Search

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.

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.

At present, new energy is introduced into the power system in large quantities. In order to make it replace the traditional hydropower and gas units as the black start power supply, segmentation restoration strategy of power grid based on the combined optical storage system is studied. Firstly, according to the structure and control mode of the optical storage system, the energy storage system establishes a stable grid-connected bus voltage is proposed, and the photovoltaic system is connected to the grid step by step. Secondly, in order to enhance the damping inertial support of photovoltaic power generation system, virtual synchronous control is proposed to be added to the inverter side of photovoltaic system. Finally, in the process of grid connection between the units to be started and the system load, the energy storage system is configured with additional damping controller to suppress the sub-synchronous oscillation generated by the grid black start, so as to ensure the stable recovery of the grid. In PSCAD/EMTDC, the electromagnetic transient simulation model of black start of the combined optical storage system is built and the simulation analysis is carried out. The results show that the busbar voltage deviation and system frequency deviation in the recovery process of the system are less than 0.65% and less than 1%, which meets the requirements of black start and verifies the feasibility of the start-up strategy proposed in the paper.

Abstract To investigate the distribution characteristics of selenium (Se) in mountainous soil-crop systems and examine the threshold value of Se-rich soil, 275 soil samples and 153 associated crop samples (rice, maize, tea, nuts, konjac, mushrooms, buckwheat, and coffee) were collected in Ximeng County, a typical mountainous area in southwest China. The total Se, available Se, organic matter, pH, sampling point elevation, and crop Se content were analyzed to examine the distribution characteristics of soil Se and the ability of primary crops to enrich Se in Ximeng County. Random forest and multiple regression models were established to identify the factors influencing the available soil Se and the crop Se enrichment coefficient. Finally, the Se-rich soil threshold was examined based on the total Se, available Se, and Se content in primary crops (rice, maize, and tea). The results showed soil Se resource abundance in the study region, with high Se soil accounting for 64.72% of the entire area. The soil Se content displayed significant spatial autocorrelation. The average Se enrichment coefficient of the main cultivated crops included mushrooms > nuts > rice > coffee > tea > maize > buckwheat > konjac. The total Se content in the soil had the highest impact on the available Se content in the soil and the Se enrichment coefficient of crops. A Se-rich soil threshold of 0.3 mg·kg−1 was used for rice and maize, while that of tea was 0.4 mg·kg−1. This result provided a theoretical basis for developing and utilizing Se resources in mountainous soil in southwestern China and dividing the Se-rich soil threshold.

The relationship between power transmission and reception in AC/DC interconnected power grids is complex， with numerous constraints on grid operation and regulation. Therefore， relying solely on manual expertise to assess the adjustment of power transmission and reception plans presents significant challenges. In response to the precise requirements of market-oriented transactions for adjusting interprovincial power transmission and reception plans， a method for analyzing the feasible domain of interprovincial transmission power is proposed. Firstly， based on the operational characteristics of AC/DC interconnected power grids， the modeling of operational constraints within the feasible scheduling domain is expanded. Subsequently， a model for the feasible domain of interprovincial transmission power is constructed， and solved using the ordered vertex search method. Finally， case studies are conducted based on the actual operational scenarios of the regional power grid in the south， and the effectiveness of the feasible domain for interprovincial transmission power is validated using the computational results of the entire network scheduling and optimization model. The calculation results of the feasible domain provide insight into the limit range of interprovincial transmission power under specific transmission and reception scenarios， thereby providing a reference basis for the verification and adjustment of medium to long-term power transmission and reception plans.

