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Abstract Human coronaviruses exhibit a spectrum of symptoms, ranging from mild seasonal colds to severe respiratory manifestations. Despite progress in understanding the host's innate defense mechanisms against coronaviruses, how these viruses manipulate the immune response to promote inflammation remains elusive. In this study, we unveil the role of the coronavirus nonstructural protein 14 (NSP14) in leveraging the host's linear ubiquitin chain assembly complex (LUBAC) to instigate NF-κB activation, thereby triggering proinflammatory responses. Our findings uncover that HOIL-1-interacting protein (HOIP) directly engages with NSP14, conferring linear polyubiquitin chains onto NSP14. Consequently, ubiquitinated NSP14 recruits NEMO and initiates the activation of the IKK complex. This NSP14-induced NF-κB activation stimulates the expression of proinflammatory factors but not type I interferon, leading to a skewed host innate immune response tilting to inflammation. Collectively, our study sheds light on a virus-initiated linear ubiquitination pathway that induces NF-κB signaling and provokes proinflammatory responses.

Abstract Alzheimer’s disease (AD) stands as the most prevalent neurodegenerative ailment, presently lacking a definitive cure. Given that primary medications for AD patients in the early or middle stages demonstrate optimal efficacy, it becomes crucial to delve into the identification of risk genes associated with early onset. In our study, we compiled and integrated three transcriptomics datasets (GSE48350, GSE36980, GSE5281) originating from the hippocampus of 37 AD patients and 66 healthy controls (CTR) for comprehensive bioinformatics analysis. Comparative analysis with CTR revealed 25 up-regulated genes and 291 down-regulated genes in AD. Those down-regulated genes were notably enriched in processes related to the transmission and transport of synaptic signals. Intriguingly, 27 differentially expressed genes implicated in AD were also correlated with the Braak stage, establishing a connection with various immune cell types that exhibit differences in AD, including cytotoxic T cells, neutrophils, CD4 T cells, Th1, Th2, and Tfh. Significantly, a Cox model, constructed using nine feature genes, effectively stratified AD samples (HR = 2.72, 95% CI 1.94 ~ 3.81, P = 3.6e–10), highlighting their promising potential for risk assessment. In conclusion, our investigation sheds light on novel genes intricately linked to the onset and progression of AD, offering potential biomarkers for the early detection of this debilitating condition. This study contributes valuable insights toward enhancing the strategies for preventing and treating AD.

Abstract Engineering the electronic band structures upon doping is crucial to improve the thermoelectric performance of materials. Understanding how dopants influence the electronic states near the Fermi level is thus a prerequisite to precisely tune band structures. Here, we demonstrate that the Sn-s states in SnTe contribute to the density of states at the top of the valence band. This is a consequence of the half-filled p-p σ-bond (metavalent bonding) and its resulting symmetry of the orbital phases at the valence band maximum (L point of the Brillouin zone). This insight provides a recipe for identifying superior dopants. The overlap between the dopant s- and the Te p-state is maximized, if the spatial overlap of both orbitals is maximized and their energetic difference is minimized. This simple design rule has enabled us to screen out Al as a very efficient dopant to enhance the local density of states for SnTe. In conjunction with doping Sb to tune the carrier concentration and alloying with AgBiTe2 to promote band convergence, as well as introducing dislocations to impede phonon propagation, a record-high average ZT of 1.15 between 300 and 873 K and a large ZT of 0.36 at 300 K is achieved in Sn0.8Al0.08Sb0.15Te-4%AgBiTe2.

Abstract Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality.

