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Abstract Cuproptosis differs from other forms of cell death, such as apoptosis, necroptosis, and ferroptosis, in its unique molecular mechanisms and signaling pathways. In this review, we delve into the cellular metabolic pathways of copper, highlighting the role of copper in biomolecule synthesis, mitochondrial respiration, and antioxidant defense. Furthermore, we elucidate the relationship between cuproptosis-related genes (CRGs) and cancer prognosis, analyzing their expression patterns across various tumor types and their impact on patient outcomes. Our review also uncovers the potential therapeutic applications of copper chelators, copper ionophores, and copper-based nanomaterials in oncology. In addition, we discuss the emerging role of cuproptosis in remodeling the tumor microenvironment, enhancing immune cell infiltration, and converting “cold tumors” into “hot tumors” that respond better to immunotherapy. In short, this review underscores the pivotal importance of cuproptosis in cancer biology and highlights its translational potential as a novel therapeutic target.

Objective: This study aimed to investigate the chest computed tomography (CT) findings of SARS-CoV-2 Omicron variants in elderly patients with underlying diseases. Methods: We retrospectively analyzed data from 140 elderly patients with underlying diseases who were infected with SARS-CoV-2 Omicron variants. The patients were divided into a moderate group and a severe/critical group based on their clinical classifications. Clinical data, laboratory results, and chest CT data (including lesion distribution, morphology, image signs, and lung lobe score) were collected and analyzed for all patients. Results: Hypertension and hyperlipidemia were the most prevalent underlying diseases among elderly patients with the Omicron variant of SARS-CoV-2. Ground-glass density opacity was the main chest CT manifestation, typically presenting as a mixed distribution across multiple lung lobes. Common clinical symptoms include fever, cough, and sputum production. The proportion of patients with fever was significantly higher in the severe/critical group compared to the moderate group. Additionally, the lymphocyte count was higher in the moderate group compared to the severe/critical group, while the procalcitonin level was significantly higher in the severe/critical group. Pleural thickening was also more prevalent in the severe/critical group. The right inferior lobe score was the highest in both groups (2 (1,3) and 3 (2,4) for moderate and severe/critical groups, respectively), with the total score and individual lobe scores being significantly higher in the severe/critical group. Conclusions: Chest CT scans play a crucial role in classifying disease severity and evaluating disease progression in elderly patients with underlying diseases infected with the Omicron variant of the novel coronavirus. These findings can also guide clinical treatment decisions.

In this paper, we develop a two-dimensional (2D) numerical model based on the finite element method to analyse the impact of fracture networks on the behaviour of pressurised lined rock caverns (LRCs). We use the discrete fracture network approach to represent the fracture system in rock obeying a power law length distribution. The LRC consisting of an inner steel lining and an outer reinforced concrete is situated within the rock mass characterised by spatially distributed and intersected fractures. An elasto-brittle constitutive relationship is adopted to characterise the deformation/failure of intact rocks, while the classical Mazars damage model is used to simulate the cracking of concrete linings. For pre-existing fractures in rock, a non-linear stress-displacement formulation is implemented to capture their normal and shear deformations. The 2D model, representing the horizontal cross-section of an LRC with its surrounding rock mass, is subject to a prescribed in situ stress condition. We explore various fracture network scenarios associated with different values of power law length exponent and fracture intensity. We analyse the damage evolution in rock/concrete and tangential strain in the concrete/steel linings. It is found that the damage within the rock mass mainly evolves in the form of wing cracks that emanate from the tips of pre-existing fractures. For damage development in the concrete lining, it is primarily induced by tensile cracking under cavern pressurisation. The damage emerges in the lining sections where pre-existing fractures are located in the tensile region around the cavern and either intersect with the cavern wall or could reach the cavern wall by promoting wing crack propagation. The results and insights obtained from our study have significant implications for the design optimisation and performance assessment of LRCs for sustainable hydrogen storage.

Abstract Background Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti–PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC. Methods and results The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p

Abstract Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.

Taking the motivation of the knowledge aggregation of age-friendly design resources as the starting point, this paper compares the development history of age-friendly design for interactive interfaces, understands the research status, hotspots, and development trend of age-friendly design for interactive interfaces from 2003 to 2022 worldwide, and summarizes and analyses them. This paper explores five aspects of aging-friendly design in the field of interactive interface design extracted from the Web of Science core collection database, including keyword co-occurrence analysis of global research literature, country/region information analysis, fundamental research areas, major research institutions, and future research directions. It explores the design methods, design trends, and design laws of aging-friendly design for interactive interfaces from a multidisciplinary perspective. The results show that: (a) Smart Home, Ambient Assisted Living (AAL), User Experience, Internet of Things (IoT), etc., are the hot topics at the forefront of interface aging design. (b) USA is the world’s leading research site for interface aging design and works closely with China, where the population aging is more serious. (c) The main research areas of interface aging are computer science and engineering ethics. (d) Udice French Research Universities, the primary publishing institution, is worth attention. (e) This review proposes three research hotspots as important development directions for interactive interface aging design, including “smart home product interaction interface aging design will become a hot topic,”“fusion of multi-source data assisted interface aging design,” and “interdisciplinary interface aging design.”

Background: Cuproptosis may represent a potential biomarker for predicting prognosis and immunotherapy response, but the available evidence is insufficient. Methods: The multiple single-cell RNA sequencing (scRNA-seq) datasets were analyzed to investigate the specific occurrence of cuproptosis in distinct cell populations. Utilizing 28 scRNA-seq datasets, TCGA pan-cancer cohort, and 10 immunotherapy cohorts, we developed a cuproptosis signature (Cup.Sig). This signature was used to construct prediction models for immunotherapy response and identify potential prognostic biomarkers for pan-cancer using 11 different machine learning algorithms. Results: Malignant cells demonstrate the higher cuproptosis scores in comparison to other cell types across diverse cancer types. The Cup.Sig exhibits significant associations with cancer hallmarks and immune cell response in multiple cancer types. Leveraging the Cup.Sig, the robust pan-cancer immunotherapy prediction model and prognostic biomarker have been established and validated using diverse datasets from various platforms. Conclusions: We developed a pan-cancer cuproptosis signature for predicting survival and immunotherapy response.

Abstract Anti‐cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin‐I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin‐I, which can self‐assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin‐I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin‐I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K‐AKT‐mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin‐I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin‐I can provide new insights into the mechanism of ACPs, and Lycosin‐I, which is characterized by high potency and specificity, can be a promising lead for the development of anti‐leukemia drugs.

