bluuebunny/crossref_metadata_2025 huggingface dataset:
The spillover effects of uncertainty and globalization on environmental quality in India: Evidence from combined cointegration test and augmented ARDL model
Authors: Ayad Hicham , Mishra Pradeep , Kumari Binita , Ray Soumik , Nuţă Florian Marcel , Gautam Rajani , Balsalobre-Lorente Daniel , Nuţă Alina Cristina , Zamfir Cristina Gabriela
Published: March 2023

Environmental quality and climate change have become hot topics among academics in all scientific fields in recent decades due to their impact on human health and economic development. Hence, this paper investigates the key factors of carbon dioxide emissions in India from 1970–2020 through the Bayer-Hanck test and Augmented ARDL framework on an augmented STIRPAT model, introducing uncertainty and globalization. We employ a set of unit-root tests and a combination of cointegration techniques (DOLS and FMOLS), which permit us to estimate the long-run and short-run relationships. Empirical findings confirmed that the series is I(1) series and there is the existence of a long-run relationship between our variables using three cointegration tests, meaning that the variables have the same behavior in the long run term. The findings revealed that India has an inverse U shape of the Environmental Kuznets curve (EKC) due to the positive association between GDP per capita and CO2 emissions until reaching a threshold, after which the link becomes inverse due to the negative impact of GDP square on CO2 emissions. Furthermore, the findings demonstrated a positive influence of uncertainty and a negative impact of globalization on long-term environmental degradation. Besides, energy consumption and population density are positively associated with CO2 emissions in the long and short run. We advocate for policies that promote more trade openness by entering new markets and cooperating with new trading partners.
iEnhancer-DCSV: Predicting enhancers and their strength based on DenseNet and improved convolutional block attention module
Authors: Jia Jianhua , Lei Rufeng , Qin Lulu , Wu Genqiang , Wei Xin
Published: March 2023

Enhancers play a crucial role in controlling gene transcription and expression. Therefore, bioinformatics puts many emphases on predicting enhancers and their strength. It is vital to create quick and accurate calculating techniques because conventional biomedical tests take too long time and are too expensive. This paper proposed a new predictor called iEnhancer-DCSV built on a modified densely connected convolutional network (DenseNet) and an improved convolutional block attention module (CBAM). Coding was performed using one-hot and nucleotide chemical property (NCP). DenseNet was used to extract advanced features from raw coding. The channel attention and spatial attention modules were used to evaluate the significance of the advanced features and then input into a fully connected neural network to yield the prediction probabilities. Finally, ensemble learning was employed on the final categorization findings via voting. According to the experimental results on the test set, the first layer of enhancer recognition achieved an accuracy of 78.95%, and the Matthews correlation coefficient value was 0.5809. The second layer of enhancer strength prediction achieved an accuracy of 80.70%, and the Matthews correlation coefficient value was 0.6609. The iEnhancer-DCSV method can be found at https://github.com/leirufeng/iEnhancer-DCSV. It is easy to obtain the desired results without using the complex mathematical formulas involved.
Multi-omics approach to study the dual effects of novel proteins on the intestinal health of juvenile largemouth bass (Micropterus salmoides) under an alternate feeding strategy
Authors: Li Lukuan , Wang Yu , Huang Yanqing , Wang Chunfang
Published: March 2023

Introduction

In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant.

Methods

Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days.

Results

The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1β/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson’s correlation.

Discussion

Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.
Hemophilia A subjects with an intron-22 gene inversion mutation show CD4+ T-effector responses to multiple epitopes in FVIII
Authors: Gunasekera Devi , Vir Pooja , Karim Ahmad Faisal , Ragni Margaret V. , Pratt Kathleen P.
Published: March 2023

Background

Almost half of severe hemophilia A (HA) is caused by an intron 22 inversion mutation (Int22Inv), which disrupts the 26-exon F8 gene. Inverted F8 mRNA exons 1-22 are transcribed, while F8B mRNA, containing F8 exons 23-26, is transcribed from a promoter within intron 22. Neither FVIII activity nor FVIII antigen (cross-reacting material, CRM) are detectable in plasma of patients with an intron-22 inversion.

Objectives

To test the hypothesis that (putative) intracellular synthesis of FVIII proteins encoded by inverted F8 and F8B mRNAs confers T-cell tolerance to almost the entire FVIII sequence, and to evaluate the immunogenicity of the region encoded by the F8 exon 22-23 junction sequence.

Patients/Methods

Peripheral blood mononuclear cells (PBMCs) from 30 severe or moderate HA subjects (17 with an Int22Inv mutation) were tested by ELISPOT assays to detect cytokine secretion in response to FVIII proteins and peptides and to map immunodominant T-cell epitopes. Potential immunogenicity of FVIII sequences encoded by the F8 exon 22-23 junction region was also tested using peptide-MHCII binding assays.

