bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota is correlated with gastrointestinal adverse events of metformin in patients with type 2 diabetes
Authors: Huang Yuxin , Lou Xudan , Jiang Cuiping , Ji Xueying , Tao Xiaoming , Sun Jiao , Bao Zhijun
Published: November 2022

Aim

Gastrointestinal discomfort is the most common adverse event in metformin treatment for type 2 diabetes. The mechanism of action of metformin is associated with gut microbiota. However, the gut microbial community structure related to metformin-induced gastrointestinal adverse events remains unclear. This study aimed to investigate it.

Methods

50 patients with newly diagnosed diabetes were treated with metformin 1500mg/d for 12 weeks. The patients were divided into two groups according to whether gastrointestinal adverse events occurred (group B) or did not occur (group A) after treatment. The fecal bacterial communities and short-chain fatty acids (SCFAs) were sequenced and compared. 70 diabetes mice were randomly divided into 8 groups and treated with metformin (Met), clindamycin (Clin) and/or SCFA, which were the Met+/Clin+, Met+/Clin-, Met-/Clin+, Met-/Clin-, Met+/SCFA+, Met+/SCFA-, Met-/SCFA+ and Met-/SCFA- group. After 4 weeks of metformin treatment, blood glucose, food intake, fecal SCFAs, gut microbiota and gut hormones were measured.

Results

Metformin increased the abundance of Phascolarctobacterium, Intestinimonas and Clostridium III. Functional prediction analysis showed that the propanoate metabolism pathway was significantly up-regulated. The concentrations of acetic acid and propanoic acid in feces were significantly increased. The abundance of Clostridium sensu stricto, Streptococcus and Akkermansia induced by metformin in group B was higher than that in group A. The propanoate metabolism pathway and propanoic acid in feces were significantly up-regulated in group B. In the animal experiments, the food intake decreased and glucose control increased in metformin groups compared with those in the control groups. The total GLP-1 level in the Met+/Clin- group was significantly higher than that in the Met-/Clin- group, while there was no statistical difference between the Met-/Clin- and Met+/Clin+ group. The total GLP-1 level in the Met-/SCFA+ group was significantly higher than that in the Met-/SCFA-group, while the levels of total GLP-1 and active GLP-1 in the Met+/SCFA- group and the Met+/SCFA+ group were significantly higher than those in the Met-/SCFA-group.

Conclusions

Our data suggest that metformin promotes the secretion of intestinal hormones such as GLP-1 by increasing the abundance of SCFA-producing bacteria, which not only plays an anti-diabetic role, but also may causes gastrointestinal adverse events.
“Short agonist stop” protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study
Authors: Mauries Charlotte , Ranisavljevic Noemie , Mollevi Caroline , Brunet Cecile , Hamamah Samir , Brouillet Sophie , Anahory Tal
Published: November 2022

Introduction

Poor responder patients remain a challenge in assisted reproductive technologies. The “short agonist stop” (SAS) stimulation protocol uses a double stimulation (flare up effect with the gonadotropin-releasing hormone (GnRH) agonist (GnRH-a) then gonadotropins) associated with a less strenuous blockage (discontinuation of GnRH-a) to favor follicular recruitment in order to obtain a better ovarian response. This study aims to compare the number of oocytes obtained after a SAS stimulation protocol with those obtained after the previous stimulation protocol, in the same women, with poor ovarian response (POR) diagnosed according to the POSEIDON criteria.

Design

This therapeutic observational retrospective cohort from 2018 to 2022, with a case-control evaluation compared with the same patients’ previous performance, included women with POR undergoing IVF with SAS stimulation protocol. The primary outcome was the number of total oocytes recovered and secondary outcomes were the numbers of mature oocytes, total embryos observed at day 2 and usable cleaved embryos and blastocysts (day 5/6).

Results

63 patients with SAS and previous cycles were included. In the SAS group, the mean number of oocytes was significantly higher: 7.3 vs 5.7, p=0.018 in comparison with the previous attempt. So was the number of mature oocytes (5.8 vs 4.1, p=0.032) and the total mean number of embryos obtained at day 2 (4.1 versus 2.7, p=0.016). The SAS stimulation generated 84 usable embryos: 57 cleaved embryos and 27 blastocysts. The mean number of usable embryos was similar in both groups (1.64 vs 1.31, respectively, p=0.178). In total, out of 63 patients, after the SAS protocol, and subsequent embryo transfers (fresh and frozen, n=54), 9 patients had ongoing pregnancies and no miscarriage occurred. The cumulative ongoing pregnancy rate (cOPR) after the SAS protocol was 14.3% (9/63) per oocyte pick-up and 16.7% (9/54) per transfer.

