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Abstract Exploiting high‐performance yet low‐cost hard carbon anodes is crucial to advancing the state‐of‐the‐art sodium‐ion batteries. However, the achievement of superior initial Coulombic efficiency (ICE) and high Na‐storage capacity via low‐temperature carbonization remains challenging due to the presence of tremendous defects with few closed pores. Here, a facile hybrid carbon framework design is proposed from the polystyrene precursor bearing distinct molecular bridges at a low pyrolysis temperature of 800°C via in situ fusion and embedding strategy. This is realized by integrating triazine‐ and carbonyl‐crosslinked polystyrene nanospheres during carbonization. The triazine crosslinking allows in situ fusion of spheres into layered carbon with low defects and abundant closed pores, which serves as a matrix for embedding the well‐retained carbon spheres with nanopores/defects derived from carbonyl crosslinking. Therefore, the hybrid hard carbon with intimate interface showcases synergistic Na ions storage behavior, showing an ICE of 70.2%, a high capacity of 279.3 mAh g−1, and long‐term 500 cycles, superior to carbons from the respective precursor and other reported carbons fabricated under the low carbonization temperature. The present protocol opens new avenues toward low‐cost hard carbon anode materials for high‐performance sodium‐ion batteries.

Researchers often need to synthesize genes of interest in this era of synthetic biology. Gene synthesis by PCR assembly of multiple DNA fragments is a quick and economical method that is widely applied. Up to now, there have been a few software solutions for designing fragments in gene synthesis. However, some of these software solutions use programming languages that are not popular now, other software products are commercial or require users to visit servers. In this study, we propose a Python program to design DNA fragments for gene synthesis. The algorithm is designed to meet the experimental needs. Also, the source code with detailed annotation is freely available for all users. Furthermore, the feasibility of the algorithm and the program is validated by experiments. Our program can be useful for the design of gene synthesis in the labs and help the study of gene structure and function.

There remains ongoing debate regarding the association of homologous recombination deficiency (HRD) with patient survival across various malignancies, highlighting the need for a comprehensive understanding of HRD's role in different cancer types. Based on data from databases, we conducted a multivariable omics analysis on HRD in 33 cancer types, focusing mainly on 23 cancers in which HRD was significantly associated with patient overall survival (OS) rates. This analysis included the mechanisms related to patient prognosis, gene expression, gene mutation, and signaling pathways. In this study, HRD was found to be significantly associated with patient prognosis, but its impact varied among different cancers. HRD was linked to different outcomes for patients with distinct tumor subtypes and was correlated with clinical features such as clinical stage and tumor grade. Driver gene mutations, including TP53, MUC4, KRAS, HRAS, FLG, ANK3, BRCA2, ATRX, FGFR3, NFE2L2, MAP3K1, PIK3CA, CIC, FUBP1, ALB, CTNNB1, and MED12, were associated with HRD across specific cancer types. We also analyzed differentially expressed genes (DEGs) and differentially methylated regions (DMRs) in relation to HRD levels in these cancers. Furthermore, we explored the correlation between HRD and signaling pathways, as well as immune cell infiltration. Overall, our findings contribute to a comprehensive understanding of HRD's multifaceted role in cancer.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder characterized by hepatic steatosis, inflammation and fibrosis. Ganfule (GFL), a traditional Chinese medicine, has demonstrated therapeutic potential in the treatment of NAFLD but the mechanisms involved are not fully understood.To evaluate the biochemical mechanisms of GFL in treating NAFLD by examining its effects on biological networks, key therapeutic targets, histopathological changes and clinical implications. Methods: Chemical component screening, key target prediction, biological functional enrichment analysis, lipid profile localization analysis and complex network analysis were performed on GFL using multi-database mining, network analysis and molecular docking. An NAFLD rat model was then established and treated with different doses of GFL. Histopathological evaluation and western blotting were used to verify the expression levels of key target proteins in GFL-treated NAFLD rats. Results: Network analysis analysis identified 12 core targets, 12 core active ingredients and 7 core Chinese medicinal herbs in GFL potentially involved in the treatment of NAFLD. Biological functional enrichment analysis revealed the involvement of lipid metabolism, apoptosis and intracellular signaling pathways. Molecular docking confirmed a strong affinity between GFL's core compounds and certain target proteins. Histopathological examination of an NAFLD rat model showed reduced hepatocellular steatosis after GFL treatment. Western blotting revealed significant downregulation of PPARA and PPARD protein expression and upregulation of PIK3CG and PRKACA protein expression in NAFLD rats treated with lower doses of GFL. Conclusions: Our results suggest that GFL modulates key proteins involved in lipid metabolism and apoptosis pathways. GFL improved the histopathological features of NAFLD rats by regulating lipid metabolism as well as reducing hepatocyte apoptosis and hepatocellular steatosis. These findings offer insights into the biochemical mechanism of action of GFL and support its use in the treatment for NAFLD.

Summary: Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

Microbubble-mediated therapeutic gene or drug delivery is a promising strategy for various cardiovascular diseases (CVDs), but the efficiency and precision need to be improved. Here, we propose a cavitation bubble-driven drug delivery strategy that can be applied to CVDs. A bubble-pulse-driving theory was proposed, and the formula of time-averaged thrust driven by bubble pulses was derived. The continuous motion of particles propelled by cavitation bubbles in the ultrasonic field is investigated experimentally by high-speed photography. The cavitation bubbles grow and collapse continuously, and generate periodic pulse thrust to drive the particles to move in the liquid. Particles attached to bubbles will move in various ways, such as ejection, collision, translation, rotation, attitude variation, and circular motion. The cavity attached to the particle is a relatively large cavitation bubble, which does not collapse to the particle surface, but to the axis of the bubble perpendicular to the particle surface. The cavitation bubble expands spherically and collapses asymmetrically, which makes the push on the particle generated by the bubble expansion greater than the pull on the particle generated by the bubble collapse. The time-averaged force of the cavitation bubble during its growth and collapse is the cavitation-bubble-driven force that propels the particle. Both the cavitation-bubble-driven force and the primary Bjerknes force act in the same position on the particle surface, but in different directions. In addition to the above two forces, particles are also affected by the mass force acting on the center of mass and the motion resistance acting on the surface, so the complex motion of particles can be explained.

This paper investigates the synchronization of a complex network based on a class of random impulsive differential equation systems. Based on the random impulsive strategy of Poisson distribution, a random impulsive dynamical network model is constructed. Using the Lyapunov principle, random process theory, linear matrix inequality method, and some basic analysis methods, we realize the global mean-square index synchronization of the model. We then get sufficient criteria for the synchronization. By presenting a numerical example, we verified the validity of the theoretical results.

