Single-dose of integrated bilayer microneedles for enhanced hypertrophic scar therapy with rapid anti-inflammatory and sustained inhibition of myofibroblasts.

Hypertrophic scar (HS) tends to raised above skin level with high inflammatory microenvironment and excessive proliferation of myofibroblasts. The HS therapy remains challenging due to dense scar tissue which makes it hard to penetrate, and the side effects resulting from intralesional corticosteroid injection which is the mainstay treatment in clinic. Herein, bilayer microneedle patches combined with dexamethasone and colchicine (DC-MNs) with differential dual-release pattern is designed. Two drugs loaded in commercially available materials HA and PLGA, respectively. Specifically, after administration, outer layer rapidly releases the anti-inflammatory drug dexamethasone, which inhibits macrophage polarization to pro-inflammatory phenotype in scar tissue. Subsequently, inner layer degrades sustainedly, releasing antimicrotubular agent colchicine, which suppresses the overproliferation of myofibroblasts with extremely narrow therapeutic window, and inhibits the overexpression of collagen, as well as promotes the regular arrangement of collagen. Only applied once, DC-MNs directly delivered drugs to the scar tissue. Compared to traditional treatment regimen, DC-MNs significantly suppressed HS at lower dosage and frequency by differential dual-release design. Therefore, this study put forward the idea of integrated DC-MNs accompany the development of HS, providing a non-invasive, self-applicable, more efficient and secure strategy for treatment of HS.

Response Surface Methodology to Explore the Influence Mechanism of Fiber Diameter in a New Multi-Needle Electrospinning Spinneret.

Multi-needle electrospinning is an efficient method for producing nanofiber membranes. However, fluctuations in the fluid flow rate during the process affect membrane quality and cause instability, an issue that remains unresolved. To address this, a multi-stage flow runner spinneret needs to be developed for large-scale nanofiber membrane production. This paper uses COMSOL finite element software to simulate polymer flow in the spinneret runner. From this, the velocity field distribution and velocity instability coefficient were obtained, providing theoretical guidance for optimal spinneret design. In addition, response surface analysis (RSM) was used to experimentally explore the process parameters, and then residual probability plots were used for reliability verification to evaluate the effect of each process parameter on fiber diameter. These process parameters can guide the controlled production of nanofibers during multi-needle electrospinning.

Abnormal platelet parameters in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Platelet dysfunction plays a critical role in the pathogenesis of inflammatory bowel disease (IBD). Despite clinical observations indicating abnormalities in platelet parameters among IBD patients, inconsistencies persist, and these parameters lack standardization for diagnosis or clinical assessment. METHODS: A comprehensive search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases for relevant articles published up to December 16th, 2023. A random-effects model was employed to pool the weighted mean difference (WMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) between IBD patients and healthy controls, and subgroup analyses were performed. RESULTS: The meta-analysis included 79 articles with 8,350 IBD patients and 13,181 healthy individuals. The results revealed significantly increased PLT and PCT levels (WMD: 69.910, 95% CI: 62.177, 77.643 109/L; WMD: 0.046%, 95% CI: 0.031%, 0.061%), and decreased MPV levels (WMD: -0.912, 95% CI: -1.086, -0.739 fL) in IBD patients compared to healthy individuals. No significant difference was found in PDW between the IBD and control groups (WMD: -0.207%, 95% CI: -0.655%, 0.241%). Subgroup analysis by disease type and disease activity showed no change in the differences for PLT, PCT, and MPV in the ulcerative colitis and Crohn's disease groups, as well as the active and inactive groups. Notably, the active group exhibited significantly lower PDW levels than the control group (WMD: -1.138%, 95% CI: -1.535%, -0.741%). CONCLUSIONS: Compared with healthy individuals, IBD patients display significantly higher PLT and PCT and significantly lower MPV. Monitoring the clinical manifestations of platelet abnormalities serves as a valuable means to obtain diagnostic and prognostic information. Conversely, proactive measures should be taken to prevent the consequences of platelet abnormalities in individuals with IBD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023493848.

