bluuebunny/crossref_metadata_2025 huggingface dataset:
Luminescence characteristics of muddy sediments in the turbidity maximum zone of the Yangtze River mouth and implications for the depositional mechanisms
Authors: Niu Wenlei , Nian Xiaomei , Zhao Luo , Zhai Yang , Meadows Michael E , Zhang Wentong , Wang Zhanghua
Published: August 2022

Muddy sediments are the most prominent constituents of sedimentary successions in tide-dominated river deltas and have highly complex depositional mechanisms. In this study, we performed fine-grained (4–11 μm) quartz optically stimulated luminescence (OSL) dating on two sediment cores collected at a shipwreck site in the turbidity maximum zone (TMZ) of the modern Yangtze River mouth, China, which were compared with previously published dating results including 45–63 um quartz OSL dating, radionuclide dating, porcelain artifacts recovered from the wreck, macro-plastics, and the morphological history recorded in marine charts. We investigate the luminescence characteristics of muddy sediments trapped in the TMZ and discuss the implications of OSL ages in understanding depositional mechanisms in tide-dominated river mouths. The results indicate that most OSL ages of muddy sediments in the delta front setting are overestimated compared with other dating methods. We suggest that OSL age overestimation reflects the trapping of sediments from offshore in the TMZ imported by saltwater intrusions and storm events. The offshore inputs contain high percentages of residual luminescence and are also subjected to incomplete bleaching due to turbid water conditions and near-bed dispersal in the salt-wedge river mouth. We thus suggest that the reduced bleaching efficiency of muddy sediments in delta front settings needs to be accounted for in understanding sedimentary processes and distinguishing between different sedimentary facies in tide-dominated river mouths. Furthermore, we propose that differences in quartz OSL ages of fine- and medium-grained fractions may arise in response to extreme events.
“Will I be molded or crushed?” Artistic representations of student teachers’ identities and emotions
Authors: Kennedy Laura M. , Glause Kaitlin
Published: August 2022

This article reports on the findings from a cross-institutional study of how arts-based reflection helped teacher candidates to identify and express their thoughts, feelings, and actions regarding the process of learning to teach. Inspired by PostSecret, teacher candidates created anonymous artwork to represent their experiences as student teachers. Through their artwork, candidates highlighted moments of perceived dissonance between their teacher preparation program and K-12 school settings. Additionally, when selecting one piece of art as inspiration for a written reflection, teacher candidates gravitated toward the artwork that provided emotional windows and mirrors into their own experiences. This study holds significance for recognizing and responding meaningfully to the difficult emotional work of learning to teach.
The role of Kisspeptin signaling in Oocyte maturation
Authors: Masumi Saeed , Lee Eun Bee , Dilower Iman , Upadhyaya Sameer , Chakravarthi V. Praveen , Fields Patrick E. , Rumi M. A. Karim
Published: August 2022

Kisspeptins (KPs) secreted from the hypothalamic KP neurons act on KP receptors (KPRs) in gonadotropin (GPN) releasing hormone (GnRH) neurons to produce GnRH. GnRH acts on pituitary gonadotrophs to induce secretion of GPNs, namely follicle stimulating hormone (FSH) and luteinizing hormone (LH), which are essential for ovarian follicle development, oocyte maturation and ovulation. Thus, hypothalamic KPs regulate oocyte maturation indirectly through GPNs. KPs and KPRs are also expressed in the ovarian follicles across species. Recent studies demonstrated that intraovarian KPs also act directly on the KPRs expressed in oocytes to promote oocyte maturation and ovulation. In this review article, we have summarized published reports on the role of hypothalamic and ovarian KP-signaling in oocyte maturation. Gonadal steroid hormones regulate KP secretion from hypothalamic KP neurons, which in turn induces GPN secretion from the hypothalamic-pituitary (HP) axis. On the other hand, GPNs secreted from the HP axis act on the granulosa cells (GCs) and upregulate the expression of ovarian KPs. While KPs are expressed predominantly in the GCs, the KPRs are in the oocytes. Expression of KPs in the ovaries increases with the progression of the estrous cycle and peaks during the preovulatory GPN surge. Intrafollicular KP levels in the ovaries rise with the advancement of developmental stages. Moreover, loss of KPRs in oocytes in mice leads to failure of oocyte maturation and ovulation similar to that of premature ovarian insufficiency (POI). These findings suggest that GC-derived KPs may act on the KPRs in oocytes during their preovulatory maturation. In addition to the intraovarian role of KP-signaling in oocyte maturation, in vivo, a direct role of KP has been identified during in vitro maturation of sheep, porcine, and rat oocytes. KP-stimulation of rat oocytes, in vitro, resulted in Ca2+ release and activation of the mitogen-activated protein kinase, extracellular signal-regulated kinase 1 and 2. In vitro treatment of rat or porcine oocytes with KPs upregulated messenger RNA levels of the factors that favor oocyte maturation. In clinical trials, human KP-54 has also been administered successfully to patients undergoing assisted reproductive technologies (ARTs) for increasing oocyte maturation. Exogenous KPs can induce GPN secretion from hypothalamus; however, the possibility of direct KP action on the oocytes cannot be excluded. Understanding the direct in vivo and in vitro roles of KP-signaling in oocyte maturation will help in developing novel KP-based ARTs.
The impact of cultural values on green purchase intentions through ecological awareness and perceived consumer effectiveness: An empirical investigation
Authors: Hussain Shahbaz , Huang Jinyan
Published: August 2022

