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Abstract Background White rot fungi produce various reactive oxygen species and ligninolytic enzymes for lignocellulose deconstruction. However, their interactions during the deconstruction of lignocellulosic structural barriers for efficient enzymatic saccharification remain unclear. Results Herein, the extracellular enzyme activities and secretomic analysis revealed the sequential expression of hydroxyl radical (⋅OH) and manganese peroxidases (MnPs) for lignocellulose deconstruction by the white rot fungus Irpex lacteus. Subsequently, in vitro functional studies found that ⋅OH possessed the ability to disrupt the smooth surface structure of corn stover, resulting in increased enzymatic saccharification and cellulose accessibility. Purified recombinant MnPs from I. lacteus were able to cleave the β-O-4 bond in phenolic and non-phenolic lignin model dimers without the help of any mediators. Furthermore, the sequential pretreatment of corn stover with ⋅OH and MnP exhibited significant synergistic effects, increasing enzymatic saccharification and cellulose accessibility by 2.9-fold and 1.8-fold, respectively. Conclusions These results proved for the first time the synergistic effects of ⋅OH and MnP pretreatment in improving the enzymatic saccharification and cellulose accessibility of corn stover. These findings also demonstrated the potential application of ⋅OH and MnP pretreatment for the efficient enzymatic saccharification of corn stover. Graphical Abstract

Abstract Background Blood and urine biomarkers have been associated with urologic tumors, but their causal relationship with urologic tumors is unclear. Methods We performed a bidirectional Mendelian randomization (MR) analysis of the association between 35 blood and urine biomarkers and urological tumors in our discovery cohort. A Bayesian weighting approach was used to validate the positive results identified in the discovery cohort, and steiger filtering analysis was used to distinguish causality from reverse causality. Bayesian colocalization analysis was used to analyze which single nucleotide polymorphisms (SNPs) specifically co-located between the positive blood and urine biomarkers and the disease phenotypes were driven, and MR-positive results from the discovery cohort and the validation cohort were combined using the MR-meta method. Results Several blood and urine biomarkers were found to be significantly and causally associated with urologic cancers. Notably, calcium (OR: 1.34, 95%CI 1.10–1.63, P = 0.0040) and sex hormone-binding globulin (SHBG) (OR: 0.81, 95%CI 0.70–0.95, P = 0.0092) were associated with bladder cancer; gamma glutamyl transferase (GGT) (OR: 0.91, 95%CI 0.83–0.99, P = 0.0209), lipoprotein A (Lp(a)) (OR: 1.12, 95%CI 1.01–1.24, P = 0.0399), and insulinlike growth factor 1 (IGF 1) (OR: 1.10, 95%CI 1.01–1.20, P = 0.0220) were linked to prostate cancer (PCa); non albumin protein (OR: 0.78, 95%CI 0.65–0.93, P = 0.0065) and total protein (OR: 0.80, 95%CI 0.64–0.99, P = 0.0380) were linked to renal cancer; and apolipoprotein A (Apo-A) (OR: 0.56, 95%CI 0.32–0.98, P = 0.0426) and urate (OR:1.89, 95%CI 1.03–3.47, P = 0.0399) were associated with renal pelvis cancer. These associations were validated in an independent cohort, with GGT, IGF 1, and Lp(a) being consistently linked to PCa. Conclusion This study identified significant biomarkers associated with urological cancers in blood and urine. These include GGT, IGF 1, and Lp(a), which are strong biomarkers for PCa. In addition, the findings of this study provide evidence for a handful of risk and protective factors for the development of urologic cancers.

Abstract Depression is a prevalent mental disorder characterized by unknown pathogenesis and challenging treatment. Recent meta-analyses reveal an association between cardiovascular risk factors and an elevated risk of depression. Despite this, the precise role of vascular injury in depression development remains unclear. In this investigation, we assess vascular system function in three established animal models of depression— chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS) and maternal separation (MS)—utilizing ultrasonography and laser Doppler measurement. All three model animals exhibit anhedonia and despair-like behavior. However, significant microvascular dysfunction (not macrovascular) is observed in animals subjected to CUMS and CSDS models, while such dysfunction is absent in the MS model. Statistical analysis further indicates that microcirculation dysfunction is not only associated with depression-like behavior but is also intricately involved in the development of depression in the CUMS and CSDS models. Furthermore, our study has proved for the first time that endothelial nitric oxide synthase-deficient (eNOS +/− ) mice, which is a classic model of vascular endothelial injury, showed depression-like behavior which occurred two months later than microvascular dysfunction. Notably, the mitigation of microvascular dysfunction successfully reverses depression-like behavior in eNOS +/− mice by enhancing nitric oxide production. In conclusion, this study unveils the pivotal role of microvascular dysfunction in the onset of depression induced by chronic stress in adulthood and proposes that modulating microvascular function may serve as a potential intervention in the treatment of depression.

Abstract Objectives To explore the performance differences of multiple annotations in radiomics analysis and provide a reference for tumour annotation in large-scale medical image analysis. Methods A total of 342 patients from two centres who underwent radical resection for rectal cancer were retrospectively studied and divided into training, internal validation, and external validation cohorts. Three predictive tasks of tumour T-stage (pT), lymph node metastasis (pLNM), and disease-free survival (pDFS) were performed. Twelve radiomics models were constructed using Lasso-Logistic or Lasso-Cox to evaluate and four annotation methods, 2D detailed annotation along tumour boundaries (2D), 3D detailed annotation along tumour boundaries (3D), 2D bounding box (2DBB), and 3D bounding box (3DBB) on T2-weighted images, were compared. Radiomics models were used to establish combined models incorporating clinical risk factors. The DeLong test was performed to compare the performance of models using the receiver operating characteristic curves. Results For radiomics models, the area under the curve values ranged from 0.627 (0.518–0.728) to 0.811 (0.705–0.917) in the internal validation cohort and from 0.619 (0.469–0.754) to 0.824 (0.689–0.918) in the external validation cohort. Most radiomics models based on four annotations did not differ significantly, except between the 3D and 3DBB models for pLNM (p = 0.0188) in the internal validation cohort. For combined models, only the 2D model significantly differed from the 2DBB (p = 0.0372) and 3D models (p = 0.0380) for pDFS. Conclusion Radiomics and combined models constructed with 2D and bounding box annotations showed comparable performances to those with 3D and detailed annotations along tumour boundaries in rectal cancer characterisation and prognosis prediction. Critical relevance statement For quantitative analysis of radiological images, the selection of 2D maximum tumour area or bounding box annotation is as representative and easy to operate as 3D whole tumour or detailed annotations along tumour boundaries. Key Points There is currently a lack of discussion on whether different annotation efforts in radiomics are predictively representative. No significant differences were observed in radiomics and combined models regardless of the annotations (2D, 3D, detailed, or bounding box). Prioritise selecting the more time and effort-saving 2D maximum area bounding box annotation. Graphical Abstract

Abstract Background Methyl methacrylate (MMA) is a key precursor of polymethyl methacrylate, extensively used as a transparent thermoplastic in various industries. Conventional MMA production poses health and environmental risks; hence, citramalate serves as an alternative bacterial compound precursor for MMA production. The highest citramalate titer was previously achieved by Escherichia coli BW25113. However, studies on further improving citramalate production through metabolic engineering are limited, and phage contamination is a persistent problem in E. coli fermentation. Results This study aimed to construct a phage-resistant E. coli BW25113 strain capable of producing high citramalate titers from glucose. First, promoters and heterologous cimA genes were screened, and an effective biosynthetic pathway for citramalate was established by overexpressing MjcimA3.7, a mutated cimA gene from Methanococcus jannaschii, regulated by the BBa_J23100 promoter in E. coli. Subsequently, a phage-resistant E. coli strain was engineered by integrating the Ssp defense system into the genome and mutating key components of the phage infection cycle. Then, the strain was engineered to include the non-oxidative glycolysis pathway while removing the acetate synthesis pathway to enhance the supply of acetyl-CoA. Furthermore, glucose utilization by the strain improved, thereby increasing citramalate production. Ultimately, 110.2 g/L of citramalate was obtained after 80 h fed-batch fermentation. The citramalate yield from glucose and productivity were 0.4 g/g glucose and 1.4 g/(L·h), respectively. Conclusion This is the highest reported citramalate titer and productivity in E. coli without the addition of expensive yeast extract and additional induction in fed-bath fermentation, emphasizing its potential for practical applications in producing citramalate and its derivatives.

