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OBJECTIVE: To investigate the diagnostic and therapeutic value of direct visualization (single-use eyeMax subscope) endoscopic management of acute uncomplicated appendicitis. METHODS: Thirty-six patients diagnosed with acute uncomplicated appendicitis, confirmed by computed tomography or ultrasonography, from Jan 2023 to Feb 2024 were enrolled in this study. We collected demographics, colonoscopy findings, subscope findings, clinical outcomes of endoscopic retrograde appendicitis therapy (ERAT), and adverse events associated with ERAT. RESULTS: Appendiceal intubation was successful for all 36 patients. Thirty-five patients (97.2%) were definitely confirmed as having acute uncomplicated appendicitis. One patient with negative appendicitis was diagnosed as having cecal diverticulitis with fecalith incarceration. The mean procedure time was 13.1 ± 13.6 min. One patient presented with worsening abdominal pain, and a computed tomography scan suggested a perforated appendix. The mean length of hospitalizations was 1.78 ± 2 days. The mean follow-up was 158 days; during this period, two patients (5.6%) experienced recurrent abdominal pain after 23 and 88 days and subsequently underwent laparoscopic appendectomy. CONCLUSION: Direct visualization ERAT may be effective for diagnosing and treating acute uncomplicated appendicitis and seems to have a low complication rate.
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PURPOSE: This study aims to explore the clinical value of autogenous tibial periosteal bone grafting in the treatment of osteochondral lesions of the talus (OLT) and analyze the three-dimensional factors in the necrotic zone of the talus. METHODS: A retrospective analysis was performed on 36 patients who underwent autogenous tibial periosteal bone grafting in the Foot and Ankle Surgery Department of our hospital between September 2018 and September 2022. The American Orthopaedic Foot and Ankle Society (AOFAS), Visual Analogue Scale (VAS), and Chinese Short-Form 36 Health Survey (SF-36) were used to evaluate treatment efficacy prior to surgery and at the last follow-up. Furthermore, Mimics 21.0 software was employed to measure the three-dimensional data of the necrotic area, including surface area, volume, and depth, in order to investigate their potential impact on patient prognosis. RESULTS: Among the 36 OLT patients who obtained complete follow-up, there were 22 males and 14 females. No complications such as surgical site infection, non-union of cartilage, post-traumatic arthritis, or donor site pain were observed. The AOFAS, VAS, and Chinese SF-36 scores of all patients at the last follow-up showed significant improvement compared to preoperative values. There was no significant correlation between the AOFAS, VAS, and Chinese SF-36 scores at the last follow-up and the depth, surface area, and volume of the necrotic zone. CONCLUSION: The use of autogenous tibial periosteal bone grafting can safely and effectively treat Hepple V OLT. Additionally, there is no significant correlation between the three-dimensional factors of the necrotic area and the prognosis of the patients.
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Transplante Ósseo , Tálus , Tíbia , Humanos , Masculino , Feminino , Tálus/cirurgia , Adulto , Estudos Retrospectivos , Transplante Ósseo/métodos , Tíbia/cirurgia , Pessoa de Meia-Idade , Adulto Jovem , Resultado do Tratamento , Periósteo/transplante , Adolescente , Transplante Autólogo/métodos , Necrose , Imageamento TridimensionalRESUMO
Transition metal ions are served as disinfectant thousand years ago. However, the in vivo antibacterial application of metal ions is strongly restricted due to its high affinity with proteins and lack of appropriate bacterial targeting method. Herein, for the first time, Zn2+ -gallic acid nanoflowers (ZGNFs) are synthesized by a facile one-pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution while can be easily decomposed in acidic environments. Besides, ZGNFs can specifically adhere onto Gram-positive bacteria, which is mediated by the interaction of quinone from ZGNFs and amino groups from teichoic acid of Gram-positive bacteria. ZGNFs exhibit high bactericidal effect toward various Gram-positive bacteria in multiple environments, which can be ascribed to the in situ Zn2+ release on bacterial surface. Transcriptome studies reveal that ZGNFs can disorder basic metabolic processes of Methicillin-resistant Staphylococcus aureus (MRSA). Moreover, in a MRSA-induced keratitis model, ZGNFs exhibit long-term retention in the infected corneal site and prominent MRSA elimination efficacy due to the self-targeting ability. This research not only reports an innovative method to prepare metal-polyphenol nanoparticles, but also provides a novel nanoplatform for targeted delivery of Zn2+ in combating Gram-positive bacterial infections.