This study conducted the CO2-PTF coal experiment to further reveal the fracturing transformation mechanism of CO2 phase transition fracturing(CO2-PTF)coal. According to the CT scanning and 3D fracture reconstruction, we analyzed the fracture structure parameters of coal before and after CO2-PTF, and clarified the evolution characteristics of the three-dimensional fracture structure of coal induced by CO2-PTF. The research results indicated that after CO2-PTF, the total number of fractures in the coal sample decreased, while the total volume and surface area of fractures increased. The CO2-PTF generated fracture expansion and transformation effects where the small-scale fractures were expanded and transformed into larger scale fractures under the CO2-PTF pressure. The number, volume, and surface area of fractures of less than 1 000 μm in length were significantly reduced, while the volume and surface area of fractures of longer than 1 000 μm in length were significantly increased. The expansion and connection between fractures caused a decrease in their quantity. CO2-PTF improves the connectivity of the three-dimensional fracture in coal and is conducive to gas migration and production. This study offers new insights into and evaluation method for the effect of CO2-PTF, and could provide references for the research on fracture evolution characteristics in other unconventional natural gas reservoirs and their modifications.

BackgroundReproductive tract infections (RTIs) represent a critical public health concern impacting women’s health, particularly pronounced in developing countries. We aim to investigates the prevalence of self-reported RTI symptoms in women aged 18 to 65 and the factors influencing gynecological examination behavior and associated risks are explored.MethodsFrom May 6, 2022, to September 20, 2022, a comprehensive survey engaged 20,864 women aged 18 to 65 in 19 townships in Lueyang, Shaanxi. Each survey team, comprising a gynecologist, two female health center staff, and a master’s student, conducted face-to-face questionnaire surveys in villages and households. The questionnaire featured three sections: prevalence of self-reported RTI symptoms, gynecological examination history, and factors influencing examination behavior.ResultsThe high response rate of 98.69% yielded 20,590 valid questionnaires. Among surveyed women, 42.04% reported RTI symptoms, with a higher prevalence in those aged 30 and above, peaking at 44.88% in the 50–59 age group. Vulvar itching (24.73%), abnormal vaginal discharge (17.41%), and urinary tract irritation signs (11.73%) were most common. Older adult women (≥60) reported higher frequency and longer duration of symptoms. Only 9.88% of symptomatic women underwent gynecological examinations in 2022. Examination likelihood decreased with age, presenting a critical gap in healthcare utilization among older women. Reasons for checkups included routine checkups (47.02%), symptom concerns (41.29%), and the availability of free medical checkup programs (9.82%). Barriers included perceived lack of serious symptoms (23.7%), lack of necessity (4.41%) and lack of time (3.98%). Among those examined, 40.58% had a diagnosis of gynecological disorders, including pelvic inflammatory disease, human papilloma virus infection and cervical cancer.ConclusionWidespread RTI symptoms, particularly in perimenopausal and older women, underscore the need for enhanced healthcare. Barriers to gynecological examinations include awareness, education, and accessibility issues. Strategies must prioritize health education, routine examinations, and improved healthcare infrastructure in underdeveloped regions.

Objetivo: Descrever caso de aloimunização eritrocitária em paciente submetida a transfusão de concentrado de hemácias e que desenvolveu aloanticorpos contra todos os antígenos negativos em sua fenotipagem. Material e métodos: Paciente foi atendida em hospital privado em Salvador - Ba. Teste de ABO Rh, PAI e compatibilidade conforme protocolo. Quando indicada, imuno-hematologia realizada em Laboratório de Referência - GSH. Dados dos testes realizados foram coletados em sistema Real Blood. Caso: Paciente com doença parenquimatosa crônica do fígado, internada em hospital privado da cidade do Salvador - Ba por sangramento relacionado a varizes esofágicas. Submetida a transfusão de concentrado de hemácias filtradas em 18/03/2023, compatibilizado ABO e Rh conforme protocolo institucional, PAI negativo. Fenótipo C-, c+, E-, e+, Jka-, Jkb+, S-, s+. Exames imunohematológicos do seguimento evidenciaram surgimento progressivo de Anti C, Anti S, Anti E e Anti Jka. Discussão: O surgimento de anticorpos contra antígenos ausentes na hemácia do receptor caracteriza a aloimunizaçãio eritrocitária. A aloimunização eritrocitária é uma complicação relacionada à transfusão com incidência de 2-3% nos pacientes internados. A exposição a antígenos ausentes na hemácia do receptor causa o surgimento de aloanticorpos que são identificados através de testes de iimunohematologia. O caso descreve o surgimento de aloimunização contra todos os antígenos negativos em suas hemácias, incomum quando avaliamos a literatura. Conclusão: : A aloimunização eritrocitária é uma complicação relacionada à transfusão que pode ocasionar complicações hemolíticas graves. Pacientes em estado inflamatório agudo podem, ainda que de forma infrequente, desenvolver múltiplos aloanticorpos com poucas transfusões, dificultando transfusões subsequentes.

