bluuebunny/crossref_metadata_2025 huggingface dataset:
PgRNA kinetics predict HBsAg reduction in pregnant chronic hepatitis B carriers after treatment cessation
Authors: Wang Chun-Rui , Liu Xiao-qin , Li Hu , Zhang Qian , Zhong Guo-Chao , Tang Qiao , Chang Yunan , Wang Jin-Song , Duan Yuan-qin , Hu Peng
Published: December 2022

Background

Pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) play significant roles in predicting discontinuing treatment outcomes. However, their role in pregnancy has rarely been reported. We aimed to evaluate the performance of pgRNA and HBcrAg kinetics in predicting HBeAg seroconversion and HBsAg reduction postpartum in HBeAg-positive pregnant women.

Methods

Pregnant HBeAg-positive patients receiving antiviral prophylaxis and ceasing treatment postpartum were included. PgRNA and HBcrAg levels were measured before treatment, at 32 weeks of gestation, and at treatment withdrawal postpartum. Other virological and biochemical parameters were regularly examined until 96 weeks postpartum.

Results

Of 76 pregnant chronic hepatitis B (CHB) carriers with a median treatment duration of 18.1 weeks, HBeAg seroconversion and HBsAg reduction >0.3 log10 IU/mL at 96 weeks postpartum occurred in 8 (10.5%) and 13 (17.1%) patients, respectively. HBsAg correlated most strongly with pgRNA, while HBeAg correlated most strongly with HBcrAg. Multivariable regression analysis revealed that postpartum pgRNA decline and peak ALT levels were independent predictors of HBsAg reduction. The area under the curve of the regression model was 0.79 and reached as high as 0.76 through bootstrapping validation. The calibration plot showed that the nomogram had a performance similar to that of the ideal model. A decision tree was established to facilitate application of the nomogram. In addition, HBcrAg kinetics, as an independent predictor, performed poorly in predicting HBeAg seroconversion.

Conclusions

Postpartum pgRNA decline together with peak ALT levels may identify patients with a higher probability of HBsAg reduction after treatment cessation postpartum among pregnant CHB carriers receiving antiviral prophylaxis.
Zunyimycin C enhances immunity and improves cognitive impairment and its mechanism
Authors: Wang Xuemei , Li Zexin , Sun Rui , Li Xueli , Guo Ruirui , Cui Xiangyi , Liu Bingxin , Li Wujuan , Yang Yi , Huang Xiaoyu , Qu Hanlin , Liu Chen , Wang Zhuoling , Lü Yuhong , Yue Changwu
Published: December 2022

This study aimed to explore the efficacy of zunyimycin C in the immunological enhancement of hypoimmune mice and improvement of cognitive impairment in a mice model of Alzheimer’s disease (AD). Zunyimycin C was administered intranasally to interfere with AD mouse models or gavage to hypoimmune animals. Results of the Morris water maze (MWM) showed that zunyimycin may improve the learning and memory abilities of the AD mice model. The results of differential expression analysis of mRNA levels of inflammatory factors and pathways in brain tissues of the AD mouse model suggested that differential expression was more obvious under Zun-Int L. Western blot revealed that the relative expression of glial fibrillary acidic protein in the brain tissue of the AD mouse model in the Zun-Pre group was significantly higher than that in the other groups, and the difference was statistically significant. The relative expression of interleukin (IL)-6 protein in the brain tissue of mice in the low-dose intervention group was significantly lower than that in the other groups, and the difference was statistically significant. As for hypoimmune animals, short chain fatty acids (SCFAs) assay and intestinal flora assay results showed that zunyimycin C may change intestinal flora diversity and SCFA biosynthesis. The prophylactic administration of zunyimycin C could not inhibit acute neuroinflammation in AD mice. Zunyimycin C may participate in the immune response by activating the Ras-Raf-MEK-ERK signaling pathway to stimulate microglia to produce more inflammatory factors. Zunyimycin C may inhibit autophagy by activating the PI3K-AKT-mTOR signaling pathway, promote cell survival, mediate neuroprotective effects of reactive microglia and reactive astrocytes, and reduce IL-1β in brain tissue and IL-6 secretion, thereby attenuating neuroinflammation in AD mice and achieving the effect of improving learning and memory impairment. Zunyimycin C may play a role in immunological enhancement by changing intestinal flora diversity and SCFAs.
An algal lectin griffithsin inhibits Hantaan virus infection in vitro and in vivo
Authors: Zhao Yajing , Zhao Ningbo , Cai Yanxing , Zhang Hui , Li Jia , Liu Jiaqi , Ye Chuantao , Wang Yuan , Dang Yamei , Li Wanying , Liu He , Zhang Lianqing , Li Yuexiang , Zhang Liang , Cheng Linfeng , Dong Yangchao , Xu Zhikai , Lei Yingfeng , Lu Lu , Wang Yingjuan , Ye Wei , Zhang Fanglin
Published: December 2022

