bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of the El Niño–Southern Oscillation (ENSO) Cycle on the Catches and Habitat Patterns of Three Swimming Crabs in the Taiwan Strait
Authors: Naimullah Muhamad , Wu Yan-Lun , Lee Ming-An , Lan Kuo-Wei
Published: October 2021

The swimming crabs is a crucial predator species in benthic habitats and a high value in commercial fishery industries in subtropical and tropical Asia. The climate variability caused by El Niño–Southern Oscillation (ENSO) events has substantial impacts on the catch and habitat of this species. In this study, a weighted habitat suitability index (HSI) model was constructed using logbooks and voyage data records from Taiwanese crab vessels (2013–2019) with the addition of environmental variables to examine the influence of ENSO events on catch rates (CRs) and habitat suitability for Charybdis feriatus, Portunus pelagicus, and Portunus sanguinolentus in the Taiwan Strait (TS). The autumn (September–October) is the major fishing season for catching these three swimming crab species in the TS. A high CR of P. sanguinolentus was observed across the TS, whereas high CRs of P. pelagicus and C. feriatus were recorded in areas in the southern and northern TS, respectively, during autumn. Moreover, the CRs for C. feriatus and P. pelagicus were higher (>7.0 and >8.0 kg/h) during La Niña events, with the increase being more than 40.0% compared with the CRs under normal and El Niño events in autumn. For P. sanguinolentus, the CRs were higher during both La Niña and El Niño events (>8.0 kg/h) compared with normal years. The high CRs for C. feriatus and P. sanguinolentus during autumn in La Niña years co-occurred with high sea temperature and low salinity, whereas the high CR of P. pelagicus co-occurred with high sea temperature and high salinity. Furthermore, the high CRs for C. feriatus and P. pelagicus were observed in areas with high HSI in the La Niña years but were distributed more widely with a lower HSI during normal and El Niño years. The low CRs for C. feriatus and P. pelagicus during normal and El Niño years and the low CR for P. sanguinolentus in normal years during autumn were highly consistent with substantial shrinkage of suitable habitats. Our findings suggest that ENSO events strongly affected the catch and habitat suitability of C. feriatus, P. pelagicus, and P. sanguinolentus during autumn in the TS.
Microbial Communities of the Hydrothermal Scaly-Foot Snails From Kairei and Longqi Vent Fields
Authors: Bai Shijie , Xu Hengchao , Peng Xiaotong
Published: October 2021

The microbial communities of the hydrothermal Scaly-foot Snails (SFSs) from independent hydrothermal vent fields have not been investigated in depth. In this study, we collected SFSs from two different hydrothermal environments located on the Central Indian Ridge (CIR) and the Southwest Indian Ridge (SWIR), the Kairei and Longqi vent fields, respectively. Additionally, one SFS collected from the Kairei vent field was reared for 16 days with in situ deep-sea seawater. The epibiotic and internal samples of SFSs, including ctenidium, esophageal gland, visceral mass, shells, and scales, were examined for microbial community compositions based on the 16S rRNA gene. Our results revealed significant differences in microbial community composition between SFSs samples collected from Kairei and Longqi vent fields. Moreover, the microbial communities of epibiotic and internal SFS samples also exhibited significant differences. Epibiotic SFS samples were dominated by the bacterial lineages of Sulfurovaceae, Desulfobulbaceae, Flavobacteriaceae, and Campylobacteraceae. While in the internal SFS samples, the genus Candidatus Thiobios, affiliated with the Chromatiaceae, was the most dominant bacterial lineage. Furthermore, the core microbial communities of all samples, which accounted for 78 ∼ 92% of sequences, were dominated by Chromatiaceae (27 ∼ 49%), Sulfurovaceae (10 ∼ 35%), Desulfobulbaceae (2 ∼ 7%), and Flavobacteriaceae (3 ∼ 7%) at the family level. Based on the results of random forest analysis, we also found the genera Desulfobulbus and Sulfurovum were the primary bacterial lineages responsible for the dissimilarity of microbial communities between the SFS samples collected from the Kairei and Longqi vent fields. Our results indicated that the microbial lineages involved in the sulfur cycle were the key microorganisms, playing a crucial role in the hydrothermal vent ecosystems. Our findings expand current knowledge on microbial diversity and composition in the epibiotic and internal microbial communities of SFS collected from different hydrothermal vent fields.
Oxidation Resistance of Double-Layer MoSi2–Borosilicate Glass Coating on Fiber-Reinforced C/SiO2 Aerogel Composite
Authors: Dai Tao , Song Zihao , Du Yuxuan , Zhao Yifan , Cui Sheng
Published: October 2021

An MoSi2–borosilicate glass coating with high emissivity and oxidation resistance was prepared on the surface of the fiber-reinforced C/SiO2 aerogel composite by the slurry method combined with the embedding sintering method under the micro-oxygen atmosphere. The microstructure and phase composition of the coatings with different MoSi2 contents before and after static oxidation were investigated. This composite material has both excellent radiating properties and outstanding oxidation resistance. The total emissivity values of the as-prepared coatings are all above 0.8450 in the wavelength of 300∼2,500 nm. Meanwhile, the as-prepared M40 coating also has superior thermal endurance after the isothermal oxidation of 1,200°C for 180 min with only 0.27% weight loss, which contributes to the appropriate viscosity of the binder to relieve thermal stress defects. This material has broad application prospects in thermal protection.
Reliability and Validity of the Function Impairment Screening Tool in Chinese Older Adults
Authors: Zhang Yaxin , Liu Pan , Pan Yiming , Li Ying , Zhang Li , Li Yun , Ma Lina
Published: October 2021

Background: Physical function gradually decreases with age in older adults, affecting their independence and quality of life and leaving them prone to adverse outcomes. Despite the importance of assessing function for older adults, most studies have focused on disability and paid less attention to functional impairment. Thus, given the lack of valid and practical methods for evaluating functional impairment for older adults, we developed the function impairment screening tool (FIST) using the Delphi method.