Understanding the vertical distribution characteristics of aerosols in dust weather is crucial for further discussion of aerosol-cloud interaction and its impacts on weather and climate. In response to a dust storm in Northwest China on 6 September 2023, Gansu Weather Modification Office conducts aircraft detection and operational flights on north slope of the Qilian Mountains, obtaining the vertical detection data of aerosols. The vertical distribution of aerosols in dust weather is analyzed, and causes of vertical distribution of dust aerosols, related meteorological factors and air mass sources are studied. Results show that the dust weather is formed under the combined action of the upper front area and the surface cold high pressure. Affected by the dust weather, the peak mass concentration of PM10 and PM2.5 reaches 1150 μg·m-3 and 282 μg·m-3, respectively, at Wuwei Environmental Monitoring Station on north slope of the Qilian Mountains. Under the influence of dust weather, aerosol particles across all size segment show an increase in number concentration and particle size. Most of the dust particles are 1.2-1.8 μm and 6.5-16.6 μm in size, and there is a large concentration of aerosol particle number at the height of 4000-4500 m and 3000-4000 m. In addition, compared with the average concentration of particles in the fine particle segment and the coarse particle segment, the average concentration of particles increases by 2 times and 3.5 times, respectively. The average particle size increases by 3 times and 1.5 times, respectively. After the transit of sand and dust, the spectrum width widens, and the high-value region of the number concentration shows an overhanging state. In the coarse particle segment, the distribution of aerosol particle spectra changes from bimodal to trimodal. The increase in aerosol particle number concentration is more pronounced in the coarse particle segment and the lower layer. At the altitude of 500-2000 m above the ground, aerosol particles mainly come from the Gurbantunggut Desert in Xinjiang, while at the altitude of 2000-3000 m, aerosol particles mainly come from the Badain Jaran Desert in Inner Mongolia. In addition, the vertical upward movement in the middle layer and the strong northwest wind speed in the lower layer may play an important role in the vertical and spectral distribution of aerosols. Various sources and transport layers of aerosols, along with the vertical distribution evolution of meteorological elements, play an important role in the vertical distribution and spectral distribution of aerosols.

【Objective】 N2O is a greenhouse gas 298 times more effective than CO2 at trapping heat in the atmosphere. Reducing its emission from agricultural soils hence plays a crucial role in mitigating global warming. In this paper, we investigate experimentally the efficacy of regulating nitrogen fertilization to reduce N2O emission from wheat-maize rotation farmlands in Northern China. 【Method】 The experiment was conducted in field, consisting of conventional nitrogen fertilization of 300 kg/hm2 (N1), and reduced nitrogen fertilization of 240 kg/hm2 (N2). Without nitrogen fertilization was taken as the control (CK). In each treatment, we measured N2O efflux during the growing season of the wheat and maize, respectively, as well as soil properties. 【Result】 ① Reducing nitrogen fertilization effectively reduced N2O efflux; N2O efflux in the maize growing season was much higher than that in the winter wheat growing season. Because of temperature difference, N2O efflux induced by nitrogen fertilization to maize was higher than that to the wheat. ② The N2O efflux was influenced by soil nitrogen and soil properties; its variation with these factors can be fitted to N2O efflux =181.952+1.450×NO3--N+8.401×NH4+-N-0.514×EC for the wheat, and N2O efflux = -354.606+4.592×NO3--N +157.848×NH4+-N to the maize, where EC is electrical conductivity of soil solution. 【Conclusion】 Appropriately reducing nitrogen fertilization can reduce N2O efflux in winter wheat-maize rotation production systems without compromising the crop yields in Northern China, with the reduction in the maize growing season more significant than in the wheat growing season.

