A quinine-squaramide catalyzed enantioselective vinylogous Mannich reaction between benzothiazolimines and γ-butenolides for efficient preparation of chiral N-benzothiazole butyrolactones.

A highly effective and enantioselective vinylogous Mannich reaction between benzothiazolimines and γ-butenolides catalyzed by a quinine based squaramide has been disclosed. A series of chiral benzothiazole amines containing a γ,γ-disubstituted butanolide scaffold bearing an adjacent chiral stereocenter have been successfully obtained in good to excellent yields (up to 91%) with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (>20 : 1 dr) with broad substrate generality under mild conditions. The new scaffold integrated with both chiral benzothiazolimine and γ-butenolide moieties may provide a possibility for the development of new pharmaceutical entities.

Study on ring-road incident duration based on latent class accelerated hazard model.

Accurately estimating the duration of freeway incidents can enhance emergency management practices and reduce the likelihood of secondary incidents. To investigate the mechanisms through which key factors influence incident duration, this study sorted out the characteristics and variables of the incident duration on a special freeway in Zhejiang Province, that is, the ring road, and developed a latent class accelerated hazard model. Heterogeneity was incorporated into the model. Three distributions (Weibull, Log-normal, and Log-logistic) were compared, and the Log-logistic distribution exhibited superior performance. The analysis revealed two distinct latent classes: Latent Class 1 and Class 2, had class membership probability of 0.53 and 0.47, respectively, with a total of 11 variables being statistically significant at the 0.05 significance level. It is worth noting that, some neglected explanatory variables are discussed in depth in this study. For example, the mechanism of which specific lane is closed has an impact on the incident duration, rather than a general discussion of the number of lane closures. Furthermore, the way in which the driver involved in the incident reports to the police has a significant impact on the duration of incidents. Notably, potential heterogeneity and its influencing mechanism are captured in the model. Additionally, by predicting class membership using posterior probabilities, it was determined that most data points were more likely to belong to Class 1, and the incident duration primarily ranged between 0 and 60 minutes. These findings are helpful to reduce the duration of incidents on ring-roads and freeways in China, and provide theoretical support for the formulation of freeway incident management and treatment policies.

Functionally improved mesenchymal stem cells via nanosecond pulsed electric fields for better treatment of osteoarthritis.

Background: Numerous approaches have been utilized to optimize mesenchymal stem cells (MSCs) performance in treating osteoarthritis (OA), however, the constrained diminished activity and chondrogenic differentiation capacity impede their therapeutic efficacy. Previous investigations have successfully shown that pretreatment with nanosecond pulsed electric fields (nsPEFs) significantly enhances the chondrogenic differentiation of MSCs. Therefore, this study aims to explore nsPEFs as a strategy to improve OA therapy by enhancing MSCs' activity and chondrogenic differentiation and also investigate its potential mechanism. Methods: In this study, a million MSCs were carefully suspended within a 0.4-cm gap cuvette and subjected to five pulses of nsPEFs (100 ns at 10 kV/cm, 1 Hz), with a 1-s interval between each pulse. A control group of MSCs was maintained without nsPEFs treatment for comparative analysis. nsPEFs were applied to regulate the MSCs performance and hinder OA progresses. In order to further explore the corresponding mechanism, we examined the changes of MSCs transcriptome after nsPEF pretreatment. Finally, we studied the properties of extracellular vesicles (EVs) secreted by MSCs affected by nsPEF and the therapeutic effect on OA. Results: We found that nsPEFs pretreatment promoted MSCs migration and viability, particularly enhancing their viability temporarily in vivo, which is also confirmed by mRNA sequencing analysis. It also significantly inhibited the development of OA-like chondrocytes in vitro and prevented OA progression in rat models. Additionally, we discovered that nsPEFs pretreatment reprogrammed MSC performance by enhancing EVs production (5.77 ± 0.92 folds), and consequently optimizing their therapeutic potential. Conclusions: In conclusion, nsPEFs pretreatment provides a simple and effective strategy for improving the MSCs performance and the therapeutic effects of MSCs for OA. EVs-nsPEFs may serve as a potent therapeutic material for OA and hold promise for future clinical applications. The translational potential of this article: This study indicates that MSCs pretreated by nsPEFs greatly inhibited the development of OA. nsPEFs pretreatment will be a promising and effective method to optimize the therapeutic effect of MSCs in the future.

