Phenolic Constituents with Glucose Uptake and GLUT4 Translocation Bioactivities from the Fruits of Cordia dichotoma.

From the fruits of Cordia dichotoma, 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H (8) and dichotomin I (9) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3, 5, 7, 17, 18, 23-25, and 27-30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 µg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 µg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).

The predictors of lymphopenia and its effects on survival in locally advanced esophageal squamous cell carcinoma.

To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (r= -0.389, p < .001) and GTV (r= -0.211, p < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group (p = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm3 group (p = .242) and GTV ≤ 68.8 cm3 group(p = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

A Whole-Course-Repair System Based on Stimulus-Responsive Multifunctional Hydrogels for Myocardial Tissue Regeneration.

Myocardial infarction (MI) has emerged as the predominant cause of cardiovascular morbidity globally. The pathogenesis of MI unfolds as a progressive process encompassing three pivotal phases: inflammation, proliferation, and remodeling. Smart stimulus-responsive hydrogels have garnered considerable attention for their capacity to deliver therapeutic drugs precisely and controllably at the MI site. Here, a smart stimulus-responsive hydrogel with a dual-crosslinked network structure is designed, which enables the precise and controlled release of therapeutic drugs in different pathological stages for the treatment of MI. The hydrogel can rapidly release curcumin (Cur) in the inflammatory phase of MI to exert anti-apoptotic/anti-inflammatory effects. Recombinant humanized collagen type III (rhCol III) is loaded in the hydrogel and released as the hydrogel swelled/degraded during the proliferative phase to promote neovascularization. RepSox (a selective TGF-ß inhibitor) releases from Pluronic F-127 grafted with aldehyde nanoparticles (PF127-CHO@RepSox NPs) in the remodeling phase to against fibrosis. The results in vitro and in vivo suggest that the hydrogel improves cardiac function and alleviates cardiac remodeling by suppressing inflammation and apoptosis, promoting neovascularization, and inhibiting myocardial fibrosis. A whole-course-repair system, leveraging stimulus-responsive multifunctional hydrogels, demonstrates notable effectiveness in enhancing post-MI cardiac function and facilitating the restoration of damaged myocardial tissue.

Glycoengineering-based anti-PD-1-iRGD peptide conjugate boosts antitumor efficacy through T cell engagement.

Despite the important breakthroughs of immune checkpoint inhibitors in recent years, the objective response rates remain limited. Here, we synthesize programmed cell death protein-1 (PD-1) antibody-iRGD cyclic peptide conjugate (αPD-1-(iRGD)2) through glycoengineering methods. In addition to enhancing tissue penetration, αPD-1-(iRGD)2 simultaneously engages tumor cells and PD-1+ T cells via dual targeting, thus mediating tumor-specific T cell activation and proliferation with mild effects on non-specific T cells. In multiple syngeneic mouse models, αPD-1-(iRGD)2 effectively reduces tumor growth with satisfactory biosafety. Moreover, results of flow cytometry and single-cell RNA-seq reveal that αPD-1-(iRGD)2 remodels the tumor microenvironment and expands a population of "better effector" CD8+ tumor infiltrating T cells expressing stem- and memory-associated genes, including Tcf7, Il7r, Lef1, and Bach2. Conclusively, αPD-1-(iRGD)2 is a promising antibody conjugate therapeutic beyond antibody-drug conjugate for cancer immunotherapy.

Theoretical study on lithium storage performance of V-doped Ti2CO2 MXene.

With the increasing application of lithium-ion batteries, the demand for high energy density, high-rate performance and high stability lithium-ion batteries is becoming more and more urgent. Ti2CO2 MXene, as a two-dimensional material with multilayer atomic structure and multiple active sites, has great advantages in lithium-ion battery electrode materials. However, the original Ti2CO2 MXene has been unable to meet the requirements of lithium-ion batteries due to its semiconductor properties. Doping is an effective means to regulate the conductivity and electrochemical properties of Ti2CO2 and improve the capacity of lithium-ion batteries and other energy storage devices. Hence, we use first-principles calculations to study the effect of V atom doping on the adsorption and diffusion of Li on the MXene surface. The density of states (DOS) and partial density of states (PDOS) of TiVCO2 and Ti2CO2 MXene indicated the transition of their conductive types from semiconductors to conductors. In addition, we observed that TiVCO2 has higher electrical conductivity and ion transport speed than the original Ti2CO2 MXene, and at the same time, Li atoms can be adsorbed well on the surface of MXene and show a lower diffusion energy barrier. Therefore, TiVCO2 is expected to become the anode material for the next generation of lithium-ion batteries and has good lithium storage performance.

Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study.

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234.

Measurement of medical students' knowledge, attitude and practice towards antibiotic use and resistance: A scoping review.

OBJECTIVE: Medical students are demanders and future suppliers of antibiotic use. Understanding their knowledge, attitude and practice is important for appropriately using antibiotics and controlling antibiotic resistance. The objective of this study was to assess the measurement properties of existed instruments and summarize measurement items and results. METHODS: Five English and Chinese databases were searched to comprehensively identify related studies between January 2000 and May 2023. Included instruments were assessed using consensus-based standards for the selection of health measurement instruments checklist. Descriptive tables and narrative texts were applied to summary the data. RESULTS: Of 3524 studies identified, 25 were finally included, from which 22 measurement instruments were included. Of these, 14 instruments were found with adequate content validity, only one study reported structural validation process and two studies reported reliability test results. Similar items were divided into different dimensions in different studies. Gaps and misconceptions in knowledge and attitude were indicated in antibiotic use principles, including antibiotic use indications and selection. CONCLUSIONS: Limitations existed in the current measurement instrument including lacking validation, inconsistent classification of item and lacking item regarding the perspective of suppliers. Scientific tools for objective and accurate measure are needed.

Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.

AURKA is a threonine or serine kinase that needs to be activated by TPX2, Bora and other factors. AURKA is located on chromosome 20 and is amplified or overexpressed in many human cancers, such as breast cancer. AURKA regulates some basic cellular processes, and this regulation is realized via the phosphorylation of downstream substrates. AURKA can function in either the cytoplasm or the nucleus. It can promote the transcription and expression of oncogenes together with other transcription factors in the nucleus, including FoxM1, C-Myc, and NF-κB. In addition, it also sustains carcinogenic signaling, such as N-Myc and Wnt signaling. This article will focus on the role of AURKA in the nucleus and its carcinogenic characteristics that are independent of its kinase activity to provide a theoretical explanation for mechanisms of resistance to kinase inhibitors and a reference for future research on targeted inhibitors.

AURKA plays an important role in the control of the proliferation, invasion, cell cycle regulation and self-renewal of cancer stem cells.Small molecule kinase inhibitors targeting AURKA have been developed, but the overall response rate of patients in clinical trials is not ideal, prompting us to pay attention to the non-kinase activity of AURKA.This review focuses on the nuclear function of AURKA and its oncogenic properties independent of kinase activity, demonstrating that the nuclear substrate of AURKA and the remote allosteric site of the kinase may be targets of anticancer therapy.

Advances in nano-immunotherapy for hematological malignancies.

Hematological malignancies (HMs) encompass a diverse group of blood neoplasms with significant morbidity and mortality. Immunotherapy has emerged as a validated and crucial treatment modality for patients with HMs. Despite notable advancements having been made in understanding and implementing immunotherapy for HMs over the past decade, several challenges persist. These challenges include immune-related adverse effects, the precise biodistribution and elimination of therapeutic antigens in vivo, immune tolerance of tumors, and immune evasion by tumor cells within the tumor microenvironment (TME). Nanotechnology, with its capacity to manipulate material properties at the nanometer scale, has the potential to tackle these obstacles and revolutionize treatment outcomes by improving various aspects such as drug targeting and stability. The convergence of nanotechnology and immunotherapy has given rise to nano-immunotherapy, a specialized branch of anti-tumor therapy. Nanotechnology has found applications in chimeric antigen receptor T cell (CAR-T) therapy, cancer vaccines, immune checkpoint inhibitors, and other immunotherapeutic strategies for HMs. In this review, we delineate recent developments and discuss current challenges in the field of nano-immunotherapy for HMs, offering novel insights into the potential of nanotechnology-based therapeutic approaches for these diseases.

Hydrogen peroxide serves as pivotal fountainhead for aerosol aqueous sulfate formation from a global perspective.

