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Abstract Neurons often grow highly branched and cell-type specific dendrite morphologies to receive and integrate information, which is the basis of precise neural circuit formation. Previous studies have identified numerous mechanisms that promote dendrite branching. In contrast, it is much less understood how this process is negatively regulated. Here we show that EAT-17/EVI5 acts together with the dynein adaptor protein BICD-1 and the motor protein dynein in C. elegans epidermal cells to restrict branching of PVD sensory dendrites. Loss-of-function mutants of these genes cause both ectopic branching and accumulation of the dendrite branching ligand SAX-7/L1CAM on epidermal plasma membranes. Mutants of genes regulating endo-lysosomal trafficking, including rab-5/RAB5 and dyn-1/DNM1, show similar defects. Biochemical characterization, genetic analysis, and imaging results support that EAT-17 and BICD-1 directly interact with each other and function in the endocytic degradation pathway to remove ectopically localized dendrite branching ligands to restrict abnormal branching.

Abstract Background Pre-frailty is a window of opportunity for frailty reversal and can be enhanced by multicomponent exercise. The Lifestyle-integrated Functional Exercise (LiFE) program may be a promising alternative to overcome traditional exercise barriers. The latest advancements in mobile health (mHealth) technology have enabled individuals to retain the advantages of supervised exercise training within group settings while providing exercise programs that can be accessed and completed at home. This study aims to assess the feasibility, acceptability, and primary efficacy of the PF-Life program, which is the Lifestyle-Integrated Functional Exercise program for Pre-Frail supported by an mHealth platform. Methods Sixteen pre-frail adults aged ≥ 65 years were recruited from five community health centers in Fuzhou, China. All participants were prescribed the PF-Life program by geriatricians using the mhealth platform (web-based portal). Participants engaged in the customized exercises program following in-app video instructions and feedback on the mhealth platform (smartphone application). Physical activity (PA) and sedentary behavior (SB) were registered daily through wearable devices. Study endpoints were feasibility (retention rate, compliance rate, adverse events), usability (system usability scale), acceptability (qualitative interviews), changes in physical function (timed up and go (TUG), handgrip strength (HGS), and 30-second chair rise tests), PA and SB. Results The intervention was feasible, 88% of participants adhered completely to the study protocol, and 95% had completed at least 75% of the prescribed experimental duration. System usability was high (85 out of 100 best imaginable). Changes were observed from baseline to follow-up for total HGS (21.41 ± 6.38 vs. 24.12 ± 6.62 kg, P

The single-phase face-centered cubic medium-entropy alloys (MEAs) normally have coarse grains in as-cast state, which exhibit insufficient strength for engineering applications. Here, a superior tensile strength-ductility synergy in a fine grained (CoCrNi)94Al3Ti3 MEA hardened by nanoscale L12 precipitates was fabricated by spark plasma sintering (SPS) and post-sintering in-situ precipitation treatment. The SPSed MEAs have a fine grain size of ⁓ 5 μm, and a high number density of L12 precipitates form after in-situ annealing within the SPS machine. A high tensile yield strength of 1141 MPa with an adequate elongation to fracture of 25.8% was achieved in (CoCrNi)94Al3Ti3 MEA after annealing at 700 °C for 4 h. Electron backscattered diffraction and transmission electron microscopy characterizations indicate that the superior mechanical properties mainly originate from fine grains and the coherent spherical L12 precipitates. The dislocation slips and stacking faults prevail in all SPSed MEAs during tensile deformation, while extra Lomer-Cottrell locks are observed in annealed MEAs. The deformation twinning is absent in these precipitation-hardened MEAs with a low stacking fault energy, which may be attributed to the fine grains and numerous nanoscale L12 precipitates. This study not only confirms the effectiveness of powder metallurgy when sintering and precipitation are combined in-situ during the SPS cycle, but also provide guidance for the microstructure regulation process and practical applications of SPSed HEAs/MEAs.

Abstract Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4–14.0; P

Abstract Background The cotton whitefly (Bemisia tabaci) is a major global pest, causing significant crop damage through viral infestation and feeding. Traditional B. tabaci recognition relies on human eyes, which requires a large amount of work and high labor costs. The pests overlapping generations, high reproductive capacity, small size, and migratory behavior present challenges for the real-time monitoring and early warning systems. This study aims to develop an efficient, high-throughput automated system for detection of the cotton whiteflies. In this work, a novel tool for cotton whitefly fast identification and quantification was developed based on deep learning-based model. This approach enhances the effectiveness of B. tabaci control by facilitating earlier detection of its establishment in cotton, thereby allowing for a quicker implementation of management strategies. Results We compiled a dataset of 1200 annotated images of whiteflies on cotton leaves, augmented using techniques like flipping and rotation. We modified the YOLO v8s model by replacing the C2f module with the Swin-Transformer and introducing a P2 structure in the Head, achieving a precision of 0.87, mAP50 of 0.92, and F1 score of 0.88 through ablation studies. Additionally, we employed SAHI for image preprocessing and integrated the whitefly detection algorithm on a Raspberry Pi, and developed a GUI-based visual interface. Our preliminary analysis revealed a higher density of whiteflies on cotton leaves in the afternoon and the middle-top, middle, and middle-down plant sections. Conclusion Utilizing the enhanced YOLO v8s deep learning model, we have achieved precise detection and counting of whiteflies, enabling its application on hardware devices like the Raspberry Pi. This approach is highly suitable for research requiring accurate quantification of cotton whiteflies, including phenotypic analyses. Future work will focus on deploying such equipment in large fields to manage whitefly infestations.

Abstract In the context of close-distance coal seam mining, the stress transfer mechanism following the extraction of the upper coal seam is crucial for the layout of roadways in the lower coal seam. This study utilizes ground-penetrating radar (GPR) to analyze the stability and plastic zone extent of residual coal pillars after upper seam extraction. A theoretical model for the stress distribution of multiple goaves and coal pillars was established. Based on a case study with variable inter-seam spacing, the stress distribution and transfer mechanisms of the floor were analyzed. The results indicate that during the transition from the center of the coal pillar to the goaf, stress concentration initially decreases significantly and then gradually returns to the original rock stress, forming a distinct stress gradient distribution. As the depth of the floor strata increases, the weight of the overlying strata is more evidently transferred through the coal pillars to the goaf. Finally, a reasonable layout range for the lower seam mining roadways under different inter-seam spacings is proposed, providing a reference for optimizing roadway layout in similar geological conditions.