Rim-differentiated pillar[5]arene-modified surfaces for rapid PFOA/PFOS detection.

A new rim-differentiated pillar[5]arene (RD-P5) has been synthesized and immobilized onto an Al2O3 surface for the rapid detection of perfluoroalkyl acids. This P5-Al2O3 surface provides a novel approach for measuring perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) using contact angle measurements, with limits of detection down to 10 ng L-1.

RNF43 in cancer: Molecular understanding and clinical significance in immunotherapy.

Identifying biomarkers to predict immune checkpoint inhibitor (ICI) efficacy is warranted. Considering that somatic mutation-derived neoantigens induce strong immune responses, patients with a high tumor mutational burden reportedly tend to respond to ICIs. Therefore, the original function of neoantigenic mutations and their impact on the tumor microenvironment (TME) require attention. RNF43 is a type of RING E3 ubiquitin ligase, and long-term survivors in most cancers had conserved patterns of mutations of RNF43. Also, high microsatellite instability patients had a higher RNF43 mutation rate compared with microsatellite stability tumor patients, who were more sensitive to ICI treatment. Therefore, RNF43 has become a promising biomarker of immunotherapy in a wide range of cancers. This review focuses on the up-to-date knowledge of RNF43 mutation in cancer. We summarize the cancer hallmarks involving activities regulated by RNF43 and highlight its extremely sophisticated regulation of WNT signaling and tumor microenvironment. The key genes interacting with RNF43 have also been summarized and discussed. Additionally, we highlight and propose new strategies of targeting RNF43 and RNF43-based combinations with established immunotherapy and combination therapy. These efforts may provide new perspectives for RNF43-based target therapy in cancer.

Effect of preoperative autologous platelet-rich plasmapheresis on postoperative bleeding in patients undergoing heart valve surgery.

Background: Cardiovascular surgeries often require deep hypothermic circulatory arrest and cardiopulmonary bypass (CPB), which can disrupt blood clotting and lead to excessive bleeding. Traditional treatments involve transfusing blood and blood products, which can have adverse effects and place significant strain on the global blood supply. Research suggests that autologous platelet-rich plasmapheresis (aPRP) may reduce the need for transfusions by preserving blood components. However, the impact of aPRP on postoperative blood loss and clinical outcomes in cardiovascular surgery remains controversial. This study aimed to examine the effects of aPRP on postoperative blood loss and recovery in patients undergoing heart valve surgery. Methods: A total of 183 patients were divided into either aPRP or control groups. The aPRP group received aPRP before CPB, whereas the control group did not. The primary endpoint was postoperative bleeding between the groups. The secondary endpoints were postoperative bleeding risk factors and clinical outcome assessment. Logistic regression analysis with covariate adjustment was used to calculate these risk factors. Results: A total of 76 patients (41.5%) in the aPRP group and 107 patients (58.5%) in the control group were included in the analysis. No significant difference was found in the occurrence of postoperative bleeding [odds ratio (OR) =0.53, 95% confidence interval (CI): 0.28-1.00, P=0.05], and the aPRP group had fewer complications than the controls (OR =0.28, 95% CI: 0.10-0.68, P=0.009). However, after adjusting for the New York Heart Association (NYHA) classification, diabetes, arrhythmology, mean activated clotting time (ACTmean), CPB, bleeding, thoracotomy, and body mass index (BMI), there was a significant difference in postoperative bleeding (adjusted OR =0.47, 95% CI: 0.22-0.98, P=0.04) and complications (adjusted OR =0.23, 95% CI: 0.07-0.64, P=0.008) between the two groups. Conclusions: Preoperative aPRP can improve postoperative outcomes and reduce complications in patients undergoing heart valve surgery.