Traditional atmospheric chemistry posits that sulfur dioxide (SO2) can be oxidized to sulfate (SO42-) through aqueous-phase reactions in clouds and gas-phase oxidation. Despite adequate knowledge of traditional mechanisms, several studies have highlighted the potential for SO2 oxidation within aerosol water. Given the widespread presence of tropospheric aerosols, SO42- production through aqueous-phase oxidation in aerosol water could have a pervasive global impact. Here, we quantify the potential contributions of aerosol aqueous pathways to global sulfate formation based on the GEOS-Chem simulations and subsequent theoretical calculations. Hydrogen peroxide (H2O2) oxidation significantly influences continental regions both horizontally and vertically. Over the past two decades, shifts in the formation pathways within typical cities reveal an intriguing trend: despite reductions in SO2 emissions, the increased atmospheric oxidation capacities, like rising H2O2 levels, prevent a steady decline in SO42- concentrations. Abating oxidants would facilitate the benefit of SO2 reduction and the positive feedback in sulfate mitigation.

Remodeling brain pathological microenvironment to lessen cerebral ischemia injury by multifunctional injectable hydrogels.

Ischemia stroke is one of the leading causes of death and disability worldwide. Owing to the limited delivery efficiency to the brain caused by the blood-brain barrier (BBB) and off-target effects of systemic treatment, it is crucial to develop an in situ drug delivery system to improve the therapeutic effect in ischemic stroke. Briefly, we report a multifunctional in situ hydrogel delivery system for the co-delivery of reactive oxygen species (ROS)-responsive nanoparticles loaded with atorvastatin calcium (DSPE-se-se-PEG@AC NPs) and ß-nerve growth factor (NGF), which is expected to remodel pathological microenvironment for improving cerebral ischemia injury. The in vitro results exhibited the multifunctional hydrogel scavenged oxygen-glucose deprivation (OGD)-induced free radical, rescued the mitochondrial function, and maintained the survival and function of neurons, hence reducing neuronal apoptosis and neuroinflammation, consequently relieving ischemia injury in hippocampal neurons cell line (HT22). In the rat ischemia stroke model, the hydrogel significantly minified cerebral infarction by regulating inflammatory response, saving apoptotic neurons, and promoting angiogenesis and neurogenesis. Besides, the hydrogel distinctly improved the rats' neurological deficits after cerebral ischemia injury over the long-term observation. In conclusion, the in-situ hydrogel platform has demonstrated promising therapeutic effects in both in vitro and in vivo studies, indicating its potential as a new and effective therapy.

Fragment-Based Deep Learning for Simultaneous Prediction of Polarizabilities and NMR Shieldings of Macromolecules and Their Aggregates.

Simultaneous prediction of the molecular response properties, such as polarizability and the NMR shielding constant, at a low computational cost is an unresolved issue. We propose to combine a linear-scaling generalized energy-based fragmentation (GEBF) method and deep learning (DL) with both molecular and atomic information-theoretic approach (ITA) quantities as effective descriptors. In GEBF, the total molecular polarizability can be assembled as a linear combination of the corresponding quantities calculated from a set of small embedded subsystems in GEBF. In the new GEBF-DL(ITA) protocol, one can predict subsystem polarizabilities based on the corresponding molecular wave function (thus electron density and ITA quantities) and DL model rather than calculate them from the computationally intensive coupled-perturbed Hartree-Fock or Kohn-Sham equations and finally obtain the total molecular polarizability via a linear combination equation. As a proof-of-concept application, we predict the molecular polarizabilities of large proteins and protein aggregates. GEBF-DL(ITA) is shown to be as accurate enough as GEBF, with mean absolute percentage error <1%. For the largest protein aggregate (>4000 atoms), GEBF-DL(ITA) gains a speedup ratio of 3 compared with GEBF. It is anticipated that when more advanced electronic structure methods are used, this advantage will be more appealing. Moreover, one can also predict the NMR chemical shieldings of proteins with reasonably good accuracy. Overall, the cost-efficient GEBF-DL(ITA) protocol should be a robust theoretical tool for simultaneously predicting polarizabilities and NMR shieldings of large systems.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Complying with ISO 26262 and ISO/SAE 21434: A Safety and Security Co-Analysis Method for Intelligent Connected Vehicle.