Hantaan virus (HTNV) is the etiological pathogen of hemorrhagic fever with renal syndrome in East Asia. There are currently no effective therapeutics approved for HTNV and other hantavirus infections. We found that griffithsin (GRFT), an algae-derived lectin with broad-spectrum antiviral activity against various enveloped viruses, can inhibit the growth and spread of HTNV. In vitro experiments using recombinant vesicular stomatitis virus (rVSV) with HTNV glycoproteins as a model revealed that the GRFT inhibited the entry of rVSV-HTNV-G into host cells. In addition, we demonstrated that GRFT prevented authentic HTNV infection in vitro by binding to the viral N-glycans. In vivo experiments showed that GRFT partially protected the suckling mice from death induced by intracranial exposure to HTNV. These results demonstrated that GRFT can be a promising agent for inhibiting HTNV infection.
Tissue-specific metabolomic profiling after cardiopulmonary bypass in fetal sheep
Authors: Wu Wentao , Teng Yun , Tian Miao , Huang Bingxin , Deng Yuhang , Li Huili , Yuan Haiyun , Chen Jimei , Li Xiaohong , Zhou Chengbin
Published: December 2022

Objective

Fetal cardiopulmonary bypass (CPB) is essential to fetal heart surgery, while its development is limited by vital organ dysfunction after CPB. Studying organ metabolism may help to solve this problem. The objective of this study was to describe the tissue-specific metabolic fingerprints of fetal sheep under CPB and to associate them with organ functions.

Methods

Ten pregnant ewes at 90–120 days of gestation were randomly divided into two groups. The bypass group underwent a 1-h fetal CPB, whereas the control group underwent only a fetal sternotomy. During bypass, echocardiography, blood gases, and blood biochemistry were measured. After bypass, lambs were sacrificed, and tissues of the heart, liver, brain, kidney, and placenta were harvested. The metabolites extracted from these tissues were analyzed using non-targeted metabolomics based on liquid chromatography-mass spectrometry techniques.

Results

All tissues except the placenta displayed significant metabolic changes, and the fetal heart displayed obvious functional changes. Fetal sheep that underwent CPB had common and tissue-specific metabolic signatures. These changes can be attributed to dysregulated lipid metabolism, altered amino acid metabolism, and the accumulation of plasticizer metabolism.

Conclusion

Fetal CPB causes tissue-specific metabolic changes in fetal sheep. Studying these metabolic changes, especially cardiac metabolism, is of great significance for the study of fetal CPB.
In silico mapping of the dynamic interactions and structure-activity relationship of flavonoid compounds against the immune checkpoint programmed-cell death 1 pathway
Authors: Sartori Geraldo Rodrigues , Albuquerque Aline de Oliveira , Santos-Costa Andrielly Henriques , Andrade Luca Milério , Almeida Diego da Silva , Gaieta Eduardo Menezes , Sampaio Jean Vieira , Albuquerque Vitória Taiana de Melo Lima , Martins Da Silva João Hermínio
Published: December 2022

Flavonoids are a class of natural products widely available in medicinal and dietary plants. Their pharmacological use has shown the potential to reduce the risk of different types of cancer, among other prevalent diseases. Their molecular scaffold inhibits the PD-1/PD-L1 axis, an important pathway related to the adaptive immune resistance of cancer cells already targeted for developing new cancer immunotherapy. However, despite the availability of kinetic and thermodynamic experimental data on the flavonoid–PD-1/PD-L1 interaction, there is still a lack of reliable information about their binding mode at the atomic level. Thus, we aimed to computationally predict the binding mode of flavonoid molecules with PD-1 and/or PD-L1 proteins using unbiased computational methodologies such as blind docking and supervised molecular dynamics simulation. The molecular interactions and dynamics of these predicted poses of protein-flavonoid complexes were further analyzed through multiple molecular dynamics simulations. This information, corroborated with the IC50 and KD values from available literature, was used to perform molecular matched-pair analysis to comprehensively describe the main interactions governing the inhibition of the complex PD-1/PD-L1 by the flavonoid scaffold. By analyzing the effect of substitutions in such a scaffold, we observed a clear correspondence with literature binding assays. Thus, we propose, for dimeric PD-L1, that the 7-O-glucoside forces the molecule displacement in the dimer interface. Furthermore, the 3-OH plays an essential role in stabilizing the buried binding mode by water-bridged hydrogen bonds with Asp122 and Gln66 in both extremities of the pocket. In PD-1, we suggest that flavonoids could bind through the BC loop by inducing a flip of Phe56 after a conformational change of the Asn58 glycosylation. Hence, our results introduced unprecedented information on flavonoid interaction and dynamics when complexed with PD-1 checkpoint pathway proteins and can pave the road for developing new flavonoid derivatives with selective anticancer activity.
Mathematical proficiency among female teachers of the first three grades in Jordan and its relationship to their mathematical thinking
Authors: Alfayez Mona Qutaifan Ershed
Published: December 2022

Aim

The present study aimed at investigating the association of the mathematical proficiency and mathematical thinking skills among female teachers of the first three grades in public schools of Amman city, Jordan.

Method

The study adopted the descriptive analytical research approach. A sample of 174 female teachers of the first three grades was recruited in the present study. To collect data, the study used a mathematical proficiency tests (39 items) covering the domains of the conceptual understanding, procedural fluency, strategic competency, adaptive reasoning, and the productive desire. In addition, the study used a mathematical thinking skills test consisted of (20) items distributed over seven mathematical thinking skills; they were: Induction skill, conclusion skill, symbolizing skill, logical thinking skill, guessing skill, demonstration skill, and modeling skill. Data were analyzed using SPSS software (v. 26).

Results

The study findings showed that female teachers of the first three grades had a moderate level of mathematical proficiency (43.60 ± 16.04), a good level of mathematical thinking skills (6.51 ± 4.628). In addition, the study found significant statistical positive correlation between mathematical proficiency and mathematical thinking skills (r= 0.681,p≤ 0.05) among female teachers of the first three grades in Amman.

Conclusion

The study concluded that mathematical proficiency is significantly associated with mathematical thinking skills in their domains. The study recommended increasing female teachers’ competencies and skills related to mathematical proficiency and mathematical thinking throughout intensive courses and workshops.
Electrical energy future of Saudi Arabia: Challenges and opportunities
Authors: Aldhubaib Hani A.
Published: December 2022

The economy of Saudi Arabia is primarily oil-based, and the energy system is heavily dependent on fossil fuel sources. Electrical demand in Saudi Arabia has been overgrowing due to the high rates of both population and economy. The real problem is that most of this demand has been met by polluting sources, which in turn causes severe economic and environmental challenges. Despite the abundant amount of clean and freely available renewable sources, the practice of benefiting from these sources is minimal and modest. Therefore, the country has launched a promising vision, one pillar of which is diversifying energy sources and reducing dependence on oil. Since Saudi Arabia is located within the equatorial Sun Belt area, the country is a candidate for leading the World’s renewable energy industry, particularly solar energy. This paper discusses the current energy policy in Saudi Arabia, the associated main energy-related challenges and promising opportunities, and the efforts and actions taken by the country’s policymakers to address these challenges and to take advantage of available opportunities–especially those related to electrical energy–to assure continued future prosperity for subsequent generations.
Perspectives for the circular chemical economy post COP26
Authors: Lamb Katie J. , Styring Peter
Published: December 2022

More global action towards climate change in the UK is needed now. Carbon dioxide levels need to be decreased globally and more sustainable practices implemented throughout all sectors in the UK. Whilst many steps have been taken in the UK to reduce its overall carbon footprint, the UK chemical sector must become more sustainable. Whilst carbon dioxide emissions must be reduced, a holistic systematic approach is needed to reduce emissions and improve sustainable manufacture. The circular economy in conjunction with reducing carbon dioxide levels can therefore be used to tackle this issue. Carbon dioxide mitigation technologies, such as carbon capture utilisation and storage amongst others, must help complement a circular economy as well as push towards a more circular carbon-based UK chemical sector. This perspective will discuss policies pledged towards tackling climate change via carbon dioxide reduction methods, pre and post COP26, and critically discuss the good and bad aspects of the conference, especially in terms of creating a circular chemical economy in the UK.
Influence of constructed rapid infiltration system on groundwater recharge and quality
Authors: Guo Chao , Li Jiake , Sun Yingying , Gao Wang , Mao Zhongan , Ye Shenglan
Published: December 2022

Infiltration of stormwater through green surfaces is an important means of groundwater recharge. However, the increase in constructed impervious area caused by intensive urbanization has led to a reduction in rainwater infiltration over the past decade. The constructed rapid infiltration system (CRIS) with an ample open space plays an important role in groundwater recharge. This study aims to explore the influence of stormwater (roof runoff) concentration infiltration on the groundwater table and quality in the CRIS. Groundwater table monitoring is conducted for more than 2 years (October 2017–December 2019) by continuous online monitoring combined with manual sampling. Results show that the addition of zeolite to the CRIS has a good removal effect on rainfall runoff pollutants, and the influence of stormwater concentration infiltration on groundwater quality is small when the CRIS enters the stable running stage. The increased proportion of chemical oxygen demand, N, and P in J1 are all less than 10% from 2018 to 2019, and they are less than 20% for heavy metals. The stormwater concentration infiltration can recharge groundwater and increase the groundwater depth, and the groundwater depth varies from 0.5 m to 1.5 m during the monitoring period. The influence scope of the concentrated infiltration on the groundwater table and quality is between 25 and 45 m. The response of the groundwater table and quality to the stormwater concentration infiltration of J1, 25 m away from the CRIS, exhibits hysteresis, and the lag time is about 3–4 months. Conclusion from relevant research can provide important theoretical support for the further study of groundwater recharge by the CRIS.
A bibliometrics review of hotspots in water footprint research based on co-words network analysis
Authors: Sun Yun , Wang Zhibin , Lee Lien-Chieh , Li Xinming , Wang Yuan
Published: December 2022

The uneven distribution of water resources and production fragmentation make the study of water footprint an important part of water resources management and environmental research. This paper provides a bibliometrics analysis of 3822 papers related to the water footprint topic before 2021, including 2381 English papers from the Science Citation Index (SCI) database and 1441 Chinese papers from the China National Knowledge Infrastructure (CNKI) database. We applied the method of co-word analysis to study the changes in hot research fields in four stages and represented a comparative analysis of highly cited papers and the application of water footprint theory in various sectors. First, water footprint can be divided into two categories: “volumetric” water footprint and “impact-oriented” water footprint. “Volumetric” water footprint methodology focuses on water consumption while “impact-oriented” water footprint methodology focuses more on the environmental impact of water use. Water scarcity, carbon footprint, and grey water are the high-frequency keywords of both two databases. The research linkage of papers related to water footprint from the SCI database has gradually shifted to climate change and carbon emission, while, those from the CNKI database are more closely linked to ecological footprint and sustainable development. Second, SCI’s highly cited papers prefer to study the water footprint through scientific experiments from a bottom-up perspective, while CNKI’s highly cited papers prefer to combine economics and management theories to study the water footprint from a top-down perspective. In addition, water footprint theory is mainly applied in agriculture and industrial sectors and less in service sectors. This paper provides a review of water footprint research on a large scale and a reference for future research on water footprint.
Changes in the height of the pollution boundary layer and their meteorological effects on the distribution of surface ozone concentrations
Authors: Liu Liangke , Zhang Xiaoye , Wang Jizhi , Yang Yuanqin , Jia Wenxing , Zhong Junting , Jiang Xiaofe , Wang Yaqiang
Published: December 2022