Results

Eight of the Int22Inv subjects showed robust cytokine secretion from PBMCs stimulated with FVIII proteins and/or peptides, consistent with earlier publications from the Conti-Fine group. Peptide ELISPOT assays identified immunogenic regions of FVIII. Specificity for sequences encoded within F8 mRNA exons 1-22 and F8B mRNA was confirmed by staining Int22Inv CD4+ T cells with peptide-loaded HLA-Class II tetramers. FVIII peptides spanning the F8 exon 22-23 junction (encoding M2124-V2125) showed limited binding to MHCII proteins and low immunogenicity, with cytokine secretion from only one Int22Inv subject.

Conclusions

PBMCs from multiple subjects with an Int22Inv mutation, with and without a current FVIII inhibitor, responded to FVIII epitopes. Furthermore, the FVIII region encoded by the exon 22-23 junction sequence was not remarkably immunoreactive and is therefore unlikely to contain an immunodominant, promiscuous CD4+ T-cell epitope. Our results indicate that putative intracellular expression of partial FVIII proteins does not confer T-cell tolerance to FVIII regions encoded by inverted F8 mRNA or F8B mRNA.
Spatiotemporal dynamics of benthic bacterial communities in the Perdido Fold Belt, Northwestern Gulf of Mexico
Authors: Sánchez-Soto Ma. Fernanda , Cerqueda-García Daniel , Aguirre-Macedo M. Leopoldina , García-Maldonado José Q.
Published: March 2023

This study analyzed the spatiotemporal dynamics of surficial benthic microbial communities in a bathymetric gradient (44 - 3573 m) across four oceanographic campaigns at the Perdido Fold Belt (PFB) in the northwestern Gulf of Mexico (nwGoM). Bioinformatic analysis of 16S rRNA gene amplicons grouped the 27 samples into three clusters according to a longitudinal bathymetric gradient. Differences in community structure among clusters, based on PERMANOVA analysis, were partially explained by cruise, water depth, temperature, salinity, nitrate plus nitrite, silicate, redox potential, Ni, Cd, Pb, and Al, as well by aliphatic and aromatic hydrocarbon concentrations. Into microbial community composition, Gemmatimonadaceae, Planctomycetaceae, and the JTB255 were detected at all depths across the four campaigns. Members of Anaerolinaceae and specific sulfate-reducing bacteria were more abundant in sites located between 43 and 1200 m, and Rhodospirillaceae, wb1-A12, OM1 clade, Desulfurellaceae, Gemmatimonadetes, Nitrospinaceae, and Clostridiaceae 1 were better represented in deeper sites. Alpha diversity was similar between the three groups and remained stable; however, 10 samples presented changes in the community structure across the four campaigns. Finally, a multivariable association analysis revealed 25 bacterial genera positively related with physicochemical parameters that characterized the environment from shallow to deep sea sites. Taken together, these results yield insights into the temporal stability of 17 of 27 sites in the PFB and revealed signature taxa with putatively ecological relevance in sedimentary environments.
Assessment of future flood risk induced by sea level rise and tropical cyclones under global warming in the Xiamen Bay, Fujian, China
Authors: Guo Wenyun , Yao Ding , Chen Zhi , Ding Pingxing , Ge Jianzhong
Published: March 2023

Tropical cyclone (TC)-induced coastal flooding can lead to severe hazards in low-lying lands and is expected to be exacerbated by sea level rise and TC climatology changes related to the warming climate. Since the dense population in Xiamen Bay, Fujian, China, it is highly valuable in understanding coastal flooding of it, but little studies involved this topic. In this study, we establish a high-resolution numerical model covering all coastal low-lying land in Xiamen Bay based on FVCOM. This model is then used to assess the flood risk in Xiamen Bay under TCs with 10-, 100-, and 1000-year pressures by applying a multi-tracks blend method. The results show that 126 km2 of low-lying area can be flooded periodically by astronomical tides; and 388, 504, and 598 km2 of low-lying area can be flooded under TCs with 10-, 100-, and 1000-year pressures, accompanied by increased average flood depths of 2.3, 2.8, and 3.4 m, respectively. By 2100 under SSP5-8.5, the well-protected Xiamen Island becomes impacted by TCs with 10-year pressure, and flood areas under TCs with 100-year pressure are estimated to be nearly equivalent to that under TCs with 1000-year pressure at the current climate. The most increased exposure area by climate change are artificial surfaces and agricultural areas, showing the potential higher flood disasters in future.
Air sea conditions facilitate a transformation of the positive Indian Ocean Dipole with distinct east pole characteristics into an extreme event
Authors: Li Zhi , Xu Zecheng , Zheng Yunxia , Fang Yue
Published: March 2023