In this article, a review focusing on the frost resistance of recycled coarse aggregate concrete (RAC) and the bond performance of RAC with rebar under freeze–thaw environment is carried out. The results show that there are still some controversies about the advantages and disadvantages of the frost resistance of RAC, and many influencing factors have not been considered. The mass of the RAC pullout specimens shows a trend of first increasing and then decreasing after freeze‒thaw cycles. The failure modes of the RAC pullout specimens after freeze‒thaw cycles include pullout failure, pullout-splitting failure, splitting failure, and rebar yielding failure. The bond performance of RAC with rebar shows a degradation trend after freeze‒thaw cycles, mainly in the decrease in bond strength and the increase in bond slip. The bond performance of RAC specimens is inferior to that of natural aggregate concrete specimens after freeze‒thaw cycles. The bond strength prediction models and the bond–slip constitutive relation prediction models of RAC with rebar after freeze‒thaw cycles have been summarized to ensure that engineers can better understand their applicability. The bond stress distribution between the RAC and rebar in the anchoring area is not uniform and constantly changes with the number of freeze‒thaw cycles. The degradation mechanism of the bond performance of RAC with rebar after freeze‒thaw cycles is analyzed.

Weather classification is an indispensable preprocessing step in photovoltaic (PV) power prediction. A new two-modal weather classification methods based on PV power clustering was proposed to finely depict the uncertainty of PV power output. Both PV power data and meteorological data were considered for weather classification, providing a novel and effective path for PV power prediction. In addition, data fusion technology was used to extract relevant information from both numeric weather prediction (NWP) data and measured meteorological data to help for weather classification. This approach reduces the model’s reliance on the accuracy of forecasted meteorological indicators and improve the robustness of the model. Experiments based on data from a PV power station in Jilin demonstrated the rationality of the proposed weather classification method. Combining the PV power probability prediction with the proposed weather classifier resulted in prediction interval coverage probabilities closer to the preassigned confidence level and narrower mean prediction interval width.

Abstract Background Pathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies. Methods Nine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them. Results Three of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn’t reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively. Conclusion Our study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.

ABSTRACTMimotope, a kind of peptide vaccine, is developed to bind natural receptor and inhibit the downstream signaling. We have demonstrated that the vaccination of Tocilizumab mimotopes could alleviate the renal fibrosis by interfering with both IL-6 and ferroptosis signaling. However, the effect of the vaccination of Tocilizumab mimotopes on the fibroblast was not investigated in previous study. Thus, we sought to explore the changes in the fibroblast induced by the Tocilizumab mimotopes vaccination. Bleomycin instillation was performed to construct the pulmonary fibrosis model after the immunization of Tocilizumab mimotopes. Lung histological analysis showed that the Tocilizumab mimotopes could significantly reduce the maladaptive repairment and abnormal remodeling. Immunoblotting assay and fluorescence staining showed that Immunization with the Tocilizumab mimotopes reduces the accumulation of fibrosis-related proteins. High level of lipid peroxidation product was observed in the animal model, while the Tocilizumab mimotopes vaccination could reduce the generation of lipid peroxidation product. Mechanism analysis further showed that Nrf-2 signaling, but not GPX-4 and FSP-1 signaling, was upregulated, and reduced the lipid peroxidation. Our results revealed that in the BLM-induced pulmonary fibrosis, high level of lipid peroxidation product was significantly accumulation in the lung tissues, which might lead to the occurrence of ferroptosis. The IL-6 pathway block therapy could inhibit lipid peroxidation product generation in the lung tissues by upregulating the Nrf-2 signaling, and further alleviate the pulmonary fibrosis.

The purpose of this work is to investigate the function of SNHG1, a long non-coding RNA implicated in disease progression, apoptosis, and proliferation, in order to solve the problem of hypoxic-ischemic encephalopathy (HIE) in newborn care. We investigated the impact of overexpressing SNHG1 on hypoxia-induced apoptosis and studied its expression in BV2 microglial cells under hypoxic circumstances. As a result of modifying YY1 expression, SNHG1′s overexpression prevents apoptosis, as our data demonstrate that it is considerably downregulated under hypoxia. We demonstrate that SNHG1 might potentially reduce microglial ischemia-reperfusion damage by using sophisticated nanoengineering drug delivery technologies to target it. This provides encouraging information for the therapy of ischemic epilepsy.

