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Abstract Spinal Cord Injury (SCI) is a condition characterized by complete or incomplete motor and sensory impairment, as well as dysfunction of the autonomic nervous system, caused by factors such as trauma, tumors, or inflammation. Current treatment methods primarily include traditional approaches like spinal canal decompression and internal fixation surgery, steroid pulse therapy, as well as newer techniques such as stem cell transplantation and brain-spinal cord interfaces. However, the above methods have limited efficacy in promoting axonal and neuronal regeneration. The challenge in medical research today lies in promoting spinal cord neuron regeneration and regulating the disrupted microenvironment of the spinal cord. Studies have shown that gas molecular therapy is increasingly used in medical research, with gasotransmitters such as hydrogen sulfide, nitric oxide, carbon monoxide, oxygen, and hydrogen exhibiting neuroprotective effects in central nervous system diseases. The gas molecular protect against neuronal death and reshape the microenvironment of spinal cord injuries by regulating oxidative, inflammatory and apoptotic processes. At present, gas therapy mainly relies on inhalation for systemic administration, which cannot effectively enrich and release gas in the spinal cord injury area, making it difficult to achieve the expected effects. With the rapid development of nanotechnology, the use of nanocarriers to achieve targeted enrichment and precise control release of gas at Sites of injury has become one of the emerging research directions in SCI. It has shown promising therapeutic effects in preclinical studies and is expected to bring new hope and opportunities for the treatment of SCI. In this review, we will briefly outline the therapeutic effects and research progress of gasotransmitters and nanogas in the treatment of SCI. Graphical Abstract

Abstract This review presents a comprehensive exploration of the pivotal role played by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, with a particular focus on Nesprin proteins, in cellular mechanics and the pathogenesis of muscular diseases. Distinguishing itself from prior works, the analysis delves deeply into the intricate interplay of the LINC complex, emphasizing its indispensable contribution to maintaining cellular structural integrity, especially in mechanically sensitive tissues such as cardiac and striated muscles. Additionally, the significant association between mutations in Nesprin proteins and the onset of Dilated Cardiomyopathy (DCM) and Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their pivotal role in disease pathogenesis. Through a comprehensive examination of DCM and EDMD cases, the review elucidates the disruptions in the LINC complex, nuclear morphology alterations, and muscular developmental disorders, thus emphasizing the essential function of an intact LINC complex in preserving muscle physiological functions. Moreover, the review provides novel insights into the implications of Nesprin mutations for cellular dynamics in the pathogenesis of muscular diseases, particularly in maintaining cardiac structural and functional integrity. Furthermore, advanced therapeutic strategies, including rectifying Nesprin gene mutations, controlling Nesprin protein expression, enhancing LINC complex functionality, and augmenting cardiac muscle cell function are proposed. By shedding light on the intricate molecular mechanisms underlying nuclear-cytoskeletal interactions, the review lays the groundwork for future research and therapeutic interventions aimed at addressing genetic muscle disorders.

Abstract Pseudomonas aeruginosa, a common nosocomial pathogen, relies on siderophores to acquire iron, crucial for its survival in various environments and during host infections. However, understanding the molecular mechanisms of siderophore regulation remains incomplete. In this study, we found that the BfmRS two-component system, previously associated with biofilm formation and quorum sensing, is essential for siderophore regulation under high osmolality stress. Activated BfmR directly bound to the promoter regions of pvd, fpv, and femARI gene clusters, thereby activating their transcription and promoting siderophore production. Subsequent proteomic and phenotypic analyses confirmed that deletion of BfmRS reduces siderophore-related proteins and impairs bacterial survival in iron-deficient conditions. Furthermore, phylogenetic analysis demonstrated the high conservation of the BfmRS system across Pseudomonas species, functional evidences also indicated that BfmR homologues from Pseudomonas putida KT2440 and Pseudomonas sp. MRSN12121 could bind to the promoter regions of key siderophore genes and osmolality-mediated increases in siderophore production were observed. This work illuminates a novel signaling pathway for siderophore regulation and enhances our understanding of siderophore-mediated bacterial interactions and community establishment.

Percutaneous coronary intervention (PCI), as a relatively rapid and effective minimally invasive treatment for coronary heart disease (CHD), can effectively relieve coronary artery stenosis and restore myocardial perfusion. However, the occurrence of major adverse cardiovascular events (MACE) is a significant challenge for post PCI care. To better understand risk/benefit indicators and provide post PCI MACE prediction, 408 patients with CHD who had undergone PCI treatment from 2018 to 2021 in Tianjin Chest hospital were retrospectively studied for their clinical characteristics in relation with the MACE occurrence during a 12-month follow-up. In the study, 194 patients had MACE and 214 patients remained MACE-free. Using uni- and multivariate regression analyses, we have shown that smoking history, elevated serum C-reactive protein levels (hs-CRP), and high haemoglobin levels A1c (HbA1c) are all independent risk factors for MACE after PCI. Furthermore, we have discovered that the serum level of IL-38, one of the latest members identified in the IL-1 cytokine family, is another predictive factor and is reversely related to the occurrence of MACE. The serum level of IL-38 alone is capable of predicting non-MACE occurrence in subcategorized patients with abnormal levels of hs-CRP and/or HbA1c.

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD+ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.

Abstract Multivalent drugs targeting homo-oligomeric viral surface proteins, such as the SARS-CoV-2 trimeric spike (S) protein, have the potential to elicit more potent and broad-spectrum therapeutic responses than monovalent drugs by synergistically engaging multiple binding sites on viral targets. However, rational design and engineering of nanoscale multivalent protein drugs are still lacking. Here, we developed a computational approach to engineer self-assembling trivalent microproteins that simultaneously bind to the three receptor binding domains (RBDs) of the S protein. This approach involves four steps: structure-guided linker design, molecular simulation evaluation of self-assembly, experimental validation of self-assembly state, and functional testing. Using this approach, we first designed trivalent constructs of the microprotein miniACE2 (MP) with different trimerization scaffolds and linkers, and found that one of the constructs (MP-5ff) showed high trimerization efficiency, good conformational homogeneity, and strong antiviral neutralizing activity. With its trimerization unit (5ff), we then engineered a trivalent nanobody (Tr67) that exhibited potent and broad neutralizing activity against the dominant Omicron variants, including XBB.1 and XBB.1.5. Cryo-EM complex structure confirmed that Tr67 stably binds to all three RBDs of the Omicron S protein in a synergistic form, locking them in the “3-RBD-up” conformation that could block human receptor (ACE2) binding and potentially facilitate immune clearance. Therefore, our approach provides an effective strategy for engineering potent protein drugs against SARS-CoV-2 and other deadly coronaviruses. Graphical Abstract

Educational institutions generate a large amount of digital data in their daily operations, which is stored in servers, forming a substantial educational data set. Extracting valuable information through practical data analysis has become a critical problem that needs to be solved urgently. Students' examination results are an essential basis for evaluating their learning status, which reflects the effect of school education to some extent. Therefore, we propose a model based on the BP network and Pandas to construct a prediction model for Pandas' performance in the first year and their successful graduation to explore the potential relationship between Pandas' performance in the freshman year and graduation, thus realizing the principle of early guidance and improvement of teaching quality. Through the random prediction experiment of 9,424 scores data of 304 students in 2017 and 2018 majoring in network engineering at a university, the accuracy rate is 96.71% after the experimental data analysis and verification, which has proved that there is a potential correlation between the students' first-year course scores and graduation. Meanwhile, the improved BP network proposed in the present research exhibits reasonable practicability and extensibility in the college student achievement prediction model.

