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Abstract Objective The diagnostic value of serum human epididymal secretory protein 4 (HE4) for endometrial cancer (EC) was assessed via evidence-based medicine (EBM) and systematic review (SR) methodologies. Methods The Cochrane Library, PubMed, Web of Science, Embase, CBM, CNKI, and Wan Fang databases were searched up to April 1st, 2024, to identify relevant literature. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was utilized to evaluate the quality of the selected studies. The meta-analysis was conducted via RevMan 5.3, STATA 16.1, and Meta-disc software. Results A total of 22 studies comprising 9036 cases (3776 cases in the case group and 5260 cases in the control group) were included. The results revealed that HE4 exhibited a pooled sensitivity of 0.59 [95% CI (0.53, 0.64)], specificity of 0.93 [95% CI (0.88, 0.96)], positive likelihood ratio (PLR) of 6.87 [95% CI (4.57, 10.33)], negative likelihood ratio (NLR) of 0.46 [95% CI (0.39, 0.54)], diagnostic odds ratio (DOR) of 14.36 [95% CI (9.37, 21.17)], and area under the receiver operating characteristic curve (AUC) of 0.78 [95% CI (0.75, 0.82)]. Conclusions Serum HE4 demonstrates high specificity and moderate sensitivity for diagnosing EC, thus serving as a valuable biomarker for clinicians either alone or in conjunction with other tumour markers.

Abstract As image–text matching (a critical task in the field of computer vision) links cross-modal data, it has captured extensive attention. Most of the existing methods intended for matching images and texts explore the local similarity levels between images and sentences to align images with texts. Even though this fine-grained approach has remarkable gains, how to further mine the deep semantics between data pairs and focus on the essential semantics in data remains to be quested. In this work, a new semantic filtering and adaptive approach (FAAR) was proposed to ease the above problem. To be specific, the filtered attention (FA) module selectively focuses on typical alignments with the interference of meaningless comparisons eliminated. Next, the adaptive regulator (AR) further adjusts the attention weights of key segments for filtered regions and words. The superiority of our proposed method was validated by a number of qualitative experiments and analyses on the Flickr30K and MSCOCO data sets.

Abstract With the continuous advancement of virtualization technology and the widespread adoption of 5G networks, the application of the Network Function Virtualization (NFV) architecture has become increasingly popular and prevalent. While the NFV architecture brings a lot of advantages, it also introduces security challenges, including the effective and efficient verification of the integrity of deployed Virtual Network Functions (VNFs) and ensuring the secure operation of VNFs. To address the challenge of efficiently conducting virtual remote attestation for VNFs and establishing trust in virtualized environments like NFV architecture, we propose TVRAVNF, which is a highly efficient and low-cost TEE-based virtual remote attestation scheme for VNFs. The scheme we proposed ensures the security and effectiveness of the virtual remote attestation process by leveraging TEE. Furthermore, we introduces a novel local attestation mechanism, which not only reduces the overall overhead of the virtual remote attestation process but also shortens the attestation interval to mitigate Time-Of-Check-Time-Of-Use attacks, thereby enhancing overall security. We conduct experiments to validate the overhead of the TVRAVNF scheme and compare its performance with that of a typical remote attestation process within a maximum unattested time interval. The experimental results demonstrate that, by employing the local attestation mechanism, our solution achieves nearly an 80% significant performance improvement with a relatively small time overhead for small to medium-sized files. This further substantiates the significant advantages of our approach in both security and efficiency.

In order to improve the efficiency of making short-term (daily and weekly) production plan, fast analysis of the completion of equipment plan and the effect of visual design and visual expression, based on the UAV image data, the paper puts forward the method of making short-term production plan quickly, and develops the Intelligent Mining Design Software System by C + + language, “IMDS” software for short. The results show that: ① the visual effect of short-term planning is enhanced by using UAV image data; ② the Stope Step Line of opencast coal mine in the range of 1 500 m × 1 500 m is automatically generated by using UAV image data; The time is 17.392 s, but the manual drawing takes 5 min; ③ the weekly plan and daily plan are made by using software platform, which reduces the need of repeated on-site inspection by miners and the complexity of calculation of traditional mining entity and block, the internal pre-equipment capability analysis module directly analyzes the short-term plan of the completion of equipment information; ④ based on image data for ramp rapid rendering, automatic calculation of ramp fill and excavation volume, to achieve the accuracy of transport road construction; ⑤ “IMDS” software provides 10 functional modules, 235 sub-functions, the short-term planning of UAV image data and the rapid monthly and annual planning of engineering quantities and precise determination of engineering positions based on three-dimensional geological entity modules can be realized; ⑥ the short-term production plan can be released to the Integrated Management and control platform of opencast coal mine by the way of data release, which can realize the visual display of plan data, realize the data one by one, and ensure the accuracy and safety of data. The development of the system software contributes to the further development of the intelligent mining design software system.

Abstract Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.

Abstract FeSe is one of the most enigmatic superconductors. Among the family of iron-based compounds, it has the simplest chemical makeup and structure, and yet it displays superconducting transition temperature ( T c $T_{\text{c}}$ ) spanning 0 to 15 K for thin films, while it is typically 8 K for single crystals. This large variation of T c $T_{\text{c}}$ within one family underscores a key challenge associated with understanding superconductivity in iron chalcogenides. Here, using a dual-beam pulsed laser deposition (PLD) approach, we have fabricated a unique lattice-constant gradient thin film of FeSe which has revealed a clear relationship between the atomic structure and the superconducting transition temperature for the first time. The dual-beam PLD that generates laser fluence gradient inside the plasma plume has resulted in a continuous variation in distribution of edge dislocations within a single film, and a precise correlation between the lattice constant and T c $T_{\text{c}}$ has been observed here, namely, T c ∝ c − c 0 $T_{\text{c}} \propto \sqrt{c- c_{0}}$ , where c is the c-axis lattice constant (and c 0 $c_{0}$ is a constant). This explicit relation in conjunction with a theoretical investigation indicates that it is the shifting of the d xy $d_{\text{xy}}$ orbital of Fe which plays a governing role in the interplay between nematicity and superconductivity in FeSe.

Abstract In order to obtain an understanding of the relationship between the optical absorption and the transverse relaxation, the influences of linearly polarized light respectively at 133Cs D1 and D2 lines on the transverse relaxation of ground-state 133Cs atoms are studied. Under different vapor temperatures, light intensities and light frequencies, transverse spin relaxation times are separately measured for 133Cs atoms in different hyperfine levels. For theoretically analyzing the measuring results, especially for an unusual trend that the transverse spin relaxation time rises with the increase of light intensity, photon absorption cross-sections of linearly polarized light by 133Cs atoms are simulated. The experimental results show that through influencing the optical absorption and spin-exchange collisions, the linearly polarized light plays a remarkable role in the transverse spin relaxation. The results obtained by this paper can provide a guide to find the optimal intensity and frequency of linearly polarized light in practical applications for decreasing the influences of linearly polarized light on the transverse relaxation.

