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This paper aims to propose a new multi-attribute decision making (MADM) method in complicated and fuzzy decision-making environment. To express both decision makers (DMs’) quantitative and qualitative evaluation information comprehensively and consider their high hesitancy in giving their assessment values in MADM process, we combine q-rung dual hesitant fuzzy sets (q-RDHFSs) with uncertain linguistic variables and develop a new tool, called the q-rung dual hesitant uncertain linguistic sets (q-RDHULSs). First, the definition, operations and comparison method of q-RDHULSs are proposed. Second, given the interrelationship among multiple q-rung dual hesitant uncertain linguistic variables (q-RDHULVs) we introduce some aggregation operators (AOs) to fuse q-rung dual hesitant uncertain linguistic (q-RDHUL) information based on the Muirhead mean, i.e. the q-RDHUL Muirhead mean operator, the q- RDHUL weighted Muirhead mean operator, the q-RDHUL dual Muirhead mean operator, and the q-RDHUL weighted dual Muirhead mean operator. To cope with MADM problems with q-RDHUL information, we propose a new method based on the proposed AOs. Afterwards, we apply the proposed method to an enterprise informatization level evaluation problem to verify its effectiveness. In addition, we also explain why our proposed method is more powerful and flexible than others.

Abstract Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

Abstract Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak.

Abstract Background Thin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs). Methods We systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included “Platelet-Rich Plasma,” “thin endometrium,” “endometrial thickness,” “infertility,” “pregnancy,” “reproduction,” and “adverse reactions”. RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity. Results Eight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias. Conclusion Intrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results. Trial registration The review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration.

Abstract Background The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes. Methods This study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999–2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality. Results During a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68–0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57–0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06–1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00–1.16). Conclusions Among US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.

Context: COVID-19 is a novel coronavirus pneumonia, which is related to abnormal liver function. Thus, it is important to explore the occurrences and causes of abnormal liver function with COVID-19. Methods: We chose 109 patients with COVID-19 in 2020 and studied the relationship between gender, age, basic diseases, antiviral drug treatment, disease classification, and abnormal liver function, and analyzed the causes of abnormal liver function in patients with COVID-19 Results: Among patients, 46 (42.20%) had abnormal liver function at admission; 37 (80.43%) had mild abnormal liver function; and 9 (19.57%) had severe liver function. Compared with other age groups, the abnormal rate of serum ALP in the group younger than 21 years old were the highest (P < 0.05). The abnormal rates and concentrations of serum ALT, AST and γ-GT in the male groups were higher than in female groups (P < 0.05), basic disease group were higher than those in the non-basic disease group (P < 0.05). Serum γ-GT concentration after 1 week of antiviral treatment was higher than that before treatment (P < 0.05). The abnormal rate of ALT and AST at discharge was lower than that after antiviral treatment for 1 week (P < 0.05). Serum TB and AST concentrations at discharge were lower than those before treatment (P < 0.05). Serum AST and γ-GT concentrations in severe/critical type group were higher than those in mild or ordinary type group (P < 0.05) Conclusions: In this study, we found male sex, basic diseases, antiviral drugs, and severe/critical types are related to the occurrence of abnormal liver function in COVID-19 patients.

Abstract Background The cerebrospinal fluid (CSF), primarily generated by the choroid plexus (ChP), is the major carrier of the glymphatic system. The alternations of CSF production and the ChP can be associated with the Alzheimer’s disease (AD). The present work investigated the roles of the ChP in the AD based on a proposed ChP image segmentation pipeline. Methods A human-in-the-loop ChP image segmentation pipeline was implemented with intermediate and active learning datasets. The performance of the proposed pipeline was evaluated on manual contours by five radiologists, compared to the FreeSurfer and FastSurfer toolboxes. The ChP volume and blood flow were investigated among AD groups. The correlations between the ChP volume and AD CSF biomarkers including phosphorylated tau (p-tau), total tau (t-tau), amyloid-β42 (Aβ42), and amyloid-β40 (Aβ40) was investigated using three models (univariate, multiple variables, and stepwise regression) on two datasets with 806 and 320 subjects. Results The proposed ChP segmentation pipeline achieved superior performance with a Dice coefficient of 0.620 on the test dataset, compared to the FreeSurfer (0.342) and FastSurfer (0.371). Significantly larger volumes (p

Abstract Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers.

Abstract Background Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. Results The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. Conclusions Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment. Graphical Abstract

Flavor plays a crucial role in the sensory perception of food and is a key determinant for consumer preference and choice. Therefore, flavor analysis methods are of paramount importance. Traditional methods for flavor analysis have limitations such as time-consuming and unable to handle large sample data. The emergence of machine learning is poised to address these problems. Machine learning possesses the capability to analyze and process vast amounts of data, identify complex patterns in high-dimensional variable spaces, autonomously learn useful information from known data, and automatically generate and optimize algorithms for prediction based on new data. The emergence of machine learning provides a new method for understanding the complex flavor characteristics of food. This article provides a comprehensive review of the advantages and disadvantages of traditional and novel machine learning methods as well as their various application scenarios in conjunction with analytical instruments such as electronic tongue, electronic nose, and gas chromatography-mass spectrometry (GC-MS). Additionally, it reviews the application of machine learning in food flavor analysis. Through research, it has been found that different scenarios of food flavor analysis require different machine learning methods. Machine learning holds significant potential for enhancing food quality, safety and consumer satisfaction. The combination of multiple machine learning models and analytical techniques will play a crucial role in food flavor analysis.