The Indian Ocean Dipole (IOD) is one of the dominant interannual variabilities in the Indian Ocean (IO), and an extreme IOD, in particular, has dramatic effects on the weather, agriculture, and ecosystem around it. Therefore, the formation of an extreme IOD has been a worldwide research focus. Among 13 positive IOD (PIOD) events, two type-east and two type-comparable PIODs developed into extreme events during the 1960–2020 period. This investigation focuses on the cause of the formation of the type-east extreme PIOD, as previous studies have discussed the origin of the type-comparable extreme PIOD. Composite analysis showed that, as an entity, the strong East Asian and Australian monsoon (EAAM) may result in an evident easterly wind anomaly around the Indonesian region of the Marine Continent during May to August of the years when type-east PIODs occurred. The easterly wind anomaly associated with the EAAM was stronger in the extreme IOD group, whereas it was relatively weak in the regular group. The difference in the easterly wind anomaly between the extreme and regular groups could result in a vertical motion anomaly by enhancing the anomalous westward current. The stronger vertical motion created an upwelling in the deep-layer cold water, resulting in a more distinct difference in the vertical temperature gradient. All these conditions promoted the transformation of the type-east PIODs that occurred in 1961 and 1994 into extreme events and are indicative of the importance of vertical advection terms in the formation of type-east extreme PIODs. This study reveals the cause of the formation of type-east extreme PIODs, which will be helpful in understanding IOD diversity.
Analysis of the expression and function of the CBL-CIPK network and MAPK cascade genes in Kandelia obovata seedlings under cold stress
Authors: Tian Kuo , Li Qi , Zhang Xiumei , Guo Haoyu , Wang Yihang , Cao Pinglin , Xu Shengyong , Li Weiye
Published: March 2023

Mangroves are an important component of coastal wetland ecosystems, and low temperature is the main factor that limits their extension to higher latitudes. Kandelia obovata as one of the most cold-tolerant species in mangrove ecosystems can provide basis for the northward migration of mangrove ecosystems. We took K. obovata seedlings from Zhoushan (Zhoushan, Zhejiang, China) as the research object in this study. Transcriptome sequencing based on the Illumina HiSeqTM 2500 platform was performed to compare the transcriptome changes of roots, stems, and leaves before and after freezing and to reveal the molecular mechanisms of frost resistance. A total of 1560, 370, and 416 genes were differentially expressed in the roots, stems, and leaves before and after cold snaps, respectively. Among these differentially expressed genes, 13 positive and negative regulators were attributed to the CBL-CIPK signaling network and MAPK cascade, which might be related to the frost resistance mechanism of K. obovata Transcription factors such as AP2/EREBP and bHLH were involved in regulating the synthesis pathways of ethylene, cytokinin, growth hormone, and flavonoids. Results provide new insights into the frost resistance mechanism of K. obovata seedlings.
A numerical study on the responses of coastal water quality to river runoff after heavy rainfall in the case of a complex coastline with two artificial islands
Authors: Wang Gang , Feng Xin , Zhang Jiabo , Huang Zhe , Bai Yuchuan , Song Wei , Xu Haijue
Published: March 2023

Heavy rainfall causes large volumes of freshwater and nutrient salts to flow from rivers into the sea. This leads to major changes in the ecological environment of estuarine waters in a short period of time. The responses of the estuarine hydro-environment become more complex with the concentrated construction of artificial structures, which is a major cause of marine ecological disasters. This paper considers the Tang Estuary in Qinhuangdao, where artificial structures (e.g., ports, artificial islands, and bridges) are concentrated, as a prototype with the weak tidal dynamic environment. A nested prototype of hydrodynamics and water quality was established using a Delft3D model, with coupled waves and flows. The model was used to simulate the spatial and ephemeral characteristics of the short-term responses of ecological environmental factors, such as dissolved inorganic nitrogen (DIN), nitrate-nitrogen (i.e., NO3-N), ammonium-nitrogen (NH4-N), and orthophosphate (i.e., PO4-P), to an episode of heavy rainfall in August 2022. The results showed that concentrations of DIN and NO3-N in the source areas remain high after the flooding process. The concentration recovered to normal values approximately 5.5 days after the flooding process. In contrast, NH4-N and PO4-P showed a response with ephemeral correspondence with the flooding process, and concentration recovery took only approximately 1 day. This paper proposes two short-term response modes of pollutant diffusion, which provide help in exploring the role of hydro-environmental changes in offshore algal hazards and the effect of permeable buildings on pollutant dispersion. This additionally provides possibilities with the forecasting of red tide and green tide, and for their prevention in the future.
Multiphysics simulation of an anisothermal reactive spontaneous capillary rise between electric rotor wires
Authors: Moisy Amélie , Comas-Cardona Sébastien , Désilles Nicolas , Genevée Pascal , Kolehmainen Jere
Published: March 2023

Introduction: The rotor is the mobile component of an electric motor. A wound rotor is composed primarily of a steel core with insulated copper wires wound around it, after which the winding is immersed into a liquid acrylate-based thermosetting resin bath whose role is to ensure the performance and durability of the motor. This impregnation with resin between the wires occurs under controlled temperature settings to facilitate resin flow and polymerization. This process does not involve any pressurization to further facilitate resin flow between the wires; this suggests that, in addition to viscous effects, capillary and gravity forces play a significant role in the impregnation process.