Substantial Energy Band Modulation of Semiconducting Hexagonal GaTe Quantum Wells by Layer Thickness and Mirror Twin Boundaries.

Exploring emerging two-dimensional (2D) van der Waals (vdW) semiconducting materials and precisely tuning their electronic properties at the atomic level have long been recognized as crucial issues for developing their high-end electronic and optoelectronic applications. As a III-VI semiconductor, ultrathin layered hexagonal GaTe (h-GaTe) remains unexplored in terms of its intrinsic electronic properties and band engineering strategies. Herein, we report the successful synthesis of ultrathin h-GaTe layers on a selected graphene/SiC(0001) substrate, via molecular beam epitaxy (MBE). The widely tunable quasiparticle band gaps (∼2.60-1.55 eV), as well as the vdW quantum well states (QWSs) that can be strictly counted by the layer numbers, are well characterized by onsite scanning tunneling microscopy/spectroscopy (STM/STS), and their origins are clearly addressed by density functional theory (DFT) calculations. More intriguingly, distinctive 8|8E and 4|4P (Ga) mirror twin boundaries (MTBs) are identified in the ultrathin h-GaTe flakes, which can induce decreased band gaps and prominent p-doping effects. This work should deepen our understanding on the electronic tunability of 2D III-VI semiconductors by thickness control and line defect engineering, which may hold promise for fabricating atomic-scale vertical and lateral homojunctions toward ultrascaled electronics and optoelectronics.

Therapeutic Effects of Qingchang Tongluo Decoction on Intestinal Fibrosis in Crohn's Disease: Network Pharmacology, Molecular Docking and Experiment Validation.

Background: Qingchang Tongluo Decoction (QTF) is clinically used for the treatment of intestinal fibrosis in Crohn's Disease (CD). However, the role of QTF in CD-associated fibrosis and its potential pharmacological mechanism remains unclear. Purpose: The objective of this study was to elucidate the potential mechanism of QTF in treating CD-associated fibrosis, employing a combination of bioinformatics approaches - encompassing network pharmacology and molecular docking - complemented by experimental validation. Methods: To investigate the material basis and potential protective mechanism of QTF, a network pharmacology analysis was conducted. The core components and targets of QTF underwent molecular docking analysis to corroborate the findings obtained from network pharmacology. In vitro, a colon fibrotic model was established by stimulating IEC-6 cells with 10 ng/mL of transforming growth factor(TGF-ß1). In vivo, an intestinal fibrosis model was induced in BALB/c mice by TNBS. The role of QTF in inhibiting the TGF-ß1/Smad signaling pathway was investigated through RT-qPCR, Western blotting, immunohistochemistry staining, and immunofluorescence staining. Results: Network pharmacology analysis revealed that QTF could exert its protective effect. Bioinformatics analysis suggested that Flavone and Isoflavone might be the key components of the study. Additionally, AKT1, IL-6, TNF, and VEGFA were identified as potential therapeutic targets. Furthermore, experimental validation and molecular docking were employed to corroborate the results obtained from network pharmacology. RT-qPCR, Immunofluorescence, and Western blotting results demonstrated that QTF significantly improved colon function and inhibited pathological intestinal fibrosis in vivo and in vitro. Conclusion: Through the application of network pharmacology, molecular docking, and experimental validation, QTF could be confirmed to inhibit the proliferation of intestinal fibroblasts associated with CD and reduce the expression of Collagen I and VEGFA. This effect is achieved through the attenuation of ECM accumulation, primarily via the inhibition of the TGF-ß1/Smad signaling pathway.

Cadmium impacts on calcium mineralization of zebrafish skeletal development and behavioral impairment.

