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Abstract The binary phase change paraffin (BP) was prepared using the melt blending method, followed by adsorption and encapsulation to produce the phase change aggregate. Phase change concrete was subsequently prepared using the volumetric replacement method. The study examined the thermal properties of BP, along with the semi-adiabatic temperature rise and thermal conductivity of the phase change concrete at different replacement rates. The results indicate that BP exhibits two plateau regions, with phase change intervals varying according to the mass ratio. The high-temperature phase change interval ranges from 18.3 °C to 47.3 °C, while the low-temperature phase change interval ranges from 0.1 °C to 4.6 °C. When the mass ratio of 48# paraffin to 5# paraffin is 7:3, the peak phase change temperatures are 2.58 °C and 44.52 °C, with corresponding enthalpies of 66.52 J/g and 102.63 J/g, respectively. The addition of phase change aggregate effectively reduces the hydration temperature rise of concrete, slows the rate of temperature increase, and decreases the thermal conductivity. The semi-adiabatic temperature rise curve of the phase change concrete exhibits an "S"-shaped variation over time, with the composite exponential function providing a more accurate representation of this process.

Abstract With the increase of wind power generation, the safety and economy of power system operations are greatly influenced by the intermittency and fluctuation of wind power. To take the advantage of the complementary characteristics between different energy storage devices, a Hybrid Energy Storage System (HESS) consisting of Battery Energy Storage System (BESS) and Flywheel Energy Storage System (FESS) can alleviate the uncertainty of wind power. This article has proposed a coordinated control strategy through group consensus algorithm based on Model Predictive Control (MPC) for Hybrid Energy Storage Array (HESA) to smooth wind power fluctuations. To allocate power commands to the FESS and BESS, the fluctuation of wind power output is extracted with different frequency domain characteristics as instructions by Empirical Mode Decomposition (EMD) technology. Moreover, a group consensus algorithm based on MPC is proposed to complete the adaptive power allocation of energy storage units. Eventually, the actual wind farm data is used for the simulation to verify the effect of control strategy proposed in this paper. It can be seen that the developed group consensus algorithm based on MPC can cope with different frequency power commands, avoid overcharging and discharging of energy storage media, and smooth wind power effectively.

Objective·To explore the effect of a prehospital multimodal prehabilitation program on the preoperative functional status and postoperative recovery of patients with gastrointestinal malignant tumors.Methods·A total of 78 patients with gastrointestinal malignant tumors, hospitalized in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from June to December 2023, were enrolled. They were divided into the standard group (SD group, n=40) and the prehospital multimodal prehabilitation group (PMP group, n=38) by using random number table. From the time the operation was agreed upon by both the doctor and patient to the day before the operation, the SD group followed the routine preoperative guidance, while the PMP group received a home-based prehospital multimodal prehabilitation program. The general data of patients were collected, and the six-minute walk distance (6MWD) was compared between the two groups at baseline and on the day before operation.The length of postoperative hospitalization, time to first flatus, time to first ambulation, time to first oral intake, drainage removal time and postoperative complication rate were also compared between the two groups.Results·There was no difference in general data and duration of preoperative intervention of patients between the two groups. At baseline, there was no significant difference in 6MWD between the two groups. On the day before operation, the 6MWD in the PMP group was higher than that in the SD group (P= 0.016). Changes in 6MWD in the PMP group were significantly higher compared to SD group during the preoperative period, with values of (23.42±13.59) m vs. (-3.75±12.08) m (P0.05).Conclusion·Prehospital multimodal prehabilitation can improve the preoperative function and accelerate the postoperative recovery in patients with gastrointestinal malignancies.

Abstract As an ultra-early response gene, Nuclear receptor 4A1 (NR4A1) has been reported to be involved in the development of various diseases through various pathological pathways, but its specific mechanism in chronic kidney disease (CKD) is unknown currently. Our study showed that the expression of NR4A1 was reduced in unilateral ureteral obstruction (UUO) mice and it could exacerbate UUO-induced renal pathological injury when knocked down NR4A1 in UUO mice. We found that the knockdown of NR4A1 could promote angiogenesis, renal inflammation, and cell apoptosis to aggravate renal fibrosis induced by UUO. As an agonist of NR4A1, Cytosporone B (Csn-B) could inhibit the renal fibrosis by attenuating angiogenesis, renal inflammation and cell apoptosis. In addition, the PI3K/AKT pathway was activated with NR4A1 knockdown in vivo and in vitro experiments. In conclusion, our study demonstrates that NR4A1 can ameliorate renal fibrosis. Furthermore, we speculate that its underlying mechanism may be related to the activation of PI3K/AKT pathway according to our present results.

Abstract Background Mesenchymal stem cells (MSCs) are multipotent stem cells that are under investigation for use in clinical trials because they are capable of self-renewal and differentiating into different cell types under defined conditions. Nonetheless, the therapeutic effects of MSCs have been constrained by low engraftment rates, cell fusion, and cell survival. Various strategies have been explored to improve the therapeutic efficacy of MSCs, with platelet-derived growth factor (PDGF)-BB emerging as a promising candidate. To enhance our comprehension of the impact of PDGF-BB on the gene expression profile and chromosomal accessibility of MSCs, RNA-sequencing and analysis of chromatin accessibility profiles were conducted on three human primary MSCs in culture, both with and without stimulation by PDGF-BB. Results Integrative analysis of gene expression and chromatin accessibility demonstrated that PDGF-BB treatment modified the chromatin accessibility landscape, marking regions for activation or repression through the AP-1 family transcription factors TEAD, CEBP, and RUNX2. These changes in AP-1 transcription factor expression, in turn, led to cell proliferation and differentiation potential towards osteoblasts, adipocytes, or chondrocytes. The degree of MSC differentiation varies among cells isolated from different donors. The presence of an enrichment of exosome-related genes is also noted among all the differentially expressed genes. Conclusions In conclusion, the observed changes in AP-1 transcription factor expression not only induced cellular proliferation and differentiation, but also revealed variations in the degree of MSC differentiation based on donor-specific differences. Moreover, the enrichment of exosome-related genes among differentially expressed genes suggests a potential significant role for PDGF-BB in facilitating intercellular communication.