The fractional Brownian field is often used to reproduce the fractal properties of complex heterogeneous media, which closely represent real-world geological materials. Studying elastic wave transport in this type of heterogeneous media is essential for advancing knowledge in geophysics, seismology, and rock mechanics. In this paper, we numerically investigate the wavefield evolution and arrival behavior of elastic wave propagation in a two-dimensional fractional Brownian field characterized by the standard deviation (σ) and the Hurst exponent (H). Using a high-fidelity finite element model, we quantify the influence of these parameters on wavefront morphology, wave arrival synchronization, and energy decay. Our results reveal that increased matrix heterogeneity with higher σ and lower H values leads to pronounced wavefront roughness, asynchronous arrival phenomena, and increscent energy decay, attributed to enhanced scattering and modulus variability. For smaller H values, rougher modulus distributions scatter wave energy more intensely, producing more coda waves and distorted wavefronts, while smoother fields with larger H fields promote smoother wave propagation. Higher σ amplifies these effects by increasing modulus variability, resulting in more attenuated wave energy and substantial wavefield disturbance. This study contributes to a quantitative understanding of how fractal heterogeneity modulates wave transport and energy attenuation in random media. Our findings hold practical significance for geophysical exploration and seismic tomography, as well as aiding in subsurface imaging and structural evaluation within fractured or stratified rock formations.

Summary: Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H2O2-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. Additionally, the inhibition of TGF-β1/SMAD3 signaling attenuated the impact of over-expression of MBNL2 in inducing senescence and cardiac fibrosis. MBNL2, by orchestrating SUMOylation of KLF4, upregulating the TGF-β1/SMAD3 signaling pathway, emerges as a significant promoter of aging-related cardiac fibrosis. This discovery identifies a novel regulatory target for managing aging-related cardiac fibrosis.

Oxidative stress and inflammation are crucial factors contributing to the occurrence and development of vascular dementia (VD). In a previous study, we demonstrated that brozopine (BZP) is an anti-ischemic drug. In this study, a model of VD in rats with modified permanent bilateral common carotid artery occlusion (2-VO) was established in vivo, a model of cellular excitotoxicity/oxidative stress was established via L-glutamate-induced PC12 cell injury, a model of neuroinflammation was established in LPS-induced BV2 cells in vitro, and the ameliorative effect of BZP on cognitive impairment was assessed. BZP treatment improved memory deficit in VD rats through inhibiting Ca2+overload and the levels of oxidative stress, ferroptosis, and inflammatory markers (IL-1β, IL-6, and COX-2) in different brain regions. Additionally, we found that the levels of inflammatory markers in the plasma were also reduced in the VD rats. BZP was further found to have antioxidative stress, antiferroptosis (ferroptosis markers: GPX4, P53, and ACSL4), and antineuroinflammatory effects in PC12 and BV2 cells. Its mechanisms of action were found to be related to the activation of the Nrf2/TLR4/NF-κB pathway; the protective effect of BZP was partially inhibited after using Nrf2-specific inhibitors. Thus, BZP has therapeutic properties for the potential mitigation of cognitive impairment.

The technology of tunnel boring machine (TBM) has been widely applied for underground construction worldwide; however, how to ensure the TBM tunneling process safe and efficient remains a major concern. Advance rate is a key parameter of TBM operation and reflects the TBM-ground interaction, for which a reliable prediction helps optimize the TBM performance. Here, we develop a hybrid neural network model, called Attention-ResNet-LSTM, for accurate prediction of the TBM advance rate. A database including geological properties and TBM operational parameters from the Yangtze River Natural Gas Pipeline Project is used to train and test this deep learning model. The evolutionary polynomial regression method is adopted to aid the selection of input parameters. The results of numerical experiments show that our Attention-ResNet-LSTM model outperforms other commonly-used intelligent models with a lower root mean square error and a lower mean absolute percentage error. Further, parametric analyses are conducted to explore the effects of the sequence length of historical data and the model architecture on the prediction accuracy. A correlation analysis between the input and output parameters is also implemented to provide guidance for adjusting relevant TBM operational parameters. The performance of our hybrid intelligent model is demonstrated in a case study of TBM tunneling through a complex ground with variable strata. Finally, data collected from the Baimang River Tunnel Project in Shenzhen of China are used to further test the generalization of our model. The results indicate that, compared to the conventional ResNet-LSTM model, our model has a better predictive capability for scenarios with unknown datasets due to its self-adaptive characteristic.

Abstract Aim As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum‐based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment. Methods A total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed. Results Positive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1‐positive samples were more common in the chemoresistant group than in the platinum‐sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p

Cowpea mild mottle virus (CPMMV) is a global plant virus that poses a threat to the production and quality of legume crops. Early and accurate diagnosis is essential for effective managing CPMMV outbreaks. With the advancement in isothermal recombinase polymerase amplification and lateral flow strips technologies, more rapid and sensitive methods have become available for detecting this pathogen. In this study, we have developed a reverse transcription recombinase polymerase amplification combined with lateral flow strips (RT-RPA-LFS) method for the detection of CPMMV, specifically targeting the CPMMV coat protein (CP) gene. The RT-RPA-LFS assay only requires 20 min at 40°C and demonstrates high specificity. Its detection limit was 10 copies/μl, which is approximately up to 100 times more sensitive than RT-PCR on agarose gel electrophoresis. The developed RT-RPA-LFS method offers a rapid, convenient, and sensitive approach for field detection of CPMMV, which contribute to controlling the spread of the virus.

During the long service period of a nuclear waste repository in crystalline rock, large earthquake(s) may occur nearby the repository site and coseismically alter the local stress field around pre-existing fractures within the geological formation. The resulting fracture normal/shear displacements may lead to fracture opening and further promote the transport of leaked radionuclides into the groundwater system. Thus, it is of central importance to analyze the consequences of potential future earthquake(s) on the hydrogeological properties of a repository site for spent nuclear fuel disposal. Based on the detailed site characterization data of the repository site at Forsmark, Sweden, we conduct a three-dimensional (3D) seismo-hydro-mechanical simulation using the 3Dimensional Distinct Element Code (3DEC). We explicitly represent a primary seismogenic fault zone and its surrounding secondary fracture network associated with a power-law size scaling and a Fisher orientation distribution. An earthquake with a magnitude of Mw = 5.6 caused by the reactivation of the primary fault zone is modeled by simulating its transient rupture propagating radially outwards from a predefined hypocenter at a specified rupture speed, with the faulting dynamics controlled by a strength weakening law. We model the coseismic response of the off-fault fracture network subject to both static and dynamic triggering effects. We further diagnose the distribution of fracture hydro-mechanical properties (e.g. mechanical/hydraulic aperture, hydraulic transmissivity) before and after the earthquake in order to quantify earthquake-induced hydraulic changes in the fracture network. It is found that earthquake-induced fracture transmissivity changes tend to follow a power-law decay with the distance to the earthquake fault. Our simulation results and insights obtained have important implications for the long-term performance assessment of nuclear waste repositories in fractured crystalline rocks.

Abstract Melatonin is a functionally conserved broad-spectrum physiological regulator found in most biological organisms in nature. Enrichment of tomato fruit with melatonin not only enhances its agronomic traits but also provides extra health benefits. In this study, we elucidate the full melatonin biosynthesis pathway in tomato fruit by identifying biosynthesis-related genes that encode caffeic acid O-methyltransferase 2 (SlCOMT2) and N-acetyl-5-hydroxytryptamine-methyltransferases 5/7 (SlASMT5/7). We further reveal that red light supplementation significantly enhances the melatonin content in tomato fruit. This induction relies on the “serotonin—N-acetylserotonin—melatonin” biosynthesis route via the SlphyB2-SlPIF4-SlCOMT2 module. Based on the regulatory mechanism, we design a gene-editing strategy to target the binding motif of SlPIF4 in the promoter of SlCOMT2, which significantly enhances the production of melatonin in tomato fruit. Our study provides a good example of how the understanding of plant metabolic pathways responding to environmental factors can guide the engineering of health-promoting foods.

