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Abstract Background For resectable adenocarcinoma of the esophagogastric junction (AEG), current treatment exploration primarily focuses on perioperative chemotherapy regimens combined with PD-1/PD-L1 inhibitors, but the long-term survival benefits of still require further investigation, and the use of upfront immunotherapy is typically restricted to patients with metastatic MSI-H (M1 MSI-H) disease due to their potential responsiveness to immunological agents. Adebrelimab, as a novel PD-L1 antibody, has not yet been proven for its efficacy and safety in adenocarcinoma of the esophagogastric junction. Methods The AEGIS study is a prospective, open-labeled, single-arm, phase II clinical trial. A total of 26 patients with AEG will be enrolled. The primary endpoint is the pathologic complete response (pCR) rate after perioperative neoadjuvant immunochemotherapy. Secondary outcomes of the study include the objective response rate (ORR), R0 resection rate, major pathological response (MPR) rate, and pCR rate in combined positive score(CPS) ≥ 5 and MSI-H populations, event-free survival (EFS), and overall survival (OS). The exploratory outcomes are the biomarkers related to therapeutic efficacy, such as PD-L1 expression, microsatellite instability (MSI), tumor mutational burden(TMB), Epstein-Barr virus(EBV) infection, and circulating tumor DNA(ctDNA). Discussion This trail aims to verify the efficacy and safety of the perioperative treatment regimen of anti-PD-L1 (Adebrelimab) combined with chemotherapy (capecitabine plus oxaliplatin, XELOX) for patients with resectable AEG. Considering the differences in chemotherapy regimen tolerance between Asian and Western populations, this study intends to evaluate the suitability of Adebrelimab combined with XELOX chemotherapy for the Asian population. Trial registration ClinicalTrials.gov: NCT06482788. The trial was prospectively registered on 22 May 2024, https://clinicaltrials.gov/study/NCT06482788 .

ObjectivesThe global prevalence of diabetes is continuously rising, and the gut microbiota is closely associated with it. The Dietary Index for Gut Microbiota (DI-GM) assesses the impact of diet on the microbiota, but its association with diabetes risk remains unclear. This study aims to investigate the association between DI-GM and the risk of diabetes and analyze the mediating roles of phenotypic age and body mass index (BMI).MethodsUtilizing data from the National Health and nutrition examination survey (NHANES) 1999–2018, we included 17,444 adults aged 20 years and older. DI-GM (score range: 0–13) was calculated based on dietary recall. Diabetes was diagnosed based on laboratory results and self-reported information. Multivariable logistic regression was used to analyze the association between DI-GM and diabetes, adjusting for relevant covariates. Mediation analysis evaluated the roles of phenotypic age and BMI.ResultsAfter adjusting for confounders, higher DI-GM scores were significantly associated with a lower risk of diabetes (OR = 0.93, 95% CI = 0.90–0.96, p

The hepatitis B virus (HBV) infects many people worldwide. As HBV infection frequently leads to liver fibrosis and carcinogenesis, developing anti-HBV therapeutic drugs is urgent. Therapeutic drugs for preventing covalently closed circular DNA (cccDNA) production, which can eliminate HBV infection, are unavailable. The host factor dedicator of cytokinesis 11 (DOCK11) is involved in the synthesis and maintenance of HBV cccDNA in vitro. However, the effectiveness of DOCK11 as a target for the in vivo elimination of HBV cccDNA remains unclear. In this study, we assess whether DOCK11 inhibitors suppress HBV cccDNA production in mouse models of HBV infection. The tocopherol-conjugate hetero- gapmer, a DNA/RNA duplex of gapmer/complementary RNA targeting the DOCK11 sequence, partially reduces the expression of DOCK11, but not that of HBV cccDNA, in the livers of HBV-infected human hepatocyte chimeric mice, along with weight loss and decreased serum human albumin levels. Lipid nanoparticle-encapsulated chemically modified siRNAs specific for DOCK11 suppress DOCK11 expression and decrease HBV cccDNA levels without adverse effects in the mice. Therefore, nucleic acid-based drugs targeting DOCK11 in hepatocytes are potentially effective anti-HBV therapeutics that can reduce HBV cccDNA levels in vivo.