Abstract Background Cellular senescence can be induced in mammalian tissues by multiple stimuli, including aging, oncogene activation and loss of tumor suppressor genes, and various types of stresses. While senescence is a tumor suppressing mechanism when induced within premalignant or malignant tumor cells, senescent cells can promote cancer development through increased secretion of growth factors, cytokines, chemokines, extracellular matrix, and degradative enzymes, collectively known as senescence-associated secretory phenotype (SASP). Previous studies indicated that senescent cells, through SASP factors, stimulate tumor cell invasion that is a critical step in cancer cell metastasis. Methods In the current study, we investigated the effect of senescent cells on the motility of breast cancer cells, which is another key step in cancer cell metastasis. We analyzed the motility of breast cancer cells co-cultured with senescent cells in vitro and metastasis of the breast cancer cells co-injected with senescent cells in orthotopic xenograft models. We also delineated the signaling pathway mediating the effect of senescent cells on cancer cell motility. Results Our results indicate that senescent cells stimulated the migration of breast cancer cells through secretion of GM-CSF and bFGF, which in turn induced activation of the JNK pathway in cancer cells. More importantly, senescent cells promoted breast cancer metastasis, with a minimum effect on the primary tumor growth, in orthotopic xenograft mouse models. Conclusions These results have revealed an additional mechanism by which senescent cells promote tumor cell metastasis and tumor progression, and will potentially lead to identification of novel targets for cancer therapies that suppress metastasis, the major cause of cancer mortality.

Abstract Seed size, a key determinant of rice yield, is regulated by brassinosteroid (BR); however, the BR pathway in rice has not been fully elucidated. Here, we report the cloning and characterization of the quantitative trait locus Rice Big Grain 1 (qRBG1) from single-segment substitution line Z499. Our data show that qRBG1 Z is an unselected rare promoter variation that reduces qRBG1 expression to increase cell number and size, resulting in larger grains, whereas qRBG1 overexpression causes smaller grains in recipient Nipponbare. We demonstrate that qRBG1 encodes a non-canonical BES1 (Bri1-EMS-Suppressor1)/BZR1(Brassinazole-Resistant1) family member, OsBZR5, that regulates grain size upon phosphorylation by OsGSK2 (GSK3-like Kinase2) and binding to D2 (DWARF2) and OFP1 (Ovate-Family-Protein1) promoters. qRBG1 interacts with OsBZR1 to synergistically repress D2, and to antagonistically mediate OFP1 for grain size. Our results reveal a regulatory network controlling grain size via OsGSK2–qRBG1–OsBZR1–D2–OFP1 module, providing a target for improving rice yield.

Abstract Background To evaluate the safety and efficacy of percutaneous biopsy and microwave ablation (B + MWA) in patients with pulmonary nodules (PNs) who are receiving antithrombotic therapy by rivaroxaban as bridging therapy. Methods The study comprised 187 patients with PNs who underwent 187 B + MWA sessions from January 1, 2020, to December 31, 2021. The enrolled patients were divided into two groups: Group A, who received antithrombotic therapy five days before the procedure and received rivaroxaban as a bridging drug during hospitalization, and group B, who had no antithrombotic treatment. Information about the technical success rate, positive biopsy rate, complete ablative rate, and major complications were collected and analyzed. Results Group A comprised 53 patients and group B comprised 134 patients. The technical success rate was 100% in both groups. The positive biopsy rates were 88.68% and 91.04%, respectively (p = 0.6211, X2 = 0.2443). In groups A and B, the complete ablative rates at 6, 12, and 24 months were 100.0% versus 99.25%, 96.23% versus 96.27%, and 88.68% versus 89.55%, respectively. There were no significant differences in bleeding and thrombotic complications between the two groups. No grade 5 complications occurred. Conclusions It is generally considered safe and effective that patients who are on antithrombotic therapy by rivaroxaban as bridging to undergo B + MWA for treating PNs.

AIM: To evaluate the outcomes of eye-sparing surgery for lacrimal gland adenoid cystic carcinoma and the impact on tumor recurrence and orbital integrity. METHODS: The study enrolled four patients with recurrent lacrimal gland adenoid cystic carcinoma. The outcome focused on the relevance of the integrity of the lateral orbital wall to the occurrence of extraorbital metastasis in the local recurrence of lacrimal gland adenoid cystic carcinoma. RESULTS: Three patients underwent eye-sparing surgery via lateral orbitotomy without postoperative radiotherapy, and one patient who underwent eye-sparing surgery via sub-brow approach. These four patients all demonstrated a recurrence involving the invasion of extraorbital tissues as metastatic form through surgical bone seams. CONCLUSION: Preserving intact orbital bone tissue is crucial for mitigating direct cross-organ metastasis of lacrimal gland adenoid cystic carcinoma. The findings suggest avoiding the lateral orbitotomy approach with no or limited orbital bone wall invasion.

Abstract: To investigate the differential expression of the chemokine signaling pathway in lacrimal gland benign lymphoepithelial lesion (LGBLEL) and lacrimal lymphoma, providing insights into the mechanisms underlying malignant transformation and aiding clinical differentiation. Transcriptome analysis was conducted on patients with LGBLEL, lymphoma, and orbital cavernous hemangioma (CH). Three cases of LGBLEL and three cases of lymphoma were randomly selected as control and experimental groups, respectively. A real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate genes associated with the chemokine signaling pathway. Immunohistochemical (IHC) staining and quantitative Western blotting (WB) were performed for precise protein quantification. Transcriptome analysis revealed differential expression of the chemokine signaling pathway between the LGBLEL and lymphoma groups, identifying ten differentially expressed genes: CCL17, VAV2, CXCR5, NRAS, HCK, RASGRP2, PREX1, GNB5, ADRBK2, and CCL22. RT-qPCR showed that, compared to the lymphoma group, the LGBLEL group had significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.001, CCR1 (p = 0.002). IHC staining and quantitative analysis confirmed significant differences in protein expression between the groups for CCL28, CCR1, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.003, 0.011, 0.001, 0.024, 0.005, 0.019, and 0.031, respectively). While IHC provided localization, WB offered greater precision. WB revealed that, compared to the lymphoma group, the LGBLEL group exhibited significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.012, 0.005, 0.009, 0.011, 0.008, and 0.003, respectively) and lower expression of CCR1 (p = 0.014). The chemokine signaling pathway plays a role in the malignant transformation of LGBLEL. The decreased expression of CCL28 and CXCL17, coupled with the increased expression of CCR1, may be linked to the progression of LGBLEL into lymphoma.

Abstract Pre-implantation genetic testing for aneuploidy (PGT-A) is used in approximately half of in vitro fertilization cycles. Given the limited understanding of the genetics of human embryos, the current use of PGT-A is based on biologically uncertain assumptions and unvalidated guidelines, leading to the possibility of disposing of embryos with pregnancy potential. We isolated and sequenced all single cells (1133) from in vitro cultured 20 human blastocysts. We found that all blastocysts exhibited mosaicism with mitotic-induced aneuploid cells and showed an ~25% aneuploidy rate per embryo. Moreover, 70% (14/20) of blastocysts contained ‘chromosome-complementary’ cells, suggesting genetic mosaicism is underestimated in routine PGT-A. Additionally, the analysis of 20,945 single cells from day 8–14 embryos (in vitro cultured) and embryonic/fetal organs showed that 97% of the analyzed embryos/organs were mosaic. Over 96% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings have revealed a high prevalence of mosaicism in human embryos.