Abstract Tumor‐derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin‐specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreover, USP22 regulates endocytosis of tumor cells and localizes to late endosomes. However, the role of USP22 in the secretion of tumor cell‐derived EVs remains unknown. In this study, it demonstrates that USP22 increases the secretion of tumor cell‐derived EVs and accelerates their migration and invasion, invadopodia formation, and angiogenesis via EV transfer. USP22 enhances EV secretion by upregulating myosin IB (MYO1B). This study further discovers that USP22 activated the SRC signaling pathway by upregulating the molecule KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1), thereby contributing to LUAD cell progression. The study provides novel insights into the role of USP22 in EV secretion and cell motility regulation in LUAD.

High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies on the regulation of heat stress by WRKY transcription factors, especially in tomato. Here, we identified a group I WRKY transcription factor, SlWRKY3, involved in thermotolerance in tomato. First, SlWRKY3 was induced and upregulated under heat stress. Accordingly, overexpression of SlWRKY3 led to an increase, whereas knock-out of SlWRKY3 resulted in decreased tolerance to heat stress. Overexpression of SlWRKY3 accumulated less reactive oxygen species (ROS), whereas knock-out of SlWRKY3 accumulated more ROS under heat stress. This indicated that SlWRKY3 positively regulates heat stress in tomato. In addition, SlWRKY3 activated the expression of a range of abiotic stress-responsive genes involved in ROS scavenging, such as a SlGRXS1 gene cluster. Further analysis showed that SlWRKY3 can bind to the promoters of the SlGRXS1 gene cluster and activate their expression. Collectively, these results imply that SlWRKY3 is a positive regulator of thermotolerance through direct binding to the promoters of the SlGRXS1 gene cluster and activating their expression and ROS scavenging.

Background Lung adenocarcinoma is the most common type of lung cancer, accounting for approximately 40% of all lung cancer cases, and has the highest incidence among lung cancer subtypes. Recent studies have suggested that long non-coding RNAs (lncRNAs) play a crucial role in the initiation and progression of lung adenocarcinoma.Methods Based on integrative analysis through databases, we screened Long intergenic non-protein coding RNA 00839 (LINC00839) as one of the most highly upregulated lncRNAs in lung adenocarcinoma. In vitro and in vivo experiments demonstrated that LINC00839 promotes lung adenocarcinoma proliferation, migration, and invasion and that it is present in exosomes secreted by lung adenocarcinoma cells.Results In the cytoplasm, LINC00839 regulates the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway by acting as a molecular sponge of miR-17-5p, thereby influencing the biological behavior of lung adenocarcinoma cells. LINC00839 binds to Polypyrimidine tract binding protein 1 (PTBP1) in the nucleus to regulate the nuclear translocation of NF-κB p65 molecules and, consequently, the transcription of downstream molecules.Conclusions Our study confirmed that LINC00839 promotes the biological progression of lung adenocarcinoma by performing dual roles in the cytoplasm and nucleus to co-regulate the NF-κB signaling pathway.

Abstract Rapid and visual detection of SARS‐CoV‐2 variants is vital for timely assessment of variant transmission in resource‐limited settings. Here, a closed‐tube, two‐stage, mixed‐dye‐based isothermal amplification method with ribonuclease‐cleavable enhanced probes (REP), termed REP‐TMAP, for dual‐visualization detection of SARS‐CoV‐2 variants including JN.1, BA.2, BA.4/5, and Delta is introduced. The first stage of REP‐TMAP is reverse transcription recombinase polymerase amplification and the second stage is dual‐visualization detection synergistically mediated by the REP and the mixed dyes of cresol red and hydroxy naphthol blue. In REP‐TMAP reaction, the color change under ambient light indicates SARS‐CoV‐2 infection, while the fluorescence change under blue light excitation specifies variant type. On detecting transcribed RNA of SARS‐CoV‐2 spike gene, this assay is rapid (within 40 min), highly sensitive (10–200 copies per reaction), and highly specific (identification of single‐base mutations). Furthermore, the assay has been clinically validated to accurately detect JN.1, BA.2, and BA.4/5 variants from 102 human oropharyngeal swabs. The proposed assay therefore holds great potentials to provide a rapid, dual‐visualization, sensitive, specific, point‐of‐care detection of SARS‐CoV‐2 variants and beyond.

Color is an important factor in determining a consumer's desire to buy and an important indicator of meat quality. Processing and storage processes affect the color of meat products. Therefore, research on how to improve the color of meat products can not only improve the quality of meat products but also enhance a consumer's desire to buy. Nitrosomyoglobin is known to be the main substance that exerts color in meat products. Meanwhile, meat products undergo a series of chemical and physical changes during the curing process that also affect the color of cured meat products. This paper reviews the six main factors currently affecting the color of cured meat products: (1) Quality of raw meat and the content of myoglobin; (2) physical structure of the muscle and achromatic aberration; (3) lipid oxidation; (4) Maillard reaction; (5) additives; and (6) packaging methods. In addition, the article also explores the relationship between pH, temperature, water retention and color in cured meat products, in order to provide more ideas for the study of color in cured meat products.

Radar is a valuable tool for noncontact vital-sign detection. Interference from respiratory harmonics presents a major challenge in radar cardiogram (RCG) extraction—mainly when the frequency of respiratory harmonics is close to or equal to that of the cardiac sub-signals. To address this problem, a respiratory harmonic suppression method employing correlation analysis and an optimized feedback notch filter is proposed, which is based on 7.29 GHz center-frequency impulse-radio ultra-wideband radar. A genetic optimization algorithm is employed to optimize the parameters of the notch filter. Performance comparison analysis is conducted on the conventional notch filter and the feedback notch filter. Contact (ECG) and non-contact (RCG) data from 10 subjects were analyzed. The results verified that the performance of the optimized feedback notch filter is much better than that of the conventional notch filter in overshoot, bandwidth, and notch depth, and the proposed method can effectively locate, identify, and suppress respiratory harmonics from the RCG band while preserving heartbeat components. Consequently, this approach markedly enhances the precision of RCG extraction. The technique shows considerable promise for deployment in diverse practical settings, including non-contact auxiliary monitoring systems in both intelligent medical environments and home healthcare.

Fermented sausage is a fermented meat product favored by a large number of of consumers. In fermented sausages, the formation of gel is one of the key steps, and its composition mainly includes meat protein and fat, among which myofibrillar protein is essential for the gel properties of fermented sausages. During the processing of fermented sausages, the myofibrillar protein and myosin in the meat are deformed, losing their original solubility and becoming a gel substance, while the metabolites and enzymes of microorganisms in the fermented sausage can interact with the protein and fat in the meat to promote the formation of gel, thereby helping to improve the texture, water retention and taste of the fermented sausage. In this paper, the formation mechanism of gel properties of fermented sausage was comprehensively discussed, the effects of lactic acid bacteria, temperature, and other factors on the gel properties of fermented sausage were analyzed, and the research methods of gel properties were introduced. The aim was to provide a basis for the control of process parameters in the processing of fermented sausage and to provide a reference for further improving the gel quality of fermented sausage.

Abstract Purpose Pulmonary sarcoidosis (PS) and pulmonary lymphangitic carcinomatosis (PLC) can be complications in tumor patients, and both involve the pulmonary interstitium and have similar imaging findings. Our objective was to distinguish PS and PLC on 18F-FDG PET/CT images. Material and methods The authors reviewed 18F-FDG PET/CT data of PS and PLC, diagnosed based on histopathology and imaging, in patients with tumors from July 2015 to January 2023. Three independent readers performed a blinded comparative analysis of 18F-FDG PET/CT signs in all patients. A multivariate logistic regression model was used to establish a differential diagnosis model. Results A total of 114 patients were included in the study: 56 patients with PS (mean age, 56 ± 11 [SD] years; 10 men) and 58 patients with PLC caused by extrapulmonary tumors (mean age, 51 ± 11 [SD] years; 21 men). For PS, breast cancer and cervical cancer were the most common primary tumors. For PLC, breast cancer and gastric cancer were the most common extrapulmonary tumors. The model constructed using multivariate logistic regression consisted of five factors: area of lymph node involvement, bronchovascular bundle diffuse thickening, interlobular septal thickening, pleural effusion, and subpleural hypermetabolic activity. The area under the model characteristic curve was 0.973 (95% CI 0.925–0.994), with a sensitivity, specificity, and positive and negative likelihood ratios of 87.50%, 98.28%, 50.75 and 0.13 respectively. Conclusion There are detailed differences in 18F-FDG PET/CT manifestations of PS in tumor patients and PLC caused by extrapulmonary tumors, and the constructed diagnostic model has high clinical application value in differentiating the two.

Abstract Background Microvascular invasion (MVI) is the main factor affecting the prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify accurate diagnostic biomarkers from urinary protein signatures for preoperative prediction. Methods We conducted label-free quantitative proteomic studies on urine samples of 91 HCC patients and 22 healthy controls. We identified candidate biomarkers capable of predicting MVI status and combined them with patient clinical information to perform a preoperative nomogram for predicting MVI status in the training cohort. Then, the nomogram was validated in the testing cohort (n = 23). Expression levels of biomarkers were further confirmed by enzyme-linked immunosorbent assay (ELISA) in an independent validation HCC cohort (n = 57). Results Urinary proteomic features of healthy controls are mainly characterized by active metabolic processes. Cell adhesion and cell proliferation-related pathways were highly defined in the HCC group, such as extracellular matrix organization, cell–cell adhesion, and cell–cell junction organization, which confirms the malignant phenotype of HCC patients. Based on the expression levels of four proteins: CETP, HGFL, L1CAM, and LAIR2, combined with tumor diameter, serum AFP, and GGT concentrations to establish a preoperative MVI status prediction model for HCC patients. The nomogram achieved good concordance indexes of 0.809 and 0.783 in predicting MVI in the training and testing cohorts. Conclusions The four-protein-related nomogram in urine samples is a promising preoperative prediction model for the MVI status of HCC patients. Using the model, the risk for an individual patient to harbor MVI can be determined.

Sodium-ion batteries (SIBs) have garnered significant interest due to their potential as viable alternatives to conventional lithium-ion batteries (LIBs), particularly in environments where low-temperature (LT) performance is crucial. This paper provides a comprehensive review of current research on LT SIBs, focusing on electrode materials, electrolytes, and operational challenges specific to sub-zero conditions. Recent advancements in electrode materials, such as carbon-based materials and titanium-based materials, are discussed for their ability to enhance ion diffusion kinetics and overall battery performance at colder temperatures. The critical role of electrolyte formulation in maintaining battery efficiency and stability under extreme cold is highlighted, alongside strategies to mitigate capacity loss and cycle degradation. Future research directions underscore the need for further improvements in energy density and durability and scalable manufacturing processes to facilitate commercial adoption. Overall, LT SIBs represent a promising frontier in energy storage technology, with ongoing efforts aimed at overcoming technical barriers to enable widespread deployment in cold-climate applications and beyond.

Aboveground biomass (AGB) is a vital indicator for studying carbon sinks in forest ecosystems. Semiarid forests harbor substantial carbon storage but received little attention due to the high spatial–temporal heterogeneity that complicates the modeling of AGB in this environment. This study assessed the performance of different data sources (annual monthly time-series radar was Sentinel-1 [S1]; annual monthly time series optical was Sentinel-2 [S2]; and single-temporal airborne light detection and ranging [LiDAR]) and seven prediction approaches to map AGB in the semiarid forests on the border between Gansu and Qinghai Provinces in China. Five experiments were conducted using different data configurations from synthetic aperture radar backscatter, multispectral reflectance, LiDAR point cloud, and their derivatives (polarimetric combination indices, texture information, vegetation indices, biophysical features, and tree height- and canopy-related indices). The results showed that S2 acquired better prediction (coefficient of determination [R2]: 0.62–0.75; root mean square error [RMSE]: 30.08–38.83 Mg/ha) than S1 (R2: 0.24–0.45; RMSE: 47.36–56.51 Mg/ha). However, their integration further improved the results (R2: 0.65–0.78; RMSE: 28.68–35.92 Mg/ha). The addition of single-temporal LiDAR highlighted its structural importance in semiarid forests. The best mapping accuracy was achieved by XGBoost, with the metrics from the S2 and S1 time series and the LiDAR-based canopy height information being combined (R2: 0.87; RMSE: 21.63 Mg/ha; relative RMSE: 14.45%). Images obtained during the dry season were effective for AGB prediction. Tree-based models generally outperformed other models in semiarid forests. Sequential variable importance analysis indicated that the most important S1 metric to estimate AGB was the polarimetric combination indices sum, and the S2 metrics were associated with red-edge spectral regions. Meanwhile, the most important LiDAR metrics were related to height percentiles. Our methodology advocates for an economical, extensive, and precise AGB retrieval tailored for semiarid forests.

Abstract Background As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. Methods We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co‐mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. Results Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI‐positive and one was MVI‐negative, and there was a co‐occurrence of TERTp and TP53 (p

Abstract Designing a theranostic probe for noninvasive bone imaging and bone disease therapy is both challenging and desirable. Herein, an ultrasmall Au nanocluster (NC,

This study investigated the alleviating effect of Lacticaseibacillus paracasei IMAUJBC1 on hyperlipidemia and explored the associated mechanism by combining microbiome, transcriptomic, and lipomic analyses. The high-fat mouse model was established with a high-fat diet (HFD), and the intervention of IMAUJBC1 was conducted for 8 weeks after modeling. The results showed that IMAUJBC1 inhibited weight gain and liver fat accumulation in HFD mice, reduced total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C) serum levels, promoted the conversion of liver cholesterol to total bile acid (TBA), and increased fecal T-CHO excretion. The IMAUJBC1 intervention decreased the ratio of Firmicutes and Bacteroidetes, while the abundance of Alistipes was increased in the mice intestinal microbiome. IMAUJBC1 may alleviate hyperlipidemia through the PPAR signaling pathway, fat digestion and absorption, cholesterol metabolism, and glycerophospholipid metabolism. In summary, IMAUJBC1 can be used as a functional lactobacillus to intervene in hyperlipidemia.

Global concern exists regarding the contamination of food and animal feed with aflatoxin B1 (AFB1), which poses a threat to the health of both humans and animals. Previously, we found that a laccase from Bacillus subtilis (BsCotA) effectively detoxified AFB1 in a reaction mediated by methyl syringate (MS), although the underlying mechanism has not been determined. Therefore, our primary objective of this study was to explore the detoxification mechanism employed by BsCotA. First, the enzyme and mediator dependence of AFB1 transformation were studied using the BsCotA-MS system, which revealed the importance of MS radical formation during the oxidation process. Aflatoxin Q1 (AFQ1) resulting from the direct oxidation of AFB1 by BsCotA, was identified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results of UPLC-MS/MS and density functional theory calculations indicated that the products included AFQ1, AFB1-, and AFD1-MS-coupled products in the BsCotA-MS system. The toxicity evaluations revealed that the substances derived from the transformation of AFB1 through the BsCotA-MS mechanism exhibited markedly reduced toxicity compared to AFB1. Finally, we proposed a set of different AFB1-transformation pathways generated by the BsCotA-MS system based on the identified products. These findings greatly enhance the understanding of the AFB1-transformation mechanism of the laccase-mediator system.

Abstract Background Lianhua Qingke (LHQK) is an effective traditional Chinese medicine used for treating acute tracheobronchitis. In this study, we evaluated the effectiveness of LHQK in managing airway mucus hypersecretion in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods The AECOPD model was established by subjecting male Wistar rats to 12 weeks of cigarette smoke (CS) exposure (80 cigarettes/day, 5 days/week for 12 weeks) and intratracheal lipopolysaccharide (LPS) exposure (200 μg, on days 1, 14, and 84). The rats were divided into six groups: control (room air exposure), model (CS + LPS exposure), LHQK (LHQK-L, LHQK-M, and LHQK-H), and a positive control group (Ambroxol). H&E staining, and AB-PAS staining were used to evaluate lung tissue pathology, inflammatory responses, and goblet cell hyperplasia. RT-qPCR, immunohistochemistry, immunofluorescence and ELISA were utilized to analyze the transcription, expression and secretion of proteins related to mucus production in vivo and in the human airway epithelial cell line NCI-H292 in vitro. To predict and screen the active ingredients of LHQK, network pharmacology analysis and NF-κB reporter system analysis were employed. Results LHQK treatment could ameliorate AECOPD-triggered pulmonary structure damage, inflammatory cell infiltration, and pro-inflammatory cytokine production. AB-PAS and immunofluorescence staining with CCSP and Muc5ac antibodies showed that LHQK reduced goblet cell hyperplasia, probably by inhibiting the transdifferentiation of Club cells into goblet cells. RT-qPCR and immunohistochemistry of Muc5ac and APQ5 showed that LHQK modulated mucus homeostasis by suppressing Muc5ac transcription and hypersecretion in vivo and in vitro, and maintaining the balance between Muc5ac and AQP5 expression. Network pharmacology analysis and NF-κB luciferase reporter system analysis provided insights into the active ingredients of LHQK that may help control airway mucus hypersecretion and regulate inflammation. Conclusion LHQK demonstrated therapeutic effects in AECOPD by reducing inflammation, suppressing goblet cell hyperplasia, preventing Club cell transdifferentiation, reducing Muc5ac hypersecretion, and modulating airway mucus homeostasis. These findings support the clinical use of LHQK as a potential treatment for AECOPD.

Ceramic microcomponents have a wide range of applications in microfluidic, sensors, etc. Stereolithography 3D printing technology provided a shortcut for the preparation of this small-size and complex component. With the development of device miniaturization, the existing stereolithography forms cannot meet the demand. To prepare smaller components, it is necessary to decrease the slice thickness (Cs). But during the stereolithography 3D printing, ceramic is usually easy to over-cure, leading to the key issue in the stereolithography of ceramic microcomponents: the mismatching between the curing thickness (Cp) and the slice thickness (Cs). To solve the problem above, this paper started from the stereolithography mechanism of the ceramic/resin slurry and adjusted the matching relationship between Cp and Cs theoretically by adding a photoabsorber. Then, from the experiments, the influence of different content of photoabsorber (carbon black) on curing thickness, printing accuracy, and sintering accuracy, were studied. Al2O3 ceramic microcomponents that met the design requirements were thus prepared. These results would help in the development of stereolithography 3D printing of ceramic microcomponents.

Abstract Background Gastric cancer (GC) ranks as the fifth most common cancer worldwide and is characterized by its significant heterogeneity and unfavorable prognosis. Thus, identifying efficient prognostic factors and understanding the underlying molecular mechanisms in GC are essential for improving patient outcomes. In this study, we aimed to investigate the role of RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the prognostic significance and molecular mechanisms of its biological function in GC. Methods Multiple bioinformatics strategies were performed to detect the potential functions and prognostic efficiency of RECK in GC. Rescue experiments revealed that the molecular mechanism by which RECK in inhibited tumor proliferation, migration, and invasion was mediated by ERK/MAPK signaling in AGS and HGC-27 cells. Using integrated bioinformatics analysis and western blot assay, we investigated the potential interaction between CALD1 and RECK. Results Our findings revealed significantly decreased RECK expression in GC samples compared to normal samples and RECK was identified as a promising predictor for the prognosis of GC patients. Moreover, upregulation of RECK demonstrated a distinctly positive association with a high-immunity and low-metastasis microenvironment in GC. Mechanistically, the antitumour effects of RECK on hampering tumor cell growth, migration, and invasion were mediated by the ERK/MAPK signaling pathway. In addition, we also illustrated that RECK inhibited the phosphorylation of CALD1 mediated by decreased phosphorylation of ERK. Conclusions RECK is a promising prognostic biomarker and may shape a high-tumor-immunity and low-metastasis microenvironment in patients with GC. Moreover, RECK exerted its tumor-suppressive effects by the inactivation of ERK/MAPK signaling in GC cells.

Abstract Background This research aimed to develop a model for individualized treatment decision-making in inoperable elderly patients with esophageal squamous cell carcinoma (ESCC) using machine learning methods and multi-modal data. Methods A total of 189 inoperable elderly ESCC patients aged 65 or older who underwent concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) were included. Multi-task learning models were created using machine learning techniques to analyze multi-modal data, including pre-treatment CT images, clinical information, and blood test results. Nomograms were constructed to predict the objective response rate (ORR) and progression-free survival (PFS) for different treatment strategies. Optimal treatment plans were recommended based on the nomograms. Patients were stratified into high-risk and low-risk groups using the nomograms, and survival analysis was performed using Kaplan–Meier curves. Results The identified risk factors influencing ORR were histologic grade (HG), T stage and three radiomic features including original shape elongation, first-order skewness and original shape flatness, while risk factors influencing PFS included BMI, HG and three radiomic features including high gray-level run emphasis, first-order minimum and first-order skewness. These risk factors were incorporated into the nomograms as independent predictive factors. PFS was substantially different between the low-risk group (total score ≤ 110) and the high-risk group (total score > 110) according to Kaplan–Meier curves (P

Objective Specular reflection is a smooth surface formed during the sliding process of rock strata, with a certain metallic and glass luster and reflective properties. In some fault zones, these smooth surfaces are also known as fault mirrors (FMs). Specular reflection can be seen in many rock types, such as mudstone, shale, coal seam, carbonate rock, silicate rock and so on. The mechanism of specular reflection is different in different lithologies, but the formation of specular reflection is related to strata sliding. Therefore, the stress, slip rate, slip distance and temperature related to rock strata sliding have important influence on the formation of specularity. Methods A large amount of specular reflection is developed in the syncline Longmaxi Formation shale in Anchang, northern Guizhou. To find out the factors influencing the formation of specular reflection and the internal relationship between them and the gas content of shale in this paper, the development characteristics and formation mechanism of specular reflection and its effects on fluid flow and shale gas preservation conditions were summarized systematically through a large number of literature reviews. Results The results show that: (1) Stress, slip rate, slip displacement and temperature have important influence on the formation of specular reflection. (2) The formation of specular reflection depends on the combination form of stress and sliding rate. It is easier to form specular reflection under high-speed and high-stress conditions. Under low-speed and low-stress conditions, the specular reflection will not be formed even if the sliding displacement is large. (3) Under the same stress and sliding rate, the overall sliding displacement will promote the increase of specular coverage, and the specular coverage can even reach 100%. (4) The temperature makes the rock particles change from brittle to plastic, which can prevent the brittle fracture of the rock particles to a certain extent, and then sinter the rock particles, prompting the formation of specular reflection. (5) The specular roughness is very low, usually in the micrometer level, the average roughness range is only a few micrometers. (6) Specular cracks and slip distances are formed, which significantly improve the flow of shale gas, accelerated loss of shale gas may lead to poor gas. Conclusion Therefore, in the absence of roof and floor conditions, specular refection may be one of the important reasons for the poor gas content of shale.