BackgroundPrevious studies on the liner associations between serum 25-hydroxyvitamin D [25(OH)D] levels and lipid profiles revealed ambiguous findings. The current study therefore tried to elucidate the possible non-linear associations between 25(OH)D and lipid profiles.MethodsThis study involved 8,516 adult participants (aged 18–74 years, males N = 3,750, females N = 4,766) recruited from the Dalian health management cohort (DHMC). The risk (OR) for specific dyslipidemias was estimated across the serum 25(OH)D levels and the cut-off value for serum 25(OH)D were determined by using logistic regression, restricted cubic spline, and piecewise linear regression methods, adjusted for age, sex, season, and ultraviolet index.ResultsIn this study, a high prevalence of 25(OH)D deficiency was observed in the participants (65.05%). The level of 25(OH)D showed the inverse U-shaped correlations with the risks (ORs) of abnormal lipid profile, with inflection points observed at 23.7 ng/ml for hypercholesterolemia, 24.3 ng/ml for hypertriglyceridemia, 18.5 ng/ml for hyper-low-density lipoprotein cholesterolemia, 23.3 ng/ml for hypo-high-density lipoprotein cholesterolemia, 23.3 ng/ml for hyper-non-high-density lipoprotein cholesterol, and 24.3 ng/ml for high remnant cholesterol. The stratified analyses showed that the risk for most dyslipidemias related to deficiency of 25(OH)D was particularly increased among females aged 50–74 (except for hypertriglyceridemia, where the highest risk was among men aged 50–74 years), during winter/spring or under low/middle ultraviolet index environments.ConclusionsNonlinear inverse U-shaped associations were observed between 25(OH)D levels and abnormal lipid profile. The risk was particularly increased among females aged 50-74, during winter/spring period or under lower ultraviolet index environments. In vitamin D deficient subjects [25(OH)D

Exposure to ambient PM2.5 is associated with neurodegenerative disorders, in which microglia activation plays a critical role. Thus far, the underlying mechanisms for PM2.5-induced microglia activation have not been well elucidated. In this study, a human microglial cell line (HMC3) was used as the in vitro model to examine the inflammatory effect (hall marker of microglia activation) of PM2.5 and regulatory pathways. The expression of inflammatory mediators including interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) as well as the brain derived neurotrophic factor (BDNF) were determined by ELISA and/or real-time PCR, respectively. Flow cytometry was used to measure the production of intracellular reactive oxygen species (ROS). Western blot was used to measure protein levels of Toll-like receptor 4 (TLR4), NF-κB inhibitor α (IκBα) and COX-2. It was shown that PM2.5 stimulation increased IL-6 and COX-2 expression but decreased BDNF expression in a dose-dependent manner. Further studies showed that PM2.5 triggered the formation of ROS and pre-treatment with the ROS scavenger acetylcysteine (NAC) significantly suppressed PM2.5-induced IL-6 and COX-2 expression. Moreover, the nuclear factor kappa B (NF-κB) inhibitor BAY11–7085 or the TLR4 neutralizing antibody markedly blocked PM2.5-induced IL-6 and COX-2 expression. However, NAC or BAY11–7085 exhibited minimal effect on PM2.5-induced BDNF down-regulation. In addition, pre-treatment with BAY11–7085 or TLR4 neutralizing antibody reduced ROS production induced by PM2.5, and NAC pre-treatment inhibited TLR4 expression and NF-κB activation induced by PM2.5. Collectively, PM2.5 treatment induced IL-6 and COX-2 but suppressed BDNF expression. PM2.5-induced IL-6 and COX-2 expression was mediated by interactive oxidative stress and TLR4/NF-κB pathway.

ABSTRACT: Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

Fusarium crown rot (FCR) is an important and devastating disease of wheat (Triticum aestivum) caused by the fungus Fusarium pseudograminearum and related pathogens. Using two distinct susceptible cultivars, we investigated the isolation frequencies of F. pseudograminearum and quantified its biomass accumulation and the levels of the associated toxins deoxynivalenol (DON) and DON-3-glucoside (D3G) in inoculated field-grown wheat plants. We detected F. pseudograminearum in stem, peduncle, rachis, and husk tissues, but not in grains, whereas DON and D3G accumulated in stem, rachis, husk, and grain tissues. Disease severity was positively correlated with the frequency of pathogen isolation, F. pseudograminearum biomass, and mycotoxin levels. The amount of F. pseudograminearum biomass and mycotoxin contents in asymptomatic tissue of diseased plants were associated with the distance of the tissue from the diseased internode and the disease severity of the plant. Thus, apparently healthy tissue may harbor F. pseudograminearum and contain associated mycotoxins. This research helps clarify the relationship between F. pseudograminearum occurrence, F. pseudograminearum biomass, and mycotoxin accumulation in tissues of susceptible wheat cultivars with or without disease symptoms, providing information that can lead to more effective control measures.

BackgroundIdentification is the first step for treatment of hypertension. However, the awareness rate of hypertension was not high globally. This study aimed to examine the potential role of health insurance for early-identifying hypertension among urban older residents in China.MethodsIn this cross-sectional study, urban residents aged 60+ years were chosen from Nanjing municipality of China in 2018. The outcome measure was hypertension status (“no hypertension,” “diagnosed hypertension” or “un-diagnosed hypertension”). Independent variable was health insurance (“Urban Employee Basic Medical Insurance scheme, UEBMI” or “Urban Resident Basic Medical Insurance scheme, URBMI”). Logistic regression models were introduced to estimate odds ratio (OR) and 95% confidence interval (CI) to examine the association between health insurance and hypertension.ResultsTotally, 19,742 participants completed the study. Among overall, URBMI and UEBMI participants, 47.2% (95%CI = 46.5, 47.9%), 38.4% (95%CI = 37.3, 39.6%) and 52.1% (95%CI = 51.2, 53.0%), separately, were diagnosed with hypertension, while the prevalence of un-diagnosed hypertension was 12.7% (95%CI = 12.2, 13.2%), 18.5% (95%CI = 17.6, 19.4%) and 9.6% (95%CI = 9.1, 10.1%), respectively. For overall participants, those with UEBMI were more likely to have hypertension identified (OR = 1.20; 95%CI = 1.11, 1.29) and at lower odds to experience un-diagnosed hypertension (OR = 0.68; 95%CI = 0.61, 0.76) compared to their counterparts with URBMI after control for potential confounders. Moreover, such associations of health insurance with diagnosed and un-diagnosed hypertension were also observed among participants stratified by age and gender.ConclusionFavorable health insurance may be a pathway for identifying hypertension among urban older residents in China. This study has important public health implications that hypertension may be identified early through favorable health insurance policies for older residents in China.

Abstract The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.

