bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Reactive Oxygen Species Generated by Inorganic Nanomaterials for Cancer Therapeutics
Authors: Zhang Lizhen , Zhu Chengyuan , Huang Rongtao , Ding Yanwen , Ruan Changping , Shen Xing-Can
Published: March 2021

Recently, inorganic nanomaterials have received considerable attention for use in biomedical applications owing to their unique physicochemical properties based on their shapes, sizes, and surface characteristics. Photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemical dynamic therapy (CDT), which are cancer therapeutics mediated by reactive oxygen species (ROS), have the potential to significantly enhance the therapeutic precision and efficacy for cancer. To facilitate cancer therapeutics, numerous inorganic nanomaterials have been developed to generate ROS. This mini review provides an overview of the generation mechanisms of ROS by representative inorganic nanomaterials for cancer therapeutics, including the structures of engineered inorganic nanomaterials, ROS production conditions, ROS types, and the applications of the inorganic nanomaterials in cancer PDT, SDT, and CDT.
Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice
Authors: Han Ci , Zhang Zhaodi , Guo Nana , Li Xueting , Yang Mengyuan , Peng Yahui , Ma Xiaohui , Yu Kaijiang , Wang Changsong
Published: March 2021

In recent years, more and more attention has been paid to intestinal microbiome. Almost all operations will go through the anesthesia process, but it is not clear whether the intervention of anesthesia alone will affect the change in the intestinal microbiome. The purpose of this study was to verify the effect of sevoflurane inhalation anesthesia on the intestinal microbiome. The animal in the experimental group was used to provide sevoflurane inhalation anesthesia for 4 hours. The control group was not intervened. The feces of the experimental group and the control group were collected on the 1st, 3rd, 7th and 14th days after anesthesia. Sevoflurane inhalation anesthesia will cause changes in the intestinal microbiome of mice. It appears on the 1st day after anesthesia and is most obvious on the 7th day. The specific manifestation is that the abundance of microbiome and the diversity of the microbiome is reduced. At the same time, Untargeted metabonomics showed that compared with the control group, the experimental group had more increased metabolites related to the different microbiome, among which 5-methylthioadenosine was related to the central nervous system. Subsequently, the intestinal microbiome diversity of mice showed a trend of recovery on the 14th day. At the genus level, the fecal samples obtained on the 14th day after anesthesia exhibited significantly increased abundances of Bacteroides, Alloprevotella, and Akkermansia and significantly decreased abundances of Lactobacillus compared with the samples obtained on the 1st day after anesthesia. However, the abundance of differential bacteria did not recover with the changing trend of diversity. Therefore, we believe that sevoflurane inhalation anesthesia is associated with changes in the internal microbiome and metabolites, and this change may be completed through the brain-gut axis, while sevoflurane inhalation anesthesia may change the intestinal microbiome for as long as 14 days or longer.
The Role of Neutrophil Extracellular Traps in Periodontitis
Authors: Wang Jingyi , Zhou Yucong , Ren Biao , Zou Ling , He Bing , Li Mingyun
Published: March 2021

Periodontitis is a chronic, destructive disease of periodontal tissues caused by multifaceted, dynamic interactions. Periodontal bacteria and host immunity jointly contribute to the pathological processes of the disease. The dysbiotic microbial communities elicit an excessive immune response, mainly by polymorphonuclear neutrophils (PMNs). As one of the main mechanisms of PMN immune response in the oral cavity, neutrophil extracellular traps (NETs) play a crucial role in the initiation and progression of late-onset periodontitis. NETs are generated and released by neutrophils stimulated by various irritants, such as pathogens, host-derived mediators, and drugs. Chromatin and proteins are the main components of NETs. Depending on the characteristics of the processes, three main pathways of NET formation have been described. NETs can trap and kill pathogens by increased expression of antibacterial components and identifying and trapping bacteria to restrict their spread. Moreover, NETs can promote and reduce inflammation, inflicting injuries on the tissues during the pro-inflammation process. During their long-term encounter with NETs, periodontal bacteria have developed various mechanisms, including breaking down DNA of NETs, degrading antibacterial proteins, and impacting NET levels in the pocket environment to resist the antibacterial function of NETs. In addition, periodontal pathogens can secrete pro-inflammatory factors to perpetuate the inflammatory environment and a friendly growth environment, which are responsible for the progressive tissue damage. By learning the strategies of pathogens, regulating the periodontal concentration of NETs becomes possible. Some practical ways to treat late-onset periodontitis are reducing the concentration of NETs, administering anti-inflammatory therapy, and prescribing broad-spectrum and specific antibacterial agents. This review mainly focuses on the mechanism of NETs, pathogenesis of periodontitis, and potential therapeutic approaches based on interactions between NETs and periodontal pathogens.
Strategic Use of (Un)certainty Expressions
Authors: Lorson Alexandra , Cummins Chris , Rohde Hannah
Published: March 2021

