bluuebunny/crossref_metadata_2025 huggingface dataset:
NanoSIMS sulfur isotopic analysis at 100 nm scale by imaging technique
Authors: Hao Jia-Long , Zhang Liu-Ping , Yang Wei , Li Zhao-Yang , Li Rui-Ying , Hu Sen , Lin Yang-Ting
Published: March 2023

NanoSIMS has been widely used for in-situ sulfur isotopic analysis (32S and 34S) of micron-sized grains or complex zoning in sulfide in terrestrial and extraterrestrial samples. However, the conventional spot mode analysis is restricted by depth effects at the spatial resolution < 0.5–1 μm. Thus sufficient signal amount cannot be achieved due to limited analytical depths, resulting in low analytical precision (1.5‰). Here we report a new method that simultaneously improves spatial resolution and precision of sulfur isotopic analysis based on the NanoSIMS imaging mode. This method uses a long acquisition time (e.g., 3 h) for each analytical area to obtain sufficient signal amount, rastered with the Cs+ primary beam of ∼100 nm in diameter. Due to the high acquisition time, primary ion beam (FCP) intensity drifting and quasi-simultaneous arrival (QSA) significantly affects the sulfur isotopic measurement of secondary ion images. Therefore, the interpolation correction was used to eliminate the effect of FCP intensity variation, and the coefficients for the QSA correction were determined with sulfide isotopic standards. Then, the sulfur isotopic composition was acquired by the segmentation and calculation of the calibrated isotopic images. The optimal spatial resolution of ∼ 100 nm (Sampling volume of 5 nm × 1.5 μm2) for sulfur isotopic analysis can be implemented with an analytical precision of ∼1‰ (1SD). Our study demonstrates that imaging analysis is superior to spot-mode analysis in irregular analytical areas where relatively high spatial resolution and precision are required and may be widely applied to other isotopic analyses.
Case report: Novel three-dimensional echocardiographic methods mapping aortic root pseudoaneurysm secondary to blood culture-negative endocarditis with bicuspid aortic valve involvement
Authors: Miao Yue , Zhang Yanchao , Yue Ling , Guan Shuang , Feng Wei
Published: March 2023

Background

Infective endocarditis (IE), though uncommon, is a potentially lethal disease. Blood culture-negative endocarditis (BCNIE) accounts for 2.5%–31% of all cases of IE and can lead to life-threatening complications, including aortic root pseudoaneurysm. It is associated with considerable diagnostic and therapeutic dilemmas. TrueVue and TrueVue Glass include the latest two technologies applied in advanced three-dimensional echocardiography, which allow for novel photorealistic images of cardiac structures, and provide abundant previously unavailable diagnostic information. Herein, based on a series of novel three-dimensional echocardiographic methods, we report a case of BCNIE with aortic valve involvement, leading to aortic valve perforation and prolapse, and developing into a giant aortic root pseudoaneurysm.

Case summary

In this study, we presented a case of a 64-year-old man exhibiting symptoms of intermittent fever, asthenia, and dyspnea following light exertion. Physical examination, laboratory tests, and electrocardiograms were suspected of IE, though the results of blood cultures were exactly negative. Three-dimensional transthoracic echocardiography, as well as a series of novel advanced techniques, was adopted to clearly visualize the lesions of the aortic valve and aortic root. However, despite active medical treatment modalities, the patient eventually suffered from a sudden, unexpected death 5 days later.

Conclusion

BCNIE with aortic valve involvement and development into a giant aortic root pseudoaneurysm is a rare and serious clinical event. In addition, TrueVue and TrueVue Glass offer unprecedented photographic stereoscopic images, enhancing the diagnostic performance of such structural heart diseases.
Young children’s ideas of energy compared with the scientific energy concept: Results of a video study with interviews about children’s own drawings
Authors: Detken Franziska
Published: March 2023

For accessing young children’s intuitive ideas about energy, twenty-five first and second graders of Swiss elementary schools (age 6–8 years,M = 7 years 6 months) were asked to draw or write what they associated with energy and subsequently interviewed about their drawing or written note. The responses were videotaped. The children’s responses, including gestures and other nonverbal responses, were analyzed using qualitative content analysis (QCA). A concept-driven approach was used to uncover links between the children’s ideas and the core aspects of the scientific energy concept: forms/manifestations, transformation, transfer, dissipation/degradation, and conservation, and a corresponding coding frame was developed. Though the participating children had not encountered energy or topics like electricity or human nutrition in formal schooling, almost all (N = 24) knew the term energy and used it in the interview. The findings indicate that already young children have nuanced ideas on how energy manifests and behaves that can be expressed by means of drawings/notes and verbally. These ideas refer to energy as an inherent feature of certain objects, as a causal agent, or as a kind of substance and are expressed in association with humans, electric sources and consumers, and vehicles, and their activities or features. The developed category systems summarize how young children express themselves about energy and enable comparison of these ideas with all core aspects of energy. The findings of this study indicate how the very first “steppingstones” for energy learning in early science classrooms might look like, and where “blind spots” or aspects that need further attention should be expected. The detailed analysis of the children’s statements with the developed coding frames is a first step towards reconstruction of the children’s mental models of energy and may serve as a basis for the development of educational and diagnostic tools.
Antibiotic-laden bone cement for diabetic foot infected wounds: A systematic review and meta-analysis
Authors: Dong Tingting , Huang Qi , Sun Zengmei
Published: March 2023

Objective

A large body of literature has demonstrated the significant efficacy of antibiotic bone cement in treating infected diabetic foot wounds, but there is less corresponding evidence-based medical evidence. Therefore, this article provides a meta-analysis of the effectiveness of antibiotic bone cement in treating infected diabetic foot wounds to provide a reference basis for clinical treatment.

