bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoplasmic Reticulum Aminopeptidase 1 Is Involved in Anti-viral Immune Response of Hepatitis B Virus by Trimming Hepatitis B Core Antigen to Generate 9-Mers Peptides
Authors: Liu Huanhuan , Hu Bingqi , Huang Junfeng , Wang Qin , Wang Feier , Pan Faming , Chen Liwen
Published: May 2022

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a processing enzyme of antigenic peptides presented to major histocompatibility complex (MHC) class I molecules. ERAP1-dependent trimming of epitope repertoire determines an efficacy of adoptive CD8+ T-cell responses in several viral diseases; however, its role in hepatitis B virus (HBV) infection remains unknown. Here, we show that the serum level of ERAP1 in patients with chronic hepatitis B (CHB) (n = 128) was significantly higher than that of healthy controls (n = 44) (8.78 ± 1.82 vs. 3.52 ± 1.61, p < 0.001). Furthermore, peripheral ERAP1 level is moderately correlated with HBV DNA level in patients with CHB (r = 0.731, p < 0.001). HBV-transfected HepG2.2.15 cells had substantially increased ERAP1 expression and secretion than the germline HepG2 cells (p < 0.001). The co-culture of ERAP1-specific inhibitor ERAP1-IN-1 pretreated HepG2.2.15 cells or ERAP1 knockdown HepG2.2.15 cells with CD8+ T cells led to 14–24% inhibition of the proliferation of CD8+ T cells. Finally, liquid chromatography tandem mass spectrometry (LC-MS/MS) test demonstrated that ERAP1-IN-1 blocks completely the production of a 9-mers peptide (30–38, LLDTASALY) derived from Hepatitis B core antigen (HBcAg). The predictive analysis by NetMHCpan-4.1 server showed that human leukocyte antigen (HLA)-C*04:01 is a strong binder for the 9-mers peptide in HepG2.2.15 cells. Taken together, our results demonstrated that ERAP1 trims HBcAg to produce 9-mers LLDTASALY peptides for binding onto HLA-C*04:01 in HepG2.2.15 cells, facilitating the potential activation of CD8+ T cells.
Identification of a Novel Astrovirus in Pinnipeds
Authors: Zhang Peijun , Su Haoxiang , Peng Ruoyan , Chan Jasper Fuk-Woo , Bai Shijie , Wang Gaoyu , Huang Yi , Hu Xiaoyuan , Luo Jun , Liu Sisi , Li Youyou , Xue Liying , Yang Fan , Zhao Mingming , Zhang Yun , Tang Chuanning , Shen Shu , Cui Xiuji , Niu Lina , Lu Gang , Yuen Kwok-Yung , Deng Fei , Zhang Weijia , Yin Feifei , Du Jiang
Published: May 2022

Astroviruses infect human and animals and cause diarrhea, fever, and vomiting. In severe cases, these infections may be fatal in infants and juvenile animals. Previous evidence showed that humans in contact with infected animals can develop serological responses to astroviruses. Mamastrovirus 11 is a species of Mamastrovirus and was first reported in 2018. It was detected in the fecal samples of a California sea lion. The genome sequence of its capsid protein (CP) was submitted to GenBank. However, the genome sequence of its non-structural protein region was not elucidated. In the present study, we characterized the genome sequences of the novel astroviruses AstroV-HMU-1 and AstroV-like-HMU-2. These were obtained from California sea lions (Zalophus californianus) and walruses (Odobenus rosmarus) presenting with loose stools. A phylogenetic analysis revealed that the CP of AstroV-HMU-1 closely clustered with Mamastrovirus 11 while its RNA-dependent RNA polymerase (RdRp) and serine protease (SP) were closely related to the mink astrovirus in the genus Mamastrovirus. The genome of AstroV-HMU-1 provided basic information regarding the NS protein regions of Mamastrovirus 11. Recombination analyses showed that the genomes of Z. californianus AstroV-HMU-1, VA2/human and the mink astrovirus may have recombined long ago. The NS of AstroV-like-HMU-2 segregated from the Astroviridae in the deep root of the phylogenetic tree and exhibited 36% amino acid identity with other mamastroviruses. Thus, AstroV-like-HMU-2 was proposed as a member of a new genus in the unclassified Astroviridae. The present study suggested that that the loose stools of pinnipeds may be the result of occasional infection by this novel astrovirus. This discovery provides a scientific basis for future investigations into other animal-borne infectious diseases.
Lactobacilli Attenuate the Effect of Aggregatibacter actinomycetemcomitans Infection in Gingival Epithelial Cells
Authors: Bueno Manuela R. , Ishikawa Karin H. , Almeida-Santos Gislane , Ando-Suguimoto Ellen S. , Shimabukuro Natali , Kawamoto Dione , Mayer Marcia P. A.
Published: May 2022