The findings of a quantitative study about Chinese consumers regarding how cultural values, environmental awareness, and perceived consumer effectiveness (PCE) influence their green purchase intentions are presented in this article. This study aimed to explain these crucial factors’ direct and indirect effects on green purchases and the impact of cultural values and environmental awareness on PCE. Specifically, a conceptual model was suggested and empirically tested using survey information gathered from 371 customers from China, and the SmartPLS-SEM approach was applied. The results indicated that PCE significantly influences consumers’ intentions to make green purchases, and through environmental awareness and PCE, cultural values, directly and indirectly, influence Chinese consumers’ green buying intentions. This study offers novel perspectives on consumer behavior for purchasing environment-friendly products.
A passion for beef: Post-domestication changes in cattle body size in China from the Late Neolithic to the Late Bronze Age
Authors: Yu Chong , Zhao Hao , Hu Songmei , Yang Miaomiao , Guo Xiaoning , Ng Chuenyan
Published: August 2022

The introduction and the later dispersal of domestic cattle in China had played an enormous part in food production, handicraft manufacture, and ritual activities. However, we lack the details of pastoral economies, herding strategies, and utilization patterns of cattle in ancient China. This study, for the first time, uses biometrical assessments to investigate post-domesticated cattle husbandry and how it changed over time. Biometric data from eight sites dating from the Late Neolithic to the Late Bronze Age were evaluated using kernel analysis and mixture analysis. Results indicated that the general body size of cattle first decrease and then increase. By combining the estimated distribution of male and female individuals, we can see that the sex ratios affect size variation during Bronze Age times. Although no breed improvement has been detected so far, the herding and slaughtering strategies over time are different.
Cuproptosis-related lncRNA: Prediction of prognosis and subtype determination in clear cell renal cell carcinoma
Authors: Huili Youlong , Nie Shiwen , Zhang Liguo , Yao Anliang , Liu Jian , Wang Yong , Wang Lei , Cao Fenghong
Published: August 2022

Background: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, accounting for approximately 70% of all RCC cases. Cuproptosis, a novel mechanism of cell death, may be a potential target for intervention in tumor development.

Methods: Cuproptosis-related prognostic lncRNAs were identified by co-expression analysis and univariable Cox regression. Five lncRNA profiles were obtained by LASSO regression analysis, and a model with high accuracy was constructed to assess the prognosis of ccRCC patients based on these cuproptosis-related lncRNAs. Survival analysis and time-dependent ROC curves were performed for the α and β groups, and the results confirmed the high accuracy of the model in predicting the prognosis of ccRCC patients. Immunoassay, principal component analysis (PCA), and drug sensitivity analysis were also performed for different risk categories. Finally, we classified ccRCC patients into two different subtypes by consistent class clustering, and performed immune checkpoint activation, tumor microenvironment analysis, PCA, and drug sensitivity analysis for different subtypes.

Results: We developed a prognostic model using five cuproptosis-associated lncRNAs, which was found to be highly accurate in predicting ccRCC patients’ prognosis. Immunotherapy may be more beneficial to the hyper-risk category and the C2 subtype.

Conclusion: The results of this study confirm that five cuproptosis-associated lncRNAs can be used as potential prognostic markers for ccRCC.
Genome-wide association study identified genes associated with ammonia nitrogen tolerance in Litopenaeus vannamei
Authors: Fu Shuo , Liu Jianyong
Published: August 2022

Ammonia nitrogen tolerance is an economically important trait of the farmed penaeid shrimp Litopenaeus vannamei. To identify the genes associated with ammonia nitrogen tolerance, we performed an extreme phenotype genome-wide association study method (XP-GWAS) on a population of 200 individuals. The single nucleotide polymorphism (SNP) genotyping array method was used to construct the libraries and 36,048 SNPs were genotyped. Using the MLM, FarmCPU and Blink models, six different SNPs, located on SEQ3, SEQ4, SEQ5, SEQ7 and SEQ8, were determined to be significantly associated with ammonia nitrogen tolerance. By integrating the results of the GWAS and the biological functions of the genes, seven candidate genes (PDI, OZF, UPF2, VPS16, TMEM19, MYCBP2, and HOX7) were found to be associated with ammonia nitrogen tolerance in L. vannamei. These genes are involved in cell transcription, cell division, metabolism, and immunity, providing the basis for further study of the genetic mechanisms of ammonia nitrogen tolerance in L. vannamei. Further candidate gene association analysis in the offspring population revealed that the SNPs in the genes zinc finger protein OZF-like (OZF) and homeobox protein Hox-B7-like (HOX7) were significantly associated with ammonia nitrogen tolerance trait of L. vannamei. Our results provide fundamental genetic information that will be useful for further investigation of the molecular mechanisms of ammonia nitrogen tolerance. These associated SNPs may also be promising candidates for improving ammonia nitrogen tolerance in L. vannamei.
Comprehensive genome sequence analysis of the devastating tobacco bacterial phytopathogen Ralstonia solanacearum strain FJ1003
Authors: Chen Kun , Zhuang Yuhui , Wang Lihui , Li Huaqi , Lei Taijie , Li Mengke , Gao Meijia , Wei Jiaxian , Dang Hao , Raza Ali , Yang Qiang , Sharif Yasir , Yang Huan , Zhang Chong , Zou Huasong , Zhuang Weijian
Published: August 2022