Intravenous thrombolysis is an effective treatment for acute ischemic stroke. The ESO recommends that tenecteplase be used for thrombolytic therapy in stroke within 4.5h of onset. However, there are few reports on the complications of intravenous thrombolysis with tenecteplase in stroke, and spinal hematomas are rare. Herein, we report the first case of spinal subdural hematoma secondary to tenecteplase treatment for stroke. A 71-year-old male patient arrived at the stroke center because of left limb weakness that had persisted for 105 min. After intravenous thrombolysis with tenecteplase, the patient experienced unbearable pain in the neck and left shoulder, progressive limb weakness, and sensory disturbance. MRI revealed a spinal subdural hematoma of the cervical vertebrae, and the prognosis was poor after surgical treatment. Once patients develop pain around the spine with intravenous thrombolysis, physicians should be aware of the possibility of a spinal subdural hematoma and promptly perform MRI.

Taking a slope as a unit, the regional vulnerability assessment based on potential disaster intensity is one of the important problems to be solved urgently. In this paper, the city of Xiangxiang in Hunan is selected as the research area. On the basis of susceptibility regionalization with the weighted information value method, the elevation, slope height, slope, slope direction and monthly average rainfall of the highest prone points of slope units are extract one by one as the characteristic parameters, which are put into the BP neural network, PSO-BP neural network, random forest and support vector machine model, respectively. A landslide volume prediction model based on BP neural network algorithm optimized by PSO is constructed through training and precision test comparison. A comprehensive vulnerability evaluation model is established with disaster volume as disaster intensity index and building density, population density and property density as vulnerability indexes. Regional vulnerability evaluation based on potential disaster intensity is carried out for the study area. The divisions of high-vulnerable areas (1.5% of the total area), medium-vulnerable areas (28.5% of the total area) and low-vulnerable areas (70% of the total area) are completed, which realize the organic combination of the disaster intensity of the disaster-causing body and the vulnerability of the disaster-bearing body in the process of regional vulnerability evaluation, and enhance the objectivity and scientific nature of the evaluation.

ABSTRACT Objective: The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. Subjects and methods: In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. Results: The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). Conclusion: Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.

This paper addresses the issue of uncertainty in the grading of geological hazard susceptibility evaluation factors and introduces the adaptive expansion factor fuzzy coverage grading method (AIFFC) to optimize the grading of geological hazard susceptibility evaluation factors. Taking Xiangxiang City, Hunan Province as the research area, nine evaluation factors, including slope, slope direction, elevation and average annual rainfall, normalized difference vegetation index for land use, roads, faults, lithology, were extracted. The AIFFC method and the natural breakpoint method were used to grade continuous factors. These graded factors were then incorporated into a weighted information model and random forest model to obtain a susceptibility zoning map for the study area. The superiority of the AIFFC classification method was tested through the comparison of single-factor grading results, disaster product ratio analysis,and ROC curve comparison of susceptibility zoning results. Based on AIFFC, the hazard accumulation ratio of the random forest model and the weighted information entropy model in the high susceptibility areas increased by 56.3% and 74.6%, respectively, while in the low susceptibility areas, it decreased by 48% and 58.1%, respectively. The AUC values increased by 7.6% and 2.7%, respectively. The AIFFC classification method is used to optimize the evaluation factor classification of geological disaster susceptibility, which significantly improves the rationality of the evaluation of geological disaster susceptibility.