Probiotics may be considered as an additional strategy to achieve a balanced microbiome in periodontitis. However, the mechanisms underlying the use of probiotics in the prevention or control of periodontitis are still not fully elucidated. This in vitro study aimed to evaluate the effect of two commercially available strains of lactobacilli on gingival epithelial cells (GECs) challenged by Aggregatibacter actinomycetemcomitans. OBA-9 GECs were infected with A. actinomycetemcomitans strain JP2 at an MOI of 1:100 and/or co-infected with Lactobacillus acidophilus La5 (La5) or Lacticaseibacillus rhamnosus Lr32 (Lr32) at an MOI of 1:10 for 2 and 24 h. The number of adherent/internalized bacteria to GECs was determined by qPCR. Production of inflammatory mediators (CXCL-8, IL-1β, GM-CSF, and IL-10) by GECs was determined by ELISA, and the expression of genes encoding cell receptors and involved in apoptosis was determined by RT-qPCR. Apoptosis was also analyzed by Annexin V staining. There was a slight loss in OBA-9 cell viability after infection with A. actinomycetemcomitans or the tested probiotics after 2 h, which was magnified after 24-h co-infection. Adherence of A. actinomycetemcomitans to GECs was 1.8 × 107 (± 1.2 × 106) cells/well in the mono-infection but reduced to 1.2 × 107 (± 1.5 × 106) in the co-infection with Lr32 and to 6 × 106 (± 1 × 106) in the co-infection with La5 (p < 0.05). GECs mono-infected with A. actinomycetemcomitans produced CXCL-8, GM-CSF, and IL-1β, and the co-infection with both probiotic strains altered this profile. While the co-infection of A. actinomycetemcomitans with La5 resulted in reduced levels of all mediators, the co-infection with Lr32 promoted reduced levels of CXCL-8 and GM-CSF but increased the production of IL-1β. The probiotics upregulated the expression of TLR2 and downregulated TLR4 in cells co-infected with A. actinomycetemcomitans. A. actinomycetemcomitans-induced the upregulation of NRLP3 was attenuated by La5 but increased by Lr32. Furthermore, the transcription of the anti-apoptotic gene BCL-2 was upregulated, whereas the pro-apoptotic BAX was downregulated in cells co-infected with A. actinomycetemcomitans and the probiotics. Infection with A. actinomycetemcomitans induced apoptosis in GECs, whereas the co-infection with lactobacilli attenuated the apoptotic phenotype. Both tested lactobacilli may interfere in A. actinomycetemcomitans colonization of the oral cavity by reducing its ability to interact with gingival epithelial cells and modulating cells response. However, L. acidophilus La5 properties suggest that this strain has a higher potential to control A. actinomycetemcomitans-associated periodontitis than L. rhamnosus Lr32.
Phenotypic and Genotypic Characteristics of a Tigecycline-Resistant Acinetobacter pittii Isolate Carrying blaNDM–1 and the Novel blaOXA Allelic Variant blaOXA–1045
Authors: Ding Zixuan , Li Zhaoyinqian , Zhao Yuanqing , Hao Jingchen , Li Tingting , Liu Yao , Zeng Zhangrui , Liu Jinbo
Published: May 2022

A tigecycline-resistant Acinetobacter pittii clinical strain from pleural fluid carrying a blaNDM–1 gene and a novel blaOXA gene, blaOXA–1045, was isolated and characterized. The AP2044 strain acquired two copies of the blaNDM–1 gene and six antibiotic resistance genes (ARGs) from other pathogens. According to the whole-genome investigation, the GC ratios of ARGs (50–60%) were greater than those of the chromosomal backbone (39.46%), indicating that ARGs were horizontally transferred. OXA-1045 belonged to the OXA-213 subfamily and the amino acid sequence of OXA-1045 showed 89% similarity to the amino acid sequences of OXA-213. Then, blaOXA–1045 and blaOXA–213 were cloned and the minimum inhibitory concentrations (MICs) of β-lactams in the transformants were determined using the broth microdilution method. OXA-1045 was able to confer a reduced susceptibility to piperacillin and piperacillin-tazobactam compared to OXA-213. AP2044 strain exhibited low pathogenicity in Galleria mellonella infection models. The observation of condensed biofilm using the crystal violet staining method and scanning electron microscopy (SEM) suggested that the AP2044 strain was a weak biofilm producer. Quantitative reverse transcription-PCR (qRT-PCR) was used to detect the expression of resistance-nodulation-cell division (RND) efflux pump-related genes. The transcription level of adeB and adeJ genes increased significantly and was correlated with tigecycline resistance. Therefore, our genomic and phenotypic investigations revealed that the AP2044 strain had significant genome plasticity and natural transformation potential, and the emergence of antibiotic resistance in these unusual bacteria should be a concern for future investigations.
Multi-Locus Sequence Analysis Reveals Diversity of the Rice Kernel Smut Populations in the United States
Authors: Khanal Sabin , Antony-Babu Sanjay , Gaire Shankar P. , Zhou Xin-Gen
Published: May 2022

