Phenylpropanoid-rich maize root extract serves as a natural antidepressant.

BACKGROUND: Depression is a serious and complex mental disease that has attracted worldwide attention because of its high incidence rate, high disability rate and high mortality. Excitotoxicity is one of the most important mechanisms involved in the pathophysiological process of depression. In our previous studies, n-butanol extract from maize roots was found to have good neuroprotective effects due to its antioxidative activity. However, the antidepressive effective constituents, efficacy in vivo and mechanism of action of maize root extracts have not been determined. PURPOSE: This study aimed to determine the main active neuroprotective compound in maize root extract and investigate its antidepressant effects and possible underlying mechanism in vitro and in vivo. METHODS: Sixteen extracts were isolated and purified from maize roots. The active components of the most active extracts of maize roots (hereafter referred to as EM 2) were identified using UF-HPLC-QTOF/MS. In vitro cell models of NMDA-induced excitotoxicity in SH-SY5Y cells were used to analyze the anti-excitatory activity of the extracts. The MTT assay and Annexin V-FITC/PI Apoptosis Detection were used to evaluate cell viability. Several network pharmacological strategies have been employed to investigate the potential mechanism of action of EM 2. The effects of EM 2 on depressive-like behaviors were evaluated in CUMS mice. Changes in the levels of related proteins were detected via western blotting. RESULTS: Among the 16 extracts extracted by n-butanol, EM 2 was determined to be the most active extract against NMDA-induced excitotoxicity by n-butanol extraction. Meanwhile, seventeen compounds were further identified as the main active components of EM 2. Mechanistically, EM 2 inhibited NMDA-induced excitatory injury in SH-SY5Y cells and alleviated the depressive-like behaviors of CUMS mice by suppressing NR2B and subsequently mediating the downstream CREB/TRKB/BDNF, PI3K/Akt and MAPK pathways, as well as the Nrf2/HO-1 antioxidant signaling pathway. CONCLUSION: The study indicated that EM 2 could potentially be developed as a potential therapeutic candidate to cure depression in NMDA-induced excitatory damage.

High-Performance Organic-Inorganic Hybrid Conductive Hydrogels for Stretchable Elastic All-Hydrogel Supercapacitors and Flexible Self-Powered Integrated Systems.

Conductive polymer hydrogels exhibit unique electrical, electrochemical, and mechanical properties, making them highly competitive electrode materials for stretchable high-capacity energy storage devices for cutting-edge wearable electronics. However, it remains extremely challenging to simultaneously achieve large mechanical stretchability, high electrical conductivity, and excellent electrochemical properties in conductive polymer hydrogels because introducing soft insulating networks for improving stretchability inevitably deteriorates the connectivity of rigid conductive domain and decreases the conductivity and electrochemical activity. This work proposes a distinct confinement self-assembly and multiple crosslinking strategy to develop a new type of organic-inorganic hybrid conductive hydrogels with biphase interpenetrating cross-linked networks. The hydrogels simultaneously exhibit high conductivity (2000 S m-1), large stretchability (200%), and high electrochemical activity, outperforming existing conductive hydrogels. The inherent mechanisms for the unparalleled comprehensive performances are thoroughly investigated. Elastic all-hydrogel supercapacitors are prepared based on the hydrogels, showing high specific capacitance (212.5 mF cm-2), excellent energy density (18.89 µWh cm-2), and large deformability. Moreover, flexible self-powered luminescent integrated systems are constructed based on the supercapacitors, which can spontaneously shine anytime and anywhere without extra power. This work provides new insights and feasible avenues for developing high-performance stretchable electrode materials and energy storage devices for wearable electronics.

Construction of a prediction model for pulmonary infection and its risk factors in Intensive Care Unit patients.