Speakers have a number of options when introducing propositions which they take to be uncertain: for instance, they can use verbs such as ‘know’, ‘believe’ or ‘think’. The production of uncertainty expressions is highly context dependent. One promising approach to capturing the semantic meaning of these expressions takes them to be available only when the speaker’s confidence in the proposition exceeds some threshold. However, it is unclear whether this approach deals satisfactorily with the full range of usages of uncertainty expressions. For instance, speakers may also use them to achieve social goals such as toning down the force of their assertion. In this case they pursue another communicative goal than just being cooperative: they also aim to be polite. The current study investigates the speakers’ motivations in choosing between uncertainty expressions such as ‘believe’ or the factive ‘know’ in two controlled contexts. More specifically, we show that speakers’ choice of expression is influenced by (i) how likely they estimate an event to be and (ii) strategic considerations relating to the communicative context in which they are working. Thus, speakers adjust their language as a manipulative process. We situate these results in the context of threshold semantics.
Minimizing Paravalvular Regurgitation With the Novel SAPIEN 3 Ultra TAVR Prosthesis: A Real-World Comparison Study
Authors: Tamm Alexander R. , Hell Michaela M. , Geyer Martin , Kreidel Felix , da Rocha e Silva Jaqueline G. , Seidl Meike , Ruf Tobias F. , Kornberger Angela , Beiras-Fernandez Andres , Münzel Thomas , von Bardeleben Ralph Stephan
Published: March 2021

Objectives: We investigated performance and outcome of the latest-generation balloon-expandable SAPIEN 3 Ultra prosthesis (S3U) compared to the established SAPIEN 3 prosthesis (S3) in a real-world cohort, with focus on paravalvular regurgitation (PVR).

Background: PVR is an adverse prognostic indicator of short- and long-term survival after transcatheter aortic valve replacement (TAVR). The S3U has been designed to improve sealing.

Methods: We enrolled 343 consecutive patients presenting with severe native aortic valve stenosis eligible for a balloon-expandable prosthesis. The established S3 was implanted in the first 200 patients, the following 143 patients received the novel S3U after introduction in our institution. Primary endpoint was PVR after TAVR. Furthermore, we investigated procedural parameters and in-hospital and 30-day outcome.

Results: PVR was significantly lower in the S3U cohort compared to the S3 cohort. They differed in their rate of mild PVR (11.2 vs. 48.0%, p < 0.001), whereas at least moderate PVR was similarly low in both cohorts (0.7 vs. 0.5%, p = 0.811). A significant reduction of post-dilatation rate, fluoroscopy time, and amount of contrast was observed in patients treated with the novel S3U (p < 0.001). The rate of adverse events in the in-hospital course and at 30 days were similarly low. At 30 days more patients receiving S3U improved in NYHA class (improvement ≥2 grades 34.6 vs. 19.9%, p = 0.003).

Conclusion: The current study provides evidence that the novel S3U strongly minimizes PVR, thereby demonstrating the efficacy of improved sealing. Further studies will have to address if the observed reduction of PVR with S3U has prognostic significance.
Source Parameters of Moderate-To-Large Chinese Earthquakes From the Time Evolution of P-Wave Peak Displacement on Strong Motion Recordings
Authors: Wang Yuan , Colombelli Simona , Zollo Aldo , Song Jindong , Li Shanyou
Published: March 2021

In this work we propose and apply a straightforward methodology for the automatic characterization of the extended earthquake source, based on the progressive measurement of the P-wave displacement amplitude at the available stations deployed around the source. Specifically, we averaged the P-wave peak displacement measurements among all the available stations and corrected the observed amplitude for distance attenuation effect to build the logarithm of amplitude vs. time function, named LPDT curve. The curves have an exponential growth shape, with an initial increase and a final plateau level. By analyzing and modelling the LPDT curves, the information about earthquake rupture process and earthquake magnitude can be obtained. We applied this method to the Chinese strong motion data from 2007 to 2015 with Ms ranging between 4 and 8. We used a refined model to reproduce the shape of the curves and different source models based on magnitude to infer the source-related parameters for the study dataset. Our study shows that the plateau level of LPDT curves has a clear scaling with magnitude, with no saturation effect for large events. By assuming a rupture velocity of 0.9 Vs, we found a consistent self-similar, constant stress drop scaling law for earthquakes in China with stress drop mainly distributed at a lower level (0.2 MPa) and a higher level (3.7 MPa). The derived relation between the magnitude and rupture length may be feasible for real-time applications of Earthquake Early Warning systems.
Depositional and Diagenetic Controls on Macroscopic Acoustic and Geomechanical Behaviors in Wufeng-Longmaxi Formation Shale
Authors: Deng Jixin , Wang Chongyi , Zhao Qun , Guo Wei , Tang Genyang , Zhao Jianguo
Published: March 2021

This integrated study provides significant insight into parameters controlling the dynamic and static elastic behaviors of shale. Acoustic and geomechanical behaviors measurement from laboratory have been coupled with detailed petrographic and geochemical analyses, and microtexture observations on shale samples from the Wufeng−Longmaxi Formation of the southeast Sichuan Basin. The major achievement is the establishment of the link between depositional environment and the subsequent microtexture development, which exerts a critical influence on the elastic properties of the shale samples. Microtexture and compositional variation between upper and lower sections of the Wufeng−Longmaxi Formation show that the former undergoes normal mechanical and chemical compaction to form clay supported matrices with apparent heterogonous mechanical interfaces between rigid clasts and the aligned clay fabric. Samples from lower sections exhibited a microcrystalline quartz-supported matrix with a homogeneous mechanical interface arising from syn-depositional reprecipitation of biogenic quartz cement. This type of microtexture transition exerts primary control on elastic behavior of the shale samples. A clear “V” shaped trend observed from acoustic velocities and static Young’s moduli document contrasting roles played by microtexture, porosity and organic matter in determining elastic properties. Samples with a quartz-supported matrix exhibit elastic deformation and splitting failure modes. The increment of the continuous biogenic quartz cemented medium with limited mechanic interface. By contrast, samples showing a predominantly clay-supported matrix exhibited more signs of plastic deformation reflecting heterogeneous mechanical interfaces at grain boundaries.
Soil Degassing From the Xianshuihe–Xiaojiang Fault System at the Eastern Boundary of the Chuan–Dian Rhombic Block, Southwest China
Authors: Sun Yutao , Zhou Xiaocheng , Yan Yucong , Li Jingchao , Fang Wenya , Wang Wanli , Liu Yongmei
Published: March 2021

