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Abstract Background This study aims to explore the effects of the iris-ciliary angle (ICA) on the accurate prediction of the vault after implantable collamer lens (ICL) using the manufacturer’s online calculation and ordering system (OCOS). Methods The participants were categorized into three groups according to the size of ICA as follows: narrow ICA group ( 60°). We compared the preoperative ocular characteristics and postoperative vault at 3 months among the three groups. Bivariate correlation was used to analyze the correlation between vault and ICA, and multiple linear regression was used to further analyze the correlation between vault and preoperative parameters. Ordered multicategorical logistic regression analyses were used to further illustrate the effect of different ICA groups on postoperative vault distribution. Results This study included 278 eyes of 157 individuals. There were no statistically significant differences in preoperative ocular parameters among the three ICA groups, while the postoperative vault was minimal in the wide ICA group, followed by the normal and then the narrow ICA group (p

Abstract Modulating and elevating the operating voltage of a given cathode is a significant challenge to enhance the energy density of secondary batteries without sacrificing power output. The chemical coordination strongly influences the energy levels of d-orbitals of redox cations in cathode materials, which tie to their operating voltage. In contrast to concentrated studies on enhancing the specific capacity, in this study, we choose bi-layered hydrated vanadium pentoxide as the model to modulate the d-orbital energy levels through local chemical coordination manipulation, achieving a higher operating voltage in rechargeable aqueous zinc ion batteries. Here we show that, by employing X-ray absorption spectroscopy (XAS) and pair distribution function (PDF) techniques, we can analyze the distortion of [VO6] octahedra and extract chemical bond information, deciphering the correlation between the chemical coordination and operating voltage in cathode materials. The fundamentals could guide the designing and developing RAZIBs with higher energy and power density.

Abstract Alzheimer’s disease (AD) is a global healthcare challenge lacking a simple and affordable detection method. We propose a novel deep learning framework, Eye-AD, to detect Early-onset Alzheimer’s Disease (EOAD) and Mild Cognitive Impairment (MCI) using OCTA images of retinal microvasculature and choriocapillaris. Eye-AD employs a multilevel graph representation to analyze intra- and inter-instance relationships in retinal layers. Using 5751 OCTA images from 1671 participants in a multi-center study, our model demonstrated superior performance in EOAD (internal data: AUC = 0.9355, external data: AUC = 0.9007) and MCI detection (internal data: AUC = 0.8630, external data: AUC = 0.8037). Furthermore, we explored the associations between retinal structural biomarkers in OCTA images and EOAD/MCI, and the results align well with the conclusions drawn from our deep learning interpretability analysis. Our findings provide further evidence that retinal OCTA imaging, coupled with artificial intelligence, will serve as a rapid, noninvasive, and affordable dementia detection.

Abstract Background To assess the relationship between postoperative implantable collamer lens (ICL) vault and lens height obtained from two different measurements. Methods A retrospective case series study enrolled eyes with horizontally implanted ICL. Crystal lens rise (CLR) and the distance between STS plane and anterior crystalline lens surface (STSL) were measured in the horizontal and vertical directions using ultrasound biomicroscopy (UBM). We compared the differences in the parameters measured in both horizontal and vertical directions. The participants were categorized into three groups according to ciliary sulcus width (CSW) which is defined as the distance between the posterior angle of the iris and the anterior angle of the ciliary process: narrow CSW group (NSG); medium CSW group (MSG); and wide CSW group (WSG). The correlations between CLR/STSL and vault were examined in each of the three groups. Biased correlation analysis was used further to contrast the correlation between CLR/STSL and vault. Results This retrospective study included 223 myopic eyes. Vertical STSL (VSTSL) and vertical CLR (VCLR) exhibited significantly greater values compared to their horizontal counterparts (both P

Abstract Background Despite expectancy theory’s widespread appeal and influence as a framework for motivation in organizational and educational settings, studies that have examined the theory’s validity for performance-based outcomes, particularly with academic performance as the criterion, have been characterized by inconsistent results. Given numerous methodological concerns associated with past studies (e.g., prevalence of between-person rather than within-person design), we examined the predictive validity of expectancy theory for academic performance using methods that were consistent with the theory’s original conceptualization. Additionally, we assessed the validity of the theory for students’ study effort. Methods The final sample included 123 undergraduate students who reported their final grades in four courses. Study effort and other variables were measured with self-report surveys. Because course grades were nested within each person, multilevel modeling was used to test study hypotheses. Results Both the valence model and the force model predicted a student’s current study effort, but contrary to expectations, neither model predicted a student’s final course grades. In contrast, both valence for academic success and the simplified force model (based only on valence and expectancy) predicted current study effort, final course grades, and explained incremental variance beyond cognitive ability. Furthermore, the predictive validity of this force model was relatively stable across the 11 weeks of the study. Conclusions Based on methods congruent with expectancy theory’s original framework, we find that the force model does not predict academic performance. An alternative version of the model, however, predicts course grades and has incremental validity over cognitive ability. Our results have several significant theoretical and practical implications.

Abstract The eyes provide insights into psychology, potentially offering a distinctive perspective for psychological health profiles. However, there exist a notable deficiency in datasets that simultaneously encompass eye features and psychological assessments. To address this gap, our study presents a dataset that included Fundus Photography, Psychological Assessment, Retina Characteristics, and Multimodal Imaging (FPRM). FPRM dataset comprise fundus images at different wavelengths (548 nm and 605 nm), image of oxygen saturation for the retina and 8 specific retinal vessels, videos of retinal blood flow and pupillary light reflex, along with 61 items of multimodal quantitative measurement from 384 participants. Additionally, it features psychological assessments across five dimensions (geriatric depression, generalized anxiety disorder, insomnia, activities of daily living, and deterioration), accompanied by fundus photographs and 6 items of retina characteristics from 1683 participants. FPRM dataset is the first to integrate multimodal ophthalmic data and psychological assessments, not only advancing the development of machine learning applications but also facilitating in-depth research into the relationship between eye health and psychological health profiles.

