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Abstract Background Pancreatitis is a digestive system disease that imposes a significant burden on society. However, there is a lack of comprehensive research on the incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of pancreatitis, as well as on health inequalities and future trends. Methods Pancreatitis burden data, including the number and age-standardized rates (ASR) of incidence, prevalence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs), were collected from the Global Burden of Diseases 2019 (GBD 2019). SDI and HDI were used to analyze the influence of societal development on the burden of pancreatitis in the population. Additionally, the Gini coefficient and the Concentration index were used to assess health inequalities in the burden of pancreatitis. Global population data from 1990 to 2034 was obtained from WHO. Based on the population data and pancreatitis burden data, a prediction model of the burden was constructed to calculate the number and ASR of incidence, prevalence, deaths, YLLs, YLDs, and DALYs from 2019 to 2034 using the BAPC package and the Nordpred package. Results From 1990 to 2019, there has been a decreasing trend in the ASR of incidence, prevalence, deaths, YLLs, YLDs, and DALYs in pancreatitis. However, despite this decline, the number of cases has been on the rise. Furthermore, pancreatitis imposes a higher burden on males in comparison to females, and there exists a negative correlation between pancreatitis burden and both the Social Development Index (SDI) and the Human Development Index (HDI). Additionally, health inequalities have progressively worsened globally between 1990 and 2019, particularly concerning the burden of pancreatitis in countries with low Social Development Index (SDI). Looking to the future, it is projected that the number of deaths and new cases will continue to increase from 2020 to 2034. Conclusions Pancreatitis remains a mounting worldwide burden. In order to alleviate this challenge, preventive strategies should focus on males and middle-aged or older individuals, specifically in countries with a low SDI. Pancreatitis is expected to predominantly impact Eastern Europe, characterized by a high ASR of incidence, and Asia, boasting a substantial population.

Abstract The tripartite motif (TRIM) protein family has been shown to play important roles in the occurrence and development of various tumors. However, the biological functions of TRIM47 and its regulatory mechanism in hepatocellular carcinoma (HCC) remain unexplored. Here, we showed that TRIM47 was upregulated in HCC tissues compared with adjacent normal tissues, especially at advanced stages, and associated with poor prognosis in HCC patients. Functional studies demonstrated that TRIM47 enhanced the migration and invasion ability of HCC cells in vitro and in vivo. Mechanistically, TRIM47 promotes HCC metastasis through interacting with SNAI1 and inhibiting its degradation by proteasome. Moreover, TRIM47 was di-methylated by CARM1 at its arginine 210 (R210) and arginine 582 (R582), which protected TRIM47 from the ubiquitination and degradation mediated by E3 ubiquitin ligase complex CRL4CRBN. Collectively, our study reveals a pro-metastasis role of TRIM47 in HCC, unveils a unique mechanism controlling TRIM47 stability by CARM1 mediated arginine methylation, and highlights the role of the CARM1-CRL4CRBN-TRIM47-SNAI1 axis in HCC metastasis. This work may provide potential therapeutic targets for metastatic HCC treatment.

Abstract Transposable elements (TEs) are crucial for genetic diversity and gene regulation. Current single-cell quantification methods often align multi-mapping reads to either ‘best-mapped’ or ‘random-mapped’ locations and categorize them at the subfamily levels, overlooking the biological necessity for accurate, locus-specific TE quantification. Moreover, these existing methods are primarily designed for and focused on transcriptomics data, which restricts their adaptability to single-cell data of other modalities. To address these challenges, here we introduce MATES, a deep-learning approach that accurately allocates multi-mapping reads to specific loci of TEs, utilizing context from adjacent read alignments flanking the TE locus. When applied to diverse single-cell omics datasets, MATES shows improved performance over existing methods, enhancing the accuracy of TE quantification and aiding in the identification of marker TEs for identified cell populations. This development facilitates the exploration of single-cell heterogeneity and gene regulation through the lens of TEs, offering an effective transposon quantification tool for the single-cell genomics community.

Reaumuria trigyna, a wild and endangered salt-secreting small shrub, is distributed in arid and semi-arid areas of Inner Mongolia, China. An H+-pyrophosphatase gene (RtVP1) was isolated from R. trigyna according to transcriptomic data, which encoded a plasma membrane and tonoplast-localized protein. RtVP1 was quickly upregulated by NaCl and exogenous abscisic acid treatment and rescued the sucrose deficiency sensitive phenotype of the AtVP1 mutant (avp1). Transgenic Arabidopsis overexpressing RtVP1 exhibited a higher leaf area, plant height, fresh weight, root length, and soluble carbohydrate accumulation compared to the wild type (WT) under normal conditions. RtVP1 overexpression increased the seed germination rate and decreased the reduction rate of fresh weight, root length, and chlorophyll content in transgenic plants under salt stress. Catalase enzyme activity, proline content, relative water content, and soluble sugar content were significantly increased in transgenic Arabidopsis under salt stresses, but the malondialdehyde content was dramatically decreased. More K+ and less Na+ were accumulated in transgenic Arabidopsis leaves, resulting in a relatively lower Na+/K+ ratio. In transgenic Arabidopsis roots, K+ was unchanged, but Na+ and the Na+/K+ ratios were reduced compared to those in WT. More Na+ and K+ were accumulated in the intracellular of transgenic yeast, and the Na+/K+ ratio was significantly reduced compared to the control. These results showed that R. trigyna RtVP1 promotes the vegetative growth of plants, mainly by regulating carbohydrate metabolism, and confers salt tolerance in transgenic Arabidopsis by maintaining Na+/K+ homeostasis and enhancing the antioxidant and osmotic regulatory capacity. These results indicated that RtVP1 can serve as an important candidate gene for genetic improvement of crop yield and salt tolerance.

Although rare earth zirconates (RE2Zr2O7) have garnered attention as viable candidates for thermal barrier coatings (TBCs), they suffer from low fracture toughness and accelerated calcium–magnesium–alumina–silicate (CMAS) melt corrosion at high service temperatures, which impedes their practical application. In this work, we developed a series of REAlO3/RE2Zr2O7 (RE = La, Nd, Sm, Eu, Gd, and Dy) composites with a eutectic composition that not only significantly enhanced the fracture toughness by more than 40% relative to that of RE2Zr2O7 but also exhibited improved resistance to CMAS corrosion. The increase in toughness arises from multiple mechanisms, such as ferroelastic toughening, fine-grain strengthening, and residual stress toughening, all of which trigger more crack defects and energy consumption. Additionally, the CMAS penetration depth of the REAlO3/RE2Zr2O7 composites is approximately 36% lower than that of RE2Zr2O7. Al–O constituents in composites can capture CaO, SiO2, and MgO in CMAS melts and increase their viscosity, resulting in enhanced CMAS corrosion resistance. The thermophysical properties of the REAlO3/RE2Zr2O7 composites were also investigated, and their coefficient of thermal expansion and thermal conductivity are comparable to those of 7–8 wt %Y2O3 partially stabilized ZrO2 (YSZ), indicating their potential as TBC materials.

