bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant Antibody-Based and Computer-Aided Comprehensive Analysis of Antibody’s Equivalent Recognition Mechanism of Alternariol and Alternariol Monomethyl Ether
Authors: Wang Zile , Chen Ling , Zheng Pimiao , Wang Jianyi , Ren Zhenhui , Zhang Huixia , Zhang Liang , Jiang Haiyang
Published: January 2023

Alternariol (AOH) and alternariol monomethyl ether (AME) are two main Alternaria mycotoxins that endanger human health. In this study, a single-chain antibody fragment (scFv) capable of equivalently and specifically recognizing AOH and AME was first expressed, and its equivalent recognition mechanism was discussed. According to molecular docking and dynamic simulation, the C9 site, which was always exposed outside the binding cavity, made the structural differences between AOH and AME negligible. Due to the high similarity of structures, AOH and AME interacted with almost the same amino acids on the scFv; thus, the same interaction mode and interaction force were produced. This was considered to be the most critical reason for the equivalent recognition. Thus, the exposure of common structures was considered a potential strategy to obtain the equivalent recognition antibodies, and C9 was considered the key site in the process of hapten modification. These results laid a theoretical foundation for further research on antibodies against Alternaria mycotoxins. It could promote the rapid detection of AOH and AME in food and provide a new idea for targeted preparation of antibodies that could recognize multiple hazards with similar structures.
Oxygen Plasma Modified Carbon Cloth with C=O Zincophilic Sites as a Stable Host for Zinc Metal Anodes
Authors: Jiang Baozheng , Liu Wenbao , Ren Zhilong , Guo Rongsheng , Huang Yongfeng , Xu Chengjun , Kang Feiyu
Published: January 2023

Aqueous zinc-ion batteries (ZIBs) are currently receiving widespread attention due to their merits of environmental-friendly properties, high safety, and low cost. However, the absence of stable zinc metal anodes severely restricts their potential applications. In this work, we demonstrate a simple oxygen plasma treatment method to modify the surface state of carbon cloth to construct an ideal substrate for zinc deposition to solve the dendrite growth problem of zinc anodes. The plasma treated carbon cloth (PTCC) electrode has lower nucleation overpotential and uniformly distributed C=O zincophilic nucleation sites, facilitating the uniform nucleation and subsequent homogeneous deposition of zinc. Benefiting from the superior properties of PTCC substrate, the enhanced zinc anodes demonstrate low voltage hysteresis (about 25 mV) and stable zinc plating/stripping behaviors (over 530 h lifespan) at 0.5 mA cm−2 with 15% depth of discharge (DOD). Besides, an extended cycling lifespan of 480 h can also be achieved at very high DOD of 60%. The potential application of the enhanced zinc anode is also confirmed in Zn|V10O24·12H2O full cell. The cells with Zn@PTCC electrode demonstrate remarkable rate capability and excellent cycling stability (95.0% capacity retention after 500 cycles).
Recent advances in the removal of radioactive iodine by bismuth-based materials
Authors: Hao Yuxun , Tian Zhenjiang , Liu Chuanying , Xiao Chengliang
Published: January 2023

Nowadays, the demand for nuclear power is continue increasing due to its safety, cleanliness, and high economic benefits. Radioactive iodine from nuclear accidents and nuclear waste treatment processes poses a threat to humans and the environment. Therefore, the capture and storage of radioactive iodine are vital. Bismuth-based (Bi-based) materials have drawn much attention as low-toxicity and economical materials for removing and immobilizing iodine. Recent advances in adsorption and immobilization of vapor iodine by the Bi-based materials are discussed in this review, in addition with the removal of iodine from solution. It points out the neglected areas in this research topic and provides suggestions for further development and application of Bi-based materials in the removal of radioactive iodine.
Metal-polyphenol polymer modified polydopamine for chemo-photothermal therapy
Authors: Xu Li , Luo Zhibing , Liu Qing , Wang Chuancui , Zhou Fei , Zhou Min
Published: January 2023

Chemotherapy combined with photothermal therapy (PTT) is a new way to improve the curative effect of cancer treatment. Here, we developed a multifunctional nanoparticle, namely PTX@mPDA@Fe-GA with the loading of a chemotherapeutic drug paclitaxel (PTX) for targeted and synergistic chemotherapy/photothermal therapy in lung cancer. Fe-gallic acid (Fe-GA) was coated on the surface of mesoporous polydopamine (mPDA) nanoparticles, and then the PTX was placed in the mesopores. The drug release of the loaded PTX exhibited pH- and thermal-dual responsive manner. Both mPDA and Fe-GA have high photothermal conversion ability and play a role in photothermal therapy. In addition, the results revealed that mPDA@Fe-GA had excellent biocompatibility and low hemolysis rate. The PTX-loaded mPDA@Fe-GA not only has excellent killing effect on lung cancer cells (A549) in vitro, but also can significantly suppress the growth of A549 subcutaneous tumor in nude mice. In a nutshell, the developed multifunctional nanoparticles integrate photothermal therapy and efficient chemotherapeutic drug delivery, providing new therapeutic ideas in the fight against lung cancer.
Rapid diagnosis of non-tuberculous mycobacterial pulmonary diseases by metagenomic next-generation sequencing in non-referral hospitals
Authors: Wang Jing , Xu Huan , Wang Xi , Lan Jian
Published: January 2023

Objectives

The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased steadily globally, but the current culture-based diagnosis of NTM-PD is difficult and time-consuming, leading to a high possibility of misdiagnosis. Therefore, new methods should be introduced to improve the processes for clinical diagnosis of this disease.

