Search

Yuxiang Deng,1,* Jianhong Peng,1,* Yujie Zhao,1 Qiaoqi Sui,1 Ruixia Zhao,2 Zhenhai Lu,1 Miaozhen Qiu,3 Junzhong Lin,1 Zhizhong Pan1 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Public Health, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Recent studies have suggested that the lymph node ratio (LNR) is a prognostic indicator for various malignancies. However, LNR has not been evaluated in colorectal liver-only metastasis (CRLM). This study aimed to investigate the prognostic value of LNR in patients with CRLM after curative resection. Patients and methods: We retrospectively investigated the clinicopathologic features of 154 CRLM patients who underwent curative resection between 2005 and 2015. We classified patients into low and high groups based on their LNR by using the X-tile software. Survival curves were plotted through Kaplan–Meier method and compared by log-rank test. Cox proportional hazards analysis was performed to identify the factors associated with recurrence-free survival (RFS) and overall survival (OS). Results: The patients were divided into two groups in which 124 patients were identified as LNR ≤0.33 and 30 patients as LNR >0.33. Compared to low LNR, high LNR was significantly associated with poor 3-year RFS (47.2% vs 16.7%, P=0.001) and OS (72.8% vs 45.3%, P=0.003) rates. Multivariate analysis indicated that the LNR was an independent predictor for 3-year RFS (hazard ratio, 2.124; 95% CI, 1.339–3.368; P=0.001) and OS (HR, 2.287; 95% CI, 1.282–4.079; P=0.005). However, the node (N) stage and lymph node distribution were not significantly associated with the 3-year RFS (P=0.071, P=0.226) or OS (P=0.452, P=0.791) in patients with CRLM. Conclusion: This study demonstrated that LNR was an independent predictor for 3-year RFS and OS in patients with CRLM who underwent curative resection and that its prognostic value was superior to that of N stage and lymph node distribution. Keywords: colorectal cancer, liver metastases, lymph node ratio, N stage, prognosis

Zihao Liu, Ying Liang, Honghua Wang, Zhenhe Lu, Jinsheng Chen, Qiaodong Huang, Lei Sheng, Yinghong Ma, Huiying Du, Qingjuan GongDepartment of Pain Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Abstract: Neuropathic pain is a common and refractory chronic pain that affects millions of people worldwide. Its underlying mechanisms are still unclear, but they may involve long noncoding RNAs (lncRNAs), which play crucial roles in a variety of biological functions, including nociception. We used microarrays to investigate the possible interactions between lncRNAs and neuropathic pain and identified 22,213 lncRNAs and 19,528 mRNAs in the spinal cord in a mouse model of spared nerve injury (SNI)-induced neuropathic pain. The abundance levels of 183 lncRNAs and 102 mRNAs were significantly modulated by both SNI and administration of minocycline. A quantitative real-time polymerase chain reaction analysis validated expression changes in three lncRNAs (NR_015491, ENSMUST00000174263, and ENSMUST00000146263). Class distribution analysis of differentially expressed lncRNAs revealed intergenic lncRNAs as the largest category. Functional analysis indicated that SNI-induced gene regulations might be involved in the activities of cytokines (IL17A and IL17F) and chemokines (CCL2, CCL5, and CCL7), whereas minocycline might exert a pain-alleviating effect on mice through actin binding, thereby regulating nociception by controlling the cytoskeleton. Thus, lncRNAs might be responsible for SNI-induced neuropathic pain and the attenuation caused by minocycline. Our study could implicate lncRNAs as potential targets for future treatment of neuropathic pain. Keywords: LncRNA, neuropathic pain, spinal cord, minocycline

Controlling defects and energy-band alignments are of paramount importance to the development of high-performance perovskite-based photodiodes. Yet, concurrent improvements in interfacial contacts and defect reduction simply by tailoring bottom contacts have not been investigated. An effective strategy is reported that can simultaneously improve energy-band alignments and structural defects by introducing low-dimensional contact (LDC) layers at the bottom interface. It is found that LDC-based perovskites considerably suppress undesirable structural defects induced by microstrains, resulting in reduced nonradiative recombination centers and improved carrier lifetimes. Additionally, the resulting LDC-based interface structures help block minority carrier injection from the electrodes by forming built-in electric fields. As a consequence, LDC-based perovskite photodiodes showed improved light detection capabilities. The result opens an avenue to yield highly efficient photodiodes.

The importance of neovascularization for primary and metastatic tumor growth fostered numerous clinical trials of angiogenesis inhibitors either alone or in combination with conventional antineoplastic therapies. One challenge with the use of molecularly t

Abstract Leeches are famous for their high medical value and wide environmental adaptability. Among them, cave leeches are a very fascinating and rare group, which is an important component in the study of adaptive evolution of leeches. However, no study has yet reported a reference genome for this group. In this study, we assembled a high-quality chromosome-level genome of the cave terrestrial leech Sinospelaeobdella cavatuses, through Illumina and PacBio sequencing, alongside chromosome conformation capture techniques. The resulting genome spans 153.67 Mb across 9 pseudochromosomes(range: 11.33 to 23.53 Mb), with a mounting rate of up to 95.37% and features an N50 length of 17.15 Mb. This genome is composed of 35.16% repetitive elements and contains 21180 predicted protein-coding genes. Decoding the S. cavatuses genome not only promotes future studies on study of its phylogeny, evolution, and behavior, but also provides valuable resources for in-depth investigation on adaptive evolution of leech.

Abstract The Rhizobium rhizogene-transformed root culture from Physalis peruviana L. (P. peruviana) may be a promising and novel source of valuable phenolics, including caffeoylputrescine (CP), which is known for antioxidant, antidiabetic, insect-resistant, disease-resistant, and neuroprotective properties. In this study, to improve the production efficiency of phytochemical components in P. peruviana hairy root cultures, we optimized various culture conditions, including the inoculum size, liquid volume, culture media type, carbon source, sucrose concentration, initial pH, and application of elicitors, to enhance the total phenolic content and CP yield in these hairy root cultures. The findings indicate that the use of sucrose as carbon source resulted in the highest biomass (13.28 g DW/L), total phenolic content (6.26 mg/g), and CP yield (2.40 mg/L). The White medium excelled in enhancing the total phenolic content (9.35 mg/g), whereas the B5 medium was most effective for the biomass (13.38 g DW/L) and CP yield (6.30 mg/L). A sucrose concentration of 5% was best for the biomass (18.40 g DW/L), whereas a sucrose concentration of 4% was ideal for the CP yield. Optimal culture conditions were as follows: an inoculum size of 0.5 g/100 mL, a liquid volume of 100 mL in a 250-mL flask, B5 medium, 4% sucrose, and a pH of 5.5. Among the tested elicitors, methyl jasmonate (MeJA) at 100 µM significantly increased the biomass (21.3 g/L), total phenolic content (23.34 mg/g), and CP yield (141.10 mg/L), which represent 0.96-, 2.12-, and 13.04-fold increases, respectively, over the control after 8 days. The optimized HR culture of P. peruviana provides a promising system to enhance the production of CP for pharmaceutical applications.