Abstract Background Compassion fatigue is common among nurses and can lead to decreased motivation, impaired physical and mental health, and turnover. Nursing interns often face environments the same as professional nurses, yet their compassion fatigue has received less attention. Therefore, this study aims to assess the prevalence and related factors of compassion fatigue among nursing interns. Methods This was a cross-sectional study involving 221 nursing interns in 2 tertiary-level hospitals in Shanghai, China. A general information questionnaire was formulated to investigate the demographic characteristics and internship-related factors of nursing interns. Compassion fatigue was assessed using the Professional Quality of Life Scale [compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS)]. Psychological resilience, empathy, and perceived stress were evaluated by the Connor-Davidson Resilience Scale, Jefferson Scales of Empathy, and Perceived Stress Scale, respectively. Personality traits were assessed using the extroversion/introversion subscale of the Eysenck Personality Inventory. Descriptive statistics, t-test, one-way analysis of variance (ANOVA), Pearson’s correlation analysis, and multiple linear regressions were used to determine the predictors of the main research variables. Results The prevalence of mild, moderate, and severe compassion fatigue in 221 nursing interns (mean age 21 years, 202 [91.4%] females) was 10.4%, 46.6%, and 43.0%, respectively, and their mean scores for CS, BO, and STS were 29.75 ± 6.39, 28.72 ± 4.78, and 28.51 ± 7.51, respectively. Psychological resilience and empathy were the strongest protective factors for CS and BO, respectively (p

Abstract Background To investigate the association between surgical removal of tonsils and risk of COVID-19 with different severity. Methods Through a nested case–control study during January 31st to December 31st 2020, including 58,888 participants of the UK Biobank, we investigated the association of tonsillectomy with the future risk of mild and severe COVID-19, using binomial logistic regression. We further examined the associations of such surgery with blood inflammatory, lipid and metabolic biomarkers to understand potential mechanisms. Finally, we replicated the analysis of severe COVID-19 in the Swedish AMORIS Cohort (n = 451,960). Results Tonsillectomy was associated with a lower risk of mild (odds ratio [95% confidence interval]: 0.80 [0.75–0.86]) and severe (0.87 [0.77–0.98]) COVID-19 in the UK Biobank. The associations did not differ substantially by sex, age, Townsend deprivation index, or polygenic risk score for critically ill COVID-19. Levels of blood inflammatory, lipid and metabolic biomarkers did, however, not differ greatly by history of surgical removal of tonsils. An inverse association between tonsillectomy and severe COVID-19 was also observed in the AMORIS Cohort, primarily among older individuals (> 70 years) and those with ≤ 12 years of education. Conclusions Surgical removal of tonsils may be associated with a lower risk of COVID-19. This association is unlikely attributed to alterations in common blood inflammatory, lipid and metabolic biomarkers.

Abstract There is limited data on the prognostic implications of residual mild coarctation (RMC) in patients with repaired native coarctation of the aorta (CoA). To explore the association of RMC with mid‐term comorbidities in post‐interventional patients, and the predictive value of the residual pressure gradient. The authors retrospectively analyzed 79 native CoA patients who received successful intervention at our hospital between October 2010 and June 2023. The outcomes of the study were late arterial hypertension (either raised blood pressure or commencement of hypotensive medications) only in normotensive patients at early follow‐up and the composite mid‐term comorbidities including new‐onset aortic injury, re‐stenosis, and re‐intervention. At a median follow‐up of 60 months, late hypertension and mid‐term comorbidities occurred in 16 (28.1%) and nine (11.4%) patients, respectively. Multivariate Cox proportional hazard regression analysis identified invasive peak systolic CoA pressure gradient (PSPG) as the best independent predictor of both outcomes. The maximally selected rank statistics indicated 10 mm Hg as the best PSPG cut‐off value for predicting late hypertension. Compared to patients with PSPG

Abstract People’s livelihood serves as the primary impetus driving all social activities. Faced with intense regional competition and stringent assessment, regional governments often resort to manipulating GDP figures. This study investigates the repercussions of such economic distortion on residents’ welfare. Our findings reveal a significant negative relationship between regional GDP manipulation and investment in livelihood improvements. This correlation is particularly pronounced during the initial phase of officials’ tenure and diminishes when officials serve in their hometowns. Moreover, we observe that the reduction in livelihood investment is exacerbated during periods of economic downturn. These conclusions contribute to the existing literature on regional GDP manipulation and livelihood investment, shedding light on the potential implications for residents’ welfare.

Abstract Background Overactivated microglia are a key contributor to Parkinson’s disease (PD) by inducing neuroinflammation. CD200R1, a membrane glycoprotein mainly found on microglia, is crucial for maintaining quiescence with its dysregulation linked to microglia’s abnormal activation. We and other groups have reported a decline in CD200R1 levels in several neurological disorders including PD. However, the mechanism regulating CD200R1 expression and the specific reasons for its reduction in PD remain largely unexplored. Given the pivotal role of transcription factors in gene expression, this study aimed to elucidate the transcriptional regulation of CD200R1 and its implications in PD. Methods The CD200R1 promoter core region was identified via luciferase assays. Potential transcription factors were predicted using the UCSC ChIP-seq database and JASPAR. NFKB1 binding to the CD200R1 core promoter was substantiated through electrophoretic mobility shift and chromatin immunoprecipitation assays. Knocking-down or overexpressing NFKB1 validated its regulatory effect on CD200R1. Correlation between decreased CD200R1 and deficient NFKB1 was studied using Genotype-Tissue Expression database. The clinical samples of the peripheral blood mononuclear cells were acquired from 44 PD patients (mean age 64.13 ± 9.78, 43.2% male, median Hoehn-Yahr stage 1.77) and 45 controls (mean age 64.70 ± 9.41, 52.1% male). NFKB1 knockout mice were utilized to study the impact of NFKB1 on CD200R1 expression and to assess their roles in PD pathophysiology. Results The study identified the CD200R1 core promoter region, located 482 to 146 bp upstream of its translation initiation site, was directly regulated by NFKB1. Significant correlation between NFKB1 and CD200R1 expression was observed in human PMBCs. Both NFKB1 and CD200R1 were significantly decreased in PD patient samples. Furthermore, NFKB1-/- mice exhibited exacerbated microglia activation and dopaminergic neuron loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Conclusion Our study identified that NFKB1 served as a direct regulator of CD200R1. Reduced NFKB1 played a critical role in CD200R1 dysregulation and subsequent microglia overactivation in PD. These findings provide evidence that targeting the NFKB1-CD200R1 axis would be a novel therapeutic strategy for PD.

Abstract Background It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. Methods This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11–14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. Results FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. Conclusion The combination of FPG and IGFBP-2 at early gestation (11–14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.

Abstract Individuals with mental illness are at higher risk of severe COVID-19 outcomes. However, previous studies on the uptake of COVID-19 vaccination in this population have reported conflicting results. Using data from seven cohort studies (N = 325,298) included in the multinational COVIDMENT consortium, and the Swedish registers (N = 8,080,234), this study investigates the association between mental illness (defined using self-report measures, clinical diagnosis and prescription data) and COVID-19 vaccination uptake. Results from the COVIDMENT cohort studies were pooled using meta-analyses, the majority of which showed no significant association between mental illness and vaccination uptake. In the Swedish register study population, we observed a very small reduction in the uptake of both the first and second dose of a COVID-19 vaccine among individuals with vs. without mental illness; the reduction was however greater among those not using psychiatric medication. Here we show that uptake of the COVID-19 vaccine is generally high among individuals both with and without mental illness, however the lower levels of vaccination uptake observed among subgroups of individuals with unmedicated mental illness warrants further attention.