Accurately predicting tunnel boring machine (TBM) performance is beneficial for excavation efficiency enhancement and risk mitigation of TBM tunneling. In this paper, we develop a long short-term memory (LSTM) based hybrid intelligent model to predict two key TBM performance parameters (advance rate and cutterhead torque). The model combines the LSTM, BN, Dropout and Dense layers to process the raw data and improve the fitting quality. The features, including the ground formation properties, tunnel route curvature, tunnel location and TBM operational parameters, are divided into historical/real-time time-varying parameters, time-invariant parameters and historical/real-time output prediction data. The effectiveness of the proposed model is verified based on a large monitoring database of the Baimang River Tunnel Project in Shenzhen, south China. We then discuss the influence of the prediction mode, neural network structure and time division interval length of historical data on the prediction accuracy. The significance evaluation of input features shows that the historical output prediction has the largest influence on the prediction accuracy, and the influence of ground properties is secondary. It is also found that the correlations between input features and the output prediction are coincident with their interrelationships with the ground properties and ease of TBM excavation. Finally, it is found that the prediction results are most affected by the total propulsion force followed by the rotation speed of the cutterhead. The established model can provide useful guidance for construction personnel to roughly grasp the possible TBM status from the prediction results when adjusting the operational parameters.

Objectives: This study aims to investigate the effectiveness of cupping therapy on low back pain (LBP). Methods: Medline, Embase, Scopus and WANFANG databases were searched for relevant cupping RCTs on low back pain articles up to 2023. A complementary search was manually made on 27 September for update screening. Full-text English and Chinese articles on all ethnic adults with LBP of cupping management were included in this study. Studies looking at acute low back pain only were excluded. Two independent reviewers screened and extracted data, with any disagreement resolved through consensus by a third reviewer. The methodological quality of the included studies was evaluated independently by two reviewers using an adapted tool. Change-from-baseline outcomes were treated as continuous variables and calculated according to the Cochrane Handbook. Data were extracted and pooled into the meta-analysis by Review Manager software (version 5.4, Nordic Cochrane Centre). Results: Eleven trials involving 921 participants were included. Five studies were assessed as being at low risk of bias, and six studies were of acceptable quality. High-quality evidence demonstrated cupping significantly improves pain at 2–8 weeks endpoint intervention (d=1.09, 95% CI: [0.35–1.83], p = 0.004). There was no continuous pain improvement observed at one month (d=0.11, 95% CI: [−1.02–1.23], p = 0.85) and 3–6 months (d=0.39, 95% CI: [−0.09–0.87], p = 0.11). Dry cupping did not improve pain (d=1.06, 95% CI: [−0.34, 2.45], p = 0.14) compared with wet cupping (d=1.5, 95% CI: [0.39–2.6], p = 0.008) at the endpoint intervention. There was no evidence indicating the association between pain reduction and different types of cupping (p = 0.2). Moderate- to low-quality evidence showed that cupping did not reduce chronic low back pain (d=0.74, 95% CI: [−0.67–2.15], p = 0.30) and non-specific chronic low back pain (d=0.27, 95% CI: [−1.69–2.24], p = 0.78) at the endpoint intervention. Cupping on acupoints showed a significant improvement in pain (d=1.29, 95% CI: [0.63–1.94], p 50%). Conclusion: High- to moderate-quality evidence indicates that cupping significantly improves pain and disability. The effectiveness of cupping for LBP varies based on treatment durations, cupping types, treatment locations, and LBP classifications. Cupping demonstrated a superior and sustained effect on pain reduction compared with medication and usual care. The notable heterogeneity among studies raises concerns about the certainty of these findings. Further research should be designed with a standardized cupping manipulation that specifies treatment sessions, frequency, cupping types, and treatment locations. The actual therapeutic effects of cupping could be confirmed by using objective pain assessments. Studies with at least six- to twelve-month follow-ups are needed to investigate the long-term efficacy of cupping in managing LBP. Trial registration: This systematic review was initially registered on PROSPERO with registration code: CRD42021271245 on 08 September 2021.

Abstract The two most prevalent subtypes of epithelial ovarian carcinoma (EOC) are ovarian clear cell carcinoma (OCCC) and high-grade serous ovarian carcinoma (HGSC). Patients with OCCC have a poor prognosis than those with HGSC due to chemoresistance, implying the need for novel treatment target. In this study, we applied single-cell RNA sequencing (scRNA-seq) together with bulk RNA-seq data from the GEO (Gene Expression Omnibus) database (the GSE189553 dataset) to characterize and compare tumor heterogeneity and cell-level evolution between OCCC and HGSC samples. To begin, we found that the smaller proportion of an epithelial OCCC cell subset in the G2/M phase might explain OCCC chemoresistance. Second, we identified a possible pathogenic OCCC epithelial cell subcluster that overexpresses LEFTY1. Third, novel biomarkers separating OCCC from HGSC were discovered and subsequently validated on a wide scale using immunohistochemistry. Amine oxidase copper containing 1 (AOC1) was preferentially expressed in OCCC over HGSC, while S100 calcium-binding protein A2 (S100A2) was detected less frequently in OCCC than in HGSC. In addition, we discovered that metabolic pathways were enriched in the epithelial compartment of the OCCC samples. In vitro experiments verified that inhibition of oxidative phosphorylation or glycolysis pathways exerted direct antitumor effects on both OCCC and HGSC cells, while targeting glutamine metabolism or ferroptosis greatly attenuated chemosensitivity only in OCCC cells. Finally, to determine whether there were any variations in immune cell subsets between OCCC and HGSC, data from scRNA-seq and mass cytometry were pooled for analysis. In summary, our work provides the first holistic insights into the cellular and molecular distinctions between OCCC and HGSC and is a valuable source for discovering new targets to leverage in clinical treatments to improve the poor prognosis of patients with OCCC.

Abstract Background Metabolites of tryptophan (Trp) metabolism in the tumor microenvironment play crucial immunosuppressive roles in various cancers. However, the role of Trp metabolism in diffuse large B‐cell lymphoma (DLBCL) or natural killer/T‐cell lymphoma (NK/TCL) remains unelucidated. Methods We investigated the potential role of Trp metabolism in a cohort of 43 patients with DLBCL and 23 with NK/TCL. We constructed tissue microarrays and performed in situ staining of Trp‐catabolizing enzymes and PD‐L1 using immunohistochemistry (IHC). Results We observed 14.0% positive staining of IDO1 in DCBCL and 60.9% in NK/TCL; 55.8% of IDO2 in DCBCL and 95.7% in NK/TCL; 79.1% of TDO2 in DCBCL and 43.5% in NK/TCL; 29.7% of IL4I1 in DCBCL and 39.1% in NK/TCL. However, IDO1, IDO2, TDO2, and IL4I1 positivity did not significantly differ between PD‐L1+ and PD‐L1− biopsy tissue samples of NK/TCL; nonetheless, a positive correlation of IDO1 (r = 0.87, p

Abstract Objectives Patients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy. Methods A retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021. Results Before January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI − 7.0–8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups. Conclusions We demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy.