Abstract Background CircRNAs have been demonstrated to play a crucial role in regulating the growth and progression of various cancers, including hepatocellular carcinoma (HCC). Nevertheless, the circRNA's expression pattern and function in HCC need more investigation. Methods Bioinformatics techniques were used to identify differentially expressed circRNAs in HCC. CircASH2L expression in HCC tissues was assessed through qRT-PCR and ISH analysis. To assess circASH2L's impact on HCC progression, a variety of experiments were carried out both in vitro and in vivo, such as CCK8, colony formation, EdU assay, flow cytometry, transwell assay, and xenograft mouse model. Various experimental techniques including qRT-PCR, dual luciferase reporter assay, FISH, RNA pull-down, and RIP experiments were utilized to evaluate the relationship between circASH2L, miR-525-3p, and MTUS2. Additionally, experiments were conducted to explore the impact of m6A modification on circASH2L expression, including RNA stability assay, m6A RNA immunoprecipitation assay (MeRIP), and Co-IP experiments. Results We found that circASH2L was downregulated in HCC tissues and the downregulation of circASH2L was significantly correlated with malignant characteristics as well as poor overall survival of patients with HCC. CircASH2L was found to inhibit cells growth, migration and invasion as well as tumorigenesis and metastasis in vivo. Mechanistically, we established that circASH2L directly interacted with miR-525-3p to enhance MTUS2 expression, subsequently leading to tumor suppression. Moreover, the influence of circASH2L on tumor suppression was attenuated by increasing miR-525-3p levels, and MTUS2 was recognized as an essential intermediary in circASH2L-induced tumor suppression. Additionally, N6−methyladenosine (m6A) modification was identified in circASH2L. Our data suggested that METTL3 was responsible for mediating m6A methylation of circASH2L, ultimately regulating circASH2L expression through the promotion of its degradation. These findings collectively highlight the role of circASH2L as a tumor suppressor through a unique circASH2L/miR-525-3p/MTUS2 axis, shedding light on the significance of m6A modification in regulating circASH2L function. Conclusion The work emphasizes circASH2L as a promising therapeutic target for treating HCC, offering new insights into the role of circRNAs in HCC development.

Abstract Background A considerable portion of patients with fever of unknown origin (FUO) present concomitant lymphadenopathy. Diseases within the spectrum of FUO accompanied by lymphadenopathy include lymphoma, infections, and rheumatic diseases. Particularly, lymphoma has emerged as the most prevalent etiology of FUO with associated lymphadenopathy. Distinguishing between benign and malignant lymph node lesions is a major challenge for physicians and an urgent clinical concern for patients. However, conventional imaging techniques, including PET/CT, often have difficulty accurately distinguishing between malignant and benign lymph node lesions. This study utilizes PET/CT radiomics to differentiate between lymphoma and benign lymph node lesions in patients with FUO, aiming to improve diagnostic accuracy. Results Data were collected from 204 patients who underwent 18F-FDG PET/CT examinations for FUO, including 114 lymphoma patients and 90 patients with benign lymph node lesions. Patients were randomly divided into training and testing groups at a ratio of 7:3. A total of 15 effective features were obtained by the least absolute shrinkage and selection operator (LASSO) algorithm. Machine learning models were constructed using logistic regression (LR), support vector machine (SVM), random forest (RF), and k-nearest neighbors (KNN) algorithms. In the training group, the area under the curve (AUC) values for predicting lymphoma and benign cases by LR, SVM, RF, and KNN models were 0.936, 0.930, 0.998, and 0.938, respectively. There were statistically significant differences in AUC between the RF and other models (all P 0.05). The decision curve analysis (DCA) curves of the RF model outperformed those of the other three models in both the training and testing groups. Conclusions PET/CT radiomics demonstrated promising performance in discriminating lymphoma from benign lymph node lesions in patients with FUO, with the RF model showing the best performance.

Abstract Background Liver organoid serves as an alternative model for liver pathophysiology in carbohydrate or lipid metabolism and xenobiotic metabolism transformation. Biomechanical cues including spaceflight mission can affect liver organoid construction and their related functions, but their underlying mechanisms are not fully understood yet. Here, a rotating cell culture device, namely Rotating Flat Chamber (RFC), was specifically designed for adhering cells or cell aggregated to elucidate the effects of altered gravity vector on HepaRG-derived liver organoids construction. Results The organoids so formed under RFC presented the fast growth rate and large projection area. Meanwhile, the expressions of two pluripotency markers of SOX9 and CD44 were enhanced. This finding was positively correlated with the increased YAP expression and nuclear translocation as well as the elevated α4β6-integrin expression. Inhibition of YAP expression and nuclear translocation decreased the expression of SOX9 and CD44 under RFC, thereby attenuating the pluripotency of HepaRG-derived liver organoids. Conclusions In conclusion, we proposed a novel liver organoid construction method using rotating culture, by which the pluripotency of liver organoids so constructed is mediated by α4β6-integrin and YAP translocation. This work furthered the understanding in how the gravity vector orientation affects the construction of liver organoids and the related mechanotransductive pathways.

Abstract Metabolism reprogramming (MR) is one of the top ten hallmarks of malignant tumors. The aberrant activation of MR has been recognized as a critical contributory factor to the malignant progression of solid tumors. Moreover, various long non-coding RNAs (lncRNAs) are implicated in the aberrant activation of MR in solid tumor cells. Therefore, in this review, we mainly focus on summarizing the functional relevance and molecular mechanistic underpinnings of lncRNAs in modulating MR of solid tumors by targeting glucose metabolism, lipid metabolism, affecting mitochondrial function, and regulating interactions between tumor and non-tumor cells in tumor microenvironment. Besides, we also underscore the potential for constructing lncRNAs-centered tumor metabolic regulation networks and developing novel anti-tumor strategies by targeting lncRNAs and abnormal MR. Ultimately, this review seeks to offer new targets and avenues for the clinical treatment of solid tumors in the future.

Abstract Our study concentrated on the expression of miRNA-375 in the hypothalamic-pituitary-gonadal axis of female Hu sheep. The investigation involved cloning the precursor sequence of miR-NA-375, followed by comparison with database entries and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In our approach, we obtained ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus, and pineal gland from fertile but nonpregnant Hu ewes. MiRNA extraction kit was used to extract miRNA from the above eight tissues. Real-time fluorescent quantitative polymerase chain reaction was used to evaluate the role of miR-375 in the hy-pothalamic-pituitary-gonadal axis. The results of miR-375 precursor sequence cloning were compared with those of Anopheles gambiae, Apis mellifera, Bos taurus, Drosophila melanogaster, Danio rerio, Fugu rubripes, Gallus gallus, Homo sapiens, Monodelphis domestica, Macaca mulatta, Mus musculus, Pan troglodytes, Rattus norvegicus, Tetraodon nigroviridis, Xenopus tropicalis miR-375 in miRBase database. It was found that oar-miR-375 was highly conserved. Notably, miR-375 expression in the pineal gland was significantly higher (p

Abstract Immune checkpoint blockade (ICB) therapy has emerged as a new therapeutic paradigm for a variety of advanced cancers, but wide clinical application is hindered by low response rate. Here we use a peptide-based, biomimetic, self-assembly strategy to generate a nanoparticle, TPM1, for binding PD-L1 on tumour cell surface. Upon binding with PD-L1, TPM1 transforms into fibrillar networks in situ to facilitate the aggregation of both bound and unbound PD-L1, thereby resulting in the blockade of the PD-1/PD-L1 pathway. Characterizations of TPM1 manifest a prolonged retention in tumour ( > 7 days) and anti-cancer effects associated with reinvigorating CD8+ T cells in multiple mice tumour models. Our results thus hint TPM1 as a potential strategy for enhancing the ICB efficacy.