Cadmium (Cd) poses significant risks to aquatic organisms due to its toxicity and ability to disrupt the cellular processes. Given the similar atomic radius of Cd and calcium (Ca), Cd may potentially affect the Ca homeostasis, which can lead to impaired mineralization of skeletal structures and behavioral abnormalities. The formation of the spinal skeleton involves Ca transport and mineralization. In this study, we conducted an in-depth investigation on the effects of Cd at environmental concentrations on zebrafish (Danio rerio) skeletal development and the underlying molecular mechanisms. As the concentration of Cd increased, the accumulation of Cd in zebrafish larvae also rose, while the Ca content decreased significantly by 3.0 %-57.3 %, and vertebral deformities were observed. Transcriptomics analysis revealed that sixteen genes involved in metal absorption were affected. Exposure to 2 µg/L Cd significantly upregulated the expression of these genes, whereas exposure to 10 µg/L resulted in their downregulation. Consequently, exposure of zebrafish larvae to 10 µg/L of Cd inhibited the body segmentation growth and skeletal mineralization development by 29.1 %-56.7 %. This inhibition was evidenced by the downregulation of mineral absorption genes and decreased Ca accumulation. The findings of this study suggested that the inhibition of skeletal mineralization was likely attributed to the disruption of mineral absorption, thus providing novel insights into the mechanisms by which metal pollutants inhibit the skeletal development of fish.

Deposition of Gadolinium in the Central and Peripheral Nervous Systems and Its Effects on Sensory, Cognitive, and Athletic Implications after Multiple Injections of Gadolinium-Based Contrast Agents in Rats.

BACKGROUND AND PURPOSE: After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications. MATERIALS AND METHODS: Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs. RESULTS: All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to "sea urchins" and was mainly located near the vascular basement membrane. CONCLUSIONS: Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.

The translocation activity of Rad54 reduces crossover outcomes during homologous recombination.

Homologous recombination (HR) is a template-based DNA double-strand break repair pathway that requires the selection of an appropriate DNA sequence to facilitate repair. Selection occurs during a homology search that must be executed rapidly and with high fidelity. Failure to efficiently perform the homology search can result in complex intermediates that generate genomic rearrangements, a hallmark of human cancers. Rad54 is an ATP dependent DNA motor protein that functions during the homology search by regulating the recombinase Rad51. How this regulation reduces genomic exchanges is currently unknown. To better understand how Rad54 can reduce these outcomes, we evaluated several amino acid mutations in Rad54 that were identified in the COSMIC database. COSMIC is a collection of amino acid mutations identified in human cancers. These substitutions led to reduced Rad54 function and the discovery of a conserved motif in Rad54. Through genetic, biochemical and single-molecule approaches, we show that disruption of this motif leads to failure in stabilizing early strand invasion intermediates, causing increased crossovers between homologous chromosomes. Our study also suggests that the translocation rate of Rad54 is a determinant in balancing genetic exchange. The latch domain's conservation implies an interaction likely fundamental to eukaryotic biology.

Downregulation of CASC15 attenuates the symptoms of polycystic ovary syndrome by affecting granulosa cell proliferation and regulating ovarian follicular development.

Polycystic ovary syndrome (PCOS) is a type of follicular dysplasia with an unclear pathogenesis, posing certain challenges in its diagnosis and treatment. Cancer susceptibility candidate 15 (CASC15), a long non-coding RNA closely associated with tumour development, has been implicated in PCOS onset and development. Therefore, this study aimed to investigate the molecular mechanisms underlying PCOS by downregulating CASC15 expression in both in vitro and in vivo models. We explored the potential regulatory relationship between CASC15 expression and PCOS by examining cell proliferation, cell cycle dynamics, cell autophagy, steroid hormone secretion capacity, and overall ovarian function in mice. We found that CASC15 expression in granulosa cells derived from patients with PCOS was significantly higher than those of the normal group (P < 0.001). In vitro experiments revealed that downregulating CASC15 significantly inhibited cell proliferation, promoted apoptosis, induced G1-phase cell cycle arrest, and influenced cellular autophagy levels. Moreover, downregulating CASC15 affected the follicular development process in newborn mouse ovaries. In vivo studies in mice demonstrated that disrupting CASC15 expression improved PCOS-related symptoms such as polycystic changes and hyperandrogenism, and significantly affected ovulation induction and embryo implantation in pregnant mice. Overall, CASC15 was highly expressed in granulosa cells of patients with PCOS and its downregulation improved PCOS-related symptoms by influencing granulosa cell function and follicular development in mice.