Abstract Background The safety of medication use among older adults is a growing concern, given the aging population. Despite widespread attention, the exploration of medication literacy in older adults, particularly from the perspective of information literacy, is in its nascent stages. Methods This study utilized the existing literature to define medication information literacy (MIL) as a theoretical framework. A two‐round Delphi survey was conducted to identify the essential components of a MIL indicator system for older adults. The analytic hierarchy process (AHP) was then used to assign weights to each indicator. Results The study observed relatively high response rates in both rounds of the questionnaire, which, along with expert authority coefficients (Cr) of 0.86 and 0.89, underscores the credibility and expertise of the panellists. Additionally, Kendall's coefficient of concordance (Kendall's W) ranging from 0.157 to 0.33 (p

PurposeTo explore ocular changes in patients with MS and NMOSD via SD-OCT and PVEP analysis.MethodsFrom August 2020 to July 2021, 82 patients (164 eyes) diagnosed with MS, 59 patients (118 eyes) diagnosed with NMOSD and 50 healthy controls (100 eyes) were retrospectively selected. SD-OCT and PVEP were performed to compare retinal nerve fibre layer (RNFL) thickness around the optic disc, ganglion cell inner plexiform layer (GCIPL) thickness in the macula and P100 latency and amplitude between the disease groups and the control group.ResultsIn the NMOSD and MS groups, the thickness of the GCIPL quadrants in eyes with optic neuritis was thinner than that in eyes without optic neuritis, and the amplitude of the P100 wave decreased. In addition, in eyes with optic neuritis, patients with NMOSD have thinner RNFL thicknesses in the temporal and superior quadrants than patients with MS, and the thickness of the GCIPL is thinner in each region. In eyes without optic neuritis, patients with MS have thinner nasal RNFL than do those with NMOSD.ConclusionSD-OCT and VEP may be useful for monitoring and distinguishing pathological changes in MS and NMOSD patients.

Ferrocenyl conjugated oxazepine/quinoline derivatives were presented through the reaction of hexadehydro-Diels–Alder (HDDA) generated arynes with ferrocenyl oxazolines under mild conditions via ring-expanding or rearrangement processes. Water molecule participated in this unexpected rearrangement process to produce quinoline skeletons, and DFT calculations supported a ring-expanding and intramolecular hydrogen migration process for the formation of oxazepine derivatives. Two variants of this chemistry, expanded the reactivity between ferrocenyl conjugated substances and arynes, further providing an innovative approach for the synthesis of ferrocene derivatives.