Rice (Oryza sativa) is the second leading cereal crop in the world and is one of the most important field crops in the US, valued at approximately $2.5 billion. Kernel smut (Tilletia horrida Tak.), once considered as a minor disease, is now an emerging economically important disease in the US. In this study, we used multi-locus sequence analysis to investigate the genetic diversity of 63 isolates of T. horrida collected from various rice-growing areas across in the US. Three different phylogeny analyses (maximum likelihood, neighbor-joining, and minimum evolution) were conducted based on the gene sequence sets, consisting of all four genes concatenated together, two rRNA regions concatenated together, and only ITS region sequences. The results of multi-gene analyses revealed the presence of four clades in the US populations, with 59% of the isolates clustering together. The populations collected from Mississippi and Louisiana were found to be the most diverse, whereas the populations from Arkansas and California were the least diverse. Similarly, ITS region-based analysis revealed that there were three clades in the T. horrida populations, with a majority (76%) of the isolates clustering together along with the 22 Tilletia spp. from eight different countries (Australia, China, India, Korea, Pakistan, Taiwan, The US, and Vietnam) that were grouped together. Two of the three clades in the ITS region-based phylogeny consisted of the isolates reported from multiple countries, suggesting potential multiple entries of T. horrida into the US. This is the first multi-locus analysis of T. horrida populations. The results will help develop effective management strategies, especially breeding for resistant cultivars, for the control of kernel smut in rice.
High Diversity and Prevalence of Borrelia burgdorferi sensu lato in Wildlife Hosts, Domestic Animals, and Ticks in Yunnan Province, Southwestern China
Authors: He Zhihai , Jiang Baogui , Huang Lin , Shao Zongti , Zhang Yun , Li Yuqiong , Pu Ennian , Duan Xingde , Jiang Hang , Wang Jian , Yao Mingguo , Wang Fan , Bie Shuangshuang , von Fricken Michael E. , Sun Yi , Dong Yi , Jiang Jiafu , Du Chunhong
Published: May 2022

Borrelia burgdorferi sensu lato (BBSL), the causative agent of Lyme disease, is commonly found in wild and domestic mammals and ticks worldwide. In China, human cases of Borrelia burgdorferi infections have been identified across a wide geographic range including Yunnan Province, but few studies have examined BBSL in reservoirs and vectors in southwestern China. Here we conducted a thorough and broad-range investigation of BBSL in small mammals, domestic mammals, and ticks collected from 159 sample sites across 42 counties in Yunnan Province. DNA was extracted from spleen tissue of small mammals, blood from domestic mammals, and homogenized ticks. Nested PCR targeting the 5S-23S rRNA intergenic spacer gene of BBSL was used for screening, with amplicons sequenced directly and analyzed using a BLAST algorithm. A total of 8,478 samples were collected, which were composed of 5,044 mammals belonging to 68 species, 1,927 livestock belonging to five species, and 1, 507 ticks belonging to 14 species. BBSL was detected in 147 mammals (2.9%) from 30 different species, 20 of which represent the first reported detection in that species. A total of 52 (2.7%) livestock samples were positive for BBSL, with dogs having the highest detection rate (6.3%, 43/687), and 103 ticks (6.8%) tested positive with high prevalence in Ixodes granulatus (44.2%, 23/52), Haemaphysalis nepalensi (33.3%, 3/9) and Haemaphysalis kolonini (19.0%, 31/163). Sequence analysis revealed six genospecies of BBSL including B. afzelii, B. burgdorferi sensu stricto, B. japonica, B. garinii, B. sinica, and B. valaisiana. Significant differences in prevalence rates of BBSL were observed by species, landscape types, altitude, and season. Our findings indicate a wide distribution of multiple endemic BBSL genospecies based on a large-scale survey within Yunnan, which underline the need to expand surveillance efforts for human in southwestern China.
Microbiota Comparison of Amur ide (Leuciscus waleckii) Intestine and Waters at Alkaline Water and Freshwater as the Living Environment
Authors: Luo Liang , Xu Yue , Chang Yumei , Sun Bo , Zhang Limin , Zhao Zhigang , Liang Liqun
Published: May 2022

The intestinal microbiota of marine animals was influenced by the water and environment in which they live. The Amur ide (Leuciscus waleckii) adapts to extremely high alkalinity and is an ideal material for aquacultural studies of alkaline adaptation. In this study, we screened intestinal indicator flora and functional redundancy of intestinal colonies in alkaline-water species (AW) and freshwater species (FW) of Amur ide (L. waleckii) in these different aquatic environments. The available vs. community composition correlations were then predicted by contrasting each other with the flora contained in environmental water samples. Here, five microbial species and six genera were identified owing to the classifiable sequence. The intestinal microbiota that existed in AW and FW had approximately 1/3 of the operational taxonomic units in the respective living water environments, meaning gut microbes in the aqueous habitats will have an influential association with gut microbes in AW and FW. Compared to the bacterial composition of the FW intestine and that present in freshwater, Moraxella osloensis, Psychrobacter maritimus, and Psychrobacter faecalis were significantly enriched in the intestine of AW and alkaline water samples. In the FW intestine and freshwater samples, however, Cryptomonas curvata and Polynucleobacter asymbioticus were highly improved, which can be summarized as Enterobacter sp., the predominant population in the AW gut, while Aeromonas and Ralstonia being primarily present in FW intestines. Photosynthetic bacteria were most significant in both water samples. The results indicated that the intestinal microbiota composition, abundance, and diversity of AW and FW were quite different. In contrast, the microbial composition of the additional alkaline water and freshwater environments showed slight differences. This study expects to enhance our understanding of the alkalinity tolerance of L. waleckii, which will be provided for the breeding of fish living in alkaline water, and push the development of alkaline water resources with increased efficiency.
Optimal NaCl Medium Enhances Squalene Accumulation in Thraustochytrium sp. ATCC 26185 and Influences the Expression Levels of Key Metabolic Genes
Authors: Zhang Aiqing , He Yaodong , Sen Biswarup , Wang Weijun , Wang Xin , Wang Guangyi
Published: May 2022