Methods

Our retrospective observational study enrolled 12 NTM-PD patients who were identified by way of metagenomic next-generation sequencing (mNGS), as well as the characteristic radiological presentation of slowly progressed, usually concomitant bronchiectasis, small cavitary opacity, and multiple nodules that respond poorly to empirical antibiotic therapy. These patients received the recommended drug regimen based on the identified non-tuberculous mycobacteria (NTM) species. Clinical data, including symptoms, laboratory tests, dynamic computed tomography imaging, treatment, and outcome, were recorded and analyzed.

Results

The results of mNGS were all positive, with the standard specifically mapped read numbers (SDSMRN) of NTM ranging from 1 to 766; this was confirmed in six patients via quantitative polymerase chain reaction (qPCR) analysis. The duration fromsample collection tomNGS results was 1–4 days. Among our 12 patients (except for one lost to follow-up) the CT imaging for 11 patients showed significant absorption of lesions.

Conclusions

Our results draw attention to NTM infection as a possible cause of community-acquired pneumonia, especially in patients with suggestive radiological presentation and poor responses to empirical antibiotic therapy. Our study also indicated that mNGS represented a potentially effective tool for the rapid identification of NTM in the respiratory sample. Improved clinician awareness combined with the utilization of mNGS could guide earlier diagnosis and targeted treatment, and finally improved the prognoses of patients with NTM-PD.
Evaluation of contemporary echocardiographic and histomorphology parameters in predicting mortality in patients with endomyocardial biopsy-proven cardiac AL amyloidosis
Authors: Koutroumpakis Efstratios , Niku Adam , Black Christopher K. , Ali Abdelrahman , Sadaf Humaira , Song Juhee , Palaskas Nicolas , Iliescu Cezar , Durand Jean-Bernard , Yusuf Syed Wamique , Lee Hans C. , Buja L. Maximilian , Deswal Anita , Banchs Jose
Published: January 2023

Introduction

This study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis.

Methods

Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization.

Results

Of 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (<13.5%) and absence of SCT as a time-varying covariate were significantly associated with increased risk of death in the multivariate cox regression analysis. Higher LV mass and lower RV tricuspid annular plane systolic excursion were associated with increased odds of having ≥5% interstitial amyloid deposition on biopsy in the multivariate logistic regression analysis.

Conclusion

Lower LA strain independently predicted mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be beneficial. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. These findings need to be confirmed by larger studies in the era of contemporary systemic therapies.
Public elementary schools' handling of student neglect and adjustment problems
Authors: Ikhrom Ikhrom , Dalmeri Dalmeri , Wahyuni Endang , Kafipour Reza
Published: January 2023

The challenge of being able to respond to student adjustment needs in elementary schools is a problem worldwide. In this manuscript, we offer one example from Indonesia. Using data from 15 public elementary schools from three small regions in Indonesia: Semarang, Surabaya, and Jakarta, we analyze conditions that result in neglect. Student neglect is any inappropriate action by an incompetent person that results in serious physical or emotional harm, or abuse, which presents a serious risk of harm to the student. The data were collected through documentation, interview, and observation. The study results showed no specific handling adjustment problems regulations and mechanisms, specialized professional staff handling adjustment, and specific room for handling adjustment problems within the public elementary school due to the unawareness, misunderstanding, ignorance, the less-caring educational system, and also the disconnection of the relationship between the educational institution and the community. The study suggests that student neglect on adjustment problems at public elementary schools should not be taken lightly because this can threaten the psychological condition of students in the future.
Comparison of S-Detect and thyroid imaging reporting and data system classifications in the diagnosis of cytologically indeterminate thyroid nodules
Authors: Zhou Ling , Zheng Lin-lin , Zhang Chuan-ju , Wei Hong-fen , Xu Li-long , Zhang Mu-rui , Li Qiang , He Gao-fei , Ghamor-Amegavi Edem Prince , Li Shi-yan
Published: January 2023

Purpose

The aim of this study was to investigate the value of S-Detect for predicting the malignant risk of cytologically indeterminate thyroid nodules (CITNs).

Methods

The preoperative prediction of 159 CITNs (Bethesda III, IV and V) were performed using S-Detect, Thyroid Imaging Reporting and Data System of American College of Radiology (ACR TI-RADS) and Chinese TI-RADS (C-TIRADS). First, Linear-by-Linear Association test and chi-square test were used to analyze the malignant risk of CITNs. McNemar’s test and receiver operating characteristic curve were used to compare the diagnostic efficacy of S-Detect and the two TI-RADS classifications for CITNs. In addition, the McNemar’s test was used to compare the diagnostic accuracy of the above three methods for different pathological types of nodules.