Focusing on the key air pollution regions in China by using hourly automatic weather data, ground-based and high-altitude meteorological sounding data, and near-surface O3 monitoring data, here, we try to quantify the relationship between boundary layer meteorological condition and near-surface O3 concentrations. The key meteorological element includes changes in solar zenith angle, cloud height, atmospheric condensation rate, and the associated change in the boundary layer height. We also try to better understand the mechanisms by which meteorological conditions affect near-surface O3 concentrations, and it is found that the exponential increase in near-surface O3 concentrations after sunrise (called the O3 concentration entrainment, EZ) is meaningfully associated with exceeding the threshold of a water vapor condensation rate (fc) that is often closely linked to a significant rise in the pollution boundary layer and that this proves to be diagnostically important for understanding the O3 EZ. Diurnal variations in solar zenith angle and boundary layer height are key meteorological factors influencing the large increase in near-surface O3 concentration entrainment.
Using mass cytometry for the analysis of samples of the human airways
Authors: Rocha-Hasler Marianne , Müller Lena , Wagner Anja , Tu Aldine , Stanek Victoria , Campion Nicholas James , Bartosik Tina , Zghaebi Mohammed , Stoshikj Slagjana , Gompelmann Daniela , Zech Andreas , Mei Henrik , Kratochwill Klaus , Spittler Andreas , Idzko Marco , Schneider Sven , Eckl-Dorna Julia
Published: December 2022

Mass cytometry (MC) is a powerful method for mapping complex cellular systems at single-cell levels, based on the detection of cellular proteins. Numerous studies have been performed using human blood, but there is a lack of protocols describing the processing and labeling of bronchoalveolar lavage fluid (BALF) and nasal polyps (NP) for acquisition by MC. These specimens are essential in the investigation of immune cell characteristics in airway diseases such as asthma and chronic rhinosinusitis with NP (CRSwNP). Here we optimized a workflow for processing, labeling, and acquisition of BALF and NP cells by MC. Among three methods tested for NP digestion, combined enzymatic/mechanical processing yielded maximum cell recovery, viability and labeling patterns compared to the other methods. Treatment with DNAse improved sample acquisition by MC. In a final step, we performed a comparison of blood, BALF and NP cell composition using a 31-marker MC antibody panel, revealing expected differences between the different tissue but also heterogeneity among the BALF and NP samples. We here introduce an optimized workflow for the MC analysis of human NP and BALF, which enables comparative analysis of different samples in larger cohorts. A deeper understanding of immune cell characteristics in these samples may guide future researchers and clinicians to a better disease management.
The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance
Authors: Lin Cheng-Hung , Anggelia Madonna Rica , Cheng Hui-Yun , Hsieh Yun-Huan , Chuang Wen-Yu , Yang Huang-Yu , Lin Chih-Hung
Published: December 2022

Introduction

Vascularized bone marrow (VBM) is essential in tolerance induction through chimerism. We hypothesized that the inclusion of VBM contributes to the induction of mystacial pad allotransplantation tolerance.

Method

In this study, 19 VBM, nine mystacial pad, and six sequential VBM and mystacial pad allografts were transplanted from Brown Norway (BN) rats to Lewis (LEW) rats to test our hypothesis. The VBM recipients were divided into antilymphocyte serum (ALS) monotherapy group (two doses of ALS on day 3 pretransplantation and day 1 posttransplantation), immunosuppressant group [a week of 2 mg/kg/day tacrolimus (Tac) and 3 weeks of 3 mg/kg/day rapamycin (RPM)], and combined therapy group. The mystacial pad recipients were divided into VBM and non-VBM transplantation groups, and both groups were treated with an immunosuppression regimen that consists of ALS, Tac, and RPM. For the recipients of sequential VBM and mystacial pad allotransplantations, additional Tac was given 1 week after mystacial pad transplantation. Allograft survival, donor-specific tolerance, and chimerism level were evaluated.

Results

With the administration of ALS and short-term Tac and RPM treatments, VBM recipients demonstrated long-term graft survival (>120 days) with persistent chimerism for 30 days. CD3+ T cells from tolerant rats showed donor-specific hyporesponsiveness and tolerance to donor skin grafts but not to third-party counterparts. Furthermore, mystacial pad graft recipients with VBM transplantation exhibited a higher allograft survival rate than those without VBM transplantation [median survival time (MST) >90 days vs. 70 days, p < 0.05].

