bluuebunny/crossref_metadata_2025 huggingface dataset:
DEVELOPMENT OF STUDENT WORKSHEETS CLASS VIII SCIENCE LESSONS ON VIBRATION MATERIAL
Authors: Ai Rohaeti  , Nur Hayati
Published: November 2022

Science learning, which relies on K-13 and teachers, is a requirement for student abilities that include cognitive, affective, and psychomotor as targets for achieving graduation abilities. Limitations in communication and other learning support are not overall needs become obstacles in student learning activities, so learning can not form optimally. Achieve maximum learning teaching materials are needed that are proportional to the needs as a learning guide for students. A Student worksheet is a teaching material that contains a summary of the material, practice questions, and some work procedures. The purpose of this development research is to describe the LKPD development process in the science subject matter of Vibration and to explain the development output after the validation process. The ADDIE model that has five complex hierarchies is the development technique chosen in this development research. Research carried out resulted in a product in the form of LKPD for the science subject of vibration material at the SMP/MTs level of class VIII that was valid with a validity percentage of 87.19%. The development process is according to the stages under the ADDIE development model output is the development product validated by three validators, namely material experts, media, and science teachers.
DEVELOPMENT OF HYDROSTATIC PRESSURE MATERIAL PROPS AT 8th GRADE OF JUNIOR HIGH SCHOOL
Authors: Arina Manasikhana  , Nur Hayati
Published: November 2022

This research and development was motivated by educators at the Al Chodidijah Integrated Junior High School which is a new junior high school, which opened in 2017. There is no laboratory room and no complete equipment. So that researchers need to develop teaching aids that are able to demonstrate the concept of hydrostatic pressure material. The purpose of this study is to describe the process of developing learning media as a teaching aid for hydrostatic pressure material and to describe the validity of learning media as a teaching aid for hydrostatic pressure material. This type of research uses the R&D (Research and Development) which was adapted from Sugiyono. Which consists of 7 stages. The results of the development of this teaching aid are 1) the process of developing hydrostatic pressure props, namely liquid pressure and Pascal's law using an R&D model through 5 stages, namely problem identification, data collection, product, validation by experts, and phase I revision, 2) has an average feasibility level of 89.09% with a very valid category.
miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress
Authors: Hayashi Chikako , Fukuda Takao , Kawakami Kentaro , Toyoda Masaaki , Nakao Yuki , Watanabe Yukari , Shinjo Takanori , Sano Tomomi , Iwashita Misaki , Yotsumoto Karen , Shida Miyu , Taketomi Takaharu , Sanui Terukazu , Uchiumi Takeshi , Kanematsu Takashi , Nishimura Fusanori
Published: November 2022

The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.
High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia
Authors: Wang Sing-Ting , Chou Chia-Huei , Chen Tzu-Ting , Lin Ching-Chan , Bai Li-Yuan , Yeh Shih-Peng , Ho Mao-Wang , Lien Ming-Yu
Published: November 2022

Background

Acute myeloid leukemia (AML) is a form of cancer that is characterized by infiltration of the bone marrow, blood, and other tissues by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells of the hematopoietic system. Patients with acute myeloid leukemia (AML) receiving azacitidine (AZA) alone or in combination with venetoclax (VEN-AZA) are at increased risk for invasive fungal infections (IFIs). We compared the incidence and risk of IFI during these treatment regimens in a single Taiwan hospital.

Materials and methods

A total of 61 patients with AML received at least one course of AZA in the hematology ward of China Medical University Hospital (Taichung, Taiwan) between September 2012 and June 2020. Thirty-eight patients (62.3%) received AZA monotherapy; 23 (37.7%) received VEN-AZA.

Results

Incidence rates of probable and proven IFI were 18% and 1.6%, respectively, during AZA treatment. One proven case of Fusarium spp. infection was isolated by skin and soft tissue culture. Most (75%) IFI cases occurred during the first cycle of AZA therapy. Half of all IFI cases occurred in patients with prolonged neutropenia. The risk of IFI was significantly higher for the European LeukemiaNet (ELN) nonfavorable-risk group (intermediate- and adverse-risk group) versus the ELN favorable-risk group and for patients with prolonged neutropenia versus those without (P<0.05 for both comparisons). In this study, median OS did not differ significantly between patients with and without IFIs during AZA-containing regimens (14.6 months vs 13.7 months; P=0.59).

