Low-cost and scalable projected light-sheet microscopy for the high-resolution imaging of cleared tissue and living samples.

Light-sheet fluorescence microscopy (LSFM) is a widely used technique for imaging cleared tissue and living samples. However, high-performance LSFM systems are typically expensive and not easily scalable. Here we introduce a low-cost, scalable and versatile LSFM framework, which we named 'projected light-sheet microscopy' (pLSM), with high imaging performance and small device and computational footprints. We characterized the capabilities of pLSM, which repurposes readily available consumer-grade components, optimized optics, over-network control architecture and software-driven light-sheet modulation, by performing high-resolution mapping of cleared mouse brains and of post-mortem pathological human brain samples, and via the molecular phenotyping of brain and blood-vessel organoids derived from human induced pluripotent stem cells. We also report a method that leverages pLSM for the live imaging of the dynamics of sparsely labelled multi-layered bacterial pellicle biofilms at an air-liquid interface. pLSM can make high-resolution LSFM for biomedical applications more accessible, affordable and scalable.

Triborane (B3H7)-mediated regioselective substitution reactions of pyridine derivatives.

There exists an interplay between borane and a Lewis base in their adducts. However, studies on these adducts so far have mainly focused on the different reactions of B-H bonds with limited attention given to the influence of borane on the chemistry of the Lewis base, except for BF3 and BAr3. Herein, we have synthesized novel borane adducts with pyridine derivatives, Py·B3H7, in which the coordination of B3H7 efficiently achieved the intra-molecular charge transfer. The strong B-N bond in these adducts resulted in the formation of stable dearomatic intermediates of pyridine derivatives, confirmed by 1H and 11B NMR spectroscopy, from which different reactions have transpired to realize C(sp3)-H and C(sp2)-H functionalization under mild conditions. The B3H7 pyridine derivatives are stable and do not dissociate or decompose during the reaction process. The high stability of the B-N bond makes this method a good option for boron-containing drugs with potential for use in boron neutron capture therapy (BNCT).

Surface Acoustic Wave-Enhanced Multi-View Acoustofluidic Rotation Cytometry (MARC) for Pre-Cytopathological Screening.

Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave-enhanced multi-view acoustofluidic rotation cytometry (MARC) technique is developed for pre-cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi-angle observations and amplifies subtle cell differences, particularly in the nuclear-to-cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC-screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening.

Prognostic Value of Magnetic Resonance Imaging Variables Combined with Neutrophil-to-Lymphocyte Ratio in Patients with Cervical Traumatic Spinal Cord Injury.

OBJECTIVE: We aimed to explore the prognostic significance of preoperative magnetic resonance imaging (MRI) variables and novel inflammatory indicators in predicting neurological recovery post-cervical traumatic spinal cord injury (TSCI) in the study. METHODS: We enrolled a total of 244 patients diagnosed with acute cervical TSCI from 2 hospitals and evaluated the prognostic value of MRI variables (intramedullary hemorrhage, intramedullary lesion length [IMLL], maximum spinal cord compression, and maximum canal compromise [MCC]) and novel inflammatory indicators (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and systemic immune-inflammatory index) in patients with acute cervical TSCI. RESULTS: Among the 244 patients, 140 (57.38%) exhibited improved AIS grade conversion at 1-year follow-up. The results revealed intramedullary hemorrhage, IMLL, MCC, neutrophils, and NLR were significantly different compared with follow-up AIS grade. Furthermore, IMLL, MCC, white blood cells, neutrophils, NLR, and lymphocyte-to-monocyte ratio correlated with the follow-up AIS grade by Spearman's correlation analysis. Multivariate analysis showed IMLL, intramedullary hemorrhage, NLR, and admission AIS grade emerged as independent predictors of AIS grade conversion. The receiver operating characteristic curve analysis showed that the novel model (combination of MRI variables, NLR, and admission AIS grade) produced a larger area under the curve compared with using only intramedullary hemorrhage, IMLL, NLR, or admission AIS grade individually. CONCLUSION: Intramedullary hemorrhage and IMLL and NLR are predictors of AIS grade conversion after cervical TSCI. Therefore, we suggest the combination of MRI variables and NLR for the prognostic prediction of AIS grade conversion in patients with cervical TSCI.

Design of probiotic delivery systems and therapeutic effects on target sites in the body.

