bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models
Authors: Kauffman Nathan , Singh Satyendra Kumar , Morrison James , Zinn Kurt R.
Published: May 2023

Intravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous radiopeptide therapies have explored the use of alpha (α)-particle emitting radioisotopes, but microspheres radiolabeled with α-particle emitters have not yet been studied. Here, FDA-approved macroaggregated albumin (MAA) particles were radiolabeled with Bismuth-212 (Bi-212-MAA) and evaluated using clonogenic and survival assays in vitro and using immune-competent mouse models of breast cancer. The in vivo biodistribution of Bi-212-MAA was investigated in Balb/c and C57BL/6 mice with 4T1 and EO771 orthotopic breast tumors, respectively. The same orthotopic breast cancer models were used to evaluate the treatment efficacy of Bi-212-MAA. Our results showed that macroaggregated albumin can be stably radiolabeled with Bi-212 and that Bi-212-MAA can deliver significant radiation therapy to reduce the growth and clonogenic potential of 4T1 and EO771 cells in vitro. Additionally, Bi-212-MAA treatment upregulated γH2AX and cleaved Caspase-3 expression in 4T1 cells. Biodistribution analyses showed 87–93% of the Bi-212-MAA remained in 4T1 and EO771 tumors 2 and 4 h after injection. Following single-tumor treatments with Bi-212-MAA there was a significant reduction in the growth of both 4T1 and EO771 breast tumors over the 18-day monitoring period. Overall, these findings showed that Bi-212-MAA was stably radiolabeled and inhibited breast cancer growth. Bi-212-MAA is an exciting platform to study α-particle therapy and will be easily translatable to larger animal models and human clinical trials.
Case report: Successful treatment of mediastinal unicentric castleman disease using cardiopulmonary bypass
Authors: Ran Wei , Cuilin Zhu , Hulin Piao , Kexiang Liu
Published: May 2023

Unicentric Castleman disease (UCD) is a rare, benign lymphoproliferative disorder. Mediastinal UCD has tumors with no clear boundaries that are highly vascularized. Resection surgery results in bleeding, leading to further challenges. Mixed-type UCD is rare. We report the case of a 38-year-old asymptomatic patient with mixed-type UCD; the tumor measured 7.8 cm in size and had unclear boundaries. The tumor was successfully resected by performing a cardiopulmonary bypass on the beating heart; the patient recovered uneventfully.
Temporal clustering of fissural eruption across multiple segments within the Ethiopian Rift
Authors: Siegburg Melanie , Gernon Thomas M. , Keir Derek , Bull Jonathan M. , Taylor Rex N. , Watts Emma J. , Greenfield Tim , Gebru Ermias F.
Published: May 2023

Magmatic continental rifts show evidence that discrete rift segments experience episodic intrusive and eruptive events, more commonly termed rifting episodes. However, whether multiple rifting episodes across adjacent rift segments are clustered in time is not well understood. To address this issue, we conduct new radiocarbon dating that constrains the timing of the most recent rifting episode at the Boset magmatic segment of the northern Ethiopian rift, and combine this with historical dating of similar rifting events in the adjacent magmatic segments. New radiocarbon dates of multiple charcoal samples from the base of the most recent fissural lava at the Boset Volcanic Complex indicate that it likely occurred between 1812 and 1919 CE. These dates are similar to those from historical accounts of fissural eruption from the neighbouring Kone (∼1810 CE), and Fantale (∼1770 to 1808 CE) magmatic segments. We conduct new analysis of major and trace element compositions from these historical fissural lavas, as well as from a fresh-looking lava flow from Beru cone near to Kone volcano. The results of the geochemistry from these flows of all three magmatic segments show compositions that vary in the basalt and trachybasalt fields, with sufficient variation to rule out them having erupted from a single dike intrusion episode. This, combined with the scatter in dates from the radiocarbon analysis and historical accounts, along with the location of each eruption in a discrete and spatially offset magmatic segment, favours an interpretation of each magmatic segment experiencing separate rifting episodes but with these being clustered in time. Mechanisms to explain the clustering of rifting episodes are more speculative but could include stress transfer from dike intrusion and deep crustal hydraulic connection in the plumbing system of multiple segments.
Serving families who face economic and related adversities: the ‘5 As’ of effective ECEC service delivery
Authors: Skattebol Jennifer , Adamson Elizabeth , Blaxland Megan
Published: May 2023

Introduction

Families with young children who face economic and related adversities are the most likely group to miss out on the advantages of regular sustained participation in high quality early childhood education and care. In Australia, there are an estimated 11% of children assessed by teachers to have two or more developmental vulnerabilities and many of these children are living in economically disadvantaged contexts. Government policy in Australia aspires to provide universal access to Early Childhood Education and Care (ECEC) services to support children’s outcomes and ensure workforce participation, but policy falls short of ensuring all families can take up high quality early childhood education and care. Government responses to the Covid crisis saw significant changes to the ECEC policy and funding mechanisms. It is timely therefore to reflect on the level of ‘competence’ in the Australian ECEC systems. Coined this term to refer to a system that is sustainable, inclusive, and effective for all families.