Conclusion

The incidence of IFI was high in this AML cohort treated with AZA-containing regiments in Taiwan. The majority of IFI cases occurred during the early cycles of AZA (cycles 1–2). Prospective studies are needed to determine the optimal choice of antifungal prophylaxis agent during VEN-AZA therapy for AML.
Proteomic profiling spotlights the molecular targets and the impact of the natural antivirulent umbelliferone on stress response, virulence factors, and the quorum sensing network of Pseudomonas aeruginosa
Authors: Kasthuri Thirupathi , Barath Sivaraj , Nandhakumar Muruganandam , Karutha Pandian Shunmugiah
Published: November 2022

Pseudomonas aeruginosa easily adapts to newer environments and acquires several genome flexibilities to overcome the effect of antibiotics during therapeutics, especially in cystic fibrosis patients. During adaptation to the host system, the bacteria employ various tactics including virulence factor production and biofilm formation to escape from the host immune system and resist antibiotics. Hence, identifying alternative strategies to combat recalcitrant pathogens is imperative for the successful elimination of drug-resistant microbes. In this context, this study portrays the anti-virulence efficacy of umbelliferone (UMB) against P. aeruginosa. UMB (7-hydroxy coumarin) is pervasively found among the plant family of Umbelliferae and Asteraceae. The UMB impeded biofilm formation in the P. aeruginosa reference strain and clinical isolates on polystyrene and glass surfaces at the concentration of 125 µg/ml. Global proteomic analysis of UMB-treated cells revealed the downregulation of major virulence-associated proteins such as RhlR, LasA, AlgL, FliD, Tpx, HtpG, KatA, FusA1, Tsf, PhzM, PhzB2, CarB, DctP, MtnA, and MscL. A functional interaction study, gene ontology, and KEGG pathway analysis revealed that UMB could modulate the global regulators, enzymes, co-factors, and transcription factors related to quorum sensing (QS), stress tolerance, siderophore production, motility, and microcolony formation. In vitro biochemical assays further affirmed the anti-virulence efficacy of UMB by reducing pyocyanin, protease, elastase, and catalase production in various strains of P. aeruginosa. Besides the antibiofilm activity, UMB-treated cells exhibited enhanced antibiotic susceptibility to various antibiotics including amikacin, kanamycin, tobramycin, ciprofloxacin, and cefotaxime. Furthermore, in vitro cytotoxicity analysis revealed the biocompatibility of UMB, and the IC50 value was determined to be 249.85 µg/ml on the HepG2 cell line. Altogether, the study substantiates the anti-virulence efficacy of UMB against P. aeruginosa, and the proteomic analysis reveals the differential expression of the regulators related to QS, stress response, and motility factors.
Workflow for health-related and brain data lifecycle
Authors: Brůha Petr , Mouček Roman , Salamon Jaromír , Vacek Vítězslav
Published: November 2022

Poor lifestyle leads potentially to chronic diseases and low-grade physical and mental fitness. However, ahead of time, we can measure and analyze multiple aspects of physical and mental health, such as body parameters, health risk factors, degrees of motivation, and the overall willingness to change the current lifestyle. In conjunction with data representing human brain activity, we can obtain and identify human health problems resulting from a long-term lifestyle more precisely and, where appropriate, improve the quality and length of human life. Currently, brain and physical health-related data are not commonly collected and evaluated together. However, doing that is supposed to be an interesting and viable concept, especially when followed by a more detailed definition and description of their whole processing lifecycle. Moreover, when best practices are used to store, annotate, analyze, and evaluate such data collections, the necessary infrastructure development and more intense cooperation among scientific teams and laboratories are facilitated. This approach also improves the reproducibility of experimental work. As a result, large collections of physical and brain health-related data could provide a robust basis for better interpretation of a person’s overall health. This work aims to overview and reflect some best practices used within global communities to ensure the reproducibility of experiments, collected datasets and related workflows. These best practices concern, e.g., data lifecycle models, FAIR principles, and definitions and implementations of terminologies and ontologies. Then, an example of how an automated workflow system could be created to support the collection, annotation, storage, analysis, and publication of findings is shown. The Body in Numbers pilot system, also utilizing software engineering best practices, was developed to implement the concept of such an automated workflow system. It is unique just due to the combination of the processing and evaluation of physical and brain (electrophysiological) data. Its implementation is explored in greater detail, and opportunities to use the gained findings and results throughout various application domains are discussed.
Role of bile acids in overweight and obese children and adolescents
Authors: Giannini Cosimo , Mastromauro Concetta , Scapaticci Serena , Gentile Cristina , Chiarelli Francesco
Published: November 2022