Methods: Our ultimate objective is to evaluate the quality of this impregnation. Doing so requires the characterization and simulation of a multi-material and multiphysics process in which heat transfer, polymerization kinetics, and resin flow are strongly coupled. This paper presents a fully coupled macroscopic multiphysics simulation of a unidirectional thermo-regulated capillary rise set-up.

Discussion: The modeling choices made produced a good level of agreement with experimental data and enable explanation of a sudden change of regime observed at 120°C, which can be attributed to the polymerization and thermal gradients and their impact on fluid dynamics.
Simulation studies of secondary electron yield with electron transport from Cu (110) surfaces containing C2, N2, CO2, or NO2 adsorbates
Authors: Maille M. , Dennis N. C. , Pokhrel Y. M. , Sanati M. , Joshi R. P.
Published: March 2023

Secondary electron yields of (110) copper surfaces, covered with either carbon, nitrogen, or their dioxides, have been studied by employing combined first principles methods for the material properties and Monte Carlo simulations for electron transport. Furthermore, by studying electron transport inside the Cu system and modeling the power loss taking account of the inelastic electron scattering within the material, changes in the thermal energy of the system have been modeled. The physical reasons behind the increase and decrease of the yield for each system from an electronic perspective are discussed. In agreement with results observed in studies of secondary electron emission, it is shown that the formation of C2 and N2 monolayers reduce the secondary electron yields, while CO2 and NO2 increase the yield significantly. It is demonstrated that in the case of C2 and N2 formation, changes in the surface electronic barrier reduce the probability of electron escape from the Cu surface, resulting in lower secondary electron emission. Formation of CO2 and NO2, on the other hand, reduce the electronic barrier effects. In addition, due to weak bonding of the CO2 layer with the Cu host, the surface provides an additional source of secondary electrons resulting in higher electronic emission yield. Moreover, the NO2 adsorbate creates a surface electric field that changes the surface electron energy and increases the electron escape probability. Additionally, it is verified that thermal change in the system is negligible and so during secondary electron emission measurements, negligible (if any) surface adsorption or desorption could occur.
First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study)
Authors: Larsen Stein Gunnar , Graf Wilhelm , Mariathasan Anthony Burton , Sørensen Olaf , Spasojevic Milan , Goscinski Mariusz Adam , Selboe Silje , Lundstrøm Nadja , Holtermann Anne , Revheim Mona-Elisabeth , Bruland Øyvind Sverre
Published: March 2023

Background

Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11–12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC.

Methods

A first-in-human phase 1 study (EudraCT 2018–002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented.

Results

Twenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28–78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3–30). The peritoneal cancer index was median 7 (3–19), operation time was 395 min (194–515), and hospital stay was 12 days (7–37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution.

Conclusion

All dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.

Clinical Trial Registration:Clinicaltrials.gov, NCT 03732781.
Kinetics of dried blood spot-measured anti-SARS-CoV2 Spike IgG in mRNA-vaccinated healthcare workers
Authors: Puccini Lucrezia , Fantini Michela , Biagetti Carlo , Angelini Raffaella , Dirani Giorgio , Grumiro Laura , Schiavone Pasqua , Sparacino Monica , Semprini Simona , Sambri Vittorio , Cricca Monica
Published: March 2023

Introduction

One of the major criticisms facing the research community during SARS-CoV2 pandemic was the lack of large-scale, longitudinal data on the efficacy of the SARS-CoV2 mRNA vaccines. Currently, even if COVID-19 antiviral treatments have been authorized by European Medicine Agency, prevention through approved specific vaccines is the best approach available in order to contain the ongoing pandemic.

Objectives

Here, we studied the antibody kinetic over a one-year period from vaccination with the Pfizer-BioNTech (Pfizer) vaccines and subsequent boosting with either the BioNTech or Moderna (Spikevax) vaccines in a large cohort of 8,071 healthcare workers (HCW). We also described the impact of SARS-CoV2 infection on antibody kinetic over the same period.

Methods

We assessed the anti SARS-CoV2 Spike IgG antibody kinetic by the high throughput dried blood spot (DBS) collection method and the GSP®/DELFIA® Anti-SARS-CoV2 IgG assay (PerkinElmer®).

Results

Our data support existing models showing that SARS-CoV2 vaccination elicits strong initial antibodies responses that decline with time but are transitorily increased by administering a vaccine booster. We also showed that using heterologous vaccine/booster combinations a stronger antibody response was elicited than utilizing a booster from the same vaccine manufacturer. Furthermore, by considering the impact of SARS-CoV2 infection occurrence in proximity to the scheduled booster administration, we confirmed that booster dose did not contribute significantly to elicit higher antibody responses.