Conclusion

SAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, that may offer promising results for those patients with low prognosis and previous failed IVF. Results must be confirmed with a randomized controlled trial.
A potential role of autophagy-mediated vascular senescence in the pathophysiology of HFpEF
Authors: Sanhueza-Olivares Fernanda , Troncoso Mayarling F. , Pino-de la Fuente Francisco , Martinez-Bilbao Javiera , Riquelme Jaime A. , Norambuena-Soto Ignacio , Villa Monica , Lavandero Sergio , Castro Pablo F. , Chiong Mario
Published: November 2022

Heart failure with preserved ejection fraction (HFpEF) is one of the most complex and most prevalent cardiometabolic diseases in aging population. Age, obesity, diabetes, and hypertension are the main comorbidities of HFpEF. Microvascular dysfunction and vascular remodeling play a major role in its development. Among the many mechanisms involved in this process, vascular stiffening has been described as one the most prevalent during HFpEF, leading to ventricular-vascular uncoupling and mismatches in aged HFpEF patients. Aged blood vessels display an increased number of senescent endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). This is consistent with the fact that EC and cardiomyocyte cell senescence has been reported during HFpEF. Autophagy plays a major role in VSMCs physiology, regulating phenotypic switch between contractile and synthetic phenotypes. It has also been described that autophagy can regulate arterial stiffening and EC and VSMC senescence. Many studies now support the notion that targeting autophagy would help with the treatment of many cardiovascular and metabolic diseases. In this review, we discuss the mechanisms involved in autophagy-mediated vascular senescence and whether this could be a driver in the development and progression of HFpEF.
A two-stage deep learning framework for early-stage lifetime prediction for lithium-ion batteries with consideration of features from multiple cycles
Authors: Yao Jiwei , Powell Kody , Gao Tao
Published: November 2022

Lithium-ion batteries are a crucial element in the electrification and adoption of renewable energy. Accurately predicting the lifetime of batteries with early-stage data is critical to facilitating battery research, production, and deployment. But this problem remains challenging because batteries are complex, nonlinear systems, and data acquired at the early-stage exhibit a weak correlation with battery lifetime. In this paper, instead of building features from specific cycles, we extract features from multiple cycles to form a time series dataset. Then the time series data is compressed with a GRU-based autoencoder to reduce feature dimensionality and eliminate the time domain. Further, different regression models are trained and tested with a feature selection method. The elastic model provides a test RMSE of 187.99 cycles and a test MAPE of 10.14%. Compared with the state-of-art early-stage lifetime prediction model, the proposed framework can lower the test RMSE by 10.22% and reduce the test MAPE by 28.44%.
The impact of digital transformation on corporate sustainability- new evidence from Chinese listed companies
Authors: Zhang Chenxi , Chen Pengyu , Hao Yuanyuan
Published: November 2022

As Industry 4.0 is seen as the core industrial stage for achieving sustainable development, more and more scholars are exploring the practical effects of Industry 4.0. This paper evaluates the impact of digital transformation on business sustainability, explores whether digital transformation breaks down perceptions, and examines the mechanisms by which it works. First, we measured the digital transformation of each firm using textual analysis. and found that the coefficient of digital transformation is 0.006 on corporate sustainability at the 1% significant level. Secondly, we found that digital transformation eases knowledge flow barriers and makes knowledge more accessible to firms. Firms with higher digital transformation attract more skilled people, which can create talent barriers. Digital transformation can exacerbate firms’ industry monopolies, while increasing the proportion of boardroom women and the inclusion of older members sends positive signals to outsiders. Finally, we find that low costs, high labor productivity, high innovation and low cost of sales are important channels for digital transformation. In addition, digital transformation increases the management costs of firms.
Transformation and upgrading path for midstream manufacturers in the chain: Taking Shennan Circuits as an example
Authors: You Lei , Yang Meiying
Published: November 2022

The restructuring of global value chain restructuring has created both opportunities and challenges for Chinese manufacturers. In the process, OEM-ODM-OBM has been a typical upgrade path for manufacturing enterprises to integrate into the global value chain. However, this path may not be appropriate for Chinese midstream enterprises in the industry chain. This paper performs a longitudinal analysis of 30-year reform of Shennan Circuits, a typical midstream manufacturing business in the industry chain in China. Based on the smiling curve theory, we systematically analyzed how Shennan Circuit constantly scanned over the industry, its customers, competitors, and leveraged its own capability and resources against the background of global value chain restructuring to successfully integrate into the global value chain, enhance competitiveness while completing business transformation and upgrade. Given the case study, this paper proposes three types of transformation solutions with eight specific paths and the ICCA opportunity scanning analysis method for China’s midstream manufacturers in the industry chain as references.
Urban spatial structure and regional smog management for environmental sustainability
Authors: Qie Hongkai , Chao Yudie , Yang Qianwen , Lu Yong
Published: November 2022