Summary Background Tuberculosis (TB) remains a persistent threat to global public health and traditional treatment monitoring approaches are limited by their potential for contamination and need for timely evaluation. Therefore, new biomarkers are urgently required for monitoring the treatment efficacy of TB. Methods This study aimed to elucidate the levels of CXCL10 and CXCL9 in pulmonary TB patients who underwent anti-TB treatment. The data was acquired from five databases, including PubMed, Ovid, Web of Science, Embase, and the Cochrane Library. A meta-analysis of CXCL10 data from all time points was conducted. Furthermore, a trend meta-analysis of temporal data of CXCL10 and CXCL9 from multiple time points was also performed. Results It was revealed that patients who responded poorly to anti-TB treatment had higher serum levels relative to those who responded well (SMD: 1.23, 95% CI: -0.37–2.84) at the end of intensive treatment (2 months). Furthermore, heterogeneity was observed in these results, which might be because patients with a prior history of TB and different treatment monitoring methods than those selected in this study were also included. The analysis of alterations in CXCL10 and CXCL9 levels since the last collection time points indicated that their levels reduced with time. Conclusion In summary, the study revealed that reductions in CXCL10 levels during the first two months of anti-TB treatment are correlated with treatment responses. Furthermore, decreasing levels of CXCL9 during the treatment suggest that it may also serve as a biomarker with a similar value to CXCL10. Future in-depth studies are thus warranted to further probe the relevance of CXCL10 and CXCL9 in monitoring the treatment efficacy of TB.

Although the market share of domestic children’s furniture is increasing annually, some potential problems limit its long-term and stable development, and there is still a gap in China compared with foreign countries. This study focused on the demand preferences for growable children’s beds and examined the design features that influence these preferences. This study introduces a combination of Hierarchical Analyses (AHP), Quality Function Development (QFD), and the Platts Conceptual Decision Matrix (PUGH) into the innovative design of a research model for children’s furniture (AHP-QFD-PUGH). This study screened and classified the decision-making indicators obtained from the research, ranked their importance by quantitative calculation, and finally proposed an optimal design solution. Additionally, to further study the structural characteristics, the function-behavior-structure (FBS) model served as a supplementary analysis tool to effectively circumvent subjective factors in product design. This integrated model accurately explored user needs and product characteristics, providing substantial guidance and new ideas for optimizing the design of growable children’s beds and enhancing growth of the children's furniture industry.

Biological reinforcement is a new branch that has developed in the field of engineering geology in recent years, among which, the microbially induced calcium carbonate precipitation (MICP) reinforcement technology is an effective method. MICP reinforcement technology utilizes the metabolic activity of widely existing microorganisms in nature to induce the precipitation of calcium carbonate with cementing and filling effects, thereby improving the strength of soil, reducing its permeability, and enhancing its engineering performance. Over the past two decades, significant progress has been made in theoretical research, model experiments, and field trials of MICP reinforcement technology. To promote a deeper understanding of MICP reinforcement technology, this paper systematically introduced the reinforcement mechanism and influencing factors of microbial-induced calcium carbonate reinforcement technology based on the current research on MICP reinforcement technology. In addition, the application of MICP reinforcement technology was discussed thoroughly. The current problems and challenges of MICP technology were analyzed in depth. The results show that the strengthening mechanism of MICP is formed based on microbial-induced mineralization, which includes the filling and cementation of soil pores by calcium carbonate precipitation. The influencing factors of the solidification effect of MICP mainly are the properties of bacterial solution and cementing solution, pH , temperature, soil type, and reinforcement method, by influencing the formation of calcium carbonate and cementing effect. The MICP reinforcement technology has shown great potential in soil reinforcement, crack resistance, impermeability, wind erosion resistance, and remediation of contaminated water/soil. At present, the MICP reinforcement technology still has some problems, including solidification uniformity, soil durability, economic benefits, environmental safety, and sustainability. To solve these problems, it is necessary to further integrate microbiology, soil mechanics, materials science, environmental science, and other disciplines to conduct in-depth research, which will help deepen the understanding of MICP reinforcement technology, promote MICP technology to achieve more comprehensive development in the engineering geological field, and further promote application of this technology.

Abstract Background The aim of this study is to analyze the trend of acute onset of chronic cor pulmonale at Chenggong Hospital of Kunming Yan’an Hospital between January 2018 and December 2022.Additionally, the study will compare the application of the ARIMA model and Holt-Winters model in predicting the number of chronic cor pulmonale cases. Methods The data on chronic cor pulmonale cases from 2018 to 2022 were collected from the electronic medical records system of Chenggong Hospital of Kunming Yan’an Hospital. The ARIMA and Holt-Winters models were constructed using monthly case numbers from January 2018 to December 2022 as training data. The performance of the model was tested using the monthly number of cases from January 2023 to December 2023 as the test set. Results The number of acute onset of chronic cor pulmonale in Chenggong Hospital of Kunming Yan’an Hospital exhibited a downward trend overall from 2018 to 2022. There were more cases in winter and spring, with peaks observed in November to December and January of the following year. The optimal ARIMA model was determined to be ARIMA (0,1,1) (0,1,1)12, while for the Holt-Winters model, the optimal choice was the Holt-Winters multiplicative model. It was found that the Holt-Winters multiplicative model yielded the lowest error. Conclusion The Holt-Winters multiplicative model predicts better accuracy. The diagnosis of acute onset of chronic cor pulmonale is related to many risk factors, therefore, when using temporal models to fit and predict the data, we must consider such factors’ influence and try to incorporate them into the models.

Abstract Small cell lung cancer (SCLC) is an aggressive pulmonary neuroendocrine malignancy featured by cold tumor immune microenvironment (TIME), limited benefit from immunotherapy, and poor survival. The spatial heterogeneity of TIME significantly associated with anti-tumor immunity has not been systemically studied in SCLC. We performed ultra-high-plex Digital Spatial Profiling on 132 tissue microarray cores from 44 treatment-naive limited-stage SCLC tumors. Incorporating single-cell RNA-sequencing data from a local cohort and published SCLC data, we established a spatial proteo-transcriptomic landscape covering over 18,000 genes and 60 key immuno-oncology proteins that participate in signaling pathways affecting tumorigenesis, immune regulation, and cancer metabolism across 3 pathologically defined spatial compartments (pan-CK-positive tumor nest; CD45/CD3-positive tumor stroma; para-tumor). Our study depicted the spatial transcriptomic and proteomic TIME architecture of SCLC, indicating clear intra-tumor heterogeneity dictated via canonical neuroendocrine subtyping markers; revealed the enrichment of innate immune cells and functionally impaired B cells in tumor nest and suggested potentially important immunoregulatory roles of monocytes/macrophages. We identified RE1 silencing factor (REST) as a potential biomarker for SCLC associated with low neuroendocrine features, more active anti-tumor immunity, and prolonged survival.

Abstract Background Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. Methods In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. Results The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. Conclusion These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage.