Bile acids (BAs) are amphipathic molecules synthetized in the liver. They are primarily involved in the digestion of nutrients. Apart from their role in dietary lipid absorption, BAs have progressively emerged as key regulators of systemic metabolism and inflammation. In the last decade, it became evident that BAs are particularly important for the regulation of glucose, lipid, and energy metabolism. Indeed, the interest in role of BA in metabolism homeostasis is further increased due to the global public health increase in obesity and related complications and a large number of research postulating that there is a close mutual relationship between BA and metabolic disorders. This strong relationship seems to derive from the role of BAs as signaling molecules involved in the regulation of a wide spectrum of metabolic pathways. These actions are mediated by different receptors, particularly nuclear farnesoid X receptor (FXR) and Takeda G protein coupled receptor 5 (TGR5), which are probably the major effectors of BA actions. These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in BA, lipid and carbohydrate metabolism, energy expenditure, and inflammation. The large correlation between BAs and metabolic disorders offers the possibility that modulation of BAs could be used as a therapeutic approach for the treatment of metabolic diseases, including obesity itself. The aim of this review is to describe the main physiological and metabolic actions of BA, focusing on its signaling pathways, which are important in the regulation of metabolism and might provide new BA -based treatments for metabolic diseases.
“Liver–gut” axis: A target of traditional Chinese medicine for the treatment of non-alcoholic fatty liver disease
Authors: Guo Kangxiao , Xu Sisheng , Zeng Zhaofeng
Published: November 2022

Non-alcoholic fatty liver disease (NAFLD) occurs when fat accumulates in the liver even without excessive alcohol intake. Among the current therapeutic approaches for NAFLD, lifestyle modification with dietary changes and regular exercise is the mainstay treatment. With the rise of intestinal microecology, regulation of the “liver–gut” axis can be an effective treatment for NAFLD. This review aimed to assess the modulation of the liver–gut microbiota axis with traditional Chinese medicine (TCM) as a therapeutic approach to NAFLD and further explored its application in the newly discovered therapeutic avenues beyond NAFLD treatment.
The impact of COVID lockdown on glycaemic control in paediatric patients with type 1 diabetes: A systematic review and meta-analysis of 22 observational studies
Authors: Han Yanping , Chen Yuqing , Sun Chenyu , Zhou Zhen
Published: November 2022

Introduction

The COVID lockdown has posted a great challenge to paediatric patients with type 1 diabetes (T1D) and their caregivers on the disease management. This systematic review and meta-analysis sought to compare the glycaemic control among paediatric patients with T1D (aged under 18 years) pre- during, and post-lockdown period.

Methods and materials

We did a systematic search of three databases (PubMed, Embase, and the WHO COVID‐19 Global literature) for the literature published between 1 Jan 2019 to 10 Sep 2022. Studies meeting the following inclusion criteria were eligible for this study: (1) a COVID-19 related study; (2) inclusion of children aged 18 years old or under with established T1D; (3) comparing the outcomes of interest during or after the COVID lockdown with that before the lockdown. Study endpoints included mean difference (MD) in HbA1c, blood glucose, time in range (TIR, 70-180 mg/dl), time above range (TAR, >180mg/dl), time below range (TBR,<70mg/dl) and glucose variability (coefficient of variation [CV]) between pre-lockdown and during lockdown and/or between pre- and post-lockdown period. The MD and its corresponding 95% CI of each endpoint were pooled using random-effect model considering the potential between-study heterogeneity in COVID restrictions and T1D management.

Results

Initial search identified 4488 records and 22 studies with 2106 paediatric patients with T1D were included in the final analysis. Compared with pre-lockdown period, blood glucose was significantly decreased by 0.11 mmol/L (95%CI: -0.18, -0.04) during lockdown period and by 0.42 mmol/L (95%CI: -0.73, -0.11) after lockdown. The improvement was also found for TIR, TAR, TBR, and CV during and post-lockdown (all p values<0.05) except for the post-lockdown TBR (p =0.35). No significant change in HbA1c was observed during and post- lockdown period when compared with the pre-lockdown value. There was moderate to high between-study heterogeneity for most of the analyses.

Conclusion

Compared with pre-lockdown period, there was significant improvement in T1D paediatric patients’ glucose metrics during and post-lockdown. The underlying reasons for this positive impact warrant further investigation to inform future paediatric diabetes management.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022359213.
Optimal low-carbon governance model of livestreaming supply chain based on multiple scenarios
Authors: Peng Liangjun , Lu Gang , Liu Mingwu , Liu Yawei , Zou Zichen
Published: November 2022

Supply chain emissions reduction is an important way to promote the development of a low-carbon economy and address climate challenges. Although the scale of livestream shopping has demonstrated unprecedented growth globally, especially since the COVID-19 outbreak, livestreaming supply chains have also contributed significantly to carbon emissions. Currently, optimisation models for the low-carbon governance of livestreaming supply chains are relatively lacking. To address the issue of carbon emission reduction in livestreaming supply chains, this study paper proposes three low-carbon governance decision-making models based on environmental and operating costs to compare which governance model is optimal. The most suitable decision result for the policymaker and supply chain is both cost-effective and environmentally successful under the model considering carbon tax and carbon trade. The results show that 1) governance based only on carbon tax and collaborative operation will decrease the total cost of the livestreaming supply chain but increase the environmental cost. 2) Governance based only on carbon trading and collaborative operation will increase the total cost of the livestreaming supply chain, while the environmental cost will not change. 3) Under governance that combines carbon tax and carbon trading, collaborative operations can effectively reduce both the total cost and the environmental cost of livestreaming supply chains. Theoretically, our study enriches the research on the low-carbon governance of livestreaming supply chains. Moreover, the research results provide useful insights into the formulation of a low-carbon policy for livestreaming supply chains.
Impact of environmental literacy on farmers’ agricultural green production behavior: Evidence from rural China
Authors: Yu Liwei , Liu Wenxin , Yang Shaoxiong , Kong Rong , He Xuesong
Published: November 2022