The study examines the influence of the urban spatial structure on smog pollution and its mechanism of action using the panel data of Chinese cities from 2012 to 2017. Research suggests that the multi-center development of Chinese cities has aggravated regional smog pollution. Robustness test results support this finding. Results of the interaction term shed light on the fact that multi-center spatial development in backward regions can exert a greater influence on smog pollution. Meanwhile, suppose the research samples are divided by different zones. In that case, it can be observed that an inverted-U shape characterizes the multi-center development of regions of East China and smog pollution. This indicates that worsening smog pollution appears only as a periodical phenomenon of the pre-stage multi-center development of Chinese cities, which can be ushered into a turning point through certain paths. Analysis of the influence mechanism shows that the transport mode and the energy consumption intensity constitute two major channels for multi-center development of Chinese cities to affect regional smog pollution.
Public willingness to pay watershed eco-compensation in China’s Taihu basin: A case study
Authors: Deng Menghua , Li Zhiqi , Chen Junfei , Tao Feifei
Published: November 2022

Eco-compensation is effective in promoting the sustainable development of a watershed. The exploration of the public’s willingness to pay for such compensation, along with the corresponding influencing factors, are important for improving the efficacy of eco-compensation programs. However, motivating the public to participate in eco-compensation remains a challenge. In this study, the influencing factors behind public willingness to participate in eco-compensation in China’s Taihu Basin are measured using a contingent valuation method and a random forest model. The main results are as follows: 1) In the Taihu Basin, the mean people are willing to pay for eco-compensation is 287.344 CNY/person/year. 2) The significant factors influencing willingness to pay are recognition of the importance of watershed protection; the impact of the watershed environment on people’s lives; annual incomes; and perceived improvements to the watershed environment over the past five years. 3) Awareness of the need for environmental protection can encourage people to pay eco-compensation. This study provides references that governments can use to formulate and implement eco-compensation policies and hence promote public participation in those policies.
miRNA–mRNA–protein dysregulated network in COPD in women
Authors: Li Chuan Xing , Gao Jing , Sköld C. Magnus , Wheelock Åsa M.
Published: November 2022

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease caused by a multitude of underlying mechanisms, and molecular mechanistic modeling of COPD, especially at a multi-molecular level, is needed to facilitate the development of molecular diagnostic and prognostic tools and efficacious treatments.

Objectives: To investigate the miRNA–mRNA–protein dysregulated network to facilitate prediction of biomarkers and disease subnetwork in COPD in women.

Measurements and Results: Three omics data blocks (mRNA, miRNA, and protein) collected from BAL cells from female current-smoker COPD patients, smokers with normal lung function, and healthy never-smokers were integrated with miRNA–mRNA–protein regulatory networks to construct a COPD-specific dysregulated network. Furthermore, downstream network topology, literature annotation, and functional enrichment analysis identified both known and novel disease-related biomarkers and pathways. Both abnormal regulations in miRNA-induced mRNA transcription and protein translation repression play roles in COPD. Finally, the let-7-AIFM1-FKBP1A pathway is highlighted in COPD pathology.

Conclusion: For the first time, a comprehensive miRNA–mRNA–protein dysregulated network of primary immune cells from the lung related to COPD in females was constructed to elucidate specific biomarkers and disease pathways. The multi-omics network provides a new molecular insight from a multi-molecular aspect and highlights dysregulated interactions. The highlighted let-7-AIFM1-FKBP1A pathway also indicates new hypotheses of COPD pathology.
Identification of four novel variants in the CDH23 gene from four affected families with hearing loss
Authors: Kang Baoling , Lu Xinshu , Xiong Jianjun , Li Yuan , Zhu Jinwen , Cai Tao
Published: November 2022

Background: Hearing loss (HL) is the most common form of sensory disorder in humans. Molecular diagnosis of HL is important for genetic counseling for the affected individuals and their families.

Methods: To identify potential genetic causes, we performed whole-exome sequencing and related biomedical informatics for 351 non-syndromic HL patients and their family members.

Results: In the present study, we report the identification of four compound heterozygous variants in the CDH23 gene from four affected families, including four novel variants (c.995C>A, p.T332K; c.2159G>A, p.R720Q; c.5534A>G, p.N1845S, and c.7055-1G>C) and two frequently reported variants (c.719C>T, p.P240L and c.4762C>T, p.R1588W).