Abstract Background Hyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS). Methods Here we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-𝜿B pathway related protein, and vascular density markers were determined. Results There were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level and increased SOD2 level, thereby reducing oxidative stress. Meanwhile, P. distasonis effectively inhibited NF-𝜿B signal pathway and reduced the production of inflammatory cytokines, including TNF-α and IL-1β, alleviating the inflammatory response. Notably, P. distasonis treatment increased the levels of vascular density markers including cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), ameliorating vascular damage in HAS rats. Conclusions Together, these findings highlighted the important role of P. distasonis in the pathogenesis of HAS, and its mechanism was involved in the regulation of gut microbiota-gut-brain axis, which implied a novel strategy against HAS.

Microfluidic technology utilizing the deterministic lateral displacement (DLD) method holds significant promise for efficiently separating micro-particles and biological cells. Despite the notable high throughput advantages associated with DLD chips, their widespread application is impeded by the substantial manufacturing costs of tens of thousands of micropillars. This study aims to explore the feasibility of employing the injection molding method for the mass production of DLD microfluidic chips. A multistage DLD chip with varied critical diameters was designed to isolate white blood cells from the human whole blood. The separation effectiveness was verified with the polydimethylsiloxane chip fabricated by standard soft lithography. Subsequently, nickel mold inserts were electroformed to fabricate thermoplastic DLD chips via the injection molding. The replication quality of micropillars under different molding parameters was studied. The capability of injection-molded chips to effectively achieve particle separation was validated. Results showed that thermoplastic chips with good replication quality were obtained, providing a scale-up production strategy for fabricating polymer-based microfluidic chips for disposable separation applications.

Objective: Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic investigations using various transgenic mice. The current study reports the development of a reproducible murine DO model. Methods: A mini-titanium lengthener was designed and fabricated. The mini-lengthener was applied on the murine femur with four threaded pins using a designed clamp as the drilling and insertion guide. After transverse osteotomy using a Gigli saw, and after 5 days of latency, DO procedures started at 0.3 mm/day for 10 days, and the consolidation period was left for 28 days. The bone formation was monitored by radiography and histology. Potential effects on animal locomotion during DO were also measured by behavior tests. Results: Separated bone segments maintained good alignment during the entire DO phases. New bone formation was found as early as the end of the distraction phase. Active bone remodeling was found between the separated bone segments at late distraction and early consolidation phases. At the mature consolidation phase, bone remodeling was mainly observed in the contact cortical bone. Mice underwent DO procedure did not have significant impairment in their locomotion. Conclusion: We have successfully developed a murine femoral DO model, which may be used to study the biological processes of DO. We also developed the mini-lengthener and the guide clamp to ensure the standardization and reproducibility of the mouse DO model.The translational potential of this article: Current study reports the development of a murine femoral DO model. A well-established murine DO model will facilitate further investigations of the biological mechanisms of DO in various transgenic and normal mice.

Facing the increasing complexity of aerial combat environments and challenges to the survivability of air platforms from new combat methods, it is necessary to adopt new hard-kill methods to counter advanced air-to-air missiles. In order to improve the success rate and efficiency of launching air-to-air missiles to intercept incoming missiles as a hard kill method, this study proposes intelligent maneuvering strategies for aircraft platforms and missile interception strategies based on reinforcement learning. Firstly, this paper designs the missile threat assessment technology, constructs the simulation environments, and determines the strategy model state and reward function. By setting various attack angles and positions of incoming air-to-air missiles and training maneuvering and intelligent interception strategies under different aircraft platform postures, this paper achieves active interception of incoming targets and effective maneuvering of the aircraft platform. Experiments show that compared to the average escape probability of 5.8% in operations research game strategies, after using maneuver and interception strategies based on reinforcement learning, the average escape probability can increase to 56.8%; Meanwhile, the utilization rate of interceptors has increased by approximately 13.3%, and the response time has remained within 24 ms. The designed strategy can adapt to different numbers of incoming missiles, can significantly improve the survival ability of the carrier platform and the success rate of intercepting incoming missiles. This study can support continuous optimization in a high-dimensional state space of air combat.

Accurately predicting the estimated ultimate recovery (EUR) of shale gas wells is key to formulating a shale gas reservoir development plan. However, in practice, determining the EUR remains challenging due to the complex dynamic characteristics of shale gas production, which first decreases rapidly and then slowly. In this study, based on material balance theory and equivalent seepage resistance theory and considering crucial factors including primary water, adsorption, and pore effects, a new production model for fractured horizontal shale gas wells is developed. The calculation process is designed by using Newton's iterative method. The shale gas well EUR prediction method is verified, and the factors influencing the EUR are analyzed. The results show that adsorption has a significant effect on production, especially on the Langmuir volume. Moreover, ignoring the influence of primary water, which exists in shale gas reservoirs in the form of bound water, results in an overestimation of the EUR. Furthermore, production positively correlates with the fracture half-length and the number of fractures, but the action mechanisms of these two factors differ. Unlike the number of fractures, which predominantly affects the initial stage of production, the fracture half-length has a more nuanced role. It is capable of altering the stimulated reservoir volume zone, thereby exerting influence over the entire production life cycle.

Abstract Since dietary intake is challenging to directly measure in large-scale cohort studies, we often rely on self-reported instruments (e.g., food frequency questionnaires, 24-hour recalls, and diet records) developed in nutritional epidemiology. Those self-reported instruments are prone to measurement errors, which can lead to inaccuracies in the calculation of nutrient profiles. Currently, few computational methods exist to address this problem. In the present study, we introduce a deep-learning approach—Microbiome-based nutrient profile corrector (METRIC), which leverages gut microbial compositions to correct random errors in self-reported dietary assessments using 24-hour recalls or diet records. We demonstrate the excellent performance of METRIC in minimizing the simulated random errors, particularly for nutrients metabolized by gut bacteria in both synthetic and three real-world datasets. Additionally, we find that METRIC can still correct the random errors well even without including gut microbial compositions. Further research is warranted to examine the utility of METRIC to correct actual measurement errors in self-reported dietary assessment instruments.

Abstract Periodontitis exacerbates Alzheimer’s disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APPswe/PS1ΔE9 (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD.