The Chuan–Dian region, situated in the middle part of the north-south seismic zone of mainland China in a highly deformed area of the eastern margin of the Tibetan Plateau, is one of the principal areas for monitoring earthquake activities in China. In this study, the geochemical characteristics of soil degassing (of CH4, H2, CO2, Rn, and Hg) and, the relationship between degassing and fault activity, were investigated in the Xianshuihe–Xiaojiang fault system (XXFS) at the eastern boundary of the Chuan–Dian rhombic block. The mean soil-gas concentrations of CH4, H2, CO2, Rn, and Hg in the XXFS were 8.1 ppm, 9.9 ppm, 0.5%, 15.1 kBq/m3 and 12.9 ng/m3, respectively. The δ13CCO2 and δ13CCH4 values of the hot-spring gases varied from −11.9‰ to −3.7‰ and −62.5‰ to 17‰, respectively. The He-C isotopic ratios indicate that the carbon in the northern and middle parts of the XXFS may have originated from deep fluids, whereas the carbon in the southern part of the XXFS is of organic origin. The high concentrations of soil gas were distributed near the faults, indicating that the faults could act as channels for gas migration. The distributions of the high soil-gas concentrations in the XXFS coincide with the highest stress and maximum strain rates, indicating that the fault activity enhanced permeability and increased the emission rates of the gases. The results of this study will be helpful for degassing in active fault zones and earthquake monitoring.
Can We Compare Effect Size of Spatial Genetic Structure Between Studies and Species Using Moran Eigenvector Maps?
Authors: Hein Celia , Abdel Moniem Hossam E. , Wagner Helene H.
Published: March 2021

As the field of landscape genetics is progressing toward comparative empirical studies and meta-analysis, it is important to know how best to compare the strength of spatial genetic structure between studies and species. Moran’s Eigenvector Maps are a promising method that does not make an assumption of isolation-by-distance in a homogeneous environment but can discern cryptic structure that may result from multiple processes operating in heterogeneous landscapes. MEMgene uses spatial filters from Moran’s Eigenvector Maps as predictor variables to explain variation in a genetic distance matrix, and it returns adjusted R2 as a measure of the amount of genetic variation that is spatially structured. However, it is unclear whether, and under which conditions, this value can be used to compare the degree of spatial genetic structure (effect size) between studies. This study addresses the fundamental question of comparability at two levels: between independent studies (meta-analysis mode) and between species sampled at the same locations (comparative mode). We used published datasets containing 9,900 haploid, biallelic, neutral loci simulated on a quasi-continuous, square landscape under four demographic scenarios (island model, isolation-by-distance, expansion from one or two refugia). We varied the genetic resolution (number of individuals and loci) and the number of random sampling locations. We considered two measures of effect size, the MEMgene adjusted R2 and multivariate Moran’s I, which is related to Moran’s Eigenvector Maps. Both metrics were highly sensitive to the number of locations, even when using standardized effect sizes, SES, and the number of individuals sampled per location, but not to the number of loci. In comparative mode, using the same Moran Eigenvector Maps for all species, even those with missing values at some sampling locations, reduced bias due to the number of locations under isolation-by-distance (stationary process) but increased it under expansion from one or two refugia (non-stationary process). More robust measures of effect size need to be developed before the strength of spatial genetic structure can be accurately compared, either in a meta-analysis of independent empirical studies or within a comparative, multispecies landscape genetic study.
Ultrabithorax Is a Micromanager of Hindwing Identity in Butterflies and Moths
Authors: Tendolkar Amruta , Pomerantz Aaron F. , Heryanto Christa , Shirk Paul D. , Patel Nipam H. , Martin Arnaud
Published: March 2021

The forewings and hindwings of butterflies and moths (Lepidoptera) are differentiated from each other, with segment-specific morphologies and color patterns that mediate a wide range of functions in flight, signaling, and protection. The Hox geneUltrabithorax(Ubx) is a master selector gene that differentiates metathoracic from mesothoracic identities across winged insects, and previous work has shown this role extends to at least some of the color patterns from the butterfly hindwing. Here we used CRISPR targeted mutagenesis to generateUbxloss-of-function somatic mutations in two nymphalid butterflies (Junonia coenia,Vanessa cardui) and a pyralid moth (Plodia interpunctella). The resulting mosaic clones yielded hindwing-to-forewing transformations, showingUbxis necessary for specifying many aspects of hindwing-specific identities, including scale morphologies, color patterns, and wing venation and structure. These homeotic phenotypes showed cell-autonomous, sharp transitions between mutant and non-mutant scales, except for clones that encroached into the border ocelli (eyespots) and resulted in composite and non-autonomous effects on eyespot ring determination. In the pyralid moth, homeotic clones converted the folding and depigmented hindwing into rigid and pigmented composites, affected the wing-coupling frenulum, and induced ectopic scent-scales in male androconia. These data confirmUbxis a master selector of lepidopteran hindwing identity and suggest it acts on many gene regulatory networks involved in wing development and patterning.
Management of Monogenic IL-1 Mediated Autoinflammatory Diseases in Childhood
Authors: Welzel Tatjana , Benseler Susanne M. , Kuemmerle-Deschner Jasmin B.
Published: March 2021

