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Maintaining exceptional product quality and boosting processing efficiency requires precise evaluation of various aspects of the turning process, including the cutting depth, feed rate, and size of the workpiece. This article presents a novel approach for observing the turning process state using modulation signal bispectrum (MSB) and motor current signals. A nonlinear model was established that clarifies the load torque oscillations during turning, which in turn affects the amplitude and phase modulation of the motor stator current. Random noise can be efficiently minimized using the MSB algorithm, allowing the extraction of the current-modulation characteristic sideband phase and amplitude from the collected current signal. This technique enables clear representation and enhanced monitoring of load torque changes throughout the turning process. The proposed method was validated via mathematical simulations and universal lathe tests, with the results indicating that the MSB phase and amplitude values effectively capture both dynamic and static torque alterations during the turning operation, making this approach a valuable tool for overseeing the turning process.

ObjectiveAlcoholic liver disease (ALD) is a liver damage disease caused by long-term heavy drinking. Currently, there is no targeted pharmaceutical intervention available for the treatment of this disease. To address this, this paper evaluates the efficacy and safety of probiotic preparation in treating ALD through conducting a meta-analysis, and provides a valuable insight for clinical decision-making.MethodsA systematic search was conducted across databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM from the inception dates to October 15, 2023, to identify clinical randomized controlled trials on probiotic preparations in the treatment of ALD. After the literature underwent screening, data extraction, and quality assessment, RevMan 5.3 and Stata 14.2 were employed for data analysis and processing.ResultsA total of 9 randomized controlled trials fulfilled the inclusion criteria. The results of the meta-analysis showed that probiotic preparation could significantly improve the liver function of patients with alcoholic liver disease compared with the control group. Probiotic intervention led to a significant reduction in the levels of alanine aminotransferase (MD=-13.36,95%CI:-15.80,-10.91;P

Laminated composites have been extensively researched due to their excellent mechanical properties, but their application in superwetting fields has been rarely reported. In this work, the surfaces with extreme wettability were prepared based on laminated composites. The Ti6Al4V/304 stainless steel (304 SS) micro-laminated composites were fabricated by diffusion bonding the Ti6Al4V foils and 304 SS foils with the thickness of 10–50 μm in vacuum. The typical interfacial microstructure and the effect of diffusion temperature on the microstructure were investigated. The bonded interface of joints is mainly composed of β-Ti, Ti2Ni, FeTi, Fe2Ti, Fe–Cr from the Ti6Al4V side to the 304 SS. The effect of diffusion temperature on the microstructure was researched. Based on the prepared Ti6Al4V/304 SS micro-laminated composites, an array structure with micro grooves was fabricated through the simple chemical etching. The 304 SS foils were etched to form grooves, while Ti6Al4V foils still remained as bulges. Due to surface modification and rough morphology, the etched surfaces exhibited the excellent hydrophobicity. Increasing the width and depth of grooves and decreasing the width of bulges led to the higher water contact angles and improved hydrophobicity. The highest water contact angles of 148.3° has been achieved under the conditions of grooves with a width of 50 μm, a depth of 60 μm, and the bulges with a width of 10 μm. The surfaces exhibited nearly superhydrophobicity and performed self-cleaning property. The processing method of this work could expand the application of laminated composite in extreme wettability fields.

Extremophile strain Monascus pilosus YX-1125 was isolated from the baijiu-making environment. It was found that this strain could use sorghum as substrate and could tolerate multiple extreme environmental stress. Based on this, Monascus and Sorghum Fermentation Filtrate (MSFF) derived from this strain was developed, and its composition, safety, and bioactivity were studied. Research findings revealed that MSFF was abundant in various bioactive substances, including short-chain fatty acids such as propionic acid, butyric acid, and acetic acid, phenolic compounds (greater than 7.0 mg/mL) and 17 amino acids (greater than 7.5 mg/mL), and had strong antioxidant potentials (80% concentration of MSFF with DPPH scavenging 67.3%, copper chelation 59.71%, iron chelation 42.62%, hydroxyl scavenging 83.31%, superoxide scavenging 55.8%, and ferric ion reducing antioxidant power 1.24 mmoL eq FeSO4/mL). The results of in vitro experiments revealed that 1% (v/v) MSFF could inhibit inflammation and reduce its damage by reducing 81.4% cell apoptosis, removing 35.8% intracellular reactive oxygen species, inhibiting the release of proinflammatory cytokines (interleukins-6 and -8) up to 83.2% and down-regulating the expression of matrix metalloproteinases (MMP-1 and MMP-9) up to 42.5%. The safety test confirmed that MSFF had high cytocompatibility. In conclusion, MSFF was a safe and highly effective antioxidant and anti-inflammatory ingredient, which had great potential applications in the fields of health food and skincare.

Abstract Background Exploration of the relationship between individual work immersion and perceived stress is critical for clinical nurses’ effective psychological interventions and human resource management, as well as to alleviate nursing staff shortages. In order to further dissect the influencing factors of perceived stress among nursing staff, our study introduces the concepts of perfectionism and social connectedness to analyze the specific pathways that influence perceived stress in terms of an individual’s intrinsic and external personality traits. This study provides relevant recommendations for the development of stress management measures for nursing staff. Methods This was a cross-sectional survey. 993 registered clinical nurses were included from four hospitals in Guangzhou through a convenience sampling method. Clinical nurses’ work immersion, perceived stress, perfectionism, and social connectedness were investigated using questionnaires based on latent profile analysis. The relationships between variables were analyzed using t-tests, analysis of variance, Pearson’s correlation analysis, latent profile analysis, and moderated mediation analysis. Results The results showed that (1) general influences on nurses’ perceived stress included only child, labor relationship, labor allowance, and family support; (2) nurses’ work immersion contained four subgroups: lowest (12.6%), medium-low (39.8%), medium-high (39.9%), and highest (7.7%); (3) positive and negative perfectionism played a mediating role between the association of work immersion and perceived stress; (4) social connectedness played a moderating role in the mediation model of perceived stress. Conclusions Work immersion, perfectionism, and social connectedness have an important impact on clinical nurses’ perceived stress. Nursing managers or leaders should pay attention to the differences of individual work immersion status, adopt reasonable stress management strategies, accurately identify positive perfectionist groups and strengthen the relationship between groups, so as to ensure the quality of nursing care, and reduce nursing turnover and alleviate the problem of staff shortage.

Salix psammophila was converted to value-added chemicals in the presence of 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) and water by the hydrothermal liquefaction method. [Bmim]Cl acted as both liquefier and catalyst, while water served as both co-solvent and reactant. The optimal reaction parameters for the highest liquefaction yield were determined by an orthogonal experiment. The possibility of application of the recycled [Bmim]Cl was investigated. FT-IR spectra results of the fresh used, the firstly reused, and the secondary reused IL [Bmim]Cl confirmed the high stability of [Bmim]Cl. Moreover, an explanation of the possible liquefaction mechanism for S. psammophila was also provided. This study may provide fundamental data for S. psammophila conversion and application.