Abstract Background Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. Methods In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. Results In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was − 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and − 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of − 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were − 1.47 (p = 0.18) in 24-h diastolic BP, − 2.86 (p = 0.13) and − 2.74 (p = 0.03) in daytime systolic and diastolic BP, and − 0.45 (p = 0.82) and − 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). Conclusions The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. Trial registration ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Abstract Degenerative cervical myelopathy (DCM) is one of the most common and serious neurological diseases. Cilostazol has protective effects of anterior horn motor neurons and prevented the cell apoptosis. However, there was no literatures of Cilostazol on DCM. In this study, we established the DCM rat model to detect the effects of Cilostazol. Meanwhile, the neurobehavioral assessments, histopathology changes, inflammatory cytokines, Thioredoxin-interacting protein (TXNIP), NOD‑like receptor pyrin domain containing 3 (NLRP3) and pro-caspase-1 expressions were detected by Basso, Beattie, and Bresnahan score assessment, Hematoxylin and Eosin Staining, Enzyme-linked immunosorbent assay, immunofluorescence and Western blotting, respectively. After treated with Cilostazol, the Basso, Beattie, and Bresnahan (BBB) score, inclined plane test and forelimb grip strength in DCM rats were significantly increased meanwhile the histopathology injury and inflammatory cytokines were decreased. Additionally, TXNIP, NLRP3 and pro-caspase-1 expressions levels were decreased in Cilostazol treated DCM rats. Interestingly, the using of siTXNIP significantly changed inflammatory cytokines, TXNIP, NLRP3 and pro-caspase-1 expressions, however there was no significance between siTXNIP and Cilostazol + siTXNIP group. These observations showed that Cilostazol rescues DCM injury and ameliorates neuronal destruction mediated by TXNIP/NLRP3/caspase-1 and pro-inflammatory cytokines. As a result of our study, these findings provide further evidence that Cilostazol may represent promising therapeutic candidates for DCM.

Abstract CircRNAs play an important role in various physiological and pathological biological processes. Despite their widespread involvement, the function of circRNAs in intermittent hypoxia (IH) remain incompletely understood. This study aims to clarify the molecular mechanism of it in IH. Differentially expressed circRNAs were identified by transcriptome sequencing analysis in intermittent hypoxia (IH) model. GO and KEGG enrichment analys were performed on the identified differentially expressed circRNAs. The circular characteristics of hsa_circ_0081065 in human umbilical vein endothelial cells (HUVECs) were detected by RT-qPCR. The sublocalization of hsa_circ_0081065 was examined by FISH. The effect of hsa_circ_0081065 on endothelial to mesenchymal transition (EndMT) was estimated by detecting the expression of EndMT related markers. Various techniques, including RNA-pull down, RIP, EMSA, dual-luciferase reporter assay and immunofluorescence staining were used to investigate the relationship among hsa_circ_0081065, miR-665 and HIF-1α. A total of 13,304 circRNAs were identified in HUVECs treatment with IH, among which 73 were differentially expressed, including 24 upregulated circRNAs and 49 downregulated circRNAs. Notably, hsa_circ_0081065 demonstrated a significantly upregulation. Hsa_circ_0081065 exhibited the circular characteristics of circRNA and was predominantly localized in the cytoplasm. Knockdown of hsa_circ_0081065 inhibited EndMT. Mechanically, we demonstrated that hsa_circ_0081065 acts as a sponge for miR-665 to up-regulate HIF-1α and exacerbate HIF-1α nuclear translocation in HUVECs. We have demonstrated that hsa_circ_0081065 is significantly upregulated in HUVECs treated with IH. Our findings indicate that hsa_circ_0081065 exacerbates IH-induced EndMT through the regulation of the miR-665/HIF-1α signal axis and facilitating HIF-1α nuclear translocation. These results provide a theoretical basis for considering of EndMT as a potential therapeutic target for OSAHS intervention.

UAVs are often limited by limited resources when performing flight tasks, especially the contradiction between storage resources and computing resources when the huge YOLOv3 model is deployed on the edge UAVs. In this paper, we tend to compress YOLOv3 model in different aspects to achieve load availability at the edge. In this paper, deep separable convolution is introduced to reduce the computation of the model. Then, PR regularization term is used as the regularization term of sparse training to better distinguish scaling factors, and then the hybrid pruning combining channel pruning and layer pruning is carried out on the model according to scaling factors, in order to reduce the number of model parameters and the amount of calculation. Finally, since the training data is a 32-bit floating point number, DoReFa-Net quantization method is used to quantify the model, so as to compress the storage capacity of the model. The experimental results show that the compression scheme proposed in this paper can effectively reduce the number of parameters by 97.5 % and the calculation amount by 82.3 %, and can maintain the original detection efficiency of UAVs.

Abstract U-10 wt.% Zr (U-10Zr) metallic fuel is the leading candidate for next-generation sodium-cooled fast reactors. Porosity is one of the most important factors that impacts the performance of U-10Zr metallic fuel. The pores generated by the fission gas accumulation can lead to changes in thermal conductivity, fuel swelling, Fuel-Cladding Chemical Interaction (FCCI) and Fuel-Cladding Mechanical Interaction (FCMI). Therefore, it is crucial to accurately segment and analyze porosity to understand the U-10Zr fuel system to design future fast reactors. To address the above issues, we introduce a workflow to process and analyze multi-source Scanning Electron Microscope (SEM) image data. Moreover, an encoder-decoder-based, deep fully convolutional network is proposed to segment pores accurately by integrating the residual unit and the densely-connected units. Two SEM 250 × field of view image datasets with different formats are utilized to evaluate the new proposed model’s performance. Sufficient comparison results demonstrate that our method quantitatively outperforms two popular deep fully convolutional networks. Furthermore, we conducted experiments on the third SEM 2500 × field of view image dataset, and the transfer learning results show the potential capability to transfer the knowledge from low-magnification images to high-magnification images. Finally, we use a pre-trained network to predict the pores of SEM images in the whole cross-sectional image and obtain quantitative porosity analysis. Our findings will guide the SEM microscopy data collection efficiently, provide a mechanistic understanding of the U-10Zr fuel system and bridge the gap between advanced characterization to fuel system design.

Abstract Gaseous fission products from nuclear fission reactions tend to form fission gas bubbles of various shapes and sizes inside nuclear fuel. The behavior of fission gas bubbles dictates nuclear fuel performances, such as fission gas release, grain growth, swelling, and fuel cladding mechanical interaction. Although mechanical understanding of the overall evolution behavior of fission gas bubbles is well known, lacking the quantitative data and high-level correlation between burnup/temperature and microstructure evolution blocks the development of predictive models and reduces the possibility of accelerating the qualification for new fuel forms. Historical characterization of fission gas bubbles in irradiated nuclear fuel relied on a simple threshold method working on low-resolution optical microscopy images. Advanced characterization of fission gas bubbles using scanning electron microscopic images reveals unprecedented details and extensive morphological data, which strains the effectiveness of conventional methods. This paper proposes a hybrid framework, based on digital image processing and deep learning models, to efficiently detect and classify fission gas bubbles from scanning electron microscopic images. The developed bubble annotation tool used a multitask deep learning network that integrates U-Net and ResNet to accomplish instance-level bubble segmentation. With limited annotated data, the model achieves a recall ratio of more than 90%, a leap forward compared to the threshold method. The model has the capability to identify fission gas bubbles with and without lanthanides to better understand the movement of lanthanide fission products and fuel cladding chemical interaction. Lastly, the deep learning model is versatile and applicable to the micro-structure segmentation of similar materials.

