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Abstract Objective To characterize the retinal microvasculature and structure in subjective cognitive decline (SCD) and identify the potential biomarker for the early stage of the Alzheimer's disease (AD) spectrum. Methods In this study, 35 patients with SCD, 36 with cognitive impairment, and 29 with normal cognition (NC) were enrolled. Optical coherence tomography angiography was employed to assess retinal vascular density, fovea avascular zone area, and retinal thickness. The parameters reflecting retinal perfusion and structure were compared among the three groups. In addition, the association between retinal parameters, cerebral blood flow (CBF), and peripheral blood biomarkers in the SCD stage was analyzed. Results The superficial vascular complex (SVC) vascular density in the macula and retinal nerve fiber layer thickness in the peripapillary were significantly reduced in individuals with SCD compared to NC. Furthermore, there was a positive correlation between macular ganglion cell complex thickness and CBF in SCD. Interpretation The retinal microvasculature and structure exhibit alterations in individuals with SCD. Macular ganglion cell complex thickness demonstrates correlations with cerebral perfusion. The retina holds potential as a novel biomarker for early detection of AD.

Abstract Aim To examine and analyze the level of spiritual care competency among community nurses. Design The study employed a cross‐sectional design. Methods From May to July 2022, 442 nurses from community health clinics were chosen as survey respondents using the convenience sample method. The General Information Questionnaire, the version in Chinese of the Nurses' Spiritual Caregiving Awareness Scale and the Chinese version of the Spiritual Caregiving Competence Scale were used in the survey. There were 442 questionnaires distributed, 422 were collected, and the response rate was 95.4%. Results The amount of spiritual care competencies of community nurses was positively correlated with the level of spiritual awareness. Simultaneously, their level of education, religious beliefs, marital status and the degree of knowledge of spirituality were all influenced.

Conventional quality control methodologies are inadequate for fully elucidating the aberrant patterns of product quality. A multitude of factors influence product quality, yet the limited number of controlled quality characteristics is insufficient for accurately diagnosing quality abnormalities. Additionally, there are asymmetries in data collection, data pre-processing, and model interpretation. In this context, a quality anomaly recognition and diagnosis model for the complex product manufacturing process is constructed based on a deep residual network, support vector machine (SVM), and Shapley additive explanation (SHAP). Given the numerous complex product quality characteristic indexes and unpredictable accidental factors in the production process, it is necessary to mine the deep relationship between quality characteristic data and quality state. This mining is achieved by utilizing the strong feature extraction ability of the deep residual shrinkage network (DRSN) through self-learning. The symmetry of the data within the model has also been taken into account to ensure a more balanced and comprehensive analysis. The excellent binary classification ability of the support vector machine is combined with the DRSN to identify the quality anomaly state. The SHAP interpretable model is employed to diagnose the quality anomaly problem of a single product and to identify and diagnose quality anomalies in the manufacturing process of complex products. The effectiveness of the model is validated through case analysis. The accuracy of the DRSN-SVM quality anomaly recognition model reaches 99%, as demonstrated by example analysis, and the model exhibits faster convergence and significantly higher accuracy compared with the naive Bayesian model classification and support vector machine classification models.

ObjectiveThe objective of this study was to explore the learning preferences and habits of medical students during the pandemic home e-learning, and to investigate the incidence of adverse emotions, optimistic character level and coping style. To explore the influencing factors of adverse emotions.MethodsA cross-sectional survey was conducted in China from March to June 2022. Medical students were recruited from three universities in China, and a questionnaire survey was conducted. The questionnaires consisted of a “e-learning preferences and habits questionnaire”, life orientation test questionnaire (LOT-R), and simple coping style questionnaire (SCSQ). Finally, a total of 492 medical students who met the inclusion and exclusion criteria became the research subjects and completed the survey.ResultsA total of 57.7% believed they experienced no adverse emotions during home e-learning. ① During the COVID-19 pandemic, the score of optimistic personality of medical students was (7.25 ± 1.933), and the score of pessimistic personality was (5.82 ± 2.240). The score of positive coping was (21.75 ± 5.379), and the score of negative coping was (11.75 ± 3.611). ② The occurrence of medical students' adverse emotions during e-learning was influenced by “Whether there is a private, quiet space to study”, “Degree of knowledge mastery”, “Physical discomfort or not”, “Keep a regular schedule or not”, “Optimistic personality tendency”.ConclusionThis study demonstrates the during home e-learning, most medical students have their own learning equipment and can meet their learning needs. Their favorite mobile device to use is a mobile phone, and their favorite method of teaching is to provide course playback. More than half of medical students believe that they have some inconvenience in conducting research during home e-learning. With regard to teacher's real-time screen, the largest number of medical students support teachers turning on live screens so that they feel like they are interacting with the teacher. The preference for blended teaching is highest among medical students. In general, medical students were highly adaptive of the newest e-learning approach. Based on the statistic analysis, the factors that “Whether there is a private, quiet space to study”, “Degree of knowledge mastery”, “Physical discomfort or not”, “Keep a regular schedule or not”, and “Optimistic personality tendency” may be the influencing factors for the occurrence of adverse emotions.