Joining C/C composites to Ni-based single crystal alloy DD3 can significantly broaden their industrial application. The currently used active brazing method (ABM) may cause harmful reactions with Ni-based alloys, generating brittle compounds and deteriorating joint performance. In this work, a two-step method involving chromium carbide (Cr–C) surface modification and brazing using pure Cu filler is first developed to explore avoiding brittle compounds in joints. Surprisingly, the brazed seam of joints is mainly composed of (Cu, Ni) solid solution (s, s) without generating brittle compounds. At the DD3 interface, only (Ni, Cu) (s, s) and (Cu, Ni) (s, s) layers are formed. Besides, (W, Mo) (s, s) particles are precipitated nearby the DD3 substrate. For the C/C interface, the Cu filler is tightly joined to the Cr–C layer without forming new phases. The joint microstructure has no significant change with the variation of the Cr–C layer thickness. As increased the Cr–C layer thickness, the joint strength first increases and then decreases. The maximum shear strength of ∼32 MPa is obtained when the Cr–C layer thickness is ∼4.6 μm. The joint shear strength decreases with increased testing temperatures, which can still be maintained at ∼28 MPa at 600 °C. The surface modification and brazing strategy in this work can be further applied to the joining of other carbon materials and ceramics with poor wettability.

Medicago truncatula is a key model plant for studying legume plants, particularly alfalfa (Medicago sativa), due to its well-defined genetic background. Plant-specific GASA (Gibberellic Acid Stimulated Arabidopsis) genes play various roles in plant growth and development, abiotic stress, and hormone responses. However, limited information is available on GASA research in Medicago. In this study, 26 MtGASAs were identified and analyzed for its structure, evolution, and expressions. Sequence alignments and phylogeny revealed that 26 MtGASAs containing conserved GASA domains were classified into three clades. The chromosomal locations and gene synteny revealed segmental and tandem repetition evolution. Analysis of cis-regulatory elements indicates that family members likely influence various hormone signaling pathways and stress-related mechanisms. Moreover, the RNA-seq and qRT-PCR analyses revealed that 26 MtGASAs were extensively involved in abiotic stresses and hormone responses. Notably, seven MtGASA genes (MtGASA1, 10, 12, 17, 23, 25 and 26) were all dramatically activated by NaCl and Mannitol treatments, and four MtGASAs (MtGASA7, 10, 23 and 24) were significant activated by GA3, PBZ, ABA, and MeJA treatments. Collectively, this study is the first to identify and describe GASA genes in Medicago on a genome-wide scale. The results establish a basis for functional characterization, showing that these proteins are essential in responding to various abiotic stresses and hormonal signals.

China’s unprecedented rapid urbanization has encroached upon ecologically sensitive areas. Since 2013, Wuhan, a central urban hub in China, has adopted Ecological Control Line Planning (ECLP) to regulate urban growth and preserve ecological integrity. This study evaluates how ECLP is implemented in the Wuhan Metropolitan Development Zone (WMDZ), a critical region for harmonizing urban expansion with ecological preservation. The assessment integrates two fundamental aspects—conformity and utilization—with evaluations across spatial and ecological dimensions. This methodology builds a technical framework for rapid identification and detailed analysis of planning effects through LULC statistics and landscape connectivity index monitoring. The findings reveal that the ECLP is spatially conformable and utilizable, successfully curbing urban expansion and channeling development towards the urban growth boundary (UGB) and ecological development area (EDA). However, ECLP has not significantly mitigated the decline in ecological connectivity. Details include the following: (1) The general spatial consistency of the ECLP was 88.53%, with the EDA and ecological baseline area (EBA) achieving 85.18% and 88.98%, respectively. (2) Most of the increase in impervious land within ecological lines originated from agricultural and water areas, with only 7.02 km2 of land transitioning to non-agricultural and non-ecological uses. (3) The integral index of connectivity (IIC) exhibited a more rapid deterioration post-ECLP implementation, suggesting the disruption or degradation of critical connectivity pathways or patches within the ecological network. (4) Core ecological patches experienced significant losses inside and outside the UGB, with losses within the UGB being 2.51 times greater. The findings underscore the importance of ecological connectivity in implementing ecological space protection planning and the need for the flexible governance of areas where protection and development conflicts arise.

In this article, we delve into the exponential stability of uncertainty systems characterized by stochastic differential equations driven by G-Brownian motion, where coefficient uncertainty exists. To stabilize the system when it is unstable, we consider incorporating a delayed stochastic term. By employing linear matrix inequalities (LMI) and Lyapunov–Krasovskii functions, we derive a sufficient condition for stabilization. Our findings demonstrate that an unstable system can be stabilized with a control interval within (θ*,1). Some numerical examples are provided at the end to validate the correctness of our theoretical results.

Objective: Inflammation and fibrosis are strongly associated with each other. Glycine is present in various traditional Chinese medicines and exhibits anti-inflammatory activity. However, the effects of glycine on myocardial fibrosis (MF) in rats with myocardial infarction (MI) have not been reported. The purpose of this study is to investigate the effects of glycine therapy on MF and comprehend its underlying mechanisms. Materials and Methods: Left anterior descending artery ligation-induced MI in Sprague Dawley rats was leveraged to assess the therapeutic effects of Glycine. Rats received either normal saline or glycine (0.5 mg/g bodyweight) for 7 days. Results: Glycine upregulated cardiac ejection fraction and fractional shortening to improve cardiac function, as evaluated by echocardiography. Histological and immunohistochemical analyses demonstrated that glycine could decrease inflammatory cell infiltration and alleviate collagen deposition. Western blotting revealed that nuclear factor-κB (NF-κB)-mediated inflammatory signaling was also downregulated by glycine treatment. The expression of signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor-α, and transforming growth factor-β (TGF-β) was decreased significantly in the glycine-treated group compared to the model group. Thus, glycine plays a protective role against myocardial ischemia and subsequent MF. Conclusion: The protective effects of glycine were achieved partly through STAT3/NF-κB/TGF-β signaling pathway.

Graphene was first employed to improve the mechanical properties of Nb/Nb5Si3 composite, which is a critical candidate for the next-generation of high-temperature structural materials for aero-engines. Microstructures and mechanical properties of graphene reinforced Nb/Nb5Si3 composites with interfacial nano-Nb4C3 phase were systematically investigated. The graphene reinforced Nb/Nb5Si3 composite with outstanding room temperature fracture toughness and compressive strength was fabricated successfully via spark plasma sintering. The microstructure of this composite changes from laminated morphology to uniformly distributed equiaxed microstructure, with the increase of fabrication temperature from 1450 °C to 1550 °C. The high compressive strength of graphene reinforced Nb/Nb5Si3 composites is attributed to the load transfer of graphene, and this load transfer efficiency is strengthened due to the anchoring effect of the interfacial nano-scale Nb4C3 phase. The high fracture toughness of this composite is attributed to the pull-out of graphene, as well as the crack deflection and crack bridging induced by graphene. The laminated architecture is also beneficial to improve fracture toughness because it can promote the minor deflection of cracks. The superior combination of strength and toughness of graphene reinforced Nb/Nb5Si3 composites validates that our design strategy can successfully break through the strength-toughness trade-off. This study is expected to offer a new strategy and theoretical basis for the development of Nb/Nb5Si3 composites with outstanding mechanical properties.