Conclusion: Our findings significantly expanded the mutation spectrum of CDH23-associated autosomal recessive hearing loss.
Genome-wide analysis of MADS-box gene family in kiwifruit (Actinidia chinensis var. chinensis) and their potential role in floral sex differentiation
Authors: Ye Li-Xia , Luo Min-Min , Wang Zhi , Bai Fu-Xi , Luo Xuan , Gao Lei , Peng Jue , Chen Qing-Hong , Zhang Lei
Published: November 2022

Kiwifruit (Actinidia chinensis Planch.) is a functionally dioecious plant, which displays diverse morphology in male and female flowers. MADS-box is an ancient and huge gene family that plays a key role in plant floral organ differentiation. In this study, we have identified 89 MADS-box genes from A. chinensis Red 5 genome. These genes are distributed on 26 chromosomes and are classified into type I (21 genes) and type II (68 genes). Overall, type II AcMADS-box genes have more complex structures than type I with more exons, protein domains, and motifs, indicating that type II genes may have more diverse functions. Gene duplication analysis showed that most collinearity occurred in type II AcMADS-box genes, which was consistent with a large number of type II genes. Analysis of cis-acting elements in promoters showed that AcMADS-box genes are mainly associated with light and phytohormone responsiveness. The expression profile of AcMADS-box genes in different tissues showed that most genes were highly expressed in flowers. Further, the qRT-PCR analysis of the floral organ ABCDE model-related genes in male and female flowers revealed that AcMADS4, AcMADS56, and AcMADS70 were significantly expressed in female flowers. It indicated that those genes may play an important role in the sex differentiation of kiwifruit. This work provided a comprehensive analysis of the AcMADS-box genes and may help facilitate our understanding of the sex differentiation regulatory mechanism in kiwifruit.
Antimicrobial Peptides Prediction method based on sequence multidimensional feature embedding
Authors: Dong Benzhi , Li Mengna , Jiang Bei , Gao Bo , Li Dan , Zhang Tianjiao
Published: November 2022

Antimicrobial peptides (AMPs) are alkaline substances with efficient bactericidal activity produced in living organisms. As the best substitute for antibiotics, they have been paid more and more attention in scientific research and clinical application. AMPs can be produced from almost all organisms and are capable of killing a wide variety of pathogenic microorganisms. In addition to being antibacterial, natural AMPs have many other therapeutically important activities, such as wound healing, antioxidant and immunomodulatory effects. To discover new AMPs, the use of wet experimental methods is expensive and difficult, and bioinformatics technology can effectively solve this problem. Recently, some deep learning methods have been applied to the prediction of AMPs and achieved good results. To further improve the prediction accuracy of AMPs, this paper designs a new deep learning method based on sequence multidimensional representation. By encoding and embedding sequence features, and then inputting the model to identify AMPs, high-precision classification of AMPs and Non-AMPs with lengths of 10–200 is achieved. The results show that our method improved accuracy by 1.05% compared to the most advanced model in independent data validation without decreasing other indicators.
Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer
Authors: Zhu Zhonglin , Zhao Qiuyan , Li Shanbao , Weng Junyong , Guo Tianan , Zhu Congcong , Xu Ye
Published: November 2022

Background: Cuproptosis is a novel form of cell death discovered in recent. A great quantity of researches has confirmed the close relationships and crucial roles between long non-coding RNAs (lncRNAs) with the progression of colorectal cancer (CRC). However, the relationship between cuproptosis and lncRNAs remains unclear in CRC.

Methods: 1,111 co-expressed lncRNAs with 16 cuproptosis regulators were retrieved from CRC samples of The Cancer Genome Atlas (TCGA) database. Through univariate Cox and least absolute shrinkage and selection operator regression analysis, a prognosis model was constructed with 15 lncRNAs. The Kaplan-Meier, receiver operating characteristic curve, C-index and principal component analysis identified the prognostic power. Furthermore, a cuproptosis-related cluster was generated based on the 15 lncRNAs by unsupervised methods. The correlations between the cuproptosis-related signatures with immune cell infiltration and anti-tumor therapy were explored by multiple algorithms.

Results: A risk score and nomogram with great prediction ability were constructed for CRC prognosis evaluation. The immune activate pathways, immune infiltration cells, immune functions, immune score and immune activation genes were remarkably enriched in the high risk group. The cuproptosis-related cluster was generated, of which the cluster 2 showed longer overall survival. The immune cell infiltration analysis indicated the similar results of cluster 2 with the high risk group, implying a significant marker for “hot tumor.” The cluster 2 also presented high expression of immune checkpoint molecules, MSI-H status and higher susceptibility to multiple immunotherapy drugs.