Conclusion

DBS sampling in our large population of HCWs was fundamental to collect a large number of specimens and to clarify the effective mRNA vaccine-induced antibody kinetic and the role of both heterologous boosters and SARS-CoV2 infection in modulating antibody responses.
Expression profile of microRNAs related with viral infectivity, inflammatory response, and immune activation in people living with HIV
Authors: Cuesta-Sancho Sara , Márquez-Ruiz Denisse , Illanes-Álvarez Francisco , Campaña-Gómez Irene , Martín-Aspas Andrés , Trujillo-Soto María Teresa , Romero Alberto , Galán Fátima , Rodríguez-Iglesias Manuel , Márquez-Coello Mercedes , Girón-González José-Antonio
Published: March 2023

Objective

To evaluate the serum expression of microRNAs (miRNAs) with ability to modulate the human immunodeficiency (HIV) replication or inflammatory status in people living with HIV (PLWH).

Methods

Forty healthy controls and two groups of PLWH were evaluated: (a) Group 1 (n = 30), patients with detectable viral load at inclusion, analyzed before receiving antiretroviral therapy (ART) and 12 months after initiating it; (b) Group 2 (n = 55), PLWH with prolonged undetectable viral load. Intestinal barrier disruption (I-FABP) and bacterial translocation (16S rDNA) markers, inflammatory markers such as interleukin (IL)-6 and sCD163, immune activation and expression of specific miRNAs were evaluated.

Results

Serum concentrations of I-FABP, 16S rDNA, IL-6, sCD163 and activated T lymphocytes were increased in PLWH. Serum miR-34a was overexpressed at inclusion and remained elevated after ART. The expression of the remaining miRNAs that modulate HIV infectivity (miR-7, mir-29a, miR-150, and miR-223) was similar in PLWH and controls. Related to miRNAs implicated in inflammation (miR-21, miR-155, and miR-210), significant overexpression were observed in miR-21 and miR-210 levels in untreated PLWH, but levels were restored in those patients treated for a long period.

Conclusion

A sustained overexpression of miR-34a was detected even after prolonged HIV controlled replication. miR-21 and miR-210 can be considered new markers of inflammation with high sensitivity to its modifications.
The cyclic peptide G4CP2 enables the modulation of galactose metabolism in yeast by interfering with GAL4 transcriptional activity
Authors: Rosa Stefano , Tagliani Andrea , Bertaso Chiara , Tadini Luca , Visentin Cristina , Gourlay Louise Jane , Pricl Sabrina , Feni Lucia , Pellegrino Sara , Pesaresi Paolo , Masiero Simona
Published: March 2023

Genetically-encoded combinatorial peptide libraries are convenient tools to identify peptides to be used as therapeutics, antimicrobials and functional synthetic biology modules. Here, we report the identification and characterization of a cyclic peptide, G4CP2, that interferes with the GAL4 protein, a transcription factor responsible for the activation of galactose catabolism in yeast and widely exploited in molecular biology. G4CP2 was identified by screening CYCLIC, a Yeast Two-Hybrid-based combinatorial library of cyclic peptides developed in our laboratory. G4CP2 interferes with GAL4-mediated activation of galactose metabolic enzymes both when expressed intracellularly, as a recombinant peptide, and when provided exogenously, as a chemically-synthesized cyclic peptide. Our results support the application of G4CP2 in microbial biotechnology and, additionally, demonstrate that CYCLIC can be used as a tool for the rapid identification of peptides, virtually without any limitations with respect to the target protein. The possible biotechnological applications of cyclic peptides are also discussed.
Effect of acupuncture on neuroinflammation in animal models of Alzheimer’s disease: A preclinical systematic review and meta-analysis
Authors: Wu Zhi-Guo , Huang Ying-Jie , Wang Tun-Yi , Deng Chu-Yu , Xu Zhi-Rui , Tang Chun-Zhi
Published: March 2023

Background

Despite neuroinflammation being an important component of the pathology of Alzheimer’s disease (AD), effective therapies to alleviate neuroinflammation are still lacking. Many animal experiments in AD have found that acupuncture may ameliorate cognition by decreasing neuroinflammation and modulating cytokines, but its effects have not been systematically examined. We aimed to assess its efficacy on neuroinflammation in AD and to investigate the potential mechanisms.

Materials and methods

The following databases were searched from inception until 24 August 2022: Web of Science, EMBASE, PubMed, the Cochrane Library, and China National Knowledge Infrastructure. Animal studies that reported the efficacy of acupuncture on neuroinflammation in AD were included. The SYRCLE Robt was utilized to evaluate methodological quality. Stata 17 was utilized to conduct a meta-analysis of cytokine levels and the results of the Morris water maze.