Abstract Background Migraine is a primary headache, which has been producing heavy disease burden globally. There is no data on the incidence of migraine among women of childbearing age worldwide, including China. This study aimed to investigate the time trend in incidence rate of migraine among women of childbearing age in China from 1999 to 2019, and to make a prediction for 2030. Methods Data on migraine incidence and population among women of childbearing age in China were derived from the Global Burden of Diseases Study 2019. Crude and age-standardized incidence rates of migraine (CIR, ASIR) were presented. The trend in migraine during 1990–2019 was examined using annual percent change and average annual percent change based on Joinpoint regression models. Age-period-cohort model was introduced to estimate the independent effect of age, period and cohort on migraine incidence rate among participants over the three decades. Bayesian age-period-cohort analysis was conducted to predict migraine incidence rate for 2030 among women of childbearing age in China. Results For women of childbearing age in China, the case number, CIR and ASIR of migraine kept rising, with a cumulative percentage increase of 10.87%, 2.01% and 5.65%, respectively, from 1990 to 2019. An annual percent increase of 0.18% in the ASIR was observed over the three decades. As for the age, period and cohort effects, the adjusted cohort-specific relative risks constantly increased from 0.91 (95% CI: 0.90, 0.93) in the 1940–1949 cohort to 1.04 (95% CI: 1.03, 1.05) in the 1995–2004 cohort, while the period-specific relative risks initially declined from 1.00 (95% CI: 0.99, 1.00) in 1990–1994 cohort to 0.99 (95% CI: 0.98, 0.99) in 1995–1999 cohort, and then increased to 1.04 (95% CI: 1.03, 1.04) in 2015–2019 cohort. Moreover, the age-specific relative risks of migraine followed a bimodal pattern with peaks at the age-group of 25–29 years (CIR = 1718.27/100000) and 35–39 years (CIR = 1635.18/100000). Projection modeling showed that the CIR and ASIR of migraine will continue to significantly increase from 2020 to 2030. Conclusion Migraine incidence remained an increasing trend from 1990 to 2019 and is projected to continually increase till 2030 among women of childbearing age in China. This study has important public health implication for population-level migraine prevention in China. Precision intervention strategies and approaches shall be considered in campaigns initiated for migraine prevention among Chinese women of childbearing age.

Systemic blood circulation is one of life activity’s most important physiological functions. Continuous noninvasive hemodynamic monitoring is essential for the management of cardiovascular status. However, it is difficult to achieve systemic hemodynamic monitoring with the daily use of current devices due to the lack of multichannel and time-synchronized operation capability over the whole body. Here, we utilize a soft microfiber Bragg grating group to monitor spatiotemporal hemodynamics by taking advantage of the high sensitivity, electromagnetic immunity, and great temporal synchronization between multiple remote sensor nodes. A continuous systemic hemodynamic measurement technique is developed using all-mechanical physiological signals, such as ballistocardiogram signals and pulse waves, to illustrate the actual mechanical process of blood circulation. Multiple hemodynamic parameters, such as systemic pulse transit time, heart rate, blood pressure, and peripheral resistance, are monitored using skin-like microfiber Bragg grating patches conformally attached at different body locations. Relying on the soft microfiber Bragg grating group, the spatiotemporal hemodynamic monitoring technique opens up new possibilities in clinical medical diagnosis and daily health management.

Background: For diabetic patients undergoing coronary artery bypass grafting (CABG), there is still a debate about whether an off-pump or on-pump approach is advantageous. Methods: A retrospective review of 1269 consecutive diabetic patients undergoing isolated, primary CABG surgery from January 1, 2013 to December 31, 2015 was conducted. Among them, 614 received non-cardiopulmonary bypass treatment during their operation (off-pump group), and 655 received cardiopulmonary bypass treatment (on-pump group). The hospitalization outcomes were compared by multiple logistic regression models with patient characteristics and operative variables as independent variables. Kaplan-Meier curves and Cox proportional-hazard regression models for mid-term (2-year) and long-term (5-year) clinical survival analyses were used to determine the effect on survival after CABG surgery. In order to further verify the reliability of the results, propensity-score matching (PSM) was also performed between the two groups. Results: Five-year all-cause death rates were 4.23% off-pump vs. 5.95% on-pump (p = 0.044), and off-pump was associated with reduced postoperative stroke and atrial fibrillation. Conclusions: These findings suggest that off-pump procedures may have benefits for diabetic patients in CABG.

Pork supply prediction is a challenging task of significant importance for pig producers and administrators, as it aids decision-making and maintains the pork supply–demand balance. Previous studies failed to consider impact factors like the month-age transfer principle of pigs, epidemic factors, and the simultaneous import and export volumes of pork, leading to the absence of a quantitative prediction model for pork supply. In this background, we proposed a novel quantitative prediction model of pork supply that incorporates pork production and pork import/export volumes. First, a prediction model for pork production that takes into account the month-age transfer principle of pigs and epidemic factors was presented, along with a recursive model of the pig-herd system. A novel method based on a modified self-organizing migrating algorithm (MSOMA) was proposed for calculating the quantity of monthly newly retained sows (NRS). Furthermore, the pork-production prediction model considered the epidemic factor as a random disturbance term (RDT), and a prediction method based on MSOMA and a back-propagation neural network (MSOMA-BPNN) was introduced to predict such disturbance terms. Second, the proposed MSOMA-BPNN was employed to predict pork import and export volumes. The pork supply was subsequently determined based on the predicted pork production, as well as the pork import and export volumes. The proposed pork supply prediction model was applied to forecast China’s pork supply from 2010 to 2023. The results validate the high effectiveness and reliability of the proposed model, providing valuable insights for decision makers. The empirical results demonstrate that the proposed model is a promising and effective tool for predicting the pork supply. To our knowledge, this is a novel tool for pork supply prediction, considering the pig-herd system and pork import and export volumes from a systemic perspective. These features allow for consideration of the scientific formulation of a pig production plan, the establishment of early warning mechanisms to deal with epidemic situations and emergencies, and the regulation of pork supply and demand balance.