Abstract Governing equations are foundations for modelling, predicting, and understanding the Earth system. The Earth system is undergoing rapid change, and the conventional approaches for establishing governing equations, such as empirical generalisations, are becoming increasingly challenging to deal with the complexity and diversity of the geoscience processes we study today. In this Perspective, we explore data-driven equation discovery, a novel scientific artificial intelligence pathway, for advancing geosciences. Data-driven equation discovery identifies hidden patterns from data and transforms them into interpretable equation representations, automating and accelerating equation discovery processes. It provides a practical approach for geoscientists to model and understand complex geoscience processes based on big Earth data. The final vision is to uncover new clear, describable, and quantifiable equations in various geoscience disciplines. We summarize opportunities and highlight that challenges in this field should be addressed by interdisciplinary collaborations.

Abstract Objective Submucosal infiltration of less than 200 μm is considered an indication for endoscopic surgery in cases of superficial esophageal cancer and precancerous lesions. This study aims to identify the risk factors associated with submucosal infiltration exceeding 200 micrometers in early esophageal cancer and precancerous lesions, as well as to establish and validate an accompanying predictive model. Methods Risk factors were identified through least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Various machine learning (ML) classification models were tested to develop and evaluate the most effective predictive model, with Shapley Additive Explanations (SHAP) employed for model visualization. Results Predictive factors for early esophageal invasion into the submucosa included endoscopic ultrasonography or magnifying endoscopy> SM1(P

Abstract Backgroud The association between the atherogenic index of plasma (AIP) and stroke risk is uncertain. Overweight and obese individuals frequently develop atherosclerosis, suggesting AIP may mediate the relationship between body mass index (BMI) and stroke risk. This study investigates whether AIP mediates the BMI-stroke association and evaluates the interaction effects of AIP and BMI on stroke risk in middle-aged and older Chinese adults. Method This study analyzes data from the China Health and Retirement Longitudinal Study (CHARLS), an ongoing nationally representative prospective cohort study that began in 2011. It includes 8 598 middle-aged and older Chinese adults without stroke at baseline. A mediation analysis, employing a novel two-stage regression method, was conducted to evaluate the indirect effect of BMI on stroke through AIP. Results During a median follow-up of 7.1 years, 615 (7.2%) participants developed a stroke. After adjusting for confounders, AIP was significantly associated with stroke risk (hazard ratio [HR] per 1-SD increase, 1.24; 95% CI 1.14–1.35). Mediation analysis indicated that compared to normal weight, obesity similarly raised stroke risk by 78.0% (HR 1.78, 95% CI 1.40–2.27), with 29.67% (95% CI 14.27–45.08%) of the association mediated through AIP (HR 1.15, 95% CI 1.08–1.23). No significant multiplicative or additive interactions were observed between BMI and AIP on stroke. Conclusions This study found that the AIP appeared to be associated with stroke risk and mediates the association between obesity and stroke among middle-aged and older Chinese adults.

Abstract Background Children with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors. Method CMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors. Results Cardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P

Abstract Radioresistance contributes to metastasis and recurrence in non-small cell lung cancer (NSCLC) patients. However, the underlying mechanism remains unclear. To provide novel clues, a complete multi-omics map of a radioresistant cancer cell line has been profiled. In this article, a lung adenocarcinoma cell line, radioresistant A549 (RA549), was generated by exposure to a series of irradiation. Subsequently, we adopted transcriptome, quantitative proteome and lysine 2-hydroxyisobutyrylome to construct a differential profile on the transcriptional to post-tanslational levels on A549 and RA549 cell lines, respectively. Our analysis revealed 920 significantly differentially expressed genes and 699 proteins. Furthermore, 2-hydroxyisobutyrylome identified 30,089 Khib modified sites on 4635 proteins, indicating that Khib modifications play vital role in regulating NSCLC radioresistance. Multi-omics combined analysis identified 19 significantly differentially expressed genes/proteins in total. Meanwhile, we found that EGFR, a well-known lung cancer-related receptor, was upregulated at both the protein and Khib modification levels in RA549. Further gain/loss of function experiments showed that Khib modified EGFR level positively correlates with NSCLC cell radioresistance. Taken together, our findings report that Khib-modified proteins enhanced resistance to radiation and represent promising therapeutic targets.

Abstract Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P

Abstract Background Cereal diseases caused by insect-transmitted viruses are challenging to forecast and control because of their intermittent outbreak patterns, which are usually attributed to increased population densities of vector insects due to cereal crop rotations and indiscriminate use of pesticides, and lack of resistance in commercial varieties. Root microbiomes are known to significantly affect plant health, but there are significant knowledge gaps concerning epidemics of cereal virus diseases at the microbiome-wide scale under a variety of environmental and biological factors. Results Here, we characterize the diversity and composition of rice (Oryza sativa) root-associated bacterial communities after infection by an insect-transmitted reovirus, rice black-streaked dwarf virus (RBSDV, genus Fijivirus, family Spinareoviridae), by sequencing the bacterial 16S rRNA gene amplified fragments from 1240 samples collected at a consecutive 3-year field experiment. The disease incidences gradually decreased from 2017 to 2019 in both Langfang (LF) and Kaifeng (KF). BRSDV infection significantly impacted the bacterial community in the rice rhizosphere, but this effect was highly susceptible to both the rice-intrinsic and external conditions. A greater correlation between the bacterial community in the rice rhizosphere and those in the root endosphere was found after virus infection, implying a potential relationship between the rice-intrinsic conditions and the rhizosphere bacterial community. The discrepant metabolites in rhizosphere soil were strongly and significantly correlated with the variation of rhizosphere bacterial communities. Glycerophosphates, amino acids, steroid esters, and triterpenoids were the metabolites most closely associated with the bacterial communities, and they mainly linked to the taxa of Proteobacteria, especially Rhodocyclaceae, Burkholderiaceae, and Xanthomonadales. In addition, the greenhouse pot experiments demonstrated that bulk soil microbiota significantly influenced the rhizosphere and endosphere communities and also regulated the RBSDV-mediated variation of rhizosphere bacterial communities. Conclusions Overall, this study reveals unprecedented spatiotemporal dynamics in rhizosphere bacterial communities triggered by RBSDV infection with potential implications for disease intermittent outbreaks. The finding has promising implications for future studies exploring virus-mediated plant-microbiome interactions. Video Abstract

This research focuses on art works depicting the history of the Cuban Red Revolution as its primary subject. It endeavors to illuminate the narrative of the Cuban Red Revolution by analyzing these art works. Additionally, it aims to create an ontology-based knowledge resource dedicated to the dissemination of Cuban art associated with the Red Revolution. The intention is to systematically organize and visually represent the knowledge embedded in art works that explore the history of the Cuban Red Revolution. The outcome of this research includes a metadata framework, an ontology specifically dedicated to the history of the Cuban Red Revolution, and a knowledge graph. These components collectively provide new insights and perspectives for studying art works themed around the Cuban Red Revolution, positioning them as valuable red cultural resources.

