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Abstract Vertical stratification of forest plays important roles in the local material balance and in maintaining forest health by distributing and redistributing precipitation materials through adsorption, fixation, and release. Differences in runoff nutrient concentrations among vertical layers are closely related to vertical stratification (factors such as the trunk, canopy, forest litter, and soil physical and chemical properties). Long-term forest observations revealed significant spatial differences in Pinus massoniana (Pinus massoniana Lamb.) forests in the Three Gorges Reservoir area. Pinus massoniana forests on downslopes were characterized by a dense canopy, green needles, and rich forest vegetation, while those on upslopes were characterized by low vegetation cover, dead trees, and decreases in the tree height, diameter at breast height, and volume per plant with increasing slope. By analyzing the soil at different sites, we found that the pH of the forest land soil differed significantly among different slope positions. Soil on upper slopes was significantly more acidic than soil on lower slopes, indicating that acidic substances were intercepted by filtration through the broad litter layer and the soil surface layer. This filtration process resulted in a normal rhizosphere environment suitable for the absorption of nutrients by vegetation on the lower slopes. In this way, downhill sites provided a good microenvironment for the growth of Pinus massoniana and other vegetation. Our results show that direct contact between needles and acid rain was not the main cause of root death. Instead, the redistribution of rainfall substances by forest spatial stratification caused changes in the soil microenvironment, which inhibited the absorption of nutrients by the roots of Pinus massoniana and the growth of understory plants in Pinus massoniana forests on upper slopes. These findings emphasize that increasing land cover with forests with vertical structural stratification plays an important role in woodland material redistribution and forest conservation.

Reservoir heterogeneity, water-oil mobility ratio, cementation degree, and strong injection and production significantly influence long-term waterflooding and polymer flooding processes in oil reservoir development, leading to the formation of low-resistance dominant seepage channels in the lower part of thick oil layers without internal laminations. Understanding the spatial distribution and evolution of dominant seepage channels in oil reservoirs during waterflooding and polymer flooding is crucial for improving reservoir development and recovery rates. It uses a streamlined numerical simulation method to quantitatively show the spatial and temporal distribution of dominant seepage channels in the oil reservoir. A model and chart were created to demonstrate the relationship between permeability and throat radius, capturing changes in reservoir permeabilities over time. The study developed a comprehensive mathematical model to identify dominant seepage channels, considering parameters such as inter-well flow ratio, injection efficiency, permeability change value, and water saturation. Research findings indicate a 14.8 % increase in reservoir permeability after polymer flooding, with slight changes in porosity and a 20.3 % decrease in clay content. The established mathematical model and identification criteria were used to comprehensively quantitatively evaluate flow channels, describing the distribution characteristics and evolution process of dominant seepage channels in the experimental area over four periods: pre-polymer flooding, low water-saturation period during polymer flooding, post-polymer injection, and subsequent 10 years of water flooding. Both polymer flooding and subsequent water flooding have significantly altered the distribution pattern of predominant fluid pathways: 254 well layers now demonstrate robust predominant fluid pathways (19 %); another 272 well layers feature moderately predominant fluid pathways (22 %); while an additional 440 well layers display weaker predominant fluid pathways (approximately 35 %). There has been a noticeable increase in both weak and moderate predominant fluid pathways, which are now more widespread in the area. However, localized occurrences of strong predominant fluid pathways persist with no significant change in their distribution characteristics. Analysis at four different time points shows a clear trend of increasing intensity as we move from polymer to subsequent water flooding in this decade. Additionally, examination along an axis from upper left to lower right reveals a linear progression that indicates clear connections among different categories of dominant seepage channel. The verification results show a strong correlation between the calculated dominant seepage channel distribution and actual water-injection profile test results, indicating that the method effectively identifies dominant seepage channels in oil reservoirs after polymer flooding and has the potential to enhance oil recovery further.

Abstract Metastasis is the major cause of treatment failure in patients with prostate adenocarcinoma (PRAD). Diverse programmed cell death (PCD) patterns play an important role in tumor metastasis and hold promise as predictive indicators for PRAD metastasis. Using the LASSO Cox regression method, we developed PCD score (PCDS) based on differentially expressed genes (DEGs) associated with PCD. Clinical correlation, external validation, functional enrichment analysis, mutation landscape analysis, tumor immune environment analysis, and immunotherapy analysis were conducted. The role of Prostaglandin D2 Synthase (PTGDS) in PRAD was examined through in vitro experiments, single-cell, and Mendelian randomization (MR) analysis. PCDS is elevated in patients with higher Gleason scores, higher T stage, biochemical recurrence (BCR), and higher prostate-specific antigen (PSA) levels. Individuals with higher PCDS are prone to metastasis, metastasis after BCR, BCR, and castration resistance. Moreover, PRAD patients with low PCDS responded positively to immunotherapy. Random forest analysis and Mendelian randomization analysis identified PTGDS as the top gene associated with PRAD metastasis and in vitro experiments revealed that PTGDS was considerably downregulated in PRAD cells against normal prostate cells. Furthermore, the overexpression of PTGDS was found to suppress the migration, invasion, proliferationof DU145 and LNCaP cells. To sum up, PCDS may be a useful biomarker for forecasting the possibility of metastasis, recurrence, castration resistance, and the efficacy of immunotherapy in PRAD patients. Additionally, PTGDS was identified as a viable therapeutic target for the management of PRAD.

Abstract Objective Bibliometrics was employed in this study to determine the research trends in the worldwide application of 3D printing technology to treat bone tumors over the previous 10 years. Methods Published from 2013 to 2022, the papers related to bone tumors treated with 3D printing were located in Web of Science Core Collection (WoSCC), PubMed, and Scopus. The screened articles were included in this bibliometric study. From these papers in WoSCC, information on annual publications, journals, keywords, countries, authors, institutions, and cited references were extracted and visualized with CiteSpace (version 6.1.R6) software to investigate the state of bone tumor treatment using 3D printing as well as research hotspots. The Carrot2 online visualization tool and Vosviewer software (version 1.6.20) were employed to visualize the publications from PubMed and Scopus, respectively, in order to ascertain the most popular research topics from both databases. Results A total of 606, 233, and 364 publications were obtained from WoSCC, PubMed, and Scopus, respectively, between the years 2013 and 2022. In WoSCC, the peak number of publications was found in 2021, with 145 publications published. Acta Biomaterialia (11 publications) and World Neurosurgery (10 publications) were the most prolific journals, and Biomaterials was the journal cited the most (244 times). Yong Zhou was the most productive author with 14 publications, while Kwok-Chuen Wong (69 citations) and William F Enneking, (69 citations) possessed the most citations. The country with the largest quantity of publications was China (207). Among all institutions, Shanghai Jiao Tong University produced the most publications (29). Rapid prototyping was the keyword with the strongest citation burst (4.73). ‘Reconstruction’, ‘surgery’, ‘resection’, and ‘design’ caught the significant attention of researchers. 3D-printed materials, pelvic reconstruction, mandibular reconstruction, computer-assisted surgical techniques, photothermal therapy, and in vitro experiments were recognized as hot subjects and trends in current research. The most frequently occurring topics in Scopus are not significantly different from those found in WoSCC. The most prevalent research areas in PubMed encompass implant, patient-specific, bioceramic, models, and pelvic.