Conclusion

This study demonstrated that VBM transplantation is an efficient strategy to induce and maintain donor-specific tolerance for an osseous-free allograft.
SOX chemotherapy with anti-PD-1 and iNKT cell immunotherapies for stage IV gastric adenocarcinoma with liver metastases: A case report
Authors: Li Dezhao , Liu Mei , Wang Jinhuan , Guo Jia , Xu Ningzhi , Lu Jun
Published: December 2022

Gastric cancer (GC) is the fourth most common cancer worldwide, with overall 5-year survival rate of approximate 20%. Although multimodal treatments that combine surgery with chemotherapy and immunotherapy have been shown to improve survival, pathological complete response (pCR) is rare in advanced GC patients with liver metastases. Pre-clinical studies and clinical trials have demonstrated the antitumor efficacy of invariant natural killer T (iNKT) cells in various malignancies, including GC. While multimodal therapy comprised of chemotherapy, anti-programmed cell death-1 (PD-1) therapy, and iNKT cell immunotherapy have not been reported in GC patients. This case report describes the treatment of an early 60s patient diagnosed with advanced stage IVB (T1N1M1) adenocarcinomas of gastric cardia with liver metastases who received multimodal therapy comprised of SOX chemotherapy, anti-programmed cell death-1 (PD-1) therapy, and iNKT cell immunotherapy followed by surgical resection. Dramatic decreases in tumor area were observed in both the primary tumor and metastatic lesions following six cycles of SOX chemotherapy and iNKT cell immunotherapy, and four cycles of anti-PD-1 therapy. This combined treatment resulted in the transformation of a remarkably large, unresectable liver metastases into a resectable tumor, and the patient received total gastrectomy with D2 lymph node dissection and liver metastasectomy. Subsequent pathological examination detected no cancer cells in either the primary site or liver metastatic lesions, supporting the likelihood that this treatment achieved pCR. To our knowledge, this report represents the first case of a metastatic gastric cancer patient displaying pCR after six months of multimodal therapy, thus supporting that a SOX chemotherapy, anti-PD-1 therapy, and iNKT cell immunotherapy combination strategy may be effective for treating, and potentially curing, patients with advanced gastric adenocarcinoma.
Potentiating pneumococcal glycoconjugate vaccine PCV13 with saponin adjuvant VSA-1
Authors: Kim Hyunjung , Yu Jigui , Bai Di , Nahm Moon H. , Wang Pengfei
Published: December 2022

VSA-1 is a semisynthetic saponin adjuvant prepared from naturally occurring Momordica saponin and capable of stimulating antigen-specific humoral and cellular immune responses. Its immunostimulating activity in enhancing the immune responses induced by the clinical glycoconjugate pneumococcal vaccine PCV13 is compared with QS-21 in female BALB/c mice. Both VSA-1 and QS-21 boosted IgG and opsonic antibodies titers against seven selected serotypes, including serotypes 3, 14, and 19A that are involved in most PCV13 breakthroughs. Since VSA-1 is much more accessible and of lower toxicity than QS-21, it can be a practical saponin immunostimulant to be included in a new glycoconjugate pneumococcal vaccine formulation.
Optimizing an immunomodulatory potency assay for Mesenchymal Stromal Cell
Authors: Hansen Stine Bangsgaard , Højgaard Lisbeth Drozd , Kastrup Jens , Ekblond Annette , Follin Bjarke , Juhl Morten
Published: December 2022

The expeditious progress of Mesenchymal Stromal Cells (MSC) for therapeutic intervention calls for means to compare differences in potency of cell products. The differences may be attributed to innumerable sources including tissue origin, production methods, or even between batches. While the immunomodulatory potential of MSC is recognized and well-documented by an expansive body of evidence, the methodologies and findings vary markedly. In this study, we utilized flowcytometric analysis of lymphocyte proliferation based on cryopreserved peripheral blood mononuclear cells for quantification of the inhibitory effect of MSC. Technical aspects of fluorescent staining and cryopreservation of peripheral blood mononuclear cells were evaluated to obtain optimal results and increase feasibility. A range of common specific and unspecific mitogens was titrated to identify the conditions, in which the effects of Adipose tissue-derived Stromal Cells (ASC; a type of MSC) were most pronounced. Specific stimulation by antibody-mediated activation of CD3 and CD28 via TransAct and Dynabeads lead to substantial proliferation of lymphocytes, which was inhibited by ASC. These results were closely mirrored when applying unspecific stimulation in form of phytohemagglutinin (PHA), but not concanavalin A or pokeweed mitogen. The mixed lymphocyte reaction is a common assay which exploits alloreactivity between donors. While arguably more physiologic, the output of the assay often varies substantially, and the extent of proliferation is limited since the frequency of alloreactive cells is low, as opposed to the mitogens. To heighten the proliferative response and robustness, combinations of 2-5 donors were tested. Maximum proliferation was observed when combining 4 or more donors, which was efficiently suppressed by ASC. Several desirable and unfavorable traits can be attributed to the tested stimuli in the form of keywords. The importance of these traits should be scored on a laboratory-level to identify the ideal mitogen. In our case the ranking listed PHA as the most suited candidate. Developing robust assays is no trivial feat. By disclosing the full methodological framework in the present study, we hope to aid others in establishing functional metrics on the road to potency assays.
Prevalence of parent-reported food allergy among children in China: A population-based cross-sectional survey
Authors: Feng Hua , Luo Nan , Lu Yuanan , Lu Justin , Zhou Jiangdong , Xiong Xiujuan , Chen Zhuo , Chen Yan , Wu Yongning
Published: December 2022

Objective

The prevalence of food allergy (FA) has been increasing in recent years and has become an important public health, food safety, and clinical nutrition problem. However, population-based studies on the prevalence of FA are very limited in China. This study aims to determine the prevalence and pattern of parent-reported FA among school children in Jiangxi Province, China.