PurposeTo investigate the effective connectivity (EC) changes after multisite repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (COG).MethodWe selected 51 patients with mild or moderate Alzheimer's disease (AD) and delivered 10 Hz rTMS over the left dorsal lateral prefrontal cortex (DLPFC) and the lateral temporal lobe (LTL) combined with COG or sham stimulation for 4 weeks. The selected AD patients were divided into real (real rTMS+COG, n = 11) or sham (sham rTMS+COG, n = 8) groups to undergo neuropsychological assessment, resting-state fMRI, and 3D brain structural imaging before (T0), immediately at the end of treatment (T4), and 4 weeks after treatment (T8). A 2 × 3 factorial design with “time” as the within-subjects factor (three levels: T0, T4, and T8) and “group” as the between-subjects factor (two levels: real and sham) was used to investigate the EC changes related to the stimulation targets in the rest of the brain, as well as the causal interactions among seven resting-state networks based on Granger causality analysis (GCA).ResultsAt the voxel level, the EC changes from the left DLPFC out to the left inferior parietal lobe and the left superior frontal gyrus, as well as from the left LTL out to the left orbital frontal cortex, had a significant group × time interaction effect. At the network level, a significant interaction effect was identified in the increase in EC from the limbic network out to the default mode network. The decrease in EC at the voxel level and the increase in EC at the network level were both associated with the improved ability to perform activities of daily living and cognitive function.ConclusionMultisite rTMS combined with cognitive training can modulate effective connectivity in patients with AD, resulting in improved ability to perform activities of daily living and cognitive function.

Abstract Background Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potential targets for therapeutic approaches in metabolic disorders, including obesity. All adipocytes, including beige adipocytes, differentiate from mesenchymal stem cells (MSCs), which may provide an important path for clinical intervention; however, the mechanism of beiging of human adipose cell-derived MSCs is not fully understood. Here, we provide insights on the role of IRISIN, which is known to be secreted by skeletal muscle and promote beiging of white fat. Results We established an IRISIN-induced mesenchymal stem cell beiging model and found that IRISIN protein interacts with the MSC membrane protein TRPC3. This interaction results in calcium influx and consequential activation of Erk and Akt signaling pathways, which causes phosphorylation of PPARγ. The phosphorylated PPARγ enters the nucleus and binds the UCP1 promoter region. Furthermore, the role of TRPC3 in the beiging of MSCs was largely abolished in Trpc3−/− mice. We additionally demonstrate that the calcium concentration in the brain of mice increases upon IRISIN stimulation, followed by an increase in the content of excitatory amino acids and norepinephrine, while Trpc3−/− mice exhibit the reverse effect. Conclusions We found that TRPC3 is a key factor in irisin-induced beiging of MSCs, which may provide a new target pathway in addressing metabolic disorders. Our results additionally suggest that the interaction of irisin with TRPC3 may affect multiple tissues, including the brain. Graphical abstract