The microbiota at different sites in the body is closely related to disease. The intake of probiotics is an effective strategy to alleviate diseases and be adjuvant in their treatment. However, probiotics may suffer from harsh environments and colonization resistance, making it difficult to maintain a sufficient number of live probiotics to reach the target sites and exert their original probiotic effects. Encapsulation of probiotics is an effective strategy. Therefore, probiotic delivery systems, as effective methods, have been continuously developed and innovated to ensure that probiotics are effectively delivered to the targeted site. In this review, initially, the design of probiotic delivery systems is reviewed from four aspects: probiotic characteristics, processing technologies, cell-derived wall materials, and interactions between wall materials. Subsequently, the review focuses on the effects of probiotic delivery systems that target four main microbial colonization sites: the oral cavity, skin, intestine, and vagina, as well as disease sites such as tumors. Finally, this review also discusses the safety concerns of probiotic delivery systems in the treatment of disease and the challenges and limitations of implementing this method in clinical studies. It is necessary to conduct more clinical studies to evaluate the effectiveness of different probiotic delivery systems in the treatment of diseases.

Multiregional dynamic contrast-enhanced MRI-based integrated system for predicting pathological complete response of axillary lymph node to neoadjuvant chemotherapy in breast cancer: multicentre study.

BACKGROUND: The accurate evaluation of axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer holds great value. This study aimed to develop an artificial intelligence system utilising multiregional dynamic contrast-enhanced MRI (DCE-MRI) and clinicopathological characteristics to predict axillary pathological complete response (pCR) after NAC in breast cancer. METHODS: This study included retrospective and prospective datasets from six medical centres in China between May 2018 and December 2023. A fully automated integrated system based on deep learning (FAIS-DL) was built to perform tumour and ALN segmentation and axillary pCR prediction sequentially. The predictive performance of FAIS-DL was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RNA sequencing analysis were conducted on 45 patients to explore the biological basis of FAIS-DL. FINDINGS: 1145 patients (mean age, 50 years ±10 [SD]) were evaluated. Among these patients, 506 were in the training and validation sets (axillary pCR rate of 40.3%), 127 in the internal test set (axillary pCR rate of 37.8%), 414 in the pooled external test set (axillary pCR rate of 48.8%), and 98 in the prospective test set (axillary pCR rate of 43.9%). For predicting axillary pCR, FAIS-DL achieved AUCs of 0.95, 0.93, and 0.94 in the internal test set, pooled external test set, and prospective test set, respectively, which were also significantly higher than those of the clinical model and deep learning models based on single-regional DCE-MRI (all P < 0.05, DeLong test). In the pooled external and prospective test sets, the FAIS-DL decreased the unnecessary axillary lymph node dissection rate from 47.9% to 6.8%, and increased the benefit rate from 52.2% to 86.5%. RNA sequencing analysis revealed that high FAIS-DL scores were associated with the upregulation of immune-mediated genes and pathways. INTERPRETATION: FAIS-DL has demonstrated satisfactory performance in predicting axillary pCR, which may guide the formulation of personalised treatment regimens for patients with breast cancer in clinical practice. FUNDING: This study was supported by the National Natural Science Foundation of China (82371933), National Natural Science Foundation of Shandong Province of China (ZR2021MH120), Mount Taishan Scholars and Young Experts Program (tsqn202211378), Key Projects of China Medicine Education Association (2022KTM030), China Postdoctoral Science Foundation (314730), and Beijing Postdoctoral Research Foundation (2023-zz-012).