Abstract Background A cost-effective pretreatment and saccharification process is a necessary prerequisite for utilizing lignocellulosic biomass (LCB) in biofuel and biomaterials production. Utilizing a multifunctional enzyme with both pretreatment and saccharification functions in a single step for simultaneous biological pretreatment and saccharification process (SPS) will be a green method of low cost and high efficiency. Manganese peroxidase (MnP, EC 1.11.1.13), a well-known lignin-degrading peroxidase, is generally preferred for the biological pretreatment of biomass. However, exploring the role and performance of MnP in LCB conversion will promote the application of MnP for lignocellulose-based biorefineries. Results In this study, we explored the ability of an MnP from Moniliophthora roreri, MrMnP, in LCB degradation. With Mn2+ and H2O2, MrMnP decomposed 5.0 g/L carboxymethyl cellulose to 0.14 mM of reducing sugar with a conversion yield of 5.0 mg/g, including 40 μM cellobiose, 70 μM cellotriose, 20 μM cellotetraose, and 10 μM cellohexaose, and degraded 1.0 g/L mannohexaose to 0.33 μM mannose, 4.08 μM mannotriose, and 4.35 μM mannopentaose. Meanwhile, MrMnP decomposed 5.0 g/L lichenan to 0.85 mM of reducing sugar with a conversion yield of 30.6 mg/g, including 10 μM cellotriose, 20 μM cellotetraose, and 80 μM cellohexose independently of Mn2+ and H2O2. Moreover, the versatility of MrMnP in LCB deconstruction was further verified by decomposing locust bean gum and wheat bran into reducing sugars with a conversion yield of 54.4 mg/g and 29.5 mg/g, respectively, including oligosaccharides such as di- and tri-saccharides. The catalytic mechanism underlying MrMnP degraded lignocellulose was proposed as that with H2O2, MrMnP oxidizes Mn2+ to Mn3+. Subsequently, it forms a complex with malonate, facilitating the degradation of CMC and mannohexaose into reducing sugars. Without H2O2, MrMnP directly oxidizes malonate to hydroperoxyl acetic acid radical to form compound I, which then attacks the glucosidic bond of lichenan. Conclusion This study identified a new function of MrMnP in the hydrolysis of cellulose and hemicellulose, suggesting that MrMnP exhibits its versatility in the pretreatment and saccharification of LCB. The results will lead to an in-depth understanding of biocatalytic saccharification and contribute to forming new enzymatic systems for using lignocellulose resources to produce sustainable and economically viable products and the long-term development of biorefinery, thereby increasing the productivity of LCB as a green resource.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed coronavirus disease 2019 (COVID-19). COVID-19 cases often experience acute respiratory distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death in infected cells. Cell death mechanisms have a vital role in maintaining a suitable environment to achieve normal cell functionality. Nonetheless, these processes are dysregulated, potentially contributing to disease pathogenesis. Over the past decades, multiple cell death pathways are becoming better understood. Growing evidence suggests that the induction of cell death by the coronavirus may significantly contributes to viral infection and pathogenicity. However, the interaction of SARS-CoV-2 with cell death, together with its associated mechanisms, is yet to be elucidated. In this review, we summarize the existing evidence concerning the molecular modulation of cell death in SARS-CoV-2 infection as well as viral-host interactions, which may shed new light on antiviral therapy against SARS-CoV-2.

This paper discussed the preparation of protein nutrients from mulberry leaves by ultrasonic extraction combined with ultrafiltration technology. In order to obtain the optimal conditions for ultrasonic assisted extraction of mulberry leaf protein, we used response surface methodology to optimize the preparation of crude extract of mulberry leaf protein. In addition, we used ultrafiltration technology to purify and concentrate the protein components in the crude protein extract of mulberry leaves, and optimized the ultrafiltration membrane flux by orthogonal test. The amino acid components of solid crude protein prepared by ultrasonic extraction coupled with ultrafiltration technology were determined by referring to the method in GB 5009.124-2016 National Standard for Food Safety and further analyzed its nutritional value. The results showed that the optimal extraction conditions were as follows: The ratio of liquid-material ratio was 29:1 mL/g, ultrasonic extraction at 360 W for 15 min, and heating in water bath at 42 ℃ for 34 min, and the protein yield was up to 5.56%. Using the ultrafiltration technology to purify and concentrate the protein components in the crude protein extract, the optimal purification conditions were as follows: Operating pressure 0.6 MPa, diluting the crude extract by 1 time, and concentration ratio: 4:1. Under these conditions, the membrane flux was 21.40 L/m2·h, and the purity of solid protein was over 35%. The total amino acid content of solid mulberry leaf protein prepared by ultrasonic extraction coupled with ultrafiltration technology was 22.22 g/100 g, and the ratio of essential amino acids to total amino acids and the ratio of essential amino acids to non-essential amino acids were higher than the FAO/WHO adult model values. It could effectively extract and purify protein components from mulberry leaves by ultrasonic extraction combined with ultrafiltration technology. The prepared mulberry leaf proteins have good nutritional value and might meet the nutritional requirements of adults.

Abstract Subsidence data acquisition methods are crucial to mining subsidence research and an essential component of achieving the goal of environmentally friendly coal mining. The origin and history of the existing methods of field monitoring, calculation, and simulation were introduced. It summarized and analyzed the main applications, flaws and solutions, and improvements of these methods. Based on this analysis, the future developing directions of subsidence data acquisition methods were prospected and suggested. The subsidence monitoring methods have evolved from conventional ground monitoring to combined methods involving ground-based, space-based, and air-based measurements. While the conventional methods are mature in technology and reliable in accuracy, emerging remote sensing technologies have obvious advantages in terms of reducing field workload and increasing data coverage. However, these remote sensing methods require further technological development to be more suitable for monitoring mining subsidence. The existing subsidence calculation methods have been applied to various geological and mining conditions, and many improvements have already been made. In the future, more attention should be paid to unifying the studies of calculation methods and mechanical principles. The simulation methods are quite dependent on the similarity of the model to the site conditions and are generally used as an auxiliary data source for subsidence studies. The cross-disciplinary studies between subsidence data acquisition methods and other technologies should be given serious consideration, as they can be expected to lead to breakthroughs in areas such as theories, devices, software, and other aspects.

Manganese oxide (MnO2) exhibits excellent activity for volatile organic compound oxidation. However, it is currently unknown whether lattice oxygen or adsorbed oxygen is more conducive to the progress of the catalytic reaction. In this study, novel hollow highly dispersed Pt/Copper modified-MnO2 catalysts were fabricated. Cu2+ was stabilized into the δ-MnO2 cladding substituting original K+, which produced lattice defects and enhance the content of adsorbed oxygen. The 2.03 wt% Pt Cu0.050-MnO2 catalyst exhibited the highest catalytic activity and excellent stability for toluene and benzene oxidation, with T100 = 160 °C under high space velocity (36,000 mL g−1 h−1). The excellent performance of catalytic oxidation of VOCs is attributed to the abundant adsorbed oxygen content, excellent low-temperature reducibility and the synergistic catalytic effect between the Pt nanoparticles and Cu0.050-MnO2. This study provides a comprehensive understanding of the Langmuir–Hinshelwood (L-H) mechanism occurring on the catalysts.

Abstract Background Heme proteins, such as hemoglobin, horseradish peroxidase and cytochrome P450 (CYP) enzyme, are highly versatile and have widespread applications in the fields of food, healthcare, medical and biological analysis. As a cofactor, heme availability plays a pivotal role in proper folding and function of heme proteins. However, the functional production of heme proteins is usually challenging mainly due to the insufficient supply of intracellular heme. Results Here, a versatile high-heme-producing Escherichia coli chassis was constructed for the efficient production of various high-value heme proteins. Initially, a heme-producing Komagataella phaffii strain was developed by reinforcing the C4 pathway-based heme synthetic route. Nevertheless, the analytical results revealed that most of the red compounds generated by the engineered K. phaffii strain were intermediates of heme synthesis which were unable to activate heme proteins. Subsequently, E. coli strain was selected as the host to develop heme-producing chassis. To fine-tune the C5 pathway-based heme synthetic route in E. coli, fifty-two recombinant strains harboring different combinations of heme synthesis genes were constructed. A high-heme-producing mutant Ec-M13 was obtained with negligible accumulation of intermediates. Then, the functional expression of three types of heme proteins including one dye-decolorizing peroxidase (Dyp), six oxygen-transport proteins (hemoglobin, myoglobin and leghemoglobin) and three CYP153A subfamily CYP enzymes was evaluated in Ec-M13. As expected, the assembly efficiencies of heme-bound Dyp and oxygen-transport proteins expressed in Ec-M13 were increased by 42.3–107.0% compared to those expressed in wild-type strain. The activities of Dyp and CYP enzymes were also significantly improved when expressed in Ec-M13. Finally, the whole-cell biocatalysts harboring three CYP enzymes were employed for nonanedioic acid production. High supply of intracellular heme could enhance the nonanedioic acid production by 1.8- to 6.5-fold. Conclusion High intracellular heme production was achieved in engineered E. coli without significant accumulation of heme synthesis intermediates. Functional expression of Dyp, hemoglobin, myoglobin, leghemoglobin and CYP enzymes was confirmed. Enhanced assembly efficiencies and activities of these heme proteins were observed. This work provides valuable guidance for constructing high-heme-producing cell factories. The developed mutant Ec-M13 could be employed as a versatile platform for the functional production of difficult-to-express heme proteins.

Abstract Background Increasing evidence has indicated that ferroptosis engages in the progression of Parkinson’s disease (PD). This study aimed to explore the role of ferroptosis-related genes (FRGs), immune infiltration and immune checkpoint genes (ICGs) in the pathogenesis and development of PD. Methods The microarray data of PD patients and healthy controls (HC) from the Gene Expression Omnibus (GEO) database was downloaded. Weighted gene co-expression network analysis (WGCNA) was processed to identify the significant modules related to PD in the GSE18838 dataset. Machine learning algorithms were used to screen the candidate biomarkers based on the intersect between WGCNA, FRGs and differentially expressed genes. Enrichment analysis of GSVA, GSEA, GO, KEGG, and immune infiltration, group comparison of ICGs were also performed. Next, candidate biomarkers were validated in clinical samples by ELISA and receiver operating characteristic curve (ROC) was used to assess diagnose ability. Results In this study, FRGs had correlations with ICGs, immune infiltration. Then, plasma levels of LPIN1 in PD was significantly lower than that in healthy controls, while the expression of TNFAIP3 was higher in PD in comparison with HC. ROC curves showed that the area under curve (AUC) of the LPIN1 and TNFAIP3 combination was 0.833 (95% CI: 0.750–0.916). Moreover, each biomarker alone could discriminate the PD from HC (LPIN1: AUC = 0.754, 95% CI: 0.659–0.849; TNFAIP3: AUC = 0.754, 95% CI: 0.660–0.849). For detection of early PD from HC, the model of combination maintained diagnostic accuracy with an AUC of 0.831 (95% CI: 0.734–0.927), LPIN1 also performed well in distinguishing the early PD from HC (AUC = 0.817, 95% CI: 0.717–0.917). However, the diagnostic efficacy was relatively poor in distinguishing the early from middle-advanced PD patients. Conclusion The combination model composed of LPIN1 and TNFAIP3, and each biomarker may serve as an efficient tool for distinguishing PD from HC.

Numerous polysaccharides isolated from plants have been used to augment traditional drugs in the treatment of cancer. In order to explore the influence to hepatocellular carcinoma, a novel cold water-soluble polysaccharide was separated from Rhodiola rosea L. root (RLP) and then its structure and anti-cancer activities were tested. The chemical compositions and high performance gel permeation chromatography (HPGPC) results indicated that RLP was an acid heteropolysaccharide with the molecular weight of about 1.15×106 Da. Furthermore, ion chromatography (IC), Fourier transform infrared (FT-IR) and nuclear magnetic resoance (NMR) further indicated that RLP was main composed of →2,4)-α-Rha(1→, →5)-α-L-Araf-(1→, α-D-Glu, →6)-β-D-Galp-(1→, β-D-Man and →4)-α-GalpA-(1→. In vivo antitumor activities of RLP were carried out by using H22 tumor-bearing mice model. The results shown that RLP (100 and 300 mg/kg) could inhibit tumor growth of H22 cells from 23.59 % to 45.52 % and protect thymuses and spleen without damage. In addition, according to cell cycle, AV-FITC/PI and JC-1, RLP could induce dose-dependent apoptosis of H22 cells via S phase arrested which was through a mitochondrial related pathway. Our data indicated that RLP has a broader application prospect in anti-tumor preparations.

In this study, the degradation system of Shewanella oneidensis MR-1 and goethite was constructed with chlorpyrifos as the target contaminant. The effects of initial pH, contaminant concentration, and temperature on the removal rate of chlorpyrifos during the degradation process were investigated. The experimental conditions were optimized by response surface methodology with a Box–Behnken design (BBD). The results show that the removal rate of chlorpyrifos is 75.71% at pH = 6.86, an initial concentration of 19.18 mg·L−1, and a temperature of 30.71 °C. LC-MS/MS analyses showed that the degradation products were C4H11O3PS, C7H7Cl3NO4P, C9H11Cl2NO3PS, C7H7Cl3NO3PS, C9H11Cl3NO4P, C4H11O2PS, and C5H2Cl3NO. Presumably, the degradation pathways involved are: enzymatic degradation, hydrolysis, dealkylation, desulfur hydrolysis, and dechlorination. The findings of this study demonstrate the efficacy of the goethite/S. oneidensis MR-1 complex system in the removal of chlorpyrifos from water. Consequently, this research contributes to the establishment of a theoretical framework for the microbial remediation of organophosphorus pesticides in aqueous environments.

Tartronic acid is known for its potential to inhibit sugar-to-lipid conversion in the human body, leading to weight loss and fat reduction. This compound is predominantly found in cucumbers and other cucurbit crops. Therefore, cultivating cucumbers with high tartronic acid content holds significant health implications. In this study, we assessed the tartronic acid content in 52 cucumber germplasms with favorable overall traits and identified 8 cucumber germplasms with elevated tartronic acid levels. Our investigation into factors influencing cucumber tartronic acid revealed a decrease in content with fruit development from the day of flowering. Furthermore, tartronic acid content was higher in early-harvested fruits compared to late-harvested ones, with the rear part of the fruit exhibiting significantly higher content than other parts. Foliar spraying of microbial agents increased tartronic acid content by 84.4%. This study provides valuable resources for breeding high tartronic acid cucumbers and offers practical insights for optimizing cucumber production practices.