Monogenic Interleukin 1 (IL-1) mediated autoinflammatory diseases (AID) are rare, often severe illnesses of the innate immune system associated with constitutively increased secretion of pro-inflammatory cytokines. Clinical characteristics include recurrent fevers, inflammation of joints, skin, and serous membranes. CNS and eye inflammation can be seen. Characteristically, clinical symptoms are coupled with elevated inflammatory markers, such as C-reactive protein (CRP) and serum amyloid A (SAA). Typically, AID affect infants and children, but late-onset and atypical phenotypes are described. An in-depth understanding of autoinflammatory pathways and progress in molecular genetics has expanded the spectrum of AID. Increasing numbers of genetic variants with undetermined pathogenicity, somatic mosaicisms and phenotype variability make the diagnosis of AID challenging. AID should be diagnosed as early as possible to prevent organ damage. The diagnostic approach includes patient/family history, ethnicity, physical examination, specific functional testing and inflammatory markers (SAA, CRP) during, and in between flares. Genetic testing should be performed, when an AID is suspected. The selection of genetic tests is guided by clinical findings. Targeted and rapid treatment is crucial to reduce morbidity, mortality and psychosocial burden after an AID diagnosis. Management includes effective treat-to-target therapy and standardized, partnered monitoring of disease activity (e.g., AIDAI), organ damage (e.g., ADDI), patient/physician global assessment and health related quality of life. Optimal AID care in childhood mandates an interdisciplinary team approach. This review will summarize the current evidence of diagnosing and managing children with common monogenic IL-1 mediated AID.
SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development
Authors: Gao Yu , Liu Ruining , He Chenfei , Basile Juan , Vesterlund Mattias , Wahren-Herlenius Marie , Espinoza Alexander , Hokka-Zakrisson Cassandra , Zadjali Fahad , Yoshimura Akihiko , Karlsson Mikael , Carow Berit , Rottenberg Martin E.
Published: March 2021

The suppressor of cytokine signaling 3 (SOCS3) is a major regulator of immune responses and inflammation as it negatively regulates cytokine signaling. Here, the role of SOCS3 in thymic T cell formation was studied inSocs3fl/flActin-creERmice (Δsocs3)with a tamoxifen inducible and ubiquitousSocs3deficiency. Δsocs3thymi showed a 90% loss of cellularity and altered cortico-medullary organization. Thymocyte differentiation and proliferation was impaired at the early double negative (CD4-CD8-) cell stage and apoptosis was increased during the double positive (CD4+CD8+) cell stage, resulting in the reduction of recent thymic emigrants in peripheral organs. Using bone marrow chimeras, transplanting thymic organoids and using mice deficient of SOCS3 in thymocytes we found that expression in thymic stromal cells rather than in thymocytes was critical for T cell development. We found that SOCS3 in thymic epithelial cells (TECs) binds to the E3 ubiquitin ligase TRIM 21 and thatTrim21−/−mice showed increased thymic cellularity. Δsocs3TECs showed alterations in the expression of genes involved in positive and negative selection and lympho-stromal interactions. SOCS3-dependent signal inhibition of the common gp130 subunit of the IL-6 receptor family was redundant for T cell formation. Together, SOCS3 expression in thymic stroma cells is critical for T cell development and for maintenance of thymus architecture.
Impact of Early Life Nutrition on Children’s Immune System and Noncommunicable Diseases Through Its Effects on the Bacterial Microbiome, Virome and Mycobiome
Authors: Fragkou Paraskevi C. , Karaviti Dareilena , Zemlin Michael , Skevaki Chrysanthi
Published: March 2021

The first 1000 days of life, including the intrauterine period, are regarded as a fundamental stepping stone for the development of a human. Unequivocally, nutrition during this period plays a key role on the proper development of a child, both directly through the intake of essential nutrients and indirectly by affecting the composition of the gut microbiota. The gut microbiota, including bacteria, viruses, fungi, protists and other microorganisms, is a highly modifiable and adaptive system that is influenced by diet, lifestyle, medicinal products and the environment. Reversely, it affects the immune system in multiple complex ways. Many noncommunicable diseases (NCDs) associated with dysbiosis are “programmed” during childhood. Nutrition is a potent determinant of the children’s microbiota composition and maturation and, therefore, a strong determinant of the NCDs’ programming. In this review we explore the interplay between nutrition during the first 1000 days of life, the gut microbiota, virome and mycobiome composition and the development of NCDs.
Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies
Authors: Giraud Julie , Chalopin Domitille , Blanc Jean-Frédéric , Saleh Maya
Published: March 2021