Abstract Long-term fetal heart rate (FHR) monitoring during the antepartum period, increasingly popularized by electronic FHR monitoring, represents a growing approach in FHR monitoring. This kind of continuous monitoring, in contrast to the short-term one, collects an extended period of fetal heart data. This offers a more comprehensive understanding of fetus’s conditions. However, the interpretation of long-term antenatal fetal heart monitoring is still in its early stages, lacking corresponding clinical standards. Furthermore, the substantial amount of data generated by continuous monitoring imposes a significant burden on clinical work when analyzed manually. To address above challenges, this study develops an automatic analysis system named LARA (Long-term Antepartum Risk Analysis system) for continuous FHR monitoring, combining deep learning and information fusion methods. LARA’s core is a well-established convolutional neural network (CNN) model. It processes long-term FHR data as input and generates a Risk Distribution Map (RDM) and Risk Index (RI) as the analysis results. We evaluate LARA on inner test dataset, the performance metrics are as follows: AUC 0.872, accuracy 0.816, specificity 0.811, sensitivity 0.806, precision 0.271, and F1 score 0.415. In our study, we observe that long-term FHR monitoring data with higher RI is more likely to result in adverse outcomes (p = 0.0021). In conclusion, this study introduces LARA, the first automated analysis system for long-term FHR monitoring, initiating the further explorations into its clinical value in the future.

The continuous growth of the global population has led to a continuous rise in the demand for meat products. However, traditional meat production methods are unable to meet the huge demand of the people, and also bring about a series of problems such as environmental pressure, animal welfare, and so on. Artificial meat technology is expected to solve these problems. At present, artificial meat can be divided into three categories: Plant protein meat, mushroom protein meat, and cell culture meat. This study mainly summarizes the production process, advantages, and market prospects of three types of artificial meat, analyzes the difficulties and technical challenges, and discusses the corresponding development proposals and solution strategies, with a view to provide references for the research of artificial meat and its industrialization.

AIM: To assess the clinical presentations and outcomes of idiopathic orbital inflammatory pseudotumor (IOIP) patients with orbital wall bone destruction (OWBD) and to propose an expanded classification system that includes bone destruction. METHODS: The study retrospectively reviewed clinical presentations, imaging findings, treatment modalities, and outcomes of six patients diagnosed histopathologically with IOIP and OWBD at the Beijing Tongren Hospital, Capital Medical University between October 2018 and June 2021. RESULTS: Over two years, 6 (10%) of 60 IOIP patients at our hospital exhibited OWBD, but this may overrepresent severe cases. The cohort consisted of three men and three women, aged 17 to 60y (mean 35.5±16.1y). Presenting symptoms included proptosis, eyelid swelling, decreased visual acuity with pain, and palpable mass. Imaging revealed multiple anatomical structures involved with the medial wall being the most common site of bone destruction. Histopathological examination showed classic type in five patients and sclerosing type in one patient. All patients underwent surgical resection followed by methylprednisolone treatment. Follow-up (mean 30.3±3.1mo) indicated three patients had no recurrence, while others had varying degrees of symptom persistence or recurrence. CONCLUSION: IOIP with bone destruction is a rare but significant subtype that mimics malignancy, leading to potential diagnostic and therapeutic challenges. Our findings suggest that complete surgical resection combined with adjunctive glucocorticoid therapy can yield favorable outcomes. However, larger-scale studies are needed to further optimize therapeutic approaches.

Check dams are widely used throughout the world to tackle soil and water loss. However, the frequency of extreme rainfall events has increased owing to global climate change and the main structure of check dam is gradually aging, which lead to an increase in the failure risk of check dams. Thus, it is necessary to carry out the study on failure risk diagnosis and assessment of check dams. In the study, machine learning algorithms (ML), including random forests (RF), support vector machine (SVM), and logistic regression (LR), were used to integrate the environmental and engineering factors and then assess the risk of check dam failure due to the “7.26” rainstorm on July 26, 2017, in the Chabagou watershed, located in the hilly-gully region of the Loess Plateau, China. To verify the generalizability of the model in this study, these models were used for the Wangmaogou catchment north of the Loess Plateau. The accuracy assessment by the receiver operating characteristic (ROC) curve indicated that the RF model with an area under the ROC curve (AUC) greater than 0.89 was the most precise model and had a higher generalization ability. In addition, the model dataset was relatively small and easy to obtain, which make the risk modeling of check dam failure in the study has the potential for application in other regions. In the RF model, each factor selected was confirmed to be important, and the importance values for engineering factors were generally higher than those for the environmental factors. The risk map of check dam failure in the RF model indicated that 56.34% of check dams in the study area had very high and high risks of dam failure under high-intensity rainfall in 2017. Based on the importance of factors and the risk map of check dam failure, the prevention and control measures for reducing the risk of check dam failure and promoting the construction of check dam are proposed. These proposals provide a scientific basis for the reinforcement of check dams and the future layout of check dams in the Chinese Loess Plateau.

Abstract Background Existing data on maternal dietary patterns and birth weight remains limited and inconsistent, especially in non-Western populations. We aimed to examine the relationship between maternal dietary patterns and birth weight among a cohort of Chinese. Methods In this study, 4,184 mother-child pairs were included from the Iodine Status in Pregnancy and Offspring Health Cohort. Maternal diet during pregnancy was evaluated using a self-administered food frequency questionnaire with 69 food items. Principal component analysis was used to identify dietary patterns. Information on birth weight and gestational age was obtained through medical records. Adverse outcomes of birth weight were defined according to standard clinical cutoffs, including low birth weight, macrosomia, small for gestational age, and large for gestational age. Results Three maternal dietary patterns were identified: plant-based, animal-based, and processed food and beverage dietary patterns, which explained 23.7% variance in the diet. In the multivariate-adjusted model, women with higher adherence to the plant-based dietary patten had a significantly higher risk of macrosomia (middle tertile vs. low tertile: odds ratio (OR) 1.45, 95% CI 1.00-2.10; high tertile vs. low tertile: OR 1.55, 95% CI 1.03–2.34; P-trend = 0.039). For individual food groups, potato intake showed positive association with macrosomia (high tertile vs. low tertile: OR 1.72, 95% CI 1.20–2.47; P-trend = 0.002). Excluding potatoes from the plant-based dietary pattern attenuated its association with macrosomia risk. No significant associations was observed for the animal-based or processed food and beverage dietary pattern with birth weight outcomes. Conclusions Adherence to a plant-based diet high in carbohydrate intake was associated with higher macrosomia risk among Chinese women. Future studies are required to replicate these findings and explore the potential mechanisms involved.