Background: Pelvic organ prolapse seriously affect women’s physical and mental health. To quantitatively analyze the structure of the pelvic floor during pregnancy and delivery, we utilized transperineal three-dimensional ultrasound (TP-3DUS) imaging combined with real-time shear wave elastography (RT-SWE). This analysis aims to provide exploratory data on female pelvic floor parameters, such as the hardness and thickness of the levator ani muscle (LAM), and to offer personalized recommendations for the prevention and treatment of early clinical pelvic organ prolapse (POP). Methods: From March 2021 to August 2022, a study was conducted at the Affiliated Hospital of Yunnan University involving 150 pregnant patients at various gestational ages, 110 primiparas at 42–45 days post-delivery, and 55 healthy non-childbearing women. RT-SWE was used to quantitatively evaluate changes in the elasticity of the puborectalis muscle (PRM), while TP-3DUS imaging was used to measure various parameters of the pelvic floor. This study investigated changes in pelvic floor structure during pregnancy and postpartum. It evaluated the efficacy of PRM elasticity, levator hiatus (LH) area (LHA), and the thickness of the LAM, along with their combined application in diagnosing early postpartum POP. Results: As gestational weeks progress, the elasticity of PRM increased, while the thickness of LAM decreased. In the control group, cesarean section group, and vaginal delivery group, the elasticity of the PRM and the thickness of the LAM progressively decreased. The area, perimeter, LH anteroposterior (LHAP) diameter and LH lateral diameter (LHLD) increased sequentially in these groups. The combination of LHA, PRM elasticity, and thickness of the LAM in both vaginal delivery and cesarean section groups demonstrated the highest diagnostic efficiency for POP. Conclusions: The combination of TP-3DUS Imaging and RT-SWE represents a novel, effective, and convenient method for evaluating the structure and muscle elasticity of the pelvic floor during pregnancy and the early postpartum period. LHA, PRM hardness, and thickness of the LAM individually possess a diagnostic value for early postpartum POP. However, their combination yields the highest diagnostic efficiency.

Gaussian road profile is widely used to study vehicle response and fatigue damage potential, while field measured road profile often is non-Gaussian. In this paper, a new amplitude modulation method which has full control of cutoff frequency (denoted as Wcut ) and amplitude of the amplitude modulation signal is firstly presented to synthesize non-Gaussian road profile with different kurtosis. The forced response of a quarter vehicle under non-Gaussian road profile excitation is then calculated using the ramp invariant digital filter method. The relationship between the vehicle response characteristics and the kurtosis of input non-Gaussian road profile are developed. A case study is used to verify the proposed method. The results show that a small Wcut should be selected so that the high kurtosis of the non-Gaussian road profile is correctly transferred to the vehicle response. The FDS of the vehicle response increases over the entire frequency range as the kurtosis of the input road profile increases.

As one of the most common malignant tumors in the world, lung cancer has limited benefits for patients despite its diverse treatment methods due to factors such as personalized medicine targeting histological type, immune checkpoint expression, and driver gene mutations. The high mortality rate of lung cancer is partly due to the immune-suppressive which limits the effectiveness of anti-cancer drugs and induces tumor cell resistance. The currently widely recognized TAM phenotypes include the anti-tumor M1 and pro-tumor M2 phenotypes. M2 macrophages promote the formation of an immune-suppressive microenvironment and hinder immune cell infiltration, thereby inhibiting activation of the anti-tumor immune system and aiding tumor cells in resisting treatment. Analyzing the relationship between different treatment methods and macrophages in the TME can help us better understand the impact of TAMs on lung cancer and confirm the feasibility of targeted TAM therapy. Targeting TAMs to reduce the M2/M1 ratio and reverse the immune-suppressive microenvironment can improve the clinical efficacy of conventional treatment methods and potentially open up more efficient combination treatment strategies, maximizing the benefit for lung cancer patients.

Copper plays a crucial role in the heterogenous dissociation of chlorothiophenols (CTPs) to form chlorothiophenoxy radicals (CTPRs), which is the initial and critical step in the formation of polychlorinated thianthrenes/dibenzothiophenes (PCTA/DTs). Here, first-principles calculations were performed to investigate the activity of Cu(111) surface towards the formation of adsorbed 2-CTPR from 2-CTP. The interaction between 2-CTP and Cu(111) surface was explored to find stable adsorption configurations. Besides, the decomposition routes of 2-CTP on the Cu(111) surface were further explored. Moreover, the effects of water on the formation of absorbed 2-CTPR on the Cu(111) surface were examined. Our results demonstrate that the flat adsorption of 2-CTP on the surface with adsorption energy in the range of −33.21 kcal/mol to −28.37 kcal/mol is more stable than the vertical adsorption with adsorption energy ranging from −23.53 kcal/mol to −13.38 kcal/mol. The Cu(111) surface catalyzes the conversion of 2-CTP into the adsorbed 2-CTPR with a modest energy barrier of 9.46 kcal/mol. Furthermore, water molecules exhibit stronger catalytic activity in this process with a decreased energy barrier of 5.87 kcal/mol through “water bridge” and hydrogen bonding. Specifically, the water accepts the hydrogen atom from 2-CTP and donates another hydrogen to the surface via “water bridge”. This research provides a molecular-level understanding of the heterogeneous formation of PCTA/DTs by fly ash, suggesting novel approaches for control strategy and legislation of dioxin analogues.

IntroductionAlthough there have been many researches on the etiology and risk factors with the onset of hemifacial spasm, researches on the risk factors related to progression rate are limited. This study aims to analyze the risk factors related to the progression rate of hemifacial spasm.MethodsThe study enrolled 142 patients who underwent microvascular decompression for hemifacial spasm. Based on the duration and severity of symptoms, patients were classified into rapid progression group and slow progression group. To analyze risk factors, univariate and multivariate logistic regression analyses were conducted. Of 142 patients with hemifacial spasm, 90(63.3%) were classified as rapid progression group, 52(36.7%) were classified as slow progression group.ResultsIn the univariate analysis, there were significant statistical differences between the two groups in terms of age of onset (P = 0.021), facial nerve angle (P < 0.01), hypertension (P = 0.01), presence of APOE ε4 expression (P < 0.01) and different degrees of brainstem compression in the Root Entry Zone (P < 0.01). In the multivariable analyses, there were significant statistical differences between the two groups in terms of age of symptom onset (P < 0.01 OR = 6.591), APOE ε4 (P < 0.01 OR = 5.691), brainstem compression (P = 0.006 OR = 5.620), and facial nerve angle (P < 0.01 OR = 5.758). Furthermore, we found no significant correlation between the severity of facial spasms and the progression rate of the disease (t = 2.47, P = 0.12>0.05).ConclusionAccording to our study, patients with facial nerve angle ≤ 96.5°, severer compression of the brainstem by offending vessels, an onset age > 45 years and positive expression of APOE ε4, may experience faster progression of hemifacial spasm.