Agricultural green production has been regarded as an effective way to solve the increasing level of agricultural environmental pollution and the frequent safety crises of agricultural products. As the main decision makers of agricultural production, farmers’ agricultural green production behavior directly determines the process of agricultural green development. However, few studies have explored farmers’ agricultural green production behavior from the perspective of environmental literacy, and the formation mechanism of farmers’ agricultural green production behavior is still unclear. This study aims to clarify the effect of environmental literacy on farmers’ agricultural green production behavior and its impact mechanism. Based on survey data from 830 farmers in China, this study constructs comprehensive index systems to evaluate farmers’ environmental literacy and agricultural green production behavior, and adopts multiple linear regression models and quantile regression model to explore the impact of environmental literacy on this behavior. Meanwhile, the mediation effect model is used to explore the mediation effect of agricultural green production cognition and agricultural green production willingness in the influence of environmental literacy on farmers’ agricultural green production behavior. Three conclusions arise. First, farmers’ environmental literacy and agricultural green production behavior are at the middle level, both of which should be strengthened. Second, environmental literacy has a significant positive impact on farmers’ agricultural green production behavior. Finally, environmental literacy influences farmers’ AGP behavior through the independent and chain mediation effects of AGP cognition and AGP willingness. Environmental literacy has heterogeneity impact on farmers’ agricultural green production behavior under different level of agricultural green production and external environment. This research not only provides theoretical support for the study of farmers’ agricultural green production behavior from the perspective of environmental literacy, it also provides a reference to the relevant government departments so that they can guide farmers to adopt more agricultural green production behavior.
Data-driven analysis to identify prognostic immune-related biomarkers in BRAF mutated cutaneous melanoma microenvironment
Authors: Huang Biao , Su Wenxing , Yu Daojiang
Published: November 2022

Skin cutaneous melanoma is one of the deadly diseases, and more than 50% of the patients have BRAF gene mutations. Evidence suggests that oncogenic BRAF modulates the immune system’s ability to recognize SKCM cells. Due to the complexity of the tumor microenvironment (TME) and a lack of a rational mechanistic basis, it is urgent to investigate the immune infiltration and identify prognostic biomarkers in BRAF mutated SKCM patients. Multiple methods including ESTIMATE algorithm, differential gene analysis, prognostic analysis and immune infiltration analysis were performed to investigate the tumor microenvironment. Based on the patient’s immune score and stromal score, immune-related genes DEGs were identified. Functional analysis revealed that these genes were mainly enriched in biological processes such as immune response, defense response and positive regulation of immune system. Furthermore, we analyzed the immune infiltrating cell components of BRAF mutated patients and revealed 4 hub genes associated with overall survival time. Several cells (Monocyte, Macrophage and Gamma delta cells) have been found to be significantly decreased in immune-high BRAF mutated SKCM group. While CD4+T, CD8+T, CD4 naïve, Tr1, Th2 and many T cell subsets were significantly increased in immune-high group. These immune cells and genes were closely related to each other. This study revealed that the dysregulation of immune function and immune cells may contribute to the poor outcomes of BRAF mutated patients. It is of great significance to our further understanding of the TME and immune dysfunction in BRAF mutated SKCM.
Integrating cell interaction with transcription factors to obtain a robust gene panel for prognostic prediction and therapies in cholangiocarcinoma
Authors: Wang Tingjie , Xu Chuanrui , Xu Dan , Yang Xiaofei , Liu Yaxin , Li Xiujuan , Li Zihang , Dang Ningxin , Lv Yi , Zhang Zhijing , Li Lei , Ye Kai
Published: November 2022

Objective: The efficacy of immunotherapy for cholangiocarcinoma (CCA) is blocked by a high degree of tumor heterogeneity. Cell communication contributes to heterogeneity in the tumor microenvironment. This study aimed to explore critical cell signaling and biomarkers induced via cell communication during immune exhaustion in CCA.

Methods: We constructed empirical Bayes and Markov random field models eLBP to determine transcription factors, interacting genes, and associated signaling pathways involved in cell-cell communication using single-cell RNAseq data. We then analyzed the mechanism of immune exhaustion during CCA progression.