PurposeThis study aimed to compare anterior segment parameters pre-and postoperatively in acute primary angle closure (APAC) and fellow primary angle closure suspect (PACS) eyes using anterior segment optical coherence tomography (AS-OCT) and evaluate the clinical effectiveness of cataract extraction in the treatment of APAC and fellow PACS eyes.MethodsQuantitative measurements of various parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV), lens vault (LV), iridocorneal angle contact index (ITCI), iris thickness (IT), iris volume (IV), and iris curvature (IC), were obtained using Tomey CASIA2 AS-OCT on 60 eyes from 30 patients (APAC eyes and their fellow PACS eyes) before and after surgery. Simultaneous analysis of the differences between the APAC eyes and fellow PACS eyes in these parameters, visual acuity (VA), and intraocular pressure (IOP) were performed.ResultsAfter surgery, both the APAC eyes and fellow PACS eyes (a total of 60 eyes) showed a significant increase in ACD and ACV, compared to preoperative measurements. Furthermore, LV and ITCI significantly decreased postoperatively. In the PACS group, IC significantly decreased postoperatively, while there was no statistically significant difference in the APAC group. In the APAC group, there was a significant decrease in IOP and improvement in VA at 1 day, 1 week, and the final follow-up compared to preoperative levels. The IOP values in the PACS group were within the normal range across various time points. VA in the PACS group showed significant improvement at 1 week postoperatively and at the final follow-up compared to preoperative levels. Significant differences of VA were observed in the initial, preoperative, first postoperative day, first postoperative week, and final follow-up, with better outcomes observed in the PACS group compared to the APAC group.ConclusionLens extraction surgery can significantly improve anterior segment crowding in APAC and PACS eyes. For APAC eyes, combined cataract extraction with intraocular lens implantation and gonioscopy-assisted goniosynechialysis under direct visualization is feasible and safe. Further, in the fellow PACS eye of APAC patients with either significant or mild cataracts, phacoemulsification can maintain or improve preoperative visual acuity to varying degrees and stabilize IOP.

Abstract Crustal deformation and hydrothermal percolation related to the India‐Asia collision have caused extensive remagnetization of the Tethyan Himalaya Terrane (THT). The present work identified three phases of regional remagnetization during 62.3–50.0 Ma for the east‐central THT. Consequently, a model of three‐stage India‐Asia collision was proposed. The east‐central THT first collided with the southward migrated southern margin of the Lhasa Terrane (LT) at 5.4 ± 0.9°N during 62.3–60.9 Ma. Subsequently, the THT continuously moved northward and pushed the southern margin of the LT back to its original position prior to the initiation of fore‐arc and back‐arc extension on both sides of the Gangdese magmatic arc. Since the final suturing of the THT with Asia at ∼10°N during 59.8–58.0 Ma, the east‐central THT remained stationary until India collided with it at 10.9 ± 5.1°N at ∼50.0 Ma.

Abstract AURKA is an established target for cancer therapy; however, the efficacy of its inhibitors in clinical trials is hindered by differential response rates across different tumor subtypes. In this study, we demonstrate AURKA regulates amino acid synthesis, rendering it a vulnerable target in KEAP1-deficient non-small cell lung cancer (NSCLC). Through CRISPR metabolic screens, we identified that KEAP1-knockdown cells showed the highest sensitivity to the AURKA inhibitor MLN8237. Subsequent investigations confirmed that KEAP1 deficiency heightens the susceptibility of NSCLC cells to AURKA inhibition both in vitro and in vivo, with the response depending on NRF2 activation. Mechanistically, AURKA interacts with the eIF2α kinase GCN2 and maintains its phosphorylation to regulate eIF2α-ATF4-mediated amino acid biosynthesis. AURKA inhibition restrains the expression of asparagine synthetase (ASNS), making KEAP1-deficient NSCLC cells vulnerable to AURKA inhibitors, in which ASNS is highly expressed. Our study unveils the pivotal role of AURKA in amino acid metabolism and identifies a specific metabolic indication for AURKA inhibitors. These findings also provide a novel clinical therapeutic target for KEAP1-mutant/deficient NSCLC, which is characterized by resistance to radiotherapy, chemotherapy, and targeted therapy.

Abstract Flatbands play an important role in correlated quantum matter and have promising applications in photonic lattices. Synthetic magnetic fields and destructive interference in lattices are traditionally used to obtain flatbands. However, such methods can only obtain a few flatbands with most bands remaining dispersive. Here we realize all-band-flat photonic lattices of an arbitrary size by precisely controlling the coupling strengths between lattice sites to mimic those in Fock-state lattices. This allows us to go beyond the perturbative regime of strain engineering and group all eigenmodes in flatbands, which simultaneously achieves high band flatness and large usable bandwidth. We map out the distribution of each flatband in the lattices and selectively excite the eigenmodes with different chiralities. Our method paves a way in controlling band structure and topology of photonic lattices.

One of the key technologies for achieving day and night flight, tracking solar peak, and reducing flight energy consumption for a near-space solar-powered unmanned aerial vehicle (UAV) is trajectory planning. However, the environmental differences faced by the near-space solar-powered UAV during long-term flight pose challenges to its online trajectory planning. This article introduces a hierarchical guidance method designed using a hierarchical reinforcement learning algorithm, which includes a two-layer neural network structure of bottom-level trajectory planning models and a top-level decision model. The top-level decision maker selects the appropriate bottom-level planner based on flight and current environmental information, while the planner outputs thrust, attack angle, and bank angle commands based on the input information. This hierarchical guidance structure can improve the UAV’s adaptability to energy environment variations and realize an autonomous flight based on energy maximization in long-term missions. Flight simulations spanning spring, summer and autumn seasons show that the guidance controller is able to switch flight policies on its own as the environment changes, allowing the UAV to maximize energy gain on each day, thereby achieving the best energy management strategy in long-term flight. The simulation results also verify the over-fitting and under-fitting effects of the neural network in the solar UAV trajectory planning task, providing support for the necessity of hierarchical guidance.