Objective: To investigate the chest computed tomography (CT) findings and dynamic changes in patients infected with SARS-CoV-2 Omicron variants. Methods: 200 patients infected with SARS-CoV-2 Omicron variants were collected in Beijing Ditan Hospital, Capital Medical University from November 2022 to January 2023. These patients were divided into mild group, moderate group and severe/critical group according to the clinical classification. All patients’ clinical, laboratory and chest CT data were retrospectively analyzed. Results: Among 200 cases infected with SARS-CoV-2 omicron variant, the main clinical manifestations were fever, cough, sore throat and fatigue. There was a statistically significant difference in white blood cell count between the mild group and the medium group, and between the mild group and the severe/critical group. There were significant differences in erythrocyte sedimentation rate between mild and moderate groups, and between mild and severe/critical groups. Most of the lesions in mild group were subpleural (53.6%), while most of the lesions in moderate group (77.9%) and severe/critical group (88.9%) were mixed. The crazy-paving sign was statistically significant between the mild and severe/critical groups, and between the mild and moderate groups. There were significant differences in air bronchogram sign between the mild and the severe/critical groups, the mild and severe/critical groups , and the mild and moderate groups. The frequency of Ground Glass Opacity (GGO) was the highest at different intervals between the onset and the first chest CT. The proportion of GGO with consolidation/consolidation and air bronchogram sign gradually increased when the interval was more than 4 days. The proportion of GGO with consolidation/consolidation and air bronchogram sign gradually increased when the interval was more than 4 days. The highest proportion (95.4%) of crazy-paving sign appeared within the interval of 5-9 days, after which the proportion decreased. The frequency of irregular linear opacities, the proportion of pleural thickening and pleural effusion increased in patients with an interval more than 14 days. The median times to occurrence of GGO, GGO with crazy-paving sign, GGO with consolidation or consolidation and irregular linear opacities respectively were 4 days (2 days, 7 days), 9 days (7 days, 11 days), 13 days (10 days, 16 days) and 16 days (13 days, 19 days). Conclusions: Chest CT can reflect the distribution, morphology, dynamic imaging development and outcome of lesions in patients infected with SARS-CoV-2 Omicron variant, which is helpful for clinical treatment decision-making and efficacy evaluation.

The application of a diammonium phosphate coating effectively mitigates direct contact between the phosphate fertilizer and the soil, thus minimizing phosphorus fixation. Humic acid holds a pivotal role in augmenting soil quality and activating the soil’s phosphorus reserves. Notably, when combined with humic acid, diammonium phosphate significantly enhances the utilization efficiency of phosphate fertilizer. However, there is a paucity of literature exploring the dynamics of nutrient transport in soil when humic acid is paired with coated phosphate fertilizers. To assess the impact of the combined application of coated diammonium phosphate and humic acid on wheat yield enhancement, we conducted pot experiments along with leaching and ammonia volatilization simulation tests, aiming to elucidate the effects of this combination on nutrient transport. The study explored the effects of three distinct treatments: coated diammonium phosphate (CP), coated diammonium phosphate combined with humic acid (PHA), and coated diammonium phosphate combined with humic acid (CPHA). The investigation focused on analyzing their impacts on wheat yield, ammonia volatilization, soil-available phosphorus, nitrate nitrogen, ammonium nitrogen, soil-available potassium, as well as the mobilization and transport of calcium and magnesium in the soil. (1) Compared to the P treatment, the PHA and CP treatments significantly increased grain yield by 17.2% and 13.5%, respectively. The PHA treatment also increased effective panicle number by 12.9%. Overall, the CP, PHA, and CPHA treatments improved grain yield by 13.5%, 17.2%, and 19.1% compared to the P treatment. (2) The CP and PHA treatments reduced available phosphorus by 95.6% and 49.2%, calcium by 2.0% and 67.0%, and magnesium by 11.6% and 46.1% compared to the P treatment. Ammonium nitrogen decreased by 37.0% and 64.3%, while nitrate nitrogen increased by 14.0% in CP and slightly decreased by 0.8% in PHA. In the leaching solution, PHA and CP treatments reduced available phosphorus by 96.7% and 62.5%, increased calcium by 5.0% and 78.9%, decreased ammonium nitrogen by 2.2% and 43.4%, and decreased nitrate nitrogen by 10.6% and 13.0%. The PHA and CPHA treatments increased available phosphorus in the 0–20 cm soil layer by 1.4 times and 25.8%, respectively. (3) The CP treatment reduced ammonia volatilization by 87.0% compared to the P treatment, while the CPHA treatment further reduced it by 87.5% compared to the PHA treatment. The application of coated diammonium phosphate efficiently delays nutrient release and reduces nutrient leaching in the soil. Additionally, the integration of humic acid significantly improves the availability of phosphorus in the soil, minimizing phosphorus loss. Notably, the combined application of humic acid and coated diammonium phosphate leads to a significant increase in soil phosphorus content, subsequently enhancing soil nutrient availability, conserving fertilizer, and ultimately resulting in an improved wheat yield.

ABSTRACTNorthern corn leaf blight (NCLB) is one of the most important foliar disease in maize, which leads to serious yield losses. It is necessary to identify resistance genes in order to control NCLB. Mitogen-activated protein kinase (MAPK) cascades play important roles in plant defense reactions. Ethylene-response factor (ERF) is involved in plant disease resistance in maize through phosphorylation by MAPK signaling pathway. Here, we found that ZmMPK6-1 positively regulates maize resistance against E. turcicum through enhancing the expression of defense-related genes and enzyme activities. Moreover, ZmMPK6-1 can interact with ZmERF061 which enhanced the transcriptional activation activity of ZmERF061. Taken together, our findings indicated that ZmMPK6-1 would act through improving ZmERF061 transcriptional activation activity to induce defensin gene expression in regulating the maize resistance against E. turcicum. These results revealed the molecular mechanism of ZmMPK6-1-ZmERF061 signaling pathway in response to E. turcicum, which is useful to maize E. turcicum resistance breeding.