To clarify the adsorption behavior of fluorocarbon surfactants on PMMA surfaces, the contact angles of two nonionic fluorocarbon surfactants (FNS-1 and FNS-2) and an anionic fluorocarbon surfactant (FAS) on polymethylmethacrylate (PMMA) surface were determined using the sessile drop method. Moreover, the effects of molecular structures on the surface tension, adhesion tension, solid–liquid interfacial tension, and adhesion work of the three fluorocarbon surfactants were investigated. The results demonstrate that the adsorption amounts for three fluorocarbon surfactants at the air–water interface are 4~5 times higher than those at the PMMA–solution interface. The three fluorocarbon surfactants adsorb on the PMMA surface by polar groups before CMC and by hydrophobic chains after CMC. Before CMC, FNS-2 with the smallest molecular size owns the highest adsorption amount, while FAS with large-branched chains and electrostatic repulsion has the smallest adsorption amount. After CMC, the three fluorocarbon surfactants form aggregates at the PMMA-liquid interface. FAS possesses the smallest adsorption amount after CMC. Besides, FNS-1 possesses a higher adsorption amount than FNS-2 due to the longer fluorocarbon chain and the lower CMC value of FNS-1. The adsorption behaviors of nonionic and anionic fluorocarbon surfactants on the PMMA surface are different. FAS forms interfacial aggregates before CMC, which may be attributed to the electrostatic interaction between the anionic head of FAS and the PMMA surface.

Non-alcoholic fatty liver disease (NAFLD) is one abnormal buildup of fat within the liver, independent of excessive alcohol intake. In type 2 diabetes, the presence of NAFLD can exacerbate chronic kidney diseases and mortality in patients. Hepatocyte nuclear factor 1 homeobox A (HNF1A) predominantly expressed in the liver, owns one crucial role in liver development, function and tumorigenesis. However, the precise regulatory role of HNF1A on the progression of type 2 diabetes combined with NAFLD keep dimness. This investigation uncovered that HNF1A levels, both in protein and mRNA expressions, were elevated in high-fat diet plus hyperglycemia (HFG) mice. Furthermore, liver steatosis was strengthened in the HFG group, which was mitigated following the HNF1A inhibition. Knockdown of HNF1A ameliorated glucose and lipid metabolism disorders in HFG mice. Lastly, the study observed an stimulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in HFG mice, but this change was neutralized uponHNF1A silencing. In conclusion, knockdown of HNF1A improved type 2 diabetes combined with NAFLD, as well as disorders in glucose and lipid metabolism, and retarded the PI3K/AKT/mTOR signaling pathway. These finding demonstrated that HNF1A may be one serviceable target for ameliorating type 2 diabetes combined with NAFLD.

In order to promote applications of FY-4B satellite data, temperature and humidity profile products of FY-4B geostationary interferometric infrared sounder (GIIRS) are verified and evaluated from February 2023 to January 2024 based on radiosonde data. Deviation characteristics are compared and analyzed under different conditions. In addition, the probability density function (PDF) matching method is employed to correct systematic errors in FY-4B/GIIRS temperature profile under cloudy condition. Results indicate that the quality of FY-4B/GIIRS temperature and humidity profiles is significantly influenced by cloud activity, leading to a notable reduction in the proportion of high-quality data when affected by the cloud. Under clear sky condition, the mean bias (MB) of temperature profiles ranges from -0.3 K to 1 K, the root mean square error (RMSE) is within 2 K, and the minimum error is approximately 1.1 K near 400 hPa height. The MB of humidity profiles ranges from 0 to 1.3 g·kg-1, and the maximum RMSE is about 2.1 g·kg-1 at the surface layer. Temperature and humidity profile errors increase under cloudy condition, while the bias of entire atmospheric layer is predominantly positive. The RMSE of temperature ranges from 2.2 K to 2.7 K, while the maximum RMSE for humidity is approximately 3 g·kg-1. The trend of errors is consistently similar at 0000 UTC and 1200 UTC. Compared with 0000 UTC, the deviation of temperature profiles at the surface layer at 1200 UTC is larger and slightly more distinct. The humidity error at 1200 UTC is greater than that at 0000 UTC at the layer below 400 hPa under clear sky condition, while the humidity error at 0000 UTC is greater than that at 1200 UTC at layer between 750 hPa and 950 hPa under cloudy condition. Significant systematic errors exist in temperature and humidity profiles under cloudy condition. Samples with quality control of 1 tend to be colder and drier compared to those with quality control of 0. The deviation distribution is more discrete, while the deviation of temperature follows an asymmetric bimodal distribution. After correction using the PDF method, systematic errors of FY-4B/GIIRS temperature profiles are effectively reduced. MBs of samples with quality control of 0 and 1 decrease from 0.74 K and 2.07 K to 0.03 K and 0.01 K, and RMSEs decrease from 1.89 K and 3.20 K to 1.73 K and 2.34 K, respectively. When the deviation is generally unbiased, the effectiveness of PDF methods is limited.

The sandstone reservoirs of the Cretaceous Bashijiqike Formation in the Yingmaili area on the southern slope of the Kuqa Depression within the Tarim Basin demonstrate favorable physical properties and considerable potential for oil and gas exploration. However, they are characterized by strong heterogeneity and unclear patterns of oil and gas distribution. In this study, the lithology and physical properties of the middle and deep reservoirs of the Bashijiqike Formation in the Yingmaili area were analyzed using core observation, a series of thin section analyses(standard, casting, cathodoluminescence, and inclusion thin sections), scanning electron microscopy(SEM), physical property testing, X-ray diffraction, and diagenesis reconstruction and physical property recovery techniques. It aims to explore the pore characteristics and preservation mechanisms, classify reservoir types, and clarify the distribution patterns and controlling factors of favorable reservoirs.The results show that the sandstone is mainly composed of feldspathic lithic sandstone and lithic feldspathic sandstone with low matrix content and medium maturity in both composition and structure. The primary pore type of the reservoir is residual primary pores, followed by secondary pores, including intergranular and intragranular dissolution pores, classifying the reservoir as a medium-to-high porosity and permeability type. The preservation of the primary pores in the middle and deep sandstones of the Bashijiqike Formation was mainly attributed to the depositional environment and subsequent diagenetic and reservoir evolution. The sandstone was initially formed in the microfacies of distributary channels at the front edge of a braided river delta with high hydrodynamics. The constantly overlapping channels formed thick and stable composite sand bodies. The strong hydrodynamics in the area led to high concentration and good sorting of sandstone clastic particles, providing the material basis for the formation of primary pores. The burial evolution process involved early long-term shallow burial and late-stage rapid deep burial, resulting in weak compaction transformation of the sandstone. Meanwhile, late-stage deep overpressure greatly enhanced the sand body's resistance to compaction, allowing for the preservation of residual primary pores. The continuously decreasing paleogeothermal gradient in the depression further contributed to the effective preservation of residual primary pores.