Abstract Background The study was designed to investigate microvascular and morphological changes in retinal vein occlusion (RVO) using multimodal imaging after intravitreal ranibizumab (IVR) with or without triamcinolone acetonide (IVTA) injections. Methods This was a retrospective and observational study. Fifty patients (52 eyes) diagnosed with RVO were enrolled. Best corrected visual acuity (BCVA), ophthalmoscopy, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SDOCT), and optical coherence tomography angiography (OCTA) were employed sequentially both before treatment and at the last visit after treatment. Results The mean logMAR VAs in BRVO eyes decreased significantly after treatment (P = 0.029). OCTA showed there was a significant difference in foveal avascular zone (FAZ) in BRVO eyes (P = 0.024), superificial foveal vessel density in both CRVO (P = 0.0004) and BRVO eyes (P = 0.02155). OCT showed the foveal thickness had significant differences after treatment in both CRVO (P

Abstract Objectives To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0–6 months old). Methods The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. Results Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. Conclusions The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.

Abstract In the past decade, the exploration of genetic resources in rice has significantly enhanced the efficacy of rice breeding. However, the exploration of genetic resources is hindered by the identification of candidate genes. To expedite the identification of candidate genes, this study examined tapetum programmed cell death-related genes OsiWAK1, OsPDT1, EAT1, TDR, and TIP2 to assess the efficacy of the Dual-Luciferase (Dual-LUC) assay in rapidly determining gene relationships. The study found that, in the Dual-LUC assay, OsiWAK1 and its various recombinant proteins exhibit comparable activation abilities on the EAT1 promoter, potentially indicating a false positive. However, the Dual-LUC assay can reveal that OsiWAK1 impacts both the function of its upstream regulatory factor OsPDT1 and the TDR/TIP2 transcription complex. By rapidly studying the relationship between diverse candidate genes and regulatory genes in a well-known trait via the Dual-LUC assay, this study provides a novel approach to expedite the determination of candidate genes such as genome-wide association study.

Abstract Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway was abnormal in tumors and affected patient prognosis. Dysregulation of the PUSs expression pattern may arise from copy number variation (CNV) mutations and aberrant DNA methylation. Functional enrichment analyses determined that the PUSs expression was closely associated with the MYC, E2F, and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 112 machine learning combinations had good prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD tumors, and is expected to guide immunotherapy for 19 tumor types. The model was also effective in identifying patients with tumors amenable to etoposide, camptothecin, cisplatin, or bexarotene treatment. In conclusion, our work highlights the dysregulated features of PUSs and their role in the TME and patient prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to lead to the development of potential diagnostic strategies and the evaluation and improvement of antitumor therapies.

Abstract Background Preventive treatment of tuberculosis infection (TBI) is considered a crucial strategy to prevent and control tuberculosis (TB). However, the acceptance and completion rates of preventive therapy for TBI are still far from optimistic. Evidence is mounting that TB knowledge and stigma may have a substantial effect on acceptance of TBI treatment. This study aimed to explore the effect of stigma on the relationship between the level of TB knowledge and acceptance of TBI treatment. Methods 7017 general population were included in the study. We adjusted for the covariates at the individual. Stepwise logistic regression was used to examine the moderating role of TB stigma and also explore the association between TB knowledge and acceptance of TBI treatment. Results The acceptance rate of TBI treatment among the respondents was 84.38% (n = 5921). Among respondents, a significant positive correlation between acceptance of TBI treatment and TB knowledge (OR = 1.096,95%CI = 1.073,1.118). Additionally, the association between TB knowledge and acceptance of TBI treatment was found to be moderated by TB stigma. In other words, TB stigma was found to weaken the impact of TB knowledge on acceptance of TBI treatment (OR = 0.994,95%CI = 0.991,0.996). Conclusion The findings of the study indicated that having a high level of awareness about TB can enhance the general population’s acceptability of TBI treatment. TB stigma moderated this association; it weakened the relationship between TB knowledge and individuals’ willingness to accept TBI treatment. To mitigate TB stigma and enhance the intention of individuals with TBI to accept preventive therapy, it is imperative to enhance TB-related health education.

Abstract Rest–activity behavior clusters within individuals to form patterns are of significant importance to their intrinsic capacity (IC), yet they have rarely been studied. A total of 1253 community-dwelling older adults were recruited between July and December 2021 based on the baseline survey database of the Fujian Prospective Cohort Study on Aging. Latent profile analysis was used to identify profiles of participants based on rest–activity behaviors, whereas logistic regression analysis was carried out to investigate the relationship between profiles and IC. We identified three latent profiles including: (1) Profile 1—labeled “Gorillas”: High physical activity (PA), moderate sedentary behaviors (SB), screen time (ST) and sleep (n = 154, 12%), (2) Profile 2—labeled as “Zebras”: Moderate PA, low SB, ST and high sleep (n = 779, 62%), and (3) Profile 3—labeled as“Koalas”: High SB, ST, low PA and sleep (n = 320, 26%). Logistic regression revealed a negative correlation between low IC and the “Gorillas” profile (β = − 0.945, P

Abstract Grout injection is an effective technique for repairing cracks in earthen sites. This study aims to address the challenges of Calcined Ginger Nuts (CGN)-based grout and enhance its engineering performance by investigating the compatibility of different superplasticizers. We examined the effects of Polycarboxylate Superplasticizer (PCE) and Naphthalene Superplasticizer (PNS) on the properties of CGN-based grout, focusing on fluidity, rheological properties, mechanical strength, volume stability, color difference, and pore structure. The engineering applicability of the optimized CGN-based grout with superplasticizers was assessed using COMSOL Multiphysics. The results show that fluidity increased with higher dosages of PCE and PNS. The grout containing these superplasticizers behaved as a shear-thinning fluid, following the power law model. Specifically, the consistency coefficient of grout with 0.5 wt% PCE and PNS decreased by 39.73% and 64.83%, respectively. Additionally, 2.9 wt% PCE and PNS reduced volume shrinkage rate by 6.86% and 6.27%, respectively. Initially, increasing the dosage of PCE and PNS improved compressive and flexural strength, but these properties later declined. XRD analysis revealed that PNS above 1.1 wt% and PCE weakened the hydration reaction, while both superplasticizers promoted carbonation. Mercury Intrusion Porosimetry (MIP) showed that 1.1 wt% PCE and PNS reduced the proportion of capillary pores by 13.79% and 10.11%, respectively. Based on these findings, 0.5 wt% PNS demonstrated the best compatibility with CGN-based grout, whereas PCE showed poor compatibility. Numerical simulations using COMSOL Multiphysics confirmed that 0.5 wt% PNS provided superior grouting effectiveness. Therefore, the CGN based grout with 0.5wt% PNS demonstrates excellent engineering performance and applicability. This study offers valuable insights into optimizing CGN-based grout for the preservation of earthen sites.

Abstract Grouting technology is the primary method for repairing cracks in earthen sites. However, there has been a long-standing lack of effective methods for evaluating grouting effectiveness. This paper proposes a field evaluation method based on P-wave velocity. This method explicitly discusses two scenarios where the P-wave velocity of the grout is either higher or lower than that of the soil, using the depth ℎ of the “hypothetical crack” as the evaluation indicator. The experimental results indicate that specimens with 20% and 40% defects show increases in ℎ values of 0.0113 m and 0.0166 m, respectively. Laboratory tests have demonstrated that this method can accurately evaluate grouting effectiveness and is not affected by the P-wave velocity of the soil. The application of this evaluation method to three typical earthen sites resulted in more reliable and easily quantifiable evaluation outcomes. By considering the width of grout, the method provides a more intuitive comparison of reparation effectiveness. The study demonstrates the feasibility of the proposed method, thereby facilitating effective crack reparation in earthen sites.

To examine the regulatory mechanisms of oligopeptides derived from soft-shelled turtle protein on tubulin activity in tumor cells, this study employed three specific oligopeptides D-7-A, E-7-W, and G-8-V obtained from soft-shelled turtle protein. The objective was to assess their impact on tubulin polymerization and depolymerization, investigate their interaction with tubulin, and elucidate the mechanisms induce apoptosis in tumor cells. The results showed that the three oligopeptides exhibited similarities to vincristine and acted as inhibitors of tubulin polymerization, their respective IC50 values was 3.72, 5.01, and 5.95 µmol/L. Furthermore, the molecular docking analysis revealed that D-7-A interacted with the active center of α-tubulin 4X1I, specifically binding to Ser178 and Thr179. The active center of E-7-W was found to be bound by Gln15, Thr225, Tyr224, Tyr210 and Arg214. Similarly, G-8-V was observed to bind to Gln11, Ser178 and Asp329 at the active center, exerting a significant impact on α-tubulin. The results of cell experiments showed that D-7-A, E-7-W and G-8-V had dose-dependent inhibitory effects on A549 cells, with IC50 values of 2003±72, 1877±102 and 1789±137 μmol/L, respectively. The G-8-V exhibited the most potent inhibitory effect on A549 cells, leading to the induction of apoptosis. Moreover, the apoptosis rate demonstrated a significant increase with prolonged drug treatment time. The underlying mechanism of action involved the inhibition of tubulin polymerization and the induction of apoptosis by perturbing the valence bond of α-tubulin.

Abstract Despite advances in therapies, glioblastoma (GBM) recurrence is almost inevitable due to the aggressive growth behavior of GBM cells and drug resistance. Temozolomide (TMZ) is the preferred drug for GBM chemotherapy, however, development of TMZ resistance is over 50% cases in GBM patients. To investigate the mechanism of TMZ resistance and invasive characteristics of GBM, analysis of combined RNA-seq and ChIP-seq was performed in GBM cells in response to TMZ treatment. We found that the PERK/eIF2α/ATF4 signaling was significantly upregulated in the GBM cells with TMZ treatment, while blockage of ATF4 effectively inhibited cell migration and invasion. SPHK1 expression was transcriptionally upregulated by ATF4 in GBM cells in response to TMZ treatment. Blockage of ATF4-SPHK1 signaling attenuated the cellular and molecular events in terms of invasive characteristics and TMZ resistance. In conclusion, GBM cells acquired chemoresistance in response to TMZ treatment via constant ER stress. ATF4 transcriptionally upregulated SPHK1 expression to promote GBM cell aggression and TMZ resistance. The ATF4-SPHK1 signaling in the regulation of the transcription factors of EMT-related genes could be the underlying mechanism contributing to the invasion ability of GBM cells and TMZ resistance. ATF4-SPHK1-targeted therapy could be a potential strategy against TMZ resistance in GBM patients.

Abstract Objective To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population. Methods A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed. Results The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up. Conclusion Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary.

Abstract Background Because the proportion of elderly individuals and the incidence of cancer worldwide are continually increasing, medical costs for elderly inpatients with cancer are being significantly increasing, which puts tremendous financial pressure on their families and society. The current study described the actual direct medical costs of elderly inpatients with cancer and analyzed the influencing factors for the costs to provide advice on the prevention and control of the high medical costs of elderly patients with cancer. Method A retrospective descriptive analysis was performed on the hospitalization expense data of 11,399 elderly inpatients with cancer at a tier-3 hospital in Dalian between June 2016 and June 2020. The differences between different groups were analyzed using univariate analysis, and the influencing factors of hospitalization expenses were explored by multiple linear regression analysis. Results The hospitalization cost of elderly cancer patients showed a decreasing trend from 2016 to 2020. Specifically, the top 3 hospitalization costs were material costs, drug costs and surgery costs, which accounted for greater than 10% of all cancers according to the classification: colorectal (23.96%), lung (21.74%), breast (12.34%) and stomach cancer (12.07%). Multiple linear regression analysis indicated that cancer type, surgery, year and length of stay (LOS) had a common impact on the four types of hospitalization costs (P

Due to the concentrated carbon emission sources and the enormous carbon emissions in the Ningxia Hui Autonomous, it is necessary to evaluate carbon sequestration potential to support future CCUS planning and major demonstrations. Based on the basic geological conditions for carbon sequestration in Ningxia, this study used the volumetric method of the US Department of Energy (US-DOE) to assess the geological potential for deep saline aquifer sequestration in Ningxia. The results show that the predicted geological potential of carbon sequestration in the deep saline aquifers in Ningxia is approximately 86.742 billion tons, with the predicted technical capacity of about 42.334 billion tons. The main reservoirs are concentrated in the Yanchi area in eastern Ningxia and the Liupan Mountain Basin. A preliminary evaluation of the suitability of saline aquifer sequestration in Ningxia was conducted by considering many factors such as the overall sequestration potential, cap rock integrity, geological stability, and socio-environmental risks. The results indicate that the Yanchi area in eastern Ningxia has favorable reservoir and cap rock conditions, stable structures, and low population density, making it a potential region for CO2 sequestration in Ningxia.

Abstract While many organizations have successfully leveraged big data analytics capabilities to improve their performance, our understanding is limited on whether and how big data analytics capabilities affect social innovation in organizations. Based on the organizational information processing theory and the organizational learning theory, this study aims to investigate how big data analytics capabilities support social innovation, and how knowledge ambidexterity mediates this relationship. A total of 354 high-tech companies in China, this study shows that big data analytics management, big data analytics technology, and big data analytics personnel capabilities all have positive effects on social innovation. In addition, both knowledge exploration and knowledge exploitation play a mediating role in this process. Furthermore, a polynomial regression and response surface analysis shows that social innovation increases when knowledge exploration and knowledge exploitation are highly consistent but declines when knowledge exploration and knowledge exploitation are inconsistent. This study not only provides new perspectives for understanding how big data analytics capabilities contribute to social innovation, complementing the existing literature on big data analytics capabilities and social innovation, but also provides important practical guidance on how organizations can develop big data analytics capabilities to improve social innovation and solve social problems in the digital age.

