Self-assembled Pt(II) metallacycles enable precise cancer combination chemotherapy.

Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acid­functionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.

Carotenoid isomerase regulates rice tillering and grain productivity by its biosynthesis pathway.

Carotenoid isomerase activity and carotenoid content maintain the appropriate tiller number, photosynthesis, and grain yield. Interactions between the strigolactone and abscisic acid pathways regulates tiller formation.

Triglyceride-glucose index, symptomatic intracranial artery stenosis and recurrence risk in minor stroke patients with hypertension.

BACKGROUND: The triglyceride-glucose (TyG) index, a simple measure of insulin resistance, is associated with intracranial atherosclerosis (ICAS) and stroke. In hypertensive populations, this association may be pronounced. The aim was to investigate the relationship between TyG and symptomatic intracranial atherosclerosis (sICAS) and recurrence risk in ischemic stroke patients with hypertension. METHODS: This prospective, multicenter cohort study included patients with acute minor ischemic stroke with a preadmission diagnosis of hypertension from September 2019 to November 2021 with a 3-month follow-up. The presence of sICAS was determined by a combination of clinical manifestations, the location of the infarction, and the corresponding artery with moderate-to-severe stenosis. ICAS burden was determined by the degree and number of ICAS occurrences. Fasting blood glucose (FBG) and triglyceride (TG) were measured to calculate TyG. The main outcome was ischemic stroke recurrence during the 90-day follow-up. Multivariate regression models were used to explore the association of TyG, sICAS, and ICAS burden with stroke recurrence. RESULTS: There were 1281 patients with a mean age of 61.6 ± 11.6 years; 70.1% were male, and 26.4% were diagnosed with sICAS. There were 117 patients who experienced stroke recurrence during follow-up. Patients were categorized according to quartiles of TyG. After adjusting for confounders, the risk of sICAS was greater (OR 1.59, 95% CI 1.04-2.43, p = 0.033) and the risk of stroke recurrence was significantly higher (HR 2.02, 95% CI 1.07-3.84, p = 0.025) in the fourth TyG quartile than in the first quartile. The restricted cubic spline (RCS) plot revealed a linear relationship between TyG and sICAS, and the threshold value for TyG was 8.4. Patients were then dichotomized into low and high TyG groups by the threshold. Patients with high TyG combined with sICAS had a higher risk of recurrence (HR 2.54, 95% CI 1.39-4.65) than patients with low TyG without sICAS. An interaction effect on stroke recurrence between TyG and sICAS was found (p = 0.043). CONCLUSION: TyG is a significant risk factor for sICAS in hypertensive patients, and there is a synergistic effect of sICAS and higher TyG on ischemic stroke recurrence. TRIAL REGISTRATION NUMBER: The study was registered on 16 August 2019 at https://www.chictr.org.cn/showprojen.aspx?proj=41160 (No. ChiCTR1900025214).

Dual Versus Mono Antiplatelet Therapy in Patients with Acute Mild-to-Moderate Stroke: A Multicentre Perspective Cohort Study.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the association between different antiplatelet therapy regimens and the functional outcomes and bleeding complications among mild-to-moderate ischaemic stroke patients based on real-world data. METHODS: We used data from the SEACOAST trial (Safety and efficacy of aspirin-clopidogrel in acute noncardiogenic minor ischaemic stroke) to analyse the data of patients with mild-to-moderate stroke within 72 h after onset who were treated with aspirin or clopidogrel alone or a combination of clopidogrel and aspirin from September 2019 to November 2021. Propensity score matching (PSM) was used to balance the differences between groups. We performed an analysis to evaluate the association of different antiplatelet regimens and 90-day disability, which was defined as a modified Rankin Scale score ≥2, as well as disability ascribed to index or recurrent stroke by the local investigator. In terms of safety, we then compared the bleeding events between the two groups. RESULTS: A total of 2822 mild-to-moderate ischaemic stroke patients were treated with either clopidogrel plus aspirin (n = 1726, 61.2%) or aspirin/clopidogrel (n = 1096, 38.8%). Of 1726 patients in the dual antiplatelet group, 1350 (78.5%) received less than or equal to 30 days of combined therapy. At 90 days, 433 (15.3%) patients were disabled. Patients who received combined therapy had a lower overall disability rate (13.7% versus 17.9%; OR 0.78 (0.6-1.01); P = 0.064). However, investigators found that index stroke was the reason for significantly fewer patients in the dual antiplatelet group having disability (8.4% versus 12%; OR, 0.72 (0.52-0.98); P = 0.038). There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the dual and mono antiplatelet drug regimens (0.4% versus 0.2%; HR 1.5 (0.25, 8.98); P = 0.657). CONCLUSION: Aspirin plus clopidogrel was associated with a reduction in the incidence of disability attributed to index stroke. There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the two antiplatelet drug regimens. TRIAL REGISTRATION NUMBER: ChiCTR1900025214.