Preparation of Quick-Dissolving Nanofiber Face Masks Based on Needleless Electrostatic Spinning.

As the global facial mask market continues to grow, consumers have put forward higher requirements for the functionality and ingredients of mask products. Ordinary facial masks mostly use ordinary non-woven fabrics as the mask base fabric and are used with essence. Preservatives are generally added. At the same time, they are susceptible to the influence of the external environment and are easily oxidized, causing the mask to deteriorate and cause skin allergic reactions. In addition, traditional facial masks have problems such as poor fit with the skin, poor breathability, insufficient absorption of nutrient solutions, and easy dripping. The high specific surface area and high porosity of a nanofiber mask prepared by electrospinning technology are beneficial to the skin's absorption of nutrients, and it has good fit with the skin and strong breathability. A unique advantage of this nanofiber mask is that it uses spray. After the mask is sprayed with water or essence, the water-soluble polymer within it can be quickly dissolved, saving a lot of time. Nanofiber facial mask products can effectively solve consumer pain points and are conducive to the high-end development of facial masks. Therefore, this article combines needleless electrospinning technology to develop a new solid-state, preservative-free, quick-dissolving nanofiber facial mask that can be prepared on a large scale. Based on needleless electrospinning technology, this article deeply explores the process parameters and their influencing mechanisms for preparing nanofiber, quick-dissolving facial masks to achieve the stable preparation of nanofiber facial masks with the best morphology; a comprehensive analysis of the structure and influence of nanofiber facial masks from micro and macro perspectives demonstrates their performance and allows evaluation of them. The experimental results show that the mask morphology is optimal under the process conditions of using a spinning liquid of 20% collagen peptide solution, a spinning voltage of 30 kV, a collection distance of 19 cm, and a liquid supply speed of 130 mL/h.

Identification and expression profiling of SmGATA genes family involved in response to light and phytohormones in eggplant.

GATA proteins are transcription factors of zinc finger proteins, which play an important role in plant growth development and abiotic stress. However, there have been no identification or systematic studies of the GATA gene family in eggplant. In this study, 28 SmGATA genes were identified in the genome database of eggplant, which could be divided into four subgroups. Plant development, hormones, and stress-related cis-acting elements were identified in promoter regions of the SmGATA gene family. RT-qPCR indicated that 4 SmGATA genes displayed upregulated expressions during fruit developmental stage, whereas 2 SmGATA genes were down-regulated expression patterns. It was also demonstrated that SmGATA genes may be involved in light signals to regulate fruit anthocyanin biosynthesis. Furthermore, the expression patterns of SmGATA genes under ABA, GA and MeJA treatments showed that the SmGATAs were involved in the process of fruit ripening. Notably, SmGATA4 and SmGATA23 were highly correlated with the expression of anthocyanin biosynthesis genes, light-responsive genes, and genes that function in multiple hormone signaling pathways and the proteins they encoded were localized in the nucleus. All these results showed GATA genes likely play a major role in regulating fruit anthocyanin biosynthesis by integrating the light, ABA, GA and MeJA signaling pathways and provided references for further research on fruit quality in eggplant.

Atomically Thin Kagome-Structured Co9Te16 Achieved through Self-Intercalation and Its Flat Band Visualization.

