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Abstract Studies have used extensive clinical information to predict time-to-heart failure (HF) in patients with and without diabetes mellitus (DM). We aimed to determine a screening method using only computed tomography calcium scoring (CTCS) to assess HF risk. We analyzed CTCS scans from 1,998 patients (336 with type 2 diabetes) from a no-charge coronary artery calcium score registry (CLARIFY Study, Clinicaltrials.gov NCT04075162). We used deep learning to segment epicardial adipose tissue (EAT) and engineered radiomic features of calcifications (“calcium-omics”) and EAT (“fat-omics”). We developed models incorporating radiomics to predict risk of incident HF in patients with and without type 2 diabetes. At a median follow-up of 1.7 years, 5% had incident HF. In the overall cohort, fat-omics (C-index: 77.3) outperformed models using clinical factors, EAT volume, Agatston score, calcium-omics, and calcium-and-fat-omics to predict HF. For DM patients, the calcium-omics model (C-index: 81.8) outperformed other models. In conclusion, CTCS-based models combining calcium and fat-omics can predict incident HF, outperforming prediction scores based on clinical factors.Please check article title if captured correctly.YesPlease check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.Yes

Abstract Phytochrome interacting factors (PIFs) serve as crucial regulators in the light signal transduction pathway and also mediate light signals to regulate secondary metabolite synthesis in plants. However, the regulator role of PIFs in secondary metabolites often varies among different plants. Isorhynchophylline (IRN), an iconic secondary metabolite of Uncaria rhynchophylla, holds significant medicinal value. Low light induces the synthesis of IRN in previous research, but PIFs in U. rhynchophylla have not been studied to date. Building on this, we identified a PIF protein, UrPIF3, which possesses the typical conserved domains of the PIFs and is localized in the nucleus. Moreover, the expression level of UrPIF3 is consistently positively correlated with the expression of two key enzyme genes (UrSGD and UrSTR) in the IRN biosynthesis pathway, regardless of whether under low light or restoring light conditions. Yeast one-hybrid and dual-luciferase assays further demonstrated that UrPIF3 can directly upregulate UrSGD. Conversely, silencing UrPIF3 inhibits IRN synthesis, and significantly reduces the expression levels of UrSGD and UrSTR. In summary, our results suggest that under low light conditions, UrPIF3 can directly upregulate UrSGD and indirectly upregulate UrSTR, thereby promoting the synthesis of IRN.

Abstract As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage response (DDR) in colorectal cancer remains unclear. GL exposure significantly reduced cell colony formation and viability with a concomitant increase in DNA fragmentation in CRC, meanwhile GL induced apoptosis by activating caspase-3. Moreover, GL induced cell cycle arrest in CRC cells at S phase, which was associated with decreased cyclin D1 in vitro. GL treatment significantly ameliorated tumor growth and promoted DDR in vivo. Mechanism analysis revealed that GL significantly downregulated the NHEJ pathway via inhibiting HMGB1. Finally, the expression of HMGB1 was abnormal regulated in CRC tissue than in adjacent normal tissues and associated with TNM stage and overall survival. Our findings indicate that HMGB1 may be a novel therapeutic target in CRC, a result that GL may serve as a promising drug for CRC treatment.

Abstract This study employed lignin-sulfonated (LS) to develop biobased carbon materials (LS-Cs) through a sulfur-doping approach to enhance their physicochemical properties, adsorption capabilities, and energy storage potentials. Various characterization techniques, including BET surface area analysis, SEM imaging, XPS, Raman spectroscopy, and elemental composition (CHNS), were employed to assess the quality of the LS-Cs adsorbent and electrode samples. Response Surface Methodology (RSM) was utilized for optimizing the two main properties (specific surface area, ABET, and mesopore area, AMESO) by evaluating three independent factors (i.e., activation temperature, ZnCl2:LS ratio, and sulfur content). According to the statistical analysis, ABET and AMESO were affected by ZnCl2 and sulfur content, while the pyrolysis temperature did not affect the responses in the studied conditions. It was found that increasing the ZnCl2 and sulfur contents led to an increment of the ABET and AMESO values. The LS-C materials exhibited very high ABETvalues up to 1993 m2 g−1 and with predominantly mesoporous features. The S-doping resulted in LS-Cs with high sulfur contents in their microstructures up to 15% (wt%). The LS-C materials were tested as adsorbents for sodium diclofenac (DCF) adsorption and reactive orange 16 dye (RO-16) and as electrodes for supercapacitors. The LS-Cs exhibited excellent adsorption capacity values for both molecules (197–372 mg g−1) for DCF, and (223–466 mg g−1) for RO-16. When tested as electrodes for supercapacitors, notably, LS-C3, which is a doped sample with sulfur, exhibited the best electrochemical performance, e.g. high specific capacitance (156 F/g at 50 mV/s), and delivered an excellent capacitance after 1000 cycles (63 F/g at 1 A/g), which denotes the noteworthy capacitive behavior of the S-doped electrode. Thus, the present work suggests an eco-friendly resource for developing effective, productive carbon materials for adsorbent and electrodes for SC application. However, further studies on the complete application of these materials as adsorbents and electrodes are needed for a deeper understanding of their behavior in environmental and energy storage applications.

