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The existing mechanical and grouting anchors mostly use the expansion shell method to form a cavity on the borehole wall, and the cement slurry is poured to form multiple enlarged head plates, but the operation is more difficult and the diameter of the formed plate is smaller. In this paper, a new type of large-diameter multi-plate soil anchor and its reaming cavity forming tool are proposed, which can make the operation easier and form a large-diameter enlarged head plate. In order to study the influence of the diameter of anchor plate, the number of anchor plates and the spacing of anchor plates on the vertical uplift capacity of the large-diameter multi-plate soil anchor, 25 sets of comparative models were established for simulation analysis. The finite difference method of FLAC 3D software is used to simulate the model. It is found that when the length of the anchor is 6 m and the diameter of the anchor rod body is 150 mm, the optimal diameter of the anchor plate of the large diameter multi-plate soil anchor is 590 mm, the optimal number of anchor plates is 6, and the optimal anchor plate spacing is 800 mm, which means the action range of the anchor plate on the lower soil is about 5 times the diameter of the bolt. When the number of anchor plates is too small or the spacing between anchor plates is too large, the structural advantages of large-diameter multi-plate soil anchor cannot be fully utilized, resulting in a decrease in the ultimate uplift capacity. When the number of anchor plates is too large or the spacing between anchor plates is too small, the stress superposition effect occurs in the soil, and the through shear failure occurs, which leads to the decline of the ultimate uplift capacity. Under the condition that the number of anchor plates and the spacing of anchor plates are fixed, the larger the diameter of the anchor plate is, the larger the ultimate pull-out capacity of the large-diameter multi-plate soil anchor is, the smaller the vertical failure displacement of the anchor head is, but the increase of the uplift capacity is gradually reduced. The creep rate of the new large-diameter multi-plate soil anchor bolt is 0.91 mm, and the creep rate of equal-diameter soil anchor bolt is 1.69 mm. It is verified that the new large-diameter multi-plate soil anchor can be effectively applied to various projects., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In the potato mechanical planting industry, the high multi-seeding rate and miss-seeding rate are problems that exist in many potato precision seed metering devices. The main potato seeds in China are cut potatoes with different shapes and sizes. However, there is a lack of research on precision seeding technology for cut potatoes, and the adaptability of many existing potato seeding devices on cut potato is poor. The mechanized precision seeding of potato can effectively reduce labor consumption, improve the seeding effect (decrease multi-seeding rate and miss-seeding rate), improve the improve production of potato per acre and improve the quality commodity potatoes. In response to the above issues, a precision seed metering device with novel scoops, which can adapt to various sizes and shapes of cut potatoes, was developed. In this study, the different seed collecting scenarios (SCSs) were constructed. Through the statics and kinematic analysis, the excess seeds removing (ESR) process was divided in to three areas. The kinematic model of seed potato was established to study the influence of different SCSs and sprocket rotational speeds on the ESR performance, and preliminary determined the appropriate sprocket rotational speed range for ESR process. Then, the coupled simulation results of EDEM and RecurDyn revealed that different sprocket speeds and SCSs had a significant influence on the ESR performance. Finally, the bench tests and field tests were conducted to verify the actual performance of the precision seed metering device. The results showed that, with the increase of the sprocket rotational speed, the ESR performance of the device improved, the multi-seeding rate significantly decreased, but the miss-seeding rate increased. High sprocket rotational speed will remove more seed potatoes and cause high miss-seeding rate. The bench tests showed the appropriate sprocket rotational speed for medium and large potato was 35 r/ min. The field tests obtained the best qualified-seeding rate of 91.54%, the miss-seeding rate of 3.08% and the multi-seeding rate of 5.38%. This study can provide theoretical reference for the design of potato precision seed metering device., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Exploring the optimization of communication strategies for animation films in the context of cross-cultural communication, this research integrates the Internet of Things (IoT) and convolutional networks. The research constructs a collaborative filtering (CF) movie recommendation model based on a graph convolutional neural network (GCN) and investigates its application in cross-cultural communication. The fusion of IoT and convolutional networks in movie communication is also analyzed, and the effectiveness of the proposed GCN-CF model is validated through comparative experiments. The results indicate that, compared to other models, the GCN-CF model achieves the lowest Root Mean Square Error (RMSE) on the MovieLens 100 K and MovieLens 1 M datasets, with values of 0.8762 and 0.8275, respectively. Compared to traditional models, the GCN-CF model exhibits significantly superior performance in terms of RMSE, with reductions ranging from 0.6 to 5.2%, highlighting its heightened detection accuracy and overall performance. Moreover, the performance of the GCN-CF model is enhanced after introducing attention mechanisms and auxiliary information on both datasets, showing an improvement of 0.4% compared to the scenario without these additions. This data demonstrates the effectiveness of attention mechanisms and auxiliary information. Finally, the research presents an animation film communication strategy based on IoT and convolutional networks, offering novel insights for film production and communication, along with positive implications for cultural exchange and the advancement of the global media industry., (© 2024. The Author(s).)

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639-1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633-1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5-15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis., (© 2024. The Author(s).)

This study presents an approach that integrates compressed sensing technology with two-dimensional hyperchaotic coupled Fourier oscillator systems (2D-HCFOS) to address the challenge of slow encryption speeds in agricultural unmanned aerial vehicles (UAVs). The primary challenge in enhancing encryption speed lies in the limited capacity inherent in traditional chaotic-based systems and the computational complexity of their processes. The 2D-HCFOS utilizes a complex two-dimensional hybrid chaotic system, which significantly enhances the security of agricultural UAV image data. Notably, the image encryption process is performed on a personal computer connected to the drone, ensuring efficient processing. By integrating advanced Fourier series and nonlinear coupled oscillators, the model surpasses existing chaotic-based methods, improving both the pseudo-randomness and robustness of encryption. Additionally, incorporating Bonouille functions into the discrete cosine transform (DCT) domain results in a sparser measurement matrix, which is essential for efficient encryption on personal computers. The effectiveness of 2D-HCFOS in securely encrypting agricultural drone images has been rigorously validated through simulations and analytical evaluations using sophisticated row, rotation, and matrix encryption techniques. The improved security performance is further verified by comparative analysis. Compared with other models, the Lyapunov index of 2D-HCFOS is 15.1039, and the sample entropy is 2.4987, indicating that it possesses superior chaotic performance and encryption reliability., (© 2024. The Author(s).)