Lycopodium japonicum Thunb. inhibits chondrocyte apoptosis, senescence and inflammation in osteoarthritis through STING/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA) is a degenerative disease, its characteristic lies in the inflammation and extracellular matrix (ECM) degradation, can lead to significant personal disability and social burden. Lycopodium japonicum Thunb. (LJT) is a lycopinaceae plant with anti-inflammatory and analgesic effects. In traditional Oriental medicine, LJT is commonly used to treat a variety of conditions, including osteoarthritis and low back pain. AIM OF THE STUDY: To investigate the anti-apoptotic, anti-inflammatory and anti-senescence properties of LJT in IL-1ß-induced mouse chondrocytes, and to clarify the underlying mechanisms involved. In addition, the study also examined the effects of LJT by establishing a mouse model of osteoarthritis. The ultimate goal is to identify the mechanism of LJT as an anti-osteoarthritis agent. MATERIALS AND METHODS: In this research, molecular docking and network pharmacology analysis were performed to identify the latent pathways and key targets of LJT action. The CCK-8 kit was used to evaluate LJT's effect on chondrocyte viability. Western blotting, Immunofluorescence, TUNEL staining kit, and SA-ß-gal staining were employed to verify LJT's impact on chondrocytes. Additionally, SO, HE, and Immunohistochemical were utilized to assess LJT's effects on osteoarthritis in mice. In vitro and in vivo experiments were performed to verify the potential mechanism of LJT in OA. RESULTS: Network pharmacology analysis revealed that AKT1, PTGS2, and ESR1 were the key candidate targets for the treatment of OA with LJT. The results of molecular docking indicated that AKT1 exhibited a low binding affinity to the principal constituents of LJT. Hence, we have chosen STING, an upstream regulator of PTGS2, as our target for investigation. Molecular docking revealed that sitosterol, formononetin, stigmasterol and alpha-Onocerin, the main components of LJT, have good binding activity with STING. In vitro experiments showed that LJT inhibited IL-1ß-mediated secretion of inflammatory mediators, apoptosis and senescence of chondrocytes. The results showed that LJT abolished cartilage degeneration induced by unstable medial meniscus (DMM) in mice. Mechanism research has shown that LJT by inhibiting the STING/NF-κB signaling pathways, down-regulating the NF-κB activation, so as to inhibit the development of OA. CONCLUSION: LJT reversed the progression of OA by inhibiting inflammation, apoptosis and senescence in animal models and chondrocytes. The effects of LJT are mediated through the STING/NF-κB pathway.

Dietary niacin Intake and its association with all-cause and cardiovascular mortality rates in individuals with metabolic syndrome.

BACKGROUND: Individuals with metabolic syndrome face elevated cardiovascular and mortality risks, and there is ongoing debate regarding the cardiovascular effects of niacin and its impact on the prognosis of metabolic syndrome. EXPOSURE: Levels of dietary niacin intake based on 24-hour dietary recall. METHODS: Kaplan-Meier survival curves were used to compare survival status among quartiles of dietary niacin intake. Weighted Cox proportional hazards models and restricted cubic splines were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of all-cause and CVD mortality associated with the exposure. RESULTS: This cohort study included 8,744 participants, and during a median follow-up period of 106 months, 1,552 (17.7%) deaths were recorded, with 511 attributed to cardiovascular disease. Kaplan-Meier curves comparing quartiles of dietary niacin intake showed significant differences in both all-cause and cardiovascular mortality rates (log-rank p < 0.001). In the fully adjusted model, the highest quartile of dietary niacin intake was associated with HRs of 0.68 (95% CI: 0.54, 0.87, P = 0.002) for all-cause mortality and 0.63 (95% CI: 0.39, 0.78, P < 0.001) for cardiovascular mortality. CONCLUSION: The results of this cohort study suggest that higher dietary niacin intake is associated with reduced cardiovascular and all-cause mortality risks in the metabolic syndrome population. Furthermore, there appears to be a dose-response relationship between dietary niacin intake and the risks of all-cause and cardiovascular mortality.

Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

Bottle Nanomotors Amplify Tumor Oxidative Stress for Enhanced Calcium Overload/Chemodynamic Therapy.

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.

Comparison of combined virtual reality combined with standing balance training vs. standard practice in patients with hemiplegia: A single-blinded, randomized controlled trial.

OBJECTIVE: To determine whether virtual reality (VR)-based dynamic standing balance training improves three elements of sensory integration and investigate whether VR-based dynamic standing balance training results in improved outcomes, especially regarding balance and gait, compared to the standard training method. DESIGN: This single-blinded, randomized, controlled trial involved 30 patients with hemiplegia. The experimental (EG, n = 15) and control (CG, n = 15) groups received VR augmented-standing balance training or standard standing balance training, respectively, for 20 minutes, 5 days a week, for 3 weeks. The patients were assessed for primary (Sensory Organization Test [SOT] and the Berg balance scale [BBS]) and secondary (the functional reaching test and timed up-and-go test [TUG]) outcomes before and after training. RESULTS: From preintervention to postintervention, the BBS score (F = 26.295, p < 0.05), TUG score (F = 18.12, p < 0.05), mean score of conditions 2 (F = 4.36, p < 0.05) and 6 (F = 5.61, p < 0.05), and composite score of the SOT (F = 5.385, p < 0.05) in both groups were significantly improved. However, there was no significant difference between EG and CG (time*group p > 0.05). CONCLUSION: VR combined with standing balance training improved sensory integration, postural control, balance, and gait ability in patients with hemiplegia, reducing fall risk. However, outcomes were comparable to general balance training regarding balance and gait.

