bluuebunny/crossref_metadata_2025 huggingface dataset:
TLR7/TLR8 activation and susceptibility genes synergize to breach gut barrier in a mouse model of lupus
Authors: Ma Longhuan , Terrell Morgan , Brown Josephine , Castellanos Garcia Abigail , Elshikha Ahmed , Morel Laurence
Published: July 2023

Background

Mounting evidence suggests that increased gut permeability, or leaky gut, and the resulting translocation of pathobionts or their metabolites contributes to the pathogenesis of Systemic Lupus Erythematosus. However, the mechanisms underlying the induction of gut leakage remain unclear. In this study, we examined the effect of a treatment with a TLR7/8 agonist in the B6.Sle1.Sle2.Sle3 triple congenic (TC) mouse, a spontaneous mouse model of lupus without gut leakage.

Materials and methods

Lupus-prone mice (TC), TC.Rag1-/- mice that lack B and T cells, and congenic B6 healthy controls were treated with R848. Gut barrier integrity was assessed by measuring FITC-dextran in the serum following oral gavage. Claudin-1 and PECAM1 expression as well as the extent of CD45+ immune cells, B220+ B cells, CD3+ T cells and CD11b+ myeloid cells were measured in the ileum by immunofluorescence. NKp46+ cells were measured in the ileum and colon by immunofluorescence. Immune cells in the ileum were also analyzed by flow cytometry.

Results

R848 decreased gut barrier integrity in TC but not in congenic control B6 mice. Immunofluorescence staining of the ileum showed a reduced expression of the tight junction protein Claudin-1, endothelial cell tight junction PECAM1, as well as an increased infiltration of immune cells, including B cells and CD11b+ cells, in R848-treated TC as compared to untreated control mice. However, NKp46+ cells which play critical role in maintaining gut barrier integrity, had a lower frequency in treated TC mice. Flow cytometry showed an increased frequency of plasma cells, dendritic cells and macrophages along with a decreased frequency of NK cells in R848 treated TC mice lamina propria. In addition, we showed that the R848 treatment did not induce gut leakage in TC.Rag1-/- mice that lack mature T and B cells.

Conclusions

These results demonstrate that TLR7/8 activation induces a leaky gut in lupus-prone mice, which is mediated by adaptive immune responses. TLR7/8 activation is however not sufficient to breach gut barrier integrity in non-autoimmune mice.
Network proteomic analysis identifies inter-alpha-trypsin inhibitor heavy chain 4 during early human Achilles tendon healing as a prognostic biomarker of good long-term outcomes
Authors: Wu Xinjie , Chen Junyu , Sun Wei , Hart David A. , Ackermann Paul W. , Ahmed Aisha S.
Published: July 2023

The suboptimal or protracted regeneration of injured connective tissues often results in significant dysfunction, pain, and functional disability. Despite the prevalence of the condition, few studies have been conducted which focused on biomarkers or key molecules involved in processes governing healing outcomes. To gain insight into injured connective tissue repair, and using the Achilles tendon as a model system, we utilized quantitative proteomic and weighted co-expression network analysis of tissues acquired from Achilles tendon rupture (ATR) patients with different outcomes at 1-year postoperatively. Two modules were detected to be associated with prognosis. The initial analysis identified inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) as a biomarker or hub protein positively associated with better healing outcomes. Additional analysis identified the beneficial role of ITIH4 in inflammation, cell viability, apoptosis, proliferation, wound healing, and for the synthesis of type I collagen in cultured fibroblasts. Functionally, the effects of ITIH4 were found to be mediated by peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathways. Taken together, these findings suggest that ITIH4 plays an important role in processes of connective tissue repair and advocate for the potential of ITIH4 as a therapeutic target for injured connective tissue repair.

Trial registration

http://clinicaltrials.gov, identifiers NCT02318472, NCT01317160.
The potential of activator protein 1 (AP-1) in cancer targeted therapy
Authors: Song Dandan , Lian Yan , Zhang Lin
Published: July 2023

Activator protein-1 (AP-1) is a transcription factor that consists of a diverse group of members including Jun, Fos, Maf, and ATF. AP-1 involves a number of processes such as proliferation, migration, and invasion in cells. Dysfunctional AP-1 activity is associated with cancer initiation, development, invasion, migration and drug resistance. Therefore, AP-1 is a potential target for cancer targeted therapy. Currently, some small molecule inhibitors targeting AP-1 have been developed and tested, showing some anticancer effects. However, AP-1 is complex and diverse in its structure and function, and different dimers may play different roles in different type of cancers. Therefore, more research is needed to reveal the specific mechanisms of AP-1 in cancer, and how to select appropriate inhibitors and treatment strategies. Ultimately, this review summarizes the potential of combination therapy for cancer.
Productive arts engagement at the Tokyo Fuji Art Museum and its health effects on the older Japanese population: results of a randomized controlled trial
Authors: Hayashi Yoko , Matskiv Jacqueline , Galery Kevin , Beauchet Olivier
Published: July 2023

Background

This randomized controlled trial aims to compare changes in mental and physical health in older Japanese community-dwellers who participated in a productive art-based activity at the Tokyo Fuji Art Museum (intervention group) and in their counterparts, who did not participate in the intervention (control group).