Highlights Inspired by the Chinese Knotting weave structure, an electromagnetic interference (EMI) nanofiber composite membrane with a twill surface was prepared. The EMI shielding efficiency (SE) of the composite membrane was 103.9 dB when the MXene/silver nanowires (MXene/AgNW) content was only 7.4 wt% and the surface twill structure improved the EMI by 38.5%. The nanofiber composite membrane demonstrated an excellent thermal management performance, hydrophobicity, non-flammability, and performance stability, which was demonstrated by an EMI SE of 97.3% in a high-temperature environment at 140 °C.

BackgroundPostmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD.MethodsIn this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism.ResultsCompared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P < 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins.ConclusionThis study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner.

The safety and efficiency of lithium‐ion batteries (LIBs) suggest a promising future for this technology, particularly in the automobile industry. However, thermal runaway—wherein a LIB undergoes an uncontrollable increase in temperature that may result in smoke, fire, or explosion—represents an important and widely studied failure type. Since the electrodes of LIBs are manufactured from porous composite materials, their heterogeneity can significantly influence the effective material characteristics and microscale behaviors of LIBs during operation. Microstructure geometric and electrochemical–thermal models are typically used to investigate these impacts. Herein, a microstructure geometric model is constructed of LIB's electrodes. A virtual multiphysics model is used to simulate the overcharging thermal runaway condition. The model's accuracy is validated through real‐world experiments. The model shows greater accuracy compared to the result from a conventional homogeneous geometric model and better reflects the heterogeneous internal phenomenon. The model is applied to a variable analysis in order to investigate how the varying heterogeneity of the cathode's porosity impacts the cell during overcharging thermal runaway behavior. Our results indicate that decreasing porosity heterogeneity at the cathode may delay thermal runaway, owing to the heterogeneous impact on particle diffusion behaviors and the side reaction rate.

Objectives Cancer screening aims to detect and treat malignant lesions at an early stage and to prolong patients’ lifetime. There is still a lack of effective cancer screening programs in China. We initiated a screening project in 2018 and this study presented the cancer screening status in China. Methods We conducted a cross-sectional study in one cancer-care medical center of China. The screening program included routine blood tests, plasma tumor markers, gastric endoscopy, colonoscopy, ultrasound, and computed tomography (CT) scans. Screening results were presented as sensitivity, specificity and positive predictive values (PPVs). Results Twenty-three (1.46%) out of 1,576 participants were eventually diagnosed with malignant tumors or high-grade intraepithelial neoplasia (HGIN). A family history of malignancy (78.26% in diagnosed cancer and HGIN vs. 46.36% in the others) was the only statistically significant parameter associated with cancer detection (p = 0.002). None of the common tumor markers were associated with the cancers screened. Except for colonoscopy (50.00%) and ultrasound for renal cancer (66.67%), the sensitivities of most screening methods were 100%. The specificities of all the screening means were above 96%. Most PPVs ranged from 30–60%. Conclusion We emphasized risk stratification for early cancer screening, such as a family history of cancer. The survey illustrated that gastric endoscopy, colonoscopy, ultrasound, and lung CT for early cancer screening had high specificity, reasonable sensitivity, and PPV. We anticipated this report would motivate larger-sample studies to estimate the risk-to-benefit ratio of cancer screening and urge the establishment of a native Chinese screening project and even guidelines.

Low-density lipoprotein receptor-related protein 2 (LRP2) is a multifunctional endocytic receptor expressed in epithelial cells. In mammals, it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis. However, little is known about the role of LRP2 in lipid homeostasis in insects. In the present study, we investigated the function of LRP2 in the migratory locust Locusta migratoria (LmLRP2). The mRNA of LmLRP2 is widely distributed in various tissues, including integument, wing pads, foregut, midgut, hindgut, Malpighian tubules and fat body, and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage. Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut. Using RNAi to silence LmLRP2 caused molting defects in nymphs (more than 60%), and the neutral lipid was found to accumulate in the midgut and surface of the integument, but not in the fat body, of dsLmLRP2-treated nymphs. The results of a lipidomics analysis showed that the main components of lipids (diglyceride and triglyceride) were significantly increased in the midgut, but decreased in the fat body and hemolymph. Furthermore, the content of total triglyceride was significantly increased in the midgut, but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs. Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells, and is required for lipid export from the midgut to the hemolymph and fat body in locusts.

Abstract Deregulation of circular RNAs (circRNAs) is widely recognized in cancer progression. Our study aims to investigate the role of circ_0020460 in the development of cervical cancer (CC) and its potential mechanism of action. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were used to detect the expression levels of circ_0020460, miR-485-3p and C-X-C motif chemokine ligand 1 (CXCL1). The roles of circ_0020460 on cell proliferation, cell migration, cell invasion, cell apoptosis, and angiogenesis were investigated using cell counting kit-8 (CCK-8) and Ethynyl deoxyuridine (Edu) assay, wound healing assay, transwell assay, flow cytometry assay, and tube formation assay, respectively. The putative relationship predicted by bioinformatics analysis was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft models were constructed to explore the role of circ_0020460 in vivo. The expression of circ_0020460 and CXCL1 expression were increased, while miR-485-3p expression was declined in CC tissues and cells. Circ_0020460 knockdown suppressed CC cell proliferation, cell migration, cell invasion, angiogenesis, and promoted cell apoptosis. Circ_0020460 functioned as a miR-485-3p sponge to inhibit miR-485-3p level, and the anti-cancer effects mediated by circ_0020460 knockdown were reversed by miR-485-3p inhibitor. MiR-485-3p bound to CXCL1 3ʹ untranslated region (3ʹUTR) to degrade CXCL1 expression, and the anti-cancer effects of miR-485-3p restoration were impaired by CXCL1 overexpression. Circ_0020460 downregulation inhibited CC xenograft tumor growth. These results suggest that circ_0020460 promoted the malignant behavior of CC cells by modulating the miR-485-3p/CXCL1 axis.

Objectives: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. Methods: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. Results: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. Conclusions: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

ABSTRACTAnimal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, ACE2 with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR – Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3 × 105 PFU) or low (2.5 × 102 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.

AbstractObjectives This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features.Methods A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell’s C-index and a calibration curve.Results The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin 3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration.Conclusions The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

AbstractObjectives This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs).Methods Between March 2011 and November 2022, 34 patients (16 males; age range, 25–72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1–5.2) cm. Survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model.Results For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0–45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8–159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS.Conclusions Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.

