Integrated image and location analysis for wound classification: a deep learning approach.

The global burden of acute and chronic wounds presents a compelling case for enhancing wound classification methods, a vital step in diagnosing and determining optimal treatments. Recognizing this need, we introduce an innovative multi-modal network based on a deep convolutional neural network for categorizing wounds into four categories: diabetic, pressure, surgical, and venous ulcers. Our multi-modal network uses wound images and their corresponding body locations for more precise classification. A unique aspect of our methodology is incorporating a body map system that facilitates accurate wound location tagging, improving upon traditional wound image classification techniques. A distinctive feature of our approach is the integration of models such as VGG16, ResNet152, and EfficientNet within a novel architecture. This architecture includes elements like spatial and channel-wise Squeeze-and-Excitation modules, Axial Attention, and an Adaptive Gated Multi-Layer Perceptron, providing a robust foundation for classification. Our multi-modal network was trained and evaluated on two distinct datasets comprising relevant images and corresponding location information. Notably, our proposed network outperformed traditional methods, reaching an accuracy range of 74.79-100% for Region of Interest (ROI) without location classifications, 73.98-100% for ROI with location classifications, and 78.10-100% for whole image classifications. This marks a significant enhancement over previously reported performance metrics in the literature. Our results indicate the potential of our multi-modal network as an effective decision-support tool for wound image classification, paving the way for its application in various clinical contexts.

Evaluation of the Protective Bioactivity and Molecular Mechanism Verification of Lactoferrin in an Alzheimer's Mouse Model with Ulcerative Enteritis.

The development of new drug therapies for Alzheimer's disease (AD) is an important research topic today, but the pathogenesis of AD has not been thoroughly studied, and there are still several shortcomings in existing drug therapies. Therefore, this study aims to explore the molecular mechanism of lactoferrin in the treatments of AD and ulcerative colitis (UC) which are susceptible to AD, starting from the principle of "one drug, two diseases, and the same treatment." This study used pathological staining and specific indicators staining to preliminarily evaluate the interventions of lactoferrin on UC injury and AD progression. And 16s RNA full-length sequencing was used to investigate the effect of lactoferrin on the abundance of intestinal microbiota in AD mice. Then, intestinal tissue and brain tissue metabolomics analysis were used to screen specific metabolic pathways and preliminarily verify the metabolic mechanism of lactoferrin in alleviating 2 diseases by regulating certain specific metabolites. Moreover, lactoferrin significantly changed the types and abundance of gut microbiota in AD mice complicated by UC. To conclude, this study proved the clinical phenomenon of AD susceptibility to UC, and verified the therapeutic effect of lactoferrin on 2 diseases. More importantly, we revealed the possible molecular mechanism of LF, not only does it enrich the cognitive level of lactoferrin in alleviating AD by regulating the gut microbiota through the brain gut axis from the perspective of the theory of "food nutrition promoting human health," but it also provides a practical basis for the subsequent research and development of lactoferrin and drug validation from the perspective of "drug food homology."

The alleviative effects comparison of four flavonoids from bamboo leaves on ulcerative colitis in an Alzheimer mouse model.

BACKGROUND: Clinically, patients with dementia are at high risk of developing enteritis, especially those with AD. This study explored the potential therapeutic benefits of bamboo leaf flavonoids (BLF) for ulcerative colitis (UC) treatment in Alzheimer's disease (AD) mouse model. METHODS: Various methods were employed, including pathological staining of brain/colon tissue, inflammatory cytokine detection in serum, and oxidative stress indicator assessment to compare ulcerative enteritis (UC) injury in normal and AD mice and determine whether AD mice were susceptible to colitis. Then, the effects of BLF on UC and AD were investigated via several unique indices further to determine whether it alleviated colitis injury and possessed beneficial properties. Moreover, four main components of BLF were utilized to treat primary colon epithelial cells and neuron cells to compare their effects in alleviating inflammation and oxidation. Furthermore, homoorientin embedded with ursolic acid was detected by HPLC and the in vitro release simulation experiments of the nanoparticles were performed. RESULTS: BLF complexes positively impacted ulcerative colitis by reducing disease activity, it also helped to reduce inflammation. Moreover, the BLF complexes decreased oxidative stress in the brain and colon tissues, indicating its potential as a neuroprotective agent. The flavonoid complexes reduced the expression levels of GFAP, Iba-1, and Aß in the brain tissue, highlighting its role in attenuating neuroinflammation and AD pathology. Additionally, the embedded homoorientin coated with ursolic acid showed stronger bioactivities when compared with the uncoated group. CONCLUSION: These results suggest that BLF complexes and its four main chemicals may be useful for treating AD- and UC-related complications, the embedded homoorientin coated with ursolic acid even demonstrated stronger bioavailability than homoorientin. Considering BLF complexes were verified to suppress the progressions of AD and UC for the first time, and the embedded homoorientin was never reported in published articles, the present study might provide a new perspective on its potential applications.

