Immunomodulatory poly(L-lactic acid) nanofibrous membranes promote diabetic wound healing by inhibiting inflammation, oxidation and bacterial infection.

Background: Given the significant impact on human health, it is imperative to develop novel treatment approaches for diabetic wounds, which are prevalent and serious complications of diabetes. The diabetic wound microenvironment has a high level of reactive oxygen species (ROS) and an imbalance between proinflammatory and anti-inflammatory cells/factors, which hamper the healing of chronic wounds. This study aimed to develop poly(L-lactic acid) (PLLA) nanofibrous membranes incorporating curcumin and silver nanoparticles (AgNPs), defined as PLLA/C/Ag, for diabetic wound healing. Methods: PLLA/C/Ag were fabricated via an air-jet spinning approach. The membranes underwent preparation and characterization through various techniques including Fourier-transform infrared spectroscopy, measurement of water contact angle, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy, assessment of in vitro release of curcumin and Ag+, testing of mechanical strength, flexibility, water absorption and biodegradability. In addition, the antioxidant, antibacterial and anti-inflammatory properties of the membranes were evaluated in vitro, and the ability of the membranes to heal wounds was tested in vivo using diabetic mice. Results: Loose hydrophilic nanofibrous membranes with uniform fibre sizes were prepared through air-jet spinning. The membranes enabled the efficient and sustained release of curcumin. More importantly, antibacterial AgNPs were successfully reduced in situ from AgNO3. The incorporation of AgNPs endowed the membrane with superior antibacterial activity, and the bioactivities of curcumin and the AgNPs gave the membrane efficient ROS scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further results from animal studies indicated that the PLLA/C/Ag membranes had the most efficient wound healing properties, which were achieved by stimulating angiogenesis and collagen deposition and inhibiting inflammation. Conclusions: In this research, we successfully fabricated PLLA/C/Ag membranes that possess properties of antioxidants, antibacterial agents and anti-inflammatory agents, which can aid in the process of wound healing. Modulating wound inflammation, these new PLLA/C/Ag membranes serve as a novel dressing to enhance the healing of diabetic wounds.

Genome-Wide Methylation Analysis Reveals a KCNK3-Prominent Causal Cascade on Hypertension.

BACKGROUND: Despite advances in understanding hypertension's genetic structure, how noncoding genetic variants influence it remains unclear. Studying their interaction with DNA methylation is crucial to deciphering this complex disease's genetic mechanisms. METHODS: We investigated the genetic and epigenetic interplay in hypertension using whole-genome bisulfite sequencing. Methylation profiling in 918 males revealed allele-specific methylation and methylation quantitative trait loci. We engineered rs1275988T/C mutant mice using CRISPR/Cas9, bred them for homozygosity, and subjected them to a high-salt diet. Telemetry captured their cardiovascular metrics. Protein-DNA interactions were elucidated using DNA pull-downs, mass spectrometry, and Western blots. A wire myograph assessed vascular function, and analysis of the Kcnk3 gene methylation highlighted the mutation's role in hypertension. RESULTS: We discovered that DNA methylation-associated genetic effects, especially in non-CpG island and noncoding distal regulatory regions, significantly contribute to hypertension predisposition. We identified distinct methylation quantitative trait locus patterns in the hypertensive population and observed that the onset of hypertension is influenced by the transmission of genetic effects through the demethylation process. By evidence-driven prioritization and in vivo experiments, we unearthed rs1275988 in a cell type-specific enhancer as a notable hypertension causal variant, intensifying hypertension through the modulation of local DNA methylation and consequential alterations in Kcnk3 gene expression and vascular remodeling. When exposed to a high-salt diet, mice with the rs1275988C/C genotype exhibited exacerbated hypertension and significant vascular remodeling, underscored by increased aortic wall thickness. The C allele of rs1275988 was associated with elevated DNA methylation levels, driving down the expression of the Kcnk3 gene by attenuating Nr2f2 binding at the enhancer locus. CONCLUSIONS: Our research reveals new insights into the complex interplay between genetic variations and DNA methylation in hypertension. We underscore hypomethylation's potential in hypertension onset and identify rs1275988 as a causal variant in vascular remodeling. This work advances our understanding of hypertension's molecular mechanisms and encourages personalized health care strategies.

Selective N-Alkylation of Aminobenzenesulfonamides with Alcohols for the Synthesis of Amino-(N-alkyl)benzenesulfonamides Catalyzed by a Metal-Ligand Bifunctional Ruthenium Catalyst.

[(p-Cymene)Ru(2,2'-bpyO)(H2O)] was proven to be an efficient catalyst for the synthesis of amino-(N-alkyl)benzenesulfonamides via selective N-alkylation of aminobenzenesulfonamides with alcohols. It was confirmed that functional groups in the bpy ligand are crucial for the activity of catalysts. Furthermore, the utilization of this catalytic system for the preparation of a biologically active compound was presented.

Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China.

Background: The promising efficacy of novel anti-HER2 antibody-drug conjugates (ADC) in HER2-low breast cancer has made HER2-low a research hotspot. However, controversy remains regarding the neoadjuvant chemotherapy (NAC) efficacy, prognosis, and the relationship with hormone receptor (HR) status of HER2-low. Methods: A retrospective analysis was conducted on 975 patients with HER2-negative breast cancer undergoing NAC at Tianjin Medical University Cancer Institute and Hospital, evaluating pathological complete response (pCR) rate and prognosis between HER2-low and HER2-zero in the overall cohort and subgroups. Results: Overall, 579 (59.4%) and 396 (40.6%) patients were HER2-low and HER2-zero disease, respectively. Compared with HER2-zero, the HER2-low cohort consists of more postmenopausal patients, with lower histological grade and higher HR positivity. In the HR-positive subgroup, HER2-low cases remain to exhibit lower histological grade, while in the HR-negative subgroup, they show higher grade. The HER2-low group had lower pCR rates than the HER2-zero group (16.4% vs. 24.0%). In the HR-positive subgroup, HER2-low consistently showed lower pCR rate (8.1% vs. 15.5%), and served as an independent suppressive factor for the pCR rate. However, no significant difference was observed in the pCR rates between HER2-low and HER2-zero in the HR-negative breast cancer. In the entire cohort and in stratified subgroups based on HR and pCR statuses, no difference in disease-free survival were observed between HER2-low and HER2-zero. Conclusions: In the Chinese population, HER2-low breast cancer exhibits distinct characteristics and efficacy of NAC in different HR subgroups. Its reduced pCR rate in HR-positive subgroup is particularly important for clinical decisions. However, HER2-low is not a reliable factor for assessing long-term survival outcomes.

Dual-mRNA Delivery Using Tumor Cell Lysate-Based Multifunctional Nanoparticles as an Efficient Colon Cancer Immunogene Therapy.

Background: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments. Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates. Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models. Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.

Thiol-ene Click Chemistry Synthesis of L-Cysteine-Grafted Graphene Oxide As a New Corrosion Inhibitor for Q235 Steel in Acidic Environment.

l-cysteine, as an eco-friendly and nontoxic corrosion inhibitor, was directly covalently linked to the carbon/carbon double bonds of the GO flakes by a thiol-ene click reaction to avoid decreasing the number of hydrophilic oxygen-containing polar functionalities. The corrosion inhibition performances of Cys-GO toward Q235 steel (QS) in diluted hydrochloric acid were studied by electrochemical methods. The corrosion was a charge transfer-controlled process, and Cys-GO manifested as a mixed-type corrosion inhibitor. The corrosion inhibition efficiency (η) for QS showed a first-increase-and-then-decrease trend with increasing Cys-GO concentrations. The optimum concentration of Cys-GO was 15 mg L-1, and the according η value was up to 90%. The Cys-GO adsorbed on the QS surface to form a protective barrier was responsible for the efficient corrosion inhibition. Langmuir adsorption isotherm model was fitted well with the experiment data, indicating a monolayer adsorption. Furthermore, the coordinate covalent bonds, π-back-donation effect, and electrostatic attraction were responsible for the Cys-GO adsorption on the QS surface.

Photocycloaddition of Zero-Dimensional Metal Halide Hybrids with Reversible Photochromism.