Hepatocellular carcinoma (HCC) is the most common liver tumor and among the deadliest cancers worldwide. Advanced HCC overall survival is meager and has not improved over the last decade despite approval of several tyrosine kinase inhibitors (TKi) for first and second-line treatments. The recent approval of immune checkpoint inhibitors (ICI) has revolutionized HCC palliative care. Unfortunately, the majority of HCC patients fail to respond to these therapies. Here, we elaborate on the immune landscapes of the normal and cirrhotic livers and of the unique HCC tumor microenvironment. We describe the molecular and immunological classifications of HCC, discuss the role of specific immune cell subsets in this cancer, with a focus on myeloid cells and pathways in anti-tumor immunity, tumor promotion and immune evasion. We also describe the challenges and opportunities of immunotherapies in HCC and discuss new avenues based on harnessing the anti-tumor activity of myeloid, NK and γδ T cells, vaccines, chimeric antigen receptors (CAR)-T or -NK cells, oncolytic viruses, and combination therapies.
Allograft or Recipient ST2 Deficiency Oppositely Affected Cardiac Allograft Vasculopathy via Differentially Altering Immune Cells Infiltration
Authors: Zhang Zhenggang , Zhang Na , Shi Junyu , Dai Chan , Wu Suo , Jiao Mengya , Tang Xuhuan , Liu Yunfei , Li Xiaoxiao , Xu Yong , Tan Zheng , Gong Feili , Zheng Fang
Published: March 2021

The role of IL-33/ST2 signaling in cardiac allograft vasculopathy (CAV) is not fully addressed. Here, we investigated the role of IL-33/ST2 signaling in allograft or recipient in CAV respectively using MHC-mismatch murine chronic cardiac allograft rejection model. We found that recipients ST2 deficiency significantly exacerbated allograft vascular occlusion and fibrosis, accompanied by increased F4/80+ macrophages and CD3+ T cells infiltration in allografts. In contrast, allografts ST2 deficiency resulted in decreased infiltration of F4/80+ macrophages, CD3+ T cells and CD20+ B cells and thus alleviated vascular occlusion and fibrosis of allografts. These findings indicated that allografts or recipients ST2 deficiency oppositely affected cardiac allograft vasculopathy/fibrosis via differentially altering immune cells infiltration, which suggest that interrupting IL-33/ST2 signaling locally or systematically after heart transplantation leads different outcome.
Autologous BMAC Therapy Improves Spinal Degenerative Joint Disease in Lower Back Pain Patients
Authors: El-Kadiry Abed El-Hakim , Lumbao Carlos , Rafei Moutih , Shammaa Riam
Published: March 2021

Spinal degenerative joint disease (DJD) is associated with lower back pain (LBP) arising from the degeneration of intervertebral discs (IVD), facet joints, intertransversarii muscles, and interspinous ligaments among other anatomical structures. To circumvent the socioeconomic burdens and often-problematic surgical options imposed by DJD therapy, cell-based biologic modalities like bone marrow aspirate concentrate (BMAC) have been investigated in pre-clinical and clinical settings, mostly for IVD degeneration (IDD), with encouraging outcomes. In this study, we evaluated the differences in therapeutic benefits of BMAC between IVD- and facet joint-originating chronic LBP. Eighteen patients diagnosed with chronic LBP met the selection criteria. Following discography and provocation testing, 13 patients tested positive and were assigned into IDD-associated LBP (1st arm), while the remaining 5 tested negative and were assigned into facetogenic LBP (2nd arm). Autologous BMAC was injected intradiscally in the 1st arm, while the 2nd arm received posterior spinal chain injections. No procedure-related serious events ensued. Clinical improvement was evaluated over 12 months based on pain and functionality questionnaires (VAS, BPI, RAND-36), opioid use, and changes in disc parameters assessed by magnetic resonance imaging (MRI). Ameliorated VAS and BPI scores differed significantly between both arms in favor of IDD patients who also took significantly less opioids. Average RAND-36 scores showed no significant difference between groups albeit a trend suggesting improvement was observed in IDD patients. MRI scans conducted on IDD patients demonstrated marked elevation in disc height and spinal canal space size without worsening disc quality. Overall, this is the first study investigating the potency of BMAC as an IDD treatment in Canada and the first globally for addressing facetogenic pain using cellular therapy.
Diversity of Weissella confusa in Pozol and Its Carbohydrate Metabolism
Authors: Hernández-Oaxaca Diana , López-Sánchez Rafael , Lozano Luis , Wacher-Rodarte Carmen , Segovia Lorenzo , López Munguía Agustín
Published: March 2021