Solar energy plays an important role in renewable energy generation, with the advantages of low pollution, easy installation, and relatively easy access. However, photovoltaic (PV) modules are susceptible to cause localized shading from external factors such as leaves in the canopy, surrounding buildings, etc., which would affect power generation efficiency and even pose safety risks. Existing methods cannot perform well in real-time conditions. This paper proposes a real-time shading monitoring method for the PV module based on computer vision. The gamma transform and histogram matching were adopted to enhance key features and adjust the global gamut strength distribution in the image of the PV module; then the gray-level slicing method finished the segmentation to detect the shadow from the video. All processing can be realized in the real-time monitor camera and the detection results can be displayed on the HMI in PC with high efficiency and low cost. According to tests in the practical complex environment, the method can have enough detection performance and high real-time performance with an accuracy of 0.98, and the F0.5 and F2 values are 0.87 and 0.85, respectively. The metrics of the proposed method are higher than those of the existing Canny detection method, the Random Forest detection method, and the CNN detection method. In addition, the average time required by the proposed method to process a frame is 0.721 s. In addition, the average time required by the method to process an image frame is 0.721 s, which has good real-time performance., (© 2024. The Author(s).)

Neoadjuvant radiotherapy is the standard care of locally advanced rectal cancer. Although a majority of patients received the same dose, the curative efficacy varies among individuals. In recent years, cancer treatment has entered the era of precise medical care, and how to identify patients for proper treatment by molecular signature is an important path of individualized therapy. This study aimed to establish and validate a genome-based model for adjusting radiation dose (GARD) for Chinese locally advanced rectal cancer through gene expression microarrays, and to evaluate the response of the GARD model in predicting the efficacy of neoadjuvant radiotherapy. Fresh-frozen primary tumor from 64 patients with locally advanced rectal cancer undergoing neoadjuvant radiotherapy from 2015 to 2018 were included. The gene expression profile was analyzed using Affymetrix 3000Dx gene-chip scanner. The radiosensitivity index (RSI) and GARD were calculated using the pGRT™ algorithm. Neoadjuvant rectal cancer score (NAR) was selected as efficacy evaluation indicators. Patients were divided into high and low NAR scoring groups, and two-sample t-test was used to analyze the differences in GARD values between different NAR subgroups. ROC curves were used to calculate the cut-off values and the area under the curve (AUC) for assessing the validity of the GARD models. The personalized radiation dose ( pGRT dose )can be computed using the formula nd = GARD / (α + βd). Among patients, 1.5% T2, 46.3% T3, and 52.2% T4. Wherein pCR (n = 10; 15.6%) and no pCR (n = 54; 84.4%). The median NAR is 8.43 (rang from 0 to 50.34, IQR 3.75-14.98). NAR > 8.43 (n = 27; 42.2%) and NAR ≤ 8.43 (n = 37; 57.8%), suggesting that there are significant individual differences in clinical efficacy of patients with similar tumor stages and under the same treatment conditions. The median RSI is 0.48 (rang from 0.22 to 0.92, IQR 0.41-0.55). Median GARD was 18.40 rang from (rang from 2.26 to 37.52, IQR 14.94-22.28) within tumor tissue, suggesting individual differences in the efficacy of radiation therapy. The RSI value was significantly lower in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (0.44 vs. 0.54, p = 0.0003). The GARD value was significantly higher in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (21.01 vs. 15.88, p = 0.0004). Using the Receiver Operating Characteristic (ROC) curve analysis, a GARD threshold of 17 was identified as optimal, covering 37.5% of the 64-patient sample, with an area under the curve (AUC) of 0.75. In the external validation cohort, the high GARD score group demonstrated superior DFS compared to the low GARD score group(p < 0.001). Only 17% of patients had pGRT dose within the guideline recommended dose (45-50 Gy). The differences in NAR values among LARC patients receiving standard neoadjuvant radiotherapy suggest significant individual differences in clinical outcomes among patients with similar tumor stage and the same treatment conditions. Patients with a GARD value exceeding 17 exhibit a more favorable prognosis. Our results suggest that the gene expression-based pGRT™ algorithm has good efficacy prediction performance in preoperative concurrent radiotherapy for locally advanced rectal cancer, suggesting the potential clinical application of this method to guide the designation of individualized radiotherapy doses., (© 2024. The Author(s).)

Bronchiolitis is a significant factor contributing to bronchial asthma in infants and young children. After treatment, recurrent wheezing symptoms often occur, especially in children with atopic constitution, who tend to have more severe conditions and poorer prognosis. Therefore, exploring the prognostic value of total serum immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) levels in children with atopic constitution who suffer from bronchiolitis is of great significance. A total of 260 children with bronchiolitis admitted to our hospital from October 2020 to June 2022 were regarded as the research subjects with prospective study, according to whether the children had atopic constitution, they were grouped into non atopic constitution group (n = 156) and atopic constitution group (n = 104); after 6 months of treatment, children with atopic constitution were grouped into a good prognosis group (n = 58) and a poor prognosis group (n = 46) based on their prognosis; in addition, 260 healthy children who underwent physical examination and had clinical data consistent with those of children with bronchiolitis were regarded as the reference group. The serum tIgE and FeNO levels of each group were compared; multivariate Logistic regression was applied to analyze the prognostic factors of children with atopic constitution bronchiolitis; ROC curve was applied to analyze the predictive value of tIgE and FeNO levels after treatment for the prognosis of children with atopic constitution bronchiolitis. The tIgE levels in the control group, non-atopic group, and atopic group [(123.54 ± 29.62) IU/mL, (245.71 ± 30.59) IU/mL, (316.46 ± 31.78) IU/mL, respectively] increased sequentially, with statistically significant differences (F = 1766.954, P = 0.000). The FeNO levels in the control group, non-atopic group, and atopic group [(8.36 ± 3.57) ppb, (15.28 ± 3.69) ppb, (19.84 ± 3.58) ppb, respectively] also increased sequentially, with statistically significant differences (F = 765.622, P = 0.000). The tIgE, FeNO, proportion of patients with asthma family history, and proportion of patients with allergic family history in the poor prognosis group were obviously higher than those in the good prognosis group (P < 0.05). Multivariate Logistic regression analysis showed that family history of asthma, family history of allergies, tIgE, and FeNO were influencing factors for the prognosis of children with atopic bronchiolitis (P < 0.05). The AUC of the combination of tIgE and FeNO in predicting the prognosis of children with atopic constitutional bronchiolitis was 0.910, with a sensitivity of 78.26% and a specificity of 93.10%, which was superior to the independent prediction of tIgE and FeNO (Z combined detection-tIgE  = 2.442, Z combined detection-FeNO  = 3.080, P = 0.015, 0.002). The levels of tIgE and FeNO in children with atopic constitution bronchiolitis are obviously increased, and the combination of the two has high predictive value for the prognosis of atopic constitution bronchiolitis., (© 2024. The Author(s).)