Abstract Purpose The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy and construct a nomogram model. Methods All enrolled subjects of the SEER database were randomly assigned to the training and testing group in a ratio of 3:2. The patients of Tangdu Hospital were seemed as validation group. Univariate cox regression analysis, lasso regression and random forest survival were used to screen variables related to the survival of advanced CRC patients received neoadjuvant therapy in the training group. Area under curves were adopted to evaluate the 1,3,5-year prediction value of the optimal model in three cohorts. Calibration curves were drawn to observe the prediction accuracy of the nomogram model. Decision curve analysis was used to assess the potential clinical value of the nomogram model. Results A total of 1833 subjects were enrolled in this study. After random allocation, 1055 cases of the SEER database served as the training group, 704 cases as the testing group and 74 patients from our center as the external validation group. Variables were screened by univariate cox regression used to construct a nomogram survival prediction model, including M, age, chemotherapy, CEA, perineural invasion, tumor size, LODDS, liver metastasis and radiation. The AUCs of the model for predicting 1-year OS in the training group, testing and validation group were 0.765 (0.703,0.827), 0.772 (0.697,0.847) and 0.742 (0.601,0.883), predicting 3-year OS were 0.761 (0.725,0.780), 0.742 (0.699,0.785), 0.733 (0.560,0.905) and 5-year OS were 0.742 (0.711,0.773), 0.746 (0.709,0.783), 0.838 (0.670,0.980), respectively. The calibration curves showed the difference between prediction probability of the model and the actual survival was not significant in three cohorts and the decision curve analysis revealed the practice clinical application value. And the prediction value of model was better for young CRC than older CRC patients. Conclusion A nomogram model including LODDS for the prognosis of advanced CRC received neoadjuvant therapy was constructed and verified based on the SEER database and single center practice. The accuracy and potential clinical application value of the model performed well, and the model had better predictive value for EOCRC than LOCRC.

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent swine pathogen, which has caused adverse impact on the global swine industry for almost 30 years. However, due to the immune suppression caused by the virus and the genetic diversity in PRRSV, no virus-targeting broad neutralizing strategy has been successfully developed yet. Antiviral peptide and nanobody have attracted extensive attention with the ease in production and the efficacy in practice. In this study, four new fusion proteins named nanobody peptide conjugates (NPCs) were developed by combining PRRSV specific non-neutralizing nanobodies with CD163-derived peptides targeting the receptor binding domain (RBD) of PRRSV proteins. Results Four NPCs were successfully constructed using two nanobodies against PRRSV N and nsp9 individually, recombining with two antiviral peptides 4H7 or 8H2 from porcine CD163 respectively. All four NPCs demonstrated specific capability of binding to PRRSV and broad inhibitory effect against various lineages of PRRSV in a dose-dependent manner. NPCs interfere with the binding of the RBD of PRRSV proteins to CD163 in the PRRSV pre-attachment stage by CD163 epitope peptides in the assistance of Nb components. NPCs also suppress viral replication during the stage of post-attachment, and the inhibitory effects depend on the antiviral functions of Nb parts in NPCs, including the interference in long viral RNA synthesis, NF-κB and IFN-β activation. Moreover, an interaction was predicted between aa K31 and T32 sites of neutralizing domain 4H7 of NPC-N/nsp9-4H7 and the motif 171NLRLTG176 of PRRSV GP2a. The motif 28SSS30 of neutralizing domain 8H2 of NPC-N/nsp9-8H2 could also form hydrogens to bind with the motif 152NAFLP156 of PRRSV GP3. The study provides valuable insights into the structural characteristics and potential functional implications of the RBD of PRRSV proteins. Finally, as indicated in a mouse model, NPC intranasally inoculated in vivo for 12–24 h sustains the significant neutralizing activity against PRRSV. These findings inspire the potential of NPC as a preventive measure to reduce the transmission risk in the host population against respiratory infectious agents like PRRSV. Conclusion The aim of the current study was to develop a peptide based bioactive compound to neutralize various PRRSV strains. The new antiviral NPC (nanobody peptide conjugate) consists of a specific nanobody targeting the viral protein and a neutralizing CD163 epitope peptide for virus blocking and provides significant antiviral activity. The study will greatly promote the antiviral drug R&D against PRRSV and enlighten a new strategy against other viral diseases. Graphical abstract image

While carbon dioxide (CO2) is a major greenhouse gas, it is also an important C1 resource. In the trend of energy conservation and emission reduction, electrocatalytic reduction has become a very promising strategy for CO2 utilization because it can convert CO2 directly to high-valued chemicals and fuels under mild conditions. In particular, the product CO and by-product H2 can be combined into syngas by an electrocatalytic CO2 reduction reaction (CO2RR) in an aqueous medium. Different molar ratios of CO and H2 may be used to produce essential bulk chemicals or liquid fuels such as methanol, alkanes, and olefins through thermochemical catalysis, Fischer–Tropsch synthesis, microbial fermentation, and other techniques. This work discusses the latest strategies in controlling the molar ratio of CO/H2 and improving the yield of CO2RR-to-syngas. The challenges of electrocatalytic syngas production are analyzed from an industrial application perspective, and the possible measures to overcome them are proposed in terms of new catalyst design, electrolyte innovation, flow reactor optimization, anodic reaction coupling, and operando technique application.

A prominent strengthened Y2O3 stabilized t-ZrO2 (YSTZ)/MgO nanocomposite coating is achieved by the plasma electrolytic oxidation (PEO) process and in-situ synthesized YSTZ reinforced phase with a quantitative control approach. The idea of activating double slip systemic semi-coherent interface dislocations in YSTZ/MgO nanocomposite coating to realize crack self-healing is proposed. High dislocation densities are associated with {101} YSTZ slip and {111} MgO slip system to coordinate interfacial deformation to stop crack initiation and propagation. This crack propagation path can absorb more fracture energy, providing more opportunities for crack deflection and bridge, which closes crack and realizes crack self-healing.

Background: The objectives of this pilot study are to compare the oral health status of institutionalised and non-institutionalised elderly people in Xiamen, China, and investigate oral health-related factors among this population. Methods: One elderly residential centre and one community centre in the same district were invited to join this study. Elderly people who were aged 65 years or older and able to participate in the oral health examination and questionnaire survey were recruited. Their demographic information, oral health-related behaviours, and oral health-related quality of life were collected through a questionnaire survey. The Decayed, Missing, and Filled Teeth (DMFT) index and the Community Periodontal Index were adopted to assess caries experience and periodontal status, respectively. A chi-square test, a t-test, and a correlation analysis were conducted for data processing. Results: Forty-nine elderly people participated in this study. There is no significant difference in the demographic background between non-institutionalised and institutionalised people. The mean DMFT index in the institutionalised group is significantly higher than that in the non-institutionalised group (p = 0.004). In contrast, the non-institutionalised group showed a significantly higher prevalence of gingival bleeding (p = 0.013) and a higher prevalence of periodontal pockets (p = 0.006) than the institutionalised group. Monthly income is also associated with the caries experience in this population. Conclusions: Institutionalised elderly people showed a higher severity of dental caries but a lower prevalence of periodontal symptoms than the non-institutionalised group. It is noteworthy that the generalisation of this pilot study is limited. Future research should be conducted to comprehensively investigate the oral health status of this population.