Abstract This study addresses the challenges in large-scale unmanned aerial vehicle (UAV) clusters, specifically the scalability issues and limitations of using reactive routing protocols for inter-cluster routing. These traditional methods place an excessive burden on cluster heads and struggle to adapt to frequently changing topologies, leading to decreased network performance. To solve these problems, we propose an innovative inter-cluster routing protocol (ICRP), which is based on a hybrid ant colony algorithm. During the route establishment phase, ICRP uses this algorithm to identify the optimal relay node. This approach is inspired by the foraging behavior of Physarum polycephalum, combining factors such as the number of hops from the source node, the load condition of the node, and its weight in the pheromone calculation. In the route maintenance phase, ICRP uses a predictive repair and contraction mechanism to dynamically maintain routes, accommodating the high mobility of UAVs. Comparative simulations in OMNeT + + showed that this protocol surpasses ad-hoc on-demand distance vector (AODV), fuzzy-logic-assisted-AODV, and Enhanced-Ant-AODV routing protocols in packet delivery rate and end-to-end transmission delay. Furthermore, it showed superior adaptation to network environments with high-speed node mobility.

Abstract Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P

Abstract Facing the untrusted threats of network elements and PKI/CA faced by SR-BE/TE (Segment Routing-BE/TE) data plane in the zero-trust network environment, firstly, this paper refines it into eight specific security issues. Secondly, an SR-BE/TE data plane security model ZbSR (ZTA-based SR) based on zero-trust architecture is proposed, which reconstructs the original SR control plane into a "trust-agent" two-layer plane based on 4 components of the controller, agent, cryptographic center and information base. On one hand, we distinguish between the two segment list generation modes and proposes corresponding data exchange security algorithms, by introducing north–south security verification based on identity authentication, trust evaluation, and key agreement before the terminal device establishes an east–west access connection, so reliable data exchange between terminal devices can be realized. On the other hand, for the network audit lacking SR-BE/TE, a network audit security algorithm based on solid authentication is proposed. By auditing the fields, behaviors, loops, labels, paths, and SIDs of messages, threats such as stream path tampering, SID tampering, DoS attacks, and loop attacks can be effectively detected. Finally, through the simulation test, the proposed model can provide security protection for the SR data plane with a 19.3% average incremental delay overhead for various threat scenarios.

Abstract Paeonia × lemoinei 'High Noon' is one of the most important cultivars in tree peony (Paeonia sect. Moutan), a traditional horticultural plant in China, with a re-blooming characteristic which was quite different from other cultivars. So, the genetic resources in 'High Noon' were incredibly valuable in flowering-time-modified molecular breeding in tree peony. However, the molecular mechanism underlying the floral bud formation of 'High Noon' was not clear yet. To explore the molecular mechanism in this process, the transcriptomes of three stages during floral bud development were deeply analyzed in this study. As a result, a total of 5816 differentially expressed genes (DEGs) were identified between the three developmental stages, and pathways including ''DNA replication'', ''metabolic pathways'', ''circadian rhythm'', and ''plant hormone signal transduction'' were mostly enriched in the functional enrichment and expression pattern analysis. Furthermore, a total of 584 genes related to the photoperiod pathway were further identified and a novel CO homolog gene PlCO was identified to be a stable hydrophilic protein, which contained both CCT domain and B-box domain. Over-expression of PlCO in Arabidopsis resulted in early flowering, which suggested a promotion role of flowering. The PlCO protein localized in nucleus and possessed a transcription activity ability, which implied that PlCO might function as a transcription factor. The transcriptome analysis revealed pathways involved in floral bud development in tree peony and provided new insight into the regulatory network underlying the floral bud development. The gene identification in 'High Noon' provided new valuable candidate genes for flowering-time-modified molecular breeding in tree peony.