Abstract Background Chronic infection with Clonorchis sinensis can cause hepatobiliary fibrosis and even lead to hepatobiliary carcinoma. Epstein-Barr virus-induced gene 3 protein (EBI3) is a subunit of interleukin 35, which can regulate inflammatory response and the occurrence of fibrotic diseases. Previous studies have reported that the expression of EBI3 in the serum of patients with liver cirrhosis is reduced. The present study aims to investigate the biological effects of EBI3 on liver fibrosis caused by C. sinensis and the underlying molecular mechanisms. Methods We first established a mouse model of liver fibrosis induced by C. sinensis infection and then measured the serum expression of EBI3 during the inflammatory and fibrotic phase. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses were performed to investigate the potential role of EBI3 in liver fibrosis by regulating the extracellular matrix structural constituent and collagen catabolic process. Recombinant protein EBI3 (rEBI3) was added to hepatic stellate cells (HSCs) in vitro with C. sinensis antigen to explore its function. Finally, the therapeutic effect of rEBI3 was verified by intravenous injection into C. sinensis-infected mice. Results The results showed that the serum expression of EBI3 increased in the inflammatory response phase but decreased in the fibrotic phase. The excretory-secretory products of C. sinensis (Cs.ESP) were able to stimulate HSC activation, while rEBI3 reduced the activation of HSCs induced by Cs.ESP. Also, the protein expression of gp130 and downstream protein expressions of JAK1, p-JAK1, STAT3 and p-STAT3 in HSCs were increased after rEBI3 incubation. Finally, intravenously injected rEBI3 inhibited hepatic epithelial-mesenchymal transition in C. sinensis-infected mice by inhibiting HSC activation and reducing liver injury. Conclusion This study confirms that rEBI3 can attenuate C. sinensis-induced liver fibrosis by inhibiting HSC activation and may be one of the potential treatments for liver fibrosis. Graphical Abstract

Abstract Synthetic biology requires efficient systems that support the well-coordinated co-expression of multiple genes. Here, we discover a 9-bp nucleotide sequence that enables efficient polycistronic gene expression in yeasts and filamentous fungi. Coupling polycistronic expression to multiplexed, markerless, CRISPR/Cas9-based genome editing, we develop a strategy termed HACKing (Highly efficient and Accessible system by CracKing genes into the genome) for the assembly of multigene pathways. HACKing allows the expression level of each enzyme to be precalibrated by linking their translation to those of host proteins with predetermined abundances under the desired fermentation conditions. We validate HACKing by rapidly constructing highly efficient Saccharomyces cerevisiae cell factories that express 13 biosynthetic genes, and produce model endogenous (1,090.41 ± 80.92 mg L−1 squalene) or heterologous (1.04 ± 0.02 mg L−1 mogrol) terpenoid products. Thus, HACKing addresses the need of synthetic biology for predictability, simplicity, scalability, and speed upon fungal pathway engineering for valuable metabolites.

Abstract Background The global prevalence of insufficient physical activity (PA) was reported to be 27.5% in 2016, and there were stable levels of insufficient PA worldwide between 2001 and 2016. The global target of a 10% reduction in insufficient PA by 2025 will not be met if the trends remain. The relevant data for trends in China were still scarce. This study aimed to determine nationwide temporal trends in insufficient PA among adults in China from 2010 to 2018. Methods 645 903 adults aged 18 years or older were randomly selected from four nationally representative cross-sectional surveys of the China Chronic Disease and Risk Factor Surveillance conducted in 2010, 2013, 2015, and 2018. PA was measured using the Global Physical Activity Questionnaire. Temporal changes in insufficient PA prevalence and participation of domain-specific moderate- to vigorous-intensity PA (MVPA) were analyzed using logistic regression. Results From 2010 to 2018, the age-adjusted prevalence of insufficient PA in China increased from 17.9% (95% confidence interval 16.3% to 19.5%) in 2010 to 22.3% (20.9% to 23.8%) in 2018 (P for trend

Abstract Background Despite advances in treatment, recurrence and mortality rates from breast cancer (BrCa) continue to rise, clinical effectiveness is limited, and prognosis remains disappointing, especially for patients with HER2-positive, triple-negative, or advanced breast cancer. Based on cuproptosis-related long noncoding RNAs (CRLs), this study aims to create a predictive signature to assess the prognosis in patients with BrCa. Methods The related CRLs RNA-seq data clinicopathological data were collected from The Cancer Genome Atlas (TCGA) database, and the predictive model was constructed after correlation analysis. Subsequently, we examined and validated connections and changes in the CRLs model with prognostic features (including risk curves, ROC curves and nomograms), pathway and functional enrichment, tumor mutation (TMB), tumor immune dysfunction and exclusion (TIDE) and treatment sensitivity. Results A prediction model formula composed of 5 CRLs was obtained, and divided breast cancer patients into high and low risk subgroups according to the obtained risk scores. The results showed that the overall survival (OS) of patients in the high-risk group was lower than that in the low-risk group, and the AUC of all samples at 1, 3 and 5 years were 0.704, 0.668 and 0.647, respectively. It was indicated that CRLs prognostic model could independently predict prognostic indicators of BrCa patients. In addition, analysis of gene set enrichment, immune function, TMB, and TIDE showed that these differentially expressed CRLs had a wealth of related pathways and functions, and might be closely related to immune response and immune microenvironment. Additionally, TP53 was found to have the highest mutation frequency in high-risk group (40%), while PIK3CA was found to have the highest mutation frequency in low-risk group (42%), which might become new targets for targeted therapy. Finally, we compared susceptibility to anticancer agents to identify potential treatment options for breast cancer. Lapatinib, Sunitinib, Phenformin, Idelalisib, Ruxolitinib, Cabozantinib were more sensitive to patients in the low-risk group, while Sorafenib, Vinorelbine, Pyrimethamine were more sensitive to patients in high-risk group, namely, these drugs could potentially be used in the future to treat breast cancer patients grouped according to the risk model. Conclusion This study identified CRLs associated with breast cancer and provided a tailored tool for predicting prognosis, immune response, and drug sensitivity in patients with BrCa.