Abstract Background Atherosclerosis (AS), a significant contributor to cardiovascular disease (CVD), is steadily rising with the aging of the global population. Pyroptosis and apoptosis, both caspase-mediated cell death mechanisms, play an essential role in the occurrence and progression of AS. The human pineal gland primarily produces melatonin (MT), an indoleamine hormone with powerful anti-oxidative, anti-pyroptotic, and anti-apoptotic properties. This study examined MT’s anti-oxidative stress and anti-pyroptotic effects on human THP-1 macrophages treated with nicotine. Methods In vitro, THP-1 macrophages were induced by 1 µM nicotine to form a pyroptosis model and performed 30 mM MT for treatment. In vivo, ApoE-/- mice were administered 0.1 mg/mL nicotine solution as drinking water, and 1 mg/mL MT solution was intragastric administrated at 10 mg/kg/day. The changes in pyroptosis, apoptosis, and oxidative stress were detected. Results MT downregulated pyroptosis, whose changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of sirtuin3 (SIRT3), and Forkhead box O3 (FOXO3α) upregulation. MT also inhibited apoptosis, mainly caused by the interaction of caspase-1 and caspase-3 proteins. Vivo studies confirmed that nicotine could accelerate plaque formation. Moreover, mice treated with MT showed a reduction in AS lesion area. Conclusions MT alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis. Importantly, our understanding of the inhibitory pathways for macrophage pyroptosis will allow us to identify other novel therapeutic targets that will help treat, prevent, and reduce AS-associated mortality.

Abstract Phosphorus (P) and nitrogen (N) are essential macronutrients necessary for plant growth and development. OsPT4 is a high-affinity phosphate (Pi) transporter that has a positive impact on nutrient uptake and seed development. In this study, the expression patterns of different Pi transporter genes in germinating seeds were determined, and the relative expression of OsPT4 was induced in Pi-deficient seeds and gradually increased with the passage of germination time. The analysis of P, N, Pi, and amino acid concentrations in germinating seeds of OsPT4 mutants showed that the OsPT4 mutation caused P and N retention and a continuous reduction in multiple amino acid concentrations in germinating seeds. Transcriptome analysis and qRT-PCR results also indicated that the OsPT4 mutation inhibits the expression of genes related to P and N transportation and amino acid synthesis in germinating seeds. In addition, the paraffin section and TUNEL assay of OsPT4 mutant germinating seeds suggests that OsPT4 mutation causes programmed cell death (PCD) delayed in the aleurone layer and inhibition of leaf outgrowth. Moreover, we also found that OsPT4 was ubiquitinated by OsAIRP2, which is a C3HC4-type RING E3 Ub ligase. Our studies illustrate that OsPT4 plays a crucial role in P and N collaborative translocation and consumption in germinating seeds. It also provides a theoretical basis for the molecules and physiological mechanisms of P and N cross-talk under suppressed Pi uptake conditions.

The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5 g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0 g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in “photosynthesis” and “photosynthesis, light reaction” in Sedum alfredii Hance leaves. Moreover, the “plant hormone signal transduction” pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants.

Facilitating the separation of photogenerated charges is a crucial process in photocatalytic degradation of pollutants. In this study, Bi2O3/In2O3 composites were prepared using a co-precipitation method and subsequently calcined at 400 ℃ for 1 h. The Mott-Schottky curves confirmed a p(Bi2O3)-n(In2O3) heterojunction was yielded. Due to the significant difference in Fermi levels between Bi2O3 and In2O3, an internal electric field was established at the interface, with field lines directed from In2O3 to Bi2O3. Under illumination, the excited electrons accumulated in the conduction band (CB) of In2O3, while holes gathered in the valence band (VB) of Bi2O3, promoting charge separation and enhancing quantum efficiency. The composite material exhibited the highest photocatalytic activity when the atomic percentage of Bi to In was 1:1, with the first-order reaction rate constant of BI-1 increasing to 0.0149 min−1, which is 4.3 and 4.4 multiples higher than that of pure In2O3 and pure Bi2O3. Recycling experiments demonstrated that the photocatalytic composite possesses good reusability and structural stability.

Owning to the factors of external mechanical loads and high heat flux deposition, various degrees of strain or stress are inevitably introduced into the structural materials of nuclear fusion reactors. The uniaxial compression effects on the geometries, electronic structures, mechanical properties, and stabilities of Fe128Hen and Fe127VacHen were studied by first-principles calculations in this work. The results show that the lattice suffers from a noticeable inclination or disorder as the strain reaches 15%. The maximum stress of the stress–strain curves implied that the mechanical characteristics decay considerably as the number of He atoms increases, but the presence of a vacancy mitigated this effect. Compressive strain decreases the stability of Fe atom in the perfect pure Fe system, but it slightly elevates the monovacancy formation energy from Fe128He3 onward. According to the binding energy of He-He, compressive strain enhanced the aggregation of He. The migration barriers of an interstitial He atom exhibit anisotropy under uniaxial compressive strain, which was explained by the variations of the surrounding architectures.

In recent years, there has been an increasing number of related studies on exosomes. Most studies have focused on exosomes derived from mammals, confirming the important role that exosomes play in cell communication. Plants, as a natural ingredient, plant-derived exosomes have been confirmed to have similar structures and functions to mammalian-derived exosomes. Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer membrane nanovesicles containing bioactive constituents such as miRNA, mRNA, protein, and lipids obtained from plant cells, that can participate in intercellular communication and mediate transboundary communication, have high bioavailability and low immunogenicity, are relatively safe, and have been shown to play an important role in maintaining cell homeostasis and preventing, and treating a variety of diseases. In this review, we describe the biogenesis, isolation and purification methods, structural composition, stability, safety, function of PELNs and challenges. The functions of PELNs in anti-inflammatory, antioxidant, antitumor and drug delivery are mainly described, and the status of research on exosome nanoparticles of Chinese herbal medicines is outlined. Overall, we summarized the importance of PELNs and the latest research results in this field and provided a theoretical basis for the future research and clinical application of PELNs.

Abstract Glutamate, the major excitatory neurotransmitter in the central nervous system, has also been found to play a role in embryonic stem (ES) cells. However, the exact mechanism and function of glutamatergic signaling in ES cells remain poorly understood. In this study, we identified a glutamatergic transmission circuit in ES cells that operates through an autocrine mechanism and regulates cell proliferation. We performed biological analyses to identify the key components involved in glutamate biosynthesis, packaging for secretion, reaction, and reuptake in ES cells, including glutaminase, vesicular glutamate transporter, glutamate N-methyl-d-aspartate (NMDA) receptor, and cell membrane excitatory amino-acid transporter (EAAT). We directly quantified the released glutamate signal using microdialysis-high performance liquid chromatography-tandem mass spectrometry (MD–HPLC–MS–MS). Pharmacological inhibition of endogenous glutamate release and the resulting tonic activation of NMDA receptors significantly affected ES cell proliferation, suggesting that ES cells establish a glutamatergic autocrine niche via releasing and responding to the transmitter for their own regulation.