Abstract Background The contribution of cholinergic degeneration to gait disturbance in Parkinson’s disease (PD) is increasingly recognized, yet its relationship with dopaminergic-resistant gait parameters has been poorly investigated. We investigated the association between comprehensive gait parameters and cholinergic nucleus degeneration in PD. Methods This cross-sectional study enrolled 84 PD patients and 69 controls. All subjects underwent brain structural magnetic resonance imaging to assess the gray matter density (GMD) and volume (GMV) of the cholinergic nuclei (Ch123/Ch4). Gait parameters under single-task (ST) and dual-task (DT) walking tests were acquired using sensor wearables in PD group. We compared cholinergic nucleus morphology and gait performance between groups and examined their association. Results PD patients exhibited significantly decreased GMD and GMV of the left Ch4 compared to controls after reaching HY stage > 2. Significant correlations were observed between multiple gait parameters and bilateral Ch123/Ch4. After multiple testing correction, the Ch123/Ch4 degeneration was significantly associated with shorter stride length, lower gait velocity, longer stance phase, smaller ankle toe-off and heel-strike angles under both ST and DT condition. For PD patients with HY stage 1–2, there were no significant degeneration of Ch123/4, and only right side Ch123/Ch4 were corrected with the gait parameters. However, as the disease progressed to HY stage > 2, bilateral Ch123/Ch4 nuclei showed correlations with gait performance, with more extensive significant correlations were observed in the right side. Conclusions Our study demonstrated the progressive association between cholinergic nuclei degeneration and gait impairment across different stages of PD, and highlighting the potential lateralization of the cholinergic nuclei’s impact on gait impairment. These findings offer insights for the design and implementation of future clinical trials investigating cholinergic treatments as a promising approach to address gait impairments in PD.

Abstract Background Myopia is a major health issue around the world. Myopia in children has increased significantly during the COVID-19 pandemic in China, but reports are scarce on the prevalence of myopia following the pandemic. This study collected vision screening data of school children in China for five consecutive years to observe the changes in myopia after the pandemic and compare the observed prevalence of myopia before and after the pandemic. Methods A school-based vision screening study used stratified samplings to collect the vision screening data in school children aged 6–13 from 45 primary schools in Hangzhou. Vision screening data including uncorrected visual acuity(UCVA) and spherical equivalent refraction(SER). Calculating the mean of SER and the prevalence of myopia and hyperopia from 2019 to 2023. Results A total of 79,068 screening results (158,136 eyes) were included in the analysis. A substantial myopic shift (approximately -0.30 diopters [D] on average) was found in 2020 and 2021 compared with 2019 in all age groups and a substantial myopic shift (approximately 0.4 D on average) was found in 2022 compared with 2021. A slight myopic shift (approximately -0.14 D on average) was found in 2023 compared with 2022. The prevalence of myopia in all age groups was the highest for five years in 2020 or 2021, which was 31.3% for 6-year-olds, 43.0% for 7-year-olds, and 53.7% for 8-year-olds. A positive change in the prevalence rate of myopia was found at 6 years old (0.59%, 0.12%, 0.36%, 0.25%, p

Abstract Radiotherapy is a curative arsenal for prostate cancer (PCa), but radioresistance seriously compromises its effectiveness. Dysregulated RNA splicing factors are extensively involved in tumor progression. Nonetheless, the role of splicing factors in radioresistance remains largely unexplored in PCa. Here, 23 splicing factors that are differentially expressed between PCa and adjacent normal tissues across multiple public PCa databases are identified. Among those genes, polypyrimidine tract binding protein 1 (PTBP1) is significantly upregulated in PCa and is positively associated with advanced clinicopathological features and poor prognosis. Gain‐ and loss‐of‐function experiments demonstrate that PTBP1 markedly reinforces genomic DNA stability to desensitize PCa cells to irradiation in vitro and in vivo. Mechanistically, PTBP1 interacts with the heterogeneous nuclear ribonucleoproteins (hnRNP) associated with lethal yellow protein homolog (RALY) and regulates exon 5 splicing of DNA methyltransferase 3b (DNMT3B) from DNMT3B‐S to DNMT3B‐L. Furthermore, upregulation of DNMT3B‐L induces promoter methylation of dual‐specificity phosphatase‐2 (DUSP2) and subsequently inhibits DUSP2 expression, thereby increasing radioresistance in PCa. The findings highlight the role of splicing factors in inducing aberrant splicing events in response to radiotherapy and the potential role of PTBP1 and DNMT3B‐L in reversing radioresistance in PCa.

Networks have been widely used to describe a range of biotic interactions in ecosystems; topological indicators of ecological networks provide systematic way to characterize patterns of different interacting systems. However, it is hampered by sampling bias and detecting the true structures to compare the stability of ecological communities. In this context, we aimed to employ innovative approach of identifying critical transition indicator to compare stable network structure by simulating dynamics of network assembly. Four epiphyte–host networks were compiled, including two groups (epiphytic bryophyte and epiphytic vascular plant) of tropical rainforest (TRF) and subtropical forest (STF). The dynamics of three structure indictors, i.e. connectance, nestedness and modularity were simulated to explore what changes occurred as sampling effort increases. The critical transition indicator was detected to compare the structure of four networks at a stable state. Meanwhile, the variation dynamics of host size and epiphyte richness were fitted to analyze the underlying processes shaping the stable network structure. Using a dynamic simulation, the network structures showed the critical transition to stable state when sampling size approximated 30 hosts for epiphytic bryophytes and 100 hosts for epiphytic vascular plants. After critical transition, connectance and nestedness were higher in the STF than in the TRF. In contrast, modularity was higher in the TRF than in the STF. The coefficient of variations (CV) of host size and epiphyte richness tended to be stable at the same critical transition point; the distribution of host size and epiphyte richness could be the fundamental factors for the assembly of stable epiphyte–host network. Our study emphasized the importance of considering sampling effort while evaluating the network structure. Combining critical transition indicator with structure indicator dynamics could be a powerful method to compare the stable structure of different ecological networks.

In the dissimilar metal welding field, electromagnetic pulse welding (EMPW) is a kind of potential technology. To further reveal the bonding mechanism of EMPW, this work carried out a Cu–Al sheet EMPW experiment with a discharge voltage of 15 kV and a gap of 1.5 mm. It analyzed the microstructure and formation mechanism of the Cu–Al EMPW joint bonding interface transition layer in detail by SEM, EDS, TEM, and FIB. The transition layer was found at the vortex zone, and there was an isolated long strip Cu particle separated from the main body of the Cu sheet. The tested results showed that the transition layer contained Al-rich intermetallic compound (IMC) Al2Cu, and some bulk particles in the transition layer were Cu-rich IMCs Al4Cu9 and AlCu4. There were Cu-rich IMCs Al4Cu9, AlCu4, and AlCu between the long strip Cu particle and the IMC transition layer. In the violent impact process between the Cu sheet and Al sheet, the Cu rapidly diffused in the Al matrix to form the Al-rich IMC (Al2Cu) as the primary transition layer, and the interface was high temperature and high pressure, forming a plastic flow and vortexes swirling. Some Cu particles separated from the Cu sheet and became the vortex piece during the plastic flow process, and continued to interact with the Al2Cu primary transition layer to form the secondary transition layer. This work could provide a basis for revealing the structure composition and formation mechanism of the Cu–Al EMPW joint interface transition layer.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA

This study presents the market for carbon management capacity via carbon capture, utilization, and storage technologies, identifying demand and supply forces, as well as clarifying the potential impact of market and non-market-based shocks on technology developers versus adopters. The paper addresses a prevailing gap in market analysis, introducing a microeconomic framework and unique dataset to identify key players, market forces, and policy incentives shaping the carbon capture, utilization, and storage landscape. The analysis equips industry stakeholders, policymakers, and investors with valuable insights regarding (1) leaders in the design, development, and manufacture of carbon capture, utilization, and storage technologies (supply), (2) early technology adopters (demand) who are at the forefront in the pursuit of sustainable carbon management, and (3) the need to use both market and non-market forces to achieve decarbonization across multiple sectors.

With a significant increase in the obesity epidemic in China, addressing adolescent obesity should be highlighted as a priority. The current qualitative study aims to explore the perspectives of key stakeholders regarding adolescent obesity, providing guidance for developing effective obesity interventions for Chinese adolescents. A total of 12 focus group discussions were convened with a range of representative stakeholders including adolescents (n = 37), parents (n = 28), and school staff (n = 21) from sample schools. Semi-structured topic guides were used for data collection. All data were transcribed verbatim and analyzed thematically. From multiple stakeholder perspectives, we finally identified 3 overarching themes ( Understanding adolescent obesity, Key healthy lifestyles, and Barriers to obesity prevention practices ) and 8 sub-themes. While participants had mixed perceptions of status and prevalence of adolescent obesity, all acknowledged the serious health consequences associated with it. As significant modifiable risk factors, unhealthy diet and physical activity were identified to be prevalent among Chinese teenagers and lead to excessive weight gain. However, a variety of individual, environmental and sociocultural factors hindered the implementation of healthy lifestyles, affecting adolescent obesity prevention and control. Given adolescent obesity is a complex, multifactorial and multilevel public issue, comprehensive lifestyle interventions are recommended that synergistically engage multiple stakeholders across key communities to fight the ongoing obesity epidemic.

Neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) is an autoimmune disease that affects the astrocytes. NMOSD-ON is one of the core clinical phenotypes of neuromyelitis optica spectrum disorder and its most-common initial symptom. NMOSD-ON is characterized by severe vision loss, poor prognosis and high recurrence, mainly affecting young and middle-aged individuals. It is a challenge to know how to improve patients’ visual outcomes. In this report, we present a refractory case of NMOSD-ON treated with satralizumab after multiple conventional therapies proved ineffective. Satralizumab was found to effectively control relapses in this patient and visual improvement was found after 18 months of treatment. Given to that, satralizumab may have a potential longitudinal effect on visual improvement in NMOSD-ON.

Background: This report describes a case of bilateral transient myopia with a shallow anterior chamber and ciliochoroidal detachment following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and indapamide intake. Case presentation: A 37-year-old man with coronavirus disease 2019 (COVID-19) was referred to our department due to bilateral blurred vision. The patient had been treated with ibuprofen for fever and indapamide for uncontrolled blood pressure. After four days of indapamide intake, the patient complained of bilateral visual blurring. On ocular examination, his uncorrected visual acuity was 20/400 in both eyes. Slit-lamp examination revealed shallow anterior chambers. The following day, the patient experienced pain and redness in both eyes, which began the previous night. Ocular examination revealed a significant decrease in intraocular pressure (IOP) compared to the previous day: 11 mmHg and 12 mmHg in the right eye (OD) and left eye (OS), respectively. Slit-lamp examination revealed conjunctival injection and the presence of inflammatory cells (2+) in the shallow anterior chambers of both eyes. Ultrasound biomicroscopy revealed ciliary body detachment and B-scan ultrasonography showed peripheral shallow choroidal detachment in both eyes. Discontinuing indapamide and initiating treatment with oral prednisolone, topical tobramycin dexamethasone and tropicamide phenylephrine eye drops resulted in the rapid recovery of signs and symptoms after three days. Discussion and conclusions: Indapamide intake may contribute to bilateral ciliochoroidal detachment, with SARS-CoV-2 infection possibly increasing susceptibility to drug-induced side effects. Timely drug withdrawal and symptomatic treatment can result in a good prognosis.

Understanding the spatiotemporal patterns and variations in vapor pressure deficit (VPD) is essential for effective water resource management in the face of climate change. VPD serves as a fundamental indicator of atmospheric dryness, directly impacting plant evapotranspiration rates, thereby affecting overall ecosystem functioning. In this study, VPD changes in five subregions and four ecological types of land in Yunnan from 1980 to 2021 were investigated using data from 108 meteorological stations. We found increasing trends in annual VPD that were larger during warmer spring and summer seasons. Among the subregions, the highland subtropical southern broadleaved evergreen forest ecoregion exhibited the largest drying trend (0.04 kPa / decade), while the subtropical (eastern) humid broadleaved evergreen forest ecoregion had the smallest drying trend (0.01 kPa / decade). Among the ecological barriers, the dry-hot valleys had significantly higher increases in VPD compared to other Yunnan regions. Increases in VPD from 1990s to 2000s in several regions of Yunnan exceeded atmospheric drying trends reported elsewhere. Additionally, we documented smaller VPD declines at higher elevations. Across different ecological land types, Shrubland exhibited the largest VPD trend (0.07 kPa / decade), while Forest displayed the smallest (0.03 kPa / decade). Decreased relative humidity through time explained 65% of the increase in VPD in Yunnan, while increasing temperatures accounted for 25%. These findings provide valuable insights into climatic dynamics of Yunnan, with implications for ecological, hydrological, and atmospheric studies.