【Objective】 Maize is a main staple crop cultivated in central and Northern China but it requires irrigation at certain stages during its growth. In this paper, we present the findings of an experimental study on the effect of irrigation amount on photosynthesis and dry matter accumulation of the crop during its tasseling-silking stage. 【Method】 The field experiment was conducted in the long-term experiment established in 2018 at the experimental base of the academy of agricultural and animal husbandry sciences of Inner Mongolia Autonomous Region. The experiment compared six irrigation amounts: 315 m3/hm2 (W1), 645 m3/hm2 (W2), 945 m3/hm2 (W3), 1 275 m3/hm2 (W4), and 1 605 m3/hm2 (W5); the control was rain-fed (W0). During the experiment, we measured photosynthetic characteristics and dry matter accumulation of the crop in each treatment. The photosynthetic characteristics and its correlation with dry matter accumulation were calculated by fitting the response curve parameters to a non-right-angle hyperbolic model. 【Result】 The leaf SPAD in W3 was lower only than that in W4 in 2019, but in 2020 it increased by 3.96%, 5.12%, 11.10%, 12.64% and 19.90%, respectively, compared with that in W4, W2, W1, W5 and W0. In 2019 and 2020, the average daily net photosynthetic rate was the highest in W3, while in 2019, the dry weights of stems, leaves and ears in W3 were the second highest among all treatments. In 2020, the physiological indexes of the crop in W3 were higher than that in other treatments. There was no significant difference in leaf photosynthesis between W3, W4 and W5. 【Conclusion】 In central and western regions of Inner Mongolia, when the total rainfall during growing season of maize exceeded 365 mm, irrigating 945 m3/hm2 of water can effectively improve photosynthetic efficiency of the maize during its tasseling-silking stage, promote dry matter accumulation and increase grain yield.

Abstract Background Madhuca longifolia, the energy-producing and medicinal tropical tree originally from southern India, faces difficulties in adapting to the low temperatures of late autumn and early winter in subtropical southern China, impacting its usability. Therefore, understanding the molecular mechanisms controlling the ability of this species to adapt to environmental challenges is essential for optimising horticulture efforts. Accordingly, this study aimed to elucidate the molecular responses of M. longifolia to low-temperature stress through genomic and transcriptomic analyses to inform strategies for its effective cultivation and utilisation in colder climates. Results Herein, the high-quality reference genome and genomic assembly for M. longifolia are presented for the first time. Using Illumina sequencing, Hi-C technology, and PacBio HiFi sequencing, we assembled a chromosome-level genome approximately 737.92 Mb in size, investigated its genomic features, and conducted an evolutionary analysis of the genus Madhuca. Additionally, using transcriptome sequencing, we identified 17,941 differentially expressed genes related to low-temperature response. Through bioinformatics analysis of the WRKY gene family, 15 genes crucial for M. longifolia low-temperature resistance were identified. Conclusions This research not only lays the groundwork for the successful ecological adaptation and cultivation of M. longifolia in China’s southern subtropical regions but also offers valuable insights for the genetic enhancement of cold tolerance in tropical species, contributing to their sustainable horticulture and broader industrial, medicinal, and agricultural use.

Abstract Video Coding for Machines (VCM) is gaining momentum in applications like autonomous driving, industry manufacturing, and surveillance, where the robustness of machine learning algorithms against coding artifacts is one of the key success factors. This work complements the MPEG/JVET standardization efforts in improving the resilience of deep neural network (DNN)-based machine models against such coding artifacts by proposing the following three advanced fine-tuning procedures for their training: (1) the progressive increase of the distortion strength as the training proceeds; (2) the incorporation of a regularization term in the original loss function to minimize the distance between predictions on compressed and original content; and (3) a joint training procedure that combines the proposed two approaches. These proposals were evaluated against a conventional fine-tuning anchor on two different machine tasks and datasets: image classification on ImageNet and semantic segmentation on Cityscapes. Our joint training procedure is shown to reduce the training time in both cases and still obtain a 2.4% coding gain in image classification and 7.4% in semantic segmentation, whereas a slight increase in training time can bring up to 9.4% better coding efficiency for the segmentation. All these coding gains are obtained without any additional inference or encoding time. As these advanced fine-tuning procedures are standard-compliant, they offer the potential to have a significant impact on visual coding for machine applications.

The 3C-like protease (3CLpro) is a crucial target in anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) drug design. Herein, we performed high-throughput synthesis of catechol derivatives from the bioactive catechol-terminal alkyne scaffold A4, by using modular click chemistry. Subsequently, we conducted two rounds of SARS-CoV-2 3CLpro inhibition screening and selected seven compounds for synthesis and further efficacy validation. Compound P1-E11 had potent inhibitory effects toward SARS-CoV-2 3CLpro (IC50 = 2.54 ± 0.46 μM); exhibited good selectivity toward the human cysteine proteases cathepsins B and L; and demonstrated superior anti-SARS-CoV-2 potency (EC50 = 4.66 ± 0.58 μM) with low cytotoxicity (CC50 > 100 μM) in A549-hACE2-TMPRSS2 cells. The irreversible covalent mechanism of P1-E11 was confirmed through time-dependent experiments, enzyme kinetic studies, and dilution and dialysis assays. The binding affinity between P1-E11 and SARS-CoV-2 3CLpro with a KD value of 0.57 μM was validated through surface plasmon resonance (SPR) experiments. Molecular docking provided insights into the binding mode of P1-E11 to the target protein. This study demonstrated the feasibility and efficacy of modular click reactions in natural-product-based structural modifications and presents a novel approach for leveraging this strategy in antiviral drug discovery.

Abstract Background Respiratory syncytial virus (RSV) is a prominent etiological agent of lower respiratory tract infections in children, responsible for approximately 80% of cases of pediatric bronchiolitis and 50% of cases of infant pneumonia. Despite notable progress in the diagnosis and management of pediatric RSV infection, the current biomarkers for early-stage detection remain insufficient to meet clinical needs. Therefore, the development of more effective biomarkers for early-stage pediatric respiratory syncytial virus infection (EPR) is imperative. Methods The datasets used in this study were derived from the Gene Expression Omnibus (GEO) database. We used GSE188427 dataset as the training set to screen for biomarkers. Biomarkers of EPR were screened by Weighted Gene Co-expression Network Analysis (WGCNA), three machine-learning algorithms (LASSO regression, Random Forest, XGBoost), and other comprehensive bioinformatics analysis techniques. To evaluate the diagnostic value of these biomarkers, multiple external and internal datasets were employed as validation sets. Next, an examination was performed to investigate the relationship between the screened biomarkers and the infiltration of immune cells. Furthermore, an investigation was carried out to identify potential small molecule compounds that interact with selected diagnostic markers. Finally, we confirmed that the expression levels of the selected biomarkers exhibited a significant increase following RSV infection, and they were further identified as having antiviral properties. Results The study found that lymphocyte antigen 6E (LY6E) and Transcobalamin-2 (TCN2) are two biomarkers with diagnostic significance in EPR. Analysis of immune cell infiltration showed that they were associated with activation of multiple immune cells. Furthermore, our analysis demonstrated that small molecules, 3ʹ-azido-3ʹ-deoxythymine, methotrexate, and theophylline, have the potential to bind to TCN2 and exhibit antiviral properties. These compounds may serve as promising therapeutic agents for the management of pediatric RSV infections. Additionally, our data revealed an upregulation of LY6E and TCN2 expression in PBMCs from patients with RSV infection. ROC analysis indicated that LY6E and TCN2 possessed diagnostic value for RSV infection. Finally, we confirmed that LY6E and TCN2 expression increased after RSV infection and further inhibited RSV infection in A549 and BEAS-2B cell lines. Importantly, based on TCN2, our findings revealed the antiviral properties of a potentially efficacious compound, vitamin B12. Conclusion LY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection. LY6E and TCN2 inhibit RSV infection, indicating that LY6E and TCN2 are potential therapeutic target for RSV infection.