Background The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

This paper focuses on the main problems of unstable neutron yield and continuous decrease in neutron yield when using static water-cooled target in the D-D neutron generator. A multifunctional compact rotating target device was developed, which adopted an integrated design and was compact in structure and small in size, equipped with functions such as high-speed rotation and water-cooled of target body, visual monitoring of target point, real-time measurement of target surface temperature, and real-time monitoring of neutron yield. This paper introduced the performance parameters of several major high current neutron generators rotating targets in the world, and elaborated on the advantages of rotating targets compared to traditional static targets. The main structure and functional design of the device were introduced. The main structure of the target was composed of a vacuum target chamber, target plates, beam pipes, circulating cooling water pipes, accompanying particle pipes, target monitoring pipes, stepper motors, and corresponding seals. The functions and structural components of each device were elaborated in detail. In order to study the influence of the structure of the rotating target device on neutron scattering, the energy spectrum distribution of source neutron at various angles in space was simulated by using TARGET software. The energy spectrum data was input into the MCNP data card, and 40 point detectors were set up, with 0°-360° distributed at a distance of 1 m from the target surface. The influence of target structure on neutron scattering was calculated using MCNP simulation. The result of simulation data shows that the target structure broadens the neutron spectrum peak by 0-0.057 7 MeV, and the relative angular yield of scattered neutrons at various angles accounts for 10.53%-26.75%. The influencing factors of neutron scattering effects at several key angles based on energy spectrum curves were analyzed. The vacuum degree, target surface temperature load, and neutron yield stability of the rotating target device were tested. First of all, the average energy of a 300 keV deuterium particle beam in a target thickness of 1 mg/cm2 deuterium titanium target was theoretically calculated. The source neutron flux was calculated using the average energy, and then the device was installed on a neutron generator at Chinese Institute of Atomic Energy to conduct preliminary tests on various performance. The test results show that the vacuum degree of the rotating target remains stable at around 3×10−5 Pa for a long time. Compared with static targets, rotating target improves neutron yield stability by one order of magnitude, and the maximum temperature of the target decreases by 13 ℃. And the cooling effect of the rotating target device was analyzed under different rotational speeds. The results show that as the rotational speed increases, the cooling effect gradually improves. Therefore, the rotating target device designed in this paper basically achieves the expected function, effectively solving the problem of continuous decrease in neutron yield, and the functional test results are normal with low neutron scattering effect. Finally, this paper also analyzes the problems in the simulation calculation results and measurement results, and proposes improvement and optimization plans.

Abstract Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48–0.85), 0.94 (0.72–1.23), 0.68 (0.50–0.92) and 1.62 (1.24–2.11) (P for trend was

Abstract The human endometrial decidualization is a transformative event in the pregnant uterus that involves the differentiation of stromal cells into decidual cells. While crucial to the establishment of a successful pregnancy, the metabolic characteristics of decidual cells in vivo remain largely unexplored. Here, we integrated the single-cell RNA sequencing (scRNA-seq) datasets on the endometrium of the menstrual cycle and the maternal-fetal interface in the first trimester to comprehensively decrypt the metabolic characteristics of stromal fibroblast cells. Our results revealed that the differentiation of stromal cells into decidual cells is accompanied by increased amino acid and sphingolipid metabolism. Furthermore, metabolic heterogeneity exists in decidual cells with differentiation maturity disparities. Decidual cells with high metabolism exhibit higher cellular activity and show a strong propensity for signaling. In addition, significant metabolic reprogramming in amino acids and lipids also occurs during the transition from non-pregnancy to pregnancy in the uteri of pigs, cattle, and mice. Our analysis provides comprehensive insights into the dynamic landscape of stromal fibroblast cell metabolism, contributing to our understanding of the metabolism at the molecular dynamics underlying the decidualization process in the human endometrium.

Abstract In photonic crystal systems, topologically protected edge states and corner states can be achieved by breaking spatial inversion symmetry, which is expected to be applied to topologically protected lasers, optical communication and integrated photonics. However, designing ultrabroadband topological photonic crystals is still a challenge. In this work, we propose a valley photonic crystal composed of dendritic structures, which can realize valley transmission with a relative bandwidth up to 59.65%. Compared with the previously reported two-dimensional broadband photonic crystals with 32.02% bandwidth, the relative bandwidth of the proposed valley transmission is increased by almost 100%. Theoretical analysis, numerical simulation and experimental measurement all confirm flexible manipulation of electromagnetic wave propagation paths. Ultrabroadband topological waveguides with the zigzag and armchair interface are demonstrated, which can achieve experimentally 58.71% and 36.78% relative bandwidth, respectively. In addition, several topological channel intersections are designed. Finally, two types of corner states with valley switchability and selectivity are demonstrated.

Efficient charge generation is essential for tandem organic light-emitting diode (OLED) devices. In this study, we introduce a p-type copper iodide (CuI) layer within the charge generation layer (CGL) that exhibits high charge generation efficiency in tandem OLED devices. Briefly, CuI is deposited as a thin layer via thermal evaporation technique. X-ray diffraction (XRD) analysis reveals the formation of γ-CuI, and the ultraviolet-visible (UV-Vis) spectral analysis demonstrates outstanding optical transparency (∼95%) of the deposited CuI films in the visible range. The current-voltage (I-V) and capacitance-voltage (C-V) analyses show that the p-type CuI layer is a vital and excellent charge generator and enhances the current density significantly. The tandem OLED device fabricated using Bphen:Liq/CuI/HAT-CN as the CGL results in a substantial 1.9-fold increase in current efficiency compared to the single-unit OLED device, approaching the theoretical two-fold increase. These findings highlight the potential of CuI as a promising p-type material for CGL design in tandem OLED devices.