The genus Weissella is composed of a group of Gram-positive facultative anaerobe bacteria with fermentative metabolism. Strains of this genus have been isolated from various ecological niches, including a wide variety of fermented cereal foods. The present study aimed to determine the relative abundance and fermentation capabilities of Weissella species isolated from pozol, a traditional maya product made of lime-cooked (nixtamalized) fermented maize. We sequenced the V3-V4 regions of 16S rDNA; Weissella was detected early in the fermentation process and reached its highest relative abundance (3.89%) after 3 h of culture. In addition, we evaluated five Weissella strains previously isolated from pozol but reported as non-amylolytic, to define alternative carbon sources such as xylan, xylooligosaccharides, and sucrose. While no growth was observed on birch xylan, growth did occur on xylooligosaccharides and sucrose. Strains WcL17 and WCP-3A were selected for genomic sequencing, as the former shows efficient growth on xylooligosaccharides and the latter displays high glycosyltransferase (GTF) activity. Genomes of both strains were assembled and recorded, with a total of 2.3 Mb in 30 contigs for WcL17 and 2.2 Mb in 45 contigs for WCP-3a. Both strains were taxonomically assigned to Weissella confusa and genomic analyses were performed to evaluate the gene products encoding active carbohydrate enzymes (CAZy). Both strains have the gene content needed to metabolize sucrose, hemicellulose, cellulose, and starch residues, all available in pozol. Our results suggest that the range of secondary enzymatic activity in Weissella confusa strains confer them with wide capabilities to participate in fermentative processes of natural products with heterogeneous carbon sources.
Disruption of Epithelial Barrier of Caco-2 Cell Monolayers by Excretory Secretory Products of Trichinella spiralis Might Be Related to Serine Protease
Authors: Li Chengyao , Bai Xue , Liu Xiaolei , Zhang Yuanyuan , Liu Lei , Zhang Lixiao , Xu Fengyan , Yang Yong , Liu Mingyuan
Published: March 2021

The physical barrier is composed of epithelial cells which are joined together through intercellular connections. It serves to prevent pathogenic microorganisms from departing the intestinal lumen to invade the host. The excretory secretory (ES) products of Trichinella spiralis are critical for invasion. However, whether ES products of T. spiralis can act on the intestinal barrier is still unknown. In this study, the role of ES products of T. spiralis muscle larvae (Ts-ML-ES) in host invasion was studied by establishing an in vitro cell monolayers model. Barrier integrity analysis by a transmembrane resistance test and a paracellular permeability assay revealed that the Ts-ML-ES was able to destroy barrier function. It occurred via a reduction in the expression of tight junction (TJ) proteins, which was induced by serine protease. Furthermore, Western bolt analysis indicated that Ts-ML-ES reduced the expression of TJ proteins via the MAPK signaling pathway. Based on these data, we conclude that serine protease are likely the main factors from Ts-ML-ES that affect host intestinal barrier integrity by reducing the expression of TJs via the P38-MAPK signaling pathway. Serine protease in Ts-ML-ES might be a key invasion factor in T. spiralis.
Identification and Validation of Reference Genes in Clostridium beijerinckii NRRL B-598 for RT-qPCR Using RNA-Seq Data
Authors: Jureckova Katerina , Raschmanova Hana , Kolek Jan , Vasylkivska Maryna , Branska Barbora , Patakova Petra , Provaznik Ivo , Sedlar Karel
Published: March 2021

Gene expression analysis through reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) depends on correct data normalization by reference genes with stable expression. Although Clostridium beijerinckii NRRL B-598 is a promising Gram-positive bacterium for the industrial production of biobutanol, validated reference genes have not yet been reported. In this study, we selected 160 genes with stable expression based on an RNA sequencing (RNA-Seq) data analysis, and among them, seven genes (zmp, rpoB1, rsmB, greA, rpoB2, topB2, and rimO) were selected for experimental validation by RT-qPCR and gene ontology (GO) enrichment analysis. According to statistical analyses, zmp and greA were the most stable and suitable reference genes for RT-qPCR normalization. Furthermore, our methodology can be useful for selection of the reference genes in other strains of C. beijerinckii and it also suggests that the RNA-Seq data can be used for the initial selection of novel reference genes, however, their validation is required.
Ribosome Rescue Pathways in Bacteria
Authors: Müller Claudia , Crowe-McAuliffe Caillan , Wilson Daniel N.
Published: March 2021

Ribosomes that become stalled on truncated or damaged mRNAs during protein synthesis must be rescued for the cell to survive. Bacteria have evolved a diverse array of rescue pathways to remove the stalled ribosomes from the aberrant mRNA and return them to the free pool of actively translating ribosomes. In addition, some of these pathways target the damaged mRNA and the incomplete nascent polypeptide chain for degradation. This review highlights the recent developments in our mechanistic understanding of bacterial ribosomal rescue systems, including drop-off, trans-translation mediated by transfer-messenger RNA and small protein B, ribosome rescue by the alternative rescue factors ArfA and ArfB, as well as Bacillus ribosome rescue factor A, an additional rescue system found in some Gram-positive bacteria, such as Bacillus subtilis. Finally, we discuss the recent findings of ribosome-associated quality control in particular bacterial lineages mediated by RqcH and RqcP. The importance of rescue pathways for bacterial survival suggests they may represent novel targets for the development of new antimicrobial agents against multi-drug resistant pathogenic bacteria.
Phylogenetic Distribution of Polysaccharide-Degrading Enzymes in Marine Bacteria
Authors: Sun Zhong-Zhi , Ji Bo-Wen , Zheng Ning , Wang Meng , Cao Ye , Wan Lu , Li Yi-Song , Rong Jin-Cheng , He Hai-Lun , Chen Xiu-Lan , Zhang Yu-Zhong , Xie Bin-Bin
Published: March 2021