BackgroundLincomycin, a natural antibiotic, is widely used by animal and fishery husbandries to prevent infections and treat diseases. It endangers people’s health when they eat foods containing lincomycin residue, especially the frequent consumption of milk and chicken products containing lincomycin. Hence, it is extremely important to evaluate the content of lincomycin in food samples. However, a direct analysis of lincomycin in milk and chicken is quite difficult because of its very low concentration level and the presence of undesirable matrix effects. Therefore, selective and efficient extraction of lincomycin from complex food samples prior to its quantification is required.ResultsIn this study, lincomycin-imprinted silica nanoparticles were prepared according to boronate affinity-based template-immobilized surface imprinting. Silica nanoparticles and boronic acid ligands 3-fluoro-4-formylphenylboronic acid were used as supporting materials and functional monomers, respectively. The prepared lincomycin-imprinted silica nanoparticles exhibited several significant results, such as good specificity, high binding capacity (19.45 mg/g), fast kinetics (6 min), and low binding pH (pH 5.0) toward lincomycin. The reproducibility of lincomycin-imprinted silica nanoparticles was satisfactory. The lincomycin-imprinted silica nanoparticles could still be reused after seven adsorption–desorption cycles, which indicated high chemical stability. In addition, the recoveries of the proposed method for lincomycin at three spiked levels of analysis in milk and chicken were 93.3–103.3% and 90.0–100.0%, respectively.ConclusionThe prepared lincomycin-imprinted silica nanoparticles are feasible for the recognition of target lincomycin with low concentrations in real food samples such as milk and chicken. Our approach makes sample pre-preparation simple, fast, selective, and efficient.

Abstract Background Infantile hemangioma (IH) is the most common tumor among infants, but the exact pathogenesis of IH is largely unknown. Our previous study revealed that glucose metabolism may play an important role in the pathogenesis of IH and that the inhibition of the glycolytic key enzyme phosphofructokinase-1 suppresses angiogenesis in IH. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a metabolic enzyme that converts fructose-6-bisphosphate to fructose-2,6-bisphosphate (F-2,6-BP), which is the most potent allosteric activator of the rate-limiting enzyme phosphofructokinase-1. This study was performed to explore the role of PFKFB3 in IH. Methods Microarray analysis was performed to screen the differentially expressed genes (DEGs) between proliferating and involuting IH tissues. PFKFB3 expression was examined by western blot and immunohistochemistry analyses. Cell migration, apoptosis and tube formation were analyzed. Metabolic analyses were performed to investigate the effect of PFKFB3 inhibition by PFK15. Mouse models were established to examine the effect of PFKFB3 inhibition in vivo. Results PFKFB3 was identified as one of the most significant DEGs and was more highly expressed in proliferating IH tissues and hemangioma-derived endothelial cells (HemECs) than in involuting IH tissues and human umbilical vein endothelial cells, respectively. PFKFB3 inhibition by PFK15 suppressed HemEC glucose metabolism mainly by affecting glycolytic metabolite metabolism and decreasing the glycolytic flux. Moreover, PFK15 inhibited HemEC angiogenesis and migration and induced apoptosis via activation of the apoptosis pathway. Treatment with the combination of PFK15 with propranolol had a synergistic inhibitory effect on HemECs. Moreover, PFKFB3 knockdown markedly suppressed HemEC angiogenesis. Mechanistically, inhibition of PFKFB3 suppressed the PI3K-Akt signaling pathway and induced apoptotic cell death. More importantly, the suppression of PFKFB3 by PFK15 or shPFKFB3 led to markedly reduced tumor growth in vivo. Conclusions Our findings suggest that PFKFB3 inhibition can suppress IH angiogenesis and induce apoptosis. Thus, targeting PFKFB3 may be a novel therapeutic strategy for IH.

Background & Aims: The adipokine CTRP3 has anti-inflammatory effects in several nonintestinal disorders. Although serum CTRP3 is reduced in patients with inflammatory bowel disease (IBD), its function in IBD has not been established. Here, we elucidate the function of CTRP3 in intestinal inflammation. Methods: CTRP3 knockout (KO) and overexpressing transgenic (Tg) mice, along with their corresponding wild-type littermates, were treated with dextran sulfate sodium for 6–10 days. Colitis phenotypes and histologic data were analyzed. CTRP3-mediated signaling was examined in murine and human intestinal mucosa and mouse intestinal organoids derived from CTRP3 KO and Tg mice. Results: CTRP3 KO mice developed more severe colitis, whereas CTRP3 Tg mice developed less severe colitis than wild-type littermates. The deletion of CTRP3 correlated with decreased levels of Sirtuin-1 (SIRT1), a histone deacetylase, and increased levels of phosphorylated/acetylated NF-κB subunit p65 and proinflammatory cytokines tumor necrosis factor-α and interleukin-6. Results from CTRP3 Tg mice were inverse to those from CTRP3 KO mice. The addition of SIRT1 activator resveratrol to KO intestinal organoids and SIRT1 inhibitor Ex-527 to Tg intestinal organoids suggest that SIRT1 is a downstream effector of CTRP3-related inflammatory changes. In patients with IBD, a similar CTRP3/SIRT1/NF-κB relationship was observed. Conclusions: CTRP3 expression levels correlate negatively with intestinal inflammation in acute mouse colitis models and patients with IBD. CTRP3 may attenuate intestinal inflammation via SIRT1/NF-κB signaling. The manipulation of CTRP3 signaling, including through the use of SIRT1 activators, may offer translational potential in the treatment of IBD.

This study aimed to compare the nutritional composition, digestive enzyme activity, nonspecific immunity, and intestinal microflora of Procambarus clarkii under different culture modes: crayfish and crab coculture, pond intensive farmed culture (PF), rice and crayfish coculture (RC), cement pond culture (CP), and wild-caught. The muscle, hepatopancreas, and intestine of crayfish with a mean weight of 25.35 ± 4.23 g were collected and examined. The results showed that the nutritive value of amino acids and fatty acids in the muscle was higher in the RC group than in the other groups. Moreover, muscle crude protein contents were the highest in the CP group. Trypsin activities in the intestines were significantly higher in the PF and CP groups than in the other groups (P

Abstract Background Red clover (Trifolium pratense L.) is a diploid perennial temperate legume with 14 chromosomes (2n = 14) native to Europe and West Asia, with high nutritional and economic value. It is a very important forage grass and is widely grown in marine climates, such as the United States and Sweden. Genetic research and molecular breeding are limited by the lack of high-quality reference genomes. In this study, we used Illumina, PacBio HiFi, and Hi-C to obtain a high-quality chromosome-scale red clover genome and used genome annotation results to analyze evolutionary relationships among related species. Results The red clover genome obtained by PacBio HiFi assembly sequencing was 423 M. The assembly quality was the highest among legume genome assemblies published to date. The contig N50 was 13 Mb, scaffold N50 was 55 Mb, and BUSCO completeness was 97.9%, accounting for 92.8% of the predicted genome. Genome annotation revealed 44,588 gene models with high confidence and 52.81% repetitive elements in red clover genome. Based on a comparison of genome annotation results, red clover was closely related to Trifolium medium and distantly related to Glycine max, Vigna radiata, Medicago truncatula, and Cicer arietinum among legumes. Analyses of gene family expansions and contractions and forward gene selection revealed gene families and genes related to environmental stress resistance and energy metabolism. Conclusions We report a high-quality de novo genome assembly for the red clover at the chromosome level, with a substantial improvement in assembly quality over those of previously published red clover genomes. These annotated gene models can provide an important resource for molecular genetic breeding and legume evolution studies. Furthermore, we analyzed the evolutionary relationships among red clover and closely related species, providing a basis for evolutionary studies of clover leaf and legumes, genomics analyses of forage grass, the improvement of agronomic traits.