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Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Positivas , Íons , Zinco/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Due to the occurrence of redundant speckle, multimode fiber (MMF) imaging is extremely challenging. Our work studies the relationship between the effective feature distribution of the speckle field and the local spatial position and area, and proves that the information distribution of the speckle is highly redundant. The effective feature refers to the phase and amplitude information of the optical field carrying the image point information and the co-exciting very redundant information due to mode dispersion, interference, coupling, and entrained noise through transmission. The neural network Swin-Unet can well learn the association information between global and local features, greatly simplifies the fitting of the MMF end-to-end global mapping relationship, and achieves high-fidelity reconstruction from the local speckle field to the global image. This work will contribute to the realization of MMF real-time large-field endoscopic imaging.
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Mesenchymal stem cells (MSCs) can promote osteogenesis and are a promising therapy for postmenopausal osteoporosis. However, the relationship between improved intraosseous microcirculation and increased bone mass induced by MSCs in postmenopausal osteoporosis remains unclear. After the primary MSCs were characterized, they were transplanted into ovariectomized mice. MSCs transplantation enhanced the trabecular number, trabecular bone volume/total volume, and trabecular bone mineral density in ovariectomized mice. To determine the role of MSCs in vascular repair, mice were subjected to femoral artery ligation. Through laser speckle flowmetry, vascular perfusion and femoral trabecular bone and cortical bone analyses, we determined the effects of MSCs in promoting intraosseous angiogenesis and preventing osteoporosis in mice. MSCs effectively prevented postmenopausal osteoporosis development, which is associated with the involvement of MSCs in reestablishment of microcirculation within the skeleton.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica , Osteoporose Pós-Menopausa/terapia , Ovariectomia/métodos , Remodelação Vascular/fisiologia , Animais , Densidade Óssea , Modelos Animais de Doenças , Feminino , Artéria Femoral/patologia , Artéria Femoral/cirurgia , Fêmur/irrigação sanguínea , Fêmur/diagnóstico por imagem , Fêmur/patologia , Citometria de Fluxo , Humanos , Ligadura , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/fisiologia , Osteogênese/fisiologia , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/patologia , Tomografia Computadorizada por Raios XRESUMO
The application of nanotechnology in antifungal therapy is gaining increasing attention. Current antifungal drugs have significant limitations, such as severe side effects, low bioavailability, and the rapid development of resistance. Nanotechnology offers an innovative solution to address these issues. This review discusses three key strategies of nanotechnology to enhance antifungal efficacy. Firstly, nanomaterials can enhance their interaction with fungal cells via ingenious surface tailoring of nanomaterials. Effective adhesion of nanoparticles to fungal cells can be achieved by electrostatic interaction or specific targeting to the fungal cell wall and cell membrane. Secondly, stimuli-responsive nanomaterials are developed to realize smart release of drugs in the specific microenvironment of pathological tissues, such as the fungal biofilm microenvironment and inflammatory microenvironment. Thirdly, nanomaterials can be designed to cross different physiological barriers, effectively addressing challenges posed by skin, corneal, and blood-brain barriers. Additionally, some new nanomaterial-based strategies in treating fungal infections are discussed, including the development of fungal vaccines, modulation of macrophage activity, phage therapy, the application of high-throughput screening in drug discovery, and so on. Despite the challenges faced in applying nanotechnology to antifungal therapy, its significant potential and innovation open new possibilities for future clinical antifungal applications.