Ras homolog gene family member V (RHOV) is an atypical Rho GTPase that participates in various important cellular processes. Although RHOV has been identified to play an oncogenic role in lung cancer and triple‐negative breast cancer, its role in other types of tumors remains unknown. In this study, we investigated the expression of RHOV in pan‐cancer analysis using The Cancer Genome Atlas (TCGA) and Gene‐Tissue Expression datasets. RHOV mRNA levels were dysregulated in several types of tumors. RHOV expression was identified as an independent prognostic factor in 7 of 33 types of tumors; however, the relationship varied according to tumor type. Higher RHOV expression was associated with a favorable prognosis in kidney renal cell carcinoma and prostate adenocarcinoma, for which RHOV expression was downregulated, whereas RHOV expression was associated with a poor prognosis for patients with adenoid cystic carcinoma, lung adenocarcinoma, pancreatic ductal adenocarcinoma, skin cutaneous melanoma, and uveal melanoma with upregulated RHOV expression. Furthermore, RHOV expression was associated with various clinicopathological parameters in these tumors. RHOV expression showed varied associations with different types of tumor‐infiltrating immune cells and demonstrated a potential impact on the response to immunotherapy depending on the cancer type. Additionally, functional enrichment analysis of RHOV‐related genes demonstrated a role in a wide range of developmental and immune‐related processes. This study provides valuable insights into the role of RHOV in pan‐cancer development, indicating its role as a tumor suppressor or oncogene according to the cancer type and tumor microenvironment.

Abstract. Background:. More than 75 million procedures with intravascular iodine-based contrast media (ICM) are performed worldwide every year, and some patients undergoing these procedures do not have normal thyroid function. The long-term effects of ICM in patients with mild thyroid dysfunction (TD) are unclear. Methods:. This prospective cohort study was conducted in China. Patients with stable angina pectoris with total triiodothyronine (TT3) reduction, normal thyroid-stimulating hormone, and reverse triiodothyronine (rT3) were enrolled and divided into high-dose (≥100 mL ICM) and low-dose groups (

Abstract Artificial intelligence has shown immense potential in cancer prediction, but existing models cannot estimate prediction uncertainty by themselves. Here, we developed a Bayesian neural network (BNN) model, BNN‐CRC15, for colorectal cancer (CRC) prediction while assessing its reliability. The model was trained on routine laboratory data obtained from 27,911 participants and provided quantified prediction uncertainty, allowing identification of a subset of participants in which the model was confident, mimicking the diagnostic process of human practitioners. Our model exhibited superior performance (area under the curve = 0.918) in the confident participant group, which accounted for 46.4% of the patients, indicating that routine laboratory data alone are sufficient for accurate predictions in this subset. For the non‐confident group, further advanced tests, such as colonoscopy, could be recommended to achieve more accurate predictions. In addition, our model demonstrated superior overall accuracy (0.848) in all patients, outperforming other five traditional algorithms (extreme gradient boosting, support vector machine, logistic regression, random forest, and artificial neural network) and fecal immunochemical test in distinguishing CRC from non‐CRC. These findings suggest that our BNN‐CRC15 model could serve as a valuable tool for improving CRC diagnosis and prevention.

Lingnan Intangible Cultural Heritage (ICH) has a long history and contains rich and unique regional culture, which can provide new thoughts and ideas for cultural and creative product design. In this paper, firstly, the cVAE-GAN network model is utilized to extract the features of the modeling symbols of Lingnan intangible cultural heritage, which helps to obtain the modeling symbols of Lingnan intangible cultural heritage for cultural and creative product design. Secondly, the HSV color space model realizes the refinement of the color elements of Lingnan intangible cultural heritage, which promotes the application of color diversity in the design of Lingnan cultural and creative products. Then, the two methods are combined with artificial intelligence technology to construct the Lingnan emotional interactive cultural and creative product design framework, which enables the computer to integrate the designer’s design emotion on the basis of learning modeling and color and promotes the enhancement of the emotional value of Lingnan non-heritage cultural and creative products. Finally, to verify the effectiveness of the method described in this paper, a relevant test analysis was conducted. The results show that when the computational order is more than 60 orders, the cVAE-GAN network in this paper extracts the styling symbol features in only about 115ms, the PSNR improvement of the HSV color space model under different color blocks is more than 2dB, and the RSD of H-channel can be found to be in the range of 0.5% to 5.0% after performing color noise removal. Carrying out the cultural and creative product design of Lingnan intangible cultural heritage in the era of artificial intelligence needs to be more clear about the shape and color of the intangible heritage and fully combine with the designer’s emotion in order to make the Lingnan intangible cultural and creative products revitalized with new vitality.

Abstract Inflammation is a prevalent pathological process that accompanies the onset and progression of numerous acute and chronic diseases including rheumatoid arthritis, sepsis, pancreatitis, atherosclerosis, ischaemic brain/heart disease and so forth. However, conventional anti‐inflammatory drugs have certain disadvantages such as nonspecific tissue distribution, low bioavailability, and a short half‐life, resulting in off‐target side effects and limited efficacy in disease control. To address these issues, nanoparticles have emerged as a novel therapeutic paradigm in this field to attain inflammation targeting and improve drug pharmacokinetic properties via the well‐recognized enhanced permeability and retention (EPR) effect at the inflammatory site. Existing reviews are predominantly centered on inflammatory pathology introduction and vector design. As a necessary complement, this review mainly elaborates on the introduction of inflammation core events, the history of the drug delivery system for anti‐inflammatory drugs, the action mechanism of inflammation targeting vectors, nanoparticle classification based on targeting moiety, methods to combine targeting moiety with core nanoparticles, techniques to assess targetability in vitro and in vivo and finally the challenges and prospects in this field. The information provided herein offers practical guidance to researchers seeking to develop and evaluate inflammation targeting vectors rationally.

Patients with chronic pain often have cognitive impairment; this is especially true in elderly patients with neurodegenerative diseases such as Alzheimer's disease (AD), but the mechanism underlying this association remains unclear. This was addressed in the present study by investigating the effect of chronic neuropathic pain on hippocampal neurogenesis and cognitive impairment using amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice subjected to spared-nerve injury (SNI). The Von Frey test was performed to determine the mechanical threshold of mouse hind limbs after SNI. The Morris water maze test was used to evaluate spatial learning and memory. Doublecortin-positive (DCX+), 5-bromo-2′-deoxyuridine (BrdU)+, BrdU+/neuronal nuclei (NeuN)+, and C-C motif chemokine ligand 2 (CCL2)+ neurons in the dentate gyrus of the hippocampus were detected by immunohistochemistry and immunofluorescence analysis. CCL2 and C-C chemokine receptor type 2 (CCR2) protein levels in the mouse hippocampus were analyzed by western blotting. The results showed that APP/PS1 mice with chronic neuropathic pain induced by SNI had significant learning and memory impairment. This was accompanied by increased CCL2 and CCR2 expression and decreases in the number of DCX+, BrdU+, and BrdU+/NeuN+ neurons. These results suggest that chronic neuropathic pain is associated with cognitive impairment, which may be caused by CCL2/CCR2 signaling-mediated inhibition of hippocampal neurogenesis. Thus, therapeutic strategies that alleviate neuropathic pain can potentially slow cognitive decline in patients with AD and other neurodegenerative diseases.