Abstract Introduction Thrombocytopenia, a common noncriteria manifestation of antiphospholipid syndrome (APS), is severe in approximately one‐third of patients with APS. However, there are no guidelines for treating such thrombocytopenia. B‐cell‐targeting therapy may be an option in refractory cases; however, its efficacy has not been firmly established. Here, we report on two patients with refractory antiphospholipid antibodies (aPLs)‐associated thrombocytopenia treated with telitacicept. Case Description Case 1, a 39‐year‐old woman, presented with systemic lupus erythematosus (SLE) and APS with diffuse alveolar hemorrhage, persistent thrombocytopenia, and recurrent miscarriages. The thrombocytopenia had been refractory to multiple lines of treatments, the most recent being mycophenolate mofetil and prednisone (5 mg/day). After receiving telitacicept (160 mg/week) for 3 months, she had presented with decreased titers of aPLs and a slight increase in platelet counts (14 × 109 to 35 × 109/L). Case 2, a 51‐year‐old woman, presented with SLE and APS with refractory thrombocytopenia. She had been diagnosed with pulmonary tuberculosis 4.5 years ago and received antituberculosis therapy for 2 years. She had also undergone pulmonary lobectomy 4 years ago for lung adenocarcinoma. Her thrombocytopenia relapsed (lowest 14 × 109/L) when prednisone was tapered to

The performance of traditional frequency hopping signal detection methods based on time frequency analysis is limited by the tradeoff of time-frequency resolution and spectrum leakage. Machine learning-based frequency hopping signal detection techniques have a high level of complexity. Therefore, this paper proposes a residual network and the optimized generalized S transform to detect frequency hopping signals. First, based on the time-frequency aggregation measure, the generalized S transform parameters $ \lambda $ and $ p $ are optimized using a multi-population genetic algorithm. Second, the optimized generalized S transform is used to determine a signal's time-frequency spectrum, which is then normalized to make this robust to noise power uncertainty. Finally, a residual network structure is designed which receives the time-frequency spectrum. To detect frequency hopping signals, the network automatically learns the time-frequency properties of signals and noise. Simulated findings indicate that the multi-population genetic algorithm not only increases optimization efficiency when compared to a regular genetic algorithm, but also has faster convergence and more stable optimization results. Compared with a hybrid convolutional network/recurrent neural network algorithm, the proposed technique is better at detection and has less computational and storage complexity.

There are lots of biochemical reactions in the biosynthetic pathway without associated enzymes. Reactions predicted by retro-biosynthetic tools are not assigned gene sequences. Besides, non-natural reactions designed with novel functions also lack suitable enzymes. All these reactions can be categorized as orphan reactions. The absence of protein-encoding genes in these orphan reactions limits their direct experimental implementation. Computational tools have been developed to find candidate enzymes for these orphan reactions. Herein, we discuss recent advances in these computational tools, including reaction similarity-based methods for calculating the substructural similarity between orphan reactions and known enzymatic reactions; sequence-based tools combine metabolic knowledge base and phenotypic information with genomic, transcriptomic, and metabolomic data to mine appropriate enzymes for orphan reactions; and approaches based on the creation of enzyme variants for orphan reactions as enzyme engineering modifications and de novo design of enzymes. We believe that our review will greatly facilitate the design of microbial cell factories and contribute to the development of the biomanufacturing field.

Abstract The central nervous system (CNS) is considered as one of the most frequently affected organs in antiphospholipid syndrome (APS). This study investigated the prevalence of CNS manifestations in APS and associated risk factors and evaluated stroke recurrence. We carried out this retrospective study from 2009 to 2021 at Peking University People’s Hospital, which enrolled 342 APS patients, and 174 neurologic events were suffered by 119 patients (34.8%). Patients with and without CNS involvement were compared regarding demographics and laboratory parameters. The analysis showed that older age, livedo reticularis, and dyslipidaemia were significant related factors for CNS manifestations (P = 0.047, 0.038, and 0.030 respectively). The use of anticoagulants (P = 0.004), and/or hydroxychloroquine (P = 0.016) appeared to associated with a lower incidence of CNS manifestations. During a median follow-up of 4.1 years, 10 individuals developed new episodes of stroke in APS patients with previous ischemic strokes. Livedo reticularis, smoking and male gender may predict the risk of recurrent stroke (P = 0.020, 0.006, and 0.026 respectively). Collectively, our results indicated the protective and risk factors for CNS manifestations, as well as demonstrated that APS patients appeared at high risk of stroke recurrence despite current therapy.

Abstract Two‐dimensional transition metal dichalcogenides (TMDs) are needed in high‐performance piezoresistive sensors due to their strong strain‐induced bandgap modification and thereby large gauge factors. However, integrating a conventional high‐temperature chemical vapor deposition (CVD)‐grown TMD with a flexible substrate necessitates a transfer process that inevitably degrades the sensing properties of the TMDs and increases the overall fabrication complexity. We present a high‐performance piezoresistive strain sensor that employs large‐area PdSe2 films grown directly on polyimide (PI) substrates via plasma‐assisted selenization of a sputtered Pd film. The reliable strain transfer from the substrate to the PdSe2 film ensures an outstanding strain‐sensing capability of the sensor. Specifically, the sensors have a gauge factor of up to −315 ± 2.1, a response time under 25 ms, a detection limit of 8 × 10−6, and an exceptional stability of over 104 loading–unloading cycles. By attaching the sensors to the skin surface, we demonstrate their application for measuring physiological parameters in health care monitoring, including motion, voice, and arterial pulse vibration. Furthermore, using the PdSe2 film sensor combined with deep learning technology, we achieved intelligent recognition of artery temperature from arterial pulse signals with only a 2% difference between predicted and actual temperatures. The excellent sensing performance, together with the advantages of low‐temperature fabrication and simple device structure, make the PdSe2 film sensor promising for wearable electronics and health care sensing systems.

Synchrotron tomography experiments are transitioning into multifunctional, cross-scale, and dynamic characterizations, enabled by new-generation synchrotron light sources and fast developments in beamline instrumentation. However, with the spatial and temporal resolving power entering a new era, this transition generates vast amounts of data, which imposes a significant burden on the data processing end. Today, as a highly accurate and efficient data processing method, deep learning shows great potential to address the big data challenge being encountered at future synchrotron beamlines. In this review, we discuss recent advances employing deep learning at different stages of the synchrotron tomography data processing pipeline. We also highlight how applications in other data-intensive fields, such as medical imaging and electron tomography, can be migrated to synchrotron tomography. Finally, we provide our thoughts on possible challenges and opportunities as well as the outlook, envisioning selected deep learning methods, curated big models, and customized learning strategies, all through an intelligent scheduling solution. Public summary: • Tomography experiments at future synchrotron beamlines face exascale big data challenges. • Deep learning is employed for various data processing tasks at current synchrotron tomography beamlines. • Future comprehensive and elongated data analysis processes require a full-stack deep learning pipeline. • The data-driven full-stack deep learning pipeline based on an intelligent scheduling center (ISC) holds the key to solve the big data challenges.

Due to the unique structure of coconuts, their cultivation heavily relies on manual experience, making it difficult to accurately and timely observe their internal characteristics. This limitation severely hinders the optimization of coconut breeding. To address this issue, we propose a new model based on the improved architecture of Deeplab V3+. We replace the original ASPP(Atrous Spatial Pyramid Pooling) structure with a dense atrous spatial pyramid pooling module and introduce CBAM(Convolutional Block Attention Module). This approach resolves the issue of information loss due to sparse sampling and effectively captures global features. Additionally, we embed a RRM(residual refinement module) after the output level of the decoder to optimize boundary information between organs. Multiple model comparisons and ablation experiments are conducted, demonstrating that the improved segmentation algorithm achieves higher accuracy when dealing with diverse coconut organ CT(Computed Tomography) images. Our work provides a new solution for accurately segmenting internal coconut organs, which facilitates scientific decision-making for coconut researchers at different stages of growth.

BackgroundIn order to improve the safety of lumbar puncture (LP), we designed a new type of LP needle, that is, an integrated and controlled LP needle, which can actively and accurately control the flow rate and retention of cerebrospinal fluid (CSF) during puncture, so as to achieve a controlled LP procedure.ObjectiveTo evaluate whether a controlled LP procedure can improve the comfort of LP and reduce the risk of complications associated with LP.MethodsPatients requiring LP (n = 63) were pierced with an integrated and controlled LP needle or a conventional LP needle. The differences in vital signs, symptom score, comfort, operation time, CSF loss, CSF pressure fluctuation and back pain before and after puncture were analyzed.ResultsAn integrated and controlled LP needle (n = 35) significantly improved patients’ headache symptoms before and after puncture. In addition, a controlled LP procedure significantly reduced the amount of unnecessary CSF loss (p

Summary: With pre-trained large models and their associated fine-tuning paradigms being constantly applied in deep learning, the performance of large models achieves a dramatic boost, mostly owing to the improvements on both data quantity and quality. Next-generation synchrotron light sources offer ultra-bright and highly coherent X-rays, which are becoming one of the largest data sources for scientific experiments. As one of the most data-intensive scanning-based imaging methodologies, ptychography produces an immense amount of data, making the adoption of large deep learning models possible. Here, we introduce and refine the architecture of a neural network model to improve the reconstruction performance, through fine-tuning large pre-trained model using a variety of datasets. The pre-trained model exhibits remarkable generalization capability, while the fine-tuning strategy enhances the reconstruction quality. We anticipate this work will contribute to the advancement of deep learning methods in ptychography, as well as in broader coherent diffraction imaging methodologies in future.

Hydrogenation and nanocrystallization of Ti6Al4V alloy were achieved by electrolytic hydrogenation and SMAT processing. The hydride δ phase appeared when the hydrogenation time reached 4 h. The grain size of Ti6Al4V alloy after surface nanocrystallization reached below 35 nm when the SMAT processing time was 2 h. Surface morphology and roughness were characterized by AFM. The diffusion bonding between Ti6Al4V alloys at low temperature was achieved under different parameters. It is demonstrated that the porosity at the interface decreased correspondingly when the hydrogenation time or nanocrystallization time was extended. The porosity of the joint reached 0 when the hydrogenation time was 24 h or the nanocrystallization time was 4 h. Then hydrogenation and nanocrystallization treatments were combined. It is found that there are more bonding defects in both hydrogenation-nanocrystallization and nanocrystallization-hydrogenation joints than in joints with single hydrogenation or nanocrystallization treatment. It can be concluded that the porosity of the joints with nanocrystallization first is lower than that with hydrogenation first.

Abstract Background The Chinese government implemented the health poverty alleviation project (HPAP) since 2016 in poverty counties (PCs). To evaluate the effect of the HPAP on hypertension health management and control in PCs is vital for the policy improvement. Methods China Chronic Disease and Risk Factors Surveillance programme were conducted from August 2018 to June 2019. A total of 95,414 participants aged 35 and above from 59 PCs and 129 non-poverty counties (NPCs) were involved in this study. Hypertension prevalence, hypertension control, treatment and health management prevalence, and physical examination proportion were calculated and compared by PCs and NPCs. Logistic regression was employed to explore the association between hypertension control and management services. Results The hypertension prevalence in NPCs was significantly higher than that in PCs (NPCs 46.1% vs. PCs 41.2%, P

Abstract Currently, microbial manufacturing is widely used in various fields, such as food, medicine and energy, for its advantages of greenness and sustainable development. Process optimization is the committed step enabling the commercialization of microbial manufacturing products. However, the present optimization processes mainly rely on experience or trial-and-error method ignoring the intrinsic connection between cellular physiological requirement and production performance, so in many cases the productivity of microbial manufacturing could not been fully exploited at economically feasible cost. Recently, the rapid development of omics technologies facilitates the comprehensive analysis of microbial metabolism and fermentation performance from multi-levels of molecules, cells and microenvironment. The use of omics technologies makes the process optimization more explicit, boosting microbial manufacturing performance and bringing significant economic benefits and social value. In this paper, the traditional and omics technologies-guided process optimization of microbial manufacturing are systematically reviewed, and the future trend of process optimization is prospected.

Abstract With the advancements in instrumentations of next-generation synchrotron light sources, methodologies for small-angle X-ray scattering (SAXS)/wide-angle X-ray diffraction (WAXD) experiments have dramatically evolved. Such experiments have developed into dynamic and multiscale in situ characterizations, leaving prolonged exposure time as well as radiation-induced damage a serious concern. However, reduction on exposure time or dose may result in noisier images with a lower signal-to-noise ratio, requiring powerful denoising mechanisms for physical information retrieval. Here, we tackle the problem from an algorithmic perspective by proposing a small yet effective machine-learning model for experimental SAXS/WAXD image denoising, allowing more redundancy for exposure time or dose reduction. Compared with classic models developed for natural image scenarios, our model provides a bespoke denoising solution, demonstrating superior performance on highly textured SAXS/WAXD images. The model is versatile and can be applied to denoising in other synchrotron imaging experiments when data volume and image complexity is concerned.

Abstract Hyperhomocysteinemia (HHcy) is a risk factor for chronic kidney diseases (CKDs) that affects about 85% CKD patients. HHcy stimulates B cells to secrete pathological antibodies, although it is unknown whether this pathway mediates kidney injury. In HHcy-treated 2-kidney, 1-clip (2K1C) hypertensive murine model, HHcy-activated B cells secreted anti-beta 2 glycoprotein I (β2GPI) antibodies that deposited in glomerular endothelial cells (GECs), exacerbating glomerulosclerosis and reducing renal function. Mechanistically, HHcy 2K1C mice increased phosphatidylethanolamine (PE) (18:0/20:4, 18:0/22:6, 16:0/20:4) in kidney tissue, as determined by lipidomics. GECs oxidative lipidomics validated the increase of oxidized phospholipids upon Hcy-activated B cells culture medium (Hcy-B CM) treatment, including PE (18:0/20:4 + 3[O], PE (18:0a/22:4 + 1[O], PE (18:0/22:4 + 2[O] and PE (18:0/22:4 + 3[O]). PE synthases ethanolamine kinase 2 (etnk2) and ethanolamine-phosphate cytidylyltransferase 2 (pcyt2) were increased in the kidney GECs of HHcy 2K1C mice and facilitated polyunsaturated PE synthesis to act as lipid peroxidation substrates. In HHcy 2K1C mice and Hcy-B CM-treated GECs, the oxidative environment induced by iron accumulation and the insufficient clearance of lipid peroxides caused by transferrin receptor (TFR) elevation and down-regulation of SLC7A11/glutathione peroxidase 4 (GPX4) contributed to GECs ferroptosis of the kidneys. In vivo, pharmacological depletion of B cells or inhibition of ferroptosis mitigated the HHcy-aggravated hypertensive renal injury. Consequently, our findings uncovered a novel mechanism by which B cell-derived pathogenic anti-β2GPI IgG generated by HHcy exacerbated hypertensive kidney damage by inducing GECs ferroptosis. Targeting B cells or ferroptosis may be viable therapeutic strategies for ameliorating lipid peroxidative renal injury in HHcy patients with hypertensive nephropathy.

