bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Organic Dopant for Spiro-OMeTAD in High-Efficiency and Stable Perovskite Solar Cells
Authors: Guo Ying
Published: July 2022

Perovskite solar cells (PSCs) have achieved excellent power conversion efficiencies (PCEs); however, there still exist some major challenges on device stability due to hydrophilic bis(trifluoromethane)sulfonimide lithium (Li-TFSI), which is commonly introduced as a p-dopant to increase the hole mobility and conductivity of 2,2′,7,7′-tetrakis-(N,N-di-4-methoxyphenylamino)-9,9′-spirobifluorene (spiro-OMeTAD) hole-transporting materials (HTMs). Ion migration, corrosiveness, and hygroscopicity induced by the additive Li-TFSI are detrimental to the device stability, which significantly hinders further commercialization of PSCs. Herein, a hydrophobic organic ionic compound, trityltetra(pentafluorophenyl)borate (TPP), is explored as a novel efficient and stable alternative p-dopant, avoiding the long-term aging process to improve the conductivity of spiro-OMeTAD. As a result, the champion efficiency of TPP-based devices delivers performance up to 23.03%, which is higher than that of the Li-TFSI–based devices (22.39%). In addition, the TPP-based devices also exhibit higher average PCE values. The excellent performance with TPP may be associated with the higher work function of doped spiro-OMeTAD and a better alignment of energy levels with the valence band of perovskite, which substantially accelerate interfacial carrier transportation and minimize the open-circuit voltage (Voc) loss of PSCs. More importantly, the un-encapsulated TPP-doped devices also display much superior operational stability under maximum power point (MPP) tracking with continuous light illumination in an ambient humid environment, which maintained 96–97% of the initial PCE over 1,100 h outputting. Thus, this work will open up new possibilities for hydrophilic Li-TFSI dopant replacements.
Essays on Conceptual Electrochemistry: I. Bridging Open-Circuit Voltage of Electrochemical Cells and Charge Distribution at Electrode–Electrolyte Interfaces
Authors: Huang Jun , Zhang Yufan
Published: July 2022

We ponder over how an electrochemical cell conforms itself to the open-circuit voltage (OCV) given by the Nernst equation, where properties of the electrodes play no role. We first show, via a pedagogical derivation of the Nernst equation, how electrode properties are canceled and then take a closer look into the electrode–electrolyte interface at one electrode by linking charge and potential distributions. We obtain an equilibrium Poisson–Nernst equation that shows how the charge distribution across an electrode–electrolyte interface can be dictated by the chemical potentials of redox species. Taking a H2/O2 fuel cell as an example, we demystify the formal analysis by showing how the two electrodes delicately regulate their “electron tails” to abide by the Nernst equation. In this example, we run into a seemingly counterintuitive phenomenon that two electrodes made of the same transition metal display two distinct potentials of zero charge. This example indicates that the double layer at transition metals with chemisorption can display distinct behaviors compared to ideally polarizable double layers at sp metals.
Synthesis and Discovery of Ligustrazine–Heterocycle Derivatives as Antitumor Agents
Authors: Ma Shitang , Zhang Ning , Hou Jiafu , Liu Shijuan , Wang Jiawen , Lu Baowei , Zhu Fucheng , Wei Peipei , Hong Ge , Liu Tianjun
Published: July 2022

Ligustrazine (TMP) is a natural pyrazine alkaloid extracted from the roots of Ligusticum Chuanxiong Hort, which has the potential as an antitumor agent. A series of 33 ligustrazine–heterocycle (TMPH) derivatives were designed, synthesized, and investigated via antitumor screening assays, molecular docking analysis, and prediction of drug-like properties. TMP was attached to other heterocyclic derivatives by an 8–12 methylene alkyl chain as a linker to obtain 33 TMPH derivatives. The structures were confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectroscopy spectral (HR-MS) data. The antiproliferative activity against human breast cancer MCF-7, MDA-MB-231, mouse breast cancer 4T1, mouse fibroblast L929, and human umbilical vein endothelial HUVEC cell lines was evaluated by MTT assay. Compound 12–9 displayed significant inhibitory activity with IC50 values in the low micromolar range (0.84 ± 0.02 µM against the MDA-MB-231 cell line). The antitumor effects of compound 12–9 were further evaluated by plate cloning, Hoechst 33 342 staining, and annexin V-FITC/PI staining. The results indicated that compound 12–9 inhibited the proliferation and apoptosis of breast cancer cells. Furthermore, molecular docking of compound 12–9 into the active site of the Bcl-2, CASP-3, and PSMB5 target proteins was performed to explore the probable binding mode. The 33 newly synthesized compounds were predicted to have good drug-like properties in a theoretical study. Overall, these results indicated that compound 12–9 inhibited cell proliferation through PSMB5 and apoptosis through Bcl-2/CASP-3 apoptotic signaling pathways and had good drug-like properties. These results provided more information, and key precursor lead derivatives, in the search for effective bioactive components from Chinese natural medicines.
Gut microbiome markers in subgroups of HLA class II genotyped infants signal future celiac disease in the general population: ABIS study
Authors: Milletich Patricia L. , Ahrens Angelica P. , Russell Jordan T. , Petrone Joseph R. , Berryman Meghan A. , Agardh Daniel , Ludvigsson Jonas F. , Triplett Eric W. , Ludvigsson Johnny
Published: July 2022