Results: We found that VEGFA-positive macrophages with high levels of LGALS9 could interact with HAVCR2 to promote the exhaustion of CD8+ T cells in CCA. Transcription factors SPI1 and IRF1 can upregulate the expression of LGALS9 in VEGFA-positive macrophages. Subsequently, we obtained a panel containing 54 genes through the model, which identified subtype S2 with high expression of immune checkpoint genes that are suitable for immunotherapy. Moreover, we found that patients with subtype S2 with a higher mutation ratio of MUC16 had immune-exhausted genes, such as HAVCR2 and TIGIT. Finally, we constructed a nine-gene eLBP-LASSO-COX risk model, which was designated the tumor microenvironment risk score (TMRS).

Conclusion: Cell communication-related genes can be used as important markers for predicting patient prognosis and immunotherapy responses. The TMRS panel is a reliable tool for prognostic prediction and chemotherapeutic decision-making in CCA.
Mechanism of herpesvirus protein kinase UL13 in immune escape and viral replication
Authors: Zhou Lin , Cheng Anchun , Wang Mingshu , Wu Ying , Yang Qiao , Tian Bin , Ou Xumin , Sun Di , Zhang Shaqiu , Mao Sai , Zhao Xin-Xin , Huang Juan , Gao Qun , Zhu Dekang , Jia Renyong , Liu Mafeng , Chen Shun
Published: November 2022

Upon infection, the herpes viruses create a cellular environment suitable for survival, but innate immunity plays a vital role in cellular resistance to viral infection. The UL13 protein of herpesviruses is conserved among all herpesviruses and is a serine/threonine protein kinase, which plays a vital role in escaping innate immunity and promoting viral replication. On the one hand, it can target various immune signaling pathways in vivo, such as the cGAS-STING pathway and the NF-κB pathway. On the other hand, it phosphorylates regulatory many cellular and viral proteins for promoting the lytic cycle. This paper reviews the research progress of the conserved herpesvirus protein kinase UL13 in immune escape and viral replication to provide a basis for elucidating the pathogenic mechanism of herpesviruses, as well as providing insights into the potential means of immune escape and viral replication of other herpesviruses that have not yet resolved the function of it.
First insight into H3K4me3 modification in the rapid growth of Alexandrium pacificum (dinoflagellates)
Authors: Qi Juan , Zhu Zhimei , Liu Yuan , Sui Zhenghong
Published: November 2022

Background

Alexandrium pacificum is a dinoflagellate species notorious for its rapid growth resulting in large-scale blooms. This study aimed to investigate the molecular mechanisms of A. pacificum under laboratory-simulated rapid growth conditions from the perspective of H3K4me3 modification regulation.

Methods and results

Western blot was used to detect the modification abundance of H3K4me3 in A. pacificum cultured under different conditions, including high light (HL), high nitrogen (HN), and f/2 medium (control, CT), in the rapid growth exponential phase. The results showed that the modification abundance of H3K4me3 under HL or HN was greater than that under CT. Chromatin immunoprecipitation-sequencing was used to explore the acting genes of H3K4me3 under different conditions for the first time. Nitrogen metabolism and endocytosis were significantly associated with H3K4me3 regulation under HL. Furthermore, H3K4me3 was also significantly associated with the vitamin metabolism pathway under HN.

Conclusions

These findings demonstrate that H3K4me3 plays a potentially important role in the regulation of the rapid growth of A. pacificum. Such knowledge of a histone modification regulatory network in this dinoflagellate, lays a necessary foundation for future research in related fields.
Kaempferol attenuated diabetic nephropathy by reducing apoptosis and promoting autophagy through AMPK/mTOR pathways
Authors: Sheng Hongqin , Zhang Duo , Zhang Jiaqi , Zhang Yanmei , Lu Zhaoyu , Mao Wei , Liu Xusheng , Zhang Lei
Published: November 2022

Introduction

Renal podocyte injury, apoptosis and autophagy are involved in the occurrence and development of diabetic nephropathy (DN). Kaempferol (KPF) has the promotion of autophagy and inhibition of apoptosis properties in the development of miscellaneous diseases, but these functions in DN have not yet been elucidated.

Methods

We used db/db mice to evaluate the protective role of KPF on DN. The anti-DN effect of KPF was evaluated by urine albumin-to-creatinine ratio and pathological changes of kidney tissue. Injury of podocytes was observed through Transmission electron microscopy. Immunofluorescence, Western blot, and Immunohistochemistry were used to detect the protein expression of podocyte-associated molecules, autophagy, and AMPK/mTOR pathway.

Results

We demonstrated that KPF treatment significantly attenuated diabetes-induced albuminuria and glycolipid metabolism dysfunction. In addition, KPF alleviated mesangial matrix expansion, glomerular basement membrane thickening and loss or fusion of podocytes. Mechanistically, KPF treatment regulated the expression of autophagic proteins (upregulated LC3II, Beclin-1, Atg7 and Atg 5, and downregulated p62/SQSTM1), accompanied by inhibited renal apoptosis (downregulated Caspase 3 and Bax, and upregulated Bcl-2). KPF could significantly regulate the AMPK/mTOR signaling pathways by increasing p-AMPK and decreasing p-mTOR expressions.