BackgroundThe World Health Organization declared mpox an international public health emergency. Since January 1, 2022, China has been ranked among the top 10 countries most affected by the mpox outbreak globally. However, there is a lack of spatial epidemiological studies on mpox, which are crucial for accurately mapping the spatial distribution and clustering of the disease. ObjectiveThis study aims to provide geographically accurate visual evidence to determine priority areas for mpox prevention and control. MethodsLocally confirmed mpox cases were collected between June and November 2023 from 31 provinces of mainland China excluding Taiwan, Macao, and Hong Kong. Spatiotemporal epidemiological analyses, including spatial autocorrelation and regression analyses, were conducted to identify the spatiotemporal characteristics and clustering patterns of mpox attack rate and its spatial relationship with sociodemographic and socioeconomic factors. ResultsFrom June to November 2023, a total of 1610 locally confirmed mpox cases were reported in 30 provinces in mainland China, resulting in an attack rate of 11.40 per 10 million people. Global spatial autocorrelation analysis showed that in July (Moran I=0.0938; P=.08), August (Moran I=0.1276; P=.08), and September (Moran I=0.0934; P=.07), the attack rates of mpox exhibited a clustered pattern and positive spatial autocorrelation. The Getis-Ord Gi* statistics identified hot spots of mpox attack rates in Beijing, Tianjin, Shanghai, Jiangsu, and Hainan. Beijing and Tianjin were consistent hot spots from June to October. No cold spots with low mpox attack rates were detected by the Getis-Ord Gi* statistics. Local Moran I statistics identified a high-high (HH) clustering of mpox attack rates in Guangdong, Beijing, and Tianjin. Guangdong province consistently exhibited HH clustering from June to November, while Beijing and Tianjin were identified as HH clusters from July to September. Low-low clusters were mainly located in Inner Mongolia, Xinjiang, Xizang, Qinghai, and Gansu. Ordinary least squares regression models showed that the cumulative mpox attack rates were significantly and positively associated with the proportion of the urban population (t0.05/2,1=2.4041 P=.02), per capita gross domestic product (t0.05/2,1=2.6955; P=.01), per capita disposable income (t0.05/2,1=2.8303; P=.008), per capita consumption expenditure (PCCE; t0.05/2,1=2.7452; P=.01), and PCCE for health care (t0.05/2,1=2.5924; P=.01). The geographically weighted regression models indicated a positive association and spatial heterogeneity between cumulative mpox attack rates and the proportion of the urban population, per capita gross domestic product, per capita disposable income, and PCCE, with high R2 values in north and northeast China. ConclusionsHot spots and HH clustering of mpox attack rates identified by local spatial autocorrelation analysis should be considered key areas for precision prevention and control of mpox. Specifically, Guangdong, Beijing, and Tianjin provinces should be prioritized for mpox prevention and control. These findings provide geographically precise and visualized evidence to assist in identifying key areas for targeted prevention and control.

IntroductionStudies focusing on coopetition and dynamic capabilities have expanded significantly over the past several decades. Coopetition strategy and dynamic capabilities are increasingly recognised as sources of sustained competitive advantage. The purpose of this paper is to provide a better understanding of the factors driving growth performance in digital healthcare ventures by examining the role of coopetition, exploration and exploitation capabilities, and environmental uncertainty. While numerous studies have examined the competitive advantage of coopetition, its specific contribution to the growth of ventures in the digital realm remains less explored. Clarifying the strategic role of coopetition in driving growth performance is critical for delineating the intricate relationship between coopetition and growth performance, particularly in the context of digital healthcare ventures. To fill in this research gap, this study uses coopetition theory and dynamic capabilities theory to look at how exploration and exploitation capabilities, as well as environmental uncertainty, affect the relationship between coopetition and growth performance in digital healthcare ventures.MethodsWe collected a total of 338 questionnaires from Chinese digital healthcare ventures between March 2023 and August 2023. We conducted data analysis using SPSS 26.0 and its macro-program PROCESS.ResultsOur results confirm that coopetition has a positive effect on growth performance in digital healthcare ventures. Furthermore, exploration and exploitation capabilities fully mediate the relationship between coopetition and growth performance. Moreover, environmental uncertainty significantly and distinctively moderates the impact of exploration and exploitation capabilities on growth performance.DiscussionThis study contributes to the existing literature by providing deeper insight into the relationship between coopetition and growth performance in digital healthcare ventures. It also offers important practical implications for public health improvement and socio-economic development.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

Ischemic stroke (IS), primarily caused by cerebrovascular obstruction, results in severe neurological deficits and has emerged as a leading cause of death and disability worldwide. Recently, there has been increasing exploration of the neuroprotective properties of the inert gas argon. Argon has exhibited impressive neuroprotection in many in vivo and ex vivo experiments without signs of adverse effects, coupled with the advantages of being inexpensive and easily available. However, the efficient administration strategy and underlying mechanisms of neuroprotection by argon in IS are still unclear. This review summarizes current research on the neuroprotective effects of argon in IS with the goal to provide effective guidance for argon application and to elucidate the potential mechanisms of argon neuroprotection. Early and appropriate argon administration at as high a concentration as possible offers favorable neuroprotection in IS. Argon inhalation has been shown to provide some long-term protection benefits. Argon provides the anti-oxidative stress, anti-inflammatory and anti-apoptotic cytoprotective effects mainly around Toll-like receptor 2/4 (TLR2/4), mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor kappa-B (NF-ĸB) and B-cell leukemia/lymphoma 2 (Bcl-2). Therefore, argon holds significant promise as a novel clinical neuroprotective gas agent for ischemic stroke after further researches to identify the optimal application strategy and elucidate the underlying mechanism.