Methods

Using a Delphi methodology, we coalesced the insights of high-level stakeholders who have expertise in delivering services to families experiencing adversities and noted points of consensus and of divergence among these stakeholders. We have taken up the challenge of considering the Australian system from the point of view of families who typically find services hard to use.

Results and Conclusion

We put forward a model that frames the characteristics of services that can inclusively engage with families - Approachable, Acceptable, Affordable, Accessible and Appropriate. We argue that more needs to be known about appropriateness and what effective pedagogy looks like on the ground for families and children.
Using an open-ended socio-technical design challenge for entrepreneurship education in a first-year engineering course
Authors: DeWaters Jan , Kotla Bhavana
Published: May 2023

Engineering graduates must be prepared with sound technical knowledge and a range of 21st century competencies and professional skills such as creativity, interdisciplinary collaboration, communication, and innovation to successfully solve today’s complex, global problems. Equally important is a deep appreciation of the degree to which technological solutions are situated within the context of human and natural environments. Despite calls from the National Academy of Engineering and several professional organizations to broaden engineering education to embrace these skills, most engineering programs persistently focus on the importance of technical skills. This paper describes an open-ended team-based design challenge that integrates entrepreneurial-minded (EM) skill development into an interdisciplinary first-year engineering course that approaches engineering from a socio-technical perspective. The challenge was implemented in two simultaneous first-year classes (n = 49), with the goal of fostering students’ broad professional skills and their appreciation of the links between engineering technologies and societal context. The action research study used a quasi-experimental design with convenience sampling and no control group to explore students’ self-perceived entrepreneurial-minded (EM) skills development. Data were collected with a retrospective questionnaire comprised of a series of 5-point Likert-type questions that asked students to assess the development of their EM skills in all three areas of the EM framework: Exhibit Curiosity, Establish Connections, and Create Value (the “3C” framework). Results indicate that students felt they developed EM skills in all three areas of the 3C Framework, with more fully developed skills in the Establish Connections and Create Value categories. Overall, this study suggests the effectiveness of using open-ended, socio-technical engineering design challenges for developing skills that will better prepare students to work collaboratively on complex and interdisciplinary problems they will face in their professional careers.
Characterization of anoikis-based molecular heterogeneity in pancreatic cancer and pancreatic neuroendocrine tumor and its association with tumor immune microenvironment and metabolic remodeling
Authors: Li Ning , Jia Xingqing , Wang Zhong , Wang Kaige , Qu Zumin , Chi Dong , Sun Zhubo , Jiang Jian , Cui Yougang , Wang Changmiao
Published: May 2023

Background

Accumulating evidence suggests that anoikis plays a crucial role in the onset and progression of pancreatic cancer (PC) and pancreatic neuroendocrine tumors (PNETs); nevertheless, the prognostic value and molecular characteristics of anoikis in cancers are yet to be determined.

Materials and methods

We gathered and collated the multi-omics data of several human malignancies using the TCGA pan-cancer cohorts. We thoroughly investigated the genomics and transcriptomics features of anoikis in pan-cancer. We then categorized a total of 930 patients with PC and 226 patients with PNETs into distinct clusters based on the anoikis scores computed through single-sample gene set enrichment analysis. We then delved deeper into the variations in drug sensitivity and immunological microenvironment between the various clusters. We constructed and validated a prognostic model founded on anoikis-related genes (ARGs). Finally, we conducted PCR experiments to explore and verify the expression levels of the model genes.

Results

Initially, we identified 40 differentially expressed anoikis-related genes (DE-ARGs) between pancreatic cancer (PC) and adjacent normal tissues based on the TCGA, GSE28735, and GSE62452 datasets. We systematically explored the pan-cancer landscape of DE-ARGs. Most DE-ARGs also displayed differential expression trends in various tumors, which were strongly linked to favorable or unfavorable prognoses of patients with cancer, especially PC. Cluster analysis successfully identified three anoikis-associated subtypes for PC patients and two anoikis-associated subtypes for PNETs patients. The C1 subtype of PC patients showed a higher anoikis score, poorer prognosis, elevated expression of oncogenes, and lower level of immune cell infiltration, whereas the C2 subtype of PC patients had the exact opposite characteristics. We developed and validated a novel and accurate prognostic model for PC patients based on the expression traits of 13 DE-ARGs. In both training and test cohorts, the low-risk subpopulations had significantly longer overall survival than the high-risk subpopulations. Dysregulation of the tumor immune microenvironment could be responsible for the differences in clinical outcomes between low- and high-risk groups.

Conclusions

These findings provide fresh insights into the significance of anoikis in PC and PNETs. The identification of subtypes and construction of models have accelerated the progress of precision oncology.
COVID‐19 and sarcopenia-related traits: a bidirectional Mendelian randomization study
Authors: Liu Chao , Liu Ningyuan , Zeng Yi , Xiao Bo , Wang Pingxiao , Zhou Chuqiao , Xia Yu , Zhao Ziyue , Xiao Tao , Li Hui
Published: May 2023

Background

Emerging evidence suggested that coronavirus disease 2019 (COVID-19) patients were more prone to acute skeletal muscle loss and suffer sequelae, including weakness, arthromyalgia, depression and anxiety. Meanwhile, it was observed that sarcopenia (SP) was associated with susceptibility, hospitalization and severity of COVID-19. However, it is not known whether there is causal relationship between COVID‐19 and SP-related traits. Mendelian randomization (MR) was a valid method for inferring causality.