UDP-N-acetylglucosamine pyrophosphorylase enhances rice survival at high temperature.

High-temperature stress inhibits normal cellular processes and results in abnormal growth and development in plants. However, the mechanisms by which rice (Oryza sativa) copes with high temperature are not yet fully understood. In this study, we identified a rice high temperature enhanced lesion spots 1 (hes1) mutant, which displayed larger and more dense necrotic spots under high temperature conditions. HES1 encoded a UDP-N-acetylglucosamine pyrophosphorylase, which had UGPase enzymatic activity. RNA sequencing analysis showed that photosystem-related genes were differentially expressed in the hes1 mutant at different temperatures, indicating that HES1 plays essential roles in maintaining chloroplast function. HES1 expression was induced under high temperature conditions. Furthermore, loss-of-function of HES1 affected heat shock factor expression and its mutation exhibited greater vulnerability to high temperature. Several experiments revealed that higher accumulation of reactive oxygen species occurred in the hes1 mutant at high temperature. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and comet experiments indicated that the hes1 underwent more severe DNA damage at high temperature. The determination of chlorophyll content and chloroplast ultrastructure showed that more severe photosystem defects occurred in the hes1 mutant under high temperature conditions. This study reveals that HES1 plays a key role in adaptation to high-temperature stress in rice.

Attred: Attribute Based Resource Discovery for IoT.

While the number of devices connected together as the Internet of Things (IoT) is growing, the demand for an efficient and secure model of resource discovery in IoT is increasing. An efficient resource discovery model distributes the registration and discovery workload among many nodes and allow the resources to be discovered based on their attributes. In most cases this discovery ability should be restricted to a number of clients based on their attributes, otherwise, any client in the system can discover any registered resource. In a binary discovery policy, any client with the shared secret key can discover and decrypt the address data of a registered resource regardless of the attributes of the client. In this paper we propose Attred, a decentralized resource discovery model using the Region-based Distributed Hash Table (RDHT) that allows secure and location-aware discovery of the resources in IoT network. Using Attribute Based Encryption (ABE) and based on predefined discovery policies by the resources, Attred allows clients only by their inherent attributes, to discover the resources in the network. Attred distributes the workload of key generations and resource registration and reduces the risk of central authority management. In addition, some of the heavy computations in our proposed model can be securely distributed using secret sharing that allows a more efficient resource registration, without affecting the required security properties. The performance analysis results showed that the distributed computation can significantly reduce the computation cost while maintaining the functionality. The performance and security analysis results also showed that our model can efficiently provide the required security properties of discovery correctness, soundness, resource privacy and client privacy.

Atomistic study of the strengthening mechanisms of graphene coated aluminum.

We have investigated the nano-indentation responses of graphene/aluminum systems via computational nano-indentation processes by using molecular dynamics simulations. The effects of system temperature, grain-orientation and bilayer graphene are also investigated. We demonstrate that, the graphene coating enlarges the load-carrying area by about 5.36 times and changes the deformation behaviors of aluminum substrate during nano-indentation processes. The load bearing capacity of graphene/Al system is significantly improved by about 4.7 times compared with that of bare Al system. It is revealed that higher system temperature weakens the ultimate indentation depth and corresponding load. The grain orientation of aluminum substrate hardly affect the indentation mechanical properties of graphene/Al system. The strengthening effect of bilayer graphene is about 1.5 times that of monolayer graphene.