Methods

PubMed, Embase, Cochrane library, Scoup, China Knowledge Network (CNKI), Wanfang database, and the ClinicalTrials.gov were searched, and the search time was from the establishment of the database to October 2022, and two investigators independently. Two investigators independently screened eligible studies, evaluated the quality of the literature using the Cochrane Evaluation Manual, and performed statistical analysis of the data using RevMan 5.3 software.

Results

A total of nine randomized controlled studies (n=532) were included and, compared with the control group, antibiotic bone cement treatment reduced the time to wound healing (MD=-7.30 95% CI [-10.38, -4.23]), length of hospital stay (MD=-6.32, 95% CI [-10.15, -2.48]), time to bacterial conversion of the wound (MD=-5.15, 95% CI [-7.15,-2.19]), and the number of procedures (MD=-2.35, 95% CI [-3.68, -1.02]).

Conclusion

Antibiotic bone cement has significant advantages over traditional treatment of diabetic foot wound infection and is worthy of clinical promotion and application.

Systematic review registration

PROSPERO identifier, CDR 362293.
Engagement opportunities in OECD NEA benchmark development
Authors: Bess John D. , Blaise Patrick , Buss Oliver , DeHart Mark , Fleming Michael , Hill Ian , Ilas Germina , Ivanova Tatiana , Ivanov Evgeny , Marshall William J. , Martin Julie-Fiona , Miller Thomas , Percher Catherine , Petruzzi Alessandro , Rohatgi Upendra S. , Valentine Timothy E.
Published: March 2023

A myriad of opportunities is available to collaborate via international benchmark exercises and experimental data preservation activities. Many such opportunities abound under the auspices of the Nuclear Science Committee of the Organisation for Economic Co-operation and Development Nuclear Energy Agency (NEA). Key projects and activities of relevance to the development of advanced reactors design include the International Criticality Safety Benchmark Evaluation Project (ICSBEP), the International Reactor Physics Experiment Evaluation Project (IRPhEP), the International Assay Data of Spent Nuclear Fuel Database (SFCOMPO), the Shielding Integral Benchmark and Archive Database (SINBAD), and The International Experimental Thermal HYdraulicS Database (TIETHYS), and various cooperative benchmark exercises. Interested participants are encouraged to contact the leadership and secretariat of the various Technical Working Groups and Working Parties to become more engaged. This paper provides a summary of the current benchmark exercises and experimental databases available for international participation.
Characterization of heterogeneous metabolism in hepatocellular carcinoma identifies new therapeutic target and treatment strategy
Authors: Yang Jiabin , Zeng Liangtang , Chen Ruiwan , Zheng Shangyou , Zhou Yu , Chen Rufu
Published: March 2023

Background

Metabolic reprogramming is a well-known hallmark of cancer. Systematical identification of clinically relevant metabolic subtypes of Hepatocellular carcinoma (HCC) is critical to understand tumor heterogeneity and develop efficient treatment strategies.

Methods

We performed an integrative analysis of genomic, transcriptomic, and clinical data from an HCC patient cohort in The Cancer Genome Atlas (TCGA).

Results

Four metabolic subtypes were defined: mHCC1, mHHC2, mHCC3, and mHCC4. These subtypes had distinct differences in mutations profiles, activities of metabolic pathways, prognostic metabolism genes, and immune features. The mHCC1 was associated with poorest outcome and was characterized by extensive metabolic alterations, abundant immune infiltration, and increased expression of immunosuppressive checkpoints. The mHHC2 displayed lowest metabolic alteration level and was associated with most significant improvement in overall survival in response to high CD8+ T cell infiltration. The mHHC3 was a “cold-tumor” with low immune infiltration and few metabolic alterations. The mHCC4 presented a medium degree of metabolic alteration and high CTNNB1 mutation rate. Based on our HCC classification and in vitro study, we identified palmitoyl-protein thioesterase 1 (PPT1) was a specific prognostic gene and therapeutic target for mHCC1.

Conclusion

Our study highlighted mechanistic differences among metabolic subtypes and identified potential therapeutic targets for subtype-specific treatment strategies targeting unique metabolic vulnerabilities. The immune heterogeneities across metabolic subtypes may help further clarify the association between metabolism and immune environment and guide the development of novel strategies through targeting both unique metabolic vulnerabilities and immunosuppressive triggers.
A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
Authors: Chen Lei , Lu Jiansheng , Yue Junjie , Wang Rong , Du Peng , Yu Yunzhou , Guo Jiazheng , Wang Xi , Jiang Yujia , Cheng Kexuan , Yang Zhixin , Zheng Tao
Published: March 2023

Background

Human adenovirus type 55 (HAdV55) has a re-emerged as pathogen causing an acute respiratory disease presenting as a severe lower respiratory illness that can cause death. To date, there is no HAdV55 vaccine or treatment available for general use.