Abstract Assessing vulnerability to natural hazards is at the heart of hazard risk reduction. However, many countries such as Australia lack measuring systems to quantity vulnerability for hazard risk evaluation. Drawing on 41 indicators from multiple data sources at the finest spatial unit of the Australian census, we re-forged the Cutter’s classic vulnerability measuring framework by involving the ‘4D’ quantification of built environment (diversity, design, density and distance), and constructed the first nationwide fine-grained measures of vulnerability for urban and rural locales, respectively. Our measures of vulnerability include five themes—(1) socioeconomic status; (2) demographics and disability; (3) minority and languages; (4) housing characteristics; and (5) built environment—that were further used to assess the inequality of vulnerability to three widely affected natural hazards in Australia (wildfires, floods, and earthquakes). We found the inequality of vulnerability in the affected areas of the three hazards in eight capital cities are more significant than that of their rural counterparts. The most vulnerable areas in capital cities were peri-urban locales which must be prioritised for hazard adaptation. Our findings contribute to the risk profiling and sustainable urban–rural development in Australia, and the broad understanding of place-based risk reduction in South Hemisphere.

Abstract Gas-bearing property evaluation and main controlling factor analysis have remained a concern in shale gas research. The application of principal component analysis, an important mathematical statistical method, in gas-bearing property evaluation and main controlling factor analysis of the Longmaxi shale in the Weirong area, Sichuan Basin, was examined. The Longmaxi shale exhibits high heterogeneity, manifested in the organic matter abundance, mineral composition, and pore structure. Seven geological factors, including the temperature, pressure, TOC content, clay content, brittle mineral content, pore volume, and specific surface area (SSA), were selected in principal component analysis. Four principal components with geological significance, such as mineral composition, formation condition, pore structure, and organic matter abundance, were extracted through principal component analysis, and further constituted a comprehensive factor. Shale gas-bearing properties were evaluated according to the score of the comprehensive factor. The Longmaxi shale could be identified as exhibiting good, medium, and poor gas-bearing properties based on the comprehensive factor scores of these samples. According to each geological factor’s contribution to the comprehensive factor, combined with geological analysis, it could be considered that gas-bearing properties are primarily controlled by pore volume, SSA, and clay content, followed by TOC content, brittle mineral content, temperature and pressure.

Abstract Segment routing (SR) technology is a new network functional technology derived from MPLS technology and based on SDN. Combining SR with software-defined perimeter (SDP), a new network security technology, is expected to solve the traditional problems such as data monitoring, denial of service, and new threats such as loop attack and label detection faced by SR data plane. Focusing on the security management of access devices in the SR data plane, first, this paper proposes an SR security model SbSR (SDP-based SR) based on SDP trust enhancement architecture, then, two-level SDP AH trust verification mechanism and 4 trust management mechanisms including initial trust value, trust evaluation, trust renewal, trust inheritance are designed. In the trust evaluation mechanism as the core of the model, System cloud grey model (1,1) weighted Markov prediction model is introduced to obtain real-time trust based on the historical behavior of device nodes, and 4 indexes, namely benign message ratio, loyal forwarding ratio, forwarding ratio stationarity coefficient, packet rate stationarity coefficient, are introduced to distinguish malicious devices from normal devices. Finally, the simulation test results of 5 security functions and security costs show that the proposed architecture can solve port scanning, traffic monitoring, topology detection, loop attack, and DoS attack of SR network data plane with an average access delay cost of 2.84 s for each new network agent, and realize multi-faceted protection of SR network data plane.

Abstract The natural forest ecosystem has been affected by wind storms for years, which have caused several down wood (DW) and dramatically modified the fabric and size. Therefore, it is very important to explain the forest system by quantifying the spatial relationship between DW and environmental parameters. However, the spatial non-stationary characteristics caused by the terrain and stand environmental changes with distinct gradients may lead to an incomplete description of DW, the local neural-network-weighted models of geographically neural-network-weighted (GNNWR) models are introduced here. To verify the validity of models, our DW and environmental factors were applied to investigate of occurrence of DW and number of DW to establish the generalized linear (logistic and Poisson) models, geographically weighted regression (GWLR and GWPR) models and GNNWR (GNNWLR and GNNWPR) models. The results show that the GNNWR models show great advantages in the model-fitting performance, prediction performance, and the spatial Moran’s I of model residuals. In addition, GNNWR models can combine the geographic information system technology for accurately expressing the spatial distribution of DW relevant information to provide the key technology that can be used as the basis for human decision-making and management planning.

Abstract Epicardial adipose tissue volume (EAT) has been linked to coronary artery disease and the risk of major adverse cardiac events. As manual quantification of EAT is time-consuming, requires specialized training, and is prone to human error, we developed a deep learning method (DeepFat) for the automatic assessment of EAT on non-contrast low-dose CT calcium score images. Our DeepFat intuitively segmented the tissue enclosed by the pericardial sac on axial slices, using two preprocessing steps. First, we applied a HU-attention-window with a window/level 350/40-HU to draw attention to the sac and reduce numerical errors. Second, we applied a novel look ahead slab-of-slices with bisection (“bisect”) in which we split the heart into halves and sequenced the lower half from bottom-to-middle and the upper half from top-to-middle, thereby presenting an always increasing curvature of the sac to the network. EAT volume was obtained by thresholding voxels within the sac in the fat window (− 190/− 30-HU). Compared to manual segmentation, our algorithm gave excellent results with volume Dice = 88.52% ± 3.3, slice Dice = 87.70% ± 7.5, EAT error = 0.5% ± 8.1, and R = 98.52% (p