Objective: To identify independent risk factors of pulmonary infection in intensive care unit (ICU) patients, and to construct a prediction model. Methods: Medical data of 398 patients treated in the ICU of Jiaxing Hospital of Traditional Chinese Medicine from January 2019 to January 2023 were analyzed. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for pulmonary infection in ICU patients. R software was used to construct a nomogram prediction model, and the prediction model was internally validated using computer simulation bootstrap method. Predictive value of the model was analyzed using the receiver operating characteristic (ROC) curve. Results: A total of 97 ICU patients (24.37%) developed pulmonary infection. Age, ICU stay time, invasive operation, diabetes, duration of mechanical ventilation, and state of consciousness were all identified as risk factors for pulmonary infection. The calibration curve of the constructed nomogram prediction model showed a good consistency between the predicted value of the model and the actual observed value. ROC curve analysis showed that the area under the curve (AUC) of the model was 0.784 (95% CI: 0.731-0.837), indicating a certain predictive value. Conclusions: Age, length of stay in ICU, invasive operation, diabetes, duration of mechanical ventilation, and state of consciousness are risk factors for pulmonary infection in ICU patients. The nomogram prediction model constructed based on the above risk factors has shown a good predictive value.

Multiomics analysis of a resistant European turnip ECD04 during clubroot infection reveals key hub genes underlying resistance mechanism.

The clubroot disease has become a worldwide threat for crucifer crop production, due to its soil-borne nature and difficulty to eradicate completely from contaminated field. In this study we used an elite resistant European fodder turnip ECD04 and investigated its resistance mechanism using transcriptome, sRNA-seq, degradome and gene editing. A total of 1751 DEGs were identified from three time points after infection, among which 7 hub genes including XTH23 for cell wall assembly and two CPK28 genes in PTI pathways. On microRNA, we identified 17 DEMs and predicted 15 miRNA-target pairs (DEM-DEG). We validated two pairs (miR395-APS4 and miR160-ARF) by degradome sequencing. We investigated the miR395-APS4 pair by CRISPR-Cas9 mediated gene editing, the result showed that knocking-out APS4 could lead to elevated clubroot resistance in B. napus. In summary, the data acquired on transcriptional response and microRNA as well as target genes provide future direction especially gene candidates for genetic improvement of clubroot resistance on Brassica species.

A new artificial intelligence system for both stomach and small-bowel capsule endoscopy.

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence in small-bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning-based SmartScan (SS), which has been described previously. A total of 1069 magnetically controlled GI CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new artificial intelligence algorithm named SS Plus. A total of 342 fully automated, magnetically controlled CE examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-assisted reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (median, 1000; interquartile range [IQR], 814.50-1000) versus 44,322.73 (median, 42,393; IQR, 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 minutes (median, 8.51; IQR, 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded deep learning-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

Designing 3d Transition Metal Cation-Doped MRuOx As Durable Acidic Oxygen Evolution Electrocatalysts for PEM Water Electrolyzers.

The continuous dissolution and oxidation of active sites in Ru-based electrocatalysts have greatly hindered their practical application in proton exchange membrane water electrolyzers (PEMWE). In this work, we first used density functional theory (DFT) to calculate the dissolution energy of Ru in the 3d transition metal-doped MRuOx (M = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) to evaluate their stability for acidic oxygen evolution reaction (OER) and screen out ZnRuOx as the best candidate. To confirm the theoretical predictions, we experimentally synthesized these MRuOx materials and found that ZnRuOx indeed displays robust acidic OER stability with a negligible decay of η10 after 15 000 CV cycles. Of importance, using ZnRuOx as the anode, the PEMWE can run stably for 120 h at 200 mA cm-2. We also further uncover the stability mechanism of ZnRuOx, i.e., Zn atoms doped in the outside of ZnRuOx nanocrystal would form a "Zn-rich" shell, which effectively shortened average Ru-O bond lengths in ZnRuOx to strengthen the Ru-O interaction and therefore boosted intrinsic stability of ZnRuOx in acidic OER. In short, this work not only provides a new study paradigm of using DFT calculations to guide the experimental synthesis but also offers a proof-of-concept with 3d metal dopants as RuO2 stabilizer as a universal principle to develop high-durability Ru-based catalysts for PEMWE.