Due to its high genetic diversity and broad host range, Ralstonia solanacearum, the causative phytopathogen of the bacterial wilt (BW) disease, is considered a “species complex”. The R. solanacearum strain FJ1003 belonged to phylotype I, and was isolated from the Fuzhou City in Fujian Province of China. The pathogen show host specificity and infects tobacco, especially in the tropical and subtropical regions. To elucidate the pathogenic mechanisms of FJ1003 infecting tobacco, a complete genome sequencing of FJ1003 using single-molecule real-time (SMRT) sequencing technology was performed. The full genome size of FJ1003 was 5.90 Mb (GC%, 67%), containing the chromosome (3.7 Mb), megaplasmid (2.0 Mb), and small plasmid (0.2 Mb). A total of 5133 coding genes (3446 and 1687 genes for chromosome and megaplasmid, respectively) were predicted. A comparative genomic analysis with other strains having the same and different hosts showed that the FJ1003 strain had 90 specific genes, possibly related to the host range of R. solanacearum. Horizontal gene transfer (HGT) was widespread in the genome. A type Ⅲ effector protein (Rs_T3E_Hyp14) was present on both the prophage and genetic island (GI), suggesting that this gene might have been acquired from other bacteria via HGT. The Rs_T3E_Hyp14 was proved to be a virulence factor in the pathogenic process of R. solanacearum through gene knockout strategy, which affects the pathogenicity and colonization ability of R. solanacearum in the host. Therefore, this study will improve our understanding of the virulence of R. solanacearum and provide a theoretical basis for tobacco disease resistance breeding.
Identification and characterization of a novel homozygous splice site variant of PATL2 causing female infertility due to oocyte germinal vesicle arrest
Authors: Sun Liwei , Tong Keya , Liu Weiwei , Tian Yin , Yang Sheng , Zhou Danni , Liu Dongyun , Huang Guoning , Li Jingyu
Published: August 2022

Background: This study aims to describe clinical and diagnostic phenotype and identify pathogenic variants of a female with unknown causes of infertility.

Methods: Clinical assessment was performed for the phenotype diagnosis. Whole-exome sequencing (WES) and the followed cDNA-PCR sequencing were applied to identify the pathogenic variant and investigate the potentially aberrant mRNA splicing event. The pathogenicity of the variant was analysed using multiple in silico prediction tools, including the 3D protein remodelling. Quantitative RT-PCR (qRT-PCR) was performed to measure PATL2 mRNA expression in the peripheral blood leukocytes of the proband and controls.

Results: The proband was diagnosed with the female infertility due to oocyte germinal vesicle (GV) arrest. A novel homozygous splice site variant of PATL2 (NM_001145112.2, c.871-1G>A), inherited from her asymptomatic heterozygous parents, was detected by WES. Sequencing of cDNA amplification products demonstrated that this variant resulted in the exon 10 skipping and in-frame loss of 54 nucleotides in the PATL2 transcript. Quantitative RT-PCR suggested that the mutant transcript escape the mRNA degradation.

Conclusion: We identified a novel pathogenic homozygous splice site of PATL2 (c.871-1G>A) underlying the oocyte GV arrest phenotype and elucidated its molecular mechanism. This study expands the variant spectrum of PATL2 and benefits our understanding of its genotype-phenotype correlations.
Clustering CITE-seq data with a canonical correlation-based deep learning method
Authors: Yuan Musu , Chen Liang , Deng Minghua
Published: August 2022

Single-cell multiomics sequencing techniques have rapidly developed in the past few years. Among these techniques, single-cell cellular indexing of transcriptomes and epitopes (CITE-seq) allows simultaneous quantification of gene expression and surface proteins. Clustering CITE-seq data have the great potential of providing us with a more comprehensive and in-depth view of cell states and interactions. However, CITE-seq data inherit the properties of scRNA-seq data, being noisy, large-dimensional, and highly sparse. Moreover, representations of RNA and surface protein are sometimes with low correlation and contribute divergently to the clustering object. To overcome these obstacles and find a combined representation well suited for clustering, we proposed scCTClust for multiomics data, especially CITE-seq data, and clustering analysis. Two omics-specific neural networks are introduced to extract cluster information from omics data. A deep canonical correlation method is adopted to find the maximumly correlated representations of two omics. A novel decentralized clustering method is utilized over the linear combination of latent representations of two omics. The fusion weights which can account for contributions of omics to clustering are adaptively updated during training. Extensive experiments over both simulated and real CITE-seq data sets demonstrated the power of scCTClust. We also applied scCTClust on transcriptome–epigenome data to illustrate its potential for generalizing.
PD-1/L1 inhibitor plus chemotherapy in the treatment of sarcomas
Authors: Tian Zhichao , Yao Weitao
Published: August 2022