Kagome materials have recently garnered substantial attention due to the intrinsic flat band feature and the stimulated magnetic and spin-related many-body physics. In contrast to their bulk counterparts, two-dimensional (2D) kagome materials feature more distinct kagome bands, beneficial for exploring novel quantum phenomena. Herein, we report the direct synthesis of an ultrathin kagome-structured Co-telluride (Co9Te16) via a molecular beam epitaxy (MBE) route and clarify its formation mechanism from the Co-intercalation in the 1T-CoTe2 layers. More significantly, we unveil the flat band states in the ultrathin Co9Te16 and identify the real-space localization of the flat band states by in situ scanning tunneling microscopy/spectroscopy (STM/STS) combined with first-principles calculations. A ferrimagnetic order is also predicted in kagome-Co9Te16. This work should provide a novel route for the direct synthesis of ultrathin kagome materials via a metal self-intercalation route, which should shed light on the exploration of the intriguing flat band physics in the related systems.

Influence of Zr Microalloying on the Microstructure and Room-/High-Temperature Mechanical Properties of an Al-Cu-Mn-Fe Alloy.

Here, 0.3 wt.%Zr was introduced in an Al-4 wt.%Cu-0.5 wt.%Mn-0.1 wt.%Fe alloy to investigate its influence on the microstructure and mechanical properties of the alloy. The microstructures of both as-cast and T6-treated Al-Cu-Mn-Fe (ACMF) and Al-Cu-Mn-Fe-Zr (ACMFZ) alloys were analyzed. The intermetallic compounds formed through the casting procedure include Al2Cu and Al7Cu2Fe, and the Al2Cu phase dissolves into the matrix and re-precipitates as θ' phase during the T6 process. The introduction of Zr results in the precipitation of L12-Al3Zr nanometric precipitates after T6, while the θ' precipitates in ACMFZ alloy are much finer than those in ACMF alloy. The L12-Al3Zr precipitates were found coherently located with θ', which was assumed beneficial for stabilizing the θ' precipitates during the high-temperature tensile process. The tensile properties of ACMF and ACMFZ alloys at room temperature and elevated temperatures (200, 300, and 400 °C) were tested. Especially, the yield strength of ACMFZ alloys can reach 128 MPa and 65 MPa at 300 °C and 400 °C, respectively, which are 31% and 33% higher than those of ACMF alloys. The strengthening mechanisms of grain size, L12-Al3Zr, and θ' precipitates on the tensile properties were discussed. This work may be referred to for designing Al-Cu alloys for application in high-temperature fields.

Large-Substrate-Terrace Confined Growth of Arrayed Ultrathin PtSe2 Ribbons on Step-Bunched Vicinal Au(001) Facets Toward Electrocatalytic Applications.

Ultrathin PtSe2 ribbons can host spin-polarized edge states and distinct edge electrocatalytic activity, emerging as a promising candidate for versatile applications in various fields. However, the direct synthesis is still challenging and the growth mechanism is still unclear. Herein, the arrayed growth of ultrathin PtSe2 ribbons on bunched vicinal Au(001) facets, via a facile chemical vapor deposition (CVD) route is reported. The ultrathin PtSe2 flakes can transform from traditional irregular shapes to desired ribbon shapes by increasing the height of bunched and unidirectionally oriented Au steps (with step height hstep) is found. This crossover, occurring at hstep ≈ 3.0 nm, defines the tailored growth from step-flow to single-terrace-confined modes, as validated by density functional theory calculations of the different system energies. On the millimeter-scale single-crystal Au(001) films with aligned steps, the arrayed ultrathin PtSe2 ribbons with tunable width of ≈20-1000 nm, which are then served as prototype electrocatalysts for hydrogen evolution reaction (HER) is achieved. This work should represent a huge leap in the direct synthesis and the mechanism exploration of arrayed ultrathin transition-metal dichalcogenides (TMDCs) ribbons, which should stimulate further explorations of the edge-related physical properties and practical applications.

Global research trend and hotspot in the low FODMAP diet: a bibliometric analysis.

BACKGROUND: According to national guidelines, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is a second-line therapy option for irritable bowel syndrome (IBS) and improves functional intestinal symptoms. Numerous noteworthy results have been published in this field over the past fifteen years. This study aims to analyze the global research trend and hotspot of the low FODMAP diet research, and provide a comprehensive perspective and direction for researchers. METHODS: The Science Citation Index-Expanded of the Web of Science Core Collection (WoSCC) was used to identify low FODMAP diet-related articles and reviews. Three bibliometric programs (CiteSpace, VOSviewer, Scimago Graphic) were utilized to analyze and visualize the annual publications, authors, countries, institutions, journals, citations, and keywords. RESULTS: In total, 843 documents related to the low FODMAP diet research were published in 227 journals by 3,343 authors in 1,233 institutions from 59 countries. The United States, which was the most engaged nation in international collaboration, had the largest annual production and the fastest growth. The most productive organization was Monash University, and the most fruitful researcher was Gibson PR. Nutrients ranked first in terms of the number of published documents. The article "A diet low in FODMAPs reduces symptoms of irritable bowel syndrome" (Halmos EP, 2014) received the most co-citations. Keywords that appear frequently in the literature mainly involve two main aspects: the clinical efficacy evaluation and mechanism exploration of the low FODMAP diet. The term "gut microbiota" stands out as the most prominent keyword among the burst keywords that have remained prevalent till date. CONCLUSION: The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet is of great interest and has become the current research hotspot.

Chemical vapor deposition growth of graphene and other nanomaterials with 3D architectures towards electrocatalysis and secondary battery-related applications.

Recently, two-dimensional (2D) layered materials, such as graphene and transition metal dichalcogenides (TMDCs), have garnered a lot of attention in energy storage/conversion-related fields due to their novel physical and chemical properties. Constructing flat graphene and TMDCs nanosheets into 3D architectures can significantly increase their exposed surface area and prevent the restacking of adjacent 2D layers, thus dramatically promoting their applications in various energy-related fields. Chemical Vapor Deposition (CVD) is a low-cost, facile, and scalable method, which has been widely employed to produce high-quality graphene and TMDCs nanosheets with 3D architectures. During the CVD process, the morphologies and properties of the 3D architectures of such 2D materials can be designed by selecting substrates with different compositions, stacking geometries, and micro-structures. In this review, we focus on the recent advances in the CVD synthesis of graphene, TMDCs, and their hybrids with 3D architectures on different 3D-structured substrates, as well as their applications in the electrocatalytic hydrogen evolution reaction (HER) and various secondary batteries. In addition, the challenges and future prospects for the CVD synthesis and energy-related applications of these unique layered materials will also be discussed.

Willed Attentional Selection of Visual Features: An EEG Study.

Visual selective attention studies generally tend to apply cuing paradigms to instructively direct observers' attention to certain locations, features or objects. However, in real situations, attention in humans often flows spontaneously without any specific instructions. Recently, a concept named "willed attention" was raised in visuospatial attention, in which participants are free to make volitional attention decisions. Several ERP components during willed attention were found, along with a perspective that ongoing alpha activity may bias the subsequent attentional choice. However, it remains unclear whether similar neural mechanisms exist in feature- or object-based willed attention. Here, we included choice cues and instruct cues in a feature-based selective attention paradigm, allowing participants to freely choose or to be instructed to attend a color for the subsequent target detection task. Pre-cue ongoing alpha oscillations, cue-evoked potentials and target-related steady-state visual evoked potentials (SSVEPs) were simultaneously measured as markers of attentional processing. As expected, SSVEP responses were similarly modulated by attention between choice and instruct cue trials. Similar to the case of spatial attention, a willed-attention component (Willed Attention Component, WAC) was isolated during the cue-related choice period by comparing choice and instruct cues. However, pre-cue ongoing alpha oscillations did not predict the color choice (yellow vs blue), as indicated by the chance level decoding accuracy (50%). Overall, our results revealed both similarities and differences between spatial and feature-based willed attention, and thus extended the understanding toward the neural mechanisms of volitional attention.