Discussion

In conclusion, KPF might have a protective effect on DN through reduced apoptosis and enhanced podocytes autophagy, which were correlated with regulating AMPK/mTOR pathways.
Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats
Authors: Liu Xiaoxue , Zhang Ming , Wang Xifan , Liu Ping , Wang Longjiao , Li Yixuan , Wang Xiaoyu , Ren Fazheng
Published: November 2022

Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.
Nourishing neonatal piglets with synthetic milk and Lactobacillus sp. at birth highly modifies the gut microbial communities at the post-weaning stage
Authors: Sampath Vetriselvi , Song Jun Ho , Jeong Jinuk , Mun Seyoung , Han Kyudong , Kim In Ho
Published: November 2022

The importance of probiotics in pig production is widely recognized. However, the precise role of probiotics in regulating the gut microbiota of piglets has not been assessed extensively. Therefore, we intend to examine whether suckling pigs ingesting with synthetic milk (SM) and probiotics along with mother milk has a carryover effect on its growth and gut health at the post-weaning stage. A total of 40 [Duroc× (Yorkshire× Landrace)] neonates with an initial BW of 1.49 ± 0.28 kg were assigned to one of two treatments groups: control (CON) and treatment (TRT). Control group piglets were nourished with synthetic milk, while TRT group piglets were nourished SM with (1 × 109 CFU/g) Lactobacillus sp. probiotics. The treatment group piglets showed higher (p < 0.05) body weight and daily gain at week 3 than the CON group piglets. 16S metagenome sequencing showed average demultiplexed reads and denoised reads counts of 157,399 and 74,945, respectively. The total ASV taxonomy number classified with a confidence threshold > 70% (default) on sequence alignment with the SILVA v138 reference database was 4,474. During week 1, Escherichia-Shigella, Clostridium sensu stricto 1, and Bacteroides were confirmed as the major dominant bacterial genera in both the groups at the genus level. However, during week 2, the relative proportion of Escherichia-Shigella, Clostridium sensu stricto 1, and Proteobacteria was decreased, while that of Lactobacillus and Bacteroidota was increased in pigs receiving the probiotic supplement. During weeks 2 and 3, Firmicutes, Proteobacteria, and Bacteroidota phyla were dominant in both groups. During week 6, the relative proportion of Proteobacteria was slightly increased in both groups. Furthermore, Prevotella was confirmed as the major dominant bacterial genus in both groups during weeks 3 and 6. This study suggests that nourishing neonatal piglets with synthetic milk and Lactobacillus sp. probiotics from birth to 21 days would be beneficial to enhance the gut health of piglets and to overcome post-weaning mortality.
Proteomics analysis of the p.G849D variant in neurexin 2 alpha may reveal insight into Parkinson’s disease pathobiology
Authors: Cuttler Katelyn , Fortuin Suereta , Müller-Nedebock Amica Corda , Vlok Maré , Cloete Ruben , Bardien Soraya
Published: November 2022

Parkinson’s disease (PD), the fastest-growing neurological disorder globally, has a complex etiology. A previous study by our group identified the p.G849D variant in neurexin 2 (NRXN2), encoding the synaptic protein, NRXN2α, as a possible causal variant of PD. Therefore, we aimed to perform functional studies using proteomics in an attempt to understand the biological pathways affected by the variant. We hypothesized that this may reveal insight into the pathobiology of PD. Wild-type and mutant NRXN2α plasmids were transfected into SH-SY5Y cells. Thereafter, total protein was extracted and prepared for mass spectrometry using a Thermo Scientific Fusion mass spectrometer equipped with a Nanospray Flex ionization source. The data were then interrogated against the UniProt H. sapiens database and afterward, pathway and enrichment analyses were performed using in silico tools. Overexpression of the wild-type protein led to the enrichment of proteins involved in neurodegenerative diseases, while overexpression of the mutant protein led to the decline of proteins involved in ribosomal functioning. Thus, we concluded that the wild-type NRXN2α may be involved in pathways related to the development of neurodegenerative disorders, and that biological processes related to the ribosome, transcription, and tRNA, specifically at the synapse, could be an important mechanism in PD. Future studies targeting translation at the synapse in PD could therefore provide further information on the pathobiology of the disease.
Odor source localization of multi-robots with swarm intelligence algorithms: A review
Authors: Wang Junhan , Lin Yuezhang , Liu Ruirui , Fu Jun
Published: November 2022