Organic orchard management has been widely adopted to enhance soil fertility by improving the sequestration of soil organic carbon (SOC). Microbial residue carbon plays an essential role in SOC accumulation; nevertheless, how fungal and bacterial residue carbon (FRC and BRC) changes with different orchard management practices (organic vs. conventional) and the factors influencing their accumulation remain poorly understood. In this study, we quantified the FRC and BRC in the two management practices, compiled this data with the comparisons of plant, soil and microbial properties, and the dominant factor affecting their sequestration was ascertained with a 4-year orchard experiment on the Jiaodong Peninsula. Compared with conventional management, organic management significantly enhanced SOC and the accumulation of FRC and BRC, while it did not alter the contribution of FRC or BRC to SOC. Furthermore, we identified that the primary determinant affecting FRC varied with management type: Plant (AGR, BGG)-soil (SOC, density)-microbe (Nitrospirae) collectively governed FRC in organic soil, whereas soil (pH, density) and microbial (Ascomycota) properties regulated FRC in conventional soil. Nitrospirae abundance and soil pH played pivotal roles in FRC accumulation under organic and conventional management, respectively. Meanwhile, the primary factor influencing BRC was independent of management type: Soil and microbial properties consistently served as the principal determinants of BRC in both management systems, with soil pH and clay being the pivotal factors in organic and conventional managements, respectively. These findings illustrate the divergent regulatory mechanisms of FRC and BRC in organic and conventional management, thereby enhancing our comprehension of microbial-mediated SOC sequestration in organic orchard management.

Abstract The BMP (Bone morphogenetic protein) signaling pathway plays a central role in metazoan biology, intricately shaping embryonic development, maintaining tissue homeostasis, and influencing disease progression. In the context of cancer, BMP signaling exhibits context-dependent dynamics, spanning from tumor suppression to promotion. Cancer stem cells (CSCs), a modest subset of neoplastic cells with stem-like attributes, exert substantial influence by steering tumor growth, orchestrating therapy resistance, and contributing to relapse. A comprehensive grasp of the intricate interplay between CSCs and their microenvironment is pivotal for effective therapeutic strategies. Among the web of signaling pathways orchestrating cellular dynamics within CSCs, BMP signaling emerges as a vital conductor, overseeing CSC self-renewal, differentiation dynamics, and the intricate symphony within the tumor microenvironment. Moreover, BMP signaling’s influence in cancer extends beyond CSCs, intricately regulating cellular migration, invasion, and metastasis. This multifaceted role underscores the imperative of comprehending BMP signaling’s contributions to cancer, serving as the foundation for crafting precise therapies to navigate multifaceted challenges posed not only by CSCs but also by various dimensions of cancer progression. This article succinctly encapsulates the diverse roles of the BMP signaling pathway across different cancers, spanning glioblastoma multiforme (GBM), diffuse intrinsic pontine glioma (DIPG), colorectal cancer, acute myeloid leukemia (AML), lung cancer, prostate cancer, and osteosarcoma. It underscores the necessity of unraveling underlying mechanisms and molecular interactions. By delving into the intricate tapestry of BMP signaling’s engagement in cancers, researchers pave the way for meticulously tailored therapies, adroitly leveraging its dualistic aspects—whether as a suppressor or promoter—to effectively counter the relentless march of tumor progression.

RNA interference (RNAi) is a specific post-transcriptional gene-silencing phenomenon, which plays an important role in the regulation of gene expression and the protection from transposable elements in eukaryotic organisms. In Drosophila melanogaster, RNAi can be induced by microRNA (miRNA), endogenous small interfering RNA (siRNA), or exogenous siRNA. However, the biogenesis of miRNA and siRNA in these RNAi pathways is aided by the double-stranded RNA binding proteins (dsRBPs) Loquacious (Loqs)-PB, Loqs-PD or R2D2. In this study, we identified three alternative splicing variants of Loqs, namely Loqs-PA, -PB, and -PC in the orthopteran Locusta migratoria. We performed in vitro and in vivo experiments to study the roles of the three Loqs variants in the miRNA- and siRNA-mediated RNAi pathways. Our results show that Loqs-PB assists the binding of pre-miRNA to Dicer−1 to lead to the cleavage of pre-miRNA to yield matured miRNA in the miRNA-mediated RNAi pathway. In contrast, different Loqs proteins participate in different siRNA-mediated RNAi pathways. In exogenous siRNA-mediated RNAi pathway, binding of Loqs-PA or LmLoqs-PB to exogenous dsRNA facilitates the cleavage of dsRNA by Dicer−2, whereas in endogenous siRNA-mediated RNAi pathway, binding of Loqs-PB or Loqs-PC to endogenous dsRNA facilitates the cleavage of dsRNA by Dicer−2. Our findings provide new insights into the functional importance of different Loqs proteins derived from alternative splicing variants of Loqs in achieving high RNAi efficiency in different RNAi pathways in insects.

Polymer-based wastewater disinfection, which is typically performed using chemical oxidation or irradiation, can result in various toxic byproducts and corrosion under harsh environments. This study introduces a robust bio-adsorbent prepared from naturally abundant polydopamine-modified medical stone (MS@PDA) for the high-efficiency removal of bacteria from water. The PDA nanocoating can be easily applied through an in situ self-polymerization process, resulting in a considerably high bacterial adsorption capacity of 6.6 k pcs mm−2 for Staphylococcus aureus. A cyclic flow-through dynamic filtration and a disinfection system was implemented using an MS@PDA porous filter with an average pore size of 21.8 ± 1.4 µm and porosity of ~83%, achieving a 5.2–6.0-fold enhancement in the cumulative removal efficiency for MS@PDA2. The underlying mechanisms were elucidated through the synergistic effects of interfacial bio-adsorption and size-dependent interception. Notably, the bacteria captured on the surface could be killed using the enhanced photothermal effects of the PDA nanocoating and the inherent antimicrobial properties of the mineral stone. Thus, this study not only provides a new type of advanced bio-adsorbent but also provides new perspectives on an efficient and cost-effective approach for sustainable wastewater treatment.

Deep neural network models are vulnerable to attacks from adversarial methods, such as gradient attacks. Evening small perturbations can cause significant differences in their predictions. Adversarial training (AT) aims to improve the model’s adversarial robustness against gradient attacks by generating adversarial samples and optimizing the adversarial training objective function of the model. Existing methods mainly focus on improving robust accuracy, balancing natural and robust accuracy and suppressing robust overfitting. They rarely consider the AT problem from the characteristics of deep neural networks themselves, such as the stability properties under certain conditions. From a mathematical perspective, deep neural networks with stable training processes may have a better ability to suppress overfitting, as their training process is smoother and avoids sudden drops in performance. We provide a proof of the existence of Ulam stability for deep neural networks. Ulam stability not only determines the existence of the solution for an operator inequality, but it also provides an error bound between the exact and approximate solutions. The feature subspace of a deep neural network with Ulam stability can be accurately characterized and constrained by a function with special properties and a controlled error boundary constant. This restricted feature subspace leads to a more stable training process. Based on these properties, we propose an adversarial training framework called Ulam stability adversarial training (US-AT). This framework can incorporate different Ulam stability conditions and benchmark AT models, optimize the construction of the optimal feature subspace, and consistently improve the model’s robustness and training stability. US-AT is simple and easy to use, and it can be easily integrated with existing multi-class AT models, such as GradAlign and TRADES. Experimental results show that US-AT methods can consistently improve the robust accuracy and training stability of benchmark models.