Background: Increasing evidence suggests that both the vaginal microbiota and human papillomavirus (HPV) may play a role in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, the relationship between the vaginal microbiome and HPV infection remains poorly understood. The objective of this study was to investigate the association between indicators of the vaginal microbiota and HPV infection. Methods: From January 2020 to June 2022, clinical data were collected from 5099 outpatients at Beijing Friendship Hospital. These patients underwent simultaneous testing for vaginal microecology and HPV type. A statistical analysis was conducted to examine the relationship between indicators of the vaginal microbiota and HPV infection. Results: HPV infections were detected in 12.47% (636/5099) of the subjects. Single, double, triple, quadruple, and quintuple infections accounted for 81.29%, 14.62%, 3.14%, 0.94%, and 0.15% of all infections, respectively. A significant disparity in HPV infection prevalence was observed between the vaginitis group and the general population. However, no variation was found among different vaginitis groups. The data indicated that individuals with clue cells and sialidase were more susceptible to HPV infection. Sialidase was identified as an independent risk factor for HPV infection in a multivariable logistic regression model. The most prevalent HPV subtypes were 16 and 52, representing 2.10% and 2.86%, 3.14% and 2.86%, 1.78% and 2.16% in the normal, bacterial vaginitis, and other groups, respectively. Conclusions: Our findings demonstrate the presence of clue cells and sialidase, which are two diagnostic criteria for bacterial vaginitis, in association with HPV infection. Furthermore, our results suggest that sialidase could potentially serve as a valuable predictor of HPV infection.

Chromium (Cr) contamination, widely present in the environment, poses a significant threat to both ecology and human health. Microbial remediation technology has become a hot topic in the field of heavy metal remediation due to its advantages, such as environmental protection, low cost, and high efficiency. This paper focused on using various characterization and analysis methods to investigate the bioreduction effect and mechanism of microorganisms on Cr(VI) under various influencing factors. The main contents and conclusions were as follows: Shewanella oneidensis MR-1 was selected as the target strain for studying its reduction of Cr(VI) at different inoculation amounts, temperatures, pH values, time intervals, etc. The results indicated that S. oneidensis MR-1 exhibited an optimal reduction effect on Cr(VI) at pH 7 and a temperature of 35 °C. Additionally, electron shuttles (ESs), including humic acid (HA) and 9,10-antraquinone-2,6-disulfonate (AQDS), were introduced into the degradation system to improve the reduction efficiency of S. oneidensis MR-1. Upon adding goethite further, S. oneidensis MR-1 significantly enhanced its reducing ability by converting Fe(III) minerals to Fe(II) and reducing Cr(VI) to Cr(III) during electron transfer.

Ovarian cancer remains a challenging disease with limited treatment options and poor prognosis. The tumor microenvironment (TME) plays a crucial role in tumor growth, progression, and therapy response. One characteristic feature of the TME is the abnormal tumor vasculature, which is associated with inadequate blood perfusion, hypoxia, and immune evasion. Vascular normalization, a therapeutic strategy aiming to rectify the abnormal tumor vasculature, has emerged as a promising approach to reshape the TME, enhance antitumor immunity, and synergize with immunotherapy in ovarian cancer. This review paper provides a comprehensive overview of vascular normalization and its potential implications in ovarian cancer. In this review, we summarize the intricate interplay between anti-angiogenesis and immune modulation, as well as ICI combined with anti-angiogenesis therapy in ovarian cancer. The compelling evidence discussed in this review contributes to the growing body of knowledge supporting the utilization of combination therapy as a promising treatment paradigm for ovarian cancer, paving the way for further clinical development and optimization of this therapeutic approach.

Notoginsenoside R1 (R1), which originated from the rhizomes and roots of Panax notoginseng, is classified as a Biopharmaceutical Classification System class III drug with good solubility but poor oral absorption. Although R1 can alleviate the inflammation of dextran sulfate sodium (DSS)-induced colitis in mice, the problem of acid degradation and low bioavailability limit its application. The purpose of this study was aimed to design one kind of pH-dependent solid dispersion for oral colon-targeted delivery of R1. Using Eudragit S100 (ES 100) and PEG 4000 as the pH-dependent carriers, R1 solid dispersion (R1-SD) was fabricated by solvent evaporation method. Scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction analysis indicated that R1-SD was completely formed, the surface was smooth surface and the strip crystal structure of R1 disappeared. The in vitro release profile of R1-SD (R1-ES 100-PEG 4000, 1:7:1, weight ratio) exhibited that R1-SD was not released in media simulating the gastric condition (pH 1.2), but better release characteristics of the drug could be obtained in media simulating the intestinal condition (less than 30% in pH 6.8 phosphate-buffered saline and more than 90% in pH 7.6 condition). The in vitro colon absorption test showed that the absorption rate and cumulative release of R1-SD were higher than those of R1. R1-SD and R1 had apparent protective effect on colon shortening, inflammatory infiltrating tissue injury, weight loss, diarrhea, blood stool in mice with ulcerative colitis induced by DSS, and the protective effect of R1-SD was better than that of R1, which indicated R1-SD has good practical application prospects.

As sorafenib is a first-line drug for treating advanced hepatocellular carcinoma, sorafenib resistance has historically attracted attention. However, most of this attention has been focused on a series of mechanisms related to drug resistance arising after sorafenib treatment. In this study, we used proteomic techniques to explore the potential mechanisms by which pretreatment factors affect sorafenib resistance. The degree of redundant pathway PI3K/AKT activation, biotransformation capacity, and autophagy level in hepatocellular carcinoma patients prior to sorafenib treatment might affect their sensitivity to sorafenib, in which ADH1A and STING1 are key molecules. These three factors could interact mechanistically to promote tumor cell survival, might be malignant features of tumor cells, and are associated with hepatocellular carcinoma prognosis. Our study suggests possible avenues of therapeutic intervention for patients with sorafenib-resistance and the potential application of immunotherapy with the aim of improving the survival of such patients.

Abstract All life forms require pH homeostasis. The disorder of pH homeostasis is associated with many severe diseases, suggesting the significance of pH‐detection for theranostic diseases. Photoacoustic imaging (PAI) technology has piqued great research interests in spatiotemporal detection of pH in vivo due to its non‐invasiveness and non‐ionization, as well as the high resolution and deep tissue penetration. This mini‐review outlines the most recent advances in activatable organic PA probes for pH‐detection with respect to molecular design, response mechanisms, and their in vivo applications. The basic understanding of PA probes is clarified. The pH‐response mechanisms of the PA probes at the molecular level are particularly emphasized to elucidate the structural design strategies. Finally, the challenges and perspectives, mainly focusing on quantitative detection, are discussed. This review aims to pave the way for further exploration of responsive organic PA probes for in vivo pH‐detection.