Inland waterways, characterized by their complex, narrow paths, see significantly higher traffic volumes compared to maritime routes, increasing the regulatory demands on traffic management. Predictive modeling of ship traffic flows, utilizing real AIS historical data, enhances route and docking planning for ships and port managers. This approach boosts transportation efficiency and safety in inland waterway navigation. Nevertheless, AIS data are flawed, marred by noise, disjointed paths, anomalies, and inconsistent timing between points. This study introduces a data processing technique to refine AIS data, encompassing segmentation, outlier elimination, missing point interpolation, and uniform interval resampling, aiming to enhance trajectory analysis reliability. Utilizing this refined data processing approach on ship trajectory data yields independent, complete motion profiles with uniform timing. Leveraging the Transformer model, denoted TRFM, this research integrates processed AIS data from the Yangtze River to create a predictive dataset, validating the efficacy of our prediction methodology. A comparative analysis with advanced models such as LSTM and its variants demonstrates TRFM’s superior accuracy, showcasing lower errors in multiple metrics. TRFM’s alignment with actual trajectories underscores its potential for enhancing navigational planning. This validation not only underscores the method’s precision in forecasting ship movements but also its utility in risk management and decision-making, contributing significantly to the advancement in maritime traffic safety and efficiency.

Abstract The complex and contrasted distribution of terrestrial biota in Asia has been linked to active tectonics and dramatic climatic changes during the Neogene. However, the timings of the emergence of these distributional patterns and the underlying climatic and tectonic mechanisms remain disputed. Here, we apply a computational data analysis technique, called redescription mining, to track these spatiotemporal phenomena by studying the associations between the prevailing herbivore dental traits of mammalian communities and climatic conditions during the Neogene. Our results indicate that the modern latitudinal zoogeographic division emerged after the Middle Miocene climatic transition, and that the modern monsoonal zoogeographic pattern emerged during the late Late Miocene. Furthermore, the presence of a montane forest biodiversity hotspot in the Hengduan Mountains alongside Alpine fauna on the Tibetan Plateau suggests that the modern distribution patterns may have already existed since the Pliocene.

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a type of hematologic tumor with malignant proliferation of hematopoietic progenitor cells. However, traditional clinical treatment of T-ALL included chemotherapy and stem cell transplantation always lead to recurrence and poor prognosis, thus new therapeutic targets and drugs are urgently needed for T-ALL treatment. In this study, we showed that TET1 (ten-eleven translocation 1), a key participant of DNA epigenetic control, which catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to modulate gene expression, was highly upregulated in human T-ALL and negatively correlated with the prognosis of patients. Knockdown of TET1 suppressed T-ALL growth and progression, suggesting that TET1 inhibition maybe an effective way to fight T-ALL via DNA epigenetic modulation. Combining structure-guided virtual screening and cell-based high-throughput screening of FDA-approved drug library, we discovered that auranofin, a gold-containing compound, is a potent TET1 inhibitor. Auranofin inhibited the catalytic activity of TET1 through competitive binding to its substrates binding pocket and thus downregulated the genomic level of 5hmC marks and particularly epigenetically reprogramed the expression of oncogene c-Myc in T-ALL in TET1-dependent manner and resulted in suppression of T-ALL in vitro and in vivo. These results revealed that TET1 is a potential therapeutic target in human T-ALL and elucidated the mechanism that TET1 inhibitor auranofin suppressed T-ALL through the TET1/5hmC/c-Myc signaling pathway. Our work thus not only provided mechanism insights for T-ALL treatment, but also discovered potential small molecule therapeutics for T-ALL.

Abstract Background Triple-negative breast cancer (TNBC) is one of the most aggressive human cancers and has poor prognosis. Approximately 80% of TNBC cases belong to the molecular basal-like subtype, which can be exploited therapeutically by inducing differentiation. However, the strategies for inducing the differentiation of TNBC remain underexplored. Methods A three-dimensional (3D) morphological screening model based on a natural compound library was used to identify possible candidate compounds that can induce TNBC cell differentiation. The efficacy of rutaecarpine was verified using assays: RT-qPCR, RNA-seq, flow cytometry, immunofluorescence, SCENITH and label-free LC–MS/MS. The direct targets of rutaecarpine were identified through drug affinity responsive target stability (DARTS) assay. A xenograft mice model was also constructed to confirm the effect of rutaecarpine in vivo. Results We identified that rutaecarpine, an indolopyridoquinazolinone, induces luminal differentiation of basal TNBC cells in both 3D spheroids and in vivo mice models. Mechanistically, rutaecarpine treatment leads to global metabolic stress and elevated ROS in 3D cultured TNBC cells. Moreover, NAC, a scavenger of ROS, impedes rutaecarpine-induced differentiation of TNBC cells in 3D culture. Finally, we identified fumarate hydratase (FH) as the direct interacting target of rutaecarpine. The inhibition of FH and the knockdown of FH consistently induced the differentiation of TNBC cells in 3D culture. Conclusions Our results provide a platform for differentiation therapy drug discovery using 3D culture models and identify rutaecarpine as a potential compound for TNBC treatment.

[Introduction] Speeding up the offshore wind power construction and development is of great significance to promoting the adjustment of China's energy structure. China is accelerating the process of its wind power development in the entire offshore area, and the geological survey is a vital foundation and key technology of offshore wind power development. [Method] By studying the marine geological survey technologies at home and abroad and combining years of experience in different sea areas, this paper proposed a new technology of engineering geological modeling for offshore wind power development based on the principle of consistency. Firstly, the survey equipment selection and survey line layout started from a three-dimensional initial model to evaluate the impact of geological changes and geohazards on the offshore wind power engineering construction and took into full account the ship selection, field in situ and laboratory tests, and correlation of geophysical prospecting and geotechnical data. Then, with abundant and continuous data obtained from the boreholes and the whole wind farm during the feasibility study and detailed survey, the methods of combination of indoor geotechnical tests with the in-situ tests, the combination of multiple geophysical prospecting devices and the combination of geotechnical and geophysical prospecting methods were used to conduct a consistency analysis of various data, manage the geological survey data platform, update the model and build the final model, and the engineering geological model was continuously optimized and iterated in the subsequent stages. The engineering geological model provided comprehensive engineering geological information for the entire life cycle of offshore wind farm design, installation, operation, maintenance and decommissioning. [Result] The research results and offshore wind power geological survey examples show that by conducting consistent comprehensive layout and data analysis, effectively connecting geotechnical investigation with engineering geophysical prospecting and constructing a three-dimensional crossing engineering geological model, it can effectively solve the problem of "ambiguities of geological survey data" and improve the reliability, accuracy and application of geological survey data. [Conclusion] The new method proposed is one of the effective methods to reduce cost and increase efficiency in offshore engineering as well as the embryonic form of digital twin of offshore wind power geological survey and the foundation for the construction of a geological survey big data base.