Background and purposeHypoperfusion of the posterior cingulate cortex (PCC) and precuneus has consistently been reported in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (COG) is effective in alleviating the symptoms of patients with mild AD. This study investigated the effects of rTMS-COG therapy on cerebral blood flow (CBF), with a special interest in the PCC/precuneus, and whether observed CBF changes are associated with changes in neuropsychological assessments in AD.Materials and methodsTwenty-one patients with mild or moderate AD were randomly divided into real rTMS (n = 11) and sham treatment (n = 10) groups, both combined with COG. Neuro-navigated 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex (DLPFC) and then the left lateral temporal lobe (LTL) for 20 min each day for 4 weeks in the real rTMS group. All patients with AD underwent neuropsychological assessment, pseudo-continuous arterial spin labeling, and structural 3D T1-weighted MRI before treatment (T0), immediately after treatment (T1), and 4 weeks after treatment (T2). CBF in the precuneus, PCC, and stimulation targets at the region-of-interest (ROI) level, as well as whole-brain CBF changes at the voxel level, were compared between the two groups at three timepoints.ResultsrTMS-COG therapy revealed significant group × time interactions for the Mini-Mental State Examination (F = 5.339, p = 0.023, η2 = 0.433) and activities of daily living (F = 5.409, p = 0.039, η2 = 0.436) scores. The regional CBF in the precuneus showed a significant group × time interaction (F = 5.833, p = 0.027, η2 = 0.593). For voxel-level analysis, a significant group main effect was found in the left limbic lobe cluster, with the maximal peak in the left parahippocampus (p < 0.001, uncorrected, peak at [−16 −8 −24]). Simple effects analysis indicated that rTMS-COG therapy induced a decrease in CBF in the precuneus at T1 (p = 0.007) and an increase in the left parahippocampus at T2 (p=0.008). CBF decrease in the precuneus was correlated with better cognitive function immediately after treatment (T1) (r =−0.732, p=0.025).ConclusionNeuropsychological assessments showed immediate and long-term effects on cognitive function and activities of daily living after rTMS-COG therapy. CBF changes induced by high-frequency rTMS-COG therapy are region-dependent, showing immediate effects in the precuneus and long-term effects in the left parahippocampus. These results provide imaging evidence to understand the underlying neurobiological mechanism for the application of rTMS-COG in AD.

BackgroundObservational studies have suggested that peripheral immune disorders are associated with amyotrophic lateral sclerosis (ALS). Previous studies predominantly focused on changes in adaptive immunity. However, emerging evidence showed natural killer (NK) cells, an essential component of innate immunity, were involved in the degeneration of motor neurons. However, the causal relationship between dysregulated NK cells-related immune traits and ALS remains unclear.ObjectiveThis study aimed to explore the causal relationship between NK cells-related immune traits and the risk of ALS.Materials and methodsSingle nucleotide polymorphisms (SNPs) significantly associated with NK cells-related immune traits were selected as instrumental variables to estimate their causal effects on ALS. SNPs from a genome-wide association study (GWAS) on NK cells-related immune traits were used as exposure instruments, including an absolute NK-cells count, absolute HLA-DR+ NK-cells count, NK cells/lymphocytes, NK cells/CD3– lymphocytes, HLA DR+ NK cells/NK cells, HLA DR+ NK cells/CD3– lymphocytes, and the median fluorescence intensities of CD16–CD56+ on NK cells and HLA-DR+ NK cells. Summary-level GWAS statistics of ALS were used as the outcome data. Exposure and outcome data were analyzed using the two-sample Mendelian randomization (MR) method.ResultsEach one standard deviation increase in the expression levels of CD16–CD56+ on NK cells and HLA-DR+ NK cells were associated with a lower risk of ALS in both the MR-Egger and inverse variance weighted methods (P < 0.05). The results proved robust under all sensitivity analyses. Neither instrumental outliers nor heterogeneity were detected.ConclusionOur results suggest that higher expression levels of CD16–CD56+ on NK cells and HLA-DR+ NK cells are associated with a lower risk of ALS.

Abstract Lung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.

A growing body of evidence suggests immune involvement in the pathology of multiple system atrophy (MSA). Research on detailed peripheral immune indices, however, is relatively sparse, and is one of the intriguing aspects of MSA yet to be elucidated. A total of 26 MSA patients and 56 age-and sex-matched healthy controls (HC) were enrolled in the current case-control study to delineate the peripheral immune traits of MSA patients. The ratio of CD4+/CD8+ T cells, natural killer cells, CD28 expression on both CD4+ T cells and CD8+ T cells increased in MSA patients compared to HC, but CD8+ T cells and active marker (HLA-DR) expression on total T cells decreased (p < 0.05). This study sheds light on the dysregulation of cellular immunity in MSA, pointing to future mechanistic research.