Biological and transcriptomic studies reveal hfq is required for swimming, biofilm formation and stress response in Xanthomonas axonpodis pv. citri.

BACKGROUND: Hfq is a widely conserved bacterial RNA-binding protein which generally mediates the global regulatory activities involv ed in physiological process and virulence. The goal of this study was to characterize the biological function of hfq gene in Xanthomonas axonpodis pv. citri (Xac), the causal agent of citrus canker disease. RESULTS: An hfq mutant in Xac was generated by plasmid integration. The loss of hfq resulted in attenuation of bacterial growth, motility and biofilm formation. In addition, the hfq mutation impaired Xac resistance to H2O2 and both high and low pH environments, but did not affect the virulence to citrus. RNA-Seq analyses indicated that Hfq played roles in regulating the expression of 746 genes. In hfq mutant, gene expression related to chemotaxis, secretion system, two-component system, quorum sensing and flagellar assembly were repressed, whereas expression of ribosomal genes were significantly up-regulated. The down-regulated expression of three bacterial chemotaxis related genes and seven flagella genes, which involved in cell growth and biofilm formation, were further validated by RT-qPCR. CONCLUSIONS: The study demonstrated that hfq was involved in multiple biological processes in Xac. The results could serve as initiate points for identifying regulatory sRNAs and genes controlled by Hfq-sRNA interactions in Xac.

Chirality and grain boundary effects on indentation mechanical properties of graphene coated on nickel foil.

We investigate chirality and grain boundary (GB) effects on indentation mechanical properties of graphene coated on nickel foil using molecular dynamics simulations. The models of graphene with different chirality angles, different numbers of layers and tilt GBs were established. It was found that the chirality angle of few-layer graphene had a significant effect on the load bearing capacity of graphene/nickel systems, and this turns out to be more significant when the number of layers is greater than one. The enhancement to the contact stiffness, elastic capacity and the load bearing capacity of graphene with tilt GBs was lower than that of pristine graphene.

Quorum sensing asaI mutants affect spoilage phenotypes, motility, and biofilm formation in a marine fish isolate of Aeromonas salmonicida.

Microbial spoilage is associated with the regulation of quorum sensing (QS). A. salmonicida AE03 with QS mediated acylated homoserine lactones (AHLs) activity was isolated from spoiled large yellow croaker (Pseudosciaena crocea). In this study the activity and role of AHLs in spoilage phenotypes, motility and biofilm formation of AE03 were investigated. The strain AE03 could induce Chromobacterium violaceum CV026 to produce the violacein pigment both at 28 °C and 4 °C in a density-dependent manner. Five types of AHLs were detected in AE03 culture by LC-MS/MS analysis, and N-butanoyl-l-homoserine lactone (C4-HSL) was a major signal molecule, reaching the highest concentration when incubated for 30 h at 28 °C. An asaI-mutant, constructed by a suicide plasmid, failed to produce short chain AHLs signal. Compared with wild type (WT) strain, the production of trimethylamine (TMA), biogenic amino and protease significantly increased in asaI-mutant during the exponential and stationary phase, while the growth rate did not differ. Swimming motility in asaI-mutant was comparatively stronger than that of WT strain, whereas, asaI-mutant resulted in the decrease of maturing biofilm. Furthermore, supplementation of exogenous C4-HSL restored the production of spoilage metablites, protease and biofilm formation in mutant. In accordance with the effect of asaI deletion on the spoilage phenotypes and motility, asaI-mutant was showed to significantly up-regulate the transcript levels of torA, cadA and fliR, as well as asaR, indicating that C4-HSL could be involved in the modulation of the spoilage related enzymes and flagella. Indeed, the asaI-mutant promoted the spoilage progress of fish fillets stored at 4 °C, while exogenous C4-HSL repressed the sensory change and TVB-N accumulation. The present study highlighted that AsaI/C4-HSL was an important regulator in spoilage, motility and biofilm formation of A. salmonicida, and spoilage potential was under the negative control of AsaI/AsaR-type system.