Animal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, ACE2 with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR – Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3 × 105 PFU) or low (2.5 × 102 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.

BackgroundProgress in immunotherapy for pancreatic ductal adenocarcinoma (PDAC) has been slow, yet the relationship between microorganisms and metabolites is crucial to PDAC development. This study compares the biliary microbiota and metabolomic profiles of PDAC patients with those of benign pancreatic disease patients to investigate PDAC pathogenesis and its relationship with immunotherapy.MethodsA total of 27 patients were recruited, including 15 diagnosed with PDAC and 12 with benign pancreaticobiliary conditions, all of whom underwent surgical treatment. Intraoperative bile samples were collected and analyzed using 16S rRNA sequencing in conjunction with liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical methods and correlation analyzes were employed to assess differences in microbial composition, structure, and function between malignant and benign pancreatic diseases. Additionally, a retrospective analysis was conducted on PDAC patients post-surgery regarding immunotherapy and its correlation with metabolic components.ResultsPDAC patients exhibited a significantly higher abundance of bile microbiota compared to controls, with notable differences in microbiota structure between the two groups (P < 0.05). At the genus level, Muribaculum was markedly enriched in the bile of PDAC patients and was strongly correlated with phosphatidic acid (PA) (10:0/a-17:0). Both of these components, along with the tumor marker CA199, formulated a predictor of PDAC. Furthermore, PA (10:0/a-17:0) demonstrated a strong correlation with PDAC immunotherapy outcomes (Rho: 0.758; P=0.011).ConclusionThese findings suggest that the biliary microbiota and associated metabolites play a crucial role in the development of PDAC and may serve as potential predictive biomarkers and therapeutic targets for disease management.

BackgroundCommon side effect of Herpes Zoster, postherpetic neuralgia (PHN), causes persistent pain that seriously affects quality of life. Lack of dependable biomarkers makes the clinical diagnosis and treatment of PHN difficult, so complicating the assessment of therapeutic efficacy. Blood metabolites are becoming more and more well known as significant disease markers. With an aim to find possible biomarkers for diagnosis and treatment, this work investigates the causal link between blood metabolites and PHN using Mendelian randomization.MethodsThis work evaluated causal relationships between PHN and 1,091 plasma metabolites using Mendelian randomization (MR). Complementing MR-Egger and weighted median approaches, the main causality analysis was done using inverse variance weighted (IVW) and Wald ratio (WR) approaches. Robustness was checked using sensitivity analyses including CAUSE, Cochran’s Q tests, leave-one-out analysis, MR-PRESSO, and MR-Egger intercept analysis. Reverse MR analysis and linkage disequilibrium score regression (LDSC) was used to assess significant correlations as well. Two-step MR analysis was also used to look at the mediating function of positively correlated metabolites in the causal pathway.ResultsThe results of this study indicated a significant association between N-acetyl-aspartyl-glutamate (NAAG) and PHN, with an odds ratio (OR) of 0.83 (95% CI: 0.76–0.91, p = 2.68E-05). Moreover, five potential associated metabolites were identified: Gamma-glutamylthreonine (OR = 1.60, 95% CI: 1.16–2.20, p = 0.004), 3-hydroxyphenylacetoylglutamine (OR = 1.43, 95% CI: 1.00–2.05, p = 0.048), Caprate (10:0) (OR = 1.86, 95% CI: 1.11–3.12, p = 0.018), X-12013 (OR = 1.64, 95% CI: 1.03–2.60, p = 0.035), and X-17328 (OR = 1.50, 95% CI: 1.04–2.18, p = 0.032). Additionally, NAAG likely acts as a complete mediator between FOLH1(CGPII) and postherpetic neuralgia in the causal pathway.ConclusionThe results of this study indicated a significant association between N-acetyl-aspartyl-glutamate (NAAG) and PHN, with an odds ratio (OR) of 0.83 (95% CI: 0.76–0.91, p = 2.68E-05). Furthermore five possible related metabolites were found: Glutamylthreonine gamma-wise (OR = 1.60, 95% CI: 1.16–2.20, p = 0.004), 3-hydroxyphenylacetoylglutamine (OR = 1.43, 95% CI: 1.00–2.05, p = 0.048), Caprate (10:0) (OR = 1.86, 95% CI: 1.11–3.12, p = 0.018), X-12013 (OR = 1.64, 95% CI: 1.03–2.60, p = 0.035), and X-17328 (OR = 1.50, 95% CI: 1.04–2.18, p = 0.032). Furthermore, in the causal pathway NAAG most certainly serves as a complete mediator between FOLH1(CGPII) and postherpetic neuralgia.