Accurate photovoltaic （PV） output power forecasting plays a crucial role in ensuring the secure and stable operation of distribution networks. In light of this， the paper proposes a short-term PV power forecasting method using cosine similarity and a hybrid TSO （tuna swarm optimization） and BP （back propagation） neural network. Firstly， the cosine similarity algorithm is utilized to identify historical data with strong resemblance to the forecast day as training samples. Subsequently， the TSO algorithm is employed to search for optimal initial weights and thresholds for the BP neural network. The TSO-BP model is then trained for short-term PV power forecasting. Finally， the TSO-BP model is applied to predict PV output power under both stable and fluctuating weather conditions. Simulation results indicate that， the proposed method， compared to traditional forecasting methods， achieves higher accuracy in predictions for both steady and fluctuating weather scenarios.

Abstract Background Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. Methods A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg− 1), curcumin (Cur, 40 mg·kg− 1) and metformin (Met, 50 mg·kg− 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml− 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. Results The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. Conclusion NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Abstract Bone implantation surgery is often accompanied by bacterial infection, resulting in infectious bone non‐union, pathological fracture and other serious consequences, which will aggravate the pain of patients. A non‐antibiotic coating consisting of sodium dodecyl sulphate (SDS) and levulinic acid (LA) with different concentrations was prepared by the authors on the zinc–aluminium alloy (ZA6‐1) using a wet chemistry treatment for orthopaedic application. The influence of SDS/LA concentrations on the surface morphology, composition and performance of the developed coating was investigated. The results showed that as‐prepared coating on a zinc alloy surface could improve the substrate's corrosion resistance and increase the degradation rate from 0.82 to 19.70 μm/year upon raising the SDS/LA concentration. Furthermore, higher hydrophilicity (100%) and morphology, as well as good cell adhesion and differentiation (ALP >95% for 7 days) were observed on coated zinc alloys. The increased SDS/LA concentration slightly weakens the biocompatibility and enhances the antibacterial performance of coated zinc alloys due to the synergistic effect of SDS/LA. Overall, the coating comprising 6 wt.% SDS and 9 wt.% LA showed excellent antibacterial action with a high level of biocompatibility, confirming its potential application for orthopaedic implants.

Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant.

Abstract Background Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment. Methods The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1. Results Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism. Conclusion USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.

Abstract Metabolic syndrome (MetS) is a cluster of clinical syndromes that is closely associated with an elevated risk of developing atherosclerotic cardiovascular disease. In a series of animal experiments and clinical trials, crocus sativus and its component crocin have demonstrated promising hypoglycemic effects. However, there is currently insufficient evidence regarding their impact on cardiometabolic parameters. Our study aimed to assess the impact of Crocus sativus and crocin on glycemic control in individuals with metabolic syndrome and associated disorders, as well as their potential effects on improving cardiometabolic parameters. We searched Cochrane Library, PubMed, Embase, and Web of Science databases to ascertain the pertinent randomized controlled trials (RCTs) until December 30, 2023. Q-test and I2 statistics were utilized to evaluate heterogeneity among the included studies. Data were merged using a random-effects model and presented as (WMD) with a 95% confidence interval (CI). The current comprehensive review and meta-analysis, encompassing 13 RCTs involving a total of 840 patients diagnosed with metabolic syndrome and associated disorders, demonstrates that Crocus sativus was superior to placebo on Hemoglobin A1c(HbA1c) (WMD: -0.31;95% CI [-0.44,-0.19]. P = 0.002) and systolic blood pressure(SBP) (WMD:-7.49;95% CI [-11.67,-3.30]. P = 0.99) respectively. Moreover, Crocus sativus improved fasting blood glucose (FBG) (WMD:-7.25;95% CI [-11.82, -2.57]. P = 0.002) when used crocin and on other chronic diseases. Crocus sativus reduced the total cholesterol (TC) among the metabolic syndromepatients (WMD:-13.64;95%CI [-26.26, -1.03]. P = 0.03). We demonstrated that Crocus sativus exerts beneficial effects on glycemic control and cardiometabolic parameters in individuals with metabolic syndrome and related disorders.

Abstract The photonic Ising machine is a new paradigm of optical computing that takes advantage of the unique properties of light wave propagation, parallel processing, and low-loss transmission. Thus, the process of solving combinatorial optimization problems can be accelerated through photonic/optoelectronic devices, but implementing photonic Ising machines that can solve arbitrary large-scale Ising problems with fast speed remains challenging. In this work, we have proposed and demonstrated the Phase Encoding and Intensity Detection Ising Annealer (PEIDIA) capable of solving arbitrary Ising problems on demand. The PEIDIA employs the heuristic algorithm and requires only one step of optical linear transformation with simplified Hamiltonian calculation by encoding the Ising spins on the phase term of the optical field and performing intensity detection during the solving process. As a proof of principle, several 20 and 30-spin Ising problems have been solved with high ground state probability (≥0.97/0.85 for the 20/30-spin Ising model).