Lumican is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting VSMCs Senescence through Interacting with Integrin α2ß1.

Vascular aging, a common pathogenesis of senile chronic diseases, significantly increases morbidity and mortality in older adults; its intricate cellular and molecular mechanisms necessitate further investigation. Lumican (LUM) and integrin α2ß1(ITGα2ß1) are profibrotic extracellular matrix proteins and vital cell regulatory receptors, respectively. However, their roles in vascular aging remain unclear. This study sought to elucidate the connection between LUM and vascular aging as well as the biological mechanism of LUM/ITGα2ß1 in this process. Using an enzyme-linked immunosorbent assay, we discovered that plasma LUM was elevated in vascular aging individuals and was positively correlated with brachial-ankle pulse wave velocity. Additionally, immunohistochemical and western blot analyses confirmed LUM upregulation in arteries of older adults and aged mice, as well as in senescent vascular smooth cells (VSMCs). Wild-type and LUM semiknockout (Lum-/+) mice, along with primary VSMCs extracted from these mice, were exposed to angiotensin II (Ang II) to induce stress-induced senescence model. LUM semiknockout mitigated Ang Ⅱ-induced arteriosclerosis, hypertension, vascular aging and remodeling in mice. Both in vitro and in vivo studies revealed that LUM deficiency suppressed p53, p21, collagen 1 and collagen 3 upregulation and synthetic phenotype formation in VSMCs stimulated by Ang Ⅱ. Treating VSMCs with a ITGα2ß1 antagonist reversed the aforementioned changes triggered by LUM proteins. Briefly, LUM functions as a potential marker and risk factor for vascular aging and promotes pathological changes by affecting ITGα2ß1 in VSMCs. This study introduces a novel molecular target for the early diagnosis and treatment of vascular aging and age-related vascular diseases.

Bibliometric analysis of Mongolian medicine and medicinal materials in China since 2000.

Aim of the study: To analyze the progress in Mongolian medicine and medicinal materials and to highlight its development process, emerging trends, and hotspots. Materials and methods: Papers on Mongolian medicine and medicinal materials from January 2000 to May 2022 were retrieved from the China National Knowledge Infrastructure (CNKI) database. Using the collaboration network analysis of CiteSpace V and VOSviewer software, the cooperation among individuals and institutions in the field of scientific research was analyzed. The functions of frequency analysis, cluster analysis, and burst analysis were employed to conduct bibliometric analysis on research hotspots and trends in the field of Mongolian medicine research. Furthermore, the data visualization function was utilized to clearly display data trends and changes. Results: A total of 8362 papers on Mongolian medicine medicinal materials from CNKI were identified and analyzed.The research on Mongolian medicine has gone through three stages: the initial stage, the exploratory stage, and the developmental stage. The top two institutions in the number of papers are Inner Mongolia Medical University and Inner Mongolia University for Nationalities. Bagenna from Inner Mongolia Medical University is the author with the most papers. "clinical efficacy", "clinical research", and "quality standards" were the most frequently used keywords. Research in the field of Mongolian medicine has focused on several diseases, including skeletal system disorders, cardiovascular diseases, and digestive system disorders. Conclusion: Since 2000, there have been growing attention and efforts made in the field of Mongolian medicine and medicinal materials. The research in the field of Mongolian medicine had undergone three stages, namely the initial stage, the exploratory stage, and the developmental stage. The focus shifted from basic research such as the analysis of medicinal ingredients in Mongolian herbs to the application-oriented directions of traditional treatment techniques and advantageous diseases in Mongolian medicine. To make breakthroughs in this field, further research is needed to improve the persuasiveness and authority of Mongolian medicine and medicinal materials in terms of mechanism, standardization, and safety, to promote the development of Mongolian medicine and medicinal materials.

The Effective Separation of Gallium, Vanadium, and Aluminum from a Simulated Bayer Solution by Resin Exchange.