In this work, two zero-dimensional (0D) metal halide hybrids L2ZnBr4 [1, L = (E)-4-(2-(1H-pyrrol-3-yl)vinyl)-1-methylpyridin-1-ium] and L6Pb3Br12 (2) were prepared, which demonstrated photochromism and photoinduced cracking. Upon irradiation at 450 nm, a single crystal-to-single crystal transformation occurred as a result of the [2 + 2] photocycloaddition of L. Interestingly, compared to the complete photocycloaddition of L in 1, only two-thirds of L monomers could be photodimerized in 2 because of the difference in L orientation. 1 shows reversible photochromic behavior including rapid response time, few cracks, high conversion rate, and good reaction reversibility, while 2 exhibits no significant color change but distinct photoinduced cracking because of the large local lattice strain induced by inhomogeneous and anisotropic deformation. Moreover, the photocycloaddition of L results in the distinct shift of photoluminescence of 1 and 2, attributed to the variation in conjugation of π electrons and distortion of metal halide clusters. As a proof-of-concept, reversible optical writing is demonstrated for 1. These findings provide new insights into the design of stimuli-responsive multifunctional materials.

RNAi-mediated knockdown of papilin gene affects the egg hatching in Nilaparvata lugens.

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. RESULTS: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. CONCLUSION: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.

PagKNAT2/6b promotes shoot branching by attenuating auxin-strigolactone signalling in poplar.

Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin-strigolactone (IAA-SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA-SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types.

Chemoproteomics enables identification of coatomer subunit zeta-1 targeted by a small molecule for enterovirus A71 inhibition.

Human enterovirus A71 (EV-A71) is a significant etiological agent responsible for epidemics of hand, foot, and mouth disease (HFMD) in Asia-Pacific regions. There are presently no licensed antivirals against EV-A71, and the druggable target for EV-A71 remains very limited. The phenotypic hit 10,10'-bis(trifluoromethyl) marinopyrrole A derivative, herein termed MPA-CF3, is a novel potent small-molecule inhibitor against EV-A71, but its pharmacological target(s) and antiviral mechanisms are not defined. Here, quantitative chemoproteomics deciphered the antiviral target of MAP-CF3 as host factor coatomer subunit zeta-1 (COPZ1). Mechanistically, MPA-CF3 disrupts the interaction of COPZ1 with the EV-A71 nonstructural protein 2C by destabilizing COPZ1 upon binding. The destruction of this interaction blocks the coatomer-mediated transport of 2C to endoplasmic reticulum, and ultimately inhibits EV-A71 replication. Taken together, our study disclosed that MPA-CF3 can be a structurally novel host-targeting anti-EV-A71 agent, providing a structural basis for developing the COPZ1-targeting broad-spectrum antivirals against enteroviruses. The mechanistic elucidation of MPA-CF3 against EV-A71 may offer an alternative COPZ1-involved therapeutic pathway for enterovirus infection.

Jianpi-Tiaoqi decoction inhibits tumour proliferation and lung metastasis in tumour-bearing mice with triple-negative breast cancer.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.

Nomograms for metastasis of non-sentinel lymph nodes or more than three lymph nodes in patients with one or two positive sentinel lymph nodes.

Purpose: The purpose of this study was to provide advice for the indication of regional nodal irradiation (RNI) in patients with one to two positive sentinel lymph nodes (SLNs) without axillary lymph node dissection (ALND). Methods: We conducted a retrospective study in Shandong Cancer Hospital, Fudan University Shanghai Cancer Center, and West China Hospital. Logistic analysis was performed in order to explore the influencing factors of positive non-SLNs (NSLNs) and >3 positive nodes among patients with one to two SLNs+. Then, nomograms were constructed. Results: Between May 2010 and 2020, among the 2,845 patients with one to two SLNs+ undergoing ALND (1,992 patients in the training set and 853 patients in the validation set), there were 34.3% harbored NSLNs+ and 15.6% harbored >3 positive nodes. Multivariate analysis showed that cN stage, the number of positive/negative SLN, pathological tumor stage, lympho-vascular invasion (LVI), multicenter, and molecular subtypes were significantly associated with NSLN metastasis. Similarly, multivariate analysis also showed that cN stage, the number of positive/negative SLNs, pathological tumor stage, and LVI could be independent predictors of >3 positive nodes. Then, nomograms for NSLN metastasis and >3 positive nodes were constructed using these parameters, respectively. Conclusions: The nomograms will be useful in estimating positive NSLNs and >3 positive nodes, and they might provide advice for the optimization of RNI.

Dynamic iterative correction algorithm for designing diffractive optical elements.

When utilizing the Gerchberg-Saxton (GS) algorithm to design diffractive optical elements, correction coefficients are introduced to improve the quality of the design results. The main design idea is to correct the target information dynamically during the iterative calculation process. The effectiveness of the proposed method is demonstrated through the verification of beam shaping and phase-type hologram designs. Compared to the traditional GS algorithm, the results of beam shaping show that the light intensity nonuniformity and the root-mean-square error (RMSE) of the shaped spot are reduced by an order of magnitude. The results of phase-type holograms show that the reconstructed image's peak signal-to-noise ratio (PSNR) is improved by about 12 dB. Finally, the paper also discusses the selection of correction coefficients, providing insights into the selection of optimal design correction coefficients. The simulation and experimental results show that the improved algorithm proposed in this paper is not only simple in design but also highly efficient in obtaining a high-quality phase structure, which is of great help in designing high-quality diffractive optical elements.

Optimizing timing for quantification of intracranial aneurysm enhancement: a multi-phase contrast-enhanced vessel wall MRI study.

OBJECTIVES: Aneurysm wall enhancement (AWE) on high-resolution contrast-enhanced vessel wall MRI (VWMRI) is an emerging biomarker for intracranial aneurysms (IAs) stability. Quantification methods of AWE in the literature, however, are variable. We aimed to determine the optimal post-contrast timing to quantify AWE in both saccular and fusiform IAs. MATERIALS AND METHODS: Consecutive patients with unruptured IAs were prospectively recruited. VWMRI was acquired on 1 pre-contrast and 4 consecutive post-contrast phases (each phase was 9 min). Signal intensity values of cerebrospinal fluid (CSF) and aneurysm wall on pre- and 4 post-contrast phases were measured to determine the aneurysm wall enhancement index (WEI). AWE was also qualitatively analyzed on post-contrast images using previous grading criteria. The dynamic changes of AWE grade and WEI were analyzed for both saccular and fusiform IAs. RESULTS: Thirty-four patients with 42 IAs (27 saccular IAs and 15 fusiform IAs) were included. The changes in AWE grade occurred in 8 (30%) saccular IAs and 6 (40%) in fusiform IAs during the 4 post-contrast phases. The WEI of fusiform IAs decreased 22.0% over time after contrast enhancement (p = 0.009), while the WEI of saccular IAs kept constant during the 4 post-contrast phases (p > 0.05). CONCLUSIONS: When performing quantitative analysis of AWE, acquiring post-contrast VWMRI immediately after contrast injection achieves the strongest AWE for fusiform IAs. While the AWE degree is stable for 36 min after contrast injection for saccular IAs. CLINICAL RELEVANCE STATEMENT: The standardization of imaging protocols and analysis methods for AWE will be helpful for imaging surveillance and further treatment decisions of patients with unruptured IAs. KEY POINTS: Imaging protocols and measurements of intracranial aneurysm wall enhancement are reported heterogeneously. Aneurysm wall enhancement for fusiform intracranial aneurysms (IAs) is strongest immediately post-contrast, and stable for 36 min for saccular IAs. Future multi-center studies should investigate aneurysm wall enhancement as an emerging marker of aneurysm growth and rupture.

Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence.

Lung cancer is a prevalent malignant tumor and a leading cause of cancer-related fatalities globally. However, current treatments all have limitations. Therefore, there is an urgent need to identify a readily available therapeutic agent to counteract lung cancer development and progression. Luteolin is a flavonoid derived from vegetables and herbs that possesses preventive and therapeutic effects on various cancers. With the goal of providing new directions for the treatment of lung cancer, we review here the recent findings on luteolin so as to provide new ideas for the development of new anti-lung cancer drugs. The search focused on studies published between January 1995 and January 2024 that explored the use of luteolin in lung cancer. A comprehensive literature search was conducted in the SCOPUS, Google Scholar, PubMed, and Web of Science databases using the keywords "luteolin" and "lung cancer." By collecting previous literature, we found that luteolin has multiple mechanisms of therapeutic effects, including promotion of apoptosis in lung cancer cells; inhibition of tumor cell proliferation, invasion and metastasis; and modulation of immune responses. In addition, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications. This review summarizes the structure, natural sources, physicochemical properties and pharmacokinetics of luteolin, and focuses on the anti-lung cancer mechanism of luteolin, so as to provide new ideas for the development of new anti-lung cancer drugs.

Reduced field-of-view DWI based on deep learning reconstruction improving diagnostic accuracy of VI-RADS for evaluating muscle invasion.

OBJECTIVES: To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. METHODS: Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). RESULTS: The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p < 0.05). The mean ADC of all cases of rFOVSTA DWI and rFOVDLR DWI was significantly lower than that of fFOV DWI (all p < 0.05). There was no difference in mean ADC value and the AUC for evaluating muscle invasion between rFOVSTA DWI and rFOVDLR DWI (p > 0.05). CONCLUSIONS: rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. CRITICAL RELEVANCE STATEMENT: The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. KEY POINTS: Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI.

DPIF-Net: a dual path network for rural road extraction based on the fusion of global and local information.

Background: Automatic extraction of roads from remote sensing images can facilitate many practical applications. However, thus far, thousands of kilometers or more of roads worldwide have not been recorded, especially low-grade roads in rural areas. Moreover, rural roads have different shapes and are influenced by complex environments and other interference factors, which has led to a scarcity of dedicated low level category road datasets. Methods: To address these issues, based on convolutional neural networks (CNNs) and tranformers, this article proposes the Dual Path Information Fusion Network (DPIF-Net). In addition, given the severe lack of low-grade road datasets, we constructed the GaoFen-2 (GF-2) rural road dataset to address this challenge, which spans three regions in China and covers an area of over 2,300 km, almost entirely composed of low-grade roads. To comprehensively test the low-grade road extraction performance and generalization ability of the model, comparative experiments are carried out on the DeepGlobe, and Massachusetts regular road datasets. Results: The results show that DPIF-Net achieves the highest IoU and F1 score on three datasets compared with methods such as U-Net, SegNet, DeepLabv3+, and D-LinkNet, with notable performance on the GF-2 dataset, reaching 0.6104 and 0.7608, respectively. Furthermore, multiple validation experiments demonstrate that DPIF-Net effectively preserves improved connectivity in low-grade road extraction with a modest parameter count of 63.9 MB. The constructed low-grade road dataset and proposed methods will facilitate further research on rural roads, which holds promise for assisting governmental authorities in making informed decisions and strategies to enhance rural road infrastructure.

Shenfu injection alleviate gut ischemia/reperfusion injury after severe hemorrhagic shock through improving intestinal microcirculation in rats.

Background: Shenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm？ inistration timing. Methods: Twenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP 'were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed. Results: SF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group. Conclusions: SF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase.

The temporal variation in the effects of extreme temperature on respiratory mortality: Evidence from 136 cities in China, 2006-2019.

BACKGROUND: In the context of climate change and urbanization, the temporal variation of the adverse health effect of extreme temperature has attracted increasing attention. METHODS: The meteorological data and the daily death records of mortality from respiratory diseases of 136 Chinese cities were from 2006 to 2019. Heat wave and cold spell were selected as the indicator events of extreme high temperature and extreme low temperature, respectively. The generalized linear model and time-varying distributed lag model were used to perform a two-stage time-series analysis to evaluate the temporal variation of the mortality risk associated with extreme temperature in the total population, sub-populations (sex- and age- specific) and different regions (climatic zone and relative humidity level). RESULTS: During the study period, relative risk (RR) of respiratory mortality associated with heat wave decreased from 1.22 (95 %CI: 1.07-1.39) to 1.13 (95 %CI: 1.01-1.26) in the total population, and RR of respiratory mortality associated with cold spell decreased from 1.30 (95 %CI: 1.14-1.49) to 1.17 (95 %CI: 1.08-1.26). The impact of heat wave reduced in the males (P = 0.044) and in the females as with cold spell (P < 0.001). The respiratory mortality risk of people over 65 associated with cold spell decreased (P = 0.040 for people aged 65-74 and P < 0.001 for people over 75). The effect of cold spell reduced in cities from tropical or arid zone (P = 0.035). The effects of both heat wave and cold spell decreased in cities with the relative humidity in the first quartile (P = 0.046 and 0.010, respectively). CONCLUSION: The impact of heat wave on mortality of respiratory diseases decreased mainly in males and cities with the lowest relative humidity, while the impact of cold spell reduced in females, people over 65 and tropical and arid zone, suggesting adaptation to extreme temperature of Chinese residents to some extent.