Squalene, a natural lipid of the terpenoid family, is well-recognized for its roles in regulating cholesterol metabolism, preventing tumor development, and improving immunity. For large-scale squalene production, the unicellular marine protists—thraustochytrids—have shown great potential. However, the growth of thraustochytrids is known to be affected by salt stress, which can eventually influence the squalene content. Here, we study the effects of an optimal concentration of NaCl on the squalene content and transcriptome of Thraustochytrium sp. ATCC 26185. Under the optimal culture conditions (glucose, 30 g/L; yeast extract, 2.5 g/L; and NaCl, 5 g/L; 28°C), the strain yielded 67.7 mg squalene/g cell dry weight, which was significantly greater than that (5.37 mg/g) under the unoptimized conditions. NaCl was determined as the most significant (R = 135.24) factor for squalene production among glucose, yeast extract, and NaCl. Further comparative transcriptomics between the ATCC 26185 culture with and without NaCl addition revealed that NaCl (5 g/L) influences the expression of certain key metabolic genes, namely, IDI, FAS-a, FAS-b, ALDH3, GS, and NDUFS4. The differential expression of these genes possibly influenced the acetyl-CoA and glutamate metabolism and resulted in an increased squalene production. Through the integration of bioprocess technology and transcriptomics, this report provides the first evidence of the possible mechanisms underscoring increased squalene production by NaCl.
High-Fat Diet and Short-Term Unpredictable Stress Increase Long-Chain Ceramides Without Enhancing Behavioral Despair
Authors: Sambolín-Escobales Lubriel , Tirado-Castro Lizmarie , Suarez Cristina , Pacheco-Cruz Dariangelly , Fonseca-Ferrer Wilfred , Deme Pragney , Haughey Norman , Chompre Gladys , Porter James T.
Published: May 2022

Clinical and preclinical studies suggest that increases in long-chain ceramides in blood may contribute to the development of depressive-like behavior. However, which factors contribute to these increases and whether the increases are sufficient to induce depressive-like behaviors is unclear. To begin to address this issue, we examined the effects of high fat diet (HFD) and short-term unpredictable (STU) stress on long-chain ceramides in the serum of male and female rats. We found that brief exposure to HFD or unpredictable stress was sufficient to induce selective increases in the serum concentrations of long-chain ceramides, associated with depression in people. Furthermore, combined exposure to HFD and unpredictable stress caused a synergistic increase in C16:0, C16:1, and C18:0 ceramides in both sexes and C18:1 and C24:1 in males. However, the increased peripheral long-chain ceramides were not associated with increases in depressive-like behaviors suggesting that increases in serum long-chain ceramides may not be associated with the development of depressive-like behaviors in rodents.
LyeTxI-b, a Synthetic Peptide Derived From a Spider Venom, Is Highly Active in Triple-Negative Breast Cancer Cells and Acts Synergistically With Cisplatin
Authors: Avelar Júnior Joaquim Teixeira de , Lima-Batista Edleusa , Castro Junior Célio José , Pimenta Adriano Monteiro de Castro , Dos Santos Raquel Gouvêa , Souza-Fagundes Elaine Maria , De Lima Maria Elena
Published: May 2022

Breast cancer is the most common cancer that affects women globally and is among the leading cause of women’s death. Triple-negative breast cancer is more difficult to treat because hormone therapy is not available for this subset of cancer. The well-established therapy against triple-negative breast cancer is mainly based on surgery, chemotherapy, and immunotherapy. Among the drugs used in the therapy are cisplatin and carboplatin. However, they cause severe toxicity to the kidneys and brain and cause nausea. Therefore, it is urgent to propose new chemotherapy techniques that provide new treatment options to patients affected by this disease. Nowadays, peptide drugs are emerging as a class of promising new anticancer agents due to their lytic nature and, apparently, a minor drug resistance compared to other conventional drugs (reviewed in Jafari et al., 2022). We have recently reported the cytotoxic effect of the antimicrobial peptide LyeTx I-b against glioblastoma cells (Abdel-Salam et al., 2019). In this research, we demonstrated the cytotoxic effect of the peptide LyeTx I-b, alone and combined with cisplatin, against triple-negative cell lines (MDA-MD-231). LyeTx-I-b showed a selectivity index 70-fold higher than cisplatin. The peptide:cisplatin combination (P:C) 1:1 presented a synergistic effect on the cell death and a selective index value 16 times greater than the cisplatin alone treatment. Therefore, an equi-effective reduction of cisplatin can be reached in the presence of LyeTx I-b. Cells treated with P:C combinations were arrested in the G2/M cell cycle phase and showed positive staining for acridine orange, which was inhibited by bafilomycin A1, indicating autophagic cell death (ACD) as a probable cell death mechanism. Furthermore, Western blot experiments indicated a decrease in P21 expression and AKT phosphorylation. The decrease in AKT phosphorylation is indicative of ACD. However, other studies are still necessary to better elucidate the pathways involved in the cell death mechanism induced by the peptide and the drug combinations. These findings confirmed that the peptide LyeTx I-b seems to be a good candidate for combined chemotherapy to treat breast cancer. In addition, in vivo studies are essential to validate the use of LyeTx I-b as a therapeutic drug candidate, alone and/or combined with cisplatin.
Associations of Parity With Change in Global Cognition and Incident Cognitive Impairment in Older Women
Authors: Zhou Rui , Liu Hua-Min , Zou Lian-Wu , Wei Hong-Xia , Huang Yi-Ning , Zhong Qi , Gu Shan-Yuan , Chen Ming-Feng , Wang Shao-Li , Sun Hai-Xia , Wu Xian-Bo
Published: May 2022

Background

The evidence of the association between parity and risk of mild cognitive impairment (MCI) or dementia is mixed, and the relationship between parity and longitudinal cognitive changes is less clear. We investigated these issues in a large population of older women who were carefully monitored for development of MCI and probable dementia.

