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Abstract Background Micropapillary (MPP) adenocarcinoma is considered one of the most aggressive pathological types of lung adenocarcinoma (LADC). This retrospective study aimed to evaluate the prognostic significance and benefit of postoperative adjuvant therapy (PAT) in stage IA LADC patients with different proportions of MPP components. Materials and methods We retrospectively examined clinical stage IA LADC patients who underwent surgical resection between August 2012 and December 2019. In terms of the proportion of MPP components (TPM), the tumors were reclassified into three categories: MPP patterns absent (TPMN); low proportions of MPP components (TPML); and high proportions of MPP components (TPMH). The dates of recurrence and metastasis were identified based on physical examinations and were confirmed by histopathological examination. Results Overall, 505 (TPMN, n = 375; TPML, n = 92; TPMH, n = 38) patients harboring EGFR mutations were enrolled in the study. Male sex (P = 0.044), high pathological stage (P

Utilizing the Multi-Voltage Threshold method, All-Digital PET technology, characterized by "All-Digital" and "accurate sampling," facilitates hardware and software decoupling and modular "LEGO-like" system construction. This innovation addresses the limitations of traditional PET system architectures, enabling a broader range of innovative applications. This paper reviews recent advancements in application-specific All-Digital PET systems, highlighting their applications and advantages in proton therapy monitoring, clinical and basic brain science research, and plant metabolism studies. Furthermore, we explore the development trends of All-Digital PET technology to meet the increasing demands of PET imaging applications.

Abstract Background Treating the coronal dens invaginatus (CDI) with pulp infection commonly involves the removal of invagination, which increases the risk of perforation and fracture, and compromises the tooth structure. Minimally invasive endodontic management of CDI is highly recommended. This report describes two cases of type II CDI with the application of personalized templates. Case presentation Two cases of type II CDI, affecting the main root canal in a maxillary canine and a lateral incisor, were diagnosed. A guided endodontics (GE) approach was applied. Cone-beam computed tomography and intraoral scans were imported and aligned in a virtual planning software to design debridement routes and templates. The MICRO principle (which involves the aspects of Mechanical (M) debridement, Irrigation (I), Access cavities (C), Rectilinear routes (R), and Obstruction (O)) was proposed for designing optimal debridement routes for future applications. The templates were innovatively personalized and designed to preserve the tooth structure maximally while effectively debriding the root canal. Root canal treatment with supplementary disinfection was then performed. The follow-up of the two patients revealed favorable clinical and radiographic outcomes. Conclusions The GE approach could be a feasible method for preserving healthy dental structure while effectively debriding the root canal, thereby achieving successful and minimally invasive endodontic treatment for CDI.

ABSTRACT The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs.IMPORTANCEOur study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Summary: The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1, and NRBP1 in regulating cell volume homeostasis. All of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK, and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK-family kinases. Our study reveals that TSC22D, WNK, and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.

The effect of Mn–N on the oxidation behavior and microstructure evolution of a novel nickel-saving Fe–26Cr–4Ni-0.3C dual-phase heat-resistant cast steel at 900 °C was investigated. After 100 h of oxidation, the H–Mn–N steel (3.14 %Mn-0.232 %N) exhibited approximately three times better oxidation resistance compared to the L-Mn-N steel (0.24 %Mn-0.084 %N). The increase of Mn–N decreased the oxidation rate from 2.30 × 10−2 mg2 ∙ cm−4 ∙ h−1 to 3.26 × 10−3 mg2 ∙ cm−4 ∙ h−1. The oxide scale structure of L-Mn-N steel consisted of outer Cr2O3, inner (Fe0.6Cr0.4)2O3, and Fe1.4Cr1.6O4, while the oxide scale of H–Mn–N steel (3.14 %Mn) was SiO2, MnCr2O4, and Mn1.5CrO4 from the matrix to the outside. Mn–N increased the proportion of austenite from 40 % to 70 %, which reduced the diffusion rate of oxygen. This hindered the formation of layered oxide Cr2O3 and promoted the formation of a dense layer of SiO2 on the matrix surface, providing a pathway for the enhancement of the trade-off between oxidation resistance and cost.

Abstract Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

Abstract In this research, we explore the few-shot object detection application for identifying concealed objects in sub-terahertz security images, using fine-tuning based frameworks. To adapt these machine learning frameworks for the (sub-)terahertz domain, we propose an innovative pseudo-annotation method to augment the object detector by sourcing high-quality training samples from unlabeled images. This approach employs multiple one-class detectors coupled with a fine-grained classifier, trained on supporting thermal-infrared images, to prevent overfitting. Consequently, our approach enhances the model’s ability to detect challenging objects (e.g., 3D-printed guns and ceramic knives) when few-shot training examples are available, especially in the real-world scenario where images of concealed dangerous items are scarce.