The effective recovery of gallium from wastewater discharge in the Bayer process is promising for the long-term development of gallium resources. The adsorption and desorption behavior of gallium (Ga), vanadium (V), and aluminum (Al) ions on a strong acidic styrene cation exchange resin (JK resin) from a simulated Bayer solution was systematically investigated by static experiments. The results showed that the optimum conditions for separating Ga from V and Al were at low temperatures and short contact times, with 78.30%, 15.16%, and 6.63% of the adsorption efficiency at 25 °C and 60 min, respectively, for Ga, V, and Al. The adsorption kinetics of Ga3+ conformed to the pseudo-second order model, and the static saturation adsorption capacity was 18.25 mg/g. The Langmuir model fitted the adsorption isotherm of gallium well, and the maximum adsorption capacity was 1.11 mg/g at 25 °C. FT-IR spectroscopy and XPS showed that the mechanism of the Ga3+ adsorption was only related to the interaction of the oxygen atoms of the amide oxime group (C=NOH). The separation of Ga, V, and Al can be achieved by desorbing 98% of Al with low concentrations of ammonia and 90% of Ga with low concentrations of hydrochloric acid. The results indicate that JK resin is an efficient adsorbent for separating gallium and vanadium in alkaline solutions.

Colorimetric detection of Staphylococcus aureus with enhanced sensitivity based on phage covalently immobilized Co3O4 nanozyme through synergistic inhibition effect.

Staphylococcus aureus (S. aureus) is a common foodborne pathogen, posing a serious threat to public health. Consequently, it is crucial to establish a platform for sensitive and specific determination of S. aureus in food. Herein, phage SapYZUH5, isolated by our lab, was covalently immobilized on Co3O4 to synthesize SapYZUH5@Co3O4. Notably, SapYZUH5@Co3O4 exhibited remarkable oxidase-like activity, enabling the catalysis of dissolved oxygen to generate superoxide anion free radicals and accelerate the TMB chromogenic reaction. Upon introduction of S. aureus, specific capture by SapYZUH5@Co3O4 resulted in inhibiting its oxidase-like activity and decelerating the 3,3',5,5'-tetramethylbenzidine (TMB) chromogenic reaction. Moreover, S. aureus can be lysed to release the reductive bacterial contents, which can further inhibit the TMB chromogenic reaction. Based on this principle, SapYZUH5@Co3O4 + TMB reaction system was employed for detection with enhanced sensitivity of S. aureus, yielding an equation: A = - 0.092 Log (CSA) + 0.79 (R2 = 0.987), with an ultralow limit of detection (LOD) of 28 CFU mL-1. This system exhibited remarkable specificity and anti-interfere towards S. aureus, owing to the excellent affinity of SapYZUH5 towards S. aureus. In addition, S. aureus in the actual food samples was detected using this system, yielding recoveries ranging from 96.34 to 109.43%, demonstrating its exceptional accuracy. Hence, our proposed covalent immobilization of phage on the nanozyme can realize sensitive and specific colorimetric determination of S. aureus in food samples.

Prognostic effect of the pretreatment prognostic nutritional index in cervical, ovarian, and endometrial cancer: a meta-analysis.

BACKGROUND: The prognostic value of the pretreatment prognostic nutritional index (PNI) for gynaecological malignancies remain unclear. This meta-analysis aimed to explore the predictive significance of the PNI for gynaecological tumours. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to January 30, 2024, to identify relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations of the PNI with overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in patients with gynaecological tumours. We examined the correlation of the PNI with clinicopathological parameters of patients with gynaecological carcinoma by utilizing pooled odds ratios (ORs) and 95% CIs. RESULTS: A total of 28 articles involving 9,428 patients were included in the meta-analysis. The results revealed that a low PNI significantly predicted worse OS (HR = 1.60, 95% CI: 1.39-1.84, P < 0.001), PFS (HR = 1.63, 95% CI: 1.20-2.23, P = 0.002), and DFS (HR = 1.73, 95% CI: 1.19-2.52, P = 0.004). In addition, the subgroup analysis confirmed that the PNI had a prognostic effect on OS for all cancer types, but a significant association with PFS was not observed in patients with cervical cancer. A low PNI was significantly associated with FIGO stages III‒IV (OR = 2.30, 95% CI: 1.89‒2.80, P < 0.001) and LN metastasis (OR = 2.76, 95% CI: 2. 05‒3.73, P < 0.001). CONCLUSION: The PNI may be noninvasive and promising biomarker for predicting the prognosis of patients with gynaecological tumours.

Elaborating the knowledge structure and emerging research trends of physical activity for multiple sclerosis: A bibliometric analysis from 1994 to 2023.

BACKGROUND: Multiple sclerosis is a common inflammatory neurological disease among young adults and is the tenth leading cause of the global burden of disease. Existing common treatments such as pharmacological and palliative therapies do not control the neurodegenerative process or cure multiple sclerosis. Numerous epidemiological surveys, randomised controlled trials, and systematic reviews with meta-analyses support the effects of physical activity on health-related outcomes among patients with multiple sclerosis. Moreover, bibliometric analysis can provide a broad evidence synthesis beyond systematic reviews and meta-analyses, allowing researchers and other stakeholders to obtain a one-stop overview of this research field. Therefore, this bibliometric analysis aims to provide insight into the knowledge structure of the field of physical activity for multiple sclerosis over the past three decades, and to predict emerging research trends. METHODS: This study strictly complied with step-by-step guidelines of bibliometric analysis, combining performance analysis and science mapping. Four indexes from the Web of Science Core Collection were selected as data sources, and articles and review articles in the field of physical activity for multiple sclerosis from 1994 to 2023 were included in this analysis. Mircrosoft Excel, RStudio, VOSviewer 1.6.20, and CiteSpace 6.3.R1 (64-bit) Advanced were used to perform performance analysis and science mapping. RESULTS: Over the past three decades, this field published a total of 1,271 documents, with the scientific output showing a rapid upward trend over the past two decades. Robbert W Motl was the most prolific author in this field, with a total of 300 publications. The USA contributed nearly half of the publications in this field (549 documents), and the University of Illinois System was the institution with the highest number of publications (222 documents). Multiple Sclerosis and Related Disorders was the journal that published the highest number of documents in this field (117 documents), while more than a third of this field's publications were included in the category: Clinical Neurology (438 documents). The Reference co-citation analysis identified three main research trends, including shifts in research methodology, changes in health outcomes in randomised controlled trials, and shifts in different types of physical activity interventions. Combining the results from reference co-citation analysis and citation burst analysis, the combination of behaviour change technique and telerehabilitation may be the emerging research trend. CONCLUSION: This bibliometric analysis identifies rapid growth in the field of physical activity for multiple sclerosis over the past two decades. Moreover, the combination of performance analysis and science mapping provides insight into knowledge structure in this field and informed future research trends for researchers and the relevant stakeholders.

FA-Net: A hierarchical feature fusion and interactive attention-based network for dose prediction in liver cancer patients.

Dose prediction is a crucial step in automated radiotherapy planning for liver cancer. Several deep learning-based approaches for dose prediction have been proposed to enhance the design efficiency and quality of radiotherapy plan. However, these approaches usually take CT images and contours of organs at risk (OARs) and planning target volume (PTV) as a multi-channel input and is thus difficult to extract sufficient feature information from each input, which results in unsatisfactory dose distribution. In this paper, we propose a novel dose prediction network for liver cancer based on hierarchical feature fusion and interactive attention. A feature extraction module is first constructed to extract multi-scale features from different inputs, and a hierarchical feature fusion module is then built to fuse these multi-scale features hierarchically. A decoder based on attention mechanism is designed to gradually reconstruct the fused features into dose distribution. Additionally, we design an autoencoder network to generate a perceptual loss during training stage, which is used to improve the accuracy of dose prediction. The proposed method is tested on private clinical dataset and obtains HI and CI of 0.31 and 0.87, respectively. The experimental results are better than those by several existing methods, indicating that the dose distribution generated by the proposed method is close to that approved in clinics. The codes are available at https://github.com/hired-ld/FA-Net.