Chronic sleep insufficiency is becoming a common issue in the young population nowadays, mostly due to life habits and work stress. Studies in animal models of neurological diseases reported that it would accelerate neurodegeneration progression and exacerbate interstitial metabolic waste accumulation in the brain. In this paper, we study whether chronic sleep insufficiency leads to neurodegenerative diseases in young wild-type animals without a genetic pre-disposition. To this aim, we modeled chronic sleep fragmentation (SF) in young wild-type mice. We detected pathological hyperphosphorylated-tau (Ser396/Tau5) and gliosis in the SF hippocampus. 18F-labeled fluorodeoxyglucose positron emission tomography scan (18F-FDG-PET) further revealed a significant increase in brain glucose metabolism, especially in the hypothalamus, hippocampus and amygdala. Hippocampal RNAseq indicated that immunological and inflammatory pathways were significantly altered in 1.5-month SF mice. More interestingly, differential expression gene lists from stress mouse models showed differential expression patterns between 1.5-month SF and control mice, while Alzheimer's disease, normal aging, and APOEε4 mutation mouse models did not exhibit any significant pattern. In summary, 1.5-month sleep fragmentation could generate AD-like pathological changes including tauopathy and gliosis, mainly linked to stress, as the incremented glucose metabolism observed with PET imaging suggested. Further investigation will show whether SF could eventually lead to chronic neurodegeneration if the stress condition is prolonged in time.

BackgroundIn this study, we evaluated the prognostic value of the plasma levels of Epstein-Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma (NPC) at different treatment stages.MethodsWe retrospectively analyzed the Data of 206 patients with NPC. Pre-neoadjuvant chemotherapy (pre-NACT), post-NACT, post-radiotherapy, and post-treatment plasma EBV DNA levels were used to establish prognostic nomograms. The concordance index (C-index) and calibration curves were used to compare the prognostic accuracy of the nomograms. The results were confirmed in a validation cohort consisting of patients who were tested for EBV DNA levels at all four stages of treatment. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Survival differences were calculated using the log-rank test.ResultsEBV DNA-positive patients had worse 3-year PFS and 5-year OS than EBV DNA-negative patients; this was true for pre-NACT (PFS: 82.7% vs. 57.3%, P < 0.001; OS: 90.9% vs. 68.7%, P = 0.08) and post-NACT (PFS: 85.0% vs. 50.6%, P < 0.001; OS: 91.7% vs. 65.7%; P = 0.001) EBV DNA levels but not for post-radiotherapy (PFS: 72.2% vs. 60.9%, P = 0.192; OS: 73.1% vs. 77.2%, P = 0.472) or post-treatment (PFS: 77.3% vs. 59.2%, P = 0.063; OS: 77.5% vs. 79.7%, P = 0.644) levels. Nomograms combining pre-NACT and post-NACT EBV DNA levels had a superior prognostic ability than those of post-radiotherapy and post-treatment EBV DNA levels.ConclusionPre-NACT EBV DNA levels combined with post-NACT EBV DNA levels can more reliably predict survival outcomes in patients with NPC.

There are lots of general parts with frequent maintenance and high interchangeability for continuous casting machine during its operation and maintenance. To acquire the service information of each general part under the environment of high temperature and serious oil pollution for predicting remaining life and preventative maintenance, a digital twin-driven monitoring and traceability system for general parts in continuous casting machine is proposed. First, the systematic architecture of proposed approach is given in detail, where a typical five-layer model for digital twin-driven monitoring and traceability is established. Second, the Web-based 3D visualization monitoring for continuous casting machine is achieved by using lightweight 3D twin model. After that, an assembly model based on polychromatic sets is built for expressing and describing the assembly relationships and assembly process of general parts. Meanwhile, an encoding rule for part and position is put forward by considering assembly position information. On the basis of that, the general parts with total process information are traced in the service life cycle. Finally, digital twin-based 3D visualization monitoring and traceability prototype system is developed and implemented, where the experiment cases verify the effectiveness and feasibility of the proposed approach.