Despite undeniable advances in modern medicine, lung cancer still has high morbidity and mortality rates. Lung cancer is preventable and treatable, and it is important to identify new risk factors for lung cancer, especially those that can be treated or reversed. Obstructive sleep apnea (OSA) is a very common sleep-breathing disorder that is grossly underestimated in clinical practice. It can cause, exacerbate, and worsen adverse outcomes, including death and various diseases, but its relationship with lung cancer is unclear. A possible causal relationship between OSA and the onset and progression of lung cancer has been established biologically. The pathophysiological processes associated with OSA, such as sleep fragmentation, intermittent hypoxia, and increased sympathetic nervous excitation, may affect normal neuroendocrine regulation, impair immune function (especially innate and cellular immunity), and ultimately contribute to the occurrence of lung cancer, accelerate progression, and induce treatment resistance. OSA may be a contributor to but a preventable cause of the progression of lung cancer. However, whether this effect exists independently of other risk factors is unclear. Therefore, by reviewing the literature on the epidemiology, pathogenesis, and treatment of lung cancer and OSA, we hope to understand the relationships between the two and promote the interdisciplinary exchange of ideas between basic medicine, clinical medicine, respiratory medicine, sleep medicine, and oncology.

Noni (Morinda citrifolia L.) is a tropical fruit rich in bioactive compounds. Little is known about its polyphenol composition at different ripeness levels and digestive characteristics. Here, we studied changes in polyphenols and antioxidant activity as noni ripened. Rutin and kaempferol-3-O-rutinoside were found in high amounts in noni, with antioxidant capacity increasing as it ripened. Under simulated digestion, polyphenols were gradually released from the oral to gastrointestinal phases, partially decomposing in the small intestine due to their instability. Conversely, fiber-bound phenols were released during colonic fermentation, leading to high bioaccessible antioxidant activity. Additionally, noni consumption affected the intestinal microbiome by reducing the Firmicutes/Bacteroidetes ratio and increasing bacteria with prebiotic properties like Prevotella and Ruminococcus. These findings demonstrate that polyphenols significantly contribute to the health benefits of noni fruit by providing absorbable antioxidants and improving the structure of the intestinal microbiome.

BackgroundEpilepsy stands as an intricate disorder of the central nervous system, subject to the influence of diverse risk factors and a significant genetic predisposition. Within the pathogenesis of temporal lobe epilepsy (TLE), the apoptosis of neurons and glial cells in the brain assumes pivotal importance. The identification of differentially expressed apoptosis-related genes (DEARGs) emerges as a critical imperative, providing essential guidance for informed treatment decisions.MethodsWe obtained datasets related to epilepsy, specifically GSE168375 and GSE186334. Utilizing differential expression analysis, we identified a set of 249 genes exhibiting significant variations. Subsequently, through an intersection with apoptosis-related genes, we pinpointed 16 genes designated as differentially expressed apoptosis-related genes (DEARGs). These DEARGs underwent a comprehensive array of analyses, including enrichment analyses, biomarker selection, disease classification modeling, immune infiltration analysis, prediction of miRNA and transcription factors, and molecular docking analysis.ResultsIn the epilepsy datasets examined, we successfully identified 16 differentially expressed apoptosis-related genes (DEARGs). Subsequent validation in the external dataset GSE140393 revealed the diagnostic potential of five biomarkers (CD38, FAIM2, IL1B, PAWR, S100A8) with remarkable accuracy, exhibiting an impressive area under curve (AUC) (The overall AUC of the model constructed by the five key genes was 0.916, and the validation set was 0.722). Furthermore, a statistically significant variance (p < 0.05) was observed in T cell CD4 naive and eosinophil cells across different diagnostic groups. Exploring interaction networks uncovered intricate connections, including gene-miRNA interactions (164 interactions involving 148 miRNAs), gene-transcription factor (TF) interactions (22 interactions with 20 TFs), and gene-drug small molecule interactions (15 interactions involving 15 drugs). Notably, IL1B and S100A8 demonstrated interactions with specific drugs.ConclusionIn the realm of TLE, we have successfully pinpointed noteworthy differentially expressed apoptosis-related genes (DEARGs), including CD38, FAIM2, IL1B, PAWR, and S100A8. A comprehensive understanding of the implications associated with these identified genes not only opens avenues for advancing our comprehension of the underlying pathophysiology but also bears considerable potential in guiding the development of innovative diagnostic methodologies and therapeutic interventions for the effective management of epilepsy in the future.

Abstract Background There is a paucity of studies examining the treatment of patients with prior myocardial infarction in the absence of obstructive coronary arteries (MINOCA) and with a concomitant left ventricular aneurysm. Our study aims to illustrate the clinical characteristics and report the mid-term surgical outcomes in this distinct entity. Methods Ten patients with MINOCA and left ventricular aneurysm were investigated. The MINOCA was diagnosed according to Scientific Statement from the American Heart Association. The indication for left ventricular reconstruction was as follows: clear evidence of both an aneurysmal and akinetic left ventricle with a history of myocardial infarction accompanied by heart failure symptoms, angina, or ventricular arrhythmias. Major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction, stroke was considered the primary endpoints. Results The median follow-up for the whole study population was 64.5 months. Seven MINOCA patients developed a left ventricular aneurysm within 4 years and three MINOCA patients were found to have a concomitant left aneurysm at the first admission. Before surgery, no patients were prescribed angiotensin-converting enzyme inhibitors. Statins, dual antiplatelet therapy, and β-blockers were prescribed in 2, 5, and 5 patients, respectively. After surgery, no MACCE occurred in the follow-up. There was a significant increase in ejection fraction (EF) in the follow-up (p = 0.0009). Conclusions Close monitoring and standard medical treatment are required before a left ventricular aneurysm occurs in MINOCA patients. Left ventricular reconstruction remains a viable option for MINOCA patients with left ventricular aneurysms and mid-term outcomes were satisfying in this distinct entity.

The complete mitochondrial genome of Pyricularia oryzae Cavara 1892 strain Guy11 is 34,865 bp in length (GenBank accession number OP095391), containing 29 tRNA genes, 2 rRNA genes, and 15 protein-coding genes (PCGs). The gene order and orientation are novel compared to other Sordariomycetes species with sequenced mitogenomes in the GenBank database. Phylogenetic analysis suggests that P. oryzae Guy11 and 19 other Sordariomycetes species form a monophyletic group. The complete mitochondrial sequence of P. oryzae Guy11 will be a valuable resource for species identification, population genetics, phylogenetics, and comparative genomics studies in Sordariomycetes and Magnaporthales.