[Research on climatic factors of ecology suitability regionalization of atractylodis].

Through study on the correlation between atractylodis lactones ingredient content and climatic factors, we research regionalization from climatic of five main producing provinces of the country, in order to provide a scientific basis for atractylodis' conscious cultivation. By sampling from 40 origins which from five main producing provinces of the country, we use SPSS to analysis variation of atractylodis lactones ingredient content in different conditions of climatic factors and the effect of each factors. Then according to the relationship between atractylodis lactones ingredient content and climatic factors, we use ArcGIS to conduct ecological suitability regionalization based on climatic factors. The most suitable climatic condition for cultivation of atractylodis: the wettest month precipitation 220-230 mm, the warmest average temperature 25 degrees C, the average temperature of driest season 10 degrees C.

Phosphorescent polymeric nanoparticles by coordination cross-linking as a platform for luminescence imaging and photodynamic therapy.

Water-soluble phosphorescent polymeric nanoparticles with an average diameter of approximately 100 nm were synthesized by a coordination cross-linking reaction. The pyridine blocks in poly(4-vinyl pyridine-b-ethylene oxide) (P4VP-b-PEO) were cross-linked by the iridium chloride-bridged dimer in DMF solution. Owing to the presence of an iridium complex with different ligands in the core of the polymeric nanoparticles, NP-1, NP-2, and NP-3 showed bright green, yellow, and red phosphorescence, respectively. PEG chains in the shell gave the polymeric nanoparticles solubility and biocompatibility, which was confirmed by an MTT assay using HeLa cells as a model cancer cell line. The flow cytometry and laser confocal fluorescence microscopy results revealed NP-2, as an example, could be effectively uptaken by HeLa cells. Therefore, these polymeric nanoparticles can be used as luminescent probes for living cells. In addition, (1) O2 could be effectively generated in the presence of NP-2 upon irradiation with visible light (λ>400 nm, 300 mW cm(-2) ), which was confirmed by a clear decrease in the fluorescence intensity of 9,10-dimethylanthracene (DMA). After incubation with NP-2 at a concentration of 200 µg mL(-1) for 6 h, approximately 90 % of HeLa cells were effectively ablated upon irradiation with visible light for only 10 min, indicating the potential for photodynamic therapy with polymeric nanoparticles.

Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease.

OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What's more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. RESULTS: Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. CONCLUSION: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.

Spatial distribution of metabolites in processing Ziziphi Spinosae Semen as revealed by matrix-assisted laser desorption/ionization mass spectrometry imaging.

Ziziphi Spinosae Semen (ZSS) is the first choice for the treatment of insomnia. This research aimed to reveal the spatial distribution of identifying quality markers of ZSS and to illustrate the metabolite quality characteristics of this herbal medicine. Here, we performed a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in situ to detect and image 33 metabolites in ZSS, including three saponins, six flavonoids, four alkaloids, eight fatty acids, and 12 amino acids. The MALDI images of the metabolites clearly showed the heterogeneous spatial distribution in different regions of ZSS tissues, such as the cotyledon, endosperm, and radicle. The distribution area of two saponins, six flavonoids, and three alkaloids increased significantly after the fried processing of ZSS. Based on the ion images, samples with different processing technologies were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 23 major influencing components exerting higher ion intensities were identified as the potential quality markers of ZSS. Results obtained in the current research demonstrate that the processing of ZSS changes its content and distribution of the medicinal components. The analysis of MALDI-MSI provides a novel MS-based molecular imaging approach to investigate and monitor traditional medicinal plants.

Minor stroke patients with mild-moderate diastolic blood pressure derive greater benefit from dual antiplatelet therapy.

Not only systolic blood pressure (SBP) but also diastolic blood pressure (DBP) increases the risk of recurrence in the short- or long-term outcomes of stroke. The interaction between DBP and antiplatelet treatment for China stroke patients is unclear. This multicenter, observational cohort study included 2976 minor ischemic stroke patients. Patients accepted single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT) after arrival, and baseline DBP levels were trichotomized into <90 mmHg, 90-110 mmHg and ≥110 mmHg. We explore the interaction effect between antiplatelet therapy and DBP on 90-days composite vascular events. A total of 257 (8.6%) patients reached a composite vascular event during follow-up. The interaction term between DBP levels and treatment group (SAPT vs. DAPT) was significant (P for interaction = 0.013). DAPT's adjusted HR for composite events in patients with DBP between 90 and 110 mmHg was 0.56 (95% confidence interval, 0.36 0.88; P = 0.011) and DBP ≥ 110 mmHg was 4.35 (95% confidence interval, 1.11-19.94; P = 0.046). The association between treatment and DBP was still consistent after propensity score matching of the baseline characteristics. The interaction term of DBP × treatment was not significant for the safety outcomes of severe bleeding (P for interaction = 0.301) or hemorrhage stroke (P for interaction = 0.831). In this cohort study based on the real world, patients with a DBP between 90 and 110 mmHg received a greater benefit from 90 days of DAPT than those with lower and higher baseline DBP. REGISTRATION: ( https://www.chictr.org.cn ; Unique identifier: ChiCTR1900025214).

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Chest physiotherapy for pneumonia in adults.

BACKGROUND: Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. OBJECTIVES: To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults. SEARCH METHODS: We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 2, 2012), EMBASE (1974 to November 2012), Physiotherapy Evidence Database (PEDro) (1929 to November 2012), CINAHL (2009 to November 2012) and CBM (1978 to November 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the efficacy of chest physiotherapy for treating pneumonia in adults. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and appraised trial quality. Primary outcomes were mortality and cure rate. We used risk ratios (RR) and mean difference (MD) for individual trial results in the data analysis. We performed meta-analysis and measured all outcomes with 95% confidence intervals (CI). MAIN RESULTS: Six RCTs (434 participants) appraised four types of chest physiotherapy (conventional chest physiotherapy; osteopathic manipulative treatment (which includes paraspinal inhibition, rib raising and myofascial release); active cycle of breathing techniques (which include active breathing control, thoracic expansion exercises and forced expiration techniques); and positive expiratory pressure).None of the physiotherapies (versus no physiotherapy or placebo) improved mortality rates of adults with pneumonia.Conventional chest physiotherapy (versus no physiotherapy), active cycle of breathing techniques (versus no physiotherapy) and osteopathic manipulative treatment (versus placebo) did not increase the cure rate or chest X-ray improvement rate.Osteopathic manipulative treatment (versus placebo) and positive expiratory pressure (versus no physiotherapy) reduced the mean duration of hospital stay by 2.0 days (mean difference (MD) -2.0 days, 95% CI -3.5 to -0.6) and 1.4 days (MD -1.4 days, 95% CI -2.8 to -0.0), respectively. Conventional chest physiotherapy and active cycle of breathing techniques did not.Positive expiratory pressure (versus no physiotherapy) reduced fever duration (MD -0.7 day, 95% CI -1.4 to -0.0). Osteopathic manipulative treatment did not.Osteopathic manipulative treatment (versus placebo) reduced the duration of intravenous (MD -2.1 days, 95% CI -3.4 to -0.9) and total antibiotic treatment (MD -1.9 days, 95% CI -3.1 to -0.7).Limitations of this review are that the studies addressing osteopathic manipulative treatment were small, and that six published studies which appear to meet the inclusion criteria are awaiting classification. AUTHORS' CONCLUSIONS: Based on current limited evidence, chest physiotherapy might not be recommended as routine additional treatment for pneumonia in adults.

DNA barcoding identification of grafted Semen Ziziphi Spinosae and transcriptome study of wild Semen Ziziphi Spinosae.

Semen Ziziphi Spinosae (SZS) is the dried and ripe seeds of Ziziphus jujuba var. spinosa. Currently, the yield of naturally grown SZS is unstable owing to environmental factors. Grafting high-quality sour jujube scions onto sour jujube or jujube tree stocks can result in a greater yield. However, the effects of grafting on the quality and gene expression of SZS have rarely been reported. This study used a DNA barcoding technique, high-performance liquid phase-evaporative luminescence detector (HPLC-ELSD), and transcriptomics to investigate the origin and genetic differences between grafted and wild jujube seeds. DNA barcoding identified all samples as Ziziphus jujuba var. spinosa. HPLC-ELSD analysis revealed a higher content of grafted SZS compared to that of the wild SZS. Transcriptome analysis of the metabolic pathways in SZS showed that 22 and 19 differentially expressed gene sequences encoded enzymes related to flavonoids and saponin synthesis, respectively. Weighted correlation network analysis (WGCNA) identified 15 core genes governing the differences in medicinal components between grafted and wild SZS. This study demonstrated the use of DNA barcoding and fingerprint methods to identify jujube seed species and effectively capture ingredient information of medicinal materials. Additionally, transcriptome technology provided data for identifying core differential genes, facilitating studies on quality differences between grafted and wild SZS.

Dual-Targeted Nanoparticle-in-Microparticle System for Ulcerative Colitis Therapy.

Conventional oral therapy for ulcerative colitis (UC) is associated with premature release or degradation of drugs in the harsh gastrointestinal environment, resulting in reduced therapeutic effectiveness. Consequently, the present study aims to develop a dual-targeted delivery system with a nanoparticle-in-microparticle (nano-in-micro) structure. The prepared Asiatic Acid-loaded delivery system (AA/CDM-BT-ALG) has pH-sensitive properties. Cellular uptake evaluation confirms that nanoparticles exhibit targeted absorption by macrophages and Caco-2 cells through mannose (Man) receptor and biotin-mediated endocytosis, respectively. Therefore, this mechanism effectively enhances intracellular drug concentration. Additionally, the biodistribution study conducted on the gastrointestinal tract of mice indicates that the colon of the microspheres group shows higher fluorescence intensity with longer duration than the other groups. This finding indicates that the microspheres exhibit selective accumulation in areas of colon inflammation. In vivo experiments in colitis mice showed that AA/CDM-BT-ALG significantly alleviates the histopathological characteristics of the colon, reduced neutrophil, and macrophage infiltration, and decreases pro-inflammatory cytokine expression. Furthermore, the effect of AA/CDM-BT-ALG on colitis is validated to be closely related to the TLR4/MyD88/NF-κB signaling pathway. The present findings suggest that the development of a dual-targeted delivery system is accomplished effectively, with the potential to serve as a drug-controlled release system for treating UC.

In situ detection and mass spectrometry imaging of protein-related metabolites in Bombyx batryticatus before and after frying with wheat bran.

Bombyx batryticatus is derived from the dried larva of Bombyx mori Linnaeus infected by Beauveria bassiana (Bals.) Vuillant. Raw Bombyx batryticatus should be stir-fried before oral administration due to its irritation to the gastrointestinal tract. Nevertheless, it is still an arduous task to uncover the intrinsic mechanism of Bombyx batryticatus processing. In this study, we collected two types of Bombyx batryticatus, one being stir-fried and the other serving as a control. Then, an informative approach, which integrated matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with chemometrics analysis, was established to screen processing-associated markers and reveal in situ spatial distribution patterns of protein-related metabolites. After optimization of experimental conditions, 21 ions were initially detected from Bombyx batryticatus, including amino acids and peptides. In addition, 15 differential markers were screened by orthogonal projection to potential structure discriminant analysis (OPLS-DA), which were localized and visualized in the transverse section of Bombyx batryticatus by MSI. Eventually, it can be demonstrated that the stir-frying process reduces toxicity while potentially boosting specific biological activities of Bombyx batryticatus. In summary, the established strategy could not only clarify the chemical transformation of protein-related metabolites from Bombyx batryticatus before and after frying with wheat bran, but also reveal the significance of Chinese medicine processing technology.