Background: Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer's disease (AD). Dysregulation of the endosomal–autophagic–lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction. Methods: We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4–7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis. To further explore the mechanism of EAL dysregulation in AD, components of the class III phosphatidylinositol 3-kinase (PI3KC3) complex, activators of Rab7 (Beclin1 and UVRAG), and the negative regulator of Rab7 (Rubicon) were also measured in this two brain regions. Results: In 7-month-old APP/PS1 brain that amyloid beta initiated to accumulate intracellularly, EAL pathway, and related PI3KC3 members, UVRAG and Beclin1 were upregulated both in cortex and hippocampus (all P < 0.05). By the age of 12 months old, when abundant amyloid plaques formed, EAL markers, UVRAG, and Beclin1 were also upregulated in the cortex (all P < 0.05). However, Rab7 was decreased significantly (P = 0.0447), accompanied by a reduction of its activating PI3KC complex component Beclin1 (P = 0.0215) and enhancement of its inhibiting component Rubicon (P = 0.0055) in the hippocampus. Conclusions: Our study implies that EAL pathway, represented as Rab7 and its PI3KC3 regulators' expressions, showed temporal and spatial variation in brains at different stages of AD. It provides new insights into the role of EAL pathway in pathogenesis and indicates potential therapeutic targets in neurodegenerative diseases.

Background: Simulations by transport codes are indispensable for extracting valuable physical information from heavy-ion collisions. Pion observables such as the π-/π+ yield ratio are expected to be sensitive to the symmetry energy at high densities. Purpose: To evaluate, understand, and reduce the uncertainties in transport-code results originating from different approximations in handling the production of Δ resonances and pions. Methods: We compare ten transport codes under controlled conditions for a system confined in a box, with periodic boundary conditions, and initialized with nucleons at saturation density and at a temperature of 60 MeV. The reactions NN↔NΔ and Δ↔Nπ are implemented, but the Pauli blocking and the mean-field potential are deactivated in the present comparison. Thus, these are cascade calculations including pions and Δ resonances. Results are compared to those from the two reference cases of a chemically equilibrated ideal gas mixture and of the rate equation. Results: For the numbers of Δ and π, deviations from the reference values are observed in many codes, and they depend significantly on the size of the time step. These deviations are tied to different ways in ordering the sequence of reactions, such as collisions and decays, that take place in the same time step. Better agreements with the reference values are seen in the reaction rates and the number ratios among the isospin species of Δ and π. Both the reaction rates and the number ratios are, however, affected by the correlations between particle positions, which are absent in the Boltzmann equation, but are induced by the way particle scatterings are treated in many of the transport calculations. The uncertainty in the transport-code predictions of the π-/π+ ratio, after letting the existing Δ resonances decay, is found to be within a few percent for the system initialized at n/p=1.5. Conclusions: The uncertainty in the final π-/π+ ratio in this simplified case of particles in a box is sufficiently small so that it does not strongly impact constraining the high-density symmetry energy from heavy-ion collisions. Most of the sources of uncertainties have been understood, and individual codes may be further improved in future applications. This investigation will be extended in the future to heavy-ion collisions to ensure the problems identified here remain under control.

Fever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, prostaglandin E2(PGE2), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase (p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels (p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1β, IL-6, and TNF-α levels (p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE2 levels (p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels (p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE2, and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, PGE2, and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. [ABSTRACT FROM AUTHOR]

The Facility for Rare Isotope Beams (FRIB) will be a world-leading laboratory for the study of nuclear structure, reactions and astrophysics. Experiments with intense beams of rare isotopes produced at FRIB will guide us toward a comprehensive description of nuclei, elucidate the origin of the elements in the cosmos, help provide an understanding of matter in neutron stars and establish the scientific foundation for innovative applications of nuclear science to society. FRIB will be essential for gaining access to key regions of the nuclear chart, where the measured nuclear properties will challenge established concepts, and highlight shortcomings and needed modifications to current theory. Conversely, nuclear theory will play a critical role in providing the intellectual framework for the science at FRIB, and will provide invaluable guidance to FRIB's experimental programs. This review overviews the broad scope of the FRIB theory effort, which reaches beyond the traditional fields of nuclear structure and reactions, and nuclear astrophysics, to explore exciting interdisciplinary boundaries with other areas. © 2014 World Scientific Publishing Company.