Methods

Data was extracted from the COVID‐19 Host Genetic Initiative and the UK Biobank without sample overlapping. The MR analysis was performed with inverse variance weighted, weighted median, MR-Egger, RAPS and CAUSE, MR-APSS. Sensitivity analysis was conducted with MR-Egger intercept test, Cochran’s Q test, MR-PRESSO to eliminate pleiotropy.

Results

There was insufficient result in the MR-APSS method to support a direct causal relationship after the Bonferroni correction. Most other MR results were also nominally consistent with the MR-APSS result.

Conclusions

Our study first explored the causal relationship between COVID-19 and SP-related traits, but the result indicated that they may indirectly interact with each other. We highlighted that older people had better absorb enough nutrition and strengthen exercise to directly cope with SP during the COVID-19 pandemic.
Selenium level correlates negatively with antibodies but positively with thyroid function in children with down syndrome: an Indonesian study
Authors: Hisbiyah Yuni , Endaryanto Anang , Setyoboedi Bagus , Rochmah Nur , Faizi Muhammad , Fedora Katherine
Published: May 2023

Background

Children with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Se’s role in AITD in Indonesian children with DS.

Methods

This cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann–Whitney, and Spearman’s rank correlation (rs). All results with p<0.05 were considered statistically significant.

Results

Among 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 and p=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (rs=−0.439 with p=1×10-5 and rs=−0.396 with p=0.001, respectively) and Tg-Ab (rs=−0.474 with p=1×10-5 and rs=−0.410 with p=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (rs=-0.252, p=0.048) in the AITD group.

Conclusion

Selenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.
Analysis and research on the thermal system of waste incineration power generation unit based on heat balance method
Authors: Xiao Jian
Published: May 2023

The thermal system of waste incineration power generation unit is simple and small in capacity, but the original parameters are few. It needs to calculate the thermal system and derive the parameters by using the conventional heat balance method to obtain the complete thermal system parameters. In this paper, an accurate and perfect thermodynamic model of waste incineration power generation is established to solve the problems of low thermal efficiency and high unit investment cost of the waste incineration power generation. To investigate the internal relationship between the incinerator unit structure, operating parameters, waste calorific value and waste combustion process, optimize the combustion status of different incinerators burning different waste, and realize its stable and efficient operation, it is necessary to study the impact of changing operating parameters and different incinerator structures on the waste incineration process, as well as the incineration law of a single incinerator unit structure burning waste with different calorific value. Based on the two-fluid model of primary oxygen supply and secondary oxygen supply, a newly developed thermodynamic model for waste incineration engineering was developed, and the direct coupling between the reciprocating grate and the incinerator was realized in the software. Using the conventional heat balance method and constant flow calculation, the flow parameters of the thermal system under the design condition are calculated through the design pressure parameters to calculate the power generation and thermal economy index of the condition; and the relevant steam extraction flow is checked and verified. The experimental results show that the net thermal efficiency of waste incineration increases from 19. 73% to 26. 40%, and the energy utilization efficiency also increases by 0. 18%. The net thermal efficiency of the optimized integrated power generation system is always higher than that of the independent power generation system more than 0.16%. The model method used in this paper can reduce the influence of incinerator arch structure on bed combustion to a greater extent, which makes the simulation results close to reality, greatly reduces the calculation cost, and is conducive to the industrial application of simulation in the field of waste incineration.
Day-ahead and intra-day two-stage low-carbon economic scheduling method considering multi-form energy-intensive load
Authors: Yuan Zhijun , Wang Yibo , Xu Yueyang , Liu Chuang , Ge Weichun , Cai Guowei , Zhou Jianing , Sun Ao , Liu Xin , Li Baihe
Published: May 2023

To solve the problem of the large gap in the regulation resources of the power system due to the large number of wind power connected to the grid and to help achieve the strategic energy goal of “carbon neutrality and carbon peaking,” the demand-side adjustable energy-intensive load is taken as the research object in this paper, and a two-stage low-carbon economic scheduling method of the wind power system with multi-form energy-intensive load (MEL) is proposed. First, the operating characteristics of the system with MEL are analyzed. At the same time, a refined mathematical model that conforms to the actual operation characteristics is established. Then, the complementary low-carbon characteristics of the source-charge side and the difference in the response characteristics of the demand-side MEL are considered. Meanwhile, combining with the energy storage system, a day-ahead and intra-day two-stage low-carbon economic scheduling model of the wind power system with MEL is constructed. Finally, an example of the improved IEEE-39 bus system is analyzed to verify the effectiveness of the proposed scheduling method in the low-carbon economic scheduling of wind power systems and to provide a reference for power grid scheduling.
Impact of house prices on household carbon emissions
Authors: Cong Ying , Wang Yanxu , Wu Yanlin
Published: May 2023