In this work, an accurate temperature-dependent drain current $I_{\mathrm { D}}$ fluctuation model valid from 10 to 300 K was proposed for 18 nm ultra-thin body and buried oxide (UTBB) n-channel field effect transistors (n-FETs). The temperature dependence of $I_{\mathrm { D}}$ fluctuation was characterized and investigated from 300 K down to 10 K. In moderate inversion mode, $I_{\mathrm { D}}$ fluctuation is more severe at sub-100 K while in the strong inversion mode, it still can be overshadowed by the charge screening effect. Cryogenic virtual source (CVS) device model was used to extract and analyze the carrier density and mobility which are used in the current fluctuation model. The current fluctuation model was experimentally verified under different inversion conditions, showing it can be used to analyze and optimize the flicker noise in the low temperature (LT) circuit applications.

[This corrects the article DOI: 10.1371/journal.ppat.1008307.].

Several COVID-19 vaccines have been approved for emergency use according to China's immunization programs. These vaccines has created hope for patients with epilepsy, because the vaccines can help to reduce their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the COVID-19 vaccine safety in patients with epilepsy. Here, we assessed the time of symptom control and the features of adverse events of seizure patients following their COVID-19 vaccinations. The results showed that adverse events of COVID-19 vaccinations for epilepsy patients included local pain at the injection site, dizziness and headache, epileptic attack, somnolence, limb weakness, limb pain, allergy, and fever. In addition, the average recovery time of the adverse events was approximately 42 h. More importantly, our study showed that it was relatively safe to vaccinate epilepsy patients who did not experience seizures for approximately 12 months prior to the immunization date.

Abstract Supercritical airfoils are critical components in the design of commercial wide-body aircraft wings due to their ability to enhance aerodynamic performance in transonic flow regimes. However, traditional design methods for supercritical airfoils can be time-consuming and require significant manual effort, not to mention the high cost associated with computational fluid dynamics analysis. To address these challenges, this paper introduces a highly automated approach for supercritical airfoil design, called Evolutionary Generative Design (EvoGD). The EvoGD approach is based on the framework of Evolutionary Computation and employs a series of sophisticated data-driven generative models incorporated with physical information to iteratively refine initial airfoil shapes, resulting in improved aerodynamic performances and reduced constraint violations. Moreover, to speed up the evaluation of the generated airfoils, a series of accurate and efficient data-driven predictors are utilized. The efficacy of the EvoGD approach was demonstrated through experiments on a dataset of 501 supercritical airfoils, including one baseline design and 500 randomly perturbed airfoils. On average, the generated airfoils showed improved performance in terms of buffet lift coefficient, cruise lift-to-drag ratio, and thickness by 5%, 4%, and 1%, respectively. The best generated airfoil outperformed the baseline design in terms of critical buffet lift coefficient and cruise lift-to-drag ratio by 7.1% and 6.4%, respectively. The entire design process was completed in less than an hour on a personal computer, highlighting the high efficiency and scalability of the EvoGD approach.

Abstract Background Perivascular adipose tissue (PVAT) in obesity critically contributes to vascular dysfunction, which might be restored by long-term exercise. Protein kinase B/nitric oxide synthase/nitric oxide (Akt/eNOS/NO) down-regulation within PVAT might be involved in the impaired anti-contractile function of arteries. Therefore, the present study evaluated the effect of long-term aerobic exercise on PVAT function and the potential regulator during this process. Methods Male Sprague Dawley rats were divided into normal diet control group (NC), normal diet exercise group (NE), high-fat diet control group (HC), and high-fat diet exercise group (HE) (n = 12 in each group). Upon the establishment of obesity (20 weeks of high-fat diet), exercise program was performed on a treadmill for 17 weeks. After the intervention, circulating biomarkers and PVAT morphology were evaluated. Vascular contraction and relaxation were determined with or without PVAT. Production of NO and the phosphorylations of Akt (Ser473) and eNOS (Ser1177) within PVAT were quantified. Results Metabolic abnormalities, systemic inflammation, and circulating adipokines in obesity were significantly restored by long-term aerobic exercise (P

Abstract Background Mouthwashes were convenient adjuncts to mechanical cleaning procedures. This review aimed to evaluate the efficacy of mouthwashes on oral microorganisms and gingivitis in orthodontic patients. Methods By April 16, 2022, multiple databases and grey literature were searched based on the PICOS strategy. Randomized controlled trials in orthodontic patients evaluating the efficacy of mouthwashes with at least one microbial parameter and/or plaque- and/or gingival inflammation-related index were included. Relevant data were extracted, and the risk of bias was evaluated using Cochrane's tool. Individual mean and standard deviation of the outcomes in mouthwashes and placebos/blank controls were pooled to estimate the weighted mean differences (WMDs) and 95% confidence intervals (95%CIs). Sensitivity analysis, and certainty of evidence were evaluated. Results Of 1684 articles, 32 studies satisfied the eligibility criteria, and nine were included for meta-analysis. Missing outcome data was the primary source of bias. Compared to blank controls, the short-term application of fluoride mouthwashes significantly reduced the colony counts of Mutans streptococci (MS), while the long-term application may not be effective. Compared to placebos or blank controls, Chlorhexidine mouthwashes significantly reduced the colony counts of multiple microorganisms in the short-term. Compared to placebos or blank controls, herbal mouthwashes showed the inhibitory effect of MS in the short-term, with some results lacking statistical significance. After meta-analysis, significant lower plaque- and gingival inflammation-related indexes were observed in the Chlorhexidine mouthwashes groups [Gingival Index: WMD = -0.45, 95%CI = -0.70 to -0.20 (placebos as control); WMD = -0.54, 95%CI = -0.96 to -0.13 (blank controls); Plaque Index: WMD = -0.70, 95%CI = -1.12 to -0.27 (blank controls)]. Significant lower gingival inflammation-related indexes were observed in the herbal mouthwashes groups [Gingival Index: WMD = -0.20, 95%CI = -0.32 to -0.09 (blank controls)]. Conclusions The short-term application of fluoride mouthwashes may reduce the colony counts of cariogenic bacteria, but the long-term effect is not evident. Chlorhexidine may reduce the colony counts of multiple microorganisms in the short-term. Short-term application Chlorhexidine and herbal mouthwashes may effectively reduce plaque- and gingival inflammation-related indexes. However, the risk of bias, inconsistency, and imprecision in the included studies may reduce the certainty of the evidence.