In this study, juvenile crayfish hatched from the same population were cultured in different growing environments: pond (D1), paddy field (D2), and aquaculture barrel (D3), and fed for 60 days. Crayfishes were selected randomly, females and males, 50 tails each from six groups (D1-♀, D1-♂, D2-♀, D2-♂, D3-♀, D3-♂) to measure the following morphological traits: full length (X1), body length (X2), chelicerae length (X3), chelicerae weight (X4), cephalothorax length (X5), cephalothorax width (X6), cephalothorax height (X7), eye spacing (X8), caudal peduncle length (X9), and caudal peduncle weight (X10). We found that the coefficient of variation (CV) of X4 was the largest in each culture mode, and males (28.58%~38.67%) were larger than females (37.76%~66.74%). The CV of X4 of crayfish cultured in D1 and D2 was larger than that of D3. All traits except X8 were positively correlated with body weight (p < 0.05). After pathway analysis, we found that X4, X5, X7, and X10 were significantly correlated with the body weight of D1-♀; the equation was YD1-♀ = −29.803 + 1.249X4 + 0.505X5 + 0.701X7 + 1.483X10 (R2 = 0.947). However, X2, X4, and X6 were significantly correlated with the body weight of D1-♂; the equation was YD1-♂ = −40.881 + 0.39X2 + 0.845X4 + 1.142X6 (R2 = 0.927). In D2-♀, X1, X4, X5, and X10 were significantly correlated with body weight; the equation was YD2-♀ = −12.248 + 0.088X1 + 1.098X4 + 0.275X5 + 0.904X10 (R2 = 0.977). X4 and X5 played a major role in the body weight of D2-♂ with the equation: YD2-♂ = −24.871 + 1.177X4 + 0.902X5 (R2 = 0.973). X3 and X10 mainly contributed to the body weight of D3-♀ with the equation: YD3-♀ = −22.476 + 0.432X3 + 3.153X10 (R2 = 0.976). X1 and X4 mainly contributed to the body weight of D3-♂ with the equation: YD3-♂ = −34.434 + 0.363X1 + 0.669X4 (R2 = 0.918). Comparing the pathway analysis with the gray relation analysis, we could conclude that the traits most correlated with body weight in D1-♀ were X10 and X7; in D1-♂, X6; in D2-♀, X10, X1, and X5; in D2-♂, X5; in D3-♀, X10; and in D3-♂, X4 and X1.

Abstract Background Idiosyncratic drug-induced liver injury (IDILI) is common in hepatology practices and, in some cases, lethal. Increasing evidence show that tricyclic antidepressants (TCAs) can induce IDILI in clinical applications but the underlying mechanisms are still poorly understood. Methods We assessed the specificity of several TCAs for NLRP3 inflammasome via MCC950 (a selective NLRP3 inhibitor) pretreatment and Nlrp3 knockout (Nlrp3 −/− ) BMDMs. Meanwhile, the role of NLRP3 inflammasome in the TCA nortriptyline-induced hepatotoxicity was demonstrated in Nlrp3 −/− mice. Results We reported here that nortriptyline, a common TCA, induced idiosyncratic hepatotoxicity in a NLRP3 inflammasome-dependent manner in mildly inflammatory states. In parallel in vitro studies, nortriptyline triggered the inflammasome activation, which was completely blocked by Nlrp3 deficiency or MCC950 pretreatment. Furthermore, nortriptyline treatment led to mitochondrial damage and subsequent mitochondrial reactive oxygen species (mtROS) production resulting in aberrant activation of the NLRP3 inflammasome; a selective mitochondrial ROS inhibitor pretreatment dramatically abrogated nortriptyline-triggered the NLRP3 inflammasome activation. Notably, exposure to other TCAs also induced aberrant activation of the NLRP3 inflammasome by triggering upstream signaling events. Conclusion Collectively, our findings revealed that the NLRP3 inflammasome may act as a crucial target for TCA agents and suggested that the core structures of TCAs may contribute to the aberrant activation of NLRP3 inflammasome induced by them, an important factor involved in the pathogenesis of TCA-induced liver injury. Video Abstract

Abstract Purpose Endothelial progenitor cells (EPCs) have been revealed to interventions in atherosclerosis (AS) progressions. Traditional Chinese medicines (TCMs) have been discovered to modulate the functions of EPCs. Herein, effects of allicin on EPCs were explored in coronary atherosclerosis (CAS). Methods Allicin (5 or 10 mg/kg/d) was used to treat the ApoE−/− mice fed with high-fat diet (HFD. TC, TG, LDL-C, and HDL-C were examined. HE staining was applied for observation of CAS lesions. In vitro, EPCs were induced by ox-LDL and then treated with allicin and an eNOS inhibitor, L-NAME. Thereafter, the cell viability, apoptosis and migration were examined using CCK-8, flow cytometry and Transwell methods. Western blot was applied for evaluating eNOS, Nrf2 and HO-1 protein expression. NO production, MDA content, and SOD activity were also measured. Results Allicin inhibited CAS progression, decreased serum levels of TC, TG, and LDL-C but increased HDL-C. Moreover, counts of circulating EPCs, and the protein levels of eNOS, Nrf2 and HO-1 were increased by allicin treatment in mice fed with HFD. Allicin suppressed MDA contents but enhanced SOD activities. In vitro, allicin reversed the impacts of ox-LDL induction in EPCs, facilitating cell mobility and NO production, and decreasing apoptosis. L-NAME treatment reversed effects of allicin. Conclusion Allicin alleviated CAS progressions in mice, modulating the cell apoptosis and migration of EPCs via eNOS/ Nrf2/HO-1 pathway.

Abstract Discoveries of tetraquarks not only enrich the hadronic spectrum but also provide more platforms to understand quantum chromodynamics. We study the production processes of hidden-charm and open-charm tetraquarks in B decays by analyzing their topological amplitudes. Relations between different channels are found, which confront tests by experiments to probe the nature of the tetraquarks. Furthermore, promising channels to find more tetraquarks are proposed.

Abstract In this paper, we investigate the existence of a least-energy sign-changing solutions for the following Kirchhoff-type equation: − ( 1 + b ∫ R 2 K ( x ) | ∇ u | 2 d x ) div ( K ( x ) ∇ u ) = K ( x ) f ( u ) , x ∈ R 2 , $$ - \biggl(1+b \int _{\mathbb{R}^{2}} K(x) \vert \nabla u \vert ^{2}\,dx \biggr) \operatorname{div} \bigl(K(x)\nabla u \bigr)=K(x)f(u),\quad x\in \mathbb{R}^{2}, $$ where f has exponential subcritical or exponential critical growth in the sense of the Trudinger–Moser inequality. By using the constrained variational methods, combining the deformation lemma and Miranda’s theorem, we prove the existence of a least-energy sign-changing solution. Moreover, we also prove that this sign-changing solution has exactly two nodal domains.

Introduction: Under the dual opportunities of low-carbon consumption preference and online consumption platforms, vendors’ low-carbon advertising incursions provide opportunities for decarbonization and market position enhancement, as well as further research on the value of low-carbon advertising. This study aims to explore the contractual choices of green vendors’ online channels participating in low-carbon advertising competition under the low-carbon goodwill effect, and to simulate and evaluate the contractual choices of supply chain members.Methods: Using differential games, through the innovative application of the traditional low-carbon goodwill model and the introduction of the low-carbon advertising competition intensity coefficient, we design one-way and two-way cost-sharing contracts under low-carbon competition, coordinate the vicious competition in the supply chain, and provide contractual choices for supply chain participants.Results and discussion: Under the low-carbon advertising competition decision, the manufacturer has an absolute low-carbon market advantage, but the interests of all supply chain members are weakened, and interestingly, the manufacturer, who dominates the market, is the facilitator of the contractual agreement. Second, well-designed pacts can provide manufacturers and traders with more options for low-carbon strategies. Although both one-way and two-way cost-sharing pacts can generate Pareto gains for the supply chain and its members in advertising competition, two-way cost-sharing pacts are superior to one-way pacts in terms of coordination advantages. In addition, an important finding is that greater profit growth can be achieved through contractual cooperation in low-intensity advertising competition. Thus, moderate competition is desirable, while excessive competition can harm the supply chain system. Manufacturers should actively urge retailers to cooperate in order to optimize profits and establish long-term stable partnerships between upstream and downstream firms in green supply chains.