Results

23 studies were included, with a total of 417 rats/mice. The overall quality of all included reports was medium. The results indicated that acupuncture significantly reduced the expressions of pro-inflammatory cytokines which included IL-1β [SMD = −3.50, 95% CI (−4.31, −2.69); I2 = 78.6%] (P < 0.05), TNF-α [SMD = −3.05, 95% CI (−3.86, −2.24); I2 = 69.6%] (P < 0.05), IL-6 [SMD = −3.22, 95% CI (−4.62, −1.81); I2 = 77.6%] and enhanced the expressions of anti-inflammatory cytokines including IL-4 [SMD = 2.77, 95% CI (1.95, 3.59); I2 = 33.9%] (P < 0.05), IL-10 [SMD = 1.84, 95% CI (1.20, 2.49); I2 = 41.0%] (P < 0.05) in an animal model of AD. Regarding the Morris water maze, compared to the control group, the acupuncture group showed a shorter escape latency [SMD = −2.23, 95% CI (−2.89, −1.57); I2 = 79.2%] (P < 0.05), longer duration in platform quadrant [SMD = 2.34, 95% CI (1.44, 3.23); I2 = 81.7%] (P < 0.05), and increased platform crossing number [SMD = 2.79, 95% CI (2.06, 3.53); I2 = 71.9%] (P < 0.05).

Conclusion

Acupuncture may reduce neuroinflammation in AD by modulating cytokine expression. This modulation significantly improved cognitive function in animal models of AD.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354878.
Importance of high-quality evidence regarding the use of Bacopa monnieri in dementia
Authors: Agarwal Ayush , Mishra Biswamohan , Gupta Anu , Srivastava M. Vasantha Padma , Basheer Aneesh , Sharma Jyoti , Vishnu Venugopalan Y.
Published: March 2023

Background

Bacopa monnieri (BM), a commonly used herb, has shown neuroprotective effects in animal and in vitro studies; but human studies on patients with Alzheimer’s Disease (AD) have been inconclusive. Further high-quality trials are required to conclusively state the utility of BM in AD and other neurodegenerative dementias.

Methods

In the present study, we did a narrative review of the current challenges in designing clinical trials of BM in dementia and their evidence-based recommendations.

Results

Many facets of the BM trials need improvement, especially effect size and sample size estimation. Current assessment and outcomes measures need a more holistic approach and newer scales for diagnosing and monitoring prodromal AD. The stringent guidelines in CONSORT and STROBE are often considered difficult to implement for clinical trials in ayurvedic medications like BM. However, adherence to these guidelines will undoubtedly improve the quality of evidence and go a long way in assessing whether BM is efficacious in treating AD/prodromal AD patients and other neurodegenerative dementias.

Conclusion

Future studies on BM should implement more randomized controlled trials (RCTs) with an appropriate sample size of accurately diagnosed AD/prodromal AD patients, administering a recommended dosage of BM and for a pre-specified time calculated to achieve adequate power for the study. Researchers should also develop and validate more sensitive cognitive scales, especially for prodromal AD. BM should be evaluated in accordance with the same rigorous standards as conventional drugs to generate the best quality evidence.
Regulation of microglia function by neural stem cells
Authors: de Almeida Monique M. A. , Goodkey Kara , Voronova Anastassia
Published: March 2023

Neural stem and precursor cells (NPCs) build and regenerate the central nervous system (CNS) by maintaining their pool (self-renewal) and differentiating into neurons, astrocytes, and oligodendrocytes (multipotency) throughout life. This has inspired research into pro-regenerative therapies that utilize transplantation of exogenous NPCs or recruitment of endogenous adult NPCs for CNS regeneration and repair. Recent advances in single-cell RNA sequencing and other “omics” have revealed that NPCs express not just traditional progenitor-related genes, but also genes involved in immune function. Here, we review how NPCs exert immunomodulatory function by regulating the biology of microglia, immune cells that are present in NPC niches and throughout the CNS. We discuss the role of transplanted and endogenous NPCs in regulating microglia fates, such as survival, proliferation, migration, phagocytosis and activation, in the developing, injured and degenerating CNS. We also provide a literature review on NPC-specific mediators that are responsible for modulating microglia biology. Our review highlights the immunomodulatory properties of NPCs and the significance of these findings in the context of designing pro-regenerative therapies for degenerating and diseased CNS.
Can non-swallowing function assessment predict nasogastric tube removal in patients with poststroke dysphagia? A clinical study
Authors: Li Bingjie , Zhang Tong , Zhao Jun , Li Pengkun , Wu Zhangwei , Zhao Shengjie
Published: March 2023

Objective

This study aimed to predict nasogastric tube (NGT) removal in patients with poststroke dysphagia (PSD) by non-swallowing function assessment.

Methods

We enrolled 232 eligible patients and performed rehabilitation. The Fugl-Meyer assessment motor (FMM) and National Institute of Health Stroke Scale (NIHSS) scores were used to measure the motor and overall nervous system functions. Predictors for NGT removal in patients with PSD after rehabilitation were analyzed.