Abstract Fourier domain optical coherence tomography (FD-OCT) is a well-established imaging technique that provides high-resolution internal structure images of an object at a fast speed. Modern FD-OCT systems typically operate at speeds of 40,000–100,000 A-scans/s, but are priced at least tens of thousands of pounds. In this study, we demonstrate a line-field FD-OCT (LF-FD-OCT) system that achieves an OCT imaging speed of 100,000 A-scan/s at a hardware cost of thousands of pounds. We demonstrate the potential of LF-FD-OCT for biomedical and industrial imaging applications such as corneas, 3D printed electronics, and printed circuit boards.

Background/purpose: Fibrosis is present in various physiologic and pathologic conditions of salivary glands (SGs). This study aimed to identify novel biomarkers of SG fibrosis by next-generation sequencing. Materials and methods: We established the SG fibrosis mouse model by excretory main duct ligation. Next-generation sequencing, differentially expressed gene (DEG) analysis, and gene set enrichment analysis was performed by comparing ligated and control SGs. We used algorithms of Cytohubba, molecular complex detection, Lasso logistic regression, and support vector machine to identify the key biomarkers. Selected key biomarkers were verified by the polymerase chain reaction and immunohistochemistry. We also retrieved and analyzed the key gene expression in the fibrosis of the heart, liver, lung, and kidney to ensure the generalization of key biomarkers in SG fibrosis. Results: Both interlobular and intralobular fibrosis was confirmed in the ligated SGs, with improved expressions of collagen I and transforming growth factor β. Next-generation sequencing identified 2666 upregulated DEGs and 336 downregulated DEGs, which were highly enriched in the extracellular matrix-related pathways. Multiple algorithms identified 15 key biomarkers in SG fibrosis, including Thrombospondin-1 (THBS1) and Prolyl 4-Hydroxylase Subunit Alpha 3 (P4HA3). The mRNA and protein expression of THBS1 and P4HA3 was verified in mice. THBS1 was also highly expressed in lung and kidney fibrosis, whereas P4HA3 was upregulated in liver fibrosis. Conclusion: THBS1 and P4HA3 may be potential biomarkers for SG fibrosis. They may be also applicable in the diagnosis of multi-organ fibrosis.

The microstructural features of a high-strength body-centered cubic Mg-Li–Al-Ag alloy are investigated and the strengthening mechanisms are discussed. The results show that obvious spinodal decomposition occurs in the alloy. Owing to the diffusion of Al atoms to Ag-vacancy pairs, co-clustering of Al and Ag is observed. The compositional redistribution of Li in the matrix reduces the interfacial lattice misfit and thus lowers the strain energy. Combinatorial spinodal strengthening with coherency strain hardening result in high strength achieved in the Mg-Li–Al-Ag alloy. The dual alloying strategy opens avenues for tuning the microstructure and enhancing mechanical properties of Mg-Li alloys.

The new-generation manned spacecraft employs a new recovery system of parachutes and airbags. In order to realize the effective cushion of the return capsule airbag, the conversion of the single-point hanging to the double points for the spacecraft is necessary. In the conversion process, the long hanging rope and the height of the return capsule will cause a large impact and disturbance to the cabin, but the traditional dynamic modeling method is not suitable for those with complex boundary conditions. In order to solve these problems, a finite element model is proposed to analyze the suspension conversion process and simplify the parachute model based on the aerodynamic load dynamic matching control method to analyze the dynamic response characteristics, such as overload, speed, and force of the cabin, quantifying the conditions of the rope in the process. Results are generally consistent with experimental data. This study provides guidance for future optimization work and will greatly support the safe-return technology of the new-generation manned spacecraft.

Objective. The aim of this study is to quantify anterior chamber parameters to provide potential risk indicators for evaluating the progression of primary angle-closure suspect (PACS) eyes to acute primary angle closure (APAC) and the degree of intraocular pressure elevation in patients with APAC utilizing anterior segment optical coherence tomography (AS-OCT). Methods. Tomey CASIA2 AS-OCT was used to quantitatively measure various anterior chamber parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV), lens thickness (LT), lens vault (LV), iris-trabecular contact index (ITC), iris thickness (IT), iris volume (IV), iris curvature (IC), iris area (IA), and iris thickness (IT), in APAC eyes (30 eyes) and contralateral PACS eyes (30 eyes) of 30 patients. The differences in these parameters between the two groups and their relationship with intraocular pressure were analyzed. Results. Compared to the PACS group, the APAC group exhibited significantly smaller IA and IC, and significantly larger pupil diameter (PD) and ITC (P

Photodynamic Therapy (PDT) holds a great promise for cancer patients, however, due to the hypoxic characteristics of most solid tumors and the limited penetration depth of light in tissues, the extensive clinical application of PDT is limited. Herein, we report microwave induced copper-cysteamine (Cu-Cy) nanoparticles-based PDT as a promising cancer treatment to overcome cancer resistance in combination with ferroptosis. The treatment efficiency of Cu-Cy-mediated microwave dynamic therapy (MWDT) tested on HCT15 colorectal cancer (CRC) cells via cell titer-blue cell viability assay and live/dead assay reveal that Cu-Cy upon MW irradiation can effectively destroy HCT15 CRC cells with average IC-50 values of 20 μg/mL. The cytotoxicity of Cu-Cy to tumor cells after MW stimulation can be alleviated by ferroptosis inhibitor. Furthermore, Cu-Cy mediated MWDT could deplete glutathione peroxide 4 (GPX4) and enhance lipid peroxides (LPO) and malondialdehyde (MDA). Our findings demonstrate that MW-activated Cu-Cy killed CRC cells by inducing ferroptosis. The superior in vivo antitumor efficacy of the Cu-Cy was corroborated by a HCT15 tumor-bearing mice model. Immunohistochemical experiments showed that the GPX4 expression level in Cu-Cy + MW group was significantly lower than that in other groups. Overall, these findings demonstrate that Cu-Cy nanoparticles have a safe and promising clinical application prospect in MWDT for deep-seated tumors and effectively inhibit tumor cell proliferation by inducing ferroptosis, which provides a potential solution for cancer resistance.

