bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Green Financing and Eco-Innovation for Energy Efficiency in Developed Countries: Contextual Evidence for Pre- and Post-COVID-19 Era
Authors: Wu Hong , Fareed Zeeshan , Wolanin Elżbieta , Rozkrut Dominik , Hajduk-Stelmachowicz Marzena
Published: August 2022

Following the environmental concerns such as global warming, climate change, and environmental degradation, scholars and policymakers discovered energy utilization as the key factor in these issues. Therefore, economies are paying more attention to green finance and eco-innovation to reduce energy usage and enhance energy efficiency. The prime objective of this study is to explore whether the mentioned variables exhibit any influence on the energy efficiency target achievement. In this sense, the current study explores the association of green finance and eco-innovation with energy intensity in the group of seven economies from 1990 to 2020. By using panel data approaches, this study employs diagnostic tests that confirm the heterogeneous slopes and the existence of panel cross-section dependence. Also, the cointegration tests validate the existence of a long-run equilibrium relationship between the variables. Based on the asymmetric distribution of the data, this study employs the method of moments quantile regression. The empirical results reveal that green finance and eco-innovation significantly reduce energy intensity across the selected quantiles. Control variables such as urban growth and trade openness also adversely affect energy intensity. However, economic growth is the only significant factor that enhances energy intensity. The results are robust as validated by the panel quantile regression and the Granger panel heterogenous causality test. Based on the findings, this study recommends that green finance be promoted and environmental-related technology innovation be encouraged to achieve the goal of energy efficiency in developed economies. This study also provides additional policies appropriate for environmental recovery.
Thermodynamic analysis of CO2 blends for vehicle heat pump at cold ambient temperature
Authors: Li Chengyu , Liu Zhaoqiang , Sun Binbin , Wang Youtang , Gao Song , Zhang Tiantian , Wang Baolong
Published: August 2022

The use of heat pump is a promising way of energy conservation to improve the driving range of electric vehicles. In this study, the thermodynamic characteristics of CO2–based blends in the operation of a subcritical heat pump cycle are evaluated at different ambient temperatures considering two operation modes. Coefficient of performance (COP) and volumetric heating capacity (VHC) are used to evaluate heat pump performance. Optimization and comparison of both transcritical and subcritical cycles are conducted using various refrigerants. The results indicated that CO2/R32 (50/50) always outputs higher COP than CO2 or other mixtures. The COP of CO2/R41 (90/10) is inferior to that of CO2 in a transcritical cycle due to the more power consumption of compressor. The blends of R1234yf and R152a with low GWP have lower COP, but a much lower operation pressure is also achieved. CO2 blends have larger VHC, which facilitates simple cycle configuration and compact compression.
Robust optimization of the active distribution network involving risk assessment
Authors: Zhang Yumin , Yang Zizhen , Ji Xingquan , Zhang Xuan , Yu Zihan , Wu Fucheng
Published: August 2022

Inherent dynamic constraints of distributed generations (DGs) and the correlation between injected variables bring great challenges to distribution network operation. In order to improve the degree of coupling and interconnection coordination between different energy devices, improve the ability of the distribution network to cope with the uncertainty of DGs, achieve low-carbon operation, and improve the environmental friendliness of distribution network operation, this article proposes a robust optimization approach involving risk assessment. The semi-invariant method and scene clustering are used to deal with the uncertainty of DGs and load, thus formulating a robust optimization model for distribution network distribution based on risk indices. To address the time-varying constraints of energy storage systems (ESSs) and gas turbines, a two-stage box-based decomposition model is established. Dynamic constraints are included in the first stage to constrain the operating state and operating domain of the unit and ESSs. In the second stage, the multi-timescale optimization problem is transformed into multiple single-timescale optimization problems, which are solved by the column and constraint generation (C&CG) algorithm to improve the solution efficiency. The feasibility of the comprehensive optimization model based on dynamic reconfiguration and distributed robust optimization (DRO) is demonstrated with the PG&E 69 bus system.
Research on the cultivation of green competitiveness among chinese heavily polluting enterprises under country/district environmental regulations
Authors: Zhang Tongjian , Zho Jian-ya , Hussain Rana Yassir , Wang Min , Ren Kai
Published: August 2022

The development of the world economy has caused serious environmental pollution, which has resulted in an ecological crisis. With the acceleration of economic development, China’s ecological crisis is becoming more serious. Green technology innovation is an important driving force in realizing green economic development, and heavily polluting enterprises are the key link to cultivating green technology innovation. The Porter hypothesis holds that environmental regulation has a promoting effect on enterprises’ green technology innovation, but this is not reflected in the context of China. As a basic administrative unit, the implementation of environmental regulations in counties and districts determines the effectiveness of environmental policies. Utilizing structural equation modeling, this study analyzes the cultivation of the green technology innovation ability of heavily polluting enterprises under environmental regulations. The results show that command-based environmental regulation can effectively promote enterprises’ green technology innovation ability. Incentive-based environmental regulation needs to be strengthened to drive the development of enterprises’ “three wastes” treatment innovation ability. Voluntary environmental regulation does not effectively promote green process innovation and “three wastes” treatment innovation. In addition, enterprises’ current “three wastes” treatment innovation capacity is not enough to promote the improvement of enterprises’ green competitiveness. The results of this article show that environmental regulation is conducive to the green innovation ability of enterprises, and this promotion effect needs to be further strengthened. Moreover, the highlighted research limitations will contribute to the subsequent research work.
The Influence of Foreign Direct Investment and Tourism on Carbon Emission in China
Authors: Wang Hong , Xu Dinghong , Mufarreh Elqahtani Zainab , Juan Zhang , Ahmad Muneeb , Ali Asad , Khan Yousaf Ali , Saghir Amir
Published: August 2022

The aim of this research is to examine the potential influence of FDI inflows and tourism industry on carbon dioxide emissions in China using System GMM models for a sample period of 1980–2019. Using FMOLS and DOLS models, this research examines the long-term relationship between the variables, as well as the long-term association among components. Co-joining the boards of FMOLS and DOLS models shows a general correlation between the investigation elements and CO2 emissions in China. FDI, tourism sector, and environment-friendly electricity use have all been major contributors to rising CO2 emissions in China for a long time. Using System GMM, FMOLS, and DOLS models in China, we examined the influence of the travel sector on carbon dioxide emissions as well as environment-friendly electricity usage and foreign direct investment. The government of China is being pushed to attract more foreign direct investment in order to improve the system and expand the transportation industry. As a reasonable responsibility to an unnatural climate change, methods for developing the movement business and theories relating to the movement business should be adopted.
A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations
Authors: Zou Xue-Lun , Yao Tian-Xing , Deng Lu , Chen Lei , Li Ye , Zhang Le
Published: August 2022

Background: The relationship between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphism with the risk of intracerebral hemorrhage (ICH) has remained to be controversial in recent years. This meta-analysis is aimed to confirm the association of these.

Methods: Systematically searching the related studies from the PubMed, Embase, Cochrane Library, China national knowledge internet database from 1 January 1990 to 1 June 2022. The odd ratio (ORs) and 95% confidence interval (CIs) of gene-disease correlation in various gene models were calculated by fixed or random effect model of meta-analysis. We included 20 case-control studies in this meta-analysis with a total of 1,989 ICH patients and 4,032 health controls originated from Asian, Caucasian, and African populations.

Results: The statistical analysis demonstrated the association of MTHFR C677T gene polymorphism with ICH in allele model [ORT VS. C = 1.20 (95%CI: 1.06–1.36)]; homozygote model [OR TT VS. CC = 1.50 (95%CI: 1.20–1.88)]; dominant model [OR CT+ TT VS. CC = 1.23 (95%CI: 1.03–1.48)] and recessive model [ORTT VS. CT+CC = 1.37 (95%CI: 1.17–1.60)]. Besides, we also found the relationship of MTHFR C677T gene polymorphism with Asian in four comparison model (ORT VS. C = 1.19.95%CI:1.09–1.37, ORTT VS. CC = 1.46.95%CI: 1.15–1.85, OR CT+ TT VS. CC = 1.25.95%CI: 1.01–1.54, ORTT VS. CT+CC = 1.34.95%CI: 1.54–1.17) and Caucasian in four comparison model (ORT VS. C = 1.90.95%CI: 1.22–2.97, ORTT VS. CC = 2.67.95%CI: 1.42–5.00, OR CT+ TT VS. CC = 1.56.95%CI: 1.05–2.32, ORTT VS. CT+CC = 2.25.95%CI: 1.46–4.00). But no statistically significant correlation between A1298C polymorphism and the occurrence of ICH was detected in four studies.

Conclusion: MTHFR C677T gene polymorphism increases the risk of ICH in Asian and Caucasian populations but has no impact on the incidence in African communities. More importantly, the risk of ICH increases in TT genotype individuals in comparison to CT and CC genotype individuals in Asian and Caucasian populations.
Hearing impairment in murine model of Down syndrome
Authors: Chen Guang-Di , Li Li , McCall Andrew , Ding Dalian , Xing Zhuo , Yu Y. Eugene , Salvi Richard
Published: August 2022

Hearing impairment is a cardinal feature of Down syndrome (DS), but its clinical manifestations have been attributed to multiple factors. Murine models could provide mechanistic insights on various causes of hearing loss in DS. To investigate mechanisms of hearing loss in DS in the absence of the cadherin 23 mutation, we backcrossed our DS mice, Dp(16)1Yey, onto normal-hearing CBA/J mice and evaluated their auditory function. Body weights of wild type (WT) and DS mice were similar at 3-months of age, but at 9-months, WT weighed 30% more than DS mice. Distortion product otoacoustic emissions (DPOAE), a test of sensory outer hair cell (OHC) function negatively impacted by conductive hearing loss, were reduced in amplitude and sensitivity across all frequencies in DS mice. The middle ear space in DS mice appeared normal with no evidence of infection. MicroCT structural imaging of DS temporal bones revealed a smaller tympanic membrane diameter, oval window, and middle ear space and localized thickening of the bony otic capsule, but no gross abnormalities of the middle ear ossicles. Histological analysis of the cochlear and vestibular sensory epithelium revealed a normal density of cochlear and vestibular hair cells; however, the cochlear basal membrane was approximately 0.6 mm shorter in DS than WT mice so that the total number of hair cells was greater in WT than DS mice. In DS mice, the early and late peaks in the auditory brainstem response (ABR), reflecting neural responses from the cochlear auditory nerve followed by subsequent neural centers in the brainstem, were reduced in amplitude and ABR thresholds were elevated to a similar degree across all frequencies, consistent with a conductive hearing impairment. The latency of the peaks in the ABR waveform were longer in DS than WT mice when compared at the same intensity; however, the latency delays disappeared when the data were compared at the same intensity above thresholds to compensate for the conductive hearing loss. Future studies using wideband tympanometry and absorbance together with detailed histological analysis of the middle ear could illuminate the nature of the conductive hearing impairment in DS mice.
Cuproptosis and cuproptosis–related genes in rheumatoid arthritis: Implication, prospects, and perspectives
Authors: Zhao Jianan , Guo Shicheng , Schrodi Steven J. , He Dongyi
Published: August 2022

Rheumatoid arthritis (RA) is an autoimmune disease that severely affects patients’ physical and mental health, leading to chronic synovitis and destruction of bone joints. Although various available clinical treatment options exist, patients respond with varying efficacies due to multiple factors, and there is an urgent need to discover new treatment options to improve clinical outcomes. Cuproptosis is a newly characterized form of cell death. Copper causes cuproptosis by binding to lipid-acylated components of the tricarboxylic acid cycle, leading to protein aggregation, loss of iron-sulfur cluster proteins, and eventually proteotoxic stress. Targeting copper cytotoxicity and cuproptosis are considered potential options for treating oncological diseases. The synovial hypoxic environment and the presence of excessive glycolysis in multiple cells appear to act as inhibitors of cuproptosis, which can lead to excessive survival and proliferation of multiple immune cells, such as fibroblast-like synoviocytes, effector T cells, and macrophages, further mediating inflammation and bone destruction in RA. Therefore, in this study, we attempted to elaborate and summarize the linkage of cuproptosis and key genes regulating cuproptosis to the pathological mechanisms of RA and their effects on a variety of immune cells. This study aimed to provide a theoretical basis and support for translating preclinical and experimental results of RA to clinical protocols.
Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy
Authors: Fan Peng , Qiang Huiping , Liu Zhenhua , Zhao Qi , Wang Ying , Liu Tingkun , Wang Xuan , Chu Tianqing , Huang Yuhui , Xu Wei , Qin Songbing
Published: August 2022

Anlotinib is a new multitarget tyrosine kinase inhibitor for tumor angiogenesis, and its monotherapy exhibits a decent clinical efficacy. However, the process of combining Anlotinib and immune checkpoint therapy to achieve optimal antitumor effects while limiting side effects remains unclear. In this study, we found that effective low-dose Anlotinib was sufficient to inhibit tumor growth while reducing side effects compared with high doses. Effective low-dose Anlotinib treatments induced durable tumor vascular normalization and improved anti-PD-1 therapy in both short- and long-term treatment regimens. Mechanistically, the combination therapy increased the proportions of intratumoral CD4+ T, CD8+ T, and NK cells. Anlotinib-associated antitumor effects were independent of interferon γ; however, the combination therapy required CD8+ T cells to suppress tumor growth. Together, these results suggest that the combination of effective low-dose Anlotinib and PD-1 blockade induces durable antitumor effects with fewer side effects. Our findings indicate that antiangiogenic treatments combined with immune checkpoint therapy at an effective low-dose, rather than a tolerable high dose, would be more efficacious and safer.
Overcoming tumor resistance mechanisms in CAR-NK cell therapy
Authors: Valeri Antonio , García-Ortiz Almudena , Castellano Eva , Córdoba Laura , Maroto-Martín Elena , Encinas Jessica , Leivas Alejandra , Río Paula , Martínez-López Joaquín
Published: August 2022

Despite the impressive results of autologous CAR-T cell therapy in refractory B lymphoproliferative diseases, CAR-NK immunotherapy emerges as a safer, faster, and cost-effective approach with no signs of severe toxicities as described for CAR-T cells. Permanently scrutinized for its efficacy, recent promising data in CAR-NK clinical trials point out the achievement of deep, high-quality responses, thus confirming its potential clinical use. Although CAR-NK cell therapy is not significantly affected by the loss or downregulation of its CAR tumor target, as in the case of CAR-T cell, a plethora of common additional tumor intrinsic or extrinsic mechanisms that could also disable NK cell function have been described. Therefore, considering lessons learned from CAR-T cell therapy, the emergence of CAR-NK cell therapy resistance can also be envisioned. In this review we highlight the processes that could be involved in its development, focusing on cytokine addiction and potential fratricide during manufacturing, poor tumor trafficking, exhaustion within the tumor microenvironment (TME), and NK cell short in vivo persistence on account of the limited expansion, replicative senescence, and rejection by patient’s immune system after lymphodepletion recovery. Finally, we outline new actively explored alternatives to overcome these resistance mechanisms, with a special emphasis on CRISPR/Cas9 mediated genetic engineering approaches, a promising platform to optimize CAR-NK cell function to eradicate refractory cancers.
C1q as a target molecule to treat human disease: What do mouse studies teach us?
Authors: Schulz Kristina , Trendelenburg Marten
Published: August 2022

The complement system is a field of growing interest for pharmacological intervention. Complement protein C1q, the pattern recognition molecule at the start of the classical pathway of the complement cascade, is a versatile molecule with additional non-canonical actions affecting numerous cellular processes. Based on observations made in patients with hereditary C1q deficiency, C1q is protective against systemic autoimmunity and bacterial infections. Accordingly, C1q deficient mice reproduce this phenotype with susceptibility to autoimmunity and infections. At the same time, beneficial effects of C1q deficiency on disease entities such as neurodegenerative diseases have also been described in murine disease models. This systematic review provides an overview of all currently available literature on the C1q knockout mouse in disease models to identify potential target diseases for treatment strategies focusing on C1q, and discusses potential side-effects when depleting and/or inhibiting C1q.
Deciphering the Trophic Ecology of Three Marlin Species Using Stable Isotope Analysis in Temperate Waters Off Southeastern Australia
Authors: Guillemin Tristan A. , Pepperell Julian G. , Gaston Troy , Williamson Jane E.
Published: August 2022

Understanding the unique feeding behaviours of oceanic fish, such as marlin, is key to their effective management. Marlin are notoriously difficult to study, however, and the limited research on marlin feeding shows that diet can vary greatly between species and geographic regions. One region where marlin feeding behaviours are particularly poorly understood are temperate eastern Australian waters. This study collected marlin tissue from game fishing tournaments between latitudes 32°43′06.5″S/152°08′50.1″E to 34°40′12.9″S/150°51′34.3″E between 2010 and 2021, and used stable isotope analysis (SIA) to assess the trophic ecology of the three species of marlin occurring in the region: black (Istiompax indica), blue (Makaira nigricans), and striped (Kajikia audax) marlin. All species had similar δ13C values, but δ15N differed between species, with higher variability observed in blue marlin than in the other two species. Sulphur isotopes were key in identifying the relative contribution of coastal or benthic influences on marlin diet, with δ34S suggesting that blue marlin had less coastal/benthic dietary influence than black or striped marlin. Incorporation of δ34S into SIA for marlin is thus recommended for future studies. Some differences in isotope values across locations and dates were found, however, the uneven sample sizes due to the opportunistic sampling limited the ability to understand spatial or seasonal differences. These findings show that marlin followed similar dietary trends to conspecifics in other regions despite temperate eastern Australian waters being one of the few with three marlin species commonly co-occuring. This suggests that interspecies resource competition is not a major force driving the demography of these species in eastern Australian waters. This research highlights a need for specific management strategies at a species level, particularly for blue marlin. Future research incorporating prey isoscapes and baselines assessed over a wider range of marlin sizes is suggested to further improve our knowledge and capacity to manage the marlin of eastern Australian waters.
Beluga (Delphinapterus leucas) response to personal watercraft and motorized whale watching vessels in the Churchill River estuary
Authors: Ausen Emma L. , Marcoux Marianne , Chan Wayne S. , Barber David G.
Published: August 2022

As interest in tourism and conservation grows worldwide, whale-watching has become a popular means of educating the public about wildlife conservation. The short-term impact of ecotourism industries on observed species has been widely studied with findings that indicate responses are most often behavior alterations or avoidance. Close vessel interactions with beluga whales (Delphinapterus leucas) are a major draw for whale-watching ecotourism in Churchill, Manitoba, Canada. As the Churchill River estuary and surrounding waters are assessed for a Marine Protected Area, information on the response of belugas to vessels are needed to inform management. To assess this, an oblique time-lapse camera system with a 5-minute photo interval was set up overlooking a section of the Churchill River estuary that is shared by belugas and tourist vessels. Measurements calculated from photos were used to compare the distance between belugas and kayaks, paddleboards, motorboats, and Zodiac whale-watching vessels. These distances were compared to an expected distribution generated from locations of belugas in photos without the presence of vessels. We found evidence that belugas are attracted to kayaks, avoid paddleboards, and are neutral regarding motorboats and Zodiacs. This is the first study to quantify the behavioral response of cetaceans to tourist vessels using a camera system and a distance-based analysis. Results could inform the development of a site-specific management system that accounts for beluga-vessel relationships.
The mechanism of maintaining intracellular homeostasis in the red alga Pyropia haitanensis under hyposaline stress
Authors: Wen Jian , Xu Kai , Ji Dehua , Xu Yan , Chen Changsheng , Wang Wenlei , Xie Chaotian
Published: August 2022

The cultivation of hyposaline-tolerant varieties of the red alga Pyropia haitanensis is not only conducive to expanding the area of intertidal seaweed cultivation, but also contributes to preventing eutrophication of coastal waters. Research on the mechanism of hyposaline tolerance of P. haitanensis is an important prerequisite for breeding hyposaline-tolerant varieties. Here, we used proteomics and targeted metabolomics technologies to identify the key proteins and metabolites in thalli of P. haitanensis that changed under two hyposaline stress treatments: 0‰, LSS 0; 5‰, LSS 5. Responses of thalli of P. haitanensis to hyposaline stress included to inhibit protein synthesis, recruit molecular chaperones, and enhance the removal of misfolded proteins to maintain the dynamic balance of protein folding and removal; the response was similar under hypersaline stress. Glycolysis was the main energy supply pathway, and thalli actively maintained the stability of the cell membrane under hyposaline stress, which was distinct from the response to hypersaline stress. Compared with the LSS 0 treatment, P. haitanensis exhibited a more adequate energy supply, more stable endoplasmic reticulum environment and more intact membrane system under the LSS 5 treatment. The results improve understanding of the hyposaline tolerance mechanism of intertidal seaweed and provide a theoretical basis for the development of hyposaline-tolerant varieties.
Mussels and canopy-forming algae as ecosystem engineers: their contribution to community organization in the rocky sublittoral
Authors: Westerbom Mats , Koivisto Maria
Published: August 2022

Understanding the influence of biogenic habitats on species assemblage structure and ecosystem productivity is crucial for successful conservation of natural systems. Brown algae, Fucus vesiculosus, and blue mussels, Mytilus trossulus, coexist on sheltered and moderately wave exposed shallow rocky reefs of the northern Baltic Proper. Here, they function as important biogenic structures for an abundant associated macroinvertebrate fauna. Despite their dominance and space sympatry, there is little understanding of how they differ in their role as provisioners of biodiversity in this system. While Fucus has been recognized as an important habitat provider for decades, the similar role of blue mussels has been seriously understudied in the northern Baltic Proper, leading to pressing knowledge gaps and an underestimation of their role for overall biodiversity. In this study, we compared macroinvertebrate species assemblages within 40 rocky reefs where Fucus and Mytilus co-occur in either intermixed or adjacent assemblages. We show that both habitats represent a species rich and abundant community that are comparable regarding diversity. However, abundance and biomass of the associated community is much higher in the Mytilus habitat in relation to the Fucus habitat, implying a far higher secondary production in the former habitat. Recognizing key habitats and understanding how they differ in their ability to support biodiversity and ecosystem productivity is necessary for predicting community responses to human pressures, including an altered climate, and for implementing efficient mitigation actions to minimize loss of biodiversity.
Consistent condom use and its associated factors among human immunodeficiency virus-positive pregnant women in Ethiopia
Authors: Tibebu Nebiyu Solomon , Kassie Belayneh Ayanaw , Kebede Azmeraw Ambachew , Anteneh Tazeb Alemu , Temesgan Wubedle Zelalem , Aklil Mastewal Belayneh , Wondie Kindu Yinges , Abegaz Marta Yimam , Ayalew Hiwotie Getaneh , Rade Bayew Kelkay
Published: August 2022

Background

Consistent condom use plays a significant role in the successful protection of the transmission of human immunodeficiency virus (HIV) infection in couples with sero-discordant HIV status, mother-to-child-transmission (MTCT), and acquiring other strains in HIV-positive concordant pairs. Limited data and information about this issue are available in low-resource setting countries, including the study setting. Therefore, this study aimed to assess the level of consistent condom use and its associated factors among HIV-positive pregnant women.

Materials and methods

An institution-based cross-sectional study was done from 17 October 2020 to 1 March 2021. A total of 423 HIV-positive pregnant women were involved in this study and selected using a systematic random sampling technique. Data were collected using a semi-structured, pretested, and interviewer-administered questionnaire and then entered into EPI INFO version 7 and analyzed using Statistical Package for Social Sciences (SPSS) version 21. Logistic regressions were performed to identify factors. P-Value ≤ 0.05 denotes statistical significance.

Results

The prevalence of consistent condom use among HIV-positive pregnant women was 14.2% [95% confidence interval (CI) 10.9%, 17.5%]. Women having a higher educational status [adjusted odds ratio (AOR) = 6.33, 95% CI 1.96, 20.42], women having a CD4 count > 600 cells/mm (AOR = 4.78, 95% CI 2.08, 10.97), women testing positive for HIV during the non-pregnant state (AOR = 5.99, 95% CI 3.01, 11.94), and women disclosing their HIV status to sexual partners (AOR = 4.85, 95% CI 1.71, 13.71) were found to be statically significant with women’s consistent condom use.

Conclusion

In this study, consistent condom use among HIV-positive pregnant women was low. Women having educational status of college and above studies, women testing positive for HIV during the non-pregnant state, women disclosing their HIV status to a sexual partner, and women having a CD4 count > 600 cells/mm had better consistent condom use. Hence, giving more emphasis on health education and counseling service about HIV testing before pregnancy, and disclosing their HIV status to their sexual partners and about the need for consistent condom use during pregnancy would be important.
Immunomodulatory therapies for COVID-19
Authors: Mathur Poonam , Kottilil Shyamasundaran
Published: August 2022

Purpose

As COVID-19 disease progresses, the host inflammatory response contributes to hypoxemia and severe and critical illness. In these latter stages of disease, patients may benefit from immunomodulatory therapies to control the aberrant host inflammatory response. In this review, we provide an overview of these therapies and provide summaries of the studies that led to issuance of FDA Emergency Use Authorization or recommendation by the Infectious Diseases Society of America (IDSA).

Materials and methods

We reviewed English-language studies, Emergency Use Authorizations (EUAs), and guidelines from March 2020 to present.

Conclusion and relevance

There are several therapies with proposed benefit in severe and critical COVID-19 disease. Few have been issued FDA EUA or recommendation by the Infectious Diseases Society of America (IDSA). Physicians should be familiar with the evidence supporting use of these therapies and the patient populations most likely to benefit from each.
The global status of research in prostate cancer bone metastasis: A bibliometric and visualized analysis
Authors: Lv Zongwei , Wang Xia , Zhu Chunming , Wang Kefeng
Published: August 2022

Background

Prostate cancer (PCa) is a serious threat to the health of elderly aged groups. It is very important to understand the occurrence and development of PCa for early diagnosis, treatment and metastasis control. This study aims to elucidate the international frontier research direction and literature distribution through bibliometric and visual analyses of PCa bone metastasis.

Methods

Data were obtained from the Web of Science core collection database, which collected 2,246 papers related to PCa bone metastasis from 1 January 2012 to 31 December 2021. The collected data were analyzed using the VOSviewer software for citation, co-authorship, co-citation, bibliometric coupling, and co-occurrence.

Results

Over the past decade, published papers have increased annually. The United States of America has published 890 papers with 29,161 citations, far more than any other country, and it has the most extensive collaboration with other countries. For example, 33 articles by Saad Fred were cited 2,721 times, and 91 articles from the University of Texas MD Anderson CANC CTR were cited 3,037 times, the most cited author and organization. Peng Xinsheng and Duke UNIV comprise the most active collaborative author and organization, respectively. The most co-cited journal was CANCER RES, with 3,195 citations. Studies of PCa bone metastasis can be divided into four categories: “basic research,” “auxiliary diagnosis and treatment,” “clinical trial,” and “prognosis.”

Conclusion

Our results provide a comprehensive overview of the research priorities and future directions of PCa bone metastasis, which can further accurately guide researchers in diagnosis, treatment, and personalized prevention.
Association between serum ferritin level and the various stages of non-alcoholic fatty liver disease: A systematic review
Authors: Wang Huanqiu , Sun Ruyu , Yang Sisi , Ma Xueqing , Yu Chengbo
Published: August 2022

Introduction

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder across the world, and non-invasive evaluation approaches are in need to assess NAFLD disease progression. Serum ferritin has been proposed as one of the biomarkers for NAFLD diagnosis in previous studies. This systematic review aims to identify, report, and synthesize studies that investigated the association of serum ferritin level with the various stages of NAFLD among the adult population.

Methods

Three databases – MEDLINE, EMBASE, and Scopus – were systematically searched to obtain potentially relevant publications before July 2022. No restrictions were applied to geographical region, study design, publication type and language. The association between serum ferritin level or different ferritin categories and the various stages of NAFLD was the primary outcome of interest. Title and abstract screenings, data extraction and coding, and quality assessment were independently completed by two authors with discrepancies resolved through discussion with a third author.

Results

Thirty-two studies were included and heterogeneity was considerable. The associations between serum ferritin level and the stages of hepatic steatosis, fibrosis, inflammation and ballooning and the occurrence of non-alcoholic steatohepatitis (NASH) were investigated but inconsistent associations were reported. Most studies identified serum ferritin to be a predictor of advanced NAFLD, while several revealed the opposite end.

Conclusions

Serum ferritin could be considered to act as a non-invasive biomarker for assessing various stages of NAFLD. Nevertheless, further studies are still in need to confirm its predictive value since this study reported inconsistent associations based on the qualitative synthesis.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021275630.
Lymphocyte trajectories are associated with prognosis in critically ill patients: A convenient way to monitor immune status
Authors: Pei Fei , Song Wenliang , Wang Luhao , Liang Liqun , Gu Bin , Chen Minying , Nie Yao , Liu Yishan , Zhou Yu , Guan Xiangdong , Wu Jianfeng
Published: August 2022

Background

Immunosuppression is a risk factor for poor prognosis of critically ill patients, but current monitoring of the immune status in clinical practice is still inadequate. Absolute lymphocyte count (ALC) is not only a convenient biomarker for immune status monitoring but is also suitable for clinical application. In this study, we aimed to explore different trajectories of ALC, and evaluate their relationship with prognosis in critically ill patients.

Methods

We retrospectively enrolled 10,619 critically ill patients admitted to a general intensive care unit (ICU) with 56 beds from February 2016 to May 2020. Dynamic ALC was defined as continuous ALC from before ICU admission to 5 days after ICU admission. Initial ALC was defined as the minimum ALC within 48 h after ICU admission. Group-based trajectory modeling (GBTM) was used to group critically ill patients according to dynamic ALC. Multivariate cox regression model was used to determine the independent association of trajectory endotypes with death and persistent inflammation, immunosuppression, catabolism syndrome (PICS).

Results

A total of 2022 critically ill patients were unsupervisedly divided into four endotypes based on dynamic ALC, including persistent lymphopenia endotype (n = 1,211; 58.5%), slowly rising endotype (n = 443; 22.6%), rapidly decreasing endotype (n = 281; 14.5%) and normal fluctuation endotype (n = 87; 4.4%). Among the four trajectory endotypes, the persistent lymphopenia endotype had the highest incidence of PICS (24.9%), hospital mortality (14.5%) and 28-day mortality (10.8%). In multivariate cox regression model, persistent lymphopenia was associated with increased risk of 28-day mortality (HR: 1.54; 95% CI: 1.06–2.23), hospital mortality (HR: 1.66; 95% CI: 1.20–2.29) and PICS (HR: 1.79; 95% CI: 1.09–2.94), respectively. Sensitivity analysis further confirmed that the ALC trajectory model of non-infected patients and non-elderly patients can accurately distinguished 91 and 90% of critically ill patients into the same endotypes as the original model, respectively.