The presence of another planetary companion in a transiting exoplanet system can impact its transit light curve, leading to sinusoidal transit-timing variations (TTV). By utilizing both χ ^2 and rms analysis, we have combined the TESS observation data with an N -body simulation to investigate the existence of an additional planet in the system and put a limit on its mass. We have developed CMAT, an efficient and user-friendly tool for fitting transit light curves and calculating TTV with a theoretical period, based on which we can give a limit on its hidden companion’s mass. We use 260 hot Jupiter systems from the complete TESS data set to demonstrate the use of CMAT. Our findings indicate that, for most systems, the upper mass limit of a companion planet can be restricted to several Jupiter masses. This constraint becomes stronger near resonance orbits, such as the 1:2, 2:1, 3:1, and 4:1 mean-motion resonance, where the limit is reduced to several Earth masses. These findings align with previous studies suggesting that a lack of companion planets with resonance in hot Jupiter systems could potentially support the high-eccentricity migration theory. Additionally, we observed that the choice between χ ^2 or rms method does not significantly affect the upper limit on companion mass; however, χ ^2 analysis may result in weaker restrictions but is statistically more robust compared to rms analysis in most cases.

Many hot Jupiters may experience orbital decays, which are manifested as long-term transit-timing variations. We have analyzed 7068 transits from the Transiting Exoplanet Survey Satellite (TESS) for a sample of 326 hot Jupiters. These new mid-transit-time data allow us to update ephemerides for these systems. By combining the new TESS transit-timing data with archival data, we searched for possible long-term variations in the orbital period in these hot Jupiters using a linear and a quadratic ephemeris model. We identified 26 candidates that exhibit possible long-term variations of the orbital period, including 18 candidates with decreasing orbital periods and eight candidates with increasing orbital periods. Among them, 12 candidates failed our leave-one-out cross validation test and thus should be considered to be marginal candidates. In addition to tidal interaction, alternative mechanisms such as apsidal precession, the Rømer effect, and the Applegate effect could also contribute to the variations during the observed period. The ephemerides derived in this work are useful for scheduling follow-up observations for these hot Jupiters in the future. The Python code ( PdotQuest , https://github.com/AeoN400/PdotQuest ) used to generate the ephemerides is made available online.

The Liangzhu culture (5300–4200 cal BP) was the most famous Neolithic culture of who settled near the lower reaches of the Yangtze River in China. The core and initial distribution area of Liangzhu originated around Taihu Lake, located on the south bank of the Yangtze River delta. Recently, archaeological studies believe that the Jianghuai area and Huanghuai area north of the Yangtze River are also important distribution areas of Liangzhu culture. The route for Liangzhu culture migrating across the Yangtze River is inferred as follows: One would have crossed the Yangtze River from Nanjing-Zhenjiang belt and continued to migrate northward; while the other would have crossed the River near the estuary before moving north along the ancient coastline to the Jianghuai during the late period of Liangzhu, or crossed the Yangtze River from the east of the present Beijing-Hangzhou Grand Canal to Jianghuai and Huanghuai. According to the formation of the Yangtze River delta during the Holocene and the evolution of the estuarine sand bar, it is believed that there were large shoals in the Yangtze River channel in the middle-Holocene. The Liangzhu ancestors around 5000 cal BP had the ability of making canoes over 8 m. Based on the archaeological research of the Neolithic period, the evolution of the Yangtze River channel in the Holocene, the history of ancient Chinese shipbuilding, and the modern examples of crossing the Yangtze River with boat, it can be concluded that the present Changzhou–Jiangyin–Zhangjiagang line should be the main and reasonable route for the Liangzhu culture migrating across the Yangtze River.

The rapid growth of distributed generation (DG) and load has highlighted the necessity of optimizing their ways of integration, as their siting and sizing significantly impact distribution networks. However, little attention has been paid to the siting and sizing of new substations which are to be installed. This paper proposes deep learning-aided joint DG-substation siting and sizing in distribution network stochastic expansion planning. First, as the model depends on an accurate forecast, Long Short-Term Memory (LSTM) deep neural network is used to forecast DG output and load, where electricity growth rate, bidding capacity of the electric expansion, and industrial difference are all considered. Then, a two-stage stochastic mixed integer bilinear programming model was established for joint DG-substation siting and sizing under uncertainties, where multiple objective functions are comprehensively addressed. By using the Fortuny-Amat McCarl Linearization, the resultant bilinear model is equivalently transformed into a mixed integer linear program, which can be efficiently solved. Finally, stochastic power flow calculation in the IEEE 69-node system is conducted to analyze the influence of electric expansion and DG integration on the node voltage and power flow distribution of the power system. The effectiveness of the proposed method is also verified by simulation tests.

Kaposiform hemangioendothelioma (KHE) is a rare borderline vascular tumor that usually presents as a mass of skin or deep soft tissue. We report a unique case of an 8-year-old KHE patient with bilateral symmetrical sites involving both femurs. The laboratory, radiographic, and pathological findings of the patient were minutely described. During the 6-month follow-up, the symptoms of pain and dysfunction of this patient were relieved. This study aimed to arouse clinicians’ concern about the symmetrical sites of KHE patients.

This study centers on the use of smart technology to improve the lifecycle management of underground facilities. It presents a comprehensive digital solution that addresses the challenges of underground facilities, particularly those related to the extensive use of underground space, as well as the requirements for safety, sustainability, and quality of services. The proposed solution emerged from discussions with experts, companies, and cities involved in the design, construction, and management of underground facilities. In this paper, we first discuss the major challenges of underground facilities, then, we present the development of a smart solution to address these challenges. This study demonstrates a promising perspective for the use of smart technology in the optimal management of underground facilities, and paves the way for its implementation.

Sweet sorghum (Sorghum dochna) is a high-quality bio-energy crop that also serves as food for humans and animals. However, there is little information on the genomic characteristics of S. dochna. In this study, we presented a high-quality assembly of S. dochna with PacBio long reads, Illumina short reads, high-throughput chromosome capture technology (Hi-C) sequencing data, gene annotation, and a comparative genome analysis. The results showed that the genome of S. dochna was assembled to 777 Mb with a contig N50 of 553.47 kb and a scaffold N50 of 727.11 kb. In addition, the gene annotation predicted 37,971 genes and 39,937 transcripts in the genome of S. dochna. A Venn analysis revealed a set of 7,988 common gene annotations by integrating five databases. A Cafe software analysis showed that 191 gene families were significantly expanded, while 3,794 were significantly contracted in S. dochna. A GO enrichment analysis showed that the expanded gene families were primarily clustered in the metabolic process, DNA reconstruction, and DNA binding among others. The high-quality genome map constructed in this study provides a biological basis for the future analysis of the biological characteristics of S. dochna, which is crucial for its breeding.

Polyion complex (PIC) materials have been widely used in biosensors due to their molecular selectivity. However, achieving both widely controllable molecular selectivity and long-term solution stability with traditional PIC materials has been challenging due to the different molecular structures of polycations (poly-C) and polyanions (poly-A). To address this issue, we propose a novel polyurethane (PU)-based PIC material in which the main chains of both poly-A and poly-C are composed of PU structures. In this study, we electrochemically detect dopamine (DA) as the analyte and L-ascorbic acid (AA) and uric acid (UA) as the interferents to evaluate the selective property of our material. The results show that AA and UA are significantly eliminated, while DA can be detected with a high sensitivity and selectivity. Moreover, we successfully tune the sensitivity and selectivity by changing the poly-A and poly-C ratios and adding nonionic polyurethane. These excellent results were employed in the development of a highly selective DA biosensor with a detection range from 500 nM to 100 μM and a 3.4 μM detection limit. Overall, our novel PIC-modified electrode has the potential to advance biosensing technologies for molecular detection.

In recent years, carbon films have attracted interest as electrode materials for electrochemical sensors due to their wide potential window and acceptable electrochemical activity. The films can be fabricated into electrodes of any shape and size. The electrochemical performance of the films depends on their structural features such as the ratio of the sp2 and sp3 bonds, and the surface functional groups. Here, we report the control of both structure and electrochemical properties based on carbon films fabricated by easily available direct current (DC) magnetron sputtering equipment. The sp3 concentration (sp3/sp3 + sp2) can be controlled from 0.22 to 0.29 by changing the substrate bias power, which can be characterized with X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The potential window became wider as the sp3 concentration increased, similar to the results we previously obtained with films formed by unbalanced magnetron (UBM) sputtering. The electrochemical properties of DC magnetron sputtered carbon films were examined with four species, namely Ru(NH3)62+/3+, Fe(CN)63−/4−, Fe2+/3+, and dopamine. The peak separation of these species depended on the content of the edge plane of the film for Fe(CN)63−/4− and surface functional groups containing oxygen for Fe2+/3+, and both edge plane and surface oxygen-containing groups for dopamine. These results indicate that our carbon films perform sufficiently well for use in electroanalysis and are not inferior to previously reported carbon film electrodes.

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that uniquely changes the chromosomal structure, although the basis of aberrant gene expression in SCLC remains largely unclear. Topologically associated domains (TADs) are structural and functional units of the human genome. Genetic and epigenetic alterations in the cancer genome can lead to the disruption of TAD boundaries and may cause gene dysregulation. To understand the potential regulatory role of this process in SCLC, we developed the TAD boundary alteration–related gene identification in tumors (TARGET) computational framework, which enables the systematic identification of candidate dysregulated genes associated with altered TAD boundaries. Using TARGET to compare gene expression profiles between SCLC and normal human lung fibroblast cell lines, we identified >100 genes in this category, of which 24 were further verified in samples from patients with SCLC using NanoString. The analysis revealed synergistic chromatin structure alteration at the A/B compartment and TAD boundary levels that underlies aberrant gene expression in SCLC. TARGET is a novel and powerful tool that can be used to explore the relationship of chromatin structure alteration to gene dysregulation related to SCLC tumorigenesis, progression, and prognosis.

The role of natural killer (NK) cells in juvenile-onset recurrent respiratory papillomatosis (JORRP) patients remains elusive. In this study, we find increased NK cell percentage, particularly CD11b-CD27- (DN) subsets in peripheral blood of JORRP patients and associated with disease activity. RNA sequencing shows a downregulated “natural killer cell-mediated cytotoxicity” feature in JORRP tumors. We also find impaired cytotoxic capacity and lower expression of NK cell-activating receptors including NKp30 and NKp46. Higher transforming growth factor-beta 1 (TGF-β1) is found both in plasma and tumor tissues of JORRP, and anti-TGF-β1 antibody could restore NK cell cytolytic activity and upregulate NKp30 and NKG2D expression. Also, we find a significantly higher Chemokine receptor type 6 (CXCR6) on NK cells in tumors compared with that in peripheral blood. Finally, RT-PCR analysis show that both HPV6-E6-E7 and HPV11-E6-E7 overexpression leads to higher TGFB1 expression compared with control SNU-1076 cell line, and higher CXCR6 expression is detected on NK coculture with HPV11-E6-E7-overexpressing cells. In conclusion, we demonstrate that TGF-β1 by papillomatosis leads to decreased NK cell cytotoxicity through downregulating NK cell-activating receptors in JORRP patients.

Controlled release phosphorus (P) fertilizers and humic acid (HA) applications are two effective and significant techniques or measures for preventing P loss and enhancing maize development. However, the underlying physiological mechanism of how the controlled release P fertilizers combined with HA affect the maize production and P-use efficiency (PUE) remains unknown. The effects of applying coated diammonium phosphate (CDAP) and HA together on soil nutrient supply intensity, soil phosphatase activity, photosynthesis, endogenous hormone contents, and yield of maize, as well as PUE, were examined in this study. In a pot experiment, two types of P fertilizers—CDAP and diammonium phosphate (DAP)– as well as two HA application rates (0 and 45 kg ha–1) and two P levels (60 and 75 kg P2O5 ha–1) were utilized. Results showed that the key elements that influence the growth and yield of the maize were the availability of P content in soil, plant photosynthesis, and hormone levels. The combination of CDAP and HA had a greater impact on yield and PUE over the course of 2 years than either DAP alone or DAP combined with HA. Besides, using CDAP in combination with HA increased the yield and PUE by 4.2 and 8.4%, respectively, as compared to the application of CDAP alone at 75 kg P2O5 ha–1. From the twelve-leaf to milk stages, the available P content in the soil was increased by an average of 38.6% with the combination of CDAP and HA compared to the application of CDAP alone at 75 kg P2O5 ha–1. In addition, the application of CDAP combined with HA boosted the activities of ATP synthase, as well as the content of cytokinin (CTK), and hence improved the maize photosynthetic rate (Pn). When compared to the application of CDAP alone or DAP combined with HA, the Pn of CDAP + HA treatments was enhanced by 17.9–35.1% at the same P rate. In conclusion, as an environmentally friendly fertilizer, the combined application of CDAP and HA improved the intensity of the soil nutrient supply, regulated photosynthetic capabilities, and increased the yield and PUE, which is important for agricultural production, P resource conservation, and environmental protection.

Abstract This letter proposes a fully domain‐independent WiFi‐based gesture recognition system based on the multi‐label adversarial network. Unlike pioneer machine learning works, our system does not require retraining in the target domain, which benefits from our key idea of eliminating fully domain information such as orientations, locations, environment information. The system proposed by us includes three parts: Feature extractor, domain discriminator, and gesture recogniser. The feature extractor attempts to deceive the domain discriminator based on the adversarial network structure so that it is difficult to judge the input domain label, thereby obtaining domain‐independent features and realising fully domain‐independent gesture recognition. Extensive experiments are conducted on the Widar 3.0 dataset and our dataset to evaluate system performance. The results show that our system can achieve an in‐domain recognition accuracy of 93.2% and a cross‐domain recognition accuracy of 87.1%, which is superior to other state‐of‐the‐art works.