Background/purpose: Analysis of endoplasmic reticulum stress (ERS)-related long noncoding RNAs (LncRNAs) may enable prognostic stratification in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to comprehensively analyze the ERS-related LncRNAs signature and its effects on the prognosis, tumorigenesis, and tumor immune microenvironment in HNSCC. Materials and methods: The transcriptome data of HNSCC were obtained from TCGA. Least absolute shrinkage selection operator algorithm, and multivariate Cox regression were used to screen LncRNAs for the signature construction. Somatic mutation, gene enrichment, and immune infiltration analyses were further performed. Results: 458 ERS-related LncRNAs were identified and 55 of which were correlated with HNSCC prognosis. Ten ERS-related LncRNAs were selected to establish a risk prediction signature. When dividing patients into high-risk and low-risk groups by signature score, high-risk group correlated with worse survival rates (hazard ratio = 1.211; 95% confidence interval 1.123–1.306, P

During the overall design phase of solar-powered unmanned aerial vehicles (UAVs), a large amount of high-fidelity (HF) propeller aerodynamic performance data is required to enhance design performance, but the acquisition cost is prohibitively expensive. To improve model accuracy and reduce modeling costs, this paper constructs a multi-fidelity aerodynamic data fusion model by associating data with different fidelity. This model utilizes a low-fidelity computational method to quickly determine the design space. The constrained Latin hypercube sampling based on the successive local enumeration (SLE-CLHS) method and the expected improvement (EI) criterion were adopted to achieve the efficient initialization and fastest convergence of the Co-Kriging surrogate model within the design space. This modeling framework was applied to acquire the aerodynamic performance of high-altitude propellers, and the model was evaluated using various performance indicators. The results demonstrate that the proposed model has excellent predictive performance. Specifically, when the surrogate model was constructed using 350 high-fidelity samples, there were improvements of 13.727%, 12.241%, and 5.484% for thrust, torque, and efficiency compared with the surrogate model constructed from low-fidelity samples.

Abstract Growth strata are important for understanding regional tectonic evolution. However, it is difficult to identify growth strata in the field, because of subsequent intensive modification and erosion. To address this problem, we studied two paleomagnetic sections at the stable deposition setting and the growth end of the Miocene growth strata of the Gengma Basin. Average inclinations of the two sections show a systematic deviation of 4.7° ± 5.2°. The anisotropy of magnetic susceptibility results for the growth end of the section A demonstrate a sedimentary fabric. However, the tilt‐corrected K3 axis deviates to the southwest from the normal direction of the bedding by 5.4° ± 3.8°, the magnetic foliation deviates to the equatorial plane by 5.3° ± 4.7°. The K3 axis is perpendicular to the bedding at the stable deposition setting. The deviation of the K3 axis from the normal direction of bedding is interpreted as the growth angle, which can be used to correct the paleomagnetic inclination data.

We study the relation between bond characteristics and corporate bond returns in China's two distinct and segmented bond markets—the interbank market and the exchange market—with a large cross-sectional dataset of 8318 corporate bonds from January 2010 to December 2022. Corporate bonds with large sizes, long maturities, old ages, poor credit ratings and large Amihud illiquidity earn high monthly returns in the interbank market. The return predictive patterns of bond size, time to maturity, and credit rating are similar in the exchange market, but bond age and Amihud illiquidity predict returns in the opposite direction, implying market segmentation. We construct two factors based on credit rating and Amihud illiquidity to represent the common risk of corporate bonds—credit risk and liquidity risk—and use the Hansen-Jagannathan distance to evaluate the performances of factors in explaining the returns of corporate bond portfolios. We find that the two characteristic-based factors help reduce the model specification errors of the five factors in Fama and French (1993).

PurposeThis study aims to develop and validate a model predictive for the incidence of grade 4 radiation-induced lymphopenia (G4RIL), based on dosiomics features and radiomics features from the planning CT of nasopharyngeal carcinoma (NPC) treated by radiation therapy.MethodsThe dataset of 125 NPC patients treated with radiotherapy from August 2018 to March 2019 was randomly divided into two sets—an 85-sample training set and a 40-sample test set. Dosiomics features and radiomics features of the CT image within the skull bone and cervical vertebrae were extracted. A feature selection process of multiple steps was employed to identify the features that most accurately forecast the data and eliminate superfluous or insignificant ones. A support vector machine learning classifier with correction for imbalanced data was trained on the patient dataset for prediction of RIL (positive classifier for G4RIL, negative otherwise). The model’s predictive capability was gauged by gauging its sensitivity (the likelihood of a positive test being administered to patients with G4RIL) and specificity in the test set. The area beneath the ROC curve (AUC) was utilized to explore the association of characteristics with the occurrence of G4RIL.ResultsThree clinical features, three dosiomics features, and three radiomics features exhibited significant correlations with G4RIL. Those features were then used for model construction. The combination model, based on nine robust features, yielded the most impressive results with an ACC value of 0.88 in the test set, while the dosiomics model, with three dosiomics features, had an ACC value of 0.82, the radiomics model, with three radiomics features, had an ACC value of 0.82, and the clinical model, with its initial features, had an ACC value of 0.6 for prediction performance.ConclusionThe findings show that radiomics and dosiomics features are correlated with the G4RIL of NPC patients. The model incorporating radiomics features and dosiomics features from planning CT can predict the incidence of G4RIL in NPC patients.

Open domain response generation is the task of creating a response given a user query in any topics/domain. Limited by context and reference information, responses generated by current systems are often “bland” or generic. In this paper, we combine a response generation model with a retrieval system that searches for relevant utterances and responses. The generation model has two main components: a keyword extraction module and a two-stage transformer. The keyword extraction module aims to extract two types of keywords in an unsupervised fashion from the retrieved results: (1) keywords in the query not found in the retrieved utterances (DiffKey), and (2) overlapping keywords among the retrieved responses (SimKey). Given these keywords, the two-stage transformer first decides where to insert the keywords in the response, and the second generates the full response given the location of the keywords. The keyword extraction module and the two-stage transformer are connected in a single network, and so our system is trained end-to-end. Experimental results on Cornell Movie-Dialog corpus, Douban and Weibo demonstrate that our model outperforms state-of-the-art systems in terms of ROUGE, relevance scores and human evaluation.

According to the static aeroelastic characteristics of Solar-Powered UAV (SP-UAV) with large aspect ratio, this paper develops a nolinear aeroelastic analysis method which takes into account both the calculation accuracy and efficiency. Firstly, we establish the finite element model of the geometric nonlinear structure, which is verified by the static test of the whole UAV to reduce the calculation error caused by the simplified method of structure model. Then, the aerodynamic model of SP-UAV is established by using Curved Vortex Lattice (CVL), and the structure-aerodynamic coupling interpolation is realized by the Thin Plate Spline-interpolation (TPS) method, so as to complete the full static aeroelastic analysis. The analysis indicate that the calculated results of the longitudinal trim are well match the first flight condition. In particular, considering the elevator efficiency loss occurred in longitudinal trim analysis of the UAV, we design an optimization scheme to improve the efficiency of the elevator by about 15%. The simulation results show that the loss of elevator efficiency of flexible solar UAV with high aspect ratio is non-negligible, with the maximum value higher than 40% under high dynamic pressure. In actual flight, the speed of UAV must be reduced as much as possible to minimize the loss of rudder efficiency, while the elastic control method should be considered in flight control.