The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels.

Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1-TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated. Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions. Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment.

Long non-coding RNA PWRN1 affects ovarian follicular development by regulating the function of granulosa cells.

RESEARCH QUESTION: What is the role of Prader-Willi region non-protein coding RNA 1 (PWRN1) in ovarian follicular development and its molecular mechanism? DESIGN: The expression and localization of PWRN1 were detected in granulosa cells from patients with different ovarian functions, and the effect of interfering with PWRN1 expression on cell function was detected by culturing granulosa cells in vitro. Furthermore, the effects of interfering with PWRN1 expression on ovarian function of female mice were explored through in-vitro and in-vivo experiments. RESULTS: The expression of PWRN1 was significantly lower in granulosa cells derived from patients with diminished ovarian reserve (DOR) compared with patients with normal ovarian function. By in-vitro culturing of primary granulosa cells or the KGN cell line, the results showed that the downregulation of PWRN1 promoted granulosa cell apoptosis, caused cell cycle arrested in S-phase, generated high levels of autophagy and led to significant decrease in steroidogenic capacity, including inhibition of oestradiol and progesterone production. In addition, SIRT1 overexpression could partially reverse the inhibitory effect of PWRN1 downregulation on cell proliferation. The results of in-vitro culturing of newborn mouse ovary showed that the downregulation of PWRN1 could slow down the early follicular development. Further, by injecting AAV-sh-PWRN1 in mouse ovarian bursa, the oestrous cycle of mouse was affected, and the number of oocytes retrieved after ovulation induction and embryos implanted after mating was significantly reduced. CONCLUSION: This study systematically elucidated the novel mechanism by which lncRNA PWRN1 participates in the regulation of granulosa cell function and follicular development.

Ocular trauma from Lawn mower accidents: Clinical insights, visual outcomes and microbial profiles.

AIMS: To characterize the clinical features of ocular trauma resulting from lawn mower, identify determinants of unfavorable final visual acuity (FVA), and assess the spectrum of microbial in posttraumatic endophthalmitis. METHODS: This retrospective study enrolled patients who experienced ocular trauma due to lawn mower at Zhongshan Ophthalmic Center from January 2013 to August 2021. Demographics, clinical features, isolated microorganisms, risk factors influencing reduced visual acuity, treatment regimens, and utilization of eyewear were collected. RESULTS: The study included 140 participants (140 eyes) (49.47 ± 12.03 years, 95% male). The predominant injury manifestations were penetrating globe injuries (75.7%) and intraocular foreign bodies (51.4%). Endophthalmitis occurred in 35 cases (25%) and Bacillus cereus (23.5%) was the primary pathogen, followed by Staphylococcus epidermidis (11.8%) and Streptococcus species (11.8%). Following the initial assessment, where 77.9% of patients had initial visual acuity (IVA) at grade IV (ranging from light perception to 4/200) and only 0.7% attained grade I (better than 20/40), post-treatment results revealed that 5.7% achieved FVA at grade I, with a concurrent decrease in patients with grade IV vision to 64.3%. Multivariate logistic regression revealed that injury protection (p < 0.001, OR = 0.237, 95% CI = 0.126-0.446), IVA (p = 0.001, OR = 4.102, 95% CI = 1.730-9.729), and retinal detachment (p = 0.042, OR = 8.105, 95% CI = 1.075-61.111) were significant independent risk factors impacting FVA. CONCLUSION: Lawn mower often cause severe ocular injuries, with high-velocity metal foreign bodies that can lead to infections, most commonly caused by Bacillus cereus. Correct use of protective gear, initial vision assessment, and detecting retinal detachment are crucial for visual prognosis.