bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of microneedle of Atractylodes macrocephala Rhizoma aqueous extract and effect on mammary gland hyperplasia based on intestinal flora
Authors: Ping Yang , Gao Qi , Li Changxu , Wang Yan , Wang Yuliang , Li Shuo , Qiu Mingjing , Zhang Linqian , Tu Ailing , Tian Yu , Zhao Hong
Published: March 2023

Background

A microneedle patch loaded with Atractylodes macrocephala Rhizoma water extract was prepared for the treatment of mammary gland hyperplasia. To explore the relationship between Mammary gland hyperplasia and intestinal flora.

Materials and methods

Preparation of the microneedle patch by micromolding method, the prescription of the microneedle was optimized by the Box-Behnken Design response surface test, and the micro-morphology, penetration, toughness, and brittleness were investigated. In vitro release of drug-loaded microneedles was measured by diffusion cell method. The rat model of mammary gland hyperplasia was prepared by the combination of estradiol benzoate-progesterone, and the microneedle patch of Atractylodes macrocephala Rhizoma aqueous extract was used for intervention treatment. The change of levels in E2, P, and PRL in rat serum was determined. The intestinal contents of rats were collected and the changes in intestinal flora in MGH rats were analyzed by 16s rRNA high-throughput sequencing.

Results

The optimized microneedle formula is a PVA concentration of 6.0%, HA concentration of 15.5%, and PVPK30 concentration of 16.0%. The prepared microneedle tip loaded with Atractylodes macrocephala Rhizoma aqueous extract has complete, sharp, and no bubbles and the needle rate of the microneedle array is in the range of 95%~100%. The bending rate of the microneedle is about 12.7%, and it has good flexibility, and the microneedle can puncture 4 layers of ParafilmⓇ membrane smoothly, and the puncture rate is more than 96%. The in vitro release of the microneedle was characterized by rapid release. The results of animal experiments showed that Atractylodes macrocephala Rhizoma aqueous extract microneedle patch could significantly reduce the E2 level, significantly reduce the PRL level, and significantly increase the P level. At the same time, it can regulate the abundance and diversity of intestinal flora in MGH rats, improve the intestinal flora disorder caused by mammary gland hyperplasia, and balance the community structure.

Conclusion

The prepared microneedle containing Atractylodes macrocephala Rhizoma aqueous extract has good toughness and brittle strength, can penetrate the skin and enter the dermis, and effectively deliver drugs to play a role in the treatment of mammary gland hyperplasia.
Effects of trigger-day progesterone in the preimplantation genetic testing cycle on the embryo quality and pregnancy outcomes of the subsequent first frozen-thawed blastocyst transfer
Authors: Li Jingdi , Cui Yueyue , Shi Hao , Bu Zhiqin , Wang Fang , Sun Bo , Zhang Yile
Published: March 2023

Objective

To assess whether progesterone (P) levels on the trigger day during preimplantation genetic testing (PGT) cycles are associated with embryo quality and pregnancy outcomes in the subsequent first frozen-thawed blastocyst transfer (FET) cycle.

Methods

In this retrospective analysis, 504 eligible patients who underwent ICSI followed by frozen-thawed embryo transfer (FET) with preimplantation genetic test (PGT) between December 2014 and December 2019 were recruited. All patients adopted the same protocol, namely, the midluteal, short-acting, gonadotropin-releasing hormone agonist long protocol. The cutoff P values were 0.5 and 1.5 ng/ml when serum P was measured on the day of human chorionic gonadotropin (HCG) administration, and cycles were grouped according to P level on the day of HCG administration. Furthermore, the effect of trigger-day progesterone on embryo quality and the subsequent clinical outcome of FET in this PGT population was evaluated.

Results

In total, 504 PGT cycles were analyzed. There was no significant difference in the number of euploid blastocysts, top-quality blastocysts, euploidy rate, or miscarriage rate among the three groups (P>0.05). The 2PN fertilization rate (80.32% vs. 80.17% vs. 79.07%) and the top-quality blastocyst rate (8.71% vs. 8.24% vs. 7.94%) showed a downward trend with increasing P, and the between-group comparisons showed no significant differences (P>0.05). The clinical pregnancy rate (41.25% vs. 64.79%; P<0.05) and live birth rate (35.00% vs. 54.93%; P<0.05) in subsequent FET cycles were substantially lower in the high-P group than in the P ≤ 0.5 ng/ml group. After adjustments were made for confounding variables, multivariate logistic regression analysis revealed that the high-P group had a lower clinical pregnancy rate (adjusted OR, 0.317; 95% CI, 0.145–0.692; P=0.004) and live birth rate (adjusted OR, 0.352; 95% CI, 0.160–0.773; P=0.009) than the low-P group in subsequent FET cycles, and the differences were significant.