The carbonate rock of the Qiulitage Formation is a significant stratum for oil and gas exploration in the Tarim Basin. To elucidate its environmental characteristics, we conducted tests and analyses of trace elements, carbon, and oxygen isotopes of the carbonate rocks of the Qiulitage Formation in the Kekeqigankake section of the Keping area. The results reveal that δ13C values range between −1.7‰ and 4.3‰, with an average value of 1.645‰. δ18O values fluctuate from −11.4‰ to −6‰, with an average value of −8.2475‰. Z values (paleosalinity) vary from 120.33 to 131.67, significantly exceeding 120 with an average value of 126.52, indicating a marine sedimentary environment. Paleotemperature values (T) range from 12.75 to 29.09 °C, with an average value of 21.36 °C, suggesting warm climate conditions. The Sr/Ba (3.42~24.39) and Sr/Cu (57.5~560) ratios are elevated, while Th/U (

Surface runoff is a key component of the hydrological cycle and is essential for water resource management and water ecological balance in river basins. It is important to accurately reveal the spatial and temporal dynamics of regional surface runoff over long time scales and to quantify the impacts of climate change and human activities on surface runoff changes for sustainable water resources management and utilization. In this study, the Minjiang River Basin (Chengdu section) was selected, which has significant natural and anthropogenic variations, and a comprehensive analysis of runoff and its drivers will help to formulate an effective regional water resource management strategy. We mainly used SWAT to simulate the monthly-scale runoff in the Chengdu section of the Minjiang River Basin from 1990 to 2019 and combined SWAT-CUP to perform sensitivity analysis on the model parameters and Partial Least Squares Structural Equation Modeling (PLS-SEM) to quantitatively analyze the main drivers of the changes in surface runoff. The results show that the average multi-year runoff in the Minjiang River Basin (Chengdu section) ranges from 628.96 to 1088.46 mm, with an average value of 834.13 mm, and that the overall annual runoff in the past 30 years shows a fluctuating tendency. The goodness-of-fit of the PLS-SEM model is 0.507; the validity and reliability assessment indicated that the model was reasonable, and its results showed that economic and landscape factors had significant negative impacts on runoff changes, while natural factors had positive impacts on runoff changes, with path coefficients of −0.210, −0.131, and 0.367, respectively. Meanwhile, this study also identified two potential indirect impact pathways, i.e., the economic factors had an indirect negative impact on runoff by changing the distribution of landscapes, and the natural factors had indirect negative impacts on runoff by influencing economic activities, reflecting the complex interactions among economic activities, landscape distribution, and natural factors in influencing surface runoff. This study provides a research framework and methodology for quantitatively modeling surface runoff and the analysis of influencing factors in watersheds, contributing to a deeper scientific understanding of long-term runoff changes and the contribution of their drivers.

The pavement is vulnerable to damage from natural disasters, accidents and other human factors, resulting in the formation of cracks. Periodic pavement monitoring can facilitate prompt detection and repair the pavement diseases, thereby minimizing casualties and property losses. Due to the presence of numerous interferences, recognizing highway pavement cracks in complex environments poses a significant challenge. Nevertheless, several computer vision approaches have demonstrated notable success in tackling this issue. We have employed a novel approach for crack recognition utilizing the ResNet34 model with a convolutional block attention module (CBAM), which not only saves parameters and computing power but also ensures seamless integration of the module as a plug-in. Initially, ResNet18, ResNet34, and ResNet50 models were trained by employing transfer learning techniques, with the ResNet34 network being selected as a fundamental model. Subsequently, CBAM was integrated into ResBlock and further training was conducted. Finally, we calculated the precision, average recall on the test set, and the recall of each class. The results demonstrate that by integrating CBAM into the ResNet34 network, the model exhibited improved test accuracy and average recall compared to its previous state. Moreover, our proposed model outperformed all other models in terms of performance. The recall rates for transverse crack, longitudinal crack, map crack, repairing, and pavement marking were 88.8%, 86.8%, 88.5%, 98.3%, and 99.9%, respectively. Our model achieves the highest precision of 92.9% and the highest average recall of 92.5%. However, the effectiveness in detecting mesh cracks was found to be unsatisfactory, despite their significant prevalence. In summary, the proposed model exhibits great potential for crack identification and serves as a crucial foundation for highway maintenance.

Background: MRI segmentation offers crucial insights for automatic analysis. Although deep learning-based segmentation methods have attained cutting-edge performance, their efficacy heavily relies on vast sets of meticulously annotated data. Methods: In this study, we propose a novel semi-supervised MRI segmentation model that is able to explore unlabeled data in multiple aspects based on various semi-supervised learning technologies. Results: We compared the performance of our proposed method with other deep learning-based methods on 2 public datasets, and the results demonstrated that we have achieved Dice scores of 90.3% and 89.4% on the LA and ACDC datasets, respectively. Conclusions: We explored the synergy of various semi-supervised learning technologies for MRI segmentation, and our investigation will inspire research that focuses on designing MRI segmentation models.

ObjectiveThe purpose of this study was to investigate the added value of color parameter imaging (CPI) in the differential diagnosis of focal liver lesions (FLLs) with “homogeneous hyperenhancement but not wash out” on contrast-enhanced ultrasound (CEUS).MethodsA total of 101 patients with 108 FLLs were enrolled in this study. All the FLLs received US and CEUS examinations. The stored CEUS clips of target lesions were postprocessed with CPI analysis by radiologists. The receiver operator characteristic (ROC) curve was used to evaluate the added value of CPI. The McNamara test was used to compare the diagnostic sensitivity, specificity, and accuracy between CEUS and CPI patterns. Univariate and multivariate logistic regression analyses were used to develop a CPI nomogram. The C index and calibration curve were used to evaluate the predictive ability of the nomogram. The intraclass correlation coefficient was used to test the reproducibility and reliability of CPI. Decision curve analysis (DCA) was used to evaluate the added value of applying CPI.ResultsThe following CPI features were more frequently observed in malignant FLLs: eccentric perfusion (malignant: 70.0% vs. benign: 29.2%, p < 0.001), feeding artery (51.7% vs. 4.2%, p < 0.001), mosaic (63.3% vs. 6.3%, p < 0.001), red ingredients >1/3 (90.0% vs. 14.6%, p < 0.001). In addition, centripetal (43.8% vs. 18.3%, p = 0.004), peripheral nodular (54.2% vs. 1.7%, p < 0.001), subcapsular vessel (12.5% vs. 0.0%, p = 0.004), spoke-wheel vessels (25.0% vs. 5.0%, p = 0.003), branched vessels (22.9% vs. 5.0%, p = 0.006), blue and pink ingredients >2/3 (85.4% vs. 10.0%, p < 0.001) were more observed in benign FLLs. A nomogram incorporating peripheral nodular, spoke-wheel vessels, and red ingredients >1/3 was constructed. The model had satisfactory discrimination (AUC = 0.937), and the optimal diagnostic threshold value was 0.740 (0.983, 0.850). By the DCA, the model offered a net benefit over the treat-all-patients scheme or the treat-none scheme at a threshold probability 5%–93%.ConclusionUsing CPI can detect and render subtle information of the main features of FLLs on CEUS; it is conducive to the radiologist for imaging interpretation, and a combining read of the CEUS and CPI of the FLLs with features of “homogenous hyperenhancement and no washout” can improve significantly the diagnostic performance of CEUS for FLLs.