We resolve the debate over the existence and magnitude of cross-sublattice (CS) contributions to spin pumping and spin-transfer torques in a two-sublattice antiferromagnet connected to a non-magnetic metal. Guided by symmetry considerations, we first relate the controversial CS terms to specific components in the spin conductance matrix. Then, we quantify these components by studying the spin-dependent electron scattering on a fully compensated interface. We ascertain the absence of all CS contributions in the collinear regime. Even in the non-collinear regime, the CS contributions only constitute a higher-order correction to the existing theory.

Summary: Background: Currently, the role of EGFR-TKIs as adjuvant therapy for stage I, especially IA NSCLC, after surgical resection remains unclear. We aimed to compare the effect of adjuvant EGFR-TKIs with observation in such patients by incorporating an established 14-gene molecular assay for risk stratification. Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Guangzhou Medical University (Study ID: ChNCRCRD-2022-GZ01). From March 2013 to February 2019, completely resected stage I NSCLC (8th TNM staging) patients with sensitive EGFR mutation were included. Patients with eligible samples for molecular risk stratification were subjected to the 14-gene prognostic assay. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics. Findings: A total of 227 stage I NSCLC patients were enrolled, with 55 in EGFR-TKI group and 172 in the observation group. The median duration of follow-up was 78.4 months. After IPTW, the 5-year DFS (HR = 0.30, 95% CI, 0.14–0.67; P = 0.003) and OS (HR = 0.26, 95% CI, 0.07–0.96; P = 0.044) of the EGFR-TKI group were significantly better than the observation group. For subgroup analyses, adjuvant EGFR-TKIs were associated with favorable 5-year DFS rates in both IA (100.0% vs. 84.5%; P = 0.007), and IB group (98.8% vs. 75.3%; P = 0.008). The 14-gene assay was performed in 180 patients. Among intermediate-high-risk patients, EGFR-TKIs were associated with a significant improvement in 5-year DFS rates compared to observation (96.0% vs. 70.5%; P = 0.012), while no difference was found in low-risk patients (100.0% vs. 94.9%; P = 0.360). Interpretation: Our study suggested that adjuvant EGFR-TKI might improve DFS and OS of stage IA and IB EGFR-mutated NSCLC, and the 14-gene molecular assay could help patients that would benefit the most from treatment. Funding: This work was supported by China National Science Foundation (82022048, 82373121).

Abstract With the rising number of large-scale multiobjective optimization problems from academia and industries, some evolutionary algorithms (EAs) with different decision variable handling strategies have been proposed in recent years. They mainly emphasize the balance between convergence enhancement and diversity maintenance for multiobjective optimization but ignore the local search tailored for large-scale optimization. Consequently, most existing EAs can hardly obtain the global or local optima. To address this issue, we propose an efficient sampling-based offspring generation method for large-scale multiobjective optimization, where convergence enhancement and diversity maintenance, together with ad hoc local search, are considered. First, the decision variables are dynamically classified into two types for solving large-scale decision space in a divide-and-conquer manner. Then, a convergence-related sampling strategy is designed to handle those decision variables related to convergence enhancement. Two additional sampling strategies are proposed for diversity maintenance and local search, respectively. Experimental results on problems with up to 5000 decision variables have indicated the effectiveness of the algorithm in large-scale multiobjective optimization.

Live-streaming commerce has become increasingly prevalent in recent years and has significantly impacted consumer purchasing behavior. This study aims to assess the impact of live-streaming environmental features, presence, and perceived trust on consumer purchase intention, building upon the stimulus-organism-response (SOR) model. The authors obtained 392 valid responses from a survey, which were analyzed using PLS-SEM to yield statistical insights. The study found that live-streaming environmental features directly impact presence, perceived trust, and purchase intention while also indirectly affecting purchase intention through perceived trust. Additionally, perceived trust directly affects purchase intention, and presence indirectly influences purchase intention through perceived trust. This research contributes to the existing literature on consumers’ purchase intention in live-streaming commerce. Additionally, this study expands the comprehension of how environmental cues during live streaming affect purchase intention by examining the mediating roles of presence and perceived trust. As a result, this research provides a reference for enhancing the marketing effectiveness of live-streaming commerce.