Parkinson's disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins, including α-synuclein, amyloid-β, and tau, in addition to the impaired elimination of these neurotoxic protein. Atypical parkinsonism, which has the same clinical presentation and neuropathology as Parkinson's disease, expands the disease landscape within the continuum of Parkinson's disease and related disorders. The glymphatic system is a waste clearance system in the brain, which is responsible for eliminating the neurotoxic proteins from the interstitial fluid. Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease, as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage. Therefore, impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration. Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson's disease and related disorders; however, many unanswered questions remain. This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson's disease and related disorders. The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins, including loss of polarization of aquaporin-4 in astrocytic endfeet, sleep and circadian rhythms, neuroinflammation, astrogliosis, and gliosis. This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson's disease and related disorders, and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

Abstract Background TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS–FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS–FTD spectrum. Methods We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS–FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS–FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease. Results SuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 types B, E and C. In contrast, the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS–FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King’s stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology. Conclusions Our findings suggest distinct neurodegenerative subtypes of disease along the ALS–FTD spectrum that can be identified in vivo, each with distinct brain atrophy, clinical, genetic and pathological patterns.

Background/Objective: This study aimed to investigate the causal relationship between urate level and female infertility using Mendelian randomization (MR) analysis. Methods: To identify instrumental variables, we selected independent genetic loci associated with serum urate levels in individuals of European ancestry, utilizing data from large-scale genome-wide association studies (GWAS). The GWAS dataset included information on serum urate levels from 288,649 CKDGen participants. Female infertility data, including different etiologic classifications, consisted of 13,142 female infertility patients and 107,564 controls. We employed four MR methods, namely inverse variance weighted (IVW), MR-Egger, weighted median, and weighted model, to investigate the causal relationship between urate levels and female infertility. The Cochran Q-test was used to assess heterogeneity among single nucleotide polymorphisms (SNPs), and the MR-Egger intercept test was employed to evaluate the presence of horizontal pleiotropy. Additionally, a “leave-one-out” sensitivity analysis was conducted to examine the influence of individual SNPs on the MR study. Results: The IVW analysis demonstrated that elevated serum urate levels increased the risk of female infertility (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07–1.33). Furthermore, serum urate levels were found to be associated with infertility due to cervical, vaginal, or other unknown causes (OR = 1.16, 95% CI: 1.06–1.26), also confirmed by other methods. Heterogeneity among instrumental variables was assessed using Cochran’s Q-test (p < 0.05), so a random-effects IVW approach was employed in the effects model. The MR-Egger intercept test indicated no presence of horizontal pleiotropy. A “leave-one-out” sensitivity analysis was conducted, demonstrating that no individual SNP had a substantial impact on the overall findings. Conclusions: In the European population, the urate level is significantly and causally associated with an increased risk of female infertility.

ABSTRACTCutaneous candidiasis, caused by Candida albicans, is a severe and frustrating condition, and finding effective treatments can be challenging. Therefore, the development of farnesol-loaded nanoparticles is an exciting breakthrough. Ethosomes are a novel transdermal drug delivery carrier that incorporates a certain concentration (10–45%) of alcohols into lipid vesicles, resulting in improved permeability and encapsulation rates compared to conventional liposomes. Farnesol is a quorum-sensing molecule involved in morphogenesis regulation in C. albicans, and these ethosomes offer a promising new approach to treating this common fungal infection. This study develops the formulation of farnesol-loaded ethosomes (farnesol-ethosomes) and assesses applications in treating cutaneous candidiasis induced by C. albicans in vitro and in vivo. Farnesol-ethosomes were successfully developed by ethanol injection method. Therapeutic properties of farnesol-ethosomes, such as particle size, zeta potential, and morphology, were well characterized. According to the results, farnesol-ethosomes demonstrated an increased inhibition effect on cells’ growth and biofilm formation in C. albicans. In Animal infection models, treating farnesol-ethosomes by transdermal administration effectively relieved symptoms caused by cutaneous candidiasis and reduced fungal burdens in quantity. We also observed that ethosomes significantly enhanced drug delivery efficacy in vitro and in vivo. These results indicate that farnesol-ethosomes can provide future promising roles in curing cutaneous candidiasis.IMPORTANCECutaneous candidiasis attributed to Candida infection is a prevalent condition that impacts individuals of all age groups. As a type of microbial community, biofilms confer benefits to host infections and mitigate the clinical effects of antifungal treatments. In C. albicans, the yeast-to-hypha transition and biofilm formation are effectively suppressed by farnesol through its modulation of multiple signaling pathway. However, the characteristics of farnesol such as hydrophobicity, volatility, degradability, and instability in various conditions can impose limitations on its effectiveness. Nanotechnology holds the potential to enhance the efficiency and utilization of this molecule. Treatment of farnesol-ethosomes by transdermal administration demonstrated a very remarkable therapeutic effect against C. albicans in infection model of cutaneous candidiasis in mice. Many patients suffering fungal skin infection will benefit from this study.

Abstract Astrocytic dysfunction contributes to the molecular pathogenesis of major depressive disorder (MDD). However, the astrocytic subtype that mainly contributes to MDD etiology and whether dysregulated autophagy in astrocytes is associated with MDD remain unknown. Using a single-nucleus RNA sequencing (snRNA-seq) atlas, three astrocyte subtypes were identified in MDD, while C2 State-1Q astrocytes showed aberrant changes in both cell proportion and most differentially expressed genes compared with other subtypes. Moreover, autophagy pathways were commonly inhibited in astrocytes in the prefrontal cortices (PFCs) of patients with MDD, especially in C2 State-1Q astrocytes. Furthermore, by integrating snRNA-seq and bulk transcriptomic data, we found significant reductions in LC3A expression levels in the PFC region of CUMS-induced depressed mice, as well as in postmortem PFC tissues and peripheral blood samples from patients with MDD. These results were further validated by qPCR using whole-blood samples from patients with MDD and healthy controls. Finally, LC3A expression in the whole blood of patients with MDD was negatively associated with the severity of depressive symptoms. Overall, our results underscore autophagy inhibition in PFC astrocytes as a common molecular characteristic in MDD and might reveal a novel potential diagnostic marker LC3A.

Abstract Purpose To evaluate the early corneal remodeling and its influencing factors after Small incision lenticule extraction (SMILE) for moderate and high myopia. Methods This was a retrospective study. Pre- and post-operative (1 week and 1, 3, 6 months) corneal volume (CV), mean keratometry (Km), and corneal thickness (CT) were measured by Scheimpflug tomography. CT at the central, thinnest point, and on concentric circles of 2, 4, and 6 mm diameter was recorded to assess corneal thickness spatial profile (CTSP) and percentage of thickness increase (PTI) in the moderate and high myopia groups, and to explore possible influencing factors. Results After SMILE, the peripheral CT decreased in the moderate myopia group and central corneal thickness (CCT) increased in the high myopia group at 1 month compared to 1 week (all P 0.05). Patients with high myopia showed greater corneal thickness changes (△CT) and higher PTI than moderate myopia (all P

Abstract This study examines the association between class size, teacher characteristics and five non-cognitive student outcomes (i.e., self-control, interpersonal skills, approaches to learning, externalizing and internalizing problem behaviors) in grades K-3. Individual fixed-effects, that control for observed and unobserved time-invariant factors, including student and school time-constant variables, are employed to analyze national data from the Early Childhood Longitudinal Study, Kindergarten Class of 2010–11 (ECLS-K:2011). Results suggest a significant linear association between reducing class size and interpersonal skills. Teacher experience is saliently, positively and significantly related with student self-control, interpersonal skills, and approaches to learning, and negatively associated with externalizing problem behaviors. Teacher education and certification were not associated with any of the five non-cognitive outcomes. Changing schools had a negative effect on student’s self-control.