Pulpitis, an inflammatory disease of dental pulp tissues, ultimately results in the loss of pulp defense properties. Existing clinical modalities cannot effectively promote inflamed pulp repair. Oxidative stress is a major obstacle inhibiting pulp repair. Due to their powerful antioxidative capacity, mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) exhibit potential for treating oxidative stress-related disorders. However, whether MSC-sEVs shield dental pulp tissues from oxidative damage is largely unknown. Here, we showed that dental follicle stem cell-derived sEVs (DFSC-sEVs) have antioxidative and prohealing effects on a rat LPS-induced pulpitis model by enhancing the survival, proliferation and odontogenesis of H2O2-injured dental pulp stem cells (DPSCs). Additionally, DFSC-sEVs restored the oxidative/antioxidative balance in DPSC mitochondria and had comparable effects on ameliorating mitochondrial dysfunction with the mitochondrion-targeted antioxidant Mito-Tempo. To improve the efficacy of DFSC-sEVs, we fabricated an intelligent and injectable hydrogel to release DFSC-sEVs by combining sodium alginate (SA) and the ROS sensor RhB-AC. The newly formed SA-RhB hydrogel efficiently encapsulates DFSC-sEVs and exhibits controlled release of DFSC-sEVs in a HClO/ClO− concentration-dependent manner, providing a synergistic antioxidant effect with DFSC-sEVs. These results suggest that DFSC-sEVs-loaded SA-RhB is a promising minimally invasive treatment for pulpitis by enhancing tissue repair in the pulp wound microenvironment.

Study Design A retrospective study. Purpose To investigate the correlation between Hounsfield unit (HU) values measured by chest computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) T-scores. HU-based thoracolumbar (T11 and T12) cutoff thresholds were calculated for a cohort of Chinese patients. Overview of Literature For patients with osteoporosis, the incidence of fractures in the thoracolumbar segment is significantly higher than that in other sites. However, most current clinical studies have focused on L1. Methods This retrospective study analyzed patients who underwent chest CT and DXA at our hospital between August 2021 and August 2022. Thoracic thoracolumbar segment HU values, lumbar T-scores, and hip T-scores were computed for comparison, and thoracic thoracolumbar segment HU thresholds suggestive of potential bone density abnormalities were established using receiver operating characteristic curves. Results In total, 470 patients (72.4% women; mean age, 65.5±12.3 years) were included in this study. DXA revealed that of the 470 patients, 90 (19%) had osteoporosis, 180 (38%) had reduced osteopenia, and 200 (43%) had normal bone mineral density (BMD). To differentiate osteoporosis from osteopenia, the HU threshold was established as 105.1 (sensitivity, 54.4%; specificity, 72.2%) for T11 and 85.7 (sensitivity, 69.4%; specificity, 61.1%) for T12. To differentiate between osteopenia and normal BMD, the HU threshold was 146.7 for T11 (sensitivity, 57.5%; specificity, 84.4%) and 135.7 for T12 (sensitivity, 59.5%; specificity, 80%). Conclusions This study supports the significance of HU values from chest CT for BMD assessment. Chest CT provides a new method for clinical opportunistic screening of osteoporosis. When the T11 HU is >146.7 or the T12 HU is >135.7, additional osteoporosis testing is not needed unless a vertebral fracture is detected. If the T11 HU is

Abstract Background Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed. Methods In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 102 live oocysts of coccidia. A total of 5 × 104 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection. Results The results showed that the proportion of CD4+ and CD8+ T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased (P

Abstract The mitogen-activated protein kinase (MAPK) cascade MEK2-SIPK/WIPK is essential for immunity in Solanaceae plants. This cascade is tightly controlled to prevent harmful hyperactivation. However, the E3 ubiquitin ligases utilized by plants to reduce MEK2- SIPK/WIPK protein levels remain largely elusive. Here, we confirmed the essential role of Nicotiana benthamiana MEK2-SIPK/WIPK in resistance to the oomycete pathogen Phytophthora capsici. Using tobacco rattle virus (TRV)-based gene silencing, we screened prevalent plant U-box protein (PUB)-type E3 ligases with Armadillo (ARM) repeats to characterize those involved in Phytophthora resistance and MEK2-SIPK/WIPK degradation. We found that pub40 knockdown mutants exhibited significantly enhanced resistance to P. capsici. NbPUB40 was under ubiquitination and proteasomal degradation in planta, with two conserved sites (Cys28 and Val41) in the U-box domain being essential for its activity. NbPUB40 was shown to interact with the whole MEK2-SIPK/WIPK cascade and promote their degradation, the ubiquitination levels of which were also notably reduced in the pub40 mutant. Our results reveal a mechanism in which a PUB E3 ubiquitin ligase negatively regulates plant P. capsici resistance by destabilizing the MEK2-SIPK/WIPK cascade.

Abstract Background Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to pathogens; however the specific regulatory mechanism underlying the protective effect of melatonin pretreated of cowpea against Fusarium oxysporum remains known. Accordingly, the study sought to evaluate changes in the physiological and biochemical indices of cowpea following melatonin treated to facilitate Fusarium oxysporum resistance and elucidate the associated molecular mechanism using a weighted gene coexpression network. Results Treatment with 100 µM melatonin was effective in increasing cowpea resistance to Fusarium oxysporum. Glutathione peroxidase (GSH-PX), catalase (CAT), and salicylic acid (SA) levels were significantly upregulated, and hydrogen peroxide (H2O2) levels were significantly downregulated in melatonin treated samples in roots. Weighted gene coexpression network analysis of melatonin- and Fusarium oxysporum-treated samples identified six expression modules comprising 2266 genes; the number of genes per module ranged from 9 to 895. In particular, 17 redox genes and 32 transcription factors within the blue module formed a complex interconnected expression network. KEGG analysis revealed that the associated pathways were enriched in secondary metabolism, peroxisomes, phenylalanine metabolism, flavonoids, and flavonol biosynthesis. More specifically, genes involved in lignin synthesis, catalase, superoxide dismutase, and peroxidase were upregulated. Additionally, exogenous melatonin induced activation of transcription factors, such as WRKY and MYB. Conclusions The study elucidated changes in the expression of genes associated with the response of cowpea to Fusarium oxysporum under melatonin treated. Specifically, multiple defence mechanisms were initiated to improve cowpea resistance to Fusarium oxysporum.

Drought is a main abiotic stress factor hindering plant growth, development, and crop productivity. Therefore, it is crucial to understand the mechanisms by which plants cope with drought stress. Here, the function of the maize peroxidase gene ZmPRX1 in drought stress tolerance was investigated by measurement of its expression in response to drought treatment both in a ZmPRX1 overexpression line and a mutant line. The higher root lignin accumulation and seedling survival rate of the overexpression line than that of the wild type or mutant support a role for ZmPRX1 in maize drought tolerance by regulating root development and lignification. Additionally, yeast one-hybrid, Dule luciferase and ChIP-qPCR assays showed that ZmPRX1 is negatively regulated by a nuclear-localized ZmWRKY86 transcription factor. The gene could potentially be used for breeding of drought-tolerant cultivars.