Results

Of the 232 included patients, the NGTs were removed from 78% of them, while 22% were dependent on a feeding tube after 4 weeks of rehabilitation. Compared to the preserved NGT group, older age, a higher rate of intubation or tracheostomy, and more severe baseline functions were found in the NGT removal group. Age [odds ratio (OR) = 0.907; 95% confidence interval (CI): 0.859–0.957; p = 0.000], difference in the FMM score after 4 weeks of rehabilitation (OR = 1.219; 95% CI: 1.145–1.299; p = 0.00), and item 9 of NIHSS (OR = 0.488; 95% CI: 0.252–0.946; p = 0.034) were predictors of NGT removal after rehabilitation.

Conclusion

We established a predictive model in patients with PSD using a non-swallowing assessment, which enabled us to predict swallowing recovery based on the non-swallowing function.
Dynamic Effective Connectivity using Physiologically informed Dynamic Causal Model with Recurrent Units: A functional Magnetic Resonance Imaging simulation study
Authors: Nag Sayan , Uludag Kamil
Published: March 2023

Functional MRI (fMRI) is an indirect reflection of neuronal activity. Using generative biophysical model of fMRI data such as Dynamic Causal Model (DCM), the underlying neuronal activities of different brain areas and their causal interactions (i.e., effective connectivity) can be calculated. Most DCM studies typically consider the effective connectivity to be static for a cognitive task within an experimental run. However, changes in experimental conditions during complex tasks such as movie-watching might result in temporal variations in the connectivity strengths. In this fMRI simulation study, we leverage state-of-the-art Physiologically informed DCM (P-DCM) along with a recurrent window approach and discretization of the equations to infer the underlying neuronal dynamics and concurrently the dynamic (time-varying) effective connectivities between various brain regions for task-based fMRI. Results from simulation studies on 3- and 10-region models showed that functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) responses and effective connectivity time-courses can be accurately predicted and distinguished from faulty graphical connectivity models representing cognitive hypotheses. In summary, we propose and validate a novel approach to determine dynamic effective connectivity between brain areas during complex cognitive tasks by combining P-DCM with recurrent units.
Demographic, clinical and biochemical correlates of the length of stay for different polarities in Chinese inpatients with bipolar disorder: A real-world study
Authors: Wang Wei , Du Jing , Li Sheng , Xie Gaoming , Xu Jinjie , Ren Yanping
Published: March 2023

Introduction: Many patients with bipolar disorder (BD) need hospitalization, while the number of hospital beds for these patients is limited. Managing the length of stay (LOS) is an effective solution to this issue. Research on LOS and its influencing factors in BD is limited in China. This study aimed to identify the factors relevant to LOS in different polarities in Chinese patients with BD.

Method: This was a real-world, cross-sectional study. Data were obtained from the electronic medical record system. Patients admitted to Beijing Anding Hospital between Jan 2014 and Dec 2017 and diagnosed with BD were included. Demographic information, clinical characteristics, and biochemical variables were collected. Patients were classified into short and long LOS groups based on a cutoff value. A univariate study and a multivariate logistic regression analysis were performed to identify variables related to LOS in various BD polarities. The receiver operating characteristic (ROC) analysis was utilized to evaluate the discrimination accuracy of the regression model.

Result: Four thousand six hundred and seventy-five visits from 4,451 individuals were included in the analysis. For the whole sample, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). There was an additive interaction between a family history of mental disorders and polarities (p < 0.05). For manic episodes, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). For depressive episodes, psychotic features and high-density lipoprotein cholesterol (HDLC) levels were positively associated with long LOS (all p < 0.05). For mixed states, unmarried status was positively associated with long LOS, while low-density lipoprotein cholesterol (LDLC) levels were negatively associated with LOS (all p < 0.05). The area under the curve (AUC) values for depressive episodes, manic episodes, and mixed states in the combined model were 0.587, 0.553, and 0.619, respectively (all p < 0.05).

Discussion: The findings suggested that LOS correlates differed by polarity, with marital status, psychotic features, a family history of mental disorders, and lipid levels strongly linked with LOS in patients with BD.
Experiment protocols for brain-body imaging of locomotion: A systematic review
Authors: Korivand Soroush , Jalili Nader , Gong Jiaqi
Published: March 2023

Introduction

Human locomotion is affected by several factors, such as growth and aging, health conditions, and physical activity levels for maintaining overall health and well-being. Notably, impaired locomotion is a prevalent cause of disability, significantly impacting the quality of life of individuals. The uniqueness and high prevalence of human locomotion have led to a surge of research to develop experimental protocols for studying the brain substrates, muscle responses, and motion signatures associated with locomotion. However, from a technical perspective, reproducing locomotion experiments has been challenging due to the lack of standardized protocols and benchmarking tools, which impairs the evaluation of research quality and the validation of previous findings.

Methods

This paper addresses the challenges by conducting a systematic review of existing neuroimaging studies on human locomotion, focusing on the settings of experimental protocols, such as locomotion intensity, duration, distance, adopted brain imaging technologies, and corresponding brain activation patterns. Also, this study provides practical recommendations for future experiment protocols.