A combination of risk stratification systems for thyroid nodules and cervical lymph nodes may improve the diagnosis and management of thyroid nodules.

Introduction: To assess the performance of the European Thyroid Association Thyroid Imaging and Reporting Data System (EU-TIRADS) and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), which combine risk stratification systems for thyroid nodules (TN-RSS) and cervical lymph nodes (LN-RSS) in diagnosing malignant and metastatic thyroid cancer in a single referral center. Methods: We retrospectively analyzed 2,055 consecutive patients who underwent thyroidectomy or fine-needle aspiration (FNA) from January 2021 to December 2022. TNs and LNs were categorized according to the ultrasonography (US) features of EU-TIRADS and K-TIRADS, respectively. The diagnostic performance and postponed malignancy rate (PMR) were compared with those of EU-TIRADS and K-TIRADS. PMR was defined as the number of patients with malignant nodules not recommended for biopsy among patients with cervical LN metastasis. Results: According to the EU-TIRADS and K-TIRADS, for TN-RSS alone, there were no significant differences in sensitivity, specificity, accuracy, unnecessary FNA rate (UFR), missed malignancy rate (MMR), and PMR between the two TIRADSs (29.0% vs. 28.8%, 50.5% vs. 51.1%, 32.3% vs. 32.2%, 23.6% vs. 23.5%, 88.6% vs. 88.5%, and 54.2% vs. 54.5%, P > 0.05 for all). Combining the LN-RSS increased the diagnostic accuracy (42.7% vs. 32.3% in EU-TIRADS; 38.8% vs. 32.2% in K-TIRADS) and decreased the PMR (54.2% vs. 33.9% in EU-TIRADS; 54.5% vs. 39.3% in K-TIRADS). EU-TIRADS had higher sensitivity and accuracy and lower PMR than K-TIRADS (41.3% vs. 36.7%, 42.7% vs. 38.8%,33.9% vs. 39.3%, P < 0.05 for all). Conclusions: A combination of TN-RSS and LN-RSS for the management of thyroid nodules may be associated with a reduction in PMR, with enhanced sensitivity and accuracy for thyroid cancers in EU-TIRADS and K-TIRADS. These results may offer a new direction for the detection of aggressive thyroid cancers.

Bidirectional remodeling of the central auditory system caused by unilateral auditory deprivation.

Unilateral auditory deprivation (UAD) results in cross-modal reorganization of the auditory cortex (AC), which can impair auditory and cognitive functions and diminish the recovery effect of cochlear implantation. Moreover, the subcortical areas provide extensive ascending projections to the AC. To date, a thorough systematic study of subcortical auditory neural plasticity has not been undertaken. Therefore, this review aims to summarize the current evidence on the bidirectional remodeling of the central auditory system caused by UAD, particularly the changes in subcortical neural plasticity. Lateral changes occur in the cochlear nucleus, lateral superior olive, medial nucleus of the trapezoid body, inferior colliculus, and AC of individuals with UAD. Moreover, asymmetric neural activity becomes less prominent in the higher auditory nuclei, which may be due to cross-projection regulation of the bilateral pathway. As a result, subcortical auditory neural plasticity caused by UAD may contribute to the outcomes of cochlear implantation in patients with single-sided deafness (SSD), and the development of intervention strategies for patients with SSD is crucial. Considering that previous studies have focused predominantly on the neural plasticity of the AC, we believe that bidirectional remodeling of subcortical areas after UAD is also crucial for investigating the mechanisms of interventions.

Carbon-Boosted and Nitrogen-Stabilized Isolated Single-Atom Sites for Direct Dehydrogenation of Lower Alkanes.