There is an urgent clinical need for new therapeutic regimens for the effective treatment of advanced sarcomas. Accumulating evidence suggests that programmed death receptor-1/programmed death protein ligand-1 (PD-1/L1) inhibitors have synergistic effects with chemotherapy and have been approved for treatment of lung cancer, gastroesophageal cancer, and breast cancer. In this review, we reviewed the synergistic mechanism of PD-1/L1 inhibitors plus chemotherapy in the treatment of cancers, and the application of this combined regimen in several cancers, followed by a summary of the current evidence on the application of this combined regimen in the treatment of sarcomas as well as the main clinical trials currently underway. Based on the findings of this review, we believe that this combined approach will play an important role in the treatment of some subtypes of sarcomas in the future.
Identification of ISCA1 as novel immunological and prognostic biomarker for bladder cancer
Authors: Zhou Renlong , Peng Naixiong , Li Wei
Published: August 2022

Background

Iron-sulfur cluster assembly 1 (ISCA1) has a significant effect on respiratory complexes and energy metabolism. Although there is some evidence that ISCA1 gene expression impacts energy metabolism and consequently has a role in tumorigenesis and cancer metastasis in different types of malignancies, no systematic pan-cancer study of the ISCA1 has been conducted. As a result, we sought to investigate ISCA1’s predictive value in 33 cancer types as well as its possible immunological function.

Methods

We included the pan-cancer expression profile dataset and clinical data from the public database. Firstly, the single-sample Gene Set Enrichment Analysis (ssGSEa) approach was employed for analyzing the immune link in pan-cancer, while the limma package was utilized for analyzing the differential expression in cancer species. Subsequently, ciberport, MCP-counter, TIMER2, quanTIseq, and xCELL were employed for analyzing bladder cancer (BLCA)’s immune infiltration. Least absolute shrinkage and selection operator (Lasso) were employed for choosing the best gene to develop the immune risk scoring model.

Results

ISCA1 gene expression was positively related to four immune signatures (chemokine, immunostimulator, MHC, and receptor) in BLCA. Samples of BLCA were sorted into two groups by the best cut-off of ISCA1 expression degree. The group with a high level of ISCA1 expression had a higher risk, suggesting that the ISCA1 gene was a risk factor in BLCA, and its high expression resulted in a poorer prognosis. Additionally, it was noted that ISCA1 was positively linked with these immune checkpoints. Moreover, there was a considerable positive link between ISCA1 and different immune properties in subgroups with different immune checkpoint inhibiting responses. Finally, an immune risk scoring model was made and it showed a better score in comparison to that of TIDE.

Conclusion

ISCA1 can be a prognostic marker for a variety of cancers, particularly BLCA. Its high level of expression has a deleterious impact on the prognosis of BLCA patients. This strongly shows that ISCA1 is a significant prognostic factor for BLCA and that it could be used as a new prognostic detection target and treatment approach.
Pharmacological ascorbate as a novel therapeutic strategy to enhance cancer immunotherapy
Authors: Zaher Amira , Stephens Laura M. , Miller Ann M. , Hartwig Stacey M. , Stolwijk Jeffrey M. , Petronek Michael S. , Zacharias Zeb R. , Wadas Thaddeus J. , Monga Varun , Cullen Joseph J. , Furqan Muhammad , Houtman Jon C. D. , Varga Steven M. , Spitz Douglas R. , Allen Bryan G.
Published: August 2022

Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues. Immune checkpoint inhibitors (ICIs) are highly promising therapies for many cancer patients but face several challenges including low response rates, primary or acquired resistance, and toxicity. Ascorbate modulates both innate and adaptive immune functions and plays a key role in maintaining the balance between pro and anti-inflammatory states. Furthermore, the success of pharmacological ascorbate as a radiosensitizer and a chemosensitizer in pre-clinical studies and early phase clinical trials suggests that it may also enhance the efficacy and expand the benefits of ICIs.
Impact of climate change on long-term variations of small yellow croaker (Larimichthys polyactis) winter fishing grounds
Authors: Zhang Rui , Liu Yang , Tian Hao , Liu Shuhao , Zu Kaiwei , Xia Xinmei
Published: August 2022

Small yellow croaker (Larimichthys polyactis) is one of the key demersal species with high economic values and wide distribution in the China Seas. In this study, a Winter Fishing ground Abundance Index (WFAI) was developed by using fisheries survey data in 1971–1982 and used as the response variable to investigate the impacts of environmental variables, including surface current velocity (SCV), sea surface salinity (SSS), sea surface temperature (SST), and depth (DE). A total of 45 combinatorial generalized additive models (GAMs), generalized linear models (GLMs), and random forest models (RFs) were used to select the optimal WFAI prediction. The final WFAI distribution results showed that the winter fishing ground hotspots of small yellow croaker were mainly distributed between 11°C and 16°C isotherms and between 50-m and 100-m isobaths, and the area of winter fishing ground hotspots (WFHA) significantly decreased and the hotspots tended to move northward over the past 50 years. The shape of hotspots was strongly affected by temperature fronts and salinity fronts. Analysis with the climate indices revealed that the Atlantic Multidecadal Oscillation (AMO) might have a large influence on the distribution of small yellow croaker by affecting SST and SSS in the China Seas more than the Pacific Decadal Oscillation (PDO), North Pacific Gyre Oscillation (NPGO), and Arctic Oscillation Index (AOI). The future prediction based on two extreme scenarios (RCP2.6 and RCP8.5) indicated that the hotspots would obviously move northward. These findings will serve effectively the fishery resources monitoring, management, and evaluation of small yellow croaker in the China Seas.
Experimental diesel spray characterization of the medium-duty injector with single- and multi-hole nozzle configurations under non-reacting, non-vaporizing conditions
Authors: Park Ji-Woong , Jouzdani Shirin , Tzanetakis Tom , Schmidt Henry , Atkinson William , Naber Jeffrey , Pei Yuanjiang , Tao Feng , Garg Rajesh , Langenderfer David , Zhang Yu , Som Sibendu
Published: August 2022