Based on the variable gain extended state observer, a finite-time fault-tolerant control strategy is developed for the quadrotor unmanned aerial vehicle with actuator faults and external disturbances. Firstly, a novel variable gain extended state observer is designed to estimate the unknown external disturbances, which mitigates the initial peaking phenomenon existing in traditional extended state observer-based methods. Meanwhile, the neural networks are applied to accurately approximate unknown couplings online. Moreover, with the help of the projection operator technique, the unknown actuator faults are observed in real time. Combined with the backstepping framework, the finite-time robust fault-tolerant control scheme is constructed and the stability is strictly proved via Lyapunov’s theory. Finally, the validity of the developed control scheme is demonstrated through numerical simulations.

Chronic hepatitis B virus (HBV) infection is a major cause of liver cirrhosis and liver cancer, despite strong prevention and treatment efforts. The study of the epigenetic modification of HBV has become a research hotspot, including the N6-methyladenosine (m6A) modification of HBV RNA, which plays complex roles in the HBV life cycle. In addition to m6A modification, 5-methylcytosine (m5C) is another major modification of eukaryotic mRNA. In this study, we explored the roles of m5C methyltransferase and demethyltransferase in the HBV life cycle. The results showed that m5C methyltransferase NSUN2 deficiency could negatively regulate the expression of HBV while m5C demethyltransferase TET2 deficiency positively regulates the expression of HBV. Subsequently, we combined both in vitro bisulfite sequencing and high-throughput bisulfite sequencing methods to determine the distribution and stoichiometry of m5C modification in HBV RNA. Two sites: C2017 and C131 with the highest-ranking methylation rates were identified, and mutations at these two sites could lead to the decreased expression and replication of HBV, while the mutation of the "fake" m5C site had no effect. Mechanistically, NSUN2-mediated m5C modification promotes the stability of HBV RNA. In addition, compared with wild-type HepG2-NTCP cells and primary human hepatocytes, the replication level of HBV after NSUN2 knockdown decreased, and the ability of the mutant virus to infect and replicate in wild-type HepG2-NTCP cells and PHHs was substantially impaired. Similar results were found in the experiments using C57BL/6JGpt-Nsun2+/- mice. Interestingly, we also found that HBV expression and core protein promoted the endogenous expression of NSUN2, which implied a positive feedback loop. In summary, our study provides an accurate and high-resolution m5C profile of HBV RNA and reveals that NSUN2-mediated m5C modification of HBV RNA positively regulates HBV replication by maintaining RNA stability.

Accumulating evidence has shown that ultrasound exposure combined with microbubbles can enhance cancer therapy. However, the underlying mechanisms at the tissue level have not been fully understood yet. The conventional cell culture in vitro lacks complex structure and interaction, while animal studies cannot provide micron-scale dynamic information. To bridge the gap, we designed and assembled a 3D vascularized microfluidic cancer model, particularly suitable for ultrasound and microbubble involved mechanistic studies. Using this model, we first studied SonoVue microbubble traveling dynamics in 3D tissue structure, then resolved SonoVue microbubble cavitation dynamics in tissue mimicking agarose gels at a frame rate of 0.675 M fps, and finally explored the impacts of ultrasound and microbubbles on cancer cell spheroids. Our results demonstrate that microbubble penetration in agarose gel was enhanced by increasing microbubble concentration, flow rate and decreasing viscosity of the gel, and little affected by mild acoustic radiation force. SonoVue microbubble exhibited larger expansion amplitudes in 2 %(w/v) agarose gels than in water, which can be explained theoretically by the relaxation of the cavitation medium. The immediate impacts of ultrasound and SonoVue microbubbles to cancer cell spheroids in the 3D tissue model included improved cancer cell spheroid penetration in micron-scale and sparse direct permanent cancer cell damage. Our study provides new insights of the mechanisms for ultrasound and microbubble enhanced cancer therapy at the tissue level.

ABSTRACTSince its discovery, QX-type avian infectious bronchitis virus (IBV) has rapidly spread worldwide and become the most prevalent dominant genotype in Asia and Europe. Currently, although the pathogenicity of QX-type IBV in the reproductive system of hens is widely and deeply understood, its pathogenicity in the reproductive system of roosters remains largely unknown. In this study, 30-week-old specific pathogen-free (SPF) roosters were used to investigate the pathogenicity of QX-type IBV in the reproductive system after infection. The results showed that QX-type IBV infection caused abnormal testicular morphology, moderate atrophy and obvious dilatation of seminiferous tubules, and produced intense inflammation and obvious pathological injuries in the ductus deferens of infected chickens. Immunohistochemistry results showed that QX-type IBV can replicate in spermatogenic cells at various stages and in the mucous layer of the ductus deferens. Further studies showed that QX-type IBV infection affects plasma levels of testosterone, luteinizing hormone, and follicle-stimulating hormone as well as causes changes in transcription levels of their receptors in the testis. Furthermore, the transcription levels of StAR, P450scc, 3βHSD and 17βHSD4 also changed during testosterone synthesis after QX-type IBV infection, indicating that the virus can directly affect steroidogenesis. Finally, we found that QX-type IBV infection leads to extensive germ cell apoptosis in the testis. Collectively, our results suggest that QX-type IBV replicates in the testis and ductus deferens, causing severe tissue damage and disruption of reproductive hormone secretion. These adverse events eventually lead to mass germ cell apoptosis in the testis, affecting the reproductive function of roosters.

AbstractObjective To evaluate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) and liver metastases adjacent to the gallbladder (GB).Materials and methods A total of 113 patients with 118 liver lesions (63 HCC lesions and 55 liver metastases) adjacent to the gallbladder underwent RFA between March 2011 and June 2019. Gallbladder-related complications and technique effectiveness rates were evaluated based on the classification of liver tumors and the distance between the lesion and the gallbladder.Results Gallbladder-related complications were observed in 13 patients. Among the patients with HCC, there was no significant difference between the ≤0.5 cm and >0.5 cm groups (p = .282). However, among the patients with liver metastases, the incidence of gallbladder-related complications in the ≤0.5 cm group was significantly higher than that in the >0.5 cm group (p = .025). The overall incidence of complications was significantly higher in the ≤0.5 cm group than in the >0.5 cm group (p = .020). Among the patients with lesions ≤3 cm, the technical effectiveness rate in the HCC group was significantly higher than in the liver metastasis group (p = .036).Conclusion RFA is a safe and effective treatment option for liver tumors adjacent to the gallbladder. Patients with lesions ≤0.5 cm from the gallbladder had higher gallbladder-related complications, especially patients with liver metastases. Among patients with lesions ≤3 cm, RFA showed greater technical effectiveness for treating HCC than for treating liver metastases.

ABSTRACT5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, negatively regulates type I interferon responses during various viral infections, including SARS-CoV-2. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 enhanced type I interferon and downstream ISGs during various viral infection in vitro. And in vivo, the antiviral innate response is more dramatically enhanced in Nsun2+/− mice than in Nsun2+/+ mice. The highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation enhanced cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), or Zika virus (ZIKV) resulted in a reduction of endogenous NSUN2 levels. Especially, SARS-CoV-2 infection (WT strain and BA.1 omicron variant) also decreased endogenous levels of NSUN2 in COVID-19 patients and K18-hACE2 KI mice, further increasing type I interferon and downstream ISGs. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease during SARS-CoV-2 and various viral infections to boost antiviral responses for effective elimination of viruses.