Methods

Using the Women’s Health Initiative Memory Study, 7,100 postmenopausal women (mean age 70.1 ± 3.8 years) with information on baseline parity (defined as the number of term pregnancies), measures of global cognition (Modified Mini-Mental State Examination score) from 1996–2007, and cognitive impairment (centrally adjudicated diagnoses of MCI and dementia) from 1996–2016 were included. Multivariable linear mixed-effects models were used to analyze the rate of changes in global cognition. Cox regression models were used to evaluate the risk of MCI/dementia across parity groups.

Results

Over an average of 10.5 years, 465 new cases of MCI/dementia were identified. Compared with nulliparous women, those with a parity of 1–3 and ≥4 had a lower MCI/dementia risk. The HRs were 0.75 (0.56–0.99) and 0.71 (0.53–0.96), respectively (P < 0.01). Similarly, a parity of 1–3 and ≥4 was related to slower cognitive decline (β = 0.164, 0.292, respectively, P < 0.05).

Conclusion

Higher parity attenuated the future risk for MCI/dementia and slowed the rates of cognitive decline in elderly women. Future studies are needed to determine how parity affects late-life cognitive function in women.
A New Vestibular Stimulation Mode for Motion Sickness With Emphatic Analysis of Pica
Authors: Zhang Zhi-Hao , Liu Li-Peng , Fang Yan , Wang Xiao-Cheng , Wang Wei , Chan Ying-Shing , Wang Lu , Li Hui , Li Yun-Qing , Zhang Fu-Xing
Published: May 2022

Motion sickness (MS) was frequently introduced for rodents in research work through passive motion that disturbed vestibular signals in the presence of visual and aleatory, proprioceptive inputs. Inducement of MS in this way causes conflicting signals that activate intermixed neural circuits representing multimodal stimulation. From reductionism, a lab setup to elicit rat MS via vestibular stimulation was configured in the present study for MS study in connection with dissection of the central vestibular component causally underlying MS. The individual animal was blinded to light with a custom-made restrainer, and positioned at an inclination of 30° for otolith organs to receive unusual actions by gravitoinertial vector. Following a 2-h double-axis (earth–vertical) rotation involving angular acceleration/deceleration, a suit of behaviors characterizing the MS was observed to be significantly changed including pica (eating non-nutritive substance like kaolin), conditioned taste avoidance and locomotion (p < 0.05). Notably, for the statistical hypothesis testing, the utility of net increased amount of kaolin consumption as independent variables in data processing was expounded. In addition, Fos-immunostained neurons in vestibular nucleus complex were significantly increased in number, suggesting the rotation-induced MS was closely related to the vestibular activation. In conclusion, our work indicated that the present setup could effectively elicit the MS by disturbing vestibular signals in rat in the context of well-controlled proprioceptive inputs and lack of visual afference.
Non-Cell-Autonomous Factors Implicated in Parvalbumin Interneuron Maturation and Critical Periods
Authors: Gibel-Russo Rachel , Benacom David , Di Nardo Ariel A.
Published: May 2022

From birth to adolescence, the brain adapts to its environmental stimuli through structural and functional remodeling of neural circuits during critical periods of heightened plasticity. They occur across modalities for proper sensory, motor, linguistic, and cognitive development. If they are disrupted by early-life adverse experiences or genetic deficiencies, lasting consequences include behavioral changes, physiological and cognitive deficits, or psychiatric illness. Critical period timing is orchestrated not only by appropriate neural activity but also by a multitude of signals that participate in the maturation of fast-spiking parvalbumin interneurons and the consolidation of neural circuits. In this review, we describe the various signaling factors that initiate critical period onset, such as BDNF, SPARCL1, or OTX2, which originate either from local neurons or glial cells or from extracortical sources such as the choroid plexus. Critical period closure is established by signals that modulate extracellular matrix and myelination, while timing and plasticity can also be influenced by circadian rhythms and by hormones and corticosteroids that affect brain oxidative stress levels or immune response. Molecular outcomes include lasting epigenetic changes which themselves can be considered signals that shape downstream cross-modal critical periods. Comprehensive knowledge of how these signals and signaling factors interplay to influence neural mechanisms will help provide an inclusive perspective on the effects of early adversity and developmental defects that permanently change perception and behavior.
Sonification of Computer Processes: The Cases of Computer Shutdown and Idle Mode
Authors: Panariello Claudio , Bresin Roberto
Published: May 2022