Characteristics of diesel sprays injected through Cummins medium-duty ISB injectors were studied experimentally in an optically accessible constant-volume combustion vessel. The experiments were performed with ultra-low-sulfur diesel (ULSD) under non-reacting and non-vaporizing conditions, including different ambient gas densities (23–65 kg/m3), injection pressures (500–1,500 bar), and injection duration times (0.5–1.5 ms). The ambient temperature of the vessel was maintained at a room temperature of 313 K for all the tests. A systematic comparison was made between single-hole (SH) and multi-hole (MH) injector configurations. A plume-to-plume variation in spray penetration length was observed for various operating conditions. A substantial deviation was observed for a specific hole against the averaged plume, indicating that arbitrary selection of the plume index may result in inaccurate spray characterization of the MH injector. The penetration length of the MH injector was shorter than that of the SH injector under the same operating conditions, indicating that a spray model calibrated on SH injector data may not accurately predict the transient spray behavior of the MH injector in practical engine simulations. A square-root correlation of the spray penetration length was applied for both the SH and MH injectors. The spray penetration length and dispersion angles of the ISB SH injector were also compared with those of the heavy-duty Cummins ISX SH injector. While the ISX SH injector showed a faster penetration than the ISB SH injector, the dispersion angle was similar. The differences in spray penetration between ISB and ISX injectors followed the expected trend based on their nozzle hole diameters.
Impact of DSA and immunosuppression minimization on rejection, graft, and patient survival after simultaneous liver–kidney transplantation
Authors: Dekeyser Manon , Taupin Jean-Luc , Elias Michelle , Ichaï Philippe , Herr Florence , Boudon Marc , Brunel Melanie , Sa cunha Antonio , Coilly Audrey , Saliba Faouzi , Durrbach Antoine
Published: August 2022

Background

Acute rejection rate is low after simultaneous liver–kidney transplantation (SLKT), leading some groups to minimize immunosuppressive (IS) regimens. However, the impact of preformed (pDSA) or de novo donor-specific antibodies (dnDSA) on the graft remains unclear.

Methods

We performed a retrospective analysis of 102 consecutive SLKT patients to study the impact of anti-HLA antibodies.

Results

Anti-HLA antibodies were detected in 75 recipients (class I 23.8%, both classes I and II 23.8%, and class II 14.3%). In total, 42.8% of the patients had pDSA and 21.7% developed dnDSA. Overall patient survival at 1–3 and 5 years, was respectively 88, 84, and 80%. Acute rejection occurred respectively in 3 (2.9%) liver and 6 kidney (5.9%) recipients. pDSA with titers over 10,000 mean fluorescence intensity (14.3%) was associated with lower patient survival (40 vs. 82%) but not with acute rejection. In a multivariable Cox regression analysis, the risk of death was associated with maleness, the highest titer of pDSA (p < 0.0007) or the sum of pDSA >10,000. Renal function did not differ between patients with class I pDSA (p = 0.631) and those with class II pDSA (p = 0.112) or between patients with and without a positive cross-match (p = 0.842). dnDSA were not associated with acute rejection, graft dysfunction or patient survival. IS minimization was not associated with rejection, graft dysfunction or death.

Conclusion

In SLKT, high levels of pDSA >10,000 were associated with lower patient survival, but not rejection or graft survival. Minimization of maintenance immunosuppression regimen was not associated with a poorer outcome.
Checkpoint molecules on infiltrating immune cells in colorectal tumor microenvironment
Authors: Talaat Iman M. , Elemam Noha M. , Zaher Shroque , Saber-Ayad Maha
Published: August 2022

Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide, with a high mortality rate due to metastasis. The tumor microenvironment (TME) contains multiple interactions between the tumor and the host, thus determining CRC initiation and progression. Various immune cells exist within the TME, such as tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs). The immunotherapy approach provides novel opportunities to treat solid tumors, especially toward immune checkpoints. Despite the advances in the immunotherapy of CRC, there are still obstacles to successful treatment. In this review, we highlighted the role of these immune cells in CRC, with a particular emphasis on immune checkpoint molecules involved in CRC pathogenesis.
Feasibility of novel approaches to detect viable Mycobacterium tuberculosis within the spectrum of the tuberculosis disease
Authors: Alebouyeh Sogol , Weinrick Brian , Achkar Jacqueline M. , García Maria J. , Prados-Rosales Rafael
Published: August 2022

Tuberculosis (TB) is a global disease caused by Mycobacterium tuberculosis (Mtb) and is manifested as a continuum spectrum of infectious states. Both, the most common and clinically asymptomatic latent tuberculosis infection (LTBI), and the symptomatic disease, active tuberculosis (TB), are at opposite ends of the spectrum. Such binary classification is insufficient to describe the existing clinical heterogeneity, which includes incipient and subclinical TB. The absence of clinically TB-related symptoms and the extremely low bacterial burden are features shared by LTBI, incipient and subclinical TB states. In addition, diagnosis relies on cytokine release after antigenic T cell stimulation, yet several studies have shown that a high proportion of individuals with immunoreactivity never developed disease, suggesting that they were no longer infected. LTBI is estimated to affect to approximately one fourth of the human population and, according to WHO data, reactivation of LTBI is the main responsible of TB cases in developed countries. Assuming the drawbacks associated to the current diagnostic tests at this part of the disease spectrum, properly assessing individuals at real risk of developing TB is a major need. Further, it would help to efficiently design preventive treatment. This quest would be achievable if information about bacterial viability during human silent Mtb infection could be determined. Here, we have evaluated the feasibility of new approaches to detect viable bacilli across the full spectrum of TB disease. We focused on methods that specifically can measure host-independent parameters relying on the viability of Mtb either by its direct or indirect detection.
Longitudinal evaluation of the impact of immunosuppressive regimen on immune responses to COVID-19 vaccination in kidney transplant recipients
Authors: Wiedemann Aurélie , Pellaton Céline , Dekeyser Manon , Guillaumat Lydia , Déchenaud Marie , Krief Corinne , Lacabaratz Christine , Grimbert Philippe , Pantaleo Giuseppe , Lévy Yves , Durrbach Antoine
Published: August 2022

Immunocompromised patients have a high risk of death from SARS-CoV-2 infection. Vaccination with an mRNA vaccine may protect these patients against severe COVID-19. Several studies have evaluated the impact of immune-suppressive drug regimens on cellular and humoral responses to SARS-CoV-2 variants of concern in this context. We performed a prospective longitudinal study assessing specific humoral (binding and neutralizing antibodies against spike (S) and T-lymphocyte (cytokine secretion and polyfunctionality) immune responses to anti-COVID-19 vaccination with at least two doses of BNT162b2 mRNA vaccine in stable kidney transplant recipients (KTR) on calcineurin inhibitor (CNI)- or belatacept-based treatment regimens. Fifty-two KTR−31 receiving CNI and 21 receiving belatacept—were enrolled in this study. After two doses of vaccine, 46.9% of patients developed anti-S IgG. Anti-spike IgG antibodies were produced in only 21.4% of the patients in the belatacept group, vs. 83.3% of those in the CNI group. The Beta and Delta variants and, more importantly, the Omicron variant, were less well neutralized than the Wuhan strain. T-cell functions were also much weaker in the belatacept group than in the CNI group. Renal transplant patients have an impaired humoral response to BNT162b2 vaccination. Belatacept-based regimens severely weaken both humoral and cellular vaccine responses. Clinically, careful evaluations of at least binding IgG responses, and prophylactic or post-exposure strategies are strongly recommended for transplant recipients on belatacept-based regimens.
Cross-reactivity of antibodies to different rumen methanogens demonstrated using immunomagnetic capture technology
Authors: Khanum Sofia , Roberts Joanna M. , Heathcott Rosemary W. , Bagley Stefanie , Wilson Tania , Gupta Sandeep K. , Kirk Michelle R. , Heiser Axel , Janssen Peter H. , Wedlock D. Neil
Published: August 2022

Methane is produced in the rumen of ruminant livestock by methanogens, accounting for approximately 14.5% of anthropogenic greenhouse gas emissions in terms of global warming potential. The rumen contains a diversity of methanogens species, and only a few of these have been cultured. Immunomagnetic capture technology (ICT) is a simple and effective method to capture and concentrate target organisms in samples containing complex microflora. We hypothesized that antibody-coated magnetic beads could be used to demonstrate antibody specificity and cross-reactivity to methanogens in rumen samples. Sheep polyclonal antibodies raised against four isolates of rumen dwelling methanogens, Methanobrevibacter ruminantium strain M1, Methanobrevibacter sp. AbM4, Methanobrevibacter sp. D5, and Methanobrevibacter sp. SM9 or an equal mix of all four isolates, were used to coat paramagnetic beads. ICT was used together with flow cytometry and qPCR to optimize key parameters: the ratio of antibody to beads, coupling time between antibody and paramagnetic beads to produce immunomagnetic beads (IMBs), and optimal incubation time for the capture of methanogen cells by IMBs. Under optimized conditions, IMBs bound strongly to their respective isolates and showed a degree of cross-reactivity with isolates of other Methanobrevibacter spp. in buffer and in rumen fluid, and with resident methanogens in rumen content samples. The evidence provided here indicates that this method can be used to study the interaction of antibodies with antigens of rumen methanogens, to understand antigen cross-reactivity and antibody binding efficiency for the evaluation of antigens used for the development of a broad-spectrum anti-methanogen vaccine for the abatement of methane production.
Simultaneous measurement of the antibody responses against SARS-CoV-2 and its multiple variants by a phage display mediated immuno-multiplex quantitative PCR-based assay
Authors: Chen Hanyi , Li Shen , Wang Jiali , He Siqi , Wang Dong , Qian Zhaohui , Hu Dandan , Qi Fangfang , Hu Keping , Luo Chenyi , Wang Jianxun
Published: August 2022

To combat the continued pandemic of COVID-19, multiplex serological assays have been developed to comprehensively monitor the humoral immune response and help to design new vaccination protocols to different SARS-CoV-2 variants. However, multiplex beads and stably transfected cell lines require stringent production and storage conditions, and assays based on flow cytometry is time-consuming and its application is therefore restricted. Here, we describe a phage display system to distinguish the differences of immune response to antigenic domains of multiple SARS-CoV-2 variants simultaneously. Compared with linear peptides, the recombinant antigens displayed on the phage surface have shown some function that requires the correct folding to form a stable structure, and the binding efficiency between the recombinant phage and existing antibodies is reduced by mutations on antigens known to be important for antigen–antibody interaction. By using Phage display mediated immuno-multiplex quantitative PCR (Pi-mqPCR), the binding efficiency between the antibody and antigens of different SARS-CoV-2 variants can be measured in one amplification reaction. Overall, these data show that this assay is a valuable tool to evaluate the humoral response to the same antigen of different SARS-CoV-2 variants or antigens of different pathogens. Combined with high-throughput DNA sequencing technology, this phage display system can be further applied in monitoring humoral immune response in a large population before and after vaccination.
Isolation, characterization, and application of a novel polyvalent lytic phage STWB21 against typhoidal and nontyphoidal Salmonella spp.
Authors: Mondal Payel , Mallick Bani , Dutta Moumita , Dutta Shanta
Published: August 2022

Salmonella is one of the common causal agents of bacterial gastroenteritis-related morbidity and mortality among children below 5 years and the elderly populations. Salmonellosis in humans is caused mainly by consuming contaminated food originating from animals. The genus Salmonella has several serovars, and many of them are recently reported to be resistant to multiple drugs. Therefore, isolation of lytic Salmonella bacteriophages in search of bactericidal activity has received importance. In this study, a Salmonella phage STWB21 was isolated from a lake water sample and found to be a novel lytic phage with promising potential against the host bacteria Salmonella typhi. However, some polyvalence was observed in their broad host range. In addition to S. typhi, the phage STWB21 was able to infect S. paratyphi, S. typhimurium, S. enteritidis, and a few other bacterial species such as Sh. flexneri 2a, Sh. flexneri 3a, and ETEC. The newly isolated phage STWB21 belongs to the Siphoviridae family with an icosahedral head and a long flexible non-contractile tail. Phage STWB21 is relatively stable under a wide range of pH (4–11) and temperatures (4°C–50°C) for different Salmonella serovars. The latent period and burst size of phage STWB21 against S. typhi were 25 min and 161 plaque-forming units per cell. Since Salmonella is a foodborne pathogen, the phage STWB21 was applied to treat a 24 h biofilm formed in onion and milk under laboratory conditions. A significant reduction was observed in the bacterial population of S. typhi biofilm in both cases. Phage STWB21 contained a dsDNA of 112,834 bp in length, and the GC content was 40.37%. Also, genomic analysis confirmed the presence of lytic genes and the absence of any lysogeny or toxin genes. Overall, the present study reveals phage STWB21 has a promising ability to be used as a biocontrol agent of Salmonella spp. and proposes its application in food industries.
Role of TRPV1 ion channel in cervical squamous cell carcinoma genesis
Authors: Wang Zhenming , Dong Junhong , Tian Wenxiu , Qiao Sen , Wang Hongmei
Published: August 2022

The transient receptor potential (TRP) family is a widely expressed superfamily of ion channels that regulate intracellular Ca2+ homeostasis and signal transduction. Abnormal expression of TRPV1 is closely related to malignant tumors of the female reproductive system such as breast, ovarian, cervical and endometrial cancers. In this study, we found a significant reduction of TRPV1 expression in cervical squamous cell carcinoma and this expression is inversely association with the risk of cervical squamous cell carcinoma. Furthermore, TRPV1 is involved in cell differentiation, iron death, inflammatory response, and metabolic regulation in cervical squamous cell carcinoma. Meanwhile TRPV1 is positively correlated with T cells and negatively associated with macrophages, indicating that TRPV is associated with tumor cell immunity. Therefore, TRPV1 may be a potential marker of cervical cancer and a promising anti-cancer drug candidate.
An exploratory causal analysis of the relationships between the brain age gap and cardiovascular risk factors
Authors: Mouches Pauline , Wilms Matthias , Bannister Jordan J. , Aulakh Agampreet , Langner Sönke , Forkert Nils D.
Published: August 2022

The brain age gap (BAG) has been shown to capture accelerated brain aging patterns and might serve as a biomarker for several neurological diseases. Moreover, it was also shown that it captures other biological information related to modifiable cardiovascular risk factors. Previous studies have explored statistical relationships between the BAG and cardiovascular risk factors. However, none of those studies explored causal relationships between the BAG and cardiovascular risk factors. In this work, we employ causal structure discovery techniques and define a Bayesian network to model the assumed causal relationships between the BAG, estimated using morphometric T1-weighted magnetic resonance imaging brain features from 2025 adults, and several cardiovascular risk factors. This setup allows us to not only assess observed conditional probability distributions of the BAG given cardiovascular risk factors, but also to isolate the causal effect of each cardiovascular risk factor on BAG using causal inference. Results demonstrate the feasibility of the proposed causal analysis approach by illustrating intuitive causal relationships between variables. For example, body-mass-index, waist-to-hip ratio, smoking, and alcohol consumption were found to impact the BAG, with the greatest impact for obesity markers resulting in higher chances of developing accelerated brain aging. Moreover, the findings show that causal effects differ from correlational effects, demonstrating the importance of accounting for variable relationships and confounders when evaluating the information captured by a biomarker. Our work demonstrates the feasibility and advantages of using causal analyses instead of purely correlation-based and univariate statistical analyses in the context of brain aging and related problems.
Retinal microvasculature and imaging markers of brain frailty in normal aging adults
Authors: Tao Wendan , Kwapong William Robert , Xie Jianyang , Wang Zetao , Guo Xiaonan , Liu Junfeng , Ye Chen , Wu Bo , Zhao Yitian , Liu Ming
Published: August 2022

Background

The retina and brain share a similar embryologic origin, blood barriers, and microvasculature features. Thus, retinal imaging has been of interest in the aging population to help in the early detection of brain disorders. Imaging evaluation of brain frailty, including brain atrophy and markers of cerebral small vessel disease (CSVD), could reflect brain health in normal aging, but is costly and time-consuming. In this study, we aimed to evaluate the retinal microvasculature and its association with radiological indicators of brain frailty in normal aging adults.

Methods

Swept-source optical coherence tomography angiography (SS-OCTA) and 3T-MRI brain scanning were performed on normal aging adults (aged ≥ 50 years). Using a deep learning algorithm, microvascular tortuosity (VT) and fractal dimension parameter (Dbox) were used to evaluate the superficial vascular complex (SVC) and deep vascular complex (DVC) of the retina. MRI markers of brain frailty include brain volumetric measures and CSVD markers that were assessed.

Results

Of the 139 normal aging individuals included, the mean age was 59.43 ± 7.31 years, and 64.0% (n = 89) of the participants were females. After adjustment of age, sex, and vascular risk factors, Dbox in the DVC showed a significant association with the presence of lacunes (β = 0.58, p = 0.007), while VT in the SVC significantly correlated with the score of cerebral deep white matter hyperintensity (β = 0.31, p = 0.027). No correlations were found between brain volumes and retinal microvasculature changes (P > 0.05).

Conclusion

Our report suggests that imaging of the retinal microvasculature may give clues to brain frailty in the aging population.
Association between playing cards/mahjong and risk of incident dementia among the Chinese older adults: a prospective cohort study
Authors: Tian Gang , Shuai Jingliang , Li Rui , Zhou Tong , Shi Yan , Cheng Gang , Yan Yan
Published: August 2022

Objectives: Studies have shown that the frequent participation of the elderly in cognitive stimulation activities is associated with a reduced risk of dementia, but the prospective evidence of this association is limited.

Methods: We used data from a prospective cohort study of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), and included 11,821 community-living Chinese individuals aged 65 years or older at 2008 baseline who were free of dementia, and were followed up every 2–3 years until 2018. Cox proportional hazards models were applied to generate the hazard ratios (HRs) and 95% confidence intervals (CIs) for analyzing the associations between the frequency of playing cards/mahjong and the incidence of dementia.

Results: A total of 821 participants were diagnosed with dementia during the 10-year follow-up. The average age of patients with dementia and non dementia were 89 and 90 years old, respectively. Compared with participants who rarely or never played cards/mahjong, participants who played cards/mahjong almost every day had a significantly lower risk of dementia (HR = 0.63; 95%CI, 0.42–0.95) after the multivariable-adjusted model. Similar results were observed in subgroup analyses based on sex (male: HR = 0.52, 0.28–0.96; female: HR = 0.62, 0.36–0.98), age (<85years: HR = 0.55, 0.32–0.89), regularly exercise (yes: HR = 0.44, 0.28–0.87) and MMSE score [above median (25): HR = 0.66, 0.41–0.92].

Conclusions: Playing cards/mahjong in the elderly may contribute to reducing the risk of dementia.
Aberrant orbitofrontal cortical activation interferes with encoding of Pavlovian fear conditioning
Authors: Sun Chung-Fu , Chang Chun-hui
Published: August 2022

Obsessive-compulsive disorder (OCD) patients were usually found with the hyper-activation of the orbitofrontal cortex (OFC) and a deficit in fear extinction learning. The OFC can be subdivided into the lateral OFC (lOFC) and the medial OFC (mOFC). Previous studies have suggested that both subregions are involved in the modulation of negative emotions. However, how aberrant activation of the OFC interacts with the encoding of Pavlovian fear remains unknown. In this study, the lOFC or the mOFC was pharmacologically activated or inactivated before the fear conditioning on Day 1, followed by a context test on Day 2 and a tone test on Day 3 in male Long-Evans rats. We found that for the animals that underwent fear conditioning under aberrant activation of either the lOFC or the mOFC, they showed normal within-session fear expression. However, the acquisition/consolidation of contextual fear was impaired under mOFC activation, while the acquisition/consolidation of cued fear was impaired under either the lOFC or the mOFC activation, in that these animals showed lower freezing compared to controls during the retrieval test. On the other hand, for the animals that underwent fear conditioning under inactivation of either the lOFC or the mOFC, they showed normal within-session fear expression, as well as intact encoding of both the contextual and cued fear. Together, our results suggested that the OFC was not actively engaged in the acquisition of Pavlovian fear conditioning, but aberrant activation of the OFC impaired fear learning.