Carbon emissions generated by household activities are an important factor in climate change; reducing household carbon emissions (HCEs) will be an essential part of future energy conservation and sustainability initiatives. Housing prices have a crucial impact on residents’ consumption, and the increase of consumption level is the main reason for the rise of household carbon emissions. Therefore, studying the impact of housing prices on HCEs not only provides guidance on expanding domestic demand and increasing consumption from the perspective of housing prices but also provides construction advice on curbing global warming and is more conducive to the development of building sustainable consumption. Taking household consumption as a starting point, this study investigates the impact of house prices on HCE in China based on the 2018 Chinese Household Tracking Survey (CFPS) and the China Energy Statistics Yearbook, using the carbon emission factor method to measure carbon emissions. It was found that increased house prices had a significant positive effect on HCEs. There is a clear wealth effect of rising house prices among homeowners, while the substitution effect also increases consumption among non-homeowners (by reducing attempts to save). Furthermore, rising house prices have a varied effect on different types of HCEs. The impact on emissions from everyday necessities such as clothing and housing is greater, and the impact on entertainment-related carbon emissions is small. In addition, rising house prices had the strongest effect on HCEs in central China. Homeowners in the east responded more to increased house prices than in the west, while the inverse effect was observed among non-homeowners. Urban homeowners and rural non-homeowners were also more sensitive to rising house prices. Policy recommendations are made based on the findings.
Coordinated development of regional resources, environment, and economic growth under the background of low-carbon economy
Authors: Wang Ziwen
Published: May 2023

Introduction

At present, the rapid growth of social and economic development has also brought great challenges to the development of regional resources and environment. With the deepening of the concept of sustainable development, the coordinated development of regional resources, environment and economic growth has attracted more and more attention. The coordinated development of resources, environment and economic growth is not only the engine of industrial growth, but also the accelerator to promote industrial transfer and optimal allocation of resources, which has injected a strong impetus into social development. However, with the continuous upgrading of the industrial structure, environmental pollution, unbalanced economic development, resource shortage and other problems have gradually emerged in various important development areas.

Methods

In order to effectively solve this dilemma, this paper takes the Beijing-Tianjin-Hebei region (BTH) as an example, based on the analysis of the current situation of the economic and environmental development of BTH region and the influencing factors, combined with the background of low-carbon economy (LCE), effectively studies the coordinated development of its resources, environment and economic growth. In order to verify the effectiveness of low-carbon economic development, this paper, based on the actual development data of BTH region, tests the three dimensions of economic benefit index, environmental benefit index and emission reduction efficiency index.

Results

The results show that the average environmental benefit index of 13 cities in the BTH region after the implementation of the target is about 0.457. The average benefit index before the implementation of the target was about 0.449.

Discussion

From the final results of the test, it can be seen that the development of low-carbon economy has strong feasibility for promoting the coordinated development of regional resources, environment and economic growth.
Dual inhibition of phosphoinositide 3-kinases delta and gamma reduces chronic B cell activation and autoantibody production in a mouse model of lupus
Authors: Olayinka-Adefemi Folayemi , Hou Sen , Marshall Aaron J.
Published: May 2023

Phosphoinositide 3-kinase delta (PI3Kδ) plays key roles in normal B cell activation and is chronically activated in malignant B cells. Targeting of PI3Kδ using FDA-approved drugs Idelalisib or Umbralisib has shown efficacy in treatment of multiple B cell malignancies. Duvelisib, an inhibitor targeting both PI3Kδ and PI3Kγ (PI3Kδγi) has also been used for treatment of several leukemias and lymphomas and was suggested to offer potential additional benefits in supressing T cell and inflammatory responses. Transcriptomics analyses indicated that while most B cell subsets predominantly express PI3Kδ, plasma cells upregulate PI3Kγ. We thus assessed whether PI3Kδγi treatment can impact chronic B cell activation in the context of an autoantibody-mediated disease. Using the TAPP1R218LxTAPP2R211L (TAPP KI) mouse model of lupus-like disease driven by dysregulated PI3K pathway activity, we performed 4 week PI3Kδγi treatments and found significant reduction in CD86+ B cells, germinal center B cells, follicular helper T cells and plasma cells in multiple tissues. This treatment also significantly attenuated the abnormally elevated serum levels of IgG isotypes observed in this model. The profile of autoantibodies generated was markedly altered by PI3Kδγi treatment, with significant reductions in IgM and IgG targeting nuclear antigens, matrix proteins and other autoantigens. Kidney pathology was also impacted, with reduced IgG deposition and glomerulonephritis. These results indicate that dual inhibition of PI3Kδ and PI3Kγ can target autoreactive B cells and may have therapeutic benefits in autoantibody-mediated disease.
Crosstalk between cholesterol metabolism and psoriatic inflammation
Authors: Luo Lingling , Guo Youming , Chen Lihao , Zhu Jing , Li Chengrang
Published: May 2023