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Foreign body response (FBR) represents an immune-mediated cascade reaction capable of inducing the rejection of foreign implants, thereby compromising their in vivo performance. Pure zwitterionic hydrogels have demonstrated the ability to resist long-term FBR, owing to their outstanding antifouling capabilities. However, achieving such a robust anti-FBR effect necessitates stringent requirements concerning the purity of zwitterionic materials, which constrains their broader functional applications. Herein, we present a biocompatible, controllably degradable, and functionalizable zwitterion-albumin hybrid hydrogel. The zwitterionic hydrogel crosslinked with serum albumin exhibits controllable degradation and excels in preventing the adsorption of various proteins and adhesion of cells and bacteria. Moreover, the hydrogel significantly alleviates the host's FBR compared with PEG hydrogels and particularly outperforms PEG-based cross-linker crosslinked zwitterionic hydrogels in reducing collagen encapsulation when subcutaneously implanted into mice. The zwitterion-albumin hybrid hydrogel shows potential as a functionalizable anti-FBR material in the context of implantable materials and biomedical devices.
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Reação a Corpo Estranho , Hidrogéis , Camundongos , Animais , Hidrogéis/farmacologia , Reação a Corpo Estranho/prevenção & controle , Materiais Biocompatíveis , Colágeno , Albuminas , FibroseRESUMO
Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.
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The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.
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Reação a Corpo Estranho , Hidrogéis , Animais , Hidrogéis/química , Camundongos , Materiais Biocompatíveis/química , Lisina/química , Primatas , Roedores , Ácido Poliglutâmico/químicaRESUMO
BACKGROUND: The distal-less homeobox (DLX) gene family plays an important role in the development of several tumors. However, the expression pattern, prognostic and diagnostic value, possible regulatory mechanisms, and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported. AIM: We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer. METHODS: Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue. cBioPortal was used to analyze DLX gene family variants. R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map. The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family. The pROC package was used to analyze the diagnostic value of the DLX gene family. R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes. The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration. The ggplot2, the survminer package, and the clusterProfiler package were used for visualization. RESULTS: DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients. The expression of DLX genes were associated with M stage, pathologic stage, primary therapy outcome, residual tumor, lymphatic invasion, T stage, N stage, age, perineural invasion, and history of colon polyps. DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis. DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways, including the Hippo signaling pathway, the Wnt signaling pathway, several signaling pathways regulating the pluripotency of stem cells, and Staphylococcus aureus infection. CONCLUSION: The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.
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Inhibition of quorum sensing (QS) is considered as an effective strategy in combatting biofilm-associated bacterial infections. However, the application of quorum sensing inhibitors (QSI) is strongly restricted by poor water-solubility and low bioavailability. We herein fabricate pH-sensitive curcumin (Cur) loaded clustered nanoparticles with active targeting ability (denoted as anti-CD54@Cur-DA NPs) to inhibit QS for enhanced antibiotic therapy. Cur-DA NPs are first prepared through electrostatic interaction between Cur loaded amino-ended poly(amidoamine) dendrimer (PAMAM) and 2,3-dimethyl maleic anhydride (DA) modified biotin-poly(ethylene glycol)-polylysine (biotin-PEG-PLys). Anti-CD54@Cur-DA NPs are then obtained by the modification of Cur-DA NPs with anti-CD54. Cur loaded PAMAM can be released from Cur-DA NPs in acidic pH, leading to simultaneous charge reversal and size decrease, which is beneficial for biofilm penetration. Cur-DA NPs are hence much better in inhibiting QS than free Cur due to enhanced biofilm penetration. Compared to free Cur, Cur-DA NPs exhibit stronger capability in inhibiting the development of biofilm architecture and maturation, thus downregulating efflux pump-related genes and improving bactericidal performance of multiple antibiotics, including Penicillin G, ciprofloxacin, and tobramycin. Moreover, since anti-CD54 can selectively bind to inflamed endothelial cells, anti-CD54@Cur-DA NPs can be targeted accumulated in bacteria-infected tissues. The sequential treatment using anti-CD54@Cur-DA NPs and free antibiotics can effectively reduce bacterial burden and alleviate inflammation in a chronic lung infection model in vivo. This research provides an effective way to improve the therapeutic performance of QSI to enhance the anti-biofilm effects of antibiotics, which radiate a vitality of conventional antibiotics in treating biofilm-associated bacterial infections.