Methods

A total of 73 older community-dwellers living in Tokyo participated in a single-blind RCT in two parallel groups (intervention group versus control group). The intervention was 2 h of productive art-based activities per week. The weekly sessions were carried out at the Tokyo Fuji Art Museum over a 12-week period. The control group did not participate in any productive art-based activity over the study period. Well-being, quality of life and frailty were assessed before the first, and after the last, art-based activity. These outcomes were assessed with the same schedule in both groups.

Results

The intervention group saw a significant improvement in their quality of life (p < 0.044) and mixed results on their physical health (i.e., decreased frailty status) when compared to the control group. The comparison of changes in frailty scores between M0 and M3 showed improvement in the intervention group (p = 0.014), but when adjusted for baseline characteristics by linear regressions, revealed only a trend (p = 0.070). No conclusive effect was shown with well-being.

Interpretation

This RCT showed mixed health effects of productive art engagement in older Japanese community-dwellers in Tokyo. Benefits were reported for quality of life and mixed effects were observed for frailty, while no significant effect was found for well-being.

Clinical Trial Registration: Ethic committee of Shobi University, Tokyo (Japan), ref. A-2021-1; Clinical Trial Number NCT03679715.
Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion
Authors: Zheng Sheng-Cai , Huang Zhong-Yin , Zhai Kan , Shi Huan-Zhong , Shao Ming-Ming
Published: July 2023

Background

The simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE.

Methods

We quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-γ) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagnostic performance of these three biomarkers was evaluated using a receiver operating characteristic (ROC) curve of subjects by age and gender.

Results

We discovered that the TPE group had much higher levels of HGF than the non-TPE group, regardless of age or gender, and that there was no statistically significant difference between the two groups’ levels of HGF expression in peripheral plasma. In female TPE patients aged ≤65 years, the AUCs of TPE and non-TPE diagnosed by HGF, ADA or IFN-γ were 0.988, 0.964, and 0.827, respectively. HGF plus ADA had the highest diagnostic efficacy in female TPE patients aged ≤65 years. With HGF plus ADA having a cut-off value of 0.219 for distinguishing TPE from non-TPE, the area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 0.998 (95% confidence interval [CI], 0.993–1.000), 100 (95% CI, 89.997–100.000), 96.667 (95% CI, 82.783–99.916), 97.222 (95% CI, 83.594–99.586), and 100.

Conclusion

This study confirmed that HGF plus ADA has high diagnostic efficacy in younger female TPE patients and has the potential to be an excellent biomarker.
Microbial taxa related to natural hydrogen and methane emissions in serpentinite-hosted hyperalkaline springs of New Caledonia
Authors: Quéméneur Marianne , Mei Nan , Monnin Christophe , Postec Anne , Guasco Sophie , Jeanpert Julie , Maurizot Pierre , Pelletier Bernard , Erauso Gaël
Published: July 2023

The southeastern part of New Caledonia main island (Grande Terre) is the location of a large ophiolitic formation that hosts several hyperalkaline springs discharging high pH (∼11) and warm (<40°C) fluids enriched in methane (CH4) and hydrogen (H2). These waters are produced by the serpentinization of the ultrabasic rock formations. Molecular surveys had previously revealed the prokaryotic diversity of some of these New Caledonian springs, especially from the submarine chimneys of Prony Bay hydrothermal field. Here we investigate the microbial community of hyperalkaline waters from on-land springs and their relationships with elevated concentrations of dissolved H2 (21.1–721.3 μmol/L) and CH4 (153.0–376.6 μmol/L). 16S rRNA gene analyses (metabarcoding and qPCR) provided evidence of abundant and diverse prokaryotic communities inhabiting hyperalkaline fluids at all the collected springs. The abundance of prokaryotes was positively correlated to the H2/CH4 ratio. Prokaryotes consisted mainly of bacteria that use H2 as an energy source, such as microaerophilic Hydrogenophaga/Serpentinimonas (detected in all sources on land) or anaerobic sulfate-reducing Desulfonatronum, which were exclusively found in the most reducing (Eh ref H2 ∼ -700 mV) and the most H2-enriched waters discharging at the intertidal spring of the Bain des Japonais. The relative abundance of a specific group of uncultured Methanosarcinales that thrive in serpentinization-driven ecosystems emitting H2, considered potential H2-consuming methanogens, was positively correlated with CH4 concentrations, and negatively correlated to the relative abundance of methylotrophic Gammaproteobacteria. Firmicutes were also numerous in hyperalkaline waters, and their relative abundance (e.g., Gracilibacter or Dethiobacter) was proportional to the dissolved H2 concentrations, but their role in the H2 budget remains to be assessed. The prokaryotic communities thriving in New Caledonia hyperalkaline waters are similar to those found in other serpentinite-hosted high-pH waters worldwide, such as Lost City (North Atlantic) and The Cedars (California).
Essential oil-grafted copper nanoparticles as a potential next-generation fungicide for holistic disease management in maize
Authors: Dorjee Lham , Gogoi Robin , Kamil Deeba , Kumar Rajesh , Mondal Tapan Kumar , Pattanayak Sudeepta , Gurung Bishal
Published: July 2023