As urbanization accelerates, a growing influx of pollutants enters the sea through land runoff, posing a threat to coastal ecosystems. In this study, we systematically determined the concentrations of nutrients and heavy metals in the water and sediments of coastal areas (Yantai, China) and assessed their sources and ecological risks. The results showed that inland rivers transported large amounts of NO3− and PO43− into coast water, which caused severe eutrophication. Regarding heavy metals, copper dominated in seawater, whereas plumbum and arsenic were dominant in sediment, which was sourced from aerosol deposition and mariculture. Zinc, chromium, copper, mercury, and cadmium contributed slightly to pollution, with low enrichment factors, mainly from natural sources. Further analysis showed that zinc, mercury, copper, and arsenic were significantly affected by the grain size composition in sediment. Ecological risk assessment indicated that the coastal zone of Yantai City is in a state of light heavy-metal pollution.

A two-year field trial was conducted to investigate the effects of partial substitution of chemical fertilizer (CF) by Trichoderma biofertilizer (TF) on nitrogen (N) use efficiency and associated mechanisms in wolfberry (Lycium chinense) in coastal saline land. As with plant biomass and fruit yield, apparent N use efficiency and plant N accumulation were also higher with TF plus 75% CF than 100% CF, indicating that TF substitution promoted plant growth and N uptake. As a reason, TF substitution stabilized soil N supply by mitigating steep deceases in soil NH4+-N and NO3–N concentrations in the second half of growing seasons. TF substitution also increased carbon (C) fixation according to higher photosynthetic rate (Pn) and stable 13C abundance with TF plus 75% CF than 100% CF. Importantly, leaf N accumulation significantly and positively related with Pn, biomass, and fruit yield, and structural equation modeling also confirmed the importance of the causal relation of N accumulation coupled with C fixation for biomass and yield formation. Consequently, physiological and agronomical N use efficiencies were significantly higher with TF plus 75% CF than 100% CF. Overall, partial substitution of CF by TF improved N use efficiency in wolfberry in coastal saline land by stabilizing soil N supply and coupling N accumulation with C fixation.

Abstract In the coming decades, coastal flooding will become more frequent due to sea‐level rise and potential changes in storms. To produce global storm surge projections from 1950 to 2050, we force the Global Tide and Surge Model with a ∼25‐km resolution climate model ensemble from the Coupled Model Intercomparison Project Phase 6 High Resolution Model Intercomparison Project (HighResMIP). This is the first time that such a high‐resolution ensemble is used to assess changes in future storm surges across the globe. We validate the present epoch (1985–2014) against the ERA5 climate reanalysis, which shows a good overall agreement. However, there is a clear spatial bias with generally a positive bias in coastal areas along semi‐enclosed seas and negative bias in equatorial regions. Comparing the future epoch (2021–2050) against the historical epoch (1951–1980), we project ensemble‐median changes up to 0.1 (or 20%) in the 1 in 10‐year storm surge levels. These changes are not uniform across the globe with decreases along the coast of Mediterranean and northern Africa and southern Australia and increases along the south coast of Australia and Alaska. There are also increases along (parts) of the coasts of northern Caribbean, eastern Africa, China and the Korean peninsula, but with less agreement among the HighResMIP ensemble. Information resulting from this study can be used to inform broad‐scale assessment of coastal impacts under future climate change.

Introduction: Lung adenocarcinoma (LUAD) is the most prevalent lung cancer. LUAD presents as ground glass nodules (GGN) and solid nodules (SN) in imaging studies. GGN is an early type of LUAD with good prognosis. However, SN exhibits a more malignant behavior than GGN, including worse pathological staging and tumor prognosis. The mechanism leading to the different malignancy levels of GGN and SN remains elusive.Methods: Three patients with GGN and three patients with SN diagnosed with early LUAD were enrolled. The tumor samples were digested to a single-cell suspension and analyzed using 10× Genomic Single-cell ribonucleic acid sequences (scRNA-seq) techniques.Results: A total of 15,902 cells were obtained and classified into nine major types. The tumor microenvironment (TME) was subsequently described in detail. ScRNA-seq revealed that ribosome-related pathways and cell adhesion played similar but distinct roles in the two groups. SN also had more active cell proliferation, enriched cell cycle regulatory pathways, and severe inflammatory responses.Conclusion: We observed changes in the cellular composition and transcriptomic profile of GGN and SN. The study improved the understanding of the underlying mechanisms of lung carcinogenesis and contributed to lung cancer prevention and treatment.

Objective To analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for pancreatic adenocarcinoma liver metastasis (PALM).Methods Between January 2010 and July 2021, 20 patients (13 males) with an average age of 58.9 ± 11.7 years who underwent RFA for PALM were included. The mean maximum diameter of PALMs was 2.6 ± 1.1 cm (1.0–6.0 cm). Survival curves were built using the Kaplan-Meier method and compared by the log-rank test. Multivariable analyses were performed by using the Cox proportional hazards model.Results Twenty patients with 29 PALMs underwent 23 RFA sessions. Technical efficacy was achieved in 28 PALMs (28/29, 96.6%). The mean overall survival (OS) after RFA was 14.6 months and the 1-, 2-year survival rates were 39.5%, 18.1%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.023) and extrahepatic metastasis before RFA (p = 0.038) were identified as independent prognostic factors for OS in patients with PALM. Additionally, the mean progression-free survival (PFS) after RFA was 11.5 months and 1-, 2- year survival rates were 26.0%, 17.3%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.016) and extrahepatic metastasis before RFA (p = 0.043) were also identified as independent prognostic factors for PFS in patients with PALM.Conclusion RFA is a safe and effective treatment for patients with PALM, especially in patients with normal serum level of CA199 or the patients without extrahepatic metastases before RFA.

Abstract Objective To compare the clinical efficacy of lumbar endoscopic Delta large channel and microscopic tubular Quadrant channel unilateral laminotomy with bilateral decompression in the treatment of elderly patients with lumbar spinal stenosis. Methods A total of 40 patients aged above 75 years with lumbar spinal stenosis admitted from June 2019 to August 2021 were reviewed, in which the observation group was treated with the Delta large channel technique and the control group was treated with Quadrant channel open decompression. The general data, duration of illness, operation time, intraoperative bleeding, VAS score preoperatively, 3 days postoperatively, 3 months postoperatively and 6 months postoperatively, and ODI index of the two groups were recorded in the two groups. Results The observation group had significantly shorter operation time (59.93 ± 10.46 min vs 77.66 ± 12.44 min, P 0.05). The ODI index 3 days postoperatively in the observation group was significantly lower than that in the control group (0.33 ± 0.06 vs 0.37 ± 0.05, P = 0.022). Conclusion Both surgical methods had good clinical outcomes for the treatment of lumbar spinal stenosis. However, Delta large channel endoscopy had a clearer vision, less trauma and lower incidence of early postoperative back pain than that of Quadrant channel open decompression.

BackgroundDisordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP.MethodIn a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two.ResultsAfter three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group (P < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella_9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin.ConclusionThis study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM.

Unlike electrons, phonons do not have the charge and spin degrees of freedom. Consequently, it is a big challenge for the control of phonon currents and the design of quantum phonon devices due to the lack of versatile degrees of freedom. In this work, we show that phonon bands of mirror-symmetric materials can be labeled by parities, which can act as a pseudospin of phonons. As a proof-of-concept, we show that perfect pseudospin filtering can be realized using mirror-symmetric graphene-nanoribbon heterojunctions. In addition, we show that the filtering takes place within a remarkably short length scale of just 3 nanometers. Our work reveals an intriguing new facet of phonon behavior and also underscores the immense potential of utilizing phonons as information carriers.

Fu et al. identify the highly conserved, transmembrane micropeptide, NEMEP, as a direct target of Nodal signaling, essential for mesendoderm differentiation. NEMEP interacts with the glucose transporters GLUT1/GLUT3 and promotes glucose uptake.

Abstract Background Direct and indirect effects of radiofrequency ablation (RFA) on tumor microenvironment of the liver tumor have been noted, which was reported to be related to a variety of tyrosine protein kinase or cytokinetic pathway, but have not been thoroughly investigated and conclusive. Purpose To elucidate direct and indirect effects of RFA on tumor microenvironment in the liver tumor model, and to explore the role of the specific inhibitor in tumor growth by targeting the key pathway of RFA. Materials and methods One hundred and ten mice with H22 liver tumor were used in animal experiments. Eighty-four mice were randomized into three groups: control, direct RFA and indirect RFA (a block slide was inside the middle of the tumor). The growth rate of the residual tumor after RFA was calculated (n = 8 each group) and the pathologic changes at different time points (6 h, 24 h, 72 h and 7d after RFA) were evaluated (n = 5 in each subgroup). After semi-quantitative analysis of the pathological staining, the most significant marker after RFA was selected. Then, the specific inhibitor (PHA) was applied with RFA and the tumor growth and pathological changes were evaluated and compared with RFA alone. The Kruskal-Wallis test was used for evaluating the significance of different treatments in the pathological positive rate of specific markers in tumor. The two-way analysis of variance was used to determine the significance of treatment in tumor growth or body weight. Results The growth rate of the residual tumor in the direct RFA group was faster than the indirect RFA group (P = 0.026). The pathological analysis showed the expression of HSP70 (73 ± 13% vs 27 ± 9% at 24 h, P

Tomato, as a typical greenhouse crop, is commonly first planted as seedlings in a variety of substrates before being transplanted into soil. However, there is rare research on the characteristics of the bacterial community in tomato roots under this planting mode. In this study, tomatoes were planted in pots containing three different cultivation media, including soil and two types of substrates in a greenhouse, followed by a transplanting treatment. After collecting tomato root samples, high-throughput sequencing and bioinformatic analysis were used to compare the differences in bacterial diversity and functions between tomato roots before and after transplanting in different cultivation media. In total, 702776 sequences were obtained, and the OTUs were belonging to 109 genera, 58 families, 41 orders, 14 classes, and 12 phyla. Among the three cultivation media, the β-diversity was significant, and there was a slight difference in bacterial species diversity along with a large difference in their abundance at the genus level. Soil and both substrates had 79 bacterial genera in common, these genera accounted for 68.70%, 76.70%, and 71.17% of the total genera found in the soil, substrate 1, and substrate 2, respectively. After being transplanted from the two substrates to the soil, the bacterial community structure and abundance exhibited similarities with those found in the soil. Furthermore, based on microbial function prediction, the microbial communities in the two-substrate environment demonstrated a greater potential for promoting growth, while the microbial communities in the soil exhibited a greater tendency to exert their antibacterial potential. Our findings offer theoretical support for the creation of artificially reconstructed microbial communities in greenhouse cultivation.

Studies of resting-state functional connectivity (rsFC) have provided rich insights into the structures and functions of the human brain. However, most rsFC studies have focused on large-scale brain connectivity. To explore rsFC at a finer scale, we used intrinsic signal optical imaging to image the ongoing activity of the anesthetized macaque visual cortex. Differential signals from functional domains were used to quantify network-specific fluctuations. In 30–60 min resting-state imaging, a series of coherent activation patterns were observed in all three visual areas we examined (V1, V2, and V4). These patterns matched the known functional maps (ocular dominance, orientation, color) obtained in visual stimulation conditions. These functional connectivity (FC) networks fluctuated independently over time and exhibited similar temporal characteristics. Coherent fluctuations, however, were observed from orientation FC networks in different areas and even across two hemispheres. Thus, FC in the macaque visual cortex was fully mapped both on a fine scale and over a long range. Hemodynamic signals can be used to explore mesoscale rsFC in a submillimeter resolution.

Abstract Background The QX-type infectious bronchitis virus (IBV) has become the predominant genotype worldwide in recent years and has caused serious economic losses to the chicken industry. The most significant feature of QX IBV is that its infection in the early growing stage can cause abnormal oviduct development, resulting in a high proportion of ‘false layers’ in poultry flocks of laying hens and breeders. However, few studies have evaluated whether infections of QX-type IBV in laying stages can also cause severe pathological changes in the oviduct. Methods In this study, 300-day-old specific-pathogen-free chickens were infected either with the QX-type strain QXL or Massachusetts (Mass)-type strain M41 to compare their pathogenicity on different segments of the oviduct. Results Both the QXL and M41 strains successfully replicated in all segments of the oviduct; however, the QXL strain was more highly distributed in mucosal layer and caused severe lesions in the lamina propria, including interstitial dilation, inflammatory cell infiltration, and distinct expansion of tubular glands. Moreover, the QXL strain induced high expression of proinflammatory cytokines and cytotoxic molecules in the majority of segments in the oviduct. Further research found that the QXL strain may affected the formation of shell membranes and eggshells by inhibiting the expression of type I collagen and CaBP-D28k. Conclusions Our results indicate that the QX-type IBV is more pathogenic than Mass-type IBV to oviduct in laying phase. Collectively, these findings provide detailed information on the pathological changes in different segments of the oviduct in laying phase, which could offer a better understanding about the pathogenicity of IBV.