Although gut microbiome dysbiosis has been illustrated in celiac disease (CD), there are disagreements about what constitutes these microbial signatures and the timeline by which they precede diagnosis is largely unknown. The study of high-genetic-risk patients or those already with CD limits our knowledge of dysbiosis that may occur early in life in a generalized population. To explore early gut microbial imbalances correlated with future celiac disease (fCD), we analyzed the stool of 1478 infants aged one year, 26 of whom later acquired CD, with a mean age of diagnosis of 10.96 ± 5.6 years. With a novel iterative control-matching algorithm using the prospective general population cohort, All Babies In Southeast Sweden, we found nine core microbes with prevalence differences and seven differentially abundant bacteria between fCD infants and controls. The differences were validated using 100 separate, iterative permutations of matched controls, which suggests the bacterial signatures are significant in fCD even when accounting for the inherent variability in a general population. This work is the first to our knowledge to demonstrate that gut microbial differences in prevalence and abundance exist in infants aged one year up to 19 years before a diagnosis of CD in a general population.
Cerebral malaria induced by plasmodium falciparum: clinical features, pathogenesis, diagnosis, and treatment
Authors: Song Xiaonan , Wei Wei , Cheng Weijia , Zhu Huiyin , Wang Wei , Dong Haifeng , Li Jian
Published: July 2022

Cerebral malaria (CM) caused byPlasmodium falciparumis a fatal neurological complication of malaria, resulting in coma and death, and even survivors may suffer long-term neurological sequelae. In sub-Saharan Africa, CM occurs mainly in children under five years of age. Although intravenous artesunate is considered the preferred treatment for CM, the clinical efficacy is still far from satisfactory. The neurological damage induced by CM is irreversible and lethal, and it is therefore of great significance to unravel the exact etiology of CM, which may be beneficial for the effective management of this severe disease. Here, we review the clinical characteristics, pathogenesis, diagnosis, and clinical therapy of CM, with the aim of providing insights into the development of novel tools for improved CM treatments.
Emerging advances in identifying signal transmission molecules involved in the interaction between Mycobacterium tuberculosis and the host
Authors: Wang Yue , Shi Qiyuan , Chen Qi , Zhou Xuebin , Yuan Huiling , Jia Xiwen , Liu Shuyuan , Li Qin , Ge Lijun
Published: July 2022

Tuberculosis caused by Mycobacterium tuberculosis (MTB) is an ancient chronic infectious disease and is still the leading cause of death worldwide due to a single infectious disease. MTB can achieve immune escape by interacting with host cells through its special cell structure and secreting a variety of effector proteins. Innate immunity-related pattern recognition receptors (PPR receptors) play a key role in the regulation of signaling pathways.

In this review, we focus on the latest research progress on related signal transduction molecules in the interaction between MTB and the host. In addition, we provide new research ideas for the development of new anti-tuberculosis drug targets and lead compounds and provide an overview of information useful for approaching future tuberculosis host-oriented treatment research approaches and strategies, which has crucial scientific guiding significance and research value.
Microbial ecosystem responses to alkalinity enhancement in the North Atlantic Subtropical Gyre
Authors: Subhas Adam V. , Marx Lukas , Reynolds Sarah , Flohr Anita , Mawji Edward W. , Brown Peter J. , Cael B. B.
Published: July 2022

In addition to reducing carbon dioxide (CO2) emissions, actively removing CO2 from the atmosphere is widely considered necessary to keep global warming well below 2°C. Ocean Alkalinity Enhancement (OAE) describes a suite of such CO2 removal processes that all involve enhancing the buffering capacity of seawater. In theory, OAE both stores carbon and offsets ocean acidification. In practice, the response of the marine biogeochemical system to OAE must be demonstrably negligible, or at least manageable, before it can be deployed at scale. We tested the OAE response of two natural seawater mixed layer microbial communities in the North Atlantic Subtropical Gyre, one at the Western gyre boundary, and one in the middle of the gyre. We conducted 4-day microcosm incubation experiments at sea, spiked with three increasing amounts of alkaline sodium salts and a 13C-bicarbonate tracer at constant pCO2. We then measured a suite of dissolved and particulate parameters to constrain the chemical and biological response to these additions. Microbial communities demonstrated occasionally measurable, but mostly negligible, responses to alkalinity enhancement. Neither site showed a significant increase in biologically produced CaCO3, even at extreme alkalinity loadings of +2,000 μmol kg−1. At the gyre boundary, alkalinity enhancement did not significantly impact net primary production rates. In contrast, net primary production in the central gyre decreased by ~30% in response to alkalinity enhancement. The central gyre incubations demonstrated a shift toward smaller particle size classes, suggesting that OAE may impact community composition and/or aggregation/disaggregation processes. In terms of chemical effects, we identify equilibration of seawater pCO2, inorganic CaCO3 precipitation, and immediate effects during mixing of alkaline solutions with seawater, as important considerations for developing experimental OAE methodologies, and for practical OAE deployment. These initial results underscore the importance of performing more studies of OAE in diverse marine environments, and the need to investigate the coupling between OAE, inorganic processes, and microbial community composition.
Role of sex on the efficacy of pharmacological and non-pharmacological treatment of heart failure with reduced ejection fraction: A systematic review
Authors: Sanromán Guerrero María Ascensión , Antoñana Ugalde Sonia , Hernández Sánchez Elena , del Prado Díaz Susana , Jiménez-Blanco Bravo Marta , Cordero Pereda David , Zamorano Gómez José Luis , Álvarez-García Jesús
Published: July 2022

Background

Heart Failure (HF) is a growing epidemic with a similar prevalence in men and women. However, women have historically been underrepresented in clinical trials, leading to uneven evidence regarding the benefit of guideline-directed medical therapy (GDMT). This review aims to outline the sex differences in the efficacy of pharmacological and non-pharmacological treatment of HF with reduced ejection fraction (HFrEF).

Methods and results

We conducted a systematic review via Medline from inception to 31 January 2022, including all randomized clinical trials published in English including adult patients suffering HFrEF that reported data on the efficacy of each drug. Baseline clinical characteristics, primary outcomes, and sex-specific effects are summarized in tables. The systemic review has been conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 29 articles were included in the systematic review. We observed that the proportion of women enrolled in clinical trials was generally low, the absence of a prespecified analysis of efficacy by sex was frequent, and the level of quality of evidence on the efficacy of GDMT and implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT-) in women was relatively poor.

Conclusions

Sex influences the response to treatment of patients suffering from HFrEF. All the results from the landmark randomized clinical trials are based on study populations composed mainly of men. Further studies specifically designed considering sex differences are warranted to elucidate if GDMT and new devices are equally effective in both sexes.
Utility of PREDICT-HF score in high-risk Asian heart failure patients receiving sacubitril/valsartan
Authors: Hsu Chien-Yi , Chang Hung-Yu , Chao Chieh-Ju , Chiou Wei-Ru , Lin Po-Lin , Chung Fa-Po , Lin Wen-Yu , Huang Jin-Long , Liang Huai-Wen , Liao Chia-Te , Lee Ying-Hsiang
Published: July 2022

Objective

The aim of this study was to investigate the application of sacubitril/valsartan in clinical practice and the utility of PREDICT-HF score for outcome prediction in Asian heart failure patients with difference risk profiles.

Methods

The TAROT-HF study was a multicenter, single-arm, observational study. Totally 1,187 outpatients with HFrEF treated with sacubitril/valsartan were enrolled and categorized by: (1) high-risk group with ≥1 of the following three risk factors: old age (≥80 years), low baseline systolic blood pressure (<100 mmHg), and renal impairment (eGFR <30 ml/min/1.73 m2), and (2) standard-risk group, those who did not have any risk factors. Clinical outcomes were assessed using the PREDICT-HF risk model.

Results

A total of 305 (25.7%) patients matched the criteria for the high-risk group. The event rates of cardiovascular death or first unplanned heart failure hospitalization (HFH) among the overall population, high-risk, and standard-risk groups were 13.7, 24.9, and 10.8 events per 100 patient-years, respectively. The C statistics for the PREDICT-HF model in the overall cohort and high-risk group for cardiovascular death or first unplanned HFH at 2 years were 0.73 (95% CI 0.70–0.76) and 0.71 (95% CI 0.65–0.76), respectively. The permanent discontinuation rate among the high-risk patients was significantly higher than that among the standard-risk patients (8.3 vs. 2.5 per 100 patient-years, p < 0.001).

Conclusions

Real-world outcomes of the TAROT-HF study demonstrated that the PREDICT-HF model performed well in Asian HFrEF patients. Three easily detected clinical profiles of age, renal function, and systolic BP could help to identify patients at risk before initiating sacubitril/valsartan.
The Blood-Brain Barrier in Space: Implications for Space Travelers and for Human Health on Earth
Authors: Amselem Shimon , Eyal Sara
Published: July 2022

Astronauts have flown to space for decades, but the effects of spaceflight on human health have not been fully clarified yet. Several pathologies have only been detected after it has become customary for astronauts to spend months rather than days in space and with the advance of inflight monitoring. Examples include the neuro-ocular spaceflight associated syndrome, changes to the brain’s white matter, and, more recently, altered cerebral blood flow and related hypercoagulability. This review outlines spaceflight-induced brain disorders in astronauts and putative contributing factors. It next presents ongoing and upcoming studies of the BBB onboard space platforms. Finally, it describes how the space environment can be harnessed for improving drug-delivery across the BBB for humans both in space and on Earth.
Composition analysis and distributed assumption GIS model of normal stress on the slope sliding surface
Authors: Yu Guo , Bu Lei , Wang Chengfeng , Farooq Asim
Published: July 2022

For the limit equilibrium method based on the assumption model of sliding surface normal stress, the more reasonable the assumed sliding surface normal stress model is, the higher the accuracy of the calculation results will be, which is of great significance to improve the theoretical calculation accuracy. Combined with the powerful spatial data analysis ability of Geographic Information Systems (GIS), the expression of the normal stress distribution function of the slip surface is deduced by establishing a GIS-based three-dimensional slope stability analysis model and limit equilibrium equations. By analyzing the composition of the normal stress distribution on the sliding surface, the composition of the normal stress on the sliding surface is obtained, and then the assumed model of the normal stress distribution on the sliding surface is constructed. Finally, the assumed GIS model of the sliding surface normal stress distribution is verified by calculating the proportion. The model overcomes the problem that the stability factor of the slope will cause large errors in the three-dimensional state, and provides a theoretical calculation basis for the establishment of a three-dimensional slope limit equilibrium method based on the assumption of normal stress on the slip surface in GIS.
Towards 2030. Enhancing 21st century skills through educational robotics
Authors: Gratani Francesca , Giannandrea Lorella
Published: July 2022

Recent technological advances require new learning and teaching methods and a reform of traditional school curricula to promote STEM and 21st-century skills. Educational robotics is considered a powerful tool, not only to learn programing, but also to enhance soft and transversal skills, such as problem-solving, metacognition, divergent thinking, creativity, and collaboration. This contribution presents a one-year research project aimed at integrating maker education and educational robotics into the primary and lower secondary school curriculum. The project is developed through a multidisciplinary and longitudinal approach and adopts the Design-Based Implementation Research methodology. It involved 50 fourth and fifth grade Italian students until the following school year. As an integrating background theme, we chose the 17 Goals outlined by the UN in the 2030 Agenda. Each selected goal was addressed by solving challenges in groups. Educational robotics became a tool for learning many concepts, such as renewable energies, human body systems or states of matter, but especially for working on creativity and ability to design, build, collaborate, and revise. We investigated students’ attitude toward STEM and 21st-century skills and their perceived school self-efficacy administrating two questionnaires pre and post the two parts of the project. This paper discusses findings on students’ attitude toward 21st-century skills. In the post analyzes of both Part 1 and 2, this field showed the highest scores compared to STEM fields. The pre-post data show an improvement in organizational, interpersonal, and leadership skills from Part 1, but also a gradual increase in personal and management skills.
Exploring the Regulation of Jiangtang Tiaozhi Formula on the Biological Network of Obese T2DM Complicated With Dyslipidemia Based on Clinical Transcriptomics
Authors: Bao Tingting , Wang Song , Yang Yingying , He Lisha , Han Lin , Zhai Tiangang , Chen Jia , Zhou Qiang , Zhao Xiyan , Lian Fengmei , Zhao Linhua , Tong Xiaolin
Published: July 2022

Objective

To use systems biology to explore the biomolecular network mechanism of the Jiangtang Tiaozhi Recipe (JTTZR) in the intervention of obese Type 2 diabetes (T2DM) patients with dyslipidemia.

Methods

Twelve patients with obese type 2 diabetes mellitus and dyslipidemia (traditional Chinese medicine syndrome differentiation was excess heat syndrome of the stomach and intestines) were treated with JTTZR for 24 weeks, and 12 patients were included in the healthy control group. First, blood samples from 6 patients in each group (disease group before treatment, disease group after treatment, and healthy control group) were collected for RNA microarray analysis. Quantitative polymerase chain reaction (qPCR) was used to validate these target lncRNAs and mRNAs. Finally, a detailed analysis of the differences in the disease group before treatment vs. the healthy control group and the disease group after treatment vs. the disease group before treatment was undertaken. In addition, we focused on disease-related pathways and analyzed the correlation between the differential expression of target lncRNAs and clinical indicators.

Results

(1) Disease group before treatment vs. healthy control group: There were 557 up-regulated lncRNAs, 273 down-regulated lncRNAs, 491 up-regulated mRNAs, and 1639 down-regulated mRNAs. GO analysis and pathway analysis showed that T2DM may be related to cell proliferation in the forebrain, post-embryonic organ development, calcium signaling pathway. qPCR validation showed that the expression of XLOC-005590 and HNF1A-AS1 as target lncRNAs increased, and this was verified by gene chip analysis. (2) Disease group after treatment vs. disease group before treatment: 128 lncRNAs were upregulated, 32 lncRNAs were downregulated, 45 mRNAs were upregulated, and 140 mRNAs were downregulated. GO analysis and pathway analysis showed that JTTZR may treat T2DM through endosome transport, the insulin signaling pathway, and glycine, serine, and threonine metabolism. qPCR validation showed that in the healthy control group, XLOC_005590 was upregulated, whereas the downstream gene (ECI2) was downregulated in the disease group before treatment. However, after 24 weeks of intervention with JTTZR, XLOC_005590 was downregulated and ECI2 was upregulated compared with the disease group before treatment (0 weeks) (P <0.05).

Conclusion

JTTZR may interfere in patients with obese T2DM with dyslipidemia by regulating pathways such as fatty acid degradation, glycolysis/gluconeogenesis, and pyruvate metabolism.
To explore association between gamma-glutamyl transferase and type 2 diabetes using a real-world study and mendelian randomization analysis
Authors: Bi Yaru , Yang Shuo , Liu Yanjing , Cao Lingxia , Gao Menghan , Liu Weixia , Li Yuting , Tian Suyan , Sun Chenglin
Published: July 2022

Aim

The association between gamma-glutamyl transferase (GGT) and type 2 diabetes mellitus (T2DM) is controversial. In this study, we investigated the association between GGT and the risk of T2DM using real-world data, Mendelian randomization (MR) analysis, and literature mining.

Methods

A cross-sectional study enrolled 3,048 participants (>40 years) from a community in Northeastern China was conducted. A generalized additive model was used to examine the relation between GGT and T2DM. A two-sample MR was performed to investigate the causal effect of GGT (61,089 individuals, mostly of European ancestry) on T2DM (29,193 cases and 182,573 controls of European ancestry).

Results

GGT was related to glucose metabolism indicators, such as fasting plasma glucose and glycosylated hemoglobin (P < 0.05). The odds ratios (ORs) [95% confidence interval (95% CI), P] for T2DM across the GGT categories (14–16, 17–20, 21–25, 26–35, ≥36) were 1.14 [(0.88-1.47), P = 0.330], 1.55 [(1.22-1.98), P < 0.001], 1.87 [(1.47-2.28), P < 0.001], 1.97 [(1.55-2.52), P < 0.001], and 2.29 [(1.78-2.94), P < 0.001] versus GGT ≤ 13 category after adjusting for potential confounding factors. A generalized additive model identified a non-linear correlation between GGT and T2DM and indicated that the risk of T2DM almost levelled out when GGT exceeded 34 IU/L. The MR analysis showed that the odds of having T2DM for a one-time increase in genetically determined GGT was 0.998 [(0.995-1.002), P = 0.34].

Conclusions

Our analysis of observational study suggested that GGT, its increment, within a certain range, is indicative of the development of T2DM. However, MR analysis provided no evidence that GGT is a linear causal factor of T2DM. Further investigation is required to determine if GGT exerts a non-linear causal effect on T2DM.
The prevalence of precocious puberty among children in Qufu City, Shandong Province, China, a population-based study
Authors: Zhang Yawen , Ni Jianmin , Zhang Lei , Yu Tingting , Li Xiaoqing , Xue Peng , Liu Yifan , Gao Bo , Xue Xinwen , Kong Huijun , Liu Shijian
Published: July 2022

Objective

We sought to investigate the prevalence of precocious puberty in children aged 6–10 years in Qufu City, Shandong Province, China.

Methods

A total of 5,169 primary school students from grades 1–3 were recruited by population-based multi-stage stratified cluster random sampling. Professional pediatricians conducted physical examinations in October 2020. Precocious puberty is defined as the onset of secondary sexual characteristics in boys aged < 9 years or girls < 8 years or menstruation in girls < 10 years old. Tanner staging was used to record the development of breast and pubic hair in girls and testicular volume and pubic hair in boys. According to the standards of the International Obesity Task Force, we diagnosed overweight, obesity, or severe obesity. In obese girls, a combination of palpation and ultrasound was used to evaluate breast development. The difference was tested by chi-squared test, and all data were statistically analyzed using IBM SPSS version 25.0.

Results

The unadjusted and adjusted prevalence rates of precocious puberty were 5.01% (11.53% for girls and 1.41% for boys) and 6.29% (14.23% for girls and 1.54% for boys), respectively. The prevalence of precocious puberty in urban (5.34%) dwellers was much higher than that in suburban residents (2.36%, P < 0.05). The prevalence of precocious puberty in the overweight (21.43% for girls and 1.97% for boys), obesity (35.48% for girls and 4.6% for boys), and severe obesity (32.35% for girls and 3.38% for boys) groups were higher than that in the normal weight group (4% for girls and 0.54% for boys, P < 0.05).

Conclusion

The prevalence of precocious puberty is high, and overweight and obesity are related to precocious puberty in Qufu, Shandong Province, China.
Stock Market Forecasting Using the Random Forest and Deep Neural Network Models Before and During the COVID-19 Period
Authors: Omar Abdullah Bin , Huang Shuai , Salameh Anas A. , Khurram Haris , Fareed Muhammad
Published: July 2022

Stock market forecasting is considered the most challenging problem to solve for analysts. In the past 2 years, Covid-19 has severely affected stock markets globally, which, in turn, created a great problem for investors. The prime objective of this study is to use a machine learning model to effectively forecast stock index prices in three time frames: the whole period, the pre-Covid-19 period, and the Covid-19 period. The model accuracy testing results of mean absolute error, root mean square error, mean absolute percentage error, and r2 suggest that the proposed machine learning models autoregressive deep neural network (AR-DNN(1, 3, 10)), autoregressive deep neural network (AR-DNN(3, 3, 10)), and autoregressive random forest (AR-RF(1)) are the best forecasting models for stock index price forecasting for the whole period, for the pre-Covid-19 period, and during the Covid-19 period, respectively, under high stock price fluctuations compared to traditional time-series forecasting models such as autoregressive moving average models. In particular, AR-DNN(1, 3, 10) is suggested when the number of observations is large, whereas AR-RF(1) is suggested for a series with a low number of observations. Our study has a practical implication as they can be used by investors and policy makers in their investment decisions and in formulating financial decisions and policies, respectively.
Data element embedding and firm performance: The influence of ESG investment
Authors: Jianqiang Gu , Rong Lu , Juan Xu
Published: July 2022

ESG is a brand-new concept about how environmental, social and corporate governance supports sustainable development in enterprises. However, little research is done on how to reshape the internal mechanism by which data element embedding drives enterprise performance based on the brand-new sustainable concept. From the perspective of contingency theory and organizational agility, a conceptual model including ESG investment, data element embedding, organizational agility and environmental uncertainty is constructed to study the internal mechanism by which data element embedding affects enterprise performance. The model is empirically researched through the data obtained from the survey of 287 manufacturing enterprises in China. The results show that, ESG investment and external data element embedding impose no direct impact on enterprise performance, but create an indirect impact through organizational agility; environmental uncertainty negatively moderates the effect of ESG investment on organizational agility. Through the hierarchical analysis of ESG investment and data elements embedded in enterprise performance, the value creation mechanism of data elements is revealed, which enriches and expands the theory of data elements and organizational agility, and provides enlightenment for ESG investment to drive the value creation of data elements.
Prognostic value of the ferroptosis-related gene SLC2A3 in gastric cancer and related immune mechanisms
Authors: Lin Liubing , Que Renye , Wang Jian , Zhu Yi , Liu Xiaolin , Xu Rongzhong
Published: July 2022

SLC2A3 is a ferroptosis marker engaged in transmembrane glucose transport. However, the effect of SLC2A3 on the prognosis of patients with cancer remains unclear. This study aimed to explore the prognostic implications of SLC2A3 and its underlying immune mechanisms in gastric cancer. The mRNA expression profiles and corresponding clinical data of patients with gastric cancer were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differentially expressed genes related to SLC2A3 were identified using the R package “limma.” Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, gene set enrichment analysis, and gene set variation analysis were used to explore the underlying mechanisms. The protein–protein and miRNA interaction networks were analyzed using Cytoscape software. Immune cell infiltration was assessed using single-sample gene set enrichment analysis. Univariate and multivariate Cox regression analyses revealed the relationship between SLC2A3 expression and prognosis. SLC2A3 was found to be highly expressed in tumor tissues and was associated with an unfavorable prognosis in patients with gastric cancer. Functional enrichment analysis showed that SLC2A3 is related to cytokine–cytokine receptor interaction, epithelial–mesenchymal transition, T cell receptor signaling pathway, B cell receptor signaling pathway, and immune checkpoints. SLC2A3 is also involved in immune response regulation and is regulated by multiple miRNAs, including miR-195-5p, miR-106a-5p, miR-424-5p, and miR-16-5p. Univariate and multivariate Cox regression analyses indicated that SLC2A3 can be used as an independent prognostic factor for predicting the outcome in patients with gastric cancer. SLC2A3 and related miRNAs are potential prognostic biomarkers and therapeutic targets.
Identification of circulating immune landscape in ischemic stroke based on bioinformatics methods
Authors: Li Danyang , Li Lifang , Quan Fei , Wang Tianfeng , Xu Si , Li Shuang , Tian Kuo , Feng Meng , He Ni , Tian Liting , Chen Biying , Zhang Huixue , Wang Lihua , Wang Jianjian
Published: July 2022

Ischemic stroke (IS) is a high-incidence disease that seriously threatens human life and health. Neuroinflammation and immune responses are key players in the pathophysiological processes of IS. However, the underlying immune mechanisms are not fully understood. In this study, we attempted to identify several immune biomarkers associated with IS. We first retrospectively collected validated human IS immune-related genes (IS-IRGs) as seed genes. Afterward, potential IS-IRGs were discovered by applying random walk with restart on the PPI network and the permutation test as a screening strategy. Doing so, the validated and potential sets of IS-IRGs were merged together as an IS-IRG catalog. Two microarray profiles were subsequently used to explore the expression patterns of the IS-IRG catalog, and only IS-IRGs that were differentially expressed between IS patients and controls in both profiles were retained for biomarker selection by the Random Forest rankings. CLEC4D and CD163 were finally identified as immune biomarkers of IS, and a classification model was constructed and verified based on the weights of two biomarkers obtained from the Neural Network algorithm. Furthermore, the CIBERSORT algorithm helped us determine the proportions of circulating immune cells. Correlation analyses between IS immune biomarkers and immune cell proportions demonstrated that CLEC4D was strongly correlated with the proportion of neutrophils (r = 0.72). These results may provide potential targets for further studies on immuno-neuroprotection therapies against reperfusion injury.
Identification of the Non-Alcoholic Fatty Liver Disease Molecular Subtypes Associated With Clinical and Immunological Features via Bioinformatics Methods
Authors: Liu Ziyu , Li Yufei , Yu Caihong
Published: July 2022

Background

Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver with varying severity. Heterogeneity in terms of molecules and immune cell infiltration drives NAFLD from one stage to the next. However, a precise molecular classification of NAFLD is still lacking, and the effects of complex clinical phenotypes on the efficacy of drugs are usually ignored.

Methods

We introduced multiple omics data to differentiate NAFLD subtypes via consensus clustering, and a weighted gene co-expression network analysis was used to identify eight co-expression modules. Further, eigengenes of eight modules were analyzed with regard to Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, the infiltration rates of 22 immune cell types were calculated with CIBERSORT and the ESTIMATE algorithm.

Results

In total, 111 NAFLD patients from three independent GEO datasets were divided into four molecular subtypes, and the corresponding clinical features and immune cell infiltration traits were determined. Based on high gene expression correlations, four molecular subtypes were further divided into eight co-expression modules. We also demonstrated a significant correlation between gene modules and clinical phenotypes. Moreover, we integrated phenotypic, immunologic, and genetic data to assess the potential for progression of different molecular subtypes. Furthermore, the efficacy of drugs against various NAFLD molecular subtypes was discussed to aid in individualized therapy.