Abstract Spin-valley and electronic band topological properties have been extensively explored in quantum material science, yet their coexistence has rarely been realized in stoichiometric two-dimensional (2D) materials. We theoretically predict the quantum spin Hall effect (QSHE) in the hydrofluorinated bismuth (Bi2HF) nanosheet where the hydrogen (H) and fluorine (F) atoms are functionalized on opposite sides of bismuth (Bi) atomic monolayer. Such Bi2HF nanosheet is found to be a 2D topological insulator with a giant band gap of 0.97 eV which might host room temperature QSHE. The atomistic structure of Bi2HF nanosheet is noncentrosymmetric and the spontaneous polarization arises from the hydrofluorinated morphology. The phonon spectrum and ab initio molecular dynamic (AIMD) calculations reveal that the proposed Bi2HF nanosheet is dynamically and thermally stable. The inversion symmetry breaking together with spin-orbit coupling (SOC) leads to the coupling between spin and valley in Bi2HF nanosheet. The emerging valley-dependent properties and the interplay between intrinsic dipole and SOC are investigated using first-principles calculations combined with an effective Hamiltonian model. The topological invariant of the Bi2HF nanosheet is confirmed by using Wilson loop method and the calculated helical metallic edge states are shown to host QSHE. The Bi2HF nanosheet is therefore a promising platform to realize room temperature QSHE and valley spintronics.

Abstract In the past decade, hand, foot, and mouth disease (HFMD) has posed a serious threat to childhood health in China; however, no epidemiological data from large HFMD epidemics have been described since 2013. In the present study, we described the epidemiological patterns of HFMD in Shandong province during 2009–2016 from a large number of symptomatic cases (n = 839,483), including >370,000 HFMD cases since 2013. Our results revealed that HFMD activity has remained at a high level and continued to cause annual epidemics in Shandong province from 2013 onwards. Although the incidence rate was significantly higher in urban areas than in rural areas, no significantly higher case-severity and case-fatality rates were found in urban areas. Furthermore, the seventeen cities of Shandong province could be classified into three distinct epidemiological groups according to the different peak times from southwest (inland) to northeast (coastal) regions. Notably, a replacement of the predominant HFMD circulating agent was seen and non-EVA71/Coxsackievirus A16 enteroviruses became dominant in 2013 and 2015, causing approximately 30% of the severe cases. Our study sheds light on the latest epidemiological characteristics of HFMD in Shandong province and should prove helpful for the prevention and control of the disease in Shandong and elsewhere.

Abstract The strongly correlated electron fluids in high temperature cuprate superconductors demonstrate an anomalous linear temperature (T) dependent resistivity behavior, which persists to a wide temperature range without exhibiting saturation. As cooling down, those electron fluids lose the resistivity and condense into the superfluid. However, the origin of the linear-T resistivity behavior and its relationship to the strongly correlated superconductivity remain a mystery. Here we report a universal relation $$d{\boldsymbol{\rho }}/{\boldsymbol{dT}}=({{\boldsymbol{\mu }}}_{{\bf{0}}}{{\boldsymbol{k}}}_{{\boldsymbol{B}}}/{\boldsymbol{\hslash }})\,{{\boldsymbol{\lambda }}}_{{\boldsymbol{L}}}^{{\bf{2}}}$$ d ρ / dT = ( μ 0 k B / ℏ ) λ L 2 , which bridges the slope of the linear-T-dependent resistivity (dρ/dT) to the London penetration depth λ L at zero temperature among cuprate superconductor Bi2Sr2CaCu2O8+δ and heavy fermion superconductors CeCoIn5, where μ 0 is vacuum permeability, k B is the Boltzmann constant and ħ is the reduced Planck constant. We extend this scaling relation to different systems and found that it holds for other cuprate, pnictide and heavy fermion superconductors as well, regardless of the significant differences in the strength of electronic correlations, transport directions, and doping levels. Our analysis suggests that the scaling relation in strongly correlated superconductors could be described as a hydrodynamic diffusive transport, with the diffusion coefficient (D) approaching the quantum limit D ~ ħ/m*, where m* is the quasi-particle effective mass.