The perception of health risks can influence people’s health behaviors. However, in the context of modern consumer society, few people delve into in-depth discussions on health consumption as a form of health protection behavior. Inspired by the Health Belief Model and Protection Motivation Theory, this study interprets health consumption behavior as a new form of health protection behavior. A survey was conducted on a sample of Chinese youth (N = 885) to explore the mechanisms of action between health risk perception and health consumption behavior using structural equation modeling. The study found that: (1) health risk perception has a significant positive impact on the health consumption behavior of young people; (2) negative emotions and information seeking play mediating roles respectively in the mechanism of the impact of health risk perception on health consumption behavior; and (3) in addition to their individual mediating roles, negative emotions and information seeking behavior collectively play a chained mediation role in this process. Implications of these results, both theoretical and practical, are further discussed.

Abstract Introduction Clinical practice of dentistry entails the use of indirect vision using a dental mirror. The Mirrosistant is a device that helps dental students become proficient with use of indirect vision mirror operation. This study aimed to explore the role of the Mirrosistant on students’ performance with the virtual simulation dental training system. Materials and methods A total of 72 dental students were equally assigned to the Control group and the Experimental group. Subsequently, Mirrosistant was used to conduct a series of mirror training exercises in the Experimental group. The training consisted of tracing the edge and filling in the blank of the prescribed shape, as well as preparing the specified figure on raw eggs using indirect vision via Mirrosistant. Next, both groups were examined using the SIMODONT system, a virtual reality dental trainer, for mirror operation. In addition, a five-point Likert scale questionnaire was used to assess student feedback by using Mirrosistant. Results The mirror operation examination conducted by the SIMODONT system revealed that mirror training using Mirrosistant had statistically improved students’ performances (score: 80.42 ± 6.43 vs. 69.89 ± 15.98, P = 0.0005) and shorten their performance time of mirror operation (time of seconds: 243.28 ± 132.83 vs. 328.53 ± 111.89, P = 0.0013). Furthermore, the questionnaire survey indicated that the participants had positive attitudes toward the mirror training using Mirrosistant. Most students believed that the mirror training device could improve their perceptions of direction and distance, as well as their sensations of dental operation and dental fulcrum. Conclusion Mirror training using Mirrosistant can enhance dental students’ mirror perceptual and operational skills on virtual simulation dental training system.

Cutaneous T cell lymphomas (CTCL) are still poorly characterised at the molecular and single-cell level. Here, the authors analyse CTCL patient samples using single-cell RNA-seq, TCR and whole-exome sequencing, revealing the molecular profiles of malignant T cells and their association with the microenvironment and clinical outcomes.

Given the inconsistency between the information value and the weight value in the weighted information value model, a weight model based on the Apriori algorithm is established in this paper to analyze the correlation between the second-level intervals of disaster factors and the susceptibility of geological disasters. The objective weight of the second-level intervals of each index factor is calculated through the mining of association rules by the Apriori algorithm. The subjective uncertainty of the existing second-level factor weighting method is eliminated. Taking the geological disaster data of Xiangtan urban area as an example, 10 evaluation indexes were selected to establish the entropy weight method-information value (EWM-IV) model and the entropy weight method-Apriori algorithm-information value (EWM-Apriori-IV) model to evaluate the geological disaster susceptibility, and the disaster area ratio and the receiver operating characteristic curve (ROC) verification method were used to test and analyze the evaluation results. The results showed that compared with the EWM-IV model, the EWM-Apriori-IV model is used to evaluate the disaster area ratio of high-prone area increased by 58.3%, and the disaster area ratio of low-prone area decreased by 43.1%, the area under the curve (AUC) increased by 7.4%, and the evaluation accuracy was relatively improved compared with the former. This paper proves the rationality and practicability of the weighting method of the geological hazard susceptibility evaluation index based on the Apriori algorithm.

BACKGROUND Immune checkpoint blockade is an emerging treatment for T cell non-Hodgkin’s lymphoma (T-NHL), but some patients with T-NHL have experienced hyperprogression with undetermined mechanisms upon anti–PD-1 therapy.METHODS Single-cell RNA-Seq, whole-genome sequencing, whole-exome sequencing, and functional assays were performed on primary malignant T cells from a patient with advanced cutaneous T cell lymphoma who experienced hyperprogression upon anti–PD-1 treatment.RESULTS The patient was enrolled in a clinical trial of anti–PD-1 therapy and experienced disease hyperprogression. Single-cell RNA-Seq revealed that PD-1 blockade elicited a remarkable activation and proliferation of the CD4+ malignant T cells, which showed functional PD-1 expression and an exhausted status. Further analyses identified somatic amplification of PRKCQ in the malignant T cells. PRKCQ encodes PKCθ; PKCθ is a key player in the T cell activation/NF-κB pathway. PRKCQ amplification led to high expressions of PKCθ and p-PKCθ (T538) on the malignant T cells, resulting in an oncogenic activation of the T cell receptor (TCR) signaling pathway. PD-1 blockade in this patient released this signaling, derepressed the proliferation of malignant T cells, and resulted in disease hyperprogression.CONCLUSION Our study provides real-world clinical evidence that PD-1 acts as a tumor suppressor for malignant T cells with oncogenic TCR activation.TRIAL REGISTRATION ClinicalTrials.gov (NCT03809767).FUNDING The National Natural Science Foundation of China (81922058), the National Science Fund for Distinguished Young Scholars (T2125002), the National Science and Technology Major Project (2019YFC1315702), the National Youth Top-Notch Talent Support Program (283812), and the Peking University Clinical Medicine plus X Youth Project (PKU2019LCXQ012) supported this work.

The malignant nature of hepatocellular carcinoma (HCC) is closely related to the presence of cancer stem cells (CSCs). Bone morphologic protein 9 (BMP9), a member of the transforming growth factor‐beta (TGF‐β) superfamily, was recently reported to be involved in liver diseases including cancer. We aimed to elucidate the role of BMP9 signaling in HCC‐CSC properties and to assess the therapeutic effect of BMP receptor inhibitors in HCC. We have identified that high BMP9 expression in tumor tissues or serum from patients with HCC leads to poorer outcome. BMP9 promoted CSC properties in epithelial cell adhesion molecule (EpCAM)‐positive HCC subtype via enhancing inhibitor of DNA‐binding protein 1 (ID1) expression in vitro. Additionally, ID1 knockdown significantly repressed BMP9‐promoted HCC‐CSC properties by suppressing Wnt/β‐catenin signaling. Interestingly, cells treated with BMP receptor inhibitors K02288 and LDN‐212854 blocked HCC‐CSC activation by inhibiting BMP9‐ID1 signaling, in contrast to cells treated with the TGF‐β receptor inhibitor galunisertib. Treatment with LDN‐212854 suppressed HCC tumor growth by repressing ID1 and EpCAM in vivo. Our study demonstrates the pivotal role of BMP9‐ID1 signaling in promoting HCC‐CSC properties and the therapeutic potential of BMP receptor inhibitors in treating EpCAM‐positive HCC. Therefore, targeting BMP9‐ID1 signaling could offer novel therapeutic options for patients with malignant HCC.

Background: Circular RNA (circRNA) is a newly-discovered endogenous transcript that has been reported to participate in osteosarcoma (OS) progression. However, the underlying mechanism of circ_0051079 modulating OS development remains unclear. Methods: RNA expressions of circ_0051079, miR-625-5p and tripartite motif containing 66 (TRIM66) were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis. The functional effects of circ_0051079 on OS cell malignancy were investigated by cell counting kit-8, clonogenicity, transwell, tube formation and flow cytometry assays. The interactions among circ_0051079, miR-625-5p and TRIM66 were identified by dual-luciferase reporter and RNA immunoprecipitation assays. Mouse xenograft model assay was performed to elucidate the effects of circ_0051079 knockdown on tumor formation in vivo. Results: Circ_0051079 and TRIM66 expressions were significantly upregulated, but miR-625-5p was downregulated in OS tissues and cells compared with control groups. Circ_0051079 expression was significantly associated with tumor-node-metastasis stage and tumor size of OS patients. Circ_0051079 knockdown inhibited OS cell proliferation, migration and invasion, repressed angiogenesis but induced cell apoptosis, accompanied by the decreases of PCNA and Bcl-2 production and an increase of Bax production. MiR-625-5p, a target miRNA of circ_0051079, participated in regulating circ_0051079-induced effects. Also, TRIM66 was identified as a target mRNA of miR-625-5p, and partially attenuated the inhibitory effects of miR-625-5p in OS cells. Circ_0051079 modulated the Wnt/β-catenin pathway through TRIM66 in vitro. Importantly, circ_0051079 silencing reduced TRIM66 expression by interacting with miR-625-5p. Further, circ_0051079 depletion inhibited tumor formation in vivo. Conclusion: Circ_0051079 regulated OS development by the miR-625-5p/TRIM66/Wnt/β-catenin pathway, providing a novel therapeutic target for OS.

Cutaneous T cell lymphoma is a generally indolent disease derived from skin-homing mature T cells. However, in advanced stages, cutaneous T cell lymphoma may manifest aggressive clinical behaviour and lead to a poor prognosis. The mechanism of disease progression in cutaneous T cell lymphoma remains unknown. This study, based on a large clinical cohort, found that IKZF2, an essential transcription factor during T cell development and differentiation, showed stage- dependent overexpression in the malignant T cells in mycosis fungoides lesions. IKZF2 is specifically over- expressed in advanced-stage mycosis fungoides lesions, and correlates with poor prognosis. Mechanistically, overexpression of IKZF2 promotes cutaneous T cell lymphoma progression via inhibiting malignant cell apoptosis and may contribute to tumour immune escape by downregulating major histocompatibility complex II molecules and up-regulating the production of anti-inflammatory cytokine interleukin-10 by malignant T cells. These results demonstrate the important role of IKZF2 in high-risk cutaneous T cell lymphoma and pave the way for future targeted therapy.

Abstract Background Rice (Oryza sativa L.) yield is seriously influenced by panicle exsertion (PE) and the uppermost internode (UI) through panicle enclosure or energy transport during grain-filling stages. We evaluated the traits of PE and UI of 205 rice accessions in two independent environments and performed genome-wide association (GWAS) to explore the key genes controlling PE and UI, which could be used to improve panicle enclosure in rice breeding. Results In this study, extensive genetic variation was found in both PE and UI among the 205 rice accessions, and 10.7% of accessions had panicle enclosure (PE/UI ≤ 0). Correlation analysis revealed that PE was significantly positively correlated with 1000-grain weight (1000-GW) but negatively correlated with heading date (HD), and UI was significantly positively correlated with HD but no significantly correlated with 1000-GW. A total of 22 and 24 quantitative trait loci (QTLs) were identified for PE and UI using GWAS, respectively. Eight loci for PE and nine loci for UI were simultaneously detected both in 2015 and in 2016, seven loci had adjacent physical positions between PE and UI, and ten loci for PE and seven loci for UI were located in previously reported QTLs. Further, we identified the CYP734A4 gene, encoding a cytochrome P450 monooxygenase, and the OsLIS-L1 gene, encoding a lissencephaly type-1-like protein, as causal genes for qPE14 and qUI14, and for qPE19, respectively. PE and UI were both significantly shorter in these two genes’ mutants than in WT. Allelic Hap.1/2/4 of CYP734A4 and Hap.1/2/4 of OsLIS-L1 increased PE, UI, PE/UI, and 1000-GW, but Hap.3 of CYP734A4 and Hap.3 of OsLIS-L1 reduced them. In addition, six candidate genes were also detected for four key novel loci, qPE16, qPE21, qUI1, and qUI18, that seemed to be related to PE and UI. Conclusions Our results provide new information on the genetic architecture of PE and UI in rice, confirming that the CYP734A4 and OsLIS-L1 genes participate in PE and UI regulation, which could improve our understanding of the regulatory mechanism of PE and UI for rice breeding in the future.

A graphene passively Q-switched Nd:YAG laser experienced resonant pumping by an 885 nm laser diode (LD), as demonstrated in this paper. In the continuous-wave operation, the maximum average output power was up to 1.8 W with the absorbed pump power being 11.7 W, and the slope efficiency was 51.2%. In the Q-switching operation, the maximum average output power was up to 639 mW with a pulse width of 2.06 μs at the repetition frequency of 102.7 kHz, while the slope efficiency and the beam quality factor M2 were 25.3% and 1.25, respectively.

Receptor-mediated transcytosis (RMT) is used to enhance the delivery of monoclonal antibodies (mAb) into the central nervous system (CNS). While the binding to endogenous receptors on the brain capillary endothelial cells (BCECs) may facilitate the uptake of mAbs in the brain, a strong affinity for the receptor may hinder the efficiency of transcytosis. To quantitatively investigate the effect of binding affinity on the pharmacokinetics (PK) of anti-transferrin receptor (TfR) mAbs in different regions of the rat brain, we conducted a microdialysis study to directly measure the concentration of free mAbs at different sites of interest. Our results confirmed that bivalent anti-TfR mAb with an optimal dissociation constant (KD) value (76 nM) among four affinity variants can have up to 10-fold higher transcytosed free mAb exposure in the brain interstitial fluid (bISF) compared to lower and higher affinity mAbs (5 and 174 nM). This bell-shaped relationship between KD values and the increased brain exposure of mAbs was also visible when using whole-brain PK data. However, we found that mAb concentrations in postvascular brain supernatant (obtained after capillary depletion) were almost always higher than the concentrations measured in bISF using microdialysis. We also observed that the increase in mAb area under the concentration curve in CSF compartments was less significant, which highlights the challenge in using CSF measurement as a surrogate for estimating the efficiency of RMT delivery. Our results also suggest that the determination of mAb concentrations in the brain using microdialysis may be necessary to accurately measure the PK of CNS-targeted antibodies at the site-of-actions in the brain.

In this paper, we propose a failure mechanism cumulative model that considers the loading history of the load sharing effect in a k-out-of-n system. Three types of failure mechanisms are considered, continuous degradation, compound point degradation, and sudden failure due to shock. By constructing a logic diagram with functional dependence gate, the load-sharing effect can be explained from the failure mechanism point of view using a mechanism-acceleration gate that shows that when one component fails, the failure mechanisms of the other surviving components will be accelerated. By deriving the total damage equation and a constructing failure behavior model, the system reliability of a k-out-of-n system with different types of failure mechanisms were evaluated. A voltage stabilizing system that contains a 1-out-of-2 subsystem, or a 2-out-of 3 subsystem was used to illustrate the practical applicability of the proposed approach. A combined Monte Carlo and binary decision diagram method was used in the numerical simulation process.

Complicated systems are always required to perform different missions each of which may include several phases. Meanwhile, these systems and their components can get exhausted and deteriorated during the operating processes, which drives systems and components into different states. These systems, which is in possession of the characteristics of multiple states and phased missions simultaneously, are called multi-state and phased-mission systems (MS-PMSs). During the last decade, some scholars have made considerable efforts to study the analyzing methods to the reliability of MS-PMSs. However, compared with the independent researches into multi-state systems or phased-mission systems, the achievement of MS-PMSs is still insufficient. Besides, these studies focused on the modeling methods to the MS-PMSs from the system level and the failure behavior was seldom mentioned. In this paper, by extending our previous studies, two accumulating rules of failure mechanism are provided and a revised hierarchical BDD-based method is proposed to model and analyze the reliability of MS-PMSs. Finally, a simplified realistic example is given to illustrate the using of the proposed method.

We report a compact mid-infrared optical parametric oscillator (OPO) seeded optical parametric amplifier (OPA) based on PPMgLN. The pump for the OPO and OPA is a split 1064 nm electro-optical Q-switched Nd:YAG laser with a pulse width of 11.7 ns and a pulse repetition frequency of 2 kHz. The idler power of 116 mW of the OPO is used for the OPA seed. Under the incident pump power of 7.36 W and the crystal temperature of 30 °C, the idler power of the OPA is 966 mW with a pulse width of 5.3 ns, corresponding to a conversion efficiency of 11.5% and a calculated peak power of 91.1 kW. The central wavelength of the OPA idler is 3731.2 nm with a linewidth of 8.8 nm at 30 °C, and decreased from 3748.8 nm to 3704.0 nm when the crystal is heated from 20 to 45 °C. The beam quality factors of the OPA are 3.4 and 3.7 in the horizontal and vertical directions, respectively. Keywords: PPMgLN, High peak power, Optical parametric oscillator, Optical parametric amplifier

The low frequency oscillation characteristics of East China Power Grid after commissioning of the first ultra-high voltage alternating current (UHVAC) project-the Huai-Hu UHVAC project are studied. Several low frequency oscillation cases occurred in East China Power Grid in the past few years are reviewed and summarized. Based on the analysis of the different typical operation modes, the main low frequency oscillation modes in East China Power Grid in the early stages of development of ultra-high voltage (UHV) are summarized, and the impacts of the significant power grid maintenance on low frequency oscillation characteristics are analyzed. Besides, the oscillation mode of UHV generators to East China Power Grid is researched, and the importance of the power system stabilizator (PSS) is emphasized. Furthermore, the comparative analysis between the time domain and the frequency domain is carried out, and the influences of the governing system on low frequency oscillation characteristics are revealed. Finally, both the focus and the direction of low frequency oscillation research are presented.

REV3L, the catalytic subunit of DNA Polymerase ζ (Polζ), plays a significant role in the DNA damage tolerance mechanism of translesion synthesis (TLS). The role of REV3L in chemosensitivity of cervical cancer needs exploration. In the present study, we evaluated the expression of the Polζ protein in paraffin-embedded tissues using immunohistochemistry and found that the expression of Polζ in cervical cancer tissues was higher than that in normal tissues. We then established some cervical cancer cell lines with REV3L suppression or overexpression. Depletion of REV3L suppresses cell proliferation and colony formation of cervical cancer cells through G1 arrest, and REV3L promotes cell proliferation and colony formation of cervical cancer cells by promoting G1 phase to S phase transition. The suppression of REV3L expression enhanced the sensitivity of cervical cancer cells to cisplatin, and the overexpression of REV3L conferred resistance to cisplatin as evidenced by the alteration of apoptosis rates, and significantly expression level changes of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax). Our data suggest that REV3L plays an important role in regulating cervical cancer cellular response to cisplatin, and thus targeting REV3L may be a promising way to alter chemosensitivity in cervical cancer patients.