We report optically-generated focused ultrasound for non-invasive brain stimulation with ultrahigh precision of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial focused ultrasound.

Lakes are essential components of the hydrological and biogeochemical cycles. Here, Pi et al develop a global lake dataset called GLAKES via high-resolution satellite images and deep learning to examine global lake changes over four decades.

AimsNon-severe hypoglycemia (NS-H) is challenging for people living with type 1 diabetes (PWT1D) and often results from relative iatrogenic hyper-insulinemia. Current guidelines recommend a one-size-fits-all approach of 15–20 g of simple carbohydrates (CHO) every 15 min regardless of the triggering conditions of the NS-H event. We aimed to test different amounts of CHO to treat insulin-induced NS-H at various glucose ranges.MethodsThis is a randomized, four-way, crossover study involving PWT1D, testing NS-H treatment outcomes with 16 g vs. 32 g CHO at two plasma glucose (PG) ranges: A: 3.0–3.5 mmol/L and B:

Background Metabolism shifts from glycolysis to mitochondrial oxidative phosphorylation are vital during the differentiation of stem cells. Mitochondria have a direct function in differentiation. However, the metabolic shift and the effect of mitochondria in regulating the osteogenic differentiation of human dental pulp stem cells (hDPSCs) remain unclear. Methods Human dental pulp stem cells were collected from five healthy donors. Osteogenic differentiation was induced by osteogenic induction medium. The activities of alkaline phosphatase, hexokinase, pyruvate kinase, and lactate dehydrogenase were analyzed by enzymatic activity kits. The extracellular acidification rate and the mitochondrial oxygen consumption rate were measured. The mRNA levels of COL-1, ALP, TFAM, and NRF1 were analyzed. The protein levels of p-AMPK and AMPK were detected by western blotting. Results Glycolysis decreased after a slight increase, while mitochondrial oxidative phosphorylation continued to increase when cells grew in osteogenic induction medium. Therefore, the metabolism of differentiating cells switched to mitochondrial respiration. Next, inhibiting mitochondrial respiration with carbonyl cyanide-chlorophenylhydrazone, a mitochondrial uncoupler inhibited hDPSCs differentiation with less ALP activity and decreased ALP and COL-1 mRNA expression. Furthermore, mitochondrial uncoupling led to AMPK activation. 5-Aminoimidazole-4-carboxamide ribonucleotide, an AMPK activator, simulated the effect of mitochondrial uncoupling by inhibiting osteogenic differentiation, mitochondrial biogenesis, and mitochondrial morphology. Mitochondrial uncoupling and activation of AMPK depressed mitochondrial oxidative phosphorylation and inhibited differentiation, suggesting that they may serve as regulators to halt osteogenic differentiation from impaired mitochondrial oxidative phosphorylation.

Summary: Hypobaric hypoxia (HH) is the primary challenge at highland. Prolonged HH exposure impairs right cardiac function. Mitochondria-associated membrane (MAM) plays a principal role in regulating mitochondrial function under hypoxia, but the mechanism was unclear. In this study, proteomics analysis identified that PACS2, a key protein in MAM, and mitophagy were downregulated in HH. Metabolomics analysis indicated suppression of glucose and fatty acids aerobic oxidation in HH conditions. Cardiomyocyte Pacs2 deficiency disrupted MAM formation and endoplasmic reticulum (ER)-mitochondria calcium flux, further inhibiting mitophagy and energy metabolism in HH. Pacs2 overexpression reversed these effects. Cardiac-specific knockout of Pacs2 exacerbated mitophagy inhibition, cardiomyocyte injury, and right cardiac dysfunction induced by HH. Conditional knock-in of Pacs2 recovered HH-induced right cardiac impairment. Thus, PACS2 is essential for protecting cardiomyocytes through ER-mitochondria calcium flux, mitophagy, and mitochondrial energy metabolism. Our work provides insight into the mechanism of HH-induced cardiomyocyte injury and potential targets for maintaining the right cardiac function at the highland.

ObjectiveThis study aims to investigate the composition and function of the gut microbiome in long-term depression using an 8-week chronic unpredictable mild stress (CUMS) rat model.Materials and methodsAnimals were sacrificed after either 4 weeks or 8 weeks under CUMS to mimic long-term depression in humans. The gut microbiome was analyzed to identify potential depression-related gut microbes, and the fecal metabolome was analyzed to detect their functional metabolites. The correlations between altered gut microbes and metabolites in the long-term depression rats were explored. The crucial metabolic pathways related to long-term depression were uncovered through enrichment analysis based on these gut microbes and metabolites.ResultsThe microbial composition of long-term depression (8-week CUMS) showed decreased species richness indices and different profiles compared with the control group and the 4-week CUMS group, characterized by disturbance of Alistipes indistinctus, Bacteroides ovatus, and Alistipes senegalensis at the species level. Additionally, long-term depression was associated with disturbances in fecal metabolomics. D-pinitol was the only increased metabolite in the 8-week CUMS group among the top 10 differential metabolites, while the top 3 decreased metabolites in the long-term depression rats included indoxyl sulfate, trimethylaminen-oxide, and 3 alpha,7 alpha-dihydroxy-12-oxocholanoic acid. The disordered fecal metabolomics in the long-term depression rats mainly involved the biosynthesis of pantothenate, CoA, valine, leucine and isoleucine.ConclusionOur findings suggest that the gut microbiome may participate in the long-term development of depression, and the mechanism may be related to the regulation of gut metabolism.