Abstract Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT −/− mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT −/− mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance. Treatment of wild type mice with paroxetine, a chemical inhibitor of SERT, also resulted in Cyp19a1 suppression, decreased circulating 17β-estradiol levels, abnormal fat accumulation, and glucose intolerance. Such effects were not observed in paroxetine-treated SERT −/− mice. Conversely, pregnant SERT −/− mice displayed normalized estrogen levels, markedly reduced fat accumulation, and improved glucose tolerance, which can be eliminated by an antagonist of estrogen receptor α (ERα). Together, these findings support that estrogen suppression is involved in SERT deficiency-induced obesity and glucose intolerance, and suggest approaches to restore 17β-estradiol levels as a novel treatment option for SERT deficiency associated obesity and metabolic abnormalities.

Abstract This study evaluates the survival outcomes of segmental ureterectomy (SU) combined with chemotherapy in patients with high-grade non-metastatic ureteral cancer (UC) using data from the SEER database. A total of 1757 patients with Grade III-IV non-metastatic UC were analyzed. Overall survival (OS) was assessed through Kaplan–Meier analysis, and independent prognostic factors were identified via Cox regression. A Nomogram model was developed and evaluated using the concordance index, area under the time-dependent ROC curve, calibration curves, and decision curve analysis. The 1-, 3-, and 5-year OS rates were 82.8%, 55.6%, and 42.8%, respectively. Age, treatment protocol, T stage, and N stage were significant prognostic factors. Both SU + chemotherapy and radical nephroureterectomy (RNU) + chemotherapy demonstrated comparable survival outcomes, outperforming surgery alone, particularly in patients aged 70 and older. The Nomogram demonstrated high predictive accuracy and clinical utility. These findings suggest that SU + chemotherapy offers survival benefits similar to RNU + chemotherapy, making it a viable option, especially for elderly patients or those with impaired renal function.

Abstract In order to improve the service life of extrusion taps and reduce their wear, this paper adopted the coating-simulation technology to investigate the influence laws of tool coating type and coating thickness on extrusion torque, extrusion temperature and wear amount. The validity of the numerical simulation results is confirmed through internal thread extrusion experiments. The results showed that the extrusion torque and extrusion temperature of single-layer coating and composite coating showed a tendency of decreasing and then increasing with the increase of the coating thickness; the extrusion torque and extrusion temperature of the double-layer coating increased with the increase of the coating thickness; the wear amount of the three types of coatings increased with the increase of the coating thickness. The TiAlN single coating demonstrates the most pronounced impact on decreasing extrusion torque and temperature (3.82 N·m and 88.4 °C), resulting in a smooth extrusion process. The TiAlN–TiAlN double coating exhibits the lowest wear amount of 0.076 mm. The utilization of numerical simulation proves to be a dependable approach for evaluating the efficacy of tool coatings, and reasonable selection of coating type and thickness can effectively reduce the extrusion torque, extrusion temperature and wear amount.

Abstract The treatment of multidrug-resistant tracheobronchial tuberculosis poses challenges, and research investigating the efficacy of bedaquiline or delamanid as treatment for this condition is limited. This retrospective cohort study was conducted from 2017 to 2021. The study extracted data of patients with multidrug-resistant tracheobronchial tuberculosis from medical records and followed up on prognoses. Participants were divided into three groups: the bedaquiline, delamanid, and control group. Clinical outcomes and the risk factors associated with early culture conversion were analyzed. This study included 101 patients, with 32, 25, and 44 patients in the bedaquiline, delamanid, and control groups respectively. The differences in the treatment success rates among the three groups did not show statistical significance. Both the bedaquiline and delamanid groups had significantly higher culture conversion rates compared to the control after 2 or 6 months of treatment, with significantly shorter median times to culture conversion (bedaquiline group: 2 weeks, delamanid group: 2 weeks, control group: 12 weeks, P

Abstract Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (P FDR = 0.001, odds ratio = 1.363, 95% confidence interval 1.178–1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development.

Abstract The cognitive problems are prominent in the context of global aging, and the traditional Mendelian randomization method is not applicable to ordered multi-categorical exposures. Therefore, we aimed to address this issue through the development of a method and to investigate the causal inference of cognitive-related lifestyle factors. The study sample was derived from the Chinese Longitudinal Healthy Longevity Survey, which included 897 older adults aged 65 + . This study used genome-wide association analysis to screen genetic loci as instrumental variables and innovatively combined maximum likelihood estimation to infer causal associations between ordered multi-categorical exposures (diet, exercise, etc.) and continuous outcomes (cognitive level). The causal inference method for ordered multi-categorical exposures developed in this study was simple, easy to implement, and able to effectively and reliably discover the potential causal associations between variables. Through this method, we found a potential positive causal association between exercise status and cognitive level in Chinese older adults ( $$\widehat{\beta }$$ β ^ = 1.883, 95%CI 0.182–3.512), in which there was no horizontal pleiotropy (p = 0.370). The study provided a causal inference method applicable to ordered multi-categorical exposures, that addressed the limitations of the traditional Mendelian randomization method.