Software is intangible, invisible, and at the same time pervasive in everyday devices, activities, and services accompanying our life. Therefore, citizens hardly realize its complexity, power, and impact in many aspects of their daily life. In this study, we report on one experiment that aims at letting citizens make sense of software presence and activity in their everyday lives, through sound: the invisible complexity of the processes involved in the shutdown of a personal computer. We used sonification to map information embedded in software events into the sound domain. The software events involved in a shutdown have names related to the physical world and its actions: write events (information is saved into digital memories), kill events (running processes are terminated), and exit events (running programs are exited). The research study presented in this article has a “double character.” It is an artistic realization that develops specific aesthetic choices, and it has also pedagogical purposes informing the causal listener about the complexity of software behavior. Two different sound design strategies have been applied: one strategy is influenced by the sonic characteristics of the Glitch music scene, which makes deliberate use of glitch-based sound materials, distortions, aliasing, quantization noise, and all the “failures” of digital technologies; and a second strategy based on the sound samples of a subcontrabass Paetzold recorder, an unusual and special acoustic instrument which unique sound has been investigated in the contemporary art music scene. Analysis of quantitative ratings and qualitative comments of 37 participants revealed that the sound design strategies succeeded in communicating the nature of the computer processes. Participants also showed in general an appreciation of the aesthetics of the peculiar sound models used in this study.
Molecular Mechanisms Underlying the Therapeutic Role of Vitamin E in Age-Related Macular Degeneration
Authors: Edwards Genea , Olson Caroline G. , Euritt Carlyn P. , Koulen Peter
Published: May 2022

The eye is particularly susceptible to oxidative stress and disruption of the delicate balance between oxygen-derived free radicals and antioxidants leading to many degenerative diseases. Attention has been called to all isoforms of vitamin E, with α-tocopherol being the most common form. Though similar in structure, each is diverse in antioxidant activity. Preclinical reports highlight vitamin E’s influence on cell physiology and survival through several signaling pathways by activating kinases and transcription factors relevant for uptake, transport, metabolism, and cellular action to promote neuroprotective effects. In the clinical setting, population-based studies on vitamin E supplementation have been inconsistent at times and follow-up studies are needed. Nonetheless, vitamin E’s health benefits outweigh the controversies. The goal of this review is to recognize the importance of vitamin E’s role in guarding against gradual central vision loss observed in age-related macular degeneration (AMD). The therapeutic role and molecular mechanisms of vitamin E’s function in the retina, clinical implications, and possible toxicity are collectively described in the present review.
Neuronal Polarity Pathways as Central Integrators of Cell-Extrinsic Information During Interactions of Neural Progenitors With Germinal Niches
Authors: Solecki David J.
Published: May 2022

Germinal niche interactions and their effect on developing neurons have become the subject of intense investigation. Dissecting the complex interplay of cell-extrinsic and cell-intrinsic factors at the heart of these interactions reveals the critical basic mechanisms of neural development and how it goes awry in pediatric neurologic disorders. A full accounting of how developing neurons navigate their niches to mature and integrate into a developing neural circuit requires a combination of genetic characterization of and physical access to neurons and their supporting cell types plus transformative imaging to determine the cell biological and gene-regulatory responses to niche cues. The mouse cerebellar cortex is a prototypical experimental system meeting all of these criteria. The lessons learned therein have been scaled to other model systems and brain regions to stimulate discoveries of how developing neurons make many developmental decisions. This review focuses on how mouse cerebellar granule neuron progenitors interact with signals in their germinal niche and how that affects the neuronal differentiation and cell polarization programs that underpin lamination of the developing cerebellum. We show how modeling of these mechanisms in other systems has added to the growing evidence of how defective neuronal polarity contributes to developmental disease.
Tracking the Effect of Therapy With Single-Trial Based Classification After Stroke
Authors: Scaglione Alessandro , Conti Emilia , Allegra Mascaro Anna Letizia , Pavone Francesco Saverio
Published: May 2022

Stroke is a debilitating disease that leads, in the 50% of cases, to permanent motor or cognitive impairments. The effectiveness of therapies that promote recovery after stroke depends on indicators of the disease state that can measure the degree of recovery or predict treatment response or both. Here, we propose to use single-trial classification of task dependent neural activity to assess the disease state and track recovery after stroke. We tested this idea on calcium imaging data of the dorsal cortex of healthy, spontaneously recovered and rehabilitated mice while performing a forelimb retraction task. Results show that, at a single-trial level for the three experimental groups, neural activation during the reward pull can be detected with high accuracy with respect to the background activity in all cortical areas of the field of view and this activation is quite stable across trials and subjects of the same group. Moreover, single-trial responses during the reward pull can be used to discriminate between healthy and stroke subjects with areas closer to the injury site displaying higher discrimination capability than areas closer to this site. Finally, a classifier built to discriminate between controls and stroke at the single-trial level can be used to generate an index of the disease state, the therapeutic score, which is validated on the group of rehabilitated mice. In conclusion, task-related neural activity can be used as an indicator of disease state and track recovery without selecting a peculiar feature of the neural responses. This novel method can be used in both the development and assessment of different therapeutic strategies.
2-Hydroxy-4-(Methylthio) Butanoic Acid Isopropyl Ester Supplementation Altered Ruminal and Cecal Bacterial Composition and Improved Growth Performance of Finishing Beef Cattle
Authors: Qin Xiaoli , Zhang Depeng , Qiu Xinjun , Zhao Kai , Zhang Siyu , Liu Chunlan , Lu Lianqiang , Cui Yafang , Shi Changxiao , Chen Zhiming , Hao Rikang , Li Yingqi , Yang Shunran , Wang Lina , Wang Huili , Cao Binghai , Su Huawei
Published: May 2022