Abstract The transformation and upgrading of China’s manufacturing industry is supported by smart and green manufacturing, which have great potential to empower the nation’s green development. This study examines the impact of the Made in China 2025 industrial policy on urban green economic growth. This study applies the super-slacks-based measure model to measure cities’ green economic growth, using the double machine learning model, which overcomes the limitations of the linear setting of traditional causal inference models and maintains estimation accuracy under high-dimensional control variables, to conduct an empirical analysis based on panel data of 281 Chinese cities from 2006 to 2021. The results reveal that the Made in China 2025 strategy significantly drives urban green economic growth, and this finding holds after a series of robustness tests. A mechanism analysis indicates that the Made in China 2025 strategy promotes green economic growth through green technology progress, optimizing energy consumption structure, upgrading industrial structure, and strengthening environmental supervision. In addition, the policy has a stronger driving effect for cities with high manufacturing concentration, industrial intelligence, and digital finance development. This study provides valuable theoretical insights and policy implications for government planning to promote high-quality development through industrial policy.

Abstract Film and movie genres play a pivotal role in captivating relevant audiences across interactive multimedia platforms. With a focus on entertainment, streaming providers are increasingly prioritizing the automatic generation of movie genres within cloud-based media services. In service management, the integration of a hybrid convolutional network proves to be instrumental in effectively distinguishing between a diverse array of video genres. This classification process not only facilitates more refined recommendations and content filtering but also enables targeted advertising. Furthermore, given the frequent amalgamation of components from various genres in cinema, there arises a need for social media networks to incorporate real-time video classification mechanisms for accurate genre identification. In this study, we propose a novel architecture leveraging deep learning techniques for the detection and classification of genres in video films. Our approach entails the utilization of a bidirectional long- and short-term memory (BiLSTM) network, augmented with video descriptors extracted from EfficientNet-B7, an ImageNet pre-trained convolutional neural network (CNN) model. By employing BiLSTM, the network acquires robust video representations and proficiently categorizes movies into multiple genres. Evaluation on the LMTD dataset demonstrates the substantial improvement in the performance of the movie genre classifier system achieved by our proposed architecture. Notably, our approach achieves both computational efficiency and precision, outperforming even the most sophisticated models. Experimental results reveal that EfficientNet-BiLSTM achieves a precision rate of 93.5%. Furthermore, our proposed architecture attains state-of-the-art performance, as evidenced by its F1 score of 0.9012.

Objectives Scoliosis associated with spondylolisthesis is a common phenomenon. Recent research has reported that scoliosis can spontaneously disappear after lumbar spinal fusion surgery. Researchers have advocated that, for scoliosis associated with vertebral slippage, surgery for the latter may be the only necessary intervention, while unnecessary surgery for scoliosis should be avoided. So we propose that minimally invasive techniques can achieve treatment effects similar to those of open surgery. Therefore, in this study, we aimed to investigate the clinical efficacy of unilateral dual‐channel endoscopic lumbar interbody fusion (ULIF) for treating lumbar spondylolisthesis with spinal scoliosis. Methods This study retrospectively analyzed patients with lumbar spondylolisthesis and spinal scoliosis who underwent ULIF between September 2021 and September 2023. Measurements of the Cobb angle, lumbar lordosis (LL) angle, sacral slope (SS), slip percentage (SP), slip angle (SA), L1 plumb line‐S1 distance (LASD), and average intervertebral height (AIH) were taken preoperatively, immediately following surgery, 3 months after surgery, and at the final follow‐up. The visual analogue scale (VAS), Oswestry disability index (ODI), and Japanese Orthopaedic Association (JOA) scoring systems were used to assess clinical results. The surgical efficacy was evaluated by comparing these parameters before and after surgery. Comparison of indicators within the same group was conducted using one‐way repeated‐measures analysis of variance or paired sample t‐tests, whereas between‐group differences were compared using an independent t‐test. Results This study included 31 individuals who underwent surgery and completed follow‐up. The follow‐up period did not show a significant loss of corrective angles. Furthermore, the Cobb angle, SP, SA, and LASD significantly decreased after surgery, whereas the LL angle, SS, and AIH significantly increased (all p 0.05). However, other parameters significantly improved during the follow‐up period at all time points, except from 3 months to the final follow‐up period (p > 0.05). Throughout the follow‐up period, the lower back and leg pain VAS, ODI, and JOA scores considerably improved compared with the preoperative levels (p

Background and aimsDysfunction of endothelial cells represents a crucial aspect in the pathogenesis of atherosclerosis. The aim of this study was to explore the protective effects of alisol A on vascular endothelial cells and its possible mechanisms.MethodsAn atherosclerosis model was established by feeding ApoE-/- mice with high-fat chow. Alisol A (150 mg/kg/d) or atorvastatin (15 mg/kg/d) was administered, and the levels of blood lipids were evaluated. The effect of the drugs on atherosclerotic plaques was observed by staining the aorta with Sudan IV. In vitro experiments were conducted using human aortic endothelial cells (HAECs) to assess the effects of alisol A on cell proliferation, migration, tubulation, secretion, and cellular integrity by CCK-8 assay, wound healing assay, angiogenesis assay, NO secretion, and release of LDH. Transcriptomics and molecular docking were used to explore the mechanism of plaque inhibition and stabilization by alisol A.ResultsAlisol A significantly reduced the aortic plaque area in ApoE−/− mice fed with high-fat chow. In vitro, alisol A had a protective effect on HAECs, which was reflected in the inhibition of vascular endothelial cell proliferation, promotion of NO secretion by vascular endothelial cells, inhibition of vascular endothelial cell migration and angiogenesis, and the maintenance of cell membrane integrity. Therefore, alisol A inhibited and stabilized atherosclerotic plaques and slowed down the process of atherosclerosis. Transcriptomics studies showed 4,086 differentially expressed genes (DEGs) in vascular endothelial cells after alisol A treatment. Enrichment analysis indicated that many genes involved in TNF signaling pathway were differentially expressed, and inflammatory genes were suppressed. The molecular docking results verified the hypothesis that alisol A has a low binding energy after docking with TNF target, and TNF could be a potential target of alisol A.ConclusionAlisol A produced protection on vascular endothelial cells, achieving inhibition and stabilization of atherosclerotic plaques.

The surgical management of extensive jugular foramen schwannomas presents a formidable challenge, aiming for gross total resection while minimizing complications. Here, we present a case with giant triple dumbbell-shaped jugular Foramen Schwannoma. A 45-year-old male with a one-year history of a left neck mass underwent surgery. Initial misdiagnosis of submandibular gland inflammation led to persistent symptoms despite anti-inflammatory treatment. Imaging revealed a large lesion in the left cerebellar peduncle-neck-jugular foramen region (39.6 x 26.2 x 90 mm). The combination of retrosigmoid and transcervical approach was selected. Sufficient drilling of the infralabyrinthine, retrofacial area of the mastoid with facial nerve transposition is important for the safe gross total removal of the tumor. The patient underwent a gross total removal of the tumor. Facial nerve function was preserved. Although dysphagia and hoarseness complicated postoperatively, he became able to take foods orally after the surgery. In conclusion, this case underscores the successful surgical approach for a large jugular foramen Schwannoma, emphasizing the importance of precise techniques to achieve complete tumor resection while minimizing postoperative complications.