Methods

A multicenter cross-sectional study on FA was conducted on primary school children aged 6-11 years old using random cluster sampling with a questionnaire survey. Parent-reported FA was used and defined as individual-reported FA by parent or guardian through a questionnaire in this study.

Result

Among the total of 8,856 (96.36%) complete questionnaires received, 727 (8.2%) children had adverse reactions to food (ARF). The prevalence rates of parent-reported FA and doctor-diagnosed FA were 6.2% and 3.3%, respectively. Animal-derived foods were the main causative source of FA, and the three leading allergenic foods were shrimp, mango, and mollusks. Skin reactions were the most common clinical manifestations of FA, accounting for 63.7%, and 45.32% of the subjects with parent-reported FA experienced severe allergic reactions. There was a significant difference in parent-reported FA between different survey centers, and FA risk increased significantly in children with other allergic diseases (P<0.001) and small family size (P=0.026). The FA prevalence was significantly higher among children aged 8-11 years than those aged 6-7 years (P=0.020).

Conclusions

A high prevalence of parent-reported FA was observed among children in general primary schools in Jiangxi Province, China. Shrimp, mango, and mollusks were the most common causative foods. The main common symptoms of FA were adverse reactions relating to the skin system. The rate of severe allergic reactions was also high in Jiangxi Children with reported FA. Local standards and policies for the prevention and management of FA need to be adjusted on a timely basis according to actual local conditions.
Determination of dissolved organic carbon and total dissolved nitrogen in seawater using High Temperature Combustion Analysis
Authors: Halewood Elisa , Opalk Keri , Custals Lillian , Carey Maverick , Hansell Dennis A. , Carlson Craig A.
Published: December 2022

This document describes best practices for analysis of dissolved organic matter (dissolved organic carbon and total dissolved nitrogen) in seawater samples. Included are SOPs for sample collection and storage, details for laboratory analysis using high temperature combustion analysis on Shimadzu TOC analyzers, and suggestions for best practices in quality control and quality assurance. Although written specifically for GO-SHIP oceanographic community practices, many aspects of sample collection and processing are relevant to DOM determination across oceanic regimes and this document aims to provide updated methodology to the wider marine community.
Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study
Authors: Wang Junkui , Hao Yan , Zhu Zhanfang , Liu Bo , Zhang Xuejun , Wei Na , Wang Ting , Lv Ying , Xu Cuixiang , Ma Meijuan , Zhang Yulian , Liu Fuqiang
Published: December 2022

Background

Observational studies have shown that calcific aortic valve stenosis (CAVS) is associated with a shorter telomere length (TL). However, the results of observational studies are often influenced by confounding factors and reverse causal associations; it is unclear whether there is a causal relationship between TL and CAVS. This study aimed to investigate the causal relationship between TL and CAVS.

Materials and methods

Genome-wide association study (GWAS) data on TL (n = 472,174) and CAVS (n = 311,437) were used to assess the effect of TL on CAVS. All the participants were of European ancestry. Three Mendelian randomization (MR) methods, namely, MR-Egger, weighted median, and inverse variance weighted (IVW), were used to assess the potential causal effect of TL on CAVS. Heterogeneity was assessed using Cochran’s Q statistic. Leave-one-out and MR-Egger regression methods were used for sensitivity and pleiotropy analyses. Forward and reverse MR analyses were performed.

Results

In total, 118 valid and independent TL genetic instrumental variants were extracted from the GWAS dataset. MR analysis showed that TL was negatively associated with CAVS (odds ratios [OR] = 0.727, 95% confidence interval [CI]: 0.565–0.936, and P = 0.013 by weighted median; OR = 0.763, 95% CI: 0.634–0.920, and P = 0.005 by IVW; OR = 0.757, 95% CI: 0.549–1.044, and P = 0.055 by MR-Egger). Sensitivity and pleiotropy analyses showed that the results of this study were relatively stable and that there was no significant pleiotropy. Reverse MR analyses consistently suggested the absence of causal effects of CAVS liability on TL levels.

Conclusion

A causal relationship between the shortening of TL and the development of CAVS in the European population was suggested in this study, and a theoretical basis was provided to investigate the pathogenesis of CAVS.
Investigations into the antibacterial effects and potential mechanism of gambogic acid and neogambogic acid
Authors: Li Mingzhu , Chen Yuan , Wang Lijuan , Lu Chujie , Chen Peiying , Jin Yuanling , Li Jiacong , Gao Fei , Shang Zhuo , Lin Wei
Published: December 2022

The growing threat of antibiotic-resistant bacterial infections to public health necessitates the development of novel antibacterial agents. Inhibiting bacterial cell wall synthesis has remained a key focus for antibiotic development. Our search for inhibitors of undecaprenyl diphosphate synthase (UPPS), an essential enzyme required for bacterial cell wall formation, revealed that two primary components of gamboge, gambogic acid (GA) and neogambogic acid (NGA), significantly inhibited the activity ofEnterococcus faecalisUPPS (EfaUPPS) with the half maximal inhibitory concentrations (IC50) of 3.08 μM and 3.07 μM, respectively. In thein vitroantibacterial assay, both GA and NGA also exhibited inhibitory activities againstE. faecaliswith the minimal inhibitory concentrations (MICs) of 2 μg/mL. Using microscale thermophoresis, molecular docking, and enzymatic assays, we further confirmed that GA and NGA occupy the substrate binding pocket ofEfaUPPS with micro-molar binding affinity, preventing the natural substrates farnesyl diphosphate (FPP) from entering. Mutagenesis analysis revealed that L91 and L146 are two key residues in the binding between GA/NGA and UPPS. Furthermore, we also demonstrated that GA and NGA can improveE. faecalis-induced undesirable inflammation in a mouse infection model. Taken together, our findings provide a basis for structural optimization of GA/NGA to develop improved antibiotic leads and enhance treatment success rates in clinical practice.
Specific DNAzymes cleave the 300–618 nt of 5′UTR to inhibit DHAV-1 translation and replication
Authors: Li Yanglin , Wei Ling , Cheng Anchun , Wang Mingshu , Ou Xumin , Mao Sai , Tian Bin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Gao Qun , Sun Di , Zhao Xinxin , Jia Renyong , Liu Mafeng , Zhu Dekang , Chen Shun , Yu Yanling , Zhang Ling , Pan Leichang
Published: December 2022