Abstract Background To investigate the current status of health information-seeking behavior (HISB) of periodontitis patients, and to identity its main influencing factors using the Comprehensive Model of Information Seeking (CMIS). Methods In total, 274 periodontitis patients were recruited from a specialized dental hospital in Hangzhou by purposive sampling method for a cross-sectional study. Demographics, direct experience, salience, beliefs, characteristics and utility were 6 variables of CMIS. Data were collected from the patients by using the general information questionnaire, the Health Information Seeking Behavior Scale, the Self-Efficacy Scale for Self-care (SESS) for measuring belief, the Short Form of Health Literacy Dental Scale (HeLD⁃14) for measuring direct experience, and the Brief Illness Perception Questionnaire (BIPQ) for measuring salience. Univariate analysis and regression analysis were utilized to determine the factors influencing the HISB. Results The HISB score of periodontitis patients in this study was 3.68 ± 0.40. The low level of HISB was negatively associated with multiple factors, including age of 40 ~ 59 (odds ratio [OR] 0.041, 95% confidence interval [CI] 0.006–0.299), age of 18 ~ 39 (OR 0.053, 95%CI 0.008–0.364), low level of understandability of information (characteristic) [OR 0.317, 95%CI 0.119–0.840] and low level of satisfaction of information (utility) [OR 0.027, 95%CI 0.008–0.089]. However, low level of HISB was positively correlated with medium self-efficacy level [OR 3.112, 95% CI 1.463–6.747] and low self-efficacy level [OR 8.061, 95% CI 1.981–32.807]. Conclusions According to the CMIS model, we identified several factors influencing health-seeking behaviors (HISB). Lower levels of HISB are closely associated with older age and lower level of understandability and satisfaction of information. Conversely, higher self-efficacy may encourage patients to seek health information more actively. Therefore, it is essential to focus on elderly patients and assess their information expectations and needs in a timely manner, while also working to enhance their self-efficacy to promote more effective access to health information.

Abstract Background Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy. Objective We aimed to explore the key genes and pathways that affect the rate progression of DN. Methods Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6). Results Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway. Conclusion Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN.

Between 1958 and 1999, notable lithic localities recorded prehistoric activities in Xiqiao Town of Nanhai District, Foshan City, Guangdong Province, from which double-shouldered and microlith-stone artefacts were uncovered. Currently, the "Xiqiaoshan site" is recognized as a substantial Neolithic quarry and processing location, dating back to 4‒7 ka B P. Subsequently, from 2011 to 2022, we conducted multiple geological environmental surveys and analyses on Xiqiaoshan Mountain. A well-preserved Quaternary stratigraphic profile was discovered north of Fuxian village in the southeast foothills of Xiqiaoshan Mountain. The sedimentological, geochemical, and geochronological results indicate the presence of two primary sedimentary strata in the Fuxian locality. The upper unit comprises the Holocene swamp facies, with a calibrated AMS14C dating range from 5052‒5409 a B P; whereas, the lower unit comprises the late Pleistocene alluvial-diluvial strata, with a calibrated AMS14C dating range from 38420‒40502 a B P, and an optically stimulated luminescence (OSL) dating range of 41.977‒43.796 ka B P. Late Pleistocene strata yielded two sand-gravel layers containing Paleolithic artefacts, which are marked as layers A1 and A2. The predominant artefacts in lower layer A1 include larger scrapers, pointed tools, tongue-shaped edged tools, and small flake tools, such as various scrapers, denticulates, notches, knives, utilized flakes, and cores, including tanged axe-shaped knives. In the upper layer A2, backed or tanged knives appear more frequently. The other small flake tools from this layer (A2) were not significantly different from those in lower layer A1. One bifacially prepared core for producing small elongated flakes is of particular interest for this artefact. Based on the average deposition rate, the computational age of the A1 layer was 46.511‒47.325 ka B P, whereas that of the A2 layer was 41.977‒42.167 ka B P. Although the number of artefacts within the Holocene sediments (>5 ka B P) overlying the late Pleistocene strata is limited, the characteristics of inheritance and development are still evident in the types of artefacts. The discovery presented in this study has completely updated and extended the connotation of Xiqiaoshan National Geopark and "Xiqiaoshan culture,"breaking through the late Pleistocene Paleolithic remains records with exact dating in the Pearl River Delta region for the first time. Therefore, a ground-breaking discovery can accurately trace the footsteps of modern humans in the coastal areas of South China from 40‒50 ka. It also reveals the rich features of lithic industry and the developmental characteristics and evolution of its cultural connotations during this period. The present study shows that during the relatively warm and humid conditions of marine isotope stages 3 (MIS3) interglacial period and the subsequent cold and arid stage of MIS2, human population in the Fuxian locality encountered environmental challenges and adopted new subsistence strategy, which is of great significance for understanding modern human responses and adaptations to global and regional environmental and climate change.