Deconstruction is an essential step of conversion of polysaccharides, and polysaccharide-degrading enzymes play a key role in this process. Although there is recent progress in the identification of these enzymes, the diversity and phylogenetic distribution of these enzymes in marine microorganisms remain largely unknown, hindering our understanding of the ecological roles of marine microorganisms in the ocean carbon cycle. Here, we studied the phylogenetic distribution of nine types of polysaccharide-degrading enzymes in marine bacterial genomes. First, we manually compiled a reference sequence database containing 961 experimentally verified enzymes. With this reference database, we annotated 9,335 enzyme sequences from 2,182 high-quality marine bacterial genomes, revealing extended distribution for six enzymes at the phylum level and for all nine enzymes at lower taxonomic levels. Next, phylogenetic analyses revealed intra-clade diversity in the encoding potentials and phylogenetic conservation of a few enzymes at the genus level. Lastly, our analyses revealed correlations between enzymes, with alginate lyases demonstrating the most extensive correlations with others. Intriguingly, chitinases showed negative correlations with cellulases, alginate lyases, and agarases in a few genera. This result suggested that intra-genus lifestyle differentiation occurred many times in marine bacteria and that the utilization of polysaccharides may act as an important driver in the recent ecological differentiation of a few lineages. This study expanded our knowledge of the phylogenetic distribution of polysaccharide enzymes and provided insights into the ecological differentiation of marine bacteria.
Elevated Heme Oxygenase-1 Correlates With Increased Brain Iron Deposition Measured by Quantitative Susceptibility Mapping and Decreased Hemoglobin in Patients With Parkinson’s Disease
Authors: Xu Jinghui , Xiao Chi , Song Weizheng , Cui Xiangqin , Pan Mengqiu , Wang Qun , Feng Yanqiu , Xu Yunqi
Published: March 2021

Background: Brain iron deposition, low hemoglobin (HGB), and increased heme oxygenase-1 (HO-1) have been implicated in Parkinson’s disease (PD). However, the association among them in PD is poorly studied.

Objective: To explore the association of the level of HO-1 with brain iron deposition and low level of HGB in PD.

Methods: A total of 32 patients with PD and 26 controls were recruited for this study. C57BL/6 male mice were used in generating 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD model. The Levels of serum HO-1 and HGB of human subjects and mice were assayed by ELISA, blood routine test, respectively. Quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in human subjects and mice. HO-1 inhibitor (Sn-protoporphyrin, SnPP) was used to suppress the function and expression of HO-1 in PD mice. Correlations between the concentration of serum HO-1 and iron deposition of the region of interests (ROIs), levels of HGB, between the three factors mentioned above, and scores of clinical scales were explored in PD patients.

Results: This study revealed significant elevation of the serum HO-1 concentration, iron deposition within bilateral substantial nigra (SN), red nucleus (RN), and putamen (PUT) and decrease of HGB level in PD patients. There was a significantly positive correlation between the serum HO-1 concentration and iron deposition within SN, an inverse correlation between the serum HO-1 concentration and HGB level in PD patients. A significant increase in HO-1 expression of serum and iron deposition in SN was also observed in the PD mouse model, and the SnPP could significantly reduce iron deposition in the SN.

Conclusions: The high level of HO-1 may be the common mechanism of iron deposition and low HGB in PD. Therefore, the findings presented in this study indicate that HO-1 correlates with brain iron deposition and anemia in PD.
Involvement of the Nucleus Incertus and Relaxin-3/RXFP3 Signaling System in Explicit and Implicit Memory
Authors: Gil-Miravet Isis , Mañas-Ojeda Aroa , Ros-Bernal Francisco , Castillo-Gómez Esther , Albert-Gascó Hector , Gundlach Andrew L. , Olucha-Bordonau Francisco E.
Published: March 2021

Telencephalic cognitive and emotional circuits/functions are strongly modulated by subcortical inputs. The main focus of past research on the nature of this modulation has been on the widespread monoamine projections to the telencephalon. However, the nucleus incertus (NI) of the pontine tegmentum provides a strong GABAergic and peptidergic innervation of the hippocampus, basal forebrain, amygdala, prefrontal cortex, and related regions; and represents a parallel source of ascending modulation of cognitive and emotional domains. NI GABAergic neurons express multiple peptides, including neuromedin-B, cholecystokinin, and relaxin-3, and receptors for stress and arousal transmitters, including corticotrophin-releasing factor and orexins/hypocretins. A functional relationship exists between NI neurons and their associated peptides, relaxin-3 and neuromedin-B, and hippocampal theta rhythm, which in turn, has a key role in the acquisition and extinction of declarative and emotional memories. Furthermore, RXFP3, the cognate receptor for relaxin-3, is a Gi/o protein-coupled receptor, and its activation inhibits the cellular accumulation of cAMP and induces phosphorylation of ERK, processes associated with memory formation in the hippocampus and amygdala. Therefore, this review summarizes the role of NI transmitter systems in relaying stress- and arousal-related signals to the higher neural circuits and processes associated with memory formation and retrieval.
Flexible Electronics and Healthcare Applications
Authors: Wang Zixian , Sun Lin , Ni Yao , Liu Lu , Xu Wentao
Published: March 2021

Flexible electronics has attracted tremendous attention in recent years. The essential requirements for flexible electronics include excellent electrical properties, flexibility and stretchability. By introducing special structures or using flexible materials, electronic devices can be given excellent flexibility and stretchability. In this paper we review the realization of flexible electronics from the perspective of structural design strategies and materials; then, healthcare application of flexible electronic systems was introduced. Finally, a brief summary and outlook are presented.
Functional and Cognitive Improvement After an Intensive Inpatient Multidisciplinary Rehabilitation Program in Mild to Severe Parkinson's Disease: A Retrospective and Observational Study
Authors: Meloni Mario , Saibene Francesca Lea , Di Tella Sonia , Di Cesare Monica , Borgnis Francesca , Nemni Raffaello , Baglio Francesca
Published: March 2021

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor (resting tremor, rigidity, bradykinesia, postural instability, and gait disturbances) and nonmotor symptoms (cognitive, neuropsychiatric, and autonomic problems). In recent years, several studies demonstrated that neurorehabilitation therapy is an effective treatment in addition to pharmacological personalized interventions in persons with PD (PwPD). The main aim of this study was to explore the short-term changes in functional, cognitive, and geriatric domains after a multidimensional rehabilitation program in PwPD (as primary condition) in mild–moderate (M-Ms) to severe (Ss) stages. Our second aim was to compare the effects of multidimensional rehabilitation in M-Ms versus Ss of PD. Twenty-four PwPD in M-Ms to Ss [age (mean ± SD) = 76.25 ± 9.42 years; male/female = 10/14; Hoehn and Yahr (median; IQR) = 4.00; 1.75] were included in a retrospective, observational study. Motor, cognitive, functional, and neuropsychiatric aspects were collected in admission (T0) and in discharge (T1). PwPD were involved in a person-tailored (to individual's needs), inpatient, intensive (5–7 days per week), multidisciplinary (combining cognitive, physical, occupational, and speech therapies), comprehensive, and rehabilitative program. According to Movement Disorders Society Unified Parkinson's Disease Rating Scale III cutoff, PwPD were classified in M-Ms or Ss (M-Ms ≤59; Ss >59); 87.50% of our sample reported significant reduction of functional disability at Barthel Index (p < 0.001). A significant improvement in Token test (p = 0.021), semantic fluency (p = 0.036), Rey's Figure-Copy (p < 0.001), and Raven's Colored Progressive Matrices (p = 0.004) was observed. The pain intensity perception (p < 0.001) and the risk of developing pressure ulcers (p < 0.001) as assessed, respectively, by the Numeric Rating Scale and by the Norton Scale were improved. With regard to the second aim, in M-Ms group, we found a positive correlation between the number of neuromotor sessions and the change in functional disability and language comprehension; in the Ss group, on the other hand, despite a higher number of hospitalization days, the total number of completed sessions was positively associated with the change in visuoconstructional abilities. Our findings suggest that an intensive, inpatient, and multidisciplinary rehabilitation program may improve functional abilities, some strategic cognitive functions, and geriatric aspects in PwPD with mild–moderate motor impairment.
Enhancement of Event-Related Desynchronization in Motor Imagery Based on Transcranial Electrical Stimulation
Authors: Xie Jiaxin , Peng Maoqin , Lu Jingqing , Xiao Chao , Zong Xin , Wang Manqing , Gao Dongrui , Qin Yun , Liu Tiejun
Published: March 2021

Due to the individual differences controlling brain-computer interfaces (BCIs), the applicability and accuracy of BCIs based on motor imagery (MI-BCIs) are limited. To improve the performance of BCIs, this article examined the effect of transcranial electrical stimulation (tES) on brain activity during MI. This article designed an experimental paradigm that combines tES and MI and examined the effects of tES based on the measurements of electroencephalogram (EEG) features in MI processing, including the power spectral density (PSD) and dynamic event-related desynchronization (ERD). Finally, we investigated the effect of tES on the accuracy of MI classification using linear discriminant analysis (LDA). The results showed that the ERD of the μ and β rhythms in the left-hand MI task was enhanced after electrical stimulation with a significant effect in the tDCS group. The average classification accuracy of the transcranial alternating current stimulation (tACS) group and transcranial direct current stimulation (tDCS) group (88.19% and 89.93% respectively) were improved significantly compared to the pre-and pseudo stimulation groups. These findings indicated that tES can improve the performance and applicability of BCI and that tDCS was a potential approach in regulating brain activity and enhancing valid features during noninvasive MI-BCI processing.
Beginning to See the Light: Lessons Learned From the Development of the Circadian System for Optimizing Light Conditions in the Neonatal Intensive Care Unit
Authors: Hazelhoff Esther M. , Dudink Jeroen , Meijer Johanna H. , Kervezee Laura
Published: March 2021

The circadian timing system optimizes health by temporally coordinating behavior and physiology. During mammalian gestation, fetal circadian rhythms are synchronized by the daily fluctuations in maternal body temperature, hormones and nutrients. Circadian disruption during pregnancy is associated with negative effects on developmental outcomes in the offspring, highlighting the importance of regular and robust 24-h rhythms over gestation. In the case of preterm birth (before 37 weeks of gestation), maternal cues no longer synchronize the neonate’s circadian system, which may adversely affect the neonate. There is increasing evidence that introducing robust light-dark cycles in the Neonatal Intensive Care Unit has beneficial effects on clinical outcomes in preterm infants, such as weight gain and hospitalization time, compared to infants exposed to constant light or constant near-darkness. However, the biological basis for these effects and the relationship with the functional and anatomical development of the circadian system is not fully understood. In this review, we provide a concise overview of the effects of light-dark cycles on clinical outcomes of preterm neonates in the NICU and its alignment with the development of the circadian system.