Currently, zinc has been considered as one new attractive biodegradable metal for medical implant applications due to its favoured properties such as biocompatibility and recyclability. However, the cast pure zinc usually possesses coarsening microstructures, which hinders it to obtain a suitable combination of mechanical strength and degradation rate. Here, the microstructural controlling of zinc was firstly realized via alloying dilute Mg contents and thermomechanical processing. Then, the in vitro biodegradation behaviour of dilute Zn–Mg alloys was investigated accordingly using the Hank's solution. Finally, the mechanisms of mechanical strengthening and in vitro biodegradation were explored. Specifically, the Mg-50wt%Zn master alloy was added into cast Zn melt to form the binary Zn–Mg alloys with different Mg addition contents (i.e. 0, 0.05wt%, 0.1wt%, and 0.4wt%). The initial reduction of grain sizes was achieved by over 90% owing to the grain refinement generated by master alloy. In the as-cast alloys, the average grain size was decreased from over 2 mm for pure Zn to 23.7 μm for Zn-0.4wt%Mg. Subsequently, the thermomechanical processing (i.e. hot rolling at room temperature, 100°C, 150°C, and 250°C) was applied onto the cast Zn–Mg alloys to achieve further microstructural manipulation. Further grain refinement occurred in the different as-rolled Zn–Mg alloys. The in vitro corrosion resistance of all samples was assessed through the potentiodynamic polarization (PDP) test in the Hanks' solution for 14 days at 37°C. The corrosion rates depended on alloying contents, grain sizes, twins and texture. The synergetic regulation of mechanical strength and degradation rate could be adjusted by appropriately using master alloys and thermomechanical processing. For practical medical applications, the present work provides some insights on solving the dilemma between mechanical properties and biodegradation process.

Triterpenoids are a class of natural products widely used in fields related to medicine and health due to their biological activities such as hepatoprotection, anti-inflammation, anti-viral, and anti-tumor. With the advancement in biotechnology, microorganisms have been used as cell factories to produce diverse natural products. Despite the significant progress that has been made in the construction of microbial cell factories for the heterogeneous biosynthesis of triterpenoids, the industrial production of triterpenoids employing microorganisms has been stymied due to the shortage of efficient enzymes as well as the low expression and low catalytic activity of heterologous proteins in microbes. Protein engineering has been demonstrated as an effective way for improving the specificity, catalytic activity, and stability of the enzyme, which can be employed to overcome these challenges. This review summarizes the current progress in the studies of Oxidosqualene cyclases (OSCs), cytochrome P450s (P450s), and UDP-glycosyltransferases (UGTs), the key enzymes in the triterpenoids synthetic pathway. The main obstacles restricting the efficient catalysis of these key enzymes are analyzed, the applications of protein engineering for the three key enzymes in the microbial synthesis of triterpenoids are systematically reviewed, and the challenges and prospects of protein engineering are also discussed.

Exopolysaccharides are natural macromolecular bioactive substances produced by lactic acid bacteria. With their unique physiological activity and structural characteristics, they are gradually showing broad application prospects in the food and pharmaceutical industries. Exopolysaccharides have various biological functions, such as exerting antioxidant and anti-tumor activities and regulating gut microbiota. Meanwhile, as a food additive, exopolysaccharides can significantly enhance the taste and quality of food, bringing consumers a better eating experience. In the field of medicine, exopolysaccharides have been widely used as drug carriers due to their non-toxic properties and good biocompatibility. This article summarizes the biological activities of exopolysaccharides produced by lactic acid bacteria, their synthesis, and their applications in food and pharmaceutical industries, aiming to promote further research and development in this field.

Cytochrome P450s (P450s), a superfamily of heme-containing enzymes, existed in animals, plants, and microorganisms. P450s can catalyze various regional and stereoselective oxidation reactions, which are widely used in natural product biosynthesis, drug metabolism, and biotechnology. In a typical catalytic cycle, P450s use redox proteins or domains to mediate electron transfer from NAD(P)H to heme iron. Therefore, the main factors determining the catalytic efficiency of P450s include not only the P450s themselves but also their redox-partners and electron transfer pathways. In this review, the electron transfer pathway engineering strategies of the P450s catalytic system are reviewed from four aspects: cofactor regeneration, selection of redox-partners, P450s and redox-partner engineering, and electrochemically or photochemically driven electron transfer.

Ecological networks in mountainous regions are vital for enhancing ecosystem functionality and ensuring regional ecological stability, alleviating the contradiction between land use and ecological development in rapid urbanization. However, the complexity of mountains and the need to establish a connection between ecosystem services and human well-being present significant challenges in constructing ecological networks. This study proposes an idea that identifies and derives an optimal scenario for ecological networks, integrating insights from ecosystem services and network analysis. The aim of the ecological network is to improve and protect the ecosystem’s stability while better guiding sustainable development in mountainous regions’ urban and rural areas. This study uses qualitative evaluation methods and a graph theory model to obtain the ecological network’s sources and links. The results indicate that (1) 58 important ecological source areas were identified, with a total area of 5746 km2, mainly covered by woodland and water bodies. (2) An optimal and feasible scenario comprising 5 horizontal and 14 longitudinal corridors was established. Corridors rely primarily on the river system and mountains. (3) A total of 5 key ecological function areas and some ecological zones in important urban development areas were identified. Control measures for these ecological lands were proposed to enhance the effectiveness of ecosystem service construction. It can be concluded that identifying and deriving an optimal scenario of ecological networks in mountainous regions from the perspectives of ecosystem services and network analysis is feasible.

Potassium deficiency is one of the important factors restricting cucumber growth and development. This experiment mainly explored the effect of Bacillus subtilis (B. subtilis) on cucumber seedling growth and the photosynthetic system under different potassium levels, and the rhizosphere bacteria (PGPR) that promote plant growth were used to solubilize potassium in soil, providing theoretical support for a further investigation of the effect of biological bacteria fertilizer on cucumber growth and potassium absorption. “Xinjin No. 4” was used as the test material for the pot experiment, and a two-factor experiment was designed. The first factor was potassium application treatment, and the second factor was bacterial application treatment. The effects of different treatments on cucumber seedling growth, photosynthetic characteristics, root morphology, and chlorophyll fluorescence parameters were studied. The results showed that potassium and B. subtilis had obvious promotion effects on the cucumber seedling growth and the photosynthesis of leaves. Compared with the blank control, the B. subtilis treatment had obvious effects on the cucumber seedling height, stem diameter, leaf area, total root length, total root surface area, total root volume, branch number, crossing number, gs, WUE, Ci, and A; the dry weight of the shoot and root increased significantly (p ≤ 0.05). Potassium application could significantly promote cucumber growth, and the effect of B. subtilis and potassium application was greater than that of potassium application alone, and the best effect was when 0.2 g/pot and B. subtilis were applied. In conclusion, potassium combined with B. subtilis could enhance the photosynthesis of cucumber leaves and promote the growth of cucumber.

Background: Small extracellular vesicles (sEVs) obtained from human umbilical cord mesenchymal stromal cells (MSCs) have shown cardioprotective efficacy in doxorubicin-induced cardiotoxicity (DIC). However, their clinical application is limited due to the low yield and high consumption. This study aims to achieve large-scale production of sEVs using a three-dimensional (3D) bioreactor system. In addition, sEVs were developed to deliver Ginsenoside Rg1 (Rg1), a compound derived from traditional Chinese medicine, Ginseng, that has cardioprotective properties but limited bioavailability, to enhance the treatment of DIC. Methods: The 3D bioreactor system with spinner flasks was used to expand human umbilical cord MSCs and collect MSC-conditioned medium. Subsequently, sEVs were isolated from the conditioned medium using differential ultra-centrifugation (dUC). The sEVs were loaded with Ginsenoside Rg1 by electroporation and evaluated for cardioprotective efficacy using Cell Counting Kit-8 (CCK-8) analysis, Annexin V/PI staining and live cell count of H9c2 cells under DIC. Results: Using the 3D bioreactor system with spinner flasks, the expansion of MSCs reached ~600 million, and the production of sEVs was up to 2.2 × 1012 particles in five days with significantly reduced bench work compared to traditional 2D flasks. With the optimized protocol, the Ginsenoside Rg1 loading efficiency of sEVs by electroporation was ~21%, higher than sonication or co-incubation. Moreover, Rg1-loaded sEVs had attenuated DOX-induced cardiotoxicity with reduced apoptosis compared to free Ginsenoside Rg1 or sEVs. Conclusions: The 3D culture system scaled up the production of sEVs, which facilitated the Rg1 delivery and attenuated cardiomyocyte apoptosis, suggesting a potential treatment of DOX-induced cardiotoxicity.

Background: Pregnancy complications of antiphospholipid syndrome (APS) are up to 20–30%. It is of great value to identify well-recognized predictors of adverse pregnancy outcomes (APOs) in APS. This study aims to explore the risk factors for APOs in patients with obstetric APS. Methods: This study included 142 women with APS delivered at Peking University People’s Hospital from February 2014 to August 2022. APOs included fetal death, neonatal death due to complications related to prematurity, preterm delivery

As one of the main factors decreasing current efficiency and product quality, the growth of nodules deserves attention in the copper electrorefining process. Three-dimensional (3D) Finite Element Method models combining tertiary current distribution and fluid flow were established in this study to investigate the details of the growth of columnar nodules, including the electrolyte flow around the nodule and its effects. Compared with an inert nodule, a significant impact of the electrochemical reaction of an active nodule has been observed on the fluid flow, which may be one of the reasons for the formation of small nodule clusters on the cathode. Furthermore, the local current density is not even on the nodule surface under the comprehensive influence of local electrolyte flow, local overvoltage, and the angle with the anode surface. Thus, the head of an active nodule grows faster than the root, and the upper parts grow faster than the lower parts, leading to asymmetric growth of the nodules.

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.

(1) Objectives: The aim of this study was to examine the relationship between mindful parenting and children’s creative tendencies and to investigate the mediating role of parent–child intimacy and connectedness to nature in the relationship between mindful parenting and children’s creative tendencies. (2) Methods: In this cross-sectional study, nearly 800 mothers of children aged 3–6 were enrolled. General sociodemographic data, the Mindfulness in Parenting Questionnaire (MIPQ), the Creativity Assessment Packet (CAP), the Child–Parent Relationship Scale—Short Form (CPRS-SF), and the Connectedness to Nature Index—Parents of Preschool Children (CNI-PPC) were all included in the questionnaire survey. (3) Results: There were significant positive correlations among mindful parenting, parent–child intimacy, connectedness to nature, and children’s creative tendencies. Mindful parenting had a positive predictive effect on children’s creative tendencies. Parent–child intimacy played a mediating role between mindful parenting and children’s creative tendencies. Connectedness to nature played a mediating role between mindful parenting and children’s creative tendencies. The correlation between mindful parenting and children’s creative tendencies may be impacted by the chain mediation effects of parent–child intimacy and connectedness to nature. (4) Conclusions: By promoting parent–child intimacy and connectedness to nature, and by utilizing the chain mediating effects of both, mindful parenting positively impacted children’s creative tendencies.

In pursuit of unsymmetrical precursors for the novel series of anthracenyl-isoxazole amide (AIM) antitumor agents, a series of substituted anthracenes were subjected to bromination and re-aromatization in our study, during which we solved four single crystal X-ray diffractometry (Sc-xrd) structures which we report herein. The C-9 nitrile oxide, after its reaction with bromine, was isolated, but when subjected to re-aromatization, it returned to the starting 10-bromo nitrile oxide 1, which did provide an accurate crystal structure, with R = 0.018. The 10-halogenated 3-(9’-anthryl)-isoxazole esters were subjected to bromination and re-aromatization. Surprisingly, the yields obtained in the presence of the isoxazole were reasonably good (62–68% isolated yields), and the major diastereomers allowed for the characterization using Sc-xrd. The penta bromo product 2 showed a trans, trans, cis relationship for the four bromines on the A-ring of the anthracene, and we observed that for the unit cell, the atropisomers displayed a 1:1 ratio at the chiral axis between the isoxazole and anthrancene rings. Similarly, the 10-chloro 3 indicated a ratio of 1:1 at the chiral axis in the crystal structure. A base-induced re-aromatization afforded 3,10-dihalogenated analogues selectively in very good yields (X = Cl, 89%; X = Br 92%), of which the dibromo 4 was characterized using Sc-xrd. The improved yields of the unique diastereomeric bromination products suggested the consideration of a novel electrophilic aromatic substitution mechanism driven by the stereo-electronic environment, imposed by the isoxazole ester substituent. The promise of the application of this chemistry in the future development of AIM antitumor agents is suggested.