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Infecções Bacterianas , Curcumina , Nanopartículas , Humanos , Percepção de Quorum , Células Endoteliais , Biotina , Nanopartículas/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Concentração de Íons de HidrogênioRESUMO
Malignant colorectal tumors and precancerous lesions are closely associated with chronic inflammation. Specific dietary patterns can increase chronic inflammation in the body, thereby promoting the occurrence of tumors and precancerous lesions. We have conducted a case-control study in Kashgar Prefecture, Xinjiang, China, to explore the association between the energy-adjusted dietary inflammatory index (E-DII) and the risk of colorectal adenomatous polyps (CAP). A total of 52 newly diagnosed patients with CAP and 192 controls at the First People's Hospital of Kashgar Prefecture were enrolled in this study. Dietary information was collected using a food frequency questionnaire. The E-DII was calculated based on dietary data, reflecting an individual's dietary inflammatory potential. Logistic regression models were used to evaluate the relationship between the E-DII and the risk of CAP, with adjustments for potential confounding factors. The results showed that the maximum anti- and pro-inflammatory values of E-DII were -4.33 and +3.48, respectively. Higher E-DII scores were associated with an increased risk of CAP, and this association remained statistically significant after adjusting for age, sex, body mass index, smoking status, and other relevant variables. Notably, a more pro-inflammatory dietary pattern may be related to an increased risk of developing CAP in Kashgar Prefecture.
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Antibiotic resistance is a big threat to public health. How to improve the therapeutic efficacy of conventional antibiotics is an effective way to address this issue. In order to enhance the antibacterial activity of conventional antibiotic erythromycin (EM), EM is conjugated to positively charged ε-poly-l-lysine (EPL) to obtain EPL modified EM (EPL-EM). The grafting ratio of EM can be calculated from the 1H NMR spectrum. EPL-EM is stable in physiological environment, while EM can be readily released from EPL-EM upon incubating with esterase which can be secreted by most bacteria. Because of the presence of cationic EPL, EPL-EM showed much stronger antibacterial activity than free EM, with much lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Moreover, compared to free EM, the development of drug resistance can be slowed down if EPL-EM is used, which can be ascribed to the reduction of EM dosage. Meanwhile, EPL-EM cannot induce hemolysis and cytotoxicity, which indicates that EPL-EM exhibits excellent biocompatibility. The design of EPL-EM with enhanced antibacterial activity and excellent biocompatibility provides an innovative way to combat antibiotic resistance.
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Background: Human epidermal growth factor receptor 2 (HER2) is a landmark protein in determining the targeted treatment of breast cancer (BC). However, the latest research shows that different intensity of HER2 protein expression levels in BC leads to different clinical characteristics, treatment, and prognosis, especially in HER2 low expression patients. Therefore, this study intends to analyze and compare the clinicopathologic features and prognosis of BC patients with low and zero HER2 expression from The Cancer Genome Atlas (TCGA) database and the data collected by our center. Methods: First, the BC dataset was downloaded from TCGA database, including 345 eligible and with complete clinical information BC patients, to compare the difference between HER2 low expression groups and HER2 zero expression groups and their correlation with estrogen receptor (ER) and progesterone receptor (PR) expression. Then, the clinicopathological data and follow-up of 405 patients with HER2 low expression and HER2 zero expression diagnosed with BC admitted to the Affiliated Hospital of Youjiang Medical University for Nationalities (YJMU) from January 2017 to December 2021 were collected to verify the consistency of the results of the two data sets. Results: Both the clinical samples and the TCGA data showed that the ER and PR rates were higher in the HER2 low expression group compared with the HER2 zero expression group. There were no significant differences in tumor size, lymph node metastasis, distant metastasis, and disease-free survival (DFS). In addition, the data analysis of 405 clinical samples also showed that the HER2 low expression group had a lower 3-year recurrence or metastasis rate compared with the HER2 zero expression group. Conclusions: Compared with HER2 zero expression, HER2 low patients express more ER and PR, and have less short-term recurrence and metastasis, but there is no obvious difference in DFS between the two groups.
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Background: The clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes. Results: A total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P<0.001). Furthermore, the 60-day mortality rate was 2.1% (1/48) in the EN group, while it was notably higher at 30.4% (7/23) in the PN group (P=0.001). To identify the independent predictors of 60-day mortality, stepwise logistic regression analysis was employed. Among different bacterial groups, Enterococcus_faecium (18.19%) and Pseudomonas_aeruginosa (1.91%) had higher average relative abundance in the PN group (P<0.05). However, the relative abundance of Ruminococcus was higher in the EN group. Further Spearman correlation analysis showed that Enterococcus_faecium was positively correlated with poor clinical prognosis, while Ruminococcus was negatively correlated with poor clinical prognosis. Conclusions: This study shows that the changes in the composition of intestinal flora in elderly COVID-19 patients receiving different nutritional support strategies may be related to different clinical outcomes. The abundance of Enterococcus_faecium in elderly COVID-19 patients receiving PN is significantly increased and is closely related to poor clinical outcomes. It highlights the potential of microbiome-centric interventions to mitigate and manage COVID-19 in older adults with different nutritional support options.
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COVID-19 , Microbioma Gastrointestinal , Humanos , Idoso , COVID-19/terapia , SARS-CoV-2 , Prognóstico , Nutrição Parenteral/métodosRESUMO
Introduction: Nettle is kind of new feed resources and benefit for animal production. However, a few studies observed that quality of nettle silage was poor under naturally fermentation. Consider of microbial activity was the mainly factors for fermentation characteristics of silage. Methods: Thus, the present study investigated the potential factors causing nettle silage failure through metabolome and bacterial community composition analyses during ensiling. Results: During ensiling, the pH was >6.22, and water-soluble carbohydrate and organic acid contents stabilized after 7 d. At the genus level, Enterococcus, Weissella, and Pediococcus were the dominant bacteria (relative abundance were 30.06-39.39, 17.29-23.34, and 3.13-7.22%, respectively), with stable trends, whereas Lactococcus and Enterobacter relative abundance decreased significantly over time (relative abundance were 5.68-13.96 and 3.86-24.1%, respectively). Lactobacillus relative abundance was <1% during the entire ensiling period, and malic acid metabolic pathway was the most important pathway. Enterococcus, Pediococcus, and Weissella were negatively correlated with malic acid, with Lactobacillus displaying an opposite trend. Discussion: The results suggested that Lactobacillus activity was the lowest among lactic acid bacteria (LAB) during ensiling, which is the main reason for nettle ensiling failure, and attributable to a low capacity to compete for fermentation substrates such as malic acid against other LAB during ensiling. Additionally, anti-bacteria activity of nettle probably inhibited Enterobacter activity during ensiling. Present study probably given a solution for improve nettle silage quality through addition with malic acid.
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Sainfoin (Onobrychis viciifolia) is rich in condensed tannins (CT). CT function includes inhibiting bacterial and fungi activity during the ensiling process. We used polyethylene glycol (PEG) to deactivate tannin activity to find out the effects of CT. The results show that the addition of PEG increased dry-matter loss (8.32% vs. 14.15%, on a dry-matter basis) after 60 d of ensiling, and also increased lactic acid (10.90% vs. 15.90%, on a dry-matter basis) and acetic-acid content (7.32% vs. 13.85%, on a dry-matter basis) after 30 d of ensiling. The PEG-treated group increased its Pediococcus relative abundance (0.37−3.38% vs. 7.82−23.5%,) during the ensiling process, increased its Gibellulopsis relative abundance after 3 d of ensiling (5.96% vs. 19.52%), increased its Vishniacozyma relative abundance after 3 d and 7 d of ensiling (2.36% vs. 17.02%, 3.65% vs. 17.17%), and increased its Aspergillus relative abundance after 7 d, 14 d and 60 d of ensiling (0.28% vs. 1.32%, 0.49% vs. 2.84% and 1.74% vs. 7.56%). However, the PEG-treated group decreased its Alternaria relative abundance during entire ensiling process (14.00−25.21% vs. 3.33−7.49%). These results suggest that condensed tannins inhibit lactic-acid bacteria fermentation though reducing Pediococcus activity, and inhibiting fungi activity depending on different strains.