Photothermal therapy (PTT) is a promising antitumor treatment that is easy to implement, minimally invasive, and precisely controllable, and evokes strong antitumor immunity. We believe that a thorough elucidation of its underlying antitumor immune mechanisms would contribute to the rational design of combination treatments with other antitumor strategies and consequently potentiate clinical use. In this study, PTT using indocyanine green (ICG) induced STING-dependent type I interferon (IFN) production in macrophages (RAW264.7 and bone marrow-derived macrophages (BMDMs)), as proven by the use of a STING inhibitor (C178), and triggered STING-independent type I IFN generation in tumor cells (CT26 and 4T1), which was inhibited by DNase pretreatment. A novel liposome coloaded with the STING agonist 2′3′-cGAMP (cGAMP) and chloroquine (CQ) was constructed to achieve synergistic effect with PTT, in which CQ increased cGAMP entrapment efficiency and prevented STING degradation after IFN signaling activation. The sequential combination treatment caused a significant increase in tumor cell apoptosis, probably due to interferon stimulating gene products 15 and 54 (ISG15 and ISG 54), and achieved a more striking antitumor inhibition effect in the CT26 tumor model than the 4T1 model, likely due to higher STAT1 expression and consequently more intense IFN signal transduction. In the tumor microenvironment, the combination treatment increased infiltrating CD8+T cells (4-fold) and M1-like TAMs (10-fold), and decreased M-MDSCs (over 2-fold) and M2-like TAMs (over 4-fold). Above all, in-depth exploration of the antitumor mechanism of PTT provides guidance for selecting sensitive tumor models and designing reasonable clinical schemes.

A field experiment was carried out to evaluate the effects of drip fertigation combined with plant hedgerows on nitrogen and phosphorus runoff losses in intensive pear orchards in the Tai Lake Basin. Nitrogen and phosphorus runoff over a whole year were measured by using successional runoff water collection devices. The four experimental treatments were conventional fertilization (CK), drip fertigation (DF), conventional fertilization combined with plant hedgerows (C+H), and drip fertigation combined with plant hedgerows (D+H). The results from one year of continuous monitoring showed a significant positive correlation between precipitation and surface runoff discharge. Surface runoff discharge under the treatments without plant hedgerows totaled 15.86% of precipitation, while surface runoff discharge under the treatments with plant hedgerows totaled 12.82% of precipitation. Plant hedgerows reduced the number of runoff events and the amount of surface runoff. Precipitation is the main driving force for the loss of nitrogen and phosphorus in surface runoff, and fertilization is an important factor affecting the losses of nitrogen and phosphorus. In CK, approximately 7.36% of nitrogen and 2.63% of phosphorus from fertilization entered the surface water through runoff. Drip fertigation reduced the accumulation of nitrogen and phosphorus in the surface soil and lowered the runoff loss concentrations of total nitrogen (TN) and total phosphorus (TP). Drip fertigation combined with plant hedgerows significantly reduced the overall TN and TP losses by 45.38 and 36.81%, respectively, in comparison to the CK totals. Drip fertigation increased the vertical migration depth of nitrogen and phosphorus nutrients and reduced the accumulation of nitrogen and phosphorus in the surface soil, which increased the pear yield. The promotion of drip fertigation combined with plant hedgerows will greatly reduce the losses of nitrogen and phosphorus to runoff and maintain the high fruit yields in the intensive orchards of the Tai Lake Basin.

Abstract Introduction Skin and soft tissue infections are common because of exposure to aquatic environment, while severe infections caused by Aeromonas veronii are rare. Case presentation We report a case of severe skin and soft tissue infection of the left upper limb caused by Aeromonas veronii. A 50-year-old Chinese woman, who had a history of cardiac disease and type 2 diabetes mellitus, accidentally injured her left thumb while cutting a fish. Early antibiotic therapy and surgical debridement was performed before the result of bacterial culture came back. Whole-genome sequencing was further performed to confirm the pathogen and reveal the drug resistance and virulence genes. The wound was gradually repaired after 1 month of treatment, and the left hand recovered well in appearance and function after 3 months of rehabilitation. Conclusion Early diagnosis, surgical intervention, and administration of appropriate antibiotics are crucial for patients who are suspected of having skin and soft tissue infection, or septicemia caused by Aeromonas veronii.

Abstract Metaproteomics can provide valuable insights into the functions of human gut microbiota (GM), but is challenging due to the extreme complexity and heterogeneity of GM. Data-independent acquisition (DIA) mass spectrometry (MS) has been an emerging quantitative technique in conventional proteomics, but is still at the early stage of development in the field of metaproteomics. Herein, we applied library-free DIA (directDIA)-based metaproteomics and compared the directDIA with other MS-based quantification techniques for metaproteomics on simulated microbial communities and feces samples spiked with bacteria with known ratios, demonstrating the superior performance of directDIA by a comprehensive consideration of proteome coverage in identification as well as accuracy and precision in quantification. We characterized human GM in two cohorts of clinical fecal samples of pancreatic cancer (PC) and mild cognitive impairment (MCI). About 70,000 microbial proteins were quantified in each cohort and annotated to profile the taxonomic and functional characteristics of GM in different diseases. Our work demonstrated the utility of directDIA in quantitative metaproteomics for investigating intestinal microbiota and its related disease pathogenesis.

Objective:. Emerging data have shown that non-coding RNAs (ncRNAs) can encode micro-peptides (≤100 amino acids) that play an important role in regulating physiological and pathological processes. Herein, we explored ncRNAs that may encode micro-peptides that are involved in the development of hepatocellular carcinoma (HCC). Methods:. High-throughput sequencing of ribosomal protein S6 (RPS6) was performed in four cancer cell lines using RNA-immunoprecipitation (RIP). UCSC databases obtained the full length of the gene sequences and quantitative polymerase chain reaction (qPCR) was used to evaluate expression levels of ncRNAs of interest. The coding activity of ncRNA was assessed in vitro by co-immunoprecipitation, plasmid transfection, western blot, immunofluorescence and RNA fluorescence in situ hybridization. Mass spectrometry was performed to explore the potential functions of candidate micro-peptide in HCC. This study involving human tissue specimens was conducted in accordance with Declaration of Helsinki and approved by the Institutional Review Board of Changhai Hospital, Naval Military Medical University, China (approval No. CHEC2020-081) on June 6, 2020. Results:. We performed RIP assay using primary antibodies for RPS6 and high-throughput sequencing. A total of 223 overlapping genes were captured by RPS6-RIP. Venn diagram analysis revealed that 60 overlapping genes were detected in four cancer cell lines. QRT-PCR showed that six of the candidate genes (RP11-298J20.4, RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, HCP5, RP11-517B11.7) were expressed in Huh7 and Hep3B cells. Further analysis of these six candidate genes and found that five (RP11-298J20.4, RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, RP11-517B11.7) displayed higher expression levels in HCC cell lines (Huh7, Hep3B) and tumor tissues than in liver cell lines (L-02, QSG-7701) and non-tumor tissues, respectively. Performed additional RIP assays and confirmed that four of the genes (RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, RP11-517B11.7) bound RPS6. We obtained the full length of the four gene sequences from the UCSC database and analyzed the open reading frames by ORF Finder; to determine the translation potential of the four candidate small open reading frames (smORFs), we subcloned a FLAG epitope tag into the C-terminal of the four selected smORFs before the stop codon, and the fusion sequences were then cloned into three different plasmid vectors (pSPT19, pcDNA3.1, and PEGFP-N1). We performed coupled transcription and translation reactions and found that the pSPT19 plasmids encoded small peptides in vitro. After then transfected the pcDNA3.1 constructs into Huh7 cells, and a single 7.2 kDa micro-peptide was encoded from the candidate smORF of RP11.119F7.5. We transfected the recombinant pEGFP-N1 plasmids with smORFs in HCC cells, and western blot analysis revealed a band above GFP in the RP11.119F7.5 recombinant plasmid lane. The coding potential of the RP11-119F7.5 vector was also confirmed by immunofluorescence assay. Fluorescence in situ hybridization assay revealed that RP11-119F7.5 was localized in the cytoplasm and nucleoplasm of HCC cells. Gene ontology enrichment analysis showed that the micro-peptide–interacting proteins were mainly involved in extracellular exosomes. We also found the identified proteins were involved in several biological functions like protein binding, poly(A) RNA binding, translational initiation, and the nuclear-transcribed mRNA catabolic process. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed the peptide-interacting proteins might participate in several critical pathways including ribosome, biosynthesis of amino acids, carbon metabolism, biosynthesis of antibiotics, glycolysis and gluconeogenesis, pathogenic Escherichia coli infection and influenza A. Conclusion:. Our study revealed a novel micro-peptide translated by ncRNA RP11-119F7.5, highlighting the coding ability and potential role of ncRNAs in HCC.