DNAzymes effectively inhibit the expression of viral genes. Duck hepatitis A virus type-1 (DHAV-1) genomic RNA carries an internal ribosome entry site (IRES). The IRES initiates the translation of DHAV-1 via a mechanism that differs from that of cap-dependent translation. Therefore, it is an attractive target for the treatment of DHAV-1. In this study, we designed 6 DNAzymes (Dzs) specifically targeting 300–618 nt sequence in the DHAV-1 5′untranslated region (UTR; a predicted IRES-like element). In the presence of divalent metal ions, three designed DNAzymes (DZ369, DZ454, and DZ514) efficiently cleaved the 300–618 nt sequence of the DHAV-1 5′UTR RNA. The activity of the Dzs was particularly dependent on Mg2+ ions. Subsequently, the translation inhibitory activity of these Dzs was determined by western blotting experiments. The Dzs effectively inhibited the translation mediated by the 300–618 nt of DHAV-1 5′UTR in duck embryo fibroblasts (DEFs). Importantly, DZ454 showed the strongest inhibitory effect, and its inhibition was time and dose dependent. However, none of the Dzs showed significant inhibition of cap-dependent translation. These results suggest that these Dzs show specificity for target RNA. Moreover, DZ454 inhibited the replication of DHAV-1. In conclusion, the designed DNAzymes can be used as inhibitors of DHAV-1 RNA translation and replication, providing new insights useful for the development of anti-DHAV-1 drugs.
Multiple relaxases contribute to the horizontal transfer of the virulence plasmids from the tumorigenic bacterium Pseudomonas syringae pv. savastanoi NCPPB 3335
Authors: Añorga Maite , Urriza Miriam , Ramos Cayo , Murillo Jesús
Published: December 2022

Pseudomonas syringae pv. savastanoi NCPPB 3335 is the causal agent of olive knot disease and contains three virulence plasmids: pPsv48A (pA), 80 kb; pPsv48B (pB), 45 kb, and pPsv48C (pC), 42 kb. Here we show that pB contains a complete MPFT (previously type IVA secretion system) and a functional origin of conjugational transfer adjacent to a relaxase of the MOBP family; pC also contains a functional oriT-MOBP array, whereas pA contains an incomplete MPFI (previously type IVB secretion system), but not a recognizable oriT. Plasmid transfer occurred on solid and in liquid media, and on leaf surfaces of a non-host plant (Phaseolus vulgaris) with high (pB) or moderate frequency (pC); pA was transferred only occasionally after cointegration with pB. We found three plasmid-borne and three chromosomal relaxase genes, although the chromosomal relaxases did not contribute to plasmid dissemination. The MOBP relaxase genes of pB and pC were functionally interchangeable, although with differing efficiencies. We also identified a functional MOBQ mobilization region in pC, which could only mobilize this plasmid. Plasmid pB could be efficiently transferred to strains of six phylogroups of P. syringae sensu lato, whereas pC could only be mobilized to two strains of phylogroup 3 (genomospecies 2). In two of the recipient strains, pB was stably maintained after 21 subcultures in liquid medium. The carriage of several relaxases by the native plasmids of P. syringae impacts their transfer frequency and, by providing functional diversity and redundancy, adds robustness to the conjugation system.
Comparative efficacy and acceptability of treatments for depressive symptoms in cognitive impairment: A systematic review and Bayesian network meta-analysis
Authors: Jin Boru , Xv Yunting , Zhang Bixuan , Qiao Lei , Liu Huayan
Published: December 2022

Background

Depressive symptoms play an essential role in cognition decline, while the benefit and acceptability of treatments for depressive symptoms in cognitive impairment are still unknown.

Objective

To comprehensively evaluate the comparative efficacy and acceptability of treatments for depressive symptoms in cognitive impairment based on the quantitative Bayesian network meta-analysis method (NMA).

Method

We searched MEDLINE, Embase, the Cochrane Library, CINAHL, and PsycINFO from inception until August 2022 to identify randomized clinical trials (RCTs) evaluating treatments for depressive symptoms in cognitive impairment. Efficacy was evaluated by the Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Geriatric Depression Scale (GDS) for depression; the Neuropsychiatric Inventory (NPI) and the Cohen–Mansfeld Agitation Inventory (CMAI) for behavior; and the Mini-Mental State Examination (MMSE) for cognition. Safety was evaluated by total adverse events (AEs), serious AEs, diarrhea, headache, and nausea.