Sustainable food production is necessary to meet the demand of the incessantly growing human population. Phytopathogens pose a major constraint in food production, and the use of conventional fungicides to manage them is under the purview of criticism due to their numerous setbacks. In the present study, essential oil-grafted copper nanoparticles (EGC) were generated, characterized, and evaluated against the maize fungal pathogens, viz., Bipolaris maydis, Rhizoctonia solani f. sp. sasakii, Macrophomina phaseolina, Fusarium verticillioides, and Sclerotium rolfsii. The ED50 for the fungi under study ranged from 43 to 56 μg ml−1, and a significant inhibition was observed at a low dose of 20 μg ml−1 under in vitro conditions. Under net house conditions, seed treatment + foliar spray at 250 and 500 mg L−1 of EGC performed remarkably against maydis leaf blight (MLB), with reduced percent disease index (PDI) by 27.116 and 25.292%, respectively, in two Kharif seasons (May-Sep, 2021, 2022). The activity of enzymatic antioxidants, viz., β-1, 3-glucanase, PAL, POX, and PPO, and a non-enzymatic antioxidant (total phenolics) was increased in treated maize plants, indicating host defense was triggered. The optimum concentrations of EGC (250 mg L−1 and 500 mg L−1) exhibited improved physiological characteristics such as photosynthetic activity, shoot biomass, plant height, germination percentage, vigor index, and root system traits. However, higher concentrations of 1,000 mg L−1 rendered phytotoxicity, reducing growth, biomass, and copper bioaccumulation to high toxic levels, mainly in the foliar-sprayed maize leaves. In addition, EGC and copper nanoparticles (CuNPs) at 1,000 mg L−1 reduced the absorption and concentration of manganese and zinc indicating a negative correlation between Cu and Mn/Zn. Our study proposes that the CuNPs combined with EO (Clove oil) exhibit astounding synergistic efficacy against maize fungal pathogens and optimized concentrations can be used as an alternative to commercial fungicides without any serious impact on environmental health.
Impact of the gut-lung axis on tuberculosis susceptibility and progression
Authors: Enjeti Aditya , Sathkumara Harindra Darshana , Kupz Andreas
Published: July 2023

Tuberculosis (TB) has remained at the forefront of the global infectious disease burden for centuries. Concerted global efforts to eliminate TB have been hindered by the complexity of Mycobacterium tuberculosis (Mtb), the emergence of antibiotic resistant Mtb strains and the recent impact of the ongoing pandemic of coronavirus disease 2019 (COVID19). Examination of the immunomodulatory role of gastrointestinal microbiota presents a new direction for TB research. The gut microbiome is well-established as a critical modulator of early immune development and inflammatory responses in humans. Recent studies in animal models have further substantiated the existence of the ‘gut-lung axis’, where distal gastrointestinal commensals modulate lung immune function. This gut microbiome-lung immune crosstalk is postulated to have an important correlation with the pathophysiology of TB. Further evaluation of this gut immunomodulation in TB may provide a novel avenue for the exploration of therapeutic targets. This mini-review assesses the proposed mechanisms by which the gut-lung axis impacts TB susceptibility and progression. It also examines the impact of current anti-TB therapy on the gut microbiome and the effects of gut dysbiosis on treatment outcomes. Finally, it investigates new therapeutic targets, particularly the use of probiotics in treatment of antibiotic resistant TB and informs future developments in the field.
Automated identification of chalcogen bonds in AlphaFold protein structure database files: is it possible?
Authors: Carugo Oliviero , Djinović-Carugo Kristina
Published: July 2023

Protein structure prediction and structural biology have entered a new era with an artificial intelligence-based approach encoded in the AlphaFold2 and the analogous RoseTTAfold methods. More than 200 million structures have been predicted by AlphaFold2 from their primary sequences and the models as well as the approach itself have naturally been examined from different points of view by experimentalists and bioinformaticians. Here, we assessed the degree to which these computational models can provide information on subtle structural details with potential implications for diverse applications in protein engineering and chemical biology and focused the attention on chalcogen bonds formed by disulphide bridges. We found that only 43% of the chalcogen bonds observed in the experimental structures are present in the computational models, suggesting that the accuracy of the computational models is, in the majority of the cases, insufficient to allow the detection of chalcogen bonds, according to the usual stereochemical criteria. High-resolution experimentally derived structures are therefore still necessary when the structure must be investigated in depth based on fine structural aspects.
Locus specific endogenous retroviral expression associated with Alzheimer’s disease
Authors: Dawson Tyson , Rentia Uzma , Sanford Jessie , Cruchaga Carlos , Kauwe John S. K. , Crandall Keith A.
Published: July 2023

Introduction

Human endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer’s disease.

Methods

We combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer’s disease and 45 healthy controls. We use telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis.

Results

We identify differentially expressed genes and differentially expressed HERVs in Alzheimer’s disease patients. Differentially expressed HERVs are scattered throughout the genome; many of them are members of the HERV-K superfamily. A number of HERVs are correlated with the expression of dysregulated genes in Alzheimer’s and are physically proximal to genes which drive disease pathways.