ABSTRACT Importance Aicardi–Goutières syndrome (AGS) is a rare genetic disorder mainly affecting the central nervous system and autoimmunity. However, research on AGS among Chinese patients is limited. Objective To summarize the neurologic phenotypes and genetic causes in pediatric AGS patients, providing insights for early recognition and diagnosis in the Chinese population. Methods Clinical features and neuroimaging results of the patients diagnosed with AGS from Beijing Children's Hospital between January 2018 and January 2022 were collected. Whole exome sequencing was used for genetic analysis. Results A total of 15 patients was included, all presenting with various neurological symptoms, including developmental delay (100%), motor skill impairment (100%), language disability (78.6%), dystonia (93.3%), microcephaly (73.3%), sleep disorders (26.7%), regression (20.0%), vessel disease (6.7%), and epilepsy (6.7%). Neuroimaging revealed intracranial calcification (86.7%), cerebral atrophy (73.3%), and leukodystrophy (73.3%). Seven genes were identified, with TREX1 being the most common (40.0%, 6/15), followed by IFIH1 (20.0%, 3/15). Variant c.294dupA (p.C99Mfs*3) was detected in four unrelated patients, accounting for 66.7% (4/6) patients with the TREX1 variant. A literature review showed that TREX1 gene mutations in 35.6% (21/59) of AGS patients among the Chinese population. Interpretation Neurological symptoms are the most prevalent and severe presentation of AGS. Diagnosis may be considered when symptoms such as developmental delay, dystonia, microcephaly, brain calcification, and leukodystrophy emerge. TREX1 mutations are predominant in the Chinese population.

Abstract Activin A and hepatic stellate cells (HSCs) are involved in tissue repair and fibrosis in liver injury. This study investigated the impact of activin A on HSC activation and migration. A microfluidic D4-chip was used for examining the cell migration of mouse hepatic stellate cell line MHSteC. The analysis of differentially expressed genes revealed that activin βA (Inhba), activin receptor type 1A (Acvr1a) and type 2A (Acvr2a) mRNAs were more significantly expressed in human HSCs than in the hepatocytes. Moreover, activin A promoted MHSteC proliferation and induced MHSteC migration. Furthermore, the MHSteCs treated with activin A exhibited increased levels of migration-related proteins, N-cadherin, Vimentin, α-SMA, MMP2 and MMP9, but a decreased level of E-cadherin. Additionally, activin A treatment significantly increased the p-Smad3 levels and p-Smad3/Smad3 ratio in the MHSteCs, and the Smad3 inhibitor SIS3 attenuated activin A-induced MHSteC proliferation and migration. Simultaneously, activin A increased the calcium levels in the MHSteCs, and the migratory effects of activin A on MHSteCs were weakened by the intracellular calcium ion-chelating agent BAPTA-AM. These data indicate that activin A can promote MHSteC activation and migration through the canonical Smad3 signaling and calcium signaling.

Abstract Analyzing three-dimensional excitation-emission matrix (3D-EEM) spectra through machine learning models has drawn increasing attention, whereas the reliability of these machine learning models remains unclear due to their “black box” nature. In this study, the convolutional neural network (CNN) for classifying numbers of fluorescent components in 3D-EEM spectra was interpreted by gradient-weighted class activation mapping (Grad-CAM), guided Grad-CAM, and structured attention graphs (SAGs). Results showed that the original CNN classifier with high classification accuracy may make a classification based on misleading attention to the non-fluorescence area in 3D-EEM spectra. By removing Rayleigh scatterings in 3D-EEM spectra and integrating convolutional block attention module (CBAM) in CNN classifiers, the correct attention of the trained CNN classifier with CBAM greatly increased from 17.6% to 57.2%. This work formulated strategies for improving CNN classifiers associated with environmental fields and would provide great help for water determination in both natural and artificial environments.

Abstract Background Childhood maltreatment (CM) has been indicated in adverse health outcomes across the lifespan, including severe infection-related outcomes. Yet, data are scarce on the potential role of CM in severe COVID-19-related outcomes as well as on mechanisms underlying this association. Methods We included 151,427 individuals in the UK Biobank who responded to questions on the history of CM in 2016 and 2017 and were alive on January 31, 2020. Binomial logistic regression models were performed to estimate the association between a history of CM and severe COVID-19 outcomes (i.e. hospitalization or death due to COVID-19), as well as COVID-19 diagnosis and vaccination as secondary outcomes. We then explored the potential mediating roles of socio-economic status, lifestyle and pre-pandemic comorbidities, and the effect modification by polygenic risk score for severe COVID-19 outcomes. Results The mean age of the study population at the start of the pandemic was 67.7 (SD = 7.72) years, and 56.5% were female. We found the number of CM types was associated with the risk of severe COVID-19 outcomes in a graded manner (p for trend 0.05). Mediation analysis revealed that 50.9% of the association between CM and severe COVID-19 outcomes was explained by suboptimal socio-economic status, lifestyle, and pre-pandemic diagnosis of psychiatric disorders or other chronic medical conditions. In contrast, any CM exposure was only weakly associated with COVID-19 diagnosis (1.06 [1.01–1.12]) while significantly associated with not being vaccinated for COVID-19 (1.21 [1.13–1.29]). Conclusions Our results add to the growing knowledge base indicating the role of childhood maltreatment in negative health outcomes across the lifespan, including severe COVID-19-related outcomes. The identified factors underlying this association represent potential intervention targets for mitigating the harmful effects of childhood maltreatment in COVID-19 and similar future pandemics.

Abstract Background Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Abstract. Background:. Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs. Methods:. We collected data from participants in the “Happy Breathing Program” in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs. Results:. A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility (n = 3304, 43.1%) and a lack of trust in primary healthcare institutions (n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half (n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation “COPD” were more willing to undergo PFTs. Conclusions:. Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

Purpose: This study aimed to identify the altered pathways and genes associated with freezing damage in human sperm during cryopreservation by multiomics analysis. Materials and Methods: Fifteen fresh human semen samples were collected for transcriptomic analysis, and another 5 fresh human semen samples were obtained for metabolomic analysis. For each semen sample, 1 mL was cryopreserved, and another 1 mL was left untreated for paired design. The results were then combined with previously published proteomic results to identify key genes/pathways. Results: Cryopreservation significantly reduced sperm motility and mitochondrial structure. Transcriptomic analysis revealed altered mitochondrial function, including changes in tRNA-methyltransferase activity and adenosine tri-phosphate/adenosine di-phosphate transmembrane transporter activity. Metabolomic analysis showed that the citrate cycle in mitochondria was significantly altered. Combining transcriptomic, proteomic, and metabolomic analyses revealed 346 genes that were altered in at least two omics analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that metabolic pathways were significantly altered and strongly associated with mitochondria. Five genes were altered in all three omics analyses: COL11A1, COL18A1, LPCAT3, NME1, and NNT. Conclusions: Five genes were identified by multiomics analysis in human cryopreserved sperm. These genes might have specific functions in cryopreservation. Explorations of the functions of these genes will be helpful for sperm cryopreservation and sperm motility improvement or even for reproduction in the future.

Backgrounds: The functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evaluation of the efficacy of Fasudil Hydrochloride at treating the sciatic nerve transection injury in rats and the mechanism involved. Materials and methods: In animal experiments, 75 Sprague Dawley rats that underwent transection and repair of the right sciatic nerve were divided into a control, Fasudil, and Fas + LY group, receiving daily intraperitoneal injection of saline, Fasudil Hydrochloride (10 mg/kg), and Fasudil Hydrochloride plus LY294002 (5 mg/kg), respectively. At day 3 after surgery, the expression of ROCK2, p-PI3K, and p-AKT in L4-5 DRG and the lumbosacral enlargement was determined using Western blotting. At day 7 and 14, axon density in the distal stump was evaluated with immunostaining using the anti-Neurofilament-200 antibody. At day 30, retrograde tracing by injecting Fluoro-gold in the distal stump was performed. Three months after surgery, remyelination was analyzed with immostaining using the anti-MPZ antibody and the transmission electron microscope; Moreover, Motion-Evoked Potential, and recovery of sensorimotor functions was evaluated with a neuromonitor, Footprint, Hot Plate and Von Frey Filaments, respectively. Moveover, the Gastrocnemius muscles were weighed, and then underwent H＆E staining, and staining of the neuromuscular junction using α-Bungarotoxin to evaluate the extent of atrophy and degeneration of the endplates in the Gastrocnemius. In vitro, spinal motor neurons (SMNs) and dorsal root ganglia (DRG) were cultured to examine the impact of Fasudil Hydrochloride and LY294002 on the axon outgrowth. Results: Three days after injury, the expression of ROCK2 increased significantly (P＜0.01), and Fasudil application significantly increased the expression of p-PI3K and p-AKT in L4-6 DRG and the lumbosacral enlargement (P

In recent years, the exploration of topological states within two-dimensional materials has emerged as a compelling focus, complementing their three-dimensional counterparts. Through theoretical calculations, we unveil the exceptional topological state in the monolayer lithium hydrosulfide, where an ideal hourglass nodal loop is identified. Notably, this nodal loop is characterized by only four bands, representing the simplest configuration for realizing hourglass dispersion. We provide detailed symmetry arguments alongside model calculations to elucidate the formation mechanism of the nodal loop and its corresponding hourglass dispersion. Moreover, the associated edge states are not only well-separated from the bulk band projection but also persist consistently throughout the Brillouin zone. Due to the lightweight constitutive elements of this material, both the hourglass dispersion and the edge states remain robust even in the presence of spin-orbit coupling. To enhance its practical applicability, we have evaluated various mechanical parameters, analyzing their anisotropic behaviors. Furthermore, we examined the material’s response to strain conditions under both compressive and tensile stress, uncovering distinct variations in energy, size, and the hourglass dispersion of the nodal loop. Overall, the hourglass nodal loop state explored in this study, along with the proposed material candidate, provides a strong foundation for future experimental investigations. This research potentially paves the way for significant advancements within this emerging field.

Background: Amyotrophic lateral sclerosis (ALS) represents a complex syndrome characterized by motor, psychiatric, and cognitive symptoms, where associations between cellular immune features and non-motor manifestations remain unknown. Methods: In this cohort study, we enrolled 250 incident people with ALS (pwALS) assessed with the Hospital Anxiety and Depression Scale, and 226 pwALS with the Montreal Cognitive Assessment, including 218 overlapping pwALS. All individuals were diagnosed between January 2015 and January 2023 in Stockholm, Sweden. We applied joint latent class models to delineate distinct trajectories of anxiety, depression, and cognition, incorporating survival outcomes. A majority of the pwALS had data on leukocyte counts and flow cytometric analyses using a comprehensive T cell panel. We then used immune cell subtypes measured at diagnosis to predict trajectories of these outcomes following ALS diagnosis. Results: We identified two distinct trajectories for anxiety, depression, and cognitive function following ALS diagnosis. PwALS with longer survival displayed more stable trajectories, while those with shorter survival showed decreasing anxiety symptom, increasing depressive symptom, and declining cognitive function. Higher count of leukocytes at the time of ALS diagnosis tended to associate with anxiety and depression trajectories related to shorter survival. Among T cell subpopulations, several CD8+ T cell subsets were associated with a stable trajectory of depressive symptom, and, in turn, better survival. Conclusion: ALS-associated psychiatric and cognitive trajectories vary significantly between pwALS with different prognosis. Certain T cell subsets measured at diagnosis might be indicative of depression trajectories post-diagnosis.

Epilepsy affects ∼ 65 million people worldwide. In this study, peripheral blood mononuclear cells were isolated from a young patient patient bearing a Nitrogen Perntease Regulator Like 3 Protein (NPRL3) mutation and suffering from Epilepsy verified by clinical and genetic diagnosis. Induced pluripotent stem cells (iPSCs) were established by a non-integrative method, using plasmids carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSCs presented typical pluripotent cells morphology, normal karyotype, and potential to differentiate into three germ layers. Our approach offers a useful model to explore pathogenesis and therapy of Epilepsy.

Background Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR.Methods 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed.Results CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P

IntroductionGestational diabetes mellitus (GDM) is a common pregnancy complication with potential short- and long-term adverse consequences for both mothers and fetuses. It is unclear whether GDM affects linear growth in the offspring; research data are limited and inconsistent.MethodsIn a prospective birth cohort in Shanghai (n=2055 children; 369 born to mothers with GDM). We sought to evaluate the impact of GDM on longitudinal linear growth in early childhood. Length/height was measured in children at birth, 6 weeks, 6 months, 1, 2 and 4 years of age. Multivariate linear regression and generalized estimating equation models were employed to assess the impact of GDM on length/height for age Z score (LAZ/HAZ).ResultsAverage birth length was similar in infants of GDM vs. euglycemic mothers. Adjusting for maternal and child characteristics, the children of mothers with GDM had consistently lower LAZ/HAZ compared to children of mothers without diabetes at ages 6 weeks, 6 months, 1, 2 and 4 years. GDM was associated with a 0.12 (95% confidence intervals 0.04-0.21) deficit in LAZ/HAZ in the growth trajectory from birth to age 4 years after adjusting for maternal and child characteristics.DiscussionGDM was associated with impaired longitudinal linear growth in early childhood. Further studies are warranted to understand the long-term impact on stature and health.

ObjectiveThis study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.Data SourcesThis study conducted a comprehensive search of Medline, Embase, and the Cochrane Central Register of Controlled Trials, covering the period from inception until 22 June 2023. Randomized clinical trials for corticosteroid use among adults with SCAP were collected.Study SelectionTwo researchers independently assessed study eligibility based on titles and abstracts, with any disagreements resolved through discussion or consultation with a third researcher.Data ExtractionTwo researchers independently collected and clarified study details, with a third researcher adjudicating in case of disputes.Data SynthesisThe data from 13 randomized clinical trials involving 2,495 patients, were analyzed using a random-effects model. Eleven trials were assessed as low risk, while two were assessed as high risk. Trials were rated as having low bias risk. Results, presented as risk ratios (RR) with a 95% confidence interval (CI), indicated that hydrocortisone outperformed prednisolone (RR 0.35; 95% CI 0.10–0.94), methylprednisolone (RR 0.41; 95% CI 0.15–0.89), and placebo (RR 0.35; 95% CI 0.16–0.59) in reducing 30-day mortality. A rankogram plot suggested that hydrocortisone had the highest probability of being the most effective treatment for this outcome within the analyzed group.ConclusionIn this network meta-analysis, while hydrocortisone showed greater efficacy than prednisolone, methylprednisolone, and placebo in reducing 30-day mortality in patients with SCAP, further Randomized Controlled Trials (RCTs) are required to confirm these findings before drawing definitive conclusions.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438389, identifier CRD42023438389.

Visual perceptual learning (VPL) refers to a long-term improvement of visual task performance through training or experience, reflecting brain plasticity even in adults. In human subjects, VPL has been mostly studied using functional magnetic resonance imaging (fMRI). However, due to the low temporal resolution of fMRI, how VPL affects the time course of visual information processing is largely unknown. To address this issue, we trained human subjects to perform a visual motion direction discrimination task. Their behavioral performance and magnetoencephalography (MEG) signals responding to the motion stimuli were measured before, immediately after, and two weeks after training. Training induced a long-lasting behavioral improvement for the trained direction. Based on the MEG signals from occipital sensors, we found that, for the trained motion direction, VPL increased the motion direction decoding accuracy, reduced the motion direction decoding latency, enhanced the direction-selective channel response, and narrowed the tuning profile. Following the MEG source reconstruction, we showed that VPL enhanced the cortical response in early visual cortex (EVC) and strengthened the feedforward connection from EVC to V3A. These VPL-induced neural changes co-occurred in 160–230 ms after stimulus onset. Complementary to previous fMRI findings on VPL, this study provides a comprehensive description on the neural mechanisms of visual motion perceptual learning from a temporal perspective and reveals how VPL shapes the time course of visual motion processing in the adult human brain.

Introduction While changes in the prevalence of depressive symptoms during the COVID-19 pandemic have been described across populations, few studies have incorporated multidimensional variables to characterise the varying effects of the pandemic on the population’s mental health.Methods This cohort study included 6423 participants aged ≥18 years from the Icelandic COVID-19 National Resilience Cohort. Data on depressive symptoms and pandemic-related and non-pandemic-related factors were obtained during three pandemic assessment periods (baseline, follow-up wave 1 and follow-up wave 2; April 2020–December 2021), while health outcomes were obtained during the post-pandemic assessment period (follow-up wave 3; September 2022–February 2023). We used latent growth mixture models to identify variation in depressive symptom trajectories during the pandemic. We then used XGBoost models with 37 pandemic-related and non-pandemic-related factors to characterise these trajectories. Moreover, we performed linear regression to assess the association between the identified trajectories and post-pandemic health outcomes.Results Of the included participants, we identified four depressive symptom trajectories, including consistently low (83.7%), consistently high (5.3%), initially high (5.1%) and late-onset high (5.9%) symptom trajectories. Individuals who exercised frequently (≥3 days/week) and enjoyed social and family support were more likely to experience a consistently low symptom trajectory. In contrast, individuals with a history of psychiatric disorders, women and young adults (18–39 years) were less likely to follow the consistently low symptom trajectory. Moreover, compared with the consistently low symptom trajectory, the other trajectories were associated with significantly higher levels of depressive, anxiety and somatic symptoms and cognitive problems during the post-pandemic period.Conclusions Our results underscore the long-lasting impact of the COVID-19 pandemic on population mental health. Interventions focusing on exercise, social support and family support may mitigate the adverse mental health effects of future pandemics.

Purpose: To elucidate the etiology of infectious uveitis through the comprehensive analysis of keratic precipitates (KPs) using in vivo confocal microscopy (IVCM). Design: Cross-sectional, observational case series. Methods: This single-center, cross-sectional study was conducted at a tertiary care eye hospital from January 2021 to October 2023. It involved a detailed ophthalmologic evaluation of all subjects and included a total of 46 eyes from 36 subjects who were diagnosed with infectious uveitis. IVCM, specifically utilizing the HRT II Rostock corneal module, was employed to study the biomicroscopic morphology of KPs. The categorization of KPs was based on cell size, morphology, and reflection. Results: Cells of KPs were assessed for size, morphology, and reflection through in vivo confocal microscopy. Patients, ranging in age from 13 to 80 years (median 51 years), exhibited diverse morphologic forms of KPs. Neutrophil-dominated KPs with uniform size were predominantly observed in bacterial and fungal endophthalmitis cases (19/19, 100 %), accompanied by small numbers of mononuclear-macrophages in three eyes (3/19, 15.8 %). Viral uveitis cases displayed a broader array of immune cell types, including characteristic striated or dendritic cells in all eyes (27/27, 100 %). Lymphocytes were commonly present (24/27, 88.9 %), forming clusters in sixteen eyes and dispersed in the corneal endothelium below the midline in eight eyes. Neutrophil infiltration was notable in three cytomegalovirus-infected eyes (3/27, 11.1 %). A marked increase in sub-basal corneal epithelial Langhans cells was associated with viral uveitis. Conclusions: Neutrophil-dominated KPs strongly indicate endogenous bacterial or fungal endophthalmitis, while the presence of dendritic cells and lymphocytes in KPs is suggestive of viral uveitis. In vivo confocal microscopy emerges as a crucial tool for differentiating the etiologic diagnosis of infectious uveitis.

Abstract The energy dissipation pathways of a photosensitizer for phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), compete directly with that of its fluorescence (FL) emission. Enriching heavy atoms on the π‐conjugated systems and aggregation‐caused quenching are two effective methods to turn off the FL emission of photosensitizers, which is expected to boost the intersystem crossing (for PDT) and nonradiative transition (for PTT) of photosensitizers for maximized phototherapeutic efficacy. Following this approach, an all‐iodine‐substituted polydiacetylene aggregate poly(diiododiacetylene) (PIDA) has been developed, which shows a superior near infrared absorption (ε808nm = 26.1 g−1 cm−1 L) with completely blocked FL, as well as high efficiency of reactive oxygen species generation (nearly 45 folds of indocyanine green) and photothermal conversion (33.4%). To make the insoluble fibrillar PIDA aggregates favorable for systemic administration, they are converted into nanospheres through a pre‐polymerization morphology transformation strategy. The in vivo study on a 4T1 tumor‐bearing mouse model demonstrates that PIDA nanospheres can almost eliminate the tumor entirely in 16 days and prolong the survival time of mice to over 60 days, validating their effective phototherapeutic response through the strategy of inhibiting FL for boosted intersystem crossing and nonradiative transition.