[Introduction] The current marine geological exploration, particularly the geotechnical investigation, often follows traditional experiences without a clear objective, and lacks the evaluations of soil sample disturbance and test results. Therefore, it is necessary to conduct in-depth research on marine geotechnical investigation technology. [Method] Based on the domestic and international research on marine geological exploration technology and multi-year working experience in different sea areas, we developed a new accurate marine geological exploration technology with emphasis on the principle of consistency. The geotechnical investigation part of the new method included two basic aspects: (1) comprehensive evaluation of soil sample disturbance; (2) comprehensive evaluation of consistency of soil strength test results. [Result] The three-dimensional cross-consistency analysis of geotechnical, geophysical, and geological models has established an accurate geological exploration system. Several examples of marine engineering projects showed that the new technology can screen good acquisition methods and data through comprehensive evaluation of clay soil sample disturbance, and conduct consistency analysis of various data by combining the laboratory geotechnical tests with in-situ tests and the routine geotechnical tests with advanced geotechnical tests to obtain richer and more continuous data at the borehole. Compared with the traditional single geotechnical test, our new technology demonstrated the improved reliability and accuracy of the data, and the missing data between the sampling points are compensated. [Conclusion] The proposed new method can reinforce the application of geological exploration data, reduce investigation costs, and provide more geotechnical parameters that are more reliable for marine engineering projects including offshore wind power.

The parity-time symmetry has led to exotic phenomena and fruitful applications in optical systems. In this paper, the authors propose a leaky-wave-enabled anti-parity-time design and realize space-wave harnessing.

BackgroundTo predict treatment response and 2 years overall survival (OS) of radio-chemotherapy in patients with esophageal cancer (EC) by radiomics based on the computed tomography (CT) images.MethodsThis study retrospectively collected 171 nonsurgical EC patients treated with radio-chemotherapy from Jan 2010 to Jan 2019. 80 patients were randomly divided into training (n=64) and validation (n=16) cohorts to predict the radiochemotherapy response. The models predicting treatment response were established by Lasso and logistic regression. A total of 156 patients were allocated into the training cohort (n=110), validation cohort (n=23) and test set (n=23) to predict 2-year OS. The Lasso Cox model and Cox proportional hazards model established the models predicting 2-year OS.ResultsTo predict the radiochemotherapy response, WFK as a radiomics feature, and clinical stages and clinical M stages (cM) as clinical features were selected to construct the clinical-radiomics model, achieving 0.78 and 0.75 AUC (area under the curve) in the training and validation sets, respectively. Furthermore, radiomics features called WFI and WGI combined with clinical features (smoking index, pathological types, cM) were the optimal predictors to predict 2-year OS. The AUC values of the clinical-radiomics model were 0.71 and 0.70 in the training set and validation set, respectively.ConclusionsThis study demonstrated that planning CT-based radiomics showed the predictability of the radiochemotherapy response and 2-year OS in nonsurgical esophageal carcinoma. The predictive results prior to treatment have the potential to assist physicians in choosing the optimal therapeutic strategy to prolong overall survival.

Multi-tandem fuel tanks have a complex structure, low flow rate between tanks, and, unlike single-fuel tanks, uneven pressure distribution, which makes their fuel supply and pressurization difficult to control. This paper uses a volume-of-fluid model based on the finite-volume method to track the fuel motion in different states of a flight vehicle and obtains the liquid-surface sloshing and the liquid flow in the connecting pipe. The model uses the dynamic meshing technique combined with the pressure at the solid wall to track the motion of the one-way stop valve diaphragm in the connecting pipe, thereby better predicting the fuel transfer in the connecting pipe. The calculation covers the whole process of flight vehicle erection, standby, flight, pumping, and pressurization and provides the distribution of pressure in different fuel tanks and the fuel flow characteristics in the connecting pipe. The calculation results are consistent with the experimental results, which verifies the accuracy of the model. By calculating different working cases, the results show that the different states of the flight vehicle strongly affect the sloshing of the liquid in the fuel tank, the pressure distribution, and the opening and closing of the valves. The maximum mass flow rate through the three valves, pressure at the bottom of the tank, and pressure at the pumping port all increase after the pressurization in the fuel tank. The flow of fuel between different tanks can be increased by changing the structure of the connecting pipe, which affects the pressure at different locations in the tank and at the pumping port.

Since the emergence of blockchain, how to improve its transaction throughput and reduce transaction latency has always been an important issue. Hostuff has introduced a pipeline mechanism and combined it with a chain structure to improve the performance of blockchain networks. HCA has introduced a revoting mechanism on the basis of Hostuff, further reducing transaction latency, but it has also brought some problems. In HCA, if the leader is malicious, it would be possible to continuously call on the replica nodes to revote, which can lead to network congestion. This paper employs the global perfect coin technology to guarantee that every replica can obtain a globally consistent and the freshest candidate proposal during the Revote phase, thereby improving the robustness of the HCA protocol. The performance improvement of RHCA in attack scenarios has been verified through experiments.

The influence of polysialic acid (PSA) and sialic acid (SA) on the gut microbial community composition and metabolites in healthy humans was investigated using a bionic gastrointestinal reactor. The results indicated that PSA and SA significantly changed the gut microbiota and metabolites to different degrees. PSA can increase the relative abundances of Faecalibacterium and Allisonella, whereas SA can increase those of Bifidobacterium and Megamonas. Both can significantly increase the content of short-chain fatty acids. The results of metabolome analysis showed that PSA can upregulate ergosterol peroxide and gallic acid and downregulate the harmful metabolite N-acetylputrescine. SA can upregulate 4-pyridoxic acid and lipoic acid. PSA and SA affect gut microbiota and metabolites in different ways and have positive effects on human health. These results will provide a reference for the further development of PSA- and SA-related functional foods and health products.

As a decentralized network infrastructure, the data sent to the blockchain are public and temper-evident. The cover of massive normal transactions in a blockchain network is ideal for constructing a stable and reliable covert channel to achieve one-to-many group covert communication. Existing blockchain-based covert communication schemes face challenges in balancing concealment, embedding rate and filtering efficiency, making them unsuitable for direct extension to group scenarios. Adopting a key-leakage scheme can increase the channel capacity while maintaining high concealment from external adversaries. However, it will also expose more knowledge to the receiver. A malicious receiver has the ability to steal a sender’s identity or replay historical transactions to control the entire channel. In this paper, we define the capabilities of malicious receivers in blockchain-based group covert communication scenarios and propose a group covert communication scheme resistant to transaction forgery attacks. Theoretical analysis and experiments prove that our covert transactions do not have any transaction correlativity, ensuring the unique authenticity of the sender’s identity while maintaining supreme concealment compared with the existing schemes. The precision and recall of machine learning detection results can reach 0.57–0.62 (0.5 is the ideal value).