Conclusion: We appraised a novel cuproptosis-related prognosis model and molecular signature associated with prognosis, immune infiltration and immunotherapy. The identification of cuproptosis-related lncRNAs improved our understanding of immune infiltration and provided a significant marker for prognosis and immunotherapy in CRC.
Increased IL-26 associates with markers of hyperinflammation and tissue damage in patients with acute COVID-19
Authors: Cardenas Eduardo I. , Ekstedt Sandra , Piersiala Krzysztof , Petro Marianne , Karlsson Agneta , Kågedal Åsa , Kumlien Georén Susanna , Cardell Lars-Olaf , Lindén Anders
Published: November 2022

Interleukin-26 (IL-26) is released by several immune and structural cells following stimulation of toll-like receptors (TLRs), whereupon it can directly inhibit viral replication and enhance neutrophil chemotaxis. Given these unique properties, IL-26 has emerged as an intriguing mediator of host defense in the lungs. However, the role of IL-26 in COVID-19 has not been thoroughly investigated. Here, we characterized the involvement of IL-26 in the hyperinflammation and tissue damage that occurs in patients with acute COVID-19. We found that IL-26 is markedly increased in blood samples from these patients, and that the concentration of IL-26 correlates with those of the neutrophil-mobilizing cytokines IL-8 and TNFα, respectively. Moreover, the increase in blood IL-26 correlates with enhanced surface expression of the “don’t eat me” signal CD47 on blood neutrophils isolated from patients with acute COVID-19. Finally, we found that the blood concentration of IL-26 correlates with that of increased lactate dehydrogenase, an established marker of tissue damage, and decreased mean corpuscular hemoglobin (MCH), a previously verified hematological aberration in COVID-19, both of which are associated with severe disease. Thus, our findings indicate that increased systemic IL-26 associates with markers of hyperinflammation and tissue damage in patients with acute COVID-19, thereby forwarding the kinocidin IL-26 as a potential target for diagnosis, monitoring, and therapy in this deadly disease.
Research progress in inducing immunogenic cell death of tumor cells
Authors: Xie Deqian , Wang Qifei , Wu Guangzhen
Published: November 2022

Immunogenic cell death (ICD) is a regulated cell death (RCD) pathway. In response to physical and chemical signals, tumor cells activate specific signaling pathways that stimulate stress responses in the endoplasmic reticulum (ER) and expose damage-associated molecular patterns (DAMPs), which promote antitumor immune responses. As a result, the tumor microenvironment is altered, and many tumor cells are killed. The ICD response in tumor cells requires inducers. These inducers can be from different sources and contribute to the development of the ICD either indirectly or directly. The combination of ICD inducers with other tumor treatments further enhances the immune response in tumor cells, and more tumor cells are killed; however, it also produces side effects of varying severity. New induction methods based on nanotechnology improve the antitumor ability and significantly reduces side effects because they can target tumor cells precisely. In this review, we introduce the characteristics and mechanisms of ICD responses in tumor cells and the DAMPs associated with ICD responses, summarize the current methods of inducing ICD response in tumor cells in five distinct categories: chemical sources, physical sources, pathogenic sources, combination therapies, and innovative therapies. At the same time, we introduce the limitations of current ICD inducers and make a summary of the use of ICD responses in clinical trials. Finally, we provide an outlook on the future of ICD inducer development and provide some constructive suggestions.
“Liquid biopsy” - extracellular vesicles as potential novel players towards precision medicine in asthma
Authors: Ambrożej Dominika , Stelmaszczyk-Emmel Anna , Czystowska-Kuźmicz Małgorzata , Feleszko Wojciech
Published: November 2022

Extracellular vesicles (EVs) have emerged as vital mediators in intracellular communication in the lung microenvironment. Environmental exposure to various triggers (e.g., viruses, allergens) stimulates the EV-mediated cascade of pro-inflammatory responses that play a key role in the asthma pathomechanism. This complex EV-mediated crosstalk in the asthmatic lung microenvironment occurs between different cell types, including airway epithelial cells and immune cells. The cargo composition of EVs mirrors hereby the type and activation status of the parent cell. Therefore, EVs collected in a noninvasive way (e.g., in nasal lavage, serum) could inform on the disease status as a “liquid biopsy”, which is particularly important in the pediatric population. As a heterogeneous disease, asthma with its distinct endotypes and phenotypes requires more investigation to develop novel diagnostics and personalized case management. Filling these knowledge gaps may be facilitated by further EV research. Here, we summarize the contribution of EVs in the lung microenvironment as potential novel players towards precision medicine in the development of asthma. Although rapidly evolving, the EV field is still in its infancy. However, it is expected that a better understanding of the role of EVs in the asthma pathomechanism will open up new horizons for precision medicine diagnostic and therapeutic solutions.
Prospective longitudinal analysis of antibody response after standard and booster doses of SARS-COV2 vaccination in patients with early breast cancer
Authors: Kim Jinyong , Jeong Jiyun , Lee Chan Mi , Lee Dae-Won , Kang Chang Kyung , Choe Pyeong Gyun , Kim Nam Joong , Oh Myoung-don , Lee Chang-Han , Park Wan Beom , Lee Kyung-Hun , Im Seock-Ah
Published: November 2022

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants brought waves of pandemics with breakthrough infections in vaccinated individuals. We analyzed the antibody responses after primary and booster vaccination in healthy controls (HC) and patients with early breast cancer (BC).

Methods

In this prospective longitudinal cohort study, the binding activity of serum antibody level against spike proteins and antigens of SARS-CoV-2 variants was measured within 21 days after each vaccination in the BC group and HC group.

Results

All participants, 40 in the BC and 20 in the HC group, had increased antibody response after vaccination. BC group, however, had weaker humoral responses than the HC group (IgG: 1.5, 2.3, 2.5-folds in BC vs. 1.9, 3.6, 4.0-folds in HC after each dose; IgA: 2.1, 3.0, 3.6-folds in BC vs. 4.2, 10.4, 5.2-folds in HC after each dose, respectively). Those under concurrent cytotoxic chemotherapy had weaker antibody response than the non-cytotoxic treatment group and HC. Adjunct use of steroids and age were not significant risk factors. The levels of binding antibody against the Delta and the Omicron (BA1) variants were lower than the wild-type, especially in BC.

Conclusion

In the waves of new sub-variants, our study suggests that an additional dose of vaccinations should be recommended according to the anti-cancer treatment modality in patients with BC who had received booster vaccination.
The adaptive immune system in early life: The shift makes it count
Authors: Pieren Daan K. J. , Boer Mardi C. , de Wit Jelle
Published: November 2022

Respiratory infectious diseases encountered early in life may result in life-threatening disease in neonates, which is primarily explained by the relatively naive neonatal immune system. Whereas vaccines are not readily available for all infectious diseases, vaccinations have greatly reduced childhood mortality. However, repeated vaccinations are required to reach protective immunity in infants and not all vaccinations are effective at young age. Moreover, protective adaptive immunity elicited by vaccination wanes more rapidly at young age compared to adulthood. The infant adaptive immune system has previously been considered immature but this paradigm has changed during the past years. Recent evidence shows that the early life adaptive immune system is equipped with a strong innate-like effector function to eliminate acute pathogenic threats. These strong innate-like effector capacities are in turn kept in check by a tolerogenic counterpart of the adaptive system that may have evolved to maintain balance and to reduce collateral damage. In this review, we provide insight into these aspects of the early life’s adaptive immune system by addressing recent literature. Moreover, we speculate that this shift from innate-like and tolerogenic adaptive immune features towards formation of immune memory may underlie different efficacy of infant vaccination in these different phases of immune development. Therefore, presence of innate-like and tolerogenic features of the adaptive immune system may be used as a biomarker to improve vaccination strategies against respiratory and other infections in early life.
What role for cellular metabolism in the control of hepatitis viruses?
Authors: Diaz Olivier , Vidalain Pierre-Olivier , Ramière Christophe , Lotteau Vincent , Perrin-Cocon Laure
Published: November 2022

Hepatitis B, C and D viruses (HBV, HCV, HDV, respectively) specifically infect human hepatocytes and often establish chronic viral infections of the liver, thus escaping antiviral immunity for years. Like other viruses, hepatitis viruses rely on the cellular machinery to meet their energy and metabolite requirements for replication. Although this was initially considered passive parasitism, studies have shown that hepatitis viruses actively rewire cellular metabolism through molecular interactions with specific enzymes such as glucokinase, the first rate-limiting enzyme of glycolysis. As part of research efforts in the field of immunometabolism, it has also been shown that metabolic changes induced by viruses could have a direct impact on the innate antiviral response. Conversely, detection of viral components by innate immunity receptors not only triggers the activation of the antiviral defense but also induces in-depth metabolic reprogramming that is essential to support immunological functions. Altogether, these complex triangular interactions between viral components, innate immunity and hepatocyte metabolism may explain why chronic hepatitis infections progressively lead to liver inflammation and progression to cirrhosis, fibrosis and hepatocellular carcinoma (HCC). In this manuscript, we first present a global overview of known connections between the innate antiviral response and cellular metabolism. We then report known molecular mechanisms by which hepatitis viruses interfere with cellular metabolism in hepatocytes and discuss potential consequences on the innate immune response. Finally, we present evidence that drugs targeting hepatocyte metabolism could be used as an innovative strategy not only to deprive viruses of key metabolites, but also to restore the innate antiviral response that is necessary to clear infection.
Age related immune modulation of experimental autoimmune encephalomyelitis in PINK1 knockout mice
Authors: Cossu Davide , Yokoyama Kazumasa , Sato Shigeto , Noda Sachiko , Sakanishi Tamami , Sechi Leonardo Antonio , Hattori Nobutaka
Published: November 2022

Objective

Recent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Because the PTEN-induced putative kinase 1 (PINK1) protein acts upstream of Parkin in a common mitochondrial quality control pathway, we hypothesized that the systemic deletion of PINK1 could also modify the clinical course of EAE, altering the peripheral and central nervous systems’ immune responses.

Methods

EAE was induced in female PINK1-/- mice of different age groups by immunization with myelin oligodendrocyte glycoprotein peptide.

Results

Compared to young wild-type controls, PINK1-/- mice showed earlier disease onset, albeit with a slightly less severe disease, while adult PINK1-/- mice displayed early onset and more severe acute symptoms than controls, showing persistent disease during the recovery phase. In adult mice, EAE severity was associated with significant increases in frequency of dendritic cells (CD11C+, IAIE+), lymphocytes (CD8+), neutrophils (Ly6G+, CD11b+), and a dysregulated cytokine profile in spleen. Furthermore, a massive macrophage (CD68+) infiltration and microglia (TMEM119+) and astrocyte (GFAP+) activation were detected in the spinal cord of adult PINK1-/- mice.

Conclusions

PINK1 plays an age-related role in modulating the peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and other associated conditions.
Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma
Authors: Xu Lei , Wei Xiu-feng , Li Can-jun , Yang Zhao-yang , Yu Yong-kui , Li Hao-miao , Xie Hou-nai , Yang Ya-fan , Jing Wei-wei , Wang Zhen , Kang Xiao-zheng , Zhang Rui-xiang , Qin Jian-jun , Xue Li-yan , Bi Nan , Chen Xian-kai , Li Yin
Published: November 2022

Background

Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC.

Methods

Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors.

Results

After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062).

Conclusion

For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.
Foxp3+ regulatory T cell therapy for tolerance in autoimmunity and solid organ transplantation
Authors: Sanders Jes M. , Jeyamogan Shareni , Mathew James M. , Leventhal Joseph R.
Published: November 2022

Regulatory T cells (Tregs) are critical for tolerance in humans. The exact mechanisms by which the loss of peripheral tolerance leads to the development of autoimmunity and the specific role Tregs play in allograft tolerance are not fully understood; however, this population of T cells presents a unique opportunity in the development of targeted therapeutics. In this review, we discuss the potential roles of Foxp3+ Tregs in the development of tolerance in transplantation and autoimmunity, and the available data regarding their use as a treatment modality.
Immunomodulatory role of metalloproteinase ADAM17 in tumor development
Authors: Wang Kai , Xuan Zixue , Liu Xiaoyan , Zheng Meiling , Yang Chao , Wang Haiyong
Published: November 2022

ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.
Clostridium butyricum potentially improves inflammation and immunity through alteration of the microbiota and metabolism of gastric cancer patients after gastrectomy
Authors: Cao Wenjie , Zheng Cihua , Xu Xuan , Jin Rui , Huang Feng , Shi Meng , He Zhipeng , Luo Yufeng , Liu Lulin , Liu Zhaoxia , Wei Jing , Deng Xiaorong , Chen Tingtao
Published: November 2022

Background

Gastrectomy is the most effective treatment to improve the clinical survival rate of patients with gastric cancer. However, the pathophysiological changes caused by gastrectomy have seriously affected the postoperative recovery.

Methods

In the present trial, Ataining (containing C. butyricum, CGMCC0313.1) was applied in patients after gastrectomy to investigate the effect of C. butyricum on the early postoperative recovery by monitoring the inflammatory immune response with blood indicators, detecting the gut microbiota with high-throughput sequencing, and analyzing the short-chain fatty acids (SCFAs) with targeted metabolomics. This study is registered with the number ChiCTR2000040915.

Results

Our outcomes revealed that C. butyricum had significantly reduced the number of Leucocyte (P < 0.001), the percentage of Neutrophil (P < 0.001), the expression of IL-1β (P < 0.01), IL-6 (P < 0.05), and TNF-α (P < 0.01), while markedly enhanced the immunity indexes (immunoglobulin and lymphocyte) (P < 0.05) and nutrition indexes (albumin and total protein) (P < 0.05). In addition, the use of the C. butyricum greatly enriched the relative abundance of beneficial bacteria Bacteroides, Faecalibacterium and Gemmiger, while the abundance of pathogenic Streptococcus, Desulfovibrio and Actinomyces were markedly decreased at genus level. We also observed significant up-regulation of SCFAs, including acetic acid, propionic acid, butyric acid and isobutyric acid, after C. butyricum administration in patients receiving gastrectomy.