Combined toxicity of trifloxystrobin and fluopyram to zebrafish embryos and the effect on bone development.

Trifloxystrobin (TRI) is a methacrylate fungicide, and fluopyram (FLU) is a new pyridylethylbenzamide fungicide and nematicide. Both are often detected in water bodies and may be highly toxic to many aquatic organisms. Unfortunately, the aquatic biological risks of single FLU or a mixture of trifloxystrobin and fluopyram have not been reported. In this study, zebrafish was selected as the test organism to investigate the combined toxicity of trifloxystrobin and fluopyram to zebrafish. After zebrafish embryos exposed to three pesticide solutions, Alcian-blue staining, Alizarin-red staining and quantitative PCR (qPCR) were performed. The results indicated that 96h-LC50 of TRI was 0.159 mg·L-1 to zebrafish embryo, which was highly toxic. The 96h-LC50 of FLU to zebrafish embryos was 4.375 mg·L-1, being moderately toxic. The joint toxicity to zebrafish embryos(FLU at 96h-LC50 and TRI at 96h-LC50 in a 1:1 weight ratio to form a series of concentration treatment groups) was antagonistic. Both trifloxystrobin and fluopyram also inhibited the skeletal development of zebrafish and showed to be antagonistic. The results of qPCR indicated upregulations of different genes upon three different treatments. TRI mainly induced Smads up-expression, which may affect the BMP-smads pathway. FLU mainly induced an up-expression of extracellular BMP ligands and type I receptor (Bmpr-1a), which may affect the BMP ligand receptor pathway. The 1:1 mixture (weight ratio) of trifloxystrobin and fluopyram induced a reduction of the genes of extracellular BMP ligand (Smads) and type I receptor (Bmpr1ba), which may down-regulate BMP signaling and thus attenuating cartilage hyperproliferation, hypertrophy and mineralization. The results warren an interest in further studying the effect of the two fungicides in a mixture on zebrafish.

Toxic effects of the insecticide tolfenpyrad on zebrafish embryos: Cardiac toxicity and mitochondrial damage.

Tolfenpyrad, a highly effective and broad-spectrum insecticide and acaricide extensively utilized in agriculture, presents a potential hazard to nontarget organisms. This study was designed to explore the toxic mechanisms of tolfenpyrad on zebrafish embryos. Between 24 and 96 h after exposure of the fertilized embryos to tolfenpyrad at concentrations ranging from 0.001 to 0.016 mg/L (96 h-LC50 = 0.017 mg/L), lethal effects were apparent, accompanied with notable anomalies including pericardial edema, increased pericardial area, diminished heart rate, and an elongated distance between the venous sinus and the arterial bulb. Tolfenpyrad elicited noteworthy alterations in the expression of genes pertinent to cardiac development and apoptosis, with the most pronounced changes observed in the cardiac development-related genes of bone morphogenetic protein 2b (bmp2b) and p53 upregulated modulator of apoptosis (puma). The findings underscore that tolfenpyrad induces severe cardiac toxicity and mitochondrial damage in zebrafish embryos. This data is imperative for a comprehensive assessment of tolfenpyrad risks to aquatic ecosystems, particularly considering the limited knowledge regarding its detrimental impact on aquatic vertebrates.

