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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 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.

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,

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.

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

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 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.

Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, presents severe threats to women’s health. Therefore, it is critical to find novel treatment approaches. Ferroptosis, a newly identified form of programmed cell death, is marked by the buildup of lipid reactive oxygen species (ROS) and high iron concentrations. According to previous studies, ferroptosis sensitivity can be controlled by a number of metabolic events in cells, such as amino acid metabolism, iron metabolism, and lipid metabolism. Given that TNBC tumors are rich in iron and lipids, inducing ferroptosis in these tumors is a potential approach for TNBC treatment. Notably, the metabolic adaptability of cancer cells allows them to coordinate an attack on one or more metabolic pathways to initiate ferroptosis, offering a novel perspective to improve the high drug resistance and clinical therapy of TNBC. However, a clear picture of ferroptosis in TNBC still needs to be completely revealed. In this review, we provide an overview of recent advancements regarding the connection between ferroptosis and amino acid, iron, and lipid metabolism in TNBC. We also discuss the probable significance of ferroptosis as an innovative target for chemotherapy, radiotherapy, immunotherapy, nanotherapy and natural product therapy in TNBC, highlighting its therapeutic potential and application prospects.

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.

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.

Cucumber (Cucumis sativus L.) is a globally prevalent and extensively cultivated vegetable whose yield is significantly influenced by various abiotic stresses, including drought, heat, and salinity. Transcription factors, such as zinc finger-homeodomain proteins (ZHDs), a plant-specific subgroup of Homeobox, play a crucial regulatory role in stress resistance. In this study, we identified 13 CsZHDs distributed across all six cucumber chromosomes except chromosome 7. Phylogenetic analysis classified these genes into five clades (ZHDI-IV and MIF) with different gene structures but similar conserved motifs. Collinearity analysis revealed that members of clades ZHD III, IV, and MIF experienced amplification through segmental duplication events. Additionally, a closer evolutionary relationship was observed between the ZHDs in Cucumis sativus (C. sativus) and Arabidopsis thaliana (A. thaliana) compared to Oryza sativa (O. sativa). Quantitative real-time PCR (qRT-PCR) analysis demonstrated the general expression of CsZHD genes across all tissues, with notable expression in leaf and flower buds. Moreover, most of the CsZHDs, particularly CsZHD9-11, exhibited varying responses to drought, heat, and salt stresses. Virus-induced gene silencing (VIGS) experiments highlighted the potential functions of CsZHD9 and CsZHD10, suggesting their positive regulation of stomatal movement and responsiveness to drought stress. In summary, these findings provide a valuable resource for future analysis of potential mechanisms underlying CsZHD genes in response to stresses.

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.

Abstract Background The methylotrophic budding yeast Pichia pastoris GS115 is a powerful expression system and hundreds of heterologous proteins have been successfully expressed in this strain. Recently, P. pastoris has also been exploited as an attractive cell factory for the production of high-value biochemicals due to Generally Recognized as Safe (GRAS) status and high growth rate of this yeast strain. However, appropriate regulation of metabolic flux distribution between cell growth and product biosynthesis is still a cumbersome task for achieving efficient biochemical production. Results In this study, P. pastoris was exploited for high inositol production using an effective dynamic regulation strategy. Through enhancing native inositol biosynthesis pathway, knocking out inositol transporters, and slowing down carbon flux of glycolysis, an inositol-producing mutant was successfully developed and low inositol production of 0.71 g/L was obtained. The inositol production was further improved by 12.7% through introduction of heterologous inositol-3-phosphate synthase (IPS) and inositol monophosphatase (IMP) which catalyzed the rate-limiting steps for inositol biosynthesis. To control metabolic flux distribution between cell growth and inositol production, the promoters of glucose-6-phosphate dehydrogenase (ZWF), glucose-6-phosphate isomerase (PGI) and 6-phosphofructokinase (PFK1) genes were replaced with a glycerol inducible promoter. Consequently, the mutant strain could be switched from growth mode to production mode by supplementing glycerol and glucose sequentially, leading to an increase of about 4.9-fold in inositol formation. Ultimately, the dissolved oxygen condition in high-cell-density fermentation was optimized, resulting in a high production of 30.71 g/L inositol (~ 40-fold higher than the baseline strain). Conclusions The GRAS P. pastoris was engineered as an efficient inositol producer for the first time. Dynamic regulation of cell growth and inositol production was achieved via substrate-dependent modulation of glycolysis and pentose phosphate pathways and the highest inositol titer reported to date by a yeast cell factory was obtained. Results from this study provide valuable guidance for engineering of P. pastoris for the production of other high-value bioproducts.

Background: To reveal candidate genes and the molecular genetic mechanism underlying primary feather color trait in ducks, a genome-wide association study (GWAS) for the primary feather color trait was performed based on the genotyping-by-sequencing (GBS) technology for a native Chinese female duck, Longyan Shan-ma ducks.Methods: Blood genomic DNA from 314 female Longyan Shan-ma duck were genotyped using GBS technology. A GWAS for the primary feather color trait with genome variations was performed using an univariate linear mixed model based on all SNPs in autosomes.Results: Seven genome-wide significant single nucleotide polymorphisms (SNPs, Bonferroni-adjusted p-value

Cell cycle regulation plays a critical role in plant growth and development. In this study, the role of a tomato cell cycle gene SlCycB1 has been characterized. Expression analysis revealed that SlCycB1 was mostly expressed in stem, root, and leaves, with relative lower expression in flower and fruit. Tomato plants overexpressing SlCycB1 exhibited a reduction in cell number and increased cell size leading to the growth retardation. Furthermore, yeast two-hybrid analysis and bimolecular fluorescence complementation revealed that SlCycB1 interacted with histone H3.2, an essential component of the nucleosome. Histone H3.2 was transcriptionally up-regulated in the SlCycB1 overexpressing tomato lines. Furthermore, the overexpression of histone H3.2 in transgenic plants showed similar phenotypes to SlCycB1 overexpressing lines. Based on these findings, we concluded that SlCycB1 overexpression altered tomato architecture in association with histone H3.2.

The transcriptional response to laminar sheer stress in human aortic endothelial cells reveals a pathway leading to inhibition of endothelial cell inflammation by autophagy induction.

Historically, biological research has relied primarily on animal models. While this led to the understanding of numerous human biological processes, inherent species-specific differences make it difficult to answer certain liver-related developmental and disease-specific questions. The advent of 3D organoid models that are either derived from pluripotent stem cells or generated from healthy or diseased tissue-derived stem cells have made it possible to recapitulate the biological aspects of human organs. Organoid technology has been instrumental in understanding the disease mechanism and complements animal models. This review underscores the advances in organoid technology and specifically how liver organoids are used to better understand human-specific biological processes in development and disease. We also discuss advances made in the application of organoid models in drug screening and personalized medicine.

The rapid development of solar energy technology has led to significant progress in recent years, but the daily maintenance of solar panels faces significant challenges. The diagnosis of solar panel failures by infrared detection devices can improve the efficiency of maintenance personnel. Currently, due to the scarcity of infrared solar panel failure samples and the problem of unclear image effective features, traditional deep neural network models can easily encounter overfitting and poor generalization performance under small sample conditions. To address these problems, this paper proposes a solar panel failure diagnosis method based on an improved Siamese network. Firstly, two types of solar panel samples of the same category are constructed. Secondly, the images of the samples are input into the feature model combining convolution, adaptive coordinate attention (ACA), and the feature fusion module (FFM) to extract features, learning the similarities between different types of solar panel samples. Finally, the trained model is used to determine the similarity of the input solar image, obtaining the failure diagnosis results. In this case, adaptive coordinate attention can effectively obtain interested effective feature information, and the feature fusion module can integrate the different effective information obtained, further enriching the feature information. The ACA-FFM Siamese network method can alleviate the problem of insufficient sample quantity and effectively improve the classification accuracy, achieving a classification accuracy rate of 83.9% on an open-accessed infrared failure dataset with high similarity.

Blue honeysuckle (Lonicera caerulea L.), which belongs to the Caprifoliaceae family, is an emerging fruit crop worldwide. For the development of a transgenic system and multipurpose tissue culture, this study for the first time established an in vitro regeneration system via somatic embryogenesis, as well as improving the previously established indirect organogenesis-based regeneration system. For embryogenesis, Murashige and Skoog (MS) medium supplemented with 1.0 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) showed the highest induction rate of the embryogenic callus (97.6%), and MS supplemented with 0.1 mg/L 6-benzyladenine (6-BA), 0.1 mg/L α-naphthaleneacetic acid (NAA), and 0.5 g/L activated carbon (AC) achieved the highest somatic embryo rate (28.3%). For indirect organogenesis, MS medium supplemented with 1.0 mg/L 6-BA and 0.1 mg/L NAA resulted in the highest non-embryogenic callus induction rate (98.9%) and adventitious shoot induction rate (51.6%). For adventitious root induction, MS supplemented with 1.0 mg/L indole-3-butyric acid (IBA) achieved the highest root induction rate (96.0%) and average root length (4.6 cm), whereas MS supplemented with 0.5 mg/L indole-3-acetic acid (IAA) resulted in the highest average regenerated root number (8.8). The total time for the regeneration from explants to soil-planted seedlings (10 euphylla) was 105 and 150 days with an efficiency of 44.1% and 23.9% through organogenesis and somatic embryogenesis, respectively. This study provides a powerful tool for rapid propagation, proliferation, and transformation, as well as laying a technological foundation for gene function research and genetic improvement of blue honeysuckle.

BackgroundSolid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated.MethodsWe conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center.ResultsAlong with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy.ConclusionsCompared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.