Results

The maximum diameter of the benign nodules was significantly larger than that of malignant nodules [0.88(0.57-1.42) vs 0.57(0.46-0.81), P=0.002]. The risk of malignant CITNs in Bethesda system and the two TI-RADS classifications increased with grade (all P for trend<0.001). In all the enrolled CITNs, the diagnostic results of S-Detect were significantly different from those of ACR TI-RADS and C-TIRADS, respectively (P=0.021 and P=0.007). The sensitivity and accuracy of S-Detect [95.9%(90.1%-98.5%) and 88.1%(81.7%-92.5%)] were higher than those of ACR TI-RADS [87.6%(80.1%-92.7%) and 81.8%(74.7%-87.3%)] (P=0.006 and P=0.021) and C-TIRADS [84.3%(76.3%-90.0%) and 78.6%(71.3%-84.5%)] (P=0.001 and P=0.001). Moreover, the negative predictive value and the area under curve value of S-Detect [82.8% (63.5%-93.5%) and 0.795%(0.724%-0.855%)] was higher than that of C-TIRADS [54.8%(38.8%-69.8%) and 0.724%(0.648%-0.792%] (P=0.024 and P=0.035). However, the specificity and positive predictive value of S-Detect were similar to those of ACR TI-RADS (P=1.000 and P=0.154) and C-TIRADS (P=1.000 and P=0.072). There was no significant difference in all the evaluated indicators between ACR TI-RADS and C-TIRADS (all P>0.05). The diagnostic accuracy of S-Detect (97.4%) for papillary thyroid carcinoma (PTC) was higher than that of ACR TI-RADS (90.4%) and C-TIRADS (87.8%) (P=0.021 and P=0.003).

Conclusion

The diagnostic performance of S-Detect in differentiating CITNs was similar to ACR TI-RADS and superior to C-TIRADS, especially for PTC.
An improved TOPSIS-ANP composite shielding material performance evaluation method based on gray relational projection algorithm
Authors: Zhang Kan , Liang Xin , Wei Hua , Liu Sishi , Su Kai
Published: January 2023

The performance of shielding materials directly affects the radiation protection effect and plays a very important role in the process of ensuring the safety of nuclear energy. Therefore, this paper introduces the performance evaluation of composite shielding materials, which firstly points out the disadvantages of the traditional TOPSIS method, proposes a weighted projection model of composite shielding materials under extended TOPSIS theory, and clarifies the principle of projection dimensional reduction and algorithm implementation. Secondly, this paper also introduces the basic assumption of non-linear mapping relationship between index dimensions, and scientifically determines the weight of index system based on ANP structural model, so as to form an improved TOPSIS-ANP composite shielding material performance evaluation method based on gray relational projection algorithm with coupling characteristics. The empirical results show that the improved TOPSIS-ANP composite shielding material evaluation method proposed in this paper is consistent with the conclusion of the ratio of lead-boron-polyethylene shielding materials optimized based on genetic algorithm, which proves the effectiveness of the evaluation method proposed in this paper. Meanwhile, the evaluation index system of this method is more comprehensive, and the evaluation method is more efficient and scientific as well, which has a good promotion prospects and application advantages.
Numerical study on the mechanism of fluid energy transfer in an axial flow pump impeller under the rotating coordinate system
Authors: Guo Yanlei , Yang Congxin , Mo Yingxiang , Wang Yan , Lv Tianzhi , Zhao Sen
Published: January 2023

It is a necessary condition to obtain the fluid movement law and energy transfer and loss mechanism in the impeller of the axial pump for achieving an efficient and accurate design of the axial flow pump. Based on the shear stress transport k-ω turbulence model, a three-dimensional unsteady numerical simulation of the whole flow field of an axial flow pump was presented at different flow rates. Combined with the Bernoulli equation of relative motion, the flow field structure in the impeller under design condition was studied quantitatively in the rotating coordinate system. The fluid movement law and energy transfer and loss mechanism in the impeller of the axial flow pump was described in detail. In the relative coordinate system, the mechanical energy of the fluid on the same flow surface conserves. The dynamic energy is continuously transformed into pressure energy from the leading edge to the trailing edge and the dynamic energy is continuously transformed into pressure energy from the leading edge to the trailing edge. The energy conversion is mainly completed in the front half of the blade. The friction loss and the mixing loss are the basic sources of losses in the impeller flow passage. Most hydraulic losses of impeller flow passage are caused by friction and the hydraulic losses near the trailing edge are dominated by mixing loss. This research has certain reference significance for further understanding the flow field structure in the impeller of the axial flow pump, improving its design theory and method, and then realizing its efficient and accurate design of the axial flow pump.
Nexus Between Economic Development and Energy Poverty to Gain Energy Efficiency: Empirical Evidence From China
Authors: Anser Muhammad Khalid , Yusop Zulkornain , Abbas Shujaat , Ali Sajid , Ahmad Munir
Published: January 2023