Abstract Objective Drug‐induced side effects, particularly serious adverse events (SAEs), often affect cancer patients enrolled in clinical trials. However, little is known about anxiety and depression in cancer patients who experienced SAEs. This study evaluated the prevalence of anxiety and depression in cancer patients enrolled in clinical trials who experienced SAEs and explored the risk factors. Methods A multi‐center, cross‐sectional survey was conducted in hospitals affiliated with the University of Science and Technology of China from December 2021 to November 2022. A total of 112 cancer patients who experienced SAEs while enrolled in clinical trials, and who completed the informed consent process and study questionnaires, were included in the final analysis. Results The rate of moderate–severe depression in cancer patients was 38.4% and that of moderate–severe anxiety was 13.4%. Among the patients who had moderate–severe anxiety, 93.3% had concurrent moderate–severe depression. Lower cognitive function and lower global quality of life were risk factors for depression in cancer patients who experienced SAEs. Pain, low emotional function, low global quality of life, and a high Impact of Events Scale score were risk factors for anxiety. Conclusions Cancer patients enrolled in a clinical trial who experienced SAEs tended to be anxious and depressed, particularly the latter. These results indicate the need to evaluate anxiety and depression, and mental health treatment among cancer patients with SAEs in clinical trials.

Abstract Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have been highly studied with their critical roles as carriers of therapeutic targets such as microRNAs (miRNAs) in the treatment of human diseases, including pulmonary arterial hypertension (PAH). Herein, we tried to study the potential of BMSC-EVs to deliver miR-200b for the regulation of macrophage polarization in PAH. Methods Rat models of PAH were induced with monocrotaline treatment, followed by miR-200b expression detection in lung tissues, pulmonary artery smooth muscle cells (PASMCs) and macrophages. miR-200b-containing BMSCs or miR-200b-deficient BMSCs were selected to extract EVs. Then, we assessed the changes in rats with PAH-associated disorders as well as in vitro macrophage polarization and the functions of PASMCs after treatment with BMSC-EVs. Moreover, the interaction between miR-200b, phosphodiesterase 1 A (PDE1A) was identified with a luciferase assay, followed by an exploration of the downstream pathway, cAMP-dependent protein kinase (PKA). Results miR-200b was reduced in lung tissues, PASMCs and macrophages of rats with PAH-like pathology. BMSC-EVs transferred miR-200b into macrophages, and subsequently accelerated their switch to the M2 phenotype and reversed the PAH-associated disorders. Furthermore, miR-200b carried by BMSC-EVs induced PKA phosphorylation by targeting PDE1A, thereby expediting macrophage polarization. Conclusion Our current study highlighted the inhibitory role of BMSC-EV-miR-200b in PAH formation.

Abstract Photothermal therapy (PTT) is a highly clinical application promising cancer treatment strategy with safe, convenient surgical procedures and excellent therapeutic efficacy on superficial tumors. However, a single PTT is difficult to eliminate tumor cells completely, and tumor recurrence and metastasis are prone to occur in the later stage. Chemo-photothermal synergistic therapy can conquer the shortcomings by further killing residual tumor cells after PTT through systemic chemotherapy. Nevertheless, chemotherapy drugs' extreme toxicity is also a problematic issue to be solved, such as anthracycline-induced cardiotoxicity. Herein, we selected polydopamine nanoparticles (PDA) as the carrier of the chemotherapeutic drug doxorubicin (DOX) to construct a versatile PDA(DOX) nanoplatform for chemo-photothermal synergistic therapy against breast cancer and simultaneously attenuated DOX-induced cardiotoxicity (DIC). The excellent photothermal properties of PDA were used to achieve the thermal ablation of tumors. DOX carried out chemotherapy to kill residual and occult distant tumors. Furthermore, the PDA(DOX) nanoparticles significantly alleviate DIC, which benefits from PDA's excellent antioxidant enzyme activity. The experimental data of the chemotherapy groups showed that the results of the PDA(DOX) group were much better than the DOX group. This study not only effectively inhibits cancer but tactfully attenuates DIC, bringing a new perspective into synergistic therapy against breast cancer. Graphical Abstract

Abstract Background Age-related hearing loss (ARHL) is one of the main illnesses afflicting the aged population and has a significant negative impact on society, economy, and health. However, there is presently no appropriate therapeutic treatment of ARHL due to the absence of comprehensive trials. Objectives The goal of this review is to systematically evaluate and analyze recent statistics on the pathologic classifications, risk factors, treatment strategies, and drug candidates of ARHL, including that from traditional Chinese medicine (TCM), to provide potential new approaches for preventing and treating ARHL. Methods Literature related to ARHL was conducted in databases such as PubMed, WOS, China National Knowledge Infrastructure (CNKI), and Wanfang from the establishment of the database to Jan, 2023. The pathology, causal factor, pathophysiological mechanism, treatment strategy, and the drug candidate of ARHL were extracted and pooled for synthesis. Results Many hypotheses about the etiology of ARHL are based on genetic and environmental elements. Most of the current research on the pathology of ARHL focuses on oxidative damage, mitochondrial dysfunction, inflammation, cochlear blood flow, ion homeostasis, etc. In TCM, herbs belonging to the kidney, lung, and liver meridians exhibit good hearing protection. Seven herbs belonging to the kidney meridian, 9 belonging to the lung meridian, and 4 belonging to the liver meridian were ultimately retrieved in this review, such as Polygonum multiflorum Thunb., Panax ginseng C.A. Mey, and Pueraria lobata (Willd.) Ohwi. Their active compounds, 2,3,4',5-Tetrahydroxystilbene-2-O-D-glucoside, ginsenoside Rb1, and puerarin, may act as the molecular substance for their anti-ARHL efficacy, and show anti-oxidative, neuroprotective, anti-inflammatory, anti-apoptotic, or mitochondrial protective effects. Conclusion Anti-oxidants, modulators of mitochondrial function, anti-inflammation agents, vasodilators, K+ channel openers, Ca2+ channel blockers, JNK inhibitors, and nerve growth factors/neurotrophic factors all contribute to hearing protection, and herbs are an important source of potential anti-ARHL drugs.

Abstract Background We aimed to identify the relationship between the genomic characteristics and clinical outcomes of oligo-metastatic breast cancer. Methods Oligo-metastatic breast cancer diagnosed by pathology from January 2001 and August 2019 were reviewed and we matched the poly-metastatic patients based on the clinicopathological features of patients included. Clinicopathological values and data of genomic alterations were collected. Oligo-recurrence (oligo-R) was defined as a situation where disease progression occurred in less than 5 anatomical sites and other anatomic areas still suppressed by the ongoing therapy. Results A total of 26 breast cancer patients were enrolled in our study, including 14 patients with strict oligo-metastatic disease (oligo-R > 6 months) and 12 with simultaneous poly-metastatic disease. PIK3CA, TP53 and ERBB2 were the most common shared alterations identified in patients included. Based on the median time of oligo-R, we divided the patients with oligo-metastasis into longer oligo-R group (oligo-R > 31.04 months) and shorter oligo-R group (oligo-R ≤ 31.04 months). The analysis of PIK3CA mutation sites showed that H1047R mutation was closely associated with oligo-metastasis, rather than poly-metastasis. H1047R mutation also predicted a better prognosis (oligo-R > 31.04 months) in oligo-metastatic breast cancer. In addition, HER2 positive was more likely to be related to a good outcome in patients with oligo-metastasis. Conclusions Through the genetic analysis of samples from oligo-metastasis, we found the prognostic values of PIK3CA H1047R and HER2 in oligo- and poly-metastasis. We improved the stratification of prognosis and provided new insights for biological behaviors of oligo-metastatic breast cancer.