Lower olefins are widely used in the chemical industry as basic carbon-based feedstocks. Here, we report the catalytic system featuring isolated single-atom sites of iridium (Ir1) that can function within the entire temperature range of 300-600 °C and transform alkanes with conversions close to thermodynamics-dictated levels. The high turnover frequency values of the Ir1 system are comparable to those of homogeneous catalytic reactions. Experimental data and theoretical calculations both indicate that Ir1 is the primary catalytic site, while the coordinating C and N atoms help to enhance the activity and stability, respectively; all three kinds of elements cooperatively contribute to the high performance of this novel active site. We have further immobilized this catalyst on particulate Al2O3, and we found that the resulting composite system under mimicked industrial conditions could still give high catalytic performances; in addition, we have also developed and established a new scheme of periodical in situ regeneration specifically for this composite particulate catalyst.

Radiogenomics nomogram based on MRI and microRNAs to predict microvascular invasion of hepatocellular carcinoma.

Purpose: This study aimed to develop and validate a radiogenomics nomogram for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) on the basis of MRI and microRNAs (miRNAs). Materials and methods: This cohort study included 168 patients (training cohort: n = 116; validation cohort: n = 52) with pathologically confirmed HCC, who underwent preoperative MRI and plasma miRNA examination. Univariate and multivariate logistic regressions were used to identify independent risk factors associated with MVI. These risk factors were used to produce a nomogram. The performance of the nomogram was evaluated by receiver operating characteristic curve (ROC) analysis, sensitivity, specificity, accuracy, and F1-score. Decision curve analysis was performed to determine whether the nomogram was clinically useful. Results: The independent risk factors for MVI were maximum tumor length, rad-score, and miRNA-21 (all P < 0.001). The sensitivity, specificity, accuracy, and F1-score of the nomogram in the validation cohort were 0.970, 0.722, 0.884, and 0.916, respectively. The AUC of the nomogram was 0.900 (95% CI: 0.808-0.992) in the validation cohort, higher than that of any other single factor model (maximum tumor length, rad-score, and miRNA-21). Conclusion: The radiogenomics nomogram shows satisfactory predictive performance in predicting MVI in HCC and provides a feasible and practical reference for tumor treatment decisions.

A novel multi-feature fusion attention neural network for the recognition of epileptic EEG signals.

Epilepsy is a common chronic brain disorder. Detecting epilepsy by observing electroencephalography (EEG) is the main method neurologists use, but this method is time-consuming. EEG signals are non-stationary, nonlinear, and often highly noisy, so it remains challenging to recognize epileptic EEG signals more accurately and automatically. This paper proposes a novel classification system of epileptic EEG signals for single-channel EEG based on the attention network that integrates time-frequency and nonlinear dynamic features. The proposed system has three novel modules. The first module constructs the Hilbert spectrum (HS) with high time-frequency resolution into a two-channel parallel convolutional network. The time-frequency features are fully extracted by complementing the high-dimensional features of the two branches. The second module constructs a grayscale recurrence plot (GRP) that contains more nonlinear dynamic features than traditional RP, fed into the residual-connected convolution module for effective learning of nonlinear dynamic features. The third module is the feature fusion module based on a self-attention mechanism to assign optimal weights to different types of features and further enhance the information extraction capability of the system. Therefore, the system is named HG-SANet. The results of several classification tasks on the Bonn EEG database and the Bern-Barcelona EEG database show that the HG-SANet can effectively capture the contribution degree of the extracted features from different domains, significantly enhance the expression ability of the model, and improve the accuracy of the recognition of epileptic EEG signals. The HG-SANet can improve the diagnosis and treatment efficiency of epilepsy and has broad application prospects in the fields of brain disease diagnosis.

Soil Acidification Can Be Improved under Different Long-Term Fertilization Regimes in a Sweetpotato-Wheat Rotation System.

Soil acidification is a significant form of agricultural soil degradation, which is accelerated by irrational fertilizer application. Sweetpotato and wheat rotation has emerged as an important rotation system and an effective strategy to optimize nutrient cycling and enhance soil fertility in hilly areas, which is also a good option to improve soil acidification and raise soil quality. Studying the effects of different fertilization regimes on soil acidification provides crucial data for managing it effectively. An eight-year field experiment explored seven fertilizer treatments: without fertilization (CK), phosphorus (P) and potassium (K) fertilization (PK), nitrogen (N) and K fertilization (NK), NP fertilization (NP), NP with K chloride fertilization (NPK1), NP with K sulfate fertilization (NPK2), and NPK combined with organic fertilization (NPKM). This study focused on the soil acidity, buffering capacity, and related indicators. After eight years of continuous fertilization in the sweetpotato-wheat rotation, all the treatments accelerated the soil acidification. Notably, N fertilization reduced the soil pH by 1.30-1.84, whereas N-deficient soil showed minimal change. Organic fertilizer addition resulted in the slowest pH reduction among the N treatments. Both N-deficient (PK) and organic fertilizer addition (NPKM) significantly increased the soil cation exchange capacity (CEC) by 8.83% and 6.55%, respectively, compared to CK. Similar trends were observed for the soil-buffering capacity (pHBC). NPK2 increased the soil K+ content more effectively than NPK1. NPKM reduced the sodium and magnesium content compared to CK, with the highest magnesium content among the treatments at 1.60 cmol·kg-1. Regression tree analysis identified the N input and soil magnesium and calcium content as the primary factors influencing the pHBC changes. Structural equation modeling showed that the soil pH is mainly influenced by the soil ammonium N content and pHBC, with coefficients of -0.28 and 0.29, respectively. Changes in the soil pH in the sweetpotato-wheat rotation were primarily associated with the pHBC and N input, where the CEC content emerged as the main factor, modulated by magnesium and calcium. Long-term organic fertilization enhances the soil pHBC and CEC, slowing the magnesium reduction and mitigating soil acidification in agricultural settings.

Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway.

The spreading of cancer cells from the primary tumor site to other parts of the body, known as metastasis, is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer (TNBC). Overexpression of epidermal growth factor receptor (EGFR) is observed in approximately 70% of TNBC patients. EGFR is crucial for promoting tumor metastasis and associated with poor prognosis. Therefore, it is vital to identify effective therapeutic strategies targeting EGFR inhibition. Ononin, an isoflavonoid found in various plants, such as clover and soybeans, has been shown to have anticancer properties in several cancers. In the present study, we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular pathways. We used various assays, including cell viability, colony formation, Transwell, wound healing, ELISA, Western blotting, and staining techniques, to achieve this objective. The results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis, as evidenced by the cell viability assay, colony formation assay, and expression of apoptosis markers, and reduced the metastatic capabilities of TNBC cells. These effects were achieved through the direct suppression of cell adhesion, invasiveness and motility. Furthermore, in TNBC xenograft lung metastatic models, ononin treatment significantly reduced tumor growth and lung metastasis. Additionally, ononin reversed the epithelial-mesenchymal transition (EMT) by downregulating the expression of EMT markers and matrix metalloproteinases, as confirmed by Western blot analysis. Furthermore, ononin treatment reduced EGFR phosphorylation and suppressed the PI3K, Akt, and mTOR signaling pathways, which was further confirmed using EGFR agonists or inhibitors. Importantly, ononin treatment did not exert any toxic effects on liver or kidney function. In conclusion, our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFR-mediated PI3K/Akt/mTOR pathway. Further studies are warranted to validate its efficacy and explore its potential clinical applications.

PLEK2 activates the PI3K/AKT signaling pathway to drive lung adenocarcinoma progression by upregulating SPC25.

Lung adenocarcinoma (LUAD) is the most common subtype of NSCLC, characterized by poor prognosis and frequently diagnosed at advanced. While previous studies have demonstrated pleckstrin-2 (PLEK2) as aberrantly expressed and implicated in tumorigenesis across various tumor types, including LUAD, the molecular mechanisms underlying PLEK2-mediated LUAD progression remain incompletely understood. In this study, we obtained data from The Cancer Genome Atlas (TCGA) database to assess PLEK2 expression in LUAD, a finding further confirmed through analysis of human tissue specimens. PLEK2-silenced LUAD cellular models were subsequently constructed to examine the functional role of PLEK2 both in vitro and in vivo. Our results showed elevated PLEK2 expression in LUAD, correlating with poor patients' prognosis. PLEK2 knockdown led to a significant suppression of LUAD cell proliferation and migration, accompanied by enhanced apoptosis. Moreover, tumor growth in mice injected with PLEK2-silencing LUAD cells was impaired. Gene expression profiling and Co-IP assays suggested direct interaction between PLEK2 and SPC25, with downregulation of SPC25 similarly impairing cell proliferation and migration. Additionally, we revealed phosphoinositide 3-kinase (PI3K)/AKT signaling activation as requisite for PLEK2-induced malignant phenotypes in LUAD. Collectively, our findings underscore PLEK2's oncogenic potential in LUAD, suggesting its utility as a prognostic indicator and therapeutic target for LUAD management.