Discussion

Dysregulated expression of ancient retroviral insertions in the human genome are present in Alzheimer’s disease and show localization patterns that may explain how these elements drive pathogenic gene expression.
Mating-induced prolactin surge is not required for subsequent neurogenesis in male mice
Authors: Smiley Kristina O. , Phillipps Hollian R. , Fang Chenyun , Brown Rosemary S. E. , Grattan David R.
Published: July 2023

Parenting involves major behavioral transitions that are supported by coordinated neuroendocrine and physiological changes to promote the onset of novel offspring-directed behaviors. In comparison to maternal care, however, the mechanisms underlying the transition to paternal care are less understood. Male laboratory mice are predominantly infanticidal as virgins but show paternal responses 2 weeks after mating. Interestingly, males show a mating-induced surge of prolactin, which we hypothesized may be involved in initiating this behavioral transition. During pregnancy, prolactin stimulates olfactory bulb neurogenesis, which is essential for maternal behavior. Mating induces olfactory bulb neurogenesis in males, but it is unknown whether this is driven by prolactin or is important for subsequent paternal care. New olfactory neurons are generated from cells in the subventricular zone (SVZ) and take about 2 weeks to migrate to the olfactory bulb, which may account for the delayed behavioral change in mated males. We investigated whether mating increases cell proliferation at the SVZ. Males were either mated, exposed to receptive female cues, or left alone (control) and injected with Bromodeoxyuridine (BrdU, a marker of cell division). Contrary to our hypothesis, we found that mating decreased cell proliferation in the caudal lateral portion of the SVZ. Next, we tested whether prolactin itself mediates cell proliferation in the SVZ and/or new cell survival in the olfactory bulb by administering bromocriptine (prolactin inhibitor), vehicle, or bromocriptine + prolactin prior to mating. While suppressing prolactin had no effect on cell proliferation in the SVZ, administering exogenous prolactin resulted in significantly higher BrdU-labeled cells in mated but not virgin male mice. No effects of prolactin were observed on new olfactory cell survival. Taken together, prolactin may have context-dependent effects on new cell division in the SVZ, while other unknown mechanisms may be driving the effects on new olfactory cell survival following mating.
A self-learning Monte Carlo tree search algorithm for robot path planning
Authors: Li Wei , Liu Yi , Ma Yan , Xu Kang , Qiu Jiang , Gan Zhongxue
Published: July 2023

This paper proposes a self-learning Monte Carlo tree search algorithm (SL-MCTS), which has the ability to continuously improve its problem-solving ability in single-player scenarios. SL-MCTS combines the MCTS algorithm with a two-branch neural network (PV-Network). The MCTS architecture can balance the search for exploration and exploitation. PV-Network replaces the rollout process of MCTS and predicts the promising search direction and the value of nodes, which increases the MCTS convergence speed and search efficiency. The paper proposes an effective method to assess the trajectory of the current model during the self-learning process by comparing the performance of the current model with that of its best-performing historical model. Additionally, this method can encourage SL-MCTS to generate optimal solutions during the self-learning process. We evaluate the performance of SL-MCTS on the robot path planning scenario. The experimental results show that the performance of SL-MCTS is far superior to the traditional MCTS and single-player MCTS algorithms in terms of path quality and time consumption, especially its time consumption is half less than that of the traditional MCTS algorithms. SL-MCTS also performs comparably to other iterative-based search algorithms designed specifically for path planning tasks.
Prospective collection of blood plasma samples to identify potential biomarkers for the prehospital stroke diagnosis (ProGrEss-Bio): study protocol for a multicenter prospective observational study
Authors: Geisler Frederik , Haacke Lisa , Lorenz Maren , Schwabauer Eugen , Wendt Matthias , Bernhardt Lydia , Dashti Eman , Freitag Erik , Kunz Alexander , Hofmann-Shen Christina , Zuber Martina , Waldschmidt Carolin , Kandil Farid I. , Kappert Kai , Dang-Heine Chantip , Lorenz-Meyer Irina , Audebert Heinrich J. , Weber Joachim E.
Published: July 2023

Introduction

Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are well-established, evidence-based, time-critical therapies that reduce morbidity and mortality in acute ischemic stroke (AIS) patients. The exclusion of intracerebral hemorrhage (ICH) is mandatory and has been performed by cerebral imaging to date. Mobile stroke units (MSUs) have been shown to improve functional outcomes by bringing cerebral imaging and IVT directly to the patient, but they have limited coverage. Blood biomarkers clearly distinguishing between AIS, ICH, and stroke mimics (SM) could provide an alternative to cerebral imaging if concentration changes are detectable in the hyperacute phase after stroke with high diagnostic accuracy. In this study, we will take blood samples in a prehospital setting to evaluate potential biomarkers. The study was registered in the German Clinical Trials Register (https://drks.de/search/de) with the identifier DRKS00023063.