Objective·To establish the early symptom network of adult intensive care unit (ICU) patients after transfer (post-ICU patients), identify the core symptoms and bridge symptoms, compare the symptom networks of two subgroups, i.e. mixed ICU and coronary care unit (CCU), and analyze the occurrence of symptoms.Methods·From December 2022 to August 2023, a total of 328 adult patients transferred to wards from mixed ICU and CCU of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were selected by convenience sampling. The general situation and clinical data questionnaire, and symptom questionnaires (including Hospital Anxiety and Depression Scale, Fatigue Severity Scale, Richards-Campbell Sleep Questionnaire, and Pain Numeric Rating Scale) were used. Based on Spearman correlation analysis and GLASSO algorithm, contemporaneous symptom network was built, and centrality indices and differences between subgroup symptom networks were computed. The edge accuracy and the stability of centrality indices of the network were tested.Results·A total of 302 valid questionnaires were collected, and the effective rate was 92.1%. The results of the centrality indices computations showed that in the early symptom network of post-ICU patients, the highest strength was “feel cheerful” (rS=1.145), the highest closeness was “enjoy something” (rC=1.851×10-3), and the highest expected influence was “（fatigue） interferes with physical function” (rE=1.143). The top three highest bridge strengths of symptoms were “worrying thoughts” (rb=10.392), “enjoy something” (rb=10.359), and pain (rb=10.221). There were no significant differences in network structure (M=0.289) and overall connection strength (GSmixed ICU=13.876, GSCCU=13.838; S=0.039) of the early symptom networks between mixed ICU and CCU patients after being transferred to wards. When comparing the centrality indices, apart from the strength and expected influence of five symptoms showing statistically significant differences (all P

Abstract Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Abstract Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5′ UTR, were specifically recognized by the m6A “reader” protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.

Abstract This study investigates the expression and significance of urinary protein and coagulation‐fibrinolysis indicators in preeclampsia, categorized into mild preeclampsia (109 cases) and severe preeclampsia (97 cases) based on disease severity. Additionally, 110 patients with gestational hypertension (gestational hypertension group) were included for comparative analysis. General information, laboratory indicators, urinary protein, and coagulation‐fibrinolysis indicator levels were collected for each group. Significant differences were observed in blood pressure among groups (P .05). Total cholesterol, triglycerides, and low‐density Lipoprotein levels in severe preeclampsia were higher than those in mild preeclampsia and gestational hypertension groups, whereas high‐density lipoprotein, albumin, and platelet levels were lower in severe preeclampsia. No significant differences were observed in prothrombin time or D‐dimer levels among groups (P > .05). Urinary protein, urinary protein quantification, activated partial thromboplastin time, thrombin time, and fibrinogen were identified as influencing factors for adverse maternal and infant outcomes in severe preeclampsia patients. The study concludes that urinary protein and coagulation‐fibrinolysis indicators are elevated in preeclampsia, particularly in severe preeclampsia cases, suggesting their potential use as diagnostic influencing factors for severe preeclampsia.

Abstract Reversible solid-state hydrogen storage of magnesium hydride, traditionally driven by external heating, is constrained by massive energy input and low systematic energy density. Herein, a single phase of Mg2Ni(Cu) alloy is designed via atomic reconstruction to achieve the ideal integration of photothermal and catalytic effects for stable solar-driven hydrogen storage of MgH2. With the intra/inter-band transitions of Mg2Ni(Cu) and its hydrogenated state, over 85% absorption in the entire spectrum is achieved, resulting in the temperature up to 261.8 °C under 2.6 W cm−2. Moreover, the hydrogen storage reaction of Mg2Ni(Cu) is thermodynamically and kinetically favored, and the imbalanced distribution of the light-induced hot electrons within CuNi and Mg2Ni(Cu) facilitates the weakening of Mg-H bonds of MgH2, enhancing the “hydrogen pump” effect of Mg2Ni(Cu)/Mg2Ni(Cu)H4. The reversible generation of Mg2Ni(Cu) upon repeated dehydrogenation process enables the continuous integration of photothermal and catalytic roles stably, ensuring the direct action of localized heat on the catalytic sites without any heat loss, thereby achieving a 6.1 wt.% H2 reversible capacity with 95% retention under 3.5 W cm−2.

Abstract Objective To investigate the effectiveness and tolerability of ketogenic diet therapy (KDT) in patients with developmental and epileptic encephalopathy (DEE) associated with genetic etiology which onset within the first 6 months of life, and to explore the association between response to KDT and genotype/clinical parameters. Methods We retrospectively reviewed data from patients with genetic DEE who started KDT at Beijing Children's Hospital between January 1, 2016, and December 31, 2021. Results A total of 32 patients were included, involving 14 pathogenic or likely pathogenic single genes, and 16 (50.0%) patients had sodium/potassium channel gene variants. The median age at onset of epilepsy was 1.0 (IQR: 0.1, 3.0) months. The median age at initiation of KDT was 10.0 (IQR: 5.3, 13.8) months and the median duration of maintenance was 14.0 (IQR: 7.0, 26.5) months, with a mean blood β‐hydroxybutyrate of 2.49 ± 0.62 mmol/L. During the maintenance period of KDT, 26 (81.3%) patients had a ≥50% reduction of seizure frequency, of which 12 (37.5%) patients achieved seizure freedom. Better responses were observed in patients with STXBP1 variants, with four out of five patients achieving seizure freedom. There were no statistically differences in the age of onset, duration of epilepsy before KDT, blood ketone values, or the presence of ion channel gene variants between the seizure‐free patients and the others. The most common adverse effects were gastrointestinal side effects, which occurred in 21 patients (65.6%), but all were mild and easily corrected. Only one patient discontinued KDT due to nephrolithiasis. Significance KDT is effective in treating early onset genetic DEE, and no statistically significant relationship has been found between genotype and effectiveness in this study. KDT is well tolerated in most young patients, with mild and reversible gastrointestinal side effects being the most common, but usually not the reason to discontinue KDT. Plain Language Summary This study evaluated the response and side effects of ketogenic diet therapy (KDT) in patients who had seizures within the first 6 months of life, and were diagnosed with genetic developmental and epileptic encephalopathy (DEE), a type of severe epilepsy with developmental delay caused by gene variants. Thirty‐two patients involving 14 gene variants who started KDT at Beijing Children's Hospital between were included. KDT was effective in treating early onset genetic DEE in this cohort, and patients with STXBP1 variants responded better; however, no statistically significant relationship was found between gene variant and response. Most young patients tolerated KDT well, with mild and reversible gastrointestinal side effects being the most common.

Purpose: This study aimed to investigate the association between hemoglobin-to-red blood cell distribution width ratio (HRR) and cognitive function. Methods: Data, including cognition assessment, general characteristics, lifestyle attributes, disease-related factors, and blood indicators, were extracted from older people from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 database. Statistical analysis included the Mann-Whitney U test, chi-square test, spearman correlation, and multiple linear regression. Results: A total of 2452 participants were included, with 631(25.7 %) identified as having low-level cognition. HRR was significantly lower in the lower cognition group (P < 0.001) and positively associated with cognition score (P < 0.001). Multiple linear logistic regression analysis indicated that HRR remained associated with cognition even after adjusting for general characteristics, lifestyle attributes, disease-related factors, and blood indicators (P = 0.046). Conclusion: Lower HRR is an independent risk factor for low cognitive performance in older adults. However, further investigation is needed to elucidate the precise mechanism underlying the impact of HRR on cognitive function.

IntroductionThe primary objective of our study was to evaluate the first use of a novel intracardiac echocardiography (ICE) catheter in human subjects. This study aimed to assess its practicality, image clarity, and guidance role during electrophysiology procedures.MethodsTwo patients underwent procedures using the novel ICE catheter. Post-procedure evaluations were conducted by four operators, who assessed the imaging quality and overall performance of the catheter. Anatomical and blood test results were also analyzed to determine the safety and impact on internal cardiac structures.ResultsBoth patients were discharged one day after the procedure without any complications. The novel ICE catheter provided comparable imaging quality to existing commercial catheters. The catheter's advanced design allowed for detailed imaging at short distances, essential for accurate diagnosis and treatment planning. Moreover, it successfully navigated complex anatomical structures like the atrial septum and left atrial appendage.DiscussionThese preliminary studies indicate that the novel ICE catheter achieves a level of safety and effectiveness comparable to previously available commercial catheters. The findings highlight its potential to meet current clinical needs, particularly in sophisticated anatomic interventions. Despite the prolonged thrombin time after anticoagulant administration, both types of ICE catheters were non-damaging to cardiac structures during routine operations. The study underscores the importance of using trans-septal large inner diameter sheaths to minimize complications when advancing the catheter into the left atrium.

Commented article: WANG, Z. Philosophical Perspective on Artistic Development and Historic Animation Thinking. Trans/Form/Ação: revista de filosofia da Unesp, v. 47, n. 5, “Eastern thought 2”, e02400159, 2024. Available at: https://revistas.marilia.unesp.br/index.php/transformacao/article/view/15071.

Summary: Background: Pulmonary embolism causes a substantial burden of morbidity and mortality. Although there are several well-established risk factors for pulmonary embolism, a substantial proportion of cases cannot be attributed to provoked or known risk factors. Accumulating evidence has suggested an association of clonal hematopoiesis of indeterminate potential (CHIP) with the risk of arterial thromboembolism. However, the association between CHIP and the risk of pulmonary embolism remains unknown. Methods: We performed a community-based cohort study (between 2006 and 2022) including 464,417 individuals with available whole exome sequencing (WES) data in the UK biobank (UKB) to examine the association between CHIP and pulmonary embolism. CHIP was ascertained by analyzing WES data. We used Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to assess the association between CHIP and pulmonary embolism. In addition, we performed analyses for several types of CHIP mutations, including DNMT3A, TET2, ASXL1, PPM1D, SRSF2, and JAK2. Findings: The study included 14,418 individuals with CHIP and 449,999 individuals without CHIP. The median age at cohort entry was 58 and 63 years among individuals without and with CHIP, respectively. We observed an increased risk of pulmonary embolism (HR 1.17, 95% CI, 1.05–1.31) among individuals with CHIP. The increased risk was mainly noted for CHIP with TET2 (HR 1.42, 95% CI 1.16–1.74) or JAK2 (HR 4.17, 95% CI 2.09–8.35) mutation, but not for DNMT3A mutation (HR 1.01, 95% CI 0.86–1.19), ASXL1 mutation (HR 1.15, 95% CI 0.83–1.60), PPM1D mutation (HR 1.22, 95% CI 0.66–2.27), or SRSF2 mutation (HR 0.62, 95% CI 0.20–1.93). Interpretation: Our results highlight the association of pulmonary embolism in individuals with CHIP, especially the TET2-mutant or JAK2-mutant CHIP. If further studies will identify a causal relationship between clonal hematopoiesis and pulmonary embolism, prioritizing early screening for pulmonary embolism in individuals with CHIP could be significantly beneficial. Funding: Initial Founding for High Level Talented Scholars in Nanfang Hospital, Southern Medical University (No. 2023G001) and the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (Grant No. 2023J009).

Background The band and loop space maintainer is used to maintain the missing space of deciduous molars which are lost early. When the second deciduous molar is lost prematurely, the stress on the first permanent molar during different degrees of development may vary when it is the abutment. The design and use of the space maintainer may also lead to damage of the loop. The purpose of this article is to use the finite element method to study the stress on the first permanent molar and the loop with or without occlusal contact, with the first permanent molar of four different degrees of development serving as the abutment. We aimed to guide the clinical design and use of the space maintainer. Methods We developed finite element models of the mandibular first permanent molar and the band and loop space maintainer, and simulated alveolar bone, periodontal ligament (PDL), enamel and dentin. The four developmental stages were 1/2 (I), 2/3 (II), 3/4 (III) and full development (IV). Ansys Workbench was used to analyze the effects of root development and occlusal contact between the loop and the opposite jaw on abutment teeth and the loop. Abutment teeth were statically loaded vertically and obliquely with a force of 70 N. The loop was statically loaded vertically with a force of 14 N. The stress on all structures and the displacement trends of the loop were calculated. Results The stress on enamel, dentin, PDL and alveolar bone were similar, and the concentration was consistent. But if there was occlusal contact, the loop produced maximum displacement at the near middle edge of contact with the anterior teeth. When the loop was in occlusal contact with the opposing occlusal tooth, the peak value of the equivalent stress on the space maintainer under vertical load was: group I > group IV > group III > group II, and the maximum principal stress peak change was: group I > group III > group II > group IV. The change of the equivalent stress peak value of the loop under oblique load was: group I > group III > group IV > group II, and the maximum principal stress peak change was: group III > group I > group II > group IV. When the loop was not in occlusal contact with the opposing occlusal tooth, the peak value of the equivalent stress on the space maintainer under vertical load was: group IV > group I > group II > group III, and the maximum principal stress peak change was: group IV > group I > group II > group III. The change of the equivalent stress peak value of the space maintainer under oblique load was: group I > group IV > group II > group III, and the maximum principal stress peak change was: group I > group IV > group II > group III. Conclusions Our results suggested that whenever possible, choosing the teeth with nearly complete root development as the abutment of the space maintainer is advisable. The design and use of the band and loop space maintainer should avoid occlusal contact with the occlusal teeth to prevent deformation of the loop.

BackgroundThe association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients.MethodsOur retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association between FAR and long-term mortality.ResultsOut of a total of 3,538 patients, 364 individuals (10.3%) experienced in-hospital mortality, and 750 patients (21.2%) succumbed within one year. The adjusted hazard ratios (HR) showed significant associations with in-hospital mortality (HR 1.61, 95% CI 1.31–1.99), 1-year mortality (HR 1.45, 95% CI 1.25–1.67), and long-term mortality (HR 1.45, 95% CI 1.28–1.64). Notably, the HR for long-term mortality remained statistically significant at 1.47 (95% CI, 1.15–1.88) even after excluding patients with 1-year mortality.ConclusionA high admission FAR was significantly correlated with an elevated HR for long-term mortality in patients with ICH. The combined assessment of the ICH score and FAR at admission showed higher predictive accuracy for long-term mortality than using the ICH score in isolation.

Losartan is widely used in the treatment of chronic kidney disease (CKD) and has achieved good clinical efficacy, but its exact mechanism is not clear. We performed high-throughput sequencing (HTS) technology to screen the potential target of losartan in treating CKD. According to the HTS results, we found that the tumor necrosis factor (TNF) signal pathway was enriched. Therefore, we conducted in vivo and in vitro experiments to verify it. We found that TNF signal pathway was activated in both unilateral ureteral obstruction (UUO) rats and human proximal renal tubular epithelial cells (HK-2) treated with transforming growth factor-β1 (TGF-β1), while losartan can significantly inhibit TNF signal pathway as well as the expression of fibrosis related genes (such as COL-1, α-SMA and Vimentin). These data suggest that losartan may ameliorate renal fibrosis through modulating the TNF pathway. Resumen: El Losartán es ampliamente utilizado en el tratamiento de la enfermedad renal crónica (CKD) y ha logrado buenos resultados clínicos, pero su mecanismo exacto aún no está claro. Utilizamos la técnica de secuenciación de alto rendimiento (HTS) para detectar posibles dianas de losartán para el tratamiento de la CKD. Según los resultados de HTS, encontramos un enriquecimiento de la vía de señalización del factor de necrosis tumoral (TNF). Así, realizamos experimentos in vivo e in vitro para verificar esto. Encontramos que, tanto en ratas con obstrucción ureteral unilateral (uuo) como en células epiteliales tubulares renales proximal humanas (HK-2) tratadas con factor de crecimiento transformador β1 (TGF-β1), se activó la vía de señalización del TNF. El losartán inhibe significativamente la expresión de las vías de señalización del TNF y genes relacionados con la fibrosis, como COL-1, α-SMA y vicentin. Estos datos sugieren que el losartán puede mejorar la fibrosis renal regulando la vía del TNF.

Abstract Background The gaps between estrogenic effect and its effect-active compounds exist frequently due to a large number of compounds that have been reported to induce this effect and the occurrence of pollutants in environments as mixtures. Therefore, identifying the estrogen-active compounds is of importance for environmental management and pollution treatment. In the current study, the effect-directed analysis (EDA) and non-targeted screening (NTS) were integrated to identify the estrogen-active compounds in soils of the rural area with different socioeconomic types (industrial, farming and plantation village) in Northeast China. Results The cytotoxicity results indicated that the industrial and farming villages showed cytotoxic effects. The detection rates of estrogenic effects for samples of winter and summer were 100% and 87%, respectively. Of which, the effects were found to be stronger in summer than in winter, with significant difference observed from the farming village (0.1–11.3 EEQ μg/kg dry weight). A total of 159 chemicals were detected by NTS. By integrating EDA, triphenyl phosphate (TPhP) and indole were successfully identified from a raw sample and its fraction, explaining up to 19.31% of the estrogen activity. Conclusions The present study demonstrates that the successful identification of seven estrogen-active compounds in rural areas of northeastern China can be achieved through the combination of effect-directed analysis (EDA) and non-targeted screening (NTS). This finding is beneficial for risk monitoring and pollution management.

Abstract As a precursor process to cloud formation, aerosol activation over the Tibetan Plateau (TP) plays a pivotal role in regional cloud-precipitation and global climate. However, its characteristics remain unclear due to the absence of targeted observations in the TP. We conducted a ground in-situ aerosol-cloud-precipitation experiment in the southern TP (GACPE-STP), thereby unveiling the aerosol activation characteristics in this crucial region. Our findings reveal a weak aerosol activation capacity with low hygroscopicity (κ) values of less than 0.1 through multi-method κ measurements, contrasting starkly with the widely recommended κ value of 0.3 for continental regions. A κ parameterization is developed for predicting aerosol activation in this region, which can significantly reduce the overestimations of cloud droplet number concentration and hence aerosol indirect effects caused by using the recommended κ of 0.3. These findings address the unclear characteristics of aerosol activation in the TP region, contributing to the enhancement of regional cloud precipitation and global climate simulations.

Introduction: Forming a bridge made of functional axons to span the lesion is essential to reconstruct the motor circuitry following spinal cord injury (SCI). Dorsal root ganglion (DRG) axons are robust in axon growth and have been proved to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. However, whether DRG transplantation affects the axon outgrowth of spinal motor neurons (SMNs) that play crucial roles in motor circuitry remains unclear. Methods: We investigated the axonal growth patterns of co-cultured DRGs and SMN aggregates (SMNAs) taking advantage of a well-designed 3D-printed in vitro system. Chondroitin sulphate proteoglycans (CSPG) induced inhibitory matrix was introduced to imitate the inhibitory environment following SCI. Axonal lengths of DRG, SMNA or DRG & SMNA cultured on the permissive or CSPG induced inhibitory matrix were measured and compared. Results: Our results indicated that under the guidance of full axonal connection generated from two opposing populations of DRGs, SMNA axons were growth-enhanced and elongated along the DRG axon bridge to distances that they could not otherwise reach. Quantitatively, the co-culture increased the SMNA axonal length by 32.1 %. Moreover, the CSPG matrix reduced the axonal length of DRGs and SMNAs by 46.2 % and 17.7 %, respectively. This inhibitory effect was antagonized by the co-culture of DRGs and SMNAs. Especially for SMNAs, they extended the axons across the CSPG-coating matrix, reached the lengths close to those of SMNAs cultured on the permissive matrix alone. Conclusions: This study deepens our understanding of axon-facilitated reconstruction of the motor circuitry. Moreover, the results support SCI treatment utilizing the enhanced outgrowth of axons to restore functional connectivity in SCI patients.

Abstract Background Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking. Methods Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (

Abstract Background Peripheral vertigo is often comorbid with psychiatric disorders. However, no longitudinal study has quantified the association between peripheral vertigo and risk of psychiatric disorders. Furthermore, it remains unknown how the white matter integrity of frontal-limbic network relates to the putative peripheral vertigo-psychiatric disorder link. Methods We conducted a cohort study including 452,053 participants of the UK Biobank with a follow-up from 2006 through 2021. We assessed the risks of depression and anxiety disorders in relation to a hospitalization episode involving peripheral vertigo using Cox proportional hazards models. We also examined the associations of peripheral vertigo, depression, and anxiety with MRI fractional anisotropy (FA) in a subsample with brain MRI data (N = 36,087), using multivariable linear regression. Results Individuals with an inpatient diagnosis of peripheral vertigo had elevated risks of incident depression (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.79–2.67) and anxiety (HR 2.11; 95% CI 1.71–2.61), compared to others, particularly within 2 years after hospitalization (HR for depression 2.91; 95% CI 2.04–4.15; HR for anxiety 4.92; 95% CI 3.62–6.69). Depression was associated with lower FA in most studied white matter regions, whereas anxiety and peripheral vertigo did not show statistically significant associations with FA. Conclusions Individuals with an inpatient diagnosis of peripheral vertigo have increased subsequent risks of depression and anxiety disorders, especially within 2 years after hospitalization. Our findings further indicate a link between depression and lower microstructural connectivity as well as integrity beyond the frontal-limbic network.

Abstract Background Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. Methods The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. Results In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. Conclusion In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.