Background: Few studies have compared the performances of those reported miRNAs as biomarkers for heart failure with reduced EF (HFrEF) in a population at high risk. The purpose of this study is to investigate comprehensively the performance of those miRNAs as biomarkers for HFrEF. Methods: By using bioinformatics methods, we also examined these miRNAs' target genes and possible signal transduction pathways. We collected serum samples from patients with HFrEF at Zhongshan Hospital. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for HFrEF. miRWALK2.0, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. Results: The study included 48 participants, of whom 30 had HFrEF and 18 had hypertension with normal left ventricular ejection fraction (LVEF). MiR-378, miR-195-5p were significantly decreased meanwhile ten miRNAs were remarkably elevated (miR-21-3p, miR-21-5p, miR-106-5p, miR-23a-3p, miR-208a-3p, miR-1-3p, miR-126-5p, miR-133a-3p, miR-133b, miR-223-3p) in the serum of the HFrEF group. Conclusion: The combination of miR 133a-3p, miR 378, miR 1-3p, miR 106b-5p, and miR 133b has excellent diagnostic performance for HFrEF, and there is a throng of mechanisms and pathways by which regulation of these miRNAs may affect the risk of HFrEF.

BackgroundEnterostomy is important for radical resection of colorectal cancer (CRC). Nevertheless, the notable occurrence of complications linked to enterostomy results in a reduction in patients’ quality of life and impedes adjuvant therapy. This study sought to forecast early stoma-related complications (ESRCs) by leveraging easily accessible nutrition-inflammation markers in CRC patients.MethodsThis study involved 470 individuals with colorectal cancer who underwent intestinal ostomy at Changhai Hospital Affiliated with Naval Medical University as the internal cohort. Between January 2016 and December 2018, the patients were enrolled and randomly allocated into a primary training group and a secondary validation group, with a ratio of 2:1 being upheld. The research encompassed collecting data on each patient’s clinical and pathological status, along with preoperative laboratory results. Independent risk factors were identified through Lasso regression and multivariate analysis, leading to the development of clinical models represented by a nomogram. The model’s utility was assessed using decision curve analysis, calibration curve, and ROC curve. The final model was validated using an external validation set of 179 individuals from January 2015 to December 2021.ResultsAmong the internal cohort, stoma complications were observed in 93 cases. Multivariate regression analysis confirmed that age, stoma site, and elevated markers (Mon, NAR, and GLR) in conjunction with diminished markers (GLB and LMR) independently contributed to an increased risk of ESRCs. The clinical model was established based on these seven factors. The training, internal, and external validation groups exhibited ROC curve areas of 0.839, 0.812, and 0.793, respectively. The calibration curve showed good concordance among the forecasted model with real incidence of ostomy complications. The model displayed outstanding predictive capability and is deemed applicable in clinical settings, as evidenced by Decision Curve Analysis.ConclusionThis study identified nutrition-inflammation markers (GLB, NAR, and GLR) in combination with demographic data as crucial predictors for forecasting ESRCs in colorectal cancer patients. A novel prognostic model was formulated and validated utilizing these markers.

Excessive residue of metronidazole (MNZ) in food is harmful to the human body. There is an urgent demand to develop a portable tool for MNZ detection on-site. In this study, fifteen aptamers were prepared through targeted base mutation. Apt1-3 with the highest enrichment was chosen for further study. Its affinity was characterized by molecular docking simulation, AuNPs colorimetric assay, graphene oxide (GO) fluorescence assay, and exonuclease assay. Kd was determined by GO fluorescence assay (Kd: 92.60 ± 25.59 nM). Its specificity was also characterized by an exonuclease assay. A novel aptasensor was constructed by using the newly identified aptamer combined with the smartphone dark box. The principle of color change is caused by the aggregation state of AuNPs. Smartphones act as reading instruments. The detection can be completed in just a few seconds without the aid of instruments, achieving a detection limit of 0.15 nmol/mL and a range of 6.7–44.4 nmol/mL (R2 = 0.9810). Therefore, the constructed smartphone colorimetric sensor based on mutant aptamers has important applications in food detection.

The Qinghai-Tibet Plateau (QTP) is critical for global carbon and nitrogen cycling and carbon sequestration because of its sensitive positive response to global warming. Although the factors affecting soil carbon and nitrogen in the sophisticated mountainous terrain of the QTP have been extensively investigated, the specific “direct” or “indirect” roles and their influence path remain unclear. In this study, the patterns of soil total carbon contents (STC) and soil total nitrogen contents (STN) were examined based on 445 soil samples collected from 89 plots in the Heihe River source region, northeastern QTP. The objective is to elucidate the interactions and driving mechanisms among climate, vegetation, geographical environmental factors, and soil properties for STC/STN. We found; (1) notable differences in STC/STN between altitudinal gradients and LULC types, exhibiting an overall increasing trend, followed by a decreasing trend with an increase in altitude; (2) the STC/STN in the 0–50 cm soil layer declined as soil depth increased, such that the distinctive “surface aggregation” characteristics were confirmed. In general, regions with higher soil total carbon densities (STCD) and soil total nitrogen densities (STND) were concentrated in the southeast of the watershed, whereas regions with lower densities were identified in the northwest. (3) Soil water content (SWC) and bulk density (BD) are critical in distributing STC/STN. Among the significant environmental factors influencing STC, SWC had the maximum direct path coefficient (0.42), suggesting a direct effect. Other factors, such as land-use and land-cover change (LULC), BD, pH, and normalized difference vegetation index (NDVI) affected the STC content via a wide variety of pathways. For STN, SWC (0.46), and pH (−0.2) showed direct path coefficients with magnitudes greater than the indirect path coefficients, suggesting direct effects. Moreover, NDVI, BD, and precipitation affected the STN through other factors. These findings provide insights into soil carbon and nitrogen dynamics in alpine soil under sophisticated mountainous terrain. They provide valuable support for studying soil carbon and nitrogen cycling, and for evaluating carbon and nitrogen stocks in cold regions.

Abstract Medical imaging AI systems and big data analytics have attracted much attention from researchers of industry and academia. The application of medical imaging AI systems and big data analytics play an important role in the technology of content based remote sensing (CBRS) development. Environmental data, information, and analysis have been produced promptly using remote sensing (RS). The method for creating a useful digital map from an image data set is called image information extraction. Image information extraction depends on target recognition (shape and color). For low-level image attributes like texture, Classifier-based Retrieval(CR) techniques are ineffective since they categorize the input images and only return images from the determined classes of RS. The issues mentioned earlier cannot be handled by the existing expertise based on a keyword/metadata remote sensing data service model. To get over these restrictions, Fuzzy Class Membership-based Image Extraction (FCMIE), a technology developed for Content-Based Remote Sensing (CBRS), is suggested. The compensation fuzzy neural network (CFNN) is used to calculate the category label and fuzzy category membership of the query image. Use a basic and balanced weighted distance metric. Feature information extraction (FIE) enhances remote sensing image processing and autonomous information retrieval of visual content based on time-frequency meaning, such as color, texture and shape attributes of images. Hierarchical nested structure and cyclic similarity measure produce faster queries when searching. The experiment’s findings indicate that applying the proposed model can have favorable outcomes for assessment measures, including Ratio of Coverage, average means precision, recall, and efficiency retrieval that are attained more effectively than the existing CR model. In the areas of feature tracking, climate forecasting, background noise reduction, and simulating nonlinear functional behaviors, CFNN has a wide range of RS applications. The proposed method CFNN-FCMIE achieves a minimum range of 4–5% for all three feature vectors, sample mean and comparison precision-recall ratio, which gives better results than the existing classifier-based retrieval model. This work provides an important reference for medical imaging artificial intelligence system and big data analysis.