Results

In this study, 13,043 participants from 107 RCTs were included, involving 28 treatments and the discontinuation of antidepressants. On CSDD, aerobic exercise (MD −4.51, 95%CrI −8.60 to −0.37), aripiprazole (MD −1.85, 95%CrI −3.66 to −0.02), behavioral training (MD −1.14, 95%CrI −2.04 to −0.34), electrical current stimulation (MD −3.30, 95%CrI −5.94 to −0.73), massage (MD −12.67, 95%CrI −14.71 to −10.59), music therapy (MD −2.63, 95%CrI −4.72 to −0.58), and reminiscence therapy (MD −2.34, 95%CrI −3.51 to −1.25) significantly outperformed the placebo. On MMSE, cognitive stimulation therapy (MD 1.42, 95%CrI 0.49 to 2.39), electrical current stimulation (MD 4.08, 95%CrI 1.07 to 7.11), and reminiscence therapy (MD 1.31, 95%CrI 0.04 to 2.91) significantly outperformed the placebo. Additionally, no treatments showed a significantly higher risk than the placebo.

Conclusion

Our NMAs indicated that non-pharmacological interventions were more efficacious and safe than pharmacological treatments for reducing depressive symptoms as well as improving cognitive impairment. Electrical current stimulation, aerobic exercise, and reminiscence therapy could be first recommended considering their beneficial performance on both depression and cognition. Hence, non-pharmacological treatments deserve more attention and extensive application and should at least be considered as an alternative or assistance in clinical settings.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021239621, identifier: CRD42021239621.
Increasing preoperative cognitive reserve to prevent postoperative delirium and postoperative cognitive decline in cardiac surgical patients (INCORE): Study protocol for a randomized clinical trial on cognitive training
Authors: Butz Marius , Meyer Rolf , Gerriets Tibo , Sammer Gebhard , Doerr Johanna M. , El-Shazly Jasmin , Doeppner Thorsten R. , Choi Yeong-Hoon , Schoenburg Markus , Juenemann Martin
Published: December 2022

Introduction

Postoperative delirium (POD) and postoperative cognitive decline (POCD) can be observed after cardiosurgical interventions. Taken together, these postoperative neurocognitive disorders (PNCDs) contribute to increased morbidity and mortality. Preoperative risk factors of PNCD, such as decreased neuropsychometric performance or decreased cognitive daily activities, can be interpreted as reduced cognitive reserve. This study aims to build up cognitive reserves to protect against the development of PNCD through preoperative, home-based, cognitive training.

Methods

The planned research project is a monocentric, two-arm randomized controlled intervention study involving 100 patients undergoing elective cardiac surgery with extracorporeal circulation. Patients will be assigned to a training group or control group. The intervention involves a standardized, paper-and-pencil-based cognitive training that will be performed by the patients at home for ~40 min per day over a preoperative period of 2–3 weeks. The control group will receive neither cognitive training nor a placebo intervention. A detailed assessment of psychological functions will be performed ~2–3 weeks before the start of training, at the end of the training, during hospitalization, at discharge from the acute clinic, and 3 months after surgery. The primary objective of this study is to investigate the interventional effect of preoperative cognitive training on the incidence of POD during the stay in the acute clinic, the incidence of POCD at the time of discharge from the acute clinic, and 3 months after surgery. Secondary objectives are to determine the training effect on objective cognitive functions before the surgery and subjective cognitive functions, as well as health-related quality of life 3 months after surgery.

Discussion

Should it become evident that the use of our cognitive training can both reduce the incidence of POCD and POD and improve health-related quality of life, this intervention may be integrated into a standardized prehabilitation program.
Altered functional hubs and connectivity in type 2 diabetes mellitus with and without mild cognitive impairment
Authors: Huang Yang , Zhang Dongsheng , Zhang Xin , Cheng Miao , Yang Zhen , Gao Jie , Tang Min , Ai Kai , Lei Xiaoyan , Zhang Xiaoling
Published: December 2022

Cognitive impairment in type 2 diabetes mellitus (T2DM) is associated with functional and structural abnormalities of brain networks, especially the damage to hub nodes in networks. This study explored the abnormal hub nodes of brain functional networks in patients with T2DM under different cognitive states. Sixty-five patients with T2DM and 34 healthy controls (HCs) underwent neuropsychological assessment. Then, degree centrality (DC) analysis and seed-based functional connectivity (FC) analysis were performed to identify the abnormal hub nodes and the FC patterns of these hubs in T2DM patients with mild cognitive impairment (MCI) (DMCI group, N = 31) and without MCI (DMCN group, N = 34). Correlation analyzes examined the relationship between abnormal DC and FC and clinical/cognitive variables. Compared with HCs, both T2DM groups showed decreased DC values in the visual cortex, and the T2DM patients with MCI (DMCI) showed more extensive alterations in the right parahippocampal gyrus (PHG), bilateral posterior cingulate cortex (PCC), and left superior frontal gyrus (SFG) regions than T2DM patients with normal cognitive function. Seed-based FC analysis of PHG and PCC nodes showed that functional disconnection mainly occurred in visual and memory connectivity in patients with DMCI. Multiple abnormal DC values correlated with neuropsychological tests in patients with T2DM. In conclusion, this study found that the DMCI group displayed more extensive alterations in hub nodes and FC in vision and memory-related brain regions, suggesting that visual-related regions dysfunctions and disconnection may be involved in the neuropathology of visuospatial function impairment in patients with DMCI.