Abstract Background Alginate oligosaccharides (AOs) are the degradation products of alginate, a natural polysaccharide abundant in brown algae. AOs generated by enzymatic hydrolysis have diverse bioactivities and show broad application potentials. AOs production via enzymolysis is now generally with sodium alginate as the raw material, which is chemically extracted from brown algae. In contrast, AOs production by direct degradation of brown algae is more advantageous on account of its cost reduction and is more eco-friendly. However, there have been only a few attempts reported in AOs production from direct degradation of brown algae. Results In this study, an efficient Laminaria japonica-decomposing strain Pseudoalteromonas agarivorans A3 was screened. Based on the secretome and mass spectrum analyses, strain A3 showed the potential as a cell factory for AOs production by secreting alginate lyases to directly degrade L. japonica. By using the L. japonica roots, which are normally discarded in the food industry, as the raw material for both fermentation and enzymatic hydrolysis, AOs were produced by the fermentation broth supernatant of strain A3 after optimization of the alginate lyase production and hydrolysis parameters. The generated AOs mainly ranged from dimers to tetramers, among which trimers and tetramers were predominant. The degradation efficiency of the roots reached 54.58%, the AOs production was 33.11%, and the AOs purity was 85.03%. Conclusion An efficient, cost-effective and green process for AOs production directly from the underutilized L. japonica roots by using strain A3 was set up, which differed from the reported processes in terms of the substrate and strain used for fermentation and the AOs composition. This study provides a promising platform for scalable production of AOs, which may have application potentials in industry and agriculture.

Background: The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation. Methods: Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments. Results: In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2. Conclusions: ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.

Abstract The unmanned aerial vehicle (UAV) assisted mobile edge computing (MEC) system leverages the high maneuverability of UAVs to provide efficient computing services to terminals. A dynamic deployment algorithm based on double deep Q-networks (DDQN) is suggested to address issues with energy limitation and obstacle avoidance when providing edge services to terminals by UAV. First, the energy consumption of the UAV and the fairness of the terminal’s geographic location are jointly optimized in the case of multiple obstacles and multiple terminals on the ground. And the UAV can avoid obstacles. Furthermore, a double deep Q-network was introduced to address the slow convergence and risk of falling into local optima during the optimization problem training process. Also included in the learning process was a pseudo count exploration strategy. Finally, the improved DDQN algorithm achieves faster convergence and a higher average system reward, according to experimental results. Regarding the fairness of geographic locations of terminals, the improved DDQN algorithm outperforms Q-learning, DQN, and DDQN algorithms by 50%, 20%, and 15.38%, respectively, and the stability of the improved algorithm is also validated.

Abstract Background Evidence on the influence of programmed death‐ligand 1 (PD‐L1) expression on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients is at variance. Methods A single‐center retrospective study was conducted to evaluate the influence of PD‐L1 expression on the efficacy of EGFR‐TKIs for NSCLC patients with EGFR mutation. Clinical information was retrieved from electronic medical records. The patients were divided into three subgroups according to PD‐L1 expression level: PD‐L1

Highlights Cerium methacrylate was prepared and ingeniously used as curing agent for epoxy, surface modifier for BN, and effective corrosion inhibitor. The coating integrates high thermal conductivity (4.29 W m−1 K−1), corrosion resistance (low-frequency impedance is 5.1 × 1011 Ω cm2 at 181 day), hydrophobicity (WCA: ~ 148.35° and WSA: ~ 20°), temperature resistance and adhesion. The coating can extend service life of metal materials without sacrificing their inherent heat conduction property.

Additive Manufacturing (AM) is a transformative manufacturing technology enabling direct fabrication of complex parts layer-by-layer from 3D modeling data. Among AM applications, the fabrication of Functionally Graded Materials (FGMs) has significant importance due to the potential to enhance component performance across several industries. FGMs are manufactured with a gradient composition transition between dissimilar materials, enabling the design of new materials with location-dependent mechanical and physical properties. This study presents a comprehensive review of published literature pertaining to the implementation of Machine Learning (ML) techniques in AM, with an emphasis on ML-based methods for optimizing FGMs fabrication processes. Through an extensive survey of the literature, this review article explores the role of ML in addressing the inherent challenges in FGMs fabrication and encompasses parameter optimization, defect detection, and real-time monitoring. The article also provides a discussion of future research directions and challenges in employing ML-based methods in the AM fabrication of FGMs.

Steel tubular column-to-steel beam (STCSB) connections are critical parts in offshore structures, where complex component connections and the stress concentration are of significant concern. This study conducted stress concentration tests on welded STCSB connections and subsequently developed a finite element (FE) model for the connections, with the experimental results validating the accuracy of the model. The discussion focused on the influence of parameters such as the width-to-diameter ratio of the beam to the column, the diameter-to-thickness ratio of the column, the diameter-to-thickness ratio of the column to the beam, and the height-to-thickness ratio of the beam web on the fatigue performance. The study proposed optimization methods including the addition of stiffeners and outer flange plates. The findings indicate that optimized connection configurations can effectively mitigate stress concentration in the connected areas, thereby enhancing the structural stability and fatigue life. The width-to-diameter ratio of the beam to the column and the diameter-to-thickness ratio of the column significantly affect the fatigue performance of welded STCSB connections, with an increased width-to-diameter ratio of the beam to the column or a reduced diameter-to-thickness ratio of the column leading to a substantial decrease in the maximum stress concentration factors (SCFs). The addition of stiffeners and adjustment of the outer flange plate can improve stress concentration effects in the connection area.

The journal retracts the article “Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis” [...]

Coffee pulp wines were produced through the mixed fermentation of Saccharomyces cerevisiae, and the flavor and sensory characteristics were comparatively evaluated. A total of 87 volatile components were identified from five coffee pulp wines, of which 68 were present in all samples, accounting for over 99% of the total concentration. The sample fermented contained significantly higher levels of volatile metabolites (56.80 mg/g). Alcohols (22 species) and esters (26 species) were the main flavor components, with the contents accounting for 56.45 ± 3.93% and 31.18 ± 4.24%, respectively, of the total. Furthermore, 14 characteristic components were identified as potential odor-active compounds, contributing to sweet and floral apple brandy flavor. Although the characteristic components are similar, the difference in the content makes the overall sensory evaluation of the samples different. The samples formed by fermentation of four strains, which obtained the highest score (86.46 ± 0.36) in sensory evaluation, were further interpreted and demonstrated through the Mantel test. The results of the component analysis were effectively distinguished by OPLS-DA and PCA, and this validation was supported by sensory evaluation. The research results provided a technical reference for the production of coffee pulp wines.