Abstract Background Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. Methods DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. Results The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. Conclusion KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

Abstract The reorientation of Earth through rotation of its solid shell relative to its spin axis is known as True polar wander (TPW). It is well-documented at present, but the occurrence of TPW in the geologic past remains controversial. This is especially so for Late Jurassic TPW, where the veracity and dynamics of a particularly large shift remain debated. Here, we report three palaeomagnetic poles at 153, 147, and 141 million years (Myr) ago from the North China craton that document an ~ 12° southward shift in palaeolatitude from 155–147 Myr ago (~1.5° Myr−1), immediately followed by an ~ 10° northward displacement between 147–141 Myr ago (~1.6° Myr−1). Our data support a large round-trip TPW oscillation in the past 200 Myr and we suggest that the shifting back-and-forth of the continents may contribute to the biota evolution in East Asia and the global Jurassic–Cretaceous extinction and endemism.

Abstract Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of β-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and β-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

High-intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate-intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved. 50 HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterward, shRNA-containing adenovectors were injected into mice, yielding five groups: control, HF, HF + HIIT + scrambled shRNA, HF + HIIT + shMetrnl, and HF + Metrnl (HF + exogenous Metrnl). Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups. Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMPK in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning. HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.

IntroductionNuclear factor kappa (NF-κB) plays a key role in cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay.MethodsThis work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells.ResultsFinally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells.ConclusionOverall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

Changji'an Formula (CJAF) is a Chinese herbal compound, which is effective against irritable bowel syndrome with predominant diarrhea (IBS-D) in clinic. However, the molecular mechanism has not been well defined. In the current study, the potential targets and signaling pathways of CJAF against IBS-D were predicted using network pharmacology analysis. The pharmacological mechanisms of CJAF against IBS-D and the potential mechanism were validated by using an IBS-D mouse model induced by enema with trinitrobenzene-sulfonic acid (TNBS) plus with restraint stress and further intervened with CJAF. A total of 232 active compounds of CJAF were obtained, a total of 397 potential targets for the active ingredients were retrieved and a total of 219 common targets were obtained as the potential targets of CJAF against IBS-D. GO and KEGG enrichment analyses showed that multiple targets were enriched and could be experimentally validated in a mouse model of IBS-D. The mechanisms were mainly converged on the immune and inflammatory pathways, especially the NF-κB, TNF and IL-17 signaling pathway, which were closely involved in the treatment of CJAF against IBS-D. Animal experiment showed that CJAF alleviated visceral hypersensitivity and diarrhea symptom of IBS-D. CJAF also restored the histological and ultrastructure damage of IBS-D. The result of Western blot showed that CJAF upregulated colonic tight junction proteins of ZO-1, Occludin and Claudin-1. Further results demonstrated that CJAF inhibited the protein expression of NF-κB/NLRP3 inflammasome pathway targets and downregulated proinflammatory mediators of IL-1β, IL-18, TNF-α. In conclusion, CJAF could effectively reduce inflammatory response and alleviate visceral hypersensitivity as well as diarrhea symptom of IBS-D by inhibiting the NF-κB/NLRP3 signaling pathway. This study not only reveals the mechanism of CJAF against IBS-D, but also provides a novel therapeutic strategy for IBS-D.

Abstract Objectives Calcifying nanoparticles (CNPs), referred to as nanobacteria (NB), are recognized to be associated with ectopic calcification. This study aims to isolate and culture CNPs from the dental plaque of patients with periodontal disease and investigate their possible role in unravelling the aetiology of periodontal disease. Material and Methods Supragingival and subgingival plaques were sampled from 30 periodontitis patients for CNPs isolation and culture. Alkaline phosphatase (ALP) content changes were tracked over time. Positive samples underwent thorough morphological identification via hematoxylin and eosin (HE) staining, Alizarin red S (ARS), and transmission electron microscopy (TEM). The chemical composition of CNPs analysis involved calcium (Ca) and phosphorus (P) content determination, Fourier transform infrared spectroscopy (FTIR), and X‐ray diffraction (XRD). Results The subgingival plaque dental group exhibited a higher CNPs isolation rate at 36.67% (11/30) compared to the supragingival dental plaque group at 66.67% (20/30). ALP activity varied among the positive, negative and control groups. Morphological observation characterized the CNPs as round, oval, and ellipsoid particles with Ca deposits. Chemical analysis revealed the Ca/P ratio was 0.6753. Hydroxyl, methyl, carbonate, phosphate, hydrogen phosphate, and dihydrogen phosphate were detected by FTIR; the main chemical components detected by XRD were hydroxyapatite and tricalcium phosphate. Conclusion CNPs were found in periodontitis‐related dental plaque and exhibited the potential to develop calcified structures resembling dental calculus. However, the potential involvement of ALP in CNPs formation requires deeper exploration, as does the precise nature of its role and the interrelation with periodontitis demand a further comprehensive investigation.

Objective: To investigate the efficacy and safety of intravenous peramivir compared to oral oseltamivir for pediatric influenza by a method of meta-analysis. Methods: Clinical trials involving intravenous peramivir versus oral oseltamivir therapy in children with influenza were searched from six databases until July 2023. Data were processed using Stata 15.0 software. Results: Seven published articles were identified in this review. The combined results exhibited that the clinical effective rate in the peramivir group (76.09 %) was higher than that in the oseltamivir group (58.85 %) (RR= 1.12, 95 %CI: 1.01∼1.24, P = 0.038). The incidence of adverse reactions in the peramivir group (13.31 %) was lower than that in the oseltamivir group (17.34 %) (RR= 0.77, 95 %CI: 0.61–0.96, P = 0.023). Compared with the oseltamivir group, the peramivir group had lower recovery time of body temperature (WMD= -19.81, 95 %CI: -27.58∼-12.04, P < 0.001). Conclusion: Compared with oral oseltamivir, intravenous peramivir has better efficacy and higher safety for pediatric influenza.

Hyalinizing clear cell carcinomas (HCCCs) are infrequent, malignant tumors characterized by their low-grade nature. They typically originate from minor salivary glands. However, these tumors can potentially emerge in any location with minor salivary glands, including the nasopharynx. This report presents two cases of HCCC in females aged 61 and 72 years, with both tumors approximately 4 cm in size. In the first case, a 72-year-old female presented with recurrent bilateral epistaxis. Imaging studies revealed a nasopharyngeal mass, surgically excised, and histopathological analysis confirmed HCCC. Postoperatively, the patient received combined chemotherapy and radiotherapy, achieving a recurrence-free status 2.5 years later. The second case involves a 61-year-old female with a two-year history of bloody nasal discharge. Imaging studies identified a nasopharyngeal lesion, surgically removed, and histopathological examination confirmed HCCC. This patient underwent radiotherapy followed by combination chemotherapy with paclitaxel and carboplatin, displaying no signs of recurrence upon reevaluation after 10 months. These cases highlight the successful management of HCCC through a comprehensive, multimodal approach, integrating surgical intervention and adjuvant therapy. The favorable outcomes emphasize the significance of a thorough treatment strategy for HCCC in the nasopharynx, providing valuable insights for clinicians. Further studies are essential to enhance our understanding of this rare entity and refine treatment protocols for optimized patient outcomes.

Abstract Ca2+ signaling is essential for oligodendrocyte (OL) development and myelin formation. Inositol 1,4,5‐trisphosphate receptor type 2 (ITPR2) is an endoplasmic reticulum calcium channel and shows stage‐dependent high levels in postmitotic oligodendrocyte precursor cells (OPCs). The role and potential mechanism of ITPR2 in OLs remain unclear. In this study, it is revealed that loss of Itpr2 in OLs disturbs Ca2+ homeostasis and inhibits myelination in adolescent mice. Animals with OL‐specific deletion of Itpr2 exhibit anxiety/depressive‐like behaviors and manifest with interrupted OPC proliferation, leading to fewer mature OLs in the brain. Detailed transcriptome profiling and signal pathway analysis suggest that MAPK/ERK‐CDK6/cyclin D1 axis underlies the interfered cell cycle progression in Itpr2 ablated OPCs. Besides, blocking MAPK/ERK pathway significantly improves the delayed OPC differentiation and myelination in Itpr2 mutant. Notably, the resting [Ca2+]i is increased in Itpr2 ablated OPCs, with the elevation of several plasma calcium channels. Antagonists against these plasma calcium channels can normalize the resting [Ca2+]i level and enhance lineage progression in Itpr2‐ablated OPCs. Together, the findings reveal novel insights for calcium homeostasis in manipulating developmental transition from OPCs to pre‐OLs; additionally, the involvement of OLs‐originated ITPR2 in depressive behaviors provides new therapeutic strategies to alleviate myelin‐associated psychiatric disorders.

Objectives: FGFR4-variant and wild-type colorectal cancer (CRC) organoids were developed to investigate the effects of FGFR4-targeted drugs, including FGFR4-IN and erdafitinib, on CRC and their possible molecular mechanism. Methods: Clinical CRC tissues were collected, seven CRC organoids were developed, and whole exome sequencing (WES) was performed. CRC organoids were cultured and organoid drug sensitivity studies were conducted. Finally, an FGFR4-variant (no wild-type) CRC patient-derived orthotopic xenograft mouse model was developed. Western blot measured ERK/AKT/STAT3 pathway-related protein levels. Results: WES results revealed the presence of FGFR4-variants in 5 of the 7 CRC organoids. The structural organization and integrity of organoids were significantly altered under the influence of targeted drugs (FGFR4-IN-1 and erdafitinib). The effects of FGFR4 targeted drugs were not selective for FGFR4 genotypes. FGFR4-IN-1 and erdafitinib significantly reduced the growth, diameter, and Adenosine Triphosphate (ATP) activity of organoids. Furthermore, chemotherapeutic drugs, including 5-fluorouracil and cisplatin, inhibited FGFR4-variant and wild-type CRC organoid activity. Moreover, the tumor volume of mice was significantly reduced at week 6, and p-ERK1/2, p-AKT, and p-STAT3 levels were down-regulated following FGFR4-IN-1 and erdafitinib treatment. Conclusions: FGFR4-targeted and chemotherapeutic drugs inhibited the activity of FGFR4-variant and wild-type CRC organoids, and targeted drugs were more effective than chemotherapeutic drugs at the same concentration. Additionally, FGFR4 inhibitors hindered tumorigenesis in FGFR4-variant CRC organoids through ERK1/2, AKT, and STAT3 pathways. However, no wild-type control was tested in this experiment, which need further confirmation in the next study.

Background: The prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes. Methods: The active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The “drug-active compound-potential target” network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses. Results: Forty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells. Conclusions: Herba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.

Objective: In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis. Methods: We screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction. Results: tRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC. Conclusion: tRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression.

Remotely sensed land surface temperature (LST) is critical for retrieving evapotranspiration (ET). However, due to cloud contamination, LST is often limited to clear-sky conditions and the differences between clear-sky and all-sky LST will lead to clear-sky biases of LST. Consequently, the accuracy of ET varies drastically under different weather conditions. To evaluate the impact of clear-sky biases on ET estimation, the monthly ET under clear-sky and all-sky conditions was estimated using a nonparametric method at several sites with different humid conditions and vegetation coverage in 2014. 35.7 % of the clear-sky LST values were acquired in the arid region (Heihe River Basin) with different vegetation coverage. As the climate became more humid, only 14.2 % of the clear-sky LST data were available (Poyang Lake Basin). The clear-sky biases of LST variation at the sites resulted in a significant reduction in the accuracy of monthly ET, with an increase in the relative error (RE) of approximately 16.6 %. The impact of clouds can be reduced by at most half by the introduction of all-sky LST products, with a significant decline (6.3 % ∼ 34.2 % of ET) in the error contribution of LST to monthly ET. The variation in vegetation coverage of land cover and the change in humidity of the climate significantly affected the influence of the clear-sky biases of LST on the ET estimation and the error contribution to ET. Replacing all-sky LST with clear-sky LST in areas with less vegetation coverage exacerbates the underestimation of ET estimation and strengthens the error contribution of LST with the decline in RE (error contribution of LST) from −7.7 % (−6.3 %) in densely vegetated areas to −29.7 % (−34.2 %) in non-vegetated areas, especially in the summer. Similarly, clear-sky biases of LST tended to have a relatively significant impact on the error contributions of LST to monthly ET estimation when the climate became humid, with a relatively significant enlarging from −6.3 % in the arid area to −10.0 % in the humid area, especially in the rainy season in the humid area (−61.3 % of ET). This study contributes to the understanding of the relationship between clear-sky biases and vegetation coverage/humidity. Quantitative analysis of the impact of clear-sky biases of LST on monthly ET estimation will be helpful for improving the accuracy of ET retrieval in the future.

Non-intrusive load identification plays a crucial role in developing a green and low-carbon energy supply and demand mechanism. Among the various load identification technologies, the low-frequency electrical signal load identification stands out due to its ability to discern user’s electricity consumption habits without increasing the user’s hardware cost, thus presenting promising application prospects. However, the challenge lies in the scarcity of available data and the uneven distribution of samples, resulting in reduced accuracy. In this paper, we present a non-intrusive load state identification method based on the combination of LSTM model and multi-head attention model. By fusing those two techniques, the model can extract and utilize richer and more essential intrinsic features in electrical signals. The use of focal loss can balance the weight importance of different states with significantly different sample numbers. The experimental results on two open data-set show that the proposed algorithm can considerably improve the identification accuracy compared to other NILM methods, and the method also has good practical value in real application.