Abstract Background Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. Methods We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. Results A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28–2.57, p

Background: Sirolimus, a mammalian target of rapamycin inhibitor, has been widely used in pediatric patients, but the safety of sirolimus in pediatric patients has not been well determined. Objective: The objective of this study was to systematically evaluate prospective studies reporting the safety of sirolimus in the treatment of childhood diseases. Methods: The following data were extracted in a standardized manner: study design, demographic characteristics, intervention, and safety outcomes. Results: In total, 9 studies were included, encompassing 575 patients who received oral sirolimus for at least 6 months. Various adverse events occurred. The most common adverse event was oral mucositis (8.2%, 95% CI: 0.054 to 0.110). Through comparative analysis of the subgroups based on the targeted concentration range, we discovered that many adverse events were significantly higher in the high concentration group (≥10 ng/mL) than in the low concentration group (p < 0.01). More interestingly, we found that oral mucositis was more frequently reported in children with vascular anomalies than tuberous sclerosis complex. Conclusions: This study shows that oral sirolimus in the treatment of childhood diseases is safe and reliable. However, sirolimus treatment in the pediatric population should be strictly monitored to reduce the occurrence of serious or fatal adverse events.

The apparent friction force of spherical convex textured rigid bodies sliding on soft materials was tested and analyzed in order to develop the technology of friction increment for frictional transmission. The rigid bodies were made of Polylactic Acid (PLA) by 3D printing, and the counterparts were made of Ethylene Propylene Diene Monomer (EPDM). Experimental results show that the spherical convex surface texture increased the friction coefficient effectively compared to that of non-textured couples. The parameters include the radius of the texture, the hardness of the soft material and the normal load play important roles in the friction increment. The mechanism of the friction increment was analyzed. The apparent friction force consists of sliding friction force and ploughing force. The ploughing force which induced by the embedment of the spherical convex texture in the soft material depends on the normal force and therefore has influence on the equivalent friction coefficient. The effective angle and embedment number were proposed to model the contact state of the friction couples. The nonlinear dependence of the embedment number on the parameters of spherical convex textures and the properties of the soft materials was analyzed. The summarized model based on the experimental result can be used to predict the equivalent friction coefficient.

Tayi tunnel is one of the component tunnels in the Jian-Ge-Yuan Highway Project located in Yunnan Province, southeast of China. It mainly passes through talus-like formations comprised of rock blocks of diverse sizes and weak interlayers with clayey soils with different fractions. Such a special composition leads to the loose and fractured structure of talus-like formations, which is highly sensitive to the excavation perturbation. Therefore, Tayi tunnel has become the controlled pot of the whole highway project as the construction speed has to be slowed down to reduce the deformation of surrounding talus-like rock mass. To better understand the tunnel-induced ground response and the interaction between the surrounding rock mass and tunnel lining, a comprehensive in situ monitoring program was set up. The in situ monitoring contents included the surrounding rock pressure on the primary lining, the primary lining deformation, and the stress of steel arches. Based on the monitoring data, the temporal and the long-term spatial characteristics of mechanical behavior of surrounding rock mass and lining structure due to the excavation process were analyzed and discussed. It is found that the excavation of lower benches released the surrounding rock pressure around upper benches, resulting in the decrease of the surrounding rock pressure on the primary lining and the stress of steel arches. In addition, the monitoring data revealed that the primary lining sustained bias pressure from the surrounding rock mass, which thereby caused unsymmetrical deformation of the primary lining, in accordance with the monitored displacement data. A dynamically adaptive support system was implemented to strengthen the bearing capacity of the lining system especially in the region of an extremely weak rock mass. After such treatment, the deformation of the primary lining has been well controlled and the construction speed has been considerably enhanced.

The most severe problem in bone regeneration is the defect in the interface. We prepared four types of implantation scaffolds of crosslinked gelatin (GE)/hydroxyapatite (HAp) to study the factors influencing interface interactions, they are film-crosslinked GE scaffold, gel-crosslinked GE scaffold, solid-crosslinked GE/HAp scaffold and gel-crosslinked GE/HAp scaffold. HAp could penetrate the entire GE matrix completely in four successive steps: physical preparation of a gel; chemical crosslinking; incubation in modified simulated body fluid (m-SBF) and freeze-drying. The penetrative nucleation and growth of HAp and the influencing factors in the GE matrix were investigated to ameliorate the interface interactions between organic and inorganic layers. During development of penetrative nucleation and growth, a tight connection was built between organic and inorganic layers, B-type carbonated HAp was formed after incubation with m-BSF, and the apatite content could be controlled. In summary, enhanced interface relies on not only the pre-seeded hydroxyapatite (HAp) as crystal nuclei but also the sufficient space for ions with high concentration to diffuse in.

Crop genetics: plants that can take the heat Researchers in China have engineered chrysanthemum plants with increased heat tolerance. Studies in model species have shown that the plant gene CPL1 is involved in their response to many kinds of stress, including temperature, drought, and salinity. Using the CPL1 sequence from studied species as a guide, Jiafu Jian’s team at Nanjing Agricultural University isolated the gene in chrysanthemum. They found that CPL1 is expressed most strongly in leaf cells and remains in the cells’ nucleus. CPL1 expression increased in plants which were exposed to stressful conditions, especially heat. When the researchers engineered chrysanthemum with artificially increased levels of CPL1, the plants were better able to tolerate heat; by contrast, plants with reduced CPL1 levels were more sensitive to heat stress. Altogether, these findings point the way towards breeding or engineering heat-tolerant chrysanthemum varieties.

Yucca schidigera Roezl (Mojave), a kind of ornamental plant belonging to the Yucca genus (Agavaceae), whose extract exhibits important roles in food, beverage, cosmetic and feed additives owing to its rich spirostanol saponins. To provide a comprehensive chemical profiling of the spirostanol saponins in it, this study was performed by using a multi-phase liquid chromatography method combining a reversed phase chromatography T3 column with a normal phase chromatography silica column for the separation and an ESI-Q-Exactive-Orbitrap MS in positive ion mode as the detector. By comparing the retention time and ion fragments with standards, thirty-one spirostanol saponins were identified. In addition, according to the summary of the chromatographic retention behaviors and the MS/MS cleavage patterns and biosynthetic pathway, another seventy-nine spirostanol saponins were speculatively identified, forty ones of which were potentially new ones. Moreover, ten novel spirostanol saponins (three pairs of (25R/S)-spirostanol saponin isomer mixtures) were targeted for isolation to verify the speculation. Then, the comprehensive chemical profiling of spirostanol saponins from Y. schidigera was reported here firstly.

AIMS:Guidelines divide patients with heart failure (HF) into 3 distinct groups based on left ventricular ejection fraction (LVEF) We used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to quantify the health-related quality of life in patients with HF. METHODS:Patients were stratified into three cohorts: preserved LVEF (>50%), mid-range LVEF (40-49%) and reduced LVEF (