Abstract Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.

Abstract Enhancing information security has become increasingly significant in the digital age. This paper investigates the concept of physical layer security (PLS) within a relay-aided power line communication (PLC) system operating over a multiple-input multiple-output (MIMO) channel based on MK model. Specifically, we examine the transmission of confidential signals between a source and a distant destination while accounting for the presence of multiple eavesdroppers, both colluding and non-colluding. We propose a two-phase jamming scheme that leverages a full-duplex (FD) amplify-and-forward (AF) relay to address this challenge. Our primary objective is to maximize the secrecy rate, which necessitates the optimization of the jamming precoding and transmitting precoding matrices at both the source and the relay while adhering to transmit power constraints. We present a formulation of this problem and demonstrate that it can be efficiently solved using an effective block coordinate descent (BCD) algorithm. Simulation results are conducted to validate the convergence and performance of the proposed algorithm. These findings confirm the effectiveness of our approach. Furthermore, the numerical analysis reveals that our proposed algorithm surpasses traditional schemes that lack jamming to achieve higher secrecy rates. As a result, the proposed algorithm offers the benefit of guaranteeing secure communications in a realistic channel model, even in scenarios involving colluding eavesdroppers.

Abstract Scanning electron microscopy (SEM) is a crucial tool for analyzing submicron-scale structures. However, the attainment of high-quality SEM images is contingent upon the high conductivity of the material due to constraints imposed by its imaging principles. For weakly conductive materials or structures induced by intrinsic properties or organic doping, the SEM imaging quality is significantly compromised, thereby impeding the accuracy of subsequent structure-related analyses. Moreover, the unavailability of paired high–low quality images in this context renders the supervised-based image processing methods ineffective in addressing this challenge. Here, an unsupervised method based on Cycle-consistent Generative Adversarial Network (CycleGAN) was proposed to enhance the quality of SEM images for weakly conductive samples. The unsupervised model can perform end-to-end learning using unpaired blurred and clear SEM images from weakly and well-conductive samples, respectively. To address the requirements of material structure analysis, an edge loss function was further introduced to recover finer details in the network-generated images. Various quantitative evaluations substantiate the efficacy of the proposed method in SEM image quality improvement with better performance than the traditional methods. Our framework broadens the application of artificial intelligence in materials analysis, holding significant implications in fields such as materials science and image restoration.

Abstract Previous studies have found that migraine patients are associated with white matter lesions (WMLs), but the causal relationship between the two remains unclear. We intend to explore the bidirectional causal relationship between migraine and WMLs using a two-sample mendelian randomization (MR) method. We employed summary-level data from a recent large-scale genome-wide association study (GWAS) that characterized three white matter (WM) phenotypes: white matter hyperintensities (WMH, N = 18,381), fractional anisotropy (FA, N = 17,673), and mean diffusivity (MD, N = 17,467), as well as migraine (N = 589,356). The inverse variance-weighted (IVW) method was used as the main approach for analyzing causality. Weighted median analysis, simple median analysis, and MR-Egger regression served as complementary methods. The bidirectional MR study affords no support for causality between WMLs and migraine. In all MR methods, there was no obvious causal evidence between them. In our bidirectional MR study, we didn't reach this conclusion that WMLs can cause migraine, migraine wouldn’t increase the risk of WMLs, either.

Abstract To explore the superiority of breast conservation surgery (BCS) to mastectomy in treating early-stage adenoid cystic carcinoma of the breast (BACC). Patients with surgically treated stage I/II BACC were enrolled between 2000 and 2019 in the SEER database; they were divided into the BCS and mastectomy groups. Overall survival (OS) and disease-specific survival (DSS) were compared between the two groups, and Cox hazard regression models were used to determine the independent predictors. Of the 583 patients in the study, 386 were included in the BCS group. The 10-year OS rates for the BCS and mastectomy groups were 78% (95% CI: 74–82%) and 76% (95% CI: 70–82%), respectively, but the difference was not statistically significant (p = 0.968). The 10-year DSS rates for the BCS and mastectomy groups were 95% (95% CI: 93–97%) and 89% (95% CI: 85–93%), respectively, and the difference was statistically significant (p = 0.002). Pathological examination of regional lymph nodes and adjuvant treatment were not associated with improved OS or DSS, but age, disease grade, and lymph node metastasis were independent prognostic factors. For stage I/II BACC, BCS can achieve more satisfactory 10-year OS and DSS than mastectomy.