Abstract Objective To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). Methods Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. Results Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P

Abstract Federated Learning (FL) suffers from the Non-IID problem in practice, which poses a challenge for efficient and accurate model training. To address this challenge, prior research has introduced clustered FL (CFL), which involves clustering clients and training them separately. Despite its potential benefits, CFL can be computationally and communicationally expensive when the data distribution is unknown beforehand. This is because CFL involves the entire neural networks of involved clients in computing the clusters during training, which can become increasingly time-consuming with large-sized models. To tackle this issue, this paper proposes an efficient CFL approach called LayerCFL that employs a Layer-wised clustering technique. In LayerCFL, clients are clustered based on a limited number of layers of neural networks that are pre-selected using statistical and experimental methods. Our experimental results demonstrate the effectiveness of LayerCFL in mitigating the impact of Non-IID data, improving the accuracy of clustering, and enhancing computational efficiency.

Introduction Over the last four decades, human immunodeficiency virus type 1 (HIV-1) infection has been a major public health concern. It is acknowledged that an effective vaccine remains the best hope for eliminating the HIV-1 pandemic. The prophylaxis of HIV-1 infection remains a central theme because of the absence of an available HIV-1 vaccine. The inability of conventional delivery strategies to induce potent immunity is a crucial task to overcome and ultimately lead to a major obstacle in HIV-1 vaccine research. Areas covered The literature search was conducted in the following databases: PubMed, Web of Science, and Embase. Nano-platforms-based vaccines have proven prophylaxis in various diseases for effectively activating the immune system. Nano-vaccines, including non-viral and viral vectored nano-vaccines, are in a position to improve the effectiveness of HIV-1 antigen delivery and enhance the innate and adaptive immune responses against HIV-1. Compared to traditional vaccination strategies, genetic immunization can elicit a long-term immune response to provide protective immunity for HIV-1 prevention. Expert opinion Research progress on nano-vaccines for gene delivery against HIV-1 was discussed. Vaccine strategies based on nano-platforms that are being applied to stimulate effective HIV-1-specific cellular and humoral immune responses were particularly emphasized.

AbstractContext Da-Yuan-Yin is a Chinese traditional prescription.Objective This study explores the therapeutic effects of the Da-Yuan-Yin decoction polyphenol fraction (DYY-4) on acute lung injury (ALI) in mice induced by lipopolysaccharide (LPS).Materials and methods The mice (n = 10) were orally administrated with DYY-4 (15, 30, and 60 mg/kg) or DXM (5 mg/kg), half an hour after LPS (2 mg/kg) instilled intratracheally. The protein content and the levels of inflammatory factors, the levels of complements, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the level of myeloperoxidase (MPO) and superoxide dismutase (SOD), the expression of the IkB kinase (IKK) and nuclear factor-kappa B (NF-κB), the lung wet-to-dry weight (W/D) ratio and lung tissue were evaluated, 24 h after LPS challenge. Network pharmacology predicted potential targets.Results DYY-4 (30, 60 mg/kg, p

Abstract Improving energy-environment efficiency is not only a requirement for constructing China’s ecological civilization but also inevitable for achieving sustainable economic and social development. Studies on energy-environment efficiency based on relational data and network perspectives are limited, which hinders the development of collaborative regional emission reduction activities. This study uses the SBM-Undesirable model to measure the energy-environment efficiency of the Yangtze River Delta Urban Agglomeration from 2010 to 2020, adopts a modified gravity model and social network analysis to reveal the structural characteristics of its spatial correlation network, and explores its driving factors through the QAP method. The study found (1) an overall upward trend in energy-environment efficiency but with problems of uneven development. (2) The spatial correlation of energy-environment efficiency shows a complex network structure, with increasing network correlation and strong network stability; the network can be divided into four plates: net benefit, net overflow, two-way spillover, and agent. (3) Differences in industrial structure, environmental regulation, economic development, and technological innovation significantly impact the formation of spatial correlation network of energy-environment efficiency. This study provides a reference for the construction of a cross-regional synergistic mechanism to improve energy-environment efficiency.

Abstract Background Colorectal cancer (CRC) is one of the most common malignancies, and early detection plays a crucial role in enhancing curative outcomes. While colonoscopy is considered the gold standard for CRC diagnosis, noninvasive screening methods of DNA methylation biomarkers can improve the early detection of CRC and precancerous lesions. Methods Bioinformatics and machine learning methods were used to evaluate CRC‐related genes within the TCGA database. By identifying the overlapped genes, potential biomarkers were selected for further validation. Methylation‐specific PCR (MSP) was utilized to identify the associated genes as biomarkers. Subsequently, a real‐time PCR assay for detecting the presence of neoplasia or cancer of the colon or rectum was established. This screening approach involved the recruitment of 978 participants from five cohorts. Results The genes with the highest specificity and sensitivity were Septin9, AXL4, and SDC2. A total of 940 participants were involved in the establishment of the final PCR system and the subsequent performance evaluation test. A multiplex TaqMan real‐time PCR system has been illustrated to greatly enhance the ability to detect precancerous lesions and achieved an accuracy of 87.8% (95% CI 82.9–91.5), a sensitivity of 82.7% (95% CI 71.8–90.1), and a specificity of 90.1% (95% CI 84.3–93.9). Moreover, the detection rate of precancerous lesions of this assay reached 55.0% (95% CI 38.7–70.4). Conclusion The combined detection of the methylation status of SEPT9, SDC2, and ALX4 in plasma holds the potential to further enhance the sensitivity of CRC detection.

Abstract In our phase Ib trial (ClinialTrials.gov Identifier: NCT03855358), benmelstobart (TQB2450), a novel humanized IgG1 antibody against PD-L1, plus antiangiogenic multikinase inhibitor, anlotinib, demonstrated promising antitumor activities in pretreated triple negative breast cancer (TNBC) patients. We conducted explorative analyses of genomic biomarkers to explore the associations with treatment response and survival outcomes. Targeted next generation sequencing (NGS) was undertaken toward circulating tumor DNA (ctDNA) collected from peripheral blood samples prior to the start of treatment and after disease progression. A total of 31 patients received targeted NGS and functional driver mutations in 29 patients were analyzed. The most frequent mutations were TP53 (72%), MLL3 (28%), and PIK3CA (17%). At a blood-based tumor mutational burden (bTMB) cutoff of 6.7 mutations per megabase, patients with low bTMB showed better response to anlotinib plus TQB2450 (50% vs. 7%, P = 0.015) and gained greater PFS benefits (7.3 vs. 4.1 months, P = 0.012) than those with high bTMB. At a maximum somatic allele frequency (MSAF) cutoff of 10%, a low MSAF indicated a better objective response (43% vs. 20%) as well as a significantly longer median PFS (7.9 vs. 2.7 months, P