Conclusion(s)

This study demonstrates that in the PGT population, elevated P on the trigger day may diminish the top-quality blastocyst rate (although there is no difference in the euploidy rate). Trigger-day P is an important factor influencing clinical outcomes in subsequent FET cycles.
Techno-economic optimal planning of an industrial microgrid considering integrated energy resources
Authors: Ahmed Mohammad Adel , Abbas Ghulam , Jumani Touqeer Ahmed , Rashid Nasr , Bhutto Aqeel Ahmed , Eldin Sayed M.
Published: March 2023

Microgrids have benefited energy systems by getting rid of the abundant use of traditional energy resources, replacing them with distributed generations (DGs). The use of DGs in microgrids not only provides clean and green energy but also reduces the gigantic losses in transmission and distribution lines. Widespread adoption of renewable energy in microgrids saves customers from high fuel prices and provides a sustainable replacement for future fossil fuel depletion. Microgrids have proven to be the latest and most advanced power systems due to their new capabilities to operate in both grid-connected and isolated modes. Microgrids use multiple energy sources simultaneously, which can offset the intermittent behavior of renewable energy sources. In this study, we planned and optimized an industrial microgrid with an annual increase in load, which contains dispatchable generation, non-dispatched generation, and energy storage. In addition, to test the different behavior of a microgrid operating independently or in grid-tied mode, four typical days were selected to show the load demand and solar and wind energy forecast data for the entire year. The power output curves for each typical day were analyzed for every year in both stand-alone and grid-connected modes. Furthermore, to validate the feasibility of the microgrid, the investment and operations costs were also calculated in the paper.
A hybrid discrete state transition algorithm for combinatorial optimization problems
Authors: Hu Enze , He Jianjun , Shen Shuai
Published: March 2023

The discrete state transition algorithm (DSTA) has been wildly applied to deal with combinatorial optimization problems. However, its low convergence accuracy limits its application in large-scale optimization problems. Aiming at the convergence performance and search intensity of the algorithm, a hybrid discrete state transition algorithm (HDSTA) is proposed in this work by introducing tabu search and elite solution set. Firstly, a searching mechanism with the integration of DSTA and tabu search (TS) is established, which allows moving to adjacent solutions at an increased cost to escape from the local optimum. Specifically, a tabu list as adaptive memory is adopted to avoid the loop when deviating from local optima. Secondly, an elite solution set is introduced to integrate the information of the previous optimal solution and the global optimal solution, and the search strategy is modified to expand the range and diversity of candidate solutions. Finally, the proposed HDSTA is verified according to the real data on two well-known optimization problems (staff assignment problem and traveling salesman problem) and the real data of an industrial case. The experimental results show the effectiveness of the proposed algorithm in large-scale optimization problems.
Coupling and interaction between science and technology finance and green development: Based on coupling coordination degree model and panel vector autoregression model
Authors: Gao Chen , Cao Mingshuo , Wen Ya , Li Chenqi
Published: March 2023

Exploring the coupling and coordination between science and technology finance and green development is a critical action that needs to be addressed in achieving high-quality development in China. Based on the coupling coordination degree model and panel vector autoregression (PVAR) model, this paper uses the relevant data of 274 cities in China from 2003 to 2020 to study the relationship between science and technology finance and green development. The results show that: 1) The relationship between science and technology finance and green development has changed from low coupling coordination to medium coupling coordination in the sample period. 2) The Beijing-Tianjin-Hebei, Yangtze River Delta, and Pearl River Delta regions are at a relatively high level of coupling and coordination as a whole, while other regions are at a relatively low level of coupling and coordination. 3) Through the analysis of the spatial characteristics of the coupling coordination degree, it is found that the coupling coordination degree of China’s urban science and technology finance and green development is generally positive spatial autocorrelation. Spatial correlations continue to strengthen over time. 4) By establishing a PVAR model, we examined the interaction between science and technology finance, green development, and their coupling coordination. Science and technology finance, green development and their coupling coordination degree are themselves affected. We have comprehensively and objectively grasped the matching status of China’s urban science and technology finance and green development, providing a reference for promoting the adaptation of science and technology finance to green development.
Chemical leaching from polyethylene mulching films to soil in strawberry farming
Authors: Scopetani Costanza , Selonen Salla , Cincinelli Alessandra , Pellinen Jukka
Published: March 2023