For a hundred years the Saint Jacques area has been known to produce rich Oligocene vertebrate fossils, yet only a handful of previous studies have focused on this area. Since 2010, we have conducted 12 field expeditions to Saint Jacques, and here we report findings from our paleontological excavations and stratigraphical investigations. Twenty-two fossiliferous blocks across the area are recognized and a chronostratigraphic framework has been established to aid fossil collection. Fossil-mammal materials have been recovered in situ from 1635 localities and additionally from surface sediments. Fossiliferous blocks in the area are correlated by lithological similarity and lateral tracing. Lithologically, the area is mainly composed of reddish silty mudstone and muddy siltstone, with three distinctive layers of grayish white sandstone. The measured composite stratigraphic column spans 239 meters and are divided into 12 lithostratigraphic units. Contrary to previous knowledge that Saint Jacques contains two Oligocene mammalian assemblages, our preliminary biostratigraphic analysis of small mammals shows that the area documents successive faunal transition from the Eocene to possibly the early Miocene. The hyracodontid perissodactyl Ardynia, the ctenodactyloid rodent Gobiomys, and the basal Glires Gomphos from the bottom litho-units imply the presence of the Eocene–Oligocene boundary, while small mammal assemblage of the top units is similar to Miocene faunas in northern China and Mongolia. Thus, rock strata in Saint Jacques likely span the Eocene through the early Miocene, bracketing an entire Oligocene sequence within. In sum, our re-exploration of Saint Jacques has greatly expanded the chronostratigraphic and taxonomic coverage of the mammalian fossil collection from this area. This long, successive Oligocene sequence makes an important record for studying the Eocene–Oligocene Transition. Further study in this area will contribute to a range of paleontological and paleoenvironmental questions.

Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear. Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary. Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)- related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT. Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT. Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC. (

Reinforcement learning (RL) is a machine learning approach that trains agents to maximize cumulative rewards through interactions with environments. The integration of RL with deep learning has recently resulted in impressive achievements in a wide range of challenging tasks, including board games, arcade games, and robot control. Despite these successes, several critical challenges remain, such as brittle convergence properties caused by sensitive hyperparameters, difficulties in temporal credit assignment with long time horizons and sparse rewards, a lack of diverse exploration, particularly in continuous search space scenarios, challenges in credit assignment in multi-agent RL, and conflicting objectives for rewards. Evolutionary computation (EC), which maintains a population of learning agents, has demonstrated promising performance in addressing these limitations. This article presents a comprehensive survey of state-of-the-art methods for integrating EC into RL, referred to as evolutionary reinforcement learning (EvoRL). We categorize EvoRL methods according to key research areas in RL, including hyperparameter optimization, policy search, exploration, reward shaping, meta-RL, and multi-objective RL. We then discuss future research directions in terms of efficient methods, benchmarks, and scalable platforms. This survey serves as a resource for researchers and practitioners interested in the field of EvoRL, highlighting the important challenges and opportunities for future research. With the help of this survey, researchers and practitioners can develop more efficient methods and tailored benchmarks for EvoRL, further advancing this promising cross-disciplinary research field.

In this paper, FLUENT software coupled with the chemical reaction mechanism is used to study the ignition characteristics of methane-air mixtures at low temperature. Variations of the main free radical concentrations, the critical conditions for a successful ignition and the chemical reaction rate of each elementary reaction for a failure ignition are obtained, respectively. Results indicate that the consumption of methane immediately affects the concentration distribution of carbon monoxide, which presents the opposite relationship with that of methane. Mass fractions of the intermediate products and H, O free radicals are low in the burnt zone and unburnt zone, whereas reach the maximum on the flame front. OH is not only the intermediate free radical, but also the combustion product remained by the intermediate reactions. At a low temperature of 150 K, the critical radius and temperature of methane ignition are 4.6 mm and 1180 K, respectively. When ignition radius is smaller than the critical value, the failed ignition of methane is caused by the termination of the elementary reactions: R8: H + O2 = OH + O, R9: OH + O = O2 + H, R12: O + H2O = 2OH and R13: 2OH = O + H2O. However, when ignition temperature is lower than the critical value, because of the failed initiation of elementary reaction R1: CH4 = CH3 + H, the combustion of methane is not occurred.