The long-term excessive use of chemical fertilizers may result in soil degradation, but manure and straw application is considered to be an effective approach for alleviating this problem. The aim of this study is to examine the long-term impacts of different fertilization patterns on soil quality variables in a wheat–sweet potato rotation system. Four treatments were conducted in a field trial for a duration of twelve years, including (1) no fertilizer (control, CK); (2) application of mineral fertilizers (NPK) alone; (3) NPK with crop straw return (NPKs); (4) combined use of NPK and farmyard manure (NPKm). Thirteen physical, chemical, and biological soil parameters were measured. The results showed that the NPKm and NPKs significantly improved the proportion of macroaggregates (>0.25 mm) by 24.7% and 21.9% compared to the NPK alone, respectively. The proportion of microaggregates (0.053–0.25 mm) under the NPKm was 47.4% significantly higher than the NPKs. Additionally, the NPKm resulted in a 22.2% and 19.6% increase in the SOC content than the NPK and NPKs, respectively. In terms of soil-available K, the NPKs resulted in levels that were 42.1% and 49.6% higher than the NPKm and NPK alone, respectively. Long-term fertilization significantly decreased soil pH by 0.95–1.85 units compared to the control, whereas manure application could alleviate soil acidification, as shown when the pH increased by 10.6–18.7%. The NPKm and NPKs resulted in significantly increased soil pHs by 10.6% and 18.7% compared to the NPK alone, respectively. In addition, the NPKm and NPKs increased N-acetyl-β-D-glucosaminidase activity by 52.6% and 60.3% compared to the NPK alone. Determined by the minimum data set method, the NPKm treatment exhibited the highest soil quality index, followed by the NPKs and NPK. Our findings suggested that the combined use of chemical fertilizers with organic amendments proved beneficial for enhancing soil quality.

Rubberized cement-based materials are widely utilized because of their good ductility, impact resistance, and fatigue resistance. This research investigated the effect of the rubber aggregates content, particle size of rubber aggregates, and water–cement ratio on the early-age mechanical properties and deformation behaviors of mortar through laboratory tests, and strength reduction coefficient fitting models were established according to the testing results. The results show that the compressive strength growth rate of cement mortar is about 15% slower than that of flexural strength. The existence of rubber aggregates lowers the strength increase rate of mortar. The reduction coefficient of strength decreases with increasing rubber aggregates content and increases with the age of mortar. Increasing rubber aggregates content and decreasing particle size of rubber aggregate can lower the autogenous shrinkage in the initial stage, but the autogenous shrinkage of the later stage increases as the rubber aggregates content increases, with a turning point between 30 h and 50 h. After 3 days, the dry shrinkage of mortar accounts for about 70–80% of the total shrinkage, and it increases with higher rubber aggregate content, smaller particle size of rubber aggregates, and higher water–cement ratios.

The temperature response of pavement is not only crucial for assessing the internal stresses within pavement structures but is also an essential parameter in pavement design. Investigating the temperature response of rubberized concrete pavements (RCP) can support the construction of large-scale rubber concrete pavements. This study constructed a pavement monitoring system based on fiber Bragg grating technology to investigate the temperature distribution, temperature strain, temperature effects, and temperature stress of RCP. The results show that the daily temperature–time history curves of concrete pavement exhibit a significant asymmetry, with the heating phase accounting for only one-third of the curve. The temperature at the middle of RCP is 1.8 °C higher than that of ordinary concrete pavement (OCP). The temperature distribution along the thickness of the pavement follows a “spindle-shaped” pattern, with higher temperatures in the center and lower temperatures at the ends. Additionally, the addition of rubber aggregates increases the temperature strain in the pavements, makes the temperature–strain hysteresis effect more pronounced, and increases the curvature of the pavement slab. However, the daily stress range at the bottom of RCP is approximately 0.7 times that of OCP.

In autonomous driving, environmental perception technology often encounters challenges such as false positives, missed detections, and low accuracy, particularly in detecting small objects and complex scenarios. Existing algorithms frequently suffer from issues like feature redundancy, insufficient contextual interaction, and inadequate information fusion, making it difficult to perform multi-task detection and segmentation efficiently. To address these challenges, this paper proposes an end-to-end multi-task environmental perception model named YOLO-Mg, designed to simultaneously perform traffic object detection, lane line detection, and drivable area segmentation. First, a multi-stage gated aggregation network (MogaNet) is employed during the feature extraction process to enhance contextual interaction by improving diversity in the channel dimension, thereby compensating for the limitations of feed-forward neural networks in contextual understanding. Second, to further improve the model’s accuracy in detecting objects of various scales, a restructured weighted bidirectional feature pyramid network (BiFPN) is introduced, optimizing cross-level information fusion and enabling the model to handle object detection at different scales more accurately. Finally, the model is equipped with one detection head and two segmentation heads to achieve efficient multi-task environmental perception, ensuring the simultaneous execution of multiple tasks. The experimental results on the BDD100K dataset demonstrate that the model achieves a mean average precision (mAP50) of 81.4% in object detection, an Intersection over Union (IoU) of 28.9% in lane detection, and a mean Intersection over Union (mIoU) of 92.6% in drivable area segmentation. The tests conducted in real-world scenarios show that the model performs effectively, significantly enhancing environmental perception in autonomous driving and laying a solid foundation for safer and more reliable autonomous driving systems.

Cloud computing, as the most widely applied and prominent domain of distributed systems, has brought numerous advantages to users, including high resource sharing efficiency, strong availability, and excellent scalability. However, the complexity of cloud computing environments also introduces various risks and challenges. In the current landscape with numerous cloud service providers and diverse hardware configurations in cloud environments, addressing challenges such as establishing trust chains, achieving general-purpose virtual remote attestation, and ensuring secure virtual machine migration becomes a crucial issue that traditional remote attestation architectures cannot adequately handle. Confronted with these issues in a heterogeneous multi-cloud environment, we present a targeted solution—a secure migration-enabled generic virtual remote attestation architecture based on improved TEE. We introduce a hardware trusted module to establish and bind with a Virtual Root of Trust (VRoT), addressing the challenge of trust chain establishment. Simultaneously, our architecture utilizes the VRoT within TEE to realize a general-purpose virtual remote attestation solution across heterogeneous hardware configurations. Furthermore, we design a controller deployed in the trusted domain to verify migration conditions, facilitate key exchange, and manage the migration process, ensuring the security and integrity of virtual machine migration. Lastly, we conduct rigorous experiments to measure the overhead and performance of our proposed remote attestation scheme and virtual machine secure migration process. The results unequivocally demonstrate that our architecture provides better generality and migration security with only marginal overhead compared to other traditional remote attestation solutions.