Abstract Narrow bandwidths are a general bottleneck for applications relying on passive, linear, subwavelength resonators. In the past decades, several efforts have been devoted to overcoming this challenge, broadening the bandwidth of small resonators by the means of analog non-Foster matching networks for radiators, antennas and metamaterials. However, most non-Foster approaches present challenges in terms of tunability, stability and power limitations. Here, by tuning a subwavelength acoustic transducer with digital non-Foster-inspired electronics, we demonstrate five-fold bandwidth enhancement compared to conventional analog non-Foster matching. Long-distance transmission over airborne acoustic channels, with approximately three orders of magnitude increase in power level, validates the performance of the proposed approach. We also demonstrate convenient reconfigurability of our non-Foster-inspired electronics. This implementation provides a viable solution to enhance the bandwidth of sub-wavelength resonance-based systems, extendable to the electromagnetic domain, and enables the practical implementation of airborne and underwater acoustic radiators.

Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.

At present， safety stability control system inspection primarily relies on independent in-plant testing， laboratory experiment and on-site joint testing， making it difficult to completely eliminate potential risks in safety and stability control systems. To address the shortcomings of existing testing methods， a remote non-real-time closed-loop testing technique for safety and stability control systems is proposed. By integrating key technologies such as hardware-in-the-loop simulation， 5G communication networking， wide-area synchronous triggering， and multi-communication protocol conversion， key modules， including the platform management system， testing master station and testing terminals， have been developed， and a remote non-real-time closed-loop testing process has been formulated. Taking the safety and stability control system for hydropower transmitted via ultra-high-voltage direct current in Sichuan power grid as an example， the feasibility of the proposed technique is validated.

Abstract Background Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. Result It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P

BackgroundThe escalating global economic burden of ischemic stroke poses a significant public health challenge amid global aging trends. The broad therapeutic efficacy of new antidiabetic drugs may offer new options in the prevention and treatment of ischemic stroke. Consistent conclusions regarding the relationship between novel antidiabetic agents and the risk of ischemic stroke remain elusive, and the causal relationship deserves further investigation.Materials and methodsThree novel antidiabetic drug targets were selected, and cis-expression quantitative trait loci (cis-eQTL) were screened as instrumental variables. Genetic association data for ischemic stroke were obtained from the Genome-wide Association Study (GWAS) database. Mendelian randomization (MR) analysis, facilitated by R software, calculated MR estimates for each single nucleotide polymorphism (SNP), and meta-analysis was performed using five methods. To ensure robustness, sensitivity analyses, heterogeneity analyses, horizontal pleiotropy analyses, and co-localization analyses were conducted for significant MR associations.ResultsThree eQTLs for antidiabetic drug genes served as instrumental variables, utilizing a GWAS dataset comprising 34,217 cases and 406,111 controls for ischemic stroke. Genetic variants in glucagon-like peptide-1 receptor agonists (GLP-1 RA) targets exhibited a positive correlation with ischemic stroke risk (OR 1.06, 95% CI 1.04–1.08, P = 0.000), while genetic variation in dipeptidyl peptidase 4 inhibitors (DPP-4i) targets showed a negative association with ischemic stroke risk (OR 0.93, 95% CI 0.89–0.97, P = 0.003). Sensitivity analyses supported robust conclusions, revealing no heterogeneity or horizontal pleiotropy.ConclusionThis study found that GLP-1 RA and DPP-4i were associated with an increased risk of ischemic stroke by MR analysis. Although sensitivity analyses provide support for this result, it contradicts previous knowledge. Therefore, the results of this study still need to treated with caution. Updated and more in-depth GWAS data and high-quality real-world data are expected to validate the results.

Objective Have you ever been frustrated when working to acquire data? Have you experienced the trials and tribulations of readying data? ‘Best laid plans often go awry’. ‘A problem shared is a problem halved’ and we’d like to share our experiences and lessons learned with you. We are a Canadian provincial organization with over 20 years experience working with large comprehensive data currently in the midst of validation work on newly acquired data. This behind the scenes and sometimes forgotten work can take considerable time, but it is crucial and integral for research. Approach Data acquisition is complex, particularly when adding new data to existing data files. Many validation steps are vital to ensuring that data used in research are the highest quality possible and limitations are understood. The process began with preparing the agreement and list of new variables to add in 2018 for 4 databases (hospital, drug, physician, emergency), to signatures in 2023, and it is ongoing. While we have a plan to do this work, it requires flexibility and constant updates based on new information learned. Conclusion Investigating errors, deciding level of acceptance of errors, managing relationships, and communication are the most critical aspects of the work. Contingency plans are important when it takes longer than expected. Data are never perfect, but a thoughtful approach to validation and documentation of limitations and decisions support using the data appropriately. Also, a kind demeanor, an open mind, and a sense of humour can go a long way!