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Background: Neoadjuvant chemotherapy (NAC) is an important treatment for breast cancer (BC) patients. However, due to the lack of specific therapeutic targets, only 1/3 of human epidermal growth factor receptor 2 (HER2)-negative patients reach pathological complete response (pCR). Therefore, there is an urgent need to identify novel biomarkers to distinguish and predict NAC sensitive in BC patients. Methods: The GSE163882 dataset, containing 159 BC patients treated with NAC, was downloaded from the Gene Expression Omnibus (GEO) database. Patients with pathological complete response (pCR) and those with residual disease (RD) were compared to obtain the differentially expressed genes (DEGs). Functional enrichment analyses were conducted on these DEGs. Then, we intersect the DEGs and immune-related genes to obtain the hub immune biomarkers, and then use the linear fitting model ("glm" package) to construct a prediction model composed of 9 immune biomarkers. Finally, the single sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze immune cell invasion in BC patients, and the correlation between immune cell content and immune gene expression levels was analyzed. Results: Nine immune-related biomarkers were obtained in the intersection of DEGs and immune-related genes. Compared with RD patients, CXCL9, CXCL10, CXCL11, CXCL13, GZMB, IDO1, and LYZ were highly expressed in pCR patients, while CXCL14 and ESR1 were lowly expressed in pCR patients. After linear fitting of the multi-gene expression model, the area under the curve (AUC) value of the ROC curve diagnosis of pCR patients was 0.844. Immunoinfiltration analysis showed that compared with RD patients, 15 of the 28 immune cell types examined showed high-infiltration in pCR patients, including activated CD8 T cells, effector memory CD8 T cells, and activated CD4 T cells. Conclusions: This investigation ultimately identified 9 immune-related biomarkers as potential tools for assessing the sensitivity of NAC in HER2-negative BC patients. These biomarkers have great potential for predicting pCR BC patients.
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BACKGROUND: An increasing number of studies have demonstrated a role for the tumor microenvironment in tumorigenesis, disease progression, and therapeutic response. This present study aimed to screen the significant immune-related genes and their possible role in the prognosis of breast cancer (BRCA). METHODS: The transcriptome data and clinical data of breast cancer were collected from The Cancer Genome Atlas (TCGA), and the immune scores and stromal scores were calculated by ESTIMATE algorithm. The differentially expressed genes were screened base on immune and stromal scores (high score vs. low score), than the intersected genes were used for subsequent functional enrichment analysis and protein-protein interaction (PPI) analysis. Furthermore, the key gene was identified by the intersection of the hub genes of PPI network and the prognostic genes of breast cancer. Finally, we explored the infiltration of immune cells of BRCA base on the CIBERSORT algorithm, and analysis the relationship between key gene and immune cells. RESULTS: High levels of CD52 expression were detected in the early stages of breast cancer and were associated with favorable prognosis. Overexpression of CD52 led to higher infiltrations of M1 macrophages, monocytes, T follicular helper cells, and resting memory CD4 T cells. Downregulation of CD52 resulted in high infiltrations of M2 macrophages. Therefore, high expression of CD52 may negatively regulate the infiltration of M2 macrophages but accelerate the infiltration of anti-cancer immune cells, and thus, high expression of CD52 may have a protective effect in breast cancer patients. CONCLUSIONS: CD52 can increase the infiltration of anti-cancer immune cells but inhibit the infiltration of M2 macrophages, thereby improving the prognosis of breast cancer patients.