The transverse polarization of Λ hyperon within reconstructed jets in hadronic collisions offers a complementary platform to probe the polarized fragmentation function D1T⊥. We illustrate that by performing a global analysis of the transverse polarization of Λ hyperons produced in different kinematic regions and in different hadronic collisions, such as pp, pp¯, pA, and γA collisions, we can pin down the flavor dependence of D1T⊥ which has been poorly constrained. Besides the single inclusive jet production, the γ/Z0-boson associated jet production supplements with more capability in removing ambiguities in the flavor dependence of D1T⊥.

In recent years, non-characteristic harmonic resonance was observed in several high-voltage direct current (HVDC) systems in China. Intuitively, additional filters can be installed to mitigate the resonance. However, such a solution does not prevent the harmonic penetration from nearby substations. As a result, the harmonic issue in HVDC systems cannot be well addressed. In view of the above, this paper presents a system-level harmonic mitigation method. The basic idea is to address the harmonic pollution by mitigating harmonic sources and harmonic resonance simultaneously. To achieve this goal, candidates of filters to suppress the resonance at the HVDC station are investigated first. Then, an optimal filter design problem is established to determine the location, type and capacity of multiple filters that can achieve the system-level harmonic mitigation with the minimum cost. Particularly, an improved particle swarm algorithm with adaptive mutation operators is tailor-designed to solve the proposed optimization problem. Finally, the proposed method is applied to address the harmonic problem faced by a real-life HVDC system in eastern China. The result demonstrates that compared with the solutions solely mitigating harmonic sources or resonance, the method presented in this paper is more cost-effectiveness.

Electrochemical synthesis serves as a green and efficient method with great application potential. However, it has not been extensively applied in the synthesis of energetic materials. Nitrogen-rich heterocyclic compounds, as a new generation of energetic materials, enjoy advantages such as eco-friendliness, high energy output, and excellent safety performance. This study reports the electrochemical cathodic synthesis of copper nitrotriazole [Cu(NTz)2] using copper chloride and 3-nitro-1,2,4-triazole as a reaction substrate and triethylamine as a deprotonation agent. The obtained Cu(NTz)2 comprises uniform spherical particles of nano lamellae. As the dosage of triethylamine increased from 50 μL to 150 μL, Cu(NTz)2 gradually grew into compact solid spherical particles, significantly increasing the energy output. Notably, the heat release increased from 711 J g−1 to 1301 J g−1, accompanied by a significant positive elevation of ignition performance and peak combustion pressure in the process of confined combustion. This greatly boosted the energetic performance of Cu(NTz)2. Moreover, Cu(NTz)2 demonstrates insensitivity to electrostatic discharge (E50＞225 mJ) and friction (FS＞360 N), suggesting excellent safety performance. Owing to its outstanding energetic and safety performance, Cu(NTz)2 boasts great potential for application as pyrotechnic compositions, including military gas-producing and incendiary agents. Moreover, it has been corroborated that Cu(NTz)2 can be applied as a micro ignitor.

Morphological and phylogenetic analyses on samples of Xylaria species associated with fallen fruits from China were carried out, and two new species were described, namely X. aleuriticola and X. microcarpa. Xylaria aleuriticola is found on fallen fruits of Aleurites moluccana, and characterized by stromata dichotomously branched several times with long acute sterile apices, fertile parts roughened with perithecia and tomentose, and ellipsoid to fusiform ascospores. Xylaria microcarpa differs in its very small stromata with dark brown tomentum, light brown ascospores with an inconspicuous straight germ slit, and grows on leguminous pods. The differences between the new species and morphologically similar species are discussed. Phylogenetic analyses on ITS-RPB2-TUB sequences confirmed that the two species are clearly separated from other species of the genus Xylaria. Xylaria liquidambaris is reported as a new record from China. A key to the Xylaria species associated with fallen fruits and seeds reported from China is provided to facilitate future studies of the genus.

Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. At initial diagnosis, approximately 20% of patients are diagnosed with metastatic CRC (mCRC). Although the APC‒Asef interaction is a well-established target for mCRC therapy, the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging endeavor. In this study, we identified a novel structural scaffold based on MAI inhibitors, the first-in-class APC‒Asef inhibitors we reported previously. ONIOM model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed, and 24-fold greater potency was obtained with the best inhibitor compared to the parental compound. In addition, the cocrystal structure validated that the two-layer π‒π stacking interactions were essential for inhibitor stabilization in the bound state. Furthermore, in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC‒Asef interaction. These results provide an intrinsic structural basis to further explore drug-like molecules for APC‒Asef-mediated CRC therapy.

Abstract The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric “heterogeneity” to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.

Background: Coronary heart disease (CHD) is the most common cardiovascular disease facing human beings. Cardiac remodelling is an important pathological factor for the progression of heart failure (HF) after CHD. At present, Chinese medicine is widely used in the treatment of HF, but there are still some drugs lack of evidence-based and mechanism evidence. Multi-omics techniques can deep explore candidate pathogenic factors and construct gene regulatory networks.This trial is intended to evaluate the effect on Huoxin pill (HXP) in the treatment of HF after programmable communication interface (PCI). Meantime, multi-omics analysis technique will be used to target the fundamental pathological links of cardiac remodelling, so as to study the mechanism of HXP in the treatment of HF after PCI. Methods: This study is a randomized, double-blind, placebo-controlled trial. Sixty patients with HF undergoing PCI are recruited from the First Affiliated Hospital of Henan University of CM. All selected patients will be randomly attributed to receive conventional treatment + HXP or placebo. The packaging, dosage and smell of placebo and heart activating pill were identical. The primary outcome is NYHA cardiac function grade, while the secondary outcomes included Lee's HF score, exercise tolerance test, and quality of life evaluation. Additional indicators include cardiac ultrasound, electrocardiogram, 24-h dynamic electrocardiogram, myocardial injury indicators, and energy metabolism indicators. Discussion: This study may provide a new treatment option for patients with HF after PCI and provide evidence for the treatment of CHD and HF with HXP. Trial registration: 2023-10-08 registered in China Clinical Trial Registry, registration number ChiCTR2300076402.

The landslide susceptibility map estimates the quantitative relationship between known landslides and control factors, and it has been used for site selection of infrastructures and geo-disaster management. As landslides and rockfalls occur frequently in mountainous areas in Hebei Province, China, due to road construction, the managing government needs to evaluate the vulnerability of geo-disasters in the road slopes to avoid unfavorable site selection for subsequent road constructions. Some typical collector road slopes were used as the study area in Pingshan County, Hebei Province. By analyzing the landslide triggering factors, we determined classification criteria and proposed a comprehensive method for determining the weighting. The respective weighting was calculated by the AHP and CRITIC method, and the combination weighting was determined by the game theory method. The landslide susceptibility of collector roads was evaluated and mapped using the ArcGIS platform. The susceptibility map was validated using landslide field investigation. The validation results show the effectiveness of the susceptibility methods, given the good number of correctly classified landslides. The landslide susceptibility map could have a significant impact on reducing the vulnerability of infrastructure to landslides in Hebei Province, China.

Abstract Background Microdeletion of the human chromosomal region 16p11.2 (16p11.2 $${}^{+/-}$$ + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 $${}^{+/-}$$ + / - syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 $${}^{+/-}$$ + / - are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 $${}^{+/-}$$ + / - , as well as the underlying molecular mechanisms. Results Mice with the 16p11.2 $${}^{+/-}$$ + / - showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. Conclusions Our study reveals that 16p11.2 $${}^{+/-}$$ + / - leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 $${}^{+/-}$$ + / - mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome. Video Abstract

Abstract Hyperthermic intraperitoneal chemotherapy’s role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer.

Due to the complexity and diversity of underwater environments, traditional object detection algorithms face challenges in maintaining robustness and detection accuracy when applied underwater. This paper proposes an underwater object detection algorithm based on an improved YOLOv8 model. First, the introduction of CIB building blocks into the backbone network, along with the optimization of the C2f structure and the incorporation of large-kernel depthwise convolutions, effectively enhances the model’s receptive field. This improvement increases the capability of detecting multi-scale objects in complex underwater environments without adding a computational burden. Next, the incorporation of a Partial Self-Attention (PSA) module at the end of the backbone network enhances model efficiency and optimizes the utilization of computational resources while maintaining high performance. Finally, the integration of the Neck component from the Gold-YOLO model improves the neck structure of the YOLOv8 model, facilitating the fusion and distribution of information across different levels, thereby achieving more efficient information integration and interaction. Experimental results show that YOLOv8-CPG significantly outperforms the traditional YOLOv8 in underwater environments. Precision and Recall show improvements of 2.76% and 2.06%. Additionally, mAP50 and mAP50-95 metrics have increased by 1.05% and 3.55%, respectively. Our approach provides an efficient solution to the difficulties encountered in underwater object detection.