The COVID-19 pandemic has changed the world and has presented the scientific community with unprecedented challenges. Infection is associated with overproduction of proinflammatory cytokines secondary to hyperactivation of the innate immune response, inducing a cytokine storm and triggering multiorgan failure and significant morbidity/mortality. No specific treatment is yet available. For thousands of years, Panax notoginseng has been used to treat various infectious diseases. Experimental evidence of P. notoginseng utility in terms of alleviating the cytokine storm, especially the cascade, and improving post-COVID-19 symptoms, suggests that P. notoginseng may serve as a valuable adjunct treatment for COVID-19 infection.

Located in Dali, Yunnan, the Zhaozhou basin is home to many precious architectural heritages, particularly the historical horse caravan architecture. These buildings face the challenge of renewal and transformation. It is of great significance to explore the local population’s awareness of the architectural heritage of the horse caravan in order to protect the architectural heritage and facilitate rural revitalization. This study reviews the related research on “space perception”, establishes a theoretical framework of space perception under the architectural dimension, and develops hypotheses. The social cluster of typical settlements in the Zhaozhou basin is selected as the research object, and empirical analyses are carried out using SPSS and AMOS software. An analytical framework model of empirical research is constructed to evaluate the space perception of the current social population. The results of the reliability and validity tests of the questionnaire show that the CR is greater than 0.7 and that the AVE is greater than 0.5. The value of the structural equation model fitting index χ2/df is 1.863, which is less than 3. The model test results show that research hypotheses H1–H5 are supported; that is, space perception has a significant positive impact on cognition and local identity, cognition has a significant positive impact on local identity and space function, and place identity has a significant positive impact on space appeal. This study demonstrates the relationship between space perception and the architectural remains of the horse caravan, and it analyzes the human psychological perception behind the material space. The findings support the need for further conservation of the horse caravan architecture. This study further deepens the theory of space perception and its application in the study of vernacular architecture, which can provide a research path for the protection and development of vernacular architectural heritage.

Abstract Background Procedural pain is very important in clinical children care. We aimed to evaluate the effects of active versus passive distraction for reducing procedural pain and anxiety in children. Methods Two researchers searched the Web of Science, PubMed, EMBASE, Cochrane, SinoMed, Wanfang, China National Knowledge Infrastructure, Weipu databases for the randomized controlled trials(RCTs) on the active versus passive distraction affecting procedural pain and anxiety in children until May 18, 2023. The literature screening and data extraction were carried out by two researchers independently. Review Manager 5.3 software was used for data analysis. Results 13 RCTs were finally included. 553 children received active distraction intervention and 551 children received passive distraction intervention. There were no significant differences in the children self-reported procedural pain betweent active and passive distraction. The parent-reported procedural pain, medical staff-reported procedural pain, children-reported procedural anxiety, parent-reported procedural anxiety, medical staff-reported procedural anxiety in the active distraction were significant less than that of active distraction. Egger regression analysis showed that there was no publication bias in the results. Conclusions Existing evidence suggests that active distraction may be more effective in reducing operational pain and anxiety in children than passive distraction. More studies on the effects of active distraction versus passive distraction in children with larger sample size are needed in the future.

The necessity of the multi-layered aluminium (Al) tabs to copper (Cu) busbars for electric vehicle (EV) batteries is increasing. Electromagnetic pulse welding (EMPW) is applicable to the welding of conductive dissimilar/similar materials. In this work, three Al sheets and a single Cu sheet are joined by the EMPW technology. The layer-wise tensile lap shear properties of the multi-layered Al–Cu EMPW joint are evaluated. The layer-wise interfacial microstructures of the joint parallel to and perpendicular to the welding direction are studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and energy-dispersive spectroscopy (EDS). The results showed that every layer achieved metallurgical bonding. The Al sheets were formed to be whole. There were three types of interfaces at the Al–Cu interface parallel to the welding direction: flat interface, wave interface, and irregular wave interface. The transition zone is found at the Al–Cu interface perpendicular to the welding direction. Due to the impact, the grains near the Al–Cu interface and Al–Al interface are both refined. Thus, the well-bonded multi-layered Al–Cu joint is successfully obtained via EMPW. The results can offer help in the manufacturing of EVs.

Abstract Background Acute disseminated encephalomyelitis is a well-known, but rare, side effect of some vaccines, or symptom following a febrile illness. Case A 69-year-old, otherwise healthy Hispanic male presented with acute fever, confusion, and later progressive weakness after receiving the first dose of the mRNA-1273 (Moderna) severe acute respiratory syndrome coronavirus 2 vaccine. Considering the progressive deterioration of the patient, despite being on multiple immunosuppressive agents, a brain biopsy was obtained, which revealed nonspecific meningoencephalitis. Conclusion In this case, we highlight the need for a regulatory framework to assist clinicians and patients with coverage of treatment for acute disseminated encephalomyelitis. The use of intravenous immunoglobulin in conjunction with glucocorticoids seems to be an effective treatment option.