Mulching is a widely practiced agricultural technique able to boost crop productivity and to reduce weed growth and water evaporation. One of the most common materials used for mulching is polyethylene. Polyethylene films are known to contain phthalates, plasticizers recognized as endocrine disruptors, thus able to endanger the hormonal system. Only few data exist on the possible transfer of plasticizers from polyethylene mulching films to agricultural soil, especially in Europe, or on the potential implications for the environment and human health. In this study, we analyzed the occurrence of plasticizers such as phthalates and acetyl tributyl citrate from polyethylene mulching films and soil samples collected from strawberry fields where polyethylene films have been used. The samples were analyzed with a gas chromatograph-mass spectrometer and the results indicated that the soil exposed to polyethylene mulches contained a significantly higher concentration, compared to the control soil, of some of the most common plasticizers, including dibuthyl phthalate, benzylbutyl phthalate and acetyl tributyl citrate. These outcomes highlight the need to carry out further research to understand the potential risks that mulching practices can cause for the environment and human health.
Conditioning on parental mating types can reduce necessary assumptions for Mendelian randomization
Authors: Ejima Keisuke , Liu Nianjun , Mestre Luis Miguel , de los Campos Gustavo , Allison David B.
Published: March 2023

Mendelian randomization (MR) has become a common tool used in epidemiological studies. However, when confounding variables are correlated with the instrumental variable (in this case, a genetic/variant/marker), the estimation can remain biased even with MR. We propose conditioning on parental mating types (a function of parental genotypes) in MR to eliminate the need for one set of assumptions, thereby plausibly reducing such bias. We illustrate a situation in which the instrumental variable and confounding variables are correlated using two unlinked diallelic genetic loci: one, an instrumental variable and the other, a confounding variable. Assortative mating or population admixture can create an association between the two unlinked loci, which can violate one of the necessary assumptions for MR. We simulated datasets involving assortative mating and population admixture and analyzed them using three different methods: 1) conventional MR, 2) MR conditioning on parental genotypes, and 3) MR conditioning on parental mating types. We demonstrated that conventional MR leads to type I error rate inflation and biased estimates for cases with assortative mating or population admixtures. In the presence of non-additive effects, MR with an adjustment for parental genotypes only partially reduced the type I error rate inflation and bias. In contrast, conditioning on parental mating types in MR eliminated the type I error inflation and bias under these circumstances. Conditioning on parental mating types is a useful strategy to reduce the burden of assumptions and the potential bias in MR when the correlation between the instrument variable and confounders is due to assortative mating or population stratification but not linkage.
Exosomal circular RNAs: New player in breast cancer progression and therapeutic targets
Authors: Hussen Bashdar Mahmud , Mohamadtahr Sayran , Abdullah Snur Rasool , Hidayat Hazha Jamal , Rasul Mohammad Fatih , Hama Faraj Goran Sedeeq , Ghafouri-Fard Soudeh , Taheri Mohammad , Khayamzadeh Maryam , Jamali Elena
Published: March 2023

Breast cancer is the most prevalent type of malignancy among women. Exosomes are extracellular vesicles of cell membrane origin that are released via exocytosis. Their cargo contains lipids, proteins, DNA, and different forms of RNA, including circular RNAs. Circular RNAs are new class of non-coding RNAs with a closed-loop shape involved in several types of cancer, including breast cancer. Exosomes contained a lot of circRNAs which are called exosomal circRNAs. By interfering with several biological pathways, exosomal circRNAs can have either a proliferative or suppressive role in cancer. The involvement of exosomal circRNAs in breast cancer has been studied with consideration to tumor development and progression as well as its effects on therapeutic resistance. However, its exact mechanism is still unclear, and there have not been available clinical implications of exo-circRNAs in breast cancer. Here, we highlight the role of exosomal circRNAs in breast cancer progression and to highlight the most recent development and potential of circRNAas therapeutic targets and diagnostics for breast cancer.
Identification of novel variations of oculocutaneous albinism type 2 with Prader–Willi syndrome/Angelman syndrome in two Chinese families
Authors: Chen XiaoFei , Fang ZiShui , Pang Ting , Li DongZhi , Lei Jie , Jiang WeiYing , Li HongYi
Published: March 2023

Objective: Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by a variety of genomic variations. Our aim is to identify the molecular basis of OCA in two families and lay the foundation for prenatal diagnosis.

Methods: Four types of OCA-causing mutations in the TYR, p, TYRP1, or SLC45A2 genes were screened. Linkage analysis was performed because the mutations found in the p gene violated the laws of classical Mendelian heredity. Primer-walking sequencing combined with microsatellite and single-nucleotide polymorphism analysis was used to ascertain deletion ranges. Bioinformatics methods were used to assess the pathogenicity of the new mutations.