The use of robot swarms for odor source localization (OSL) can better adapt to the reality of unstable turbulence and find chemical contamination or hazard sources faster. Inspired by the collective behavior in nature, swarm intelligence (SI) is recognized as an appropriate algorithm framework for multi-robot system due to its parallelism, scalability and robustness. Applications of SI-based multi-robots for OSL problems have attracted great interest over the last two decades. In this review, we firstly summarize the trending issues in general robot OSL field through comparing some basic counterpart concepts, and then provide a detailed survey of various representative SI algorithms in multi-robot system for odor source localization. The research field originates from the first introduction of the standard particle swarm optimization (PSO) and flourishes in applying ever-increasing quantity of its variants as modified PSOs and hybrid PSOs. Moreover, other nature-inspired SI algorithms have also demonstrated the diversity and exploration of this field. The computer simulations and real-world applications reported in the literatures show that those algorithms could well solve the main problems of odor source localization but still retain the potential for further development. Lastly, we provide an outlook on possible future research directions.
Caspase-dependent apoptosis induces reactivation and gliogenesis of astrocytes in adult mice
Authors: Kim Seung-Chan , Park Jae-Yong , Hwang Eun Mi
Published: November 2022

Astrocytes play an important role in increasing synaptic plasticity, regulating endogenous homeostasis, and contributing to neuroprotection but become overactivated or apoptotic in persistent neuroinflammatory responses or pathological conditions. Although gliogenesis under these conditions may be essential for neuronal protection, much remains unknown. Here, we generated new conditional transgenic mice (cTg) that can induce apoptosis via Cre-dependent active caspase-3 (taCasp3-2A-TEVp) without pathological conditions. We induced apoptosis of hippocampal CA1 astrocytes in cTg mice using GFAP promoter-driven adeno-associated virus (AAV) containing Cre recombinase. Activated caspase-3 was detected in astrocytes of the hippocampal CA1, and the number of astrocytes decreased sharply at 1 week but recovered at 2 weeks and was maintained until 4 weeks. Nuclear factor 1A (NF1A) mRNA, an important transcription factor for hippocampal reactive astrocytes, was significantly increased only at week 1. Interestingly, all reactive markers (pan, A1, A2) increased despite the decreased number of astrocytes at week 1, and there was no change in monoamine oxidase B (MAOB) observed in astrocytes of animal models of degenerative brain disease. Extensive CA1 astrocyte depletion at week 1 induced cognitive deficits; however, both recovered at weeks 2 and 4. Overall, transient hippocampal astrocyte depletion caused by apoptosis restored cell number and function within 2 weeks and did not induce significant neurotoxicity. Therefore, cTg mice are valuable as an in vivo animal model for studying gliogenesis in multiple regions of the adult brain.
Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
Authors: Zeng Jing , Sun Lu , Huang Jiaming , Yang Xia , Hu Wanming
Published: November 2022

Background

Enhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, that mainly regulates histone H3 lysine 27 trimethylation (H3K27me3) through histone methyltransferase, and participates in promoting the development of tumors. At present, the loss of H3K27me3 expression in meningioma is a poor prognostic factor, but the research of EZH2 in meningioma is rare. Therefore, we aim to explore the expression of EZH2 in the meningioma and its correlation with the prognosis and immune microenvironment and lay the foundation for the subsequently potential targeted therapy and immunotherapy for meningioma.

Methods

Tissue microarray immunohistochemistry staining was performed on 276 meningioma samples from Sun Yat-sen University Cancer Center. Expression levels of EZH2, H3K27me3, Ki67, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), CD4, CD8, CD20, FOXP3, CD68, and CD163 were evaluated. Cox regression analyses were performed, and the Kaplan–Meier (KM) method was used to construct survival curves. In addition, we use biological information methods to analyze the mRNA expression of EZH2 and its relationship with the prognosis and immune microenvironment in the gene expression omnibus (GEO) database.

Results

Enhancer of zeste homolog 2 expression is concentrated in World Health Organization (WHO) grades 2 and 3 meningiomas (8.3+ and 33.3%+). We found that EZH2 expression was associated with a worse prognosis in meningioma (P < 0.001), the same results were confirmed in the GEO database (P < 0.001). Both EZH2 expression and H3K27me3 deletion (P = 0.035) predicted a worse prognosis, but EZH2 has no correlation with H3K27me3 expression. EZH2 expression was closely associated with increased Ki67 index (P < 0.001). In addition, EZH2 was associated with the immune microenvironment and positively correlated with PD-L1 expression (P < 0.001).