Abstract Participation in outdoor play is beneficial for the health, well-being, and development of children. Early childhood education centers (ECECs) can provide equitable access to outdoor play. The PROmoting Early Childhood Outside (PRO-ECO) study is a pilot randomized trial that evaluates the PRO-ECO intervention on children’s outdoor play participation. The PRO-ECO intervention included four components: ECEC outdoor play policy; educator training; ECEC outdoor space modification; and parent engagement. This study included eight ECECs delivering licensed care to children (n = 217) aged 2.5 to 6 years in Greater Vancouver, British Columbia, Canada. Using a wait-list control cluster randomized trial design, ECECs were randomly allocated to either the intervention arm (n = 4) or the wait-list control arm (n = 4). Change in the proportion and diversity of observed outdoor play behaviour during scheduled outdoor time was measured. Outcome data were collected at baseline, 6-month follow-up, and 12-month follow-up. The intervention effect on children’s outdoor play participation was examined using logistic regression mixed effect models. Controlling for gender, weather and temperature, there were no changes in children’s outdoor play participation following implementation of the PRO-ECO intervention in the between-group analysis. Within-group comparisons also revealed no change in play participation following the PRO-ECO intervention, however, the intervention group showed a positive effect (OR = 1.28, 95% CI = 0.97, 1.70) in play participation 6 months after implementation of the intervention. The findings indicate that further analyses on child- and ECEC-level outcomes collected as part of the PRO-ECO study, including the diversity of children’s play, is required to effectively assess the impact of this intervention.

Abstract Objective The cross-sectional study was designed to evaluate the association of ocular surface inflammation with systemic conditions in patients with systemic lupus erythematosus (SLE). Methods The study enrolled 30 SLE patients and 30 controls. Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Tear samples from all participants were collected for tear multi-cytokine and chemokine concentration analysis. All participants were assessed for dry eye disease (DED), including Schirmer I test, tear break-up time (TBUT), corneal fluorescein staining (CFS), meibomian gland secretion (MGS), lid-parallel conjunctival folds (LIPCOF), corneal clarity, and symblepharon. Besides, all participants were also examined for conjunctival impression cytology to measure the density of conjunctival goblet cells (CGCs). The peripheral blood indicators from SLE patients were also collected to measure the SLE-associated autoantibody specificities and systemic inflammatory indicators. Pearson and Spearman’s analysis were uesd to examine the correlation between tear cytokines, CGCs, DED-related indicators, and systemic conditions. Results The two groups were matched for age and gender in this study. 36.67% of eyes (11 in 30) of SLE patients and 13.33% of eyes (4 in 30) of controls were diagnosed with DED. OSDI scores, abnormal TBUT percentages, CFS percentages, and DED grading were all higher in SLE patients than in control group, while density of CGCs was lower. There were no significant differences in Schirmer I test, MGS, LIPCOF, corneal clarity, and symblepharon between SLE patients and controls. The levels of tear chemokine (C-X-C motif) ligand 11 (CXCL11) and cytokine interleukin-7 (IL-7) in patients with SLE were significantly higher than those in control group. Moreover, among SLE patients, the severity of DED and the level of tear chemokine CXCL11 were significantly positively correlated with SLE-associated autoantibody specificities. Conclusion Dry eye and tear cytokines and chemokines-mediated ocular surface inflammation persist in SLE patients and are associated with systemic conditions. Therefore, it is necessary for patients with SLE to combine systemic and ocular assessments.

Abstract Transplantation remains the definitive treatment for end‐stage organ failures, but its efficacy is frequently compromised by immune rejection. This study introduces a novel strategy by utilizing tumor‐derived exosomes from B16‐F10 melanoma cells (B16‐Exo), diverging from the conventional use of immune cell‐derived exosomes, to alleviate post‐transplantation immune rejection. Utilizing murine corneal transplantation as a model, it is demonstrated that B16‐Exo significantly reduces immune rejection, evidenced by decreased corneal opacity, neovascularization, and immune dysregulation, while enhancing postoperative survival. Proteomic analyses reveal differential expression of pivotal proteins in B16‐Exo, notably the JAK2 protein within the JAK‐STAT signaling pathway, which has been mechanistically demonstrated to amplify the activity of myeloid‐derived suppressor cells (MDSCs) and inhibit T cell proliferation. These findings demonstrate the significant immunomodulatory effect of B16‐Exo in transplant immunology, supporting the continued exploration of tumor‐derived exosomes as a platform to uncover novel immunosuppressive mechanisms in transplantation.

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks.Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed.Results: This analysis included 901 patients. Within 1–2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p