Automated parking stands as a cornerstone technology for autonomous vehicles operating in low-speed scenarios and has been extensively integrated into various vehicle models. Motion planning represents a pivotal technical module that generates planned trajectories to ensure vehicle movement from its initial pose to the target pose without collisions while aligning with kinematics rules, epitomizing the intelligence level of automated parking. In the context of ongoing transitions of automated driving technology from preliminary prototype research to industrial applications, automated parking technology in the realm of low-speed autonomous driving emerges as a critical area primed for breakthroughs. This paper offers a thorough review of the motion planning methods applied within the automated parking domain, categorizing them into geometric methods, sampling methods, search methods, numerical optimization methods, and machine learning methods. This paper also retrospectively examines their development and characteristics. Furthermore, this paper delves into the future directions of motion planning research for automated parking, with a particular focus on constructing more generalized models, enhancing the stability of planning methods, emphasizing the capabilities for online real-time high-quality re-planning and defensive driving, and addressing interactions with other traffic participants.

The effect of pollutants on flux during the treatment of desulfurization wastewater by polyvinylidene fluoride（PVDF） membranes were investingated. Then，the pioneer pollutants and dominant pollutants causing flux changes at different periods in the treatment process were determined. The flow rate playd a dominant role in the distribution of the membrane fouling layer. A three-dimensional single-phase computational fluid dynamics（CFD） method was used to evaluate the flow state in the membrane module system，while SEM，X-ray energy dispersive spectrometer（SEM-EDS），and FTIR were used to analyze the distribution，composition and structure of pollutants on the membrane surface in the horizontal and vertical directions in different fouling periods. It was found that the change in membrane flux is divided into two main phases： a slowly decreasing phase and a rapidly decreasing phase， and the distinct flux variation in the two phases were attributed to differences in the dominant pollutants. Organic pollutants were the pioneer pollutants that lead to a slow decline in flux in the early stage，and mineral scaling was the dominant factor in the rapid decline of flux in the later stage. Organic pollutants mainly included humic acid and fulvic acid， which first deposited on the membrane surface during the membrane distillation process through hydrophobic-hydrophobic interaction with the membrane surface， causing a slow decrease in flux. Mineral contaminants， mainly calcium sulfate， nucleate and crystallize in the bulk solution as the concentration process， and grew rapidly on the membrane surface resulting in a rapid decrease in flux.

Incorporating cultural aspects into science education has recently been stressed in many non-Western societies. However, Chinese traditional cultures are rarely discussed in Chinese science classrooms. Hence, a teaching intervention integrating Confucian ecological ethics and education for sustainable development in secondary chemistry classrooms was designed, implemented online due to the COVID-19 pandemic, and analyzed. It focuses on discussing aspects of Confucian ecological ethics in the context of a lesson plan on the socio-scientific issue of plastic use. Sixty-five 10th-grade students from an urban key public high school in Beijing voluntarily attended this research. Based on the analysis of their feedback it is suggested that Confucian ecological ethics can improve students’ environmental awareness. Most students acknowledged that Confucian ecological ethics could promote Chinese sustainability-oriented chemistry education with a value-oriented approach.

The main acne-causing bacteria are Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. Quorum sensing, an important factor for bacterial survival, is closely associated with expression of bacterial virulence factors and biofilm formation. Although the quorum sensing types of Staphylococcus aureus and Staphylococcus epidermidis have been identified, the quorum sensing types of Propionibacterium acnes are still controversial. Plant-orginated quorum sensing inhibitors with few side effects have a greater potential in the treatment of acne. This article reviews the progress on the mechanisms by which plant-originated quorum sensing inhibitors inhibit pathogenic bacteria of acne.