Case of idiopathic left ventricular summit premature ventricular contractions successfully treated by catheter ablation.

Key Clinical Message: CA of LVS premature beats complexes is difficult due to anatomical limitations. We report a patient with PVCs originating from the LVS region who was successfully ablated by ablation. Abstract: Catheter ablation (CA) of premature ventricular contractions (PVCs) arising from the left ventricular summit (LVS) presents technical challenges due to the regional anatomy and frequently intramural site of origin. Herein, we demonstrated a case of a successful CA, originating from the LVS region. We further discussed the detailed anatomical background and clinical feasibility of CA as an alternative ablation route for PVCs originating from the LVS.

Associations of 24-hour movement guidelines adherence with fruit and vegetable intake in university students.

Background: Unhealthy eating habits, such as low vegetable and fruit intake, are associated with many health problems. 24-h movement behaviors have been reported to be positively associated with numerous health-related outcomes. Despite the importance of these two modifiable lifestyle behaviors in building healthy habits in university students, there is a paucity of relevant research in this population. Therefore, this study aims to examine the correlation between compliance with 24-h movement guideline (24-h MG) and intake of fruits and vegetables (IFV) in Chinese university students. Methods: This study investigated the relationship between the compliance with 24-h MG and IFV in 1,793 Chinese university students using a convenience sampling method online. Physical activity (PA) and sedentary behavior (SB) were assessed by the International Physical Activity Questionnaire-Short Form, while sleep was measured using the Pittsburgh Sleep Quality Index. The Chinese version of the Health Promoting Lifestyle Profile II was used to measure IFV. Generalized linear models were applied to examine the correlation between compliance with the 24-h MG and eating habits. Results: The proportion of participants who routinely consumed vegetables and fruits was 24.6% and 43.1%, respectively, while the proportion of meeting the three 24-h MG and a combination of any two guidelines was 27.8% and 40.1%, respectively. Meeting all three guidelines was associated with a greater IFV intake compared to not meeting either guideline. Meeting all three guidelines (OR = 2.42 [1.63, 3.58]) and the combination of moderate to vigorous PA (MVPA) and sleep (OR = 2.06 [1.37, 3.10]) were positively associated with the frequency of vegetable consumption (p < 0.05). As well, meeting all three guidelines (OR = 2.06 [1.37, 3.10]), the combination of MVPA and sleep (OR = 1.72 [1.04, 2.84]), and sleep only (OR = 1.88 [1.21, 2.92]) were positively associated with fruits consumption (p < 0.05). Conclusion: Almost a third of the university students met the three 24-h MG, and compliance with all three guidelines was associated with a higher frequency of IFV. Furthermore, meeting the sleep guideline alone or in conjunction with the PA, and meeting the entire 24-h MG was associated with greater consumption of fruits.

Construction and Analysis of the Physical Fitness Evaluation Index System for Elite Male Singles Badminton Players: Based on Delphi and AHP Methods.

OBJECTIVE: To construct and validate a physical fitness evaluation index system for elite male singles badminton players. METHODS: Utilizing the Delphi method to establish a comprehensive evaluation system, the analytic hierarchy process (AHP) was employed to calculate the influence weights of various indicators. The validity of the comprehensive evaluation system was verified using testing methods. RESULTS: After three rounds of expert selection, the physical fitness evaluation index system for elite male singles badminton players includes three primary indicators, nine secondary indicators, and twenty-one tertiary indicators. Among the primary indicators, specialized physical fitness holds a significant weight in the evaluation with a value of 0.651, whereas body morphology has a smaller weight of 0.077. Among the secondary indicators, specialized agility, strength, and endurance have higher weights of 0.223, 0.217, and 0.210, respectively. Among the tertiary indicators, four-corner ball touch, 400 m × 5 shuttle run, smash-and-rush, and vertical jump height hold higher weights of 0.119, 0.114, 0.104, and 0.096, respectively. The results after randomly selecting ten elite male singles badminton players and applying the evaluation index system demonstrated that this system has high feasibility and validity. It can not only comprehensively assess the physical fitness of athletes but also provide significant practical guidance for enhancing their competitive performance. CONCLUSIONS: The evaluation system and weight assignments constructed in this study can scientifically and comprehensively reflect the physical fitness status of athletes. It can guide coaches in formulating targeted training plans and optimizing training outcomes.