Tenascin C+ papillary fibroblasts facilitate neuro-immune interaction in a mouse model of psoriasis.

Dermal fibroblasts and cutaneous nerves are important players in skin diseases, while their reciprocal roles during skin inflammation have not been characterized. Here we identify an inflammation-induced subset of papillary fibroblasts that promotes aberrant neurite outgrowth and psoriasiform skin inflammation by secreting the extracellular matrix protein tenascin-C (TNC). Single-cell analysis of fibroblast lineages reveals a Tnc+ papillary fibroblast subset with pro-axonogenesis and neuro-regulation transcriptomic hallmarks. TNC overexpression in fibroblasts boosts neurite outgrowth in co-cultured neurons, while fibroblast-specific TNC ablation suppresses hyperinnervation and alleviates skin inflammation in male mice modeling psoriasis. Dermal γδT cells, the main producers of type 17 pathogenic cytokines, frequently contact nerve fibers in mouse psoriasiform lesions and are likely modulated by postsynaptic signals. Overall, our results highlight the role of an inflammation-responsive fibroblast subset in facilitating neuro-immune synapse formation and suggest potential avenues for future therapeutic research.

MicroRNA-7 modulates cellular senescence to relieve gemcitabine resistance by targeting PARP1/NF-κB signaling in pancreatic cancer cells.

Senescence is activated in response to gemcitabine to prevent the propagation of cancer cells. However, there is little evidence on whether senescence is involved in gemcitabine resistance in pancreatic cancer. Increasing evidence has demonstrated that microRNAs (miRs) are potential regulators of cellular senescence. The present study aimed to investigate whether aberrant miR-7 expression modulated senescence to influence pancreatic cancer resistance to chemotherapy. In the present study, cell senescence assay, ALDEFLUOR™ assay, luciferase reporter assay, flow cytometry, quantitative PCR, immunohistochemistry and western blot analysis were performed to explore the association between senescence and gemcitabine therapy response, and to clarify the underlying mechanisms. The present study revealed that gemcitabine-induced chronically existing senescent pancreatic cells possessed stemness markers. Therapy-induced senescence led to gemcitabine resistance. Additionally, it was found that miR-7 expression was decreased in gemcitabine-resistant pancreatic cancer cells, and that miR-7 acted as an important regulator of cellular senescence by targeting poly (ADP-ribose) polymerase 1 (PARP1)/NF-κB signaling. When miR-7 expression was restored, it was able to sensitize pancreatic cancer cells to gemcitabine. In conclusion, the present study demonstrated that miR-7 regulated cellular senescence and relieved gemcitabine resistance by targeting the PARP1/NF-κB axis in pancreatic cancer cells.

Targeting the Dvl-1/ß-arrestin2/JNK3 interaction disrupts Wnt5a-JNK3 signaling and protects hippocampal CA1 neurons during cerebral ischemia reperfusion.

It is well known that Wnt5a activation plays a pivotal role in brain injury and ß-arrestin2 induces c-Jun N-terminal kinase (JNK3) activation is involved in neuronal cell death. Nonetheless, the relationship between Wnt5a and JNK3 remains unexplored during cerebral ischemia/reperfusion (I/R). In the present study, we tested the hypothesis that Wnt5a-mediated JNK3 activation via the Wnt5a-Dvl-1-ß-arrestin2-JNK3 signaling pathway was correlated with I/R brain injury. We found that cerebral I/R could enhance the assembly of the Dvl-1-ß-arrestin2-JNK3 signaling module, Dvl-1 phosphorylation and JNK3 activation. Activated JNK3 could phosphorylate the transcription factor c-Jun, prompt caspase-3 activation and ultimately lead to neuronal cell death. To further explore specifically Wnt5a mediated JNK3 pathway activation in neuronal injury, we used Foxy-5 (a peptide that mimics the effects of Wnt5a) and Box5 (a Wnt5a antagonist) both in vitro and in vivo. AS-ß-arrestin2 (an antisense oligonucleotide against ß-arrestin2) and RRSLHL (a small peptide that competes with ß-arrestin2 for binding to JNK3) were applied to confirm the positive signal transduction effect of the Dvl-1-ß-arrestin2-JNK3 signaling module during cerebral I/R. Furthermore, Box5 and the RRSLHL peptide were found to play protective roles in neuronal death both in vivo global and focal cerebral I/R rat models and in vitro oxygen glucose deprivation (OGD) neural cells. In summary, our results indicate that Wnt5a-mediated JNK3 activation participates in I/R brain injury by targeting the Dvl-1-ß-arrestin2/JNK3 interaction. Our results also point to the possibility that disrupting Wnt5a-JNK3 signaling pathway may provide a new approach for stroke therapy.