Methods and analysis

We plan a prospective, observational study involving 300 patients with suspected stroke and symptom onset of ≤4.5 h before the collection of biomarkers. Study participants will be recruited from three sites in Berlin, Germany during MSU deployments. The focus of the study is the collection of blood samples from participants at the prehospital scene and from participants with AIS or ICH at a second-time point. All samples will be analyzed using targeted and untargeted analytical approaches. Study-related information about participants, including medical information and discharge diagnoses from the subsequent treating hospital, will be collected and documented in an electronic case report form (eCRF).

Discussion

This study will evaluate whether a single blood biomarker or a combination of biomarkers can distinguish patients with AIS and ICH from patients with stroke and SM in the early phase after symptom onset in the prehospital setting. In addition, the kinetics of blood biomarkers in AIS and ICH patients will be investigated. Our goal is to evaluate new ways to reliably diagnose stroke in the prehospital setting and thus accelerate the application of evidence-based therapies to stroke patients.
The vascular role of CGRP: a systematic review of human studies
Authors: Al-Karagholi Mohammad Al-Mahdi , Kalatharan Veberka , Fagerberg Peter Schunck , Amin Faisal Mohammad
Published: July 2023

Intravenous infusion of human alpha calcitonin gene-related peptide (h-α-CGRP) has been applied to explore migraine pathogenesis and cerebral hemodynamics during the past three decades. Cumulative data implicate h-α-CGRP in regulating the vascular tone. In this systematic review, we searched PubMed and EMBASE for clinical studies investigating the vascular changes upon intravenous infusion of h-α-CGRP in humans. A total of 386 studies were screened by title and abstract. Of these, 11 studies with 61 healthy participants and 177 participants diagnosed with migraine were included. Several studies reported hemodynamic effects including flushing, palpitation, warm sensation, heart rate (HR), mean arterial blood pressure (MABP), mean blood flow velocity of middle cerebral artery (mean VMCA), and diameter of superficial temporal artery (STA). Upon the start of h-α-CGRP infusion, 163 of 165 (99%) participants had flushing, 98 of 155 (63%) participants reported palpitation, and 160 of 165 (97%) participants reported warm sensation. HR increased with 14%–58% and MABP decreased with 7%–12%. The mean VMCA was decreased with 9.5%–21%, and the diameter of the STA was dilated with 41%–43%. The vascular changes lasted from 20 to >120 min. Intravenous infusion of h-α-CGRP caused a universal vasodilation without any serious adverse events. The involvement of CGRP in the systemic hemodynamic raises concerns regarding long-term blockade of CGRP in migraine patients with and without cardiovascular complications.
Reflecting on what is “skill” in human motor skill learning
Authors: Yadav Goldy , Duque Julie
Published: July 2023

Humans have an exceptional ability to execute a variety of skilled movements. Researchers have been long interested in understanding behavioral and neurophysiological basis of human motor skill learning for advancing both fundamental neuroscientific knowledge and clinical outcomes. However, despite decades of work in this field there is a lack of consensus about what is meant by “skill” in skill learning. With an advent of various task paradigms testing human motor behavior and increasing heterogeneity in motor learning assessments methods, it is very crucial to identify key features of skill in order to avoid any ambiguity that may result in misinterpretation or over-generalization of findings, which could have serious implications for replication and translational research. In this review, we attempt to highlight the features of skill following a historical approach, considering the seminal work that led to the first definitions of skill and including some contemporary concepts emerging from human motor learning research. Overall, based on this literature, we emphasize that skill has some fundamental characteristics, such as- (i) optimal movement selection and execution, (ii) improved movement speed and accuracy, and (iii) reduced movement variability and error. These features of skill can emerge as a consequence of extensive practice/training/learning, thus resulting in an improved performance state beyond baseline levels. Finally we provide some examples of model tasks that can appropriately capture these features of skill, and conclude that any neuroscientific endeavor aimed at understanding the essence of skill in human motor skill learning should focus on these aspects.
Hand-worn devices for assessment and rehabilitation of motor function and their potential use in BCI protocols: a review
Authors: Bates Madison , Sunderam Sridhar
Published: July 2023

Introduction

Various neurological conditions can impair hand function. Affected individuals cannot fully participate in activities of daily living due to the lack of fine motor control. Neurorehabilitation emphasizes repetitive movement and subjective clinical assessments that require clinical experience to administer.

Methods

Here, we perform a review of literature focused on the use of hand-worn devices for rehabilitation and assessment of hand function. We paid particular attention to protocols that involve brain-computer interfaces (BCIs) since BCIs are gaining ground as a means for detecting volitional signals as the basis for interactive motor training protocols to augment recovery. All devices reviewed either monitor, assist, stimulate, or support hand and finger movement.

Results

A majority of studies reviewed here test or validate devices through clinical trials, especially for stroke. Even though sensor gloves are the most commonly employed type of device in this domain, they have certain limitations. Many such gloves use bend or inertial sensors to monitor the movement of individual digits, but few monitor both movement and applied pressure. The use of such devices in BCI protocols is also uncommon.

Discussion

We conclude that hand-worn devices that monitor both flexion and grip will benefit both clinical diagnostic assessment of function during treatment and closed-loop BCI protocols aimed at rehabilitation.
Investigating the lateralisation of experimentally induced auditory verbal hallucinations
Authors: Mak Olivia , Couth Samuel , Plack Christopher J. , Kotz Sonja A. , Yao Bo
Published: July 2023

Introduction

Auditory verbal hallucinations (AVHs), or hearing non-existent voices, are a common symptom in psychosis. Recent research suggests that AVHs are also experienced by neurotypical individuals. Individuals with schizophrenia experiencing AVHs and neurotypicals who are highly prone to hallucinate both produce false positive responses in auditory signal detection. These findings suggest that voice-hearing may lie on a continuum with similar mechanisms underlying AVHs in both populations.

Methods

The current study used a monaural auditory stimulus in a signal detection task to test to what extent experimentally induced verbal hallucinations are (1) left-lateralised (i.e., more likely to occur when presented to the right ear compared to the left ear due to the left-hemisphere dominance for language processing), and (2) predicted by self-reported hallucination proneness and auditory imagery tendencies. In a conditioning task, fifty neurotypical participants associated a negative word on-screen with the same word being played via headphones through successive simultaneous audio-visual presentations. A signal detection task followed where participants were presented with a target word on-screen and indicated whether they heard the word being played concurrently amongst white noise.

Results

Results showed that Pavlovian audio-visual conditioning reliably elicited a significant number of false positives (FPs). However, FP rates, perceptual sensitivities, and response biases did not differ between either ear. They were neither predicted by hallucination proneness nor auditory imagery.

Discussion

The results show that experimentally induced FPs in neurotypicals are not left-lateralised, adding further weight to the argument that lateralisation may not be a defining feature of hallucinations in clinical or non-clinical populations. The findings also support the idea that AVHs may be a continuous phenomenon that varies in severity and frequency across the population. Studying induced AVHs in neurotypicals may help identify the underlying cognitive and neural mechanisms contributing to AVHs in individuals with psychotic disorders.
Mixture of personality improved spiking actor network for efficient multi-agent cooperation
Authors: Li Xiyun , Ni Ziyi , Ruan Jingqing , Meng Linghui , Shi Jing , Zhang Tielin , Xu Bo
Published: July 2023

Adaptive multi-agent cooperation with especially unseen partners is becoming more challenging in multi-agent reinforcement learning (MARL) research, whereby conventional deep-learning-based algorithms suffer from the poor new-player-generalization problem, possibly caused by not considering theory-of-mind theory (ToM). Inspired by the ToM personality in cognitive psychology, where a human can easily resolve this problem by predicting others' intuitive personality first before complex actions, we propose a biologically-plausible algorithm named the mixture of personality (MoP) improved spiking actor network (SAN). The MoP module contains a determinantal point process to simulate the formation and integration of different personality types, and the SAN module contains spiking neurons for efficient reinforcement learning. The experimental results on the benchmark cooperative overcooked task showed that the proposed MoP-SAN algorithm could achieve higher performance for the paradigms with (learning) and without (generalization) unseen partners. Furthermore, ablation experiments highlighted the contribution of MoP in SAN learning, and some visualization analysis explained why the proposed algorithm is superior to some counterpart deep actor networks.
CRISPR/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis
Authors: Shi Yajun , Zhao Yan , Lu Likui , Gao Qinqin , Yu Dongyi , Sun Miao
Published: July 2023

Amyotrophic lateral sclerosis (ALS) is a deadly neurological disease with a complicated and variable pathophysiology yet to be fully understood. There is currently no effective treatment available to either slow or terminate it. However, recent advances in ALS genomics have linked genes to phenotypes, encouraging the creation of novel therapeutic approaches and giving researchers more tools to create efficient animal models. Genetically engineered rodent models replicating ALS disease pathology have a high predictive value for translational research. This review addresses the history of the evolution of gene editing tools, the most recent ALS disease models, and the application of CRISPR/Cas9 against ALS disease.
Maternal protein deficiency alters primary cilia length in renal tubular and impairs kidney development in fetal rat
Authors: Wang Jun , Zhou Pei , Zhu Liangliang , Guan Hongbo , Gou Jian , Liu Xiaomei
Published: July 2023

Introduction

Intrauterine malnutrition impairs embryo kidney development and leads to kidney disease and hypertension in adulthood, yet the underlying mechanism remains unclear.

Methods

With a maternal protein restriction (MPR) rat model, we investigated the critical ciliogenesis factors and β-catenin pathway in FGR fetal kidneys and analyzed the impact of aberrant primary cilia on renal tubular epithelium.

Results

The data showed decreased nephron number and renal tubular dysgenesis in FGR fetus. FGR fetus showed deregulated expression of ciliogenesis factors including upregulation of IFT88 and downregulation of DYNLT1, accompanied with cilia elongation in renal tubular epithelial cells. Wnt7b, the key ligand for Wnt/β-catenin signaling, was downregulated and nuclear translocation of β-catenin was decreased. The proapoptotic protein was upregulated. In vitro study with HK-2 cells showed that overexpression of IFT88 lengthened the cilia, inhibited β-catenin signaling. Besides, IFT88 overexpression suppressed cell proliferation, activated autophagy, and induced cell apoptosis. Inhibition of autophagy partly restored the cilia length and cell viability. Likewise, knockdown of DYNLT1 led to cilia elongation, suppressed cell proliferation, and promoted apoptosis in HK-2 cell. However, the cilia elongation induced by DYNLT1 knockdown was not autophagy-dependent, but associated with reactive oxygen species (ROS) accumulation.