This study aimed to establish an efficient in vitro cell-based assay to measure the activity of teriparatide (PTH1–34). In this study, a rat osteosarcoma cell line (UMR-106) was treated with various concentrations of PTH1–34, and the biological activity of PTH1–34 was determined by quantitatively measuring intracellular cyclic adenosine monophosphate levels using a time-resolved fluoroimmunoassay. A four-parameter fitting analysis was used to calculate the relative potency of the samples. The experimental conditions were optimized. The method's specificity, relative accuracy, precision, and linearity were validated. Our data suggested that this method had good specificity, a relative bias of relative accuracy ranging from −0.8 to 1.4%, a correlation coefficient for the linear regression equation of 0.9953, a geometric coefficient of variation for intermediate precision ranges from 2.0 to 3.5%, and a linear range of 50 to 150%. This method significantly improves the quality control and release inspection efficiency of PTH1–34 and may be further developed and validated as an alternative to the existing United States Pharmacopeia and European Pharmacopoeia inclusion methods. This method also provides a platform for the high-throughput screening of PTH1–34 analogs.

ABSTRACT In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population.IMPORTANCEThis study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.

Maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV) are members of a group of genetically highly homologous lentiviruses collectively referred to as small ruminant lentiviruses (SRLVs). SRLVs can infect sheep, goats and other small ruminants, causing multisystemic disease with progressive and persistent inflammatory changes, severely reducing animal productivity and impeding animal trade. The capsid protein of SRLVs, p28, is highly conserved among strains and is a commonly used marker for the detection of SRLVs. In this study, two monoclonal antibodies (mAbs), designated G8F7 and A10C12, against p28 were generated using a recombinant p28 protein expressed in Escherichia coli as an immunogen. Functional analysis showed that these two monoclonal antibodies could be used in iELISA, immunofluorescence assays (IFA) and western blot assays to detect p28 or Gag precursor proteins of SRLVs. Two linear epitopes, 61GNRAQKELIQGKLNEEA77 (E61-77) and 187CQKQMDRVLGTRVQQATVEEKMQACR212 (E187-212), which are recognized by G8F7 and A10C12, respectively, were identified through truncation of the GST-fused p28. Amino acid sequence alignment showed that the epitope E61-77 is conserved among SRLVs, with a dominant mutation site (K72R) that does not disrupt recognition by G8F7. E187-212 was found to exhibit variability among SRLVs, but the majority of mutant epitopes are recognized by A10C12, with the exception of a mutant epitope from an isolate with undefined subtypes from Ovis aries, which was not recognized. These findings may facilitate future study of SRLVs and promote the development of methods for the detection of these viruses.

BackgroundHypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone?ObjectiveWe aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults.MethodsData from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014–2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship.ResultsDuring a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs

Abstract Quasi‐2D perovskite quantum wells are increasingly recognized as promising candidates for direct‐conversion X‐ray detection. However, the fabrication of oriented and uniformly thick quasi‐2D perovskite films, crucial for effective high‐energy X‐ray detection, is hindered by the inherent challenges of preferential crystallization at the gas‐liquid interface, resulting in poor film quality. In addressing this limitation, a carbonyl array‐synergized crystallization (CSC) strategy is employed for the fabrication of thick films of a quasi‐2D Ruddlesden‐Popper (RP) phase perovskite, specifically PEA2MA4Pb5I16. The CSC strategy involves incorporating two forms of carbonyls in the perovskite precursor, generating large and dense intermediates. This design reduces the nucleation rate at the gas‐liquid interface, enhances the binding energies of Pb2+ at (202) and (111) planes, and passivates ion vacancy defects. Consequently, the construction of high‐quality thick films of PEA2MA4Pb5I16 RP perovskite quantum wells is achieved and characterized by vertical orientation and a pure well‐width distribution. The corresponding PEA2MA4Pb5I16 RP perovskite X‐ray detectors exhibit multi‐dimensional advantages in performance compared to previous approaches and commercially available a‐Se detectors. This CSC strategy promotes 2D perovskites as a candidate for next‐generation large‐area flat‐panel X‐ray detection systems.

Background The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient‐specific factors predicting the RDN response. Methods and Results We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta‐analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24‐hour systolic BP reduction (weighted mean difference, −4.05 [95% CI, −7.33 to −0.77]; weighted mean difference, −7.20 [95% CI, −9.79 to −4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. Conclusions In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Hepatitis B virus (HBV)-related liver disease poses a major threat to human health worldwide. Although interferon and nucleoside analogues are commonly administered for treating chronic HBV infection, their use is limited by considerable side effects, drug resistance and incapacity for HBV elimination. Hence, novel HBV therapeutics are urgently required. For numerous years, traditional Chinese botanical drugs have been widely used to treat HBV-related diseases. The natural metabolites derived from these traditional drugs exhibit significant anti-HBV effects and serve as potential novel drugs for treating HBV. For overall understanding the therapeutic potential of these metabolites, the anti-HBV effects and mechanisms of action of 107 natural metabolites are summarized in this article. Mechanistically, these natural metabolites exert their anti-HBV effects by influencing the expression and function of host and/or viral genes, which differs from the mechanism of action of nucleoside analogues. Indeed, combining natural metabolites with nucleoside analogues can exert synergistic effects. Accordingly, natural metabolites or their chemically modified derivatives represent potential novel drugs and adjuvants for anti-HBV treatment.