Psoriasis is a chronic autoinflammatory skin disease associated with multiple comorbidities, with a prevalence ranging from 2 to 3% in the general population. Decades of preclinical and clinical studies have revealed that alterations in cholesterol and lipid metabolism are strongly associated with psoriasis. Cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-17), which are important in the pathogenesis of psoriasis, have been shown to affect cholesterol and lipid metabolism. Cholesterol metabolites and metabolic enzymes, on the other hand, influence not only the biofunction of keratinocytes (a primary type of cell in the epidermis) in psoriasis, but also the immune response and inflammation. However, the relationship between cholesterol metabolism and psoriasis has not been thoroughly reviewed. This review mainly focuses on cholesterol metabolism disturbances in psoriasis and their crosstalk with psoriatic inflammation.
Whole intestinal microbiota transplantation is more effective than fecal microbiota transplantation in reducing the susceptibility of DSS-induced germ-free mice colitis
Authors: Yang Yapeng , He Jinhui , Wang Yuqing , Liang Lifeng , Zhang Zeyue , Tan Xiang , Tao Shiyu , Wu Zhifeng , Dong Miaomiao , Zheng Jixia , Zhang Hang , Feng Shuaifei , Cheng Wei , Chen Qiyi , Wei Hong
Published: May 2023

Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of inflammatory bowel disease (IBD). Previous studies have reported that compared with FMT, whole intestinal microbiota transplantation (WIMT) can more precisely replicate the community structure and reduce the inflammatory response of the host. However, it remains unclear whether WIMT is more effective in alleviating IBD. To examine the efficacy of WIMT and FMT in the intervention of IBD, GF (Germ-free) BALB/c mice were pre-colonized with whole intestinal microbiota or fecal microbiota before being treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by both WIMT and FMT, as demonstrated by the prevention of body weight loss and decreased the Disease activity index and histological scores in mice. However, WIMT’s anti-inflammatory effect was superior to that of FMT. In addition, the inflammatory markers myeloperoxidase (MPO) and eosinophil peroxidase were dramatically downregulated by WIMT and FMT. Furthermore, the use of two different types of donors facilitated the regulation of cytokine homeostasis in colitis mice; the level of the pro-inflammatory cytokine IL-1β in the WIMT group was significantly lower than that in the FMT group, while the level of the anti-inflammatory factor IL-10 was significantly higher than that in the FMT group. Both groups showed enhanced expression of occludin to protect the intestinal barrier in comparison with the DSS group, and the WIMT group demonstrated considerably increased levels of ZO-1. The sequencing results showed that the WIMT group was highly enriched in Bifidobacterium, whereas the FMT group was significantly enriched in Lactobacillus and Ochrobactrum. Correlation analysis revealed that Bifidobacterium was negatively correlated with TNF-α, whereas Ochrobactrum was positively correlated with MPO and negatively correlated with IL-10, which might be related to different efficacies. Functional prediction using PICRUSt2 revealed that the FMT group was considerably enriched in the L-arginine biosynthesis I and L-arginine biosynthesis IV pathway, whereas the WIMT group was enriched in the L-lysine fermentation to acetate and butanoate pathway. In conclusion, the symptoms of colitis were subsided to varying degrees by the two different types of donors, with the WIMT group being more effective than the FMT group. This study provides new information on clinical interventions for IBD.
T cell immunity following COVID-19 vaccination in adult patients with primary antibody deficiency – a 22-month follow-up
Authors: Hurme Antti , Jalkanen Pinja , Marttila-Vaara Minna , Heroum Jemna , Jokinen Heidi , Vara Saimi , Liedes Oona , Lempainen Johanna , Melin Merit , Julkunen Ilkka , Kainulainen Leena
Published: May 2023

Primary antibody deficiencies, such as common variable immunodeficiency (CVID), are heterogenous disease entities consisting of primary hypogammaglobulinemia and impaired antibody responses to vaccination and natural infection. CVID is the most common primary immunodeficiency in adults, presenting with recurrent bacterial infections, enteropathy, autoimmune disorders, interstitial lung diseases and increased risk of malignancies. Patients with CVID are recommended to be vaccinated against SARS-CoV-2, but there are relatively few studies investigating humoral and cellular responses to immunization. We studied the dynamics of humoral and cell-mediated immunity responses up to 22 months in 28 patients with primary immunodeficiency and three patients with secondary immunodeficiency receiving ChAdOx1, BNT162b2 and mRNA-1273 COVID-19 vaccines. Despite inadequate humoral response to immunization, we demonstrate a robust T cell activation likely protecting from severe COVID-19.
Crosstalk between colorectal cancer cells and cancer-associated fibroblasts in the tumor microenvironment mediated by exosomal noncoding RNAs
Authors: Sun Shichen , Zhang Yanyu , Li Yubing , Wei Linlin
Published: May 2023