Methods

Herein, a monoclonal antibody specific for HAdV55, mAb 9-8, was isolated from an scFv-phage display library derived from mice immunized with the purified inactived-HAdV55 virions. By using ELISA and a virus micro-neutralization assay, we evaluated the binding and neutralizing activity of mAb 9-8 following humanization. Western blotting analysis and antigen-antibody molecular docking analysis were used to identify the antigenic epitopes that the humanized monoclonal antibody 9-8-h2 recognized. After that, their thermal stability was determined.

Results

MAb 9-8 showed potent neutralization activity against HAdV55. After humanization, the humanized neutralizing monoclonal antibody (9-8-h2) was identified to neutralize HAdV55 infection with an IC50 of 0.6050 nM. The mAb 9-8-h2 recognized HAdV55 and HAdV7 virus particles, but not HAdV4 particles. Although mAb 9-8-h2 could recognize HAdV7, it could not neutralize HAdV7. Furthermore, mAb 9-8-h2 recognized a conformational neutralization epitope of the fiber protein and the crucial amino acid residues (Arg 288, Asp 157, and Asn 200) were identified. MAb 9-8-h2 also showed favorable general physicochemical properties, including good thermostability and pH stability.

Conclusions

Overall, mAb 9-8-h2 might be a promising molecule for the prevention and treatment of HAdV55.
Pan-Cancer analysis and experimental validation identify the oncogenic nature of ESPL1: Potential therapeutic target in colorectal cancer
Authors: Zhong Yuchen , Zheng Chaojing , Zhang Weiyuan , Wu Hongyu , Wang Meng , Zhang Qian , Feng Haiyang , Wang Guiyu
Published: March 2023

Introduction

Extra spindle pole bodies like 1 (ESPL1) are required to continue the cell cycle, and its primary role is to initiate the final segregation of sister chromatids. Although prior research has revealed a link between ESPL1 and the development of cancer, no systematic pan-cancer analysis has been conducted. Combining multi-omics data with bioinformatics, we have thoroughly described the function of ESPL1 in cancer. In addition, we examined the impact of ESPL1 on the proliferation of numerous cancer cell lines. In addition, the connection between ESPL1 and medication sensitivity was verified using organoids obtained from colorectal cancer patients. All these results confirm the oncogene nature of ESPL1.

Methods

Herein, we downloaded raw data from numerous publicly available databases and then applied R software and online tools to explore the association of ESPL1 expression with prognosis, survival, tumor microenvironment, tumor heterogeneity, and mutational profiles. To validate the oncogene nature of ESPL1, we have performed a knockdown of the target gene in various cancer cell lines to verify the effect of ESPL1 on proliferation and migration. In addition, patients’ derived organoids were used to verify drug sensitivity.

Results

The study found that ESPL1 expression was markedly upregulated in tumorous tissues compared to normal tissues, and high expression of ESPL1 was significantly associated with poor prognosis in a range of cancers. Furthermore, the study revealed that tumors with high ESPL1 expression tended to be more heterogeneous based on various tumor heterogeneity indicators. Enrichment analysis showed that ESPL1 is involved in mediating multiple cancer-related pathways. Notably, the study found that interference with ESPL1 expression significantly inhibited the proliferation of tumor cells. Additionally, the higher the expression of ESPL1 in organoids, the greater the sensitivity to PHA-793887, PAC-1, and AZD7762.

Discussion

Taken together, our study provides evidence that ESPL1 may implicate tumorigenesis and disease progression across multiple cancer types, highlighting its potential utility as both a prognostic indicator and therapeutic target.
Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammation in vivo
Authors: Gu QinLei , Tung Kenneth S. , Lorenz Ulrike M.
Published: March 2023

Introduction

To achieve a healthy and functional immune system, a delicate balance exists between the activation of conventional T cells (Tcon cells) and the suppression by regulatory T cells (Treg). The tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, shapes this ‘activation-suppression’ balance by modulating Tcon cell resistance to Treg-mediated suppression. Treg cells also express SHP-1, but its role in influencing Treg function is still not fully understood.

Methods

We generated a Treg-specific SHP-1 deletion model, Foxp3Cre+ Shp-1f/f, to address how SHP-1 affects Treg function and thereby contributes to T cell homeostasis using a combination of ex vivo studies and in vivo models of inflammation and autoimmunity.

Results

We show that SHP-1 modulates Treg suppressive function at different levels. First, at the intracellular signaling level in Treg cells, SHP-1 attenuates TCR-dependent Akt phosphorylation, with loss of SHP-1 driving Treg cells towards a glycolysis pathway. At the functional level, SHP-1 expression limits the in vivo accumulation of CD44hiCD62Llo T cells within the steady state Tcon populations (both CD8+ as well as CD4+ Tcon). Further, SHP-1-deficient Treg cells are less efficient in suppressing inflammation in vivo; mechanistically, this appears to be due to a failure to survive or a defect in migration of SHP-1-deficient Treg cells to peripheral inflammation sites.

Conclusion

Our data identify SHP-1 as an important intracellular mediator for fine-tuning the balance between Treg-mediated suppression and Tcon activation/resistance.
Dietary grape extract can, at an appropriate level, improve the growth performance and antioxidant activity of the white shrimp Litopenaeus vannamei
Authors: Chien Angela , Cheng Ya Chi , Sheen Shyn Shin , Kirby Ralph
Published: March 2023

This study evaluated the growth performance and in vivo antioxidant capacity of the white shrimp, Litopenaeus vannamei, fed diets containing the grape extract Nor-grape 80. A control diet containing 1000 ppm vitamin E without added grape extract and four other diets containing 250, 500, 750 and 1000 ppm grape extract were formulated. Shrimp, twenty 0.02 g of individuals in each aquarium, were randomly assigned to one of the above five treatment diets in triplicate and fed three times daily to satiation for six weeks. The final weight, weight gain percentage and specific growth rate of the shrimp larvae fed diets containing 250 and 500 ppm Nor-grape 80 were significantly higher than those fed the other treatment diets. The levels of superoxide dismutase activity of the shrimp fed diets containing 250 and 500 ppm Nor-grape 80 were significantly higher than those of shrimp fed the control diet. On the other hand, the thiobarbituric acid-reactive substance levels of the shrimp fed diets containing 250 and 500 ppm of Nor-grape 80 were significantly lower than those fed the other diets. Furthermore, the highest levels of dietary Nor-grape 80, namely 750 and 1000 ppm, gave rise to reduced growth performance, as well as lower levels of in vivo antioxidant activity. Therefore, for the best growth performance and highest level of in vivo antioxidant activity, it is suggested that the optimal level of Nor-grape 80 as part of a white shrimp diet falls between 250 and 500 ppm.
Testing of a helix twine off-bottom trawl on Georges Bank
Authors: Chosid David M. , Pol Michael
Published: March 2023

The massive biomass of Eastern Georges Bank haddock (Melanogrammus aeglefinus) is difficult to harvest without capturing less robust, but still valuable groundfish stocks like Atlantic cod (Gadus morhua) and some flatfish species. Specialized haddock trawls that raise the mouth of the nets off-bottom have reduced bycatch but the very poor status of Atlantic cod prioritizes even greater reduction to prevent exceeding regulatory fishing quotas. Raising the entire fishing gear off-bottom may further reduce bycatch while eliminating benthic impacts, expanding access to grounds previously off-limits to bottom-tending trawls. We evaluated an off-bottom trawl (OBT) to harvest Eastern Georges Bank haddock while reducing catches of overexploited stocks. The OBT net has very large meshes at the front end, made with innovative “helix” twine that produces lateral hydraulic forces while towing, resulting in self-spreading of the meshes. We established optimal gear configurations to achieve the target OBT net shape and distance to the seafloor by using an assortment of mensuration sensors/loggers and cameras. The OBT caught similar amounts of haddock and reduced some bycatch more than a standard bottom “Ruhle trawl”, but also caught fish of the same lengths despite the OBT using a smaller mesh-sized codend. The OBT also demonstrated similar requirements in vessel RPMs as the Ruhle trawl, despite having a larger swept area.
Vitamin D in pediatric age: Current evidence, recommendations, and misunderstandings
Authors: Corsello Antonio , Spolidoro Giulia C. I. , Milani Gregorio P. , Agostoni Carlo
Published: March 2023

In recent years vitamin D has been in the spotlight of many researchers for its possible role in various disorders, including autoimmune and infectious diseases. Even if vitamin D deficiency remains a major public health problem, its symptomatic manifestations are less and less common in clinical practice, and pediatric age represents a “gray area” where vitamin D supplementation is often administered in the absence of an effective evaluation of its status. Moreover, a poor knowledge about different definitions of “deficiency,” “insufficiency,” and similar terms is spread among clinicians, while guidelines are not univocal, especially after the first year of life. The aim of this brief opinion paper is to sum up recent evidence about vitamin D status and its supplementation in pediatrics, in order to better clarify a common definition of its deficiency. The aim of this opinion article is to raise awareness on this topic among clinicians and encourage a discussion on the real need for routine 25-hydroxycholecalciferol serum evaluation and its supplementation.
Changes of intestinal microbiota in the giant salamander (Andrias davidianus) during growth based on high-throughput sequencing
Authors: Cai Mingcheng , Deng Huan , Sun Hanchang , Si Wantong , Li Xiaoying , Hu Jing , Huang Mengjun , Fan Wenqiao
Published: March 2023

Despite an increasing appreciation of the importance of host–microbe interaction in healthy growth, information on gut microbiota changes of the Chinese giant salamander (Andrias davidianus) during growth is still lacking. Moreover, it is interesting to identify gut microbial structure for further monitoring A. davidianus health. This study explored the composition and functional characteristics of gut bacteria in different growth periods, including tadpole stage (ADT), gills internalization stage (ADG), 1 year age (ADY), 2 year age (ADE), and 3 year age (ADS), using high-throughput sequencing. The results showed that significant differences were observed in microbial community composition and abundance among different growth groups. The diversity and abundance of intestinal flora gradually reduced from larvae to adult stages. Overall, the gut microbial communities were mainly composed of Fusobacteriota, Firmicutes, Bacteroidota, and Proteobacteria. More specifically, the Cetobacterium genus was the most dominant, followed by Lactobacillus and Candidatus Amphibiichlamydia. Interestingly, Candidatus Amphibiichlamydia, a special species related to amphibian diseases, could be a promising indicator for healthy monitoring during A. davidianus growth. These results could be an important reference for future research on the relationship between the host and microbiota and also provide basic data for the artificial feeding of A. davidianus.
Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep
Authors: Rehemujiang Halidai , Yusuf Hassan Ali , Ma Tao , Diao QiYu , Kong Luxin , Kang Lingyun , Tu Yan
Published: March 2023

Background

This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group).

Results

The three groups’ intake of dry matter differed significantly (p < 0.05). In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism.

Conclusion

The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. Replacement of SBM with F-CSM increased VFA yield and further promoted the performance of Hu sheep.
Faecalibacterium prausnitzii prevents hepatic damage in a mouse model of NASH induced by a high-fructose high-fat diet
Authors: Shin Ji-Hee , Lee Yoonmi , Song Eun-Ji , Lee Dokyung , Jang Seo-Yul , Byeon Hye Rim , Hong Moon-Gi , Lee Sang-Nam , Kim Hyun-Jin , Seo Jae-Gu , Jun Dae Won , Nam Young-Do
Published: March 2023

Introduction

Nonalcoholic steatohepatitis (NASH) is an advanced nonalcoholic fatty liver disease characterized by chronic inflammation and fibrosis. A dysbiosis of the gut microbiota has been associated with the pathophysiology of NASH, and probiotics have proven helpful in its treatment and prevention. Although both traditional and next-generation probiotics have the potential to alleviate various diseases, studies that observe the therapeutic effect of next-generation probiotics on NASH are lacking. Therefore, we investigated whether a next-generation probiotic candidate, Faecalibacterium prausnitzii, contributed to the mitigation of NASH.

Methods

In this study, we conducted 16S rRNA sequencing analyses in patients with NASH and healthy controls. To test F. prausnitzii could alleviate NASH symptoms, we isolated four F. prausnitzii strains (EB-FPDK3, EB-FPDK9, EB-FPDK11, and EB-FPYYK1) from fecal samples collected from four healthy individuals. Mice were maintained on a high-fructose high-fat diet for 16 weeks to induce a NASH model and received oral administration of the bacterial strains. Changes in characteristic NASH phenotypes were assessed via oral glucose tolerance tests, biochemical assays, and histological analyses.

Results

16S rRNA sequencing analyses confirmed that the relative abundance of F. prausnitzii reduced significantly in patients with NASH compared to healthy controls (p < 0.05). In the NASH mice, F. prausnitzii supplementation improved glucose homeostasis, prevented hepatic lipid accumulation, curbed liver damage and fibrosis, restored damaged gut barrier functions, and alleviated hepatic steatosis and liver inflammation. Furthermore, real-time PCR assays documented that the four F. prausnitzii strains regulated the expression of genes related to hepatic steatosis in these mice.

Discussion

Our study, therefore, confirms that the administration of F. prausnitzii bacteria can alleviate NASH symptoms. We propose that F. prausnitzii has the potential to contribute to the next-generation probiotic treatment of NASH.
Pleiotropic effects of PipX, PipY, or RelQ overexpression on growth, cell size, photosynthesis, and polyphosphate accumulation in the cyanobacterium Synechococcus elongatus PCC7942
Authors: Llop Antonio , Labella Jose I. , Borisova Marina , Forchhammer Karl , Selim Khaled A. , Contreras Asunción
Published: March 2023

The cyanobacterial protein PipY belongs to the Pyridoxal-phosphate (PLP)-binding proteins (PLPBP/COG0325) family of pyridoxal-phosphate-binding proteins, which are represented in all three domains of life. These proteins share a high degree of sequence conservation, appear to have purely regulatory functions, and are involved in the homeostasis of vitamin B6 vitamers and amino/keto acids. Intriguingly, the genomic context of the pipY gene in cyanobacteria connects PipY with PipX, a protein involved in signaling the intracellular energy status and carbon-to-nitrogen balance. PipX regulates its cellular targets via protein–protein interactions. These targets include the PII signaling protein, the ribosome assembly GTPase EngA, and the transcriptional regulators NtcA and PlmA. PipX is thus involved in the transmission of multiple signals that are relevant for metabolic homeostasis and stress responses in cyanobacteria, but the exact function of PipY is still elusive. Preliminary data indicated that PipY might also be involved in signaling pathways related to the stringent stress response, a pathway that can be induced in the unicellular cyanobacterium Synechococcus elongatus PCC7942 by overexpression of the (p)ppGpp synthase, RelQ. To get insights into the cellular functions of PipY, we performed a comparative study of PipX, PipY, or RelQ overexpression in S. elongatus PCC7942. Overexpression of PipY or RelQ caused similar phenotypic responses, such as growth arrest, loss of photosynthetic activity and viability, increased cell size, and accumulation of large polyphosphate granules. In contrast, PipX overexpression decreased cell length, indicating that PipX and PipY play antagonistic roles on cell elongation or cell division. Since ppGpp levels were not induced by overexpression of PipY or PipX, it is apparent that the production of polyphosphate in cyanobacteria does not require induction of the stringent response.
The effect of allyl isothiocyanate on chondrocyte phenotype is matrix stiffness-dependent: Possible involvement of TRPA1 activation
Authors: Che Hui , Shao Zhiqiang , Ding Jiangchen , Gao Hua , Liu Xiangyu , Chen Hailong , Cai Shuangyu , Ge Jiaying , Wang Chengqiang , Wu Jun , Hao Yuefeng
Published: March 2023

Osteoarthritis (OA) is a chronic joint disease with increasing prevalence. Chondrocytes (CHs) are highly differentiated end-stage cells with a secretory phenotype that keeps the extracellular matrix (ECM) balanced and the cartilage environment stable. Osteoarthritis dedifferentiation causes cartilage matrix breakdown, accounting for one of the key pathogenesis of osteoarthritis. Recently, the activation of transient receptor potential ankyrin 1 (TRPA1) was claimed to be a risk factor in osteoarthritis by causing inflammation and extracellular matrix degradation. However, the underlying mechanism is still unknown. Due to its mechanosensitive property, we speculated that the role of TRPA1 activation during osteoarthritis is matrix stiffness-dependent. In this study, we cultured the chondrocytes from patients with osteoarthritis on stiff vs. soft substrates, treated them with allyl isothiocyanate (AITC), a transient receptor potential ankyrin 1 agonist, and compared the chondrogenic phenotype, containing cell shape, F-actin cytoskeleton, vinculin, synthesized collagen profiles and their transcriptional regulatory factor, and inflammation-related interleukins. The data suggest that allyl isothiocyanate treatment activates transient receptor potential ankyrin 1 and results in both positive and harmful effects on chondrocytes. In addition, a softer matrix could help enhance the positive effects and alleviate the harmful ones. Thus, the effect of allyl isothiocyanate on chondrocytes is conditionally controllable, which could be associated with transient receptor potential ankyrin 1 activation, and is a promising strategy for osteoarthritis treatment.
The effect of cerium dioxide nanoparticles on the viability of hippocampal neurons in Alzheimer’s disease modeling
Authors: Hanzha Vita V. , Rozumna Nataliia M. , Kravenska Yevheniia V. , Spivak Mykola Ya. , Lukyanetz Elena A.
Published: March 2023

The possibilities of using nanoparticle materials based on cerium dioxide (CNPs) are exciting since they are low toxic and have specific redox, antiradical properties. It can be supposed that CNPs’ biomedical use is also relevant in neurodegenerative diseases, especially Alzheimer’s disease (AD). AD is known as the pathologies leading to progressive dementia in the elderly. The factor that provokes nerve cell death and cognitive impairment in AD is the pathological accumulation of beta-amyloid peptide (Aβ) in the brain tissue. In our studies, we examined the impact of Aβ 1-42 on neuronal death and evaluated the potential neuroprotective properties of CNPs during AD modeling in cell culture. Our findings show that, under AD modeling conditions, the number of necrotic neurons increased from 9.4% in the control to 42.7% when Aβ 1-42 was used. In contrast, CNPs alone showed low toxicity, with no significant increase in the number of necrotic cells compared to control conditions. We further explored the potential of CNPs as a neuroprotective agent against Aβ-induced neuronal death. We found that introducing CNPs 24 h after Aβ 1-42 incubation or prophylactically incubating hippocampal cells with CNPs 24 h before amyloid administration significantly reduced the percentage of necrotic cells to 17.8 and 13.3%, respectively. Our results suggest that CNPs in the cultural media can significantly reduce the number of dead hippocampal neurons in the presence of Aβ, highlighting their neuroprotective properties. These findings suggest that CNPs may hold promise for developing new treatments for AD based on their neuroprotective properties.
Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma
Authors: Zhu Dan , Zhu Yamei , Liu Lin , He Xiaoxue , Fu Shizhong
Published: March 2023

Introduction

Screening for metabolically relevant differentially expressed genes (DEGs) shared by hepatocellular carcinoma (HCC) and vascular cognitive impairment (VCI) to explore the possible mechanisms of HCC-induced VCI.

Methods

Based on metabolomic and gene expression data for HCC and VCI, 14 genes were identified as being associated with changes in HCC metabolites, and 71 genes were associated with changes in VCI metabolites. Multi-omics analysis was used to screen 360 DEGs associated with HCC metabolism and 63 DEGs associated with VCI metabolism.

Results

According to the Cancer Genome Atlas (TCGA) database, 882 HCC-associated DEGs were identified and 343 VCI-associated DEGs were identified. Eight genes were found at the intersection of these two gene sets: NNMT, PHGDH, NR1I2, CYP2J2, PON1, APOC2, CCL2, and SOCS3. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. Following principal component analyses (PCA), functional enrichment analyses, immune function analyses, and TMB analyses, these eight DEGs were identified as possibly affecting HCC-induced VCI and the immune microenvironment. As well as gene expression and gene set enrichment analyses (GSEA), a potential drug screen was conducted to investigate the possible mechanisms involved in HCC-induced VCI. The drug screening revealed the potential clinical efficacy of A-443654, A-770041, AP-24534, BI-2536, BMS- 509744, CGP-60474, and CGP-082996.

Conclusion

HCC-associated metabolic DEGs may influence the development of VCI in HCC patients.
Effects of cerebellar transcranial direct current stimulation on rehabilitation of upper limb motor function after stroke
Authors: Gong Qiuwen , Yan Rubing , Chen Han , Duan Xia , Wu Xiaoyu , Zhang Xin , Zhou Yi , Feng Zhou , Chen Ya , Liu Jianbo , Xu Peng , Qiu Jing , Liu Hongliang , Hou Jingming
Published: March 2023

Background

The cerebellum is involved in the control and coordination of movements but it remains unclear whether stimulation of the cerebellum could improve the recovery of upper limb motor function. Therefore, this study aimed to explore whether cerebellar transcranial direct current stimulation (tDCS) therapy could promote the recovery of upper limb motor function in patients who suffered a stroke.

Methods

In this randomized, double-blind, and sham-controlled prospective study, 77 stroke patients were recruited and randomly assigned to the tDCS group (n = 39) or the control group (n = 38). The patients received anodal (2 mA, 20 min) or sham tDCS therapy for 4 weeks. The primary outcome was the change in the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score from baseline to the first day after 4 weeks of treatment (T1) and 60 days after 4 weeks of treatment (T2). The secondary outcomes were the FMA-UE response rates assessed at T1 and T2. Adverse events (AEs) related to the tDCS treatment were also recorded.

Results

At T1, the mean FMA-UE score increased by 10.7 points [standard error of the mean (SEM) = 1.4] in the tDCS group and by 5.8 points (SEM = 1.3) in the control group (difference between the two groups was 4.9 points, P = 0.013). At T2, the mean FMA-UE score increased by 18.9 points (SEM = 2.1) in the tDCS group and by 12.7 points (SEM = 2.1) in the control group (the difference between the two groups was 6.2 points, P = 0.043). At T1, 26 (70.3%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared to 12 (34.3%) patients in the control group (the difference between the two groups was 36.0%, P =0.002). At T2, 33 (89.2%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared with 19 (54.3%) patients in the control group (the difference between the two groups was 34.9%, P = 0.001). There was no statistically significant difference in the incidence of adverse events between the two groups. In the subgroup analysis of different hemiplegic sides, the rehabilitation effect of patients with right hemiplegia was better than that of patients with left hemiplegia (P < 0.05); in the age subgroup analysis, different age groups of patients did not show a significant difference in the rehabilitation effect (P > 0.05).

Conclusion

Cerebellar tDCS can be used as an effective and safe treatment to promote recovery of upper limb motor function in stroke patients.

Trial registration

ChiCTR.org.cn, identifier: ChiCTR2200061838.
Cryptogenic recurrent spontaneous intracranial epidural hematoma: A case report and literature review
Authors: Xu Min , Xue Ya , Chao Xiaofeng , Chen Zhenglou , Wang Yunjiang , Huo Xuqi , Ji Xiang , Wang Hongshen
Published: March 2023

Background

Spontaneous epidural hematoma (EDH) has been suggested to be associated with adjacent infective pathologies, dural vascular malformations, extradural metastases, or coagulopathies. Cryptogenic spontaneous EDH is extremely rare.

Case presentation

The present study reports the case of a cryptogenic spontaneous EDH in a young woman following sexual intercourse. She was diagnosed with consecutive EDH at three different sites within a short time. After three timely operations, a satisfactory outcome was achieved.

Conclusion

EDH should be investigated when a young patient develops headaches and shows signs of increased ICP after emotional hyperactivity or hyperventilation. If early diagnosis and surgical decompression can be carried out in time, the prognosis would be satisfactory.
Clinical features of persistent postural-perceptual dizziness with isolated otolith dysfunction as revealed by VEMP and vHIT findings
Authors: Azami Masato , Fushiki Hiroaki , Tsunoda Reiko , Kamo Tomohiko , Ogihara Hirofumi , Tanaka Ryozo , Kato Takumi
Published: March 2023

Background

Persistent postural-perceptual dizziness (PPPD) is a relatively new disease entity, with diagnostic criteria published by the Bárány Society. PPPD is often preceded by a peripheral or central vestibular disorder. It is not clear how coexisting deficits due to preceding vestibular disorders affect PPPD symptoms.

Objective

This study aimed to characterize the clinical features of PPPD with or without isolated otolith dysfunction using vestibular function tests.

Methods

The study included 43 patients (12 males and 31 females) who were diagnosed with PPPD and completed oculomotor-vestibular function tests. The Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS), Niigata PPPD Questionnaire (NPQ), and Romberg test for stabilometry were examined. The 43 patients with PPPD were classified into four categories based on vestibular evoked myogenic potential (VEMP) and video head impulse test (vHIT) results: normal function for both semicircular canals and otoliths (normal), isolated otolith dysfunction (iOtoDys), isolated semicircular canal dysfunction (iCanalDys), and dysfunction of both otoliths and semicircular canals (OtoCanalDys).