Abstract Background To analyze the relationship between axial length and levels of high-density lipoprotein (HDL) cholesterol in children. Methods A retrospective, hospital-based cross-sectional research with 69 right eyes from 69 children who underwent health examination by Zhejiang Provincial People’s Hospital was carried out. The participants were split into three groups: Group A (axial length 24 mm). Demographic epidemiological information, blood biochemical parameters and ophthalmic characteristics including refractive status and ocular geometric parameters were obtained and analyzed. Results 69 right eyes from 69 patients (25 males and 44 females) with a median age of 10.00 years old (IQR: 8.00–11.00 years) were included in the study. Within Group A, there were a total of 17 individuals; Group B consisted of 22 individuals; Group C included 30 individuals. The mean axial length of three groups was 22.148(0.360), 23.503(0.342) and 24.770(0.556) mm, respectively (p

Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease. In this meta-analysis, we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to differentiate between Alzheimer’s disease and control subjects. Scientific databases including Google Scholar, Web of Science, and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects. Seventy-three studies (5850 participants, including 2249 Alzheimer’s disease patients and 3601 controls) were included in this meta-analysis. Relative to controls, Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness (standardized mean difference [SMD] = –0.79, 95% confidence intervals [CI]: –1.03 to –0.54, P < 0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls. Regarding macular parameters, values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness (pooled SMD: –0.44, 95% CI: –0.67 to –0.20, P = 0.0003), foveal thickness (pooled SMD = –0.39, 95% CI: –0.58 to –0.19, P < 0.0001), ganglion cell inner plexiform layer (SMD = –1.26, 95% CI: –2.24 to –0.27, P = 0.01) and macular volume (pooled SMD = –0.41, 95% CI –0.76 to –0.07, P = 0.02). Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls. Superficial vessel density (pooled SMD = –0.42, 95% CI: –0.68 to –0.17, P = 0.0001) and deep vessel density (pooled SMD = –0.46, 95% CI: –0.75 to –0.18, P = 0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone (SMD = 0.84, 95% CI: 0.17–1.51, P = 0.01) was larger in controls. Vascular density and thickness of various retinal layers were decreased in Alzheimer’s disease patients compared to controls. Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monitoring and early diagnosis methods.

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein (SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.

Abstract The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson’s disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain’s glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson’s Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.

As a non-heat input solid-state joining technology, electromagnetic pulse welding (EMPW) has many advantages in the connection of dissimilar metals. Finite element (FE) methods are often used to design the EMPW equipment, explore the parameters and analyze the transient process. However, it is difficult to reflect the welding effect directly. This work proposed a welding effect evaluation model based on the welding window theory and the Vc-β trajectory curve obtained in the FE simulation. A FE model coupling the circuit-magnetic-structure field was established in COMSOL software to simulate the EMPW process of the Cu plate and Al plate. The Vc-β trajectory curve and welding traces were obtained according to the simulation results. An experimental platform WD-28 was used to carry out the welding experiments of Cu–Al plates at different discharging voltages. The welding traces were measured through SEM method and compared with the simulation results. According to the comparative result, the empirical constant of the calculation formula for the lower boundary of the welding window was adjusted into 1.6, so that the evaluation result was consistent with the experimental result. This work can provide a new method for evaluating directly the welding effect through the FE simulation results.

Orchids have been long fascinating biologists and ecologists because of their remarkable range of life history strategies, floral and vegetative morphology, pollination syndromes, and symbiotic fungi. However, the diversity and distribution patterns of orchids remain unclear in several regions, seriously hindering the understanding of orchid diversity and their maintenance mechanisms. In this study, species richness, abundance, and environmental conditions of epiphytic and terrestrial orchids were investigated along an elevation gradient of Mt. Victoria, Myanmar, ranging from 600 to 3000 m with 200-m intervals. A binary species-based network was structured between epiphytic orchids and their hosts to further address the effect of hosts on orchid distribution. In total, 94 orchid species were recorded, including 58 epiphytic and 36 terrestrial orchids. A hump-shaped pattern of epiphytic orchid richness occurred along the elevation gradient, with the highest richness at ca. 2200 m, whereas terrestrial orchid richness follows a monotonous decrease. Both elevation and slope significantly affected the species composition and diversity of epiphytic and terrestrial orchids, while terrestrial orchids were also affected by herb coverage. The network between epiphytic orchids and their hosts exhibited a low level of connectance, and significant nestedness with a high level of modularity and specialization. Interactions in the network were heterogeneously distributed among hosts, as Lithocarpus variolosus, Rhododendron arboretum, and Lyonia ovalifolia hosted a wide variety of orchid species and hence played an important role in maintaining the diversity pattern of epiphytic orchids, while the bulk of species exhibited few interactions. Twenty epiphytic orchids (such as Sunipia grandiflora, Liparis viridiflora, Porpax grandiflora and Liparis tsii), which were only attached to specific host species, may be exposed to a high risk of extinction with the intensification of human activities. This study provides basic data for the conservation and management of orchids in Mt. Victoria, Myanmar.

PurposeTo investigate changes in retinal circulation and the choroid in patients with acute myeloid leukemia (AML) in the acute and remission stages, to analyze the correlation between retinal circulation and laboratory parameters, and to assess risk factors associated with leukemic retinopathy.MethodsForty-eight patients (93 eyes) with AML were enrolled and divided into two groups according to fundus examination findings: the retinopathy and no retinopathy groups. Patients underwent eye measurements before treatment and after remission. Macular vessel density (VD), perfusion density (PD), foveal avascular zone (FAZ), and choroidal thickness (ChT) were measured using optical coherence tomography angiography. Patients with healthy eyes were recruited as control participants.ResultsPatients with leukemic retinopathy had higher measurements of white blood cells (WBCs), circulating blasts, fibrin degradation products, and cross-linked fibrin degradation products (D-dimer) and a lower hemoglobin (HB) count (p

Electromagnetic pulse crimping (EMPC) technology is expected to be applied to the connection of high-voltage (HV) wiring harnesses and terminals for electric vehicle (EV). As an important part of the EMPC system, the assembly of the field shaper and the coil can directly affect the effect of EMPC. An EMPC system was established in this work, including the control part, energy storage capacitor bank, discharge switch, coil, and field shaper. The relationship between structure parameters of the field shaper and the coil was analyzed through the EMPC experiment of Al tubes. The results showed that the relative position and height of field shaper and coil have no obvious effect on the deformation length of the Al tube. When the angle between the gap of the field shaper and the gap of the coil is 90°, the deformation of Al tube is the most uniform. When the total height of field shaper is slightly less than the welding coil, the crimping effect is the best. This work can help design the field shaper and the coil for EMPC.

Electromagnetic pulse spot welding technology (EPSW) has great application prospects in the field of electric vehicles due to the realization of spot welding without gasket. The EPSW of Cu/Al alloy in this article is carried out in two steps. The first step uses electromagnetic force to pre-process the aluminum plate to punch a hump through electromagnetic pulse forming (EMPF). The second step uses electromagnetic force to realize spot welding between the hump and the copper plate. This article studied effects of stamping and spot welding with discharge voltage between 10 kV and 15 kV and compared welding effects of spot welding with coils of different widths. The results show: electromagnetic pulse spot welding technology without gasket was realized; the higher the discharge voltage, the better the stamping effect and spot welding performance; the wide coil can achieve a flat welding interface while the narrow coil can achieve reliable connection at a lower discharge voltage.