Volatile accumulation during tomato ripening greatly affects the fruit flavor. In this study, four accessions from each of the three tomato subgroups (BIG, S. lycopersicum, CER, S. lycopersicumvar. Cerasiforme, and PIM, S. pimpinellifolium) were subjected to a sensory evaluation. The CER subgroup had the highest fruit-flavor score. Using a Headspace solid-phase microextraction/gas chromatography-mass spectrometer (HP-SPME/GC-MS), a volatile database containing 94 volatiles was created. Pentanal accumulated in green fruits and 1-pentanol in red fruits. 1-Octen-3-ol was discovered to underlie the bitterness of green tomatoes, and it was most abundant in PIM green fruits. Phenylethyl alcohol affected the acidity and sweetness of red tomatoes, and it was most abundant in CER red fruits. Branched-chain volatiles were most abundant in PIM and BIG red fruits, while apocarotenoids were most abundant in CER red fruits. These findings suggest that domestication and improvement have influenced volatile content, and apocarotenoids and branched-chain volatiles synergistically mediated aromatic flavors in red fruits. This study provides a metabolic basis for analyses of the molecular mechanisms of fruit-flavor formation.

In the original publication [...]

Introduction: Both CRISPR/dCas9 and CRISPR/dCpf1 genome editing systems have shown exciting promises in modulating yeast cell metabolic pathways. However, each system has its deficiencies to overcome. In this study, to achieve a compensatory effect, we successfully constructed a dual functional CRISPR activation/inhibition (CRISPRa/i) system based on Sp-dCas9 and Fn-dCpf1 proteins, along with their corresponding complementary RNAs.Methods: We validated the high orthogonality and precise quantity targeting of selected yeast promoters. Various activating effector proteins (VP64, p65, Rta, and VP64-p65-Rta) and inhibiting effector proteins (KRAB, MeCP2, and KRAB-MeCP2), along with RNA scaffolds of MS2, PP7 and crRNA arrays were implemented in different combinations to investigate quantitative promoter strength. In the CRISPR/dCas9 system, the regulation rate ranged from 81.9% suppression to 627% activation in the mCherry gene reporter system. Studies on crRNA point mutations and crRNA arrays were conducted in the CRISPR/dCpf1 system, with the highest transcriptional inhibitory rate reaching up to 530% higher than the control. Furthermore, the orthogonal CRISPR/dCas9-dCpf1 inhibition system displayed distinct dual functions, simultaneously regulating the mCherry gene by dCas9/gRNA (54.6% efficiency) and eGFP gene by dCpf1/crRNA (62.4% efficiency) without signal crosstalk.Results and discussion: Finally, we established an engineered yeast cell factory for β-carotene production using the CRISPR/dCas9-dCpf1 bifunctional system to achieve targeted modulation of both heterologous and endogenous metabolic pathways in Saccharomyces cerevisiae. The system includes an activation module of CRISPRa/dCas9 corresponding to a gRNA-protein complex library of 136 plasmids, and an inhibition module of CRISPRi/dCpf1 corresponding to a small crRNA array library. Results show that this CRISPR/dCas9-dCpf1 bifunctional orthogonal system is more quantitatively effective and expandable for simultaneous CRISPRa/i network control compared to single-guide edition, demonstrating higher potential of future application in yeast biotechnology.

Photodynamic Therapy (PDT) is an effective tumor treatment strategy that not only induces photocytotoxicity to kill tumor cells directly but also activates the immune system in the body to generate tumor-specific immunity, preventing cancer metastasis and recurrence. However, some limitations of PDT limit the therapeutic efficacy in deep tumors. Previous studies have used different types of nanoparticles (NPs) as drug carriers of photosensitizers (PSs) to overcome the shortcomings of PDT and improve therapeutic efficacy. Among them, bacterial outer membrane vesicles (OMVs) have natural advantages as carriers for PS delivery. In addition to the targeted delivery of PSs into tumor cells, their unique immunogenicity helps them to serve as immune adjuvants to enhance the PDT-induced immune effect, providing new ideas for photodynamic anticancer therapy. Therefore, in this review, we will introduce the biogenesis and anticancer functions of OMVs and the research on them as drug delivery carriers in PDT. Finally, we also discuss the challenges and prospects of OMVs as a versatile drug delivery carrier for photodynamic anticancer therapy.

Virus assembly from structural protein monomers to virus shells is a key step of virus replication. Some drug targets were found in this process. It consists of two steps. Virus structural protein monomers firstly polymerize to building blocks, then these building blocks assemble into virus shells. So, these building block synthesis reactions in the first step are fundamental for virus assembly. Typically, virus building blocks are made up of less than six monomers. They are of five types, including dimer, trimer, tetramer, pentamer and hexamer. In this work, we develop five synthesis reaction dynamical models for these five types, respectively. Then, we prove the existence and uniqueness of the positive equilibrium solution for these dynamical models one by one. Subsequently, we also analyze the stability of the equilibrium states, respectively. We got the function of monomer and dimer concentrations for dimer building blocks in the equilibrium state. We also got the function of all intermediate polymers and monomers for trimer, tetramer, pentamer and hexamer building blocks in the equilibrium state, respectively. Based on our analysis, dimer building blocks in the equilibrium state will decrease as the ratio of the off-rate constant to the on-rate constant increases. Trimer building blocks in the equilibrium state will decrease with the increasing ratio of the off-rate constant to the on-rate constant of trimers. These results may provide further insight into the virus-building block synthesis dynamic property in vitro.

Abstract Sauropterygia is the largest, most successful group of Mesozoic marine diapsids, spanning from the late Early Triassic to the Late Cretaceous. Plesiomorphic for sauropterygians, pachypleurosauroids are important for our understanding on the early evolution of this group. Here, we present a new pachypleurosaurid, Luopingosaurus imparilis gen. et sp. nov., based on an exceptionally preserved skeleton from the early Middle Triassic Luoping Lagerstätte in Yunnan, China. The discovery documents the first long-snouted pachypleurosaurid with an unexpected hyperphalangy in the manus, providing new insights into the morphological diversification, ecological adaption and biogeographic evolution of this clade. The discovery further indicates that there is a morphological divergence between short-snouted (brevirostrine) keichousaurids and relatively long-snouted (longirostrine) pachypleurosaurids, which was probably driven by ecological specializations related to feeding and foraging. Additionally, an evolutionary trend towards the reduction of the ratio of the hyoid length to mandibular length (HM ratio) is recognized in pachypleurosauroids. This reduction of HM ratio, associated with the increase of the snout length, might implicate a gradual recession of suction feeding in pachypleurosauroid evolution. Phylogenetic studies incorporating Luopingosaurus recover European pachypleurosaurids as successive sister groups to Chinese derived pachypleurosaurids, supporting a western Tethyan origin for this family.

Diamond bit is an important tool for drilling. In recent years, with the application of new composite materials and the continuous progress in precision machining technology, combined with the continuous innovation of drilling equipment, diamond bits have achieved rapid development. This paper briefly introduces some new progress of efficient rock breaking technology with diamond bit, and puts forward the possible development directions in the future.