Understanding the genetic basis of salt resistance in crops is crucial for agricultural productivity. This study investigates the phenotypic and genetic basis of salt stress response in rice (Oryza sativa L.), focusing on germination and seedling traits. Under salt stress conditions, significant differences were observed in seed germination and seedling traits between parental LH99 (Indica rice LuHui 99) and SN265 (japonica rice ShenNong 265). Transgressive segregation was evident within the RIL population, indicating complex genetic interactions. Nine QTLs were detected at germination and seedling stages under salt stress, namely qSGE5 and qSGE7 for seed germination energy (SGE); qSGP7 for seed germination percentage (SGP); qSSH7, qSSH9-1, and qSSH9-2 for seeding height (SSH); qSRN6 for root number (SRN); and qSDW6 and qSDW9 for dry weight (SDW). Among them, qSSH9-1 and qSDW9 were localized in the same interval, derived from the salt-resistant parent SN265. PCA revealed distinct trait patterns under salt stress, captured by six PCs explaining 81.12% of the total variance. PC composite scores were used to localize a QTL associated with early salt resistance in rice qESC9, which was located in the same interval as qSSH9-1 and qSDW9, and was subsequently unified under the name qESC9, an important QTL for early-growth salt tolerance in rice. Correlation analysis also confirmed a relationship between alleles of qESC9 and the resistance to salt, underscoring the critical role this locus plays in the determination of overall salt tolerance in rice. Physiological analyses of extreme phenotype lines highlighted the importance of ion exclusion mechanisms in salt-resistant lines, while salt-susceptible lines exhibited elevated oxidative stress and impaired antioxidant defense, contributing to cellular damage. This comprehensive analysis sheds light on the genetic and physiological mechanisms underlying salt stress response in rice, providing valuable insights for breeding programs aimed at enhancing salt resistance in rice.

Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality globally. tRNA-derived small RNAs (tsRNAs) have emerged as potential targets for cancer treatment. However, the specific impact of tsRNAs on HCC remains undiscovered. In this study, we aimed to investigate the biological significance of tsRNAs in HCC. First, we screened the differentially expressed tsRNAs in HCC tissues and normal tissues adjacent to the tumor (NAT) using high-throughput sequencing and the results showed that tRF-39-8HM2OSRNLNKSEKH9 was more highly expressed in HCC tissues than NATs. Agarose gel electrophoresis (AGE), nuclear-cytoplasmic separation assays and fluorescence in situ hybridization (FISH) were employed to assess the characterization of tRF-39-8HM2OSRNLNKSEKH9. The relationship between the expression of tRF-39-8HM2OSRNLNKSEKH9 and clinicopathological parameters was evaluated and we found that it was positively associated with tumor size. The cell counting kit-8 (CCK8) assay, colony formation assay and EdU staining assay were employed to investigate the role of tRF-39-8HM2OSRNLNKSEKH9 in the proliferation of HCC cells. Additionally, transwell assays demonstrated that overexpression of tRF-39-8HM2OSRNLNKSEKH9 could accelerate cell migration capability. Taken together, tRF-39-8HM2OSRNLNKSEKH9 was highly expressed in HCC cells, serum and tissues, and it may play an oncogenic role in HCC cells through interacting with downstream mRNA targets.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

Objective This study aimed to examine the differential magnitude of associations between specific dimensions of patient experience and overall patient satisfaction.Design A descriptive, cross-sectional design was used to collect patient experience and overall satisfaction data.Setting Participants were recruited at one tertiary general hospital, one tertiary specialised hospital, and one secondary hospital in Shanghai, China. These three institutes represent the main kinds of hospitals in the Chinese healthcare system.Participants 1532 inpatients were recruited, and 1469 were included. The inclusion criteria were as follows: (1) having received inpatient service for at least 2 days; (2) able to understand the questions in the questionnaires; and (3) aged>18 years old. Patients who had impaired cognitive function and completed the questionnaires with missing information were excluded.Primary and secondary outcome measure Patient experience was measured using the Inpatient Experience with Nursing Care Scale, which is widely used in the China. The overall patient satisfaction was measured with 10-point response option.Results The LASSO (least absolute shrinkage and selection operator) regression results showed that as the penalty factor (λ) = 0.0162, age, marriage status, financial status, length of hospital stay and numbers of previous of hospitalisation and six dimensions of nursing care remained in the model. As λ increases to 0.1862, only four patient experience variables, potentially the most influential on patient satisfaction, remained in the model. Patient experience with emotional support was the most significant dimension explaining patient satisfaction (β=0.1564), the second most significant dimension was admission and discharge management (β=0.1562), and the third was monitoring and coping with the progress of diseases (β=0.0613).Conclusion Patient experience with emotional support, admission and discharge management, monitoring and coping with the progress of diseases, and information and education are the most significant dimensions explaining patient satisfaction.

Objectives: The aim of this study was to conduct a bibliometric analysis of the literature on stem cell treatment for spinal cord injury to gain an intuitive understanding of how the field is progressing, discover topics of interest, and determine what development trends are emerging in this field.Background: Spinal cord injury and its complications often cause an enormous economic burden, and postinjury repair and treatment have always been challenging in clinical and scientific research. Stem cell therapy for spinal cord injury can prevent immune rejection and induce the release of neuroprotective and anti-inflammatory factors to reduce the production of stress-related proteins, reactive oxygen species, and inflammatory reactions.Methods: We analyzed the number and quality of publications in the field of stem cell therapy in spinal cord injury between 2018.01.01 and 2023.06.30 in the core collection database of Web of Science. CiteSpace and VOSviewer were used to sort and summarize these studies by country, institution, authors' publications, and collaborative networks. In addition, the research topics of interest were identified and summarized.Results: This study ultimately included 2,150 valid papers, with the number of publications showing a gradual upward trend. The country, institution, author and journal with the greatest number of publications and citations are China, the Chinese Academy of Sciences, Dai JW, and the International Journal of Molecular Sciences, respectively. The top three high-frequency keyword clusters were hereditary paraplegia, reactive astrocytes and tissue engineering.Conclusion: With the help of visual analysis, we identified general trends and research topics of interest in the field of spinal cord injury over the last 5 years. Our findings suggest that stem cell transplantation for spinal cord injury and exosome therapy may be a focus of future research. This study provides a foundation for future research on stem cell therapy as well as clinical efforts in this field.

Abstract Data on the association between uric acid (UA) levels and clinical outcomes, such as readmission and mortality, in patients with heart failure are scarce. This study explores whether UA exhibits an independent association with the composite endpoint (clinical outcome during 6 months after discharge, including mortality and 6-month readmission) in patients with chronic heart failure while controlling for other covariates. This study was an observational retrospective study. A cohort of 1943 consecutive patients diagnosed with chronic heart failure, who were admitted between December 2016 and June 2019, was included in the study. Data were sourced from PhysioNet. The independent variable analyzed was the UA level, and the dependent variable was a composite endpoint comprising mortality and 6-month readmission. The study had 1943 participants, of which 91.04% were aged more than 60 years and 58.05% were female. The fully-adjusted model yielded a positive correlation between UA levels (per 10 µmol/L) and the composite endpoint as well as readmission, following adjustment for confounding variables (HR = 1.01, 95% CI 1.00–1.01). Notably, a non-linear relationship was observed between UA levels and the composite endpoint, particularly readmission, with a J-shaped correlation observed between UA levels and both the composite endpoint and readmission. Overall, we found that the serum UA levels at admission were independently and positively associated with the risk of the composite endpoint (clinical outcomes during 6 months after discharge), especially readmission after adjusting other covariates. A J-shaped relationship was observed between UA levels and the composite endpoint and readmission.