Results

The findings indicate that EEG is the preferred neuroimaging sensor for detecting brain activity patterns, compared to fMRI, fNIRS, and PET. Walking is the most studied human locomotion task, likely due to its fundamental nature and status as a reference task. In contrast, running has received little attention in research. Additionally, cycling on an ergometer at a speed of 60 rpm using fNIRS has provided some research basis. Dual-task walking tasks are typically used to observe changes in cognitive function. Moreover, research on locomotion has primarily focused on healthy individuals, as this is the scenario most closely resembling free-living activity in real-world environments.

Discussion

Finally, the paper outlines the standards and recommendations for setting up future experiment protocols based on the review findings. It discusses the impact of neurological and musculoskeletal factors, as well as the cognitive and locomotive demands, on the experiment design. It also considers the limitations imposed by the sensing techniques used, including the acceptable level of motion artifacts in brain-body imaging experiments and the effects of spatial and temporal resolutions on brain sensor performance. Additionally, various experiment protocol constraints that need to be addressed and analyzed are explained.
Post-stroke cognitive impairment and synaptic plasticity: A review about the mechanisms and Chinese herbal drugs strategies
Authors: Chi Xiansu , Wang Liuding , Liu Hongxi , Zhang Yunling , Shen Wei
Published: March 2023

Post-stroke cognitive impairment, is a major complication of stroke, characterized by cognitive dysfunction, which directly affects the quality of life. Post-stroke cognitive impairment highlights the causal relationship between stroke and cognitive impairment. The pathological damage of stroke, including the increased release of excitatory amino acids, oxidative stress, inflammatory responses, apoptosis, changed neurotrophic factor levels and gene expression, influence synaptic plasticity. Synaptic plasticity refers to the activity-dependent changes in the strength of synaptic connections and efficiency of synaptic transmission at pre-existing synapses and can be divided into structural synaptic plasticity and functional synaptic plasticity. Changes in synaptic plasticity have been proven to play important roles in the occurrence and treatment of post-stroke cognitive impairment. Evidence has indicated that Chinese herbal drugs have effect of treating post-stroke cognitive impairment. In this review, we overview the influence of pathological damage of stroke on synaptic plasticity, analyze the changes of synaptic plasticity in post-stroke cognitive impairment, and summarize the commonly used Chinese herbal drugs whose active ingredient or extracts can regulate synaptic plasticity. This review will summarize the relationship between post-stroke cognitive impairment and synaptic plasticity, provide new ideas for future exploration of the mechanism of post-stroke cognitive impairment, compile evidence of applying Chinese herbal drugs to treat post-stroke cognitive impairment and lay a foundation for the development of novel formulas for treating post-stroke cognitive impairment.
Nutritional evaluation of some potential wild edible plants of North Eastern region of India
Authors: Talang Hammylliende , Yanthan Aabon , Rathi Ranbir Singh , Pradheep Kanakasabapathi , Longkumer Soyimchiten , Imsong Bendangla , Singh Laishram Hemanta , Assumi Ruth S. , Devi M. Bilashini , Vanlalruati  , Kumar Ashok , Ahlawat Sudhir Pal , Bhatt Kailash C. , Bhardwaj Rakesh
Published: March 2023

Introduction

India’s north-eastern hill region (NEH) is one of the biodiversity hotspots, inhabited by several tribal communities still maintaining their traditional food habits. Much of their food resources are drawn from wild sources.

Materials and methods

Fourteen species of wild edible plants of high ethnic importance were collected from remote localities of Nagaland and Meghalaya states of the NEH region of India for nutritional profiling. Nutritional profiling of leaves of six species comprising Gynura cusimbua, Garcinia cowa, Herpetospermum operculatum, Plukenetia corniculata, Trichodesma khasianum, and Elatostemma sessile is conducted first time under present study. Samples were analyzed as per the Official Method of Analysis (AOAC) and standard methods.

Results and discussion

The range of variation in proximate composition was observed for moisture (72–92%), protein (1.71–6.66%), fat (0.22–1.36%), dietary fibre (5.16–14.58%), sugar (0.30–3.41%), and starch (0.07–2.14%). The highest protein content (6.66%) was recorded in Herpetospermum operculatum, followed by Trichodesma khasianum (5.89%) and Plukenetia corniculata (5.27%). Incidentally, two of these also have high iron (>7.0 mg/100 g) and high zinc (>2.0 mg/100 g) contents, except Trichodesma khasianum, which has low zinc content. High antioxidant activities in terms of gallic acid equivalent (GAE) by the cupric ion reducing antioxidant capacity (CUPRAC) method ranged from 1.10 to 8.40 mg/100 g, and by the Fluorescence recovery after photobleaching (FRAP) method ranged from 0.10 to 1.9 mg/100 g, while phenol content ranged between 0.30 and 6.00 mg/100 g. These wild vegetables have high potential because of their nutritional properties and are fully capable of enhancing sustainability and improving ecosystem services. Efforts were also initiated to mainstream these resources, mainly for widening the food basket of native peoples.