Conclusion

Overall, this study could provide new insights into the underlying pathogenesis of and drug targets for NAFLD.
Transcriptome analysis revealed the roles of long non-coding RNA and mRNA in the bursa of Fabricius during pigeon (Columba livia) development
Authors: Wang Xun , Wu Jie , Hu Silu , Peng Qiyi , Yang Fuxing , Zhao Ling , Lin Yu , Tang Qianzi , Jin Long , Ma Jideng , Guo Hongrui , Tang Huaqiao , Jiang Anan , Li Xuewei , Li Mingzhou
Published: July 2022

The bursa of Fabricius (BF) is the critical humoral immune organ to birds, playing an essential role in B lymphocyte differentiation. However, unlike other poultries, surgical removal of pigeon BF did not limit humoral immune responsiveness. To investigate the expression profiles and the potential role of mRNA and long non-coding RNA (LncRNA) in squab BFs, transcriptome analysis was performed by RNA-Sequencing (RNA-Seq) over three developmental stages (1-day, 13 and 26 days old). We identified 13,072 mRNAs and 19,129 lncRNAs, of which 2,752 mRNAs and 1,515 lncRNAs were differential expressed (DE) in pigeon BFs over three developmental stages. Cluster analysis presented different expression patterns in DE mRNAs and lncRNAs. Functional enrichment analysis revealed that DE lncRNAs and mRNAs with distinct expression patterns might play crucial roles in the immune system process and tissue morphogenesis. In particular, some DE genes and lncRNAs with higher expression levels in 13D or 26D are related to lymphocyte activation and differentiation, adaptive immune response, positive regulation of immune response, leukocyte migration, etc. Protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) analysis sreened six significant modules containing 37 genes from immune-related DE gene cluster, which is closely linked in B cell activation, lymphocyte differentiation, B cell receptor signaling pathway, etc. Our study characterizes mRNA and lncRNA transcriptomic variability in pigeon BFs over different developmental stages and enhances understanding of the mechanisms underlying physiological functions of pigeon BF.
The yin–yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma
Authors: Yi Zhigang , Ma Tao , Liu Jia , Tie Wenting , Li Yanhong , Bai Jun , Li Lijuan , Zhang Liansheng
Published: July 2022

Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precursor states. In this process, the immune microenvironment interacts with the MM cells to exert yin and yang effects, promoting tumor progression on the one hand and inhibiting it on the other. Despite significant therapeutic advances, MM remains incurable, and the main reason for this may be related to the complex and variable immune microenvironment. Therefore, it is crucial to investigate the dynamic relationship between the immune microenvironment and tumors, to elucidate the molecular mechanisms of different factors in the microenvironment, and to develop novel therapeutic agents targeting the immune microenvironment of MM. In this paper, we review the latest research progress and describe the dual influences of the immune microenvironment on the development and progression of MM from the perspective of immune cells and molecules.
The effect of reparixin on survival in patients at high risk for in-hospital mortality: a meta-analysis of randomized trials
Authors: Landoni Giovanni , Zangrillo Alberto , Piersanti Gioia , Scquizzato Tommaso , Piemonti Lorenzo
Published: July 2022

Introduction

A great number of anti-inflammatory drugs have been suggested in the treatment of SARS-CoV-2 infection. Reparixin, a non-competitive allosteric inhibitor of the CXCL8 (IL-8) receptors C-X-C chemokine receptor type 1 (CXCR1) and C-X-C chemokine receptor type 2 (CXCR2), has already been tried out as a treatment in different critical settings. Due to the contrasting existing literature, we decided to perform the present meta-analysis of randomized controlled trials (RCTs) to investigate the effect of the use of reparixin on survival in patients at high risk for in-hospital mortality.

Methods

We created a search strategy to include any human RCTs performed with reparixin utilization in patients at high risk for in-hospital mortality, excluding oncological patients. Two trained, independent authors searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for appropriate studies. Furthermore, references of review articles and included RCTs were screened to identify more studies. No language restrictions were enforced. To assess the risk of bias of included trials, the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) was used.

Results

Overall, six studies were included and involved 406 patients (220 received reparixin and 186 received the comparator). The all-cause mortality in the reparixin group was significantly lower than that in the control group [5/220 (2.3%) in the reparixin group vs. 12/186 (6.5%) in the control group, odds ratio = 0.33 (95% confidence interval 0.12 to 0.96), p-value for effect 0.04, p for heterogeneity 0.20, I2 = 36%]. In addition, no difference in the rate of pneumonia, sepsis, or non-serious infections was shown between the two groups.

Conclusion

Our meta-analysis of randomized trials suggests that short-term inhibition of CXCL8 activity improved survival in patients at high risk for in-hospital mortality without increasing the risk of infection.

Meta-analysis registration

PROSPERO, identifier CRD42021254467.
The Correlation Between MicroRNAs and Diabetic Retinopathy
Authors: Zhao Xin , Ling Feng , Zhang Guang wei , Yu Na , Yang Jing , Xin Xiang yang
Published: July 2022

Micro ribonucleic acids (miRNAs), as a category of post-transcriptional gene inhibitors, have a wide range of biological functions, are involved in many pathological processes, and are attractive therapeutic targets. Considerable evidence in ophthalmology indicates that miRNAs play an important role in diabetic retinopathy (DR), especially in inflammation, oxidative stress, and neurodegeneration. Targeting specific miRNAs for the treatment of DR has attracted much attention. This is a review focusing on the pathophysiological roles of miRNAs in DR, diabetic macular edema, and proliferative DR complex multifactorial retinal diseases, with particular emphasis on how miRNAs regulate complex molecular pathways and underlying pathomechanisms. Moreover, the future development potential and application limitations of therapy that targets specific miRNAs for DR are discussed.
Advances in understanding interferon-mediated immune responses to enteric viruses in intestinal organoids
Authors: Nolan Lila S. , Baldridge Megan T.
Published: July 2022