Results

Among the 43 patients with PPPD, the iOtoDys group was the largest (44.2%), followed by the normal group (37.2%), iCanalDys group (9.3%), and OtoCanalDys group (9.3%). Eight of the 19 iOtoDys patients showed both abnormal cVEMP and oVEMP responses unilaterally or bilaterally (both sacculus and utriculus damage type), whereas 11 showed either an abnormal cVEMP or an abnormal oVEMP response (either sacculus or utriculus damage type). In a three-group comparison of the both sacculus and utriculus damage type, the either sacculus or utriculus damage type, and the normal group, the mean total, functional, and emotional DHI scores were significantly higher for the both sacculus and utriculus damage type than for the either sacculus or utriculus damage type. The Romberg ratio, a measure of stabilometry, was significantly higher for the normal group than for the both sacculus and utriculus damage type and the sacculus or utriculus damage type in the iOtoDys group.

Conclusions

The coexistence of sacculus and utriculus damage may exacerbate dizziness symptoms in patients with PPPD. Determining the presence and extent of otolith damage in PPPD may provide useful information on the pathophysiology and treatment strategies of PPPD.
A virtual reality program to assess cognitive function in multiple sclerosis: A pilot study
Authors: Hsu Wan-Yu , Anguera Joaquin A. , Rizzo Albert , Campusano Richard , Chiaravalloti Nancy D. , DeLuca John , Gazzaley Adam , Bove Riley M.
Published: March 2023

Introduction: Cognitive impairment is a debilitating symptom in people with multiple sclerosis (MS). Most of the neuropsychological tasks have little resemblance to everyday life. There is a need for ecologically valid tools for assessing cognition in real-life functional contexts in MS. One potential solution would involve the use of virtual reality (VR) to exert finer control over the task presentation environment; however, VR studies in the MS population are scarce.

Objectives: To explore the utility and feasibility of a VR program for cognitive assessment in MS.

Methods: A VR classroom embedded with a continuous performance task (CPT) was assessed in 10 non-MS adults and 10 people with MS with low cognitive functioning. Participants performed the CPT with distractors (i.e., WD) and without distractors (i.e., ND). The Symbol Digit Modalities Test (SDMT), California Verbal Learning Test—II (CVLT-II), and a feedback survey on the VR program was administered.

Results: People with MS exhibited greater reaction time variability (RTV) compared to non-MS participants, and greater RTV in both WD and ND conditions was associated with lower SDMT.

Conclusions: VR tools warrant further research to determine their value as an ecologically valid platform for assessing cognition and everyday functioning in people with MS.
Listening loops and the adapting auditory brain
Authors: McAlpine David , de Hoz Livia
Published: March 2023

Analysing complex auditory scenes depends in part on learning the long-term statistical structure of sounds comprising those scenes. One way in which the listening brain achieves this is by analysing the statistical structure of acoustic environments over multiple time courses and separating background from foreground sounds. A critical component of this statistical learning in the auditory brain is the interplay between feedforward and feedback pathways—“listening loops”—connecting the inner ear to higher cortical regions and back. These loops are likely important in setting and adjusting the different cadences over which learned listening occurs through adaptive processes that tailor neural responses to sound environments that unfold over seconds, days, development, and the life-course. Here, we posit that exploring listening loops at different scales of investigation—from in vivo recording to human assessment—their role in detecting different timescales of regularity, and the consequences this has for background detection, will reveal the fundamental processes that transform hearing into the essential task of listening.
Effects of intrauterine growth restriction on embryonic hippocampal dentate gyrus neurogenesis and postnatal critical period of synaptic plasticity that govern learning and memory function
Authors: Fung Camille M.
Published: March 2023

Intrauterine growth restriction (IUGR) complicates up to 10% of human pregnancies and is the second leading cause of perinatal morbidity and mortality after prematurity. The most common etiology of IUGR in developed countries is uteroplacental insufficiency (UPI). For survivors of IUGR pregnancies, long-term studies consistently show a fivefold increased risk for impaired cognition including learning and memory deficits. Among these, only a few human studies have highlighted sex differences with males and females having differing susceptibilities to different impairments. Moreover, it is well established from brain magnetic resonance imaging that IUGR affects both white and gray matter. The hippocampus, composed of the dentate gyrus (DG) and cornu ammonis (CA) subregions, is an important gray matter structure critical to learning and memory, and is particularly vulnerable to the chronic hypoxic-ischemic effects of UPI. Decreased hippocampal volume is a strong predictor for learning and memory deficits. Decreased neuron number and attenuated dendritic and axonal morphologies in both the DG and CA are additionally seen in animal models. What is largely unexplored is the prenatal changes that predispose an IUGR offspring to postnatal learning and memory deficits. This lack of knowledge will continue to hinder the design of future therapy to improve learning and memory. In this review, we will first present the clinical susceptibilities and human epidemiology data regarding the neurological sequelae after IUGR. We will follow with data generated using our laboratory’s mouse model of IUGR, that mimics the human IUGR phenotype, to dissect at the cellular and molecular alterations in embryonic hippocampal DG neurogenesis. We will lastly present a newer topic of postnatal neuron development, namely the critical period of synaptic plasticity that is crucial in achieving an excitatory/inhibitory balance in the developing brain. To our knowledge, these findings are the first to describe the prenatal changes that lead to an alteration in postnatal hippocampal excitatory/inhibitory imbalance, a mechanism that is now recognized to be a cause of neurocognitive/neuropsychiatric disorders in at-risk individuals. Studies are ongoing in our laboratory to elucidate additional mechanisms that underlie IUGR-induced learning and memory impairment and to design therapy aimed at ameliorating such impairment.