Good-quality urban street space is crucial for improving walkability. Frequency and amplitude are the main spatial characteristics of the street interface rhythm, known as a “virtual–real” relation. Exploring the mechanism influencing the urban street interface rhythm can help grasp the movement trend. In this study, the correlation between frequency and urban form is explored through a Pearson correlation analysis with multisource data, and the factors influencing the urban street interface rhythm are presented. The results indicate that frequency has a moderate negative correlation with the block scale and a moderate positive correlation with the number of pedestrian access entrances (PAE-n); the PAE-n also has a strong negative correlation with the block scale. Some spatial characteristics of outstanding streets from different countries are analyzed and discussed based on waveform classification. The regularities of interface rhythm that exist within multiple streets are found: multiple gaps on the street interface exist, acting as a “beat”, which regularly integrates or separates the street interface rhythm. The frequency and amplitude of the “beat” significantly affect streets’ walkability, and the amplitude is generally low and uniform, with good visual accessibility in all directions. A “Small Block and Dense Grid” becomes a key factor in improving walkability. Basic knowledge of the street interface rhythm in urban walking space research is supplemented by this study. Furthermore, theoretical guidance and parametric evidence are provided to improve walkability and promote the continuation of the traditional context.

The use of distributed photovoltaics (PVs) on a large scale often causes voltage over-limit problems in distribution networks. This paper proposes a distributed photovoltaic cluster collaborative optimization voltage control strategy based on an improved community algorithm to address the issue of centralized control being unable to respond quickly to the randomness of distributed photovoltaics and the difficulty of achieving overall coordination with local control. First, by improving the community algorithm, the division of reactive and active clusters, considering the power balance and node coupling degree, is realized. Then, the cluster-coordinated voltage control strategy is proposed by making full use of the power control ability of a photovoltaic inverter. Finally, a voltage regulation ability evaluation index is proposed to assess the node regulation ability within the cluster and select key nodes. This effectively reduces the number of control nodes. The simulation analysis of the improved IEEE 69 distribution network shows that the proposed voltage control strategy can mitigate the issue of voltage over-limit in high-permeability distributed photovoltaic access distribution and enhance the photovoltaic consumption capacity.

Abstract Beta diversity patterns along environmental gradients and underlying mechanisms constitute key research inquiries in biogeography. However, ecological processes often also influence the functional traits of biological communities, making the assessment of functional β‐diversity crucial. Ground beetles (Coleoptera: Carabidae) are one of the most species‐rich groups in the insect community, displaying strong habitat specificity and morphological differences. In this study, we explored the patterns of taxonomic and functional beta diversity in ground beetle communities along the altitudinal gradient of warm‐temperature forests. By partitioning beta diversity into turnover and nestedness components, we evaluated their relationship with spatial distance. Our findings indicate a decline in species and functional trait similarity with increasing elevation and geographic distance. Further analysis attributed both types of beta diversity in carabids to a combination of dispersal limitation and environmental filtering, with elevation and geographic distance emerging as significant factors. Interestingly, forest‐type variations were found to have no impact on the beta diversity of these communities. Our study reveals the impact of environmental filtering and dispersal limitation on both taxonomic and functional beta‐diversity, shedding light on carabid community assembly in localized warm‐temperature forest areas in eastern China.

Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS ( P

PurposeTo investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma (LANPC).MethodsPatients with stage III–IVA NPC who received IC or IC + PD-1 inhibitor were included. The chi-square test and multivariate logistic regression analysis were used for statistical analysis.ResultsA total of 225 patients were identified, including 193 (85.8%) and 32 (14.2%) who received IC alone and IC + PD-1 inhibitor, respectively. The addition of PD-1 inhibitor to IC significantly improved the tumor response than those treated with IC alone. The complete response (CR), partial response, stable disease, and progressive disease rates of 4.7% vs. 31.3%, 69.4% vs. 62.5%, 24.9% vs. 6.3%, and 1.0% vs. 0% in patients receiving IC alone and IC + PD-1 inhibitor, respectively (P