Aerosol insecticides are widely used in stored product insect management programs in food facilities. Previous research has shown spatial variation in aerosol efficacy within facilities, but information on how spatial patterns of aerosol droplet concentration, size distribution, dispersal, and deposition contribute to this variation in efficacy is limited. This study involved two aerosol application systems: a high-pressure cylinder containing TurboCide Py-75® with pyriproxyfen IGR (ChemTech Ltd., Des Moines, IA, USA) and a hand-held fogger containing Pyrocide 100® (MGK, Minneapolis, MN, USA) with Diacon II which contains methoprene IGR (Wellmark, Schaumburg, IL, USA). These systems were used at single or multiple application locations. The spray trials were conducted in a small-scale flour mill, Hall Ross Flour Mill (Kansas State University, Manhattan, KS, USA). The droplet size distributions were monitored at multiple positions within the room using nine aerodynamic particle sizing (APS, TSI Incorp, Shoreview, MN, USA) instruments. The APS data collected over the treatment period were summarized into a mass concentration index (MCI), which ranged from 155 to 2549 mg/m3 for Turbocide and 235–5658 mg/m3 for Pyrocide. A second parameter called the Deposition Index (Dep.Idx) was derived to estimate potential insecticide depositions on the floor and has units of g/m2. The Dep.Idx was below 5.3 g/m2 for most Turbocide applications, while the Dep.Idx was below 8.4 g/m2 for most Pyrocide applications. The MCI and Dep.Idx values varied with APS position and spray application location, with proximity to the aerosol application location and degree of obstruction between the release point and APS position contributing to this variation. We assessed the relationship between aerosol droplet parameters and insect efficacy using Tribolium confusum Jacqueline DuVal, the confused flour beetle. The adults were treated directly, while the larvae were treated two weeks later during the residual test (previously published). For Turbocide, efficacy against adults increased with MCI and Dep.Idx values, but for residual efficacy of the IGR, efficacy was high at all aerosol droplet values, so no relationship was apparent. In contrast, the relationship between Pyrocide deposition and adult insect efficacy was highly variable. But with larval insect efficacy, residual larvae control was directly related to increases in Pyrocide MCI and Dep.Idx. Contour plots of Dep.Idx values were developed, which could be used to predict areas of the mill that are not receiving an adequate application rate, and this could be used to develop more effective application strategies for aerosol insecticides in food facilities.

Taking a certain coastal area of Jiangsu province as the research background, this study scientifically predicts the runoff on the medium and long-term time scale according to the changes of various climate factors such as atmospheric circulation, sea surface temperature, and solar activity in the first half of the year. A lag correlation is established between various related climate factors and the monthly runoff process in the research area for the previous 1–6 months. Selecting advantageous factors and constructing a significant factor set. Using the improved BP (Back-Propagation) artificial neural network model and combining it with the sensitivity analysis method, a specific number of 8-factor combinations are selected from the set of significant factors for medium and long-term runoff prediction. After that, the prediction results are compared with the forecasting effects of two multi-factor combination runoff simulation schemes formed by stepwise regression and Spearman rank correlation methods. The study concluded that the multi-factor combination simulation effect formed through sensitivity analysis was the best. The 20% standard forecast qualification rate of the three schemes is not significantly different. The Mean Absolute Relative Error of the multi-factor combination training and validation periods simulated through sensitivity analysis is the smallest among the three schemes, which are 36.61% and 38.01%, respectively. The Nash Efficiency Coefficient in the validation period is 0.45, which is far better than other schemes and has better generalization ability. The Standard Deviation of Relative Error in the training and validation periods is much smaller than other schemes, and the dispersion of relative errors is the smallest.

ABSTRACT: Aims: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. Methods: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. Results: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25–34 years (87.50%). Conclusions: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

Abstract Cardiac damage in non-severe patients with coronavirus disease 2019 (COVID-19) is poorly explored. This study aimed to explore the manifestations of cardiac damage at presentation in non-severe patients with COVID-19. In this study, 113 non-severe patients with COVID-19 were grouped according to the duration from symptoms onset to hospital admission: group 1 (≤ 1 week, n = 27), group 2 (> 1 to 2 weeks, n = 28), group 3 (> 2 to 3 weeks, n = 27), group 4 (> 3 weeks, n = 31). Clinical, cardiovascular, and radiological data on hospital admission were compared across the four groups. The level of high sensitivity troponin I (hs-cTnI) in group 2 [10.25 (IQR 6.75–15.63) ng/L] was significantly higher than those in group 1 [1.90 (IQR 1.90–8.80) ng/L] and group 4 [1.90 (IQR 1.90–5.80) ng/L] (all P bonferroni

Semantic segmentation of remote sensing images is increasingly important in urban planning, autonomous driving, disaster monitoring, and land cover classification. With the development of high-resolution remote sensing satellite technology, multilevel, large-scale, and high-precision segmentation has become the focus of current research. High-resolution remote sensing images have high intraclass diversity and low interclass separability, which pose challenges to the precision of the detailed representation of multiscale information. In this paper, a semantic segmentation method for remote sensing images based on Swin Transformer fusion with a Gabor filter is proposed. First, a Swin Transformer is used as the backbone network to extract image information at different levels. Then, the texture and edge features of the input image are extracted with a Gabor filter, and the multilevel features are merged by introducing a feature aggregation module (FAM) and an attentional embedding module (AEM). Finally, the segmentation result is optimized with the fully connected conditional random field (FC-CRF). Our proposed method, called Swin-S-GF, its mean Intersection over Union (mIoU) scored 80.14%, 66.50%, and 70.61% on the large-scale classification set, the fine land-cover classification set, and the “AI + Remote Sensing imaging dataset” (AI+RS dataset), respectively. Compared with DeepLabV3, mIoU increased by 0.67%, 3.43%, and 3.80%, respectively. Therefore, we believe that this model provides a good tool for the semantic segmentation of high-precision remote sensing images.

The increasing abundance of fine particulate matter (PM2.5) in the environment has increased susceptibility to acute exacerbation of COPD (AECOPD). During PM2.5 exposure, excessive reactive oxygen species (ROS) production triggers a redox imbalance, which contributes to damage to organelles and disruption of homeostasis. At present, there are limited data on whether NOX4/Nrf2 redox imbalance increases susceptibility to acute exacerbation of COPD (AECOPD), and the underlying mechanism is unclear. Therefore, the current study was aimed to evaluate the role of NOX4/Nrf2 redox balance on AECOPD induced by PM2.5-CS-exposure. Here, we report that PM2.5 exacerbates cytotoxicity by enhancing NOX4/Nrf2 redox imbalance-mediated mitophagy. First, exposure to a low-dose of PM2.5 (200 μg/ml) significantly exacerbated oxidative stress and mitochondrial damage by increasing the ROS overproduction, enhancing the excessive NOX4/Nrf2 redox imbalance, decreasing the mitochondrial membrane potential (MMP), and enhancing the mitochondrial fragmentation that were caused by a low-dose of CSE (2.5%). Second, coexposure to PM2.5 and CSE (PM2.5-CSE) induced excessive mitophagy. Third, PM2.5 exacerbated CS-induced COPD, as shown by excessive inflammatory cell infiltration, inflammatory cytokine production and mucus hypersecretion, goblet cell hyperplasia, NOX4/Nrf2 redox imbalance, and mitophagy, these effects triggered excessive ROS production and mitochondrial damage in mice. Mechanistically, PM2.5-CS-induced excessive levels of mitophagy by triggering redox imbalance, leading to greater cytotoxicity and AECOPD; however, reestablishing the NOX4/Nrf2 redox balance via NOX4 blockade or mitochondria-specific ROS inhibitor treatment alleviated this cytotoxicity and ameliorated AECOPD. PM2.5 may exacerbate NOX4/Nrf2 redox imbalance and subsequently enhance mitophagy by increasing the ROS and mito-ROS levels, thereby increasing susceptibility to AECOPD.

Background. Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods. The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results. Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions. Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.