Colorectal cancer (CRC) is a common malignant tumor of the digestive system, and its morbidity rates are increasing worldwide. Cancer-associated fibroblasts (CAFs), as part of the tumor microenvironment (TME), are not only closely linked to normal fibroblasts, but also can secrete a variety of substances (including exosomes) to participate in the regulation of the TME. Exosomes can play a key role in intercellular communication by delivering intracellular signaling substances (e.g., proteins, nucleic acids, non-coding RNAs), and an increasing number of studies have shown that non-coding RNAs of exosomal origin from CAFs are not only closely associated with the formation of the CRC microenvironment, but also increase the ability of CRC to grow in metastasis, mediate tumor immunosuppression, and are involved in the mechanism of drug resistance in CRC patients receiving. It is also involved in the mechanism of drug resistance after radiotherapy in CRC patients. In this paper, we review the current status and progress of research on CAFs-derived exosomal non-coding RNAs in CRC.
Molecular mechanisms and cellular functions of liquid-liquid phase separation during antiviral immune responses
Authors: Yang Shuai , Shen Weishan , Hu Jiajia , Cai Sihui , Zhang Chenqiu , Jin Shouheng , Guan Xiangdong , Wu Jianfeng , Wu Yaoxing , Cui Jun
Published: May 2023

Spatiotemporal separation of cellular components is vital to ensure biochemical processes. Membrane-bound organelles such as mitochondria and nuclei play a major role in isolating intracellular components, while membraneless organelles (MLOs) are accumulatively uncovered via liquid-liquid phase separation (LLPS) to mediate cellular spatiotemporal organization. MLOs orchestrate various key cellular processes, including protein localization, supramolecular assembly, gene expression, and signal transduction. During viral infection, LLPS not only participates in viral replication but also contributes to host antiviral immune responses. Therefore, a more comprehensive understanding of the roles of LLPS in virus infection may open up new avenues for treating viral infectious diseases. In this review, we focus on the antiviral defense mechanisms of LLPS in innate immunity and discuss the involvement of LLPS during viral replication and immune evasion escape, as well as the strategy of targeting LLPS to treat viral infectious diseases.
Immunotherapy of hepatocellular carcinoma: recent progress and new strategy
Authors: Li Jiarui , Xuan Shihai , Dong Peng , Xiang Ze , Gao Ce , Li Mo , Huang Lan , Wu Jian
Published: May 2023

Due to its widespread occurrence and high mortality rate, hepatocellular carcinoma (HCC) is an abhorrent kind of cancer. Immunotherapy is a hot spot in the field of cancer treatment, represented by immune checkpoint inhibitors (ICIs), which aim to improve the immune system’s ability to recognize, target and eliminate cancer cells. The composition of the HCC immune microenvironment is the result of the interaction of immunosuppressive cells, immune effector cells, cytokine environment, and tumor cell intrinsic signaling pathway, and immunotherapy with strong anti-tumor immunity has received more and more research attention due to the limited responsiveness of HCC to ICI monotherapy. There is evidence of an organic combination of radiotherapy, chemotherapy, anti-angiogenic agents and ICI catering to the unmet medical needs of HCC. Moreover, immunotherapies such as adoptive cellular therapy (ACT), cancer vaccines and cytokines also show encouraging efficacy. It can significantly improve the ability of the immune system to eradicate tumor cells. This article reviews the role of immunotherapy in HCC, hoping to improve the effect of immunotherapy and develop personalized treatment regimens.
Potential negative effects of the Brazilian Space Program on coastal sharks
Authors: Wosnick Natascha , Chaves Ana Paula , Leite Renata Daldin , Nunes Jorge Luiz Silva , Hauser-Davis Rachel Ann
Published: May 2023

The Brazilian government recently announced its first partnerships with the private sector, including American and Canadian companies, to use the Alcântara Space Center (Maranhão, northern Brazil). This center is known for its privileged location, saving up to 30% of fuel in launches. Its operationalization is an offshoot of the Technological Safeguards Agreement, which is important for the Brazilian Space Program due to greater space sector investments and environmentally relevant projects. In 2003, a major fire at the Alcântara Space Center destroyed a rocket and killed 21 workers, halting Brazilian Space Program activities. Recently, our research group reported serious environmental consequences of this accident, i.e., extremely high amounts of Rubidium (Rb) in apex predatory sharks near the Alcântara Space Center. This element is used in fuels and in space propulsion systems and is potentially toxic, displaying bioaccumulating and biomagnifying capabilities. The observed concentrations are the highest ever detected in any living organism (up to 24.65 mg kg-1 dry weight). The launch base is located on the Brazilian Amazon Coast, and population recruitment impacts may compromise biota conservation and biodiversity. Local shark meat consumption is also worrying, as consumers may be exposed to Rb, whose effects in humans are unknown. We, therefore, indicate an urgent need for biomonitoring efforts in the area, as the Alcântara Space Center is about to operate at its maximum capacity.
Erosion and accretion of salt marsh in extremely shallow water stages
Authors: Chen Dezhi , Tang Jieping , Xing Fei , Cheng Jun , Li Mingliang , Zhang Yiyi , Shi Benwei , Shi Lianqiang , Wang Ya Ping
Published: May 2023

Salt marshes, which commonly exist on the upper tidal flat, provide a natural barrier against sea level rise and coastal storm. The extremely shallow water stages (water depth< 0.2 m), including the initial stage of flood tides and the last stage of ebb tides, can induce a significant impact on sediment dynamics of saltmarshes and associated tidal flats, despite lasting for only a short time (around 10 min), which has been less studied. In this study, two parallel field sites were established to quantify erosion-accretion processes and morphological changes during extremely shallow water stages in salt marshes within Doulonggang tidal flat along the Jiangsu coast. Our results revealed that obvious accretion occurred during extremely shallow water stages, with a total deposition amount of +33.8 mm in vegetated areas and +20.8 mm in unvegetated areas. In contrast, erosion dominated during deep water stages, with a total erosion amount of -22.3 mm at the vegetated site and -32.7 mm at the unvegetated site. The magnitude of bed-level change during extremely shallow water stages was 7~8 times greater than that during deep water stages, even though the duration of extremely shallow water stages was only about 14~15% of the entire tidal cycle. Furthermore, strong winds significantly impacted deposition during extremely shallow water stages compared to calm weather. During the strong wind period, the average bed level change rate reached +0.15 mm/min and +0.12 mm/min in the vegetated and unvegetated areas, respectively. This is significantly higher than the +0.05 mm/min and +0.01 mm/min during the calm weather period. These results reveal that extremely shallow water stages have substantial impacts on sedimentary processes, which are vital for the maintenance of tidal flat systems.
Study on the effect of activated coal gangue on the mechanical and hydration properties of cement
Authors: Zhu Zewen , Liu Chaoqun , Mao Lin , Han Zhixing , Chen Leiwei , Zou Huijie , Li Lianghua , Yu Pengfei , Dong Jingliang , Zhang Yonggang
Published: May 2023

This study aims to minimize the carbon emissions of cement and investigate the viability of employing activated coal gangue (CG) as an additional cementitious ingredient. This paper investigated the effects of water-cement ratio, ages, and amount of activated CG dosing on the compressive and flexural strength of cement mortar as well as the effects of activated CG on hydration products, hydration process, and hydration degree. The impacts of activated CG on the hydration products and microstructure of cement were examined using XRD, SEM, and TG/DTG systems. A large amount of active SiO2 and Al2O3 in the activated CG react with Ca(OH)2 leading to a secondary hydration reaction in cement. The hydrated calcium silicate and hydrated calcium aluminate gels produced by the subsequent hydration process can reduce the porosity of hardened cement and boost cement mortar strength. The 28 days flexural and compressive strengths of specimens with 30wt.% activated CG rise by 11.69% and 11.82%, respectively, in comparison to that of specimens with 30wt.% quartz powder. When activated CG is mixed with cement, the early hydration rate of the cement can be decreased while the later hydration rate is increased.
Multidrug-resistant organism-peritoneal dialysis associated peritonitis: clinical and microbiological features and risk factors of treatment failure
Authors: Guo Shizheng , Yang Liming , Zhu Xueyan , Zhang Xiaoxuan , Meng Lingfei , Li Xinyang , Cheng Siyu , Zhuang Xiaohua , Liu Shengmao , Cui Wenpeng
Published: May 2023

Background

Multidrug-resistant (MDR) bacterial infection causes difficulty in the therapy of peritoneal dialysis-associated peritonitis (PDAP); however, there are few studies on multidrug-resistant organism (MDRO)-PDAP. In view of growing concerns about MDRO-PDAP, the aim of this study was to investigate the clinical features, risk factors of treatment failure, and causative pathogens of MDRO-PDAP.

Methods

In total, 318 patients who underwent PD between 2013 and 2019 were included in this multicenter retrospective study. Clinical features, patient outcomes, factors related to treatment failure, and microbiological profiles associated with MDRO-PDAP were analyzed and risk factors for treatment failure associated with MDR-Escherichia coli (E. coli) were further discussed.

Results

Of 1,155 peritonitis episodes, 146 eligible episodes of MDRO-PDAP, which occurred in 87 patients, were screened. There was no significant difference in the composition ratio of MDRO-PDAP between 2013–2016 and 2017–2019 (p > 0.05). E. coli was the most prevalent MDRO-PDAP isolate, with high sensitivity to meropenem (96.0%) and piperacillin/tazobactam (89.1%). Staphylococcus aureus was the second most common isolate and was susceptible to vancomycin (100%) and linezolid (100%). Compared to non-multidrug-resistant organism-PDAP, MDRO-PDAP was associated with a lower cure rate (66.4% vs. 85.5%), higher relapse rate (16.4% vs. 8.0%), and higher treatment failure rate (17.1% vs.6.5%). Dialysis age [odds ratio (OR): 1.034, 95% confidence interval (CI): 1.016–1.052, p < 0.001] and >2 previous peritonitis episodes (OR: 3.400, 95% CI: 1.014–11.400, p = 0.047) were independently associated with treatment failure. Furthermore, longer dialysis age (OR: 1.033, 95% CI: 1.003–1.064, p = 0.031) and lower blood albumin level (OR: 0.834, 95% CI: 0.700–0.993, p = 0.041) increased the risk of therapeutic failure for MDR-E. coli infection.