AbstractFreshwater lakes are subjected to increasing eutrophication and algal blooms worldwide, which have dramatically impacted the aquatic biodiversity. This situation is especially true in the Yangtze River Floodplain, China. However, few researches have been focused on differences in the spatial and temporal patterns of benthic macroinvertebrates assemblages between the two adjacent lakes in this floodplain. In this study, we conducted seasonal investigations in 2021 to compare the spatial and temporal patterns of macroinvertebrates in Lakes Taihu and Lake Chaohu. Non-metric multidimensional scaling (NMDS) analyses showed Lake Taihu was found to have differences in assemblages within the lake, but Lake Chaohu was found to have uniform assemblage across the entire lake. Macrophyte-dominated lake regions (eastern Lake Taihu) were characterised by the highest species richness and diversity indices than those in other lake regions. The pollution sensitive species (e.g. EPT: Ephemeroptera, Plecoptera and Trichoptera) were only distributed in the macrophytic areas of Lake Taihu. Corbicula fluminea, polychaetes Nephtys oligobranchia and Capitella sp. were dominant in the middle central lake regions in Lake Taihu. Lake Chaohu and the northern Lake Taihu, with turbid algal-dominated state, were characterised by dominance of Oligochaetes and Chironomids. These differences were attributed to varying habitats and environmental parameters among different lake regions. Canonical correspondence analysis (CCA) demonstrated that macrophytes, chemical oxygen demand (CODMn), temperature, ammonium (NH3-N) and electric conductivity (EC) were detected as important factors influencing such macroinvertebrate assemblage patterns between these two lakes. This study contributes to the scientific knowledge of within lake habitats, community assemblages, nutrients and pollution within these lakes.

The Gram-negative marine bacterium GXY010T, which has been isolated from the surface seawater of the western Pacific Ocean, is aerobic, non-motile and non-flagellated. Strain GXY010T exhibits growth across a temperature range of 10–42 °C (optimal at 37 °C), pH tolerance from 7.0 to 11.0 (optimal at 7.5) and a NaCl concentration ranging from 1.0 to 15.0% (w/v, optimal at 5.0%). Ubiquinone-8 (Q-8) was the predominant isoprenoid quinone in strain GXY010T. The dominant fatty acids (>10%) of strain GXY010T were iso-C15:0 (14.65%), summed feature 9 (iso-C17:1 ω9c and/or 10-methyl C16:0) (12.41%), iso-C17:0 (10.85%) and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) (10.41%). Phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), unidentifiable glycolipid (GL) and four non-identifiable aminolipids (AL1-AL4) were the predominant polar lipids of strain GXY010T. The genomic DNA G+C content was identified as a result of 48.0% for strain GXY010T. The strain GXY010T genome consisted of 2,766,857 bp, with 2664 Open Reading Frames (ORFs), including 2586 Coding sequences (CDSs) and 78 RNAs. Strain GXY010T showed Average Nucleotide Identity (ANI) values of 73.4% and 70.6% and DNA–DNA hybridization (DDH) values of 19.2% and 14.5% with reference species Pseudidiomarina tainanensis MCCC 1A02633T (=PIN1T) and Pseudidiomarina taiwanensis MCCC 1A00163T (=PIT1T). From the results of the polyphasic analysis, a newly named species, Pseudidiomarina fusca sp. nov. within the genus Pseudidiomarina, was proposed. The type strain of Pseudidiomarina fusca is GXY010T (=JCM 35760T = MCCC M28199T = KCTC 92693T).

In this investigation, we leverage the combination of the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys Data Release 9, Survey Validation 3, and Year 1 data sets to estimate the conditional luminosity functions and conditional stellar mass functions (CLFs and CSMFs) of galaxies across various halo mass bins and redshift ranges. To support our analysis, we utilize a realistic DESI mock galaxy redshift survey (MGRS) generated from a high-resolution Jiutian simulation. An extended halo-based group finder is applied to both MGRS catalogs and DESI observation. By comparing the r - and z -band luminosity functions (LFs) and stellar mass functions (SMFs) derived using both photometric and spectroscopic data, we quantified the impact of photometric redshift (photo- z ) errors on the galaxy LFs and SMFs, especially in the low-redshift bin at the low-luminosity/mass end. By conducting prior evaluations of the group finder using MGRS, we successfully obtain a set of CLF and CSMF measurements from observational data. We find that at low redshift, the faint-end slopes of CLFs and CSMFs below ∼10 ^9 h ^−2 L _⊙ (or h ^−2 M _⊙ ) evince a compelling concordance with the subhalo mass functions. After correcting the cosmic variance effect of our local Universe following Chen et al., the faint-end slopes of the LFs/SMFs turn out to also be in good agreement with the slope of the halo mass function.

Anthurium andraeanum Linden is a prominent ornamental plant belonging to the family Araceae and is cultivated worldwide. The morphology characteristics are crucial because they significantly impact ornamental values, commercial properties, and the efficiency of space utilization in production. However, only a few related investigations have been conducted in anthurium to date. In this study, an F1 genetic segregation population containing 160 progenies was generated through hybridization between potted and cut anthurium varieties. Fifteen morphological traits were assessed and revealed substantial levels of genetic variation and widespread positive correlation. Based on specific length amplified fragment (SLAF) sequencing technology, 8171 single nucleotide polymorphism (SNP) markers were developed, and the high-density linkage map of 2202.27 cM in length distributed on 15 linkage groups was constructed successfully, with an average distance of 0.30 cM. Using the inclusive composite interval mapping (ICIM) method, 59 QTLs related to 15 key morphological traits were successfully identified, which explained phenotypic variance (PVE) ranging from 6.21% to 17.74%. Thirty-three of those associated with 13 traits were designated as major QTLs with PVE > 10%. These findings offer valuable insights into the genetic basis of quantitative traits and are beneficial for molecular marker-assisted selection (MAS) in anthurium breeding.

Vehicle type and brand information constitute a crucial element in intelligent transportation systems (ITSs). While numerous appearance-based classification methods have studied frontal view images of vehicles, the challenge of multi-pose and multi-angle vehicle distribution has largely been overlooked. This paper proposes an appearance-based classification approach for multi-angle vehicle information recognition, addressing the aforementioned issues. By utilizing faster regional convolution neural networks, this method automatically captures crucial features for vehicle type and brand identification, departing from traditional handcrafted feature extraction techniques. To extract rich and discriminative vehicle information, ZFNet and VGG16 are employed. Vehicle feature maps are then imported into the region proposal network and classification location refinement network, with the former generating candidate regions potentially containing vehicle targets on the feature map. Subsequently, the latter network refines vehicle locations and classifies vehicle types. Additionally, a comprehensive vehicle dataset, Car5_48, is constructed to evaluate the performance of the proposed method, encompassing multi-angle images across five vehicle types and 48 vehicle brands. The experimental results on this public dataset demonstrate the effectiveness of the proposed approach in accurately classifying vehicle types and brands.

Abstract Alternative RNA splicing is one of the most important mechanisms of posttranscriptional gene regulation, which contributes to protein diversity in eukaryotes. It is well known that RNA splicing dysregulation is a critical mechanism in tumor pathogenesis and the rationale for the promising splice-switching therapeutics for cancer treatment. Although we have a comprehensive understanding of DNA mutations, abnormal gene expression profiles, epigenomics, and proteomics in lung adenocarcinoma (LUAD), little is known about its aberrant alternative splicing profiles. Here, based on the multi-omics data generated from over 1000 samples, we systematically studied the RNA splicing alterations in LUAD and revealed their biological and clinical implications. We identified 3688 aberrant alternative splicing events (AASEs) in LUAD, most of which were alternative promoter and exon skip. The specific regulatory roles of RNA binding proteins, somatic mutations, and DNA methylations on AASEs were comprehensively interrogated. We dissected the functional implications of AASEs and concluded that AASEs mainly affected biological processes related to tumor proliferation and metastasis. We also found that one subtype of LUAD with a particular AASEs pattern was immunogenic and had a better prognosis and response rate to immunotherapy. These findings revealed novel events related to tumorigenesis and tumor immune microenvironment and laid the foundation for the development of splice-switching therapies for LUAD.