Mediating the nexus between economic development, energy poverty, and energy efficiency has become a major issue for governments. Evidence from China shows that both sectors have an important role in determining economic development policies and alleviating poverty. Economic development in China is examined experimentally in this research. This study makes use of the Data Envelopment Analysis and the entropy approach between 2007/08 and 2010/11 on the 17 provinces of china. For every unit increase in economic growth pressure, the development indicator of energy efficiency falls by 3.4 percent. Energy poverty and energy efficiency in China are strongly linked to economic development, according to the model’s economic development findings. Economic inequalities in China have increased as a result of greater economic development or China’s economic development to be of high quality, we believe that our results will be useful in understanding the function of national economic growth management and coordination in wealth distribution and energy use. For rural and male-headed families, the economic development is more consistent. Employees are most likely to be economic developmentt from an increase in economic development, which is expected to reduce energy poverty the most and improve energy efficiency the most.
Gender bias and inequity holds women back in their conservation careers
Authors: James Robyn , Fisher Jonathan R. B. , Carlos-Grotjahn Chelsea , Boylan Marissa S. , Dembereldash Baigalmaa , Demissie Meaza Z. , Diaz De Villegas Crystal , Gibbs Bridget , Konia Ruth , Lyons Kristen , Possingham Hugh , Robinson Cathy J. , Tang Tiantian , Butt Nathalie
Published: January 2023

The planet is facing climate and biodiversity loss crises that impact all of humanity and yet globally, women remain underrepresented in leading solutions to these urgent conservation challenges. As one of the world’s largest conservation non-profit organizations, The Nature Conservancy (TNC) provided a large case-study for understanding inequity for women in the conservation sector. In 2018, all 1,789 conservation and science staff at TNC were surveyed to understand how they are able to develop their careers and contribute to conservation research and decision making. Of the 904 responses (490 men and 414 women), results show that men influence conservation and science decisions more than women; women face multiple barriers across their conservation careers due to gender bias; women experience sexual harassment and discrimination, as well as fear retaliation more than men; and men reported the sector as a more equitable and favorable place for women than women themselves experienced. Our data demonstrates that gender equality (equal representation of men and women) does not automatically mean that women no longer face systemic inequity and that intersectional issues such as race, location and caring responsibilities can all make it even more difficult for women to excel. Respondents drew from experiences across their conservation careers, to suggest how the conservation sector could address these issues. Based on our findings, we recommend practical ways the conservation sector can improve gender equity, including via workplace and cultural change measures, as well as changes to recruitment, pay transparency, and career development policies.
MetaDamage tool: Examining post-mortem damage in sedaDNA on a metagenomic scale
Authors: Everett Rosie , Cribdon Becky
Published: January 2023

The use of metagenomic datasets to support ancient sedimentary DNA (sedaDNA) for paleoecological reconstruction has been demonstrated to be a powerful tool to understand multi-organism responses to climatic shifts and events. Authentication remains integral to the ancient DNA discipline, and this extends to sedaDNA analysis. Furthermore, distinguishing authentic sedaDNA from contamination or modern material also allows for a better understanding of broader questions in sedaDNA research, such as formation processes, source and catchment, and post-depositional processes. Existing tools for the detection of damage signals are designed for single-taxon input, require a priori organism specification, and require a significant number of input sequences to establish a signal. It is therefore often difficult to identify an established cytosine deamination rate consistent with ancient DNA across a sediment sample. In this study, we present MetaDamage, a tool that examines cytosine deamination on a metagenomic (all organisms) scale for multiple previously undetermined taxa and can produce a damage profile based on a few hundred reads. We outline the development and testing of the MetaDamage tool using both authentic sedaDNA sequences and simulated data to demonstrate the resolution in which MetaDamage can identify deamination levels consistent with the presence of ancient DNA. The MetaDamage tool offers a method for the initial assessment of the presence of sedaDNA and a better understanding of key questions of preservation for paleoecological reconstruction.
Synergistic effects of climate warming and atmospheric nutrient deposition on the alpine lake ecosystem in the south-eastern Tibetan Plateau during the Anthropocene
Authors: Zhang Can , Kong Xiangzhen , Xue Bin , Zhao Cheng , Yang Xiangdong , Cheng Longjuan , Lin Qi , Zhang Ke , Shen Ji
Published: January 2023