The release of the generative pre-trained transformer (GPT) series has brought artificial general intelligence (AGI) to the forefront of the artificial intelligence (AI) field once again. However, the questions of how to define and evaluate AGI remain unclear. This perspective article proposes that the evaluation of AGI should be rooted in dynamic embodied physical and social interactions (DEPSI). More specifically, we propose five critical characteristics to be considered as AGI benchmarks and suggest the Tong test as an AGI evaluation system. The Tong test describes a value- and ability-oriented testing system that delineates five levels of AGI milestones through a virtual environment with DEPSI, allowing for infinite task generation. We contrast the Tong test with classical AI testing systems in terms of various aspects and propose a systematic evaluation system to promote standardized, quantitative, and objective benchmarks and evaluation of AGI.

Motivated by the concepts of low carbon and environmental protection, electric vehicles have received much attention and become more and more popular all around the world. The expanding demand for electric vehicles has driven the rapid development of the charging pile industry. One of the prominent issues in charging pile industry is to determine their sites, which is a complex decision-making problem. As a matter of factor, the process of charging piles sites selection can be regarded as multi-attribute group decision-making (MAGDM), which is the main topic of this paper. The recently proposed linguistic spherical fuzzy sets (LSFSs) composed of the linguistic membership degree, linguistic abstinence degree and linguistic non-membership degree are powerful tools to express the evaluation information of decision makers (DMs). Based on the concept of LSFSs, we introduce probabilistic multi-valued linguistic spherical fuzzy sets (PMVLSFSs), which can describe DMs’ fuzzy evaluation information in a more refined and accurate way. The operation rules of PMVLSFSs are also developed in this article. To effectively aggregate PMVLSFSs, the probabilistic multi-valued linguistic spherical fuzzy power generalized Maclaurin symmetric mean operator and the probabilistic multi-valued linguistic spherical fuzzy power weighted generalized Maclaurin symmetric mean are put forward. Based on the above aggregation operators, a new method for MAGDM problem with PMVLSFSs is established. Further, a practical case of suitable site selection of charging pile is used to verify the practicability of this method. Lastly, comparative analysis with other methods is performed to illustrate the advantages and stability of proposed method.

Abstract Hexavalent chromium (Cr(VI)) is still a common contaminant in water. In this work, we studied the Cr(VI) adsorption by polyphenol-rich bacterial cellulose(BC) gel, synthesized by the Komagataeibacter rhaeticus K15 using wine pomace. The results showed that the equilibrium removal capacity was 473.09 ± 1.41 mg g−1 (dry weight). The quasi-second-order kinetics model and the Langmuir removal isotherm model was the most suitable for describing the Cr(VI) removal process. Toxic Cr(VI) was converted to the low toxic Cr(III) during the removal process via the reduction of Cr(VI) to Cr(III) by polyphenols released into the solution by the BC gel. The FTIR, XRD, XPS, SEM-EDX results indicated the physical adsorption on the surface of BC and the reduction reaction between polyphenol groups and Cr(VI) is the critical mechanism of Cr(VI) removal by BC. The finding of this study demonstrates that polyphenols-rich BC gel produced from wine pomace has a superior feature for future Cr(VI)-wastewater purification.

Abstract Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an “epitope-focused” vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design.

Abstract Metal-halide perovskite thin monocrystals featuring efficient carrier collection and transport capabilities are well suited for radiation detectors, yet their growth in a generic, well-controlled manner remains challenging. Here, we reveal that mass transfer is one major limiting factor during solution growth of perovskite thin monocrystals. A general approach is developed to overcome synthetic limitation by using a high solute flux system, in which mass diffusion coefficient is improved from 1.7×10–10 to 5.4×10–10 m2 s–1 by suppressing monomer aggregation. The generality of this approach is validated by the synthesis of 29 types of perovskite thin monocrystals at 40–90 °C with the growth velocity up to 27.2 μm min–1. The as-grown perovskite monocrystals deliver a high X-ray sensitivity of 1.74×105 µC Gy−1 cm−2 without applied bias. The findings regarding limited mass transfer and high-flux crystallization are crucial towards advancing the preparation and application of perovskite thin monocrystals.

Abstract Background The family Rhabdiasidae (Nematoda: Rhabditida) is a globally distributed group of nematode parasites, with over 110 species parasitic mainly in amphibians and reptiles. However, the systematic position of the family Rhabdiasidae in the order Rhabditida remains unsolved, and the evolutionary relationships among its genera are still unclear. Moreover, the present knowledge of the mitochondrial genomes of rhabdiasids remains limited. Methods Two rhabdiasid species: Rhabdias kafunata Sata, Takeuchi & Nakano, 2020 and R. bufonis (Schrank, 1788) collected from the Asiatic toad Bufo gargarizans Cantor (Amphibia: Anura) in China, were identified based on morphology (light and scanning electron microscopy) and molecular characterization (sequencing of the nuclear 28S and ITS regions and mitochondrial cox1 and 12S genes). The complete mitochondrial genomes of R. kafunata and R. bufonis were also sequenced and annotated for the first time. Moreover, phylogenetic analyses based on the amino acid sequences of 12 protein-coding genes (PCGs) of the mitochondrial genomes were performed to clarify the systematic position of the family Rhabdiasidae in the order Rhabditida using maximum likelihood (ML) and Bayesian inference (BI). The phylogenetic analyses based on the 28S + ITS sequences, were also inferred to assess the evolutionary relationships among the genera within Rhabdiasidae. Results The detailed morphology of the cephalic structures, vulva and eggs in R. kafunata and R. bufonis was revealed using scanning electron microscopy (SEM) for the first time. The characterization of 28S and ITS regions of R. kafunata was reported for the first time. The mitogenomes of R. kafunata and R. bufonis are 15,437 bp and 15,128 bp long, respectively, and both contain 36 genes, including 12 PCGs (missing atp8). Comparative mitogenomics revealed that the gene arrangement of R. kafunata and R. bufonis is different from all of the currently available mitogenomes of nematodes. Phylogenetic analyses based on the ITS + 28S data showed Neoentomelas and Kurilonema as sister lineages, and supported the monophyly of Entomelas, Pneumonema, Serpentirhabdias and Rhabdias. Mitochondrial phylogenomic results supported Rhabdiasidae as a member of the superfamily Rhabditoidea in the suborder Rhabditina, and its occurrance as sister to the family Rhabditidae. Conclusions The complete mitochondrial genome of R. kafunata and R. bufonis were reported for the first time, and two new gene arrangements of mitogenomes in Nematoda were revealed. Mitogenomic phylogenetic results indicated that the family Rhabdiasidae is a member of Rhabditoidea in Rhabditina, and is closely related to Rhabditidae. Molecular phylogenies based on the ITS + 28S sequence data supported the validity of Kurilonema, and showed that Kurilonema is sister to Neoentomelas. The present phylogenetic results also indicated that the ancestors of rhabdiasids seem to have initially infected reptiles, then spreading to amphibians. Graphical Abstract