Abstract Hypertension is the most common comorbidity in patients with coronavirus disease 2019 (COVID‐19) and increases in‐hospital mortality. Day‐by‐day blood pressure (BP) variability (BPV) is associated with clinical outcomes in hypertensive patients. However, little information is available on the association of BPV with the outcomes of COVID‐19 patients with hypertension. This study aimed to demonstrate whether day‐by‐day in‐hospital BPV had prognostic significance in these patients. The authors included 702 COVID‐19 patients with hypertension from Huoshenshan Hospital (Wuhan, China), who underwent valid in‐hospital BP measurements on at least seven consecutive days. Day‐by‐day BPV was assessed by standard deviation (SD), coefficient of variation (CV), and variation independent of mean (VIM). Overall, patients with severe COVID‐19 and non‐survivors had higher BPV than moderate cases and survivors, respectively. Additionally, higher BPV was correlated with greater age and higher levels of C‐reactive protein, procalcitonin, high‐sensitive cardiac troponin I, and B‐type natriuretic peptide. In multivariable Cox regression, SD of systolic BP (SBP) was predictive of mortality [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.05–1.30] as well as acute respiratory distress syndrome (ARDS) (HR 1.09, 95% CI 1.01–1.16). Similar trends were observed for CV and VIM of SBP, but not indices of diastolic BP variability. The authors demonstrated that day‐by‐day in‐hospital SBP variability can independently predict mortality and ARDS in COVID‐19 patients with hypertension. And high BPV might be correlated with severe inflammation and myocardial injury. Further studies are needed to clarify whether early reduction of BPV will improve the prognosis of these patients.

Electrical manipulation of antiferromagnetic order is crucial for future memory devices, but existing switching schemes require a large current density. Here, the authors achieve record low current density switching in FeRh by taking advantage of its antiferromagnetic to ferromagnetic phase transition.

ABSTRACT Introduction Rosai–Dorfman disease (RDD) is an uncommon, benign, and idiopathic histiocytic proliferative disorder. Multiple intracranial RDD is extremely rare and treatment varies. Case presentation A 9‐year‐old girl was admitted with 3‐month history of blurred vision and facial paralysis, a 2‐month history of recurrent giggle, and cognitive impairment. Computed tomography and magnetic resonance imaging scans revealed bilateral ventricular masses based on the dural membrane and the diameters of the masses were 9.1 cm and 9.2 cm, respectively. The lesions were completely removed with staging surgeries. Fifteen months after operation, blurred vision was still present but facial paralysis and giggle and cognitive impairment disappeared. Imaging examinations suggested that there were no new or recurring lesions. Conclusion For multiple large intracranial masses, surgical treatment is necessary and staged surgery benefits perioperative safety. Active follow‐up with magnetic resonance imaging is necessary.

Abstract Background Elymus breviaristatus and Elymus sinosubmuticus are perennial herbs, not only morphologically similar but also sympatric distribution. The genome composition of E. sinosubmuticus has not been reported, and the relationship between E. sinosubmuticus and E. breviaristatus is still controversial. We performed artificial hybridization, genomic in situ hybridization, and phylogenetic analyses to clarify whether the two taxa were the same species. Results The high frequency bivalent (with an average of 20.62 bivalents per cell) at metaphase I of pollen mother cells of the artificial hybrids of E. breviaristatus (StYH) × E. sinosubmuticus was observed. It illustrated that E. sinosubmuticus was closely related to E. breviaristatus. Based on genomic in situ hybridization results, we confirmed that E. sinosubmuticus was an allohexaploid, and the genomic constitution was StYH. Phylogenetic analysis results also supported that this species contained St, Y, and H genomes. In their F1 hybrids, pollen activity was 53.90%, and the seed setting rate was 22.46%. Those indicated that the relationship between E. sinosubmuticus and E. breviaristatus is intersubspecific rather than interspecific, and it is reasonable to treated E. sinosubmuticus as the subspecies of E. breviaristatus. Conclusions In all, the genomic constitutions of E. sinosubmuticus and E. breviaristatus were StYH, and they are species in the genus Campeiostachys. Because E. breviaristatus was treated as Campeistachys breviaristata, Elymus sinosubmuticus should be renamed Campeiostachys breviaristata (Keng) Y. H. Zhou, H. Q. Zhang et C. R. Yang subsp. sinosubmuticus (S. L. Chen) Y. H. Zhou, H. Q. Zhang et L. Tan.

Endothelial progenitor cell (EPCs) proliferation decreased, accompanied by mitochondrial dysfunction and mitophagy impairment via the PINK1-PARK2 pathway in atherosclerosis. Statins induce mitophagy to protect EPCs by mitochondrial calcium release and CAMK1-mediated PINK1 phosphorylation.

LKB1 tumour suppressor gene is frequently mutated in lung adenocarcinoma. Here the authors show that in genetically engineered mouse models of lung cancer Lkb1 restoration induces growth arrest and drives neoplastic cells toward a more differentiated and less proliferative alveolar type II cell-like state via C/EBP-mediated reprogramming.

A physics-based model and the corresponding simulation framework for the mobile-ionic field-effect transistor (MIFET) exhibiting the ferroelectric-like behaviors are innovatively proposed based on two-dimensional (2D) Poisson’s equation and non-equilibrium Green’s function (NEGF), coupling with ion drift-diffusion equations. The simulation framework captures the dynamic distribution of mobile ions’ concentrations within dielectric along the external electric field. TaN/amorphous-ZrO2/TaN capacitors are experimentally characterized for the model calibration. It is proved that the mobile ions dominate the ferroelectric-like behaviors in MIFETs. Sub-60 mV/decade can be achieved in MIFETs based on the proposed model, which is consistent with the experimental results.

The objectives of this study were to explore the mechanism of stem mechanical strength in direct-seeded rice (DSR) as affected by paclobutrazol, especially its related endogenous hormone and cell wall component changes in culm tissue and response to the application of paclobutrazol. Field experiments were conducted in Changchun County, Jilin Province, China, by using two japonica rice varieties, Jiyujing and Jijing305, with soaking seeds in paclobutrazol at concentrations of (0 mg L−1, S0; 50 mg L−1; S1; 100 mg L−1; S2; 150 mg L−1, S3; 200 mg L−1, S4) in 2021 and 2022. The results suggest that the application of paclobutrazol increased the grain yield and reduced the lodging rate of DSR. Compared with the S0 treatments, soaking the seeds in paclobutrazol treatments rapidly shortened the length of the basal internode by decreasing the endogenous indole acetic acid (IAA) and gibberellin A3 (GA3) contents in culm tissue. The larger breaking strength (M) was attributed to a higher section modulus (SM) and bending stress (BS). The higher mechanical tissue thickness in culm tissue under paclobutrazol treatments, which was raised by higher endogenous zeatin and zeatin riboside (Z+ZR) content in culm tissue, increased the culm diameter, culm wall thickness, and section modulus (SM) of the internode. Compared with the S0 treatments, soaking the seeds in paclobutrazol treatments increased the cellulose content, lignin content, activities of lignin-related enzymes, and expression of key genes in lignin biosynthesis, as well as resulted in a higher bending stress (BS) to enhance the culm breaking strength (M). [ABSTRACT FROM AUTHOR]

Abstract For the goal of automated design of high-performance deep convolutional neural networks (CNNs), neural architecture search (NAS) methodology is becoming increasingly important for both academia and industries. Due to the costly stochastic gradient descent training of CNNs for performance evaluation, most existing NAS methods are computationally expensive for real-world deployments. To address this issue, we first introduce a new performance estimation metric, named random-weight evaluation (RWE) to quantify the quality of CNNs in a cost-efficient manner. Instead of fully training the entire CNN, the RWE only trains its last layer and leaves the remainders with randomly initialized weights, which results in a single network evaluation in seconds. Second, a complexity metric is adopted for multi-objective NAS to balance the model size and performance. Overall, our proposed method obtains a set of efficient models with state-of-the-art performance in two real-world search spaces. Then the results obtained on the CIFAR-10 dataset are transferred to the ImageNet dataset to validate the practicality of the proposed algorithm. Moreover, ablation studies on NAS-Bench-301 datasets reveal the effectiveness of the proposed RWE in estimating the performance compared to existing methods.

Abstract Background A nomogram is a tool that transforms complex regression equations into simple and visual graphs and enables clinicians and patients to conveniently compute output probabilities without needing medical knowledge and complex formulas. The aim of this study was to develop and validate a predictive nomogram to screen for severe caries among 12-year-old children based on risk factors in Sichuan Province, China. Methods A cross-sectional study of 4573 12-year-olds was conducted up to May 2016 in middle schools from three districts and three counties in Sichuan Province, China. All the children underwent oral examinations and completed questionnaires to assess general information, oral impacts on daily performance, dietary habits, subjective health conditions, history of dental trauma, frequency of toothache, dental visits, and knowledge, attitudes, and behaviours toward oral hygiene. Univariate analysis and multivariate logistic regression analysis were used to determine which variables were significantly associated with severe caries (operationalized as DMFT ≥ 3). A nomogram was developed and validated by using the ‘rms’ package and two cross-validation methods. Results Severe caries was found in 537 of the 4573 children (11.74%). Multivariate logistic regression analysis revealed that the following variables predicted a higher risk of severe caries: ‘female’ [odds ratio (OR) = 1.985, 95% confidence interval (95% CI): 1.63–2.411], ‘urban’ (OR = 2.389, 95% CI: 1.96–2.91), ‘non-only child’ (OR = 1.317, 95% CI: 1.07–1.625), ‘very poor self-assessment of oral health status’ (OR = 2.157, 95% CI: 1.34–3.467) and ‘visited a dentist less than 6 months’ (OR = 1.861, 95% CI: 1.38–2.505). Multivariate logistic regression analysis also indicated that the following variables predicted a lower risk of severe caries: ‘middle level of urbanization’ (OR = 0.395, 95% CI: 0.32–0.495) and ‘high level of urbanization’ (OR = 0.466, 95% CI: 0.37–0.596). Both the fivefold and leave-one-out cross-validation methods indicated that the nomogram model built by these 6 variables displayed good disease recognition ability. Conclusions The nomogram was a simple-to-use model to screen children for severe caries. This model was found to facilitate non-dental professionals in assessing risk values without oral examinations and making referrals to dental professionals.