Conclusion

The proportion of MDRO-PDAP has remained high in recent years. MDRO infection is more likely to result in worse outcomes. Dialysis age and previous multiple peritonitis infections were significantly associated with treatment failure. Treatment should be promptly individualized based on local empirical antibiotic and drug sensitivity analyses.
Case report: Concurrent pylephlebitis and subarachnoid hemorrhage in an octogenarian patient with Escherichia coli sepsis
Authors: Zhao Yong , Feng Dandan , Wang Xinyu , Sun Yuanyuan , Liu Junni , Li Xiaodong , Zhou Nannan , Wang Jianchun
Published: May 2023

Background

Pylephlebitis refers to an infective suppurative thrombosis that occurs in the portal vein and its branches. Concurrent pylephlebitis and subarachnoid hemorrhage (SAH) are rare but fatal for patients with sepsis. This scenario drives the clinicians into a dilemma of how to deal with coagulation and bleeding simultaneously.

Case summary

An 86-year-old man was admitted to hospital for chills and fever. After admission, he developed headache and abdominal distension. Neck stiffness, Kernig's and Brudzinski's sign were present. Laboratory tests discovered decreased platelet count, elevated inflammatory parameters, aggravated transaminitis, and acute kidney injury. Escherichia coli (E. coli) were identified in blood culture. Computed tomography (CT) revealed thrombosis in the superior mesenteric vein and portal veins. Lumbar puncture and Brain CT indicated SAH. The patient had eaten cooked oysters prior to illness. It was speculated that the debris from oyster shell might have injured his intestinal mucosa and resulted in bacterial embolus and secondary thrombosis in portal veins. The patient was treated with effective antibiotics, fluid resuscitation, and anticoagulation. The dose titration of low molecular weight heparin (LMWH) under close monitoring attributed to diminution of the thrombosis and absorption of SAH. He recovered and was discharged after 33-day treatment. One-year follow-up indicated that the post-discharge course was uneventful.

Conclusion

This report describes a case of an octogenarian with E. coli septicemia who survived from concurrent pylephlebitis and SAH along with multiple organ dysfunction syndrome. For such patients with life-threatening complications, even in the acute stage of SAH, decisive employment of LMWH is essential to resolve thrombosis and confers a favorable prognosis.
New pattern of individualized management of chronic diseases: focusing on inflammatory bowel diseases and looking to the future
Authors: Guo Xi , Cai Liyang , Cao Yuchen , Liu Zining , Zhang Jiexin , Liu Danni , Jiang Zhujun , Chen Yanxia , Fu Min , Xia Zhaoxia , Yi Guoguo
Published: May 2023

Non-infectious chronic diseases, especially inflammatory bowel diseases (IBDs), hypertension, and diabetes mellitus, are characterized by a prolonged and multisystemic course, and their incidence increases annually, usually causing serious economic burden and psychological stress for patients. Therefore, these diseases deserve scientific and consistent disease management. In addition, the lack of a comprehensive “early disease clues tracking—personalized treatment system—follow-up” model in hospitals also exacerbates this dilemma. Based on these facts, we propose an individualized prediction management system for IBDs based on chronic diseases, focusing on the established IBDs-related prediction models and summarizing their advantages and disadvantages. We call on researchers to pay attention to the integration of models with clinical practice and the continuous correction of models to achieve truly individualized medical treatment for chronic diseases, thus providing substantial value for the rapid diagnosis and adequate treatment of chronic diseases such as IBDs, which follow the “relapse-remission” disease model, and realizing long-term drug use and precise disease management for patients. The goal is to achieve a new level of chronic disease management by scientifically improving long-term medication, precise disease management, and individualized medical treatment, effectively prolonging the remission period and reducing morbidity and disability rates.
Fungal network composition and stability in two soils impacted by trifluralin
Authors: He Hairong , Huang Jiarui , Zhao Zhenzhu , Xu Huifang , Zheng Xiaoke , Zhang Changpeng , Du Pengqiang
Published: May 2023

Introduction

The composition and stability of soil fungal network are important for soil function, but the effect of trifluralin on network complexity and stability is not well understood.

Methods

In this study, two agricultural soils were used to test the impact of trifluralin on a fungal network. The two soils were treated with trifluralin (0, 0.84, 8.4, and 84 mg kg−1) and kept in artificial weather boxes.

Results and discussion

Under the impact of trifluralin, the fungal network nodes, edges, and average degrees were increased by 6–45, 134–392, and 0.169–1.468 in the two soils, respectively; however, the average path length was decreased by 0.304–0.70 in both soils. The keystone nodes were also changed in trifluralin treatments in the two soils. In the two soils, trifluralin treatments shared 219–285 nodes and 16–27 links with control treatments, and the network dissimilarity was 0.98–0.99. These results indicated that fungal network composition was significantly influenced. After trifluralin treatment, fungal network stability was increased. Specifically, the network robustness was increased by trifluralin with 0.002–0.009, and vulnerability was decreased by trifluralin with 0.0001–0.00032 in the two soils. Fungal network community functions were also impacted by trifluralin in both soils. Trifluralin significantly impacts the fungal network.