A cyber-physical system (CPS) integrates communication and automation technologies into the operational processes of physical systems. Nowadays, as a complex CPS, an intelligent connected vehicle (ICV) may be exposed to accidental functional failures and malicious attacks. Therefore, ensuring the ICV's safety and security is crucial. Traditional safety/security analysis methods, such as failure mode and effect analysis and attack tree analysis, cannot provide a comprehensive analysis for the interactions between the system components of the ICV. In this work, we merge system-theoretic process analysis (STPA) with the concept phase of ISO 26262 and ISO/SAE 21434. We focus on the interactions between components while analyzing the safety and security of ICVs to reduce redundant efforts and inconsistencies in determining safety and security requirements. To conquer STPA's abstraction in describing causal scenarios, we improved the physical component diagram of STPA-SafeSec by adding interface elements. In addition, we proposed the loss scenario tree to describe specific scenarios that lead to unsafe/unsecure control actions. After hazard/threat analysis, a unified risk assessment process is proposed to ensure consistency in assessment criteria and to streamline the process. A case study is implemented on the autonomous emergency braking system to demonstrate the validation of the proposed method.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.

Effectiveness of musculoskeletal manipulations in patients with neck pain: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Neck pain is a common problem that severely affects physical and mental health. While musculoskeletal manipulations are recommended as the first-line treatment for adults with neck pain, the comparative effectiveness of different musculoskeletal manipulations remains unclear. This systematic review and network meta-analysis of randomised controlled trials (RCTs) will compare the effectiveness of different types of musculoskeletal manipulations, with the overarching aim of guiding clinical practice. METHODS AND ANALYSIS: Two independent reviewers will search four English electronic databases (Web of Science, Cochrane Library, EMBASE, PubMed) and three Chinese electronic databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang) for relevant RCTs published from 1 January 2013 to 30 April 2023. The Clinical Trials Registry (ClinicalTrials.gov) will be searched for completed but unpublished RCTs. English and Chinese will be used to search English databases and Chinese databases, respectively. RCTs of musculoskeletal manipulations for adults (aged ≥18 years) with neck pain will be considered eligible for inclusion. A pairwise meta-analysis and network meta-analysis will be performed, and pooled risk ratios, standardised mean differences and 95% CIs will be determined. ETHICS AND DISSEMINATION: Ethics approval is not required as this study is a literature review. The results of this review will be published in peer-reviewed journals or disseminated at conferences. PROSPERO REGISTRATION NUMBER: CRD42023420775.

Transcriptomic and Proteomic Analyses Unveil the Role of Nitrogen Metabolism in the Formation of Chinese Cabbage Petiole Spot.

Chinese cabbage is the most widely consumed vegetable crop due to its high nutritional value and rock-bottom price. Notably, the presence of the physiological disease petiole spot significantly impacts the appearance quality and marketability of Chinese cabbage. It is well known that excessive nitrogen fertilizer is a crucial factor in the occurrence of petiole spots; however, the mechanism by which excessive nitrogen triggers the formation of petiole spots is not yet clear. In this study, we found that petiole spots initially gather in the intercellular or extracellular regions, then gradually extend into intracellular regions, and finally affect adjacent cells, accompanied by cell death. Transcriptomic and proteomic as well as physiology analyses revealed that the genes/proteins involved in nitrogen metabolism exhibited different expression patterns in resistant and susceptible Chinese cabbage lines. The resistant Chinese cabbage line has high assimilation ability of NH4+, whereas the susceptible one accumulates excessive NH4+, thus inducing a burst of reactive oxygen species (ROS). These results introduce a novel perspective to the investigation of petiole spot induced by the nitrogen metabolism pathway, offering a theoretical foundation for the development of resistant strains in the control of petiole spot.

An injectable carrier for spatiotemporal and sequential release of therapeutic substances to treat myocardial infarction.

Myocardial infarction (MI) has become the primary cause of cardiovascular mortality, while the current treatment methods in clinical all have their shortcomings. Injectable biomaterials have emerged as a promising solution for cardiac tissue repair after MI. In this study, we designed a smart multifunctional carrier that could meet the treatment needs of different MI pathological processes by programmatically releasing different therapeutic substances. The carrier could respond to inflammatory microenvironment in the early stage of MI with rapid release of curcumin (Cur), and then sustained release recombinant humanized collagen type III (rhCol III) to treat MI. The rapid release of Cur reduced inflammation and apoptosis in the early stages, while the sustained release of rhCol III promoted angiogenesis and cardiac repair in the later stages. In vitro and in vivo results suggested that the multifunctional carrier could effectively improve cardiac function, promote the repair of infarcted tissue, and inhibit ventricular remodeling by reducing cell apoptosis and inflammation, and promoting angiogenesis in the different pathological processes of MI. Therefore, this programmed-release carrier provides a promising protocol for MI therapy.