Adaptation of Ustilago maydis to phenolic and alkaloid responsive metabolites in maize B73.

The adaptation of pathogenic fungi to plant-specialized metabolites is necessary for their survival and reproduction. The biotrophic fungus Ustilago maydis can cause maize smut and produce tumors in maize (Zea mays), resulting in reduced maize yield and significant economic losses. Qualitative analysis using UPLC-MS/MS revealed that the infection of maize variety B73 with U. maydis resulted in increased levels of phytohormones, phenolics, and alkaloids in maize seedling tissues. However, correlation analysis showed that nearly all compounds in the mechanical damage group were significantly negatively correlated with the shoot growth indexes of maize B73. The correlation coefficients of 2-hydroxy-7-methoxy-1,4-benzoxazin-3-one (HMBOA) and maize B73 shoot length and shoot weight were r = -0.56 (p < 0.01) and r = -0.75 (p < 0.001), respectively. In the inoculation group, these correlations weakened, with the correlation coefficients between HMBOA and maize B73 shoot length and shoot weight being r = 0.02 and r = -0.1, respectively. The correlation coefficients between 6-methoxy-2-benzoxazolinone (MBOA) and the shoot weight were r = -0.73 (p < 0.001) and r = -0.15 in the mechanical damage group and inoculation group, respectively. These findings suggest that increased concentrations of these compounds are more positively associated with mechanical damage than with U. maydis infection. At high concentrations, most of these compounds had an inhibitory effect on U. maydis. This study investigated the ability of U. maydis to regulate various compounds, including phytohormones, phenolic acids, and alkaloids in maize B73, providing evidence that U. maydis has adapted to the specialized metabolites produced by maize B73.

PDL1/HER2-Targeted Lipid-Encapsulated Oxygen Nanobubbles Combined with Photodynamic Therapy for HER2+ Breast Cancer Immunotherapy.

Programmed death (PD) 1/PD ligand 1 (PDL1) inhibitors are immune checkpoint inhibitors (ICIs) that may facilitate HER2-positive breast cancer treatment; however, their clinical efficacy remains elusive. Oxygen-enhanced photodynamic therapy (PDT) increases immunogenic cell death (ICD), providing a promising strategy to render the tumor microenvironment more sensitive to the ICIs. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O2) obtained using nanobubbles (NBs) water for oxygen delivery in vivo can facilitate enhanced PDT. Here, dual-receptor targeted Lipo-NBs-O2 (DRT@Lipo-NBs-O2) is prepared by modifying Lipo-NBs-O2 with anti-PDL1 scFv and the fusion protein anti-HER2 scFv-tandem-repeat cytochrome c (anti-HER2-nCytc). Copper phthalocyanine is the photosensitizer (PS). DRT@Lipo-PS-NBs-O2 plus near-infrared irradiation leads to robust ICD induction, increasing DC activation and CD8+ T-cell numbers. Modification with anti-PDL1 scFv improves tumor distribution of DRT@Lipo-PS-NBs-O2 and plays the ICI role, invigorating CD8+ T cells and boosting the effects of immunotherapy. Oxygen supplied through DRT@Lipo-PS-NBs-O2 reduces P-glycoprotein expression. Enhanced PDT and Cytc can cause tumor cell death, thereby reducing the immune burden. Under dual receptor targeting and laser local irradiation, tumor cells become subject to the combination effects of PDT, ICD, ICIs, and apoptosis; this effectively suppresses tumor growth and metastasis. Lipo-NBs-O2 affords a combination of oxygen delivery and multidrug therapy to alleviate HER2-positive breast cancer.