Conclusion

Therefore, evidence supported that oral administration of C. butyricum after gastrectomy can reduce early postoperative inflammation, enhance immune ability, restore intestinal microbiota eubiosis, increase intestinal SCFAs, reduce the occurrence of postoperative complications, and ultimately promote the early recovery of the patient.

Clinical trial registration

http://www.chictr.org.cn/, identifier (ChiCTR2000040915).
Biogenic calcium carbonate derived from waste shells for advanced material applications: A review
Authors: Azarian Mohammad Hossein , Sutapun Wimonlak
Published: November 2022

Biogenic calcium carbonate derived from waste shells has received significant attention in the last 2 decades as a replacement for limestone due to its contribution to reducing environmental impact by turning wastes into value-added biomaterial and moving global society toward net-zero waste. Recently, several review papers have been published regarding applying biogenic derived calcium carbonate in engineering, biomedical, electrochemical, and environmental technologies. This review stands apart from other reviews on this topic in terms of focusing and reviewing the published papers used and reported indirect methods only to obtain calcium carbonate from biogenic waste shells and not by direct methods. The direct or untreated methods include simple grinding, ball milling, or mortar and pestle techniques. In contrast, the indirect methods covered in this review paper consist of precipitation and different chemical treatment techniques. Therefore, this review paper aims to comprehensively summarize the usage of calcium carbonate derived from eggshells and seashells by indirect methods and glance at its recent development for advanced material applications including water treatment, bio-filler, and reinforcement in polymer composites, energy application, pharmaceutical, biomedical, and drug delivery applications.
Intra-articular injection of clioquinol ameliorates osteoarthritis in a rabbit model
Authors: Wu Xiaoqing , Xu Peng , Shi Xuanren , Shang Jian , Chen Xiaoyong , Guo Anyun , Wang Fuming , Yin Zhanhai
Published: November 2022

Osteoarthritis (OA) is characterized by the degeneration of articular cartilage. Decreased autophagy is tightly associated with chondrocyte death, which contributes to the progression of OA. Thus, pharmacological activation of autophagy may be a promising therapeutic approach for OA. Here, we discovered that clioquinol, an antibiotic, significantly induces autophagy in OA chondrocytes from human tissue and rabbit model. Meanwhile, clioquinol can also augment the expression of extracellular matrix (ECM) components and suppress inflammatory mediators to improve OA microenvironment. Intra-articular injection of clioquinol can greatly prevent or slow down the development of this disease in a trauma-induced rabbit model of osteoarthritis. Such protective effect induced by clioquinol was at least in part explained by decreasing chondrocyte apoptosis and increasing autophagy. This study reveals the therapeutic potential of clioquinol in OA treatment.
Hospital-acquired bloodstream infections in patients deceased with COVID-19 in Italy (2020–2021)
Authors: Monaco Monica , Floridia Marco , Giuliano Marina , Palmieri Luigi , Lo Noce Cinzia , Pantosti Annalisa , Palamara Anna Teresa , Brusaferro Silvio , Onder Graziano ,   The Italian National Institute of Health COVID-19 Mortality Group
Published: November 2022

Introduction

In hospitalized patients with COVID-19, bloodstream infections (BSI) are associated with high mortality and high antibiotic resistance rates. The aim of this study was to describe BSI etiology, antimicrobial resistance profile and risk factors in a sample of patients deceased with COVID-19 from the Italian National COVID-19 surveillance.

Methods

Hospital charts of patients who developed BSI during hospitalization were reviewed to describe the causative microorganisms and their antimicrobial susceptibility profiles. Risk factors were analyzed in univariate and multivariate analyses.

Results

The study included 73 patients (71.2% male, median age 70): 40 of them (54.8%) received antibiotics and 30 (41.1%) systemic steroids within 48 h after admission; 53 (72.6%) were admitted to intensive care unit. Early steroid use was associated with a significantly shorter interval between admission and BSI occurrence. Among 107 isolated microorganisms, the most frequent were Enterococcus spp., Candida spp., Acinetobacter baumannii, and Klebsiella pneumoniae. Median time from admission to BSI was shorter for Staphylococcus aureus compared to all other bacteria (8 vs. 24 days, p = 0.003), and longer for Enterococcus spp., compared to all other bacteria (26 vs. 18 days, p = 0.009). Susceptibility tests showed a high rate of resistance, with 37.6% of the bacterial isolates resistant to key antibiotics. Resistance was associated with geographical area [adjusted odds ratio (AOR) for Central/South Italy compared to North Italy: 6.775, p = 0.002], and with early use of systemic steroids (AOR 6.971, p = 0.018).

Conclusions

In patients deceased with COVID-19, a large proportion of BSI are caused by antibiotic-resistant bacteria. Early steroid use may facilitate this occurrence.