Background: To describe the past, present and future burden of pancreatitis in older adults, and to explore cross-national inequalities across socio-demographic index (SDI). Methods: Data on pancreatitis in older adults, including mortality and disability-adjusted life years (DALYs) rates, were collected from the Global Burden of Disease (GBD) 2019 study. Temporal trends were measured using joinpoint analyses and predicted using a Bayesian age-period-cohort model. Additionally, the unequal distribution of the burden of pancreatitis in older adults was quantified. Results: From 1990 to 2019, the number of deaths and DALYs due to pancreatitis in older adults has been increasing annually. However, in most regions of the world, age-standardized death rates (ASDR) and age-standardized DALYs rates have been declining. The burden of pancreatitis in older adults was highest in low SDI region, primarily affecting the population aged 65–74, with a greater burden on males than females. Furthermore, from 1990 to 2019, absolute and relative cross-national inequalities in pancreatitis among older adults have remained largely unchanged. It is projected that in the next 11 years, the number of deaths in older adults due to pancreatitis will continue to increase, but the ASDR is expected to decline. Conclusion: Over the past 30 years, the ASDR and age-standardized DALYs rate of pancreatitis in older adults have shown a decline globally, but the absolute burden continues to increase. Cross-national health inequalities persist. Therefore, it is necessary to develop targeted intervention measures and enhance awareness among this vulnerable population regarding the risk factors associated with pancreatitis.

Abstract Background Peri‐implantitis and periodontitis have similar immunological bioprocesses and inflammatory phenotypes. In the inflammatory process, the adaptive immune cells can drive the development of disease. This research investigated the differences and diagnostic significance of peri‐implantitis and periodontitis in adaptive immune responses. Methods We acquired four GEO datasets of gene expressions in surrounding tissues in healthy person, healthy implant, periodontitis, and peri‐implantitis patients. The structural characteristics and enrichment analyses of differential expression genes were examined. The adaptive immune landscapes in peri‐implantitis and periodontitis were then evaluated using single sample gene set enrichment analysis. The STRING database and Cytoscape were used to identify adaptive hub genes, and the ROC curve was used to verify them. Finally, qRT‐PCR method was used to verify the expression level of Hub gene in activated T cells on the titanium‐containing or titanium‐free culture plates. Results At the transcriptome level, the data of healthy implant, peri‐implantitis and periodontitis were highly dissimilar. The peri‐implantitis and periodontitis both exhibited adaptive immune response. Except for the activated CD4+T cells, there was no significant difference in other adaptive immune cells between peri‐implantitis and periodontitis. In addition, correlation analysis showed that CD53, CYBB, and PLEK were significantly positively linked with activated CD4+T cells in the immune microenvironment of peri‐implantitis, making them effective biomarkers to differentiate it from periodontitis. Conclusions Peri‐implantitis has a uniquely immunogenomic landscape that differs from periodontitis. This study provides new insights and ideas into the activated CD4+T cells and hub genes that underpin the immunological bioprocess of peri‐implantitis.

Abstract Splicing factor polyglutamine binding protein‐1 (PQBP1) is abundantly expressed in the central nervous system during development, and mutations in the gene cause intellectual disability. However, the roles of PQBP1 in cancer progression remain largely unknown. Here, it is shown that PQBP1 overexpression promotes tumor progression and indicates worse prognosis in ovarian cancer. Integrative analysis of spyCLIP‐seq and RNA‐seq data reveals that PQBP1 preferentially binds to exon regions and modulates exon skipping. Mechanistically, it is shown that PQBP1 regulates the splicing of genes related to the apoptotic signaling pathway, including BAX. PQBP1 promotes BAX exon 2 skipping to generate a truncated isoform that undergoes degradation by nonsense‐mediated mRNA decay, thus making cancer cells resistant to apoptosis. In contrast, PQBP1 depletion or splice‐switching antisense oligonucleotides promote exon 2 inclusion and thus increase BAX expression, leading to inhibition of tumor growth. Together, the results demonstrate an oncogenic role of PQBP1 in ovarian cancer and suggest that targeting the aberrant splicing mediated by PQBP1 has therapeutic potential in cancer treatment.