Abstract Background Ambient particulate matter (PM) exposure is recognized as a risk factor for cardiovascular disease (CVD). However, the extent to which PM exposure is associated with CVD via triglyceride glucose (TyG)-related indicators remains unknown. This study examines the relationship between long-term PM exposure and CVD events, further assessing whether TyG-related indicators mediate this association. Methods This cohort study involved 7,532 individuals aged at least 45 years who were not diagnosed with CVD in 2011 from the China Longitudinal Study of Health and Retirement (CHARLS) and were followed up for the occurrence of CVD until 2020. The annual PM concentration data at the city level, with aerodynamic diameters ≤ 1 μm (PM1), ≤ 2.5 μm (PM2.5), and ≤ 10 μm (PM10), were obtained from the ChinaHighAirPollutants (CHAP). The average concentration of PM in the 3 years before the baseline survey in 2011 was defined as the long-term exposure level of the individual. The relationship between PM exposure and CVD incidence was examined via Cox proportional hazards models, with a focus on probing the role of TyG-related indicators through mediation analysis. Results A total of 1,865 individuals with CVD were diagnosed over the span of a 7.4-year follow-up period. The 3-year average concentrations before baseline were 31.29 µg/m³ for PM1, 56.03 µg/m³ for PM2.5, and 95.73 µg/m³ for PM10. In fully adjusted model, the Cox proportional hazards models revealed that an increase of 10 µg/m³ in the PM1, PM2.5, and PM10 exposure concentrations corresponded to elevated CVD risk, with HRs (95% CI) of 1.135 (1.078–1.195), 1.092 (1.062–1.123), and 1.075 (1.059–1.090), respectively. Mediation analyses further suggested that the correlation between PM exposure and CVD could be partly mediated via TyG-BMI, TyG-WC, and TyG-WHtR, with mediation proportions varying from 5.54 to 15.30%. Conclusion A significant correlation was observed between long-term PM exposure and increased CVD risk, with TyG-related indicators, such as TyG-BMI, TyG-WC, and TyG-WHtR, partially mediating this relationship.

Abstract Background Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA. Results Among these 153 fetuses, 99 (64.7%) with isolated RAA and 54 (35.3%) with non-isolated RAA; 25.5% (39/153) with additional intracardiac anomalies (ICA), and 19.0% (29/153) with extracardiac anomalies (ECA). Tetralogy of Fallot (n = 10) and persistent left superior vena cava (n = 11) are the most common ICA and ECA, respectively. CMA detected 15 clinically significant copy number variations (CNVs) in 14 cases (9.2%); microdeletion of 22q11.21 was the most common pathogenic CNVs (7.8%). The chromosomal abnormalities rate was higher in non-isolated RAA and RAA with ICA groups than in isolated RAA group (16.7% vs. 5.1%; 20% vs. 5.1%, both p < 0.05). From five cases further undergoing WES, a diagnostic variant in MTOR gene (c.7255G > A, de novo) was first reported in prenatal, extending the prenatal manifestation of Smith–Kingsmore syndrome (OMIM: 616638); a clinically relevant variant c.3407A > T in STAG2 was identified, being inherited from the healthy mother. Moreover, the premature birth and termination rates were higher in non-isolated RAA group than in isolated RAA group (11.1% vs. 1.0%; 37.0% vs. 2.0%, both p < 0.01). Conclusions We demonstrate that CMA and WES are useful diagnostic tools for fetal RAA, particularly non-isolated RAA, and all fetuses with RAA should be referred for CMA. The data probably aids in prenatal diagnosis and prenatal counseling of fetal RAA.

In recent years, the issue of PM2.5-O3 compound pollution has become a significant global environmental concern. This study examines the spatial and temporal patterns of global PM2.5-O3 compound pollution and exposure risks, firstly at the global and urban scale, using spatial statistical regression, exposure risk assessment, and trend analyses based on the datasets of daily PM2.5 and surface O3 concentrations monitored in 120 cities around the world from 2019 to 2022. Additionally, on the basis of the common emission sources, spatial heterogeneity, interacting chemical mechanisms, and synergistic exposure risk levels between PM2.5 and O3 pollution, we proposed a synergistic PM2.5-O3 control framework for the joint control of PM2.5 and O3. The results indicated that: (1) Nearly 50% of cities worldwide were affected by PM2.5-O3 compound pollution, with China, South Korea, Japan, and India being the global hotspots for PM2.5-O3 compound pollution; (2) Cities with PM2.5-O3 compound pollution have exposure risk levels dominated by ST + ST (Stabilization) and ST + HR (High Risk). Exposure risk levels of compound pollution in developing countries are significantly higher than those in developed countries, with unequal exposure characteristics; (3) The selected cities showed significant positive spatial correlations between PM2.5 and O3 concentrations, which were consistent with the spatial distribution of the precursors NOx and VOCs; (4) During the study period, 52.5% of cities worldwide achieved synergistic reductions in annual average PM2.5 and O3 concentrations. The average PM2.5 concentration in these cities decreased by 13.97%, while the average O3 concentration decreased by 19.18%. This new solution offers the opportunity to construct intelligent and healthy cities in the upcoming low–carbon transition.

Abstract Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.

Abstract Cis-dichlorodiammineplatinum(II) (CDDP), while widely utilized in tumor therapy, results in toxic side effects that patients find intolerable. The specific mechanism by which CDDP inflicts ovarian damage remains unclear. This study aimed to explore the involvement of ferrostatin-1 (FER-1) and ferroptosis in CDDP-induced ovarian toxicity. This study established models of CDDP-induced injury in granulosa cells (GCs) and rat model of premature ovarian failure (POF). CCK-8 assessed the effects of CDDP and FER-1 on GC viability. FerroOrange and Mito-FerroGreen, DCFH-DA and MitoSox-Red, Rhodamine 123 and Transmission electron microscopy (TEM) measured Fe2+, reactive oxygen species (ROS), mitochondrial membrane potential and the mitochondrial morphology in GC cells, respectively. Serum hormone levels; organ indices; malondialdehyde, superoxide dismutase, and glutathione analyses; and western blotting were performed to examine ferroptosis's role in vitro. Molecular docking simulation was evaluated the interaction between FER-1 and GPX4 or FER-1 and NRF2. Molecular docking simulations were conducted to evaluate the interactions between FER-1 and GPX4, as well as FER-1 and NRF2. The findings revealed that CDDP-induced ovarian toxicity involved iron accumulation, increased ROS accumulation, and mitochondrial dysfunction, leading to endocrine disruption and tissue damage in rats. These changes correlated with NRF2, HO-1, and GPX4 levels. However, FER-1 decreased the extent of ferroptosis. Thus, ferroptosis appears to be a crucial mechanism of CDDP-induced ovarian injury, with GPX4 as potential protective targets.

