bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Vaccination of Mice With Trichinella spiralis Putative Serine Protease and Murine Interleukin-4 DNA Delivered by Invasive Lactiplantibacillus plantarum Elicits Protective Immunity
Authors: Xue Ying , Zhang Bo , Wang Nan , Huang Hai-Bin , Quan Yu , Lu Hui-Nan , Zhu Zhi-Yu , Li Jun-Yi , Pan Tian-Xu , Tang Yue , Jiang Yan-Long , Shi Chun-Wei , Yang Gui-Lian , Wang Chun-Feng
Published: May 2022

Trichinellosis is a serious zoonotic parasitic disease caused by Trichinella spiralis (T. spiralis) that causes considerable economic losses for the global pig breeding and food industries. As such, there is an urgent need for a vaccine that can prevent T. spiralis infection. Previous studies have reported that recombinant invasive Lactococcus lactis (LL) expressing Staphylococcus aureus fibronectin binding protein A (LL-FnBPA+) can transfer DNA vaccines directly to dendritic cells (DCs) across an epithelial cell monolayer, leading to significantly higher amounts of heterologous protein expression compared to non-invasive Lactococcus lactis. In this study, the invasive bacterium Lactiplantibacillus plantarum (L. plantarum) expressing FnBPA was used as a carrier to deliver a novel oral DNA vaccine consisting of T. spiralis adult putative serine protease (Ts-ADpsp) and murine interleukin (IL)-4 DNA to mouse intestinal epithelial cells. Experimental mice were orally immunized 3 times at 10-day intervals. At 10 days after the last vaccination, mice were challenged with 350 T. spiralis infective larvae by oral inoculation. Immunization with invasive L. plantarum harboring pValac-Ts-ADpsp/pSIP409-FnBPA induced the production of anti-Ts-ADpsp-specific IgG of serum, type 1 and 2 helper T cell cytokines of mesenteric lymph node (MLN) and spleen, secreted (s) IgA of intestinal lavage, and decreased T. spiralis burden and intestinal damage compared to immunization with non-invasive L. plantarum expressing Ts-ADpsp (pValac-Ts-ADpsp/pSIP409). Thus, invasive L. plantarum expressing FnBPA and IL-4 stimulates both mucosal and cellular immune response to protect against T. spiralis infection, highlighting its therapeutic potential as an effective DNA vaccine for trichinellosis.
Genomic Sequencing and Analysis of a Novel Human Cowpox Virus With Mosaic Sequences From North America and Old World Orthopoxvirus
Authors: Diaz-Cánova Diana , Moens Ugo L. , Brinkmann Annika , Nitsche Andreas , Okeke Malachy Ifeanyi
Published: May 2022

Orthopoxviruses (OPXVs) not only infect their natural hosts, but some OPXVs can also cause disease in humans. Previously, we partially characterized an OPXV isolated from an 18-year-old male living in Northern Norway. Restriction enzyme analysis and partial genome sequencing characterized this virus as an atypical cowpox virus (CPXV), which we named CPXV-No-H2. In this study, we determined the complete genome sequence of CPXV-No-H2 using Illumina and Nanopore sequencing. Our results showed that the whole CPXV-No-H2 genome is 220,276 base pairs (bp) in length, with inverted terminal repeat regions of approximately 7 kbp, containing 217 predicted genes. Seventeen predicted CPXV-No-H2 proteins were most similar to OPXV proteins from the Old World, including Ectromelia virus (ECTV) and Vaccinia virus, and North America, Alaskapox virus (AKPV). CPXV-No-H2 has a mosaic genome with genes most similar to other OPXV genes, and seven potential recombination events were identified. The phylogenetic analysis showed that CPXV-No-H2 formed a separate clade with the German CPXV isolates CPXV_GerMygEK938_17 and CPXV_Ger2010_MKY, sharing 96.4 and 96.3% nucleotide identity, respectively, and this clade clustered closely with the ECTV-OPXV Abatino clade. CPXV-No-H2 is a mosaic virus that may have arisen out of several recombination events between OPXVs, and its phylogenetic clustering suggests that ECTV-Abatino-like cowpox viruses form a distinct, new clade of cowpox viruses.
Comparative Analyses of Rhizosphere Bacteria Along an Elevational Gradient of Thuja sutchuenensis
Authors: Zuo You-wei , Zhang Jia-hui , Ning Deng-hao , Zeng Yu-lian , Li Wen-qiao , Xia Chang-ying , Zhang Huan , Deng Hong-ping
Published: May 2022

Thuja sutchuenensis Franch. is an endangered species in southwestern China, primarily distributed in 800–2,100 m of inaccessible mountainous areas. Rhizosphere soil physicochemical properties and bacterial communities play an essential role in managing plant growth and survival. Nonetheless, the study investigating rhizosphere soil properties and bacterial communities of T. sutchuenensis is limited. The present study investigated soil properties, including soil pH, organic matter, water content, nitrogen, phosphorus, and potassium contents, and bacterial communities in nearly all extant T. sutchuenensis populations at five elevational gradients. Our results demonstrated that the increase in elevation decreased rhizosphere and bulk soil phosphorus content but increased potassium content. In addition, the elevational gradient was the dominant driver for the community composition differentiation of soil bacterial community. Proteobacteria and Acidobacteria were the dominant bacterial phyla distributed in the rhizosphere and bulk soils. Co-occurrence network analysis identified key genera, including Bradyrhizobium, Acidicapsa, Catenulispora, and Singulisphaera, that displayed densely connected interactions with many genera in the rhizosphere soil. The dominant KEGG functional pathways of the rhizosphere bacteria included ABC transporters, butanoate metabolism, and methane metabolism. Further correlation analysis found that soil phosphorus and potassium were the dominant drivers for the diversity of soil bacteria, which were distinctively contributed to the phylum of Planctomycetes and the genera of Blastopirellula, Planctomycetes, and Singulisphaera. Collectively, this comprehensive study generated multi-dimensional perspectives for understanding the soil bacterial community structures of T. sutchuenensis, and provided valuable findings for species conservation at large-scale views.
Identification and Functional Characterization of Peptides With Antimicrobial Activity From the Syphilis Spirochete, Treponema pallidum
Authors: Houston Simon , Schovanek Ethan , Conway Kate M. E. , Mustafa Sarah , Gomez Alloysius , Ramaswamy Raghavendran , Haimour Ayman , Boulanger Martin J. , Reynolds Lisa A. , Cameron Caroline E.
Published: May 2022

The etiological agent of syphilis,Treponema pallidumssp.pallidum, is a highly invasive “stealth” pathogen that can evade the host immune response and persist within the host for decades. This obligate human pathogen is adept at establishing infection and surviving at sites within the host that have a multitude of competing microbes, sometimes including pathogens. One survival strategy employed by bacteria found at polymicrobial sites is elimination of competing microorganisms by production of antimicrobial peptides (AMPs). Antimicrobial peptides are low molecular weight proteins (miniproteins) that function directly via inhibition and killing of microbes and/or indirectly via modulation of the host immune response, which can facilitate immune evasion. In the current study, we used bioinformatics to show that approximately 7% of theT. pallidumproteome is comprised of miniproteins of 150 amino acids or less with unknown functions. To investigate the possibility that AMP production is an unrecognized defense strategy used byT. pallidumduring infection, we developed a bioinformatics pipeline to analyze the complement ofT. pallidumminiproteins of unknown function for the identification of potential AMPs. This analysis identified 45T. pallidumAMP candidates; of these, Tp0451a and Tp0749 were subjected to further bioinformatic analyses to identify AMP critical core regions (AMPCCRs). Four potential AMPCCRs from the two predicted AMPs were identified and peptides corresponding to these AMPCCRs were experimentally confirmed to exhibit bacteriostatic and bactericidal activity against a panel of biologically relevant Gram-positive and Gram-negative bacteria. Immunomodulation assays performed under inflammatory conditions demonstrated that one of the AMPCCRs was also capable of differentially regulating expression of two pro-inflammatory chemokines [monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8)]. These findings demonstrate proof-of-concept for our developed AMP identification pipeline and are consistent with the novel concept thatT. pallidumexpresses AMPs to defend against competing microbes and modulate the host immune response.
Genetic and Epigenetic Interplay Define Disease Onset and Severity in Repeat Diseases
Authors: Barbé Lise , Finkbeiner Steve
Published: May 2022

Repeat diseases, such as fragile X syndrome, myotonic dystrophy, Friedreich ataxia, Huntington disease, spinocerebellar ataxias, and some forms of amyotrophic lateral sclerosis, are caused by repetitive DNA sequences that are expanded in affected individuals. The age at which an individual begins to experience symptoms, and the severity of disease, are partially determined by the size of the repeat. However, the epigenetic state of the area in and around the repeat also plays an important role in determining the age of disease onset and the rate of disease progression. Many repeat diseases share a common epigenetic pattern of increased methylation at CpG islands near the repeat region. CpG islands are CG-rich sequences that are tightly regulated by methylation and are often found at gene enhancer or insulator elements in the genome. Methylation of CpG islands can inhibit binding of the transcriptional regulator CTCF, resulting in a closed chromatin state and gene down regulation. The downregulation of these genes leads to some disease-specific symptoms. Additionally, a genetic and epigenetic interplay is suggested by an effect of methylation on repeat instability, a hallmark of large repeat expansions that leads to increasing disease severity in successive generations. In this review, we will discuss the common epigenetic patterns shared across repeat diseases, how the genetics and epigenetics interact, and how this could be involved in disease manifestation. We also discuss the currently available stem cell and mouse models, which frequently do not recapitulate epigenetic patterns observed in human disease, and propose alternative strategies to study the role of epigenetics in repeat diseases.
Advances and Perspective on Antimicrobial Nanomaterials for Biomedical Applications
Authors: Garg Preeti , Attri Prerna , Sharma Rohit , Chauhan Moondeep , Chaudhary Ganga Ram
Published: May 2022

Microbial infection and antibiotic resistance is recognized as a serious problem to society from both an economical perspective and a health concern. To tackle this problem, “nanotechnology,” a multidisciplinary field of research, has provided a plethora of nanomaterials for potential applications in the antimicrobial sector. This letter discusses how antimicrobial nanomaterials are shaping this challenging field and being evaluated as therapeutic and medication delivery agents. The recently designed smart antimicrobial surfaces with switchable features that displayed synergistic antibacterial action were also highlighted. To end, we provide the current scenario and future perspectives with regards to emerging antimicrobial nano-engineered materials and nanotechnology.
Effects of Congenital Blindness on Ultrasonic Vocalizations and Social Behaviors in the ZRDBA Mouse
Authors: Bouguiyoud Nouhaila , Morales-Grahl Elena , Bronchti Gilles , Frasnelli Johannes , Roullet Florence I. , Al Aïn Syrina
Published: May 2022

Mice produce ultrasonic vocalizations (USVs) at different ages and social contexts, including maternal-pup separation, social play in juveniles, social interactions, and mating in adults. The USVs' recording can be used as an index of sensory detection, internal state, and social motivation. While sensory deprivation may alter USVs' emission and some social behaviors in deaf and anosmic rodents, little is known about the effects of visual deprivation in rodents. This longitudinal study aimed to assess acoustic communication and social behaviors using a mouse model of congenital blindness. Anophthalmic and sighted mice were assayed to a series of behavioral tests at three different ages, namely, the maternal isolation-induced pup USV test and the home odor discrimination and preference test on postnatal day (PND) 7, the juvenile social test on PND 30–35, and the female urine-induced USVs and scent-marking behavior at 2–3 months. Our results evidenced that (1) at PND 7, USVs' total number between both groups was similar, all mice vocalized less during the second isolation period than the first period, and both phenotypes showed similar discrimination and preference, favoring exploration of the home bedding odor; (2) at PND 30–35, anophthalmic mice engaged less in social behaviors in the juvenile play test than sighted ones, but the number of total USVs produced is not affected; and (3) at adulthood, when exposed to a female urine spot, anophthalmic male mice displayed faster responses in terms of USVs' emission and sniffing behavior, associated with a longer time spent exploring the female urinary odor. Interestingly, acoustic behavior in the pups and adults was correlated in sighted mice only. Together, our study reveals that congenital visual deprivation had no effect on the number of USVs emitted in the pups and juveniles, but affected the USVs' emission in the adult male and impacted the social behavior in juvenile and adult mice.
Automated Evaluation of Conventional Clock-Drawing Test Using Deep Neural Network: Potential as a Mass Screening Tool to Detect Individuals With Cognitive Decline
Authors: Sato Kenichiro , Niimi Yoshiki , Mano Tatsuo , Iwata Atsushi , Iwatsubo Takeshi
Published: May 2022

Introduction

The Clock-Drawing Test (CDT) is a simple cognitive tool to examine multiple domains of cognition including executive function. We aimed to build a CDT-based deep neural network (DNN) model using data from a large cohort of older adults, to automatically detect cognitive decline, and explore its potential as a mass screening tool.

Methods

Over 40,000 CDT images were obtained from the National Health and Aging Trends Study (NHATS) database, which collects the annual surveys of nationally representative community-dwelling older adults in the United States. A convolutional neural network was utilized in deep learning architecture to predict the cognitive status of participants based on drawn clock images.

Results

The trained DNN model achieved balanced accuracy of 90.1 ± 0.6% in identifying those with a decline in executive function compared to those without [positive likelihood ratio (PLH) = 16.3 ± 6.8, negative likelihood ratio (NLH) = 0.14 ± 0.03], and 77.2 ± 2.7 % balanced accuracy for identifying those with probable dementia from those without (PLH = 5.1 ± 0.5, NLH = 0.37 ± 0.07).

Conclusions

This study demonstrated the feasibility of implementing conventional CDT to be automatically evaluated by DNN with a fair performance in a larger scale than ever, suggesting its potential as a mass screening test for ruling-in or ruling-out those with executive dysfunction or with probable dementia.
Comparisons of Glutamate in the Brains of Alzheimer’s Disease Mice Under Chemical Exchange Saturation Transfer Imaging Based on Machine Learning Analysis
Authors: Liu Yixuan , Li Jie , Ji Hongfei , Zhuang Jie
Published: May 2022

Chemical exchange saturation transfer (CEST) is one of the molecular magnetic resonance imaging (MRI) techniques that indirectly measures low-concentration metabolite or free protein signals that are difficult to detect by conventional MRI techniques. We applied CEST to Alzheimer’s disease (AD) and analyzed both region of interest (ROI) and pixel dimensions. Through the analysis of the ROI dimension, we found that the content of glutamate in the brains of AD mice was higher than that of normal mice of the same age. In the pixel-dimensional analysis, we obtained a map of the distribution of glutamate in the mouse brain. According to the experimental data of this study, we designed an algorithm framework based on data migration and used Resnet neural network to classify the glutamate distribution images of AD mice, with an accuracy rate of 75.6%. We evaluate the possibility of glutamate imaging as a biomarker for AD detection for the first time, with important implications for the detection and treatment of AD.
DeePred-BBB: A Blood Brain Barrier Permeability Prediction Model With Improved Accuracy
Authors: Kumar Rajnish , Sharma Anju , Alexiou Athanasios , Bilgrami Anwar L. , Kamal Mohammad Amjad , Ashraf Ghulam Md
Published: May 2022

The blood-brain barrier (BBB) is a selective and semipermeable boundary that maintains homeostasis inside the central nervous system (CNS). The BBB permeability of compounds is an important consideration during CNS-acting drug development and is difficult to formulate in a succinct manner. Clinical experiments are the most accurate method of measuring BBB permeability. However, they are time taking and labor-intensive. Therefore, numerous efforts have been made to predict the BBB permeability of compounds using computational methods. However, the accuracy of BBB permeability prediction models has always been an issue. To improve the accuracy of the BBB permeability prediction, we applied deep learning and machine learning algorithms to a dataset of 3,605 diverse compounds. Each compound was encoded with 1,917 features containing 1,444 physicochemical (1D and 2D) properties, 166 molecular access system fingerprints (MACCS), and 307 substructure fingerprints. The prediction performance metrics of the developed models were compared and analyzed. The prediction accuracy of the deep neural network (DNN), one-dimensional convolutional neural network, and convolutional neural network by transfer learning was found to be 98.07, 97.44, and 97.61%, respectively. The best performing DNN-based model was selected for the development of the “DeePred-BBB” model, which can predict the BBB permeability of compounds using their simplified molecular input line entry system (SMILES) notations. It could be useful in the screening of compounds based on their BBB permeability at the preliminary stages of drug development. The DeePred-BBB is made available at https://github.com/12rajnish/DeePred-BBB.
Pyrroloquinoline Quinone Regulates Enteric Neurochemical Plasticity of Weaned Rats Challenged With Lipopolysaccharide
Authors: Shi Chenyu , Xu Song , Huang Caiyun , Wang Zijie , Wang Wenhui , Ming Dongxu , Yin Xindi , Liu Hu , Wang Fenglai
Published: May 2022

The enteric nervous system (ENS) is important for the intestinal barrier to defend and regulate inflammation in the intestine. The aim of this study was to investigate the effect of pyrroloquinoline quinone (PQQ) on regulating neuropeptide secretion by ENS neurons of rats challenged with lipopolysaccharide (LPS) to create enteritis. Thirty Sprague Dawley rats were divided into five groups, namely, basal (CTRL), basal plus LPS challenge (LPS), basal with 2.5 mg/kg b.w./day of PQQ plus challenge with LPS (PQQ 2.5), basal with 5.0 mg/kg b.w./day PQQ plus challenge with LPS (PQQ 5), and basal with 10.0 mg/kg b.w./day PQQ plus challenge with LPS (PQQ 10). After treatment with basal diet or PQQ for 14 days, rats were challenged with LPS except for the CTRL group. Rats were euthanized 6 h after the LPS challenge. Rats showed an increased average daily gain in PQQ treatment groups (P < 0.05). Compared with the LPS group, PQQ 5 and PQQ 10 rats showed increased villus height and villus height/crypt depth of jejunum (P < 0.05). In PQQ treatment groups, concentrations of IL-1β and TNF-α in serum and intestine of rats were decreased, and IL-10 concentration was increased in serum compared with the LPS group (P < 0.05). Compared with the LPS group, the concentration of neuropeptide Y (NPY), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and brain-derived neurotropic factor (BDNF) in serum were decreased in PQQ treatment groups (P < 0.05). Compared with the LPS group, ileal mRNA levels of BDNF, NPY, and NGF were decreased in PQQ treatment groups (P < 0.05). Jejunal concentrations of SP, CGRP, VIP, BDNF, NPY, and NGF were decreased in PQQ treatment groups compared with the LPS group (P < 0.05). Compared with the LPS group, phosphor-protein kinase B (p-Akt)/Akt levels in jejunum and colon were decreased in PQQ treatment groups (P < 0.05). In conclusion, daily treatment with PQQ improved daily gain, jejunal morphology, immune responses. PQQ-regulated enteric neurochemical plasticity of ENS via the Akt signaling pathway of weaned rats suffering from enteritis.
Study on Group Differences in Migrant Workers’ Urban Integration in China
Authors: Li Haibo , Li Haitao , Guo Shengyu , Fan Xuelong , Liu Feiyue
Published: May 2022

Objective

This manuscript evaluates and tests the group differences in migrant workers’ urban integration from the perspectives of individual characteristics and migration characteristics, so as to provide theoretical support and practical guidance for the government to issue more effective assistance policies.

Methods

Multilevel comprehensive evaluation method and Entropy method are used to calculate the urban integration level of migrant workers, and one-way ANOVA and optimal scaling regression are used to test the group differences in migrant workers’ urban integration.

Results

Based on the questionnaire data of 854 migrant workers in China, the scale of migrant workers’ urban integration has good reliability and validity. The overall level of migrant workers’ urban integration is 49.61% and there exist group differences in migrant workers’ urban integration. The impact of education level, income level, and migration time on migrant workers’ urban integration is significantly positive, whereas the impact of migration distance on migrant workers’ urban integration is significantly negative. The urban integration level of migrant workers who have family members accompanying them is higher than that of migrant workers who have no family members accompanying them. Gender, age, and marriage have no significant impact on migrant workers’ urban integration.

Strengths and Limitations of This Study

This study aims to measure and test the group differences in migrant workers’ urban integration using ANOVA and optimal scaling regression. However, the shortcomings of this study are the selection of the “migrant workers’ urban integration” scale and the representativeness of the sample used in this study.

Conclusion

There are group differences in migrant workers’ urban integration with different education levels, income levels, migration distances, migration times, and statuses of family members accompanying. In the policy of promoting migrant workers’ urban integration, we should accurately count the characteristics of migrant workers and give more attention to migrant workers with low education levels, low-income levels, long migration distances, short migration times, and no family accompany.
Environmental Enrichment and Estrogen Upregulate Beta-Hydroxybutyrate Underlying Functional Improvement
Authors: Pyo Soonil , Kim Joohee , Hwang Jihye , Heo Jeong Hyun , Kim Kyungri , Cho Sung-Rae
Published: May 2022

Environmental enrichment (EE) is a promising therapeutic strategy in improving metabolic and neuronal responses, especially due to its non-invasive nature. However, the exact mechanism underlying the sex-differential effects remains unclear. The aim of the current study was to investigate the effects of EE on metabolism, body composition, and behavioral phenotype based on sex. Long-term exposure to EE for 8 weeks induced metabolic changes and fat reduction. In response to the change in metabolism, the level of βHB were influenced by sex and EE possibly in accordance to the phases of estrogen cycle. The expression of β-hydroxybutyrate (βHB)-related genes and proteins such as monocarboxylate transporters, histone deacetylases (HDAC), and brain-derived neurotrophic factor (BDNF) were significantly regulated. In cerebral cortex and hippocampus, EE resulted in a significant increase in the level of βHB and a significant reduction in HDAC, consequently enhancing BDNF expression. Moreover, EE exerted significant effects on motor and cognitive behaviors, indicating a significant functional improvement in female mice under the condition that asserts the influence of estrogen cycle. Using an ovariectomized mice model, the effects of EE and estrogen treatment proved the hypothesis that EE upregulates β-hydroxybutyrate and BDNF underlying functional improvement in female mice. The above findings demonstrate that long-term exposure to EE can possibly alter metabolism by increasing the level of βHB, regulate the expression of βHB-related proteins, and improve behavioral function as reflected by motor and cognitive presentation following the changes in estrogen level. This finding may lead to a marked improvement in metabolism and neuroplasticity by EE and estrogen level.
Cc2d1b Contributes to the Regulation of Developmental Myelination in the Central Nervous System
Authors: Acheta Jenica , Hong Jiayue , Jeanette Haley , Brar Simrandeep , Yalamanchili Anish , Feltri M. Laura , Manzini M. Chiara , Belin Sophie , Poitelon Yannick
Published: May 2022

Background

Numerous studies have indicated that myelination is the result of the interplay between extracellular signals and an intricate network of transcription factors. Yet, the identification and characterization of the full repertoire of transcription factors that modulate myelination are still incomplete. CC2D1B is a member of the Lgd/CC2D1 family of proteins highly expressed in myelinating cells in the central and peripheral nervous systems. In addition, the absence of CC2D1B limits myelin formation in vitro. Here we propose to delineate the function of CC2D1B in myelinating cells during developmental myelination in vivo in the central and peripheral nervous systems.

Methods

We used a Cc2d1b constitutive knockout mouse model and then performed morphological analyses on semithin sections of sciatic nerves and electron micrographs of optic nerves. We also performed immunohistological studies on coronal brain sections. All analyses were performed at 30 days of age.

Results

In the peripheral nervous system, animals ablated for Cc2d1b did not show any myelin thickness difference compared to control animals. In the central nervous system, immunohistological studies did not show any difference in the number of oligodendrocytes or the level of myelin proteins in the cortex, corpus callosum, and striatum. However, optic nerves showed a hypomyelination (0.844 ± 0.022) compared to control animals (0.832 ± 0.016) of large diameter myelinated fibers.

Conclusions

We found that CC2D1B plays a role in developmental myelination in the central nervous system. These results suggest that CC2D1B could contribute to gene regulation during oligodendrocytes myelination in optic nerves.
Shifts in Fecal Metabolite Profiles Associated With Ramadan Fasting Among Chinese and Pakistani Individuals
Authors: Chen Siyu , Ali Ikram , Li Xin , Long Danfeng , Zhang Ying , Long Ruijun , Huang Xiaodan
Published: May 2022

The human gut microbiota has been proposed to serve as a multifunctional organ in host metabolism, contributing effects to nutrient acquisition, immune response, and digestive health. Fasting during Ramadan may alter the composition of gut microbiota through changes in dietary behavior, which ultimately affects the contents of various metabolites in the gut. Here, we used liquid chromatography–mass spectrometry-based metabolomics to investigate the composition of fecal metabolites in Chinese and Pakistani individuals before and after Ramadan fasting. Principal component analysis showed distinct separation of metabolite profiles among ethnic groups as well as between pre- and post-fasting samples. After Ramadan fasting, the Chinese and Pakistani groups showed significant differences in their respective contents of various fecal metabolites. In particular, L-histidine, lycofawcine, and cordycepin concentrations were higher after Ramadan fasting in the Chinese group, while brucine was enriched in the Pakistani group. The KEGG analysis suggested that metabolites related to purine metabolism, 2-oxocarboxylic acid metabolism, and lysine degradation were significantly enriched in the total subject population pre-fasting vs. post-fasting comparisons. Several bacterial taxa were significantly correlated with specific metabolites unique to each ethnic group, suggesting that changes in fecal metabolite profiles related to Ramadan fasting may be influenced by associated shifts in gut microbiota. The fasting-related differences in fecal metabolite profile, together with these group-specific correlations between taxa and metabolites, support our previous findings that ethnic differences in dietary composition also drive variation in gut microbial composition and diversity. This landscape view of interconnected dietary behaviors, microbiota, and metabolites contributes to the future development of personalized, diet-based therapeutic strategies for gut-related disorders.
Effects of Low-Carbohydrate Diet and Exercise Training on Gut Microbiota
Authors: Sun Shengyan , Lei On Kei , Nie Jinlei , Shi Qingde , Xu Yuming , Kong Zhaowei
Published: May 2022

Objective

This study was aimed to evaluate the effects of low-carbohydrate diet (LC) and incorporated high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on gut microbiota, and the associations between changes in gut microbiota and cardiometabolic health-related profiles.

Methods

Fifty overweight/obese Chinese females (age 22.2 ± 3.3 years, body mass index 25.1 ± 3.1 kg/m–2) were randomized to the groups of LC, LC and HIIT (LC-HIIT, 10 repetitions of 6-s sprints and 9-s rest), and LC and MICT group (LC-MICT, cycling at 50–60% V̇O2peak for 30 min). The LC-HIIT and LC-MICT experienced 20 training sessions over 4 weeks.

Results

The 4-week LC intervention with/without additional training failed to change the Shannon, Chao 1, and Simpson indexes (p > 0.05), LC increased Phascolarctobacterium genus, and LC-HIIT reduced Bifidobacterium genus after intervention (p < 0.05). Groups with extra exercise training increased short-chain fatty acid-producing Blautia genus (p < 0.05) and reduced type 2 diabetes-related genus Alistipes (p < 0.05) compared to LC. Sutterella (r = −0.335) and Enterobacter (r = 0.334) were associated with changes in body composition (p < 0.05). Changes in Ruminococcus, Eubacterium, and Roseburia genera were positively associated with blood pressure (BP) changes (r = 0.392–0.445, p < 0.05), whereas the changes in Bacteroides, Faecalibacterium, and Parabacteroides genera were negatively associated with BP changes (r = −0.567 to −0.362, p < 0.05).

Conclusion

LC intervention did not change the α-diversity and overall structure of gut microbiota. Combining LC with exercise training may have additional benefits on gut physiology. Specific microbial genera were associated with LC- and exercise-induced regulation of cardiometabolic health.
The Use of Probiotic Therapy in Metabolic and Neurological Diseases
Authors: Lee Shirley H. F. , Ahmad Siti R. , Lim Ya C. , Zulkipli Ihsan N.
Published: May 2022

The human gut is home to trillions of microbes that interact with host cells to influence and contribute to body functions. The number of scientific studies focusing on the gut microbiome has exponentially increased in recent years. Studies investigating factors that may potentially affect the gut microbiome and may be used for therapeutic purposes in diseases where dysbioses in the gut microbiome have been shown are of particular interest. This review compiles current evidence available in the scientific literature on the use of probiotics to treat metabolic diseases and autism spectrum disorders (ASDs) to analyze the efficacy of probiotics in these diseases. To do this, we must first define the healthy gut microbiome before looking at the interplay between the gut microbiome and diseases, and how probiotics affect this interaction. In metabolic diseases, such as obesity and diabetes, probiotic supplementation positively impacts pathological parameters. Conversely, the gut–brain axis significantly impacts neurodevelopmental disorders such as ASDs. However, manipulating the gut microbiome and disease symptoms using probiotics has less pronounced effects on neurodevelopmental diseases. This may be due to a more complex interplay between genetics and the environment in these diseases. In conclusion, the use of microbe-based probiotic therapy may potentially have beneficial effects in ameliorating the pathology of various diseases. Validation of available data for the development of personalized treatment regimens for affected patients is still required.
Clinical Characteristics, Laboratory Findings, Management, and Outcome of Severe Coronavirus Disease 2019 in Children at a Tertiary Care Center in Riyadh, Saudi Arabia: A Retrospective Study
Authors: AlMayouf AbdulAziz , AlShahrani Dayel , AlGhain Salwan , AlFaraj Sarah , Bashawri Yara , AlFawaz Tariq , AlDosari Egab , Al-Awdah Laila , AlShehri Mohammed , AlGoraini Yara
Published: May 2022

Background

Numerous studies worldwide have reported COVID-19 in children; however, the clinical symptoms and consequences of COVID-19 in children have only been reported in a few studies in Saudi and gulf region. Therefore, we aimed to investigate the clinical features and outcomes of COVID-19 infection in children and the therapeutic interventions used.

Methods

This retrospective cohort study included 96 patients with confirmed severe acute respiratory syndrome coronavirus 2 infection aged ≤14 years who were admitted to a tertiary governmental care hospital in Riyadh, Saudi Arabia between March 2020 and November 2020. Data on children with COVID-19, including demographics, comorbidities, symptoms, imaging and laboratory results, therapies, and clinical outcomes, were analyzed.

Results

Of 96 children admitted with a confirmed diagnosis of COVID-19, 63.8% were aged ≤ 3 years, 52.1% were male, 56.2% had an unknown source of infection, and 51% had no comorbidities. Most cases had severe infection (71.88%) as they required oxygen, 10.42% of whom were critical. The most common symptoms were respiratory-related (98%), and the common physical sign was fever (49%). High D-dimer (90.7%) and C-reactive protein (72.09%) levels were found in most cases. Oxygen (71.88%) was the most commonly used treatment. Most patients were discharged home and fully recovered (97.92%). We reported two deaths (2.08%).

Conclusions

Our findings showed that the majority of the admitted children with COVID-19 were ≤3 years of age (52.1%) and infected with an unknown source (56.2%). Moreover, the majority of the cases had severe COVID-19 infection as they required oxygen (71.88%), although they had favorable outcomes. However, some cases were critical and resulted in death. Future studies will be crucial to better understand the disease spectrum and potential therapeutic options for COVID-19 in children.
Phytotherapy for Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-analysis
Authors: Dutta Tusheema , Anand Uttpal , Mitra Shreya Sikdar , Ghorai Mimosa , Jha Niraj Kumar , Shaikh Nusratbanu K. , Shekhawat Mahipal S , Pandey Devendra Kumar , Proćków Jarosław , Dey Abhijit
Published: May 2022

Attention deficit hyperactivity disorder (ADHD) is commonly a neurodevelopmental behavioural disorder in children and adolescents. Mainly characterized by symptoms like lack of attention, hyperactivity, and impulsiveness, it can impact the overall mental development of the one affected. Several factors, both genetic and non-genetic, can be responsible for this disorder. Although several traditional treatment methods involve medication and other counselling techniques, they also come with different side effects. Hence, the choice is now shifting to alternative treatment techniques. Herbal treatments are considered one of the most popular complementary and alternative medicine (CAM) administered. However, issues related to the safety and efficacy of herbal remedies for the treatment of ADHD need to be investigated further. This study aims to find out the recent advancement in evidence-based use of herbal remedies for ADHD by a comprehensive and systematic review that depicts the results of the published works on herbal therapy for the disorder. The electronic databases and the references retrieved from the included studies present related randomized controlled trials (RCTs) and open-label studies. Seven RCTs involving children and adolescents diagnosed with ADHD met the inclusion criteria. There is a fair indication of the efficacy and safety of Melissa officinalis L., Bacopa monnieri (L.) Wettst., Matricaria chamomilla L., and Valeriana officinalis L. from the studies evaluated in this systematic review for the treatment of various symptoms of ADHD. Limited evidence was found for Ginkgo biloba L. and pine bark extract. However, various other preparations from other plants did not show significant efficacy. There is inadequate proof to strongly support and recommend the administration of herbal medicines for ADHD, but more research is needed in the relevant field to popularize the alternative treatment approach.
Machine Learning in Antibacterial Drug Design
Authors: Jukič Marko , Bren Urban
Published: May 2022

Advances in computer hardware and the availability of high-performance supercomputing platforms and parallel computing, along with artificial intelligence methods are successfully complementing traditional approaches in medicinal chemistry. In particular, machine learning is gaining importance with the growth of the available data collections. One of the critical areas where this methodology can be successfully applied is in the development of new antibacterial agents. The latter is essential because of the high attrition rates in new drug discovery, both in industry and in academic research programs. Scientific involvement in this area is even more urgent as antibacterial drug resistance becomes a public health concern worldwide and pushes us increasingly into the post-antibiotic era. In this review, we focus on the latest machine learning approaches used in the discovery of new antibacterial agents and targets, covering both small molecules and antibacterial peptides. For the benefit of the reader, we summarize all applied machine learning approaches and available databases useful for the design of new antibacterial agents and address the current shortcomings.
Autophagy Inhibition Enhances the Anti-Tumor Activity of Methylseleninic Acid in Cisplatin-Resistance Human Lung Adenocarcinoma Cells
Authors: Xin Ming , Gao Qi , Xiang Xindong , Xu Juanjuan , Jiao Yuhan , Li Xuan , Zhang Xianzhen , Jia Xiuqin
Published: May 2022

Cisplatin (DDP)-based chemotherapy remains one of the standard treatment options for patients with advanced lung adenocarcinoma (LUAD), and cisplatin resistance is the biggest challenge to this therapy. Autophagy is also closely associated with chemoresistance in LUAD. Desperately need to find a way to improve the treatment efficiency of cisplatin-resistant LUAD in clinical practice. Previous studies reported that methylseleninic acid (MSA) has good anti-proliferation and pro-apoptotic activities in tumor cells. However, the effectiveness of MSA on cisplatin-resistant LUAD and its effect on the induction of autophagy is still unclear. In the current study, we found that MSA effectively inhibited the proliferation of LUAD cell lines and triggered mitochondrial pathway-mediated apoptosis. This effect was more pronounced in cisplatin-resistant LUAD cells with high MDR1 expression. In contrast, the mitochondrial damage caused by MSA treatment can be degraded by inducing selective autophagy in LUAD cells, thereby exerting a self-protective effect on tumor cells. Mechanistically, MSA inhibits proliferation, promotes apoptosis, and induces autophagy in LUAD cells by inhibiting of the Akt/mTOR pathway. Combination with autophagy inhibitors reduces the effect of this selective autophagy-induced resistance, and thus enhancing even more the anti-tumor effect of MSA on cisplatin-resistant LUAD cells. Finally, We speculate that MSA in combination with autophagy inhibitors may be a promising new therapeutic strategy for the treatment of cisplatin-resistant LUAD.
Using Wearable Inertial Sensors to Estimate Clinical Scores of Upper Limb Movement Quality in Stroke
Authors: Werner Charlotte , Schönhammer Josef G. , Steitz Marianne K. , Lambercy Olivier , Luft Andreas R. , Demkó László , Easthope Chris Awai
Published: May 2022

Neurorehabilitation is progressively shifting from purely in-clinic treatment to therapy that is provided in both clinical and home-based settings. This transition generates a pressing need for assessments that can be performed across the entire continuum of care, a need that might be accommodated by application of wearable sensors. A first step toward ubiquitous assessments is to augment validated and well-understood standard clinical tests. This route has been pursued for the assessment of motor functioning, which in clinical research and practice is observation-based and requires specially trained personnel. In our study, 21 patients performed movement tasks of the Action Research Arm Test (ARAT), one of the most widely used clinical tests of upper limb motor functioning, while trained evaluators scored each task on pre-defined criteria. We collected data with just two wrist-worn inertial sensors to guarantee applicability across the continuum of care and used machine learning algorithms to estimate the ARAT task scores from sensor-derived features. Tasks scores were classified with approximately 80% accuracy. Linear regression between summed clinical task scores (across all tasks per patient) and estimates of sum task scores yielded a good fit (R2 = 0.93; range reported in previous studies: 0.61–0.97). Estimates of the sum scores showed a mean absolute error of 2.9 points, 5.1% of the total score, which is smaller than the minimally detectable change and minimally clinically important difference of the ARAT when rated by a trained evaluator. We conclude that it is feasible to obtain accurate estimates of ARAT scores with just two wrist worn sensors. The approach enables administration of the ARAT in an objective, minimally supervised or remote fashion and provides the basis for a widespread use of wearable sensors in neurorehabilitation.
The Molecular Properties and Roles of Pannier in Harmonia axyridis’s Metamorphosis and Melanin Synthesis
Authors: Tian Renbin , Chen Xu , Wu Mengmeng , Xu Qingxuan , Wang Su , Zang Liansheng , Xiao Da
Published: May 2022

The GATA transcription factor Pannier is identified as the major regulatory gene in color pattern formation in the Asian multi-colored ladybird beetle (Harmonia axyridis). however, the mechanisms of Pannier in regulating melanin synthesis and development in H. axyridis remain elusive. In this study, we identified and characterized Pannier in H. axyridis (HaPnr) and showed it to have two alternative spliced variants named HaPnr-α and HaPnr-β. Analyses of developmental stage expression patterns revealed that HaPnr, HaPnr-α and HaPnr-β were constitutively expressed throughout all developmental stages. To examine the role of HaPnr in H. axyridis development, RNA interference was performed in late larvae (the fourth instar) and early pupae (the first day of pupa stage). The transcript levels of HaPnr were effectively suppressed after the injection of double-stranded RNA of HaPnr (dsHaPnr). The fourth instar larvae injected with dsHaPnr reduced the pupation rates to only 61.50%, compared with 88.5% in the dsGFP-injected group. The un-pupated larvae gradually died after 1 week, and visually unaffected pupae emerged into abnormal adults with malformed hind wings and melanin absent from the cuticle. These abnormal adults gradually died 10 days after eclosion. However, when early pupae were injected with dsHaPnr, the normal eclosion rate was achieved at 88.41% on day 6 after the injection. In addition, these successful eclosion adults also showed an absence of melanin in the cuticle, but they could mate normally and have normal fecundity as compared with the control. We further demonstrated that the suppression of HaPnr-α or HaPnr-β individually did not affect the pupation and eclosion process. The suppression of HaPnr-α expression resulted in elytra melanin decreasing in both the conspicua and the succinea subgroup in H. axyridis. Even though the suppression of HaPnr-β expression only affected the melanin synthesis in the succinea subgroup, it significantly prolonged the time taken for melanin synthesis to occur in the conspicua subgroup in H. axyridis. These results indicate that HaPnr plays an essential role in insect development, especially during their metamorphosis, and also support our hypothesis that HaPnr could regulate melanin synthesis in H. axyridis under the combined action with its two splicing variants, HaPnr-α and HaPnr-β.
Apple Disease Recognition Based on Convolutional Neural Networks With Modified Softmax
Authors: Li Ping , Jing Rongzhi , Shi Xiaoli
Published: May 2022

Accurate and rapid identification of apple diseases is the basis for preventing and treating the apple diseases, and is very significant for assessing disease disaster. Apple disease recognition from its diseased leaf images is one of the interesting research areas in computer and agriculture field. An apple disease recognition method is proposed based on modified convolutional neural networks (MCNN). In MCNN, Inception is introduced into MCNN, global average pooling (GAP) operator is employed instead of several fully connected layers to speedup training model, and modified Softmax classifier is used in the output layer to improve the recognition performance. The modified Softmax classifier uses the modified linear element as the activation function in the hidden layer and adds the local response normalization in MCNN to avoid the gradient disappearance problem effectively. A series of experiments are conducted on two kinds of apple disease image datasets. The results show the feasibility of the algorithm.