Results: Proband 1 was diagnosed as OCA2 with Prader–Willi syndrome (PWS) due to a novel atypical paternal deletion (chromosome 15: 22330347–26089649) and a pathogenic mutation, c.1327G>A (Val443Ile), in the p gene of the maternal chromosome. The prenatal diagnosis results for family 1 indicated the fetus was a heterozygous carrier (c.1327G>A in the p gene) with a normal phenotype. Proband 2 was diagnosed as OCA2 with Angelman syndrome (AS) due to a typical maternal deletion of chromosome 15q11-q13 and a novel mutation, c.1514T>C (Phe505Ser), in the p gene of the paternal chromosome. This novel mutation c.1514T>C (Phe505Ser) in the p gene was predicted as a pathogenic mutation.

Conclusion: Our study has shown clear genotype–phenotype correlations in patients affected by distinct deletions of the PWS or AS region and missense mutations in the p gene. Our results have enriched the mutation spectrum of albinism diseases and provided insights for more accurate diagnosis and genetic counseling.
Prediction of apoptosis protein subcellular location based on amphiphilic pseudo amino acid composition
Authors: Su Wenxia , Deng Shuyi , Gu Zhifeng , Yang Keli , Ding Hui , Chen Hui , Zhang Zhaoyue
Published: March 2023

Introduction: Apoptosis proteins play an important role in the process of cell apoptosis, which makes the rate of cell proliferation and death reach a relative balance. The function of apoptosis protein is closely related to its subcellular location, it is of great significance to study the subcellular locations of apoptosis proteins. Many efforts in bioinformatics research have been aimed at predicting their subcellular location. However, the subcellular localization of apoptotic proteins needs to be carefully studied.

Methods: In this paper, based on amphiphilic pseudo amino acid composition and support vector machine algorithm, a new method was proposed for the prediction of apoptosis proteins\x{2019} subcellular location.

Results and Discussion: The method achieved good performance on three data sets. The Jackknife test accuracy of the three data sets reached 90.5%, 93.9% and 84.0%, respectively. Compared with previous methods, the prediction accuracies of APACC_SVM were improved.
Unique profile on the progress free survival and overall survival in patients with advanced non-small cell lung cancer in the Qujing area, Southwest China
Authors: Ma Yuhui , Shi Hutao , Zhao Guangqiang , Liu Xin , Cai Jingjing , Li Guangjian , Chen Wanlin , Lei Yujie , Ye Lianhua , Fu Chaojiang , Zhao Li , Zhou Yongchun , Huang Yunchao
Published: March 2023

Background

China’s southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing.

Methods

Tissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy.

Results

In cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations.

Conclusions

These findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.
Characteristics of cardiac involvement in immune-mediated necrotizing myopathy
Authors: Liu Mengyang , Lin Ying , Qiao Lingya , Chen Juan , Shi Qiang
Published: March 2023

Objective

To investigate the characteristics of cardiac involvement due to Immune-mediated Necrotizing Myopathy (IMNM).

Methods

Patients diagnosed with Immune-mediated Necrotizing Myopathy (IMNM) who attended the Department of Neurology and the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital between February 2011 and June 2022 were collected. Clinicopathological diagnosis of IMNM was performed according to the criteria established by the European Neuromuscular Center (ENMC). All patients underwent muscle biopsy and Myositis-specific antibodies (MSAs) testing. Information included age, gender, disease duration, intramuscular and extramuscular manifestations, laboratory findings (including creatine kinase, lactate dehydrogenase levels, troponin T, myoglobin and atrial natriuretic peptide), electromyography, skeletal muscle pathology and immunohistochemical staining.

Results

A total of 57 patients were included in this study. Of the serological tests, 56.1% (32/57) were positive for SRP, 21.1% (12/57) were positive for HMGCR and 22.8% (13/57) were seronegative. Thirty patients (52.6%, 30/57) presented with varying degrees of cardiac involvement. We performed ECG in 23 patients and found 6 patients with arrhythmia (26.1%), 12 patients with myocardial ischemia (52.2%), and 7 patients with acute coronary syndrome (ST elevation and non-ST elevation myocardial infarction) (30.4%), and 4 patients with left axis deviation or left ventricular high voltage, suggesting left ventricular hypertrophy (17.4%). Cardiac ultrasound was performed in 14 patients and 3 showed pericardial effusion (21.4%); Decreased left ventricular ejection fraction and atrial enlargement were 2 each; 8 showed a decrease in left ventricular diastolic function (57.1%). In addition, one patient had myocardial edema.

Conclusion

Cardiac involvement is not uncommon in IMNM. However, besides clearly statistically significant differences in the disease course, and in the values of troponin T and myoglobin, our data did not show any statistically significant difference in other features of cardiac involvement between patients with different subtypes of IMNM.
Partial immune responses in Sichuan bream (Sinibrama taeniatus) after starvation
Authors: Shi Jinfeng , Zhuo Dayou , Lu Minfang , Wang Haoyu , Gu Haoran , Liu Xiaohong , Wang Zhijian
Published: March 2023

Background

Food deprivation is a severe stress across multiple fields and it might be a challenge to immune system.

Methods

In the present study, adult male Sinibrama taeniatus were deprived of feed for 7 to 28 days. We explored the effects of starvation on immunity in S. taeniatus through hematological analysis, antioxidant capacity analysis, detection of the content or activity of immune factors in plasma, and transcriptomic analysis.

Results

The results indicated that biometric indexes significantly decreased in the fish after starvation, the proportion of thrombocyte, neutrophil and monocyte increased and, conversely, the proportion of lymphocyte decreased. The antioxidant indexes (SOD and CAT) and innate immune parameters (LZM, C3) were upregulated in fish suffering from a short period of starvation, while adaptive immune parameter (IgM) conversely declined. The transcriptome analysis revealed the changes of various metabolic regulatory pathways involved in fatty acids and amino acids, as well as the immune responses and antioxidant capacity.

Conclusions

Taken together, this research in the present study suggested an induced innate immunity while a partly suppressed adaptive immunity under a short period starvation.
Unraveling cross-reactivity of anti-glycan IgG responses in filarial nematode infections
Authors: Petralia Laudine M. C. , van Diepen Angela , Nguyen Dieu-Linh , Lokker Lena A. , Sartono Erliyani , Bennuru Sasisekhar , Nutman Thomas B. , Pfarr Kenneth , Hoerauf Achim , Wanji Samuel , Foster Jeremy M. , Hokke Cornelis H.
Published: March 2023

Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode Brugia malayi and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing Brugia malayi glycans with plasma from uninfected individuals and from individuals infected with Loa loa, Onchocerca volvulus, Mansonella perstans and Wuchereria bancrofti, four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from Onchocerca volvulus and Mansonella perstans infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of Brugia malayi infected individuals. For these infection groups, Brugia malayi, Onchocerca volvulus and Mansonella perstans, we further studied the different IgG subclasses to Brugia malayi glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in Brugia malayi infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of Brugia malayi glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.
Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells
Authors: Hiltensperger Michael , Krackhardt Angela M.
Published: March 2023

Adoptive cell therapy (ACT) has seen a steep rise of new therapeutic approaches in its immune-oncology pipeline over the last years. This is in great part due to the recent approvals of chimeric antigen receptor (CAR)-T cell therapies and their remarkable efficacy in certain soluble tumors. A big focus of ACT lies on T cells and how to genetically modify them to target and kill tumor cells. Genetically modified T cells that are currently utilized are either equipped with an engineered CAR or a T cell receptor (TCR) for this purpose. Both strategies have their advantages and limitations. While CAR-T cell therapies are already used in the clinic, these therapies face challenges when it comes to the treatment of solid tumors. New designs of next-generation CAR-T cells might be able to overcome these hurdles. Moreover, CARs are restricted to surface antigens. Genetically engineered TCR-T cells targeting intracellular antigens might provide necessary qualities for the treatment of solid tumors. In this review, we will summarize the major advancements of the CAR-T and TCR-T cell technology. Moreover, we will cover ongoing clinical trials, discuss current challenges, and provide an assessment of future directions within the field.
Blockade of endothelin-1 receptor B regulates molecules of the major histocompatibility complex in sickle cell disease
Authors: Inostroza-Nieves Yaritza , Rivera Alicia , Romero José R.
Published: March 2023

Major Histocompatibility Complex (MHC) molecules have been proposed to play a role in Sickle Cell Disease (SCD) pathophysiology. Endothelial cells express MHC molecules following exposure to cytokines. SCD is characterized, in part, by vascular endothelial cell activation, increased oxidative stress, sickle cell adhesion, and excess levels of endothelin-1 (ET-1) contributing to vaso-occlusive crises. ET-1 activates endothelial cells, induces oxidative stress and inflammation, and alters erythrocyte volume homeostasis. However, the role of ET-1 on MHC regulation in SCD is unclear. We first studied two sickle transgenic knockout mouse models of moderate to severe disease phenotype, βS-Antilles and Berkeley (BERK) mice. We observed significant increases in H2-Aa mRNA levels in spleens, lungs, and kidneys from transgenic sickle mice when compared to transgenic knockout mice expressing human hemoglobin A (HbA). Mice treated for 14 days with ET-1 receptor antagonists significantly reduced H2-Aa mRNA levels. We characterized the effect of ET-1 on MHC class II expression in the human endothelial cell line EA.hy926. We observed dose-dependent increases in the expression of MHC class II (HLA-DRA) and MHC transcription factor (CIITA) that were significantly blocked by treatment with BQ788, a selective blocker of ET-1 type B receptors. Chromatin immunoprecipitation studies in EA.hy926 cells showed that ET-1 increased Histone H3 acetylation of the HLA-DRA promoter, an event blocked by BQ788 treatment. These results implicate ET-1 as a novel regulator of MHC class II molecules and suggest that ET-1 receptor blockade represents a promising therapeutic approach to regulate both immune and vascular responses in SCD.
Case report: Novel variants in RELA associated with familial Behcet’s-like disease
Authors: An Jason W. , Pimpale-Chavan Pallavi , Stone Deborah L. , Bandeira Marcia , Dedeoglu Fatma , Lo Jeffrey , Bohnsack John , Rosenzweig Sofia , Schnappauf Oskar , Dissanayake Dilan , Hiraki Linda T. , Kastner Daniel L. , Pelajo Christina , Laxer Ronald M. , Aksentijevich Ivona
Published: March 2023

RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet’s Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.
Clonal relationships of memory B cell subsets in autoimmune mice
Authors: Aranburu Alaitz , Engström Erik , Gerasimcik Natalija , Alsén Samuel , Camponeschi Alessandro , Yrlid Ulf , Grimsholm Ola , Mårtensson Inga-Lill
Published: March 2023

Immunological memory protects our body from re-infection and it is composed of a cellular and a humoral arm. The B-cell branch with its memory B cells (MBCs), plasma cells and antibodies, formed either in a germinal centre (GC) -dependent or -independent manner, ensure that we can rapidly mount a recall immune response. Previous work in immunised wildtype (WT) mice have identified several subsets of MBCs whereas less is known under autoimmune conditions. Here, we have investigated the heterogeneity of the MBC compartment in autoimmune mouse models and examined the clonal relationships between MBC subsets and GC B cells in one of the models. We demonstrate the presence of at least four different MBC subsets based on their differential expression pattern of CD73, CD80 and PD-L2 in surrogate light chain-deficient (SLC-/-), MRL+/+ and MRLlpr/lpr mice, where most of the MBCs express IgM. Likewise, four MBC subsets could be identified in WT immunised mice. In SLC-/- mice, high-throughput sequencing of Ig heavy chains demonstrates that the two CD73-positive subsets are generally more mutated. Lineage tree analyses on expanded clones show overlaps between all MBC subsets and GC B cells primarily in the IgM sequences. Moreover, each of the three IgM MBC subsets could be found both as ancestor and progeny to GC B cells. This was also observed in the IgG sequences except for the CD73-negative subset. Thus, our findings demonstrate that several MBC subsets are present in autoimmune and WT mice. In SLC-/- mice, these MBC subsets are clonally related to each other and to GC B cells. Our results also indicate that different MBC subsets can seed the GC reaction.
An external quality assessment feasibility study; cross laboratory comparison of haemagglutination inhibition assay and microneutralization assay performance for seasonal influenza serology testing: A FLUCOP study
Authors: Waldock Joanna , Weiss Carol D. , Wang Wei , Levine Min Z. , Jefferson Stacie N. , Ho Sammy , Hoschler Katja , Londt Brandon Z. , Masat Elisa , Carolan Louise , Sánchez-Ovando Stephany , Fox Annette , Watanabe Shinji , Akimoto Miki , Sato Aya , Kishida Noriko , Buys Amelia , Maake Lorens , Fourie Cardia , Caillet Catherine , Raynaud Sandrine , Webby Richard J. , DeBeauchamp Jennifer , Cox Rebecca J. , Lartey Sarah L. , Trombetta Claudia M. , Marchi Serena , Montomoli Emanuele , Sanz-Muñoz Iván , Eiros José María , Sánchez-Martínez Javier , Duijsings Danny , Engelhardt Othmar G.
Published: March 2023

Introduction

External Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods.

Methods

We invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays.

Results

Within run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter-laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization.

Discussion

This study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing.
Immune response and drug therapy based on ac4C-modified gene in pancreatic cancer typing
Authors: Xu Dong , Huang Kaige , Chen Yang , Yang Fei , Xia Cunbing , Yang Hongbao
Published: March 2023

N-4 cytidine acetylation (ac4C) is an epitranscriptome modification catalyzed by N-acetyltransferase 10 (NAT10) and is essential for cellular mRNA stability, rRNA biosynthesis, cell proliferation, and epithelial-mesenchymal transition (EMT). Numerous studies have confirmed the inextricable link between NAT10 and the clinical characteristics of malignancies. It is unclear, however, how NAT10 might affect pancreatic ductal adenocarcinoma. We downloaded pancreatic ductal adenocarcinoma patients from the TCGA database. We obtained the corresponding clinical data for data analysis, model construction, differential gene expression analysis, and the GEO database for external validation. We screened the published papers for NAT10-mediated ac4C modifications in 2156 genes. We confirmed that the expression levels and genomic mutation rates of NAT10 differed significantly between cancer and normal tissues. Additionally, we constructed a NAT10 prognostic model and examined immune infiltration and altered biological pathways across the models. The NAT10 isoforms identified in this study can effectively predict clinical outcomes in pancreatic ductal adenocarcinoma. Furthermore, our study showed that elevated levels of NAT10 expression correlated with gemcitabine resistance, that aberrant NAT10 expression may promote the angiogenic capacity of pancreatic ductal adenocarcinoma through activation of the TGF-β pathway, which in turn promotes distal metastasis of pancreatic ductal adenocarcinoma, and that NAT10 knockdown significantly inhibited the migration and clonogenic capacity of pancreatic ductal adenocarcinoma cells. In conclusion, we proposed a predictive model based on NAT10 expression levels, a non-invasive predictive approach for genomic profiling, which showed satisfactory and effective performance in predicting patients’ survival outcomes and treatment response. Medicine and electronics will be combined in more interdisciplinary areas in the future.
Appropriate pre-transplant strategy for patients with myelodysplastic syndromes receiving allogeneic haematopoietic stem cell transplantation after myeloablative conditioning
Authors: Wang Hong , Wang Qingyuan , Qi Jiaqian , Li Xueqian , Chu Tiantian , Qiu Huiying , Fu Chengcheng , Tang Xiaowen , Ruan Changgeng , Wu Depei , Han Yue
Published: March 2023

Purpose

Appropriate pre-transplant strategies in patients with myelodysplastic syndromes (MDS) remain challenging. We sought to assess the effect of different pre-transplant therapies and transplantation interval times on patient prognosis.

Methods

We retrospectively analysed clinical data for 371 consecutive MDS patients after myeloablative transplantation between 2007 and 2019.

Results

The median age of the patients was 38 years (range, 12–64 years). A total of 114 patients (31%) received supportive care (SC), 108 (29%) hypomethylating agents (HMAs), and 149 (40%) chemotherapy-based therapy before transplantation. In patients who received HMA or SC, there was no significant difference in overall survival (OS; P=0.151) or relapse-free survival (RFS; P=0.330), except that HMA-treated patients had a lower rate of non-relapse mortality (5-year NRM: 18% vs. 32%, P=0.035). However, compared with patients who received HMA, those who received chemotherapy-based therapy had a lower 5-year OS rate (56% vs. 69%, P=0.020) and a slightly higher 5-year NRM rate (28% vs. 18%, P=0.067). Compared to the delayed transplant group (transplant interval ≥6 months), the early transplant group (transplant interval <6 months) had a superior 5-year OS (66% vs. 51%, P=0.001) and a lower 5-year cumulative incidence of NRM (22% vs. 36%, P=0.001).

Conclusion

The findings of the study indicate that receiving an appropriate pre-transplant strategy (SC/HMA + <6 months) significantly improves OS and decreases NRM in MDS patients after myeloablative transplantation.
Ophiotholia (Echinodermata: Ophiuroidea): A little-known deep-sea genus present in polymetallic nodule fields with the description of a new species
Authors: Eichsteller Angelina , Martynov Alexander , O’Hara Timothy D. , Christodoulou Magdalini , Korshunova Tatiana , Bribiesca-Contreras Guadalupe , Martinez Arbizu Pedro
Published: March 2023

Introduction

The Clarion Clipperton Zone (CCZ) in the Northeast Pacific Ocean holds the largest deposits of polymetallic nodules at abyssal depths. These nodules are rock formations containing valuable metals and minerals targeted for mining. They further provide diverse habitat for a range of deep-sea species. Little is known so far on the taxonomy, natural history and biogeography of these deep-sea animals which is vital for accurate assessment of the risk of species extinctions from large-scale mining. One of the most abundant megafaunal groups in the CCZ is the Ophiuroidea (brittle stars), of which Ophiotholia is one of the more abundant genera found in the area. The genus Ophiotholia has a world-wide distribution and currently holds six species.

Methods

Material collected from seven scientific cruises to the CCZ was examined, morphologically, together with comparative material from all the known species. The small size and the damage caused during sampling often impeded their identification. The specimens were also genetically analyzed using a fragment of the mitochondrial COI gene. Scanning Electron Microscope images of the key microstructural characters were made using selected specimens from CCZ as well as from the comparative material.

Result and discussion

One morphotype was identified as the known species Ophiotholia supplicans Lyman, 1880, while the second is new to science and is described in this paper. The umbrella spines and the arrangement of their articulations on the lateral arm plate, were selected as the most relevant morphological characters in the taxonomy of the genus Ophiotholia and a revised identification key of all characters from all known Ophiotholia species is provided as a table in the supplement material. The identification and description of such a little-known genus improves the evaluation of the biodiversity not only in the CCZ but also for the deep sea.
Role of fungi in bioremediation of emerging pollutants
Authors: Vaksmaa Annika , Guerrero-Cruz Simon , Ghosh Pooja , Zeghal Emna , Hernando-Morales Victor , Niemann Helge
Published: March 2023

Advancements in chemical, medical, cosmetic, and plastic producing industries have improved agricultural yields, health and human life in general. As a negative consequence, a plethora of chemicals are intentionally and unintentionally released to terrestrial and aquatic environments with sometimes devastating effects for entire ecosystems. One mitigation strategy to counteract this pollution is bioremediation. Bioremediation is an umbrella term for biologically mediated processes during which an undesired compound is transformed, degraded, sequestered and/or entirely removed from the ecosystem. Organisms across all domains of life may mediate bioremediation; yet, fungi are particularly promising candidates. They possess metabolic capabilities to break down complex molecules which make fungi the ultimate degraders of recalcitrant organic matter in nature. Bioremediation by fungi, also termed mycoremediation, has been more frequently investigated in terrestrial than aquatic ecosystems, although fungi also thrive in lacustrine and marine environments. Here, we focus on mycoremediation of emerging pollutants in aquatic environments. In this context, we draw parallels between terrestrial and aquatic fungal taxa, and their role in mycoremediation. We discuss the ability of fungi to break-down (i) pesticides, (ii) pharmaceuticals and personal care products, (iii) plastics, both conventional types and (iv) bioplastics, and fungal role, (v) mitigation of heavy metal pollution. Furthermore, we (vi) discuss possible mycoremediation strategies in applied settings and highlight novel enzyme based mycoremediation strategies.
Effects of river input flux on spatiotemporal patterns of total nitrogen and phosphorus in the Pearl River Estuary, China
Authors: Ke Sheng , Cai Zhimei , Zhang Peng , Zhang Junxiao , Zhang Jibiao
Published: March 2023

The increasing riverine nutrient sources have significantly affected the ecological environment of estuaries and coastal waters, resulting in deteriorating land-sea water quality and intensified eutrophication. However, the effects of river input flux on spatiotemporal patterns of total nitrogen (TN) and total phosphorus (TP) were poorly understood in the Pearl River Estuary (PRE). In this study, the spatiotemporal patterns of TN and TP concentrations and river input flux of PRE were studied based on the seasonal nutrients monitoring data obtained for the rivers and estuary in 2019. The results showed the spatiotemporal patterns of the TN and TP concentrations in the eight rivers of the PRE were different, and the annual average concentrations of TN and TP in the rivers entering the PRE were 207.18 ± 105.13 and 3.51 ± 1.70 μmol/L, respectively. The annual river TN and TP fluxes discharged into the PRE were 8.61 × 1010 and 1.55 × 109 mol/year, respectively. In addition, the significantly decreasing trends in of TN and TP concentrations from upper estuary to offshore seawater were observed in the PRE, which implied TN and TP showed conservative behaviour in all season and only the dry season, respectively. Moreover, the annual average concentrations of TN and TP in the estuary were 70.64 ± 10.10 and 1.67 ± 0.78 μmol/L, respectively. The annual average ratios of TN/TP for rivers, freshwater, mixed and seawater were 59.31 ± 5.98, 59.45 ± 3.75, 45.73 ± 21.27 and 330.94 ± 434.71 respectively, which were higher than the Redfield ratios. These results indicated that the water quality in most areas of the PRE is significantly polluted and that the TN and TP in seawater were significantly influenced by river inputs. Therefore, monitoring and management of unified TN and TP nutrient indicators discharge from rivers entering the sea can be strengthened in the PRE, and eutrophication mitigation strategy should be established and implemented across river-estuary-coast continuum systems in the Great Bay Area.