A Z-type heterojunction MnO2@g-C3N4 photocatalyst with excellent performance was synthesized by an easy high-temperature thermal polymerization approach and combined with peroxymonosulfate (PMS) oxidation technology for highly efficient degrading of tetracycline hydrochloride (TC). Analysis of the morphological structural and photoelectric properties of the catalysts was achieved through different characterization approaches, showing that the addition of MnO2 heightened visible light absorption by g-C3N4. The Mn1-CN1/PMS system showed the best degradation of TC wastewater, with a TC degradation efficiency of 96.97% following 180 min of treatment. This was an approximate 38.65% increase over the g-C3N4/PMS system. Additionally, the Mn1-CN1 catalyst exhibited excellent stability and reusability. The active species trapping experiment indicated •OH and SO4•− remained the primary active species to degrade TC in the combined system. TC degradation pathways and intermediate products were determined. The Three-Dimensional Excitation-Emission Matrix (3DEEM) was employed for analyzing changes in the molecular structure in TC photocatalytic degradation. The biological toxicity of TC and its degradation intermediates were investigated via the Toxicity Estimation Software Test (T.E.S.T.). The research offers fresh thinking for water environment pollution treatment.

Abstract Reliable and contactless measurements of vital signs, such as respiration and heart rate, are still unmet needs in clinical and home settings. Mm-wave radar and video-based technologies are promising, but currently, the signal processing-based vital sign extraction methods are prone to body motion disruptions or illumination variations in the surrounding environment. Here we propose an image segmentation-based method to extract vital signs from the recorded video and mm-wave radar signals. The proposed method analyses time–frequency spectrograms obtained from Short-Time Fourier Transform rather than individual time-domain signals. This leads to much-improved robustness and accuracy of the heart rate and respiration rate extraction over existing methods. The experiments were conducted under pre- and post-exercise conditions and were repeated on multiple individuals. The results are evaluated by using four metrics against the gold standard contact-based measurements. Significant improvements were observed in terms of precision, accuracy, and stability. The performance was reflected by achieving an averaged Pearson correlation coefficient (PCC) of 93.8% on multiple subjects. We believe that the proposed estimation method will help address the needs for the increasingly popular remote cardiovascular sensing and diagnosing posed by Covid-19.

Nakamoto consensus is prevailing in the world largest blockchain-based cryptocurrency systems, such as Bitcoin and Ethereum. Since then, various attempts have been studied to attack Nakamoto consensus worldwide. In recent years, network delay has won more attention for making inconsistent ledgers in blockchain-based applications by virtue of attacking Nakamoto consensus. However, so far as we know, most of the existing works mainly focus on constructing inconsistent ledgers for blockchain systems, but not offering fine-grained theoretical analysis for how to optimize the success probability by flexibly dividing computational power and network delay from the viewpoint of adversary. The paper first utilizes network delay and the partition of controlled computation power of honest miners for making forks as long as possible. Then, formally analysis is provided to show the success probability of the proposed attack, and compute the optimal network delay and splitting for adversarial computation power in theory. Finally, simulation experiments validate the correctness of the formal analysis.

The formation of paralogs through gene duplication is a core evolutionary process. For paralogs that encode components of protein complexes such as the ribosome, a central question is whether they encode functionally distinct proteins or whether they exist to maintain appropriate total expression of equivalent proteins. Here, we systematically tested evolutionary models of paralog function using the ribosomal protein paralogs Rps27 (eS27) and Rps27l (eS27L) as a case study. Evolutionary analysis suggests that Rps27 and Rps27l likely arose during whole-genome duplication(s) in a common vertebrate ancestor. We show that Rps27 and Rps27l have inversely correlated mRNA abundance across mouse cell types, with the highest Rps27 in lymphocytes and the highest Rps27l in mammary alveolar cells and hepatocytes. By endogenously tagging the Rps27 and Rps27l proteins, we demonstrate that Rps27- and Rps27l-ribosomes associate preferentially with different transcripts. Furthermore, murine Rps27 and Rps27l loss-of-function alleles are homozygous lethal at different developmental stages. However, strikingly, expressing Rps27 protein from the endogenous Rps27l locus or vice versa completely rescues loss-of-function lethality and yields mice with no detectable deficits. Together, these findings suggest that Rps27 and Rps27l are evolutionarily retained because their subfunctionalized expression patterns render both genes necessary to achieve the requisite total expression of two equivalent proteins across cell types. Our work represents the most in-depth characterization of a mammalian ribosomal protein paralog to date and highlights the importance of considering both protein function and expression when investigating paralogs.

Abstract CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.

Abstract DNA methylation plays vital roles in both prokaryotes and eukaryotes. There are three forms of DNA methylation in prokaryotes: N 6-methyladenine (6mA), N 4-methylcytosine (4mC), and 5-methylcytosine (5mC). Although many sequencing methods have been developed to sequence specific types of methylation, few technologies can be used for efficiently mapping multiple types of methylation. Here, we present NT-seq for mapping all three types of methylation simultaneously. NT-seq reliably detects all known methylation motifs in two bacterial genomes and can be used for identifying de novo methylation motifs. NT-seq provides a simple and efficient solution for detecting multiple types of DNA methylation.

Detonation initiation is a prerequisite to normal operations of an oblique detonation engine (ODE), and initiation-assistant measures are imperative in cases of initiation failure that occur in a length-limited combustor under wide-range flight conditions. This study numerically investigates the initiation characteristics of oblique detonation waves (ODWs) in H2-fueled ODE combustors at wide-range flight Mach numbers Maf or flight altitudes Hf. Failures of ODW initiation are observed at both low Maf and high Hf if no measure is taken to assist initiation. Through analyses of the flow fields and theoretical predictions of the ignition induction length Lind, the data reveal that the detonation failure at low Maf is raised by the significant decrease in the post-shock temperature due to insufficient shock compression, leading to a significant increase in Lind. The detonation failure at high Hf is caused by the rapid decrease in the combustor inflow pressure as Hf increases, which also results in an increase in Lind. With further identifications of the key flow structures crucial to detonation initiation, an initiation-assistant concept employing a transverse H2 jet is proposed. The simulation results show that through an interaction between the incident oblique shock wave and the jet shock wave, the transverse jet helps to initiate an ODW in the combustor at a low Maf, and the initiation location is relatively fixed and determined by the jet location. At high Hf, a Mach reflection pattern is formed in the combustor under the effects of the transverse jet, and detonative combustion is achieved by the generated Mach stem and its reflected shock waves. The proposed concept of using transverse jets to assist detonation initiation provides a practical reference for future development of ODEs that are expected to operate under wide-range flight conditions.