The objective of this study was to evaluate the effects of isopropyl ester of 2-hydroxy-4-(methylthio)-butyrate acid (HMBi) on ruminal and cecal fermentation, microbial composition, nutrient digestibility, plasma biochemical parameters, and growth performance in finishing beef cattle. The experiment was conducted for 120 days by a complete randomized block design. Sixty 24-month-old Angus steers (723.9 ± 11.6 kg) were randomly assigned to one of the flowing three treatments: basal diet (the concentrate: 7.6 kg/head·d−1, the rice straw: ad libitum) supplemented with 0 g/d MetaSmart® (H0), a basal diet supplemented with 15 g/d of MetaSmart® (H15), and a basal diet supplemented with 30 g/d of MetaSmart® (H30). Results showed that the average daily gain (ADG) increased linearly (P = 0.004) and the feed conversion ratio (FCR) decreased linearly (P < 0.01) with the increasing HMBi supplementation. Blood urea nitrogen (BUN) concentration significantly decreased in the H30 group (P < 0.05) compared with H0 or H15. The ruminal pH value tended to increase linearly (P = 0.086) on day 56 with the increased HMBi supplementation. The concentrations of ammonia–nitrogen (NH3-N), propionate, isobutyrate, butyrate, isovalerate, valerate, and total volatile fatty acid (VFA) were linearly decreased in the cecum (P < 0.05). The results of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that the abundance of most pathways with a significant difference was higher in the rumen and lower in the cecum in the H30 group compared to the H0 group, and those pathways were mainly related to the metabolism of amino acids, carbohydrates, and lipids. Correlation analysis showed that ADG was positively associated with the ratio of firmicutes/bacteroidetes both in the rumen and cecum. Additionally, the abundance of Lachnospiraceae, Saccharofermentans, Lachnospiraceae_XPB1014_group, and Ruminococcus_1 was positively correlated with ADG and negatively correlated with FCR and BUN in the rumen. In the cecum, ADG was positively correlated with the abundances of Peptostreptococcaceae, Romboutsia, Ruminococcaceae_UCG-013, and Paeniclostridium, and negatively correlated with the abundances of Bacteroidaceae and Bacteroides. Overall, these results indicated that dietary supplementation of HMBi can improve the growth performance and the feed efficiency of finishing beef cattle by potentially changing bacterial community and fermentation patterns of rumen and cecum.
Dietary Antioxidant Indices in Relation to All-Cause and Cause-Specific Mortality Among Adults With Diabetes: A Prospective Cohort Study
Authors: Wang Wenjie , Wang Xiaoyan , Cao Shiling , Duan Yiting , Xu Chengquan , Gan Da , He Wei
Published: May 2022

Background

The potential beneficial effect of individual antioxidants on mortality has been reported. However, the association of overall intakes of dietary antioxidants with all-cause and cause-specific mortality among adults with diabetes remained unclear.

Methods

A total of 4,699 US adults with diabetes were enrolled in 2003–2014 in the National Health and Nutrition Examination Survey (NHANES) and followed for mortality until 31 December 2015. The Dietary Antioxidant Quality Score (DAQS) and the Dietary Antioxidant Index (DAI), which indicate the total antioxidant properties, were calculated based on the intakes of vitamins A, C, E, zinc, selenium, and magnesium. The Cox proportional hazards regression models were used to investigate the associations of the DAQS or the DAI with all-cause and cause-specific mortality.

Results

A total of 913 deaths occurred during 27,735 person-years of follow-up, including 215 deaths due to cardiovascular disease (CVD) and 173 deaths due to cancer. The higher intakes of antioxidant vitamins A, E, magnesium, and selenium were associated with lower all-cause mortality. The adjusted hazard ratios (HRs) (95% CIs) comparing the highest DAQS (5–6) to the lowest DAQS (0–2) were 0.70 (0.53–0.92) for all-cause mortality, 0.56 (0.35–0.90) for CVD mortality, and 0.59 (0.33–1.04) for cancer mortality. Consistent inverse associations were found between the DAI and mortality.

Conclusion

Higher intake of overall dietary antioxidants was associated with lower risk of death from all-cause and CVD in adults with diabetes. Future dietary intervention studies are needed to determine whether increasing overall antioxidant micronutrients intake could prevent premature death among adults with diabetes.
A Novel Clinically Prognostic Stratification Based on Prognostic Nutritional Index Status and Histological Grade in Patients With Gallbladder Cancer After Radical Surgery
Authors: Cao Peng , Hong Haijie , Yu Zijian , Chen Guodong , Qi Shuo
Published: May 2022

Purpose

Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a 5-year survival rate of 5%. The prognostic models to predict the prognosis of patients with GBC remain controversial. Therefore, to construct a prognosis prediction of GBC, a retrospective cohort study was carried out to investigate the prognostic nutritional index and histological grade in the long-term outcome of patients with GBC after radical surgery (RS).

Methods

A retrospective study of a total of 198 patients with GBC who underwent surgical treatment were enrolled. The hematological indicators, imageological data, and perioperative clinical data were acquired for statistical analysis and poor prognosis model construction.