Abstract To find the manufacturer's optimal recycling mode under the dual factors of government subsidies and consumers' low‐carbon preference, we construct three game models by taking the wholesale price, retail price, recovery rate, and carbon emission reduction level as the decision variables. Then, Stackelberg Game and Mathematica 12.0 are used to work out the equilibrium strategies of the recovery model, then we reveal the impact of government subsidies and consumers' low‐carbon preference on the closed‐loop supply chain. (1) Entrusting retailers to recycle is the best choice. (2) The government subsidy to the manufacturer and retailer within a certain range is conducive to promoting recycling activities and has a positive impact on the manufacturer's cost savings and carbon emission reduction investment. Nevertheless, the effect of subsidizing the third party is not obvious. (3) Cultivating consumers' low‐carbon preference for low‐carbon/remanufactured products can not only directly promote the overall profit of the closed‐loop supply chain, but also increase the rate of recovery and level of carbon emission reduction. Thus, the government should increase the subsidized prices of manufacturers and retailers and there is no need to subsidize third parties. It is necessary to cultivate consumers' low‐carbon preference, which is conducive to promoting manufacturers' carbon emission reduction activities.

Remote sensing has become an essential tool for geological exploration, disaster monitoring, emergency rescue, and environmental supervision, while the limited number of remote sensing satellites and ground stations restricts the timeliness of remote sensing services. Satellite Internet has features of large bandwidth, low latency, and wide coverage, which can provide ubiquitous high-speed access for time-sensitive remote sensing users. This study proposes a near real-time remote sensing (NRRS) architecture, which allows satellites to transmit remote sensing data via inter-satellite links and offload to the Earth Stations from the satellite that moves overhead. The NRRS architecture has the advantages of instant response, ubiquitous access, and intelligent integration. Based on a test communication constellation, a vehicle-mounted Satcom on-the-move experiment was conducted to validate the presented NRRS architecture. The results show that the whole process from demand collection to image acquisition takes no more than 25 min, which provides an engineering reference for the subsequent implementation of near real-time remote sensing.

MR perfusion imaging is important in the clinical evaluation of primary brain tumors, particularly in differentiating between true progression and treatment-induced change. The utility of velocity-selective ASL (VSASL) compared to the more commonly utilized DSC perfusion technique was assessed in routine clinical surveillance MR exams of 28 patients with high-grade gliomas at 1.5T. Using RANO criteria, patients were assigned to two groups, one with detectable residual/recurrent tumor (“RT”, n = 9), and the other with no detectable residual/recurrent tumor (“NRT”, n = 19). An ROI was drawn to encompass the largest dimension of the lesion with measures normalized against normal gray matter to yield rCBF and tSNR from VSASL, as well as rCBF and leakage-corrected relative CBV (lc-rCBV) from DSC. VSASL (rCBF and tSNR) and DSC (rCBF and lc-rCBV) metrics were significantly higher in the RT group than the NRT group allowing adequate discrimination (p < 0.05, Mann–Whitney test). Lin’s concordance analyses showed moderate to excellent concordance between the two methods, with a stronger, moderate correlation between VSASL rCBF and DSC lc-rCBV (r = 0.57, p = 0.002; Pearson’s correlation). These results suggest that VSASL is clinically feasible at 1.5T and has the potential to offer a noninvasive alternative to DSC perfusion in monitoring high-grade gliomas following therapy.

Abstract Pyroptosis is an immunogenic cell death and would trigger robust antitumor immunity. However, due to cytoxicity of pyroptosis executors, Gasdermin family proteins, it is indispensable to construct tumor‐specific vectors. Here, we report the development of a novel vector named lipid‐coated poly(lactide‐co‐glycolide) (PLGA) nanoparticles coloaded with Gasdermin E expressing plasmid DNA (GSDME‐pDNA) with a heat‐inducible mouse heat shock protein 70 (mHSP70) as the promoter and a photosensitizer indocyanine green (ICG) to activate the mHSP70 element. The cellular internalization and transfection rate of the vector were remarkably enhanced by photothermal treatment. And the mHSP70 promoter further improved the gene transfection rate for about 15‐fold. With the combination of oxaliplatin (OXA), the mechanism switch between apoptosis and pyroptosis was fulfilled by cleavage of GSDME through activated caspase‐3, which promoted damage‐associated molecular patterns (DAMPs) release and increased the infiltration of immune cells at the tumor site. This combination strategy not only prominently inhibited the growth of the treated tumor, but also exhibited a lethal effect on the distal tumors. Besides, mouse colon cancer cell CT26 overexpressing GSDME after OXA treatment had the potential to be the preventive tumor vaccine. This study provides a novel thought and feasible method for the clinical treatment of colon cancer.

ABSTRACTVibrio alginolyticus, an emergent species of Vibrio genus, exists in aquatic and marine environments. It has undergone genetic diversification, but its detailed genomic diversity is still unclear. Here, we performed a multi-dimensional comparative genomic analysis to explore the population phylogeny, virulence-related genes and potential drug resistance genes of 184 V. alginolyticus isolates. Although genetic diversity is complex, we analysed the population structure using three sub-datasets, including the subdivision for three lineages into sublineages and the distribution of strains in the marine ecological niche. Accessory genes, most of which reclassified V. alginolyticus genomes as different but with relatively close affinities, were nonuniformly distributed among these isolates. We demonstrated that the spread of some post-evolutionary isolates (mainly L3 strains isolated from Chinese territorial seas) was likely to be closely related to human activities, whereas other more ancestral strains (strains in the L1 and L2) tended to be locally endemic and formed clonal complex groups. In terms of pathogenicity, the potential virulence factors were mainly associated with toxin, adherence, motility, chemotaxis, and the type III secretion system (T3SS). We also found five types of antibacterial drug resistance genes. The prevalence of β-lactam resistance genes was 100%, which indicated that there may be a potential risk of natural resistance to β-lactam drugs. Our study reveals insights into genomic characteristics, evolution and potential virulence-associated gene profiles of V. alginolyticus.

Abstract The decay width of the $$D_s^{*}$$ D s ∗ meson is dominated by the electromagnetic mode $$D_s^*\rightarrow D_s \gamma $$ D s ∗ → D s γ , and it is thus the longest-lived charged vector meson. In light of this point, we perform the first QCD LCSRs calculation of $$D_s^{*}\rightarrow \phi $$ D s ∗ → ϕ helicity form factors and discuss the experiment potential of discovering exclusive $$D_s^{*}$$ D s ∗ weak decays. The main result is the partial decay widths, which read as $$\varGamma _{D_s^*\rightarrow l \nu } = 2.44 \times 10^{-12} \, \textrm{GeV}$$ Γ D s ∗ → l ν = 2.44 × 10 - 12 GeV , $$\varGamma _{D_s^*\rightarrow \phi l \nu } = (3.28^{+0.82}_{-0.71}) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ l ν = ( 3 . 28 - 0.71 + 0.82 ) × 10 - 14 GeV , $$\varGamma _{D_s^{*} \rightarrow \phi \pi } = ( 3.81^{+1.52}_{-1.33} ) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ π = ( 3 . 81 - 1.33 + 1.52 ) × 10 - 14 GeV and $$\varGamma _{D_s^{*}\rightarrow \phi \rho } = ( 1.16^{+0.42}_{-0.39} ) \times 10^{-13} \, \textrm{GeV}$$ Γ D s ∗ → ϕ ρ = ( 1 . 16 - 0.39 + 0.42 ) × 10 - 13 GeV . We show that these channels are promising in the near future, serving as the first experimental observation of weak decays of a vector meson, and would open up a new playground for precision test of the standard model.