Abstract Acute high‐altitude (HA) exposure induces physiological responses of the heart and blood pressure (BP). However, few studies have investigated the responses associated with dipper and non‐dipper BP patterns. In this prospective study, 72 patients underwent echocardiography and 24‐h ambulatory BP testing at sea level and HA. Patients were divided into dipper and non‐dipper groups according to BP at sea level. Acute HA exposure elevated 24‐h systolic and diastolic BP and increased BP variability, particularly in the morning. Moreover, acute exposure increased left ventricular torsion, end‐systolic elastance, effective arterial elastance, and untwisting rate, but reduced peak early diastolic velocity/late diastolic velocity and peak early diastolic velocity/early diastolic velocity, implying enhanced left ventricular systolic function but impaired filling. Dippers showed pronounced increases in night‐time BP, while non‐dippers showed significant elevation in day‐time BP, which blunted differences in nocturnal BP fall, and lowest night‐time and evening BP. Dippers had higher global longitudinal strain, torsion, and untwisting rates after acute HA exposure. Variations in night‐time systolic BP correlated with variations in torsion and global longitudinal strain. Our study firstly demonstrates BP and cardiac function variations during acute HA exposure in different BP patterns and BP increases in dippers at night, while non‐dippers showed day‐time increases. Furthermore, enhanced left ventricular torsion and global longitudinal strain are associated with BP changes. Non‐dippers showed poor cardiac compensatory and maladaptive to acute HA exposure. However, the exact mechanisms involved need further illumination.

Van der Waals magnetic materials (vdWs) have allowed for the exploration of the two dimensional limit of magnetism, however, most vdWs are only magnetic at low temperature. Herein, the authors overcome this limitation, observing room temperature magnetic ordering in Cobalt doped graphene-like Zinc-Oxide.

Abstract. Background:. Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. Methods:. Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0–3 months) and a follow-up phase (3–12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). Results:. Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. Conclusions:. The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. Trial Registration:. ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Objectives: To investigate the factors and virological significance of serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after long-term antiviral therapy with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). Methods: In total, 51 treatment-naïve patients with CHB were included in the study. Clinical data were collected at baseline, during 5 years and at year 10 of NA treatment. Serum HBV pgRNA status of 51 patients was determined at year 5. Results: At year 5, 45% of the patients remained positive for HBV pgRNA. There were significant differences in baseline hepatitis B e antigen (HBeAg) status, HBV DNA load and hepatitis B surface antigen (HBsAg) levels between patients testing positive and negative for HBV pgRNA at year 5. Serum HBV pgRNA status and serum HBV DNA load were correlated after 5 years of NA treatment (r = 0.347, P = 0.013). Being HBV pgRNA positive at year 5 was an independent risk factor for sustainedly undetectable HBV DNA after 10 years of NA treatment (odds ratio 13.638, 95% confidence interval 1.32–140.81; P = 0.028). Furthermore, HBV pgRNA status at year 5 was associated with HBV DNA re-appearance at year 10 (P = 0.009). Conclusions: HBV pgRNA status at year 5 can reveal HBV covalently closed circular DNA (cccDNA) activity, and HBV pgRNA positivity after long-term antiviral therapy may indicate higher transcriptional activity of HBV cccDNA. Long-term dynamic monitoring of HBV pgRNA should be considered.

The intrinsic magnetic topological insulator MnBi_{2}Te_{4} is believed to be an axion insulator in its antiferromagnetic ground state. However, the direct identification of axion insulators remains experimentally elusive because the observed vanishing Hall resistance, while indicating the onset of the axion field, is inadequate to distinguish the system from a trivial normal insulator. Using numerical Green's functions, we theoretically demonstrate the quantized magnetoelectric current in a tunnel junction of atomically thin MnBi_{2}Te_{4} sandwiched between two contacts, which is a smoking-gun signal that unambiguously confirms antiferromagnetic MnBi_{2}Te_{4} to be an axion insulator. Our predictions can be verified directly by experiments.

Abstract Background The high prevalence of periodontal diseases is an important oral health problem worldwide. It is necessary to increase public knowledge on and influence attitudes towards periodontal diseases in order to prevent them. However, the effect of oral health education (OHE) as a primary preventive method in China is unsatisfactory. The aim of this study is to investigate the feasibility of extending an e-learning course regarding periodontal health by comparing the effects of oral health education regarding periodontal health (OHE-PH) on dental and non-dental students and the effects between a traditional course and an e-learning course among non-dental students at Sichuan University. Methods A quasi-experimental study with a pre-test and a post-test was performed. A total of 217 dental students and 134 non-dental students attended a traditional course; 69 non-dental students attended an e-learning course. Before- and after-course questionnaires about periodontal health knowledge, attitudes and behaviours were administered. Results After the traditional/e-learning course, the knowledge of both dental and non-dental students about periodontal diseases and self-reported behaviours for gingival bleeding and oral care improved. The non-dental students reached or surpassed the level of dental students before the course. The non-dental students taking the e-learning course performed better in some areas than those taking the traditional course. Conclusions OHE-PH was effective for dental and non-dental students. The e-learning course on OHE-PH was sufficient for improving knowledge and self-reported behaviours among non-dental undergraduates and was even better than the traditional course in some areas. The e-learning course may be an effective method for periodontal health education and oral health promotion among undergraduates.

Abstract Background Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients. Methods This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots. Results The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742–0.806) and 0.820 (95% CI: 0.762–0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT. Conclusions The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.