Results

Prognostic nutrition index (PNI) < 45.88, maximum tumor diameter (MTD) > 2.24 cm, and jaundice (JD) were all associated with a poor prognosis in multivariate logistic regression analysis. The prognosis prediction model was based on the three risk factors, which indicated a superior predictive ability in the primary cohort [area under the curve (AUC) = 0.951] and validation cohort (AUC = 0.888). In multivariate Cox regression analysis, poorly differentiation (PD) was associated with poor 3-year survival. In addition, Kaplan–Meier (KM) survival analysis suggested that GBC patients with high-risk scores and PD had a better prognosis after RS (p < 0.05), but there was no significant difference in prognosis for patients with non-poorly differentiation (NPD) or low-risk scores after RS (p > 0.05).

Conclusion

Our prediction model for GBC patients with prognosis evaluation is accurate and effective. For patients with PD and high-risk scores, RS is highly recommended; a simple cholecystectomy can also be considered for acceptance for patients with NPD or low-risk score. The significant findings provide a new therapeutic strategy for the clinical treatment of GBC.
Association Between Systemic Lupus Erythematosus and Cancer Morbidity and Mortality: Findings From Cohort Studies
Authors: Zhang Min , Wang Yizhou , Wang Yutong , Bai Ye , Gu Dongqing
Published: May 2022

Background

Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.

Methods

A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.

Results

A total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, P<0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70, P<0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin’s lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004, P=0.0035).

Conclusions

Findings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, CRD42021243635.
Identification by Bioinformatics Analysis of Potential Key Genes Related to the Progression and Prognosis of Gastric Cancer
Authors: Gao Wencang , Yang Min
Published: May 2022

Objective

Despite increasingly sophisticated medical technology, the prognosis of patients with advanced gastric cancer is still not objectively certain. Therefore, it is urgent to identify new diagnostic and prognostic biomarkers. To identify potential critical genes related to gastric cancer’s staging mechanism and to the prognosis of gastric cancer.

Methods

Dynamic trend analysis was conducted to find genes with similar trends in gastric cancer staging in order to explore the differentially expressed genes in gastric cancer and identify the intersection of the results of the dynamic trend analysis. Functional predictive analysis were performed on the obtained genes to observe the expression of prognostic genes in gastric cancer and in gastric cancer stages as well as the correlation with tumor immune cell infiltration. Gastric cancer samples were collected and sequenced for follow-up analysis based on the results of the Cancer Genome Atlas (TCGA) database analysis.

Results

The expression of genes enriched in module 0 had a similar trend in gastric cancer staging. 3213 differential genes were screened. A total of 50 intersection genes were obtained among genes with similar trends, of which only 10 genes have prognostic significance in gastric cancer. These 10 genes were correlated with macrophage infiltration in varying degrees. In addition, we found that AGT was significantly abnormally expressed in the results of sample sequencing. AGT was related to the occurrence of gastric cancer and interacted with brd9, golph3, nom1, klhl25, and psmd11.

Conclusion

AGT has prominent abnormal expression in gastric cancer and may promote gastric cancer progression. This study provides a new direction for further exploring potential biomarkers and molecular targeted gastric cancer therapy.
Differences in Characteristics and Outcomes Between Large-Cell Neuroendocrine Carcinoma of the Ovary and High-Grade Serous Ovarian Cancer: A Retrospective Observational Cohort Study
Authors: Pang Li , Guo Zhiqiang
Published: May 2022

Background

Owing to its extremely low incidence and the paucity of relevant reports, there is currently no recognized first-line treatment strategy for ovarian large-cell neuroendocrine carcinoma, and there are no statistics related to prognosis derived from large samples. This study aimed to investigate the characteristics, outcomes, and independent predictors of survival for ovarian large-cell neuroendocrine carcinoma and compare them with those of high-grade serous ovarian cancer.

Methods

The Surveillance, Epidemiology, and End Results database was used to identify women diagnosed with ovarian large-cell neuroendocrine carcinoma or high-grade serous ovarian cancer from 1988 to 2015. Clinical, demographic, and treatment characteristics were compared between the groups. Propensity-score matching, Cox risk regression analysis, and Kaplan–Meier survival curves were used to analyze the data.

Results

In total, 23,917 women, including 23,698 (99.1%) diagnosed with high-grade serous ovarian cancer and 219 (0.9%) diagnosed with ovarian large-cell neuroendocrine carcinoma, were identified. Age >77 years, diagnosis before 2003–2010, and advanced-stage disease were more common in patients with ovarian large-cell neuroendocrine carcinoma than in those with high-grade serous ovarian cancer. Women with ovarian large-cell neuroendocrine carcinoma were less likely to receive adjuvant chemotherapy (54.8% vs. 81.9%) but more likely to receive radiotherapy (3.2% vs. 1.5%; both P<0.001) than women with high-grade serous ovarian cancer. Stage, chemotherapy, and tumor size were independent predictors of overall survival, and the risk of death was greater in the advanced stage than in the early stage (P=0.047). Chemotherapy and tumor size were also independent predictors of cancer-specific survival. Overall and cancer-specific survival rates were significantly low for ovarian large-cell neuroendocrine carcinoma than for more malignant high-grade serous ovarian cancer.

Conclusions

Compared to patients with high-grade serous ovarian cancer, those with ovarian large-cell neuroendocrine carcinoma presented more often with advanced-stage disease and had decreased overall and cancer-specific survival rates.