Gliomas are the most common primary malignant brain tumors in adults. The fifth edition of the WHO Classification of Tumors of the Central Nervous System, published in 2021, provided molecular and practical approaches to CNS tumor taxonomy. Currently, molecular features are essential for differentiating the histological subtypes of gliomas, and recent studies have emphasized the importance of isocitrate dehydrogenase (IDH) mutations in stratifying biologically distinct subgroups of gliomas. IDH plays a significant role in gliomagenesis, and the association of IDH status with prognosis is very clear. Recently, there has been much progress in conventional MR imaging (cMRI), advanced MR imaging (aMRI), and radiomics, which are widely used in the study of gliomas. These advances have resulted in an improved correlation between MR signs and IDH mutation status, which will complement the prediction of the IDH phenotype. Although imaging cannot currently substitute for genetic tests, imaging findings have shown promising signs of diagnosing glioma subtypes and evaluating the efficacy and prognosis of individualized molecular targeted therapy. This review focuses on the correlation between MRI and MRI-based radiomics and IDH gene-phenotype prediction, discussing the value and application of these techniques in the diagnosis and evaluation of the prognosis of gliomas.

High-efficiency fertilizers suitable for mechanical spraying can improve the fertilizer application and utilization efficiency. In this study, two types of granular compound fertilizers suitable for unmanned air vehicle spraying were developed using urea, potassium chloride, humic acid, and an amino acid synergist according to the fertilization requirements of rice at the booting stage. The physical and chemical properties of the compound fertilizers were analyzed by Fourier transform infrared spectroscopy and scanning electron microscopy. The release kinetics of the fertilizer was studied via a soil column leaching experiment. The effect of fertilizer particles on unmanned air vehicle spraying uniformity was studied via an orthogonal simulation experiment. Results showed that the chemical interaction between compound-fertilizer raw materials formed complexes such as C-NH-C and -CO-NH-, which caused a change in fertilizer particle morphology. This led to chemical monolayer adsorption or internal fertilizer diffusion, which in turn delayed the fertilizer release by 5−10 d. A simulation bench test showed that the fertilizer particle hardness and roundness exceeded 20 N and 85%, respectively, while the particle size was in the range of 2.07−5.13 mm, which resulted in good unmanned air vehicle spraying uniformity with a lateral variation coefficient of less than 15%. Finally, the experimental field results demonstrated that the new compound fertilizers, when sprayed by an unmanned air vehicle, could improve the economic benefit by 916−2742 CNY ha−1 without reducing the nitrogen utilization rate and rice yield. The new compound fertilizers exhibit delayed release, good spraying uniformity, and improved economic benefit, rendering them suitable for large-scale promotion and application.

Most genetic studies of disease have been done in European ancestry cohorts, and the relevance to other populations is not guaranteed. Here, the authors use data from 22,000 British South Asian individuals and find that the transferability of polygenic scores was high for lipids and blood pressure, and lower for BMI and coronary artery disease.

Abstract Increased medical application of psychotropic drugs raised attention concerning their toxicological effects. In fact, more than 160 psychotropic drugs including antidepressants and antipsychotics, have been shown to cause liver side effects, but the underlying mechanisms are still poorly understood. Here, we discovered that fluoxetine, a common antidepressant, was specifically sensed by NLRP3 inflammasome, whose subsequent activation resulted in the maturation of caspase-1 and IL-1β, as well as gasdermin D (GSDMD) cleavage, which could be completely abrogated by a selective NLRP3 inhibitor MCC950 or Nlrp3 knockout (Nlrp3 −/− ). Mechanistically, mitochondrial damage and the subsequent mitochondrial reactive oxygen species (mtROS) accumulation were crucial upstream signaling events in fluoxetine-triggered NLRP3 inflammasome activation. In fluoxetine hepatotoxicity models, mice showed the alterations of aminotransferase levels, hepatic inflammation and hepatocyte death in an NLRP3-dependent manner, and MCC950 pretreatment could reverse these side effects of fluoxetine. Notably, we also found that multiple antidepressants, such as amitriptyline, paroxetine, and imipramine, and antipsychotics, such as asenapine, could specifically trigger the NLRP3 inflammasome activation. Collectively, our findings implicate multiple psychotropic drugs may act as danger signals sensed by the NLRP3 inflammasome and result in hepatic injury.

Velocity-selective inversion (VSI) based velocity-selective arterial spin labeling (VSASL) has been developed to measure cerebral blood flow (CBF) with low susceptibility to the prolonged arterial transit time and high sensitivity to brain perfusion signal. The purpose of this magnetic resonance imaging study is to evaluate the test-retest reliability of a VSI-prepared 3D VSASL protocol with whole-brain coverage to detect baseline CBF variations among cognitively normal participants in different brain regions. Coefficients of variation (CoV) of both absolute and relative CBF across scans or sessions, subjects, and gray matter regions were calculated, and corresponding intraclass correlation coefficients (ICC) were computed. The higher between-subject CoV of absolute CBF (13.4 ± 2.0%) over within-subject CoV (within-session: 3.8 ± 1.1%; between-session: 4.9 ± 0.9%) yielded moderate to excellent ICC (within-session: 0.88±0.08; between-session: 0.77±0.14) to detect normal variations of individual CBF. The higher between-region CoV of relative CBF (11.4 ± 3.0%) over within-region CoV (within-session: 2.3 ± 0.9%; between-session: 3.3 ± 1.0%) yielded excellent ICC (within-session: 0.92±0.06; between-session: 0.85±0.12) to detect normal variations of regional CBF. Age, blood pressure, end-tidal CO2, and hematocrit partially explained the variability of CBF across subjects. Together these results show excellent test-retest reliability of VSASL to detect both between-subject and between-region variations supporting its clinical utility.

ZnTiO3/TiO2 composite photocatalysts were synthesized via the sol–gel technique, and the impact of varying heat treatment temperatures (470, 570, 670 °C) on their crystalline arrangement, surface morphology, elemental composition, chemical state, specific surface area, optical characteristics, and photocatalytic efficacy was systematically investigated. The outcomes revealed that, as the temperature ascends, pure TiO2 undergoes a transition from anatase to rutile, ultimately forming a hybrid crystal structure at 670 °C. The incorporation of ZnTiO3 engenders a reduction in the TiO2 grain dimensions and retards the anatase-to-rutile phase transition. Consequently, the specimens manifest a composite constitution of anatase and ZnTiO3. In contrast, for pure TiO2, the specimen subjected to 670 °C annealing demonstrates superior photocatalytic performance due to its amalgamated crystal arrangement. The degradation efficacy of methylene blue (MB) aqueous solution attains 91% within a 60-min interval, with a calculated first-order reaction rate constant of 0.039 min−1. Interestingly, the ZnTiO3/TiO2 composite photocatalysts exhibit diminished photocatalytic activity in comparison to pristine TiO2 across all three temperature variations. Elucidation of the photocatalytic mechanism underscores that ZnTiO3 coupling augments the generation of photogenerated charge carriers. Nonetheless, concurrently, it undermines the crystalline integrity of the composite, yielding an excess of amorphous constituents that impede the mobility of photoinduced carriers. This dual effect also fosters escalated recombination of photogenerated charges, culminating in diminished quantum efficiency and reduced photocatalytic performance.