High-performance flexible pressure sensors provide comprehensive tactile perception and are applied in human activity monitoring, soft robotics, medical treatment, and human-computer interface. However, these flexible pressure sensors require extensive nano-architectural design and complicated manufacturing and are time-consuming. Herein, a highly sensitive, flexible piezoresistive tactile sensor is designed and fabricated, consisting of three main parts: the randomly distributed microstructure on T-ZnOw/PDMS film as a top substrate, multilayer Ti3C2-MXene film as an intermediate conductive filler, and the few-layer Ti3C2-MXene nanosheet-based interdigital electrodes as the bottom substrate. The MXene-based piezoresistive sensor with randomly distributed microstructure exhibits a high sensitivity over a broad pressure range (less than 10 ​kPa for 175 ​kPa−1) and possesses an out-standing permanence of up to 5000 cycles. Moreover, a 16-pixel sensor array is designed, and its potential applications in visualizing pressure distribution and an example of tactile feedback are demonstrated. This fully sprayed MXene-based pressure sensor, with high sensitivity and excellent durability, can be widely used in, electronic skin, intelligent robots, and many other emerging technologies.

Abstract For classical waves, phase matching is vital for enabling efficient energy transfer in many scenarios, such as waveguide coupling and nonlinear optical frequency conversion. Here, we propose a temporal quasi-phase matching method and realize robust and complete acoustical energy transfer between arbitrarily detuned cavities. In a set of three cavities, A, B, and C, the time-varying coupling is established between adjacent elements. Analogy to the concept of stimulated Raman adiabatic passage, amplitudes of the two couplings are modulated as time-delayed Gaussian functions, and the couplings’ signs are periodically flipped to eliminate temporal phase mismatching. As a result, robust and complete acoustic energy transfer from A to C is achieved. The non-reciprocal frequency conversion properties of our design are demonstrated. Our research takes a pivotal step towards expanding wave steering through time-dependent modulations and is promising to extend the frequency conversion based on state evolution in various linear Hermitian systems to nonlinear and non-Hermitian regimes.

Abstract Topological photonics provides a new degree of freedom to robustly control electromagnetic fields. To date, most of established topological states in photonics have been employed in Euclidean space. Motivated by unique properties of hyperbolic lattices, which are regular tessellations in non-Euclidean space with a constant negative curvature, the boundary-dominated hyperbolic topological states have been proposed. However, limited by highly crowded boundary resonators and complicated site couplings, the hyperbolic topological insulator has only been experimentally constructed in electric circuits. How to achieve hyperbolic photonic topological insulators is still an open question. Here, we report the experimental realization of hyperbolic photonic topological insulators using coupled ring resonators on silicon chips. Boundary-dominated one-way edge states with pseudospin-dependent propagation directions have been observed. Furthermore, the robustness of edge states in hyperbolic photonic topological insulators is also verified. Our findings have potential applications in the field of designing high-efficient topological photonic devices with enhanced boundary responses.

Abstract High performance X-ray detector with ultra-high spatial and temporal resolution are crucial for biomedical imaging. This study reports a dynamic direct-conversion CMOS X-ray detector assembled with screen-printed CsPbBr3, whose mobility-lifetime product is 5.2 × 10−4 cm2 V–1 and X-ray sensitivity is 1.6 × 104 µC Gyair –1 cm–2. Samples larger than 5 cm $$\times$$ × 10 cm can be rapidly imaged by scanning this detector at a speed of 300 frames per second along the vertical and horizontal directions. In comparison to traditional indirect-conversion CMOS X-ray detector, this perovskite CMOS detector offers high spatial resolution (5.0 lp mm−1) X-ray radiographic imaging capability at low radiation dose (260 nGy). Moreover, 3D tomographic images of a biological specimen are also successfully reconstructed. These results highlight the perovskite CMOS detector’s potential in high-resolution, large-area, low-dose dynamic biomedical X-ray and CT imaging, as well as in non-destructive X-ray testing and security scanning.