Determination of antibacterial ofloxacin in human serum samples by a resonance light scattering technique with alizarin violet 3B.

A method for the determination of ofloxacin (OFL) has been developed, based on the enhancement of resonance light scattering (RLS) of OFL in the presence of alizarin violet 3B (AV3B). Under the experimental conditions, the RLS intensity of AV3B was greatly enhanced by adding OFL. At pH 5.09, the enhancement of the RLS intensity at 439.5 nm was proportional to the concentration of OFL in the range 0.10-2.50 microg/ml. The detection limit (3sigma) was 0.013 microg/ml. At pH 6.90, the enhancement of the RLS intensity at 405.0 nm was proportional to the concentration of OFL in the range 0.05-3.00 microg/ml. The detection limit (3sigma) was 0.021 microg/ml. The proposed method with high sensitivity, selectivity and reproducibility was satisfactorily applied to the determination of OFL in human serum.

Resonance light scattering spectroscopy of beta-cyclodextrin-sodium dodecylsulfate-protein ternary system and its analytical applications.

A simple, highly sensitive and dye-less assay for proteins was reported using a resonance light-scattering (RLS) technique based on the enhanced RLS intensity of beta-cyclodextrin (beta-CD)-sodium dodecylsulfate (SDS)-protein system. Under the optimum conditions, the enhanced RLS intensity is in proportion to the concentration of proteins in the range of 0.01 to 2.3 microg ml(-1) for bovine serum albumin (BSA), 0.01 to 2.0 microg ml(-1) for human serum albumin (HSA), 0.015 to 5.0 microg ml(-1) for gamma-globulin (gamma-G), 0.02 to 3.5 microg ml(-1) for egg albumin (EA), 0.02 to 4.0 microg ml(-1) for pepsin (Pep), and 0.02 to 3.6 microg ml(-1) for alpha-chymotrypsin (Chy). Their detection limits (S/N = 3) are 1.1, 1.6, 2.4, 6.7, 5.4 and 4.2 ng ml(-1), respectively. Synthetic samples and human serum samples were determined satisfactorily, and the results were in reasonable agreement with those obtained by a documented spectrophotometric (Bradford) method.

Resonance light scattering spectroscopy study of interaction between norfloxacin and calf thymus DNA and its analytical application.

The interaction between norfloxacin and calf thymus double-stranded DNA (dsDNA) has been studied by a resonance light scattering (RLS) technique with a common spectrofluorometer. The characteristics of RLS spectra, the effective factors and optimum conditions of the reaction have been investigated. In Britton-Robinson (BR) buffer (pH 5.87), norfloxacin has a maximum peak 405.5 nm and the RLS intensity is remarkably enhanced by trace amount of calf thymus dsDNA due to the interaction between norfloxacin and dsDNA. The binding of norfloxacin to DNA forms large particles, which were characterized by RLS spectrum, scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrum, and fluorescence spectrum. Based on the enhanced RLS intensity, a novel method for sensitive determination of calf thymus dsDNA concentration ranging from 0.02 to 2.3 microg ml(-1) was developed. The determination limit (3 sigma) was 1.2 ng ml(-1). The method is simple, rapid, practical and relatively free from interference generated by coexisting substance, as well as much more sensitive than most of the reported methods. Three synthetic samples of ctDNA were determined with satisfactory results.