Abstract Backgroud Systemic lupus erythematosus is an unexplained autoimmune disease involving multiple systems throughout the body, and its ocular changes include dry eye, monocular or binocular visual field defects, vaso-occlusive diseases, or ischemic optic neuropathy. Case presentation This article reports a patient with SLE complicated with bilateral Purtscher like retinopathy, who had a sudden decrease in ocular vision as the first symptom, the autoantibodies related to phospholipid syndrome showed no abnormality, and both anti-dsDNA antibodies and anti-SM antibodies were significantly positive, indicating that anti-dsDNA antibodies and anti-SM antibodies were also important factors in the pathogenesis of Purtscher like retinopathy. Conclusion The close relationship between SLE retinopathy and systemic inflammatory activities and emphasize the importance of systemic immunotherapy.

Abstract Objective This study aims to investigate the effect of CD206 on the progression of hepatocellular carcinoma (HCC) and the regulation of the tumour immune microenvironment. Methods A subcutaneous mouse model of HCC was established and treated with CD206-overexpressing adenovirus by tail vein injection or CD206 antibody C068C2 by intratumoral injection. The hepatocarcinoma-bearing mice were divided into four groups (IgG+ tail vein adenovirus group, IgG group, C068C2+ tail vein adenovirus group and C068C2 group) to observe the changes in tumour weight and volume with different expression levels of CD206. The proportion of M2-type tumour-associated macrophages (TAMs) was detected by flow cytometry and immunofluorescence. The apoptosis of tumour cells was detected using terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining, and inflammatory factors in serum and tissues were detected using the ENZYME-LINKED IMMUNOSORBENT ASSAY. Results Compared with the mice with low CD206 expression, the hepatocarcinoma-bearing mice with high CD206 expression in HCC exhibited faster tumour growth and more aggressive progression. Flow cytometry and immunofluorescence staining revealed that the expression level of CD206-positive M2-type TAMs was highest in the IgG + adenovirus group and lowest in the C068C2 group (p

Diabetic retinopathy(DR)is one of the major complications of diabetes mellitus, characterized by neurodegeneration and microangiopathy. Currently, the treatment of DR is mainly focused on the management of late complications and has not achieved the desired clinical outcome. Evidence suggests that the PI3K/AKT pathway, as one of the important intracellular signaling pathways during the cell cycle, is involved in the whole process of DR pathogenesis. This article focuses on the structural composition, activation and blocking pathways, conduction pathways, regulatory mechanisms and biological functions of the PI3K/AKT signaling pathway to review its role in DR and to explore the potential of targeting the PI3K/AKT pathway for the treatment of DR.