Interferons (IFN) are antiviral cytokines with critical roles in regulating pathogens at epithelial barriers, but their capacity to restrict human enteric viruses has been incompletely characterized in part due to challenges in cultivating some viruses in vitro, particularly human norovirus. Accordingly, advancements in the development of antiviral therapies and vaccine strategies for enteric viral infections have been similarly constrained. Currently emerging is the use of human intestinal enteroids (HIEs) to investigate mechanisms of human enteric viral pathogenesis. HIEs provide a unique opportunity to investigate host-virus interactions using an in vitro system that recapitulates the cellular complexity of the in vivo gastrointestinal epithelium. This approach permits the exploration of intestinal epithelial cell interactions with enteric viruses as well as the innate immune responses mediated by IFNs and IFN-stimulated genes. Here, we describe recent findings related to the production, signaling, and function of IFNs in the response to enteric viral infections, which will ultimately help to reveal important aspects of pathogenesis and facilitate the future development of therapeutics and vaccines.
Development of mouse model for oral allergy syndrome to identify IgE cross-reactive pollen and food allergens: ragweed pollen cross-reacts with fennel and black pepper
Authors: Kamei Anna , Izawa Kumi , Ando Tomoaki , Kaitani Ayako , Yamamoto Risa , Maehara Akie , Ide Takuma , Yamada Hiromichi , Kojima Mayuki , Wang Hexing , Tokushige Koji , Nakano Nobuhiro , Shimizu Toshiaki , Ogawa Hideoki , Okumura Ko , Kitaura Jiro
Published: July 2022

Oral allergy syndrome (OAS) is an IgE-mediated immediate food allergy that is localized to the oral mucosa. Pollen food allergy syndrome (PFAS), a pollinosis-associated OAS, is caused by cross-reactivity between food and pollen allergens. However, we need to more precisely understand the underlying pathogenesis of OAS/PFAS. In the present study, we developed a method to comprehensively identify cross-reactive allergens by using murine model of OAS and protein microarray technology. We focused on lip angioedema, which is one of the most common symptoms of OAS, and confirmed that mast cells reside in the tissues inside the lower lip of the mice. Interestingly, when the food allergen ovalbumin (OVA) was injected inside the lower lip of mice with high levels of OVA-specific IgE followed by an intravenous injection of the Evans blue dye, we found immediate dye extravasation in the skin of the neck in a mast cell-dependent manner. In addition, the degree of mast cell degranulation in the oral cavity, reflecting the severity of oral allergic responses, can be estimated by measuring the amount of extravasated dye in the skin. Therefore, we used this model of OAS to examine IgE cross-reactive allergens in vivo. Protein microarray analysis showed that serum IgE from mice intraperitoneally sensitized with ragweed pollen, one of the major pollens causing pollinosis, bound highly to protein extracts from several edible plants including black peppercorn and fennel. We confirmed that the levels of black pepper-specific IgE and fennel-specific IgE were significantly higher in the serum from ragweed pollen-sensitized mice than in the serum from non-sensitized control mice. Importantly, analysis of murine model of OAS showed that the injection of black pepper or fennel extract induced apparent oral allergic responses in ragweed pollen-sensitized mice. These results indicate IgE cross-reactivity of ragweed pollen with black pepper and fennel. In conclusion, we developed mouse model of OAS to identify IgE cross-reactive pollen and food allergens, which will help understand the pathogenesis of OAS/PFAS.
Role of human metapneumovirus glycoprotein G in modulation of immune responses
Authors: Velayutham Thangam Sudha , Ivanciuc Teodora , Garofalo Roberto P. , Casola Antonella
Published: July 2022

Human metapneumovirus (hMPV) is an important pathogen responsible for acute respiratory tract infections in children, the elderly, and immunocompromised patients, with no effective treatment or vaccine currently available. Knowledge of virus- and host-specific mechanisms contributing to the pathogenesis of hMPV infection is still limited. Studies have shown that hMPV surface glycoprotein G is an important virulence factor, by inhibiting innate immune signaling in airway epithelial cells and immune cells. In this study, we investigated the role of G protein in modulating innate and adaptive immune responses in mice infected with a recombinant virus with deletion of G protein (rhMPV-ΔG). Results show that rhMPV-ΔG was strongly attenuated, as it did not induce significant clinical disease, airway obstruction and airway hyperresponsiveness (AHR), compared to infection with a control strain (rhMPV-WT). By analysis of cells in bronchoalveolar fluid and lung tissue, as well as cytokine production, we found that G protein mediates aspects of both innate and adaptive immune responses, including neutrophils, dendritic cells, natural killer cells and B cells. Lung T cells recruited in response to rhMPV-ΔG had a significantly higher activated phenotype compared to those present after rhMPV-WT infection. Despite highly attenuation characterized by low levels of replication in the lung, rhMPV-ΔG was able to induce neutralizing antibodies and to protect mice from a secondary hMPV challenge. However, challenged mice that had received rhMPV-ΔG as primary infection showed some signs of lung disease at the earliest time points, which were less evident in mice that had received the rhMPV-WT strain as primary infection. These results demonstrate some of the mechanisms by which G protein could contribute to airway disease and modulate immune response to hMPV infection.