Abstract Bacterial cellulose (BC) is a high-strong cellulose with high-purity produced by bacteria. The aim of this study was to explore the feasibility of using tofu soy whey as a novel and cheap culture medium to produce bacterial cellulose (BC) through the fermentation of kombucha. In this study, the statistical optimization of the culture medium for producing BC from kombucha was carried out by selecting different parameters. A three-level, three-factor Box-Behnken design (BBD) was used to determine the optimal levels for three significant variables (sucrose addition, kombucha inoculation amount and fermentation temperature). According to the results, the optimal fermentation conditions were found as follows: sucrose addition 8.5%, kombucha inoculation amount 10%, fermentation temperature 32℃, the BC yield can be up to 4.20 g/100 mL (D.W) under 11d fermentation. Besides, the BC was determined with strong tensile strength and water absorption capacity. By scanning electron microscopy (SEM) observation, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) determination, BC produced by soy whey and Hestrin-Schramm (HS) medium were compared. The results showed that BC produced from soy whey has a typical cellulose structure, characteristic peaks of typical functional groups of cellulose, and crystal diffraction peaks of type I natural cellulose. In conclusion, this study utilized the nutrients in the soy whey to obtain a high yield of bacterial cellulose, make full use of industrial waste water, which was more environmentally friendly and cheaper. Graphical Abstract

Background: Immunotherapy favors patients with tumors; however, only 3–26.3% of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors. Combined immunotherapy and chemotherapy has been explored against tumor; however, the combination remains controversial. This study aimed to investigate the tumor immune microenvironment (TIME) and the effects of platinum-based neoadjuvant chemotherapy (NACT) in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy. Methods: Multiplex immunohistochemistry (IHC) with 11 markers (cluster of differentiation [CD]3, CD8, CD4, CD11c, CD68, forkhead box P3 [Foxp3], programmed cell death 1 [PD-1], programmed cell death 1 ligand 1 [PD-L1], indoleamine 2,3-dioxygenase [IDO], cyclin-dependent kinase inhibitor 2A [p16], and cytokeratin [CK]) was performed to evaluate TIME from 108 matched pre- and post-NACT cervical cancer samples. The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing (RNA-seq) from four paired samples and subsequently verified in 41 samples using IHC. Results: The infiltration rate of the CD8+ T cells in treatment-naive cervical cancer was 0.73%, and those of Foxp3+ regulatory T cells (Tregs) and IDO+ cells were 0.87% and 17.15%, respectively. Moreover, immunoreactive T cells, dendritic cells, and macrophages were more in the stromal than the intratumor region. NACT increased dendritic, CD3+ T, CD8+ T, and CD4+ T cells and decreased Tregs. The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders. Non-responders primarily showed decreased Tregs and no increase in CD8+ T or dendritic cell infiltration. Furthermore, dendritic cells interacted more closely with CD3+ T cells after NACT, an effect primarily observed in responders. RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex (MHC) I and MHC II after chemotherapy, validated using IHC. Conclusions: NACT can reduce Tregs, and when tumor cells are effectively killed, antigen presentation is enhanced, subsequently activating antitumor immunity finitely. Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.

Abstract Background Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women. Method The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids. Result Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and β-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and β-carotene became significantly negatively correlated with BV. Conclusion This study found an inverse correlation between serum carotenoids and the prevalence of BV.

High-resolution image reconstruction from partial observations plays an important role in modern electronic information systems and has attracted widespread intense attention in both the academic and industrial fields. It is often difficult for the traditional handcrafted prior image reconstruction methods to recover delicate image details because of the inferior prior characterization abilities of these methods; this is especially true in the presence of complex electromagnetic perturbations in real-world environment scenes. Therefore, in this paper, an efficient image high-resolution reconstruction and perturbation defense model, named DGMR, is proposed based on deep Gaussian mixture learning. In particular, a simultaneous maximum a posterior (MAP) reconstruction-defense framework is designed based on the learned deep Gaussian mixture prior. Moreover, a channel attention mechanism is designed for image spatial correlation exploitation. Both the external and internal information are explored using a deep Gaussian mixture. A deep residual Swin transformer module is constructed to further characterize the image and learn Gaussian mixture priors, including both the image means and variances; in contrast, existing methods calculate only the image means but ignore the variances. Furthermore, sparse regularized united learning is developed to improve invariant representation learning ability, and the model is customized by internal learning with spatial constraints and regularization. Extensive qualitative and quantitative experiments are performed, confirming that DGMR is superior to the existing state-of-the-art systems.

Abstract Radioresistance is a major constraint on the efficacy of lung cancer radiotherapy, but its mechanism has not been fully elucidated. Here, we found that FBXO22 was aberrantly highly expressed in lung cancer and that FBXO22 knockdown increased the radiosensitivity of lung cancer cells. Mechanistically, FBXO22 promoted Rad51 gene transcription by increasing the level of FOXM1 at the Rad51 promoter, thereby inducing the formation of lung cancer radioresistance. Furthermore, we found that deguelin, a potential inhibitor of FBXO22, enhanced radiosensitivity in an FBXO22/Rad51-dependent manner and was safely tolerated in vivo. Collectively, our results illustrate that FBXO22 induces lung cancer radioresistance by activating the FOXM1/Rad51 axis and provide preclinical evidence for the clinical translation of this critical target.