The role of enhancer variants in hepatocellular carcinoma (HCC) predisposition remains unknown. Here, the authors perform a genome-wide survey of HCC-susceptible enhancer variants in 11,958 individuals, identify rs73613962 within the intronic region of PRMT7 and find that PRMT7 upregulation predisposes to HCC.

As a common emerging environmental pollutant, microplastics (MPs) have been detected in a variety of environmental media and human bodies. The potential toxic effects and mechanisms of MPs need to be revealed urgently. MPs can be deposited in the kidney, and exposure to high doses of MPs can cause nephrotoxicity in experimental animals. In this study, we investigated the effects of exposure to polystyrene microplastics (PS-MPs) at environmentally relevant doses (0.1 and 1 mg/L) on kidney structure, function, and transcriptome in mice. We found that mice exposed to PS-MPs in drinking water for eight weeks had no change in body weight or kidney coefficient. PS-MPs administration decreased the levels of blood urea nitrogen (BUN) in mice, while serum creatinine (CRE) and uric acid (UA) concentrations were unaffected. Through using periodic acid–Schiff (PAS) and Masson staining, we discovered that the glomerular tuft area increased in the PS-MP-treated mice, while the degree of renal fibrosis remained unchanged. Furthermore, renal cortex transcriptomic analysis identified 388 and 303 differentially expressed genes (DEGs) in the 0.1 and 1 mg/L dose groups, respectively. The DEGs were highly enriched in mitochondrial-related terms and pathways of thermogenesis and oxidative phosphorylation. Moreover, protein–protein interaction (PPI) network analysis revealed that cytochrome b-c1 complex subunit 10 (UQCR11) and cytochrome c oxidase subunit 3 (MT-CO3) were important node proteins. These findings suggest that environmental exposure to MPs can cause abnormalities in renal structure and filtration function and that long-term exposure to MPs may be a risk factor for renal disease.

Panax polysaccharides are biopolymers that are isolated and purified from the roots, stems, leaves, flowers, and fruits of Panax L. plants, which have attracted considerable attention because of their immunomodulatory activities. In this paper, the composition and structural characteristics of purified polysaccharides are reviewed. Moreover, the immunomodulatory activities of polysaccharides are described both in vivo and in vitro. In vitro, Panax polysaccharides exert immunomodulatory functions mainly by activating macrophages, dendritic cells, and the complement system. In vivo, Panax polysaccharides can increase the immune organ indices and stimulate lymphocytes. In addition, this paper also discusses the membrane receptors and various signalling pathways of immune cells. Panax polysaccharides have many beneficial therapeutic effects, including enhancing or activating the immune response, and may be helpful in treating cancer, sepsis, osteoporosis, and other conditions. Panax polysaccharides have the potential for use in the development of novel therapeutic agents or adjuvants with beneficial immunomodulatory properties.

Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. Results indicated that RPAP administration effectively alleviated LPS-induced intestinal damage in dose dependent. Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota.

BackgroundAnaerobic digestion (AD) is important in treating of food waste, and thousands of metagenome-assembled genomes (MAGs) have been constructed for the microbiome in AD. However, due to the limitations of the short-read sequencing and assembly technologies, most of these MAGs are grouped from hundreds of short contigs by binning algorithms, and the errors are easily introduced.ResultsIn this study, we constructed a total of 60 non-redundant microbial genomes from 64.5 Gb of PacBio high-fidelity (HiFi) long reads, generated from the digestate samples of a full-scale biogas plant fed with food waste. Of the 60 microbial genomes, all genomes have at least one copy of rRNA operons (16S, 23S, and 5S rRNA), 54 have ≥18 types of standard tRNA genes, and 39 are circular complete genomes. In comparison with the published short-read derived MAGs for AD, we found 23 genomes with average nucleotide identity less than 95% to any known MAGs. Besides, our HiFi-derived genomes have much higher average contig N50 size, slightly higher average genome size and lower contamination. GTDB-Tk classification of these genomes revealed two genomes belonging to novel genus and four genomes belonging to novel species, since their 16S rRNA genes have identities lower than 95 and 97% to any known 16S rRNA genes, respectively. Microbial community analysis based on the these assembled genomes reveals the most predominant phylum was Thermotogae (70.5%), followed by Euryarchaeota (6.1%), and Bacteroidetes (4.7%), and the most predominant bacterial and archaeal genera were Defluviitoga (69.1%) and Methanothrix (5.4%), respectively. Analysis of the full-length 16S rRNA genes identified from the HiFi reads gave similar microbial compositions to that derived from the 60 assembled genomes.ConclusionHigh-fidelity sequencing not only generated microbial genomes with obviously improved quality but also recovered a substantial portion of novel genomes missed in previous short-read based studies, and the novel genomes will deepen our understanding of the microbial composition in AD of food waste.

Purpose: To investigate the clinical features and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia (MP) with secondary MRSA bloodstream infections (MRSA-BSI) (termed MP-BSI) compared with MP alone and to study the incidence of MP-BSI among patients with MP. Methods: This was a retrospective, single-center study with clinical data derived from previous medical records. The cases were divided into groups: MP alone and MP-BSI. The determination of independent risk factors for MP-BSI relied on logistic regression analysis. Additionally, the crude outcomes were compared. Results: A total of 435 patients with MP were recruited, with 18.9% (82/435) having MP-BSI. The median age was 62 (interquartile range, 51,72) years, and 74.5% of the patients were male. Multivariate analysis revealed that immunosuppression, community-acquired MP (CA-MP), time from initial to targeted antibiotic use, high Sequential Organ Failure Assessment (SOFA) score, increased respiratory rate, and elevated γ-GT level (all p < 0.05) were independent risk factors for MP-BSI, while targeted treatment with linezolid was a protective factor. Patients with MP-BSI had a longer duration of hospitalization (median days, 27.5 vs. 19, p = 0.001), a higher 28-day mortality rate (24.4% vs. 11.0%, p = 0.001), and a higher in-hospital mortality rate (26.8% vs. 14.7%, p = 0.009) than those with MP alone. Conclusion: Secondary MRSA-BSI among patients with MP is not rare. Immunosuppression, CA-MP, time from initial to targeted antibiotic use, high SOFA score, increased respiratory rate and elevated γ-GT level are all independent risk factors for MP-BSI; however, linezolid, as a targeted antibiotic, is a protective factor. Moreover, patients with MP may have worse clinical outcomes when they develop MRSA-BSI.