Ultra-Low-Power Non-Volatile Memory (UltraRAM), as a promising storage device, has attracted wide research attention from the scientific community. Non-volatile data retention in combination with switching at ≤2.6 V is achieved through the use of the extraordinary 2.1 eV conduction band offsets of InAs/AlSb and a triple-barrier resonant tunnelling structure. Along these lines, in this work, the structure, storage mechanism, and improvement strategies of UltraRAM were systematically investigated to enhance storage window clarity and speed performance. First, the basic structure and working principle of UltraRAM were introduced, and its comparative advantages over traditional memory devices were highlighted. Furthermore, through the validation of the band structure and storage mechanism, the superior performance of UltraRAM, including its low operating voltage and excellent non-volatility, was further demonstrated. To address the issue of the small storage window, an improvement strategy was proposed by reducing the thickness of the channel layer to increase the storage window. The feasibility of this strategy was validated by performing a series of simulation-based experiments. From our analysis, a significant 80% increase in the storage window after thinning the channel layer was demonstrated, providing an important foundation for enhancing the performance of UltraRAM. Additionally, the data storage capability of this strategy was examined under the application of short pulse widths, and a data storage operation with a 10 ns pulse width was successfully achieved. In conclusion, valuable insights into the application of UltraRAM in the field of non-volatile storage were provided. Our work paves the way for further optimizing the memory performance and expanding the functionalities of UltraRAM.

Although deformations are mostly insignificant, they can be catastrophic when accumulated to certain amounts. Precise point positioning (PPP) can work with one receiver, preventing problems caused by the base station constrain upon employment of current methods such as real-time kinematics (RTK). However, current methods employing PPP focus on high-frequency monitoring such as earthquake or geological calamity monitoring, and these methods are not suitable for structures. Thus, this study proposes a new method for the deformation monitoring of structures via PPP. First, we obtained the coordinate sequence of structures via static PPP when setting the interval. Then, we transformed the coordinates to the same coordinate system with the same basis. Finally, we decomposed the sequences via empirical mode decomposition (EMD) to obtain a low-frequency part, which is the deformation of the target structure. The result of the monitoring experimentation on IGS stations shows that the monitoring index, Sd, of the sequence under different intervals using this method could be 1–2 mm on average in the directions of E, N, and U, which is much better than the original monitoring sequence. Alongside that, it prevented a fall in accuracy when the interval decreased. Therefore, all results proved the feasibility and validity of the method.

Background: One of the features of tumor immunity is the immunosuppressive tumor microenvironment (TME). In this study, TME gene signatures were used to define the characteristics of Cervical squamous cell carcinoma (CESC) immune subtypes and construct a new prognostic model.Methods: Single sample gene set enrichment analysis (ssGSEA) was used to quantify pathway activity. RNA-seq of 291 CESC were obtained from the Cancer Genome Atlas (TCGA) database as a training set. Microarray-based data of 400 cases of CESC were obtained from the Gene Expression Compilation (GEO) database as an independent validation set. 29 TME related gene signatures were consulted from previous study. Consensus Cluster Plus was employed to identify molecular subtype. Univariate cox regression analysis and random survival forest (RSF) were used to establish the immune-related gene risk model based on the TCGA data set of CESC, and the accuracy of prognosis prediction was verified by GEO data set. ESTIMATE algorithm was used to perform immune and matrix scores on the data set.Results: three molecular subtypes (C1, C2, C3) were screened in TCGA-CESC on account of 29 TME gene signatures. Among, C3 with better survival outcome had higher immune related gene signatures, while C1 with worse prognosis time had enhanced matrix related features. Increased immune infiltration, inhibition of tumor related pathways, widespread genomic mutations and prone immunotherapy were observed in C3. Furthermore, a five immune genes signature was constructed and predicted overall survival for CESC, which successfully validated in GSE44001 dataset. A positive phenomenon was observed between five hub genes expressions and methylation. Similarly, high group enriched in matrix related features, while immune related gene signatures were enriched in low group. Immune cell, immune checkpoints genes expression levels were negatively, while most TME gene signatures were positively correlated with Risk Score. In addition, high group was more sensitive to drug resistance.Conclusion: This work identified three distinct immune subtypes and a five genes signature for predicting prognosis in CESC patients, which provided a promising treatment strategy for CESC.

IntroductionMajor depressive disorder (MDD) is a highly recurrent mental illness accompanied by impairment of neurocognitive function. Lack of insight may affect patients’ motivation to seek treatment, resulting in poor clinical outcomes. This study explores the relationship of insight to neurocognitive function and the risk of recurrence of depressive episodes in patients with MDD.MethodsDemographic, clinical variables, and neurocognitive function measured with Intra-Extra Dimensional Set Shift (IED) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were collected from 277 patients with MDD. Among them, 141 participants completed a follow-up visit within 1–5 years. Insight was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). To explore the factors associated with recurrence, binary logistic regression models were used.ResultsPatients with MDD, without insight, had significantly higher total and factor scores (anxiety/somatization, weight, retardation, and sleep) on the HAM-D and worse performance in the neurocognition task, compared to those with insight. Furthermore, binary logistic regression revealed that insight and retardation can predict recurrence.ConclusionLack of insight is associated with recurrence and impaired cognitive flexibility in patients with MDD.

BackgroundAllograft kidney rejection can lead to graft dysfunction and graft loss. Protocol biopsy poses additional risk for recipients with normal renal function. The transcriptome of peripheral blood mononuclear cells (PBMCs) contains tremendous information and has potential application value for non-invasive diagnosis.MethodsFrom the Gene Expression Omnibus database, we collected three datasets containing 109 rejected samples and 215 normal controls. After data filter and normalization, we performed deconvolution of bulk RNA sequencing data to predict cell type and cell-type specific gene expression. Subsequently, we calculated cell communication analysis by Tensor-cell2cell and conducted the least absolute shrinkage and selection operator (LASSO) logistic regression to screen the robust differentially expressed genes (DEGs). These gene expression levels were validated in mice kidney transplantation acute rejection model. The function of the novel gene ISG15 in monocytes was further confirmed by gene knockdown and lymphocyte-stimulated assay.ResultsThe bulk RNA-seq hardly predicted kidney transplant rejection accurately. Seven types of immune cells and transcriptomic characteristics were predicted from the gene expression data. The monocytes showed significant differences in amount and gene expression of rejection. The cell-to-cell communication indicated the enrichment of antigen presentation and T cell activation ligand-receptor pairs. Then 10 robust genes were found by Lasso regression and a novel gene ISG15 remained differential expression in monocytes between rejection samples and normal control both in public data and animal model. Furthermore, ISG15 also showed a critical role in promoting the proliferation of T cells.ConclusionThis study identified and validated a novel gene ISG15 associated with rejection in peripheral blood after kidney transplantation, which is a significant non-invasive diagnosis and a potential therapeutic target.