Abstract The existence of heavy neutrinos is the most prominent feature of type-I seesaw-like mechanisms, which naturally explain tiny masses of observed neutrinos. Various experiments have been conducted to search for heavy neutrinos, with meson decays sensitive to heavy neutrinos lighter than B mesons and high energy collider experiments sensitive to the ones with masses larger than $${\mathcal {O}}(0.1)$$ O ( 0.1 ) TeV. In between, there is a mass gap uncovered by these two kinds of experiments, and by this work, we investigate the 3–15 GeV neutrino searches at future Z-factories via the process $$e^{-}e^{+}\rightarrow Z \rightarrow \nu N \rightarrow \nu \ell {\bar{q}}q'$$ e - e + → Z → ν N → ν ℓ q ¯ q ′ with $$\ell =e,\mu $$ ℓ = e , μ . Based on the simulation of signal and background events, we find that the signals appear as monojet events owning to the large Lorentz boost of the heavy neutrinos. Furthermore, the substructures of such monojet are essential to reconstruct the signal and suppress the background. The upper bounds on the cross section of the signal process and the mixing parameter $${\left| V_{\ell N} \right| }^2$$ V ℓ N 2 are obtained. Compared with other experiments, the monojet method at future Z-factories will be able to fill the gap around this mass range.

Abstract To alleviate the social contradiction between limited medical resources and increasing medical needs, the medical image-assisted diagnosis based on deep learning has become the research focus in Wise Information Technology of med. Most of the existing medical segmentation models based on Convolution or Transformer have achieved relatively sound effects. However, the Convolution-based model with a limited receptive field cannot establish long-distance dependencies between features as the Network deepens. The Transformer-based model produces large computation overhead and cannot generalize the bias of local features and perceive the position feature of medical images, which are essential in medical image segmentation. To address those issues, we present Triple Gate MultiLayer Perceptron U-Net (TGMLP U-Net), a medical image segmentation model based on MLP, in which we design the Triple Gate MultiLayer Perceptron (TGMLP), composed of three parts. Firstly, considering encoding the position information of features, we propose the Triple MLP module based on MultiLayer Perceptron in this model. It uses linear projection to encode features from the high, wide, and channel dimensions, enabling the model to capture the long-distance dependence of features along the spatial dimension and the precise position information of features in three dimensions with less computational overhead. Then, we design the Local Priors and Global Perceptron module. The Global Perceptron divides the feature map into different partitions and conducts correlation modelling for each partition to establish the global dependency between partitions. The Local Priors uses multi-scale Convolution with high local feature extraction ability to explore further the relationship of context feature information within the structure. At last, we suggest a Gate-controlled Mechanism to effectively solves the problem that the dependence of position embeddings between Patches and within Patches in medical images cannot be well learned due to the relatively small number of samples in medical images segmentation data. Experimental results indicate that the proposed model outperforms other state-of-the-art models in most evaluation indicators, demonstrating its excellent performance in segmenting medical images.

Abstract Background The prevalence of anxiety and depression symptoms among caretakers of children with atopic dermatitis (AD) and associated factors is unclear. The study was designed to explore anxiety and depression symptoms among caretakers of AD, and screen factors associated with anxiety and depression symptoms. Methods A total of 901 children with AD and their caretakers were continuously enrolled and interviewed at dermatology department of Capital Institute of Pediatrics, Beijing, China. Children’s medication was administered by their caretakers. Caretakers’ anxiety and depression symptoms were evaluated by Hamilton Depression Rating Scale-17 and Hamilton Depression Rating Scale, while medication compliance was evaluated and divided into poor ( 7 points) by Morisky Medication Adherence Scale. Multilevel ordered logistic regression was used to screen factors associated with caretakers’ anxiety and depression. Results Among caretakers, 41.5% had anxiety symptoms, 39.6% had depression symptoms, 51.4% have any of the two and 29.7% had both of the two. Factors associated with caretakers’ anxiety symptoms included longer duration of the illness (OR, 0.99, 95% CI 0.98–0.99) and taking care of children with severe AD (OR, 2.55, 95% CI 1.43–4.55). Factors associated with caretakers’ depression symptoms included higher educational level (OR, 0.56, 95% CI 0.39–0.80), taking care of children with moderate (OR, 2.01, 95% CI 1.15–3.50) and severe AD (OR, 3.99, 95% CI 2.10–7.59) and poor medication compliance (OR, 3.45, 95% CI 1.13–10.56). Conclusions Prevalence of anxiety and depression symptoms among caretakers of AD were high. Attention should be paid to caretakers of AD at higher risk for those psychological problems.

The morphology of urban residential blocks in China, which is strictly affected by regulations, can potentially improve or deteriorate microclimates. This paper first proposes a framework for identifying typical residential block typologies using Nanjing as an example. A thorough investigation, consisting of 114 samples, was conducted, and 18 typical residential block typologies were summarized. Second, 3D non-isothermal numerical simulations were performed on the hottest days of summer using the ENVI-met. The effect of morphological indices on the microclimate at the pedestrian level was explored using statistical methods and a novel graphic method named m-SpaceMate. The results revealed a strong correlation between the urban heat island intensity (UHII), mean radiation temperature, and universal thermal climate index (UTCI) and floor area ratio (FAR), as well as between wind velocity (U) and building coverage ratio (BCR). A significant increase in FAR (by approximately 1.0) can result in a low UTCI that was driven by MRT and shading conditions. Six-floor blocks, with FAR between 1.8 and 2.1, had a better overall thermal environment (except for lower U) than that of 11-floor blocks. When considering a similar BCR, blocks with slab-type buildings tended to have a U that was higher by approximately 30%.

Organelles are responsible for the efficient storage and transport of substances in living systems. A myriad of extracellular vesicles (EVs) acts as a bridge to exchange signaling molecules in cell–cell communication, and the highly dynamic tubulins and actins contribute to efficient intracellular substance transport. The inexhaustible cues of natural cargo delivery by organelles inspire researchers to explore the construction of biomimetic architectures for “smart” delivery carriers. Herein, we report a 10-hydroxycamptothecin (HCPT)-peptide conjugate HpYss that simulates the artificial EV-to-filament transformation process for precise liver cancer therapy. Under the sequential stimulus of extracellular alkaline phosphatase (ALP) and intracellular glutathione (GSH), HpYss proceeds via tandem self-assembly with a morphological transformation from nanoparticles to nanofibers. The experimental phase diagram elucidates the influence of ALP and GSH contents on the self-assembled nanostructures. In addition, the dynamic transformation of organelle-mimetic architectures that are formed by HpYss in HepG2 cells enables the efficient delivery of the anticancer drug HCPT to the nucleus, and the size–shape change from extracellular nanoparticles (50–100 nm) to intracellular nanofibers (4–9 nm) is verified to be of key importance for nuclear delivery. Nuclear targeting of HpYss amplifies apoptosis, thus significantly enhancing the inhibitory effect of HCPT (>10-fold) to HepG2 cells. Benefitting from the spatiotemporally controlled nanostructures, HpYss exhibited deep penetration, enhanced accumulation, and long-term retention in multicellular spheroid and xenograft models, potently abolishing liver tumor growth and preventing lung metastasis. We envision that our organelle-mimicking delivery strategy provides a novel paradigm for designing nanomedicine to cancer therapy.