Synthesis and antitumor activities of novel 3-(6-aminopyridin-3-yl)benzamide derivatives: Inducing cell cycle arrest and apoptosis via AURKB transcription inhibition.

Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC50 value of 0.04 ± 0.01 µM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers.

Effects of sleep disturbance, cancer-related fatigue, and psychological distress on breast cancer patients' quality of life: a prospective longitudinal observational study.

More attention has gone to researching the cancer-related fatigue (CRF)-sleep disturbance (SD)-psychological distress (PD) symptom cluster in breast cancer patients during the chemotherapy period, but the change trend and heterogeneous development track in the whole treatment stage remain unclear, and it is also unclear whether the appearance of and changes in one symptom cause changes in other symptoms and quality of life (QoL). This study, using breast cancer patients' data collected through a validated questionnaire, examined the relationships between SD, CRF, PD, and QoL using latent growth modeling analyses. CRF developmental trajectories showed an upward trend over five surveys (slope = 0.649, P < 0.001); PD showed a significant weakening trend (slope = - 0.583, P < 0.001); SD showed an increasing trend (slope = 0.345, P < 0.001), and QoL showed a statistically significant weakening trend (slope = - 0.373, P < 0.001). The initial CRF (coefficient = - 0.233, P < 0.01), PD (coefficient = - 0.296, P < 0.01), and SD (coefficient = - 0.388, P < 0.001) levels had a statistically significant negative effect on initial QoL level. The linear development rate of PD was statistically significant and negatively affected that of QoL (coefficient = - 0.305, P < 0.05), whereas the quadratic development rate of SD negatively affected that of QoL (coefficient = - 0.391, P < 0.05). Medical staff should identify the change characteristics of different variables based on SD, CRF, PD, and QoL change trajectories, and advance the intervention time, as changes in variables affect other variables' subsequent changes.

Lead-free Cs2AgBiBr6 double perovskite microcrystals for effective visible-light photocatalytic thio/selenocyanation.

Lead-free perovskite microcrystals (MCs) have been regarded as promising potential photocatalysts, owing to their high molar extinction coefficient, low economic cost, adjustable light absorption range, and ample surface-active sites. Herein, C-3 thio/selenocyanation of indoles is demonstrated in high selectivity and yield by using lead-free double perovskite Cs2AgBiBr6 MCs under visible light irradiation. Moreover, the photocatalyst can be recycled at least 5 times without a significant decrease in catalytic activity.

Multifunctional ZnO@DOX/ICG-LMHP Nanoparticles for Synergistic Multimodal Antitumor Activity.

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O2) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.

CXCL12-CXCR4 mediates CD57+ CD8+ T cell responses in the progression of type 1 diabetes.

CD57+ CD8+ T cells, also referred as effector memory cells, are implicated in various conditions including tumor immunity, virus immunity, and most recently with autoimmunity. However, their roles in the progression and remission of T1D are still unclear. Here, we noted an increase in peripheral CD57+ CD8+ T cells in a T1D patient harboring an activator of transcription 3 (STAT3) mutation. Our in-depth study on the role of CD57+ CD8+ T cells within a T1D patient cohort revealed that these cells undergo significant compositional shifts during the disease's progression. Longitudinal cohort data suggested that CD57+ CD8+ T cell prevalence may be a harbinger of ß-cell function decline in T1D patients. Characterized by robust cytotoxic activity, heightened production of pro-inflammatory cytokines, and increased intracellular glucose uptake, these cells may be key players in the pathophysiology of T1D. Moreover, in vitro assays showed that the CXCL12-CXCR4 axis promotes the expansion and function of CD57+ CD8+ T cells via Erk1/2 signaling. Notably, the changes of serum CXCL12 concentrations were also found in individuals during the peri-remission phase of T1D. Furthermore, treatment with the CXCR4 antagonist LY2510924 reduced the immunological infiltration of CD57+ CD8+ T cells and mitigated hyperglycemia in a STZ-induced T1D mouse model. Taken together, our work has uncovered a novel role of the CXCL12-CXCR4 axis in driving CD57+ CD8+ T cells responses in T1D, and presented a promising therapeutic strategy for delaying the onset and progression of diabetes.

Learning Spatiotemporal Manifold Representation for Probabilistic Land Deformation Prediction.

Landslides refer to occurrences of massive ground movements due to geological (and meteorological) factors, and can have disastrous impacts on property, economy, and even lead to the loss of life. The advances in remote sensing provide accurate and continuous terrain monitoring, enabling the study and analysis of land deformation which, in turn, can be used for land deformation prediction. Prior studies either rely on predefined factors and patterns or model static land observations without considering the subtle interactions between different point locations and the dynamic changes of the surface conditions, causing the prediction model to be less generalized and unable to capture the temporal deformation characteristics. To address these issues, we present DyLand, a dynamic manifold learning framework that models the dynamic structures of the terrain surface. We contribute to the land deformation prediction literature in four directions. First, DyLand learns the spatial connections of interferometric synthetic aperture radar (InSAR) measurements and estimates the conditional distributions on a dynamic terrain manifold with a novel normalizing flow-based method. Second, instead of modeling the stable terrains, we incorporate surface permutations and capture the innate dynamics of the land surface while allowing for tractable likelihood estimations on the manifold. Third, we formulate the spatiotemporal learning of land deformations as a dynamic system and unify the learning of spatial embeddings and surface deformation. Finally, extensive experiments on curated real-world InSAR datasets (land slopes prone to landslides) show that DyLand outperforms existing benchmark models.

Glycaemia risk index uncovers distinct glycaemic variability patterns associated with remission status in type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this work was to define a unique remission status using glycaemia risk index (GRI) and other continuous glucose monitoring (CGM) metrics in individuals with type 1 diabetes for improved phenotyping. METHODS: A group of 140 individuals with type 1 diabetes were recruited for a cross-sectional study. The participants were categorised into four groups based on their remission status, which was defined as insulin-dose-adjusted A1c (IDAA1c) <9 or C-peptide ≥300 pmol/l: new-onset (n=24); mid-remission (n=44); post-remission (n=44); and non-remission (individuals who did not experience remission, n=28). Participants in the remission phase were referred to as 'remitters', while those who were not in the remission phase were referred to as 'non-remitters', the latter group including new-onset, post-remission and non-remission participants. Clinical variables such as HbA1c, C-peptide and insulin daily dose, as well as IDAA1C and CGM data, were collected. The patterns of CGM metrics were analysed for each group using generalised estimating equations to investigate the glycaemic variability patterns associated with remission status. Then, unsupervised hierarchical clustering was used to place the participants into subgroups based on GRI and other CGM core metrics. RESULTS: The glycaemic variability patterns associated with remission status were found to be distinct based on the circadian CGM metrics. Remitters showed improved control of blood glucose levels over 14 days within the range of 3.9-10 mmol/l, and lower GRI compared with non-remitters (p<0.001). Moreover, GRI strongly correlated with IDAA1C (r=0.62; p<0.001) and was sufficient to distinguish remitters from non-remitters. Further, four subgroups demonstrating distinct patterns of glycaemic variability associated with different remission status were identified by clustering on CGM metrics: remitters with low risk of dysglycaemia; non-remitters with high risk of hypoglycaemia; non-remitters with high risk of hyperglycaemia; and non-remitters with moderate risk of dysglycaemia. CONCLUSIONS/INTERPRETATION: GRI, an integrative index, together with other traditional CGM metrics, helps to identify different glycaemic variability patterns; this might provide specifically tailored monitoring and management strategies for individuals in the various subclusters.

Co-Delivery of Bioengineered Exosomes and Oxygen for Treating Critical Limb Ischemia in Diabetic Mice.

Diabetic patients with critical limb ischemia face a high rate of limb amputation. Regeneration of the vasculature and skeletal muscles can salvage diseased limbs. Therapy using stem cell-derived exosomes that contain multiple proangiogenic and promyogenic factors represents a promising strategy. Yet the therapeutic efficacy is not optimal because exosomes alone cannot efficiently rescue and recruit endothelial and skeletal muscle cells and restore their functions under hyperglycemic and ischemic conditions. To address these limitations, we fabricated ischemic-limb-targeting stem cell-derived exosomes and oxygen-releasing nanoparticles and codelivered them in order to recruit endothelial and skeletal muscle cells, improve cell survival under ischemia before vasculature is established, and restore cell morphogenic function under high glucose and ischemic conditions. The exosomes and oxygen-releasing nanoparticles, delivered by intravenous injection, specifically accumulated in the ischemic limbs. Following 4 weeks of delivery, the exosomes and released oxygen synergistically stimulated angiogenesis and muscle regeneration without inducing substantial inflammation and reactive oxygen species overproduction. Our work demonstrates that codelivery of exosomes and oxygen is a promising treatment solution for saving diabetic ischemic limbs.

Hardness and superconductivity in tetragonal LiB4 and NaB4.

Boron-based compounds have triggered substantial attention due to their multifunctional properties, incorporating excellent hardness and superconductivity. While tetragonal metal borides LiB4 and NaB4 with BaAl4-type structure and striking clathrate boron motif have been induced under compression, there is still a lack of deep understanding of their potential properties at ambient pressure. We herein conduct a comprehensive study on I4/mmm-structured LiB4 and NaB4 under ambient pressure via first-principles calculations. Remarkably, both LiB4 and NaB4 are found to possess high Vickers hardness of 39 GPa, which is ascribed to the robust boron framework with strong covalency. Furthermore, their high hardness values together with distinguished stability make them highly potential superhard materials. Meanwhile, electron-phonon coupling analysis reveals that both LiB4 and NaB4 are conventional phonon-mediated superconductors, with critical temperatures of 6 and 8 K at 1 atmosphere pressure (atm), respectively, mainly arising from the coupling of B 2p electronic states and the low-frequency phonon modes associated with Li-, Na-, and B-derived vibrations. This work provides valuable insights into the mechanical and superconducting behaviors of metal borides and will boost further studies of emergent borides with multiple functionalities.

[Effect of different suspension moxibustion methods on syndrome characteristics of rats with rheumatoid arthritis of heat bi syndrome based on "moxibustion can be used for heat syndrome"].

OBJECTIVE: To observe the effects of different suspension moxibustion methods on the syndrome characteristics and inflammatory factors of rats with rheumatoid arthritis (RA) of heat bi syndrome and to prove the concept of "moxibustion can be used for heat syndrome". METHODS: Among seventy Wistar rats, 12 rats were randomly selected as a normal group, and the remaining rats were induced by collagen combined with wind, dampness, and heat environmental stimulation to establish the RA model of heat bi syndrome. Forty-eight rats with successful model establishment were further randomly divided into a model group and three moxibustion groups (mild moxibustion group, rotating moxibustion group and sparrow-pecking moxibustion group), with 12 rats in each group. The acupoints "Quchi" (LI 11), "Dazhui" (GV 14) and ashi point were used in all moxibustion groups, with mild moxibustion, rotating moxibustion, and sparrow-pecking moxibustion intervention given respectively, each acupoint was treated with moxibustion for 10 min a day, and 6 days were considered one course of treatment, with a total of three courses. After the intervention, the arthritis index (AI), the Evans blue (EB) extravasated volume in the soft tissue of the right hind paw, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in the serum were measured by ELISA in each group. The volume of the bilateral hind paw was measured; the infrared thermal imaging was collected to analyze the temperature of the plantar area of the bilateral foot pads, and the reaction time of plantar heat pain was calculated before and after modeling, as well as after the 1st, 2nd and 3rd courses of interrention. The ankle dorsiflexion angle of the right hind foot was also measured before and after modeling, as well as after the intervention. RESULTS: After modeling, compared with the normal group, the rats in the model group had more high-temperature areas in the bilateral hind limbs, abnormal AI score, abnormal bilateral hind paw volume, abnormal temperature of the plantar area of the bilateral foot pads, abnormal foot pain response time, abnormal right hind ankle dorsiflexion angle, abnormal right hind paw soft tissue EB extravasation, and abnormal serum TNF-α and IL-10 levels (P<0.01, P<0.05). After the intervention, compared with the model group, the rats in each moxibustion group had decreased or disappeared high-temperature areas in the bilateral hind limbs, EB extravasated volume in the soft tissue of the right hind paw was reduced (P<0.05), and the right ankle dorsiflexion angle was increased (P<0.05), serum level of TNF-α was reduced, and level of IL-10 increased (P<0.05); the AI scores in the mild moxibustion group and the sparrow-pecking moxibustion group was decreased (P<0.01, P<0.05). After the 1st, 2nd and 3rd courses of intervention, compared with the model group, the bilateral hind paw volume of rats in each moxibustion group was decreased (P<0.05, P<0.01), and plantar heat pain reaction time was increased (P<0.05). After the 2nd course and the 3rd course of intervention, the temperature of the right hind paw pad area was decreased in each moribustion group (P<0.05); after the 3rd courses of intervention, the temperature of the left hind paw pad area was decreased in the mild moxibustion group (P<0.05). CONCLUSION: Suspension moxibustion could adjust the serum levels of TNF-α and IL-10 to improve the syndrome characteristics of RA rats of heat bi syndrome, such as joint redness, swelling, heat, pain and activity restriction. The effect of mild moxibustion is the most prominent. The findings could provide scientific basis for "moxibustion can be used for heat syndrome".

Genetic Divergence and Population Structure of Xanthomonas albilineans Strains Infecting Saccharum spp. Hybrid and Saccharum officinarum.

Leaf scald caused by Xanthomonas albilineans (Xa) is a major bacterial disease in sugarcane that represents a threat to the global sugar industry. Little is known about the population structure and genetic evolution of this pathogen. In this study, 39 Xa strains were collected from 6 provinces in China. Of these strains, 15 and 24 were isolated from Saccharum spp. hybrid and S. officinarum plants, respectively. Based on multilocus sequence analysis (MLSA), with five housekeeping genes, these strains were clustered into two distinct phylogenetic groups (I and II). Group I included 26 strains from 2 host plants, Saccharum spp. hybrid and S. officinarum collected from 6 provinces, while Group II consisted of 13 strains from S. officinarum plants in the Zhejiang province. Among the 39 Xa strains, nucleotide sequence identities from 5 housekeeping genes were: ABC (99.6-100%), gyrB (99.3-100%), rpoD (98.4-100%), atpD (97.0-100%), and glnA (97.6-100%). These strains were clustered into six groups (A-F), based on the rep-PCR fingerprinting, using primers for ERIC2, BOX A1R, and (GTG)5. UPGMA and PCoA analyses revealed that group A had the most strains (24), followed by group C with 11 strains, while there was 1 strain each in groups B and D-F. Neutral tests showed that the Xa population in S. officinarum had a trend toward population expansion. Selection pressure analysis showed purification selection on five concatenated housekeeping genes from all tested strains. Significant genetic differentiation and infrequent gene flow were found between two Xa populations hosted in Saccharum spp. hybrids and S. officinarum. Altogether, these results provide evidence of obvious genetic divergence and population structures among Xa strains from China.

Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFß pathways promote diabetic wound healing.

Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFß receptor II inhibitor (PTßR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTßR2I inhibits the TGFß1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTßR2I does not interfere with the TGFß1/Smad2/3 pathway that is required to regulate myofibroblasts, a critical cell type for wound healing. The hydrogel's ability to scavenge ROS in diabetic wounds further decreases inflammation. Single-dose application of the wound dressing significantly accelerates wound healing with complete wound closure after 14 days. Overall, using wound dressings capable of adaptively modulating TGFß pathways provides a new strategy for diabetic wound treatment.

Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release.

Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (1O2) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with 1O2 responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates 1O2-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of 1O2. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications.