The mechanism of phonetic information in voice identity discrimination: a comparative study based on sighted and blind people.

Purpose: The purpose of this study is to examine whether phonetic information functions and how phonetic information affects voice identity processing in blind people. Method: To address the first inquiry, 25 normal sighted participants and 30 blind participants discriminated voice identity, when listening forward speech and backward speech from their own native language and another unfamiliar language. To address the second inquiry, combining articulatory suppression paradigm, 26 normal sighted participants and 26 blind participants discriminated voice identity, when listening forward speech from their own native language and another unfamiliar language. Results: In Experiment 1, not only in the voice identity discrimination task with forward speech, but also in the discrimination task with backward speech, both the sighted and blind groups showed the superiority of the native language. This finding supports the view that backward speech still retains some phonetic information, and indicates that phonetic information can affect voice identity processing in sighted and blind people. In addition, only the superiority of the native language of sighted people was regulated by the speech manner, which is related to articulatory rehearsal. In Experiment 2, only the superiority of the native language of sighted people was regulated by articulatory suppression. This indicates that phonetic information may act in different ways on voice identity processing in sighted and blind people. Conclusion: The heightened dependence on voice source information in blind people appears not to undermine the function of phonetic information, but it appears to change the functional mechanism of phonetic information. These findings suggest that the present phonetic familiarity model needs to be improved with respect to the mechanism of phonetic information.

Place perception and restorative experience of recreationists in the natural environment of rural tourism.

Introduction: In contemporary society, people spend long periods under high stress, and tourism activities have gradually been internalized as a new means of stress release and self-recovery. Studies have found that the high-quality natural environment of rural tourism destinations has a higher restorative effect than other places, and the rural natural environment can provide psychological recovery to visitors on top of offering visual beauty and other experiences. Methods: This paper starts with the relationship between rural place perception and restorative experience evaluation. Based on theories such as the restorative environments theory, we investigates whether rural natural environmental factors have a restorative effect on recreationists through collecting 300 questionnaires and using SPSS 26.0 structural equation modeling for analysis. Results: The study found that there is a positive correlation between rural natural perception, place dependence, and restorative experience, forming a positive feedback loop dynamic system. The analysis suggests that enhancing the perception of the rural natural environment and place attachment can improve the restorative experience of recreationists in rural settings. Discussion: This research establishes a systematic research framework for the relationship between rural natural perception, place attachment, and restorative experience, to deeply understand the dynamic interaction between them. It reveals the relationship between rural natural perception and restorative experience, suggesting that enriching the perceptual elements in rural natural spaces can meet the diverse needs of recreationists, enhance the sense of dependence and identification with rural spaces, and thus promote the psychological well-being and restorative experience of recreationists. The study also finds that place dependence plays a mediating role between rural natural perception and restorative experience. Place attachment and place identity, as mediating variables, act as bridges and catalysts in the process of rural natural perception affecting restorative experience.

20-Week Intramuscular Toxicity Study of Rotigotine Behenate Extended-Release Microspheres for Injection via Intramuscular Injection in Cynomolgus Monkeys.

Continuous dopaminergic stimulation (CDS) has become an important strategy for the development of drugs to treat Parkinson's disease(PD). Rotigotine behenate extended-release microspheres (RBEM) for injection represents a new treatment regime for CDS and is being applied for clinical trial. Our study in cynomolgus monkeys was a 20-week repeat dose toxicity investigation with RBEM at dosages of 90, 180, 360, with a 12-week recovery period. The results observed some irritations in the application site and surrounding tissues in Placebo microspheres and each dose of RBEM, was accompanied with increased white blood count and fibrinogen. RBEM-treated monkeys were additionally noted with a pharmacological action-related decrease in prolactin. These findings showed certain reversibility after the 12-week recovery phase. No clear sex difference was noted in the plasma exposure to rotigotine. The exposure generally increased in a dose-proportional manner. In summary, major toxicological effects are associated with the dopamine agonist-related properties of rotigotine, and the removal of foreign bodies caused by p oly(lactide-co-glycolide) (PLGA)and sodium carboxymethyl cellulose (SCMC), and the no-observed-adverse-effect-level (NOAEL) was 360 mg/kg.

Systematic review and meta-analysis of root morphology and canal configuration of permanent premolars using cone-beam computed tomography.

INTRODUCTION: The efficacy of root canal treatment is greatly impacted by a thorough understanding of root canal anatomy. This systematic review and meta-analysis aim to thoroughly investigate the root morphology and canal configuration (RMCC) of permanent premolars (PMs). METHODOLOGY: A comprehensive analysis was conducted following the PRISMA guidelines. Literature exploration was carried out across four electronic databases (PubMed, Embase, Cochrane, and Web of Science). The risk of bias assessment was conducted for the included studies utilizing the Anatomical Quality Assessment (AQUA) tool. Data analysis was performed utilizing SPSS and RevMAN5.3.3. The meta-analysis was applied with a 95% confidence interval to calculate odds ratios (OR). RESULTS: Among the 82 selected studies, 59 studies exhibited potential bias in domain one (objective(s) and subject characteristics), followed by domain three (methodology characterization). The majority of maxillary PM1s had either single root (46.7%) or double roots (51.9%), while three-rooted variants were uncommon (1.4%). Conversely, most other PMs exhibited a single root. In terms of canal configuration, maxillary PM1s predominantly featured double distinct canals (87.2%), with the majority of maxillary PM2s displaying either a single canal (51.4%) or double canals (48.3%). Mandibular PMs were primarily characterized by single canals, accounting for 78.3% of mandibular PM1s and 90.3% of mandibular PM2s. Subgroup analyses revealed higher incidences of single-rooted and single-canalled PMs among Asians compared to Caucasians. Additionally, women exhibited a higher incidence of single-rooted PMs, while men showed a greater frequency of double-rooted PMs. CONCLUSIONS: The comprehensive analysis indicated that maxillary PM1s predominantly possess double roots and double canals, whereas maxillary PM2s and mandibular PMs were primarily characterized by single-rooted with a single canal. Notably, single root and single canal were more prevalent among women and Asian samples.

From wings to whiskers to stem cells: why every model matters in fragile X syndrome research.

Fragile X syndrome (FXS) is caused by epigenetic silencing of the X-linked fragile X messenger ribonucleoprotein 1 (FMR1) gene located on chromosome Xq27.3, which leads to the loss of its protein product, fragile X messenger ribonucleoprotein (FMRP). It is the most prevalent inherited form of intellectual disability and the highest single genetic cause of autism. Since the discovery of the genetic basis of FXS, extensive studies using animal models and human pluripotent stem cells have unveiled the functions of FMRP and mechanisms underlying FXS. However, clinical trials have not yielded successful treatment. Here we review what we have learned from commonly used models for FXS, potential limitations of these models, and recommendations for future steps.

Up-regulating GABA transporter-3 in the zona incerta prevents surgery-induced memory impairment in mice.

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.

Multi-risk factors joint prediction model for risk prediction of retinopathy of prematurity.

Purpose: Retinopathy of prematurity (ROP) is a retinal vascular proliferative disease common in low birth weight and premature infants and is one of the main causes of blindness in children.In the context of predictive, preventive and personalized medicine (PPPM/3PM), early screening, identification and treatment of ROP will directly contribute to improve patients' long-term visual prognosis and reduce the risk of blindness. Thus, our objective is to establish an artificial intelligence (AI) algorithm combined with clinical demographics to create a risk model for ROP including treatment-requiring retinopathy of prematurity (TR-ROP) infants. Methods: A total of 22,569 infants who underwent routine ROP screening in Shenzhen Eye Hospital from March 2003 to September 2023 were collected, including 3335 infants with ROP and 1234 infants with TR-ROP among ROP infants. Two machine learning methods of logistic regression and decision tree and a deep learning method of multi-layer perceptron were trained by using the relevant combination of risk factors such as birth weight (BW), gestational age (GA), gender, whether multiple births (MB) and mode of delivery (MD) to achieve the risk prediction of ROP and TR-ROP. We used five evaluation metrics to evaluate the performance of the risk prediction model. The area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) were the main measurement metrics. Results: In the risk prediction for ROP, the BW + GA demonstrated the optimal performance (mean ± SD, AUCPR: 0.4849 ± 0.0175, AUC: 0.8124 ± 0.0033). In the risk prediction of TR-ROP, reasonable performance can be achieved by using GA + BW + Gender + MD + MB (AUCPR: 0.2713 ± 0.0214, AUC: 0.8328 ± 0.0088). Conclusions: Combining risk factors with AI in screening programs for ROP could achieve risk prediction of ROP and TR-ROP, detect TR-ROP earlier and reduce the number of ROP examinations and unnecessary physiological stress in low-risk infants. Therefore, combining ROP-related biometric information with AI is a cost-effective strategy for predictive diagnostic, targeted prevention, and personalization of medical services in early screening and treatment of ROP.

CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.

The human genome has many short tandem repeats, yet the normal functions of these repeats are unclear. The 5' untranslated region (UTR) of the fragile X messenger ribonucleoprotein 1 (FMR1) gene contains polymorphic CGG repeats, the length of which has differing effects on FMR1 expression and human health, including the neurodevelopmental disorder fragile X syndrome. We deleted the CGG repeats in the FMR1 gene (0CGG) in human stem cells and examined the effects on differentiated neurons. 0CGG neurons have altered subcellular localization of FMR1 mRNA and protein, and differential expression of cellular stress proteins compared with neurons with normal repeats (31CGG). In addition, 0CGG neurons have altered responses to glucocorticoid receptor (GR) activation, including FMR1 mRNA localization, GR chaperone HSP90α expression, GR localization, and cellular stress protein levels. Therefore, the CGG repeats in the FMR1 gene are important for the homeostatic responses of neurons to stress signals.

Determination of nitrobenzene potential genotoxic impurities in nifedipine with GC-MS.

There is an increasing scientific interest in the detection of genotoxic impurities (GTIs), with nitrobenzene compounds being considered potential genotoxic impurities due to their structural alerts, which demonstrates a threat to drug safety for patient. While current reports on the detection of nifedipine impurity primarily focus on general impurities in nifedipine. In this study, an effective and simple gas chromatography-mass spectrometry (GC-MS) method was established and verified for the separation and quantification of 2-nitrotoluene, 2-nitrobenzyl alcohol, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, and 2-nitrobenzyl bromide in nifedipine, which have not been previously reported. The validation of this GC-MS method was conducted following the International Conference of Harmonization (ICH) guidelines, exhibiting good linearity within the range of 2-40 µg/g and accuracy between 84.6 % and 107.8 %, the RSD% of intra-day and inter-day precision was in the range of 1.77-4.55 %, stability and robustness also met acceptance criteria. This method filled the gap in detection method for nitrobenzene compounds in nifedipine, offering a novel method and technical support for nifedipine quality control.

Inter and intralaminar excitation of parvalbumin interneurons in mouse barrel cortex.

Parvalbumin (PV) interneurons are inhibitory fast-spiking cells with essential roles in directing the flow of information through cortical circuits. These neurons set the balance between excitation and inhibition and control rhythmic activity. PV interneurons differ between cortical layers in their morphology, circuitry, and function, but how their electrophysiological properties vary has received little attention. Here we investigate responses of PV interneurons in different layers of primary somatosensory barrel cortex (BC) to different excitatory inputs. With the genetically-encoded hybrid voltage sensor, hVOS, we recorded voltage changes in many L2/3 and L4 PV interneurons simultaneously, with stimulation applied to either L2/3 or L4. A semi-automated procedure was developed to identify small regions of interest corresponding to single responsive PV interneurons. Amplitude, half-width, and rise-time were greater for PV interneurons residing in L2/3 compared to L4. Stimulation in L2/3 elicited responses in both L2/3 and L4 with longer latency compared to stimulation in L4. These differences in latency between layers could influence their windows for temporal integration. Thus, PV interneurons in different cortical layers of BC respond in a layer specific and input specific manner, and these differences have potential roles in cortical computations.

LED Junction Temperature Measurement: From Steady State to Transient State.

In this review, we meticulously analyze and consolidate various techniques used for measuring the junction temperature of light-emitting diodes (LEDs) by examining recent advancements in the field as reported in the literature. We initiate our exploration by delineating the evolution of LED technology and underscore the criticality of junction temperature detection. Subsequently, we delve into two key facets of LED junction temperature assessment: steady-state and transient measurements. Beginning with an examination of innovations in steady-state junction temperature detection, we cover a spectrum of approaches ranging from traditional one-dimensional methods to more advanced three-dimensional techniques. These include micro-thermocouple, liquid crystal thermography (LCT), temperature sensitive optical parameters (TSOPs), and infrared (IR) thermography methods. We provide a comprehensive summary of the contributions made by researchers in this domain, while also elucidating the merits and demerits of each method. Transitioning to transient detection, we offer a detailed overview of various techniques such as the improved T3ster method, an enhanced one-dimensional continuous rectangular wave method (CRWM), and thermal reflection imaging. Additionally, we introduce novel methods leveraging high-speed camera technology and reflected light intensity (h-SCRLI), as well as micro high-speed transient imaging based on reflected light (µ_HSTI). Finally, we provide a critical appraisal of the advantages and limitations inherent in several transient detection methods and offer prognostications on future developments in this burgeoning field.