Abstract The identification effector targets and characterization of their functions are crucial for understanding pathogen infection mechanisms and components of plant immunity. Here, we identify the effector UgsL, a ustilaginoidin synthetase with a key role in regulating virulence of the rice false smut fungus Ustilaginoidea virens. Heterologous expression of UgsL in rice (Oryza sativa) enhances plant susceptibility to multiple pathogens, and host-induced gene silencing of UgsL enhances plant resistance to U. virens, indicating that UgsL inhibits rice immunity. UgsL interacts with STRUBBELIG RECEPTOR KINASE 3 (OsSRF3). Genome editing and overexpression of OsSRF3 demonstrate that OsSRF3 plays a pivotal role in the resistance of rice to multiple pathogens. Remarkably, overexpressing OsSRF3 enhances resistance without adversely affecting plant growth or yield. We show that BRASSINOSTEROID RECEPTOR-ASSOCIATED KINASE 1 (OsBAK1) interacts with and phosphorylates OsSRF3 to activate pathogen-triggered immunity, inducing the mitogen-activated protein kinase cascade, a reactive oxygen species burst, callose deposition, and expression of defense-related genes. UgsL interferes with the phosphorylation of OsSRF3 by OsBAK1. Furthermore, UgsL mediates OsSRF3 degradation by facilitating its association with the ubiquitin-26S proteasome. Our results reveal that OsSRF3 positively regulates immunity in rice and that UgsL mediates its degradation, thereby inhibiting the activation of OsBAK1–OsSRF3-mediated immune pathways.

Abstract The large mid-infrared (MIR) spectral region, ranging from 2.5 µm to 25 µm, has remained under-exploited in the electromagnetic spectrum, primarily due to the absence of viable transceiver technologies. Notably, the 8–14 µm long-wave infrared (LWIR) atmospheric transmission window is particularly suitable for free-space optical (FSO) communication, owing to its combination of low atmospheric propagation loss and relatively high resilience to turbulence and other atmospheric disturbances. Here, we demonstrate a direct modulation and direct detection LWIR FSO communication system at 9.1 µm wavelength based on unipolar quantum optoelectronic devices with a unprecedented net bitrate exceeding 55 Gbit s−1. A directly modulated distributed feedback quantum cascade laser (DFB-QCL) with high modulation efficiency and improved RF-design was used as a transmitter while two high speed detectors utilizing meta-materials to enhance their responsivity are employed as receivers; a quantum cascade detector (QCD) and a quantum-well infrared photodetector (QWIP). We investigate system tradeoffs and constraints, and indicate pathways forward for this technology beyond 100 Gbit s−1 communication.

Abstract Background There is increasing evidence that inflammation plays a key role in the pathophysiology of periodontitis (PT) and Alzheimer’s disease (AD), but the roles of inflammation in linking PT and AD are not clear. Our aim is to analyze the potential molecular mechanisms between these two diseases using bioinformatics and systems biology approaches. Methods To elucidate the link between PT and AD, we selected shared genes (SGs) with gene-disease-association scores of ≥ 0.1 from the Disease Gene Network (DisGeNET) database, followed by extracting the hub genes. Based on these genes, we constructed gene ontology (GO) enrichment analysis, pathway enrichment analysis, protein-protein interaction (PPI) networks, transcription factors (TFs)-gene networks, microRNAs (miRNAs)-gene regulatory networks, and gene-disease association analyses. Finally, the Drug Signatures database (DSigDB) was utilized to predict candidate molecular drugs related to hub genes. Results A total of 21 common SGs between PT and AD were obtained. Cell cytokine activity, inflammatory response, and extracellular membrane were the most important enriched items in GO analysis. Interleukin-10 Signaling, LTF Danger Signal Response Pathway, and RAGE Pathway were identified as important shared pathways. IL6, IL10, IL1B, TNF, IFNG, CXCL8, CCL2, MMP9, TLR4 were identified as hub genes. Both shared pathways and hub genes are closely related to endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Importantly, glutathione, simvastatin, and dexamethasone were identified as important candidate drugs for the treatment of PT and AD. Conclusions There is a close link between PT and AD pathogenesis, which may involve in the inflammation, ER and mitochondrial function.

Painted during the Yuan Dynasty, Taoist Celestial Beings Worshiping is a Taoist propaganda painting. It is one of the largest surviving ancient murals worldwide, featuring a variety of images of these beings dressed in costumes that vividly illustrate the blend of religious and artistic values in Chinese culture. To record and present the mural more intuitively and improve the study of Taoist Celestial Beings Worshiping, this article takes the example of five goddesses centered Queen Mother of the West in the mural and analyzes the styles, structures, colors, and patterns of the costumes from the perspective of costume engineering. Human models are established and the costumes at multiple levels are reconstruction by means of 3D virtual simulation technology. The display images are accompanied by QR codes, which can be scanned to view the 3D model. Finally, the Fuzzy Analytic Hierarchy Process was used to comprehensively evaluate the reconstruction effect of clothing, and the result was “good.” The resulting digital figure can realize the “revitalization of cultural relics” and provides a new perspective for the digital exhibition of murals, which is conducive to the development of digital tourism and promotes the development of traditional culture.

Abstract Background Exploring the physiological and molecular mechanisms underlying goat sexual maturation can enhance breeding practices and optimize reproductive efficiency and is therefore substantially important for practical breeding purposes. As an essential neuroendocrine organ in animals, the hypothalamus is involved in sexual development and other reproductive processes in female animals. Although microRNAs (miRNAs) have been identified as significant regulators of goat reproduction, there is a lack of research on the molecular regulatory mechanisms of hypothalamic miRNAs that are involved in the sexual development of goats. Therefore, we examined the dynamic changes in serum hormone profiles and hypothalamic miRNA expression profiles at four developmental stages (1 day (neonatal, D1, n = 5), 2 months (prepubertal, M2, n = 5), 4 months (sexual maturity, M4, n = 5), and 6 months (breeding period, M6, n = 5)) during sexual development in Jining grey goats. Results Transcriptome analysis revealed 95 differentially expressed miRNAs (DEMs) in the hypothalamus of goats across the four developmental stages. The target genes of these miRNAs were significantly enriched in the GnRH signalling pathway, the PI3K-Akt signalling pathway, and the Ras signalling pathway (P

Abstract The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy.