechanisms of key genes and their roles in the tumor microenvironment using scRNA-seq, single-cell assays for transposase-accessible chromatin sequencing (scATAC-seq), and the spatial transcriptomics sequencing (stRNA-seq) data of KIRC provided by the GEO database.

Result

We obtained 1,428 samples and 216,155 single cells. After the rational screening, we constructed a 13-gene diagnostic model for KIRC, which had high diagnostic efficacy in the exoRBase KIRC cohort (training set: AUC = 1; testing set: AUC = 0.965) and TCGA KIRC cohort (training set: AUC = 1; testing set: AUC = 0.982), with an additional validation cohort from GEO databases presenting an AUC value of 0.914. The results of a subsequent analysis revealed a specific tumor epithelial cell of TRIB3high subset. Moreover, the results of a mechanical analysis showed the relatively elevated chromatin accessibility of TRIB3 in tumor epithelial cells in the scATAC data, while stRNA-seq verified that TRIB3 was predominantly expressed in cancer tissues.

Conclusions

The 13-gene diagnostic model yielded high accuracy in KIRC screening, and TRIB3high tumor epithelial cells could be a promising therapeutic target for KIRC.
Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics
Authors: Zhang Tangxin , Hu Chunmiao , Zhang Wenting , Ruan Yongdui , Ma Yuhe , Chen Dongsheng , Huang Yuhe , Fan Shuhao , Lin Wensen , Huang Yifan , Liao Kangsheng , Lu Hongemi , Xu Jun-Fa , Pi Jiang , Guo Xinrong
Published: April 2023

As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms.
Single-sex schistosomiasis: a mini review
Authors: Zhong Haoran , Jin Yamei
Published: April 2023

Schistosomiasis is a neglected tropical disease caused by dioecious blood flukes of the genus Schistosoma and second to malaria as a parasitic disease with significant socio-economic impacts. Mating is essential for maturation of male and female schistosomes and for females to lay of eggs, which are responsible for the pathogenesis and propagation of the life cycle beyond the mammalian host. Single-sex schistosomes, which do not produce viable eggs without mating, have been overlooked given the symptomatic paucity of the single-sex schistosomiasis and limited diagnostic toolkit. Besides, single-sex schistosomes are less sensitive to praziquantel. Therefore, these issues should be considered to achieve the elimination of this infection disease. The aim of this review is to summarize current progress in research of single-sex schistosomes and host-parasite interactions.
Opportunities for Treg cell therapy for the treatment of human disease
Authors: Bluestone Jeffrey A. , McKenzie Brent S. , Beilke Joshua , Ramsdell Fred
Published: April 2023

Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmunity, and limiting chronic inflammatory diseases. This small CD4+ T cell population can develop in the thymus and in the peripheral tissues of the immune system through the expression of an epigenetically stabilized transcription factor, FOXP3. Treg cells mediate their tolerogenic effects using multiple modes of action, including the production of inhibitory cytokines, cytokine starvation of T effector (e.g., IL-2), Teff suppression by metabolic disruption, and modulation of antigen-presenting cell maturation or function. These activities together result in the broad control of various immune cell subsets, leading to the suppression of cell activation/expansion and effector functions. Moreover, these cells can facilitate tissue repair to complement their suppressive effects. In recent years, there has been an effort to harness Treg cells as a new therapeutic approach to treat autoimmune and other immunological diseases and, importantly, to re-establish tolerance. Recent synthetic biological advances have enabled the cells to be genetically engineered to achieve tolerance and antigen-specific immune suppression by increasing their specific activity, stability, and efficacy. These cells are now being tested in clinical trials. In this review, we highlight both the advances and the challenges in this arena, focusing on the efforts to develop this new pillar of medicine to treat and cure a variety of diseases.
Immune interference in effectiveness of influenza and COVID-19 vaccination
Authors: Xie Yiwen , Tian Xuebin , Zhang Xiaodi , Yao Hangping , Wu Nanping
Published: April 2023

Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely and polio is almost extinct because of vaccines. Rabies vaccines and Bacille Calmette-Guérin (BCG) vaccines could effectively protect humans against respective infections. However, both influenza vaccines and COVID-19 vaccines are unable to eliminate these two infectious diseases of their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) could be negatively influenced (i.e., interfered with) by immune imprinting of previous infections or vaccinations, and repeated vaccinations could interfere with VE against infections due to mismatch between vaccine strains and endemic viral strains. Moreover, VE could also be interfered with when more than one kind of vaccine is administrated concomitantly (i.e., co-administrated), suggesting that the VE could be modulated by the vaccine-induced immunity. In this review, we revisit the evidence that support the interfered VE result from immune imprinting or repeated vaccinations in influenza and COVID-19 vaccine, and the interference in co-administration of these two types of vaccines is also discussed. Regarding the development of next-generation COVID-19 vaccines, the researchers should focus on the induction of cross-reactive T-cell responses and naive B-cell responses to overcome negative effects from the immune system itself. The strategy of co-administrating influenza and COVID-19 vaccine needs to be considered more carefully and more clinical data is needed to verify this strategy to be safe and immunogenic.
Syngeneic mouse model of human HER2+ metastatic breast cancer for the evaluation of trastuzumab emtansine combined with oncolytic rhabdovirus
Authors: Taha Zaid , Crupi Mathieu J.F. , Alluqmani Nouf , Fareez Faiha , Ng Kristy , Sobh Judy , Lee Emily , Chen Andrew , Thomson Max , Spinelli Marcus M. , Ilkow Carolina S. , Bell John C. , Arulanandam Rozanne , Diallo Jean-Simon
Published: April 2023

Background

Established mouse models of HER2+ cancer are based on the over-expression of rodent Neu/Erbb2 homologues, which are incompatible with human HER2 (huHER2) targeted therapeutics. Additionally, the use of immune-deficient xenograft or transgenic models precludes assessment of native anti-tumour immune responses. These hurdles have been a challenge for our understanding of the immune mechanisms behind huHER2-targeting immunotherapies.

Methods

To assess the immune impacts of our huHER2-targeted combination strategy, we generated a syngeneic mouse model of huHER2+ breast cancer, using a truncated form of huHER2, HER2T. Following validation of this model, we next treated tumour-bearing with our immunotherapy strategy: oncolytic vesicular stomatitis virus (VSVΔ51) with clinically approved antibody-drug conjugate targeting huHER2, trastuzumab emtansine (T-DM1). We assessed efficacy through tumour control, survival, and immune analyses.

Results

The generated truncated HER2T construct was non-immunogenic in wildtype BALB/c mice upon expression in murine mammary carcinoma 4T1.2 cells. Treatment of 4T1.2-HER2T tumours with VSVΔ51+T-DM1 yielded robust curative efficacy compared to controls, and broad immunologic memory. Interrogation of anti-tumour immunity revealed tumour infiltration by CD4+ T cells, and activation of B, NK, and dendritic cell responses, as well as tumour-reactive serum IgG.

Conclusions

The 4T1.2-HER2T model was used to evaluate the anti-tumour immune responses following our complex pharmacoviral treatment strategy. These data demonstrate utility of the syngeneic HER2T model for assessment of huHER2-targeted therapies in an immune-competent in vivo setting. We further demonstrated that HER2T can be implemented in multiple other syngeneic tumour models, including but not limited to colorectal and ovarian models. These data also suggest that the HER2T platform may be used to assess a range of surface-HER2T targeting approaches, such as CAR-T, T-cell engagers, antibodies, or even retargeted oncolytic viruses.
Biotechnological potential of Ulva ohnoi epiphytic bacteria: enzyme production and antimicrobial activities
Authors: Hmani I. , Ktari L. , Ismail A. , EL Bour M.
Published: April 2023

Seaweed surfaces harbor diverse epibiotic bacterial communities with functions related to morphogenesis, host health, and defense. Among seaweed holobionts, culturable strains can represent innovative sources of bioactive compounds and enzymes. The global industrial demand for microbial enzymes is continually growing in order to improve certain manufacturing processes with new perspectives of industrial exploitation. In this regard, the present study focuses on the enzymatic production and the antimicrobial activities of culturable epibiotic bacteria of Ulva from the Tunisian coast. Culturable associated bacteria were isolated and molecular identification was realized by 16S rRNA gene sequencing. For each strain, eight enzymatic activities were investigated: amylase, hemolysis, DNase, cellulase, lecithinase, lipase, gelatinase, and chitinase. The antimicrobial activity of Ulva-associated bacteria was evaluated against seven pathogenic bacteria, Escherichia coli, Vibrio anguillarum, Vibrio alginoliticus, Pseudomonas aeruginosa, Aeromonas hydrophila, Salmonella typhymurium, and Staphylococcus aureus, and one yeast, Candida albicans. The antibiotic resistance of isolated strains was determined for 15 commonly used antibiotics. The phylogenetic analysis revealed that the isolates belonged to Alphaproteobacteria (3), Gammaproteobacteria (5), Actinobacteria (3), and Firmicutes (4) phyllum. The majority of the isolates (66%) produced simultaneously more than one enzyme. Hemolysis was produced by 46.6% of isolates, while DNase was produced by 33% of strains. On the other hand, 13% of strains produced lecithinase, gelatinase, cellulase, and lipase. No chitinase was produced by the isolated bacteria. In addition, 60% of isolates displayed antimicrobial activity against at least one pathogenic strain. All Ulva ohnoi-associated bacteria were resistant to at least seven commonly used antibiotics. These results highlighted the occurrence of several enzymatic activities within Ulva-associated bacteria that can have potential uses in the industrial sector.
Differential response of chlorophyll-a concentrations to explosive volcanism in the western South Pacific
Authors: Yoon Joo-Eun , King David , Longman Jack , Cronin Shane J.
Published: April 2023

When it is deposited in the ocean, volcanic ash has the potential to release iron and other nutrients into surface water to stimulate ocean productivity. In the western South Pacific Ocean (SPO), one of the most important volcanic ash deposition regions, occasional widespread transport of volcanic ash may supply the nutrients not only locally around source islands but also within the wider the western SPO, accompanied by phytoplankton response. Through a comparative analysis of satellite and reanalysis data for the past 19 years (2004–2022), this study reveals that four explosive volcanic eruptions, Rabaul volcano, Papua New Guinea (October, 2006), Ambae volcano, Vanuatu (July, 2018), Ulawun volcano, Papua New Guinea (June, 2019), and Hunga volcano, Tonga (January, 2022), had the most strong stratospheric injection (>15 km) and mass loading of volcanic materials over the wider the western SPO (covering an area of >765,000 km2). The transport of 2006, 2018, 2019 volcanic emissions, was not likely associated with significant ash deposition over the western SPO. However, the Hunga eruption led to the deposition of ash-laden volcanic plumes over a wide area (~2,000 km from source), and was followed by the increase in chlorophyll-a concentrations (Chl-a) in the region (~70% increase). Minor changes related to other nutrient sources (e.g., hydrothermal input) suggest a link between the increase in Chl-a and 2022 Hunga ash falls over the western SPO. Our results indicate that volcanic ash deposition has implications for phytoplankton productivity in the western SPO, and highlights the need for further research into understanding how nutrient supply alleviated limitations of phytoplankton at the community level.
Categorisation of the length of bowhead whales from British Arctic whaling records
Authors: Wilkinson Jeremy , Veyssière Gaëlle , Hughes Nick , Ayre Matthew , Murray Maribeth , Headland Robert , Charles Ryan
Published: April 2023

British whalers were the first and last from Europe to hunt bowhead whales (Balaena mysticetus) commercially from the Arctic whaling grounds of the Greenland Sea (East Greenland-Svalbard-Barents stock) and Davis Strait (East Canada-West Greenland stock). Thus, British Arctic whaling records are unique, as they include both the beginning and the final story of the near extirpation of the species from these waters. By consolidating, cross-checking, and updating the work of numerous colleagues over the years, a database of over 11,000 individual records of British whaling voyages to these grounds between 1725 and 1913 has been established. Using conversion algorithms, it has been possible to derive statistically robust information on the length of the bowheads caught from the amount of oil they yielded. Translating oil yield to whale length is an important step as oil yield is one of the most common parameters documented within historical whaling records. Analysis suggests the length of whales caught at these two whaling grounds, Greenland Sea and Davis Strait, were different. A higher proportion within the East Greenland-Svalbard-Barents stock, taken from the Greenland Sea grounds, measured less than 12.5m (classed as juveniles), whilst the East Canada-West Greenland stock, taken from Davis Strait grounds, were skewed towards larger whales, 13 to 14 m long (classed as sexually mature). Furthermore, there was clear evidence that a shift in the distribution of whale length occurred when the whalers extended their hunting grounds to encompass additional regions within the Greenland Sea and Davis Strait in 1814 and 1817 respectively. Prior to expansion, we find that that the vast majority (85%) of the East Canada-West Greenland stock were of the length that are classified as sexually mature (>13.0 m), whereas only 39% of East Greenland-Svalbard-Barents stock taken were of this size. After the enlargement of the whaling grounds, the length distribution shifted with a reduction to 50% of the East Canada-West Greenland stock and an increase to 44% of the East Greenland-Svalbard-Barents stock being categorised as sexually mature. These results show the important information that may be derived from historical whaling records. Since the commercial hunt of the bowheads ceased in the European Arctic there have been substantial changes in both the oceanographic and sea ice regime in the region, thus understanding the past through whaling records can help to understand the implications of future climate-induced changes in bowhead whale populations and their habitat.
Nature-based coastal restoration: Development of an early-rearing production protocol of sugar kelp (Saccharina latissima Linnaeus) for bottom planting activities in the Gulf of St-Lawrence (Québec, Canada)
Authors: Le François Nathalie R. , Tremblay-Gratton Anne , Drouin-Johnson Charles , Prégent Jasmine , Presne-Poissant Marie-Pomme , Boussin Jean-Christophe , Piché-Lebel Florence , Gendron-Lemieux Isabelle
Published: April 2023

Successful bottom planting of indigenous macroalgae Saccharina latissima aimed at coastal restoration purposes require the mass production in controlled conditions of strongly fixed, healthy sporophytes followed by optimal transfer techniques in order to ensure viability and vigor of the young seedlings about to be directly introduced in the coastal environment. Early development of S. latissima submitted to different combinations of substrate type (natural vs artificial brick-shaped substrate), gametophyte spraying method (water-based vs binder-based) and water velocity (0.1 vs 0.2 m s-1) was evaluated during a growth trial that lasted 42 days. Overall, all experimental groups (8 in triplicate) reached the targeted length of 15 mm between 35-42 days post-seeding. No strong indications that the proposed 2×2×2 factorial design generated long lasting effects on growth and development indicators were observed (thallus length, SGR and % coverage). The observation of no persistent difference in the growth response of S. latissima under all experimental conditions, demonstrates that it is well suited for mass production of seedlings. Our results and evidenced-based practices led us to conclude that the use of an artificial substrate in combination with a binder-based gametophyte pulverization and the application of a velocity 0.2 m s-1 during early-growth could be adopted in a standardized protocol. We argue that 1) artificial substrates (uniform shape, stackable and rough surface) will most likely allow better use of a vessel’s open deck space and adherence of the developing holdfast; 2) the use of a binder may slow down the dehydration of the propagules and promote adhesiveness to the substrate during rearing, handling and transfer operations and under varying flow rates or wave actions respectively and 3) highest velocity should promote the selection of propagules with strongest attachment and thus possibly limit post-transfer dislodgement. We suggest further studies should 1) focus on identifying optimal gametophyte concentration at the spraying step, in order to reduce production costs and maximise productivity of seedling operations and 2) include biomass determination (g of tissue per cm2) in combination to the semi-quantitative density evaluation (% coverage) based on image-analysis, in order to improve our global assessment of growth.