Discussion

We elucidated that intrauterine protein malnutrition led to deregulation of ciliogenesis factors and cilia elongation in renal tubular epithelial, inhibited β-catenin signaling, and induced cell apoptosis and ultimately, compromised kidney development.
Development, characterization and in vivo zinc absorption capacity of a novel soy meal hydrolysate-zinc complexes
Authors: Wang Rongxin , Ye Meijun , Zhu Suyin , Zeng Qingzhu , Yuan Yang
Published: July 2023

Background

Zinc is an essential trace element for the human body. Recently, a novel Zn-binding peptide, Lys-Tyr-Lys-Arg-Gln-Arg-Trp (PP), was purified and identified from soy protein hydrolysates with high Zn-binding capacity (83.21 ± 2.65%) by our previous study. The preparation of soy meal hydrolysates (SMHs)-Zn complexes is convenient and low-cost, while PP (Lys-Tyr-Lys-Arg-Gln-Arg-Trp)-Zn complexes have a higher coordination rate but a relatively high cost. The aim of this study was to investigate the effect of soy meal hydrolysates (SMHs)-Zn complexes on zinc absorption in mice model, and synthetic soy peptide (PP)-Zn complexes with high Zn-binding capacity were used as control. Firstly, SMHs were prepared by enzymolysis, and the PP (Lys-Tyr-Lys-Arg-Gln-Arg-Trp) were synthesized based on previous studies. The binding mechanism of soy hydrolysates and zinc was analyzed by spectral analysis. Furthermore, the cytotoxicity of the SMHs-Zn complexes was also studied using the CCK-8 method. The effect of zinc absorption was evaluated based on Zn content, total protein and albumin content, relevant enzyme system, and the PeT1 and ZnT1 mRNA expression levels.

Result

The result showed that zinc was bound with carboxyl oxygen and amino nitrogen atoms on SMHs, with hydrophobic and electrostatic interactions as auxiliary stabilizing forces. SMHs-Zn were proved to have great solubility and a small particle size at different pH values, and it showed a beneficial effect on Caco-2 cells growth. Moreover, it was proved that SMHs-Zn and PP-Zn could increase the levels of zinc and the activity of Zn-related enzymes in mice. SMHs-Zn possessed higher PepT1 and ZnT1 mRNA expression levels than PP-Zn in the small intestine.

Conclusion

SMHs-Zn with a lower Zn-binding capacity had similar effects on zinc absorption in mice as PP-Zn, suggesting that the bioavailability of peptide-zinc complexes in mice was not completely dependent on their Zn-binding capacity, but may also be related to the amino acid composition.
Analysis of prognostic factors affecting immune checkpoint inhibitor therapy in tumor patients exposed to antibiotics
Authors: Chen Qian , Zhang Zhen , Li Xiaoli , Feng Shaomei , Liu Shui
Published: July 2023

Objective

Meta-analysis was performed to evaluate the prognostic factors in tumor patients treated with immune checkpoint inhibitors (ICIs) under antibiotic exposure.

Method

Literature on the effect of antibiotics on the prognosis of tumor patients receiving ICIs was retrieved from Pubmed, Cochrane Library, EMbase, EBSCO Evidence-Based Medicine Database, China Biomedical Literature Database (CBM), and China National Knowledge Network (CNKI), and relevant influencing factors were extracted. Meta-analysis of efficacy was performed using RevMan 5.4 software.

Results

A total of nine studies for 1,677 patients were included. The meta-analysis results showed that, in terms of progression-free survival, gender (male vs. female), Eastern Cooperative Oncology Group performance status (ECOG PS) (1–2 vs. 0), history of another cancer (yes vs. no), liver metastasis (yes vs. no), antibiotics (within the previous 2 months), PD-L1 (1%–49%), and PD-L1 (≥50%) factors are associated with progression-free survival in patients treated with ICIs under antibiotic exposure. In terms of overall survival, gender (male vs. female), ECOG score (1–2 vs. 0), history of another cancer (yes vs. no), brain metastasis (yes vs. no), liver metastasis (yes vs. no), radiation (within the previous 3 months), antibiotics (within the previous 2 months), PD-L1 (1%–49%), and PD-L1 (≥50%) factors are associated with overall survival in patients with antibiotic exposure receiving ICIs for tumor treatment.

Conclusion

Gender, ECOG score, history of another cancer, brain metastasis, liver metastasis, radiation (within the previous 3 months), antibiotics (within the previous 2 months), PD-L1 (1%–49%), and PD-L1 (≥50%) were associated with clinical benefit in patients with antibiotic exposure receiving ICIs for tumor treatment. Based on the above-mentioned factors, clinicians can screen cancer patients who receive ICIs under antibiotic exposure and rationally use antibiotics and ICIs in combination.
Chronic small intestinal helminth infection perturbs bile acid homeostasis and disrupts bile acid signaling in the murine small intestine
Authors: Lane Jenna M. , Brosschot Tara P. , Gatti Dominique M. , Gauthier Courtney M. , Lawrence Katherine M. , Pluzhnikova Victoria , Reynolds Lisa A.
Published: July 2023

Intestinal helminths have evolved an abundance of immunomodulatory mechanisms to ensure long-lived infections in mammalian hosts. To manipulate mammalian immune responses helminths can directly produce immunomodulatory molecules, but helminth infection can also elicit functional changes in the intestinal microbiome which can impact immune functioning. Here we examined how bile acids (BA)s, a group of host-produced, microbiota-modified immunomodulatory metabolites, were altered in abundance and composition during a murine small intestinal helminth infection. We found that murine helminth infection resulted in consistently reduced concentrations of specific taurine-conjugated primary BAs (T-α-MCA and T-CDCA) in the small intestinal luminal contents of mice. BA transporters facilitate the uptake of BAs from the small intestinal lumen, allowing BAs to engage with nuclear BA receptors, and helminth infected mice showed reduced expression of genes encoding basal BA transporters in the small intestine. Finally, we report that there is reduced signaling through the nuclear BA receptor FXR in both the proximal small intestine and ileum of mice during small intestinal helminth infection. Together, our data reveal disruptions to BA homeostasis and signaling in the small intestine during helminth infection. As BAs are known to impact many aspects of mucosal physiology and immunity, examining the functional consequences of BA disruptions during helminth infection will be an important avenue for future research.
Anaphylactoid reactions induced by Shuanghuanglian injection and Shenmai injection and metabolomics analysis
Authors: Zhang Chi , Ouyang Linqi , Zhang Xili , Wen Wen , Xu Yuqin , Li Shan , Li Yingyu , He Fuyuan , Liu Wenlong , Liu Hongyu
Published: July 2023

Introduction: Shuanghuanglian injection (lyophilized) (SHLI) is commonly used to treat respiratory tract infection. Shenmai injection (SMI) is mainly used to treat cardiovascular diseases. Despite their widespread clinical use, anaphylactoid reactions (ARs) induced by SHLI and SMI have been reported, which have attracted broad attention. However, the impact of ARs on metabolic changes and the underlying mechanisms are still unclear.

Methods: ICR mice were used as model animals and were treated with normal saline, C48/80, SHLI and SMI, respectively. The behavior of mice, auricle blue staining and Evans Blue exudation were used as indexes to evaluate the sensitization of SHLI and SMI and determine the optimal sensitization dose. Anaphylactoid mice model was established based on the optimal dose and enzyme-linked immunosorbent assay (ELISA) was used to model verification. Afterwards, plasma samples of administered mice were profiled by LC-MS metabolomics and analyzed to evaluate the changes in metabolites.

Results: High doses of both SHLI and SMI can induce severe anaphylactoid reactions while the reaction induced by SMI was weaker. A Partial Least-Squares Discriminant Analysis (PLS-DA) score plot indicated that following administration, significant metabolic changes occurred in mice. 23 distinct metabolites, including deoxycholic acid, histamine, and 5-hydroxytryptophan, were identified in the SHLI groups. 11 distinct metabolites, including androsterone, 17α-hydroxypregnenolone, and 5-hydroxyindoleacetate, were identified in the SMI groups. Meanwhile, different metabolic pathways of SHLI and SMI were predicted by different metabolites. The associated metabolic pathways include steroid hormone biosynthesis, tryptophan metabolism, histidine metabolism, arachidonic acid metabolism, nicotinate and nicotinamide metabolism, and primary bile acid biosynthesis.

Conclusion: Study showed that both SHLI and SMI can induce varying degrees of anaphylactoid reactions, a positive correlation between response intensity and dose was observed. Metabolomics showed that SHLI and SMI may promote the simultaneous release of hormones and inflammatory factors by disturbing relevant metabolic pathways, while SMI may also inhibit the release of inflammatory factors in arachidonic acid metabolic pathway, indicating both pro-inflammatory and anti-inflammatory effects. This study will serve as a reference for developing a new approach to evaluate the safety of SHLI and SMI from perspective of susceptible drug varieties. However, ARs mechanism requires further verification.
Fuzzy fractional Gardner and Cahn–Hilliard equations with the Atangana–Baleanu operator
Authors: Shah Manzoor Ali , Yasmin Humaira , Ghani Fazal , Abdullah Saleem , Khan Imran , Shah Rasool
Published: July 2023

This article focuses on the investigation and computation of solutions to fuzzy fractional-order Cahn–Hilliard and Gardner equations. The study hybridizes the fuzzy Gardner and Cahn–Hilliard equation into two equations using hybrid techniques and the concept of a parametric fuzzy number. To explore these equations, a combination of a novel iterative approach and the Shehu transformation is employed. The article presents detailed procedures for computing a series of solutions to the fractional-order Cahn–Hilliard and Gardner problem. The applied techniques not only offer precision, simplicity, and efficacy but also outperform other existing technologies. Additionally, several examples are solved to validate the proposed theoretical solution.