Objective: This study aimed to evaluate the reliability and validity of the FIST in Chinese older adults.

Methods: A total of 489 participants aged 60 years or older, and who had completed the FIST were included. A subgroup of 50 participants completed the FIST a second time, 1 week after the first round, and the test–retest reliability was evaluated using the intraclass correlation coefficient (ICC). Reliability was tested using Cronbach's alpha. Validity was examined using exploratory factor analysis. Criterion-related validity was assessed using correlations between the FIST and the Barthel Index activities of daily living (ADL), Lawton, and Brody instrumental activities of daily living (LB-IADL).

Results: The Cronbach's alpha coefficient for the FIST was 0.930 (P < 0.001). The test–retest reliability was good, with an ICC of 0.928 (95% confidence interval [0.874, 0.960]). Exploratory factor analyses revealed one factor accounting for 60.14% of the scale's variance and the load values of every item were >0.4 (0.489–0.872). The correlation coefficient was 0.572 (P < 0.001) between the FIST score and ADL, and was 0.793 (P < 0.001) between the FIST score and IADL. The FIST score was positively correlated with walking speed (r = 0.475, P < 0.001) and grip strength (r = 0.307, P < 0.001), and negatively correlated with age (r = −0.588, P < 0.001) and Fried frailty phenotype (r = −0.594, P < 0.001).

Conclusion: The FIST is a reliable and valid instrument for assessing physical function impairment in older adults.
Efficacy of Jinhua Qinggan Granules Combined With Western Medicine in the Treatment of Confirmed and Suspected COVID-19: A Randomized Controlled Trial
Authors: An XueDong , Xu Xi , Xiao MingZhong , Min XiaoJun , Lyu Yi , Tian JiaXing , Ke Jia , Lang SuPing , Zhang Qing , Fan An , Liu BinBin , Zhang Ying , Hu YaLing , Zhou YaNa , Shao JiaKai , Li XiaoDong , Lian FengMei , Tong XiaoLin
Published: October 2021

Objective: To conduct a randomized controlled clinical trial to evaluate the clinical efficacy and prognostic value of Jinhua Qinggan granules in patients with confirmed and suspected coronavirus disease 2019 (COVID-19).

Methods: A total of 123 suspected and confirmed COVID-19 patients participated in this clinical trial and were randomly divided into Jinhua and Western medicine groups. For 14 days, the Jinhua group was treated with Jinhua Qinggan granules and antiviral drugs, and the Western medicine group was treated with antiviral drugs alone. We collected information on clinical symptoms, disease aggravation rates, and negative conversion rates of nucleic acids in patients, and observed the effects of anti-infective drugs.

Results: There was no significant difference in symptom improvement rates between the two groups, both confirmed and suspected patients (P > 0.05). Both treatments relieved symptoms such as fever, fatigue, and diarrhea. However, the Jinhua treatment was superior in relieving fever and poor appetite. Anti-infective drug use rates were significantly lower in the Jinhua group than in the control group.

Conclusion: Jinhua Qinggan granules combined with Western medicine could relieve the clinical symptoms of fever and poor appetite in COVID-19 patients, reduce the use of antibiotics to a certain extent.

Clinical Trial Registration: The registration number at China Clinical Trial Registry is ChiCTR2000029601.
The Challenges of Telemedicine in Rheumatology
Authors: Song Yujie , Bernard Laurène , Jorgensen Christian , Dusfour Gilles , Pers Yves-Marie
Published: October 2021

During the past 20 years, the development of telemedicine has accelerated due to the rapid advancement and implementation of more sophisticated connected technologies. In rheumatology, e-health interventions in the diagnosis, monitoring and mentoring of rheumatic diseases are applied in different forms: teleconsultation and telecommunications, mobile applications, mobile devices, digital therapy, and artificial intelligence or machine learning. Telemedicine offers several advantages, in particular by facilitating access to healthcare and providing personalized and continuous patient monitoring. However, some limitations remain to be solved, such as data security, legal problems, reimbursement method, accessibility, as well as the application of recommendations in the development of the tools.
Lactobacillus reuteri Alleviates Gastrointestinal Toxicity of Rituximab by Regulating the Proinflammatory T Cells in vivo
Authors: Zhao Binyan , Zhou Bailing , Dong Chunyan , Zhang Rui , Xie Daoyuan , Tian Yaomei , Yang Li
Published: October 2021

Rituximab (RTX) is a widely used anticancer drug with gastrointestinal side effects, such as nausea, vomiting, and diarrhea. The reason for these side effects is still poorly understood. Previous studies have reported that the intestinal microbiota is associated with the occurrence of disease and the therapeutic effect of drugs. In this study, we observed mucosal damage, inflammatory cell infiltration and increased intestinal inflammatory factor expression in RTX-treated mice. RTX also changed the diversity of the intestinal microbiota in mice, and decreased abundance of Lactobacillus reuteri was observed in RTX-treated mice. Further experiments revealed that intragastric administration of L. reuteri in RTX-treated mice attenuated the intestinal inflammatory response induced by RTX and regulated the proportion of helper T (Th) cells. In conclusion, our data characterize the effect of the intestinal microbiota on RTX-induced intestinal inflammation, suggesting that modifying the gut microbiota may represent a positive strategy for managing adverse reactions.
Effects of Zinc Source and Enzyme Addition on the Fecal Microbiota of Dogs
Authors: Pereira Ana Margarida , Maia Margarida R. G. , Pinna Carlo , Biagi Giacomo , Matos Elisabete , Segundo Marcela A. , Fonseca António J. M. , Cabrita Ana R. J.
Published: October 2021

Supplemental zinc from organic sources has been suggested to be more bioavailable than inorganic ones for dog foods. However, the bioavailability of zinc might be affected by dietary constituents such as phytates. The present study aimed to evaluate the effects of two zinc sources (zinc sulfate and zinc proteinate) and the addition of a multi-enzymatic complex from the solid-state fermentation ofAspergillus nigeron end-products of fecal fermentation and fecal microbiota of adult Beagles fed a high-phytate diet. The experimental design consisted of three 4 × 4 Latin Squares with a 2 × 2 factorial arrangement of treatments (n= 12 Beagles), with four periods and four diets: zinc sulfate without (IZ) or with (IZ +) enzyme addition, and zinc proteinate without (OZ) or with (OZ +) enzyme addition. Enzyme addition significantly affected Faith’s phylogenetic diversity index, whereas zinc source did not affect either beta or alpha diversity measures. Linear discriminant analysis effect size detected nine taxa as markers for organic zinc, 18 for inorganic source, and none for enzyme addition. However, with the use of a negative binomial generalized linear model, further effects were observed. Organic zinc was associated with a significantly higher abundance of Firmicutes and lower Proteobacteria and Bacteroidetes, although at a genus level, the response varied. The DNA abundance ofClostridiumcluster I,Clostridiumcluster XIV,Campylobacterspp., Ruminococcaceae,Turicibacter, andBlautiawas significantly higher in dogs fed IZ and IZ + diets. Higher abundance of genusLactobacilluswas observed in dogs fed enzyme-supplemented diets. End-products of fecal fermentation were not affected by zinc source or enzymes. An increase in some taxa of the phyla Actinobacteria and Firmicutes was observed in feces of dogs fed organic zinc with enzyme addition but not with inorganic zinc. This study fills a gap in knowledge regarding the effect of zinc source and enzyme addition on the fecal microbiota of dogs. An association of zinc bioavailability and bacteria abundance is suggested, but the implications for the host (dog) are not clear. Further studies are required to unveil the effects of the interaction between zinc sources and enzyme addition on the fecal microbial community.
A Review on Occurrence and Spread of Antibiotic Resistance in Wastewaters and in Wastewater Treatment Plants: Mechanisms and Perspectives
Authors: Uluseker Cansu , Kaster Krista Michelle , Thorsen Kristian , Basiry Daniel , Shobana Sutha , Jain Monika , Kumar Gopalakrishnan , Kommedal Roald , Pala-Ozkok Ilke
Published: October 2021

This paper reviews current knowledge on sources, spread and removal mechanisms of antibiotic resistance genes (ARGs) in microbial communities of wastewaters, treatment plants and downstream recipients. Antibiotic is the most important tool to cure bacterial infections in humans and animals. The over- and misuse of antibiotics have played a major role in the development, spread, and prevalence of antibiotic resistance (AR) in the microbiomes of humans and animals, and microbial ecosystems worldwide. AR can be transferred and spread amongst bacteria via intra- and interspecies horizontal gene transfer (HGT). Wastewater treatment plants (WWTPs) receive wastewater containing an enormous variety of pollutants, including antibiotics, and chemicals from different sources. They contain large and diverse communities of microorganisms and provide a favorable environment for the spread and reproduction of AR. Existing WWTPs are not designed to remove micropollutants, antibiotic resistant bacteria (ARB) and ARGs, which therefore remain present in the effluent. Studies have shown that raw and treated wastewaters carry a higher amount of ARB in comparison to surface water, and such reports have led to further studies on more advanced treatment processes. This review summarizes what is known about AR removal efficiencies of different wastewater treatment methods, and it shows the variations among different methods. Results vary, but the trend is that conventional activated sludge treatment, with aerobic and/or anaerobic reactors alone or in series, followed by advanced post treatment methods like UV, ozonation, and oxidation removes considerably more ARGs and ARB than activated sludge treatment alone. In addition to AR levels in treated wastewater, it examines AR levels in biosolids, settled by-product from wastewater treatment, and discusses AR removal efficiency of different biosolids treatment procedures. Finally, it puts forward key-points and suggestions for dealing with and preventing further increase of AR in WWTPs and other aquatic environments, together with a discussion on the use of mathematical models to quantify and simulate the spread of ARGs in WWTPs. Mathematical models already play a role in the analysis and development of WWTPs, but they do not consider AR and challenges remain before models can be used to reliably study the dynamics and reduction of AR in such systems.
Dimethylsulfoniopropionate Biosynthetic Bacteria in the Subseafloor Sediments of the South China Sea
Authors: Zhang Yunhui , Sun Kai , Sun Chuang , Shi Xiaochong , Todd Jonathan D. , Zhang Xiao-Hua
Published: October 2021

Dimethylsulfoniopropionate (DMSP) is one of Earth’s most abundant organosulfur molecules, and bacteria in marine sediments have been considered significant producers. However, the vertical profiles of DMSP content and DMSP-producing bacteria in subseafloor sediment have not been described. Here, we used culture-dependent and -independent methods to investigate microbial DMSP production and cycling potential in South China Sea (SCS) sediment. The DMSP content of SCS sediment decreased from 11.25 to 20.90 nmol g–1 in the surface to 0.56–2.08 nmol g–1 in the bottom layers of 8-m-deep subseafloor sediment cores (n = 10). Very few eukaryotic plastid sequences were detected in the sediment, supporting bacteria and not algae as important sediment DMSP producers. Known bacterial DMSP biosynthesis genes (dsyB and mmtN) were only predicted to be in 0.0007–0.0195% of sediment bacteria, but novel DMSP-producing isolates with potentially unknown DMSP synthesis genes and/or pathways were identified in these sediments, including Marinobacter (Gammaproteobacteria) and Erythrobacter (Alphaproteobacteria) sp. The abundance of bacteria with the potential to produce DMSP decreased with sediment depth and was extremely low at 690 cm. Furthermore, distinct DMSP-producing bacterial groups existed in surface and subseafloor sediment samples, and their abundance increased when samples were incubated under conditions known to enrich for DMSP-producing bacteria. Bacterial DMSP catabolic genes were also most abundant in the surface oxic sediments with high DMSP concentrations. This study extends the current knowledge of bacterial DMSP biosynthesis in marine sediments and implies that DMSP biosynthesis is not only confined to the surface oxic sediment zones. It highlights the importance of future work to uncover the DMSP biosynthesis genes/pathways in novel DMSP-producing bacteria.
Differences in Diet and Gut Microbiota Between Lactating and Non-lactating Asian Particolored Bats (Vespertilio sinensis): Implication for a Connection Between Diet and Gut Microbiota
Authors: Li Jingjing , Chu Yujia , Yao Wenwen , Wu Hui , Feng Jiang
Published: October 2021

In mammals, lactation is considered the most energetically costly phase for females. To meet nutritional and energy demands, lactating females usually change feeding patterns by eating food that is higher in protein and calories. Their gut microbes respond accordingly to help adapt to the changes in diet. In this study, we examined differences in diet and gut microbial composition between lactating and non-lactating Asian particolored bats (Vespertilio sinensis) using COI and 16S amplicon sequencing. When compared with non-lactating bats, we found that the diversity and composition of lactating bats’ diets differed; the proportion of Diptera increased and Coleoptera and Orthoptera decreased significantly. This could be attributed to the easy availability and high protein content of Diptera. Comparative analysis of the gut microbiota of lactating and non-lactating females showed that although the diversity of gut microbiota did not change, the relative abundance of specific gut microbiota associated with a particular diet did change. For example, when the consumption of Coleoptera decreased in lactating bats, the relative abundance of Lactobacillaceae was also reduced. Lactobacillaceae are thought to be involved in the digestion of Coleopteran exoskeletons. This study suggests that during lactation, Asian particolored bats eat a diet that yields higher levels of protein, and at the same time, the abundance of specific gut microbes change to help their hosts adapt to these changes in diet.
Effect of Calcium and Manganese Supplementation on Heat Resistance of Spores of Bacillus Species Associated With Food Poisoning, Spoilage, and Fermentation
Authors: Sinnelä Martti Tapani , Pawluk Alixander Mattay , Jin Young Hun , Kim Dabin , Mah Jae-Hyung
Published: October 2021

Bacterial spores often survive thermal processing used in the food industry, while heat treatment leads not only to a decrease in the nutritional and organoleptic properties of foods, but also to a delay in fermentation of fermented foods. Selective reduction of undesirable spores without such impediments is an ongoing challenge for food scientists. Thus, increased knowledge of the spore-forming bacteria is required to control them. In this study, the heat resistance results (D100°C) of the spores of four Bacillus species were determined and compared to previous literature, and found that B. cereus has significantly lower heat resistance than the other Bacillus species, B. coagulans, B. subtilis, and B. licheniformis. Using the spores of these strains, this study also evaluated the effects of single and combined supplementation of calcium (0.00–2.00 mM) and manganese (0.00–0.50 mM) on heat resistance (D100°C). The results revealed that the spores of B. licheniformis and B. cereus displayed the smallest heat resistance when sporulated on media rich in calcium. Conversely, B. coagulans spores and B. subtilis spores exhibited the greatest heat resistance when sporulated under calcium-rich conditions. The opposite results (stronger heat resistance for B. licheniformis spores and B. cereus spores, and smaller heat resistance for B. coagulans spores and B. subtilis spores) were obtained when the spores were formed on media poor in the minerals (particularly calcium). Based on the results, the Bacillus species were divided into two groups: B. licheniformis and B. cereus; and B. coagulans and B. subtilis. The study provides valuable insight to selectively reduce spores of undesirable Bacillus species in the food industry.
Zinc Influx Restricts Enterovirus D68 Replication
Authors: Liu Shunan , Cao Xia , Guo Haoran , Wei Wei
Published: October 2021

Enterovirus D68 (EV-D68) is a respiratory viral pathogen that causes severe respiratory diseases and neurologic manifestations. Since the 2014 outbreak, EV-D68 has been reported to cause severe complications worldwide. However, there are currently no approved antiviral agents or vaccines for EV-D68. In this study, we found that zinc ions exerted substantial antiviral activity against EV-D68 infection in vitro. Zinc salt treatment potently suppressed EV-D68 RNA replication, protein synthesis, and infectious virion production and inhibited cytopathic effects without producing significant cytotoxicity at virucidal concentrations (EC50=0.033mM). Zinc chloride (ZnCl2) treatment moderately inhibited EV-D68 attachment. Time-dose analysis of EV-D68 structural protein VP1 synthesis showed stronger suppression of VP1 in the culture medium than that in the cell lysates. Furthermore, a zinc ionophore, pyrrolidine dithiocarbamate, which can transport zinc ions into cells, also enhanced the anti-EV-D68 activity of ZnCl2 treatment. Taken together, our results demonstrated that the enhancement of zinc influx could serve as a powerful strategy for the therapeutic treatment of EV-D68 infections.
Membrane Depolarization and Apoptosis-Like Cell Death in an Alkaline Environment in the Rice Pathogen Burkholderia glumae
Authors: Nam Yewon , Goo Eunhye , Kang Yongsung , Hwang Ingyu
Published: October 2021

The rice pathogen Burkholderia glumae uses amino acids as a principal carbon source and thus produces ammonia in amino acid-rich culture medium such as Luria–Bertani (LB) broth. To counteract ammonia-mediated environmental alkaline toxicity, the bacterium produces a public good, oxalate, in a quorum sensing (QS)-dependent manner. QS mutants of B. glumae experience alkaline toxicity and may undergo cell death at the stationary phase when grown in LB medium. Here, we show that the cell-death processes of QS mutants due to alkaline environmental conditions are similar to the apoptosis-like cell death reported in other bacteria. Staining QS mutants with bis-(1,3-dibutylbarbituric acid)-trimethine oxonol revealed membrane depolarization. CellROX™ staining showed excessive generation of reactive oxygen species (ROS) in QS mutants. The expression of genes encoding HNH endonuclease (BGLU_1G15690), oligoribonuclease (BGLU_1G09120), ribonuclease E (BGLU_1G09400), and Hu-beta (BGLU_1G13530) was significantly elevated in QS mutants compared to that in wild-type BGR1, consistent with the degradation of cellular materials as observed under transmission electron microscopy (TEM). A homeostatic neutral pH was not attainable by QS mutants grown in LB broth or by wild-type BGR1 grown in an artificially amended alkaline environment. At an artificially adjusted alkaline pH, wild-type BGR1 underwent apoptosis-like cell death similar to that observed in QS mutants. These results show that environmental alkaline stress interferes with homeostatic neutral cellular pH, induces membrane depolarization, and causes apoptosis-like cell death in B. glumae.
A Novel Rice Curl Dwarf-Associated Picornavirus Encodes a 3C Serine Protease Recognizing Uncommon EPT/S Cleavage Sites
Authors: Zhang Tianze , Li Chenyang , Cao Mengji , Wang Dan , Wang Qi , Xie Yi , Gao Shibo , Fu Shuai , Zhou Xueping , Wu Jianxiang
Published: October 2021

Picornaviruses cause diseases in a wide range of vertebrates, invertebrates and plants. Here, a novel picornavirus was identified by RNA-seq technology from rice plants showing dwarfing and curling symptoms, and the name rice curl dwarf-associated virus (RCDaV) is tentatively proposed. The RCDaV genome consists of an 8,987 nt positive-stranded RNA molecule, excluding a poly(A) tail, that encodes two large polyproteins. Using in vitro cleavage assays, we have identified that the RCDaV 3C protease (3Cpro) as a serine protease recognizes the conserved EPT/S cleavage site which differs from the classic Q(E)/G(S) sites cleaved by most picornaviral 3C chymotrypsin-like cysteine proteases. Therefore, we comprehensively deciphered the RCDaV genome organization and showed that the two polyproteins of RCDaV can be cleaved into 12 mature proteins. We found that seven unclassified picornaviruses also encode a 3Cpro similar to RCDaV, and use the highly conserved EPT/S as the cleavage site. The precise genome organizations of these viruses were illustrated. Moreover, RCDaV and the seven unclassified picornaviruses share high sequence identities and similar genome organizations, and cluster into a distinct clade in the order Picornavirales. Our study provides valuable information for the understanding of picornaviral 3Cpros, deciphers the genome organization of a few relatively obscure picornaviruses, and lays the foundation for further pathogenesis research on these viruses.
Varenicline Prevents LPS-Induced Inflammatory Response via Nicotinic Acetylcholine Receptors in RAW 264.7 Macrophages
Authors: Baris Elif , Efe Hande , Gumustekin Mukaddes , Arici Mualla Aylin , Tosun Metiner
Published: October 2021

The cholinergic anti-inflammatory pathway plays an important role in controlling inflammation. This study investigated the effects of varenicline, an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, on inflammatory cytokine levels, cell proliferation, and migration rates in a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 murine macrophage cell lines. The cells were treated with increasing concentrations of varenicline, followed by LPS incubation for 24 h. Prior to receptor-mediated events, anti-inflammatory effects of varenicline on different cytokines and chemokines were investigated using a cytokine array. Nicotinic AChR–mediated effects of varenicline were investigated by using a non-selective nAChR antagonist mecamylamine hydrochloride and a selective α7nAChR antagonist methyllycaconitine citrate. TNFα, IL-1β, and IL-6 levels were determined by the ELISA test in cell media 24 h after LPS administration and compared with those of dexamethasone. The rates of cellular proliferation and migration were monitored for 24 h after drug treatment using a real-time cell analysis system. Varenicline decreased LPS-induced cytokines and chemokines including TNFα, IL-6, and IL-1β via α7nAChRs to a similar level that observed with dexamethasone. Varenicline treatment decreased LPS-induced cell proliferation, without any nAChR involvement. On the other hand, the LPS-induced cell migration rate decreased with varenicline via α7nAChR. Our data suggest that varenicline inhibits LPS-induced inflammatory response by activating α7nAChRs within the cholinergic anti-inflammatory pathway, reducing the cytokine levels and cell migration.
Biosurfactants: Potential Agents for Controlling Cellular Communication, Motility, and Antagonism
Authors: Sharma Jyoti , Sundar Durai , Srivastava Preeti
Published: October 2021

Biosurfactants are surface-active molecules produced by microorganisms, either on the cell surface or secreted extracellularly. They form a thin film on the surface of microorganisms and help in their detachment or attachment to other cell surfaces. They are involved in regulating the motility of bacteria and quorum sensing. Here, we describe the various types of biosurfactants produced by microorganisms and their role in controlling motility, antagonism, virulence, and cellular communication.
Engineered Removal of PD-1 From the Surface of CD19 CAR-T Cells Results in Increased Activation and Diminished Survival
Authors: Kalinin R. S. , Ukrainskaya V. M. , Chumakov S. P. , Moysenovich A. M. , Tereshchuk V. M. , Volkov D. V. , Pershin D. S. , Maksimov E. G. , Zhang H. , Maschan M. A. , Rubtsov Y. P. , Stepanov A. V.
Published: October 2021

CAR-T cell therapy is the most advanced way to treat therapy resistant hematologic cancers, in particular B cell lymphomas and leukemias, with high efficiency. Donor T cells equipped ex vivo with chimeric receptor recognize target tumor cells and kill them using lytic granules. CAR-T cells that recognize CD19 marker of B cells (CD19 CAR-T) are considered the gold standard of CAR-T therapy and are approved by FDA. But in some cases, CD19 CAR-T cell therapy fails due to immune suppressive microenvironment. It is shown that tumor cells upregulate expression of PD-L1 surface molecule that binds and increases level and signal provided by PD-1 receptor on the surface of therapeutic CAR-T cells. Induction of this negative signaling results in functional impairment of cytotoxic program in CAR-T cells. Multiple attempts were made to block PD-1 signaling by reducing binding or surface level of PD-1 in CAR-T cells by various means. In this study we co-expressed CD19-CAR with PD-1-specific VHH domain of anti-PD-1 nanobody to block PD-1/PD-L1 signaling in CD19 CAR-T cells. Unexpectedly, despite increased activation of CAR-T cells with low level of PD-1, these T cells had reduced survival and diminished cytotoxicity. Functional impairment caused by disrupted PD-1 signaling was accompanied by faster maturation and upregulation of exhaustion marker TIGIT in CAR-T cells. We conclude that PD-1 in addition to its direct negative effect on CAR-induced signaling is required for attenuation of strong stimulation leading to cell death and functional exhaustion. These observations suggest that PD-1 downregulation should not be considered as the way to improve the quality of therapeutic CAR-T cells.
Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids
Authors: Luo Ailin , Li Shan , Wang Xuan , Xie Zheng , Li Shiyong , Hua Dongyu
Published: October 2021

Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The composition of gut microbiota may be influenced by various antibiotics. However, how perioperative use of antibiotics affects POCD needs more explorations. In the present study, we explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, BBB integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice. Significant BBB disruptions and decreased levels of tight junction proteins, zonula occludens-1 (ZO-1) and Occludin (OCLN) were seen in the mice of POCD model. Cefazolin treatment attenuated these changes induced by anesthesia and surgery. Furthermore, cefazolin reversed the changes in several fecal bacteria (β-, γ/δ-, ε-Proteobacteria, and Bacteroidetes) as determined by qPCR tests. Analysis of plasma SCFAs showed that almost all types of SCFAs were reduced in POCD and cefazolin administration reversed the changes in expression of the two most abundant SCFAs (acetic and propionic acids). In conclusion, this study demonstrated that cefazolin improved POCD. Mechanistically, cefazolin suppressed the disruption of BBB, gut microbiota or SCFAs, thereby ameliorating POCD.
Functional Abnormality Associated With Tau Deposition in Alzheimer’s Disease – A Hybrid Positron Emission Tomography/MRI Study
Authors: Fu Liping , Zhou Zhi , Liu Linwen , Zhang Jinming , Xie Hengge , Zhang Xiaojun , Zhu Mingwei , Wang Ruimin
Published: October 2021

Objective: To investigate the characteristics of tau deposition and its impact on functional connectivity (FC) in Alzheimer’s disease (AD).

Methods: Hybrid PET/MRI scans with [18F]-THK5317 and neuropsychological assessments were undertaken in 26 participants with AD and 19 healthy controls (HC). The standardized uptake value ratio (SUVR) of [18F]-THK5317 PET imaging was compared between the AD and HC groups. Significant clusters that revealed higher tau deposition in the AD group compared to the HC group were selected as regions of interest (ROI) for FC analysis. We evaluated the difference in the FC between the two groups for each ROI pair. The clinical and radiological characteristics were compared between the AD patients with negative FC and AD patients with positive FC for exploratory analysis.

Results: The bilateral inferior lateral temporal lobe, dorsal prefrontal cortex, precuneus, posterior cingulate cortex, hippocampus, and occipital lobe showed significantly higher [18F]-THK5317 accumulation in AD patients. Decreased FC in regions with higher SUVR was observed in AD patients, and the FC strength was negatively correlated with regional SUVR. Patients with a positive FC exhibited older ages, better cognitive performances, and a lower SUVR than patients with a negative FC.

Conclusions: An impact of tau deposition was observed on FC at the individual level in AD patients. Our findings suggested that the combination of tau-PET and rs-fMRI might help predict AD progression.
Nitric Oxide Signaling in the Auditory Pathway
Authors: Kopp-Scheinpflug Conny , Forsythe Ian D.
Published: October 2021

Nitric oxide (NO) is of fundamental importance in regulating immune, cardiovascular, reproductive, neuromuscular, and nervous system function. It is rapidly synthesized and cannot be confined, it is highly reactive, so its lifetime is measured in seconds. These distinctive properties (contrasting with classical neurotransmitters and neuromodulators) give rise to the concept of NO as a “volume transmitter,” where it is generated from an active source, diffuses to interact with proteins and receptors within a sphere of influence or volume, but limited in distance and time by its short half-life. In the auditory system, the neuronal NO-synthetizing enzyme, nNOS, is highly expressed and tightly coupled to postsynaptic calcium influx at excitatory synapses. This provides a powerful activity-dependent control of postsynaptic intrinsic excitability via cGMP generation, protein kinase G activation and modulation of voltage-gated conductances. NO may also regulate vesicle mobility via retrograde signaling. This Mini Review focuses on the auditory system, but highlights general mechanisms by which NO mediates neuronal intrinsic plasticity and synaptic transmission. The dependence of NO generation on synaptic and sound-evoked activity has important local modulatory actions and NO serves as a “volume transmitter” in the auditory brainstem. It also has potentially destructive consequences during intense activity or on spill-over from other NO sources during pathological conditions, when aberrant signaling may interfere with the precisely timed and tonotopically organized auditory system.
The Neurobehavioral Effects of Buprenorphine and Meloxicam on a Blast-Induced Traumatic Brain Injury Model in the Rat
Authors: Anderson Laura M. , Samineni Sridhar , Wilder Donna M. , Lara Marisela , Eken Ondine , Urioste Rodrigo , Long Joseph B. , Arun Peethambaran
Published: October 2021

Previous findings have indicated that pain relieving medications such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs) may be neuroprotective after traumatic brain injury in rodents, but only limited studies have been performed in a blast-induced traumatic brain injury (bTBI) model. In addition, many pre-clinical TBI studies performed in rodents did not use analgesics due to the possibility of neuroprotection or other changes in cognitive, behavioral, and pathology outcomes. To examine this in a pre-clinical setting, we examined the neurobehavioral changes in rats given a single pre-blast dose of meloxicam, buprenorphine, or no pain relieving medication and exposed to tightly-coupled repeated blasts in an advanced blast simulator and evaluated neurobehavioral functions up to 28 days post-blast. A 16.7% mortality rate was recorded in the rats treated with buprenorphine, which might be attributed to the physiologically depressive side effects of buprenorphine in combination with isoflurane anesthesia and acute brain injury. Rats given buprenorphine, but not meloxicam, took more time to recover from the isoflurane anesthesia given just before blast. We found that treatment with meloxicam protected repeated blast-exposed rats from vestibulomotor dysfunctions up to day 14, but by day 28 the protective effects had receded. Both pain relieving medications seemed to promote short-term memory deficits in blast-exposed animals, whereas vehicle-treated blast-exposed animals showed only a non-significant trend toward worsening short-term memory by day 27. Open field exploratory behavior results showed that blast exposed rats treated with meloxicam engaged in significantly more locomotor activities and possibly a lesser degree of responses thought to reflect anxiety and depressive-like behaviors than any of the other groups. Rats treated with analgesics to alleviate possible pain from the blast ate more than their counterparts that were not treated with analgesics, which supports that both analgesics were effective in alleviating some of the discomfort that these rats potentially experienced post-blast injury. These results suggest that meloxicam and, to a lesser extent buprenorphine alter a variety of neurobehavioral functions in a rat bTBI model and, because of their impact on these neurobehavioral changes, may be less than ideal analgesic agents for pre-clinical studies evaluating these neurobehavioral responses after TBI.
The Effect of Cognitive Load on the Retrieval of Long-Term Memory: An fMRI Study
Authors: Sisakhti Minoo , Sachdev Perminder S. , Batouli Seyed Amir Hossein
Published: October 2021

One of the less well-understood aspects of memory function is the mechanism by which the brain responds to an increasing load of memory, either during encoding or retrieval. Identifying the brain structures which manage this increasing cognitive demand would enhance our knowledge of human memory. Despite numerous studies about the effect of cognitive loads on working memory processes, whether these can be applied to long-term memory processes is unclear. We asked 32 healthy young volunteers to memorize all possible details of 24 images over a 12-day period ending 2 days before the fMRI scan. The images were of 12 categories relevant to daily events, with each category including a high and a low load image. Behavioral assessments on a separate group of participants (#22) provided the average loads of the images. The participants had to retrieve these previously memorized images during the fMRI scan in 15 s, with their eyes closed. We observed seven brain structures showing the highest activation with increasing load of the retrieved images, viz. parahippocampus, cerebellum, superior lateral occipital, fusiform and lingual gyri, precuneus, and posterior cingulate gyrus. Some structures showed reduced activation when retrieving higher load images, such as the anterior cingulate, insula, and supramarginal and postcentral gyri. The findings of this study revealed that the mechanism by which a difficult-to-retrieve memory is handled is mainly by elevating the activation of the responsible brain areas and not by getting other brain regions involved, which is a help to better understand the LTM retrieval process in the human brain.
Similarities in the Biophysical Properties of Spiral-Ganglion and Vestibular-Ganglion Neurons in Neonatal Rats
Authors: Kalluri Radha
Published: October 2021

The membranes of auditory and vestibular afferent neurons each contain diverse groups of ion channels that lead to heterogeneity in their intrinsic biophysical properties. Pioneering work in both auditory- and vestibular-ganglion physiology have individually examined this remarkable diversity, but there are few direct comparisons between the two ganglia. Here the firing patterns recorded by whole-cell patch-clamping in neonatal vestibular- and spiral ganglion neurons are compared. Indicative of an overall heterogeneity in ion channel composition, both ganglia exhibit qualitatively similar firing patterns ranging from sustained-spiking to transient-spiking in response to current injection. The range of resting potentials, voltage thresholds, current thresholds, input-resistances, and first-spike latencies are similarly broad in both ganglion groups. The covariance between several biophysical properties (e.g., resting potential to voltage threshold and their dependence on postnatal age) was similar between the two ganglia. Cell sizes were on average larger and more variable in VGN than in SGN. One sub-group of VGN stood out as having extra-large somata with transient-firing patterns, very low-input resistance, fast first-spike latencies, and required large current amplitudes to induce spiking. Despite these differences, the input resistance per unit area of the large-bodied transient neurons was like that of smaller-bodied transient-firing neurons in both VGN and SGN, thus appearing to be size-scaled versions of other transient-firing neurons. Our analysis reveals that although auditory and vestibular afferents serve very different functions in distinct sensory modalities, their biophysical properties are more closely related by firing pattern and cell size than by sensory modality.
Safety and Effectiveness of Cell Therapy in Neurodegenerative Diseases: Take-Home Messages From a Pilot Feasibility Phase I Study of Progressive Supranuclear Palsy
Authors: Giordano Rosaria , Canesi Margherita , Isalberti Maurizio , Marfia Giovanni , Campanella Rolando , Vincenti Daniele , Cereda Viviana , Ranghetti Alessandra , Palmisano Chiara , Isaias Ioannis Ugo , Benti Riccardo , Marotta Giorgio , Lazzari Lorenza , Montemurro Tiziana , Viganò Mariele , Budelli Silvia , Montelatici Elisa , Lavazza Cristiana , Rivera-Ordaz Araceli , Pezzoli Gianni
Published: October 2021

Mesenchymal stromal cells (MSCs) are multipotent cells with anti-inflammatory properties. Here we tested the safety of MSCs in patients with progressive supranuclear palsy (PSP; ClinicalTrials.gov: NCT01824121; Eudract No. 2011-004051-39). Seven patients were treated. To improve the safety, protocol adjustments were made during the performance of the study. The objectives of our work were: (1) to assess the safety of MSCs and (2) to identify critical issues in cell therapies for neurodegenerative diseases. Autologous MSCs from the bone marrow of PSP patients were administered through the internal carotid arteries. 1-year survival and number of severe adverse events were considered as safety endpoints. Clinical rating scales, neuropsychological assessments, gait and posture analysis, single-photon emission computed tomography, positron emission tomography, and brain magnetic resonance (BMR) were performed at different follow-up times. Peripheral blood levels of inflammatory cytokines were measured before and after cell infusion. Six of the seven treated patients were living 1 year after cell infusion. Asymptomatic spotty lesions were observed at BMR after 24 h in six of the seven treated patients. The last patient in the preliminary cohort (Case 5) exhibited transiently symptomatic BMR ischemic alterations. No severe adverse events were recorded in the last two treated patients. Interleukin-8 serum concentrations decreased in three patients (Case 2, 3, and 4). An adaptive study design, appropriate and up-to-date efficacy measures, adequate sample size estimation, and, possibly, the use of a cellular and/or allogeneic cell sources may help in performing phase II trials in the field.
Lesion Area in the Cerebral Cortex Determines the Patterns of Axon Rewiring of Motor and Sensory Corticospinal Tracts After Stroke
Authors: Sato Tokiharu , Nakamura Yuka , Takeda Akinori , Ueno Masaki
Published: October 2021

The corticospinal tract (CST) is an essential neural pathway for reorganization that recovers motor functions after brain injuries such as stroke. CST comprises multiple pathways derived from different sensorimotor areas of the cerebral cortex; however, the patterns of reorganization in such complex pathways postinjury are largely unknown. Here we comprehensively examined the rewiring patterns of the CST pathways of multiple cerebral origins in a mouse stroke model that varied in size and location in the sensorimotor cortex. We found that spared contralesional motor and sensory CST axons crossed the midline and sprouted into the denervated side of the cervical spinal cord after stroke in a large cortical area. In contrast, the contralesional CST fibers did not sprout in a small stroke, whereas the ipsilesional axons from the spared motor area grew on the denervated side. We further showed that motor and sensory CST axons did not innervate the projecting areas mutually when either one was injured. The present results reveal the basic principles that generate the patterns of CST rewiring, which depend on stroke location and CST subtype. Our data indicate the importance of targeting different neural substrates to restore function among the types of injury.