bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactic Acid Bacteria as Potential Biocontrol Agents for Fusarium Head Blight Disease of Spring Barley
Authors: Byrne Micheal B. , Thapa Ganesh , Doohan FIona M. , Burke James I.
Published: July 2022

Fusarium head blight (FHB) is a devastating disease encountered by spring-grown barley. Traditionally, synthetic chemicals have been used to control this disease on small grain cereals. A move toward biological control agents as part of sustainable agriculture is pertinent due to the evolutionary mechanisms employed by fungal diseases to circumvent current protection strategies. This study evaluated the effect of six lactic acid bacteria isolates on the development of FHB under in vitro and glasshouse conditions. The relative expression of Fusarium marker genes and transcription factors under Fusarium infection was examined. Dual-culture assays observed inhibition zones of up to 10 and 17% of total plate area for L. amylovorus FST 2.11 and L. brevis R2Δ, respectively. Detached leaf assays validated the antifungal activity and showed the potential of all test isolates to significantly inhibit sporulation of Fusarium culmorum and Fusarium graminearum strains. Spray inoculation of lactic acid bacteria to barley spikelets prior to Fusarium spore application significantly reduced disease severity for five candidates (P < 0.05) under glasshouse conditions. Mycotoxin analysis revealed the ability of L. amylovorus DSM20552 to significantly reduce deoxynivalenol content in spikelets (P < 0.05). A preliminary gene expression study showed the positive influence of lactic acid bacteria on the expression of important defense-related marker genes and transcription factors upon FHB. These results indicate the potential of lactic acid bacteria to be included as part of an integrated pest management strategy for the management of FHB disease. This strategy will reduce FHB severity and deoxynivalenol (DON) contamination of spring barley, leading to high acceptance in the grain market.
Creation of an Industrial Bacillus thuringiensis Strain With High Melanin Production and UV Tolerance by Gene Editing
Authors: Zhu Lingyi , Chu Yawen , Zhang Bowen , Yuan Ximu , Wang Kai , Liu Zhiyu , Sun Ming
Published: July 2022

Bacillus thuringiensis produces insecticidal crystal proteins (ICPs) which exhibit strong insecticidal toxicity. But when used in the field, ICPs would be destroyed by ultraviolet (UV) radiation in sunlight, thus decreasing the insecticidal activity and shortening the persistence. To improve the duration of B. thuringiensis preparations, we endowed a highly toxic industrial B. thuringiensis HD-1 with UV tolerance by making it produce melanin, a pigment that absorbs UV radiation. In B. thuringiensis, melanin is derived from homogentisate (HGA), an intermediate in the tyrosine pathway. And the absence of homogentisate-1,2-dioxygenase (HmgA) will lead to the formation of melanin. In this study, we used the CRISPR/Cas9 system to knock out the hmgA gene and obtained a melanin-producing mutant HD-1-ΔhmgA from strain HD-1. The melanin yield by mutant HD-1-ΔhmgA reached 3.60 mg/mL. And the anti-UV test showed that melanin serves as a protection to both the organism and the ICPs. After UV irradiation for 3 h, mutant HD-1-ΔhmgA still had an 80% insecticidal activity against the cotton bollworm, Helicoverpa armigera, while the control line only had about 20%. This study creates a light-stable biopesticide prototype based on a classic industrial strain that can be applied directly and takes the melanin-producing strain as a concept to improve the preparation validity.
Early life administration of Bifidobacterium bifidum BD-1 alleviates long-term colitis by remodeling the gut microbiota and promoting intestinal barrier development
Authors: Peng Chenrui , Li Jinxing , Miao Zhonghua , Wang Yunyi , Wu Simou , Wang Yimei , Wang Silu , Cheng Ruyue , He Fang , Shen Xi
Published: July 2022

Inflammatory bowel disease (IBD) is a chronic intestinal disease characterized by microbiota disturbance and intestinal mucosal damage. The current study aimed to investigate the preventive effects of Bifidobacterium bifidum BD-1 (BD-1) against long-term IBD and possible mechanism by which it alters the gut microbiota, immune response, and mucosal barrier. Our study found that early treatment of BD-1 + Ceftri (ceftriaxone followed by BD-1) and BD-1 confers a certain protective effect against the occurrence of long-term Dextran sulfate sodium-induced colitis, which manifests as a decrease in inflammation scores and MPO activity levels, as well as a relatively intact intestinal epithelial structure. Moreover, compared to BD-1, Ceftri, and NS, early treatment with BD-1 + Ceftri promoted greater expression levels of mucosal barrier-related proteins [KI67, MUC2, ZO-1, secretory immunoglobulin A (slgA), Clauding-1, and Occludin], better local immune responses activation, and moderately better modulation of systemic immune responses during long-term colitis. This may be due to the fact that BD-1 + Ceftri can deliberately prolong the colonization time of some beneficial microbiota (e.g., Bifidobacterium) and reduce the relative abundance of inflammation-related microbiota (e.g., Escherichia/Shigella and Ruminococcus). Interestingly, we found that the changes in the gut barrier and immunity were already present immediately after early intervention with BD-1 + Ceftri, implying that early effects can persist with appropriate intervention. Furthermore, intervention with BD-1 alone in early life confers an anti-inflammatory effect to a certain degree in the long-term, which may be due to the interaction between BD-1 and the host’s native gut microbiota affecting intestinal metabolites. In conclusion, BD-1 was not as effective as BD-1 + Ceftri in early life, perhaps due to its failure to fully play the role of the strain itself under the influence of the host’s complex microbiota. Therefore, further research is needed to explore specific mechanisms for single strain and native microbiota or the combination between probiotics and antibiotics.
Microbial degradation of aristolochic acid I by endophytic fungus A.h-Fs-1 of Asarum heterotropoides
Authors: Wang Xiaohan , Jiang Dan , Shi Qijin , Ren Guangxi , Liu Chunsheng
Published: July 2022

Asari Radix et Rhizoma is commonly used in classic prescriptions of herbal medicine in several Asian countries for resuscitation, pain relief, and sore treatment, and Asarum heterotropoides (A. heterotropoides) is an important source material of Asari Radix et Rhizoma. However, the plants of the Asari Radix et Rhizoma and some plants in Asarum spp. contain aristolochic acid I (AAI), which is considered as a carcinogen. The objective of the current study is to detoxify Asarum spp. through microbial degradation of AAI in order to ensure drug safety. Based on the observation of the close correlation between endophytic fungi of A. heterotropoides and AAI, we identified an AAI-degrading fungus and screened for candidate genes involved in AAI degradation. Full-length O-demethylase genes (ODMs) were cloned including A.h-ODM-5, Fs-ODM-4, and Fs-ODM-1, and their ability to degrade AAI was tested in vitro. The results showed that the AAI-degrading fungus was identified as Neocosmospora solani (A.h-Fs-1, endophytic fungi of A. heterotropoides), and verified the capability of specific O-demethylation to modify the structure of AAI. We further identified the functional ODMs in A.h-Fs-1 capable of degrading AAI and uncovered the AAI degradation mechanism of A.h-Fs-1. The microbial degradation of AAI demonstrated in the present study offers a new method to detoxify plant materials used for herbal medicine, and would enhance the regulation of toxic ingredients content in herbal medicine source materials.
Alcaligenes ammonioxydans HO-1 antagonizes Bacillus velezensis via hydroxylamine-triggered population response
Authors: Gao Xi-Yan , Xie Wei , Liu Ying , Ma Lan , Liu Zhi-Pei
Published: July 2022

Antagonism is a common behavior seen between microbes in nature. Alcaligenes ammonioxydans HO-1 converts ammonia to nitrogen under aerobic conditions, which leads to the accumulation of extracellular hydroxylamine (HA), providing pronounced growth advantages against many bacterial genera, including Bacillus velezensis V4. In contrast, a mutant variant of A. ammonioxydans, strain 2-29, that cannot produce HA fails to antagonize other bacteria. In this article, we demonstrate that cell-free supernatants derived from the antagonistic HO-1 strain were sufficient to reproduce the antagonistic behavior and the efficiency of this inhibition correlated strongly with the HA content of the supernatant. Furthermore, reintroducing the capacity to produce HA to the 2-29 strain or supplementing bacterial co-cultures with HA restored antagonistic behavior. The HA-mediated antagonism was dose-dependent and affected by the temperature, but not by pH. HA caused a decline in biomass, cell aggregation, and hydrolysis of the cell wall in exponentially growing B. velezensis bulk cultures. Analysis of differential gene expression identified a series of genes modulating multicellular behavior in B. velezensis. Genes involved in motility, chemotaxis, sporulation, polypeptide synthesis, and non-ribosomal peptide synthesis were all significantly downregulated in the presence of HA, whereas autolysis-related genes showed upregulation. Taken together, these findings indicate that HA affects the population response of coexisting strains and also suggest that A. ammonioxydans HO-1 antagonize other bacteria by producing extracellular HA that, in turn, acts as a signaling molecule.
Comparative genomic analysis reveals cellulase plays an important role in the pathogenicity of Setosphaeria turcica f. sp. zeae
Authors: Ma Zhoujie , Huang Yufei , Zhang Zhaoran , Liu Xiaodi , Xuan Yuanhu , Liu Bo , Gao Zenggui
Published: July 2022

Setosphaeria turcica f. sp. zeae and S. turcica f. sp. sorghi, the two formae speciales of S. turcica, cause northern leaf blight disease of corn and sorghum, respectively, and often cause serious economic losses. They have obvious physiological differentiation and show complete host specificity. Host specificity is often closely related to pathogen virulence factors, including secreted protein effectors and secondary metabolites. Genomic sequencing can provide more information for understanding the virulence mechanisms of pathogens. However, the complete genomic sequence of S. turcica f. sp. sorghi has not yet been reported, and no comparative genomic information is available for the two formae speciales. In this study, S. turcica f. sp. zeae was predicted to have fewer secreted proteins, pathogen-host interaction (PHI) genes and carbohydrate-active enzymes (CAZys) than S. turcica f. sp. sorghi. Fifteen and 20 polyketide synthase (PKS) genes were identified in S. turcica f. sp. zeae and S. turcica f. sp. sorghi, respectively, which maintained high homology. There were eight functionally annotated effector protein-encoding genes specifically in S. turcica f. sp. zeae, among which the encoding gene StCEL2 of endo-1, 4-β-D-glucanase, an important component of cellulase, was significantly up-regulated during the interaction process. Finally, gluconolactone inhibited cellulase activity and decreased infection rate and pathogenicity, which indicates that cellulase is essential for maintaining virulence. These findings demonstrate that cellulase plays an important role in the pathogenicity of S. turcica f. sp. zeae. Our results also provide a theoretical basis for future research on the molecular mechanisms underlying the pathogenicity of the two formae speciales and for identifying any associated genes.
Targeting Emerging RNA Viruses by Engineered Human Superantibody to Hepatitis C Virus RNA-Dependent RNA Polymerase
Authors: Glab-ampai Kittirat , Kaewchim Kanasap , Thavorasak Techit , Saenlom Thanatsaran , Thepsawat Watayagorn , Mahasongkram Kodchakorn , Thueng-In Kanyarat , Sookrung Nitat , Chaicumpa Wanpen , Chulanetra Monrat
Published: July 2022

RNA-dependent RNA polymerase (RdRp) is a unique and highly conserved enzyme across all members of the RNA virus superfamilies. Besides, humans do not have a homolog of this protein. Therefore, the RdRp is an attractive target for a broadly effective therapeutic agent against RNA viruses. In this study, a formerly generated cell-penetrating human single-chain antibody variable fragment (superantibody) to a conformational epitope of hepatitis C virus (HCV) RdRp, which inhibited the polymerase activity leading to the HCV replication inhibition and the host innate immunity restoration, was tested against emerging/reemerging RNA viruses. The superantibody could inhibit the replication of the other members of the Flaviviridae (DENV serotypes 1−4, ZIKV, and JEV), Picornaviridae (genus Enterovirus: EV71, CVA16), and Coronaviridae (genus Alphacoronavirus: PEDV, and genus Betacoronavirus: SARS-CoV-2 (Wuhan wild-type and the variants of concern), in a dose-dependent manner, as demonstrated by the reduction of intracellular viral RNAs and numbers of the released infectious particles. Computerized simulation indicated that the superantibody formed contact interfaces with many residues at the back of the thumb domain (thumb II site, T2) of DENV, ZIKV, JEV, EV71, and CVA16 and fingers and thumb domains of the HCV and coronaviruses (PEDV and SARS-CoV-2). The superantibody binding may cause allosteric change in the spatial conformation of the enzyme and disrupt the catalytic activity, leading to replication inhibition. Although the speculated molecular mechanism of the superantibody needs experimental support, existing data indicate that the superantibody has high potential as a non-chemical broadly effective anti-positive sense-RNA virus agent.
Association Between Plasma Exosomes S100A9/C4BPA and Latent Tuberculosis Infection Treatment: Proteomic Analysis Based on a Randomized Controlled Study
Authors: Du Ying , Xin Henan , Cao Xuefang , Liu Zisen , He Yijun , Zhang Bin , Yan Jiaoxia , Wang Dakuan , Guan Ling , Shen Fei , Feng Boxuan , He Yongpeng , Liu Jianmin , Jin Qi , Pan Shouguo , Zhang Haoran , Gao Lei
Published: July 2022

Background

Identifying host plasma exosome proteins associated with host response to latent tuberculosis infection (LTBI) treatment might promote our understanding of tuberculosis (TB) pathogenesis and provide useful tools for implementing the precise intervention.

Methods

Based on an open-label randomized controlled trial (RCT) aiming to evaluate the short-course regimens for LTBI treatment, plasma exosomes from pre- and post-LTBI treatment were retrospectively detected by label-free quantitative protein mass spectrometry and validated by a parallel reaction monitoring method for participants with changed or not changed infection testing results after LTBI treatment. Eligible participants for both screening and verification sets were randomly selected from the based-RCT in a 1:1 ratio by age and gender. Reversion was defined as a decrease in IFN-γ levels from >0.70 IU/ml prior to treatment to 0.20 IU/ml within 1 week of treatment. The predictive ability of the candidate proteins was evaluated by receiver operating characteristic (ROC) analysis.

Results

Totally, two sample sets for screening (n= 40) and validation (n= 60) were included. Each of them included an equal number of subjects with persistent positive or reversed QuantiFERON-TB Gold In-Tube (QFT) results after LTBI. A total of 2,321 exosome proteins were detected and 102 differentially expressed proteins were identified to be associated with QFT reversion. Proteins with high confidence and original values intact were selected to be further verified. Totally, 9 downregulated proteins met the criteria and were validated. After verification, C4BPA and S100A9 were confirmed to be still significantly downregulated (fold change <0.67,p< 0.05). The respective areas under the ROC curve were 0.73 (95% CI: 0.57–0.89) and 0.69 (95% CI: 0.52–0.86) for C4BPA and S100A9, with a combined value of 0.78 (95% CI: 0.63–0.93). The positive and negative predictive values for combined markers were 70.10% (95% CI: 50.22–86.30%) and 55.63% (95% CI: 29.17–61.00%).

Conclusion

Our findings suggest that downregulated C4BPA and S100A9 in plasma exosomes might be associated with a host positive response to LTBI treatment. Further studies are warranted to verify the findings and potential underlying mechanisms in varied populations with a larger sample size.
Impact of a phage cocktail targeting Escherichia coli and Enterococcus faecalis as members of a gut bacterial consortium in vitro and in vivo
Authors: Buttimer Colin , Sutton Tom , Colom Joan , Murray Ellen , Bettio Pedro H. , Smith Linda , Bolocan Andrei S. , Shkoporov Andrey , Oka Akihiko , Liu Bo , Herzog Jeremy W. , Sartor R. Balfour , Draper Lorraine A. , Ross R. Paul , Hill Colin
Published: July 2022

Escherichia coli and Enterococcus faecalis have been implicated as important players in human gut health that have been associated with the onset of inflammatory bowel disease (IBD). Bacteriophage (phage) therapy has been used for decades to target pathogens as an alternative to antibiotics, but the ability of phage to shape complex bacterial consortia in the lower gastrointestinal tract is not clearly understood. We administered a cocktail of six phages (either viable or heat-inactivated) targeting pro-inflammatory Escherichia coli LF82 and Enterococcus faecalis OG1RF as members of a defined community in both a continuous fermenter and a murine colitis model. The two target strains were members of a six species simplified human microbiome consortium (SIHUMI-6). In a 72-h continuous fermentation, the phage cocktail caused a 1.1 and 1.5 log (log10 genome copies/mL) reduction in E. faecalis and E. coli numbers, respectively. This interaction was accompanied by changes in the numbers of other SIHUMI-6 members, with an increase of Lactiplantibacillus plantarum (1.7 log) and Faecalibacterium prausnitzii (1.8 log). However, in germ-free mice colonized by the same bacterial consortium, the same phage cocktail administered twice a week over nine weeks did not cause a significant reduction of the target strains. Mice treated with active or inactive phage had similar levels of pro-inflammatory cytokines (IFN-y/IL12p40) in unstimulated colorectal colonic strip cultures. However, histology scores of the murine lower GIT (cecum and distal colon) were lower in the viable phage-treated mice, suggesting that the phage cocktail did influence the functionality of the SIHUMI-6 consortium. For this study, we conclude that the observed potential of phages to reduce host populations in in vitro models did not translate to a similar outcome in an in vivo setting, with this effect likely brought about by the reduction of phage numbers during transit of the mouse GIT.
Root attributes dominate the community assembly of soil fungal functional guilds across arid inland river basin
Authors: Wang Yin , Wang Jianming , Qu Mengjun , Li Jingwen
Published: July 2022

Plant attributes are increasingly acknowledged as key drivers shaping soil fungal communities, but considerable uncertainty exists over fungal community assembly mechanisms and their plant drivers based only on inferences from plant aboveground attributes. To date, empirical evidences of how root attributes are integrated into microbiome–plant linkages remain limited. Using 162 soil samples from a typical arid inland river basin in China, we assessed the drivers that regulate the distribution patterns and assembly processes of total, mycorrhizal, saprotrophic and pathotrophic fungi in surface (0–15 cm) and subsurface soils (15–30 cm). Total fungi and fungal functional guilds exhibited similar distribution patterns in arid inland river basins. Null-model and variance partitioning analysis revealed that the heterogeneous selection induced by root attributes, rather than dispersal limitation, predominated the fungal community assembly. Multiple regressions on matrices further demonstrated that specific root length were the most important predictors of fungal community assembly, which mediated the balance of assembly processes of soil fungal communities. Heterogeneous selection decreased for total, mycorrhizal and saprotrophic fungi, but increased for pathotrophic fungi with increasing specific root length. Additionally, fine-root biomass exerted important effects on fungal assembly processes in subsurface soil but not in surface soil, suggesting root attributes differently affected fungal community assembly between surface and subsurface soil. Collectively, our study highlights the importance of considering root attributes in differentiating the balance of stochastic and deterministic processes in microbial community assembly.
Matrine@chitosan-D-proline nanocapsules as antifouling agents with antibacterial properties and biofilm dispersibility in the marine environment
Authors: Hao Xiangping , Yan Weilu , Yang Jingzhi , Bai Yun , Qian Hongchang , Lou Yuntian , Ju Pengfei , Zhang Dawei
Published: July 2022

Antifoulants are the most vital substances in antifouling coatings to prevent marine organisms from colonizing the undersea substrate surfaces. In addition to antibacterial performance, inhibition of biofilm formation is an important criterion for antifouling coatings. In this study, we synthesized pH-responsive matrine@chitosan-D-proline (Mat@CS-Pro) nanocapsules of about 280 nm with antibacterial properties and biofilm dispersibility. The prepared Mat@CS-Pro nanocapsules exhibited high-level antibacterial properties, reaching about 93, 88, and 96% for E. coli, S. aureus, and P. aeruginosa, respectively. Such nanocapsules can cause irreversible damage to bacteria and cause them to lose their intact cell structures. Moreover, Mat@CS-Pro nanocapsules also possessed outstanding dispersal biofilm performances, in which the biofilm thickness of E. coli, S. aureus, and P. aeruginosa was decreased by 33, 74, and 42%, respectively, after 3 days of incubation. Besides, the Mat@CS-Pro nanocapsules had remarkable pH-responsive properties. As the environmental pH became acidic, the nanocapsules swelled to about 475 nm and the released concentration could reach 28.5 ppm after immersion for 10 h but maintained a low releasing rate in pH 8 conditions.
Strategies of Epstein-Barr virus to evade innate antiviral immunity of its human host
Authors: Albanese Manuel , Tagawa Takanobu , Hammerschmidt Wolfgang
Published: July 2022

Epstein-Barr virus (EBV) is a double-stranded DNA virus of the Herpesviridae family. This virus preferentially infects human primary B cells and persists in the human B cell compartment for a lifetime. Latent EBV infection can lead to the development of different types of lymphomas as well as carcinomas such as nasopharyngeal and gastric carcinoma in immunocompetent and immunocompromised patients. The early phase of viral infection is crucial for EBV to establish latency, but different viral components are sensed by cellular sensors called pattern recognition receptors (PRRs) as the first line of host defense. The efficacy of innate immunity, in particular the interferon-mediated response, is critical to control viral infection initially and to trigger a broad spectrum of specific adaptive immune responses against EBV later. Despite these restrictions, the virus has developed various strategies to evade the immune reaction of its host and to establish its lifelong latency. In its different phases of infection, EBV expresses up to 44 different viral miRNAs. Some act as viral immunoevasins because they have been shown to counteract innate as well as adaptive immune responses. Similarly, certain virally encoded proteins also control antiviral immunity. In this review, we discuss how the virus governs innate immune responses of its host and exploits them to its advantage.
Hanstruepera marina sp. nov. and Hanstruepera flava sp. nov., two novel species in the family Flavobacteriaceae isolated by a modified in situ cultivation technique from marine sediment
Authors: Ding Hong , Liu Jiahui , Yang Chen , Guo Chaobo , Ding Lijian , Jung Dawoon , Zhang Weiyan
Published: July 2022

A modified in situ cultivation technique was developed and applied to resource mining of uncultured microbes from marine sediments of Meishan Island in the East China Sea. Two novel strains NBU2968T and NBU2984T were isolated by this method but not standard Petri dish, which indicated the modified technique was more effective compared to conventional approaches for isolating uncultured microbes and could be popularized and applied to other aquatic environments. The two novel strains were identified by the polyphasic taxonomic approach. Cells of both strains were observed to be Gram-staining-negative, rod-shaped, nonmotile, aerobic, and yellow-pigmented. Catalase and oxidase activities and hydrolysis of Tweens 40, 60, and 80 of two novel strains were positive. Methyl red reaction, H2S production, and hydrolysis of Tween 20 were negative. According to 16S rRNA gene sequence analysis, two novel strains shared the highest similarities (96.4–97.7%) to the species with a validated name in the genus Hanstruepera, while shared lower sequence similarities (<95.6%) to all other genera. Phylogenetic analysis revealed that strains NBU2968T and NBU2984T were affiliated with the genus Hanstruepera. ANI and dDDH values between the two novel strains and Hanstruepera species were 77.4–78.3% and 20.4–20.9%, respectively, which were below the thresholds for species delineation. The 16S rRNA gene sequence similarity, ANI, and dDDH values between the two novel strains were 99.3, 88.9, and 36.3%, respectively, indicating that the two strains represent different species. The genomes of NBU2968T and NBU2984T were 3.28 Mbp with a G+C content of 34.2% and 3.09 Mbp with a G+C content of 34.4%, respectively. The only respiratory quinone was menaquinone-6 (MK-6). The major cellular fatty acids were iso-C15:0, iso-C15:1G, and iso-C17:0 3-OH. The major polar lipids of the two strains were phosphatidylethanolamine, unidentified amino lipids, and unidentified lipids. Based on the above polyphasic characteristics, strains NBU2968T and NBU2984T represent two novel species within the genus Hanstruepera, for which the names Hanstruepera marina sp. nov. and Hanstruepera flava sp. nov. are proposed. The type strains are NBU2968T (= MCCC 1K06392T= KCTC 82913T) and NBU2984T (= MCCC 1K07472T= KCTC 92511T), respectively.
Cytotoxic indole alkaloids and polyketides produced by a marine-derived fungus Aspergillus flavipes DS720
Authors: Xu An , Xu Xiang-Nan , Zhang Mi , Li Chun-Lian , Liu Li , Fu De-Yuan
Published: July 2022

Marine-derived microorganisms possess the unique metabolic pathways to produce structurally novel secondary metabolites with potent biological activities. In this study, bioactivity-guided isolation of the marine deep-sea-derived fungus Aspergillus flavipes DS720 led to the characterization of four indole alkaloids (compounds 1–4) and four polyketides (compounds 5–8), such as two new indoles, flavonoids A (1) and B (2) with a C-6 reversed prenylation, and a new azaphilone, flaviazaphilone A (5). Their chemical structures were unambiguously established by an extensive interpretation of spectroscopic data, such as 1D/2D NMR and HRESIMS data. The absolute configurations of the new compound 5 were solved by comparing the experimental and calculated Electronic Circular Dichroism (ECD) spectra. Since sufficient amount of flavonoids A (1) was obtained, 1 was subjected to a large-scale cytotoxic activity screening against 20 different human tumor cell lines. The results revealed that 1 showed broad-spectrum cytotoxicities against HeLa, 5637, CAL-62, PATU8988T, A-375, and A-673 cell lines, with the inhibition rates of more than 90%. This study indicated that the newly discovered indole alkaloid 1 may possess certain potential for the development of lead compounds in the future.
Targeting 17β-estradiol biosynthesis in neural stem cells improves stroke outcome
Authors: Patkar Shalmali , Uwanogho Dafe , Modo Michel , Tate Rothwelle J. , Plevin Robin , Carswell Hilary V. O.
Published: July 2022

Dax-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital region on X-chromosome gene 1) blocks 17β-estradiol biosynthesis and its knockdown would be expected to increase 17β-estradiol production. We hypothesized that knockdown of Dax-1 in a conditionally immortalized neural stem cell (NSC) line, MHP36, is a useful approach to increase 17β-estradiol production. Short hairpin (sh) RNA targeted to Dax-1 in NSCs, namely MHP36-Dax1KD cells, resulted in the degradation of Dax-1 RNA and attenuation of Dax-1 protein expression. In vitro, MHP36-Dax1KD cells exhibited overexpression of aromatase and increased 17β-estradiol secretion compared to MHP36 cells. As 17β-estradiol has been shown to promote the efficacy of cell therapy, we interrogated the application of 17β-estradiol-enriched NSCs in a relevant in vivo disease model. We hypothesized that MHP36-Dax1KD cells will enhance functional recovery after transplantation in a stroke model. C57BL/6 male adult mice underwent ischemia/reperfusion by left middle cerebral artery occlusion for 45 min using an intraluminal thread. Two days later male mice randomly received vehicle, MHP36 cells, MHP36-Dax1KD cells, and MHP36 cells suspended in 17β-estradiol (100 nm) or 17β-estradiol alone (100 nm) with serial behavioral testing over 28 days followed by post-mortem histology and blinded analysis. Recovery of sensorimotor function was accelerated and enhanced, and lesion volume was reduced by MHP36-Dax1KD transplants. Regarding mechanisms, immunofluorescence indicated increased synaptic plasticity and neuronal differentiation after MHP36-Dax1KD transplants. In conclusion, knockdown of Dax-1 is a useful target to increase 17β-estradiol biosynthesis in NSCs and improves functional recovery after stroke in vivo, possibly mediated through neuroprotection and improved synaptic plasticity. Therefore, targeting 17β-estradiol biosynthesis in stem cells may be a promising therapeutic strategy for enhancing the efficacy of stem cell-based therapies for stroke.
Immune-Triggered Forms of Plasticity Across Brain Regions
Authors: Hikosaka Momoka , Kawano Takeo , Wada Yayoi , Maeda Tomoki , Sakurai Takeshi , Ohtsuki Gen
Published: July 2022

Immune cells play numerous roles in the host defense against the invasion of microorganisms and pathogens, which induces the release of inflammatory mediators (e.g., cytokines and chemokines). In the CNS, microglia is the major resident immune cell. Recent efforts have revealed the diversity of the cell types and the heterogeneity of their functions. The refinement of the synapse structure was a hallmark feature of the microglia, while they are also involved in the myelination and capillary dynamics. Another promising feature is the modulation of the synaptic transmission as synaptic plasticity and the intrinsic excitability of neurons as non-synaptic plasticity. Those modulations of physiological properties of neurons are considered induced by both transient and chronic exposures to inflammatory mediators, which cause behavioral disorders seen in mental illness. It is plausible for astrocytes and pericytes other than microglia and macrophage to induce the immune-triggered plasticity of neurons. However, current understanding has yet achieved to unveil what inflammatory mediators from what immune cells or glia induce a form of plasticity modulating pre-, post-synaptic functions and intrinsic excitability of neurons. It is still unclear what ion channels and intracellular signaling of what types of neurons in which brain regions of the CNS are involved. In this review, we introduce the ubiquitous modulation of the synaptic efficacy and the intrinsic excitability across the brain by immune cells and related inflammatory cytokines with the mechanism for induction. Specifically, we compare neuro-modulation mechanisms by microglia of the intrinsic excitability of cerebellar Purkinje neurons with cerebral pyramidal neurons, stressing the inverted directionality of the plasticity. We also discuss the suppression and augmentation of the extent of plasticity by inflammatory mediators, as the meta-plasticity by immunity. Lastly, we sum up forms of immune-triggered plasticity in the different brain regions with disease relevance. Together, brain immunity influences our cognition, sense, memory, and behaviorviaimmune-triggered plasticity.
Brain Activities Responding to Acupuncture at ST36 (zusanli) in Healthy Subjects: A Systematic Review and Meta-Analysis of Task-Based fMRI Studies
Authors: Huang Haoming , Yue Xiaomei , Huang Xi , Long Wenjie , Kang Shangyu , Rao Yawen , Zeng Jingchun , Zuo Junling , Wang Lin , Li Hongjuan , Wang Yeqing , Qiu Shijun , Zhao Weixuan
Published: July 2022

Purpose

Stomach 36 (ST36, zusanli) is one of the important acupoints in acupuncture. Despite clinical functional magnetic resonance imaging (fMRI) studies of ST36 acupuncture, the brain activities and the neural mechanism following acupuncture at ST36 remain unclear.

Methods

Literature searches were conducted on online databases, including MEDLINE, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, WeiPu database, and China Biology Medicine, for task-based fMRI studies of acupuncture at ST36 in healthy subjects. Brain regions activated by ST36 acupuncture were systematically evaluated and subjected to seed-based d mapping meta-analysis. Subgroup analysis was conducted on control procedures, manual acupuncture, electrical acupuncture (EA), and acupuncture-specific activations. Meta-regression analysis was performed to explore the effects of needle retention time on brain activities following ST36 acupuncture stimulation. The activated brain regions were further decoded and mapped on large-scale functional networks to further decipher the clinical relevance of acupuncturing at ST36.

Results

A total of sixteen studies, involving a total of 401 right-handed healthy participants, that satisfied the inclusion criteria were included in the present meta-analysis. Meta-analysis showed that acupuncturing on ST36 positively activates the opercular part of the right inferior frontal gyrus (IFG.R), left superior temporal gyrus (STG.L), and right median cingulate/paracingulate gyri (MCG.R) regions. Needle retention time in an acupuncture session positively correlates with the activation of the left olfactory cortex, as shown in meta-regression analysis. Subgroup analysis revealed that EA stimulation may be a source of heterogeneity in the pooled results. Functional network mappings showed that the activated areas were mapped to the auditory network and salience network. Further functional decoding analysis showed that acupuncture on ST36 was associated with pain, secondary somatosensory, sound and language processing, and mood regulation.

Conclusion

Acupuncture at ST36 in healthy individuals positively activates the opercular part of IFG.R, STG.L, and MCG.R. The left olfactory cortex may exhibit positive needle retention time-dependent activities. Our findings may have clinical implications for acupuncture in analgesia, language processing, and mood disorders.

Systematic Review Registration

https://inplasy.com/inplasy-2021-12-0035.
Monosynaptic targets of utricular afferents in the larval zebrafish
Authors: Jia Yizhen , Bagnall Martha W.
Published: July 2022

The larval zebrafish acquires a repertoire of vestibular-driven behaviors that aid survival early in development. These behaviors rely mostly on the utricular otolith, which senses inertial (tilt and translational) head movements. We previously characterized the known central brainstem targets of utricular afferents using serial-section electron microscopy of a larval zebrafish brain. Here we describe the rest of the central targets of utricular afferents, focusing on the neurons whose identities are less certain in our dataset. We find that central neurons with commissural projections have a wide range of predicted directional tuning, just as in other vertebrates. In addition, somata of central neurons with inferred responses to contralateral tilt are located more laterally than those with inferred responses to ipsilateral tilt. Many dorsally located central utricular neurons are unipolar, with an ipsilateral dendritic ramification and commissurally projecting axon emerging from a shared process. Ventrally located central utricular neurons tended to receive otolith afferent synaptic input at a shorter distance from the soma than in dorsally located neurons. Finally, we observe an unexpected synaptic target of utricular afferents: afferents from the medial (horizontal) semicircular canal. Collectively, these data provide a better picture of the gravity-sensing circuit. Furthermore, we suggest that vestibular circuits important for survival behaviors develop first, followed by the circuits that refine these behaviors.
Morphological characteristics of lenticulostriate arteries in a large age-span population: Results from 7T TOF-MRA
Authors: Wei Ning , Jing Jing , Zhuo Yan , Zhang Zihao
Published: July 2022

Lenticulostriate arteries (LSAs) originate from the middle cerebral artery (MCA) and supply blood to the basal ganglia. The evaluation of its structure and function is essential for the etiological diagnosis of subcortical infarction. However, the characteristics of LSA in a healthy population remain poorly described. Our study aims to acquire morphological measurements of LSA by 7T TOF-MRA on 140 healthy volunteers with a large age range (21–68 years). The results show that the number of branches of LSA gradually decreases with age (r = −0.328, p < 0.001), and the maximum visible length becomes shorter (r = −0.385, p < 0.001). Moreover, there is a significant correlation between the volume of the basal ganglia nuclei and the morphology of LSA. The volume of the putamen is associated with the number of stems (r = 0.267, p < 0.001) and branches (r = 0.236, p < 0.001) of LSAs, while the volume of caudate is closely related to the maximum visible length of LSAs (r = 0.199, p = 0.001). In conclusion, this study is the first in-vivo study to report the morphology of LSA with a large sample size of more than one hundred cases. These findings are valuable in understanding the degeneration of LSAs during aging.
Concentric needle jitter: Reference values in stimulated Tibialis Anterior muscle
Authors: Kouyoumdjian João Aris , Graca Carla Renata
Published: July 2022

Calculating the reference values for jitter parameters utilizing a disposable concentric needle have been already done for the most often tested muscles. Jitter, expressed as the mean consecutive difference (MCD), was measured in the Tibialis Anterior (TA), not routinely tested muscle. Jitter measurement was taken using the intramuscular microaxonal stimulation technique in 32 healthy subjects. The mean MCD and the mean MCD of the 27th value from the 32 subjects had a normal distribution and were 19.79 ± 2.72 μs and 26.88 ± 3.56 μs, respectively. The suggested limit for the mean MCD is ≥ 26 μs and for the individual values is > 34 μs.
Nomograms predict prognosis and hospitalization time using non-contrast CT and CT perfusion in patients with ischemic stroke
Authors: Sui He , Wu Jiaojiao , Zhou Qing , Liu Lin , Lv Zhongwen , Zhang Xintan , Yang Haibo , Shen Yi , Liao Shu , Shi Feng , Mo Zhanhao
Published: July 2022

Background

Stroke is a major disease with high morbidity and mortality worldwide. Currently, there is no quantitative method to evaluate the short-term prognosis and length of hospitalization of patients.

Purpose

We aimed to develop nomograms as prognosis predictors based on imaging characteristics from non-contrast computed tomography (NCCT) and CT perfusion (CTP) and clinical characteristics for predicting activity of daily living (ADL) and hospitalization time of patients with ischemic stroke.

Materials and methods

A total of 476 patients were enrolled in the study and divided into the training set (n = 381) and testing set (n = 95). Each of them owned NCCT and CTP images. We propose to extract imaging features representing as the Alberta stroke program early CT score (ASPECTS) values from NCCT, ischemic lesion volumes from CBF, and TMAX maps from CTP. Based on imaging features and clinical characteristics, we addressed two main issues: (1) predicting prognosis according to the Barthel index (BI)–binary logistic regression analysis was employed for feature selection, and the resulting nomogram was assessed in terms of discrimination capability, calibration, and clinical utility and (2) predicting the hospitalization time of patients–the Cox proportional hazard model was used for this purpose. After feature selection, another specific nomogram was established with calibration curves and time-dependent ROC curves for evaluation.

Results

In the task of predicting binary prognosis outcome, a nomogram was constructed with the area under the curve (AUC) value of 0.883 (95% CI: 0.781–0.985), the accuracy of 0.853, and F1-scores of 0.909 in the testing set. We further tried to predict discharge BI into four classes. Similar performance was achieved as an AUC of 0.890 in the testing set. In the task of predicting hospitalization time, the Cox proportional hazard model was used. The concordance index of the model was 0.700 (SE = 0.019), and AUCs for predicting discharge at a specific week were higher than 0.80, which demonstrated the superior performance of the model.

Conclusion

The novel non-invasive NCCT- and CTP-based nomograms could predict short-term ADL and hospitalization time of patients with ischemic stroke, thus allowing a personalized clinical outcome prediction and showing great potential in improving clinical efficiency.

Combining NCCT- and CTP-based nomograms could accurately predict short-term outcomes of patients with ischemic stroke, including whose discharge BI and the length of hospital stay.

Key Results

Using a large dataset of 1,310 patients, we show a novel nomogram with a good performance in predicting discharge BI class of patients (AUCs > 0.850). The second nomogram owns an excellent ability to predict the length of hospital stay (AUCs > 0.800).
NKCC1 and KCC2: Structural insights into phospho-regulation
Authors: Hartmann Anna-Maria , Nothwang Hans Gerd
Published: July 2022

Inhibitory neurotransmission plays a fundamental role in the central nervous system, with about 30–50% of synaptic connections being inhibitory. The action of both inhibitory neurotransmitter, gamma-aminobutyric-acid (GABA) and glycine, mainly relies on the intracellular Cl– concentration in neurons. This is set by the interplay of the cation chloride cotransporters NKCC1 (Na+, K+, Cl– cotransporter), a main Cl– uptake transporter, and KCC2 (K+, Cl– cotransporter), the principle Cl– extruder in neurons. Accordingly, their dysfunction is associated with severe neurological, psychiatric, and neurodegenerative disorders. This has triggered great interest in understanding their regulation, with a strong focus on phosphorylation. Recent structural data by cryogenic electron microscopy provide the unique possibility to gain insight into the action of these phosphorylations. Interestingly, in KCC2, six out of ten (60%) known regulatory phospho-sites reside within a region of 134 amino acid residues (12% of the total residues) between helices α8 and α9 that lacks fixed or ordered three-dimensional structures. It thus represents a so-called intrinsically disordered region. Two further phospho-sites, Tyr903 and Thr906, are also located in a disordered region between the ß8 strand and the α8 helix. We make the case that especially the disordered region between helices α8 and α9 acts as a platform to integrate different signaling pathways and simultaneously constitute a flexible, highly dynamic linker that can survey a wide variety of distinct conformations. As each conformation can have distinct binding affinities and specificity properties, this enables regulation of [Cl–]i and thus the ionic driving force in a history-dependent way. This region might thus act as a molecular processor underlying the well described phenomenon of ionic plasticity that has been ascribed to inhibitory neurotransmission. Finally, it might explain the stunning long-range effects of mutations on phospho-sites in KCC2.
“I Like the One With Minions”: The Influence of Marketing on Packages of Ultra-Processed Snacks on Children's Food Choices
Authors: Sato Priscila de Morais , Leite Fernanda Helena Marrocos , Khandpur Neha , Martins Ana Paula Bortoletto , Mais Laís Amaral
Published: July 2022

Objective

This study aimed to assess the most consumed school snacks using the free listing and understand how marketing strategies on food labels influenced children's perceptions of snacks via focus groups.

Design

The study design involved free lists and semi-structured focus group interviews.

Setting

São Paulo, Brazil.

Participants

A total of 69 children were involved in this study.

Phenomenon of Interest

Children's perceptions of food labels.

Analysis

Food groups mentioned on the free lists were analyzed for their frequency and priority of occurrence. The focus groups were analyzed through content analysis.

Results

Juices and chips were the most salient snacks, with availability and flavor as reasons for their consumption. Children found images on labels appealing, which created a desire for the food, although could be deceptive. Snacks perceived as healthy were encouraged by parents, and children could more easily convince them to buy snacks with health claims. Colors and brands were important to catch children's attention and make the snack recognizable. Television commercials and mascots reinforced marketing strategies on labels.

Conclusions and Implications

Our results point to the need for public health strategies to deal with the obesity epidemic through creating and implementing specific legislation to regulate food labels to discourage the consumption of unhealthy snacks and prohibit food marketing targeted at children.
Study on the Interaction Mechanism Between Soybean Protein Isolates and Lemon Flavor: Isomerization and Degradation of Citral
Authors: Guo Jun , Xu Jicheng , Chen Jie
Published: July 2022

By headspace solid-phase microextraction/gas chromatography–mass spectrometry, the effects of 1% (w/v) alcohol denatured soybean protein isolates (L-SPI), native soybean protein isolates (N-SPI), as well as the thermal denaturation of soybean protein isolates (H-SPI) on low concentration (24 μmol/L) of citral was studied in aqueous. The results shows that the SPI could catalyze citral isomerization and yield methyl heptenone and acetaldehyde by inverse aldol condensation degradation. 3-Hydroxycitronelloal was formed as an intermediate in this reaction. The catalytic efficiency of the L-SPI was higher than that of N-SPI, whereas the catalytic efficiency of H-SPI was the lowest. Additionally, it shows that the catalytic efficiency increased as the pH increased. The catalytic efficiency of 7S (Soybean β-Conglycinin) was greater than that of 11S (Soy bean Proglycinin).