Abstract Gastric cancer (GC) is one of the major causes of cancer deaths with 5-year survival ratio of 20%. RNU12 is one of long noncoding RNAs (lncRNAs) regulating the tumor progression. However, how RNU12 affecting GC is not clear. qRT-PCR was utilized for determining the RNU12 expression in cell lines, 113 cases of paired gastric cancer (GC) and their adjacent normal gastric tissues. The biofunction alterations of RNU12 were assessed by its overexpression or knockdown in GC cells. MTT and cloning assay were assayed for the cell proliferation, the flow cytometry for the detection of cell cycle and the wound healing assay (WHA) and transwell invasion assay (TIA) for examining the migration and invasion of cells. The expressions of a set of genes related proliferation and migration were investigated with the Western Blotting (WB). RNA immunoprecipitation (RIP), biotinylated RNA pull-down and dual luciferase reporter tests were used to detect the interactions of RNU12 with miR-575/BLID. The in vivo proliferation and migration ability of RNU12 infected cells were determined in zebrafish system. This study revealed that RNU12 inhibited proliferation, invasion and metastasis by sponging of miR-575 and regulating the downstream BLID and modulated EMT of GC cells. The RNU12/miR-575/BLID axis is likely to be the prognosis biomarkers and drug targets of GC.

Abstract To compare the stability and biomechanical characteristics of four commonly used triangular osteosynthesis techniques to treat unilateral vertical sacral fractures and provide a clinical application reference. Finite element models of Tile C-type pelvic ring injury (unilateral Denis II sacral fracture) were produced. In four models, sacral fractures were fixed with a combination of unilateral L5, unilateral L4, and L5 iliac lumbar fixation with lengthened or normal sacroiliac screws. The biomechanical properties of the four fixation models were measured and compared under bipedal stance and lumbar rotation. The fixation stability of the model with the lengthened sacroiliac screw was excellent, and the fracture end was stable. The stability of fixation using unilateral L4 and L5 segments was close to that of unilateral L5 segment fixation. Triangular osteosynthesis transverse stabilization devices using lengthened sacroiliac screws can increase the vertical stability of the sacrum after internal fixation and increase the stability of the fracture. When triangular osteosynthesis lumbar fixation segments were selected, simultaneous fixation of L4 and L5 segments versus only L5 segments did not significantly enhance the vertical stability of the sacrum or the stability of the fracture end.

Abstract Previous studies have shown certain exposure factors (such as lifestyle and metabolism) are associated with colorectal cancer (CRC) events. However, the application of the exposome theoretical frame and the extent to which the exposome domain can modulate the risk of CRC remain unknown. Our study aimed to construct valid exposome measurements and examine the relationship between exposome counts and the risk of CRC. This study included 335,370 individuals in the UK Biobank. We used exploratory factor analysis to identify a valid construct of exposome factors. We then summed the exposome counts within each domain. Cox proportional hazard models were used to estimate the hazard ratios and 95% confidence intervals of CRC risk related to the exposome factors and counts. During an 8.69 year median follow-up, 10,702 CRC cases were identified. Five domains were extracted from 12 variables, including ecosystem, lifestyle, tobacco and alcohol use, social economics, and social support. The Cox model results showed that the ecosystem was positively related to the reduced CRC risk (HR = 0.970; 95% CI 0.952–0.989). Similar results were also found among the domains of healthy lifestyles (HR = 0. 889; 95% CI 0.871–0.907), and no tobacco and alcohol use (HR = 0.892; 95% CI 0.876–0.909). The disadvantageous social economic (HR = 1.081; 95% CI 1.058–1.105) and insufficient social support domains (HR = 1.036; 95% CI 1.017–1.056) were associated with an increased risk of CRC. Similar risk trends were also observed across the exposome count groups with CRC incidence. Our findings suggest that certain exposure domains are related to the incidence of CRC. Ecosystem, lifestyle, and social factors can be incorporated into prediction models to identify individuals at high risk of CRC.

Abstract Steroid induced osteonecrosis of the femoral head (ONFH) frequently leads to femoral head collapse and subsequent hip arthritis. This study aimed to investigate the potential therapeutic mechanism of miR‐27a on steroid-induced ONFH. Levels of IL-6, TNF-α, miR-27a, Runx2, PPAR-γ and ApoA5 were first examined in bone marrow tissues from steroid-induced ONFH and controls. Subsequently, we overexpressed or knocked down miR-27a in bone marrow mesenchymal stem cells (BMSCs) and detected cell proliferation, osteogenic differentiation, adipogenic differentiation. In addition, miR-27a mimics and BMSCs were injected into the established steroid-induced ONFH rats, and the osteoprotective effects of both were evaluated. Dual luciferase reporter was used to test the targeting effect of miR-27a-3p and PPARG. miR-27a and Runx2 were lowly expressed in steroid-induced ONFH, PPAR-γ and ApoA5 were highly expressed. Overexpression of miR-27a in BMSCs promoted cell proliferation and osteogenic differentiation, inhibited adipogenic differentiation. Furthermore, increasing miR-27a and BMSCs obviously reduced bone loss in steroid induced ONFH rats. The expressions of Runx2 in BMSCs and steroid-induced ONFH rats was significantly up‐regulated, while IL-6, TNF-α, PPAR-γ and ApoA5 were down‐regulated with miR-27a overexpression. Additionally, PPARG was the target of miR-27a-3p. The results of the present study reveal a role for miR-27a in promoting osteogenesis and may have a synergistic effect with BMSCs.