Alpine lakes on the Tibetan Plateau are highly sensitive to global change and have been recognized as the sentinel of climate warming. However, anthropogenic impacts in populated area are migrating to these remote areas via transporting particulate nutrients by atmospheric deposition. Whether warming and nutrient deposition would impose additive or synergistic effects on the lake ecosystem remains largely unknown. Here, we present multi-proxy (sediment pigment and geochemistry) records during the past two centuries at the Cuoqia Lake in the southeast Tibetan Plateau. We found that the lake exhibited rapid ecological changes since 1980 AD characterized by an increase in primary productivity due to algal proliferation, with more rapid growth of green algae and diatoms. These findings are in concert with many other lakes (e.g., Moon Lake and Shade Co) in the same area, suggesting a consistent pattern of ecosystem evolution at the region scale. Statistical analyses suggested that nutrient deposition and climate warming were strongly associated with the variations in primary productivity and algae composition, exerting both individual and interactive effects. In addition, scenario analyses with a well-established process-based ecosystem model further revealed that the two factors not only individually, but also synergistically promoted the algal proliferation and community succession. Such synergy is evident in that the effect of lake warming would be more pronounced under higher nutrient deposition scenario, which is potentially due to higher temperature-driven mineralization in warmer conditions, and higher efficiency of nutrient utilization under enhanced light availability attributing to declining ice thickness and duration in cold seasons. Overall, our study proposes the existence and quantifies the synergistic impacts of climate warming and anthropogenic activities in driving the ecological changes in remote alpine lakes on the Tibetan Plateau. The lake ecological consequences driven by individual factor would be worsen by such synergy, so that we cannot predict the lake ecosystem trajectory in the future based on each factor separately, and more efforts than previously expected would be needed for the lake restoration and management.
The computational implementation of a platform of relative identity-by-descent scores algorithm for introgressive mapping
Authors: Cui Bo , Guo Zhongxu , Cao Hongbo , Calus Mario , Zhang Qianqian
Published: January 2023

With the development of genotyping and sequencing technology, researchers working in the area of conservation genetics are able to obtain the genotypes or even the sequences of a representative sample of individuals from the population. It is of great importance to examine the genomic variants and genes that are highly preferred or pruned during the process of adaptive introgression or long-term hybridization. To the best of our knowledge, we are the first to develop a platform with computational integration of a relative identity-by-descent (rIBD) scores algorithm for introgressive mapping. The rIBD algorithm is designed for mapping the fine-scaled genomic regions under adaptive introgression between the source breeds and the admixed breed. Our rIBD calculation platform provides compact functions including reading input information and uploading of files, rIBD calculation, and presentation of the rIBD scores. We analyzed the simulated data using the rIBD calculation platform and calculated the average IBD score of 0.061 with a standard deviation of 0.124. The rIBD scores generally follow a normal distribution, and a cut-off of 0.432 and −0.310 for both positive and negative rIBD scores is derived to enable the identification of genomic regions showing significant introgression signals from the source breed to the admixed breed. A list of genomic regions with detailed calculated rIBD scores is reported, and all the rIBD scores for each of the considered windows are presented in plots on the rIBD calculation platform. Our rIBD calculation platform provides a user-friendly tool for the calculation of fine-scaled rIBD scores for each of the genomic regions to map possible functional genomic variants due to adaptive introgression or long-term hybridization.
Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction
Authors: Wu Wenqi , Liu Su , Tian Linyan , Li Cheng , Jiang Yanan , Wang Jinhuan , Lv Yangyang , Guo Jing , Xing Donghui , Zhai Yixin , Sun Huimeng , Li Yuhang , Zhang Luying , He Xiang , Luo Kaiping , Zhan Hongjie , Zhao Zhigang
Published: January 2023

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs).

Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed.

Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably.

Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.
Enhanced cross-recognition of SARS-CoV-2 Omicron variant by peptide vaccine-induced antibodies
Authors: Aparicio Belén , Ruiz Marta , Casares Noelia , Silva Leyre , Egea Josune , Pérez Patricia , Albericio Guillermo , Esteban Mariano , García-Arriaza Juan , Lasarte Juan J. , Sarobe Pablo
Published: January 2023

Current vaccines against SARS-CoV-2, based on the original Wuhan sequence, induce antibodies with different degrees of cross-recognition of new viral variants of concern. Despite potent responses generated in vaccinated and infected individuals, the Omicron (B.1.1.529) variant causes breakthrough infections, facilitating viral transmission. We previously reported a vaccine based on a cyclic peptide containing the 446-488 S1 sequence (446-488cc) of the SARS-CoV-2 spike (S) protein from Wuhan isolate. To provide the best immunity against Omicron, here we compared Omicron-specific immunity induced by a Wuhan-based 446-488cc peptide, by a Wuhan-based recombinant receptor-binding domain (RBD) vaccine and by a new 446-488cc peptide vaccine based on the Omicron sequence. Antibodies induced by Wuhan peptide 446-488cc in three murine strains not only recognized the Wuhan and Omicron 446-488 peptides similarly, but also Wuhan and Omicron RBD protein variants. By contrast, antibodies induced by the Wuhan recombinant RBD vaccine showed a much poorer cross-reactivity for the Omicron RBD despite similar recognition of Wuhan and Omicron peptide variants. Finally, although the Omicron-based 446-488cc peptide vaccine was poorly immunogenic in mice due to the loss of T cell epitopes, co-immunization with Omicron peptide 446-488cc and exogenous T cell epitopes induced strong cross-reactive antibodies that neutralized Omicron SARS-CoV-2 virus. Since mutations occurring within this sequence do not alter T cell epitopes in humans, these results indicate the robust immunogenicity of 446-488cc-based peptide vaccines that induce antibodies with a high cross-recognition capacity against Omicron, and suggest that this sequence could be included in future vaccines targeting the Omicron variant.
Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia
Authors: Zhang Yu , Ye Chenjing , Zhu Haojie , Zhuang Youran , Chen Shaozhen , Weng Yingxi , Ren Jinhua , Luo Xiaofeng , Zheng Jing , Zheng Xiaoyun , Li Jing , Lan Lingqiong , Xie Yongxin , Han Zhongchao , Hu Jianda , Yang Ting
Published: January 2023

Objectives

Killer cell immunoglobulin like receptor (KIR) can trigger the alloreactivity of NK cells. However, there is no clear consensus as to their function. Here, we investigated the potential influence of KIR mismatch and KIR alleles on the outcome of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in acute myeloid leukemia (AML) patients.

Method

Data from 79 AML patients treated with haplo-HSCT were retrospectively analyzed. HLA-C genotyping was determined by the PCR-rSSO method. KIR, HLA-A and HLA-B genotyping was performed by the PCR-SSP method. Cox proportional hazards model and Kaplan-Meier survival curves were used for analysis.

Results

Both KIR ligand mismatch (KLM) group and KIR receptor-ligand mismatch (RLM) group were associated with a decreased risk in aGVHD and relapse rate (RR), and better overall survival (OS) compared to the KIR ligand matching and receptor-ligand matching groups, respectively (aGVHD: KLM: p=0.047, HR:0.235; RLM: p<0.001, HR:0.129; RR: KLM: p=0.049, HR:0.686, RLM: p=0.017, HR:0.200;OS:KLM: p=0.012, HR: 0.298, RLM: p=0.021, HR:0.301). RLM was more accurate at predicting relapse and aGVHD compared with KLM (aGVHD: p=0.009; RR: p=0.039). Patients with greater number of donor activating KIRs (aKIR) had a lower incidence of aGVHD and relapse, and the benefits correlated with the increase in the number of donor aKIRs (aGVHD: p=0.019, HR:0.156; RR: p=0.037, HR:0.211). Patients with RLM and the highest number of donor aKIRs had the lowest RR, lowest incidence of aGVHD and best OS.

Conclusions

Both KLM and RLM reduced the risk of aGVHD and relapse after haplo-HSCT in AML patients, and RLM showed superiority in predicting HSCT outcome. The synergistic effects of RLM and donor aKIRs can provide a better donor selection strategy to improve haplo-HSCT outcome in AML patients.
Intravenous iron supplementation in heart failure patients induces temporary endothelial dysfunction with release of endothelial microvesicles
Authors: Mause Sebastian F. , Berger Martin , Lim Hwee Ying , Vogt Felix , Brandenburg Vincent , Stöhr Robert
Published: January 2023

Background

Intravenous iron supplementation is an established therapy for patients with heart failure (HF) and concomitant iron deficiency reducing the risk of HF hospitalization. However, concerns persist regarding potential adverse vascular effects, since iron may induce oxidative stress, inflammation, and apoptosis of endothelial cells. To assess endothelial health following ferric carboxymaltose (FCM) administration, we analyzed the profile of circulating endothelial microvesicles (EMVs) and endothelial progenitor cells (EPCs) in a cohort of 23 HF patients using flow cytometry.

Results

Compared to healthy subjects, baseline levels of CD31+/CD41- EMVs were higher and EMVs featured a more apoptotic phenotype in HF patients. Following FCM administration, EMV levels showed a rapid but transient increase and displayed an altered phenotype profile with dominant augmentation of EMVs expressing inducible markers CD62E and CD54, indicating endothelial inflammatory activation and injury. Levels of circulating vasoregenerative CD45lowCD34+KDR+ EPCs were lower in HF patients and FCM application resulted in an early decrease of EPCs followed by substantial mobilization into the circulation after one week. Levels of EMVs and EPCs returned to baseline values within two and four weeks, respectively. HF patients with additional chronic kidney disease showed an elevated EMV/EPC ratio and diminished EPC mobilization, suggesting impaired vascular repair capacity. Providing a mechanistic link, in vitro experiments with cultured endothelial cells revealed that FCM dose-dependently promotes endothelial apoptosis, increases expression of adhesion molecules and CXCL12, and triggers generation of EMVs.

Conclusion

Intravenous iron supplementation with FCM in HF patients induces a biphasic response with initial increased release of CD62E+ and CD54+ enriched EMVs and subsequent mobilization of EPCs, indicating endothelial dysfunction upon FCM and suggesting consecutive engagement of a defense program aimed to reconstitute vascular health.
GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses
Authors: Krieg Paula F. , Sonner Jana K. , Kurelic Roberta , Engler Jan Broder , Scharenberg Marlena F. , Bauer Simone , Nikolaev Viacheslav O. , Friese Manuel A.
Published: January 2023

G-protein coupled receptors (GPCR) regulate 3’,5’-cyclic adenosine monophosphate (cAMP) levels in T cells. cAMP as ubiquitous second messenger is crucial for adequate physiology of T cells by mediating effector T cell (Teff) function as well as regulatory T cell (Treg)-mediated immunosuppression. Several GPCRs have been identified to be crucial for Teff and Treg function. However, the role of the orphan, constitutively active Gs-coupled GPCR GPR52 is unknown. Here we show that GPR52 regulates cAMP levels in T cells but does not affect T cell function. We found that stimulation of transfected HEK cells or primary T cells with a GPR52 agonist results in a rise of intracellular cAMP. However, neither Gpr52 deficiency nor pharmacological modulation of GPR52 by antagonists or agonists affected T cell activation, differentiation, and proliferation or Treg-mediated immunosuppression. Moreover, Gpr52 deletion did not modify the clinical disease course of experimental autoimmune encephalomyelitis (EAE). Our results demonstrate that a modulation of cAMP levels in T cells does not inevitably result in altered T cell function. While we could not identify an obvious role of GPR52 in in vitro T cell assays and in vivo CNS autoimmunity, it might regulate T cell function in a different context or affect the function of other GPR52-expressing cells.
Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment
Authors: Lin Yanjie , Shen Ge , Xie Si , Bi Xiaoyue , Lu Huihui , Yang Liu , Jiang Tingting , Deng Wen , Wang Shiyu , Zhang Lu , Lu Yao , Gao Yuanjiao , Hao Hongxiao , Wu Shuling , Liu Ruyu , Chang Min , Xu Mengjiao , Hu Leiping , Chen Xiaoxue , Huang Ronghai , Li Minghui , Xie Yao
Published: January 2023

Background

To investigate the changes of human leukocyte antigen DR (HLA-DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB).

Methods

A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs]-treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry.

Results

In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR+CD38dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR+CD38hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR+CD38hi subset percentage. The persistent high proportion of HLA-DR+CD38hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR+CD38hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR+CD38hi subsets significantly increased, but it was still lower than that at the baseline level.

Conclusions

The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR+CD38hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR+CD38hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment.
Bright future or blind alley? CAR-T cell therapy for solid tumors
Authors: Zhang Kai , Chen Hong , Li Fuqiang , Huang Sheng , Chen Fei , Li Yi
Published: January 2023

Chimeric antigen receptor (CAR) T cells therapy has emerged as a significant breakthrough in adoptive immunotherapy for hematological malignancies with FDA approval. However, the application of CAR-T cell therapy in solid tumors remains challenging, mostly due to lack of suitable CAR-T target antigens, insufficient trafficking and extravasation to tumor sites, and limited CAR-T survival in the hostile tumor microenvironment (TME). Herein, we reviewed the development of CARs and the clinical trials in solid tumors. Meanwhile, a “key-and-lock” relationship was used to describe the recognition of tumor antigen via CAR T cells. Some strategies, including dual-targets and receptor system switches or filter, have been explored to help CAR T cells matching targets specifically and to minimize on-target/off-tumor toxicities in normal tissues. Furthermore, the complex TME restricts CAT T cells activity through dense extracellular matrix, suppressive immune cells and cytokines. Recent innovations in engineered CARs to shield the inhibitory signaling molecules were also discussed, which efficiently promote CAR T functions in terms of expansion and survival to overcome the hurdles in the TME of solid tumors.
The research development of STAT3 in hepatic ischemia-reperfusion injury
Authors: Yang Hanwen , Zhang Pengpeng , Wang Qiang , Cheng Ke , Zhao Yujun
Published: January 2023

Ischemia-reperfusion injury (IRI) is a common complication of surgery, which can cause rapid deterioration of the liver function, increase the risk of graft rejection, and seriously affect the prognosis of patients. The signal transducer and activator of transcription 3 (STAT3) protein has been implicated in pathogenesis of IRI. STAT3 influences the mitochondria through multiple pathways and is also involved in apoptosis and other forms of programmed cell death. STAT3 is associated with Janus kinase (JAK), phosphoinositide-3 kinase (PI3K), and heme oxygenase-1 (HO-1) in liver IRI. The STAT3 pathway plays a dual role in IRI as it can also regulate lipid metabolism which may have potential for treating IRI fatty liver. In this review, we summarize research on the function of STAT3 in liver IRI to provide references for its application in the clinic.
Macrophage activity at the site of tumor ablation can promote murine urothelial cancer via transforming growth factor-β1
Authors: Kimura Yasushi , Fujimori Masashi , Rajagopalan Neeraj Raghuraman , Poudel Krish , Kim Kwanghee , Nagar Karan , Vroomen Laurien GPH. , Reis Henning , Al-Ahmadie Hikmat , Coleman Jonathan A. , Srimathveeravalli Govindarajan
Published: January 2023

Cell death and injury at the site of tumor ablation attracts macrophages. We sought to understand the status and activity of these cells while focusing on transforming growth factor-β1 (TGF-β1), a potent immunosuppressive and tumorigenic cytokine. Patients with urothelial cancer who underwent ablation using electrocautery or laser demonstrated increased infiltration and numbers of CD8+ T cells, along with FoxP3+ regulatory T cells, CD68+ macrophages and elevated levels of TGF-β1 in recurrent tumors. Similar findings were reproduced in a mouse model of urothelial cancer (MB49) by partial tumor ablation with irreversible electroporation (IRE). Stimulation of bone marrow derived macrophages with MB49 cell debris produced using IRE elicited strong M2 polarization, with exuberant secretion of TGF-β1. The motility, phenotypic markers and cytokine secretion by macrophages could be muted by treatment with Pirfenidone (PFD), a clinically approved drug targeting TGF-β1 signaling. MB49 cancer cells exposed to TGF-β1 exhibited increased migration, invasiveness and upregulation of epithelial-mesenchymal transition markers α-Smooth Muscle Actin and Vimentin. Such changes in MB49 cells were reduced by treatment with PFD even during stimulation with TGF-β1. IRE alone yielded better local tumor control when compared with control or PFD alone, while also reducing the overall number of lung metastases. Adjuvant PFD treatment did not provide additional benefit under in vivo conditions.
Silent neonatal influenza A virus infection primes systemic antimicrobial immunity
Authors: Heinemann Anna Sophie , Stalp Jan Lennart , Bonifacio João Pedro Pereira , Silva Filo , Willers Maike , Heckmann Julia , Fehlhaber Beate , Völlger Lena , Raafat Dina , Normann Nicole , Klos Andreas , Hansen Gesine , Schmolke Mirco , Viemann Dorothee
Published: January 2023

Infections with influenza A viruses (IAV) cause seasonal epidemics and global pandemics. The majority of these infections remain asymptomatic, especially among children below five years of age. Importantly, this is a time, when immunological imprinting takes place. Whether early-life infections with IAV affect the development of antimicrobial immunity is unknown. Using a preclinical mouse model, we demonstrate here that silent neonatal influenza infections have a remote beneficial impact on the later control of systemic juvenile-onset and adult-onset infections with an unrelated pathogen, Staphylococcus aureus, due to improved pathogen clearance and clinical resolution. Strategic vaccination with a live attenuated IAV vaccine elicited a similar protection phenotype. Mechanistically, the IAV priming effect primarily targets antimicrobial functions of the developing innate immune system including increased antimicrobial plasma activity and enhanced phagocyte functions and antigen-presenting properties at mucosal sites. Our results suggest a long-term benefit from an exposure to IAV during the neonatal phase, which might be exploited by strategic vaccination against influenza early in life to enforce the host’s resistance to later bacterial infections.
A novel defined TLR3 agonist as an effective vaccine adjuvant
Authors: Ko Kwang Hyun , Cha Seung Bin , Lee Seung-Hwan , Bae Hyun Shik , Ham Chul Soo , Lee Min-Gyu , Kim Dong-Ho , Han Seung Hyun
Published: January 2023

Synthetic double-stranded RNA analogs recognized by Toll-like receptor 3 (TLR3) are an attractive adjuvant candidate for vaccines, especially against intracellular pathogens or tumors, because of their ability to enhance T cell and antibody responses. Although poly(I:C) is a representative dsRNA with potent adjuvanticity, its clinical application has been limited due to heterogeneous molecular size, inconsistent activity, poor stability, and toxicity. To overcome these limitations, we developed a novel dsRNA-based TLR3 agonist named NexaVant (NVT) by using PCR-coupled bidirectional in vitro transcription. Agarose gel electrophoresis and reverse phase-HPLC analysis demonstrated that NVT is a single 275-kDa homogeneous molecule. NVT appears to be stable since its appearance, concentration, and molecular size were unaffected under 6 months of accelerated storage conditions. Moreover, preclinical evaluation of toxicity under good laboratory practices showed that NVT is a safe substance without any signs of serious toxicity. NVT stimulated TLR3 and increased the expression of viral nucleic acid sensors TLR3, MDA-5, and RIG-1. When intramuscularly injected into C57BL/6 mice, ovalbumin (OVA) plus NVT highly increased the migration of dendritic cells (DCs), macrophages, and neutrophils into inguinal lymph node (iLN) compared with OVA alone. In addition, NVT substantially induced the phenotypic markers of DC maturation and activation including MHC-II, CD40, CD80, and CD86 together with IFN-β production. Furthermore, NVT exhibited an appropriate adjuvanticity because it elevated OVA-specific IgG, in particular, higher levels of IgG2c (Th1-type) but lower IgG1 (Th2-type). Concomitantly, NVT increased the levels of Th1-type T cells such as IFN-γ+CD4+ and IFN-γ+CD8+ cells in response to OVA stimulation. Collectively, we suggest that NVT with appropriate safety and effectiveness is a novel and promising adjuvant for vaccines, especially those requiring T cell mediated immunity such as viral and cancer vaccines.