Objectives: Diamond tools are crucial in stone processing, and their performance is directly related to processing quality and cost. With the rise of stone and labor costs, the performance requirements on diamond tools are also increasing, including sharpness, self sharpening, tool life, and cutting efficiency. To improve efficiency and reduce costs, users often increase the cutting machine power and speed, which further requires diamond tools to have higher sharpness and strength at the risk of breakage. A practical method method is to increase the content of tin (Sn) in the segment to enhance its brittleness without changing the diamond concentration and particle size. However, an increase in Sn content will reduce the strength of the segment and may lead to a decrease in the holding force between CuSn alloy and diamond. For example, the commonly used CuSn10 and CuSn15 pre alloy powders in industry have low strength and weak holding force on diamond. Therefore, it is necessary to improve the powder properties and processing technology. Methods: Adding Zn element to CuSn10 alloy powder can improve powder strength and holding force. CuSnZn-x alloy powder (mass fraction of Zn, x=10.00%, 15.00%, 20.00%, 25.00%, 30.00%) was prepared by atomization process. The hot pressing sintering temperatures were 610 ℃, 615 ℃, 630 ℃, 645 ℃, 655 ℃, and the sintering pressure was 21 MPa. The melting temperature of CuSnZn alloy powder was tested using a differential thermal analyzer. The density of the sintered segment was tested using Archimedes drainage method. The bending strength of the sintered segment was tested using mechanical performance testing equipment. The Rockwell hardness of the sintered segment was measured using a Rockwell hardness tester. The microstructure morphology of the sintered segment and its fracture were analyzed using scanning electron microscopy. Other performances of samples with different Zn contents were analyzed and compared as well, namely theoretical density, Rockwell hardness, and flexural strength, to study the influence of Zn content on sample microstructure. Results: With the increase of Zn content, the rate of decrease in melting temperature of CuSnZn alloy powder first increases and then decreases. When the Zn mass fraction is 30%, the melting temperature decreases to 848 ℃, which is 164 ℃ lower than that of CuSn10. As the Zn content increases, the brass in the sintered segment gradually transforms from the α phase to the α+β phase and then the α+β+β´ phase, resulting in a significant increase in the Rockwell hardness of the segment. The bending strength of the sintered segment first increases and then decreases, reaching a maximum value of 542 MPa when the Zn mass fraction is 20.00%. When the mass fraction of Zn is 10.00% and 15.00%, obvious toughness dimples are observed on the fracture surface of the sintered segment, and particle peeling is observed on the fracture surface. The peeling surface is smooth and flat, indicating grain boundary peeling fracture of the phase structure. When the mass fraction of Zn is 20.00% and 25.00%, a large number of cleavage fracture surfaces are observed on the fracture surface of the sintered segment, and a small amount of smooth concave transgranular fracture is observed, which is partially intergranular fracture and partially transgranular fracture. When the mass fraction of Zn is 30.00%, the fracture surface of the sintered segment is flat and smooth, and the crack passes through the phase interface and grain along the hard and brittle structure, which is transgranular fracture. Conclusions: Adding Zn element can effectively reduce the melting point of alloy powder, and with the increase of Zn content, the hardness of sintered samples increases while the toughness decreases. When the Zn content is 30.00%, the melting temperature of CuSnZn alloy powder reaches its minimum value. When the Zn content exceeds 25.00%, the strength of the sintered samples will gradually decrease. Therefore, in actual production, the appropriate amount of Zn addition and sintering process should be selected based on comprehensive consideration of demand.

Abstract Background Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening. Methods This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated. Results A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p

Abstract Background Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy. Methods Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification. Results Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy. Conclusions This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes.

[Objective] In order to solve the issue of excessive redundant information in near-infrared spectroscopy, enhance the accuracy of wine quality evaluation models, a rapid and non-destructive method was established for wine quality evaluation. [Methods] A wine quality evaluation model was proposed based on competitive adaptive reweighting sampling method for feature wavelength screening and extreme learning machine improved by whale optimization algorithm. Various feature wavelength screening methods such as competitive adaptive reweighting sampling was used, and the most suitable method for wine spectral feature wavelength screening was determined. In response to the problem of initial value and hidden layer bias in ELM, the whale optimization method was used to optimize the initial value and hidden layer bias of ELM, and an wine quality evaluation model based on extreme learning machine improved by whale optimization algorithm was constructed. [Results] Compared with GA-ELM, PSO-ELM, and the traditional ELM model, the accuracy of WOA-ELM was the highest, reaching 0.944 5, which was better than GA-ELM (0.929 0), PSO-ELM (0.906 1) and traditional ELM (0.817 7). [Conclusion] The parameters of the ELM model optimized by intelligent algorithms can effectively improve the accuracy of wine quality evaluation.