Abstract Ovarian cancer is resistant to immune checkpoint blockade (ICB) treatment. Combination of targeted therapy and immunotherapy is a promising strategy for ovarian cancer treatment benefit from an improved immune microenvironment. In this study, Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) cohorts were used to screen prognosis and cytotoxic lymphocyte infiltration-associated genes in upregulated genes of ovarian cancer, tissue microarrays were built for further verification. In vitro experiments and mouse (C57/BL6) ovarian tumor (ID8) models were built to evaluate the synergistic effect of the combination of SF3B1 inhibitor and PD-L1 antibody in the treatment of ovarian cancer. The results show that SF3B1 is shown to be overexpressed and related to low cytotoxic immune cell infiltration in ovarian cancer. Inhibition of SF3B1 induces pyroptosis in ovarian cancer cells and releases mitochondrial DNA (mtDNA), which is englobed by macrophages and subsequently activates them (polarization to M1). Moreover, pladienolide B increases cytotoxic immune cell infiltration in the ID8 mouse model as a SF3B1 inhibitor and increases the expression of PD-L1 which can enhance the antitumor effect of αPDL1 in ovarian cancer. The data suggests that inhibition of SF3B1 improves the immune microenvironment of ovarian cancer and synergizes ICB immunotherapy, which provides preclinical evidence for the combination of SF3B1 inhibitor and ICB to ovarian cancer treatment.

The current machine vision-based surface roughness measurement mainly relies on the design of feature indicators associated with roughness to measure the surface roughness. However, the process is tedious and complicated. Moreover, most existing deep learning methods for workpiece surface roughness measurement use a monochromatic light source to acquire images. In the case of surface roughness in a grinding process with low roughness and random texture characteristics, the feature information obtained by monochromatic light source acquisition is relatively small. It is difficult to extract the workpiece surface roughness features, which can easily cause problems for subsequent measurement. Based on the problems above, this paper proposes a grinding surface roughness measurement method combining red-green information and a convolutional neural network. The technique uses a particular red-green block to highlight the grinding surface texture features. Finally, it classifies the grinding surface roughness measurement with a classification detection technique of the convolutional neural network. Experimental results show that the accuracy of the grinding surface roughness measurement method combining red-green information and the convolutional neural network is significantly improved compared with that of the grinding surface roughness measurement method without using the red-green data.

Abstract Background The therapeutic effect of poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive in breast cancer susceptibility genes (BRCA)1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse. Methods BRCA1/2-mutated patients with secondary platinum-sensitive relapse included in this study did not receive any maintenance regimen after first- and second-line platinum-based chemotherapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy without restriction. Progression-free survival (PFS) was defined as the time from third-line therapy to disease progression or death, PFS2 was defined as the time from platinum-based chemotherapy after PARPi resistance to next subsequent therapy or death. Post-recurrence survival (PRS) refers to the survival time after secondary platinum-sensitive relapse. Results A total of 119 patients were retrospectively analyzed, including 71 (59.7%) in study group and 48 (40.3%) in control group. The objective response rate (ORR: 77.5% vs. 80.0%, p=0.766) and PFS (median: 11.2 vs. 11.0 months, p=0.962) were comparable. The benefit of subsequent platinum-based chemotherapy after PARPi resistance was more pronounced in patients with PARPi treatment for more than 12 months (median PFS2: 8.6 vs. 4.3 months, p=0.040). PARPi monotherapy had no adverse effect on PRS compared with platinum-based chemotherapy (median PRS:41.2 vs. 42.8 months, p=0.323). Compared to patients in control group who had never received PARPi, PARPi monotherapy (median PRS: 41.2 vs. 33.7 months, p=0.019) and post-line treatment with PARPi in the control group (median PRS: 48.1 vs. 33.7 months, p=0.002) could prolong PRS for patients with secondary platinum-sensitive relapse. Conclusions PARPi monotherapy was similar to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.

An in-depth study of the phylogenetic relationships of Xylaria species associated with nutshells of fruits and seeds within the genus Xylaria and related genera of Xylaceaecea was conducted in China. The multi-gene phylogenetic analyses were carried out based on ITS, RPB2, and TUB sequences of 100 species of 16 known genera in Xylariaceae around the world. Based on molecular phylogenetic analyses, morphological observations, and ecological habitats, a new genus, Heteroxylaria, is established to accommodate four new species, viz. H. cordiicola, H. juglandicola, H. meliicola, and H. terminaliicola, and four new combinations, viz. H. oxyacanthae, H. palmicola, H. reevesiae, and H. rohrensis. The genus is characterized by cylindrical stromata with conspicuous to inconspicuous perithecial mounds, surface black, having brown to dark brown ascospores with a germ slit, and it grows on nutshell of fruits. The combined ITS+RPB2+TUB sequence dataset of representative taxa in the Xylariaceae demonstrate that Heteroxylaria is grouped with Hypocreodendron but forms a monophyletic lineage. All novelties described herein are morphologically illustrated and compared to similar species and phylogeny is investigated to establish new genera and species.