Conclusion

The ALC trajectory model is helpful for grouping critically ill patients, and early persistent lymphopenia is associated with poor prognosis. Notably, persistent lymphopenia may be a robust signal of immunosuppression in critically ill patients.
Mortality prediction in pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation: A comparison of scoring systems
Authors: Jin Yu , Gao Peng , Zhang Peiyao , Bai Liting , Li Yixuan , Wang Wenting , Feng Zhengyi , Wang Xu , Liu Jinping
Published: August 2022

Background

Pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients have high mortality and morbidity. There are currently three scoring systems available to predict mortality: the Pediatric Extracorporeal Membrane Oxygenation Prediction (PEP) model, Precannulation Pediatric Survival After VA-ECMO (Pedi-SAVE) score, and Postcannulation Pedi-SAVE score. These methods provide risk stratification scores for pediatric patients requiring ECMO for cardiac support. However, comparative validation of these scoring systems remains scarce. We aim to assess the ability of these models to predict outcomes in a cohort of pediatric patients undergoing VA-ECMO after cardiac surgery, and identify predictors of in-hospital mortality.

Methods

A retrospective analysis of 101 children admitted to Fuwai Hospital who received VA-ECMO from January 1, 2010 to December 31, 2020 was performed. Patients were divided into two groups, survivors (n = 49) and non-survivors (n = 52) according to in-hospital mortality. PEP model and Pedi-SAVE scores were calculated. The primary outcomes were the risk factors of in-hospital mortality, and the ability of the PEP model, Precannulation Pedi-SAVE and Postcannulation Pedi-SAVE scores to predict in-hospital mortality.

Results

Postcannulation Pedi-SAVE score accessing the entire ECMO process had the greatest area under receiver operator curve (AUROC), 0.816 [95% confidence interval (CI): 0.733–0.899]. Pre-ECMO PEP model could predict in-hospital mortality [AUROC = 0.691 (95% CI: 0.565–0.817)], and Precannulation Pedi-SAVE score had the poorest prediction [AUROC = 0.582(95% CI: 0.471–0.694)]. Lactate value at ECMO implantation [OR = 1.199 (1.064–1.351), P = 0.003] and infectious complications [OR = 5.169 (1.652–16.172), P = 0.005] were independent risk factors for in-hospital mortality.

Conclusion

Pediatric cardiac ECMO scoring systems, including multiple risk factors before and during ECMO, were found to be useful in this cohort. Both the pre-ECMO PEP model and the Postcannulation Pedi-SAVE score were found to have high predictive value for in-hospital mortality in pediatric postcardiotomy VA-ECMO.
The treatment effects of Trametes Robiniophila Murr against colorectal cancer: A mini-review
Authors: Li Bo , Cao Qian , Liu Zhuo
Published: August 2022

Colorectal cancer (CRC) is a worldwide disease threatening people's lives. Surgery and chemotherapy are still the main methods for CRC treatment. However, the side effects and chemotherapeutic drug resistance restrict the application of chemotherapy. Trametes Robiniophila Murr, also known as Huaier, is a traditional Chinese medicine that has been used for more than 1,600 years. Huaier extracts have promising anti-cancer effects on hepatoma, breast cancer, and gastric cancer. Nowadays, the tumor inhibition of Huaier on CRC has attracted more and more attention. This review mainly provides the possible anti-tumor mechanisms of Huaier for CRC treatment in apoptosis and inhibiting proliferation of tumor cells, preventing epithelial-mesenchymal transformation (EMT), weakening proliferation and differentiation of CRC stem cells, decreasing the vessel density in tumor tissues, and enhancing the immune system and chemotherapeutic efficacy. Huaier extract may be a good candidate for CRC treatment, especially when combined with other chemotherapeutic agents.
Bacteriophages: Underestimated vehicles of antibiotic resistance genes in the soil
Authors: Zhang Yue , Guo Yajie , Qiu Tianlei , Gao Min , Wang Xuming
Published: August 2022

Bacteriophages (phages), the most abundant biological entities on Earth, have a significant effect on the composition and dynamics of microbial communities, biogeochemical cycles of global ecosystems, and bacterial evolution. A variety of antibiotic resistance genes (ARGs) have been identified in phage genomes in different soil samples. Phages can mediate the transfer of ARGs between bacteria via transduction. Recent studies have suggested that anthropogenic activities promote phage-mediated horizontal gene transfer events. Therefore, the role of phages in the dissemination of ARGs, which are a potential threat to human health, may be underestimated. However, the contribution of phages to the transfer of ARGs is still poorly understood. Considering the growing and wide concerns of antibiotic resistance, phages should be considered a research focus in the mobile resistome. This review aimed to provide an overview of phages as vehicles of ARGs in soil. Here, we summarized the current knowledge on the diversity and abundance of ARGs in soilborne phages and analyzed the contribution of phages to the horizontal transfer of ARGs. Finally, research deficiencies and future perspectives were discussed. This study provides a reference for preventing and controlling ARG pollution in agricultural systems.
EmCyclinD-EmCDK4/6 complex is involved in the host EGF-mediated proliferation of Echinococcus multilocularis germinative cells via the EGFR-ERK pathway
Authors: Feng Chonglv , Cheng Zhe , Xu Zhijian , Tian Ye , Tian Huimin , Liu Fan , Luo Damin , Wang Yanhai
Published: August 2022

The larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. The tumor-like growth and development of the metacestode larvae within host organs are driven by a population of somatic stem cells, the germinative cells, which represent the only proliferative cells in the parasite. Host-derived factors have been shown to promote germinative cell proliferation. Since cells sense the external signal mainly in G1 phase of the cell cycle, host factors are expected to exert impacts on the machinery regulating G1/S phase of the germinative cells, which still remains largely unknown in E. multilocularis. In this study, we described the characterization of two key members of the G1/S phase cell-cycle regulation, EmCyclinD and EmCDK4/6. Our data show that EmCyclinD and EmCDK4/6 display significant sequence similarity to their respective mammalian homologs, and that EmCyclinD interacts with EmCDK4/6, forming a kinase-active complex to activate its substrate Rb1. EmCyclinD was actively expressed in the germinative cells. Addition of human EGF caused an elevated expression of EmCyclinD while inhibition of the EGFR-ERK signaling pathway in the parasite reduced the expression of EmCyclinD and downstream transcriptional factors. Treatment with Palbociclib, a specific CDK4/6 inhibitor, downregulated the expression of cell cycle-related factors and impeded germinative cell proliferation and vesicle formation from protoscoleces. Our data demonstrated that the EmCyclinD-EmCDK4/6 complex participates in the cell cycle regulation of germinative cells which is mediated by host EGF via the EGFR-ERK-EmCyclinD pathway in E. multilocularis.
The BcLAE1 is involved in the regulation of ABA biosynthesis in Botrytis cinerea TB-31
Authors: Wei Zhao , Shu Dan , Sun Qun , Chen Dong-bo , Li Zhe-min , Luo Di , Yang Jie , Tan Hong
Published: August 2022

Abscisic acid (ABA), as a classic plant hormone, is a key factor in balancing the metabolism of endogenous plant hormones, and plays an important role in regulating the activation of mammalian innate immune cells and glucose homeostasis. Currently, Botrytis cinerea has been used for fermentation to produce ABA. However, the mechanism of the regulation of ABA biosynthesis in B. cinerea is still not fully understood. The putative methyltransferase LaeA/LAE1 is a global regulator involved in the biosynthesis of a variety of secondary metabolites in filamentous fungi. In this study, we demonstrated that BcLAE1 plays an important role in the regulation of ABA biosynthesis in B. cinerea TB-31 by knockout experiment. The deletion of Bclae1 caused a 95% reduction in ABA yields, accompanied by a decrease of the transcriptional level of the ABA synthesis gene cluster Bcaba1-4. Further RNA-seq analysis indicated that deletion of Bclae1 also affected the expression level of key enzymes of BOA and BOT in secondary metabolism, and accompanied by clustering regulatory features. Meanwhile, we found that BcLAE1 is involved in epigenetic regulation as a methyltransferase, with enhanced H3K9me3 modification and attenuated H3K4me2 modification in ΔBclae1 mutant, and this may be a strategy for BcLAE1 to regulate ABA synthesis.
Diversity of clonal complex 22 methicillin-resistant Staphylococcus aureus isolates in Kuwait hospitals
Authors: Boswihi Samar S. , Verghese Tina , Udo Edet E.
Published: August 2022

CC22-MRSA is a major MRSA lineage that is widely reported globally. To characterize CC22-MRSA for trends in antibiotic resistance and emergence of variants, a total of 636 CC22 isolates identified by DNA microarray in 2016 (n = 195), 2017 (n = 227) and 2018 (n = 214) were investigated further using staphylococcal protein A (spa) typing and multilocus sequence typing. The isolates belonged to 109 spa types dominated by t223 (n = 160), t032 (n = 60), t852 (n = 59), t005 (n = 56) and t309 (n = 30) and 10 sequence types (STs) dominated by ST22 (85.5%). Genotypes CC22-MRSA-IV [tst1+]; CC22-MRSA-IV UK-EMRSA-15/Barnim EMRSA variants, CC22-MRSA-IV [PVL+], CC22-MRSA-IV [tst1+/PVL+] and CC22-MRSA-IV + V constituted >50% of the isolates. An increase from 2016 to 2018 were shown in isolates belonging to spa types t223 (43 to 62), t032 (18 to 27) and t309 (10 to 15) and genotypes CC22-MRSA-IV [tst1+] (89 to 102), CC22-MRSA-IV + V (12 to 30) and CC22-MRSA-IV [tst1+/PVL+] (12 to 22). Ninety-nine CC22-MRSA isolates were multi-resistant to three or more antibiotic classes with 76.7% of them belonging to CC22-MRSA-IV [PVL+] and CC22-MRSA-IV [tst1+/PVL+]. The study revealed an ongoing domination of the CC22-MRSA-[tst1+] genotype and the emergence of new clones bearing SCCmec IV + V and multiply resistant variants.