Abstract Researchers have identified an association between lifestyle factors and colorectal cancer (CRC) risk. This study examined the relationship between sleep patterns and CRC events. 392,252 individuals were sampled from the UK Biobank. Chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness were combined to measure a healthy sleep score. A number of healthy sleep factors were defined, along with factors for healthy lifestyle scores. Using Cox proportional hazards regression, computed hazard ratios (HRs) were used to examine the associations between sleep patterns, healthy lifestyles, and the incidence of CRC. Healthy sleep scores were inversely associated with CRC events. The HRs for CRC were 0.90 (95% CI, 0.88–0.92) and 0.95 (95% CI, 0.92–0.98) for a 1-point healthy sleep score increase among males and females. When analyzing sleep components, sleeping 7–8 h/day, no frequent insomnia, no snoring, and no frequent daytime sleepiness were independently associated with a 9%, 14%, 8%, and 14% lower risk of CRC, respectively, whilst healthy lifestyle scores were inversely associated with CRC incidence across all models. Sleep pattern and lifestyle are significantly correlated with CRC risk. The healthier the subject’s lifestyle and sleep pattern, the lower their CRC risk.

Abstract To explore and compare the clinical control of three atomized inhalation budesonide (BUD) regimens for Chinese preschool children with recurrent wheezing using Test for Respiratory and Asthma Control (TRACK) scores. A total of 474 preschool children with positive Modified Asthma Predictive Index (mAPI) were randomly assigned to a daily group (initially given inhaled BUD 1 mg once a day and assessed every 4 weeks; if symptom were well controlled for 12 weeks, the dose was reduced to 25–50% of the previous dose until afinal dose of 0.25 mg once a day, maintained until 52 weeks), an intermittent high-dose group (1 mg twice daily for 7 days starting early during a predefined respiratory tract illness) and an intermittent medium-dose group (0.5 mg twice daily as soon as they contacted allergens or experienced nasal congestion, a runny nose, cough or other suspicious respiratory symptoms and continuing until symptoms were reduced or risk factors were absent for 3 days) for 52 weeks of treatment. The TRACK questionnaire was administered every 4 weeks. When TRACK scores were ≥ 80, symptoms were considered to be controlled. The average TRACK scores of the three groups after treatment were significantly higher than those before treatment (P 0.05). Te number of systemic glucocorticoid courses, urgent care visits for wheezing, and wheezing episodes before and after treatment were significantly different within each of the three groups (P 0.05). In clinical treatment of children, one of the three treatment options can be selected according to the specific situation case of mAPI- positive recurrent wheezing children.

Abstract Network function virtualization (NFV) decouples network functions from hardware devices. However, it introduces security challenges due to its reliance on software, which facilitates attacks. This security problem has a significant negative impact on the interests of users. Existing deployment methods are not suitable for SFC requests with a security demand, causing the use of substrate resources unreasonable and lower acceptance ratio. Moreover, a strict delay requirement is another challenge for NFV. To make the use of the substrate resources more reasonable and reduce the transmission delay, this paper proposes a security-constraint and function-mutex-constraint consolidation (SFMC) method for virtual network function (VNF) to reduce resource consumption and transmission delay. In addition, a security-aware service function chain (SASFC) deployment method for load balance and delay optimization is presented, which deploys service function chains according to the consolidated results of the SFMC method. The SASFC method first obtains a candidate server node set using resource, hosting capacity, security and node load constraints. It then obtains candidate paths according to the metric of the minimum transmission delay and link load constraint using the Viterbi algorithm. Finally, the path with the highest VNF security level match degree among the candidate paths is adopted to deploy virtual links, and the corresponding server nodes are employed to deploy VNFs. As a result, the SASFC method makes the use of substrate resources more reasonable. It improves the acceptance ratio and long-term average revenue to cost ratio, reduces transmission delay, and achieves load balancing. Experiment results show that when the number of VNFs is five, the acceptance ratio and long-term average revenue to cost ratio of the SASFC method are close to 0.75 and 0.88, which are higher than those of the compared methods. Its transmission delay and proportion of bottleneck nodes are 7.71 and 0.024, which are lower than those of the compared methods. The simulations demonstrate the effectiveness of the SASFC method.