Conclusion

Enhancer of zeste homolog 2 is a new prognostic biomarker in meningioma. It correlates with PD-L1 expression and closely related to tumor immunosuppression. Our research can provide a reference for the potential targeted therapy and immunotherapy of meningioma in the future.
The role of microfibrillar‐associated protein 2 in cancer
Authors: Xu Wanzhen , Wang Manfeng , Bai Yang , Chen Yong , Ma Xiaoshan , Yang Zhiqing , Zhao Liyan , Li Yunqian
Published: November 2022

Microfibrillar-associated protein 2 (MFAP2), a component of the extracellular matrix, is important in controlling growth factor signal transduction. Recent studies have shown that MFAP2, an effective prognostic molecule for various tumors, is associated with tumor occurrence and development and may be involved in remodeling the extracellular matrix and regulating proliferation, apoptosis, invasion, tumor cell metastasis, and tumor angiogenesis. However, MFAP2’s specific mechanism in these tumor processes remains unclear. This article reviewed the possible mechanism of MFAP2 in tumorigenesis and progression and provided a reference for the clinical prognosis of patients with cancer and new therapeutic target discovery.
Laryngeal extra-skeletal Ewing sarcoma treated with DC-CTL immunotherapy: A case report and review of the literature
Authors: Wang Hanrui , Wang Jianwei , Wang Qiang , Yang Yujuan , Guo Jing , Ren Chao , Mou Yakui , Jia Chuanliang , Song Xicheng
Published: November 2022

Extra-skeletal Ewing sarcoma (EES) is a rare sarcoma composed primarily of small round cells, capable of metastasizing and relapsing. Few cases of EES originating from the larynx have been reported, and no publications regarding laryngeal EES treated with dendritic cells-cytotoxic T lymphocytes (DC-CTL) immunotherapy have been found. We described a 29-year-old woman with a mass found in the larynx. Diffuse small round cells with scanty cytoplasm shown by histology test and extremely positive staining of CD99 revealed by immunohistochemistry helped determine the diagnosis of laryngeal EES. The patient survived for seven years with no signs of recurrence or metastasis after six cycles of DC-CTL immunotherapy based on traditional treatments. This case indicates that DC-CTL immunotherapy could be considered a new option for treating EES.
The combination of a seven-autoantibody panel with computed tomography scanning can enhance the diagnostic efficiency of non-small cell lung cancer
Authors: He Tianyu , Wu Ziheng , Xia Pinghui , Wang Weidong , Sun Hua , Yu Li , Lv Wang , Hu Jian
Published: November 2022

Background

Non-small cell lung cancer (NSCLC) is still of concern in differentiating it from benign disease. This study aims to validate the diagnostic efficacy of a novel seven-autoantibody (7-AAB) panel for the diagnosis of NSCLC.

Methods

We retrospectively enrolled 2650 patients who underwent both the 7-AAB panel test and CT scanning. We compared the sensitivity, specificity, and PPV of 7-AAB, CT, and PET-CT in the diagnosis of NSCLC in different subgroups. Then, we established a nomogram based on CT image features and the 7-AAB panel to further improve diagnostic efficiency. Moreover, we compared the pathological and molecular results of NSCLC patients in the 7-AABs positive group and the negative group to verify the prognostic value of the 7-AAB panel.

Results

The strategy of a “both-positive rule” combination of 7-AABs and CT had a specificity of 95.4% and a positive predictive value (PPV) of 95.8%, significantly higher than those of CT or PET-CT used alone (P<0.05). The nomogram we established has passed the calibration test (P=0.987>0.05) with an AUC of 0.791. Interestingly, it was found that the 7-AABs positive group was associated with higher proportion of EGFR mutations (P<0.001), lower pathological differentiation degrees (P=0.018), more advanced pathological stages (P=0.040) and higher Ki-67 indexes (P=0.011) in patients with adenocarcinoma.

Conclusion

This study shows that combination of a 7-AAB panel with CT has can significantly enhance the diagnostic efficiency of lung cancer. Moreover, the 7-AAB panel also has potential prognostic value and has reference significance for the formulation of the treatment plan.
Tumor microenvironment penetrating chitosan nanoparticles for elimination of cancer relapse and minimal residual disease
Authors: Mahmudi Hossein , Adili-Aghdam Mohammad Amin , Shahpouri Mohammad , Jaymand Mehdi , Amoozgar Zohreh , Jahanban-Esfahlan Rana
Published: November 2022

Chitosan and its derivatives are among biomaterials with numerous medical applications, especially in cancer. Chitosan is amenable to forming innumerable shapes such as micelles, niosomes, hydrogels, nanoparticles, and scaffolds, among others. Chitosan derivatives can also bring unprecedented potential to cross numerous biological barriers. Combined with other biomaterials, hybrid and multitasking chitosan-based systems can be realized for many applications. These include controlled drug release, targeted drug delivery, post-surgery implants (immunovaccines), theranostics, biosensing of tumor-derived circulating materials, multimodal systems, and combination therapy platforms with the potential to eliminate bulk tumors as well as lingering tumor cells to treat minimal residual disease (MRD) and recurrent cancer. We first introduce different formats, derivatives, and properties of chitosan. Next, given the barriers to therapeutic efficacy in solid tumors, we review advanced formulations of chitosan modules as efficient drug delivery systems to overcome tumor heterogeneity, multi-drug resistance, MRD, and metastasis. Finally, we discuss chitosan NPs for clinical translation and treatment of recurrent cancer and their future perspective.