The objective of this study is to examine the potential cardiovascular risk of climate-related declines in seafood consumption among First Nations in British Columbia by assessing the combined effects of reduced omega-3 fatty acids and mercury intake from seafood on the risk of myocardial infarction (MI) in 2050 relative to 2009. The data were derived from the First Nations Food, Nutrition, and Environment Study. Seafood consumption among 369 randomly selected participants was estimated, and hair mercury concentrations were measured. Declines in seafood consumption were modelled based on previously projected climate change scenarios, and the associated changes in nutrients and contaminants were used to estimate the cardiovascular risk. Reduced seafood consumption was projected to increase the risk of MI by 4.5%–6.5% among older individuals (≥50 years), by 1.9%–2.6% in men, and by 1.3%–1.8% in women under lower and upper climate change scenarios, respectively. Reduced seafood consumption may have profound cardiovascular implications. Effective strategies are needed to promote sustainable seafood harvests and access to seafood for coastal First Nations.

Background Cushing’s syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters.Methods A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD.Results A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p

ABSTRACTTo investigate the HPV vaccine coverage and post-vaccination adverse reactions in Gansu Province, Western China, from 2018 to 2021. Data on suspected adverse reactions to HPV vaccines were collected from the Chinese Vaccine Adverse Event Following Immunization (AEFI). Estimate the incidence rates of Common Adverse Reaction and Rare Adverse Reaction. HPV vaccine coverage among females in different age groups was calculated using data from the Gansu Provincial Immunization Information Platform. The first-dose HPV vaccine coverage rate among females aged 9 to 45 was 2.02%, with the lowest rate of less than 1% observed in females aged 9 to 14. From 2018 to 2021, the incidence rates of Common Adverse Reaction and Rare Adverse Reaction reported in females after HPV vaccination were 11.82 and 0.39 per 100,000 doses, respectively. Common Adverse Reaction included fever (5.52 per 100,000 doses), local redness and swelling (3.33 per 100,000 doses), fatigue (3.15 per 100,000 doses), headache (2.76 per 100,000 doses), as well as local induration and nausea/vomiting (1.97 per 100,000 doses). Adverse reactions mainly occurred within 1 day after vaccination, followed by 1 to 3 days after vaccination. The HPV vaccine coverage rate among females aged 9 to 14 in Gansu Province is remarkably low, and there is an urgent need to enhance vaccine coverage. From 2018 to 2021, the incidence of Adverse reaction Following Immunization HPV vaccination fell within the expected range, indicating the vaccine’s safety profile.

Abstract Objective To analyze the risk factors associated with intubated critically ill patients in the emergency department (ED) and develop a prediction model by machine learning algorithms. Methods This study was conducted in an academic tertiary hospital in Hangzhou, China. Critically ill patients admitted to the ED were retrospectively analyzed from May 2018 to July 2022. The demographic characteristics, distribution of organ dysfunction, parameters for different organs’ examination, and status of mechanical ventilation were recorded. These patients were assigned to the intubation and non‐intubation groups according to ventilation support. We used the eXtreme Gradient Boosting (XGBoost) algorithm to develop the prediction model and compared it with other algorithms, such as logistic regression, artificial neural network, and random forest. SHapley Additive exPlanations was used to analyze the risk factors of intubated critically ill patients in the ED. Results Of 14,589 critically ill patients, 10,212 comprised the training group and 4377 comprised the test group; 2289 intubated patients were obtained from the electronic medical records. The mean age, mean scores of vital signs, parameters of different organs, and blood oxygen examination results differed significantly between the two groups (p

Coastal water level information is crucial for understanding flood occurrences and changing risks. Here, we validate the preliminary version (0.9) of NOAA’s Coastal Ocean Reanalysis (CORA), which is a 43-year reanalysis (1979–2021) of hourly coastal water levels for the Gulf of Mexico and Atlantic Ocean (i.e., the Gulf and East Coast region, or GEC). CORA-GEC v0.9 was conducted by the Renaissance Computing Institute using the coupled ADCIRC+SWAN coastal circulation and wave model. The model uses an unstructured mesh of nodes with varying spatial resolution that averages 400 m near the coast and is much coarser in the open ocean. Water level variations associated with tides and meteorological forcing are explicitly modeled, while lower-frequency water level variations are included by dynamically assimilating observations from NOAA’s National Water Level Observation Network. We compare CORA to water level observations that were either assimilated or not, and find that the reanalysis generally performs better than a state-of-the-art global ocean reanalysis (GLORYS12) in capturing the variability on monthly, seasonal, and interannual timescales as well as the long-term trend. The variability of hourly non-tidal residuals is also shown to be well resolved in CORA when compared to water level observations. Lastly, we present a case study of extreme water levels and coastal inundations around Miami, Florida to demonstrate an application of CORA for studying flood risks. Our assessment suggests that NOAA’s CORA-GEC v0.9 provides valuable information on water levels and flooding occurrence from 1979–2021 in areas that are experiencing changes across multiple time scales. CORA potentially can enhance flood risk assessment along parts of the U.S. Coast that do not have historical water level observations.