Clinical features of ocular damage in systemic lupus erythematosus and risk factors of hydroxychloroquine related complications.

Ocular damage in systemic lupus erythematosus (SLE) may cause insidious visual impairment, but its clinical features and the risk of hydroxychloroquine (HCQ)-related complications are still controversial. We performed a meta-analysis to evaluate ocular damage in SLE, the correlation between eye and systemic involvement, and the ocular side effects of treatment. The database PubMed, Embase, and Ovid were used for literature from reception to July, 2023, and the calculation was carried out with R. About 48,693 patients from 66 studies were included. The results indicated that ocular damage in SLE was insidious, appearing in 28% of patients with no complaints. The most common symptoms and manifestations were dry eye (30%) and keratoconjunctivitis sicca (26%). Retinopathy was detected in 10% of patients and was related to antiphospholipid antibodies (25% versus 8%). The proportion of retinopathy also significantly increased in patients with lupus nephropathy or neuropsychiatric systemic lupus erythematosus (risk ratio of 2.29 and 1.95, respectively). HCQ was used in 82% of patients, of which 4% suffered from ocular toxicity. HCQ-related retinopathy was dose-dependent. Dosage below 5mg/kg/d was relatively effective and safe for long-term use, while routine examination was recommended.

Extracellular vesicle biomarkers in circulation for colorectal cancer detection: a systematic review and meta-analysis.

We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August 2022.Weidentified 48 studies that involved 7727 participants and evaluated 162 plasma/serum individual EV biomarkers including 117 RNAs and 45 proteins, as well as 45 EV biomarker panels for CRC detection. 12 studies evaluated the diagnostic performance of EV biomarkers for early CRC. The summarized sensitivity, specificity, and AUC value of individual EV RNAs and EV RNA panels were 76%, 75%, 0.87 and 82%, 79% and 0.90, respectively. Meanwhile, those of individual EV proteins and EV protein panels were 85%, 84%, 0.92 and 87%, 83%, 0.92, respectively. These results indicated that EV biomarker panels revealed superior diagnostic performance than the corresponding individual biomarkers. In early CRC, EV biomarkers showed available diagnostic value with the sensitivity, specificity, and AUC value of 80%, 75%, and 0.89.In subgroup analyses, EV miRNAs and LncRNAs held similar diagnostic value with the sensitivity, specificity and AUC value of 75%, 78%, 0.90 and 79%, 72%, 0.83, which was highly consistent with the whole EV RNAs. Significantly, the diagnostic values of EV miRNAs in plasma were marginally higher than those based on serum. In detail, the sensitivity, specificity, and AUC values were 79%, 81%, and 0.92 in plasma, as well as 74%, 77%, and 0.88 in serum, respectively. Therefore, circulation EV biomarkers could be considered as a promising biomarker for the early detection of CRC.

A fundus image dataset for intelligent retinopathy of prematurity system.

Image-based artificial intelligence (AI) systems stand as the major modality for evaluating ophthalmic conditions. However, most of the currently available AI systems are designed for experimental research using single-central datasets. Most of them fell short of application in real-world clinical settings. In this study, we collected a dataset of 1,099 fundus images in both normal and pathologic eyes from 483 premature infants for intelligent retinopathy of prematurity (ROP) system development and validation. Dataset diversity was visualized with a spatial scatter plot. Image classification was conducted by three annotators. To the best of our knowledge, this is one of the largest fundus datasets on ROP, and we believe it is conducive to the real-world application of AI systems.

Nanolignin-containing cellulose nanofibrils (LCNF)-enabled multifunctional ratiometric fluorescent bio-nanocomposite films for food freshness monitoring.

Herein, the nanolignin-containing cellulose nanofibrils (LCNF)-enabled ratiometric fluorescent bio-nanocomposite film is developed. Interestingly, the inclusion of LCNF in the cellulose-based film enhances the detecting performance of food freshness, such as high sensitivity to biogenic amines (BAs) (limit of detection (LOD) of up to 1.83 ppm) and ultrahigh discernible fluorescence color difference (ΔE = 113.11). The underlying mechanisms are the fluorescence resonance energy transfer (FRET), π - π interaction, and cation - π interaction between LCNF and fluorescein isothiocyanate (FITC), as well as the increased hydrophobicity due to lignin, which increases the interactions of amines with FITC. Its color stability (up to 28 days) and mechanical property (49.4 Mpa) are simultaneously improved. Furthermore, a smartphone based detecting platform is developed to achieve access to food safety. This work presents a novel technology, which can have a great potential in the field of food packaging and safety.

Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway.

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.

Fiber-Optic Photoacoustic Gas Microsensor Dual Enhanced by Helmholtz Resonator and Interferometric Cantilever.

A high-sensitivity fiber-optic photoacoustic (PA) gas microsensor is demonstrated with dual enhancement based on acoustics and detection. Due to the characteristic of small size, a Helmholtz resonator is integrated into a miniature PA sensor. The acoustically amplified PA signal is detected by a high-sensitivity fiber Fabry-Perot (F-P) interferometric cantilever. The first-order resonant frequencies of the interferometric cantilever and Helmholtz resonator are matched by subtle adjustments. The weak PA signal is significantly enhanced in a volume of only 0.35 mL, which breaks the volume limitation of the resonance modes in traditional PA sensing systems. To improve the resolution of the microsensor, a white light interferometry (WLI)-based spectral demodulation algorithm is utilized. The experimental results indicate that the minimum detection limit of acetylene (C2H2) drops to about 15 ppb with an averaging time of 100 s, corresponding to the normalized noise equivalent absorption (NNEA) coefficient of 2.7 × 10-9 W·cm-1·Hz-1/2. The dual resonance enhanced fiber-optic PA gas microsensor has the merits of high sensitivity, intrinsic safety, and compact structure.

Relationship between family resilience and dyadic coping in colorectal cancer patients and their spouses, based on the actor-partner interdependence model.

PURPOSE: To explore the relationship between dyadic coping and family resistance in colorectal cancer patients and their spouses. METHODS: 178 pairs of colorectal cancer patients and their spouses hospitalized in a three tertiary hospital in Changsha were selected from July 2021 to March 2022. The Family Resilience Assessment Scale and the Dyadic Coping Inventory were used to investigate, which relationship was analyzed by APIM. RESULTS: The total score of patients' dyadic coping was 121.51 ± 16.8, and spouses' score was 123.72 ± 16.6. The total score of family resilience was 176.42 ± 16.0, and spouses' score was 182.72 ± 17.03. There was a significant positive relationship between dyadic coping and family resistance of colorectal cancer patients and their spouses (r > 0.7, P < 0.001). The positive dyadic coping of colorectal cancer patients and their spouses had a positive effect on their own and their spouses' family resilience and the effect was the same. The negative dyadic coping of colorectal cancer patients and their spouses had a negative impact on their own family resilience, and the overall model showed a subject pattern. CONCLUSIONS: The level of family resilience of colorectal cancer patients and their spouses was affected by the level of dyadic coping. Medical workers should regard patients and their spouses as a whole and formulate mutually supportive coping strategies with family as the center, so as to increase positive coping behavior and enhance their family's ability to cope with cancer.

Rigor and reproducibility in human brain organoid research: Where we are and where we need to go.

Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.

Nanomedicine-based disulfiram and metal ion co-delivery strategies for cancer treatment.

Disulfiram (DSF) is a second-line drug for the clinical treatment of alcoholism and has long been proven to be safe for use in clinical practice. In recent years, researchers have discovered the cancer-killing activity of DSF, which is highly dependent on the presence of metal ions, particularly copper ions. Additionally, free DSF is highly unstable and easily degraded within few minutes in blood circulation. Therefore, an ideal DSF formulation should facilitate the co-delivery of metal ions and safeguard the DSF throughout its biological journey before reaching the targeted site. Extensive research have proved that nanotechnology based formulations can effectively realize this goal by strategic encapsulation therapeutic agents within nanoparticle. To be more specific, this is accomplished through precise delivery, coordinated release of metal ions at the tumor site, thereby amplifying its cytotoxic potential. Beyond traditional co-loading techniques, innovative approaches such as DSF-metal complex and metal nanomaterials, have also demonstrated promising results at the animal model stage. This review aims to elucidate the anticancer mechanism associated with DSF and its reliance on metal ions, as well as to provide a comprehensive overview of recent advances in the arena of nanomedicine based co-delivery strategies for DSF and metal ion in the context of cancer therapy.