Genetic and fragmented palaeoanthropological data suggest that Denisovans were once widely distributed across eastern Eurasia 1-3 . Despite limited archaeological evidence, this indicates that Denisovans were capable of adapting to a highly diverse range of environments. Here we integrate zooarchaeological and proteomic analyses of the late Middle to Late Pleistocene faunal assemblage from Baishiya Karst Cave on the Tibetan Plateau, where a Denisovan mandible and Denisovan sedimentary mitochondrial DNA were found 3,4 . Using zooarchaeology by mass spectrometry, we identify a new hominin rib specimen that dates to approximately 48-32 thousand years ago (layer 3). Shotgun proteomic analysis taxonomically assigns this specimen to the Denisovan lineage, extending their presence at Baishiya Karst Cave well into the Late Pleistocene. Throughout the stratigraphic sequence, the faunal assemblage is dominated by Caprinae, together with megaherbivores, carnivores, small mammals and birds. The high proportion of anthropogenic modifications on the bone surfaces suggests that Denisovans were the primary agent of faunal accumulation. The chaîne opératoire of carcass processing indicates that animal taxa were exploited for their meat, marrow and hides, while bone was also used as raw material for the production of tools. Our results shed light on the behaviour of Denisovans and their adaptations to the diverse and fluctuating environments of the late Middle and Late Pleistocene of eastern Eurasia., (© 2024. The Author(s).)

To investigate the mechanism of curcumin (CUR) on vascular calcification (VC), we screen for common targets of CUR and atherosclerosis and verify the targets genes in vivo and in vitro experiments. The common targets of CUR and AS were screened and obtained using different databases. These target genes were analyzed by GO and KEGG pathway enrichment analysis. PPI network analysis was performed and to analyze the key targets. A rat VC model was constructed and CUR was fed for three weeks. The changes of vascular structure and calcium salt deposition were observed in H&E and Von Kossa staining. Further, the expression of these target proteins was detected in the primary VSMCs of VC. The 31 common targets were obtained. GO functional enrichment analysis obtained 1284 terms and KEGG pathway enriched 66 pathways. The key genes were identified in the cytoHubba plugin. The molecular docking analysis showed that CUR bound strongly to EGFR, STAT3 and BCL2. The animal experiments showed the deposition calcium salt reduced by the CUR administration. These proteins BMP2, RUNX2, EGFR, STAT3 and BAX expression were upregulated in VC group and CUR attenuated the upregulated expression. The signal protein Akt and p65 expression increased in VC group and decreased in CUR group. We identified some common target genes of CUR and AS and identified these key genes. The anti-VC effect of CUR was associated with the inhibition of upregulation of EGFR, STAT3 and RUNX2 expression in VSMCs., (© 2024. The Author(s).)

To investigate the role of miR-223-3p in the modulatory effect of paeonol (Pae) on high glucose (HG)-induced endothelial cell apoptosis. HG (25 mmol/L) was used to induce cellular damage and apoptosis in the mouse cardiac microvascular endothelial cells (MCMECs). Various concentration of Pae was tested and 60 μmol/L Pae was selected for the subsequent studies. MCMECs were transfected with exogenous miR-223-3p mimics or anti-miR-223-3p inhibitors. Cell viability was assessed by MTT assay and apoptosis was quantified by flow cytometry. The expression of miR-223-3p and NLRP3 mRNA was measured using real-time quantitative RT-PCR, and protein level of NLRP3 and apoptosis-related proteins was detected by immunoblotting. Pae significantly attenuated HG-induced apoptosis of MCMECs in a concentration-dependent manner. In addition, Pae (60 µmol/L) significantly reversed HG-induced down-regulation of miR-223-3p and up-regulation of NLRP3. Pae (60 µmol/L) also significantly blocked HG-induced up-regulation of Bax and Caspase-3 as well as down-regulation of Bcl-2. Moreover, exogenous miR-223-3p mimics not only significantly attenuated HG-induced apoptosis, but also significantly suppressed NRLP-3 and pro-apoptotic proteins in the MCMECs. In contrast, transfection of exogenous miR-223-3p inhibitors into the MCMECs resulted in not only significantly increased apoptosis of the cells, but also significant suppression of NLRP3 and pro-apoptotic proteins in the cells. Pae attenuated HG-induced apoptosis of MCMECs in a concentration-dependent manner. MiR-223-3p may mediate the modulatory effects of Pae on MCMEC survival or apoptosis through targeting NLRP3 and regulating apoptosis-associated proteins., (© 2024. The Author(s).)

This study presented a comprehensive computational fluid dynamics-based model for fused filament fabrication (FFF) three-dimensional (3D) printing multiphase and multiphysics coupling. A model based on the framework of computational fluid dynamics was built, utilizing the front-tracking method for high precision of multiphase material interfaces, a fully resolved simulation at the mesoscale explores the underlying physical mechanism of the self-supported horizontal printing. The study investigated the influence of printing temperature and velocity on the FFF process, exhibiting a certain self-supporting forming ability over a specific range. The results indicated that during the printing of large-span horizontal extension structures, the bridge deck material transitions from initial straight extension to sagging deformation, ultimately adopting a curved shape. The straight extension distance is inversely proportional to the depth of the sagging deformation. Additionally, the study revealed that printing temperature primarily affected the curing time of the molten material, while printing velocity fundamentally affected the relaxation time of both thermal and dynamic characteristics of the material., (© 2024. The Author(s).)

Breast cancer, as the most common cancer, has surpassed lung cancer worldwide. The neutrophil-to-lymphocyte ratio (NLR) has been linked to the onset of cancer and its prognosis in recent studies. However, quite a few studies have shown that there is a link between NLR and lymph node metastases in cN0 hormone receptor-positive (HR(+)) breast cancer. The purpose of this study was to evaluate the correlation between NLR and lymph node metastases in cN0 HR(+) breast cancer patients. From January 2012 to January 2022, 220 patients with cN0 HR(+) invasive breast cancers were enrolled in this study. The relationship between NLR and pathological data was statistically examined. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff of NLR, a chi-squared test was used for the univariate analysis, and logistic analysis was used for the multivariate analysis. The NLR had an optimal cutoff of 2.4 when the Jorden index was at a maximum. Patients with axillary lymph node metastases had a higher NLR (P < 0.05). A Univariate analysis showed that there were significant differences in cN0 HR(+) breast cancer with axillary lymph node metastasis among different clinical stages, histological grades, Ki-67 levels, tumor sizes, and NLR levels (P < 0.05). Clinical stage, tumor size, and NLR were found to be independent risk factors for lymph node metastases in multifactorial analysis. In cN0 HR(+) breast cancer, NLR is an independent risk factor for lymph node metastases. An NLR ≥ 2.4 indicates an increased probability of lymph node metastases. An elevated preoperative NLR has a high predictive value for axillary lymph node metastases., (© 2024. The Author(s).)

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC., (© 2024. The Author(s).)

Aedes aegypti is a primary vector for transmitting various arboviruses, including Yellow fever, dengue and Zika virus. The mosquito midgut is the principal organ for blood meal digestion, nutrient absorption and the initial site of arbovirus infection. Although a previous study delineated midgut's transcriptome of Ae. aegypti at the single-nucleus resolution, there still lacks an established protocol for isolating and RNA sequencing of single cells of Ae. aegypti midgut, which is required for investigating arbovirus-midgut interaction at the single-cell level. Here, we established an atlas of the midgut cells for Ae. aegypti by single-cell RNA sequencing. We annotated the cell clusters including intestinal stem cells/enteroblasts (ISC/EB), cardia cells (Cardia), enterocytes (EC, EC-like), enteroendocrine cells (EE), visceral muscle (VM), fat body cells (FBC) and hemocyte cells (HC). This study will provide a foundation for further studies of arbovirus infection in mosquito midgut at the single-cell level., (© 2024. The Author(s).)

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe 1 . Local hybridization between the two groups occurred 2 , but not on all occasions 3 . Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups 4 . One such technocomplex for which the makers are unknown is the Lincombian-Ranisian-Jerzmanowician (LRJ), which has been described in northwestern and central Europe 5-8 . Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period., (© 2024. The Author(s).)

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health 1 . Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study 2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A high-fat diet (HFD) may be linked to an increased colorectal cancer (CRC) risk. Stem cell proliferation and adipokine release under inflammatory and obese conditions are the main factors regulating CRC progression. Furthermore, alterations in intestinal flora have been linked to tumorigenesis and tumour progression. However, whether a HFD can promote CRC occurrence by altering intestinal flora remains unclear. The objective of this study was to identify bacterial strains enriched by a HFD and investigate the association and mechanism by which a HFD and bacterial enrichment promote CRC occurrence and development. In this study, the intestinal microbiota of mice was assessed using 16S rRNA and metagenomic sequencing. Serum metabolites of HFD-fed mice were assessed using tandem liquid chromatography-mass spectrometry. CRC cell lines and organoids were co-cultured with Coriobacteriaceae to evaluate the effect of these bacteria on the CPT1A-ERK signalling pathway. We found that Coriobacteriaceae were enriched in the colons of HFD-fed mice. An endogenous Coriobacteriaceae strain, designated as Cori.ST1911, was successfully isolated and cultured from the stools of HFD-fed mice, and the tumorigenic potential of Cori.ST1911 in CRC was validated in several CRC mouse models. Furthermore, Cori.ST1911 increased acylcarnitine levels by activating CPT1A, demonstrating the involvement of the CPT1A-ERK axis. We also found that the endogenous Lactobacillus strain La.mu730 can interfere with Cori.ST1911 colonisation and restore gut barrier function. In conclusion, we identified a novel endogenous intestinal Coriobacteriaceae, Cori.ST1911, which might lead to a new gut microbiota intervention strategy for the prevention and treatment of CRC., (© 2024. The Author(s).)

This retrospective study aimed to investigate the changes in choroidal vascularity index (CVI) before and after surgery for idiopathic macular hole (MH). Enhanced depth imaging optical coherence tomography (EDI-OCT) images were analyzed at baseline and at 1-week, 1-month, and 3-month postoperative visits. A total of 97 patients (97 eyes) were included in the study. At baseline, overall CVI and macular CVI showed negative correlation with axial length (AL) and positive correlation with central corneal thickness (CCT). There were no significant differences in macular CVI or overall CVI between affected and healthy eyes, as well as in subgroup analysis of different stages of macular CVI. Following surgery, there was a significant decrease in CVI at 1 week postoperatively, followed by a gradual recovery to baseline levels over time. The observed changes in CVI may be attributed to factors such as air tamponade, pressure changes, and photoreceptor metabolism. This study provides insights into the pattern of CVI changes associated with MH surgery. The findings suggest that stage 4 MH is associated with decreased macular CVI in affected eyes. These results contribute to a better understanding of the effects of surgery on choroidal blood flow in MH patients., (© 2024. The Author(s).)

Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field., (© 2023. The Author(s).)

Pathogens typically responsible for hospital-acquired infections (HAIs) constitute a major threat to healthcare systems worldwide. They spread via hospital (or hospital-community) networks by readmissions or patient transfers. Therefore, knowledge of these networks is essential to develop and test strategies to mitigate and control the HAI spread. Until now, no methods for comparing healthcare networks across different systems were proposed. Based on healthcare insurance data from four German federal states (Bavaria, Lower Saxony, Saxony and Thuringia), we constructed hospital networks and compared them in a systematic approach regarding population, hospital characteristics, and patient transfer patterns. Direct patient transfers between hospitals had only a limited impact on HAI spread. Whereas, with low colonization clearance rates, readmissions to the same hospitals posed the biggest transmission risk of all inter-hospital transfers. We then generated hospital-community networks, in which patients either stay in communities or in hospitals. We found that network characteristics affect the final prevalence and the time to reach it. However, depending on the characteristics of the pathogen (colonization clearance rate and transmission rate or even the relationship between transmission rate in hospitals and in the community), the studied networks performed differently. The differences were not large, but justify further studies., (© 2024. The Author(s).)

In vitro-transcribed (IVT) mRNA has arisen as a rapid method for the production of nucleic acid drugs. Here, we have constructed an oncolytic IVT mRNA that utilizes human rhinovirus type 2 (HRV2) internal ribosomal entry sites (IRESs) to selectively trigger translation in cancer cells with high expression of EIF4G2 and PTBP1. The oncolytic effect was provided by a long hGSDMD c .825 T>A/c.884 A>G -F1L CT mutant mRNA sequence with mitochondrial inner membrane cardiolipin targeting toxicity that triggers mitophagy. Utilizing the permuted intron-exon (PIE) splicing circularization strategy and lipid nanoparticle (LNP) encapsulation reduced immunogenicity of the mRNA and enabled delivery to eukaryotic cells in vivo. Engineered HRV2 IRESs-GSDMD p.D275E/E295G -F1L CT circRNA-LNPs (GSDMD ENG circRNA) successfully inhibited EIF4G2 + /PTBP1 + pan-adenocarcinoma xenografts growth. Importantly, in a spontaneous tumor model with abnormal EIF4G2 and PTBP1 caused by KRAS G12D mutation, GSDMD ENG circRNA significantly prevented the occurrence of pancreatic, lung and colon adenocarcinoma, improved the survival rate and induced persistent KRAS G12D tumor antigen-specific cytotoxic T lymphocyte responses., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The combination of flexible sensors and deep learning has attracted much attention as an efficient method for the recognition of human postures. In this paper, an in situ polymerized MXene/polypyrrole (PPy) composite is dip-coated on a polydimethylsiloxane (PDMS) sponge to fabricate an MXene/PPy@PDMS (MPP) piezoresistive sensor. The sponge sensor achieves ultrahigh sensitivity (6.8925 kPa -1 ) at 0-15 kPa, a short response/recovery time (100/110 ms), excellent stability (5000 cycles) and wash resistance. The synergistic effect of PPy and MXene improves the performance of the composite materials and facilitates the transfer of electrons, making the MPP sponge at least five times more sensitive than sponges based on each of the individual single materials. The large-area conductive network allows the MPP sensor to maintain excellent electrical performance over a large-scale pressure range. The MPP sensor can detect a variety of human body activity signals, such as radial artery pulse and different joint movements. The detection and analysis of human motion data, which is assisted by convolutional neural network (CNN) deep learning algorithms, enable the recognition and judgment of 16 types of human postures. The MXene/PPy flexible pressure sensor based on a PDMS sponge has broad application prospects in human motion detection, intelligent sensing and wearable devices., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2023.)

Background: Hirschsprung disease (HSCR) is a congenital intestinal malformation. Previous HSCR animal model needs invasive operation on adult animal. The aim of this study is to establish an early-onset animal model which is consistent with the clinical manifestation of HSCR patients., Methods: The neonatal mice were randomly divided into the benzalkonium chloride (BAC) group, treated with BAC via enema, and the control group, treated with saline. Weight changes, excretion time of carmine, CT scan, hematoxylin-eosin staining and immunofluorescence staining were used to evaluate the effect of the model. Differentially expressed genes (DEGs) in the HSCR mice were analyzed by using DAVID 6.8 database and compared with DEGs from HSCR patients., Results: The weight of mice was lower and the excretion time of carmine was longer in the BAC group. Moreover, distal colon stenosis and proximal colon enlargement appeared in the BAC group. Neurons in the distal colon decreased significantly after 4 weeks of BAC treatment and almost disappeared completely after 12 weeks. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression., Conclusions: An economical and reliable HSCR animal model which has similar clinical characteristics to HSCR patients was successfully established., Impact: The animal model of Hirschsprung disease was first established in BALB/c mice. This model is an animal model of early-onset HSCR that is easy to operate and consistent with clinical manifestations. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression., (© 2023. The Author(s).)

The coronavirus disease 2019 (COVID-19), which affects multiple organs, is causing an unprecedented global public health crisis. Most COVID-19 patients recover gradually upon appropriate interventions. Viruses were reported to utilize the small extracellular vesicles (sEVs), containing a cell-specific cargo of proteins, lipids, and nucleic acids, to escape the attack from the host's immune system. This study aimed to examine the sEVs lipid profile of plasma of recovered COVID-19 patients (RCs). Plasma sEVs were separated from 83 RCs 3 months after discharge without underlying diseases, including 18 recovered asymptomatic patients (RAs), 32 recovered moderate patients (RMs), and 33 recovered severe and critical patients (RSs), and 19 healthy controls (HCs) by Total Exosome Isolation Kit. Lipids were extracted from sEVs and then subjected to targeted liquid chromatography-mass spectrometry. The size, concentration, and distribution of sEVs did not differ in RCs and HCs as validated by transmission electron microscopy, nanoparticle tracking analysis, and immunoblot analysis. Fifteen subclasses of 508 lipids were detected in plasma sEVs from HCs, RAs, RMs, and RSs, such as phosphatidylcholines (PCs) and diacylglycerols (DAGs), etc. Total lipid intensity displayed downregulation in RCs compared with HCs. The relative abundance of DAGs gradually dropped, whereas PCs, lysophosphatidylcholines, and sphingomyelins were higher in RCs relative to HCs, especially in RSs. 88 lipids out of 241 in sEVs of RCs were significantly different and a conspicuous increase was revealed with disease status. The sEVs lipids alternations were found to be significantly correlated with the clinical indices in RCs and HCs, suggesting that the impact of COVID-19 on lipid metabolism lingered for a long time. The lipid abnormalities bore an intimate link with glycerophospholipid metabolism and glycosylphosphatidylinositol anchor biosynthesis. Furthermore, the lipidomic analysis showed that RCs were at higher risk of developing diabetes and sustaining hepatic impairment. The abnormality of immunomodulation in RCs might still exist. The study may offer new insights into the mechanism of organ dysfunction and help identify novel therapeutic targets in the RCs., (© 2023. Springer Nature Limited.)

3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) is the rate-limiting enzyme for ketone body synthesis, and most current studies focus on mitochondrial maturation and metabolic reprogramming. The role of HMGCS2 was evaluated in a pan-cancer multi-database using R language, and HMGCS2 was lowly expressed or not differentially expressed in all tumor tissues compared with normal tissues. Correlation analysis of clinical case characteristics, genomic heterogeneity, tumor stemness, and overall survival revealed that HMGCS2 is closely related to clear cell renal cell carcinoma (KIRC). Single-cell sequencing data from normal human kidneys revealed that HMGCS2 is specifically expressed in proximal tubular cells of normal adults. In addition, HMGCS2 is associated with tumor immune infiltration and microenvironment, and KIRC patients with low expression of HMGCS2 have worse prognosis. Finally, the results of cell counting kit 8 assays, colony formation assays, flow cytometry, and Western blot analysis suggested that upregulation of HMGCS2 increased the expression of key tumor suppressor proteins, inhibited the proliferation of clear cell renal cell carcinoma cells and promoted cell apoptosis. In conclusion, HMGCS2 is abnormally expressed in pan-cancer, may play an important role in anti-tumor immunity, and is expected to be a potential tumor prognostic marker, especially in clear cell renal cell carcinoma., (© 2023. Springer Nature Limited.)

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank., (© 2023. Springer Nature Limited.)

Duct-dependent congenital heart diseases (CHDs) are a serious form of CHD with a low detection rate, especially in underdeveloped countries and areas. Although existing studies have developed models for fetal heart structure identification, there is a lack of comprehensive evaluation of the long axis of the aorta. In this study, a total of 6698 images and 48 videos are collected to develop and test a two-stage deep transfer learning model named DDCHD-DenseNet for screening critical duct-dependent CHDs. The model achieves a sensitivity of 0.973, 0.843, 0.769, and 0.759, and a specificity of 0.985, 0.967, 0.956, and 0.759, respectively, on the four multicenter test sets. It is expected to be employed as a potential automatic screening tool for hierarchical care and computer-aided diagnosis. Our two-stage strategy effectively improves the robustness of the model and can be extended to screen for other fetal heart development defects., (© 2023. Springer Nature Limited.)

Lung cancer ranks as one of the top malignancies and the leading cause of cancer death in both males and females in the US. Using a cancer database covering the entire population, this study was to determine the gender disparities in lung cancer incidence during 2001-2019. Cancer patients were obtained from the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology and End Results (SEER) database. The SEER*Stat software was applied to calculate the age-adjusted incidence rates (AAIR). Temporal changes in lung cancer incidence were analyzed by the Joinpoint software. A total of 4,086,432 patients (53.3% of males) were diagnosed with lung cancer. Among them, 52.1% were 70 years or older, 82.7% non-Hispanic white, 39.7% from the South, and 72.6% non-small cell lung cancer (NSCLC). The AAIR of lung cancer continuously reduced from 91.0 per 100000 to 59.2 in males during the study period, while it increased from 55.0 in 2001 to 56.8 in 2006 in females, then decreased to 48.1 in 2019. The female to male incidence rate ratio of lung cancer continuously increased from 2001 to 2019. Gender disparities were observed among age groups, races, and histological types. In those aged 0-54 years, females had higher overall incidence rates of lung cancer than males in recent years, which was observed in all races (except non-Hispanic black), all regions, and adenocarcinoma and small cell (but not squamous cell). Non-Hispanic black females aged 0-54 years had a faster decline rate than males since 2013. API females demonstrated an increased trend during the study period. Lung cancer incidence continues to decrease with gender disparities among age groups, races, regions, and histological types. Continuous anti-smoking programs plus reduction of related risk factors are necessary to lower lung cancer incidence further., (© 2023. Springer Nature Limited.)

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods., (© 2023. The Author(s).)

Studies in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis, Huntington's disease, and so on, have suggested that inflammation is not only a result of neurodegeneration but also a crucial player in this process. Protein aggregates which are very common pathological phenomenon in neurodegeneration can induce neuroinflammation which further aggravates protein aggregation and neurodegeneration. Actually, inflammation even happens earlier than protein aggregation. Neuroinflammation induced by genetic variations in CNS cells or by peripheral immune cells may induce protein deposition in some susceptible population. Numerous signaling pathways and a range of CNS cells have been suggested to be involved in the pathogenesis of neurodegeneration, although they are still far from being completely understood. Due to the limited success of traditional treatment methods, blocking or enhancing inflammatory signaling pathways involved in neurodegeneration are considered to be promising strategies for the therapy of neurodegenerative diseases, and many of them have got exciting results in animal models or clinical trials. Some of them, although very few, have been approved by FDA for clinical usage. Here we comprehensively review the factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. We also summarize the current strategies, both in animal models and in the clinic, for the treatment of neurodegenerative diseases., (© 2023. The Author(s).)

Although bisphenol S (BPS), as a bisphenol A (BPA) substitute, has been widely used in the commodity, it is embryotoxic in recent experiments. Nowadays, it remains unclear how BPS affects preimplantation embryos. Here, my team investigated the effects of BPS on preimplantation embryos and the possible molecular mechanisms in mice. The results showed that 10 -6  mol/L BPS exposure delayed the blastocysts stage, and exposure to 10 -4  mol/L BPS induced 2-cell block in mice preimplantation embryos. A significant increase in reactive oxygen species (ROS) level and antioxidant enzyme genes Sod1, Gpx1, Gpx6, and Prdx2 expression were shown, but the level of apoptosis was normal in 2-cell blocked embryos. Further experiments demonstrated that embryonic genome activation (EGA) specific genes Hsp70.1 and Hsc70 were significantly decreased, which implied that ROS and EGA activation have the potential to block 2-cell development. Antioxidant enzymes, including superoxide dismutase (SOD), coenzyme Q10 (CoQ10), and folic acid (FA) were used to further explore the roles of ROS and EGA in 2-cell block. Only 1200 U/mL SOD was found to alleviate the phenomenon of 2-cell block, reduce oxidative damage, and restore the expression of EGA-specific genes Hsp70.1 and Hsc70. Conclusively, this study demonstrates for the first time that BPS can induce 2-cell block, which is mainly mediated by ROS aggregation and results in the failure of EGA activation., (© 2023. The Author(s).)

In this study, we simulated the spatial and temporal processes of a particulate matter (PM) pollution episode from December 10-29, 2019, in Zhengzhou, the provincial capital of Henan, China, which has a large population and severe PM pollution. As winter is the high incidence period of particulate pollution, winter statistical data were selected from the pollutant observation stations in the study area. During this period, the highest concentrations of PM 2.5 (atmospheric PM with a diameter of less than 2.5 µm) and PM 10 (atmospheric PM with a diameter of less than 10 µm) peaked at 283 μg m -3 and 316 μg m -3 , respectively. The contribution rates of local and surrounding regional emissions within Henan (emissions from the regions to the south, northwest, and northeast of Zhengzhou) to PM concentrations in Zhengzhou were quantitatively analyzed based on the regional Weather Research and Forecasting model coupled with Chemistry (WRF/Chem). Model evaluation showed that the WRF/Chem can accurately simulate the spatial and temporal variations in the PM concentrations in Zhengzhou. We found that the anthropogenic emissions south of Zhengzhou were the main causes of high PM concentrations during the studied episode, with contribution rates of 14.39% and 16.34% to PM 2.5 and PM 10 , respectively. The contributions of anthropogenic emissions from Zhengzhou to the PM 2.5 and PM 10 concentrations in Zhengzhou were 7.94% and 7.29%, respectively. The contributions of anthropogenic emissions from the area northeast of Zhengzhou to the PM 2.5 and PM 10 concentrations in Zhengzhou were 7.42% and 7.18%, respectively. These two areas had similar contributions to PM pollution in Zhengzhou. The area northeast of Zhengzhou had the lowest contributions to the PM 2.5 and PM 10 concentrations in Zhengzhou (5.96% and 5.40%, respectively)., (© 2023. The Author(s).)

Arthropod-borne virus (arbovirus) and arthropod-specific virus (ASV) are viruses circulating amongst hematophagous arthropods that are broadly transmitted in ecological systems. Arbovirus may replicate in both vertebrates and invertebrates and some are known to be pathogenic to animals or humans. ASV only replicate in invertebrate arthropods yet they are basal to many types of arboviruses. We built a comprehensive dataset of arbovirus and ASV by curating globally available data from the Arbovirus Catalog, the arbovirus list in Section VIII-F of the Biosafety in Microbiological and Biomedical Laboratories 6th edition, Virus Metadata Resource of International Committee on Taxonomy of Viruses, and GenBank. Revealing the diversity, distribution and biosafety recommendation of arbovirus and ASV at a global scale is essential to the understanding of potential interactions, evolution, and risks associated with these viruses. Moreover, the genomic sequences associated with the dataset will enable the investigation of genetic patterns distinguishing the two groups, as well as aid in predicting the vector/host relationships of the newly discovered viruses., (© 2023. The Author(s).)

Epithelial cell damage-initiated chronic obstructive pulmonary disease (COPD) is implicated in regulated cell death (RCD) including ferroptosis triggered by complex gene-environment interactions. Our data showed that iron overload and ferroptosis are associated with COPD progression in COPD patients and in experimental COPD. Furthermore, we found that, in lung tissues of COPD patients, circSAV1 was associated with COPD progression by circRNA-seq screening. Knockdown of circSAV1 reversed cigarette smoke extract (CSE)-induced ferroptosis. Mechanistically, m6A-modified circSAV1 formed an RNA-protein ternary complex of circSAV1/YTHDF1/IREB2 to facilitate the translation of IREB2 mRNA. Elevated protein levels of IREB2 disrupted iron homeostasis, resulting in accumulation of a labile iron pool (LIP) and lipid peroxidation, which contribute to ferroptosis. Here we demonstrate, by use of an experimental COPD model induced by cigarette smoke (CS), that silencing of circSAV1 and the treatment with deferoxamine (DFO) blocked CS-induced ferroptosis of lung epithelial cells, which attenuated COPD progression in mice. Our results reveal that N6-methyladenosine-modified circSAV1 triggers ferroptosis in COPD through recruiting YTHDF1 to facilitate the translation of IREB2, indicating that circSAV1 is a mediator of ferroptosis and that circSAV1-dependent ferroptosis is a therapeutic target for COPD. In lung epithelial cell, m6A-modified circSAV1, via recruiting YTHDF1, induces the formation of a circSAV1/YTHDF1/IREB2 mRNA protein ternary complex, which promotes translation of IREB2 mRNA. Further, elevated IREB2 contributes to the accumulation of a labile iron pool (LIP) and lipid peroxidation, then triggers ferroptosis of lung epithelial cells. The ferroptosis of airway epithelial cells and alveolar epithelial cells induces airway remodeling and emphysema, respectively, which causes COPD., (© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

This paper introduces a new type of steel-concrete composite pylon that has been applied to Nanjing Fifth Yangtze River Bridge (a three-pylon cable-stayed bridge with a main span of 600 m). For this new type of pylon, the steel shells are connected with concrete through PBL shear connectors and studs, and the inner steel shells are connected with the outer steel shells by angle steels. Numerical analysis and full-scale model tests show that the pylon structure exhibits excellent mechanical properties and construction performance. The application of BIM technology, the research and development of special spreaders and construction platforms ensure the precise installation of structures. Highly factory-manufactured modular assembly of the reinforced steel shell structure can effectively reduce the intensity and difficulty of on-site operations, and improve the quality of the project, with low construction risks. Whereas, the successful application of this steel-concrete-steel sandwich composite pylon marks the formation of a complete set of construction technology of steel-concrete-steel sandwich composite pylon, which can be widely used in similar bridges., (© 2023. The Author(s).)

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells 1-14 . The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies 15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8 + T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The most commercialized kiwifruit, Actinidia chinensis var. deliciosa (Acd), is an allohexaploid (2n = 6x = 174), making high-quality assemblage genome challenging. We previously discovered a rare naturally occurring diploid Acd plant. Here, chromosome-level de novo genome assembly for this diploid Acd was reported, reaching approximately 621.98 Mb in length with contig and scaffold N50 values of 10.08 and 21.09 Mb, respectively, 99.66% of the bases anchored to 29 pseudochromosomes, and 38,990 protein-coding genes and 42.29% repetitive elements annotated. The divergence time of A. chinensis cv. 'Red5' and 'Hongyang' (11.1-27.7 mya) was more recent compared with the divergence time of them and Acd (19.9-41.2 mya), with the divergence time of A. eriantha cv. 'White' being the earliest (22.9-45.7 mya) among that of the four Actinidia species. The 4DTv distance distribution highlighted three recent whole-genome duplication events in Acd. This is the first high-quality diploid Acd genome, which lays an important foundation for not only kiwifruit functional genomics studies but also further elucidating genome evolution of allohexaploid Acd., (© 2023. The Author(s).)

New and old subgrade stability is a crucial problem for widening projects in soft soil foundations because uncoordinated deformations can cause serious engineering accidents, even disasters. In order to ensure the stability of a widening expressway project near a pond in the Qinbei section, a series of on-site investigations, lab tests, and numerical analyses was performed. The settlement and displacement of on-site monitoring were carried out during the construction period to verify the analyzed results. It was found that the uneven settlement caused heavy settlement and displacement of the embankment; thus, net cracks and longitudinal cracks occurred in the expressway. The new embankment was also affected by the weak foundation; therefore, the foundation should be reinforced before the construction of the widening part. Considering the economy and effectiveness of the widening project, the replacement method was recommended for the weak foundation reinforcement based on the numerical analysis and on-site motoring results. Water pumping had a significant effect on the settlement of the embankment. Water pumping caused seepage in the foundation and increased the effective stress of the soil, making the foundation more consolidated. The pond slope should be reinforced before the construction of the embankment because it was not confined by the surrounding soil. Therefore, the slope soil could not provide sufficient passive soil pressure and easily slide., (© 2023. The Author(s).)

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8 + T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy., (© 2022. The Author(s).)

Chronic kidney disease (CKD) has become a worldwide public health problem and accurate assessment of renal function in CKD patients is important for the treatment. Although the glomerular filtration rate (GFR) can accurately evaluate the renal function, the procedure of measurement is complicated. Therefore, endogenous markers are often chosen to estimate GFR indirectly. However, the accuracy of the equations for estimating GFR is not optimistic. To estimate GFR more precisely, we constructed a classification decision tree model to select the most befitting GFR estimation equation for CKD patients. By searching the HIS system of the First Affiliated Hospital of Zhejiang Chinese Medicine University for all CKD patients who visited the hospital from December 1, 2018 to December 1, 2021 and underwent Gate's method of 99m Tc-DTPA renal dynamic imaging to detect GFR, we eventually collected 518 eligible subjects, who were randomly divided into a training set (70%, 362) and a test set (30%, 156). Then, we used the training set data to build a classification decision tree model that would choose the most accurate equation from the four equations of BIS-2, CKD-EPI(CysC), CKD-EPI(Cr-CysC) and Ruijin, and the equation was selected by the model to estimate GFR. Next, we utilized the test set data to verify our tree model, and compared the GFR estimated by the tree model with other 13 equations. Root Mean Square Error (RMSE), Mean Absolute Error (MAE) and Bland-Altman plot were used to evaluate the accuracy of the estimates by different methods. A classification decision tree model, including BSA, BMI, 24-hour Urine protein quantity, diabetic nephropathy, age and RASi, was eventually retrieved. In the test set, the RMSE and MAE of GFR estimated by the classification decision tree model were 12.2 and 8.5 respectively, which were lower than other GFR estimation equations. According to Bland-Altman plot of patients in the test set, the eGFR was calculated based on this model and had the smallest degree of variation. We applied the classification decision tree model to select an appropriate GFR estimation equation for CKD patients, and the final GFR estimation was based on the model selection results, which provided us with greater accuracy in GFR estimation., (© 2022. The Author(s).)

Metastasis is the leading cause of cancer-related death. The interactions between circulating tumor cells and endothelial adhesion molecules in distant organs is a key step during extravasation in hematogenous metastasis. Surgery is a common intervention for most primary solid tumors. However, surgical trauma-related systemic inflammation facilitates distant tumor metastasis by increasing the spread and adhesion of tumor cells to vascular endothelial cells (ECs). Currently, there are no effective interventions to prevent distant metastasis. Here, we show that HECTD3 deficiency in ECs significantly reduces tumor metastasis in multiple mouse models. HECTD3 depletion downregulates expression of adhesion molecules, such as VCAM-1, ICAM-1 and E-selectin, in mouse primary ECs and HUVECs stimulated by inflammatory factors and inhibits adhesion of tumor cells to ECs both in vitro and in vivo. We demonstrate that HECTD3 promotes stabilization, nuclear localization and kinase activity of IKKα by ubiquitinating IKKα with K27- and K63-linked polyubiquitin chains at K296, increasing phosphorylation of histone H3 to promote NF-κB target gene transcription. Knockout of HECTD3 in endothelium significantly inhibits tumor cells lung colonization, while conditional knockin promotes that. IKKα kinase inhibitors prevented LPS-induced pulmonary metastasis. These findings reveal the promotional role of the HECTD3-IKKα axis in tumor hematogenous metastasis and provide a potential strategy for tumor metastasis prevention., (© 2022. The Author(s).)

Endemic to Australia, jade perch (Scortum barcoo) is a highly profitable freshwater bass species. It has extraordinarily high levels of omega-3 polyunsaturated fatty acids (PUFAs), which detailed genes involved in are largely unclear. Meanwhile, there were four chromosome-level bass species have been previous sequenced, while the bass ancestor genome karyotypes have not been estimated. Therefore, we sequenced, assembled and annotated a genome of jade perch to characterize the detailed genes for biosynthesis of omega-3 PUFAs and to deduce the bass ancestor genome karyotypes. We constructed a chromosome-level genome assembly with 24 pairs of chromosomes, 657.7 Mb in total length, and the contig and the scaffold N50 of 4.8 Mb and 28.6 Mb respectively. We also identified repetitive elements (accounting for 19.7% of the genome assembly) and predicted 26,905 protein-coding genes. Meanwhile, we performed genome-wide localization and characterization of several important genes encoding some key enzymes in the biosynthesis pathway of PUFAs. These genes may contribute to the high concentration of omega-3 in jade perch. Moreover, we conducted a series of comparative genomic analyses among four representative bass species at a chromosome level, resulting in a series of sequences of a deductive bass ancestor genome., (© 2022. The Author(s).)

Hepatocellular carcinoma (HCC) is one of the deadliest cancer types worldwide. The centromere proteins (CENPs) are critical for the mitosis-related protein complex and are involved in kinetochore assembly and spindle checkpoint signaling during mitosis. However, the clinical significance of CENPs in the recurrence and progression of HCC remains poorly understood. Here, we examined the expression of all CENPs and their association with recurrence and survival of HCC patients using the global gene expression profile dataset established in our laboratory. The effect of silencing CENPF on cell viability, migration, and epithelial-mesenchymal transition (EMT) were detected using CCK-8, transwell, and western blot, respectively. RT-qPCR and western blot were performed to confirm the silencing of CENPF and the relationship between STAT5A and CENPF, while tumorigenesis was tested using the HCC Huh7 xenograft mouse model. Most of the CENPs is overexpressed in HCC, and overexpression of CENPF was significantly associated with the poor survival of HCC patients. CENPF promoted HCC cell lines migration and EMT progression. Knockdown CENPF inhibited cell growth activity against human HCC cells in vitro and xenograft tumors in vivo. Bioinformatics analysis revealed that CENPF genes are enriched in the cell cycle. Silencing CENPF arrested cell cycle at the G2/M phase and inhibited Cyclin B1 and Cyclin E1 expressions. Meanwhile, silencing CENPF prohibited phosphorylation of ERK and the expression of NEK2. Additionally, we found that STAT5A down-regulated CENPF expression and inhibited cancer cell growth viability. In conclusion, our data suggested that CENPF could be potentially developed into a theranostic biomarker to tackle HCC progression., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

As the most primordial signaling pathway in animal physiology, the Hippo pathway and innate immunity play crucial roles not only in sensing cellular conditions or infections, but also in various metabolite homeostasis and tumorigenesis. However, the correlation between cellular homeostasis and antiviral defense is not well understood. The core kinase LATS1/2, could either enhance or inhibit the anti-tumor immunity in different cellular contexts. In this study, we found that LATS2 can interact with PQBP1, the co-factor of cGAS, thus enhanced the cGAS-STING mediated innate immune response to HIV-1 challenge. LATS2 was observed to upregulate type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA and inhibited HIV-1 infection. Due to the involvement of PQBP1, the function of LATS2 in regulating cGAS activity is not relying on the downstream YAP/TAZ as that in the canonical Hippo pathway. The related kinase activity of LATS2 was verified, and the potential phosphorylation site of PQBP1 was identified. Our study established a novel connection between Hippo signaling and innate immunity, thus may provide new potential intervention target on antiviral therapeutics., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Colorectal carcinoma (CRC) has a high morbidity and mortality. Current studies have confirmed a variety of microRNA polymorphisms were associated with tumor susceptibility, however, the mechanisms are still unknown. In this study, we were aimed to clarify how polymorphism rs2682818 participated in the progression of CRC. First of all, the differential expression of miR-618 was assessed by quantitative real-time polymerase chain reaction in CRC patients with different genotypes of polymorphism rs2682818, including homozygous (TT) genotype, homozygous (GG) genotype and heterozygous (TG) genotype. Secondly, plasmids carried miR-168 precursor sequences harboring rs2682818 (SNP type) or without rs2682818 (wild type) were transfected into 293T cells to verify that polymorphism rs2682818 affected miR-618 expression. Thirdly, CCK-8 assay, flow cytometry assay, transwell assay and mouse xenograft assay were performed to measure the biological functions of miR-618 in CRC. Fourthly, the candidate target genes of miR-618 which were predicted by bioinformatics tools were verified by luciferase reporter assay. Finally, in order to explain the potential molecular mechanisms, western blotting was performed to demonstrate the differential expression and phosphorylation of pathway related proteins. The results showed that miR-618 was down-regulated in colon cancer, especially in CRC patients with rs2682818 GG homozygous genotype. Higher expression of mature miR-618 occurred in patients with TT homozygous genotype, and these patients usually had a longer survival time. Moreover, miR-618 mimic obviously impaired the growth and invasion ability of CRC cells, and miR-618 mimic also remarkably promoted CRC cell apoptosis. Our luciferase experiments confirmed that TIMP1 was a target of miR-618 in CRC cells. Knockdown of TIMP1 also significantly inhibited the malignant cytological features of CRC, including malignant growth and invasion as well as apoptosis resistance. In summary, polymorphism rs2682818 participated in the progression of CRC via affecting the expression of mature miR-618 in CRC cells, and miR-618 inhibited the progression of CRC via targeting TIMP1expression., (© 2021. The Author(s).)

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8 + T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders., (© 2021. The Author(s).)