Epiphytes typically exhibit clustered distribution patterns, but predicting the spatial variation of their distribution at fine scales has long been a challenge. Taking advantage of a canopy crane giving access to 1.1 ha of lowland seasonal rainforest in Yunnan (China), we assess here which factors promote the probability that a given tree hosts epiphytes, and the variation of species richness and abundance of epiphytic spermatophytes and ferns among trees. Variation in epiphyte species richness as a function of host tree size, characteristics of its surrounding environment, topography and microclimatic conditions, were analyzed by Random Forest. Epiphytic spermatophytes and ferns occupied 2.3 and 10.8% of the available host trees, respectively. Significant models predicting which trees are more likely to host epiphytes than others were obtained, indicating that host tree characteristics and their local environment play a significant role in determining which host tree is most likely to be colonized. These models, as well as models for species richness and abundance, however, exhibited a moderate to low accuracy (r2 0.28 and 0.24 and of 0.12 and 0.14 for spermatophyte and fern richness and abundance, respectively). The best predictor of the presence of epiphytes on a tree, of its epiphytic species richness and abundance, was its DBH. In ferns, however, two peaks of species richness were observed, representing shade-loving ferns on small trees and sun-loving ferns on large trees. Microclimatic conditions and light intensity were the second best factor accounting for variation in species richness and abundance among trees. The contribution of liana infestation, host tree identity, and characteristics of neighboring trees were marginal. Our inclusion of a large number of host-tree characteristics and their local environment did not allow for an apparent improvement of model accuracy over studies with a more limited number of predictors, pointing to the role of chance upon tree colonization. Our results confirm the utmost importance of large trees with emergent canopies for the conservation of the epiphytic flora, but also indicate that epiphytic diversity assessments in tropical forests must also include small understorey trees, which should be further considered for conservation. The importance of the micro-climatic conditions that prevail at the level of each individual host tree further points to the necessity of maintaining a buffer zone around large host trees targeted for conservation.

Purpose: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck, while metastasis is the main cause of OSCC-related death. There is an urgent need to explore novel prognostic biomarkers and identify biological targets related to metastasis in OSCC treatment.Methods: Analysis of differential expression was performed using datasets in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) was conducted to assess the expression of betacellulin (BTC) in OSCC. SCC4 and CAL27 cells were used for in vitro experiments, in which CCK-8, transwell assays, and wounding healing assays were performed to verify the biological functions of BTC. The role of BTC in EMT was analyzed by EMT score and Western blot.Results: Through the analysis of the mRNA expression profile data from TCGA database in OSCC, we found that only low expression of BTC was significantly correlated with a poor prognosis in OSCC patients. The results of IHC assays and TCGA databases showed that the expression level of BTC was related to the tumor stage, histological grade, and metastasis status. In vitro analysis showed that overexpression of BTC significantly suppressed the proliferation and migration of OSCC cells. Furthermore, we confirmed that BTC could affect EMT through the PI3K-AKT signaling pathway.Conclusion: The overexpression of BTC suppresses the proliferation, migration, and EMT of OSCC cells via the PI3K-AKT pathways, leading to a better prognosis in OSCC. BTC may be used as a novel molecular marker to assess the prognosis of OSCC patients.

Background: Protopanaxatriol (PPT) is a secondary intestinal metabolite of ginsenoside in ginseng. Although the effects of PPT have been reported in various diseases including cancer, diabetes and inflammatory diseases, the skin protective effects of PPT are poorly understood. Methods: HaCaT cells were treated with PPT in a dose-dependent manner. mRNA and protein levels which related to skin barrier and hydration were detected compared with retinol. Luciferase assay was performed to explore the relative signaling pathway. Western blot was conducted to confirm these pathways and excavated further signals. Results: PPT enhanced the expression of filaggrin (FLG), transglutaminase (TGM)-1, claudin, occludin and hyaluronic acid synthase (HAS) −1, −2 and −3. The mRNA expression levels of FLG, TGM-1, HAS-1 and HAS-2 were suppressed under NF-κB inhibition. PPT significantly augmented NF-κB-luc activity and upregulated Src/AKT/NF-κB signaling. In addition, PPT also increased phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK, JNK and p38 and upstream MAPK activators (MEK and MKK). Furthermore, transcriptional activity of AP-1 and CREB, which are downstream signaling targets of MAPK, was enhanced by PPT. Conclusion: PPT improves skin barrier function and hydration through Src/AKT/NF-κB and MAPK signaling. Therefore, PPT may be a valuable component for cosmetics or treating skin disorders.

Abstract Background The neuropathological hallmarks of Alzheimer’s disease (AD) are amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The amyloid cascade theory is the leading hypothesis of AD pathology. Aβ deposition precedes the aggregation of tau pathology and Aβ pathology precipitates tau pathology. Evidence also indicates the reciprocal interactions between amyloid and tau pathology. However, the detailed relationship between amyloid and tau pathology in AD remains elusive. Metformin might have a positive effect on cognitive impairments. However, whether metformin can reduce AD-related pathologies is still unconclusive. Methods Brain extracts containing tau aggregates were unilaterally injected into the hippocampus and the overlying cerebral cortex of 9-month-old APPswe/PS1DE9 (APP/PS1) mice and age-matched wild-type (WT) mice. Metformin was administrated in the drinking water for 2 months. Aβ pathology, tau pathology, plaque-associated microgliosis, and autophagy marker were analyzed by immunohistochemical staining and immunofluorescence analysis 2 months after injection of proteopathic tau seeds. The effects of metformin on both pathologies were explored. Results We observed tau aggregates in dystrophic neurites surrounding Aβ plaques (NP tau) in the bilateral hippocampi and cortices of tau-injected APP/PS1 mice but not WT mice. Aβ plaques promoted the aggregation of NP tau pathology. Injection of proteopathic tau seeds exacerbated Aβ deposits and decreased the number of microglia around Aβ plaques in the hippocampus and cortex of APP/PS1 mice. Metformin ameliorated the microglial autophagy impairment, increased the number of microglia around Aβ plaques, promoted the phagocytosis of NP tau, and reduced Aβ load and NP tau pathology in APP/PS1 mice. Conclusion These findings indicate the existence of the crosstalk between amyloid and NP tau pathology. Metformin promoted the phagocytosis of pathological Aβ and tau proteins by enhancing microglial autophagy capability. It reduced Aβ deposits and limited the spreading of NP tau pathology in APP/PS1 mice, which exerts a beneficial effect on both pathologies.